FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Ashcraft, KA
Peace, RM
Betof, AS
Dewhirst, MW
Jones, LW
AF Ashcraft, Kathleen A.
Peace, Ralph M.
Betof, Allison S.
Dewhirst, Mark W.
Jones, Lee W.
TI Efficacy and Mechanisms of Aerobic Exercise on Cancer Initiation,
Progression, and Metastasis: A Critical Systematic Review of In Vivo
Preclinical Data
SO CANCER RESEARCH
LA English
DT Review
ID TUMOR-BEARING RATS; INDUCED MAMMARY CARCINOGENESIS; INDUCED COLON
CARCINOGENESIS; RANDOMIZED CONTROLLED-TRIAL; HIGH-INTENSITY EXERCISE;
HEALTHY FOOD CHOICES; MALE F344 RATS; BREAST-CANCER; PHYSICAL-ACTIVITY;
VOLUNTARY EXERCISE
AB A major objective of the emerging field of exercise-oncology research is to determine the efficacy of, and biological mechanisms by which, aerobic exercise affects cancer incidence, progression, and/or metastasis. There is a strong inverse association between self-reported exercise and the primary incidence of several forms of cancer; similarly, emerging data suggest that exercise exposure after a cancer diagnosis may improve outcomes for early-stage breast, colorectal, or prostate cancer. Arguably, critical next steps in the development of exercise as a candidate treatment in cancer control require preclinical studies to validate the biological efficacy of exercise, identify the optimal "dose", and pinpoint mechanisms of action. To evaluate the current evidence base, we conducted a critical systematic review of in vivo studies investigating the effects of exercise in cancer prevention and progression. Studies were evaluated on the basis of tumor outcomes (e.g., incidence, growth, latency, metastasis), dose-response, and mechanisms of action, when available. A total of 53 studies were identified and evaluated on tumor incidence (n = 24), tumor growth (n = 33), or metastasis (n = 10). We report that the current evidence base is plagued by considerable methodologic heterogeneity in all aspects of study design, endpoints, and efficacy. Such heterogeneity precludes meaningful comparisons and conclusions at present. To this end, we provide a framework of methodologic and data reporting standards to strengthen the field to guide the conduct of high-quality studies required to inform translational, mechanism-driven clinical trials. (C)2016 AACR.
C1 [Ashcraft, Kathleen A.; Peace, Ralph M.; Dewhirst, Mark W.] Duke Univ, Med Ctr, Durham, NC 27710 USA.
[Betof, Allison S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jones, Lee W.] Mem Sloan Kettering Canc Ctr, New York, NY 10017 USA.
RP Jones, LW (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, 485 Lexington Ave, New York, NY 10017 USA.; Dewhirst, MW (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3455,Med Sci Res Bldg 1,Room 201, Durham, NC 27710 USA.
EM mark.dewhirst@duke.edu; jonesl3@mskcc.org
FU NCI NIH HHS [P30 CA008748, R01 CA040355]
NR 106
TC 1
Z9 1
U1 10
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2016
VL 76
IS 14
BP 4032
EP 4050
DI 10.1158/0008-5472.CAN-16-0887
PG 19
WC Oncology
SC Oncology
GA DS9NY
UT WOS:000381111400003
PM 27381680
ER
PT J
AU Weygant, N
Ge, Y
Qu, DF
Kaddis, JS
Berry, WL
May, R
Chandrakesan, P
Bannerman-Menson, E
Vega, KJ
Tomasek, JJ
Bronze, MS
An, GY
Houchen, CW
AF Weygant, Nathaniel
Ge, Yang
Qu, Dongfeng
Kaddis, John S.
Berry, William L.
May, Randal
Chandrakesan, Parthasarathy
Bannerman-Menson, Edwin
Vega, Kenneth J.
Tomasek, James J.
Bronze, Michael S.
An, Guangyu
Houchen, Courtney W.
TI Survival of Patients with Gastrointestinal Cancers Can Be Predicted by a
Surrogate microRNA Signature for Cancer Stem-like Cells Marked by DCLK1
Kinase
SO CANCER RESEARCH
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; GASTRIC-CANCER; COLORECTAL-CANCER;
TUMOR-GROWTH; TUFT CELLS; DEPENDENT MECHANISM; RADIATION-INJURY;
IDENTIFICATION; DOUBLECORTIN; EXPRESSION
AB Doublecortin-like kinase 1 (DCLK1) is a gastrointestinal (GI) tuft cell kinase that has been investigated as a biomarker of cancer stem-like cells in colon and pancreatic cancers. However, its utility as a biomarker may be limited in principle by signal instability and dilution in heterogeneous tumors, where the proliferation of diverse tumor cell lineages obscures the direct measurement of DCLK1 activity. To address this issue, we explored the definition of a miRNA signature as a surrogate biomarker for DCLK1 in cancer stem-like cells. Utilizing RNA/miRNA-sequencing datasets from the Cancer Genome Atlas, we identified a surrogate 15-miRNA expression signature for DCLK1 activity across several GI cancers, including colon, pancreatic, and stomach cancers. Notably, Cox regression and Kaplan-Meier analysis demonstrated that this signature could predict the survival of patients with these cancers. Moreover, we identified patient subgroups that predicted the clinical utility of this DCLK1 surrogate biomarker. Our findings greatly strengthen the clinical significance for DCLK1 expression across GI cancers. Further, they provide an initial guidepost toward the development of improved prognostic biomarkers or companion biomarkers for DCLK1-targeted therapies to eradicate cancer stem-like cells in these malignancies. (C)2016 AACR.
C1 [Weygant, Nathaniel; Qu, Dongfeng; May, Randal; Chandrakesan, Parthasarathy; Vega, Kenneth J.; Bronze, Michael S.; Houchen, Courtney W.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Ge, Yang; An, Guangyu] Capital Med Univ, Beijing Chao Yang Hosp, Dept Oncol, Beijing, Peoples R China.
[Qu, Dongfeng; May, Randal; Chandrakesan, Parthasarathy; Vega, Kenneth J.; Houchen, Courtney W.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA.
[Qu, Dongfeng; Chandrakesan, Parthasarathy; Houchen, Courtney W.] Peggy & Charles Stephenson Canc Ctr, Oklahoma City, OK USA.
[Kaddis, John S.] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA.
[Berry, William L.; Tomasek, James J.] Univ Oklahoma, Hlth Sci Ctr, Dept Cell Biol, Oklahoma City, OK USA.
[Bannerman-Menson, Edwin; Houchen, Courtney W.] COARE Biotechnol Inc, Oklahoma City, OK USA.
RP Houchen, CW (reprint author), 920 Stanton L Young Blvd,WP 1345, Oklahoma City, OK 73104 USA.; An, GY (reprint author), 8 Gongren Tiyuchang Nanlu Rd, Beijing 100020, Peoples R China.
EM anguangyu@hotmail.com; courtney-houchen@ouhsc.edu
OI Berry, William/0000-0002-1661-5443
FU BLRD VA [I01 BX001952]; NCI NIH HHS [R01 CA182869, R21 CA186175]
NR 40
TC 1
Z9 1
U1 4
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 15
PY 2016
VL 76
IS 14
BP 4090
EP 4099
DI 10.1158/0008-5472.CAN-16-0029
PG 10
WC Oncology
SC Oncology
GA DS9NY
UT WOS:000381111400008
PM 27287716
ER
PT J
AU Vo, KT
Edwards, JV
Epling, CL
Sinclair, E
Hawkins, DS
Grier, HE
Janeway, KA
Barnette, P
Mcllvaine, E
Krailo, MD
Barkauskas, DA
Matthay, KK
Womer, RB
Gorlick, RG
Lessnick, SL
Mackall, CL
DuBois, SG
AF Vo, Kieuhoa T.
Edwards, Jeremy V.
Epling, C. Lorrie
Sinclair, Elizabeth
Hawkins, Douglas S.
Grier, Holcombe E.
Janeway, Katherine A.
Barnette, Phillip
Mcllvaine, Elizabeth
Krailo, Mark D.
Barkauskas, Donald A.
Matthay, Katherine K.
Womer, Richard B.
Gorlick, Richard G.
Lessnick, Stephen L.
Mackall, Crystal L.
DuBois, Steven G.
TI Impact of Two Measures of Micrometastatic Disease on Clinical Outcomes
in Patients with Newly Diagnosed Ewing Sarcoma: A Report from the
Children's Oncology Group
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID HEMATOPOIETIC PROGENITOR CELLS; CIRCULATING TUMOR-CELLS; BONE-MARROW;
GROWTH-FACTOR; RT-PCR; RECEPTOR ANTIBODY; PERIPHERAL-BLOOD;
FLOW-CYTOMETRY; PHASE-II; EXPRESSION
AB Purpose: Flow cytometry and RT-PCR can detect occult Ewing sarcoma cells in the blood and bone marrow. These techniques were used to evaluate the prognostic significance of micrometastatic disease in Ewing sarcoma.
Experimental Design: Newly diagnosed patients with Ewing sarcoma were enrolled on two prospective multicenter studies. In the flow cytometry cohort, patients were defined as "positive" for bone marrow micrometastatic disease if their CD99(+)/CD45(-) values were above the upper limit in 22 control patients. In the PCR cohort, RT-PCR on blood or bone marrow samples classified the patients as "positive" or "negative" for EWSR1/FLI1 translocations. The association between micrometastatic disease burden with clinical features and outcome was assessed. Coexpression of insulin-like growth factor-1 receptor (IGF-1R) on detected tumor cells was performed in a subset of flow cytometry samples.
Results: The median total bone marrow CD99(+)CD45(-) percent was 0.0012%(range0%-1.10%) in the flow cytometry cohort, with 14 of 109 (12.8%) of Ewing sarcoma patients defined as "positive." In the PCR cohort, 19.6%(44/225) patients were "positive" for any EWSR1/FLI1 translocation in blood or bone marrow. There were no differences in baseline clinical features or event-free or overall survival between patients classified as "positive" versus "negative" by either method. CD99(+)CD45(-) cells had significantly higher IGF-1R expression compared with CD45(+) hematopoietic cells (mean geometric mean fluorescence intensity 982.7 vs. 190.9; P < 0.001).
Conclusions: The detection of micrometastatic disease at initial diagnosis by flow cytometry or RT-PCR is not associated with outcome in newly diagnosed patients with Ewing sarcoma. Flow cytometry provides a tool to characterize occult micrometastatic tumor cells for proteins of interest. (C) 2016 AACR.
C1 [Vo, Kieuhoa T.; Matthay, Katherine K.; DuBois, Steven G.] Univ Calif San Francisco, Sch Med, Dept Pediat, UCSF Benioff Childrens Hosp, San Francisco, CA 94143 USA.
[Edwards, Jeremy V.] Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA.
[Epling, C. Lorrie; Sinclair, Elizabeth] Univ Calif San Francisco, Sch Med, UCSF Benioff Childrens Hosp, Div Expt Med,Core Immunol Lab, San Francisco, CA USA.
[Hawkins, Douglas S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle Childrens Hosp, Div Hematol Oncol, Seattle, WA 98195 USA.
[Grier, Holcombe E.; Janeway, Katherine A.] Harvard Med Sch, Dana Farber Boston Childrens Canc & Blood Disords, Boston, MA USA.
[Barnette, Phillip] Univ Utah, Huntsman Canc Inst, Ctr Childrens Canc Res, Dept Pediat Hematol Oncol, Salt Lake City, UT USA.
[Mcllvaine, Elizabeth; Krailo, Mark D.; Barkauskas, Donald A.] Univ Southern Calif, Keck Sch Med, Dept Preventat Med, Los Angeles, CA 90033 USA.
[Womer, Richard B.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Pediat, Philadelphia, PA 19104 USA.
[Gorlick, Richard G.] Albert Einstein Coll Med, Childrens Hosp Montefiore, Div Pediat Hematol Oncol, Bronx, NY 10467 USA.
[Lessnick, Stephen L.] Ohio State Univ, Ctr Childhood Canc & Blood Disorders, Nationwide Childrens Hosp, Columbus, OH 43210 USA.
[Lessnick, Stephen L.] Ohio State Univ, Div Hematol Oncol & BMT, Columbus, OH 43210 USA.
[Mackall, Crystal L.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP DuBois, SG (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Dana 3, Boston, MA 02215 USA.
EM steven_dubois@dfci.harvard.edu
FU NIH [K23 CA154530, P30AI027763]; NIH Intramural Research Program; Alex's
Lemonade Stand Foundation; Frank A. Campini Foundation; Hope Street
Kids; Sarcoma Foundation of America; CureSearch for Children's Cancer;
John M. Gilbertson Foundation; Daniel P. Sullivan Fund; WWWW (QuadW)
Foundation; Children's Oncology Group grants [U10CA180886, U10CA180899,
U10CA098543, U10CA098413]
FX This work was supported in part by the NIH grant K23 CA154530 (to S.G.
DuBois); NIH Intramural Research Program (to C.L. Mackall); NIH grant
P30AI027763 to the UCSF-GIVI Center for AIDS Research (UCSF Flow
Cytometry Core Laboratory); Alex's Lemonade Stand Foundation (to K.T.
Vo, K.K. Matthay, and S.G. DuBois); Frank A. Campini Foundation (to K.K.
Matthay and S.G. DuBois); Hope Street Kids (to S.G. DuBois); Sarcoma
Foundation of America (to S.G. DuBois); CureSearch for Children's Cancer
(to S.G. DuBois); John M. Gilbertson Foundation (to D.S. Hawkins);
Daniel P. Sullivan Fund (to R.B. Womer); WWWW (QuadW) Foundation (to
M.D. Krailo and D.A. Barkauskas); Children's Oncology Group grants
(U10CA180886, U10CA180899, U10CA098543, and U10CA098413).
NR 27
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2016
VL 22
IS 14
BP 3643
EP 3650
DI 10.1158/1078-0432.CCR-15-2516
PG 8
WC Oncology
SC Oncology
GA DS9ON
UT WOS:000381113000023
PM 26861456
ER
PT J
AU Gao, S
Ye, HH
Gerrin, S
Wang, HY
Sharma, A
Chen, S
Patnaik, A
Sowalsky, AG
Voznesensky, O
Han, WT
Yu, ZY
Mostaghel, EA
Nelson, PS
Taplin, ME
Balk, SP
Cai, CM
AF Gao, Shuai
Ye, Huihui
Gerrin, Sean
Wang, Hongyun
Sharma, Ankur
Chen, Sen
Patnaik, Akash
Sowalsky, Adam G.
Voznesensky, Olga
Han, Wanting
Yu, Ziyang
Mostaghel, Elahe A.
Nelson, Peter S.
Taplin, Mary-Ellen
Balk, Steven P.
Cai, Changmeng
TI ErbB2 Signaling Increases Androgen Receptor Expression in
Abiraterone-Resistant Prostate Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PHASE-II TRIAL; HER-2/NEU EXPRESSION; TYROSINE KINASE; TUMOR-GROWTH;
CELLS; INHIBITION; PHOSPHORYLATION; TRASTUZUMAB; PROGRESSION; INDUCTION
AB Purpose: ErbB2 signaling appears to be increased and may enhance androgen receptor (AR) activity in a subset of patients with castration-resistant prostate cancer (CRPC), but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer and to determine whether it may contribute to AR signaling in these tumors.
Experimental Design: AR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model.
Results: We found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Furthermore, concomitantly treating CRPC cells with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression.
Conclusions: ErbB2 signaling is elevated in a subset of patients with abiraterone-resistant prostate cancer and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity. (C) 2016 AACR.
C1 [Gao, Shuai; Han, Wanting; Cai, Changmeng] Univ Massachusetts, Ctr Personalized Canc Therapy, Boston, MA 02125 USA.
[Gao, Shuai; Ye, Huihui; Gerrin, Sean; Wang, Hongyun; Sharma, Ankur; Chen, Sen; Patnaik, Akash; Sowalsky, Adam G.; Voznesensky, Olga; Yu, Ziyang; Balk, Steven P.; Cai, Changmeng] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA.
[Patnaik, Akash] Univ Chicago, Dept Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Mostaghel, Elahe A.; Nelson, Peter S.] Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
[Taplin, Mary-Ellen] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
RP Cai, CM (reprint author), Univ Massachusetts, 100 Morrissey Blvd, Boston, MA 02125 USA.; Balk, SP (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA.
EM sbalk@bidmc.harvard.edu; changmeng.cai@umb.edu
OI Sowalsky, Adam/0000-0003-2760-1853; Cai, Changmeng/0000-0002-8701-2586
FU NIH [R00CA166507, P01CA163227, P50CA090381-13, P50CA097186]; DOD
[W81XWH-11-1-0295, W81XWH-13-1-0266]; DF/HCC Mazzone Impact Award;
Prostate Cancer Foundation
FX This work is supported by grants from NIH (R00CA166507, to C. Cai;
P01CA163227, to S.P. Balk, P.S. Nelson, E.A. Mostaghel.; and SPORE in
Prostate Cancer P50CA090381-13, to C. Cai, S.P. Balk; and P50CA097186,
to P.S. Nelson and E.A. Mostaghel), and DOD (W81XWH-11-1-0295 and
W81XWH-13-1-0266; to S.P. Balk), a DF/HCC Mazzone Impact Award, and by
Awards from the Prostate Cancer Foundation.
NR 51
TC 2
Z9 2
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 15
PY 2016
VL 22
IS 14
BP 3672
EP 3682
DI 10.1158/1078-0432.CCR-15-2309
PG 11
WC Oncology
SC Oncology
GA DS9ON
UT WOS:000381113000026
PM 26936914
ER
PT J
AU Pell, VR
Chouchani, ET
Frezza, C
Murphy, MP
Krieg, T
AF Pell, Victoria R.
Chouchani, Edward T.
Frezza, Christian
Murphy, Michael P.
Krieg, Thomas
TI Succinate metabolism: a new therapeutic target for myocardial
reperfusion injury
SO CARDIOVASCULAR RESEARCH
LA English
DT Review
DE Succinate; Reactive oxygen species; Mitochondria; Ischaemia; reperfusion
ID MITOCHONDRIAL PERMEABILITY TRANSITION; SENSITIVE POTASSIUM CHANNELS;
RANDOMIZED CONTROLLED-TRIAL; ELECTRON-TRANSPORT CHAIN;
ISCHEMIA-REPERFUSION; COMPLEX-I; RAT-HEART; S-NITROSATION; CARDIAC
MITOCHONDRIA; INHIBITOR MALONATE
AB Myocardial ischaemia/reperfusion (IR) injury is a major cause of death worldwide and remains a disease for which current clinical therapies are strikingly deficient. While the production of mitochondrial reactive oxygen species (ROS) is a critical driver of tissue damage upon reperfusion, the precise mechanisms underlying ROS production have remained elusive. More recently, it has been demonstrated that a specific metabolic mechanism occurs during ischaemia that underlies elevated ROS at reperfusion, suggesting a unifying model as to why so many different compounds have been found to be cardioprotective against IR injury. This review will discuss the role of the citric acid cycle intermediate succinate in IR pathology focusing on the mechanism by which this metabolite accumulates during ischaemia and how it can drive ROS production at Complex I via reverse electron transport. We will then examine the potential for manipulating succinate accumulation and metabolism during IR injury in order to protect the heart against IR damage and discuss targets for novel therapeutics designed to reduce reperfusion injury in patients.
C1 [Pell, Victoria R.; Krieg, Thomas] Univ Cambridge, Addenbrookes Hosp, Dept Med, Hills Rd, Cambridge CB2 0QQ, England.
[Chouchani, Edward T.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Chouchani, Edward T.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA.
[Frezza, Christian] Univ Cambridge, Hutchison MRC Res Ctr, MRC Canc Unit, Box 197,Cambridge Biomed Campus, Cambridge CB2 0XZ, England.
[Murphy, Michael P.] MRC Mitochondrial Biol Unit, Hills Rd, Cambridge CB2 0XY, England.
RP Krieg, T (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Med, Hills Rd, Cambridge CB2 0QQ, England.
EM tk382@medschl.cam.ac.uk
FU Medical Research Council [MC_U105663142, MC_UU_12022/6]
NR 83
TC 4
Z9 4
U1 13
U2 13
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD JUL 15
PY 2016
VL 111
IS 2
BP 134
EP 141
DI 10.1093/cvr/cvw100
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DT1TF
UT WOS:000381264300006
PM 27194563
ER
PT J
AU Ebrahimi, R
Uberoi, A
Treadwell, M
Rafie, AHS
AF Ebrahimi, Ramin
Uberoi, Abhimanyu
Treadwell, Michelle
Rafie, Amir H. Sadrzadeh
TI Effect of Low-Frame Invasive Coronary Angiography on Radiation and Image
Quality
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID IONIZING-RADIATION; CATARACT FORMATION; EXPOSURE; LENS; FLUOROSCOPY;
COHORT
AB Invasive coronary angiography (ICA) uses harmful x-ray energy. To date, there are no studies evaluating the effect of performing ICA at lower than the standard 15 frames per second (f/s) on radiation dose and image quality. In this study, we investigated the effect of performing IC As at 7.5 f/s as opposed to the standard 15 f/s on radiation exposure and image quality. Thirty-nine patients referred for ICA for clinical indications were assigned to have their ICA performed at 7.5 f/s or 15 f/s in a 2:1 ratio, respectively. All studies were performed by one experienced operator in the same laboratory. Magnification, table height, collimation, number of images, and specific angles for image acquisition were kept constant to account for these variables that also effect radiation. Studies performed at 7.5 f/s had significantly less radiation exposure than those performed at 15 f/s (252.2 mGy vs 433.7 mGy, p < 0.01). In addition, radiation per unit time was also significantly reduced in the 7.5 f/s versus the 15 f/s group (140.0 mGy/min vs 254.7 mGy/min, p < 0.01). Image quality was evaluated by an experienced operator blinded to the goals of the study; all studies were graded as good to excellent. In conclusion, performing ICA at 7.5 f/s versus 15 f/s significantly reduces x-ray exposure without compromising image quality. The results of this single-center study warrant a larger randomized clinical trial. Published by Elsevier Inc.
C1 [Ebrahimi, Ramin; Treadwell, Michelle] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Cardiol, Los Angeles, CA USA.
[Ebrahimi, Ramin] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA.
[Uberoi, Abhimanyu] Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA.
[Rafie, Amir H. Sadrzadeh] Glendale Heart Inst Med Grp Inc, Dept Med, Div Cardiol, Glendale, CA USA.
RP Ebrahimi, R (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Cardiol, Los Angeles, CA USA.; Ebrahimi, R (reprint author), Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA.
EM ebrahimi@ucla.edu
NR 13
TC 1
Z9 1
U1 1
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 15
PY 2016
VL 118
IS 2
BP 195
EP 197
DI 10.1016/j.amjcard.2016.04.041
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DR8XA
UT WOS:000380180500007
PM 27241835
ER
PT J
AU Barbash, IJ
Kahn, JM
Thompson, BT
AF Barbash, Ian J.
Kahn, Jeremy M.
Thompson, B. Taylor
TI OPENING THE DEBATE ON THE NEW SEPSIS DEFINITION Medicare's Sepsis
Reporting Program: Two Steps Forward, One Step Back
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID INTERNATIONAL CONSENSUS DEFINITIONS; SEPTIC SHOCK SEPSIS-3;
CLINICAL-CRITERIA; CARE; PERFORMANCE
C1 [Barbash, Ian J.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA.
[Barbash, Ian J.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA.
[Kahn, Jeremy M.] Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Dept Crit Care Med, Pittsburgh, PA USA.
[Kahn, Jeremy M.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA.
[Thompson, B. Taylor] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
RP Barbash, IJ (reprint author), Univ Pittsburgh, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15260 USA.; Barbash, IJ (reprint author), Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA.
FU NHLBI NIH HHS [F32 HL132461, T32 HL007563]
NR 13
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL 15
PY 2016
VL 194
IS 2
BP 139
EP 141
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DT7VY
UT WOS:000381697500010
PM 27167169
ER
PT J
AU Prescott, HC
Calfee, CS
Thompson, BT
Angus, DC
Liu, VX
AF Prescott, Hallie C.
Calfee, Carolyn S.
Thompson, B. Taylor
Angus, Derek C.
Liu, Vincent X.
TI Toward Smarter Lumping and Smarter Splitting: Rethinking Strategies for
Sepsis and Acute Respiratory Distress Syndrome Clinical Trial Design
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE sepsis; acute respiratory distress syndrome; endotype; prognostic
enrichment; predictive enrichment
ID COMMUNITY-ACQUIRED PNEUMONIA; CRITICALLY-ILL PATIENTS; PEDIATRIC SEPTIC
SHOCK; ACUTE LUNG INJURY; INFLAMMATORY RESPONSE; PERSONALIZED MEDICINE;
BERLIN DEFINITION; MORTALITY; CARE; CORTICOSTEROIDS
AB Both quality improvement and clinical research efforts over the past fewdecades have focused on consensus definition of sepsis and acute respiratory distress syndrome (ARDS). Although clinical definitions based on readily available clinical data have advanced recognition and timely use of broad supportive treatments, they likely hinder the identification of more targeted therapies that manipulate select biological mechanisms underlying critical illness. Sepsis and ARDS are by definition heterogeneous, and patients vary in both their underlying biology and their severity of illness. We have long been able to identify subtypes of sepsis and ARDS that confer different prognoses. The key is that we are now on the verge of identifying subtypes that may confer different response to therapy. In this perspective, inspired by a 2015 American Thoracic Society International Conference Symposium entitled "Lumpers and Splitters: Phenotyping in Critical Illness," we highlight promising approaches to uncovering patient subtypes that may predict treatment responsiveness and not just differences in prognosis. We then discuss how this information can be leveraged to improve the success and translatability of clinical trials by using predictive enrichment and other design strategies. Last, we discuss the challenges and limitations to identifying biomarkers and endotypes and incorporating them into routine clinical practice.
C1 [Prescott, Hallie C.] Univ Michigan, Dept Med, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Prescott, Hallie C.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA.
[Calfee, Carolyn S.] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA.
[Calfee, Carolyn S.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA.
[Thompson, B. Taylor] Harvard Sch Med, Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA USA.
[Angus, Derek C.] Univ Pittsburgh, Sch Med, Clin Res Invest & Syst Modeling Acute Illness Ctr, Dept Crit Care Med, Pittsburgh, PA USA.
[Liu, Vincent X.] Kaiser Permanente, Div Res, Oakland, CA USA.
RP Prescott, HC (reprint author), NCRC Bldg 16,341E,2800 Plymouth Rd, Ann Arbor, MI 48109 USA.
EM hprescot@med.umich.edu
OI Prescott, Hallie/0000-0002-8442-6724
FU National Institutes of Health [K08 GM115859, HL131621, GM107650, K23
GM112018, U01 HL 123009-01]
FX Supported by National Institutes of Health grants K08 GM115859 (H.C.P.),
HL131621 (C.S.C.), GM107650 (D.C.A.), K23 GM112018 (V.X.L.), and U01 HL
123009-01 (D.C.A. and B.T.T.).
NR 62
TC 6
Z9 6
U1 1
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL 15
PY 2016
VL 194
IS 2
BP 147
EP 155
DI 10.1164/rccm.201512-2544CP
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DT7VY
UT WOS:000381697500012
PM 27244481
ER
PT J
AU Bhatt, SP
Soler, X
Wang, X
Murray, S
Anzueto, AR
Beaty, TH
Boriek, AM
Casaburi, R
Criner, GJ
Diaz, AA
Dransfield, MT
Curran-Everett, D
Galban, CJ
Hoffman, EA
Hogg, JC
Kazerooni, EA
Kim, V
Kinney, GL
Lagstein, A
Lynch, DA
Make, BJ
Martinez, FJ
Ramsdell, JW
Reddy, R
Ross, BD
Rossiter, HB
Steiner, RM
Strand, MJ
van Beek, EJR
Wan, ES
Washko, GR
Wells, JM
Wendt, CH
Wise, RA
Silverman, EK
Crapo, JD
Bowler, RP
Han, MLK
AF Bhatt, Surya P.
Soler, Xavier
Wang, Xin
Murray, Susan
Anzueto, Antonio R.
Beaty, Terri H.
Boriek, Aladin M.
Casaburi, Richard
Criner, Gerard J.
Diaz, Alejandro A.
Dransfield, Mark T.
Curran-Everett, Douglas
Galban, Craig J.
Hoffman, Eric A.
Hogg, James C.
Kazerooni, Ella A.
Kim, Victor
Kinney, Gregory L.
Lagstein, Amir
Lynch, David A.
Make, Barry J.
Martinez, Fernando J.
Ramsdell, Joe W.
Reddy, Rishindra
Ross, Brian D.
Rossiter, Harry B.
Steiner, Robert M.
Strand, Matthew J.
van Beek, Edwin J. R.
Wan, Emily S.
Washko, George R.
Wells, J. Michael
Wendt, Chris H.
Wise, Robert A.
Silverman, Edwin K.
Crapo, James D.
Bowler, Russell P.
Han, MeiLan K.
CA COPDGene Investigators
TI Association between Functional Small Airway Disease and FEV1 Decline in
Chronic Obstructive Pulmonary Disease
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE FEV1; lung function; parametric response mapping
ID COPD; FLOW; EPIDEMIOLOGY; SPIROMETRY; SMOKERS; TIME; SITE
AB Rationale: The small conducting airways are the major site of airflow obstruction in chronic obstructive pulmonary disease and may precede emphysema development.
Objectives: We hypothesized a novel computed tomography (CT) biomarker of small airway disease predicts FEV1 decline.
Methods: We analyzed 1,508 current and former smokers from COPDGene with linear regression to assess predictors of change in FEV1 (ml/yr) over 5 years. Separate models for subjects without and with airflow obstruction were generated using baseline clinical and physiologic predictors in addition to two novel CT metrics created by parametric response mapping (PRM), a technique pairing inspiratory and expiratory CT images to define emphysema (PRMemph) and functional small airways disease (PRMfSAD), a measure of nonemphysematous air trapping.
Measurements and Main Results: Mean (SD) rate of FEV1 decline in ml/yr for GOLD (Global Initiative for Chronic Obstructive Lung Disease) 0-4 was as follows: 41.8 (47.7), 53.8 (57.1), 45.6 (61.1), 31.6 (43.6), and 5.1 (35.8), respectively (trend test for grades 1-4; P < 0.001). In multivariable linear regression, for participants without airflow obstruction, PRMfSAD but not PRMemph was associated with FEV1 decline (P < 0.001). In GOLD 1-4 participants, both PRMfSAD and PRMemph were associated with FEV1 decline (P, 0.001 and P = 0.001, respectively). Based on the model, the proportional contribution of the two CT metrics to FEV1 decline, relative to each other, was 87% versus 13% and 68% versus 32% for PRMfSAD and PRMemph in GOLD 1/2 and 3/4, respectively.
Conclusions: CT-assessed functional small airway disease and emphysema are associated with FEV1 decline, but the association with functional small airway disease has greatest importance in mild-to-moderate stage chronic obstructive pulmonary disease where the rate of FEV1 decline is the greatest.
C1 [Bhatt, Surya P.; Dransfield, Mark T.; Wells, J. Michael] Univ Alabama Birmingham, Div Pulm Allergy & Crit Care Med, Birmingham, AL USA.
[Bhatt, Surya P.; Dransfield, Mark T.; Wells, J. Michael] Univ Alabama Birmingham, UAB Lung Hlth Ctr, Birmingham, AL USA.
[Soler, Xavier; Ramsdell, Joe W.] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, San Diego, CA 92103 USA.
[Wang, Xin; Murray, Susan] Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA.
[Galban, Craig J.; Ross, Brian D.] Univ Michigan, Dept Radiol, Ctr Mol Imaging, Ann Arbor, MI 48109 USA.
[Kazerooni, Ella A.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA.
[Lagstein, Amir] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Martinez, Fernando J.; Han, MeiLan K.] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
[Reddy, Rishindra] Univ Michigan, Div Thorac Surg, Ann Arbor, MI 48109 USA.
[Anzueto, Antonio R.] Univ Texas Hlth Sci Ctr San Antonio, Div Pulm & Crit Care Med, San Antonio, TX 78229 USA.
[Anzueto, Antonio R.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Beaty, Terri H.] Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Wise, Robert A.] Johns Hopkins Univ, Div Pulm & Crit Care Med, Baltimore, MD USA.
[Boriek, Aladin M.] Baylor Coll Med, Pulm Crit Care & Sleep Med, Houston, TX 77030 USA.
[Casaburi, Richard; Rossiter, Harry B.] Harbor UCLA Med Ctr, Div Pulm & Crit Care Physiol & Med, Torrance, CA 90509 USA.
[Anzueto, Antonio R.] Harbor UCLA Med Ctr, Rehabil Clin Trials Ctr, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA.
[Criner, Gerard J.; Kim, Victor] Temple Univ Hosp & Med Sch, Pulm & Crit Care Med, Philadelphia, PA 19140 USA.
[Steiner, Robert M.] Temple Univ Hosp & Med Sch, Dept Radiol, Philadelphia, PA 19140 USA.
[Diaz, Alejandro A.; Washko, George R.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
[Curran-Everett, Douglas; Strand, Matthew J.] Natl Jewish Hlth, Dept Biostat & Bioinformat, Denver, CO USA.
[Lynch, David A.] Natl Jewish Hlth, Dept Radiol, Denver, CO USA.
[Make, Barry J.; Crapo, James D.; Bowler, Russell P.] Natl Jewish Hlth, Div Pulm Crit Care & Sleep Med, Denver, CO USA.
[Curran-Everett, Douglas; Strand, Matthew J.] Univ Colorado, Dept Biostat & Informat, Colorado Sch Publ Hlth, Denver, CO 80202 USA.
[Kinney, Gregory L.] Univ Colorado, Dept Epidemiol, Colorado Sch Publ Hlth, Denver, CO 80202 USA.
[Hoffman, Eric A.] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA.
[Hoffman, Eric A.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
[Hoffman, Eric A.] Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA.
[Hogg, James C.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada.
[Hogg, James C.] St Pauls Hosp, James Hogg Res Ctr, Vancouver, BC, Canada.
[van Beek, Edwin J. R.] Univ Edinburgh, Clin Res Imaging Ctr, Edinburgh, Midlothian, Scotland.
[Wan, Emily S.; Silverman, Edwin K.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA.
[Wendt, Chris H.] Univ Minnesota, Pulm Allergy Crit Care & Sleep Med Sect, Minneapolis VAMC, Minneapolis, MN USA.
RP Han, MLK (reprint author), Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA.
EM mrking@med.umich.edu
FU NHLBI [R01 HL089897, R01 HL089856, R01 HL122438, R44 HL118837]; COPD
Foundation
FX Supported by Award R01 HL089897, R01 HL089856, R01 HL122438, and R44
HL118837 from the NHLBI. The COPDGene project is also supported by the
COPD Foundation through contributions made to an Industry Advisory Board
composed of AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer,
Siemens, Sunovion, and GlaxoSmithKline.
NR 22
TC 14
Z9 14
U1 2
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD JUL 15
PY 2016
VL 194
IS 2
BP 178
EP 184
DI 10.1164/rccm.201511-2219OC
PG 7
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DT7VY
UT WOS:000381697500015
PM 26808615
ER
PT J
AU Khanna, S
Pardi, DS
Kelly, CR
Kraft, CS
Dhere, T
Henn, MR
Lombardo, MJ
Vulic, M
Ohsumi, T
Winkler, J
Pindar, C
McGovern, BH
Pomerantz, RJ
Aunins, JG
Cook, DN
Hohmann, EL
AF Khanna, Sahil
Pardi, Darrell S.
Kelly, Colleen R.
Kraft, Colleen S.
Dhere, Tanvi
Henn, Matthew R.
Lombardo, Mary-Jane
Vulic, Marin
Ohsumi, Toshiro
Winkler, Jonathan
Pindar, Christina
McGovern, Barbara H.
Pomerantz, Roger J.
Aunins, John G.
Cook, David N.
Hohmann, Elizabeth L.
TI A Novel Microbiome Therapeutic Increases Gut Microbial Diversity and
Prevents Recurrent Clostridium difficile Infection
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Clostridium difficile infection; microbiome; dysbiosis;
vancomycin-resistant Enterococcus; Clostridium difficile treatment
ID RANDOMIZED CLINICAL-TRIAL; FECAL MICROBIOTA; SACCHAROMYCES-BOULARDII;
TRANSPLANTATION; VANCOMYCIN; BURDEN; PATHOGENS; COLITIS; DISEASE
AB Background. Patients with recurrent Clostridium difficile infection (CDI) have a = 60% risk of relapse, as conventional therapies do not address the underlying gastrointestinal dysbiosis. This exploratory study evaluated the safety and efficacy of bacterial spores for preventing recurrent CDI. Methods. Stool specimens from healthy donors were treated with ethanol to eliminate pathogens. The resulting spores were fractionated and encapsulated for oral delivery as SER-109. Following their response to standard-of-care antibiotics, patients in cohort 1 were treated with SER-109 on 2 consecutive days (geometric mean dose, 1.7 x 109 spores), and those in cohort 2 were treated on 1 day (geometric mean dose, 1.1 x 108 spores). The primary efficacy end point was absence of C. difficile-positive diarrhea during an 8-week follow-up period. Microbiome alterations were assessed. Results. Thirty patients (median age, 66.5 years; 67% female) were enrolled, and 26 (86.7%) met the primary efficacy end point. Three patients with early, self-limiting C. difficile-positive diarrhea did not require antibiotics and tested negative for C. difficile at 8 weeks; thus, 96.7% (29 of 30) achieved clinical resolution. In parallel, gut microbiota rapidly diversified, with durable engraftment of spores and no outgrowth of non-spore-forming bacteria found after SER-109 treatment. Adverse events included mild diarrhea, abdominal pain, and nausea. Conclusions. SER-109 successfully prevented CDI and had a favorable safety profile, supporting a novel microbiome-based intervention as a potential therapy for recurrent CDI.
C1 [Khanna, Sahil; Pardi, Darrell S.] Mayo Clin, Rochester, MN USA.
[Kelly, Colleen R.] Miriam Hosp, Womens Med Collaborat, Providence, RI 02906 USA.
[Kraft, Colleen S.; Dhere, Tanvi] Emory Univ, Sch Med, Atlanta, GA USA.
[Henn, Matthew R.; Lombardo, Mary-Jane; Vulic, Marin; Ohsumi, Toshiro; Winkler, Jonathan; McGovern, Barbara H.; Pomerantz, Roger J.; Aunins, John G.; Cook, David N.] Seres Therapeut, Cambridge, MA USA.
[Pindar, Christina; Hohmann, Elizabeth L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP McGovern, BH (reprint author), Seres Therapeut, Needham, MA 02494 USA.
EM bmcgovern@serestherapeutics.com
FU Mayo Clinic Foundation, Rochester; Seres Therapeutics
FX S. K., D. S. P., C. R. K., C. S. K., T. D., and E. L. H. were
investigators in the SER-001 trial. D. S. P. is a consulting member of
the clinical advisory board at Seres Therapeutics, and his fees in that
capacity are paid to Mayo Clinic Foundation, Rochester, rather than to
him. M. R. H., M.-J. L., M. V., T. O., J. W., B. H. M., R. J. P., J. G.
A., and D. N. C. are employees of and hold equity positions in Seres
Therapeutics, which funded the trial. All authors have submitted the
ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts
that the editors consider relevant to the content of the manuscript have
been disclosed.
NR 49
TC 29
Z9 30
U1 11
U2 23
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD JUL 15
PY 2016
VL 214
IS 2
BP 173
EP 181
DI 10.1093/infdis/jiv766
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DR3SM
UT WOS:000379822900003
PM 26908752
ER
PT J
AU Williams, DR
Mohammed, SA
Shields, AE
AF Williams, David R.
Mohammed, Selina A.
Shields, Alexandra E.
TI Understanding and effectively addressing breast cancer in African
American women: Unpacking the social context
SO CANCER
LA English
DT Review
DE African American women; breast cancer; race; socioeconomic status (SES);
stress
ID GLUCOCORTICOID-RECEPTOR GENE; US BLACK-WOMEN; SOCIOECONOMIC-STATUS;
HEALTH DISPARITIES; ALLOSTATIC LOAD; EARLY-LIFE; RACIAL DISPARITIES;
UNITED-STATES; INCREASES VULNERABILITY; CHILDHOOD MALTREATMENT
AB Black women have a higher incidence of breast cancer before the age of 40 years, more severe disease at all ages, and an elevated mortality risk in comparison with white women. There is limited understanding of the contribution of social factors to these patterns. Elucidating the role of the social determinants of health in breast cancer disparities requires greater attention to how risk factors for breast cancer unfold over the lifecourse and to the complex ways in which socioeconomic status and racism shape exposure to psychosocial, physical, chemical, and other individual and community-level assaults that increase the risk of breast cancer. Research that takes seriously the social context in which black women live is also needed to maximize the opportunities to prevent breast cancer in this underserved group. Cancer 2016;122:2138-49. (c) 2016 American Cancer Society.
Insufficient attention has been paid to how risk factors for breast cancer in African American women begin in childhood and are closely tied to the conditions in which they live and work. Future research needs to pay additional attention to how researchers, clinicians and the larger society can best understand and address the myriad factors linked to racial status that are associated with breast cancer risk among African American women.
C1 [Williams, David R.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,6th Floor, Boston, MA 02115 USA.
[Williams, David R.] Harvard Univ, Dept African & African Amer Studies, Cambridge, MA 02138 USA.
[Williams, David R.] Univ Cape Town, Dept Psychiat & Mental Hlth, Cape Town, South Africa.
[Mohammed, Selina A.] Univ Washington Bothell, Sch Nursing & Hlth Studies, Bothell, WA USA.
[Shields, Alexandra E.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Boston, MA 02114 USA.
[Shields, Alexandra E.] Harvard Med Sch, Dept Med, Boston, MA USA.
RP Williams, DR (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, 677 Huntington Ave,6th Floor, Boston, MA 02115 USA.
EM dwilliam@hsph.harvard.edu
FU National Cancer Institute [P50 CA 148596]; John Templeton Foundation
[48424]
FX The preparation of this article was supported by the National Cancer
Institute (grant P50 CA 148596) and the John Templeton Foundation (grant
48424).
NR 95
TC 3
Z9 3
U1 4
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 15
PY 2016
VL 122
IS 14
BP 2138
EP 2149
DI 10.1002/cncr.29935
PG 12
WC Oncology
SC Oncology
GA DR4SY
UT WOS:000379894000006
PM 26930024
ER
PT J
AU Font-Gonzalez, A
Mulder, RL
Loeffen, EAH
Byrne, J
van Dulmen-den Broeder, E
van den Heuvel-Eibrink, MM
Hudson, MM
Kenney, LB
Levine, JM
Tissing, WJE
van de Wetering, MD
Kremer, LCM
AF Font-Gonzalez, Anna
Mulder, Renee L.
Loeffen, Erik A. H.
Byrne, Julianne
van Dulmen-den Broeder, Eline
van den Heuvel-Eibrink, Marry M.
Hudson, Melissa M.
Kenney, Lisa B.
Levine, Jennifer M.
Tissing, Wim J. E.
van de Wetering, Marianne D.
Kremer, Leontien C. M.
CA PanCareLIFE Consortium
TI Fertility preservation in children, adolescents, and young adults with
cancer: Quality of clinical practice guidelines and variations in
recommendations
SO CANCER
LA English
DT Article
DE childhood cancer; evidence-based medicine; fertility preservation;
guidelines; pediatric oncology
ID CHILDHOOD-CANCER; HARMONIZATION GROUP; FEMALE SURVIVORS; BREAST-CANCER;
ONCOLOGY; ISSUES; SURVEILLANCE; MANAGEMENT; CONSENSUS; SOCIETY
AB BACKGROUNDFertility preservation care for children, adolescents, and young adults (CAYAs) with cancer is not uniform among practitioners. To ensure high-quality care, evidence-based clinical practice guidelines (CPGs) are essential. The authors identified existing CPGs for fertility preservation in CAYAs with cancer, evaluated their quality, and explored differences in recommendations.
METHODSA systematic search in PubMed (January 2000-October 2014); guideline databases; and Web sites of oncology, pediatric, and fertility organizations was performed. Two reviewers evaluated the quality of the identified CPGs using the Appraisal of Guidelines for Research and Evaluation II Instrument (AGREE II). From high-quality CPGs, the authors evaluated concordant and discordant areas among the recommendations.
RESULTSA total of 25 CPGs regarding fertility preservation were identified. The average AGREE II domain scores (scale of 0%-100%) varied from 15% on applicability to 100% on clarity of presentation. The authors considered 8 CPGs (32%) to be of high quality, which was defined as scores 60% in any 4 domains. Large variations in the recommendations of the high-quality CPGs were observed, with 87.2% and 88.6%, respectively, of discordant guideline areas among the fertility preservation recommendations for female and male patients with cancer.
CONCLUSIONSOnly approximately one-third of the identified CPGs were found to be of sufficient quality. Of these CPGs, the fertility preservation recommendations varied substantially, which can be a reflection of inadequate evidence for specific recommendations, thereby hindering the ability of providers to deliver high-quality care. CPGs including a transparent decision process for fertility preservation can help health care providers to deliver optimal and uniform care, thus improving the quality of life of CAYAs with cancer and cancer survivors. Cancer 2016;122:2216-23. (c) 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Only approximately one-third of the identified clinical practice guidelines for fertility preservation in children, adolescents, and young adults with cancer were found to be of sufficient quality, and among these, the recommendations varied substantially. This finding supports the need for well-developed and transparent harmonized clinical practice guidelines for children and young adults diagnosed with cancer who are at risk of fertility impairment.
C1 [Font-Gonzalez, Anna; Mulder, Renee L.; van de Wetering, Marianne D.; Kremer, Leontien C. M.] Emma Childrens Hosp, Dept Pediat Oncol, Acad Med Ctr, POB 22660, NL-1100 DD Amsterdam, Netherlands.
[Loeffen, Erik A. H.; Tissing, Wim J. E.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Oncol Hematol, Groningen, Netherlands.
[Byrne, Julianne] Boyne Res Inst, Drogheda, Ireland.
[van Dulmen-den Broeder, Eline] Vrije Univ Amsterdam, Dept Pediat Oncol Hematol, Med Ctr, Amsterdam, Netherlands.
[van den Heuvel-Eibrink, Marry M.] Princess Maxima Ctr Pediat Oncol, Dept Pediat Oncol Hematol, Utrecht, Netherlands.
[Hudson, Melissa M.] St Jude Childrens Res Hosp, Dept Pediat Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Kenney, Lisa B.] Harvard Med Sch, Childrens Hosp, Dept Pediat Oncol, Boston, MA USA.
[Kenney, Lisa B.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[Levine, Jennifer M.] Columbia Univ, Med Ctr, Div Pediat Hematol Oncol & Stem Cell Transplantat, New York, NY USA.
RP Font-Gonzalez, A (reprint author), Emma Childrens Hosp, Dept Pediat Oncol, Acad Med Ctr, POB 22660, NL-1100 DD Amsterdam, Netherlands.
EM a.fontgonzalez@amc.uva.nl
FU European Union's Seventh Framework program [602030]
FX This project received funding from the European Union's Seventh
Framework program for research, technological development, and
demonstration under grant agreement 602030. The funding source had no
role in the study design; in the collection, analysis, and
interpretation of the data; in the preparation of the article; or in the
decision to submit the article for publication.
NR 53
TC 2
Z9 2
U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD JUL 15
PY 2016
VL 122
IS 14
BP 2216
EP 2223
DI 10.1002/cncr.30047
PG 8
WC Oncology
SC Oncology
GA DR4SY
UT WOS:000379894000014
PM 27175973
ER
PT J
AU Sartelli, M
Weber, DG
Ruppe, E
Bassetti, M
Wright, BJ
Ansaloni, L
Catena, F
Coccolini, F
Abu-Zidan, FM
Coimbra, R
Moore, EE
Moore, FA
Maier, RV
De Waele, JJ
Kirkpatrick, AW
Griffiths, EA
Eckmann, C
Brink, AJ
Mazuski, JE
May, AK
Sawyer, RG
Mertz, D
Montravers, P
Kumar, A
Roberts, JA
Vincent, JL
Watkins, RR
Lowman, W
Spellberg, B
Abbott, IJ
Adesunkanmi, AK
Al-Dahir, S
Al-Hasan, MN
Agresta, F
Althani, AA
Ansari, S
Ansumana, R
Augustin, G
Bala, M
Balogh, ZJ
Baraket, O
Bhangu, A
Beltran, MA
Bernhard, M
Biffl, WL
Boermeester, MA
Brecher, SM
Cherry-Bukowiec, JR
Buyne, OR
Cainzos, MA
Cairns, KA
Camacho-Ortiz, A
Chandy, SJ
Jusoh, AC
Chichom-Mefire, A
Colijn, C
Corcione, F
Cui, YF
Curcio, D
Delibegovic, S
Demetrashvili, Z
De Simone, B
Dhingra, S
Diaz, JJ
Di Carlo, I
Dillip, A
Di Saverio, S
Doyle, MP
Dorj, G
Dogjani, A
Dupont, H
Eachempati, SR
Enani, MA
Egiev, VN
Elmangory, MM
Ferrada, P
Fitchett, JR
Fraga, GP
Guessennd, N
Giamarellou, H
Ghnnam, W
Gkiokas, G
Goldberg, SR
Gomes, CA
Gomi, H
Guzman-Blanco, M
Haque, M
Hansen, S
Hecker, A
Heizmann, WR
Herzog, T
Hodonou, AM
Hong, SK
Kafka-Ritsch, R
Kaplan, LJ
Kapoor, G
Karamarkovic, A
Kees, MG
Kenig, J
Kiguba, R
Kim, PK
Kluger, Y
Khokha, V
Koike, K
Kok, KYY
Kong, V
Knox, MC
Inaba, K
Isik, A
Iskandar, K
Ivatury, RR
Labbate, M
Labricciosa, FM
Laterre, PF
Latifi, R
Lee, JG
Lee, YR
Leone, M
Leppaniemi, A
Li, YS
Liang, SY
Loho, T
Maegele, M
Malama, S
Marei, HE
Martin-Loeches, I
Marwah, S
Massele, A
McFarlane, M
Melo, RB
Negoi, I
Nicolau, DP
Nord, CE
Ofori-Asenso, R
Omari, AH
Ordonez, CA
Ouadii, M
Pereira, GA
Piazza, D
Pupelis, G
Rawson, TM
Rems, M
Rizoli, S
Rocha, C
Sakakhushev, B
Sanchez-Garcia, M
Sato, N
Lohse, HAS
Sganga, G
Siribumrungwong, B
Shelat, VG
Soreide, K
Soto, R
Talving, P
Tilsed, JV
Timsit, JF
Trueba, G
Trung, NT
Ulrych, J
van Goor, H
Vereczkei, A
Vohra, RS
Wani, I
Uhl, W
Xiao, YH
Yuan, KC
Zachariah, SK
Zahar, JR
Zakrison, TL
Corcione, A
Melotti, RM
Viscoli, C
Viale, P
AF Sartelli, Massimo
Weber, Dieter G.
Ruppe, Etienne
Bassetti, Matteo
Wright, Brian J.
Ansaloni, Luca
Catena, Fausto
Coccolini, Federico
Abu-Zidan, Fikri M.
Coimbra, Raul
Moore, Ernest E.
Moore, Frederick A.
Maier, Ronald V.
De Waele, Jan J.
Kirkpatrick, Andrew W.
Griffiths, Ewen A.
Eckmann, Christian
Brink, Adrian J.
Mazuski, John E.
May, Addison K.
Sawyer, Rob G.
Mertz, Dominik
Montravers, Philippe
Kumar, Anand
Roberts, Jason A.
Vincent, Jean-Louis
Watkins, Richard R.
Lowman, Warren
Spellberg, Brad
Abbott, Iain J.
Adesunkanmi, Abdulrashid Kayode
Al-Dahir, Sara
Al-Hasan, Majdi N.
Agresta, Ferdinando
Althani, Asma A.
Ansari, Shamshul
Ansumana, Rashid
Augustin, Goran
Bala, Miklosh
Balogh, Zsolt J.
Baraket, Oussama
Bhangu, Aneel
Beltran, Marcelo A.
Bernhard, Michael
Biffl, Walter L.
Boermeester, Marja A.
Brecher, Stephen M.
Cherry-Bukowiec, Jill R.
Buyne, Otmar R.
Cainzos, Miguel A.
Cairns, Kelly A.
Camacho-Ortiz, Adrian
Chandy, Sujith J.
Jusoh, Asri Che
Chichom-Mefire, Alain
Colijn, Caroline
Corcione, Francesco
Cui, Yunfeng
Curcio, Daniel
Delibegovic, Samir
Demetrashvili, Zaza
De Simone, Belinda
Dhingra, Sameer
Diaz, Jose J.
Di Carlo, Isidoro
Dillip, Angel
Di Saverio, Salomone
Doyle, Michael P.
Dorj, Gereltuya
Dogjani, Agron
Dupont, Herve
Eachempati, Soumitra R.
Enani, Mushira Abdulaziz
Egiev, Valery N.
Elmangory, Mutasim M.
Ferrada, Paula
Fitchett, Joseph R.
Fraga, Gustavo P.
Guessennd, Nathalie
Giamarellou, Helen
Ghnnam, Wagih
Gkiokas, George
Goldberg, Staphanie R.
Gomes, Carlos Augusto
Gomi, Harumi
Guzman-Blanco, Manuel
Haque, Mainul
Hansen, Sonja
Hecker, Andreas
Heizmann, Wolfgang R.
Herzog, Torsten
Hodonou, Adrien Montcho
Hong, Suk-Kyung
Kafka-Ritsch, Reinhold
Kaplan, Lewis J.
Kapoor, Garima
Karamarkovic, Aleksandar
Kees, Martin G.
Kenig, Jakub
Kiguba, Ronald
Kim, Peter K.
Kluger, Yoram
Khokha, Vladimir
Koike, Kaoru
Kok, Kenneth Y. Y.
Kong, Victory
Knox, Matthew C.
Inaba, Kenji
Isik, Arda
Iskandar, Katia
Ivatury, Rao R.
Labbate, Maurizio
Labricciosa, Francesco M.
Laterre, Pierre-Francois
Latifi, Rifat
Lee, Jae Gil
Lee, Young Ran
Leone, Marc
Leppaniemi, Ari
Li, Yousheng
Liang, Stephen Y.
Loho, Tonny
Maegele, Marc
Malama, Sydney
Marei, Hany E.
Martin-Loeches, Ignacio
Marwah, Sanjay
Massele, Amos
McFarlane, Michael
Melo, Renato Bessa
Negoi, Ionut
Nicolau, David P.
Nord, Carl Erik
Ofori-Asenso, Richard
Omari, AbdelKarim H.
Ordonez, Carlos A.
Ouadii, Mouaqit
Pereira Junior, Gerson Alves
Piazza, Diego
Pupelis, Guntars
Rawson, Timothy Miles
Rems, Miran
Rizoli, Sandro
Rocha, Claudio
Sakakhushev, Boris
Sanchez-Garcia, Miguel
Sato, Norio
Lohse, Helmut A. Segovia
Sganga, Gabriele
Siribumrungwong, Boonying
Shelat, Vishal G.
Soreide, Kjetil
Soto, Rodolfo
Talving, Peep
Tilsed, Jonathan V.
Timsit, Jean-Francois
Trueba, Gabriel
Trung, Ngo Tat
Ulrych, Jan
van Goor, Harry
Vereczkei, Andras
Vohra, Ravinder S.
Wani, Imtiaz
Uhl, Waldemar
Xiao, Yonghong
Yuan, Kuo-Ching
Zachariah, Sanoop K.
Zahar, Jean-Ralph
Zakrison, Tanya L.
Corcione, Antonio
Melotti, Rita M.
Viscoli, Claudio
Viale, Perluigi
TI Antimicrobials: a global alliance for optimizing their rational use in
intra-abdominal infections (AGORA)
SO WORLD JOURNAL OF EMERGENCY SURGERY
LA English
DT Review
ID INTENSIVE-CARE-UNIT; SPECTRUM-BETA-LACTAMASE; CRITICALLY-ILL PATIENTS;
GRAM-NEGATIVE BACTERIA; VANCOMYCIN-RESISTANT ENTEROCOCCI;
CLOSTRIDIUM-DIFFICILE INFECTION; VENTILATOR-ASSOCIATED PNEUMONIA;
BLOOD-STREAM INFECTIONS; CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE;
CLINICAL-PRACTICE GUIDELINES
AB Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients.
The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance.
The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in individual patients, and for the continued development of antimicrobial resistance globally. The growing emergence of multi-drug resistant organisms and the limited development of new agents available to counteract them have caused an impending crisis with alarming implications, especially with regards to Gram-negative bacteria.
An international task force from 79 different countries has joined this project by sharing a document on the rational use of antimicrobials for patients with IAIs. The project has been termed AGORA (Antimicrobials: A Global Alliance for Optimizing their Rational Use in Intra-Abdominal Infections). The authors hope that AGORA, involving many of the world's leading experts, can actively raise awareness in health workers and can improve prescribing behavior in treating IAIs.
C1 [Sartelli, Massimo] Macerata Hosp, Dept Surg, Via Santa Lucia 2, I-62100 Macerata, Italy.
[Weber, Dieter G.] Royal Perth Hosp, Dept Trauma Surg, Perth, WA, Australia.
[Ruppe, Etienne] Univ Hosp Geneva, Genom Res Lab, Geneva, Switzerland.
[Bassetti, Matteo] Santa Maria Misericordia Univ Hosp, Infect Dis Div, Udine, Italy.
[Wright, Brian J.] SUNY Stony Brook, Sch Med, Dept Emergency Med & Surg, Stony Brook, NY USA.
[Ansaloni, Luca] Papa Giovanni XXIII Hosp, Gen Surg Dept, Bergamo, Italy.
[Catena, Fausto] Maggiore Hosp, Dept Gen, Parma, Italy.
[Coccolini, Federico] Infermi Hosp, Dept Surg, Rimini, Italy.
[Abu-Zidan, Fikri M.] UAE Univ, Coll Med & Hlth Sci, Dept Surg, Al Ain, U Arab Emirates.
[Coimbra, Raul] UC San Diego Med Ctr, Dept Surg, San Diego, CA USA.
[Moore, Ernest E.] Univ Colorado, Denver Hlth Med Ctr, Dept Surg, Denver, CO USA.
[Moore, Frederick A.] Univ Florida, Coll Med, Dept Surg, Div Acute Care Surg, Gainesville, FL USA.
[Moore, Frederick A.] Univ Florida, Coll Med, Ctr Sepsis & Crit Illness Res, Gainesville, FL USA.
[Maier, Ronald V.] Univ Washington, Dept Surg, Seattle, WA USA.
[De Waele, Jan J.] Ghent Univ Hosp, Dept Crit Care Med, Ghent, Belgium.
[Kirkpatrick, Andrew W.] Foothills Med Ctr, Gen Acute Care & Trauma Surg, Calgary, AB, Canada.
[Griffiths, Ewen A.] Queen Elizabeth Hosp, Gen & Upper GI Surg, Birmingham, W Midlands, England.
[Eckmann, Christian] Hannover Med Sch, Acad Hosp, Klinikum Peine, Dept Gen Visceral & Thorac Surg, Peine, Germany.
[Brink, Adrian J.] Milpark Hosp, Dept Clin Microbiol, Ampath Natl Lab Serv, Johannesburg, South Africa.
[Mazuski, John E.] Washington Univ, Sch Med, Dept Surg, St Louis, MO USA.
[May, Addison K.] Vanderbilt Univ, Med Ctr, Dept Surg, Div Trauma & Surg Crit Care, Nashville, TN USA.
[May, Addison K.] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Div Trauma & Surg Crit Care, Nashville, TN USA.
[Sawyer, Rob G.] Univ Virginia Hlth Syst, Dept Surg, Charlottesville, VA USA.
[Mertz, Dominik] McMaster Univ, Dept Med, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada.
[Mertz, Dominik] McMaster Univ, Dept Pathol & Lab Med, Hamilton, ON, Canada.
[Montravers, Philippe] Univ Paris 07, AP HP, CHU Bichat Claude Bernard HUPNVS, Dept Anesthesie & Reanimat, Paris, France.
[Kumar, Anand] Univ Manitoba, Dept Med Med Microbiol & Pharmacol Therapeut, Sect Crit Care Med, Winnipeg, MB, Canada.
[Kumar, Anand] Univ Manitoba, Dept Med Med Microbiol & Pharmacol Therapeut, Infect Dis Sect, Winnipeg, MB, Canada.
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[Vincent, Jean-Louis] Univ Libre Bruxelles, Erasme Hosp, Dept Intens Care, Brussels, Belgium.
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[Abbott, Iain J.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia.
[Adesunkanmi, Abdulrashid Kayode] Obafemi Awolowo Univ, Coll Hlth Sci, Dept Surg, Ife, Nigeria.
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[Al-Hasan, Majdi N.] Univ S Carolina, Sch Med, Dept Med, Div Infect Dis, Columbia, SC USA.
[Agresta, Ferdinando] Adria Hosp, ULSS19 Veneto, Gen Surg, Ro, Italy.
[Althani, Asma A.; Marei, Hany E.] Qatar Univ, Biomed Res Ctr, Doha, Qatar.
[Ansari, Shamshul] Oita Univ, Chitwan Med Coll, Dept Microbiol, Oita, Japan.
[Ansari, Shamshul] Oita Univ, Dept Environm & Prevent Med, Oita, Japan.
[Ansumana, Rashid] Univ Liverpool, Liverpool Sch Trop Med, Ctr Neglected Trop Dis, Bo, Sierra Leone.
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[Bala, Miklosh] Hadassah Hebrew Univ, Med Ctr, Trauma & Acute Care Surg Unit, Jerusalem, Israel.
[Balogh, Zsolt J.] John Hunter Hosp, Dept Traumatol, Newcastle, NSW, Australia.
[Balogh, Zsolt J.] Univ Newcastle, Newcastle, NSW, Australia.
[Baraket, Oussama] Bizerte Hosp, Dept Surg, Bizerte, Tunisia.
[Bhangu, Aneel] Queen Elizabeth Hosp, Acad Dept Surg, Birmingham, W Midlands, England.
[Beltran, Marcelo A.] Hosp San Juan Dios Serena, Dept Gen Surg, La Serena, Chile.
[Bernhard, Michael] Univ Leipzig, Dept Emergency, Leipzig, Germany.
[Biffl, Walter L.] Univ Colorado, Dept Surg, Denver, CO USA.
[Boermeester, Marja A.] Acad Med Ctr, Dept Surg, Amsterdam, Netherlands.
[Brecher, Stephen M.] Boston Univ, Sch Med, VA Boston HealthCare Syst, Dept Pathol & Lab Med, Boston, MA USA.
[Brecher, Stephen M.] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA USA.
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[Buyne, Otmar R.; van Goor, Harry] Radboud Univ Nijmegen, Med Ctr, Dept Surg, Nijmegen, Netherlands.
[Cainzos, Miguel A.] Hosp Clin Univ, Dept Surg, Santiago De Compostela, Spain.
[Cairns, Kelly A.] Alfred Hlth, Dept Pharm, Melbourne, Vic, Australia.
[Camacho-Ortiz, Adrian] Hosp Univ Dr Jose Eleuterio Gonzalez, Hosp Epidemiol & Infect Dis, Monterrey, Mexico.
[Chandy, Sujith J.] Pushpagiri Inst Med Sci & Res Ctr, Dept Pharmacol, Thiruvalla, Kerala, India.
[Jusoh, Asri Che] Kuala Krai Hosp, Dept Gen Surg, Kuala Krai, Kelantan, Malaysia.
[Chichom-Mefire, Alain] Reg Hosp, Dept Surg & Obstet Gynaecol, Limbe, Cameroon.
[Colijn, Caroline] Imperial Coll London, Dept Math, London, England.
[Corcione, Francesco] Colli Monaldi Hosp, Dept Laparoscop & Robot Surg, Naples, Italy.
[Cui, Yunfeng] Tianjin Med Univ, Tianjin Nankai Hosp, Nankai Clin Sch Med, Dept Surg, Tianjin, Peoples R China.
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[Di Carlo, Isidoro] Univ Catania, Cannizzaro Hosp, Dept Surg Sci, Catania, Italy.
[Dillip, Angel] Ifakara Hlth Inst, Dar Es Salaam, Tanzania.
[Di Saverio, Salomone] Maggiore Hosp, Dept Surg, Bologna, Italy.
[Doyle, Michael P.] Univ Georgia, Ctr Food Safety, Dept Food Sci & Technol, Griffin, GA USA.
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[Dupont, Herve] Univ Picardie Jules Verne, INSERM U1088, Dept Anesthesie Reanimat, Amiens, France.
[Eachempati, Soumitra R.] New York Presbyterian Hosp, Weill Cornell Med College, Dept Surg, Div Burn Crit Care & Trauma Surg KPS SRE, New York, NY USA.
[Enani, Mushira Abdulaziz] King Fahad Med City, Dept Med, Div Infect Dis, Riyadh, Saudi Arabia.
[Egiev, Valery N.] Russian Natl Res Med Univ, Dept Surg, Moscow, Russia.
[Elmangory, Mutasim M.] Fed Minist Hlth, Sudan Natl Publ Hlth Lab, Khartoum, Sudan.
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[Guessennd, Nathalie] Inst Pasteur, Abidjan, Cote Ivoire.
[Giamarellou, Helen] Hygeia Gen Hosp, Dept Internal Med 6, Athens, Greece.
[Ghnnam, Wagih] Mansoura Univ, Mansoura Fac Med, Dept Gen Surg, Mansoura, Egypt.
[Gkiokas, George] Univ Athens, Aretaie Univ Hosp, Dept Surg 2, Athens, Greece.
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[Gomi, Harumi] Univ Tsukuba, Mito Kyodo Gen Hosp, Ctr Global Hlth, Mito, Ibaraki, Japan.
[Guzman-Blanco, Manuel] Hosp Privado Ctr Med Caracas, Caracas, Venezuela.
[Guzman-Blanco, Manuel] Hosp Vargas Caracas, Caracas, Venezuela.
[Haque, Mainul] Natl Def Univ Malaysia, Fac Med & Def Hlth, Unit Pharmacol, Kuala Lumpur, Malaysia.
[Hansen, Sonja] Charite, Inst Hyg, Hindenburgdamm 27, D-12203 Berlin, Germany.
[Hecker, Andreas] Univ Hosp Giessen, Dept Gen & Thorac Surg, Giessen, Germany.
[Heizmann, Wolfgang R.] Orgamed Consulting, Bad Griesbach, Germany.
[Herzog, Torsten; Uhl, Waldemar] Ruhr Univ Bochum, St Josef Hosp, Dept Surg, Bochum, Germany.
[Hodonou, Adrien Montcho] Univ Parakou, Fac Med, Dept Surg, BP 123, Parakou, Benin.
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[Kafka-Ritsch, Reinhold] Med Univ Innsbruck, Dept Visceral Transplant & Thorac Surg, Innsbruck, Austria.
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[Kapoor, Garima] Gandhi Med Coll, Dept Microbiol, Bhopal, India.
[Karamarkovic, Aleksandar] Univ Belgrade, Fac Med, Clin Emergency Surg, Belgrade, Serbia.
[Kees, Martin G.] Charite, Dept Anesthesiol & Intens Care, Campus Benjamin Franklin, Berlin, Germany.
[Kenig, Jakub] Jagiellonian Univ, Coll Med, Dept Gen Surg 3, Krakow, Poland.
[Kiguba, Ronald] Makerere Univ, Coll Hlth Sci, Dept Pharmacol & Therapeut, Kampala, Uganda.
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[Koike, Kaoru; Sato, Norio] Kyoto Univ, Grad Sch Med, Dept Primary Care & Emergency Med, Kyoto, Japan.
[Kok, Kenneth Y. Y.] Brunei Canc Ctr, Dept Surg, Jerudong Pk, Brunei.
[Kong, Victory] Edendale Hosp, Dept Surg, Pietermaritzburg, South Africa.
[Knox, Matthew C.] Univ Western Sydney, Sch Med, Campbelltown, NSW, Australia.
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[Labbate, Maurizio] Univ Technol, Ithree Inst, Sydney, NSW, Australia.
[Labricciosa, Francesco M.] UNIVMP, Dept Biomed Sci & Publ Hlth, Unit Hyg Prevent Med & Publ Hlth, Ancona, Italy.
[Laterre, Pierre-Francois] UCL, Clin Univ St Luc, Dept Crit Care Med, Brussels, Belgium.
[Latifi, Rifat] Univ Arizona, Dept Surg, Div Trauma, Tucson, AZ USA.
[Lee, Jae Gil] Yonsei Univ, Coll Med, Dept Surg, Seoul, South Korea.
[Lee, Young Ran] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Abilene, TX USA.
[Leone, Marc] Aix Marseille Univ, Hop Nord, AP HP, Dept Anaesthesiol & Crit Care, Marseille, France.
[Leppaniemi, Ari] Univ Hosp Meilahti, Abdominal Ctr, Helsinki, Finland.
[Li, Yousheng] Nanjing Univ, Inling Hosp, Sch Med, Dept Surg, Nanjing, Jiangsu, Peoples R China.
[Liang, Stephen Y.] Washington Univ, Sch Med, Div Emergency Med, Div Infect Dis, St Louis, MO USA.
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[Maegele, Marc] UW H, CMMC, Dept Traumatol & Orthoped Surg, Cologne, Germany.
[Malama, Sydney] Univ Zambia, Inst Econ & Social Res, Hlth Res Program, Lusaka, Zambia.
[Martin-Loeches, Ignacio; Nicolau, David P.] St James Univ Hosp, Trinity Ctr Hlth Sci, MICRO, Dept Clin Med,Wellcome Trust HRB Clin Res, Dublin, Ireland.
[Marwah, Sanjay] Postgrad Inst Med Sci, Dept Surg, Rohtak, Haryana, India.
[Massele, Amos] Univ Botswana, Sch Med, Dept Clin Pharmacol, Gaborone, Botswana.
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[Melo, Renato Bessa] Ctr Hosp Sao Joao, Dept Gen Surg, Oporto, Portugal.
[Negoi, Ionut] Emergency Hosp Bucharest, Dept Surg, Bucharest, Romania.
[Nicolau, David P.] Ctr Antiinfect Res & Dev, Hartford, CT USA.
[Nord, Carl Erik] Karolinska Univ Hosp Huddinge, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
[Ofori-Asenso, Richard] Hlth Policy Consult, Res Unit, Weija Accra, Ghana.
[Omari, AbdelKarim H.] King Abdullah Univ Hosp, Dept Surg, Irbid, Jordan.
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[Piazza, Diego] Vittorio Emanuele Hosp, Div Surg, Catania, Italy.
[Pupelis, Guntars] Riga East Univ Hosp Gailezers, Dept Gen & Emergency Surg, Riga, Latvia.
[Rawson, Timothy Miles] Imperial Coll London, Healthcare Associated Infect & Antimicrobial Resi, Natl Inst Hlth Res, Hlth Protect Res Unit, Hammersmith Campus, London, England.
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[Tilsed, Jonathan V.] Hull & East Yorkshire Hosp NHS Trust, Surg Hlth Care Grp, Kingston Upon Hull, N Humberside, England.
[Timsit, Jean-Francois] Hop Xavier Bichat, APHP Med & Infect Dis ICU, Paris, France.
[Trueba, Gabriel] Univ San Francisco Quito, Biol & Environm Sci Coll, Inst Microbiol, Quito, Ecuador.
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[Zachariah, Sanoop K.] MOSC Med Coll Kolenchery, Dept Surg, Cochin, Kerala, India.
[Zahar, Jean-Ralph] Univ Angers, CHU Angers, Infect Control Unit, Angers, France.
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[Corcione, Antonio] AORN Colli Vincenzo Monaldi Hosp, Anesthesia & Intens Care Unit, Naples, Italy.
[Melotti, Rita M.] SantOrsola Univ Hosp, Anesthesiol & Intens Care Unit, Bologna, Italy.
[Viscoli, Claudio] Univ Genoa DISSAL, Infect Dis Unit, Genoa, Italy.
[Viscoli, Claudio] IRCCS San Martino IST, Genoa, Italy.
[Viale, Perluigi] Univ Bologna, Sant Orsola Hosp, Dept Med & Surg Sci, Infect Dis Unit, Bologna, Italy.
RP Sartelli, M (reprint author), Macerata Hosp, Dept Surg, Via Santa Lucia 2, I-62100 Macerata, Italy.
EM massimosartelli@gmail.com
RI Talving, Peep/G-8621-2015; RUPPE, ETIENNE/H-1073-2016;
OI Talving, Peep/0000-0002-9741-2073; MELOTTI, RITA
MARIA/0000-0001-6258-6607; Haque, Mainul/0000-0002-6124-7993; Marei,
Hany/0000-0002-0069-4212; Kiguba, Ronald/0000-0002-2636-4115; Labbate,
Maurizio/0000-0003-1428-3382; Trueba, Gabriel/0000-0003-2617-9021;
Rawson, Timothy Miles/0000-0002-2630-9722; Ofori-Asenso,
Richard/0000-0002-6643-3269
FU NIAID NIH HHS [R01 AI117211]
NR 300
TC 2
Z9 2
U1 21
U2 28
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1749-7922
J9 WORLD J EMERG SURG
JI World J. Emerg. Surg.
PD JUL 15
PY 2016
VL 11
AR 33
DI 10.1186/s13017-016-0089-y
PG 32
WC Emergency Medicine; Surgery
SC Emergency Medicine; Surgery
GA DR2IG
UT WOS:000379727600001
PM 27429642
ER
PT J
AU Guo, SZ
Lok, J
Zhao, S
Leung, W
Som, AT
Hayakawa, K
Wang, QZ
Xing, CH
Wang, XY
Ji, XM
Zhou, YM
Lo, EH
AF Guo, Shuzhen
Lok, Josephine
Zhao, Song
Leung, Wendy
Som, Angel T.
Hayakawa, Kazuhide
Wang, Qingzhi
Xing, Changhong
Wang, Xiaoying
Ji, Xunming
Zhou, Yiming
Lo, Eng H.
TI Effects of Controlled Cortical Impact on the Mouse Brain Vasculome
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE extracellular matrix; inflammation; microvessels; neurovascular unit;
traumatic brain injury
ID ENDOTHELIAL GROWTH-FACTOR; FOCAL CEREBRAL-ISCHEMIA; LONG PENTRAXIN PTX3;
GENE-EXPRESSION; XANTHINE-OXIDASE; ACTIVIN-A; EXTRACELLULAR-MATRIX;
ALZHEIMERS-DISEASE; CELL PROLIFERATION; TUMOR ANGIOGENESIS
AB Perturbations in blood vessels play a critical role in the pathophysiology of brain injury and neurodegeneration. Here, we use a systematic genome-wide transcriptome screening approach to investigate the vasculome after brain trauma in mice. Mice were subjected to controlled cortical impact and brains were extracted for analysis at 24 h post-injury. The core of the traumatic lesion was removed and then cortical microvesels were isolated from nondirectly damaged ipsilateral cortex. Compared to contralateral cortex and normal cortex from sham-operated mice, we identified a wide spectrum of responses in the vasculome after trauma. Up-regulated pathways included those involved in regulation of inflammation and extracellular matrix processes. Decreased pathways included those involved in regulation of metabolism, mitochondrial function, and transport systems. These findings suggest that microvascular perturbations can be widespread and not necessarily localized to core areas of direct injury per se and may further provide a broader gene network context for existing knowledge regarding inflammation, metabolism, and blood-brain barrier alterations after brain trauma. Further efforts are warranted to map the vasculome with higher spatial and temporal resolution from acute to delayed phase post-trauma. Investigating the widespread network responses in the vasculome may reveal potential mechanisms, therapeutic targets, and biomarkers for traumatic brain injury.
C1 [Guo, Shuzhen; Lok, Josephine; Leung, Wendy; Som, Angel T.; Hayakawa, Kazuhide; Wang, Qingzhi; Xing, Changhong; Wang, Xiaoying; Zhou, Yiming; Lo, Eng H.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA.
[Guo, Shuzhen; Lok, Josephine; Leung, Wendy; Som, Angel T.; Hayakawa, Kazuhide; Wang, Qingzhi; Xing, Changhong; Wang, Xiaoying; Zhou, Yiming; Lo, Eng H.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA.
[Lok, Josephine] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA.
[Zhao, Song] Jilin Univ, Hosp 1, Dept Spine Surg, Changchun, Peoples R China.
[Ji, Xunming] Capital Med Univ, Xuanwu Hosp, Cerebrovasc Res Ctr, Dept Neurosurg, Beijing, Peoples R China.
RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, 149 13th St,Room 2401, Charlestown, MA 02129 USA.
EM lo@helix.mgh.harvard.edu
NR 148
TC 0
Z9 0
U1 6
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 15
PY 2016
VL 33
IS 14
BP 1303
EP 1316
DI 10.1089/neu.2015.4101
PG 14
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DQ5CX
UT WOS:000379223100003
PM 26528928
ER
PT J
AU Pagulayan, KF
Temkin, NR
Machamer, JE
Dikmen, SS
AF Pagulayan, Kathleen F.
Temkin, Nancy R.
Machamer, Joan E.
Dikmen, Sureyya S.
TI Patterns of Alcohol Use after Traumatic Brain Injury
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE alcohol; traumatic brain
ID SPINAL-CORD-INJURY; SUBSTANCE-ABUSE; PSYCHIATRIC-DISORDERS;
RANDOMIZED-TRIAL; HEAD-INJURY; FOLLOW-UP; DRUG-USE; AXIS-I;
REHABILITATION; VALPROATE
AB Alcohol misuse and traumatic brain injury (TBI) frequently co-occur. The negative consequences of this interaction are well documented, but the patterns of long-term post-injury alcohol consumption are less clear. This study examined patterns of alcohol use among 170 adults with a history of complicated mild to severe TBI. Participants were recruited from a Level 1 Trauma Center at the time of their injury and completed evaluations at 1 month, 6 months, 12 months, and 3-5 years post-injury. Pre-injury alcohol use was also assessed at the time of the 1-month assessment. A modified Quantity-Frequency Index of alcohol consumption was then calculated for each time point. The results revealed high levels of pre-injury alcohol consumption, followed by a reduction in consumption at 1-month post-injury. A significant increase in consumption was noted by 6 months post-injury, followed by more gradual increases in alcohol consumption at 1 year. Post-injury alcohol consumption was comparable to the general public at 6 months, 12 months, and 3-5 years post-injury. These results suggest that the first 6 months post-injury may be the critical window of opportunity for alcohol intervention.
C1 [Pagulayan, Kathleen F.] VA Puget Sound Mental Illness Res Educ & Clin Ctr, Seattle, WA USA.
[Pagulayan, Kathleen F.; Dikmen, Sureyya S.] Univ Washington, Dept Psychiat & Behav Med, Seattle, WA 98195 USA.
[Temkin, Nancy R.; Machamer, Joan E.; Dikmen, Sureyya S.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Temkin, Nancy R.; Dikmen, Sureyya S.] Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA.
[Temkin, Nancy R.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Pagulayan, KF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way S-116-MIRECC, Seattle, WA 98108 USA.
EM farkat@u.washington.edu
FU CSRD VA [IK2 CX000516]
NR 41
TC 0
Z9 0
U1 8
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
EI 1557-9042
J9 J NEUROTRAUM
JI J. Neurotrauma
PD JUL 15
PY 2016
VL 33
IS 14
BP 1390
EP 1396
DI 10.1089/neu.2015.4071
PG 7
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DQ5CX
UT WOS:000379223100011
PM 26530335
ER
PT J
AU Krystal, JH
Abi-Dargham, A
Akbarian, S
Arnsten, AFT
Barch, DM
Bearden, CE
Braff, DL
Brown, ES
Bullmore, ET
Carlezon, WA
Carter, CS
Cook, EH
Daskalakis, ZJ
DiLeone, RJ
Duman, RS
Grace, AA
Hariri, AR
Harrison, PJ
Hiroi, N
Kenny, PJ
Kleinman, JE
Krystal, AD
Lewis, DA
Lipska, BK
Marder, SR
Mason, GF
Mathalon, DH
McClung, CA
McDougle, CJ
McIntosh, AM
McMahon, FJ
Mirnics, K
Monteggia, LM
Narendran, R
Nestler, EJ
Neumeister, A
O'Donovan, MC
Ongur, D
Pariante, CM
Paulus, MP
Pearlson, G
Phillips, ML
Pine, DS
Pizzagalli, DA
Pletnikov, MV
Ragland, JD
Rapoport, JL
Ressler, KJ
Russo, SJ
Sanacora, G
Sawa, A
Schatzberg, AF
Shaham, Y
Shamay-Tsoory, SG
Sklar, P
State, MW
Stein, MB
Strakowski, SM
Taylor, SF
Turecki, G
Turetsky, BI
Weissman, MM
Zachariou, V
Zarate, CA
Zubieta, JK
AF Krystal, John H.
Abi-Dargham, Anissa
Akbarian, Schahram
Arnsten, Amy F. T.
Barch, Deanna M.
Bearden, Carrie E.
Braff, David L.
Brown, E. Sherwood
Bullmore, Edward T.
Carlezon, William A., Jr.
Carter, Cameron S.
Cook, Edwin H., Jr.
Daskalakis, Zafiris Jeff
DiLeone, Ralph J.
Duman, Ronald S.
Grace, Anthony A.
Hariri, Ahmad R.
Harrison, Paul J.
Hiroi, Noboru
Kenny, Paul J.
Kleinman, Joel E.
Krystal, Andrew D.
Lewis, David A.
Lipska, Barbara K.
Marder, Stephen R.
Mason, Graeme F.
Mathalon, Daniel H.
McClung, Colleen A.
McDougle, Christopher J.
McIntosh, Andrew M.
McMahon, Francis J.
Mirnics, Karoly
Monteggia, Lisa M.
Narendran, Rajesh
Nestler, Eric J.
Neumeister, Alexander
O'Donovan, Michael C.
Ongur, Dost
Pariante, Carmine M.
Paulus, Martin P.
Pearlson, Godfrey
Phillips, Mary L.
Pine, Daniel S.
Pizzagalli, Diego A.
Pletnikov, Mikhail V.
Ragland, J. Daniel
Rapoport, Judith L.
Ressler, Kerry J.
Russo, Scott J.
Sanacora, Gerard
Sawa, Akira
Schatzberg, Alan F.
Shaham, Yavin
Shamay-Tsoory, Simone G.
Sklar, Pamela
State, Matthew W.
Stein, Murray B.
Strakowski, Stephen M.
Taylor, Stephan F.
Turecki, Gustavo
Turetsky, Bruce I.
Weissman, Myrna M.
Zachariou, Venetia
Zarate, Carlos A., Jr.
Zubieta, Jon-Kar
TI Constance E. Lieber, Theodore R. Stanley, and the Enduring Impact of
Philanthropy on Psychiatry Research
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
C1 [Krystal, John H.; Arnsten, Amy F. T.; Duman, Ronald S.] Yale Univ, Sch Med, Dept Psychiat & Neurosci, New Haven, CT 06511 USA.
[Krystal, John H.] Yale New Haven Med Ctr, Behav Hlth Serv, 20 York St, New Haven, CT 06504 USA.
[Krystal, John H.] VA Connecticut Healthcare Syst, Clin Neurosci Div, West Haven, CT USA.
[Abi-Dargham, Anissa] Columbia Univ, Dept Psychiat, New York, NY USA.
[Abi-Dargham, Anissa] Columbia Univ, Dept Radiol, New York, NY USA.
[Abi-Dargham, Anissa] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Akbarian, Schahram] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Arnsten, Amy F. T.] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06511 USA.
[Barch, Deanna M.] Washington Univ, Dept Psychol, St Louis, MO 63130 USA.
[Barch, Deanna M.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychiat, Los Angeles, CA 90024 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Psychol, Los Angeles, CA 90024 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Brain Res Inst, Los Angeles, CA 90024 USA.
[Braff, David L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Brown, E. Sherwood] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA.
[Bullmore, Edward T.] Univ Cambridge, Dept Psychiat & Behav, Cambridge, England.
[Bullmore, Edward T.] Univ Cambridge, Neurosci Inst, Cambridge, England.
[Bullmore, Edward T.] GlaxoSmithKline, ImmunoPsychiat, Cambridge, England.
[Carlezon, William A., Jr.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat & Neurosci, Belmont, MA 02178 USA.
[Carter, Cameron S.] Univ Calif Davis, Dept Psychiat & Behav Sci, Imaging Res Ctr, Davis, CA 95616 USA.
[Carter, Cameron S.] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA.
[Cook, Edwin H., Jr.] Univ Illinois, Dept Psychiat, Inst Juvenile Res, Chicago, IL 60612 USA.
[Daskalakis, Zafiris Jeff] Ctr Addict & Mental Hlth, Mood & Anxiety Div, Temerty Ctr Therapeut Brain Intervent, Toronto, ON, Canada.
[Daskalakis, Zafiris Jeff] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[DiLeone, Ralph J.] Yale Univ, Dept Psychiat, New Haven, CT 06511 USA.
[Grace, Anthony A.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA.
[Grace, Anthony A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Grace, Anthony A.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Hariri, Ahmad R.] Duke Univ, Dept Psychol & Neurosci, Durham, NC USA.
[Harrison, Paul J.] Univ Oxford, Dept Psychiat, Oxford, England.
[Hiroi, Noboru] Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA.
[Hiroi, Noboru] Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10467 USA.
[Hiroi, Noboru] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA.
[Kenny, Paul J.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA.
[Kleinman, Joel E.] Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Genet Neuropathol Sect, Baltimore, MD USA.
[Kleinman, Joel E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Krystal, Andrew D.] Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC USA.
[Lewis, David A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Lipska, Barbara K.] NIMH, Human Brain Collect Core, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
[Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst Neurosci, Los Angeles, CA USA.
[Marder, Stephen R.] VA Desert Pacific Mental Illness Res Educ & Clin, Los Angeles, CA USA.
[Mason, Graeme F.] Yale Univ, Sch Med, Dept Radiol & Biomed Imaging, New Haven, CT 06511 USA.
[Mason, Graeme F.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA.
[Mathalon, Daniel H.; State, Matthew W.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Mathalon, Daniel H.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA USA.
[McClung, Colleen A.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[McDougle, Christopher J.] Massachusetts Gen Hosp, Lexington, MA USA.
[McDougle, Christopher J.] MassGen Hosp Children, Lurie Ctr Autism, Lexington, MA USA.
[McDougle, Christopher J.; Pizzagalli, Diego A.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[McIntosh, Andrew M.] Univ Edinburgh, Div Psychiat, Edinburgh, Midlothian, Scotland.
[McMahon, Francis J.] NIMH, Human Genet Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[McMahon, Francis J.] NIMH, Intramural Res Program, Genet Basis Mood & Anxiety Disorders Sect, Bethesda, MD 20892 USA.
[Mirnics, Karoly] Vanderbilt Univ, Dept Psychiat, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Monteggia, Lisa M.] Univ Texas SW Med Ctr Dallas, Dept Neurosci, Dallas, TX 75390 USA.
[Narendran, Rajesh] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA.
[Narendran, Rajesh] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Nestler, Eric J.; Russo, Scott J.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY 10029 USA.
[Nestler, Eric J.; Russo, Scott J.] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
[Neumeister, Alexander] Mitsubishi Tanabe Pharma Dev Amer Inc, Jersey City, NJ USA.
[O'Donovan, Michael C.] Cardiff Univ, MRC Ctr Neuropsychiat Genet & Genom, Cardiff CF10 3AX, S Glam, Wales.
[Ongur, Dost; Ressler, Kerry J.] Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, Belmont, MA USA.
[Pariante, Carmine M.] Kings Coll London, Inst Psychiat, Dept Psychol, London, England.
[Pariante, Carmine M.] Kings Coll London, Inst Psychiat, Dept Neurosci, London, England.
[Pariante, Carmine M.] Maurice Wohl Clin Neurosci Inst, Psychiat & Immunol Lab & Perinatal Psychiat, London, England.
[Paulus, Martin P.] Laureate Inst Brain Res, Tulsa, OK USA.
[Pearlson, Godfrey] Yale Univ, Dept Psychiat, Hartford, CT USA.
[Pearlson, Godfrey] Yale Univ, Dept Neurobiol, Hartford, CT USA.
[Pearlson, Godfrey] Olin Neuropsychiat Res Ctr, Hartford, CT USA.
[Phillips, Mary L.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA.
[Pine, Daniel S.] NIMH, Intramural Res Program, Bethesda, MD 20892 USA.
[Pizzagalli, Diego A.] McLean Hosp, McLean Imaging Ctr, 115 Mill St, Belmont, MA 02178 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA.
[Ragland, J. Daniel] Univ Calif Davis, Imaging Res Ctr, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA.
[Rapoport, Judith L.] NIMH, Child Psychiat Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.
[Sanacora, Gerard] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Sawa, Akira] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[Schatzberg, Alan F.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA USA.
[Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD USA.
[Shamay-Tsoory, Simone G.] Univ Haifa, Dept Psychol, IL-31999 Haifa, Israel.
[Sklar, Pamela] Icahn Sch Med Mt Sinai, Div Psychiat Genom, Dept Psychiat, New York, NY 10029 USA.
[Stein, Murray B.] Univ Calif San Diego, Sch Med, Dept Psychiat, 9500 Gillman Dr, La Jolla, CA 92093 USA.
[Stein, Murray B.] Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, La Jolla, CA USA.
[Strakowski, Stephen M.] Univ Texas Austin, Dept Psychiat, Dell Med Sch, Austin, TX USA.
[Taylor, Stephan F.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Turecki, Gustavo] McGill Univ, Dept Psychiat, Montreal, PQ, Canada.
[Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Weissman, Myrna M.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA.
[Weissman, Myrna M.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Zachariou, Venetia] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY USA.
[Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Zubieta, Jon-Kar] Univ Utah, Hlth Sci Ctr, Dept Psychiat, Univ Neuropsychiat Inst, Salt Lake City, UT USA.
RP Krystal, JH (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA.
EM john.krystal@yale.edu
RI Lipska, Barbara/E-4569-2017;
OI McIntosh, Andrew/0000-0002-0198-4588
FU Medical Research Council [G1000183, MR/K026992/1]
NR 2
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 15
PY 2016
VL 80
IS 2
BP 84
EP 86
DI 10.1016/j.biopsych.2016.05.004
PG 3
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DP5IT
UT WOS:000378530200002
PM 27346079
ER
PT J
AU Hippolyte, L
Maillard, AM
Rodriguez-Herreros, B
Pain, A
Martin-Brevet, S
Ferrari, C
Conus, P
Mace, A
Hadjikhani, N
Metspalu, A
Reigo, A
Kolk, A
Mannik, K
Barker, M
Isidor, B
Le Caignec, C
Mignot, C
Schneider, L
Mottron, L
Keren, B
David, A
Doco-Fenzy, M
Gerard, M
Bernier, R
Goin-Kochel, RP
Hanson, E
Snyder, LG
Ramus, F
Beckmann, JS
Draganski, B
Reymond, A
Jacquemont, S
AF Hippolyte, Loyse
Maillard, Anne M.
Rodriguez-Herreros, Borja
Pain, Aurelie
Martin-Brevet, Sandra
Ferrari, Carina
Conus, Philippe
Mace, Aurelien
Hadjikhani, Nouchine
Metspalu, Andres
Reigo, Anu
Kolk, Anneli
Maennik, Katrin
Barker, Mandy
Isidor, Bertrand
Le Caignec, Cedric
Mignot, Cyril
Schneider, Laurence
Mottron, Laurent
Keren, Boris
David, Albert
Doco-Fenzy, Martine
Gerard, Marion
Bernier, Raphael
Goin-Kochel, Robin P.
Hanson, Ellen
Snyder, LeeAnne Green
Ramus, Franck
Beckmann, Jacques S.
Draganski, Bogdan
Reymond, Alexandre
Jacquemont, Sebastien
CA 16p11 2 European Consortium
Simons Variation Individuals Proje
TI The Number of Genomic Copies at the 16p11.2 Locus Modulates Language,
Verbal Memory, and Inhibition
SO BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE 16p11.2; ASD; Copy number variation; Inhibition; Language; Memory
ID NEUROPSYCHIATRIC DISORDERS; DIAGNOSTIC INTERVIEW; SYNAPTIC PLASTICITY;
CHROMOSOME 16P11.2; DELETION SYNDROME; AUTISM; SCHIZOPHRENIA; BRAIN;
OBESITY; SPEECH
AB BACKGROUND: Deletions and duplications of the 16p11.2 BP4-BP5 locus are prevalent copy number variations (CNVs), highly associated with autism spectrum disorder and schizophrenia. Beyond language and global cognition, neuropsychological assessments of these two CNVs have not yet been reported.
METHODS: This study investigates the relationship between the number of genomic copies at the 16p11.2 locus and cognitive domains assessed in 62 deletion carriers, 44 duplication carriers, and 71 intrafamilial control subjects.
RESULTS: IQ is decreased in deletion and duplication carriers, but we demonstrate contrasting cognitive profiles in these reciprocal CNVs. Deletion carriers present with severe impairments of phonology and of inhibition skills beyond what is expected for their IQ level. In contrast, for verbal memory and phonology, the data may suggest that duplication carriers outperform intrafamilial control subjects with the same IQ level. This finding is reminiscent of special isolated skills as well as contrasting language performance observed in autism spectrum disorder. Some domains, such as visuospatial and working memory, are unaffected by the 16p11.2 locus beyond the effect of decreased IQ. Neuroimaging analyses reveal that measures of inhibition covary with neuroanatomic structures previously identified as sensitive to 16p11.2 CNVs.
CONCLUSIONS: The simultaneous study of reciprocal CNVs suggests that the 16p11.2 genomic locus modulates specific cognitive skills according to the number of genomic copies. Further research is warranted to replicate these findings and elucidate the molecular mechanisms modulating these cognitive performances.
C1 [Hippolyte, Loyse; Rodriguez-Herreros, Borja; Pain, Aurelie; Martin-Brevet, Sandra; Beckmann, Jacques S.; Jacquemont, Sebastien] CHU Vaudois, Serv Genet Med, Lausanne, Switzerland.
[Rodriguez-Herreros, Borja; Martin-Brevet, Sandra; Draganski, Bogdan] CHU Vaudois, Lab Res Neuroimaging, Dept Neurosci Clin, Lausanne, Switzerland.
[Ferrari, Carina; Conus, Philippe] CHU Vaudois, Dept Psychiat, Lausanne, Switzerland.
[Barker, Mandy] CHU Vaudois, CERY Hosp, Dept Child Psychiat, Lausanne, Switzerland.
[Schneider, Laurence] CHU Vaudois, SUPEA, Lausanne, Switzerland.
[Schneider, Laurence] CHU Vaudois, Serv Neuropsychol & Neurorehabil, Lausanne, Switzerland.
Univ Lausanne, CH-1015 Lausanne, Switzerland.
[Mace, Aurelien] Univ Lausanne, Dept Med Genet, CH-1015 Lausanne, Switzerland.
[Mace, Aurelien; Beckmann, Jacques S.] Univ Lausanne, SIB Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
[Maennik, Katrin; Reymond, Alexandre] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland.
[Hadjikhani, Nouchine] Ecole Polytech Fed Lausanne, Sch Life Sci, Brain Mind Inst, Lausanne, Switzerland.
[Metspalu, Andres; Reigo, Anu; Maennik, Katrin] Tartu Univ Hosp, Dept Neurol & Neurorehabil, Dept Genet, Tartu, Estonia.
[Kolk, Anneli] Tartu Univ Hosp, Dept Neurol & Neurorehabil, United Labs, Tartu, Estonia.
[Kolk, Anneli] Tartu Univ Hosp, Dept Neurol & Neurorehabil, Childrens Clin, Tartu, Estonia.
[Isidor, Bertrand; Le Caignec, Cedric; David, Albert] CHU Nantes, Gen Med Serv, Nantes, France.
[Le Caignec, Cedric] Fac Med, INSERM, UMR957, Nantes, France.
[Mignot, Cyril; Keren, Boris; Gerard, Marion] Grp Hosp Pitie Salpetriere, AP HP, Unite Fonct Genet Clin, Dept Genet & Cytogenet, Paris, France.
[Mignot, Cyril] UPMC, Ctr Reference Deficiences Intellectuelles Causes, Paris, France.
[Mignot, Cyril] UPMC, Grp Rech Clin Deficience Intellectuelle & Autisme, Paris, France.
[Mottron, Laurent] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada.
Hop Riviere Prairies, Montreal, PQ, Canada.
[Doco-Fenzy, Martine] CHU, Serv Genet, Reims, France.
[Gerard, Marion] Univ Paris VII Paris Diderot, Hop Robert Debre, Dept Genet, Paris, France.
[Bernier, Raphael] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Goin-Kochel, Robin P.] Baylor Coll Med, Psychol Sect, Dept Pediat, Houston, TX 77030 USA.
[Hanson, Ellen] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Psychiat, Boston, MA USA.
[Snyder, LeeAnne Green] Clin Res Associates, New York, NY USA.
[Ramus, Franck] PSL Res Univ, Dept Etud Cognit, CNRS, Ecole Normale Super,EHESS,Lab Sci Cognit & Psycho, Paris, France.
[Draganski, Bogdan] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany.
[Hadjikhani, Nouchine] Univ Gothenburg, Sahlgrenska Acad, Gillberg Neuropsychiat Ctr, Gothenburg, Sweden.
[Hadjikhani, Nouchine] Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA USA.
[Jacquemont, Sebastien] Univ Montreal, Fac Med, Dept Pediat, Montreal, PQ H3C 3J7, Canada.
RP Jacquemont, S (reprint author), Dept Pediat, Serv Genet, 3175 Ch Cote Sainte Catherine, Montreal, PQ H3T 1C4, Canada.
EM sebastien.jacquemont@umontreal.ca
RI Ramus, Franck/A-1755-2009; Centre d'imagerie Biomedicale,
CIBM/B-5740-2012; Beckmann, Jacques S /A-9772-2008;
OI Ramus, Franck/0000-0002-1122-5913; Beckmann, Jacques S
/0000-0002-9741-1900; Hadjikhani, Nouchine/0000-0003-4075-3106;
Draganski, Bogdan/0000-0002-5159-5919
FU Leenaards Foundation Prize; Swiss National Science Foundation (SNSF)
Sinergia Grant [CRIS FN CRSII33-133044]; National Center of Competence
in Research Synapsy Project Grant [320030_135679]; Special Program
University Medicin [33CM30_140332/1]; Simons Foundation Autism Research
Initiative (SFARI) Grant [SFARI274424]; Foundation Parkinson
Switzerland; Foundation Synapsis; Human Brain Project, a European Union
initiative; SNSF Grant [PP00P3_144902/2]; Canada Research Chair; Jeanne
and Jean Louis Levesque Foundation; Center of Excellence in Genomics
(Estonian Genome Center, the University of Tartu [EGCUT]); University of
Tartu [SP1GVARENG]; Estonian Research Council [IUT20-60]; Swiss
Scientific Exchange New Member States Program; doctoral school of the
Faculty of Biology and Medicine, University of Lausanne; Roger de
Spoelberg Foundation; Partridge Foundation; Agence Nationale
[ANR-10-LABX-0087 IEC, ANR-10-IDEX-0001-02 PSL]
FX This work was supported by the Leenaards Foundation Prize (SJ, ARey,
NH), Swiss National Science Foundation (SNSF) Sinergia Grant No. CRIS FN
CRSII33-133044 (ARey, SJ), National Center of Competence in Research
Synapsy Project Grant Nos. 320030_135679 and Special Program University
Medicin 33CM30_140332/1 (BD), Simons Foundation Autism Research
Initiative (SFARI) Grant No. SFARI274424 (ARey), Foundation Parkinson
Switzerland (BD), Foundation Synapsis (BD), Human Brain Project, a
European Union initiative (BD), SNSF Grant No. PP00P3_144902/2 (SJ), a
Canada Research Chair (SJ), Jeanne and Jean Louis Levesque Foundation
(SJ), Center of Excellence in Genomics (Estonian Genome Center, the
University of Tartu [EGCUT] [AMe, ARei, AK, KM]), University of Tartu
Grant No. SP1GVARENG (EGCUT [AMe, ARei, AK, KM]), Estonian Research
Council Grant No. IUT20-60 (EGCUT [AMe, ARei, AK, KM]), Swiss Scientific
Exchange New Member States Program (KM), and a fellowship from the
doctoral school of the Faculty of Biology and Medicine, University of
Lausanne (MZ). Laboratory for Research in Neuroimaging is supported by
the Roger de Spoelberg and Partridge Foundations. FR received funding
from Agence Nationale (contracts ANR-10-LABX-0087 IEC and
ANR-10-IDEX-0001-02 PSL). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 63
TC 2
Z9 2
U1 7
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD JUL 15
PY 2016
VL 80
IS 2
BP 129
EP 139
DI 10.1016/j.biopsych.2015.10.021
PG 11
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DP5IT
UT WOS:000378530200010
PM 26742926
ER
PT J
AU Zietman, AL
Smith, J
Klein, E
Droller, M
Dasgupta, P
Catto, J
AF Zietman, Anthony L.
Smith, Joseph
Klein, Eric
Droller, Michael
Dasgupta, Prokar
Catto, James
TI Editorial Statement on Gleason Scoring for Prostate Cancer
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Editorial Material
C1 [Zietman, Anthony L.] Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA.
RP Zietman, AL (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA.
EM azietman@partners.org
OI catto, james/0000-0003-2787-8828
NR 1
TC 2
Z9 2
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2016
VL 95
IS 4
BP 1092
EP 1092
DI 10.1016/j.ijrobp.2016.02.055
PG 1
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DP0VC
UT WOS:000378207000002
PM 27354124
ER
PT J
AU Verma, V
Shah, C
Lautenschlaeger, T
Lin, C
Beriwal, S
Zhen, WN
Mehta, MP
Zietman, AL
AF Verma, Vivek
Shah, Chirag
Lautenschlaeger, Tim
Lin, Chi
Beriwal, Sushil
Zhen, Weining
Mehta, Minesh P.
Zietman, Anthony L.
TI International Medical Graduates in Radiation Oncology: Historical Trends
and Comparison With Other Medical Specialties
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID RESIDENCY; WORKFORCE
AB Purpose: This is the first National Resident Matching Program analysis evaluating historical patterns of international medical graduates (IMGs) in radiation oncology (RO) and providing comparison with American (MD) medical graduates (AMGs), osteopathic students (DOs), unfilled positions, and other specialties.
Methods and Materials: National Resident Matching Program data for IMGs were available from 2003 to 2015, with limited data for other specialty matches. The following RO-specific figures were obtained per year: total positions available; total matched positions; number of unfilled positions; and number of IMG, AMG, and DO matches. In addition, the number of IMG matches and total matched positions were obtained for 19 other specialties. Fisher exact tests and chi(2) tests were considered significant at alpha < .05.
Results: From 2010 to 2015, 0.8% of RO matches were IMGs, a decline from 2.4% in 2003 to 2009 ( P=. 006). Proportions of DO matches during these intervals increased by 40% (from 1.0% to 1.4%), significantly lower than IMGs for 2003 to 2009 (P =. 03) but not 2010 to 2015 (P =. 26). From 2003 to 2015, the percentage of IMG matches, at 1.5%, was significantly lower than the percentage of unfilled seats, at 3.5% (P <. 001). In comparison with other specialties (2003-2015), RO had the fewest IMG matches (1.5%), followed by otolaryngology (1.9%) and orthopedics (2.2%); specialties with the highest IMG proportions were internal medicine (37.1%), family medicine (35.7%), and neurology (31.1%).
Conclusions: Presently, IMGs represent < 1% of RO matches, the lowest among major specialties. There are several speculative factors associated with this low proportion. There are significantly more unfilled positions than those filled by IMGs; programs at risk of not matching could weigh the advantages and disadvantages of interviewing IMGs. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Verma, Vivek; Lin, Chi; Zhen, Weining] Univ Nebraska Med Ctr, Dept Radiat Oncol, 987521 Nebraska Med Ctr, Omaha, NE 68198 USA.
[Shah, Chirag] Cleveland Clin, Dept Radiat Oncol, Taussig Canc Inst, Cleveland, OH 44106 USA.
[Lautenschlaeger, Tim] Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA.
[Beriwal, Sushil] Univ Pittsburgh, Dept Radiat Oncol, Med Ctr, Pittsburgh, PA USA.
[Mehta, Minesh P.] Miami Canc Inst, Dept Radiat Oncol, Coral Gables, FL USA.
[Zietman, Anthony L.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Verma, V (reprint author), Univ Nebraska Med Ctr, Dept Radiat Oncol, 987521 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM vivek333@gmail.com
OI mehta, minesh/0000-0002-4812-5713
NR 11
TC 2
Z9 2
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2016
VL 95
IS 4
BP 1102
EP 1106
DI 10.1016/j.ijrobp.2016.03.008
PG 5
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DP0VC
UT WOS:000378207000004
PM 27209507
ER
PT J
AU Huynh, MA
Chen, MH
Wu, J
Braccioforte, MH
Moran, BJ
D'Amico, AV
AF Mai Anh Huynh
Chen, Ming-Hui
Wu, Jing
Braccioforte, Michelle H.
Moran, Brian J.
D'Amico, Anthony V.
TI Influence of Comorbidity on the Risk of Mortality in Men With
Unfavorable-Risk Prostate Cancer Undergoing High-Dose Radiation Therapy
Alone
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID RANDOMIZED-TRIAL; ANDROGEN SUPPRESSION; DISEASE; ASSOCIATION;
DEPRIVATION; SURVIVAL; FAILURE; UPDATE; DEATH; AGE
AB Purpose: To explore whether a subgroup of men with unfavorable-risk prostate cancer (PC) exists in whom high-dose radiation therapy (RT) alone is sufficient to avoid excess PC death due to competing risk from cardiometabolic comorbidity.
Methods and Materials: This was a cohort study of 7399 men in whom comorbidity (including congestive heart failure, diabetes mellitus, or myocardial infarction) was assessed and recorded with T1-3NxM0 PC treated with brachytherapy with or without neoadjuvant RT, October 1997 to May 2013 at a single providing institution. Cox and competing risks regression analyses were used to assess whether men with unfavorable-intermediate/high-risk versus favorable-intermediate/low-risk PC were at increased risk of PC-specific, all-cause, or other-cause mortality (PCSM, ACM, OCM), adjusting for number of comorbidities, age at and year of brachytherapy, RT use, and an RT treatment propensity score.
Results: After a median follow-up of 7.7 years, 935 men died: 80 of PC and 855 of other causes. Among men with no comorbidity, PCSM risk (adjusted hazard ratio [AHR] 2.74 [95% confidence interval (CI) 1.49-5.06], P = .001) and ACM risk (AHR 1.30 [95% CI 1.07-1.58], P = .007) were significantly increased in men with unfavorable-intermediate/high-risk PC versus favorable-intermediate/low-risk PC, with no difference in OCM (P = .07). Although PCSM risk was increased in men with 1 comorbidity (AHR 2.87 [95% CI 1.11-7.40], P = .029), ACM risk was not (AHR 1.03 [95% CI 0.78-1.36], P = .84). Neither PCSM risk (AHR 4.39 [95% CI 0.37-51.98], P = .24) or ACM risk (AHR 1.43 [95% CI 0.83-2.45], P = .20) was increased in men with 2 comorbidities.
Conclusions: To minimize death from PC, high-dose RT alone may be sufficient treatment in men with 2 or more cardiometabolic comorbidities and unfavorablee intermediate- and high-risk PC. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Mai Anh Huynh] Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA.
[Chen, Ming-Hui; Wu, Jing] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA.
[Braccioforte, Michelle H.; Moran, Brian J.] Prostate Canc Fdn Chicago, Westmont, IL USA.
[D'Amico, Anthony V.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
RP Huynh, MA (reprint author), Brigham & Womens Hosp, Harvard Radiat Oncol Program, 75 Francis St, Boston, MA 02115 USA.
EM mahuynh@lroc.harvard.edu
NR 28
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2016
VL 95
IS 4
BP 1158
EP 1167
DI 10.1016/j.ijrobp.2016.03.004
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DP0VC
UT WOS:000378207000011
PM 27209511
ER
PT J
AU Gaffney, DK
King, B
Viswanathan, AN
Barkati, M
Beriwal, S
Eifel, P
Erickson, B
Fyles, A
Goulart, J
Harkenrider, M
Jhingran, A
Klopp, A
Koh, WJ
Lim, K
Petersen, I
Portelance, L
Small, W
Stewart, A
Wiebe, E
Wolfson, A
Yashar, C
Bosch, W
AF Gaffney, David K.
King, Bronwyn
Viswanathan, Akila N.
Barkati, Maroie
Beriwal, Sushil
Eifel, Patricia
Erickson, Beth
Fyles, Anthony
Goulart, Jennifer
Harkenrider, Matthew
Jhingran, Anuja
Klopp, Ann
Koh, Wui-Jin
Lim, Karen
Petersen, Ivy
Portelance, Lorraine
Small, William, Jr.
Stewart, Alexandra
Wiebe, Ericka
Wolfson, Aaron
Yashar, Catheryn
Bosch, Walter
TI Consensus Recommendations for Radiation Therapy Contouring and Treatment
of Vulvar Carcinoma
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID INTENSITY-MODULATED RADIOTHERAPY; SQUAMOUS-CELL CARCINOMA;
GYNECOLOGIC-ONCOLOGY-GROUP; PELVIC NODE RESECTION; LYMPH-NODES;
PHASE-II; CANCER; CHEMOTHERAPY; DELINEATION; RECURRENCE
AB Purpose: The purpose of this study was to develop a radiation therapy (RT) contouring atlas and recommendations for women with postoperative and locally advanced vulvar carcinoma.
Methods and Materials: An international committee of 35 expert gynecologic radiation oncologists completed a survey of the treatment of vulvar carcinoma. An initial set of recommendations for contouring was discussed and generated by consensus. Two cases, 1 locally advanced and 1 postoperative, were contoured by 14 physicians. Contours were compared and analyzed using an expectation-maximization algorithm for simultaneous truth and performance level estimation (STAPLE), and a 95% confidence interval contour was developed. The level of agreement among contours was assessed using a kappa statistic. STAPLE contours underwent full committee editing to generate the final atlas consensus contours.
Results: Analysis of the 14 contours showed substantial agreement, with kappa statistics of 0.69 and 0.64 for cases 1 and 2, respectively. There was high specificity for both cases (>= 99%) and only moderate sensitivity of 71.3% and 64.9% for cases 1 and 2, respectively. Expert review and discussion generated consensus recommendations for contouring target volumes and treatment for postoperative and locally advanced vulvar cancer.
Conclusions: These consensus recommendations for contouring and treatment of vulvar cancer identified areas of complexity and controversy. Given the lack of clinical research evidence in vulvar cancer radiation therapy, the committee advocates a conservative and consistent approach using standardized recommendations. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Gaffney, David K.] Huntsman Canc Hosp, Dept Radiat Oncol, Salt Lake City, UT 84112 USA.
[King, Bronwyn] Peter MacCallum Canc Ctr & Epworth Radiat Oncol, Dept Radiat Oncol & Canc Imaging, Melbourne, Vic, Australia.
[Viswanathan, Akila N.] Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA.
[Barkati, Maroie] Univ Montreal, Ctr Hosp, Dept Radiat Oncol, Montreal, PQ, Canada.
[Beriwal, Sushil] Univ Pittsburgh, Inst Canc, Dept Radiat Oncol, Pittsburgh, PA USA.
[Eifel, Patricia; Jhingran, Anuja; Klopp, Ann] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Erickson, Beth] Proedtert & Med Coll Clin Canc Ctr, Dept Radiat Oncol, Milwaukee, WI USA.
[Fyles, Anthony] Princess Margaret Canc Ctr, Dept Radiat Oncol, Toronto, ON, Canada.
[Goulart, Jennifer] British Columbia Canc Agcy, Dept Radiat Oncol, Victoria, BC, Canada.
[Harkenrider, Matthew; Small, William, Jr.] Loyola Univ, Stritch Sch Med, Dept Radiat Oncol, 2160 S 1st Ave, Maywood, IL 60153 USA.
[Koh, Wui-Jin] Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA.
[Lim, Karen] Liverpool Canc Therapy Ctr, Radiat Oncol Unit, Sydney, NSW, Australia.
[Petersen, Ivy] Mayo Clin, Dept Radiat Oncol, Rochester, MN USA.
[Portelance, Lorraine; Wolfson, Aaron] Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA.
[Stewart, Alexandra] Royal Surrey Country Hosp, St Lukes Canc Ctr, Surrey, England.
[Wiebe, Ericka] Cross Canc Inst, Dept Radiat Oncol, Edmonton, AB T6G 1Z2, Canada.
[Yashar, Catheryn] Univ Calif San Diego, Radiat Med & Appl Sci, San Diego, CA 92103 USA.
[Bosch, Walter] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA.
RP Gaffney, DK (reprint author), Huntsman Canc Hosp, Dept Radiat Oncol, Salt Lake City, UT 84112 USA.
EM david.gaffney@hci.utah.edu
OI Fyles, Anthony/0000-0002-3633-2483
FU NCI NIH HHS [U10 CA180818, U10 CA180868, U24 CA180803]
NR 25
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD JUL 15
PY 2016
VL 95
IS 4
BP 1191
EP 1200
DI 10.1016/j.ijrobp.2016.02.043
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DP0VC
UT WOS:000378207000015
PM 27130794
ER
PT J
AU Mirzaalian, H
Ning, L
Savadjiev, P
Pasternak, O
Bouix, S
Michailovich, O
Grant, G
Marx, CE
Morey, RA
Flashman, LA
George, MS
McAllister, TW
Andaluz, N
Shutter, L
Coimbra, R
Zafonte, RD
Coleman, MJ
Kubicki, M
Westin, CF
Stein, MB
Shenton, ME
Rathi, Y
AF Mirzaalian, H.
Ning, L.
Savadjiev, P.
Pasternak, O.
Bouix, S.
Michailovich, O.
Grant, G.
Marx, C. E.
Morey, R. A.
Flashman, L. A.
George, M. S.
McAllister, T. W.
Andaluz, N.
Shutter, L.
Coimbra, R.
Zafonte, R. D.
Coleman, M. J.
Kubicki, M.
Westin, C. F.
Stein, M. B.
Shenton, M. E.
Rathi, Y.
TI Inter-site and inter-scanner diffusion MRI data harmonization
SO NEUROIMAGE
LA English
DT Article
DE Diffusion MRI; Harmonization; Multi-site; Inter-scanner; Intra-site
ID MAGNETIC-RESONANCE IMAGES; SPATIAL STATISTICS; RELIABILITY; MULTISITE;
MULTICENTER; VARIABILITY
AB We propose a novel method to harmonize diffusion MRI data acquired from multiple sites and scanners, which is imperative for joint analysis of the data to significantly increase sample size and statistical power of neuroimaging studies. Our method incorporates the following main novelties: i) we take into account the scanner-dependent spatial variability of the diffusion signal in different parts of the brain; ii) our method is independent of compartmental modeling of diffusion (e.g., tensor, and intra/extra cellular compartments) and the acquired signal itself is corrected for scanner related differences; and iii) inter-subject variability as measured by the coefficient of variation is maintained at each site. We represent the signal in a basis of spherical harmonics and compute several rotation invariant spherical harmonic features to estimate a region and tissue specific linear mapping between the signal from different sites (and scanners). We validate our method on diffusion data acquired from seven different sites (including two GE, three Philips, and two Siemens scanners) on a group of age-matched healthy subjects. Since the extracted rotation invariant spherical harmonic features depend on the accuracy of the brain parcellation provided by Freesurfer, we propose a feature based refinement of the original parcellation such that it better characterizes the anatomy and provides robust linear mappings to harmonize the dMRI data. We demonstrate the efficacy of our method by statistically comparing diffusion measures such as fractional anisotropy, mean diffusivity and generalized fractional anisotropy across multiple sites before and after data harmonization. We also show results using tract-based spatial statistics before and after harmonization for independent validation of the proposed methodology. Our experimental results demonstrate that, for nearly identical acquisition protocol across sites, scanner-specific differences can be accurately removed using the proposed method. (C) 2016 Published by Elsevier Inc.
C1 [Mirzaalian, H.; Ning, L.; Savadjiev, P.; Pasternak, O.; Bouix, S.; Zafonte, R. D.; Coleman, M. J.; Kubicki, M.; Westin, C. F.; Shenton, M. E.; Rathi, Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Mirzaalian, H.; Ning, L.; Savadjiev, P.; Pasternak, O.; Bouix, S.; Coleman, M. J.; Kubicki, M.; Westin, C. F.; Shenton, M. E.; Rathi, Y.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Michailovich, O.] Univ Waterloo, Waterloo, ON N2L 3G1, Canada.
[Grant, G.] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA.
[Grant, G.; Shutter, L.] Duke Univ, Durham, NC 27706 USA.
[Marx, C. E.; Morey, R. A.] Duke Univ, Med Ctr, Durham, NC 27706 USA.
[Marx, C. E.; Morey, R. A.] VA Midatlantic MIRECC, Durham, NC USA.
[Flashman, L. A.] Dartmouth Coll, Hanover, NH USA.
[Flashman, L. A.; McAllister, T. W.] Geisel Sch Med Dartmouth, Hanover, NH USA.
[George, M. S.] Med Univ S Carolina, Charleston, SC 29425 USA.
[George, M. S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[McAllister, T. W.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Andaluz, N.] Univ Cincinnati, Coll Med, Dept Neurosurg, Cincinnati, OH 45267 USA.
[Andaluz, N.] UC Neurosci Inst, Neurotrauma Ctr, Cincinnati, OH USA.
[Andaluz, N.] Mayfield Clin, Cincinnati, OH USA.
[Shutter, L.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Coimbra, R.] Univ Calif San Diego, Dept Surg, San Diego, CA 92103 USA.
[Zafonte, R. D.] Spaulding Rehabil Hosp, Boston, MA USA.
[Stein, M. B.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Shenton, M. E.] VA Boston Healthcare Syst, Boston, MA USA.
RP Mirzaalian, H (reprint author), Psychiat Neuroimaging Lab, 1249 Boylston St, Boston, MA 02215 USA.
EM hengameh.mirzaalian@gmail.com
OI Shutter, Lori/0000-0002-1390-0628
FU Swedish Research Council (VR) [2012-3682]; Swedish Foundation for
Strategic Research (SSF) [AM13-0090]; VA Merit (PI: Shenton);
[W81XWH-08-2-0159]; [R01MH099797]; [R01MH074794]; [P41EB015902]
FX The authors would like to acknowledge the following grants which
supported this work: W81XWH-08-2-0159 (Imaging Core PI: Shenton, Contact
PI: Stein, Site PIs: George, Grant, Marx, McCallister, Zafonte; Other:
Bouix, Coleman, Bouix, Kubicki, Mirzaalian, Pasternak, Savadjiev,
Rathi), R01MH099797 (PI: Rathi), R01MH074794 (PI: Westin), P41EB015902
(PI: Kikinis), Swedish Research Council (VR) grant 2012-3682, Swedish
Foundation for Strategic Research (SSF) grant AM13-0090, and VA Merit
(PI: Shenton).
NR 34
TC 2
Z9 2
U1 3
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD JUL 15
PY 2016
VL 135
BP 311
EP 323
DI 10.1016/j.neuroimage.2016.04.041
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DO8QF
UT WOS:000378047600028
PM 27138209
ER
PT J
AU Sharma, A
Sharma, SK
Vallakati, A
Garg, A
Lavie, CJ
Mukherjee, D
Marmur, JD
AF Sharma, Abhishek
Sharma, Samin K.
Vallakati, Ajay
Garg, Akash
Lavie, Carl J.
Mukherjee, Debabrata
Marmur, Jonathan D.
TI Duration of dual antiplatelet therapy after various drug-eluting stent
implantation
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Dual anti-platelet therapy; Drug-eluting stents
ID PERCUTANEOUS CORONARY INTERVENTION; RANDOMIZED CONTROLLED-TRIALS;
NETWORK METAANALYSIS; THROMBOSIS; TERM; ENDOTHELIALIZATION; MULTICENTER;
GUIDELINES; MORTALITY; PAIRWISE
AB Objective: To evaluate efficacy and safety of long duration dual anti-platelet therapy i.e., >12 months (L-DAPT) and short duration DAPT i.e., <= 12 months (S-DAPT) after various drug-eluting stent (DES) implantation.
Methods: We searched Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify randomized controlled trials (RCTs) assessing the effect of L-DAPT versus S-DAPT after sirolimus-eluting (Cypher (R)); paclitaxel-eluting stents (Taxus (R)); zotarolimus-eluting (Endeavor (R)) and everolimus-eluting stents (Xience V (R)) implantation. Odds ratio (OR) and 95% confidence intervals (CI) were calculated using random-effects models. Subgroup analyses were performed comparing two second generation DES and for RCTs comparing S-DAPT and L-DAPT.
Results: We included six RCTs that randomized 19,012 patients to S-DAPT versus L-DAPT (4638 in first generation DES; 14,374 in second generation DES; 8099 EES; 4876 in ZES). Compared with L-DAPT, S-DAPT was associated with a higher rate of myocardial infarction (MI) and stent thrombosis (ST) after first [2.65 (1.88, 3.73) and 3.85 (2.14-6.93) respectively] and a higher rate of MI after second generation DES [1.33 (1.06, 1.67)]. There were no significant differences in the rates of all cause mortality, cardiovascular (CV) mortality and stroke with L-DAPT and S-DAPT after implantation of first [0.97 (0.52, 1.81); 1.19 (0.52-2.70); and 1.12 (0.36-3.52) respectively] and second generation DES [0.93 (0.69, 1.25); 0.93 (0.63, 1.36); and 0.58 (0.19, 1.75), respectively]. On further analysis of type of second generation DES, S-DAPT continues to show a higher rate of MI and ST after EES implantation [1.54 (1.11, 2.13) and 2.68 (1.20-5.94) respectively]; however there was no significant difference in the rate of MI and ST with S-DAPT and L-DAPT after ZES implantation [1.07 (0.44, 2.61) and 1.11(0.39, 3.13), respectively].
Conclusion: 1) Compared with L-DAPT, S-DAPT was associated with a higher rate of MI without any significant difference in the rate of all cause mortality, CV mortality and stroke after first and second generation DES. 2) Rate of ST was also higher with S-DAPT compared to L-DAPT after first generation DES implantation; however, it was not significantly different after second generation DES. 3) On further subgroup analysis of second generation stent there was no significant difference in the rate of all cause mortality, CV mortality, MI, ST and stroke with S-DAPT and L-DAPT after ZES implantation. S-DAPT may be optimal for newer generation stents particularly ZES. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Sharma, Abhishek; Marmur, Jonathan D.] Suny Downstate Med Ctr, Div Cardiovasc Med, New York, NY USA.
[Sharma, Samin K.] Mt Sinai Med Ctr, Icahn Sch Med Mt Sinai, Inst Heart & Vasc, Dept Cardiovasc Med, New York, NY 10029 USA.
[Vallakati, Ajay] Case Western Reserve Univ, Metrohlth Med Ctr, Div Cardiol, Cleveland, OH USA.
[Garg, Akash] James J Peters VA Med Ctr, Mt Sinai Sch Med, Dept Med, New York, NY USA.
[Lavie, Carl J.] Univ Queensland, John Ochsner Heart & Vasc Inst, Ochsner Clin Sch, Dept Cardiovasc Dis,Sch Med, New Orleans, LA USA.
[Mukherjee, Debabrata] Texas Tech Univ, Div Cardiol, El Paso, TX USA.
RP Sharma, A (reprint author), Suny Downstate Med Ctr, Div Cardiovasc Med, 450 Clarkson Ave, Brooklyn, NY 11203 USA.
EM abhisheksharma4mamc@gmail.com
RI Lavie, Carl/A-6014-2011
NR 31
TC 0
Z9 0
U1 0
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 15
PY 2016
VL 215
BP 157
EP 166
DI 10.1016/j.ijcard.2016.04.118
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DM4DX
UT WOS:000376297100040
PM 27116326
ER
PT J
AU Kalra, A
Pokharel, Y
Glusenkamp, N
Wei, J
Kerkar, PG
Oetgen, WJ
Virani, SS
AF Kalra, Ankur
Pokharel, Yashashwi
Glusenkamp, Nathan
Wei, Jessica
Kerkar, Prafulla G.
Oetgen, William J.
Virani, Salim S.
CA PINNACLE India Quality Improvement
TI Gender disparities in cardiovascular care access and delivery in India:
Insights from the American College of Cardiology's PINNACLE India
Quality Improvement Program (PIQIP)
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Gender disparity; Cardiovascular care; India; Quality improvement;
American College of Cardiology
ID HEART-DISEASE; DOUBLE BURDEN; WOMEN; MORTALITY; HEALTH; MEN
AB Background: Limited data are available to assess whether access to and quality of cardiovascular disease (CVD) care are comparable among men and women in India. We analyzed data from the American College of Cardiology's PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP) to evaluate gender disparities in CVD care delivery.
Methods and results: Between 2011 and 2015, we collected data on performance measures for patients with coronary artery disease (CAD) (n = 14,010), heart failure (HF) (n = 11,965) and atrial fibrillation (AF) (n = 496) in PIQIP, among 17 participating practices.
The total number of women was 31,796 (32.0%). Women had fewer total encounters compared to men during the study interval (mean number of encounters = 2.59 vs. 2.82 for women and men, respectively, p <= 0.001). Women were significantly younger (48.9 years vs. 51.5 years, p <= 0.01), but had a higher co-morbidity burden compared to men - hypertension (62.0% vs. 45.6%, p <= 0.01), diabetes (39.4% vs. 35%, p <= 0.01), and hyperlipidemia (3.7% vs. 3.1%, p = 0.19). On the contrary, the guideline-directed medication prescriptions were strikingly lower in women with CAD compared to men - aspirin (38% vs. 50.4%, p <= 0.001), aspirin or thienopyridine combination (46.9% vs. 57.2%, p <= 0.001), and beta-blockers (36.8% vs. 47.8%, p <= 0.001). Similarly, among women with ejection fraction <= 40%, the use of guideline-directed medical therapy was significantly lower compared to men for beta-blockers (30.8% vs. 37.0%, p <= 0.001), angiotensin-converting enzyme inhibitors (ACE-i) or angiotensin receptor blockers (ARBs) (29.3% vs. 34.9%, p <= 0.001), and beta-blockers/ACE-i or ARBs (24.6% vs. 31.0%, p <= 0.001). Among patients with atrial fibrillation and CHADS2 score >= 2, more women were on oral anticoagulation (19.6% vs. 14.6%, p = 0.34), although this was not significantly different, and the overall number of patients with atrial fibrillation was low.
Conclusions: Despite a significantly higher co-morbidity burden in women, we found fewer women receiving guideline-directed medical therapy for CVD compared with men. If such disparities are confirmed in the larger Indian population, it is important to find potential causes for, and seek solutions to narrow this gap. Published by Elsevier Ireland Ltd.
C1 [Kalra, Ankur] Kalra Hosp SRCNC Sri Ram Cardiothorac & Neurosci, Dept Med, Div Cardiol, New Delhi, India.
[Kalra, Ankur] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Intervent Cardiol, Boston, MA 02215 USA.
[Kalra, Ankur] Harvard Univ, Sch Med, Safety Qual Informat & Leadership Program, Boston, MA USA.
[Pokharel, Yashashwi] Univ Missouri, Dept Cardiovasc Res, St Lukes Mid Amer Heart Inst, Kansas City, MO 64110 USA.
[Glusenkamp, Nathan; Wei, Jessica; Oetgen, William J.] Amer Coll Cardiol Fdn, Washington, DC USA.
[Kerkar, Prafulla G.] King Edward VII Mem Hosp & Seth GS Med Coll, Bombay, Maharashtra, India.
[Virani, Salim S.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Hlth Serv Res & Dev Ctr Innovat, Houston, TX 77030 USA.
[Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA.
RP Virani, SS (reprint author), Michael E DeBakey VA Med Ctr, Hlth Serv Res & Dev 152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM virani@bcm.edu
OI Virani, Salim/0000-0001-9541-6954
FU American College of Cardiology Foundation, Washington, DC; Bristol
Myers-Squibb; Pfizer, Inc.
FX This work was supported by the American College of Cardiology
Foundation, Washington, DC. Bristol Myers-Squibb and Pfizer, Inc. are
Founding Sponsors of PIQIP.
NR 10
TC 0
Z9 0
U1 2
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 15
PY 2016
VL 215
BP 248
EP 251
DI 10.1016/j.ijcard.2016.04.058
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DM4DX
UT WOS:000376297100057
PM 27128540
ER
PT J
AU Krishnaswami, A
Go, AS
Forman, DE
Leong, TK
Lee, H
Maurer, MS
McCulloch, CE
AF Krishnaswami, Ashok
Go, Alan S.
Forman, Daniel E.
Leong, Thomas K.
Lee, Hon
Maurer, Mathew S.
McCulloch, Charles E.
TI Multimorbidity is strongly associated with long-term but not short-term
mortality after cardiac valve replacement
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Multiple chronic conditions; Multimorbidity; Valvular heart disease;
Cardiac valve replacement; Mortality; Proportional hazards models
ID HEART-FAILURE; DIALYSIS PATIENTS; OLDER-ADULTS; RISK; DISEASE; SURGERY;
COMORBIDITY; SURVIVAL; HEALTH; CARE
AB Background: The presence of multimorbidity is known to be related to adverse clinical outcomes. However, its association with mortality in patients undergoing cardiac valve replacement is not known.
Methods: Multimorbidity (as a continuous variable) was characterized in adults receiving cardiac valve replacement surgery between 2008 and 2012 within Kaiser Permanente Northern California based on information from health plan electronic health records. Our primary outcome was 3-year all-causemortality after surgery. We used Cox proportional hazards regression to evaluate the independent association of each additional comorbidity with mortality.
Results: Among 3686 eligible patients, mean age was 67.9 +/- 13.5 years and median comorbidity burden was 3 (IQR: 2). The presence of most individual comorbidities except hypertension and hyperlipidemia did not occur in isolation. The unadjusted annual incidence (per 100 person-years) of death increased with higher comorbidity burden: <= 1: 4.61 (95% CI: 3.29-6.45), 2-3: 13.7 (95% CI: 11.9-15.8), 4-5: 23.6 (95% CI: 20.6-26.9), and >= 6: 43.4(95% CI: 34.654.4). Advancing age, diabetes mellitus, cerebrovascular accident, heart failure, lung disease, urgent status and use of aldosterone-receptor antagonists were independently associated with an increased risk of mortality. Inmultivariable analyses, each additional comorbidity was significantly associated with an increased risk of long-term (adjusted hazard ratio (HR) 1.30, 95% CI: 1.22-1.39) but not short-term mortality (HR 0.92, 95% CI: 0.80-1.07).
Conclusions: Our study demonstrated that multimorbidity in patients undergoing cardiac valve replacement is significantly associated with long-term but not short-term mortality. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Krishnaswami, Ashok] Kaiser Permanente San Jose Med Ctr, Div Cardiol, San Jose, CA USA.
[Go, Alan S.; Leong, Thomas K.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Go, Alan S.; McCulloch, Charles E.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Go, Alan S.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Forman, Daniel E.] Univ Pittsburgh, Div Geriatr Cardiol, Pittsburgh, PA USA.
[Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
[Lee, Hon] Kaiser Permanente Santa Clara Med Ctr, Dept Cardiovasc Surg, Santa Clara, CA USA.
[Maurer, Mathew S.] Columbia Univ, Med Ctr, Div Cardiol, New York, NY USA.
RP Krishnaswami, A (reprint author), Kaiser Permanente San Jose Med Ctr, 270 Int Circle,2nd Floor, San Jose, CA 95119 USA.
EM ashok.krishnaswami@kp.org
FU Kaiser Permanente Northern California Community Benefit grant
[KR021350]; NIA grant [P30 AG024827]; VA Office of Rehabilitation
Research and Development grant [F0834-R]; Mid-Career Mentoring Award in
Geriatric Cardiology from NIA [K24-AG036778-06]
FX Dr. Krishnaswami was supported by a Kaiser Permanente Northern
California Community Benefit grant (KR021350). The funders had no role
in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; preparation, review, or
approval of themanuscript; and the decision to submit themanuscript for
publication. No other disclosures are present.; Dr. Forman is supported
in part by NIA grant P30 AG024827 and VA Office of Rehabilitation
Research and Development grant F0834-R.; Dr. Maurer is supported by a
Mid-Career Mentoring Award in Geriatric Cardiology from NIA
(K24-AG036778-06).
NR 37
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U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 15
PY 2016
VL 215
BP 417
EP 421
DI 10.1016/j.ijcard.2016.04.110
PG 5
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DM4DX
UT WOS:000376297100091
PM 27131261
ER
PT J
AU Poulsen, CB
Al-Mashhadi, AL
von Wachenfeldt, K
Bentzon, JF
Nielsen, LB
Al-Mashhadi, RH
Thygesen, J
Tolbod, L
Larsen, JR
Frokiaer, J
Tawakol, A
Vucic, E
Fredrickson, J
Baruch, A
Frendeus, B
Robertson, AKL
Moestrup, SK
Drouet, L
Falk, E
AF Poulsen, Christian Bo
Al-Mashhadi, Ahmed Ludvigsen
von Wachenfeldt, Karin
Bentzon, Jacob Fog
Nielsen, Lars Bo
Al-Mashhadi, Rozh H.
Thygesen, Jesper
Tolbod, Lars
Larsen, Jens Rolighed
Frokiaer, Jorgen
Tawakol, Ahmed
Vucic, Esad
Fredrickson, Jill
Baruch, Amos
Frendeus, Bjorn
Robertson, Anna-Karin L.
Moestrup, Soren Kragh
Drouet, Ludovic
Falk, Erling
TI Treatment with a human recombinant monoclonal IgG antibody against
oxidized LDL in atherosclerosis-prone pigs reduces cathepsin S in
coronary lesions
SO INTERNATIONAL JOURNAL OF CARDIOLOGY
LA English
DT Article
DE Atherosclerosis; Cholesterol; Antibody
ID LOW-DENSITY-LIPOPROTEIN; POSITRON-EMISSION-TOMOGRAPHY; INHIBIT
ATHEROSCLEROSIS; INSULIN SENSITIVITY; VULNERABLE PLAQUE; ARTERY-DISEASE;
/-MICE; INFLAMMATION; MACROPHAGES; MECHANISMS
AB Background: Immunization with oxidized LDL (oxLDL) reduces atherosclerosis in rodents. We tested the hypothesis that treatment with a human recombinant monoclonal antibody against oxLDL will reduce the burden or composition of atherosclerotic lesions in hypercholesterolemic minipigs.
Methods and results: Thirty-eight hypercholesterolemic minipigs with defective LDL receptors were injected with an oxLDL antibody or placebo weekly for 12 weeks. An 18F-fluorodeoxyglucose positron emission tomography (FDG PET) scan (n = 9) was performed before inclusion and after 3 months of treatment. Blood samples were obtained prior to each injection. Following the last injection all animals were sacrificed, and the heart, aorta, and iliac arteries were removed. The left anterior descending coronary artery was sectioned at 5 mm intervals for quantitative and qualitative assessments of atherosclerosis, including immunohistochemical phenotyping of macrophages using a pan-macrophage marker (CD68) and markers for putative pro-atherogenic (cathepsin S) and atheroprotective (CD163) macrophages. Aorta, right coronary artery, and left iliac artery were stained en face with Sudan IV and the amount of atherosclerosis quantified. There was no effect of treatment on plasma lipid profile, vascular FDG-PET signal or the amount of atherosclerosis in any of the examined arteries. However, immunostaining of coronary lesions revealed reduced cathepsin S positivity in the treated group compared with placebo (4.8% versus 8.2% of intima area, p = 0.03) with no difference in CD68 or CD163 positivity.
Conclusions: In hypercholesterolemic minipigs, treatment with a human recombinant monoclonal antibody against oxLDL reduced cathepsin S in coronary lesions without any effect on the burden of atherosclerosis or aortic FDG-PET signal. (C) 2016 Published by Elsevier Ireland Ltd.
C1 [Poulsen, Christian Bo; Al-Mashhadi, Ahmed Ludvigsen; Bentzon, Jacob Fog; Al-Mashhadi, Rozh H.; Falk, Erling] Aarhus Univ, Dept Clin Med, Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
[von Wachenfeldt, Karin] Truly Translat, Lund, Sweden.
[Nielsen, Lars Bo] Univ Copenhagen, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark.
[Thygesen, Jesper] Aarhus Univ Hosp, Dept Clin Engn, DK-8000 Aarhus, Denmark.
[Tolbod, Lars; Frokiaer, Jorgen] Aarhus Univ Hosp, Dept Nucl Med, DK-8000 Aarhus, Denmark.
[Tolbod, Lars; Frokiaer, Jorgen] Aarhus Univ Hosp, PET Ctr, DK-8000 Aarhus, Denmark.
[Larsen, Jens Rolighed] Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, DK-8000 Aarhus, Denmark.
[Tawakol, Ahmed; Vucic, Esad] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Tawakol, Ahmed; Vucic, Esad] Harvard Univ, Sch Med, Boston, MA USA.
[Fredrickson, Jill; Baruch, Amos] Genentech Inc, 460 Point San Bruno Blvd, San Francisco, CA 94080 USA.
[Frendeus, Bjorn; Robertson, Anna-Karin L.] BioInvent Int AB, Lund, Sweden.
[Moestrup, Soren Kragh] Univ Southern Denmark, Dept Mol Med, Odense, Denmark.
[Drouet, Ludovic] Hosp Lariboisiere, Dept Angiohematol, Paris, France.
RP Poulsen, CB (reprint author), Aarhus Univ Hosp, Dept Cardiol, Palle Juul Jensens Blvd 99, DK-8000 Aarhus, Denmark.
EM cbpoulsen@clin.au.dk
RI Poulsen Tolbod, Lars/A-7768-2008; Bentzon, Jacob/B-5302-2016;
OI Poulsen Tolbod, Lars/0000-0002-8105-7046; Bentzon,
Jacob/0000-0002-3020-5002; Al-Mashhadi, Rozh/0000-0001-9721-8054;
Frokiaer, Jorgen/0000-0002-6206-8065
FU BioInvent International (Lund, Sweden); Faculty of Health, Aarhus
University [904606]; [MLDL1278A]
FX The study was funded by BioInvent International (Lund, Sweden), which
also provided the drug (MLDL1278A), and the Faculty of Health, Aarhus
University (904606).
NR 53
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U1 3
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-5273
EI 1874-1754
J9 INT J CARDIOL
JI Int. J. Cardiol.
PD JUL 15
PY 2016
VL 215
BP 506
EP 515
DI 10.1016/j.ijcard.2016.03.222
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DM4DX
UT WOS:000376297100111
PM 27135822
ER
PT J
AU Ng, EX
Miller, MA
Jing, TY
Chen, CH
AF Ng, Ee Xien
Miller, Miles A.
Jing, Tengyang
Chen, Chia-Hung
TI Single cell multiplexed assay for proteolytic activity using droplet
microfluidics
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Single cell assay; Proteolytic activity matrix analysis; Droplet
microfluidics; FRET-sensors
ID EPITHELIAL-MESENCHYMAL TRANSITION; MATRIX METALLOPROTEINASES;
BREAST-CANCER; PROTEASE; CLEAVAGE; SYSTEM; HETEROGENEITY; TECHNOLOGIES;
EXPRESSION; BIOLOGY
AB Cellular enzymes interact in a post-translationally regulated fashion to govern individual cell behaviors, yet current platform technologies are limited in their ability to measure multiple enzyme activities simultaneously in single cells. Here, we developed multi-color Forster resonance energy transfer (FRET) based enzymatic substrates and use them in a microfluidics platform to simultaneously measure multiple specific protease activities from water-in-oil droplets that contain single cells. By integrating the microfluidic platform with a computational analytical method, Proteolytic Activity Matrix Analysis (PrAMA), we are able to infer six different protease activity signals from individual cells in a high throughput manner (similar to 100 cells/experimental run). We characterized protease activity profiles at single cell resolution for several cancer cell lines including breast cancer cell MDA-MB-231, lung cancer cell line PC-9, and leukemia cell line K-562 using both live-cell and in-situ cell lysis assay formats, with special focus on metalloproteinases important in metastasis. The ability to measure multiple proteases secreted from or expressed in individual cells allows us to characterize cell heterogeneity and has potential applications including systems biology, pharmacology, cancer diagnosis and stem cell biology. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Ng, Ee Xien; Jing, Tengyang; Chen, Chia-Hung] Natl Univ Singapore, Dept Biomed Engn, Block E4,04-08,4 Engn Dr 3, Singapore 117583, Singapore.
[Miller, Miles A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Jing, Tengyang] Singapore MIT Alliance Res & Technol SMART Ctr, Singapore 1385602, Singapore.
[Chen, Chia-Hung] Singapore Inst Neurotechnol, 28 Med Dr 05 COR, Singapore 117456, Singapore.
RP Chen, CH (reprint author), Natl Univ Singapore, Dept Biomed Engn, Block E4,04-08,4 Engn Dr 3, Singapore 117583, Singapore.
EM biecch@nus.edu.sg
FU NUS Tier-1 Grant, Ministry of Health (MOH) IAF [R-397-000-213-112,
R-397-000-153-112, Cat-1 R-397-000-230-511]; Singapore-MIT Alliance for
Research and Technology (SMART) research Grant [R-397-000-146-592]
FX We would like to thank Dr. Marcia L. Moss for her kind assist in
substrate FRET pair selection. We gratefully acknowledge the funding
provided by the NUS Tier-1 Grants R-397-000-213-112, R-397-000-153-112,
Ministry of Health (MOH) IAF Cat-1 R-397-000-230-511, the Singapore-MIT
Alliance for Research and Technology (SMART) research Grant
R-397-000-146-592, and the facilities provided by Singapore Institute
for Neurotechnology (SINAPSE).
NR 34
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U1 18
U2 71
PU ELSEVIER ADVANCED TECHNOLOGY
PI OXFORD
PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON,
OXFORD OX5 1GB, OXON, ENGLAND
SN 0956-5663
EI 1873-4235
J9 BIOSENS BIOELECTRON
JI Biosens. Bioelectron.
PD JUL 15
PY 2016
VL 81
BP 408
EP 414
DI 10.1016/j.bios.2016.03.002
PG 7
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA DK3JB
UT WOS:000374811800056
PM 26995287
ER
PT J
AU Ryan, KA
Assari, S
Pester, BD
Hinrichs, K
Angers, K
Baker, A
Marshall, DF
Stringer, D
Saunders, EFH
Kamali, M
McInnis, MG
Langenecker, SA
AF Ryan, Kelly A.
Assari, Shervin
Pester, Bethany D.
Hinrichs, Kristin
Angers, Kaley
Baker, Amanda
Marshall, David F.
Stringer, Deborah
Saunders, Erika F. H.
Kamali, Masoud
McInnis, Melvin G.
Langenecker, Scott A.
TI Similar Trajectory of Executive Functioning Performance over 5 years
among individuals with Bipolar Disorder and Unaffected Controls using
Latent Growth Modeling
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Bipolar disorder; Neurodegenerative; Cognition; Affective disorders
ID FOLLOW-UP; COGNITIVE IMPAIRMENT; OLDER-ADULTS; I DISORDER; 1ST-DEGREE
RELATIVES; UNIPOLAR DEPRESSION; EUTHYMIC PATIENTS; LITHIUM;
METAANALYSIS; SYMPTOMS
AB Objective: Executive Functioning (EF) deficits in bipolar disorder (BD) are commonly present regardless of mood state and therefore are considered core features of the illness. However, very little is known about the temporal stability of these deficits. We examined the natural course of EF over a five year period in BD and healthy control (HC) samples.
Method: Using a 5-year longitudinal cohort, 91 individuals with BD and 17 HC were administered a battery of neuropsychological tests that captured four main areas of EF: Processing Speed with Interference Resolution, Verbal Fluency with Processing Speed, Inhibitory Control, and Conceptual Reasoning and Set Shifting. Evaluations occurred at study entry, one, and five years later.
Results: Latent Growth Curve Modeling demonstrated that the BD group performed significantly worse in all EF areas than the HC group. Changes in EF from baseline to 5-year follow-up were similar across both diagnostic groups. Older age at baseline, above and beyond education and diagnosis, was associated with worse initial performance in EF. Being of older age was associated with greater decline in Processing Speed with Interference Resolution, and Verbal Fluency with Processing Speed. Higher education was marginally associated with a smaller declining slope for Processing Speed with Interference Resolution.
Conclusions: Executive functioning deficits in BD persist over time, and in the context of normative age related decline, may place individuals at greater risk for cognitive disability as the disease progresses. Age and having a BD diagnosis together, however, do not accelerate executive functioning decline over time. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Ryan, Kelly A.; Assari, Shervin; Pester, Bethany D.; Hinrichs, Kristin; Angers, Kaley; Baker, Amanda; Marshall, David F.; Stringer, Deborah; Kamali, Masoud; McInnis, Melvin G.] Univ Michigan, Dept Psychiat, 2101 Commonwealth Blvd,Suite C, Ann Arbor, MI 48109 USA.
[Langenecker, Scott A.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Saunders, Erika F. H.] Penn State Coll Med, Dept Psychiat, Hershey, PA USA.
[Kamali, Masoud] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Ryan, KA (reprint author), Univ Michigan, Dept Psychiat, 2101 Commonwealth Blvd,Suite C, Ann Arbor, MI 48109 USA.
EM karyan@umich.edu
FU Heinz C. Prechter Bipolar Research Fund at the University of Michigan
Depression Center; Richard Tam Foundation; National Center for Advancing
Translational Sciences of the National Institutes of Health
[2KL2TR000434]
FX This research was supported by the Heinz C. Prechter Bipolar Research
Fund at the University of Michigan Depression Center and the Richard Tam
Foundation (KR, SA, BP, KH, DM, AB, KA, DS, MK, MM), and grant support
from the National Center for Advancing Translational Sciences of the
National Institutes of Health under Award Number 2KL2TR000434 (KR). We
would like to express appreciation to our research participants in the
Prechter Longitudinal Study of Bipolar Disorder. We would also like to
acknowledge and thank our research team consisting of Holli Bertram,
Christine Brucksch, Brent Doil, Valerie Foster, Laura Gabriel, Nicole
Greer, Lauren Grove, Brennan Haase, Gloria Harrington, Alexander Hayek,
Michelle Kassel, Marisa Kelly, Katie Lavin, Kortni Meyers, Jennifer
Montgomery, Lisa O'Donnell, Philip Presnell, Anne Weldon, and the rest
of the staff of the Prechter Bipolar Research Team for their
contributions to this project.
NR 63
TC 0
Z9 0
U1 3
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD JUL 15
PY 2016
VL 199
BP 87
EP 94
DI 10.1016/j.jad.2016.04.016
PG 8
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DL1OL
UT WOS:000375401500012
PM 27093492
ER
PT J
AU Lampson, BL
Kasar, SN
Matos, TR
Morgan, EA
Rassenti, L
Davids, MS
Fisher, DC
Freedman, AS
Jacobson, CA
Armand, P
Abramson, JS
Arnason, JE
Kipps, TJ
Fein, J
Fernandes, S
Hanna, J
Ritz, J
Kim, HT
Brown, JR
AF Lampson, Benjamin L.
Kasar, Siddha N.
Matos, Tiago R.
Morgan, Elizabeth A.
Rassenti, Laura
Davids, Matthew S.
Fisher, David C.
Freedman, Arnold S.
Jacobson, Caron A.
Armand, Philippe
Abramson, Jeremy S.
Arnason, Jon E.
Kipps, Thomas J.
Fein, Joshua
Fernandes, Stacey
Hanna, John
Ritz, Jerome
Kim, Haesook T.
Brown, Jennifer R.
TI Idelalisib given front-line for treatment of chronic lymphocytic
leukemia causes frequent immune-mediated hepatotoxicity
SO BLOOD
LA English
DT Article
ID REGULATORY T-CELLS; B-CELL; PHOSPHATIDYLINOSITOL 3-KINASE; MUTATION
STATUS; LIVER-INJURY; P110-DELTA; DISEASE; ZAP-70; CANCER; IMGT
AB Idelalisib is a small-molecule inhibitor of PI3Kd with demonstrated efficacy for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as front-line therapy, we enrolled 24 subjects in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab. After a median follow-up period of 14.7 months, hepatotoxicity was found to be a frequent and often severe adverse event. A total of 19 subjects (79%) experienced either grade >= 1 ALT or AST elevation during the study, and 13 subjects (54%) experienced grade >= 3 transaminitis. The median time to development of transaminitis was 28 days, occurring before ofatumumab introduction. Younger age and mutated immunoglobulin heavy chain status were significant risk factors for the development of hepatotoxicity. Multiple lines of evidence suggest that this hepatotoxicity was immune mediated. A lymphocytic infiltrate was seen on liver biopsy specimens taken from 2 subjects with transaminitis, and levels of the proinflammatory cytokines CCL-3 and CCL-4 were higher in subjects experiencing hepatotoxicity. All cases of transaminitis resolved either by holding the drug, initiating immunosuppressants, or both, and rates of recurrent toxicity were lower in patients taking steroids when idelalisib was reinitiated. A decrease in peripheral blood regulatory T cells was seen in patients experiencing toxicity on therapy, which is consistent with an immune-mediated mechanism. These results suggest that caution should be taken as drugs within this class are developed for CLL, particularly in younger patients who have not received prior disease-specific therapy. This study was registered at www.clinicaltrials.gov as #NCT02135133.
C1 [Lampson, Benjamin L.; Kasar, Siddha N.; Matos, Tiago R.; Davids, Matthew S.; Fisher, David C.; Freedman, Arnold S.; Jacobson, Caron A.; Armand, Philippe; Fein, Joshua; Fernandes, Stacey; Hanna, John; Ritz, Jerome; Brown, Jennifer R.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Lampson, Benjamin L.; Kasar, Siddha N.; Matos, Tiago R.; Davids, Matthew S.; Fisher, David C.; Freedman, Arnold S.; Jacobson, Caron A.; Armand, Philippe; Fein, Joshua; Fernandes, Stacey; Hanna, John; Ritz, Jerome; Brown, Jennifer R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Morgan, Elizabeth A.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Rassenti, Laura; Kipps, Thomas J.] Univ Calif San Diego, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA.
[Rassenti, Laura; Davids, Matthew S.; Kipps, Thomas J.; Fernandes, Stacey; Brown, Jennifer R.] Moores UCSD Canc Ctr, CLL Res Consortium, La Jolla, CA USA.
[Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA.
[Arnason, Jon E.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Matos, Tiago R.] Univ Lisbon, Fac Med, Inst Mol Med, Lisbon, Portugal.
[Fein, Joshua] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel.
RP Brown, JR (reprint author), Dana Farber Canc Inst, Mayer Bldg,Room 226,450 Brookline Ave, Boston, MA 02215 USA.
EM jennifer_brown@dfci.harvard.edu
OI Matos, Tiago R./0000-0003-2864-8207; Morgan,
Elizabeth/0000-0001-5880-9337
FU Gilead; Novartis; Dana-Farber Cancer Institute Medical Oncology Grant
program; Melton Family Fund for CLL Research; Susan and Gary Rosenbach
Fund for Lymphoma Research; National Institutes of Health, National
Cancer Institute of the CLL Research Consortium [P01-CA81534]
FX This study is an investigator-initiated trial run by J.R.B. and funded
by Gilead and Novartis; both companies provided their study drug at no
cost. Correlative studies were funded by the Dana-Farber Cancer
Institute Medical Oncology Grant program 2015, as well as the Melton
Family Fund for CLL Research and the Susan and Gary Rosenbach Fund for
Lymphoma Research. This work was supported in part by a grant from the
National Institutes of Health, National Cancer Institute (P01-CA81534)
of the CLL Research Consortium (L.R. and T.J.K.).
NR 37
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U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 14
PY 2016
VL 128
IS 2
BP 195
EP 203
DI 10.1182/blood-2016-03-707133
PG 9
WC Hematology
SC Hematology
GA DW7KQ
UT WOS:000383830000011
PM 27247136
ER
PT J
AU Kim, PG
Canver, MC
Rhee, C
Ross, SJ
Harriss, JV
Tu, HC
Orkin, SH
Tucker, HO
Daley, GQ
AF Kim, Peter Geon
Canver, Matthew C.
Rhee, Catherine
Ross, Samantha J.
Harriss, June V.
Tu, Ho-Chou
Orkin, Stuart H.
Tucker, Haley O.
Daley, George Q.
TI Interferon-alpha signaling promotes embryonic HSC maturation
SO BLOOD
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; DEFINITIVE HEMATOPOIESIS; AORTIC ENDOTHELIUM;
IN-VIVO; DEPENDENCE DISTINGUISHES; PROGENITOR CELLS; BINDING PROTEIN;
FETAL LIVER; MOUSE; EXPRESSION
AB In the developing mouse embryo, the first hematopoietic stem cells (HSCs) arise in the aorta-gonad-mesonephros (AGM) and mature as they transit through the fetal liver (FL). Compared with FL and adult HSCs, AGM HSCs have reduced repopulation potential in irradiated adult transplant recipients but mechanisms underlying this deficiency in AGM HSCs are poorly understood. By co-expression gene network analysis, we deduced that AGM HSCs show lower levels of interferon-alpha (IFN-alpha)/Jak-Stat1-associated gene expression than FL HSCs. Treatment of AGM HSCs with IFN-alpha enhanced long-term hematopoietic engraftment and donor chimerism. Conversely, IFN-alpha receptor-deficient AGMs (Ifnar1(-/-)), had significantly reduced donor chimerism. We identify adenine-thymine-rich interactive domain-3a (Arid3a), a factor essential for FL and B lymphopoiesis, as a key transcriptional co-regulator of IFN-alpha/Stat1 signaling. Arid3a occupies the genomic loci of Stat1 as well as several IFN-alpha effector genes, acting to regulate their expression. Accordingly, Arid3a(-/-) AGM HSCs had significantly reduced transplant potential, which was rescued by IFN-alpha treatment. Our results implicate the inflammatory IFN-alpha/Jak-Stat pathway in the developmental maturation of embryonic HSCs, whose manipulation may lead to increased potency of reprogrammed HSCs for transplantation.
C1 [Kim, Peter Geon; Canver, Matthew C.; Ross, Samantha J.; Tu, Ho-Chou; Orkin, Stuart H.; Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA USA.
[Kim, Peter Geon; Canver, Matthew C.; Ross, Samantha J.; Tu, Ho-Chou; Orkin, Stuart H.; Daley, George Q.] Harvard Med Sch, Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA USA.
[Kim, Peter Geon; Ross, Samantha J.; Tu, Ho-Chou; Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA USA.
[Kim, Peter Geon; Ross, Samantha J.; Tu, Ho-Chou; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kim, Peter Geon; Ross, Samantha J.; Tu, Ho-Chou; Daley, George Q.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA.
[Rhee, Catherine; Harriss, June V.; Tucker, Haley O.] Univ Texas Austin, Inst Cellular & Mol Biol, Dept Mol Biosci, Austin, TX 78712 USA.
RP Daley, GQ (reprint author), Boston Childrens Hosp, Howard Hughes Med Inst, Karp Family Res Bldg,7th Floor,300 Longwood Ave, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
FU National Institutes of Health National Institute of Diabetes and
Digestive and Kidney Diseases [R24-DK092760]; National Heart, Lung, and
Blood Institute Progenitor Cell Biology Consortium [UO1-HL100001]; Doris
Duke Medical Foundation; National Institutes of Health National Cancer
Institute [RO1CA31534]; Cancer Prevention and Research Institute of
Texas [RP120459]; Marie Betzner Morrow Centennial Endowment; Center of
Excellence in Molecular Hematology [P01HL032262, P30DK049216]
FX G.Q.D. is supported by grants from the National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases
(R24-DK092760), the National Heart, Lung, and Blood Institute Progenitor
Cell Biology Consortium (UO1-HL100001), and the Doris Duke Medical
Foundation. G.Q.D. is an associate member of the Broad Institute, and an
investigator of the Howard Hughes Medical Institute and the Manton
Center for Orphan Disease Research. H.O.T. is supported by grants from
the National Institutes of Health National Cancer Institute
(RO1CA31534), the Cancer Prevention and Research Institute of Texas
(RP120459), and the Marie Betzner Morrow Centennial Endowment. S.H.O. is
supported by the Center of Excellence in Molecular Hematology
(P01HL032262 and P30DK049216).
NR 66
TC 4
Z9 4
U1 1
U2 1
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 14
PY 2016
VL 128
IS 2
BP 204
EP 216
DI 10.1182/blood-2016-01-689281
PG 13
WC Hematology
SC Hematology
GA DW7KQ
UT WOS:000383830000012
PM 27095787
ER
PT J
AU Matthews, JM
Bhatt, S
Patricelli, MP
Nomanbhoy, TK
Jiang, XY
Natkunam, Y
Gentles, AJ
Martinez, E
Zhu, DX
Chapman, JR
Cortizas, E
Shyam, R
Chinichian, S
Advani, R
Tan, L
Zhang, JM
Choi, HG
Tibshirani, R
Buhrlage, SJ
Gratzinger, D
Verdun, R
Gray, NS
Lossos, IS
AF Matthews, Julie Marie
Bhatt, Shruti
Patricelli, Matthew P.
Nomanbhoy, Tyzoon K.
Jiang, Xiaoyu
Natkunam, Yasodha
Gentles, Andrew J.
Martinez, Ezequiel
Zhu, Daxing
Chapman, Jennifer Rose
Cortizas, Elena
Shyam, Ragini
Chinichian, Shideh
Advani, Ranjana
Tan, Li
Zhang, Jianming
Choi, Hwan Geun
Tibshirani, Robert
Buhrlage, Sara J.
Gratzinger, Dita
Verdun, Ramiro
Gray, Nathanael S.
Lossos, Izidore S.
TI Pathophysiological significance and therapeutic targeting of germinal
center kinase in diffuse large B-cell lymphoma
SO BLOOD
LA English
DT Article
ID ACTIVATION; EXPRESSION; RECEPTOR; SURVIVAL; CHEMOTHERAPY; INHIBITOR;
PATHWAYS; CHOP; PATHOGENESIS; MUTATIONS
AB Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, yet 40% to 50% of patients will eventually succumb to their disease, demonstrating a pressing need for novel therapeutic options. Gene expression profiling has identified messenger RNAs that lead to transformation, but critical events transforming cells are normally executed by kinases. Therefore, we hypothesized that previously unrecognized kinases may contribute to DLBCL pathogenesis. We performed the first comprehensive analysis of global kinase activity in DLBCL, to identify novel therapeutic targets, and discovered that germinal center kinase (GCK) was extensively activated. GCK RNA interference and small molecule inhibition induced cell-cycle arrest and apoptosis in DLBCL cell lines and primary tumors in vitro and decreased the tumor growth rate in vivo, resulting in a significantly extended lifespan of mice bearing DLBCL xenografts. GCK expression was also linked to adverse clinical outcome in a cohort of 151 primary DLBCL patients. These studies demonstrate, for the first time, that GCK is a molecular therapeutic target in DLBCL tumors and that inhibiting GCK may significantly extend DLBCL patient survival. Because the majority of DLBCL tumors (similar to 80%) exhibit activation of GCK, this therapy may be applicable to most patients.
C1 [Matthews, Julie Marie; Jiang, Xiaoyu; Zhu, Daxing; Lossos, Izidore S.] Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Div Hematol Oncol, Miami, FL USA.
[Matthews, Julie Marie; Bhatt, Shruti; Lossos, Izidore S.] Univ Miami, Dept Mol & Cellular Pharmacol, Miami, FL USA.
[Patricelli, Matthew P.; Nomanbhoy, Tyzoon K.] ActivX Biosci Inc, La Jolla, CA USA.
[Natkunam, Yasodha; Gratzinger, Dita] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
[Gentles, Andrew J.] Stanford Univ, Sch Med, Ctr Canc Syst Biol, Stanford, CA 94305 USA.
[Gentles, Andrew J.] Stanford Univ, Dept Radiol, Stanford, CA 94305 USA.
[Martinez, Ezequiel; Lossos, Izidore S.] Univ Miami, Dept Canc Biol, Miami, FL USA.
[Chapman, Jennifer Rose] Univ Miami, Sylvester Comprehens Canc Ctr, Dept Pathol, Miami, FL USA.
[Cortizas, Elena] Univ Miami, Dept Med, Sylvester Comprehens Canc Ctr, Div Gerontol & Geriatr Med, Miami, FL USA.
[Shyam, Ragini; Chinichian, Shideh; Advani, Ranjana] Stanford Univ, Sch Med, Div Oncol, Stanford, CA 94305 USA.
[Tan, Li; Zhang, Jianming; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA.
[Tan, Li; Zhang, Jianming; Choi, Hwan Geun; Buhrlage, Sara J.; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Tibshirani, Robert] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Tibshirani, Robert] Stanford Univ, Dept Stat, Stanford, CA 94305 USA.
RP Lossos, IS (reprint author), Univ Miami, Sylvester Comprehens Canc Ctr, Div Hematol & Oncol, 1475 NW 12th Ave D8-4, Miami, FL 33136 USA.
EM ilossos@med.miami.edu
OI Gratzinger, Dita/0000-0002-9182-8123
FU Dwoskin Family Foundation; Recio Family Foundation; Anthony Rizzo Family
Foundation; Greg Olsen Foundation; National Institutes of Health
National Cancer Institute [CA173469-01]; Linde Family chemical biology
funds; Lymphoma Research Foundation
FX I.S.L. is supported by the Dwoskin Family, Recio Family, Anthony Rizzo
Family, and Greg Olsen Foundations. N.S.G., S.B., and L.T. were
supported by National Institutes of Health National Cancer Institute
grant CA173469-01 and the Linde Family chemical biology funds.; This
work was funded by Lymphoma Research Foundation (I.S.L. and N.S.G.).
NR 42
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 14
PY 2016
VL 128
IS 2
BP 239
EP 248
DI 10.1182/blood-2016-02-696856
PG 10
WC Hematology
SC Hematology
GA DW7KQ
UT WOS:000383830000015
PM 27151888
ER
PT J
AU Lin, JH
Zhang, WH
Zhao, JJ
Kwart, AH
Yang, C
Ma, DD
Ren, XB
Tai, YT
Anderson, KC
Handin, RI
Munshi, NC
AF Lin, Jianhong
Zhang, Weihong
Zhao, Jian-Jun
Kwart, Ariel H.
Yang, Chun
Ma, Dongdong
Ren, Xiubao
Tai, Yu-Tzu
Anderson, Kenneth C.
Handin, Robert I.
Munshi, Nikhil C.
TI A clinically relevant in vivo zebrafish model of human multiple myeloma
to study preclinical therapeutic efficacy
SO BLOOD
LA English
DT Article
ID IMMUNE-SYSTEM; MOUSE MODEL; MATURATION; INHIBITOR
AB Patient-derived multiple myeloma (MM) cells are difficult to establish in culture or propagate in vivo in murine model. Here, we describe a zebrafish xenograft model that permits rapid, reliable growth of human MM cells injected into the perivitelline space of albino zebrafish (Casper) embryos 48 hours postfertilization. MM1S and MM1R MM cell lines and primary CD138(+) MM cells were stained with CM-Dil red fluorescent dye and suspended in Matrigel prior to their injection. The cells grew at the site of injection and disseminated throughout the developing embryos and larvae. Tumor size was quantified by fluorescent microscopy, and cell fate was followed for 4 days. All of the cell line xenografts showed responses similar to those previously observed with in vitro assays. CD138(+) plasma cell xenografts derived from MM patients also grew and were inhibited by the same drugs patients had responded to clinically. Using this technique, we can assess drug sensitivity or resistance with a small number of MM cells in a short period. This raises the possibility that one might be able to assess drug sensitivity in real time with readily obtainable clinical samples.
C1 [Lin, Jianhong; Zhang, Weihong; Zhao, Jian-Jun; Kwart, Ariel H.; Yang, Chun; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Med Sch, Dana Farber Canc Inst, Med Oncol, Boston, MA USA.
[Lin, Jianhong; Zhang, Weihong; Kwart, Ariel H.; Yang, Chun; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Med Sch, Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA USA.
[Lin, Jianhong; Zhang, Weihong; Kwart, Ariel H.; Yang, Chun; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Ctr Multiple Myeloma Res, Boston, MA USA.
[Zhang, Weihong; Ren, Xiubao] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Biotherapy Ctr,Key Lab Canc Immunol & Biotherapy, Tianjin, Peoples R China.
[Yang, Chun] Haerbin Med Univ, Hosp 4, Dept Clin Lab, Harbin, Heilongjiang, Peoples R China.
[Ma, Dongdong; Handin, Robert I.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA.
[Munshi, Nikhil C.] VA Boston Healthcare Syst, Boston, MA USA.
RP Munshi, NC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.; Handin, RI (reprint author), Brigham & Womens Hosp, Div Hematol, Karp Family Res Bldg,Room 6210, Boston, MA 02115 USA.
EM rhandin@partners.org; nikhil_munshi@dfci.harvard.edu
FU Veterans Administration [I01-BX001584]; National Institutes of Health,
National Cancer Institute [R01-124929, P50-100007, P01-78378,
P01-155258, R01-50947]; Leukemia Society of America; Dana-Farber/Harvard
Cancer Center Specialized Programs of Research Excellence in Multiple
Myeloma Career Development Award
FX This work was supported in part by grants from the Veterans
Administration (I01-BX001584), National Institutes of Health, National
Cancer Institute (R01-124929; P50-100007, P01-78378, and P01-155258
[N.C.M. and K.C.A.]; and R01-50947 [K.C.A.]), and Leukemia Society of
America (N.C.M.); and by a Dana-Farber/Harvard Cancer Center Specialized
Programs of Research Excellence in Multiple Myeloma Career Development
Award (J.L.). K.C.A. is an American Cancer Society Clinical Research
Professor.
NR 13
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 14
PY 2016
VL 128
IS 2
BP 249
EP 252
DI 10.1182/blood-2016-03-704460
PG 4
WC Hematology
SC Hematology
GA DW7KQ
UT WOS:000383830000016
PM 27207793
ER
PT J
AU Hoggatt, J
AF Hoggatt, Jonathan
TI Gene Therapy for "Bubble Boy" Disease
SO CELL
LA English
DT Editorial Material
C1 [Hoggatt, Jonathan] Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02129 USA.
[Hoggatt, Jonathan] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02129 USA.
RP Hoggatt, J (reprint author), Massachusetts Gen Hosp, Canc Ctr, Boston, MA 02129 USA.; Hoggatt, J (reprint author), Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02129 USA.
EM hoggatt.jonathan@mgh.harvard.edu
NR 0
TC 1
Z9 1
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JUL 14
PY 2016
VL 166
IS 2
BP 263
EP 263
DI 10.1016/j.cell.2016.06.049
PG 1
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DR9ZR
UT WOS:000380255400002
PM 27419862
ER
PT J
AU Long, JZ
Svensson, KJ
Bateman, LA
Lin, H
Kamenecka, T
Lokurkar, IA
Lou, J
Rao, RR
Chang, MR
Jedrychowski, MP
Paulo, JA
Gygi, SP
Griffin, PR
Nomura, DK
Spiegelman, BM
AF Long, Jonathan Z.
Svensson, Katrin J.
Bateman, Leslie A.
Lin, Hua
Kamenecka, Theodore
Lokurkar, Isha A.
Lou, Jesse
Rao, Rajesh R.
Chang, Mi Ra
Jedrychowski, Mark P.
Paulo, Joao A.
Gygi, Steven P.
Griffin, Patrick R.
Nomura, Daniel K.
Spiegelman, Bruce M.
TI The Secreted Enzyme PM20D1 Regulates Lipidated Amino Acid Uncouplers of
Mitochondria
SO CELL
LA English
DT Article
ID BROWN ADIPOSE-TISSUE; BEIGE FAT; THERMOGENESIS; MICE; ABLATION;
IDENTIFICATION; DIPEPTIDASE; PROTEINS; OBESITY; PRDM16
AB Brown and beige adipocytes are specialized cells that express uncoupling protein 1 ( UCP1) and dissipate chemical energy as heat. These cells likely possess alternative UCP1-independent thermogenic mechanisms. Here, we identify a secreted enzyme, peptidase M20 domain containing 1 ( PM20D1), that is enriched in UCP1(+) versus UCP1(-) adipocytes. We demonstrate that PM20D1 is a bidirectional enzyme in vitro, catalyzing both the condensation of fatty acids and amino acids to generate N-acyl amino acids and also the reverse hydrolytic reaction. N-acyl amino acids directly bind mitochondria and function as endogenous uncouplers of UCP1-independent respiration. Mice with increased circulating PM20D1 have augmented respiration and increased N-acyl amino acids in blood. Lastly, administration of N-acyl amino acids to mice improves glucose homeostasis and increases energy expenditure. These data identify an enzymatic node and a family of metabolites that regulate energy homeostasis. This pathway might be useful for treating obesity and associated disorders.
C1 [Long, Jonathan Z.; Svensson, Katrin J.; Lokurkar, Isha A.; Lou, Jesse; Rao, Rajesh R.; Jedrychowski, Mark P.; Spiegelman, Bruce M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Long, Jonathan Z.; Svensson, Katrin J.; Rao, Rajesh R.; Jedrychowski, Mark P.; Paulo, Joao A.; Gygi, Steven P.; Spiegelman, Bruce M.] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
[Bateman, Leslie A.; Nomura, Daniel K.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Bateman, Leslie A.; Nomura, Daniel K.] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
[Bateman, Leslie A.; Nomura, Daniel K.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Lin, Hua; Kamenecka, Theodore; Chang, Mi Ra; Griffin, Patrick R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA.
[Rao, Rajesh R.] Novartis Res Fdn GNF, Genom Inst, San Diego, CA 92121 USA.
RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.; Spiegelman, BM (reprint author), Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.; Nomura, DK (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.; Nomura, DK (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.; Nomura, DK (reprint author), Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
EM dnomura@berkeley.edu; bruce_spiegelman@dfci.harvard.edu
FU NIH [DK105203, DK098285, R01CA172667, DK5447, DK31405]; Swedish Research
Council [PE2013/613]; American Cancer Society [RSG14-242-01-TBE]; JPB
Foundation
FX We thank Marc Kirschner for many critical discussions as well as members
of the B.M.S., D.K.N., and P.R.G. labs for helpful comments. We are
grateful to Julie J. Johnson and Arbansjit Sandhu at the University of
Pennsylvania Vector Core for AAV production. This work was supported by
grants to J.Z.L. (NIH DK105203), K.J.S. (Swedish Research Council
Postdoctoral Fellowship PE2013/613), J.A.P. (NIH DK098285), D.K.N.
(American Cancer Society Research Scholar Award RSG14-242-01-TBE and NIH
R01CA172667), and B.M.S. (NIH DK5447, DK31405 and the JPB Foundation).
B.M.S. is a consultant for Calico Life Sciences, LLC.
NR 30
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U1 8
U2 16
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0092-8674
EI 1097-4172
J9 CELL
JI Cell
PD JUL 14
PY 2016
VL 166
IS 2
BP 424
EP 435
DI 10.1016/j.cell.2016.05.071
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DR9ZR
UT WOS:000380255400019
PM 27374330
ER
PT J
AU Vidadala, RSR
Rivas, KL
Ojo, KK
HuIverson, MA
Zambriski, JA
Bruzual, I
Schultz, TL
Huang, WL
Zhang, ZS
Scheele, S
DeRocher, AE
Choi, R
Barrett, LK
Siddaramaiah, LK
Hol, WGJ
Fan, EK
Merritt, EA
Parsons, M
Freiberg, G
Marsh, K
Kempf, DJ
Carruthers, VB
Isoherranen, N
Doggett, JS
Van Voorhis, WC
Maly, DJ
AF Vidadala, Rama Subba Rao
Rivas, Kasey L.
Ojo, Kayode K.
HuIverson, Matthew A.
Zambriski, Jennifer A.
Bruzual, Igor
Schultz, Tracey L.
Huang, Wenlin
Zhang, Zhongsheng
Scheele, Suzanne
DeRocher, Amy E.
Choi, Ryan
Barrett, Lynn K.
Siddaramaiah, Latha Kallur
Hol, Wim G. J.
Fan, Erkang
Merritt, Ethan A.
Parsons, Marilyn
Freiberg, Gail
Marsh, Kennan
Kempf, Dale J.
Carruthers, Vern B.
Isoherranen, Nina
Doggett, J. Stone
Van Voorhis, Wesley C.
Maly, Dustin J.
TI Development of an Orally Available and Central Nervous System (CNS)
Penetrant Toxoplasma gondii Calcium-Dependent Protein Kinase 1 (TgCDPK1)
Inhibitor with Minimal Human Ether-a-go-go-Related Gene (hERG) Activity
for the Treatment of Toxoplasmosis
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID SELECTIVE INHIBITORS; C. PARVUM; T. GONDII; IN-VITRO; POTENT; INFECTION;
CDPK1; DRUG; TRANSMISSION; DISCOVERY
AB New therapies are needed for the treatment of toxoplasmosis, which is a disease caused by the protozoan parasite Toxoplasma gondii. To this end, we previously developed a potent and selective inhibitor (compound 1) of Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) that possesses antitoxoplasmosis activity in vitro and in vivo. Unfortunately, 1 has potent human ether-a-go-go-related gene (hERG) inhibitory activity, associated with long Q-T syndrome, and consequently presents a cardiotoxicity risk. Here, we describe the identification of an optimized TgCDPK1 inhibitor 32, which does not have a hERG liability and possesses a favorable pharmacokinetic profile in small and large animals. 32 is CNS-penetrant and highly effective in acute and latent mouse models of T. gondii infection, significantly reducing the amount of parasite in the brain, spleen, and peritoneal fluid and reducing brain cysts by >85%. These properties make 32 a promising lead for the development of a new antitoxoplasmosis therapy.
C1 [Huang, Wenlin; Zhang, Zhongsheng; Siddaramaiah, Latha Kallur; Hol, Wim G. J.; Fan, Erkang; Merritt, Ethan A.; Maly, Dustin J.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Rivas, Kasey L.; Ojo, Kayode K.; HuIverson, Matthew A.; Choi, Ryan; Barrett, Lynn K.; Van Voorhis, Wesley C.] Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98109 USA.
[Rivas, Kasey L.; Ojo, Kayode K.; HuIverson, Matthew A.; Choi, Ryan; Barrett, Lynn K.; Van Voorhis, Wesley C.] Univ Washington, Ctr Emerging & Re Emerging Infect Dis CERID, Seattle, WA 98109 USA.
[Vidadala, Rama Subba Rao; Parsons, Marilyn; Maly, Dustin J.] Univ Washington, Dept Chem, Seattle, WA 98195 USA.
[Scheele, Suzanne; DeRocher, Amy E.; Parsons, Marilyn] Seattle Biomed Res Inst, Ctr Infect Dis Res, 4 Nickerson St, Seattle, WA 98109 USA.
[Parsons, Marilyn; Van Voorhis, Wesley C.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Bruzual, Igor; Doggett, J. Stone] Portland VA Med Ctr, Portland, OR 97239 USA.
[Zambriski, Jennifer A.] Washington State Univ, Paul G Allen Sch Global Anim Hlth, Coll Vet Med, Pullman, WA 99164 USA.
[Schultz, Tracey L.; Carruthers, Vern B.] Univ Michigan, Dept Microbiol & Immunol, Sch Med, Ann Arbor, MI 48109 USA.
[Isoherranen, Nina] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA.
[Freiberg, Gail; Marsh, Kennan; Kempf, Dale J.] AbbVie, N Chicago, IL 60064 USA.
RP Maly, DJ (reprint author), Univ Washington, Dept Biochem, Seattle, WA 98195 USA.; Van Voorhis, WC (reprint author), Univ Washington, Dept Med, Div Allergy & Infect Dis, Seattle, WA 98109 USA.; Van Voorhis, WC (reprint author), Univ Washington, Ctr Emerging & Re Emerging Infect Dis CERID, Seattle, WA 98109 USA.; Maly, DJ (reprint author), Univ Washington, Dept Chem, Seattle, WA 98195 USA.; Van Voorhis, WC (reprint author), Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
EM wesley@uw.edu; maly@chem.washington.edu
OI Parsons, Marilyn/0000-0003-3994-8096
FU National Institute of General Medical Sciences, National Institute of
Allergy and Infectious Diseases; National Institute of Child Health and
Human Development of the National Institutes of Health [R01GM086858,
R01AI089441, R01AI111341, R01HD080670]; United States Department of
Agriculture [2014-06183]; United States Department of Veterans Affairs
Biomedical Laboratory Research and Development [BX002440]; Stanley
Medical Research Institute [07R1857]; U.S. Department of Energy Office
of Basic Energy Sciences [DE-AC02-76SF00515]; National Institutes of
Health [P41GM103393]
FX We thank DeAnne Stolarik (AbbVie) and Lance Heinle (AbbVie) for
assistance with the dog and monkey PK studies. Research reported in this
publication was supported by the National Institute of General Medical
Sciences, National Institute of Allergy and Infectious Diseases, and
National Institute of Child Health and Human Development of the National
Institutes of Health under Awards R01GM086858, R01AI089441, R01AI111341,
and R01HD080670. This work was also supported in part by Award
2014-06183 from the United States Department of Agriculture, by Career
Development Award BX002440 from the United States Department of Veterans
Affairs Biomedical Laboratory Research and Development, and by Award
07R1857 from the Stanley Medical Research Institute. Crystallography
performed in support of the work benefitted from remote access to
resources at the Stanford Synchrotron Radiation Lightsource supported by
the U.S. Department of Energy Office of Basic Energy Sciences under
Contract DE-AC02-76SF00515 and by the National Institutes of Health
(Grant P41GM103393). The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health.
NR 36
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Z9 7
U1 7
U2 12
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0022-2623
EI 1520-4804
J9 J MED CHEM
JI J. Med. Chem.
PD JUL 14
PY 2016
VL 59
IS 13
BP 6531
EP 6546
DI 10.1021/acs.jmedchem.6b00760
PG 16
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DR6CN
UT WOS:000379989800040
PM 27309760
ER
PT J
AU Powers, JT
Tsanov, KM
Pearson, DS
Roels, F
Spina, CS
Ebright, R
Seligson, M
de Soysa, Y
Cahan, P
Theissen, J
Tu, HC
Han, A
Kurek, KC
LaPier, GS
Osborne, JK
Ross, SJ
Cesana, M
Collins, JJ
Berthold, F
Daley, GQ
AF Powers, John T.
Tsanov, Kaloyan M.
Pearson, Daniel S.
Roels, Frederik
Spina, Catherine S.
Ebright, Richard
Seligson, Marc
de Soysa, Yvanka
Cahan, Patrick
Theissen, Jessica
Tu, Ho-Chou
Han, Areum
Kurek, Kyle C.
LaPier, Grace S.
Osborne, Jihan K.
Ross, Samantha J.
Cesana, Marcella
Collins, James J.
Berthold, Frank
Daley, George Q.
TI Multiple mechanisms disrupt the let-7 microRNA family in neuroblastoma
SO NATURE
LA English
DT Article
ID COMPARATIVE GENOMIC HYBRIDIZATION; COMPETITIVE ENDOGENOUS RNA;
GENE-EXPRESSION; N-MYC; CANCER; TUMOR; LIN28B; CELLS; MIRNA;
AMPLIFICATION
AB Poor prognosis in neuroblastoma is associated with genetic amplification of MYCN. MYCN is itself a target of let-7, a tumour suppressor family of microRNAs implicated in numerous cancers. LIN28B, an inhibitor of let-7 biogenesis, is overexpressed in neuroblastoma and has been reported to regulate MYCN. Here we show, however, that LIN28B is dispensable in MYCN-amplified neuroblastoma cell lines, despite de-repression of let-7. We further demonstrate that MYCN messenger RNA levels in amplified disease are exceptionally high and sufficient to sponge let-7, which reconciles the dispensability of LIN28B. We found that genetic loss of let-7 is common in neuroblastoma, inversely associated with MYCN amplification, and independently associated with poor outcomes, providing a rationale for chromosomal loss patterns in neuroblastoma. We propose that let-7 disruption by LIN28B, MYCN sponging, or genetic loss is a unifying mechanism of neuroblastoma development with broad implications for cancer pathogenesis.
C1 [Powers, John T.; Tsanov, Kaloyan M.; Pearson, Daniel S.; Ebright, Richard; Seligson, Marc; de Soysa, Yvanka; Cahan, Patrick; Tu, Ho-Chou; Han, Areum; LaPier, Grace S.; Osborne, Jihan K.; Ross, Samantha J.; Cesana, Marcella; Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Roels, Frederik; Theissen, Jessica; Berthold, Frank] Univ Hosp Koln, Dept Pediat Oncol, D-50937 Cologne, Germany.
[Spina, Catherine S.; Collins, James J.] Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Kurek, Kyle C.] Boston Childrens Hosp, Dept Pathol, Boston, MA 02215 USA.
[Collins, James J.] Broad Inst MIT & Harvard, MIT, Dept Biol Engn, Cambridge, MA 02142 USA.
[Daley, George Q.] Dana Farber Canc Inst, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[Daley, George Q.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Daley, George Q.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Daley, George Q.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Daley, GQ (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Dana Farber Canc Inst, Stem Cell Transplantat Program, Boston, MA 02115 USA.; Daley, GQ (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA.; Daley, GQ (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
EM george.daley@childrens.harvard.edu
FU National Institutes of Health [R01GM107536]; Alex's Lemonade Stand
Foundation; Ellison Medical Foundation; National Institute of General
Medical Sciences [T32GM007753]
FX G.Q.D. is supported by National Institutes of Health grant R01GM107536,
Alex's Lemonade Stand Foundation, and the Ellison Medical Foundation.
G.Q.D. is an affiliate member of the Broad Institute, and an
investigator of the Howard Hughes Medical Institute and the Manton
Center for Orphan Disease Research. J.T.P. was supported by Alex's
Lemonade Stand Foundation. K.M.T. was supported as a Howard Hughes
Medical Institute International Student Research Fellow and as a Herchel
Smith Graduate Fellow. D.S.P. and R.E. were supported by award number
T32GM007753 from the National Institute of General Medical Sciences.
NR 58
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U1 16
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 14
PY 2016
VL 535
IS 7611
BP 246
EP U112
DI 10.1038/nature18632
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR4ZN
UT WOS:000379912600049
PM 27383785
ER
PT J
AU Debruyne, DN
Bhatnagar, N
Sharma, B
Luther, W
Moore, NF
Cheung, K
Gray, NS
George, RE
AF Debruyne, D. N.
Bhatnagar, N.
Sharma, B.
Luther, W.
Moore, N. F.
Cheung, K.
Gray, N. S.
George, R. E.
TI ALK inhibitor resistance in ALK(F1174L)-driven neuroblastoma is
associated with AXL activation and induction of EMT
SO ONCOGENE
LA English
DT Article
ID RECEPTOR TYROSINE KINASE; GENE-EXPRESSION SIGNATURE; CANCER-CELLS;
LUNG-CANCER; BREAST-CANCER; THERAPEUTIC TARGET; PROLONGS SURVIVAL;
MUTATIONS; GROWTH; EGFR
AB The crizotinib-resistant ALK(F1174L) mutation arises de novo in neuroblastoma (NB) and is acquired in ALK translocation-driven cancers, lending impetus to the development of novel anaplastic lymphoma kinase (ALK) inhibitors with different modes of action. The diaminopyrimidine TAE684 and its derivative ceritinib (LDK378), which are structurally distinct from crizotinib, are active against NB cells expressing ALK(F1174L). Here we demonstrate acquired resistance to TAE684 and LDK378 in ALK(F1174L)-driven human NB cells that is linked to overexpression and activation of the AXL tyrosine kinase and epithelial-to-mesenchymal transition (EMT). AXL phosphorylation conferred TAE684 resistance to NB cells through upregulated extracellular signal-regulated kinase (ERK) signaling. Inhibition of AXL partly rescued TAE684 resistance, resensitizing these cells to this compound. AXL activation in resistant cells was mediated through increased expression of the active form of its ligand, GAS6, that also served to stabilize the AXL protein. Although ectopic expression of AXL and TWIST2 individually in TAE684-sensitive parental cells led to the elevated expression of mesenchymal markers and invasive capacity, only AXL overexpression induced resistance to TAE684 as well. TAE684-resistant cells showed greater sensitivity to HSP90 inhibition than did their parental counterparts, with downregulation of AXL and AXL-mediated ERK signaling. Our studies indicate that aberrant AXL signaling and development of an EMT phenotype underlie resistance of ALK(F1174L)-driven NB cells to TAE684 and its derivatives. We suggest that the combination of ALK and AXL or HSP90 inhibitors be considered to delay the emergence of such resistance.
C1 [Debruyne, D. N.; Bhatnagar, N.; Sharma, B.; Luther, W.; Moore, N. F.; George, R. E.] Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA.
[Debruyne, D. N.; Bhatnagar, N.; Sharma, B.; Luther, W.; Moore, N. F.; George, R. E.] Boston Childrens Hosp, Boston, MA USA.
[Cheung, K.] Mem Sloan Kettering Canc Ctr, Dept Pediat Oncol, 1275 York Ave, New York, NY 10021 USA.
[Gray, N. S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Gray, N. S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA.
[George, R. E.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
RP George, RE (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Dana 640E,450 Brookline Ave, Boston, MA 02215 USA.
EM rani_george@dfci.harvard.edu
FU NIH/NCI [R01 CA148688]; Friends for Life Neuroblastoma Fellowship; Ruth
L Kirschstein NRSA [F32CA183566]
FX This study was supported by NIH/NCI R01 CA148688 (to REG), Friends for
Life Neuroblastoma Fellowship (to DND) and a Ruth L Kirschstein NRSA
F32CA183566 (to NFM).
NR 47
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Z9 7
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL 14
PY 2016
VL 35
IS 28
BP 3681
EP 3691
DI 10.1038/onc.2015.434
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DR0UQ
UT WOS:000379622800007
PM 26616860
ER
PT J
AU Kussman, BD
Aasted, CM
Yucel, MA
Steele, SC
Alexander, ME
Boas, DA
Borsook, D
Becerra, L
AF Kussman, Barry D.
Aasted, Christopher M.
Yucel, Meryem A.
Steele, Sarah C.
Alexander, Mark E.
Boas, David A.
Borsook, David
Becerra, Lino
TI Capturing Pain in the Cortex during General Anesthesia: Near Infrared
Spectroscopy Measures in Patients Undergoing Catheter Ablation of
Arrhythmias
SO PLOS ONE
LA English
DT Article
ID MEDIAL PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW;
POSTTRAUMATIC-STRESS-DISORDER; POSITRON-EMISSION-TOMOGRAPHY; DIFFUSE
OPTICAL TOMOGRAPHY; PULMONARY VEIN ISOLATION; FRONTAL-CORTEX;
RADIOFREQUENCY ABLATION; BRAIN ACTIVATION; CENTRAL SENSITIZATION
AB The predictability of pain makes surgery an ideal model for the study of pain and the development of strategies for analgesia and reduction of perioperative pain. As functional near-infrared spectroscopy reproduces the known functional magnetic resonance imaging activations in response to a painful stimulus, we evaluated the feasibility of functional near-infrared spectroscopy to measure cortical responses to noxious stimulation during general anesthesia. A multichannel continuous wave near-infrared imager was used to measure somatosensory and frontal cortical activation in patients undergoing catheter ablation of arrhythmias under general anesthesia. Anesthetic technique was standardized and intra-operative NIRS signals recorded continuously with markers placed in the data set for the timing and duration of each cardiac ablation event. Frontal cortical signals only were suitable for analysis in five of eight patients studied (mean age 14 +/- 1 years, weight 66.7 +/- 17.6 kg, 2 males). Thirty ablative lesions were recorded for the five patients. Radiofrequency or cryoablation was temporally associated with a hemodynamic response function in the frontal cortex characterized by a significant decrease in oxyhemoglobin concentration (paired t-test, p<0.05) with the nadir occurring in the period 4 to 6 seconds after application of the ablative lesion. Cortical signals produced by catheter ablation of arrhythmias in patients under general anesthesia mirrored those seen with noxious stimulation in awake, healthy volunteers, during sedation for colonoscopy, and functional Magnetic Resonance Imaging activations in response to pain. This study demonstrates the feasibility and potential utility of functional near-infrared spectroscopy as an objective measure of cortical activation under general anesthesia.
C1 [Kussman, Barry D.; Aasted, Christopher M.; Steele, Sarah C.; Borsook, David; Becerra, Lino] Harvard Med Sch, Ctr Pain & Brain, Boston, MA 02115 USA.
[Kussman, Barry D.; Aasted, Christopher M.; Steele, Sarah C.; Borsook, David; Becerra, Lino] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Kussman, Barry D.; Aasted, Christopher M.; Yucel, Meryem A.; Steele, Sarah C.; Alexander, Mark E.; Boas, David A.; Borsook, David; Becerra, Lino] Harvard Med Sch, Boston, MA 02115 USA.
[Aasted, Christopher M.; Yucel, Meryem A.; Steele, Sarah C.; Boas, David A.; Borsook, David; Becerra, Lino] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, 32 Fruit St, Boston, MA 02114 USA.
[Alexander, Mark E.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
RP Becerra, L (reprint author), Harvard Med Sch, Ctr Pain & Brain, Boston, MA 02115 USA.; Becerra, L (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.; Becerra, L (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Becerra, L (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, 32 Fruit St, Boston, MA 02114 USA.
EM Lino.Becerra@childrens.harvard.edu
FU Mayday Foundation; Anesthesia Research Distinguished Trailblazer Award;
National Institute of General Medical Science of the National Institutes
of Health [R01GM104986]
FX Research reported in this article was supported by the Mayday
Foundation, the Anesthesia Research Distinguished Trailblazer Award, and
the National Institute of General Medical Science of the National
Institutes of Health under award number R01GM104986. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 66
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U1 5
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 14
PY 2016
VL 11
IS 7
AR e0158975
DI 10.1371/journal.pone.0158975
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR0DZ
UT WOS:000379579500056
PM 27415436
ER
PT J
AU Lin, MV
Sise, ME
Pavlakis, M
Amundsen, BM
Chute, D
Rutherford, AE
Chung, RT
Curry, MP
Hanifi, JM
Gabardi, S
Chandraker, A
Heher, EC
Elias, N
Riella, LV
AF Lin, Ming V.
Sise, Meghan E.
Pavlakis, Martha
Amundsen, Beth M.
Chute, Donald
Rutherford, Anna E.
Chung, Raymond T.
Curry, Michael P.
Hanifi, Jasmine M.
Gabardi, Steve
Chandraker, Anil
Heher, Eliot C.
Elias, Nahel
Riella, Leonardo V.
TI Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant
Recipients with Chronic Hepatitis C Virus Infection
SO PLOS ONE
LA English
DT Article
ID RENAL-REPLACEMENT THERAPY; LIVER-TRANSPLANT; GENOTYPE 1; DISEASE;
IMPACT; METAANALYSIS; SOFOSBUVIR; SURVIVAL; SIMEPREVIR; EXPERIENCE
AB The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.
C1 [Lin, Ming V.; Rutherford, Anna E.] Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.
[Sise, Meghan E.; Heher, Eliot C.] Harvard Med Sch, Massachusetts Gen Hosp, Div Nephrol, Boston, MA USA.
[Pavlakis, Martha] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA USA.
[Amundsen, Beth M.; Heher, Eliot C.; Elias, Nahel] Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA.
[Chute, Donald; Chung, Raymond T.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Liver, Div Gastroenterol, Boston, MA USA.
[Curry, Michael P.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Div Gastroenterol & Hepatol, Boston, MA USA.
[Hanifi, Jasmine M.] Harvard Med Sch, Brigham & Womens Hosp, Dept Internal Med, Boston, MA USA.
[Gabardi, Steve; Chandraker, Anil; Riella, Leonardo V.] Harvard Med Sch, Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA USA.
RP Lin, MV (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, Boston, MA 02115 USA.; Riella, LV (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA USA.
EM mvlin@partners.org; lriella@bwh.harvard.edu
OI Gabardi, Steven/0000-0001-8022-2751
NR 33
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U1 1
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 14
PY 2016
VL 11
IS 7
AR e0158431
DI 10.1371/journal.pone.0158431
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR0DZ
UT WOS:000379579500021
PM 27415632
ER
PT J
AU Davids, MS
Kim, HT
Bachireddy, P
Costello, C
Liguori, R
Savell, A
Lukez, AP
Avigan, D
Chen, YB
McSweeney, P
LeBoeuf, NR
Rooney, MS
Bowden, M
Zhou, CSW
Granter, SR
Hornick, JL
Rodig, SJ
Hirakawa, M
Severgnini, M
Hodi, FS
Wu, CJ
Ho, VT
Cutler, C
Koreth, J
Alyea, EP
Antin, JH
Armand, P
Streicher, H
Ball, ED
Ritz, J
Bashey, A
Soiffer, RJ
AF Davids, Matthew S.
Kim, Haesook T.
Bachireddy, Pavan
Costello, Caitlin
Liguori, Rebecca
Savell, Alexandra
Lukez, Alexander P.
Avigan, David
Chen, Yi-Bin
McSweeney, Peter
LeBoeuf, Nicole R.
Rooney, Michael S.
Bowden, Michaela
Zhou, Chensheng W.
Granter, Scott R.
Hornick, Jason L.
Rodig, Scott J.
Hirakawa, Masahiro
Severgnini, Mariano
Hodi, F. Stephen
Wu, Catherine J.
Ho, Vincent T.
Cutler, Corey
Koreth, John
Alyea, Edwin P.
Antin, Joseph H.
Armand, Philippe
Streicher, Howard
Ball, Edward D.
Ritz, Jerome
Bashey, Asad
Soiffer, Robert J.
CA Leukemia Lymphoma Soc Blood Canc R
TI Ipilimumab for Patients with Relapse after Allogeneic Transplantation
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; VERSUS-HOST-DISEASE;
HEMATOLOGIC MALIGNANCIES; T-CELLS; BLOCKADE; CTLA-4; PATTERN; HLA
AB BACKGROUND
Loss of donor-mediated immune antitumor activity after allogeneic hematopoietic stem-cell transplantation (HSCT) permits relapse of hematologic cancers. We hypothesized that immune checkpoint blockade established by targeting cytotoxic T-lymphocyte-associated protein 4 with ipilimumab could restore antitumor reactivity through a graft-versus-tumor effect.
METHODS
We conducted a phase 1/1b multicenter, investigator-initiated study to determine the safety and efficacy of ipilimumab in patients with relapsed hematologic cancer after allogeneic HSCT. Patients received induction therapy with ipilimumab at a dose of 3 or 10 mg per kilogram of body weight every 3 weeks for a total of 4 doses, with additional doses every 12 weeks for up to 60 weeks in patients who had a clinical benefit.
RESULTS
A total of 28 patients were enrolled. Immune-related adverse events, including one death, were observed in 6 patients (21%), and graft-versus-host disease (GVHD) that precluded further administration of ipilimumab was observed in 4 patients (14%). No responses that met formal response criteria occurred in patients who received a dose of 3 mg per kilogram. Among 22 patients who received a dose of 10 mg per kilogram, 5 (23%) had a complete response, 2 (9%) had a partial response, and 6 (27%) had decreased tumor burden. Complete responses occurred in 4 patients with extramedullary acute myeloid leukemia and 1 patient with the myelodysplastic syndrome developing into acute myeloid leukemia. Four patients had a durable response for more than 1 year. Responses were associated with in situ infiltration of cytotoxic CD8+ T cells, decreased activation of regulatory T cells, and expansion of subpopulations of effector T cells in the blood.
CONCLUSIONS
Our early-phase data showed that administration of ipilimumab was feasible in patients with recurrent hematologic cancers after allogeneic HSCT, although immune-mediated toxic effects and GVHD occurred. Durable responses were observed in association with several histologic subtypes of these cancers, including extramedullary acute myeloid leukemia.
C1 [Davids, Matthew S.; Kim, Haesook T.; Bachireddy, Pavan; Liguori, Rebecca; Savell, Alexandra; Lukez, Alexander P.; Hirakawa, Masahiro; Severgnini, Mariano; Hodi, F. Stephen; Wu, Catherine J.; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Armand, Philippe; Ritz, Jerome; Soiffer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
[Davids, Matthew S.; Kim, Haesook T.; Bachireddy, Pavan; Liguori, Rebecca; Savell, Alexandra; Lukez, Alexander P.; Avigan, David; Chen, Yi-Bin; Hirakawa, Masahiro; Severgnini, Mariano; Hodi, F. Stephen; Wu, Catherine J.; Ho, Vincent T.; Cutler, Corey; Koreth, John; Alyea, Edwin P.; Antin, Joseph H.; Armand, Philippe; Ritz, Jerome; Soiffer, Robert J.] Harvard Med Sch, Boston, MA USA.
[Avigan, David] Beth Israel Deaconess Med Ctr, Bone Marrow Transplant Program, Boston, MA 02215 USA.
[Chen, Yi-Bin] Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Program, Boston, MA USA.
[LeBoeuf, Nicole R.] Dana Farber & Brigham & Womens Canc Ctr, Dept Dermatol, Boston, MA USA.
[Granter, Scott R.; Hornick, Jason L.; Rodig, Scott J.] Dana Farber & Brigham & Womens Canc Ctr, Dept Pathol, Boston, MA USA.
[Bowden, Michaela; Zhou, Chensheng W.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Bachireddy, Pavan; Wu, Catherine J.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA.
[Rooney, Michael S.] Neon Therapeut, Cambridge, MA USA.
[Costello, Caitlin; Ball, Edward D.] Univ Calif San Diego, Blood & Marrow Transplant Program, Moores Canc Ctr, La Jolla, CA 92093 USA.
[McSweeney, Peter] Colorado Blood Canc Inst, Denver, CO USA.
[Streicher, Howard] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Bashey, Asad] Northside Hosp, Blood & Marrow Transplant Grp Georgia, Atlanta, GA USA.
RP Davids, MS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM matthew_davids@dfci.harvard.edu
FU National Institutes of Health
FX Funded by the National Institutes of Health and others;
ClinicalTrials.gov number, NCT01822509.
NR 22
TC 17
Z9 17
U1 3
U2 6
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 14
PY 2016
VL 375
IS 2
BP 143
EP 153
DI 10.1056/NEJMoa1601202
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ9KY
UT WOS:000379530000007
PM 27410923
ER
PT J
AU Fenves, AZ
Schaefer, PW
Luther, J
Pierce, VM
AF Fenves, Andrew Z.
Schaefer, Pamela W.
Luther, Jay
Pierce, Virginia M.
TI Case 21-2016: A 32-Year-Old Man in an Unresponsive State
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID HEPATITIS-B-VIRUS; ACUTE-LIVER-FAILURE; ACETAMINOPHEN; PREVALENCE;
INFECTION; OUTCOMES; DISEASE; TESTS
C1 [Fenves, Andrew Z.; Luther, Jay] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Schaefer, Pamela W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Pierce, Virginia M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Fenves, Andrew Z.; Luther, Jay] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Schaefer, Pamela W.] Harvard Med Sch, Dept Radiol, Boston, MA USA.
[Pierce, Virginia M.] Harvard Med Sch, Dept Pathol, Boston, MA USA.
RP Fenves, AZ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.; Fenves, AZ (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
NR 27
TC 0
Z9 0
U1 3
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 14
PY 2016
VL 375
IS 2
BP 163
EP 171
DI 10.1056/NEJMcpc1600838
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ9KY
UT WOS:000379530000011
PM 27410926
ER
PT J
AU Birrer, MJ
AF Birrer, Michael J.
TI Premedicate with the Standard Regimen (Aprepitant, Ondansetron, and
Dexamethasone)
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
C1 [Birrer, Michael J.] Massachusetts Gen Hosp, Gynecol Oncol Res Program, Boston, MA 02114 USA.
RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Gynecol Oncol Res Program, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 14
PY 2016
VL 375
IS 2
BP 177
EP 178
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ9KY
UT WOS:000379530000015
ER
PT J
AU Sepulcre, J
Schultz, AP
Sabuncu, M
Gomez-Isla, T
Chhatwal, J
Becker, A
Sperling, R
Johnson, KA
AF Sepulcre, Jorge
Schultz, Aaron P.
Sabuncu, Mert
Gomez-Isla, Teresa
Chhatwal, Jasmeer
Becker, Alex
Sperling, Reisa
Johnson, Keith A.
TI In Vivo Tau, Amyloid, and Gray Matter Profiles in the Aging Brain
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE aging; Alzheimer's disease; amyloid; gray matter; Tau
ID EARLY ALZHEIMERS-DISEASE; POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH
COMPOUND-B; MILD AD DEMENTIA; NEURODEGENERATIVE DISEASES;
NEUROPATHOLOGIC ASSESSMENT; NEUROFIBRILLARY CHANGES; CORTICAL SIGNATURE;
CEREBRAL-CORTEX; BETA
AB We provide a comparative in vivo examination of the brain network-based distribution of two hallmarks of Alzheimer's disease (AD) pathology in cognitively normal individuals: (1) Tau, detected with a novel positron emission tomography (PET) tracer known as F-18-AV-1451; and (2) amyloid-beta, quantified with C-11-PiB PET. We used a high-resolution graph-based approach to investigate local-to-local and local-to-distributed cortical associations between the maps of Tau, amyloid-beta, and gray matter intensity. Our study shows that Tau and amyloid-beta deposits are associated with distinctive spatial patterns of brain tissue loss. Moreover, Tau and amyloid-beta accumulations have strong network interdigitations in heteromodal and associative areas of the cortical mantle, particularly the inferior-lateral temporal lobe. These findings contribute significantly to our understanding of how these two main hallmarks of AD pathology propagate across the elderly human brain.
C1 [Sepulcre, Jorge; Becker, Alex; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Gomez-Isla, Teresa; Sperling, Reisa; Johnson, Keith A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Gomez-Isla, Teresa; Sperling, Reisa; Johnson, Keith A.] Harvard Med Sch, Boston, MA 02114 USA.
[Sepulcre, Jorge; Schultz, Aaron P.; Sabuncu, Mert; Chhatwal, Jasmeer; Sperling, Reisa] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[Sperling, Reisa; Johnson, Keith A.] Brigham & Womens Hosp, Dept Neurol, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA.
[Sperling, Reisa; Johnson, Keith A.] Harvard Med Sch, Boston, MA 02115 USA.
RP Sepulcre, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med & Mol Imaging, 149 13th St,Suite 5-209, Charlestown, MA 02129 USA.
EM sepulcre@nmr.mgh.harvard.edu
FU National Institutes of Health [K23-EB019023, R01-AG046396,
R01-AG027435-S1, P50-AG00513421, P01-AG036694, K25-EB013649,
K23-AG049087]; Massachusetts Alzheimer's Disease Research Center,
Alzheimer's Association [NIRG-11-205690, IIRG-06-32444, ZEN-10-174210];
Bright-Focus Foundation/American Health Assistance Foundation [A2012333,
A2013003]; American Brain Foundation/American Academy of Neurology
FX This research was supported by National Institutes of Health Grants
K23-EB019023 (J.S.), R01-AG046396 (K.A.J.), R01-AG027435-S1 (R.A.S. and
K.A.J.), P50-AG00513421 (K.A.J. and R.A.S.), P01-AG036694 (R.A.S. and
K.A.J.), K25-EB013649 (M.R.S.), and K23-AG049087 (J.P.C.), Massachusetts
Alzheimer's Disease Research Center, Alzheimer's Association Grants
NIRG-11-205690 (J.S.), IIRG-06-32444 (R.A.S. and K.A.J.), and
ZEN-10-174210 (K.A.J.), Bright-Focus Foundation/American Health
Assistance Foundation Grants A2012333 (M.R.S.) and A2013003 (J.P.C.),
and the American Brain Foundation/American Academy of Neurology
(J.P.C.). We thank the investigators and staff of the Harvard Aging
Brain Study and the Massachusetts Alzheimer's Disease Research Center,
the individual research participants, and their families and caregivers.
We also thank the PET Core of Massachusetts General Hospital, and the
Athinoula A. Martinos Center for imaging support.
NR 65
TC 7
Z9 8
U1 2
U2 7
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD JUL 13
PY 2016
VL 36
IS 28
BP 7364
EP 7374
DI 10.1523/JNEUROSCI.0639-16.2016
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA DS1ST
UT WOS:000380380500005
PM 27413148
ER
PT J
AU Shaw, KA
Bertha, M
Hofmekler, T
Chopra, P
Vatanen, T
Srivatsa, A
Prince, J
Kumar, A
Sauer, C
Zwick, ME
Satten, GA
Kostic, AD
Mulle, JG
Xavier, RJ
Kugathasan, S
AF Shaw, Kelly A.
Bertha, Madeline
Hofmekler, Tatyana
Chopra, Pankaj
Vatanen, Tommi
Srivatsa, Abhiram
Prince, Jarod
Kumar, Archana
Sauer, Cary
Zwick, Michael E.
Satten, Glen A.
Kostic, Aleksandar D.
Mulle, Jennifer G.
Xavier, Ramnik J.
Kugathasan, Subra
TI Dysbiosis, inflammation, and response to treatment: a longitudinal study
of pediatric subjects with newly diagnosed inflammatory bowel disease
SO GENOME MEDICINE
LA English
DT Article
DE Inflammatory bowel disease; Microbiome; Crohn's disease; Dysbiosis
ID CROHNS-DISEASE; ULCERATIVE-COLITIS; ACTIVITY INDEX;
FUSOBACTERIUM-NECROPHORUM; BACTERIAL DIVERSITY; GUT MICROBIOTA; HOST
GENETICS; VALIDATION; INFECTIONS; PREVALENCE
AB Background: Gut microbiome dysbiosis has been demonstrated in subjects with newly diagnosed and chronic inflammatory bowel disease (IBD). In this study we sought to explore longitudinal changes in dysbiosis and ascertain associations between dysbiosis and markers of disease activity and treatment outcome.
Methods: We performed a prospective cohort study of 19 treatment-naive pediatric IBD subjects and 10 healthy controls, measuring fecal calprotectin and assessing the gut microbiome via repeated stool samples. Associations between clinical characteristics and the microbiome were tested using generalized estimating equations. Random forest classification was used to predict ultimate treatment response (presence of mucosal healing at follow-up colonoscopy) or non-response using patients' pretreatment samples.
Results: Patients with Crohn's disease had increased markers of inflammation and dysbiosis compared to controls. Patients with ulcerative colitis had even higher inflammation and dysbiosis compared to those with Crohn's disease. For all cases, the gut microbial dysbiosis index associated significantly with clinical and biological measures of disease severity, but did not associate with treatment response. We found differences in specific gut microbiome genera between cases/controls and responders/non-responders including Akkermansia, Coprococcus, Fusobacterium, Veillonella, Faecalibacterium, and Adlercreutzia. Using pretreatment microbiome data in a weighted random forest classifier, we were able to obtain 76.5 % accuracy for prediction of responder status.
Conclusions: Patient dysbiosis improved over time but persisted even among those who responded to treatment and achieved mucosal healing. Although dysbiosis index was not significantly different between responders and non-responders, we found specific genus-level differences. We found that pretreatment microbiome signatures are a promising avenue for prediction of remission and response to treatment.
C1 [Shaw, Kelly A.] Emory Univ, Grad Div Biol & Biomed Sci, Grad Program Genet & Mol Biol, Atlanta, GA 30322 USA.
[Bertha, Madeline; Hofmekler, Tatyana; Chopra, Pankaj; Srivatsa, Abhiram; Prince, Jarod; Kumar, Archana; Sauer, Cary; Kugathasan, Subra] Emory Univ, Dept Pediat, Sch Med, 2015 Uppergate Dr,Room 248, Atlanta, GA 30322 USA.
[Bertha, Madeline; Hofmekler, Tatyana; Chopra, Pankaj; Srivatsa, Abhiram; Prince, Jarod; Kumar, Archana; Sauer, Cary; Kugathasan, Subra] Childrens Healthcare Atlanta, 2015 Uppergate Dr,Room 248, Atlanta, GA 30322 USA.
[Vatanen, Tommi; Kostic, Aleksandar D.; Xavier, Ramnik J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Vatanen, Tommi] Aalto Univ, Dept Comp Sci, Sch Sci, Espoo 02150, Finland.
[Zwick, Michael E.; Mulle, Jennifer G.; Kugathasan, Subra] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Satten, Glen A.] Ctr Dis Control & Prevent, Atlanta, GA 30341 USA.
[Kostic, Aleksandar D.; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Kostic, Aleksandar D.; Xavier, Ramnik J.] Harvard Med Sch, Boston, MA 02114 USA.
[Mulle, Jennifer G.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
RP Kugathasan, S (reprint author), Emory Univ, Dept Pediat, Sch Med, 2015 Uppergate Dr,Room 248, Atlanta, GA 30322 USA.; Kugathasan, S (reprint author), Childrens Healthcare Atlanta, 2015 Uppergate Dr,Room 248, Atlanta, GA 30322 USA.; Kugathasan, S (reprint author), Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
EM skugath@emory.edu
FU Marcus Foundation [DK087694, DK098231]; BWF [1008188]; NIH [NRSA
F31DK107229]
FX The Marcus Foundation (to SK) primarily supported this work, with
further support from DK087694 (SK) and DK098231 (SK). KAS received
support from BWF training grant ID 1008188 and NIH NRSA F31DK107229.
NR 50
TC 6
Z9 6
U1 3
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-994X
J9 GENOME MED
JI Genome Med.
PD JUL 13
PY 2016
VL 8
AR 75
DI 10.1186/s13073-016-0331-y
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA DR9IB
UT WOS:000380209200001
PM 27412252
ER
PT J
AU Cleary, JM
Mamon, HJ
Szymonifka, J
Bueno, R
Choi, N
Donahue, DM
Fidias, PM
Gaissert, HA
Jaklitsch, MT
Kulke, MH
Lynch, TP
Mentzer, SJ
Meyerhardt, JA
Swanson, RS
Wain, J
Fuchs, CS
Enzinger, PC
AF Cleary, James M.
Mamon, Harvey J.
Szymonifka, Jackie
Bueno, Raphael
Choi, Noah
Donahue, Dean M.
Fidias, Panos M.
Gaissert, Henning A.
Jaklitsch, Michael T.
Kulke, Matthew H.
Lynch, Thomas P.
Mentzer, Steven J.
Meyerhardt, Jeffrey A.
Swanson, Richard S.
Wain, John
Fuchs, Charles S.
Enzinger, Peter C.
TI Neoadjuvant irinotecan, cisplatin, and concurrent radiation therapy with
celecoxib for patients with locally advanced esophageal cancer
SO BMC CANCER
LA English
DT Article
DE Esophageal cancer; Neoadjuvant therapy; Chemoradiation; Cyclooxygenase 2
inhibition
ID SQUAMOUS-CELL CARCINOMA; PLUS CISPLATIN; CYCLOOXYGENASE-2 EXPRESSION;
COLORECTAL ADENOMAS; SURVIVAL; CHEMORADIOTHERAPY; ADENOCARCINOMA;
METAANALYSIS; TRIAL; RADIOTHERAPY
AB Background: Patients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation.
Methods: This single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery.
Results: Forty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases.
Conclusions: The addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.
C1 [Cleary, James M.; Mamon, Harvey J.; Szymonifka, Jackie; Bueno, Raphael; Jaklitsch, Michael T.; Kulke, Matthew H.; Mentzer, Steven J.; Meyerhardt, Jeffrey A.; Swanson, Richard S.; Fuchs, Charles S.; Enzinger, Peter C.] Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Ctr Esophageal & Gastr Canc, 450 Brookline Ave, Boston, MA 02215 USA.
[Cleary, James M.; Mamon, Harvey J.; Szymonifka, Jackie; Bueno, Raphael; Jaklitsch, Michael T.; Kulke, Matthew H.; Mentzer, Steven J.; Meyerhardt, Jeffrey A.; Swanson, Richard S.; Fuchs, Charles S.; Enzinger, Peter C.] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Cleary, James M.; Mamon, Harvey J.; Szymonifka, Jackie; Bueno, Raphael; Jaklitsch, Michael T.; Kulke, Matthew H.; Mentzer, Steven J.; Meyerhardt, Jeffrey A.; Swanson, Richard S.; Fuchs, Charles S.; Enzinger, Peter C.] Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA.
[Choi, Noah; Donahue, Dean M.; Fidias, Panos M.; Gaissert, Henning A.; Lynch, Thomas P.; Wain, John] Harvard Med Sch, Ctr Canc, Massachusetts Gen Hosp, Boston, MA USA.
[Fidias, Panos M.] Univ Arizona, Ctr Canc, St Josephs Hosp & Med Ctr, Phoenix, AZ USA.
RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Dana Farber Brigham & Womens Canc Ctr, Ctr Esophageal & Gastr Canc, 450 Brookline Ave, Boston, MA 02215 USA.; Enzinger, PC (reprint author), Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.; Enzinger, PC (reprint author), Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA.
EM peter_enzinger@dfci.harvard.edu
FU National Institute of Health [P50CA127003]; Pharmacia Oncology
FX This work was supported by a grant from the National Institute of Health
(P50CA127003). Pharmacia Oncology supported the trial by providing the
Celecoxib to each of the participants.
NR 47
TC 0
Z9 0
U1 3
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUL 13
PY 2016
VL 16
AR 468
DI 10.1186/s12885-016-2485-9
PG 9
WC Oncology
SC Oncology
GA DR8ZN
UT WOS:000380187000001
PM 27412386
ER
PT J
AU Burberry, A
Suzuki, N
Wang, JY
Moccia, R
Mordes, DA
Stewart, MH
Suzuki-Uematsu, S
Ghosh, S
Singh, A
Merkle, FT
Koszka, K
Li, QZ
Zon, L
Rossi, DJ
Trowbridge, JJ
Notarangelo, LD
Eggan, K
AF Burberry, Aaron
Suzuki, Naoki
Wang, Jin-Yuan
Moccia, Rob
Mordes, Daniel A.
Stewart, Morag H.
Suzuki-Uematsu, Satomi
Ghosh, Sulagna
Singh, Ajay
Merkle, Florian T.
Koszka, Kathryn
Li, Quan-Zhen
Zon, Leonard
Rossi, Derrick J.
Trowbridge, Jennifer J.
Notarangelo, Luigi D.
Eggan, Kevin
TI Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal
autoimmune disease
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
SPINAL-CORD; ALS; REPEAT; MECHANISMS; EXPANSION; CELLS; TBK1; MICE
AB C9ORF72 mutations are found in a significant fraction of patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia, yet the function of the C9ORF72 gene product remains poorly understood. We show that mice harboring loss-of-function mutations in the ortholog of C9ORF72 develop splenomegaly, neutrophilia, thrombocytopenia, increased expression of inflammatory cytokines, and severe autoimmunity, ultimately leading to a high mortality rate. Transplantation of mutant mouse bone marrow into wild-type recipients was sufficient to recapitulate the phenotypes observed in the mutant animals, including autoimmunity and premature mortality. Reciprocally, transplantation of wild-type mouse bone marrow into mutant mice improved their phenotype. We conclude that C9ORF72 serves an important function within the hematopoietic system to restrict inflammation and the development of autoimmunity.
C1 [Burberry, Aaron; Suzuki, Naoki; Wang, Jin-Yuan; Moccia, Rob; Mordes, Daniel A.; Stewart, Morag H.; Suzuki-Uematsu, Satomi; Ghosh, Sulagna; Singh, Ajay; Merkle, Florian T.; Koszka, Kathryn; Zon, Leonard; Rossi, Derrick J.; Eggan, Kevin] Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Burberry, Aaron; Suzuki, Naoki; Wang, Jin-Yuan; Moccia, Rob; Mordes, Daniel A.; Suzuki-Uematsu, Satomi; Ghosh, Sulagna; Singh, Ajay; Merkle, Florian T.; Koszka, Kathryn; Eggan, Kevin] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Mordes, Daniel A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Stewart, Morag H.; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Li, Quan-Zhen] Univ Texas Southwestern Med Ctr, Dept Immunol, Dallas, TX 75390 USA.
[Li, Quan-Zhen] Univ Texas Southwestern Med Ctr, Dept Internal Med, Dallas, TX 75390 USA.
[Zon, Leonard; Rossi, Derrick J.; Notarangelo, Luigi D.] Harvard Med Sch, Boston, MA 02115 USA.
[Trowbridge, Jennifer J.] Jackson Lab Mammalian Genet, Bar Harbor, ME 04609 USA.
[Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
RP Eggan, K (reprint author), Harvard Univ, Harvard Stem Cell Inst, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.; Eggan, K (reprint author), Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
EM eggan@mcb.harvard.edu
FU Howard Hughes Medical Institute; p2ALS; Target ALS; NIH [5K99NS083713];
Wellcome Trust; Academy of Medical Sciences; Medical Research Council
[MR/P501967/1]; [NIH5R01NS089742]
FX K.E. was supported by the Howard Hughes Medical Institute, p2ALS, Target
ALS, and NIH5R01NS089742. F.T.M. was supported by the NIH
(5K99NS083713), the Wellcome Trust, the Academy of Medical Sciences, and
the Medical Research Council (MR/P501967/1).
NR 45
TC 7
Z9 7
U1 2
U2 23
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1946-6234
EI 1946-6242
J9 SCI TRANSL MED
JI Sci. Transl. Med.
PD JUL 13
PY 2016
VL 8
IS 347
AR 347ra93
DI 10.1126/scitranslmed.aaf6038
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DR6RW
UT WOS:000380030000002
PM 27412785
ER
PT J
AU Loscertales, M
Nicolaou, F
Jeanne, M
Longoni, M
Gould, DB
Sun, YW
Maalouf, FI
Nagy, N
Donahoe, PK
AF Loscertales, Maria
Nicolaou, Fotini
Jeanne, Marion
Longoni, Mauro
Gould, Douglas B.
Sun, Yunwei
Maalouf, Faouzi I.
Nagy, Nandor
Donahoe, Patricia K.
TI Type IV collagen drives alveolar epithelial-endothelial association and
the morphogenetic movements of septation
SO BMC BIOLOGY
LA English
DT Article
DE Type IV collagen; Basement membrane; Blood-gas barrier; Alveolar
development; Lung epithelium; Lung vasculature; Alveolar myofibroblast
migration and differentiation
ID CHRONIC LUNG-DISEASE; GROWTH-FACTOR; BASEMENT-MEMBRANE; COL4A2
MUTATIONS; GENE-EXPRESSION; MOUSE-LUNG; BRONCHOPULMONARY DYSPLASIA;
PERINATAL LETHALITY; HEMORRHAGIC STROKE; DEFICIENT MICE
AB Background: Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown.
Results: We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture.
Conclusions: Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum.
C1 [Loscertales, Maria; Nicolaou, Fotini; Longoni, Mauro; Sun, Yunwei; Maalouf, Faouzi I.; Nagy, Nandor; Donahoe, Patricia K.] Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA.
[Loscertales, Maria; Longoni, Mauro; Nagy, Nandor; Donahoe, Patricia K.] Harvard Med Sch, Dept Surg, Boston, MA 02115 USA.
[Jeanne, Marion; Gould, Douglas B.] Univ Calif San Francisco, Sch Med, Inst Human Genet, Dept Ophthalmol, San Francisco, CA 94143 USA.
[Jeanne, Marion; Gould, Douglas B.] Univ Calif San Francisco, Sch Med, Inst Human Genet, Dept Anat, San Francisco, CA 94143 USA.
[Nagy, Nandor] Semmelweis Univ, Dept Human Anat Histol & Embryol, Fac Med, H-1094 Budapest, Hungary.
[Donahoe, Patricia K.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Loscertales, M (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA.; Loscertales, M (reprint author), Harvard Med Sch, Dept Surg, Boston, MA 02115 USA.
EM MLOSCERTALES@mgh.harvard.edu
FU NICHD [P01HD068250]; NINDS [R01NS083830]
FX We thank Adam Tracy, Regis Hila and Pooja Bhayani for technical
assistance, and Drucilla J Roberts, M.D., Allan Goldstein, M.D., and
Casey Kelleher, M.D., for advice, discussions and careful revision of
the manuscript. Funding was provided by NICHD P01HD068250 (to PKD) and
NINDS R01NS083830 (to DBG).
NR 74
TC 3
Z9 3
U1 3
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1741-7007
J9 BMC BIOL
JI BMC Biol.
PD JUL 13
PY 2016
VL 14
AR 59
DI 10.1186/s12915-016-0281-2
PG 21
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA DR3BJ
UT WOS:000379777300001
PM 27412481
ER
PT J
AU Huang, F
Dong, JX
Kong, J
Wang, HC
Meng, H
Spaeth, RB
Camhi, S
Liao, X
Li, X
Zhai, X
Li, SY
Zhu, B
Rong, PJ
AF Huang, Feng
Dong, Jianxun
Kong, Jian
Wang, Hongcai
Meng, Hong
Spaeth, Rosa B.
Camhi, Stephanie
Liao, Xing
Li, Xia
Zhai, Xu
Li, Shaoyuan
Zhu, Bing
Rong, Peijing
TI Effect of transcutaneous auricular vagus nerve stimulation on impaired
glucose tolerance: a pilot randomized study (vol 14, 203, 2016)
SO BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE
LA English
DT Correction
C1 [Huang, Feng; Wang, Hongcai; Meng, Hong; Zhai, Xu; Li, Shaoyuan; Zhu, Bing; Rong, Peijing] China Acad Chinese Med Sci, Inst Acu Mox, 16 Nanxiao St, Beijing 100700, Peoples R China.
[Huang, Feng; Li, Xia] Beijing Univ Chinese Med, Beijing 100029, Peoples R China.
[Dong, Jianxun] Capital Univ Med Sci, Beijing Hosp TCM, Beijing 100010, Peoples R China.
[Kong, Jian; Spaeth, Rosa B.; Camhi, Stephanie] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
[Camhi, Stephanie] Endicott Coll, Dept Psychol, Beverly, MA USA.
[Liao, Xing] China Acad Chinese Med Sci, Inst Basic Res Clin Med, Beijing 100700, Peoples R China.
RP Rong, PJ (reprint author), China Acad Chinese Med Sci, Inst Acu Mox, 16 Nanxiao St, Beijing 100700, Peoples R China.
EM drrongpj@163.com
NR 1
TC 0
Z9 0
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-6882
J9 BMC COMPLEM ALTERN M
JI BMC Complement. Altern. Med.
PD JUL 13
PY 2016
VL 16
AR 218
DI 10.1186/s12906-016-1190-1
PG 4
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA DR3RG
UT WOS:000379819700007
ER
PT J
AU Cox, AR
Barrandon, O
Cai, EP
Rios, JS
Chavez, J
Bonnyman, CW
Lam, CJ
Yi, P
Melton, DA
Kushner, JA
AF Cox, Aaron R.
Barrandon, Ornella
Cai, Erica P.
Rios, Jacqueline S.
Chavez, Julia
Bonnyman, Claire W.
Lam, Carol J.
Yi, Peng
Melton, Douglas A.
Kushner, Jake A.
TI Resolving Discrepant Findings on ANGPTL8 in beta-Cell Proliferation: A
Collaborative Approach to Resolving the Betatrophin Controversy
SO PLOS ONE
LA English
DT Article
ID MALTOSE-BINDING-PROTEIN; METABOLISM; GENE; MICE
AB The beta-cell mitogenic effects of ANGPTL8 have been subjected to substantial debate. The original findings suggested that ANGPTL8 overexpression in mice induced a 17-fold increase in beta-cell proliferation. Subsequent studies in mice contested this claim, but a more recent report in rats supported the original observations. These conflicting results might be explained by variable ANGPTL8 expression and differing methods of beta-cell quantification. To resolve the controversy, three independent labs collaborated on a blinded study to test the effects of ANGPTL8 upon beta-cell proliferation. Recombinant human betatrophin (hBT) fused to maltose binding protein (MBP) was delivered to mice by intravenous injection. The results demonstrate that ANGPTL8 does not stimulate significant beta-cell proliferation. Each lab employed different methods for beta-cell identification, resulting in variable quantification of beta-cell proliferation and suggests a need for standardizing practices for beta-cell quantification. We also observed a new action of ANGPTL8 in stimulating CD45(+) hematopoietic-derived cell proliferation which may explain, in part, published discrepancies. Overall, the hypothesis that ANGPTL8 induces dramatic and specific beta-cell proliferation can no longer be supported. However, while ANGPTL8 does not stimulate robust beta-cell proliferation, the original experimental model using drug-induced (S961) insulin resistance was validated in subsequent studies, and thus still represents a robust system for studying signals that are either necessary or sufficient for beta-cell expansion. As an added note, we would like to commend collaborative group efforts, with repetition of results and procedures in multiple laboratories, as an effective method to resolve discrepancies in the literature.
C1 [Cox, Aaron R.; Rios, Jacqueline S.; Chavez, Julia; Bonnyman, Claire W.; Lam, Carol J.; Kushner, Jake A.] Texas Childrens Hosp, Baylor Coll Med, McNair Med Inst, Pediat Diabet & Endocrinol, Houston, TX 77030 USA.
[Barrandon, Ornella; Cai, Erica P.; Yi, Peng; Melton, Douglas A.] Harvard Univ, Harvard Stem Cell Inst, Stem Cell & Regenerat Biol, Cambridge, MA USA.
[Cai, Erica P.; Yi, Peng] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA.
RP Kushner, JA (reprint author), Texas Childrens Hosp, Baylor Coll Med, McNair Med Inst, Pediat Diabet & Endocrinol, Houston, TX 77030 USA.
EM kushner@bcm.edu
FU National Institutes of Health (NIH NIA) [1R01AG04101]; Howard Hughes
Medical Institute (HHMI); Harvard Stem Cell Institute; Robert and Janice
McNair Foundation; Diabetes Research Center at Baylor College of
Medicine
FX This work was supported by the National Institutes of Health (NIH NIA -
1R01AG04101) (www.nia.nih.gov), the Howard Hughes Medical Institute
(HHMI) (www.hhmi.org), the Harvard Stem Cell Institute
(hsci.harvard.edu), the Robert and Janice McNair Foundation
(www.mcnairfoundation.org) and the Diabetes Research Center at Baylor
College of Medicine (www.bcm.edu/research/centers/diabetesresearch/).
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 14
TC 1
Z9 1
U1 5
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 13
PY 2016
VL 11
IS 7
AR e0159276
DI 10.1371/journal.pone.0159276
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ9CP
UT WOS:000379508300076
PM 27410263
ER
PT J
AU Iandiorio, MJ
Fair, JM
Chatzipanagiotou, S
Ioannidis, A
Trikka-Graphakos, E
Charalampaki, N
Sereti, C
Tegos, GP
Hoogesteijn, AL
Rivas, AL
AF Iandiorio, Michelle J.
Fair, Jeanne M.
Chatzipanagiotou, Stylianos
Ioannidis, Anastasios
Trikka-Graphakos, Eleftheria
Charalampaki, Nikoletta
Sereti, Christina
Tegos, George P.
Hoogesteijn, Almira L.
Rivas, Ariel L.
TI Preventing Data Ambiguity in Infectious Diseases with Four-Dimensional
and Personalized Evaluations
SO PLOS ONE
LA English
DT Article
ID RESISTANT STAPHYLOCOCCUS-AUREUS; SYSTEMS BIOLOGY; IN-VITRO; EMERGENCE;
CHALLENGES; IMMUNITY; MODELS; HETEROGENEITY; HOMEOSTASIS; UNFOLDOMICS
AB Background
Diagnostic errors can occur, in infectious diseases, when anti-microbial immune responses involve several temporal scales. When responses span from nanosecond to week and larger temporal scales, any pre-selected temporal scale is likely to miss some (faster or slower) responses. Hoping to prevent diagnostic errors, a pilot study was conducted to evaluate a four-dimensional (4D) method that captures the complexity and dynamics of infectious diseases.
Methods
Leukocyte-microbial-temporal data were explored in canine and human (bacterial and/or viral) infections, with: (i) a non-structured approach, which measures leukocytes or microbes in isolation; and (ii) a structured method that assesses numerous combinations of interacting variables. Four alternatives of the structured method were tested: (i) a noise-reduction oriented version, which generates a single (one data point-wide) line of observations; (ii) a version that measures complex, three-dimensional (3D) data interactions; (iii) a non-numerical version that displays temporal data directionality (arrows that connect pairs of consecutive observations); and (iv) a full 4D (single line-, complexity-, directionality-based) version.
Results
In all studies, the non-structured approach revealed non-interpretable ( ambiguous) data: observations numerically similar expressed different biological conditions, such as recovery and lack of recovery from infections. Ambiguity was also found when the data were structured as single lines. In contrast, two or more data subsets were distinguished and ambiguity was avoided when the data were structured as complex, 3D, single lines and, in addition, temporal data directionality was determined. The 4D method detected, even within one day, changes in immune profiles that occurred after antibiotics were prescribed.
Conclusions
Infectious disease data may be ambiguous. Four-dimensional methods may prevent ambiguity, providing earlier, in vivo, dynamic, complex, and personalized information that facilitates both diagnostics and selection or evaluation of anti-microbial therapies.
C1 [Iandiorio, Michelle J.; Rivas, Ariel L.] Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA.
[Fair, Jeanne M.] Los Alamos Natl Lab, Global Secur, Mailstop M888, Los Alamos, NM 87545 USA.
[Chatzipanagiotou, Stylianos] Univ Athens, Sch Med, Aeginition Hosp, Dept Biopathol & Clin Microbiol, Athens, Greece.
[Ioannidis, Anastasios] Univ Peloponnese, Fac Human Movement & Qual Life Sci, Dept Nursing, Sparta, Greece.
[Trikka-Graphakos, Eleftheria; Charalampaki, Nikoletta; Sereti, Christina] Thriasio Gen Hosp, Dept Clin Microbiol, Magoula, Greece.
[Tegos, George P.] Torrey Pines Inst Mol Studies, Port St Lucie, FL USA.
[Tegos, George P.] Harvard Med Sch, Dept Dermatol, Boston, MA USA.
[Tegos, George P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Hoogesteijn, Almira L.] Ctr Invest Avanzadas, Dept Human Ecol, Merida, Mexico.
[Rivas, Ariel L.] Univ New Mexico, Sch Med, Ctr Global Hlth, Div Infect Dis, Albuquerque, NM 87131 USA.
RP Rivas, AL (reprint author), Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA.; Rivas, AL (reprint author), Univ New Mexico, Sch Med, Ctr Global Hlth, Div Infect Dis, Albuquerque, NM 87131 USA.
EM alrivas@unm.edu
NR 58
TC 0
Z9 0
U1 4
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 13
PY 2016
VL 11
IS 7
AR e0159001
DI 10.1371/journal.pone.0159001
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ9CP
UT WOS:000379508300047
PM 27411058
ER
PT J
AU Gao, L
Hong, XF
Guo, XP
Cao, DF
Gao, XH
DeLaney, TF
Gong, XQ
Chen, RR
Ni, JJ
Yao, Y
Wang, RZ
Chen, X
Tian, PZH
Xing, B
AF Gao, Lu
Hong, Xiafei
Guo, Xiaopeng
Cao, Dengfeng
Gao, Xiaohuan
DeLaney, Thomas F.
Gong, Xinqi
Chen, Rongrong
Ni, Jianjiao
Yao, Yong
Wang, Renzhi
Chen, Xi
Tian, Pangzehuan
Xing, Bing
TI Targeted next-generation sequencing of dedifferentiated chondrosarcoma
in the skull base reveals combined TP53 and PTEN mutations with
increased proliferation index, an implication for pathogenesis
SO ONCOTARGET
LA English
DT Article
DE dedifferentiated; chondrosarcoma; TP53; PTEN; proliferation
ID DE-DIFFERENTIATED CHONDROSARCOMA; PROGNOSTIC-FACTORS; CANCER GENOMICS;
P53 EXPRESSION; REARRANGEMENTS; OSTEOSARCOMA; DISTINCTION; COMPONENT;
LYMPHOMA; PATTERNS
AB Dedifferentiated chondrosarcoma (DDCS) is a rare disease with a dismal prognosis. DDCS consists of two morphologically distinct components: the cartilaginous and noncartilaginous components. Whether the two components originate from the same progenitor cells has been controversial. Recurrent DDCS commonly displays increased proliferation compared with the primary tumor. However, there is no conclusive explanation for this mechanism. In this paper, we present two DDCSs in the sellar region. Patient 1 exclusively exhibited a noncartilaginous component with a TP53 frameshift mutation in the pathological specimens from the first surgery. The tumor recurred after radiation therapy with an exceedingly increased proliferation index. Targeted next-generation sequencing (NGS) revealed the presence of both a TP53 mutation and a PTEN deletion in the cartilaginous and the noncartilaginous components of the recurrent tumor. Fluorescence in situ hybridization and immunostaining confirmed reduced DNA copy number and protein levels of the PTEN gene as a result of the PTEN deletion. Patient 2 exhibited both cartilaginous and noncartilaginous components in the surgical specimens. Targeted NGS of cells from both components showed neither TP53 nor PTEN mutations, making Patient 2 a naive TP53 and PTEN control for comparison. In conclusion, additional PTEN loss in the background of the TP53 mutation could be the cause of increased proliferation capacity in the recurrent tumor.
C1 [Gao, Lu; Guo, Xiaopeng; Yao, Yong; Wang, Renzhi; Xing, Bing] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, Beijing, Peoples R China.
[Gao, Lu; Hong, Xiafei; Guo, Xiaopeng; Chen, Rongrong; Ni, Jianjiao; Yao, Yong; Wang, Renzhi; Xing, Bing] Peking Union Med Coll, Beijing, Peoples R China.
[Hong, Xiafei] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Gen Surg, Beijing, Peoples R China.
[Cao, Dengfeng] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA.
[Gao, Xiaohuan; Chen, Xi; Tian, Pangzehuan] BGI Tianjin, Binhai Genom Inst, Tianjin, Peoples R China.
[Gao, Xiaohuan; Chen, Xi; Tian, Pangzehuan] BGI Tianjin, Tianjin Translat Genom Ctr, Tianjin, Peoples R China.
[DeLaney, Thomas F.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA.
[Gong, Xinqi] Renmin Univ China, Inst Math Sci, Beijing, Peoples R China.
[Chen, Rongrong] Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Beijing, Peoples R China.
[Chen, Rongrong] Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, Beijing, Peoples R China.
[Ni, Jianjiao] Chinese Acad Med Sci, Peking Union Med Coll, Dept Med Oncol, Beijing, Peoples R China.
[Gao, Xiaohuan] Jingke Biotech, Dept Canc Res, Guangzhou, Guangdong, Peoples R China.
RP Xing, B (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, Beijing, Peoples R China.; Xing, B (reprint author), Peking Union Med Coll, Beijing, Peoples R China.
EM xingbingemail@aliyun.com
NR 43
TC 0
Z9 0
U1 3
U2 3
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 12
PY 2016
VL 7
IS 28
BP 43557
EP 43569
DI 10.18632/oncotarget.9618
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY8QU
UT WOS:000385395700054
PM 27248819
ER
PT J
AU Loffler, H
Pfarr, N
Kriegsmann, M
Endris, V
Hielscher, T
Lohneis, P
Folprecht, G
Stenzinger, A
Dietel, M
Weichert, W
Kramer, A
AF Loeffler, Harald
Pfarr, Nicole
Kriegsmann, Mark
Endris, Volker
Hielscher, Thomas
Lohneis, Philipp
Folprecht, Gunnar
Stenzinger, Albrecht
Dietel, Manfred
Weichert, Wilko
Kraemer, Alwin
TI Molecular driver alterations and their clinical relevance in cancer of
unknown primary site
SO ONCOTARGET
LA English
DT Article
DE CUP; carcinoma of unknown primary; massive parallel sequencing; driver
mutations; p53
ID LUNG-CANCER; PERSONALIZED MEDICINE; BREAST-CANCER; TP53 MUTATION;
PRIMARY TUMOR; P53 GENE; CARCINOMA; DIAGNOSIS; SURVIVAL; THERAPY
AB Cancer of unknown primary (CUP) is defined as metastatic solid malignancy where no primary tumor is detected despite appropriate staging. About 90% of CUP represent adenocarcinoma or undifferentiated carcinoma. Since therapy regimens are only modestly effective, identification of the molecular landscape of these neoplasms might be a promising approach to direct CUP therapy and aid in tumor classification. We screened a cohort of 128 patients with adenocarcinoma or undifferentiated carcinoma meeting the definition of CUP. Massive parallel multigene sequencing of 50 genes, which had been selected due to their relevance as oncogenic drivers or druggable molecular targets could ultimately be performed on samples from 55 patients for whom complete clinical datasets were also available. Overall, 60 tumor-specific mutations and 29 amplifications/deletions, as revealed by coverage analysis, were detected in 46 cases (84%). The most frequently mutated genes were TP53 (30 cases, 55%), KRAS (9 cases, 16%), CDKN2A (5 cases, 9%), and SMAD4 (5 cases, 9%). The most frequently deleted gene was CDKN2A (8 cases, 15%). KRAS and CDKN2A mutations significantly correlated with poor progression-free survival (PFS) and, in case of KRAS, overall survival (OS). WIldtype TP53 and female sex defined a relatively favorable category, with favorable PFS and OS. 8 cases (15%) harbored mutations that may be targetable by currently approved drugs. Taken together, Mutations of relevant driver genes are present in the vast majority of CUP tumors. Some of them impact on prognosis and a subset is putatively druggable.
C1 [Loeffler, Harald; Kraemer, Alwin] Heidelberg Univ, Clin Cooperat Unit Mol Hematol Oncol, German Canc Res Ctr DKFZ, Heidelberg, Germany.
[Loeffler, Harald; Kraemer, Alwin] Heidelberg Univ, Dept Med 5, Heidelberg, Germany.
[Pfarr, Nicole; Kriegsmann, Mark; Endris, Volker; Stenzinger, Albrecht; Weichert, Wilko] Heidelberg Univ, Inst Pathol, Heidelberg, Germany.
[Pfarr, Nicole; Weichert, Wilko] Tech Univ Munich, Inst Pathol, Munich, Germany.
[Hielscher, Thomas] German Canc Res Ctr, Div Biostat, Heidelberg, Germany.
[Lohneis, Philipp; Dietel, Manfred] Charite, Inst Pathol, Berlin, Germany.
[Folprecht, Gunnar] Univ Hosp Carl Gustav Carus, Dept Med 1, Dresden, Germany.
[Stenzinger, Albrecht] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Integrated Diagnost, Dept Pathol, Boston, MA USA.
[Weichert, Wilko] Natl Ctr Tumor Dis NCT, Heidelberg, Germany.
[Weichert, Wilko; Kraemer, Alwin] German Canc Consortium DKTK, Heidelberg, Germany.
RP Kramer, A (reprint author), Heidelberg Univ, Clin Cooperat Unit Mol Hematol Oncol, German Canc Res Ctr DKFZ, Heidelberg, Germany.; Kramer, A (reprint author), Heidelberg Univ, Dept Med 5, Heidelberg, Germany.; Weichert, W (reprint author), Heidelberg Univ, Inst Pathol, Heidelberg, Germany.; Weichert, W (reprint author), Tech Univ Munich, Inst Pathol, Munich, Germany.; Weichert, W (reprint author), Natl Ctr Tumor Dis NCT, Heidelberg, Germany.; Weichert, W; Kramer, A (reprint author), German Canc Consortium DKTK, Heidelberg, Germany.
EM wilko.weichert@tum.de; a.kraemer@dkfz.de
RI Folprecht, Gunnar/F-8638-2011
OI Folprecht, Gunnar/0000-0002-9321-9911
FU Arbeitsgemeinschaft Internistische Onkologie; Deutsche Krebsgesellschaft
(German Cancer Society); German Cancer Consortium (DKTK)
FX This work was supported by the Arbeitsgemeinschaft Internistische
Onkologie, Deutsche Krebsgesellschaft (German Cancer Society) and the
German Cancer Consortium (DKTK). Further, we acknowledge excellent
technical assistance by Kathrin Ridinger, Katja Lorenz and Jennifer
Gruber.
NR 38
TC 0
Z9 0
U1 1
U2 1
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 12
PY 2016
VL 7
IS 28
BP 44322
EP 44329
DI 10.18632/oncotarget.10035
PG 8
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY8QU
UT WOS:000385395700109
PM 27322425
ER
PT J
AU Han, SW
Ma, XM
Zhao, YX
Zhao, HY
Batista, A
Zhou, S
Zhou, XN
Yang, Y
Wang, TT
Bi, JT
Xia, Z
Bai, ZG
Garkavtsev, I
Zhang, ZT
AF Han, Shiwei
Ma, Xuemei
Zhao, Yanxia
Zhao, Hongying
Batista, Ana
Zhou, Sheng
Zhou, Xiaona
Yang, Yao
Wang, Tingting
Bi, Jingtao
Xia, Zheng
Bai, Zhigang
Garkavtsev, Igor
Zhang, Zhongtao
TI Identification of Glypican-3 as a potential metastasis suppressor gene
in gastric cancer
SO ONCOTARGET
LA English
DT Article
DE gastric cancer; Glypican-3; metastasis; FoxM1; Erk1/2
ID GOLABI-BEHMEL-SYNDROME; FOXM1; OVERGROWTH; EXPRESSION; PATHWAYS;
THERAPY; KINASE; TARGET; TUMORS; CELLS
AB Gastric cancer is a prevalent tumor that is usually detected at an advanced metastatic stage. Currently, standard therapies are mostly ineffective. Here, we report that Glypican-3 (GPC3) is absent in invasive tumors and metastatic lymph nodes, in particular in aggressive and highly disseminated signet ring cell carcinomas. We demonstrate that loss of GPC3 correlates with poor overall survival in patients. Moreover, we show that absence of GPC3 causes up-regulation of MAPK/FoxM1 signaling and that blockade of this pathway alters cellular invasion. An inverse correlation between GPC3 and FoxM1 is also shown in patient samples. These data identify GPC3 as a potential metastasis suppressor gene and suggest its value as a prognostic marker in gastric cancer. Development of therapies targeting signaling downstream of GPC3 are warranted.
C1 [Han, Shiwei; Ma, Xuemei; Zhou, Xiaona; Yang, Yao; Wang, Tingting; Bai, Zhigang; Zhang, Zhongtao] Capital Med Univ, Beijing Friendship Hosp, Dept Gen Surg, Beijing, Peoples R China.
[Han, Shiwei; Batista, Ana; Garkavtsev, Igor] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Han, Shiwei; Ma, Xuemei; Zhou, Xiaona; Yang, Yao; Wang, Tingting; Bai, Zhigang; Zhang, Zhongtao] Beijing Key Lab Canc Invas & Metastasis Res, Beijing, Peoples R China.
[Han, Shiwei; Ma, Xuemei; Zhou, Xiaona; Yang, Yao; Wang, Tingting; Bai, Zhigang; Zhang, Zhongtao] Natl Clin Res Ctr Digest Dis, Beijing, Peoples R China.
[Zhao, Yanxia] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Ctr Canc, Wuhan, Peoples R China.
[Zhao, Hongying] Capital Med Univ, Beijing Chaoyang Hosp, Dept Pathol, Beijing, Peoples R China.
[Zhou, Sheng] Huazhong Univ Sci & Technol, Inst Pathol, Union Hosp, Tongji Med Coll, Wuhan, Peoples R China.
[Bi, Jingtao] Peking Univ, Dept Gen Surg, Beijing Jishuitan Hosp, Med Coll 4, Beijing, Peoples R China.
[Xia, Zheng] Cent S Univ, Dept Surg, Xiangya Hosp, Changsha, Hunan, Peoples R China.
RP Han, SW; Zhang, ZT (reprint author), Capital Med Univ, Beijing Friendship Hosp, Dept Gen Surg, Beijing, Peoples R China.; Han, SW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Han, SW; Zhang, ZT (reprint author), Beijing Key Lab Canc Invas & Metastasis Res, Beijing, Peoples R China.; Han, SW; Zhang, ZT (reprint author), Natl Clin Res Ctr Digest Dis, Beijing, Peoples R China.
EM shiwei@steele.mgh.harvard.edu; zhangzht@medmail.com.cn
FU National Natural Science Foundation of China [30972887, 81402197,
81172317]; Beijing Municipal Administration of Hospitals Clinical
Medicine Development of Special Funding [ZYLX201504]; Capital Medical
University
FX We would like to thank Dr. Susan Hagen (Beth Israel Deaconess Medical
Center, Harvard Medical School) for providing the human MKN28 cell line;
Drs. Mitchell Ho (NIH), Genevieve Boland, Jelena Grahovac, Julien
Daubriac, Mei Ng, Thomas Reiberger (Massachusetts General Hospital,
Harvard Medicial School) for critically reviewing the manuscript; and
Victoria Xiao (Massachusetts General Hospital) for editing the
manuscript. This research was supported by grants from the National
Natural Science Foundation of China (no. 30972887 to ZZ), the Beijing
Municipal Administration of Hospitals Clinical Medicine Development of
Special Funding (no. ZYLX201504 to ZZ), the National Natural Science
Foundation of China (no. 81402197 to YZ) and the National Natural
Science Foundation of China (no. 81172317 to ZB). S.H. received a
doctoral joint training fellowship from Capital Medical University.
NR 30
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PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 12
PY 2016
VL 7
IS 28
BP 44406
EP 44416
DI 10.18632/oncotarget.9763
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY8QU
UT WOS:000385395700116
PM 27259271
ER
PT J
AU Zhang, W
Yu, XQ
Kwak, M
Xu, L
Zhang, LJ
Yu, Q
Jin, JO
AF Zhang, Wei
Yu, Xiaoqian
Kwak, Minseok
Xu, Li
Zhang, Lijun
Yu, Qing
Jin, Jun-O
TI Maturation of dendritic cells by pullulan promotes anti-cancer effect
SO ONCOTARGET
LA English
DT Article
DE pullulan; adjuvant; dendritic cell; immunotherapy; anti-cancer
ID IMMUNE-RESPONSES; CANCER-IMMUNOTHERAPY; T-CELLS; ADJUVANT; VACCINES;
SURVIVAL; NANOGEL; SUBSET; SYSTEM; BLOOD
AB Previous studies have demonstrated that pullulan, a polysaccharide purified from Aureobasidium pullulans, has immune-stimulatory effects on T and B cells. Moreover, pullulan has been used as a carrier in the delivery of the antigen (Ag) peptide to lymphoid tissues. However, the in vivo effect of pullulan on dendritic cells (DC) has not been well characterized. In this study, we assessed the effect of pullulan on DC activation and anti-cancer immunity. The results showed that the pullulan treatment up-regulated co-stimulatory molecule expression and enhanced pro-inflammatory cytokine production in bone marrow-derived DCs (BMDC) in vitro and in spleen DCs in vivo. Moreover, the combination of ovalbumin (OVA) and pullulan induced OVA antigen-specific T cell activations in vivo. In tumor-bearing mice, pullulan induced the maturation of DCs in spleen and tumor draining lymph node (drLN), and promoted the OVA-specific T cell activation and migration of the T cells into the tumor. In addition, the combination of OVA and pullulan inhibited B16-OVA tumor growth and liver metastasis. The combination of tyrosinase-related protein 2 (TRP2) peptide and pullulan treatment also suppressed B16 melanoma growth. Thus, the results demonstrated that pullulan enhanced DC maturation and function, and it acted as an adjuvant in promoting Ag-specific immune responses in mice. Thus, pullulan could be a new and useful adjuvant for use in therapeutic cancer vaccines.
C1 [Zhang, Wei; Xu, Li; Zhang, Lijun; Jin, Jun-O] Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China.
[Yu, Xiaoqian] Peking Univ, Periodontal Dept, Sch & Hosp Stomatol, Beijing, Peoples R China.
[Kwak, Minseok] Pukyong Natl Univ, Dept Chem, Busan, South Korea.
[Yu, Qing] Forsyth Inst, Dept Immunol & Infect Dis, Cambridge, MA USA.
[Yu, Qing] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA.
RP Jin, JO (reprint author), Fudan Univ, Shanghai Med Coll, Shanghai Publ Hlth Clin Ctr, Shanghai, Peoples R China.
EM Junojin1@gmail.com
OI Kwak, Minseok/0000-0002-0480-1804
FU National Natural Science Foundation of China [81550110507, 81271834,
81470740]; National 863 Project of China [2014AA021403]; National
Research Foundation of Korea Grant; Korean Government
[NRF-2014R1A1A2059063]
FX We thank the Shanghai Public Health Clinical Center animal facility for
maintaining the animals in this study. This study was supported by
Research Fund for International Young Scientists from National Natural
Science Foundation of China (81550110507). LiJun Zhang was supported by
the National Natural Science Foundation of China (81271834) and the
National 863 Project of China (2014AA021403). Xiaoqian Yu was supported
by the National Nature Science Foundation of China (81470740). Minseok
Kwak was supported by the National Research Foundation of Korea Grant,
which is funded by the Korean Government (NRF-2014R1A1A2059063).
NR 35
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U2 4
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 12
PY 2016
VL 7
IS 28
BP 44644
EP 44659
DI 10.18632/oncotarget.10183
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY8QU
UT WOS:000385395700135
PM 27341129
ER
PT J
AU Patel, KR
Ramsey, LE
Metcalf, NV
Shulman, GL
Corbetta, M
AF Patel, Kevin R.
Ramsey, Lenny E.
Metcalf, Nicholas V.
Shulman, Gordon L.
Corbetta, Maurizio
TI Early diffusion evidence of retrograde transsynaptic degeneration in the
human visual system
SO NEUROLOGY
LA English
DT Article
ID OPTICAL COHERENCE TOMOGRAPHY; RETINAL GANGLION-CELLS; HOMONYMOUS
HEMIANOPIA; AXONAL DEGENERATION; AUTOMATED PERIMETRY; TRACT
DEGENERATION; MULTIPLE-SCLEROSIS; FIELD DEFECTS; INFARCTION; RECOVERY
AB Objective: We investigated whether diffusion tensor imaging (DTI) indices of white matter integrity would offer early markers of retrograde transsynaptic degeneration (RTD) in the visual system after stroke.
Methods: We performed a prospective longitudinal analysis of the sensitivity of DTI markers of optic tract health in 12 patients with postsynaptic visual pathway stroke, 12 stroke controls, and 28 healthy controls. We examined group differences in (1) optic tract fractional anisotropy (FA-asymmetry), (2) perimetric measures of visual impairment, and (3) the relationship between FA-asymmetry and perimetric assessment.
Results: FA-asymmetry was higher in patients with visual pathway lesions than in control groups. These differences were evident 3 months from the time of injury and did not change significantly at 12 months. Perimetric measures showed evidence of impairment in participants with visual pathway stroke but not in control groups. A significant association was observed between FA-asymmetry and perimetric measures at 3 months, which persisted at 12 months.
Conclusions: DTI markers of RTD are apparent 3 months from the time of injury. This represents the earliest noninvasive evidence of RTD in any species. Furthermore, these measures associate with measures of visual impairment. DTI measures offer a reproducible, noninvasive, and sensitive method of investigating RTD and its role in visual impairment.
C1 [Patel, Kevin R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Ramsey, Lenny E.; Metcalf, Nicholas V.; Shulman, Gordon L.; Corbetta, Maurizio] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Corbetta, Maurizio] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Corbetta, Maurizio] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA.
[Corbetta, Maurizio] Univ Padua, Dept Neurosci, I-35100 Padua, Italy.
RP Patel, KR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
EM kpatel40@mgh.harvard.edu
FU National Institute of Mental Health [RO1 NS095741, 5R01HD061117-07];
Rehabilitation Institute of St. Louis
FX This study was supported by the National Institute of Mental Health (RO1
NS095741 to M.C.) and the Rehabilitation Institute of St. Louis. The
author(s) disclosed receipt of the following financial support for the
research and/or authorship of this article: This study was supported by
the National Institute of Mental Health (5R01HD061117-07 to M.C.) and
the Rehabilitation Institute of St. Louis.
NR 34
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U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 12
PY 2016
VL 87
IS 2
BP 198
EP 205
DI 10.1212/WNL.0000000000002841
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DT4SI
UT WOS:000381470700040
PM 27306632
ER
PT J
AU Sridharan, V
Margalit, DN
Lynch, SA
Severgnini, M
Zhou, J
Chau, NG
Rabinowits, G
Lorch, JH
Hammerman, PS
Hodi, FS
Haddad, RI
Tishler, RB
Schoenfeld, JD
AF Sridharan, Vishwajith
Margalit, Danielle N.
Lynch, Stephanie A.
Severgnini, Mariano
Zhou, Jun
Chau, Nicole G.
Rabinowits, Guilherme
Lorch, Jochen H.
Hammerman, Peter S.
Hodi, F. Stephen
Haddad, Robert I.
Tishler, Roy B.
Schoenfeld, Jonathan D.
TI Definitive chemoradiation alters the immunologic landscape and immune
checkpoints in head and neck cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE immune checkpoint; cytokines; radiation; head and neck cancer; PD-1;
tumour antigens; anti-tumour immunity; abscopal
ID CELL LUNG-CANCER; TUMOR-INFILTRATING LYMPHOCYTES; DEATH LIGAND 1;
T-CELLS; ANTITUMOR IMMUNITY; CHEMOKINE CXCL16; OROPHARYNGEAL CANCER;
HUMAN-PAPILLOMAVIRUS; METASTATIC MELANOMA; COLORECTAL-CANCER
AB Background: Preclinical and clinical studies suggest potential synergy between high dose per fraction focal radiation and immunotherapy. However, conventionally fractionated radiation regimens in combination with concurrent chemotherapy are more commonly administered to patients as definitive treatment and may have both immune-stimulating and -suppressive effects.
Methods: We prospectively collected longitudinal samples from head and neck squamous cell carcinoma patients receiving definitive radiation therapy. We quantified changes in populations of circulating immune cells and chemokines CXCL9, 10, and 16. Analyses of humoral and cellular immune responses were conducted in select patients via proteomic analysis and T-cell receptor sequencing.
Results: Treatment not only increased circulating CD-8+ T-effector cells, but also myeloid-derived suppressor cells, regulatory T cells, and checkpoint receptor-expressing T cells, particularly PD-1+ T cells. Significant decreases in CXCL10 and increases in CXLC16 were noted. Treatment also increased the percentage of unique and dominant TCR clones, and increased humoral responses as measured by proteomic array.
Conclusions: Our results suggest that fractionated chemoradiation leads to quantifiable effects in circulating immune mediators, including a balance of stimulatory and suppressive mechanisms. These results suggest future combinations with immune checkpoint blockade.
C1 [Sridharan, Vishwajith; Margalit, Danielle N.; Lynch, Stephanie A.; Tishler, Roy B.; Schoenfeld, Jonathan D.] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
[Sridharan, Vishwajith] Harvard Med Sch, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA.
[Severgnini, Mariano; Zhou, Jun; Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA.
[Chau, Nicole G.; Rabinowits, Guilherme; Lorch, Jochen H.; Hammerman, Peter S.; Hodi, F. Stephen; Haddad, Robert I.] Brigham & Womens Hosp, Dept Med Oncol, Dana Farber Canc Ctr, 75 Francis St, Boston, MA 02115 USA.
RP Schoenfeld, JD (reprint author), Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.
EM jdschoenfeld@partners.org
FU Claudia Adams Barr Program for Innovative Cancer Research; Joint Center
for Radiation Therapy; Harvard Catalyst; Harvard Clinical and
Translational Science Center (National Center for Research Resources);
Harvard Clinical and Translational Science Center (National Center for
Advancing Translational Sciences, National Institutes of Health) [UL1
TR001102]; Harvard University and its affiliated academic health-care
centres
FX JDS is supported by the Claudia Adams Barr Program for Innovative Cancer
Research and the Joint Center for Radiation Therapy. We acknowledge
assistance provided by the Center for Immuno-Oncology at the Dana-Farber
Cancer Institute. This work was conducted with support from Harvard
Catalyst, The Harvard Clinical and Translational Science Center
(National Center for Research Resources and the National Center for
Advancing Translational Sciences, National Institutes of Health Award
UL1 TR001102), and financial contributions from Harvard University and
its affiliated academic health-care centres. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of Harvard Catalyst, Harvard University, and its
affiliated academic health-care centres, or the National Institutes of
Health.
NR 58
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUL 12
PY 2016
VL 115
IS 2
BP 252
EP 260
DI 10.1038/bjc.2016.166
PG 9
WC Oncology
SC Oncology
GA DS1SR
UT WOS:000380380300014
PM 27380136
ER
PT J
AU Jarvis, D
Mitchell, JS
Law, PJ
Palin, K
Tuupanen, S
Gylfe, A
Hanninen, UA
Cajuso, T
Tanskanen, T
Kondelin, J
Kaasinen, E
Sarin, AP
Kaprio, J
Eriksson, JG
Rissanen, H
Knekt, P
Pukkala, E
Jousilahti, P
Salomaa, V
Ripatti, S
Palotie, A
Jarvinen, H
Renkonen-Sinisalo, L
Lepisto, A
Bohm, J
Mecklin, JP
Al-Tassan, NA
Palles, C
Martin, L
Barclay, E
Farrington, SM
Timofeeva, MN
Meyer, BF
Wakil, SM
Campbell, H
Smith, CG
Idziaszczyk, S
Maughan, TS
Kaplan, R
Kerr, R
Kerr, D
Buchanan, DD
Win, AK
Hopper, JL
Jenkins, MA
Lindor, NM
Newcomb, PA
Gallinger, S
Conti, D
Schumacher, F
Casey, G
Taipale, J
Aaltonen, LA
Cheadle, JP
Dunlop, MG
Tomlinson, IP
Houlston, RS
AF Jarvis, David
Mitchell, Jonathan S.
Law, Philip J.
Palin, Kimmo
Tuupanen, Sari
Gylfe, Alexandra
Hanninen, Ulrika A.
Cajuso, Tatiana
Tanskanen, Tomas
Kondelin, Johanna
Kaasinen, Eevi
Sarin, Antti-Pekka
Kaprio, Jaakko
Eriksson, Johan G.
Rissanen, Harri
Knekt, Paul
Pukkala, Eero
Jousilahti, Pekka
Salomaa, Veikko
Ripatti, Samuli
Palotie, Aarno
Jarvinen, Heikki
Renkonen-Sinisalo, Laura
Lepisto, Anna
Bohm, Jan
Mecklin, Jukka-Pekka
Al-Tassan, Nada A.
Palles, Claire
Martin, Lynn
Barclay, Ella
Farrington, Susan M.
Timofeeva, Maria N.
Meyer, Brian F.
Wakil, Salma M.
Campbell, Harry
Smith, Christopher G.
Idziaszczyk, Shelley
Maughan, Timothy S.
Kaplan, Richard
Kerr, Rachel
Kerr, David
Buchanan, Daniel D.
Win, Aung K.
Hopper, John L.
Jenkins, Mark A.
Lindor, Noralane M.
Newcomb, Polly A.
Gallinger, Steve
Conti, David
Schumacher, Fred
Casey, Graham
Taipale, Jussi
Aaltonen, Lauri A.
Cheadle, Jeremy P.
Dunlop, Malcolm G.
Tomlinson, Ian P.
Houlston, Richard S.
TI Mendelian randomisation analysis strongly implicates adiposity with risk
of developing colorectal cancer
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Mendelian randomisation; adiposity; colorectal cancer
ID BODY-MASS INDEX; OBESITY; METAANALYSIS; EPIDEMIOLOGY; INSTRUMENTS;
WEIGHT; COMMON
AB Background: Observational studies have associated adiposity with an increased risk of colorectal cancer (CRC). However, such studies do not establish a causal relationship. To minimise bias from confounding we performed a Mendelian randomisation (MR) analysis to examine the relationship between adiposity and CRC.
Methods: We used SNPs associated with adult body mass index (BMI), waist-hip ratio (WHR), childhood obesity and birth weight as instrumental variables in a MR analysis of 9254 CRC cases and 18 386 controls.
Results: In the MR analysis, the odds ratios (ORs) of CRC risk per unit increase in BMI, WHR and childhood obesity were 1.23 (95% CI: 1.02-1.49, P = 0.033), 1.59 (95% CI: 1.08-2.34, P = 0.019) and 1.07 (95% CI: 1.03-1.13, P = 0.018), respectively. There was no evidence for association between birth weight and CRC (OR = 1.22, 95% CI: 0.89-1.67, P = 0.22). Combining these data with a concurrent MR-based analysis for BMI and WHR with CRC risk (totalling to 18 190 cases, 27 617 controls) provided increased support, ORs for BMI and WHR were 1.26 (95% CI: 1.10-1.44, P = 7.7 x 10(-4)) and 1.40 (95% CI: 1.14-1.72, P = 1.2 x 10(-3)), respectively.
Conclusions: These data provide further evidence for a strong causal relationship between adiposity and the risk of developing CRC highlighting the urgent need for prevention and treatment of adiposity.
C1 [Gylfe, Alexandra] Human Longev Inc, La Jolla, CA 92121 USA.
[Jarvis, David; Mitchell, Jonathan S.; Law, Philip J.; Houlston, Richard S.] Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
[Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Taipale, Jussi; Aaltonen, Lauri A.] Univ Helsinki, Res Programs Unit, Genome Scale Biol Res Program, FIN-00014 Helsinki, Finland.
[Palin, Kimmo; Tuupanen, Sari; Gylfe, Alexandra; Hanninen, Ulrika A.; Cajuso, Tatiana; Tanskanen, Tomas; Kondelin, Johanna; Kaasinen, Eevi; Taipale, Jussi; Aaltonen, Lauri A.] Univ Helsinki, Med, Dept Med & Clin Genet, FIN-00014 Helsinki, Finland.
[Sarin, Antti-Pekka; Kaprio, Jaakko; Ripatti, Samuli; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland, FIN-00014 Helsinki, Finland.
[Kaprio, Jaakko; Eriksson, Johan G.; Rissanen, Harri; Knekt, Paul; Jousilahti, Pekka; Salomaa, Veikko] Natl Inst Hlth & Welf, Helsinki 00271, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki 00250, Finland.
[Eriksson, Johan G.] Univ Helsinki, Helsinki Univ Hosp, Unit Gen Practice & Primary Hlth Care, FIN-00014 Helsinki, Finland.
[Pukkala, Eero] Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, Helsinki 00130, Finland.
[Pukkala, Eero] Univ Tampere, Sch Hlth Sci, Tampere 33014, Finland.
[Palotie, Aarno] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA.
[Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Palotie, Aarno] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Jarvinen, Heikki] Univ Helsinki, Cent Hosp, Hosp Dist Helsinki & Uusimaa, Dept Surg, Helsinki 00029, Finland.
[Renkonen-Sinisalo, Laura; Lepisto, Anna] Helsinki Univ Hosp Helsinki, Abdominal Ctr, Dept Surg, Helsinki 00029, Finland.
[Bohm, Jan] Cent Finland Cent Hosp, Dept Pathol, Jyvaskyla 40620, Finland.
[Mecklin, Jukka-Pekka] Univ Eastern Finland, Dept Surg, Jyvaskyla Cent Hosp, Jyvaskyla 40620, Finland.
[Al-Tassan, Nada A.; Meyer, Brian F.; Wakil, Salma M.] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 12713, Saudi Arabia.
[Palles, Claire; Martin, Lynn; Barclay, Ella; Tomlinson, Ian P.] Wellcome Trust Ctr Human Genet, NIHR Comprehens Biomed Res Ctr, Oxford OX3 7BN, England.
[Farrington, Susan M.; Timofeeva, Maria N.; Dunlop, Malcolm G.] Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Colon Canc Genet Grp, Edinburgh EH4 2XU, Midlothian, Scotland.
[Farrington, Susan M.] Univ Edinburgh, Roslin Inst, Roslin EH25 9RG, Midlothian, Scotland.
[Campbell, Harry] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Smith, Christopher G.; Idziaszczyk, Shelley; Cheadle, Jeremy P.] Cardiff Univ, Sch Med, Inst Canc & Genet, Cardiff CF14 4XN, S Glam, Wales.
[Maughan, Timothy S.] Univ Oxford, CRUK MRC Oxford Inst Radiat Oncol, Oxford OX3 7DQ, England.
[Kaplan, Richard] MRC Clin Trials Unit, Aviat House, London WC2B 6NH, England.
[Kerr, Rachel] Univ Oxford, Churchill Hosp, Oxford Canc Ctr, Dept Oncol, Oxford OX3 7LE, England.
[Kerr, David] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England.
[Buchanan, Daniel D.] Univ Melbourne, Colorectal Oncogenom Grp, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic 3010, Australia.
[Buchanan, Daniel D.; Win, Aung K.; Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ 85259 USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98109 USA.
[Gallinger, Steve] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Conti, David; Schumacher, Fred; Casey, Graham] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Taipale, Jussi] Karolinska Inst, SciLife Ctr, Dept Biosci & Nutr, SE-14183 Solna, Sweden.
RP Houlston, RS (reprint author), Inst Canc Res, Div Genet & Epidemiol, London SW7 3RP, England.
EM richard.houlston@icr.ac.uk
RI Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Dunlop,
Malcolm/F-1973-2011;
OI Jenkins, Mark/0000-0002-8964-6160; Dunlop, Malcolm/0000-0002-3033-5851;
Kaprio, Jaakko/0000-0002-3716-2455; Win, Aung Ko/0000-0002-2794-5261;
Houlston, Richard/0000-0002-5268-0242
FU Cancer Research UK (Bobby Moore Fund for Cancer Research UK)
[C1298/A8362]; National Cancer Research Network; BBRSC; Programme Grant
funding from Cancer Research UK [C348/A12076]; Oxford Comprehensive
Biomedical Research Centre; EU FP7 CHIBCHA grant; European Union
[258236]; FP7 collaborative project SYSCOL; COST Action in the UK
[BM1206]; Medical Research Council; National Institute of Health
Research Cancer Research Network; Bobby Moore Fund from Cancer Research
UK; Tenovus; Kidani Trust; Cancer Research Wales; National Institute for
Social Care and Health Research Cancer Genetics Biomedical Research
Unit; KFSHRC; Academy of Finland (Finnish Center of Excellence Program)
[250345]; Jane and Aatos Erkko Foundation; Finnish Cancer Society;
European Research Council (ERC) [268648]; Sigrid Juselius Foundation;
SYSCOL; Nordic Information for Action eScience Center (NIASC); Nordic
Center of Excellence - NordForsk [62721]; State Research Funding of
Kuopio University Hospital [B1401]; Academy of Finland [271642, 263164,
100499, 205585, 265240, 263278]; Ministry of Education and Culture,
Finland; Finnish Academy [139635]; National Institute of Alcohol Abuse
and Alcoholism [AA-12502, AA-00145, K02AA018755]; Wellcome Trust Sanger
Institute; ENGAGE-European Network for Genetic and Genomic Epidemiology,
FP7-HEALTH-F4 [201413]; National Cancer Institute [UM1 CA167551];
National Institutes of Health; CCFR centre: Australasian Colorectal
Cancer Family Registry [U01 CA074778, U01/U24 CA097735]; CCFR centre:
USC Consortium Colorectal Cancer Family Registry [U01/U24 CA074799];
CCFR centre: Mayo Clinic Cooperative Familial Registry for Colon Cancer
Studies [U01/U24 CA074800]; CCFR centre: Ontario Familial Colorectal
Cancer Registry [U01/U24 CA074783]; CCFR centre: Seattle Colorectal
Cancer Family Registry [U01/U24 CA074794]; CCFR centre: University of
Hawaii Colorectal Cancer Family Registry [U01/U24 CA074806]; National
Cancer Institute, National Institutes of Health [U01 CA122839, R01
CA143237]; Cancer Surveillance System of the Fred Hutchinson Cancer
Research Center-Control [N01-CN-67009, N01-PC-35142]; Surveillance,
Epidemiology and End Results (SEER) Program of the National Cancer
Institute [HHSN2612013000121]; Fred Hutchinson Cancer Research Center;
Hawaii Department of Health as part of the statewide cancer reporting
program; National Cancer Institute's Surveillance, Epidemiology and End
Results Program (SEER) [N01-PC-67001, N01-PC-35137, HHSN26120100037C,
HHSN261201300009I]; California Department of Public Health as part of
the statewide cancer reporting program; National Cancer Institute's
Surveillance, Epidemiology and End Results Program [HHSN261201000035C,
HHSN261201000034C]; Centers for Disease Control and Prevention's
National Program of Cancer Registries [U58DP003862-01]; [090532/Z/09/Z]
FX We are grateful to all individuals who participated in the various
studies. This study made use of genotyping data from the 1958 Birth
Cohort, kindly made available by the Wellcome Trust Case Control
Consortium 2. A full list of the investigators who contributed to the
generation of the data is available at http://www.wtccc.org.uk/. At the
Institute of Cancer Research, this work was supported by Cancer Research
UK (C1298/A8362-Bobby Moore Fund for Cancer Research UK). Additional
support was provided by the National Cancer Research Network. DJ was
supported by a summer student grant from the BBRSC. In Edinburgh, the
work was supported by Programme Grant funding from Cancer Research UK
(C348/A12076). In Oxford, additional funding was provided by the Oxford
Comprehensive Biomedical Research Centre and the EU FP7 CHIBCHA grant.
Core infrastructure support to the Wellcome Trust Centre for Human
Genetics, Oxford was provided by grant (090532/Z/09/Z). We are grateful
to many colleagues within UK Clinical Genetics Departments (for CORGI)
and to many collaborators who participated in the VICTOR and QUASAR2
trials. We also thank colleagues from the UK National Cancer Research
Network (for NSCCG). Support from the European Union (FP7/207-2013,
grant 258236) and FP7 collaborative project SYSCOL and COST Action in
the UK is also acknowledged (BM1206). The COIN and COIN-B trials were
funded by Cancer Research UK and the Medical Research Council and were
conducted with the support of the National Institute of Health Research
Cancer Research Network. COIN and COIN-B translational studies were
supported by the Bobby Moore Fund from Cancer Research UK, Tenovus, the
Kidani Trust, Cancer Research Wales and the National Institute for
Social Care and Health Research Cancer Genetics Biomedical Research Unit
(2011-2014). NAA, RPM and SMW were funded and supported by KFSHRC. In
Finland, this work was supported by grants from the Academy of Finland
(Finnish Center of Excellence Program 2012-2017, 250345), the Jane and
Aatos Erkko Foundation, the Finnish Cancer Society (to KP), the European
Research Council (ERC; 268648), the Sigrid Juselius Foundation, SYSCOL,
the Nordic Information for Action eScience Center (NIASC), the Nordic
Center of Excellence financed by NordForsk (project 62721, to KP) and
State Research Funding of Kuopio University Hospital (B1401). We
acknowledge the computational resources provided by the ELIXIR node,
hosted at the CSC-IT Center for Science, Finland, and funded by the
Academy of Finland (grants 271642 and 263164), the Ministry of Education
and Culture, Finland. VS was supported by the Finnish Academy (grant
number 139635). Sample collection and genotyping in the Finnish Twin
Cohort has been supported by the Wellcome Trust Sanger Institute,
ENGAGE-European Network for Genetic and Genomic Epidemiology,
FP7-HEALTH-F4-2007 (201413), the National Institute of Alcohol Abuse and
Alcoholism (grants AA-12502 and AA-00145 to Richard J Rose, and
K02AA018755 to Danielle M Dick) and the Academy of Finland (100499,
205585, 265240 and 263278 to Jaakko Ka.prio (JK)).; The work of the
Colon Cancer Family Registry (CCFR) was supported by the National Cancer
Institute (UM1 CA167551), National Institutes of Health and through
cooperative agreements with the following CCFR centres: Australasian
Colorectal Cancer Family Registry (U01 CA074778, U01/U24 CA097735), USC
Consortium Colorectal Cancer Family Registry (U01/U24 CA074799), Mayo
Clinic Cooperative Familial Registry for Colon Cancer Studies (U01/U24
CA074800), Ontario Familial Colorectal Cancer Registry (U01/U24
CA074783), Seattle Colorectal Cancer Family Registry (U01/U24 CA074794)
and University of Hawaii Colorectal Cancer Family Registry (U01/U24
CA074806). The CCFR Illumina GWAS was supported by funding from the
National Cancer Institute, National Institutes of Health (U01 CA122839
and R01 CA143237 to GC). Seattle CCFR research was also supported by the
Cancer Surveillance System of the Fred Hutchinson Cancer Research
Center-Control Nos. N01-CN-67009 (1996-2003), N01-PC-35142 (2003-2010)
and the Surveillance, Epidemiology and End Results (SEER) Program of the
National Cancer Institute (Contract No. HHSN2612013000121, 2010-2017)
with additional support from the Fred Hutchinson Cancer Research Center.
The collection of cancer incidence data for the State of Hawaii used in
this study was supported by the Hawaii Department of Health as part of
the statewide cancer reporting program mandated by Hawai`i Revised
Statutes; the National Cancer Institute's Surveillance, Epidemiology and
End Results Program (SEER) awarded to the University of Hawaii (Control
Nos. N01-PC-67001 1996-2003, N01-PC-35137 2003-10, Contract Nos.
HHSN26120100037C 2010-13, HHSN261201300009I 2010-). The collection of
cancer incidence data used in this study was supported by the California
Department of Public Health as part of the statewide cancer reporting
program mandated by California Health and Safety Code Section 103885;
the National Cancer Institute's Surveillance, Epidemiology and End
Results Program contract HHSN261201000035C-awarded to the University of
Southern California, and contract HHSN261201000034C-awarded to the
Public Health Institute; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under
agreement-U58DP003862-01-awarded to the California Department of Public
Health.
NR 25
TC 1
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U1 5
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0007-0920
EI 1532-1827
J9 BRIT J CANCER
JI Br. J. Cancer
PD JUL 12
PY 2016
VL 115
IS 2
BP 266
EP 272
DI 10.1038/bjc.2016.188
PG 7
WC Oncology
SC Oncology
GA DS1SR
UT WOS:000380380300016
PM 27336604
ER
PT J
AU Ron-Harel, N
Santos, D
Ghergurovich, JM
Sage, PT
Reddy, A
Lovitch, SB
Dephoure, N
Satterstrom, FK
Sheffer, M
Spinelli, JB
Gygi, S
Rabinowitz, JD
Sharpe, AH
Haigis, MC
AF Ron-Harel, Noga
Santos, Daniel
Ghergurovich, Jonathan M.
Sage, Peter T.
Reddy, Anita
Lovitch, Scott B.
Dephoure, Noah
Satterstrom, F. Kyle
Sheffer, Michal
Spinelli, Jessica B.
Gygi, Steven
Rabinowitz, Joshua D.
Sharpe, Arlene H.
Haigis, Marcia C.
TI Mitochondrial Biogenesis and Proteome Remodeling Promote One-Carbon
Metabolism for T Cell Activation
SO Cell Metabolism
LA English
DT Article
ID CALORIE RESTRICTION; LYMPHOCYTE ACTIVATION; SKELETAL-MUSCLE; REGULATORY
T; FOLATE; CANCER; SERINE; PATHWAY; PROLIFERATION; BIOSYNTHESIS
AB Naive T cell stimulation activates anabolic metabolism to fuel the transition from quiescence to growth and proliferation. Here we show that naive CD4(+) T cell activation induces a unique program of mitochondrial biogenesis and remodeling. Using mass spectrometry, we quantified protein dynamics during T cell activation. We identified substantial remodeling of the mitochondrial proteome over the first 24 hr of T cell activation to generate mitochondria with a distinct metabolic signature, with one-carbon metabolism as the most induced pathway. Salvage pathways and mitochondrial one-carbon metabolism, fed by serine, contribute to purine and thymidine synthesis to enable T cell proliferation and survival. Genetic inhibition of the mitochondrial serine catabolic enzyme SHMT2 impaired T cell survival in culture and antigen-specific T cell abundance in vivo. Thus, during T cell activation, mitochondrial proteome remodeling generates specialized mitochondria with enhanced one-carbon metabolism that is critical for T cell activation and survival.
C1 [Ron-Harel, Noga; Santos, Daniel; Reddy, Anita; Dephoure, Noah; Satterstrom, F. Kyle; Spinelli, Jessica B.; Gygi, Steven; Haigis, Marcia C.] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
[Santos, Daniel] Univ Coimbra, CNC Ctr Neurosci & Cell Biol, P-3004504 Coimbra, Portugal.
[Ghergurovich, Jonathan M.; Rabinowitz, Joshua D.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
[Ghergurovich, Jonathan M.] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA.
[Sage, Peter T.; Lovitch, Scott B.; Sharpe, Arlene H.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Sage, Peter T.; Lovitch, Scott B.; Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Sheffer, Michal] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Rabinowitz, Joshua D.] Princeton Univ, Dept Chem, Princeton, NJ 08544 USA.
RP Haigis, MC (reprint author), Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
EM marcia_haigis@hms.harvard.edu
FU NIH/NIAID [HHSN272201100018C]; F. Hoffmann-La Roche Ltd.; Glenn
Foundation for Medical Research; Ludwig center at Harvard; European
Molecular Biology Organization; Portuguese Foundation for Science and
Technology (FCT-MCTES)
FX The authors thank the Electron Microscopy Core at BIDMC. This study was
supported in part by grants from NIH/NIAID HHSN272201100018C (to M.C.H.
and A.H.S.), F. Hoffmann-La Roche Ltd. (to A.H.S. and M.C.H.), the Glenn
Foundation for Medical Research (to M.C.H.), and the Ludwig center at
Harvard (to M.C.H.). N.R.-H. was supported by The European Molecular
Biology Organization long-term postdoctoral fellowship. D.S. was
supported by a PhD Fellowship from Portuguese Foundation for Science and
Technology (FCT-MCTES).
NR 40
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Z9 10
U1 4
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1550-4131
EI 1932-7420
J9 CELL METAB
JI Cell Metab.
PD JUL 12
PY 2016
VL 24
IS 1
BP 104
EP 117
DI 10.1016/j.cmet.2016.06.007
PG 14
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DS5AR
UT WOS:000380793400015
PM 27411012
ER
PT J
AU Fontana, L
Cummings, NE
Apelo, SIA
Neuman, JC
Kasza, I
Schmidt, BA
Cava, E
Spelta, F
Tosti, V
Syed, FA
Baar, EL
Veronese, N
Cottrell, SE
Fenske, RJ
Bertozzi, B
Brar, HK
Pietka, T
Bullock, AD
Figenshau, RS
Andriole, GL
Merrins, MJ
Alexander, CM
Kimple, ME
Lamming, DW
AF Fontana, Luigi
Cummings, Nicole E.
Apelo, Sebastian I. Arriola
Neuman, Joshua C.
Kasza, Ildiko
Schmidt, Brian A.
Cava, Edda
Spelta, Francesco
Tosti, Valeria
Syed, Faizan A.
Baar, Emma L.
Veronese, Nicola
Cottrell, Sara E.
Fenske, Rachel J.
Bertozzi, Beatrice
Brar, Harpreet K.
Pietka, Terri
Bullock, Arnold D.
Figenshau, Robert S.
Andriole, Gerald L.
Merrins, Matthew J.
Alexander, Caroline M.
Kimple, Michelle E.
Lamming, Dudley W.
TI Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic
Health
SO CELL REPORTS
LA English
DT Article
ID ISLET BETA-CELLS; CALORIC RESTRICTION; INSULIN-RESISTANCE;
DIETARY-PROTEIN; LIFE-SPAN; METHIONINE RESTRICTION; GLUCOSE-METABOLISM;
ADIPOSE-TISSUE; VISCERAL FAT; MICE
AB Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR diet also improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.
C1 [Fontana, Luigi; Cava, Edda; Spelta, Francesco; Tosti, Valeria; Veronese, Nicola; Bertozzi, Beatrice; Pietka, Terri] Washington Univ, Div Geriatr & Nutr Sci, St Louis, MO 63130 USA.
[Fontana, Luigi] Univ Brescia, Sch Med, Dept Clin & Expt Sci, I-25121 Brescia, Italy.
[Fontana, Luigi] CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.
[Cummings, Nicole E.; Apelo, Sebastian I. Arriola; Neuman, Joshua C.; Schmidt, Brian A.; Syed, Faizan A.; Baar, Emma L.; Cottrell, Sara E.; Fenske, Rachel J.; Brar, Harpreet K.; Merrins, Matthew J.; Kimple, Michelle E.; Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI 53705 USA.
[Cummings, Nicole E.; Apelo, Sebastian I. Arriola; Neuman, Joshua C.; Schmidt, Brian A.; Syed, Faizan A.; Baar, Emma L.; Cottrell, Sara E.; Fenske, Rachel J.; Brar, Harpreet K.; Merrins, Matthew J.; Kimple, Michelle E.; Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
[Cummings, Nicole E.; Kimple, Michelle E.; Lamming, Dudley W.] Univ Wisconsin, Endocrinol & Reprod Physiol Grad Training Program, Madison, WI 53706 USA.
[Neuman, Joshua C.; Fenske, Rachel J.; Kimple, Michelle E.; Lamming, Dudley W.] Univ Wisconsin, Interdisciplinary Grad Program Nutr Sci, Madison, WI 53706 USA.
[Kasza, Ildiko; Alexander, Caroline M.] Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53705 USA.
[Cava, Edda] Sapienza Univ Rome, Dept Expt Med, I-00185 Rome, Italy.
[Spelta, Francesco; Tosti, Valeria] Univ Verona, Dept Med, I-37129 Verona, Italy.
[Veronese, Nicola] Univ Padua, Dept Med, Div Geriatr, I-35122 Padua, Italy.
[Cottrell, Sara E.; Lamming, Dudley W.] Univ Wisconsin, Rural & Urban Scholars Community Hlth Program, Madison, WI 53706 USA.
[Bullock, Arnold D.; Figenshau, Robert S.; Andriole, Gerald L.] Washington Univ, Sch Med St Louis, Div Urol, St Louis, MO 63110 USA.
[Merrins, Matthew J.] Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA.
[Kimple, Michelle E.] Univ Wisconsin, Dept Cell & Regenerat Biol, Madison, WI 53705 USA.
RP Fontana, L (reprint author), Washington Univ, Div Geriatr & Nutr Sci, St Louis, MO 63130 USA.; Fontana, L (reprint author), Univ Brescia, Sch Med, Dept Clin & Expt Sci, I-25121 Brescia, Italy.; Fontana, L (reprint author), CEINGE Biotecnol Avanzate, I-80145 Naples, Italy.; Lamming, DW (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53705 USA.; Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.; Lamming, DW (reprint author), Univ Wisconsin, Endocrinol & Reprod Physiol Grad Training Program, Madison, WI 53706 USA.; Lamming, DW (reprint author), Univ Wisconsin, Interdisciplinary Grad Program Nutr Sci, Madison, WI 53706 USA.; Lamming, DW (reprint author), Univ Wisconsin, Rural & Urban Scholars Community Hlth Program, Madison, WI 53706 USA.
EM lfontana@dom.wustl.edu; dlamming@medicine.wisc.edu
OI Lamming, Dudley/0000-0002-0079-4467
FU NIH/National Institute on Aging [K99/R00, AG041765]; Wisconsin
Partnership Program; Glenn Foundation Award for Research in the
Biological Mechanisms of Aging; UW-Madison School of Medicine and Public
Health; UW-Madison Department of Medicine; American Federation for Aging
Research; Bakewell Foundation; Longer Life Foundation (an RGA/Washington
University Partnership); National Center for Research Resources [UL1
RR024992]; American Diabetes Association [1-14-BS-115, 1-16-IBS-212,
1-16-PMF-001]; NIH/NIDDK [R01 DK102598, K01 DK101683]; UW Institute on
Aging (NIA) [T32 AG000213]; McArdle Departmental Funds; Rural and Urban
Scholars in Community Health Program
FX We would like to thank all the members of the D.W.L., L.F., C.M.A.,
M.E.K., and M.J.M. labs for their assistance and insight, and the Davis
lab for their continual support. We would like to thank Dena Cohen for
advice and consultation, Tina Herfel (Envigo) for assistance with the
formulation of the amino-acid-defined diets, and the reviewers of this
manuscript, who greatly aided us with their suggestions. We thank
Kathleen Obert, MS, RD, LD for the photograph of a sample dinner used in
the slider image accompanying this manuscript and Clint Thayer for
assistance with preparation of the slider image. The D.W.L. lab is
supported by a K99/R00 Pathway to Independence Award to D.W.L. from the
NIH/National Institute on Aging (AG041765), a New Investigator Program
Award from the Wisconsin Partnership Program, and a Glenn Foundation
Award for Research in the Biological Mechanisms of Aging, as well as
startup funds from the UW-Madison School of Medicine and Public Health
and the UW-Madison Department of Medicine. This research was conducted
while D.W.L. was an AFAR Research Grant recipient from the American
Federation for Aging Research. The L.F. lab is supported by grants from
the Bakewell Foundation, the Longer Life Foundation (an RGA/Washington
University Partnership), and the National Center for Research Resources
(UL1 RR024992). This work was also supported by grants from the American
Diabetes Association (1-14-BS-115) and the NIH/NIDDK (R01 DK102598) to
M.E.K. The M.J.M. lab is supported in part by a Research Scientist
Development Award from the NIH/NIDDK (K01 DK101683) and an Innovative
Basic Science Award from the American Diabetes Association
(1-16-IBS-212) to M.J.M. S.I.A.A. is supported in part by a fellowship
from the American Diabetes Association (1-16-PMF-001). J.C.N. is
supported in part by a training grant from the UW Institute on Aging
(NIA T32 AG000213). I.K. is supported in part by McArdle Departmental
Funds. S.E.C. was supported by the Rural and Urban Scholars in Community
Health Program. This work was supported using facilities and resources
from the William S. Middleton Memorial Veterans Hospital. This work does
not represent the views of the Department of Veterans Affairs or the
United States Government.
NR 47
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U1 10
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUL 12
PY 2016
VL 16
IS 2
BP 520
EP 530
DI 10.1016/j.celrep.2016.05.092
PG 11
WC Cell Biology
SC Cell Biology
GA DS0CG
UT WOS:000380262300022
PM 27346343
ER
PT J
AU Li, H
Kuwajima, T
Oakley, D
Nikulina, E
Hou, JW
Yang, WS
Lowry, ER
Lamas, NJ
Amoroso, MW
Croft, GF
Hosur, R
Wichterle, H
Sebti, S
Filbin, MT
Stockwell, B
Henderson, CE
AF Li, Hai
Kuwajima, Takaaki
Oakley, Derek
Nikulina, Elena
Hou, Jianwei
Yang, Wan Seok
Lowry, Emily Rhodes
Lamas, Nuno Jorge
Amoroso, Mackenzie Weygandt
Croft, Gist F.
Hosur, Raghavendra
Wichterle, Hynek
Sebti, Said
Filbin, Marie T.
Stockwell, Brent
Henderson, Christopher E.
TI Protein Prenylation Constitutes an Endogenous Brake on Axonal Growth
SO CELL REPORTS
LA English
DT Article
ID CHONDROITIN SULFATE PROTEOGLYCANS; AMYOTROPHIC-LATERAL-SCLEROSIS;
CENTRAL-NERVOUS-SYSTEM; NEURITE OUTGROWTH; STEM-CELLS; NEURONAL
PROTECTION; CHEMICAL SCREEN; MOTOR-NEURONS; CYCLIC-AMP; STATIN USE
AB Suboptimal axonal regeneration contributes to the consequences of nervous system trauma and neurodegenerative disease, but the intrinsic mechanisms that regulate axon growth remain unclear. We screened 50,400 small molecules for their ability to promote axon outgrowth on inhibitory substrata. The most potent hits were the statins, which stimulated growth of all mouse- and human-patient-derived neurons tested, both in vitro and in vivo, as did combined inhibition of the protein prenylation enzymes farnesyltransferase (PFT) and geranylgeranyl transferase I (PGGT-1). Compensatory sprouting of motor axons may delay clinical onset of amyotrophic lateral sclerosis (ALS). Accordingly, elevated levels of PGGT1B, which would be predicted to reduce sprouting, were found in motor neurons of early-versus late-onset ALS patients postmortem. The mevalonate-prenylation pathway therefore constitutes an endogenous brake on axonal growth, and its inhibition provides a potential therapeutic approach to accelerate neuronal regeneration in humans.
C1 [Li, Hai; Kuwajima, Takaaki; Yang, Wan Seok; Wichterle, Hynek; Stockwell, Brent; Henderson, Christopher E.] Columbia Univ, Ctr Motor Neuron Biol & Dis Columbia Stem Cell In, New York, NY 10032 USA.
[Henderson, Christopher E.] Columbia Univ, Coll Phys & Surg, Dept Rehabil & Regenerat Med, New York, NY 10032 USA.
[Li, Hai; Kuwajima, Takaaki; Lamas, Nuno Jorge; Wichterle, Hynek; Henderson, Christopher E.] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol Neurol & Neurosci, New York, NY 10032 USA.
[Nikulina, Elena; Hou, Jianwei; Filbin, Marie T.] CUNY, Hunter Coll, Dept Biol Sci, New York, NY 10065 USA.
[Yang, Wan Seok; Stockwell, Brent] Columbia Univ, Howard Hughes Med Inst, New York, NY 10027 USA.
[Yang, Wan Seok; Stockwell, Brent] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Yang, Wan Seok; Stockwell, Brent] Columbia Univ, Dept Chem, New York, NY 10027 USA.
[Oakley, Derek; Lowry, Emily Rhodes; Lamas, Nuno Jorge; Amoroso, Mackenzie Weygandt; Croft, Gist F.; Wichterle, Hynek; Henderson, Christopher E.] Project ALS Jenifer Estess Lab Stem Cell Res, New York, NY 10032 USA.
[Lamas, Nuno Jorge] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst, P-4710057 Braga, Minho, Portugal.
[Sebti, Said] Univ S Florida, Moffitt Canc Ctr, Tampa, FL 33612 USA.
[Sebti, Said] Univ S Florida, Res Inst, Tampa, FL 33612 USA.
[Hosur, Raghavendra] Biogen Inc, Computat Biol, Cambridge, MA 02142 USA.
[Henderson, Christopher E.] Target ALS Fdn, New York, NY 10032 USA.
[Oakley, Derek] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Yang, Wan Seok] St Johns Univ, Dept Biol Sci, Jamaica, NY 11439 USA.
[Amoroso, Mackenzie Weygandt] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Croft, Gist F.] Rockefeller Univ, Lab Stem Cell Biol & Mol Embryol, New York, NY 10066 USA.
[Henderson, Christopher E.] Biogen Inc, Neurol Res, Cambridge, MA 02142 USA.
RP Henderson, CE (reprint author), Columbia Univ, Ctr Motor Neuron Biol & Dis Columbia Stem Cell In, New York, NY 10032 USA.; Henderson, CE (reprint author), Columbia Univ, Coll Phys & Surg, Dept Rehabil & Regenerat Med, New York, NY 10032 USA.; Henderson, CE (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol Neurol & Neurosci, New York, NY 10032 USA.; Henderson, CE (reprint author), Project ALS Jenifer Estess Lab Stem Cell Res, New York, NY 10032 USA.; Henderson, CE (reprint author), Target ALS Fdn, New York, NY 10032 USA.; Henderson, CE (reprint author), Biogen Inc, Neurol Res, Cambridge, MA 02142 USA.
EM chris.henderson@biogen.com
FU New York State Spinal Cord Injury Research Board (NYS-SCIRB) [C020923];
P2ALS; Target ALS; Tow Foundation; SMA Foundation; Project A.L.S.;
NYSTEM [C026715]; Helmsley Charitable Trust; NINDS [R01-NS056422,
NS072428]; Columbia MD-PhD program; NIH [5R01CA097061, R01CA161061]; New
York State Stem Cell Science [C026715]
FX We thank Samaher Fageiry and Cyndel Vollmer for help with the culture
model, Kevin Eggan and collaborators for kindly providing Hb9::GFP human
ESC reporter lines, and Chuck Karan and members of the High-Throughput
Screening and Chemistry Shared Facility for support and technical
guidance. We thank the He lab (Harvard) for training in optic nerve
crush. We are grateful to members of the Project A.L.S., Henderson,
Wichterle, and Stockwell laboratories at Columbia University for much
help and continuous critical discussion. We thank our Biogen colleagues
Alex McCampbell, Sha Mi, and Richard Ransohoff for critical reading of
the manuscript. This work received invaluable support from the New York
State Spinal Cord Injury Research Board (NYS-SCIRB C020923), P2ALS,
Target ALS, the Tow Foundation, the SMA Foundation, Project A.L.S.,
NYSTEM (C026715), The Helmsley Charitable Trust, NINDS R01-NS056422 and
NS072428, and the Columbia MD-PhD program. Brent R. Stockwell is an
Early Career Scientist of the Howard Hughes Medical Institute, and this
research was additionally funded by the NIH (5R01CA097061 and
R01CA161061, to B.S.) and New York State Stem Cell Science (C026715).
NR 58
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Z9 1
U1 3
U2 3
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD JUL 12
PY 2016
VL 16
IS 2
BP 545
EP 558
DI 10.1016/j.celrep.2016.06.013
PG 14
WC Cell Biology
SC Cell Biology
GA DS0CG
UT WOS:000380262300024
PM 27373155
ER
PT J
AU Gordon, LB
Kleinman, ME
Massaro, J
D'Agostino, RB
Shappell, H
Gerhard-Herman, M
Smoot, LB
Gordon, CM
Cleveland, RH
Nazarian, A
Snyder, BD
Ullrich, NJ
Silvera, VM
Liang, MG
Quinn, N
Miller, DT
Huh, SY
Dowton, AA
Littlefield, K
Greer, MM
Kieran, MW
AF Gordon, Leslie B.
Kleinman, Monica E.
Massaro, Joe
D'Agostino, Ralph B.
Shappell, Heather
Gerhard-Herman, Marie
Smoot, Leslie B.
Gordon, Catherine M.
Cleveland, Robert H.
Nazarian, Ara
Snyder, Brian D.
Ullrich, Nicole J.
Silvera, V. Michelle
Liang, Marilyn G.
Quinn, Nicolle
Miller, David T.
Huh, Susanna Y.
Dowton, Anne A.
Littlefield, Kelly
Greer, Maya M.
Kieran, Mark W.
TI Clinical Trial of the Protein Farnesylation Inhibitors Lonafarnib,
Pravastatin, and Zoledronic Acid in Children With Hutchinson-Gilford
Progeria Syndrome
SO CIRCULATION
LA English
DT Article
DE aging; atherosclerosis; progeria
ID MUTANT LAMIN-A; FARNESYLTRANSFERASE INHIBITOR; MOUSE MODEL; VASCULAR
MEDICINE; SYNDROME MUTATION; AMERICAN SOCIETY; DISEASE;
ECHOCARDIOGRAPHY; PROGRESSION; MORTALITY
AB Background: Hutchinson-Gilford progeria syndrome is an extremely rare, fatal, segmental premature aging syndrome caused by a mutation in LMNA yielding the farnesylated aberrant protein progerin. Without progerin-specific treatment, death occurs at an average age of 14.6 years from an accelerated atherosclerosis. A previous single-arm clinical trial demonstrated that the protein farnesyltransferase inhibitor lonafarnib ameliorates some aspects of cardiovascular and bone disease. This present trial sought to further improve disease by additionally inhibiting progerin prenylation.
Methods: Thirty-seven participants with Hutchinson-Gilford progeria syndrome received pravastatin, zoledronic acid, and lonafarnib. This combination therapy was evaluated, in addition to descriptive comparisons with the prior lonafarnib monotherapy trial.
Results: No participants withdrew because of side effects. Primary outcome success was predefined by improved per-patient rate of weight gain or carotid artery echodensity; 71.0% of participants succeeded (P < 0.0001). Key cardiovascular and skeletal secondary variables were predefined. Secondary improvements included increased areal (P = 0.001) and volumetric (P < 0.001-0.006) bone mineral density and 1.5- to 1.8-fold increases in radial bone structure (P< 0.001). Median carotid artery wall echodensity and carotid-femoral pulse wave velocity demonstrated no significant changes. Percentages of participants with carotid (5% to 50%; P = 0.001) and femoral (0% to 12%; P = 0.13) artery plaques and extraskeletal calcifications (34.4% to 65.6%; P = 0.006) increased. Other than increased bone mineral density, no improvement rates exceeded those of the prior lonafarnib monotherapy treatment trial.
Conclusions: Comparisons with lonafarnib monotherapy treatment reveal additional bone mineral density benefit but likely no added cardiovascular benefit with the addition of pravastatin and zoledronic acid.
C1 [Gordon, Leslie B.] Hasbro Childrens Hosp, Dept Pediat, 593 Eddy St, Providence, RI 02903 USA.
[Gordon, Leslie B.; Kleinman, Monica E.; Dowton, Anne A.; Littlefield, Kelly; Greer, Maya M.] Boston Childrens Hosp, Dept Anesthesia, Boston, MA USA.
[Smoot, Leslie B.] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.
[Cleveland, Robert H.; Silvera, V. Michelle] Boston Childrens Hosp, Dept Radiol, Boston, MA USA.
[Snyder, Brian D.] Boston Childrens Hosp, Dept Orthoped, Boston, MA USA.
[Ullrich, Nicole J.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
[Liang, Marilyn G.] Boston Childrens Hosp, Dept Dermatol, Boston, MA USA.
[Miller, David T.] Boston Childrens Hosp, Dept Genet & Genom, Boston, MA USA.
[Huh, Susanna Y.] Boston Childrens Hosp, Dept Gastroenterol & Nutr, Boston, MA USA.
[Kieran, Mark W.] Boston Childrens Hosp, Dept Hematol Oncol, Boston, MA USA.
[Quinn, Nicolle] Boston Childrens Hosp, Clin Translat Study Unit, Boston, MA USA.
[Gerhard-Herman, Marie; Nazarian, Ara] Harvard Med Sch, Boston, MA USA.
[Gordon, Leslie B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Massaro, Joe; D'Agostino, Ralph B.; Shappell, Heather] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Massaro, Joe; D'Agostino, Ralph B.; Shappell, Heather] Harvard Clin Res Inst, Boston, MA USA.
[Gerhard-Herman, Marie] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
[Gordon, Catherine M.] Univ Cincinnati, Med Ctr, Cincinnati Childrens Hosp, Coll Med,Dept Pediat, Cincinnati, OH 45267 USA.
[Nazarian, Ara] Beth Israel Deaconess Med Ctr, Dept Orthoped Surg, Ctr Adv Orthopaed Studies, Boston, MA 02215 USA.
[Kieran, Mark W.] Harvard Med Sch, Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA USA.
RP Gordon, LB (reprint author), Hasbro Childrens Hosp, Dept Pediat, 593 Eddy St, Providence, RI 02903 USA.; Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
EM Leslie_Gordon@brown.edu; Mark_Kieran@dfci.harvard.edu
FU Progeria Research Foundation [PRFCLIN2007-02, PRFCLIN2009-03]; National
Institutes of Health National Heart, Lung, and Blood Institute
[1RC2HL101631-0]; Harvard Clinical and Translational Science Center
(National Center for Research Resources); Harvard Clinical and
Translational Science Center (National Center for Advancing
Translational Sciences, National Institutes of Health) [UL1 TR001102]
FX Funding was received from The Progeria Research Foundation
(PRFCLIN2007-02 and PRFCLIN2009-03), National Institutes of Health
National Heart, Lung, and Blood Institute grant 1RC2HL101631-0, and the
Harvard Clinical and Translational Science Center (National Center for
Research Resources and the National Center for Advancing Translational
Sciences, National Institutes of Health Award UL1 TR001102).
NR 38
TC 3
Z9 3
U1 18
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 12
PY 2016
VL 134
IS 2
BP 114
EP +
DI 10.1161/CIRCULATIONAHA.116.022188
PG 26
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DR8EA
UT WOS:000380130000009
PM 27400896
ER
PT J
AU Piccini, JP
Hellkamp, AS
Washam, JB
Becker, RC
Breithardt, G
Berkowitz, SD
Halperin, JL
Hankey, GJ
Hacke, W
Mahaffey, KW
Nessel, CC
Singer, DE
Fox, KAA
Patel, MR
AF Piccini, Jonathan P.
Hellkamp, Anne S.
Washam, Jeffrey B.
Becker, Richard C.
Breithardt, Guenter
Berkowitz, Scott D.
Halperin, Jonathan L.
Hankey, Graeme J.
Hacke, Werner
Mahaffey, Kenneth W.
Nessel, Christopher C.
Singer, Daniel E.
Fox, Keith A. A.
Patel, Manesh R.
TI Response by Piccini et al to Letters Regarding Article, "Polypharmacy
and the Efficacy and Safety of Rivaroxaban Versus Warfarin in the
Prevention of Stroke in Patients With Nonvalvular Atrial Fibrillation"
SO CIRCULATION
LA English
DT Letter
C1 [Piccini, Jonathan P.; Hellkamp, Anne S.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Piccini, Jonathan P.; Washam, Jeffrey B.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA.
[Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Breithardt, Guenter] Hosp Univ Munster, Munster, Germany.
[Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Parsippany, NJ USA.
[Halperin, Jonathan L.] Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia.
[Hacke, Werner] Heidelberg Univ, Heidelberg, Germany.
[Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Nessel, Christopher C.] Janssen Pharmaceut Res & Dev, Raritan, NJ USA.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Med Sch, Boston, MA USA.
[Fox, Keith A. A.] Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
RP Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.; Piccini, JP (reprint author), Duke Univ, Med Ctr, Duke Heart Ctr, Durham, NC 27710 USA.
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
NR 3
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 12
PY 2016
VL 134
IS 2
BP E7
EP E8
DI 10.1161/CIRCULATIONAHA.116.022737
PG 2
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DR8EA
UT WOS:000380130000003
PM 27400902
ER
PT J
AU Joseph, TT
Mincer, JS
AF Joseph, Thomas T.
Mincer, Joshua S.
TI Common Internal Allosteric Network Links Anesthetic Binding Sites in a
Pentameric Ligand-Gated Ion Channel
SO PLOS ONE
LA English
DT Article
ID GENERAL-ANESTHETICS; TRANSMEMBRANE DOMAIN; DYNAMICS; ACETYLCHOLINE;
PROPOFOL; KETAMINE; RECEPTOR; MODULATION; MECHANISMS; SIMULATION
AB General anesthetics bind reversibly to ion channels, modifying their global conformational distributions, but the underlying atomic mechanisms are not completely known. We examine this issue by way of the model protein Gloeobacter violaceous ligand-gated ion channel (GLIC) using computational molecular dynamics, with a coarse-grained model to enhance sampling. We find that in flooding simulations, both propofol and a generic particle localize to the crystallographic transmembrane anesthetic binding region, and that propofol also localizes to an extracellular region shared with the crystallographic ketamine binding site. Subsequent simulations to probe these binding modes in greater detail demonstrate that ligand binding induces structural asymmetry in GLIC. Consequently, we employ residue interaction correlation analysis to describe the internal allosteric network underlying the coupling of ligand and distant effector sites necessary for conformational change. Overall, the results suggest that the same allosteric network may underlie the actions of various anesthetics, regardless of binding site.
C1 [Joseph, Thomas T.; Mincer, Joshua S.] Icahn Sch Med Mt Sinai, Dept Anesthesiol, New York, NY 10029 USA.
[Mincer, Joshua S.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
RP Mincer, JS (reprint author), Icahn Sch Med Mt Sinai, Dept Anesthesiol, New York, NY 10029 USA.; Mincer, JS (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
EM joshua.mincer@mountsinai.org
RI Mincer, Joshua/B-4785-2008
OI Mincer, Joshua/0000-0002-2482-3154
FU Eliasberg Clinical Scientist Training Program of the Department of
Anesthesiology at Icahn School of Medicine at Mount Sinai; National
Science Foundation's XSEDE program [TG-MCB140093]; Department of
Scientific Computing at the Icahn School of Medicine at Mount Sinai
FX Support to T.T.J. is acknowledged from the Eliasberg Clinical Scientist
Training Program of the Department of Anesthesiology at Icahn School of
Medicine at Mount Sinai. Computational resources on the Stampede
computer cluster at the Texas Advanced Computing Center, University of
Texas, were supplied through the National Science Foundation's XSEDE
program (allocation TG-MCB140093). This work was supported in part
through the computational resources and staff expertise provided by the
Department of Scientific Computing at the Icahn School of Medicine at
Mount Sinai. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 43
TC 0
Z9 0
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 12
PY 2016
VL 11
IS 7
AR e0158795
DI 10.1371/journal.pone.0158795
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ9CO
UT WOS:000379508200015
PM 27403526
ER
PT J
AU Liu, YL
Gunda, V
Zhu, X
Xu, XD
Wu, J
Askhatova, D
Farokhzad, OC
Parangi, S
Shi, JJ
AF Liu, Yanlan
Gunda, Viswanath
Zhu, Xi
Xu, Xiaoding
Wu, Jun
Askhatova, Diana
Farokhzad, Omid C.
Parangi, Sareh
Shi, Jinjun
TI Theranostic near-infrared fluorescent nanoplatform for imaging and
systemic siRNA delivery to metastatic anaplastic thyroid cancer
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE theranostic; nanoparticle; NIR imaging; siRNA delivery; anaplastic
thyroid cancer
ID DRUG-DELIVERY; IN-VIVO; NANOPARTICLES; THERAPEUTICS; ACTIVATION;
MECHANISMS; CARCINOMA; TOXICITY; THERAPY; TUMORS
AB Anaplastic thyroid cancer (ATC), one of the most aggressive solid tumors, is characterized by rapid tumor growth and severe metastasis to other organs. Owing to the lack of effective treatment options, ATC has a mortality rate of similar to 100% and median survival of less than 5 months. RNAi nanotechnology represents a promising strategy for cancer therapy through nanoparticle (NP)-mediated delivery of RNAi agents (e.g., siRNA) to solid tumors for specific silencing of target genes driving growth and/or metastasis. Nevertheless, the clinical success of RNAi cancer nanotherapies remains elusive in large part because of the suboptimal systemic siRNA NP delivery to tumors and the fact that tumor heterogeneity produces variable NP accumulation and thus, therapeutic response. To address these challenges, we here present an innovative theranostic NP platform composed of a near-infrared (NIR) fluorescent polymer for effective in vivo siRNA delivery to ATC tumors and simultaneous tracking of the tumor accumulation by noninvasive NIR imaging. The NIR polymeric NPs are small (similar to 50 nm), show long blood circulation and high tumor accumulation, and facilitate tumor imaging. Systemic siRNA delivery using these NPs efficiently silences the expression of V-Raf murine sarcoma viral oncogene homolog B (BRAF) in tumor tissues and significantly suppresses tumor growth and metastasis in an orthotopic mouse model of ATC. These results suggest that this theranostic NP system could become an effective tool for NIR imaging-guided siRNA delivery for personalized treatment of advanced malignancies.
C1 [Liu, Yanlan; Zhu, Xi; Xu, Xiaoding; Wu, Jun; Askhatova, Diana; Farokhzad, Omid C.; Shi, Jinjun] Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.
[Gunda, Viswanath; Parangi, Sareh] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02214 USA.
RP Farokhzad, OC; Shi, JJ (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol, Boston, MA 02115 USA.; Parangi, S (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02214 USA.
EM ofarokhzad@bwh.harvard.edu; sparangi@partners.org; jshi@bwh.harvard.edu
FU NIH [R00CA160350, CA200900, CA149738, EB015419, U54-CA151884];
Department of Defense Prostate Cancer Research Program Synergistic Idea
Development Award; Movember-Prostate Cancer Foundation (PCF) Challenge
Award; PCF Young Investigator Award; Koch PCF Program in
Nanotherapeutics; National Research Foundation of Korea [K1A1A2048701]
FX This work was supported by NIH Grants R00CA160350 (to J.S.), CA200900
(to J.S.), CA149738 (to S.P.), EB015419 (to O.C.F.), and U54-CA151884
(to O.C.F.); the Department of Defense Prostate Cancer Research Program
Synergistic Idea Development Award (to O.C.F. and J.S.); the
Movember-Prostate Cancer Foundation (PCF) Challenge Award (to O.C.F. and
J.S.); the PCF Young Investigator Award (to J.S.); the Koch PCF Program
in Nanotherapeutics (O.C.F.); and National Research Foundation of Korea
Grant K1A1A2048701 (to O.C.F.).
NR 29
TC 2
Z9 2
U1 25
U2 40
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 12
PY 2016
VL 113
IS 28
BP 7750
EP 7755
DI 10.1073/pnas.1605841113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR1VX
UT WOS:000379694100035
PM 27342857
ER
PT J
AU Lin, SG
Ba, ZQ
Du, Z
Zhang, Y
Hu, JZ
Alt, FW
AF Lin, Sherry G.
Ba, Zhaoqing
Du, Zhou
Zhang, Yu
Hu, Jiazhi
Alt, Frederick W.
TI Highly sensitive and unbiased approach for elucidating antibody
repertoires
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antibody repertoires; HTGTS-Rep-seq; V(D)J recombination
ID DOUBLE-STRANDED BREAKS; B-CELL DEVELOPMENT; HEAVY-CHAIN LOCUS; V(D)J
RECOMBINATION; ALLELIC EXCLUSION; VARIABLE-REGION; GENOMIC INSTABILITY;
GENE SEGMENTS; EXPRESSION; IGH
AB Developing B lymphocytes undergo V(D)J recombination to assemble germ-line V, D, and J gene segments into exons that encode the antigen-binding variable region of Ig heavy (H) and light (L) chains. IgH and IgL chains associate to form the B-cell receptor (BCR), which, upon antigen binding, activates B cells to secrete BCR as an antibody. Each of the huge number of clonally independent B cells expresses a unique set of IgH and IgL variable regions. The ability of V(D)J recombination to generate vast primary B-cell repertoires results from a combinatorial assortment of large numbers of different V, D, and J segments, coupled with diversification of the junctions between them to generate the complementary determining region 3 (CDR3) for antigen contact. Approaches to evaluate in depth the content of primary antibody repertoires and, ultimately, to study how they are further molded by secondary mutation and affinity maturation processes are of great importance to the B-cell development, vaccine, and antibody fields. We now describe an unbiased, sensitive, and readily accessible assay, referred to as high-throughput genome-wide translocation sequencing-adapted repertoire sequencing (HTGTS-Rep-seq), to quantify antibody repertoires. HTGTS-Rep-seq quantitatively identifies the vast majority of IgH and IgL V(D)J exons, including their unique CDR3 sequences, from progenitor and mature mouse B lineage cells via the use of specific J primers. HTGTS-Rep-seq also accurately quantifies DJ(H) intermediates and V(D)J exons in either productive or nonproductive configurations. HTGTS-Rep-seq should be useful for studies of human samples, including clonal B-cell expansions, and also for following antibody affinity maturation processes.
C1 [Lin, Sherry G.; Ba, Zhaoqing; Zhang, Yu; Hu, Jiazhi; Alt, Frederick W.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Lin, Sherry G.; Ba, Zhaoqing; Du, Zhou; Zhang, Yu; Hu, Jiazhi; Alt, Frederick W.] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
[Du, Zhou; Alt, Frederick W.] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Hu, JZ; Alt, FW (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Hu, JZ; Alt, FW (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.; Alt, FW (reprint author), Harvard Med Sch, Howard Hughes Med Inst, Boston, MA 02115 USA.
EM jiazhi.hu@childrens.harvard.edu; alt@enders.tch.harvard.edu
FU National Institutes of Health [R01AI020047, F31-AI117920]; Cancer
Research Institute; Robertson Foundation/Cancer Research Institute;
Leukemia and Lymphoma Society
FX We thank members of the F.W.A. laboratory for stimulating discussions
and Dr. Richard Frock for experimental advice. This work is supported by
National Institutes of Health Grant R01AI020047 (to F.W.A.) and Grant
F31-AI117920 (to S.G.L.). Z.B. is supported by a Cancer Research
Institute Irvington Fellowship; J.H. by a Robertson Foundation/Cancer
Research Institute Irvington Fellowship; and Y.Z. by a career
development fellowship from the Leukemia and Lymphoma Society. F.W.A. is
an investigator of the Howard Hughes Medical Institute.
NR 38
TC 1
Z9 1
U1 5
U2 9
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 12
PY 2016
VL 113
IS 28
BP 7846
EP 7851
DI 10.1073/pnas.1608649113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR1VX
UT WOS:000379694100051
PM 27354528
ER
PT J
AU Gunthard, HF
Saag, MS
Benson, CA
del Rio, C
Eron, JJ
Gallant, JE
Hoy, JF
Mugavero, MJ
Sax, PE
Thompson, MA
Gandhi, RT
Landovitz, RJ
Smith, DM
Jacobsen, DM
Volberding, PA
AF Gunthard, Huldrych F.
Saag, Michael S.
Benson, Constance A.
del Rio, Carlos
Eron, Joseph J.
Gallant, Joel E.
Hoy, Jennifer F.
Mugavero, Michael J.
Sax, Paul E.
Thompson, Melanie A.
Gandhi, Rajesh T.
Landovitz, Raphael J.
Smith, Davey M.
Jacobsen, Donna M.
Volberding, Paul A.
TI Antiretroviral Drugs for Treatment and Prevention of HIV Infection in
Adults 2016 Recommendations of the International Antiviral Society-USA
Panel
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID NON-INFERIORITY TRIAL; TENOFOVIR DISOPROXIL FUMARATE; RANDOMIZED
CONTROLLED-TRIAL; VIROLOGICALLY SUPPRESSED ADULTS; RITONAVIR PLUS
LAMIVUDINE; ONCE-DAILY DOLUTEGRAVIR; MYCOBACTERIUM-TUBERCULOSIS
INFECTION; REVERSE-TRANSCRIPTASE INHIBITORS; COGNITIVE-BEHAVIORAL
THERAPY; BOOSTED PROTEASE INHIBITOR
AB IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults.
OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged >= 18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis.
EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence.
FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and monitoring during treatment is recommended to assess response, adverse effects, and adherence. Approaches are recommended to improve linkage to and retention in care are provided. Daily tenofovir disoproxil fumarate/emtricitabine is recommended for use as preexposure prophylaxis to prevent HIV infection in persons at high risk. When indicated, postexposure prophylaxis should be started as soon as possible after exposure.
CONCLUSIONS AND RELEVANCE Antiretroviral agents remain the cornerstone of HIV treatment and prevention. All HIV-infected individuals with detectable plasma virus should receive treatment with recommended initial regimens consisting of an InSTI plus 2 NRTIs. Preexposure prophylaxis should be considered as part of an HIV prevention strategy for at-risk individuals. When used effectively, currently available ARVs can sustain HIV suppression and can prevent new HIV infection. With these treatment regimens, survival rates among HIV-infected adults who are retained in care can approach those of uninfected adults.
C1 [Gunthard, Huldrych F.] Univ Zurich, Univ Zurich Hosp, Zurich, Switzerland.
[Gunthard, Huldrych F.] Univ Zurich, Inst Med Virol, Zurich, Switzerland.
[Saag, Michael S.; Mugavero, Michael J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Benson, Constance A.] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[del Rio, Carlos] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[del Rio, Carlos] Emory Univ, Sch Med, Atlanta, GA USA.
[Eron, Joseph J.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Gallant, Joel E.] Southwest CARE Ctr, Santa Fe, NM USA.
[Hoy, Jennifer F.] Alfred Hosp, Melbourne, Vic, Australia.
[Hoy, Jennifer F.] Monash Univ, Melbourne, Vic, Australia.
[Sax, Paul E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Sax, Paul E.; Gandhi, Rajesh T.] Harvard Med Sch, Boston, MA USA.
[Thompson, Melanie A.] AIDS Res Consortium Atlanta, Atlanta, GA USA.
[Gandhi, Rajesh T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Landovitz, Raphael J.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA.
[Smith, Davey M.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Jacobsen, Donna M.] Int Antiviral Soc USA, San Francisco, CA USA.
[Volberding, Paul A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Gunthard, HF (reprint author), Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Ramistr 100, CH-8091 Zurich, Switzerland.
EM huldrych.guenthard@usz.ch
RI del Rio, Carlos/B-3763-2012; Infektiologie, USZ/A-6921-2011; gunthard,
huldrych/F-1724-2011
OI del Rio, Carlos/0000-0002-0153-3517; gunthard,
huldrych/0000-0002-1142-6723
FU International Antiviral Society-USA (IAS-USA); AbbVie; Bristol-Myers
Squibb; Gilead Sciences; GlaxoSmithKline; Janssen Therapeutics; Merck;
Mylan; Pfizer; Salix Pharmaceuticals; ViiV Healthcare
FX The work is sponsored and funded by the International Antiviral
Society-USA (IAS-USA), a mission-based, nonmembership, 501(c)(3)
not-for-profit organization. In the last 5 years, the IAS-USA has
received grants for selected CME activities that are pooled (ie, no
single company supports any single effort) from AbbVie, Bristol-Myers
Squibb, Gilead Sciences, GlaxoSmithKline, Janssen Therapeutics, Merck,
Mylan, Pfizer, Salix Pharmaceuticals, and ViiV Healthcare.
NR 206
TC 28
Z9 28
U1 18
U2 23
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 12
PY 2016
VL 316
IS 2
BP 191
EP 210
DI 10.1001/jama.2016.8900
PG 20
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ9CW
UT WOS:000379509000015
PM 27404187
ER
PT J
AU Lee, JS
Giesler, DL
Fine, MJ
AF Lee, Jonathan S.
Giesler, Daniel L.
Fine, Michael J.
TI Management of Community-Acquired Pneumonia Reply
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Letter
C1 [Lee, Jonathan S.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Giesler, Daniel L.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA.
[Fine, Michael J.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr 151C,Bldg 30, Pittsburgh, PA 15240 USA.
RP Fine, MJ (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr 151C,Bldg 30, Pittsburgh, PA 15240 USA.
EM michael.fine@va.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 12
PY 2016
VL 316
IS 2
BP 222
EP 223
DI 10.1001/jama.2016.5028
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ9CW
UT WOS:000379509000023
PM 27404195
ER
PT J
AU Semigran, MJ
AF Semigran, Marc J.
TI Transthyretin Amyloidosis A "Zebra" of Many Stripes
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE amyloid; heart failure; transthyretin
ID POLYNEUROPATHY; DIFLUNISAL; DEPOSITION; TAFAMIDIS; TRIAL
C1 [Semigran, Marc J.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA.
[Semigran, Marc J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, Fruit St,Bigelow 800, Boston, MA 02114 USA.
EM msemigran@partners.org
NR 13
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 12
PY 2016
VL 68
IS 2
BP 173
EP 175
DI 10.1016/j.jacc.2016.05.020
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DQ3SV
UT WOS:000379123800006
PM 27386770
ER
PT J
AU Kadian-Dodov, D
Gornik, HL
Gu, XK
Froehlich, J
Bacharach, JM
Chi, YW
Gray, BH
Jaff, MR
Kim, ESH
Mace, P
Sharma, A
Kline-Rogers, E
White, C
Olin, JW
AF Kadian-Dodov, Daniella
Gornik, Heather L.
Gu, Xiaokui
Froehlich, James
Bacharach, J. Michael
Chi, Yung-Wei
Gray, Bruce H.
Jaff, Michael R.
Kim, Esther S. H.
Mace, Pamela
Sharma, Aditya
Kline-Rogers, Eva
White, Christopher
Olin, Jeffrey W.
TI Dissection and Aneurysm in Patients With Fibromuscular Dysplasia
Findings From the US Registry for FMD
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Article
DE angiography; beading; stenosis; tortuosity
ID CORONARY-ARTERY DISSECTION; UNRUPTURED INTRACRANIAL ANEURYSMS;
UNITED-STATES REGISTRY; CONNECTIVE-TISSUE DISORDERS;
AMERICAN-HEART-ASSOCIATION; VASCULAR ABNORMALITIES; CLINICAL-FEATURES;
NATURAL-HISTORY; PREVALENCE; MANAGEMENT
AB BACKGROUND Fibromuscular dysplasia (FMD) is a noninflammatory arterial disease that predominantly affects women. The arterial manifestations may include beading, stenosis, aneurysm, dissection, or tortuosity.
OBJECTIVES This study compared the frequency, location, and outcomes of FMD patients with aneurysm and/or dissection to those of patients without.
METHODS The U.S. Registry for FMD involves 12 clinical centers. This analysis included clinical history, diagnostic, and therapeutic procedure results for 921 FMD patients enrolled in the registry as of October 17, 2014.
RESULTS Aneurysm occurred in 200 patients (21.7%) and dissection in 237 patients (25.7%); in total, 384 patients (41.7%) had an aneurysm and/or a dissection by the time of FMD diagnosis. The extracranial carotid, renal, and intracranial arteries were the most common sites of aneurysm; dissection most often occurred in the extracranial carotid, vertebral, renal, and coronary arteries. FMD patients with dissection were younger at presentation (48.4 vs. 53.5 years of age, respectively; p < 0.0001) and experienced more neurological symptoms and other end-organ ischemic events than those without dissection. One-third of aneurysm patients (63 of 200) underwent therapeutic intervention for aneurysm repair.
CONCLUSIONS Patients with FMD have a high prevalence of aneurysm and/or dissection prior to or at the time of FMD diagnosis. Patients with dissection were more likely to experience ischemic events, and a significant number of patients with dissection or aneurysm underwent therapeutic procedures for these vascular events. Because of the high prevalence and associated morbidity in patients with FMD who have an aneurysm and/ or dissection, it is recommended that every patient with FMD undergo one-time cross-sectional imaging from head to pelvis with computed tomographic angiography or magnetic resonance angiography. (C) 2016 by the American College of Cardiology Foundation.
C1 [Kadian-Dodov, Daniella; Olin, Jeffrey W.] Icahn Sch Med Mt Sinai, Zena & Michael Wiener Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1033, New York, NY 10029 USA.
[Kadian-Dodov, Daniella; Olin, Jeffrey W.] Icahn Sch Med Mt Sinai, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, 1 Gustave L Levy Pl,Box 1033, New York, NY 10029 USA.
[Gornik, Heather L.; Kim, Esther S. H.; Kline-Rogers, Eva] Cleveland Clin Heart & Vasc Inst, Dept Cardiovasc Med, Vasc Med Sect, Cleveland, OH USA.
[Gu, Xiaokui; Froehlich, James] Univ Michigan, Cardiovasc Ctr, Ann Arbor, MI 48109 USA.
[Bacharach, J. Michael] Avera Heart Hosp South Dakota, Dept Cardiol, Sioux Falls, SD USA.
[Chi, Yung-Wei] Univ Calif Davis, Med Ctr, Div Cardiovasc Med, Sacramento, CA USA.
[Gray, Bruce H.] Vasc Hlth Alliance, Greenville, SC USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Fireman Vasc Ctr, Boston, MA 02114 USA.
[Mace, Pamela] Fibromuscular Dysplasia Soc Amer, Rocky River, OH USA.
[Sharma, Aditya] Univ Virginia, Div Cardiovasc Med, Charlottesville, VA USA.
[White, Christopher] Univ Queensland, Ochsner Clin Sch, Ochsner Med Ctr, Dept Cardiovasc Dis,John Ochsner Heart & Vasc Ins, New Orleans, LA USA.
RP Olin, JW (reprint author), Icahn Sch Med Mt Sinai, Zena & Michael Wiener Cardiovasc Inst, 1 Gustave L Levy Pl,Box 1033, New York, NY 10029 USA.; Olin, JW (reprint author), Icahn Sch Med Mt Sinai, Marie Josee & Henry R Kravis Ctr Cardiovasc Hlth, 1 Gustave L Levy Pl,Box 1033, New York, NY 10029 USA.
EM jeffrey.olin@mountsinai.org
FU FMD Society of America (FMDSA)
FX From the aZena and Michael A. Wiener Cardiovascular Institute
and Marie-Josee and Henry R. Kravis Center for Cardiovascular Health,
Icahn School of Medicine at Mount Sinai, New York, New York;
bVascular Medicine Section, Department of Cardiovascular
Medicine, Cleveland Clinic Heart and Vascular Institute, Cleveland,
Ohio; cCardiovascular Center, University of Michigan, Ann
Arbor, Michigan; dDepartment of Cardiology, Avera Heart
Hospital of South Dakota, Sioux Falls, South Dakota;
eDivision of Cardiovascular Medicine, University of
California Davis Medical Center, Sacremento, California;
fVascular Health Alliance, Greenville, South Carolina;
gFireman Vascular Center, Massachusetts General Hospital,
Boston, Massachusetts; hFibromuscular Dysplasia Society of
America, Rocky River, Ohio; iDivision of Cardiovascular
Medicine, University of Virginia, Charlottesville, Virginia; and the
jDepartment of Cardiovascular Diseases, John Ochsner Heart
and Vascular Institute, Ochsner Medical Center, University of Queensland
Ochsner Clinical School, New Orleans, Louisiana. The U.S. Registry for
Fibromuscular Dysplasia (FMD) is supported by the FMD Society of America
(FMDSA). Dr. Gornik is an FMDSA Medical Advisory Board member. Dr.
Froehlich is a consultant for Pfizer, Merck, Novartis, Janssen, and
Boehringer-Ingelheim. Ms. Mace is FMDSA Executive Board Director. Dr.
Olin is FMDSA Medical Advisory Board Chair. Dr. Jaff is a VIVA
Physicians and Society for Cardiovascular Angiography and Intervention
board member. Dr. Kim is consultant for Philips Ultrasound. All other
authors have reported that they have no relationships relevant to the
contents of this paper to disclose. Mark Creager, MD, served as Guest
Editor for this paper.
NR 54
TC 2
Z9 2
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 12
PY 2016
VL 68
IS 2
BP 176
EP 185
DI 10.1016/j.jacc.2016.04.044
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DQ3SV
UT WOS:000379123800007
PM 27386771
ER
PT J
AU Gyuricza, MR
Manheimer, KB
Apte, V
Krishnan, B
Joyce, EF
Mckee, BD
McKim, KS
AF Gyuricza, Mercedes R.
Manheimer, Kathryn B.
Apte, Vandana
Krishnan, Badri
Joyce, Eric F.
Mckee, Bruce D.
McKim, Kim S.
TI Dynamic and Stable Cohesins Regulate Synaptonemal Complex Assembly and
Chromosome Segregation
SO CURRENT BIOLOGY
LA English
DT Article
ID SISTER-CHROMATID COHESION; DROSOPHILA OOCYTES; MEIOTIC PROPHASE; AXIAL
ELEMENT; CROSSING-OVER; PROTEIN ORD; NIPPED-B; SYNAPSIS; MEIOSIS;
MELANOGASTER
AB Assembly of the synaptonemal complex (SC) in Drosophila depends on two independent pathways defined by the chromosome axis proteins C(2) M and ORD. Because C(2) M encodes a Kleisin-like protein and ORD is required for sister-chromatid cohesion, we tested the hypothesis that these two SC assembly pathways depend on two cohesin complexes. Through single-and double-mutant analysis to study the mitotic cohesion proteins Stromalin (SA) and Nipped-B (SCC2) in meiosis, we provide evidence that there are at least two meiosis-specific cohesin complexes. One complex depends on C(2) M, SA, and Nipped-B. Despite the presence of mitotic cohesins SA and Nipped-B, this pathway has only a minor role in meiotic sister-centromere cohesion and is primarily required for homolog interactions. C(2) M is continuously incorporated into pachytene chromosomes even though SC assembly is complete. In contrast, the second complex, which depends on meiosis-specific proteins SOLO, SUNN, and ORD is required for sister-chromatid cohesion, localizes to the centromeres and is not incorporated during prophase. Our results show that the two cohesin complexes have unique functions and are regulated differently. Multiple cohesin complexes may provide the diversity of activities required by the meiotic cell. For example, a dynamic complex may allow the chromosomes to regulate meiotic recombination, and a stable complex may be required for sister- chromatid cohesion.
C1 [Gyuricza, Mercedes R.; Manheimer, Kathryn B.; Apte, Vandana; Joyce, Eric F.; McKim, Kim S.] Rutgers State Univ, Waksman Inst, POB 759, Piscataway, NJ 08854 USA.
[Gyuricza, Mercedes R.; Manheimer, Kathryn B.; Apte, Vandana; Joyce, Eric F.; McKim, Kim S.] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA.
[Krishnan, Badri; Mckee, Bruce D.] Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA.
[Manheimer, Kathryn B.] Grad Sch Biomed Sci Mt Sinai, New York, NY 10029 USA.
[Krishnan, Badri] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Krishnan, Badri] Harvard Med Sch, Boston, MA 02114 USA.
[Joyce, Eric F.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
RP McKim, KS (reprint author), Rutgers State Univ, Waksman Inst, POB 759, Piscataway, NJ 08854 USA.; McKim, KS (reprint author), Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA.
EM mckim@rci.rutgers.edu
FU Busch Predoctoral Fellowship; Aresty Foundation Summer Research
Fellowship; NIH [GM101955, GM040489]
FX We thank Li Nguyen for technical assistance; Scott Hawley, Gary Karpen,
Christian Lehner, and Claudio Sunkel for providing antibodies; Oren
Schuldiner for an SMC1 clone; and Sarah Radford for helpful comments on
the manuscript. We thank the TRiP at Harvard Medical School for
providing transgenic RNAi fly stocks used in this study. Fly stocks
obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537)
were also used in this study. M.R.G. was funded by a Busch Predoctoral
Fellowship, and V.A. was funded by an Aresty Foundation Summer Research
Fellowship. This work was supported by NIH grant GM101955 to K.S.M. and
GM040489 to B.D.M.
NR 50
TC 2
Z9 2
U1 6
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0960-9822
EI 1879-0445
J9 CURR BIOL
JI Curr. Biol.
PD JUL 11
PY 2016
VL 26
IS 13
BP 1688
EP 1698
DI 10.1016/j.cub.2016.05.006
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DY0PU
UT WOS:000384799500034
PM 27291057
ER
PT J
AU Fassbender, P
Herbstreit, F
Eikermann, M
Teschler, H
Peters, J
AF Fassbender, Philipp
Herbstreit, Frank
Eikermann, Matthias
Teschler, Helmut
Peters, Juergen
TI Obstructive Sleep Apnea-Perioperative Risk Factor
SO DEUTSCHES ARZTEBLATT INTERNATIONAL
LA English
DT Review
ID RESIDUAL NEUROMUSCULAR BLOCKADE; NEGATIVE PHARYNGEAL PRESSURE;
GENIOGLOSSUS MUSCLE-ACTIVITY; NATIONWIDE INPATIENT SAMPLE; UPPER-AIRWAY
COLLAPSIBILITY; OF-THE-LITERATURE; STOP-BANG SCORE; POSTOPERATIVE
COMPLICATIONS; BERLIN QUESTIONNAIRE; GENERAL-POPULATION
AB Background: Obstructive sleep apnea (OSA) is a common disorder of breathing but is probably underappreciated as a perioperative risk factor.
Methods: This review is based on pertinent articles, published up to 15 August 2015, that were retrieved by a selective search in PubMed based on the terms "sleep apnea AND anesthesia" OR "sleep apnea AND pathophysiology." The guidelines of multiple specialty societies were considered as well.
Results: OSA is characterized by phases of upper airway obstruction accompanied by apnea/hypoventilation, with hypoxemia, hypercapnia, and recurrent overactivation of the sympathetic nervous system. It has been reported that 22% to 82% of all adults who are about to undergo surgery have OSA. The causes of OSA are multifactorial and include, among others, an anatomical predisposition and / or a reduced inspiratory activation of the bronchodilator muscles, particularly when the patient is sleeping or has taken a sedative drug, anesthetic agent, or muscle relaxant. OSA is associated with arterial hypertension, coronary heart disease, and congestive heart failure. It can be assessed before the planned intervention with polysomnography and structured questionnaires (STOP/STOP-BANG), with sensitivities of 62% and 88%. The utility of miniaturized screening devices is debated. Patients with OSA are at risk for perioperative problems including difficult or ineffective mask ventilation and/or intubation, postoperative airway obstruction, and complications arising from other comorbid conditions. They should be appropriately monitored postoperatively depending on the type of intervention they have undergone, and depending on individually varying, patient-related factors; postoperative management in an intensive care unit may be indicated, although no validated data on this topic are yet available.
Conclusion: OSA patients need care by specialists from multiple disciplines, including anesthesiologists with experience in recognizing OSA, securing the airway of OSA patients, and managing them postoperatively. No randomized trials have yet compared the modalities of general anesthesia for OSA patients with respect to postoperative complications or phases of apnea or hypopnea.
C1 [Fassbender, Philipp; Herbstreit, Frank; Peters, Juergen] Clin Anesthesiol & Intens Care, Essen, Germany.
[Fassbender, Philipp; Herbstreit, Frank; Peters, Juergen] Essen Univ Hosp, Essen, Germany.
[Eikermann, Matthias] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Eikermann, Matthias] Harvard Med Sch, Boston, MA USA.
[Eikermann, Matthias] Univ Duisburg Essen, Essen, Germany.
[Teschler, Helmut] Univ Hosp Essen, Ruhrlandklin, Dept Intervent Pneumol, Essen, Germany.
RP Fassbender, P (reprint author), Univ Klinikum Essen, Klin Anasthesiol & Intens Med, Hufelandstr 55, D-45122 Essen, Germany.
EM philipp.fassbender@uk-essen.de
FU Merck; ResMed company
FX Prof. Eikermann owns stock in Calabash Bioscience Incorporated as well
as patents for the use of acyclic curcurbiturile (also known as
calabadione) to reverse pharmacological muscle relaxation. He has
received third-party research funding from Merck.; Prof. Teschler has
served as a paid consultant for the ResMed company, from which he has
also received lecture honoraria, third-party research funding, and
reimbursement of meeting participation fees and travel expenses.
NR 90
TC 0
Z9 0
U1 2
U2 2
PU DEUTSCHER AERZTE-VERLAG GMBH
PI COLOGNE
PA DIESELSTRABE 2, POSTFACH 400265, D-50859 COLOGNE, GERMANY
SN 1866-0452
J9 DTSCH ARZTEBL INT
JI Dtsch. Arztebl. Int.
PD JUL 11
PY 2016
VL 113
IS 27-28
BP 463
EP +
DI 10.3238/arztebl.2016.0463
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS5VY
UT WOS:000380852300001
PM 27476705
ER
PT J
AU Singhal, S
Bhojnagarwala, PS
O'Brien, S
Moon, EK
Garfall, AL
Rao, AS
Quatromoni, JG
Stephen, TL
Litzky, L
Deshpande, C
Feldman, MD
Hancock, WW
Conejo-Garcia, JR
Albelda, SM
Eruslanov, EB
AF Singhal, Sunil
Bhojnagarwala, Pratik S.
O'Brien, Shaun
Moon, Edmund K.
Garfall, Alfred L.
Rao, Abhishek S.
Quatromoni, Jon G.
Stephen, Tom Li
Litzky, Leslie
Deshpande, Charuhas
Feldman, Michael D.
Hancock, Wayne W.
Conejo-Garcia, Jose R.
Albelda, Steven M.
Eruslanov, Evgeniy B.
TI Origin and Role of a Subset of Tumor-Associated Neutrophils with
Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer
SO CANCER CELL
LA English
DT Article
ID POLYMORPHONUCLEAR NEUTROPHILS; CLASS-II; T-CELLS; INDUCTION; GROWTH;
TRANSDIFFERENTIATION; DIFFERENTIATION; PROLIFERATION; ACTIVATION;
NY-ESO-1
AB Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-g and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.
C1 [Singhal, Sunil; Bhojnagarwala, Pratik S.; Rao, Abhishek S.; Quatromoni, Jon G.; Eruslanov, Evgeniy B.] Univ Penn, Perelman Sch Med, Dept Surg, Div Thorac Surg, Philadelphia, PA 19104 USA.
[O'Brien, Shaun; Moon, Edmund K.; Albelda, Steven M.] Univ Penn, Perelman Sch Med, Div Pulm Allergy & Crit Care, Dept Med, Philadelphia, PA 19104 USA.
[Garfall, Alfred L.] Univ Penn, Perelman Sch Med, Div Hematol Oncol, Dept Med, Philadelphia, PA 19104 USA.
[Litzky, Leslie; Deshpande, Charuhas; Feldman, Michael D.; Hancock, Wayne W.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Singhal, Sunil] Philadelphia VA Med Ctr, Div Thorac Surg, Dept Surg, Philadelphia, PA 19104 USA.
[Stephen, Tom Li; Conejo-Garcia, Jose R.] Wistar Inst Anat & Biol, Tumor Microenvironm & Metastasis Program, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Hancock, Wayne W.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
RP Eruslanov, EB (reprint author), Univ Penn, Perelman Sch Med, Dept Surg, Div Thorac Surg, Philadelphia, PA 19104 USA.
EM evgeniy.eruslanov@uphs.upenn.edu
FU Department of Defense [LC140199]; NIH [RO1 CA187392-01A1, R01 CA193556,
K12CA076931]; Lung Cancer Translation Center of Excellence of the
Abramson Cancer Center at the University of Pennsylvania
FX This work was supported by the Department of Defense (LC140199 to E.E.),
NIH (RO1 CA187392-01A1 to E.E.), NIH (R01 CA193556 to S.S.), NIH
(K12CA076931 to A.G.), and the Lung Cancer Translation Center of
Excellence of the Abramson Cancer Center at the University of
Pennsylvania.
NR 38
TC 10
Z9 11
U1 9
U2 12
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1535-6108
EI 1878-3686
J9 CANCER CELL
JI Cancer Cell
PD JUL 11
PY 2016
VL 30
IS 1
BP 120
EP 135
DI 10.1016/j.ccell.2016.06.001
PG 16
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DR7JY
UT WOS:000380077100016
PM 27374224
ER
PT J
AU Okello, S
Churchill, C
Owori, R
Nasasira, B
Tumuhimbise, C
Abonga, CL
Mutiibwa, D
Christiani, DC
Corey, KE
AF Okello, Samson
Churchill, Cristina
Owori, Rogers
Nasasira, Benson
Tumuhimbise, Christine
Abonga, Charles Lagoro
Mutiibwa, David
Christiani, David C.
Corey, Kathleen E.
TI Population attributable fraction of Esophageal squamous cell carcinoma
due to smoking and alcohol in Uganda
SO BMC CANCER
LA English
DT Article
DE Population attributable fraction; Esophageal squamous cell carcinoma;
Alcohol; Smoking; Africa
ID RISK-FACTORS; HUMAN-PAPILLOMAVIRUS; GASTRIC CANCERS; LINXIAN; TOBACCO;
METHYLATION; DRINKING; COHORT; CHINA; TRIAL
AB Background: Despite the high rates and regional variation of esophageal squamous cell carcinoma (ESCC) in East Africa, the contributions of smoking and alcohol to the ESCC burden in the general population are unknown.
Methods: We conducted a case-control study of patients presenting for upper gastrointestinal endoscopic examination at Mbarara Regional Referral Hospital, Uganda. Sociodemographic data including smoking and alcohol intake were collected prior to endoscopy. Cases were those with histological diagnosis of ESCC and controls were participants with normal endoscopic examination and gastritis/duodentitis or normal histology. We used odds ratios associated with ESCC risk to determine the population attributable fractions for smoking, alcohol use, and a combination of smoking and alcohol use among adults aged 30 years or greater who underwent upper gastrointestinal endoscopy.
Results: Our study consisted of 67 cases and 142 controls. Median age was 51 years (IQR 40-64); and participants were predominantly male (59 %). Dysphagia and/or odynophagia as indications for endoscopy were significantly more in cases compared to controls (72 % vs 6 %, p < 0.0001). Male gender and increasing age were statistically associated with ESCC. In the unadjusted models, the population attributable fraction of ESCC due to male gender was 55 %, female gender - 49 %, smoking 20 %, alcohol 9 % and a combination of alcohol & smoking 15 %. After adjusting for gender and age, the population attributable fraction of ESCC due to smoking, alcohol intake and a combination of alcohol & smoking were 16, 10, and 13 % respectively.
Conclusion: In this population, 13 % of esophageal squamous cell carcinoma cases would be avoided if smoking and alcohol use were discontinued. These results suggest that other important risk factors for ESCC in southwestern Uganda remain unknown.
C1 [Okello, Samson; Nasasira, Benson; Tumuhimbise, Christine; Abonga, Charles Lagoro] Mbarara Univ Sci & Technol, Dept Internal Med, POB 1410, Mbarara, Uganda.
[Okello, Samson] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Churchill, Cristina] Univ Virginia, Dept Med, Charlottesville, VA USA.
[Owori, Rogers] Gwatiiro Hosp, Wakiso, Uganda.
[Mutiibwa, David] Mbarara Univ Sci & Technol, Dept Surg, Mbarara, Uganda.
[Christiani, David C.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Christiani, David C.; Corey, Kathleen E.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA.
[Corey, Kathleen E.] Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
RP Okello, S (reprint author), Mbarara Univ Sci & Technol, Dept Internal Med, POB 1410, Mbarara, Uganda.; Okello, S (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
EM okello.samson@must.ac.ug
OI Okello, Samson/0000-0001-7377-6094
NR 34
TC 0
Z9 0
U1 3
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD JUL 11
PY 2016
VL 16
AR 446
DI 10.1186/s12885-016-2492-x
PG 6
WC Oncology
SC Oncology
GA DR6LZ
UT WOS:000380014700001
PM 27400987
ER
PT J
AU Shin, M
Suzuki, M
Guan, XM
Smith, CE
Bartlett, JD
AF Shin, Masashi
Suzuki, Maiko
Guan, Xiaomu
Smith, Charles E.
Bartlett, John D.
TI Murine matrix metalloproteinase-20 overexpression stimulates cell
invasion into the enamel layer via enhanced Wnt signaling
SO SCIENTIFIC REPORTS
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; GENE-EXPRESSION; MOUSE INCISOR;
BETA-CATENIN; E-CADHERIN; ELECTRON-MICROSCOPY; ENDOTHELIAL-CELLS; DENTAL
ENAMEL; TOOTH; AMELOBLASTS
AB Matrix metalloproteinase-20 (MMP20) is expressed by ameloblasts in developing teeth and MMP20 mutations cause enamel malformation. We established a stably transfected Tet-Off Mmp20-inducible ameloblast-lineage cell line and found that MMP20 expression promoted cell invasion. Previously, we engineered transgenic mice (Tg) that drive Mmp20 expression and showed that Mmp20(+/+) Tg mice had soft enamel. Here we asked if Mmp20 overexpression disrupts ameloblast function. Incisors from Mmp20(+/+) mice expressing the Mmp20 Tg had a striking cell infiltrate which nearly replaced the entire enamel layer. A thin layer of enamel-like material remained over the dentin and at the outer tooth surface, but between these regions were invading fibroblasts and epithelial cells that surrounded ectopic bone-like calcifications. Mmp20(+/+) Tg mice had decreased enamel organ cadherin levels compared to the Mmp20 ablated and WT mice and, instead of predominantly locating adjacent to the ameloblast cell membrane, beta-catenin was predominantly present within the nuclei of invading cells. Our data suggest that increased cadherin cleavage by transgenic MMP20 in the WT background releases excess beta-catenin, which translocates to ameloblast nuclei to promote cell migration/invasion. Therefore, we conclude that MMP20 plays a role in normal ameloblast migration through tightly controlled Wnt signaling and that MMP20 overexpression disrupts this process.
C1 [Shin, Masashi; Suzuki, Maiko; Bartlett, John D.] Ohio State Univ, Coll Dent, Div Biosci, Columbus, OH 43210 USA.
[Guan, Xiaomu] Dept Mineralized Tissue Biol, Cambridge, MA 02142 USA.
[Guan, Xiaomu] Harvard Sch Dent Med, Forsyth Inst, Cambridge, MA 02142 USA.
[Smith, Charles E.] McGill Univ, Facil Electron Microscopy Res, Dept Anat & Cell Biol, Montreal, PQ H3A 0C7, Canada.
RP Bartlett, JD (reprint author), Ohio State Univ, Coll Dent, Div Biosci, Columbus, OH 43210 USA.
EM bartlett.196@osu.edu
FU National Institute of Dental and Craniofacial Research of the National
Institutes of Health [R01DE016276]
FX The authors thank Dr. Toshihiro Sugiyama for his generous gift of ALC
cells and Justine Dobeck for providing mouse incisor sections. Research
reported in this publication was supported by National Institute of
Dental and Craniofacial Research of the National Institutes of Health
under award number R01DE016276 (JDB).
NR 61
TC 0
Z9 0
U1 4
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 11
PY 2016
VL 6
AR 29492
DI 10.1038/srep29492
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ9LF
UT WOS:000379530700001
PM 27403713
ER
PT J
AU Stifter, K
Schuster, C
Schlosser, M
Boehm, BO
Schirmbeck, R
AF Stifter, Katja
Schuster, Cornelia
Schlosser, Michael
Boehm, Bernhard Otto
Schirmbeck, Reinhold
TI Exploring the induction of preproinsulin-specific Foxp3(+) CD4(+) Treg
cells that inhibit CD8(+) T cell-mediated autoimmune diabetes by DNA
vaccination
SO SCIENTIFIC REPORTS
LA English
DT Article
ID PD-1 PATHWAY; CD8+T CELLS; NOD MICE; TGF-BETA; TYPE-1; INSULIN;
EXPRESSION; ANTIGEN; TOLERANCE; RESPONSES
AB DNA vaccination is a promising strategy to induce effector T cells but also regulatory Foxp3(+) CD25(+) CD4(+) Treg cells and inhibit autoimmune disorders such as type 1 diabetes. Little is known about the antigen requirements that facilitate priming of Treg cells but not autoreactive effector CD8(+) T cells. We have shown that the injection of preproinsulin (ppins)-expressing pCI/ppins vector into PD-1- or PD-L1-deficient mice induced K-b/A12-21-monospecific CD8(+) T cells and autoimmune diabetes. A pCI/ppins Delta A12-21 vector (lacking the critical K-b/A12-21 epitope) did not induce autoimmune diabetes but elicited a systemic Foxp3(+) CD25(+) Treg cell immunity that suppressed diabetes induction by a subsequent injection of the diabetogenic pCI/ppins. TGF-beta expression was significantly enhanced in the Foxp3(+) CD25(+) Treg cell population of vaccinated/ppins-primed mice. Ablation of Treg cells in vaccinated/ppins-primed mice by anti-CD25 antibody treatment abolished the protective effect of the vaccine and enabled diabetes induction by pCI/ppins. Adoptive transfer of Treg cells from vaccinated/ppins-primed mice into PD-L1(-/-) hosts efficiently suppressed diabetes induction by pCI/ppins. We narrowed down the Treg-stimulating domain to a 15-residue ppins76-90 peptide. Vaccine-induced Treg cells thus play a crucial role in the control of de novo primed autoreactive effector CD8(+) T cells in this diabetes model.
C1 [Stifter, Katja; Schuster, Cornelia; Schirmbeck, Reinhold] Univ Ulm, Dept Internal Med 1, Med Ctr, Ulm, Germany.
[Schlosser, Michael] Univ Med Ctr Greifswald, Dept Med Biochem & Mol Biol, Res Grp Predict Diagnost, Karlsburg, Germany.
[Boehm, Bernhard Otto] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 636921, Singapore.
[Boehm, Bernhard Otto] Imperial Coll London, London, England.
[Schuster, Cornelia] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA.
RP Schirmbeck, R (reprint author), Univ Ulm, Dept Internal Med 1, Med Ctr, Ulm, Germany.
EM reinhold.schirmbeck@uni-ulm.de
FU Deutsche Forschungsgemeinschaft [GRK-1789, DFG SCHI-505/4-1]
FX We thank Ellen Allmendinger and Andrea Wissmann for outstanding
technical assistance. We thank Dr. T. Honjo (Department of Immunology
and Genomic Medicine, Kyoto University, Kyoto, Japan) for
PD-1-/- mice and Dr. Lieping Chen (Department of Oncology,
Johns Hopkins University School of Medicine, Baltimore, Maryland, USA)
for PD-L1 (B7-H1)-/- mice. We thank Dr. Erik Lindblad
(Brenntag Biosector, Frederikssund, Denmark) for providing Alhydrogel.
This work was supported by grants from the Deutsche
Forschungsgemeinschaft: GRK-1789 'CEMMA' and DFG SCHI-505/4-1 to R.S.
NR 52
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 11
PY 2016
VL 6
AR 29419
DI 10.1038/srep29419
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ8FT
UT WOS:000379445200001
PM 27406624
ER
PT J
AU Zietman, AL
AF Zietman, Anthony L.
TI Making Radiation Therapy for Prostate Cancer More Economical and More
Convenient
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RANDOMIZED-TRIAL; BREAST-CANCER; RADIOTHERAPY; FRACTIONATION; SCHEDULES;
LONG
C1 [Zietman, Anthony L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 10
TC 1
Z9 1
U1 0
U2 1
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2016
VL 34
IS 20
BP 2323
EP U30
DI 10.1200/JCO.2016.67.3764
PG 3
WC Oncology
SC Oncology
GA DQ3TW
UT WOS:000379127400001
PM 27091711
ER
PT J
AU Lee, WR
Dignam, JJ
Amin, MB
Bruner, DW
Low, D
Swanson, GP
Shah, AB
D'Souza, DP
Michalski, JM
Dayes, IS
Seaward, SA
Hall, WA
Nguyen, PL
Pisansky, TM
Faria, SL
Chen, Y
Koontz, BF
Paulus, R
Sandler, HM
AF Lee, W. Robert
Dignam, James J.
Amin, Mahul B.
Bruner, Deborah W.
Low, Daniel
Swanson, Gregory P.
Shah, Amit B.
D'Souza, David P.
Michalski, Jeff M.
Dayes, Ian S.
Seaward, Samantha A.
Hall, William A.
Nguyen, Paul L.
Pisansky, Thomas M.
Faria, Sergio L.
Chen, Yuhchyau
Koontz, Bridget F.
Paulus, Rebecca
Sandler, Howard M.
TI Randomized Phase III Noninferiority Study Comparing Two Radiotherapy
Fractionation Schedules in Patients With Low-Risk Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID INTENSITY-MODULATED RADIOTHERAPY; RADIATION-THERAPY; CONTROLLED-TRIAL;
HYPOFRACTIONATION; FAILURE; MEN; TOXICITY
AB Purpose
Conventional radiotherapy (C-RT) treatment schedules for patients with prostate cancer typically require 40 to 45 treatments that take place from. 8 to 9 weeks. Preclinical and clinical research suggest that hypofractionation-fewer treatments but at a higher dose per treatment-may produce similar outcomes. This trial was designed to assess whether the efficacy of a hypofractionated radiotherapy (H-RT) treatment schedule is no worse than a C-RT schedule in men with low-risk prostate cancer.
Patients and Methods
A total of 1,115 men with low-risk prostate cancer were randomly assigned 1: 1 to C-RT (73.8 Gy in 41 fractions over 8.2 weeks) or to H-RT (70 Gy in 28 fractions over 5.6 weeks). This trial was designed to establish (with 90% power and an alpha of .05) that treatment with H-RT results in 5-year disease-free survival (DFS) that is not worse than C-RT by more than 7.65% (H-RT/C-RT hazard ratio [HR] < 1.52).
Results
A total of 1,092 men were protocol eligible and had follow-up information; 542 patients were assigned to C-RT and 550 to H-RT. Median follow-up was 5.8 years. Baseline characteristics were not different according to treatment assignment. The estimated 5-year DFS was 85.3% (95% CI, 81.9 to 88.1) in the C-RT arm and 86.3% (95% CI, 83.1 to 89.0) in the H-RT arm. The DFS HR was 0.85 (95% CI, 0.64 to 1.14), and the predefined noninferiority criterion that required that DFS outcomes be consistent with HR < 1.52 was met (P<.001). Late grade 2 and 3 GI and genitourinary adverse events were increased (HR, 1.31 to 1.59) in patients who were treated with H-RT.
Conclusion
In men with low-risk prostate cancer, the efficacy of 70 Gy in 28 fractions over 5.6 weeks is not inferior to 73.8 Gy in 41 fractions over 8.2 weeks, although an increase in late GI/genitourinary adverse events was observed in patients treated with H-RT. (C) 2016 by American Society of Clinical Oncology
C1 [Lee, W. Robert; Koontz, Bridget F.] Duke Univ, Med Ctr, Durham, NC USA.
[Dignam, James J.] Univ Chicago, Chicago, IL USA.
[Amin, Mahul B.; Sandler, Howard M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Low, Daniel] Univ Calif Los Angeles, Los Angeles, CA USA.
[Seaward, Samantha A.] Kaiser Permanente No Calif, Santa Clara, CA USA.
[Bruner, Deborah W.] Emory Univ, Atlanta, GA 30322 USA.
[Swanson, Gregory P.] Baylor Scott & White Healthcare Temple Clin, Temple, TX USA.
[Shah, Amit B.] York Canc Ctr, York, N Yorkshire, England.
[Dignam, James J.; Paulus, Rebecca] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA.
[D'Souza, David P.] London Reg Canc Program, London, ON, Canada.
[Dayes, Ian S.] McMaster Univ, Hamilton, ON, Canada.
[Faria, Sergio L.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada.
[Michalski, Jeff M.] Washington Univ, Sch Med, St Louis, MO USA.
[Hall, William A.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Nguyen, Paul L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Nguyen, Paul L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Pisansky, Thomas M.] Mayo Clin, Rochester, MN USA.
[Chen, Yuhchyau] Univ Rochester, Rochester, NY USA.
RP Lee, WR (reprint author), Duke Univ, Med Ctr, Dept Radiat Oncol, Box 3085, Durham, NC 27710 USA.
EM w.robert.lee@duke.edu
FU National Cancer Institute [U10CA21661, U10CA37422, CA81647, U10CA180868,
U10CA180822]
FX Supported by National Cancer Institute Grants No. U10CA21661 (Radiation
Therapy Oncology Group Statistical Operations), U10CA37422 (Community
Clinical Oncology Program), CA81647 (Advanced Technology Quality
Assurance Center), U10CA180868 (NRG Oncology Operations), and
U10CA180822 (NRG Oncology Data Monitoring Committee).
NR 29
TC 20
Z9 20
U1 1
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2016
VL 34
IS 20
BP 2325
EP U39
DI 10.1200/JCO.2016.67.0448
PG 9
WC Oncology
SC Oncology
GA DQ3TW
UT WOS:000379127400002
PM 27044935
ER
PT J
AU Denduluri, N
Somerfield, MR
Eisen, A
Holloway, JN
Hurria, A
King, TA
Lyman, GH
Partridge, AH
Telli, ML
Trudeau, ME
Wolff, AC
AF Denduluri, Neelima
Somerfield, Mark R.
Eisen, Andrea
Holloway, Jamie N.
Hurria, Arti
King, Tari A.
Lyman, Gary H.
Partridge, Ann H.
Telli, Melinda L.
Trudeau, Maureen E.
Wolff, Antonio C.
TI Selection of Optimal Adjuvant Chemotherapy Regimens for Human Epidermal
Growth Factor Receptor 2 (HER2) -Negative and Adjuvant Targeted Therapy
for HER2-Positive Breast Cancers: An American Society of Clinical
Oncology Guideline Adaptation of the Cancer Care Ontario Clinical
Practice Guideline
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID COMPLETE RESPONSE RATES; RANDOMIZED-TRIALS; SYSTEMIC THERAPY; PLUS
TRASTUZUMAB; OLDER-ADULTS; CYCLOPHOSPHAMIDE; WOMEN; DOXORUBICIN;
PACLITAXEL; DOCETAXEL
AB Purpose
A Cancer Care Ontario (CCO) guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer including adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancers was identified for adaptation.
Methods
The American Society of Clinical Oncology (ASCO) has a policy and set of procedures for adapting clinical practice guidelines developed by other organizations. The CCO guideline was reviewed for developmental rigor and content applicability.
Results
On the basis of the content review of the CCO guideline, the ASCO Panel agreed that, in general, the recommendations were clear and thorough and were based on the most relevant scientific evidence, and they presented options that will be acceptable to patients. However, for some topics addressed in the CCO guideline, the ASCO Panel formulated a set of adapted recommendations on the basis of local context and practice beliefs of the Panel members.
Recommendations
Decisions regarding adjuvant chemotherapy regimens should take into account baseline recurrence risk, toxicities, likelihood of benefit, and host factors such as comorbidities. In high-risk HER2-negative populations with excellent performance status, anthracycline-and taxane-containing regimens are the standard of care. Docetaxel and cyclophosphamide for four cycles is an acceptable non-anthracycline regimen. In high-risk HER2-positive disease, sequential anthracycline and taxanes administered concurrently with trastuzumab or docetaxel, carboplatin, and trastuzumab for six cycles are recommended. An alternative regimen in a lower-risk, node-negative, HER2-positive population is paclitaxel and trastuzumab once per week for 12 cycles. Trastuzumab should be given for 1 year. Platinum salts should not be routinely administered in the adjuvant triple-negative population until survival efficacy data become available. (C) 2016 by American Society of Clinical Oncology
C1 [Denduluri, Neelima] US Oncol Network, Virginia Canc Specialists, Arlington, VA USA.
[Somerfield, Mark R.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Eisen, Andrea; Trudeau, Maureen E.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada.
[Eisen, Andrea; Trudeau, Maureen E.] Canc Care Ontario, Toronto, ON, Canada.
[Hurria, Arti] City Hope Natl Med Ctr, Duarte, CA USA.
[Telli, Melinda L.] Stanford Univ, Palo Alto, CA 94304 USA.
[King, Tari A.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lyman, Gary H.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Wolff, Antonio C.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Denduluri, N (reprint author), Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
EM guidelines@asco.org
NR 32
TC 13
Z9 13
U1 3
U2 3
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD JUL 10
PY 2016
VL 34
IS 20
BP 2416
EP U186
DI 10.1200/JCO.2016.67.0182
PG 14
WC Oncology
SC Oncology
GA DQ3TW
UT WOS:000379127400013
PM 27091714
ER
PT J
AU Kimball, AB
Javorsky, E
Ron, ES
Crowley, W
Langer, R
AF Kimball, A. B.
Javorsky, E.
Ron, E. S.
Crowley, W., Jr.
Langer, R.
TI A novel approach to administration of peptides in women: Systemic
absorption of a GnRH agonist via transvaginal ring delivery system
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Intravaginal Ring; EVA; GnRH Agonist; Peptide; Phase 1; Transepithelial
ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC PRECOCIOUS PUBERTY;
DRUG-DELIVERY; LHRH AGONIST; CONTRACEPTION; POLYMERS; ANALOG; ROUTE
AB trans-Epithelial delivery of medication across the vagina has proven successful for administration of small, lipophilic molecules such as sex steroids. However, little information is available regarding the vaginal delivery of larger and more polar molecules that currently require parenteral administration because the vaginal epithelium is perceived as a barrier to absorption of larger molecular weight (MW) molecules. Six healthy women underwent administration of 18 or 36 mg of leuprolide, a GnRH agonist and a larger MW peptide, via a novel ethylene vinyl acetate (EVA) ring transvaginal drug delivery system (TVDS). Serum levels rose within 8 h following insertion: low dose at 310 pg/ml and high dose at 1220 pg/ml, i.e. levels typically following parenteral injections of leuprolide. GnRHa biological activity was validated by secretion of gonadotropins and sex steroids. These results demonstrate that the non-keratinized vaginal epithelium permits a rapid absorption of a biologically active peptide and that there is significant potential for a novel TVDS to deliver peptides and possibly other macromolecules therapeutically.
Significance statement: Current routes of administration of medications can include oral, subcutaneous, intravenous, intramuscular, transcutaneous, etc. Many of these approaches have limitations, including pain, poor tolerability, lack of adherence, and inadequate delivery. Peptides, in particular, cannot typically be given orally because they are broken down in the intestinal tract before they are absorbed. While the skin is an attractive way to deliver medications, its superb intrinsic barrier function often makes this route untenable at times. The vaginal epithelium, in contrast, is not keratinized and can allow absorption of other molecules. In this study, we demonstrate that a novel transvaginal drug delivery system(TVDS) is capable of delivering peptide therapeutics to women in a non-parenteral fashion as demonstrated by both blood levels and biologic effects of its delivery. (C) 2016 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
C1 [Kimball, A. B.; Javorsky, E.; Crowley, W., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Ron, E. S.] Madash LLC, Lexington, MA USA.
[Langer, R.] MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RP Kimball, AB (reprint author), Massachusetts Gen Hosp, 50 Staniford St 240, Boston, MA 02114 USA.
EM harvardskinstudies@partners.org
FU Swensrud Foundation and Combinent Biomedical Systems; Juniper
Pharmaceuticals
FX Funding for this study was supplied in part by The Swensrud Foundation
and Combinent Biomedical Systems. An exclusive worldwide license to the
novel vaginal ring delivery system was acquired by Juniper
Pharmaceuticals, Inc., in April 2015. Final editing of the manuscript
and the submission thereof was funded by Juniper Pharmaceuticals.
NR 22
TC 2
Z9 2
U1 10
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-3659
EI 1873-4995
J9 J CONTROL RELEASE
JI J. Control. Release
PD JUL 10
PY 2016
VL 233
BP 19
EP 28
DI 10.1016/j.jconrel.2016.04.035
PG 10
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DO8TJ
UT WOS:000378056400003
PM 27130696
ER
PT J
AU Das, F
Dey, N
Bera, A
Kasinath, BS
Ghosh-Choudhury, N
Choudhury, GG
AF Das, Falguni
Dey, Nirmalya
Bera, Amit
Kasinath, Balakuntalam S.
Ghosh-Choudhury, Nandini
Choudhury, Goutam Ghosh
TI MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor
Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE Akt PKB; cancer; cell signaling; microRNA (miRNA); mTOR complex (mTORC)
ID PHASE-III TRIAL; MAMMALIAN TARGET; CLEAR-CELL; MESSENGER-RNA;
TRANSLATION INITIATION; TUMOR PROGRESSION; PROMOTER ACTIVITY; MESANGIAL
CELLS; CANCER; RAPAMYCIN
AB Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells. We identified an miR-214 recognition element in the 3UTR of IGF-1R mRNA and confirmed its responsiveness to miR-214. Overexpression of miR-214 decreased the IGF-1R protein levels, resulting in the inhibition of Akt kinase activity in both types of renal cancer cells. IGF-1 provoked phosphorylation and inactivation of PRAS40 in an Akt-dependent manner, leading to the activation of mTORC1 signal transduction to increase phosphorylation of S6 kinase and 4EBP-1. Phosphorylation-deficient mutants of PRAS40 and 4EBP-1 significantly inhibited IGF-1R-driven proliferation of renal cancer cells. Expression of miR-214 suppressed IGF-1R-induced phosphorylation of PRAS40, S6 kinase, and 4EBP-1, indicating inhibition of mTORC1 activity. Finally, miR-214 significantly blocked IGF-1R-forced renal cancer cell proliferation, which was reversed by expression of 3UTR-less IGF-1R and constitutively active mTORC1. Together, our results identify a reciprocal regulation of IGF-1R levels and miR-214 expression in renal cancer cells independent of VHL status. Our data provide evidence for a novel mechanism for IGF-1R-driven renal cancer cell proliferation involving miR-214 and mTORC1.
C1 [Kasinath, Balakuntalam S.; Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Vet Affairs Res & Geriatr Res, San Antonio, TX 78229 USA.
[Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Educ & Clin Ctr, San Antonio, TX 78229 USA.
[Das, Falguni; Dey, Nirmalya; Bera, Amit; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
[Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
RP Choudhury, GG (reprint author), South Texas Vet Hlth Care Syst, Vet Affairs Res & Geriatr Res, San Antonio, TX 78229 USA.; Choudhury, GG (reprint author), South Texas Vet Hlth Care Syst, Educ & Clin Ctr, San Antonio, TX 78229 USA.; Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
EM choudhuryg@uthscsa.edu
FU Veterans Affairs Research Service Merit Review Grant [2 I01 BX000926];
National Institutes of Health [RO1 DK50190]; Veterans Affairs Merit
Review Grant [5I01BX001340, 5I01BX000150]; Veterans Affairs Senior
Research Career Scientist Award
FX This work was supported in part by the Veterans Affairs Research Service
Merit Review Grant 2 I01 BX000926 and National Institutes of Health
Grant RO1 DK50190 (to G. G. C.). The authors declare that they have no
conflicts of interest with the contents of this article. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.;
Supported by Veterans Affairs Merit Review Grant 5I01BX001340.;
Supported by Veterans Affairs Merit Review Grant 5I01BX000150.;
Recipient of a Veterans Affairs Senior Research Career Scientist Award.
To whom correspondence should be addressed. E-mail:
choudhuryg@uthscsa.edu.
NR 91
TC 2
Z9 2
U1 3
U2 3
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 8
PY 2016
VL 291
IS 28
BP 14662
EP 14676
DI 10.1074/jbc.M115.694331
PG 15
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DS1OV
UT WOS:000380366700021
PM 27226530
ER
PT J
AU Valm, AM
Oldenbourg, R
Borisy, GG
AF Valm, Alex M.
Oldenbourg, Rudolf
Borisy, Gary G.
TI Multiplexed Spectral Imaging of 120 Different Fluorescent Labels
SO PLOS ONE
LA English
DT Article
ID ARCHITECTURE; MICROSCOPY; PROTEINS
AB The number of fluorescent labels that can unambiguously be distinguished in a single image when acquired through band pass filters is severely limited by the spectral overlap of available fluorophores. The recent development of spectral microscopy and the application of linear unmixing algorithms to spectrally recorded image data have allowed simultaneous imaging of fluorophores with highly overlapping spectra. However, the number of distinguishable fluorophores is still limited by the unavoidable decrease in signal to noise ratio when fluorescence signals are fractionated over multiple wavelength bins. Here we present a spectral image analysis algorithm to greatly expand the number of distinguishable objects labeled with binary combinations of fluorophores. Our algorithm utilizes a priori knowledge about labeled specimens and imposes a binary label constraint on the unmixing solution. We have applied our labeling and analysis strategy to identify microbes labeled by fluorescence in situ hybridization and here demonstrate the ability to distinguish 120 differently labeled microbes in a single image.
C1 [Valm, Alex M.; Oldenbourg, Rudolf] Marine Biol Lab, Woods Hole, MA 02543 USA.
[Valm, Alex M.; Oldenbourg, Rudolf] Brown Univ, Providence, RI 02912 USA.
[Borisy, Gary G.] Forsyth Inst, Cambridge, MA USA.
[Valm, Alex M.] NICHHD, NIH, NIH NICHD, Bethesda, MD 20892 USA.
RP Valm, AM (reprint author), Marine Biol Lab, Woods Hole, MA 02543 USA.; Valm, AM (reprint author), Brown Univ, Providence, RI 02912 USA.; Valm, AM (reprint author), NICHHD, NIH, NIH NICHD, Bethesda, MD 20892 USA.
EM Alex.Valm@nih.gov
FU Alfred P. Sloan Foundation [2007-3-13]; National Institutes of Health
from the National Institute of Dental and Craniofacial Research (NIDCR)
[1RC1-DE020630]; National Institutes of Health from NIDCR
[1F31-DE019576]
FX This work was supported by Grant 2007-3-13 from the Alfred P. Sloan
Foundation (to GGB), National Institutes of Health Grant 1RC1-DE020630
from the National Institute of Dental and Craniofacial Research (NIDCR)
(to GGB) and by National Institutes of Health Fellowship 1F31-DE019576
from NIDCR (to AMV). The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 17
TC 0
Z9 0
U1 2
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 8
PY 2016
VL 11
IS 7
AR e0158495
DI 10.1371/journal.pone.0158495
PG 17
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR6IK
UT WOS:000380005400069
PM 27391327
ER
PT J
AU Mpondo, BCT
Neilson, E
Ernest, A
AF Mpondo, Bonaventura C. T.
Neilson, Eric
Ernest, Alex
TI Prevalence of chronic kidney disease in diabetic adult out-patients in
Tanzania
SO BMC NEPHROLOGY
LA English
DT Editorial Material
DE Diabetes mellitus; Schistosomiasis; Microalbuminuria; Proteinuria;
Chronic kidney disease
ID SCHISTOSOMIASIS; EPIDEMIOLOGY; ALBUMINURIA
AB Despite the increasing number of patients with Diabetes Mellitus in sub-Saharan Africa, the magnitude of chronic kidney disease among diabetics has not been well established. A study done by Janmohamed et al. found chronic kidney disease in 83.7 % of diabetics which is relatively higher than the prevalence reported elsewhere. However this study was conducted in schistosoma endemic area along the shores of Lake Victoria. Schistosomiasis has been reported to cause a range of renal diseases. Interpretation of these findings should therefore take into account the possibility of schistosomiasis as a possible confounder.
C1 [Mpondo, Bonaventura C. T.] Univ Dodoma, Coll Hlth & Allied Sci, Sch Med & Dent, Dept Internal Med, Dodoma, Tanzania.
[Neilson, Eric] Massachusetts Gen Hosp Ctr Global Hlth, Peace Corps SEED Global Hlth Serv Partnership, Boston, MA USA.
[Ernest, Alex] Univ Dodoma, Coll Hlth & Allied Sci, Sch Med & Dent, Dept Surg & Maternal Hlth, Dodoma, Tanzania.
RP Mpondo, BCT (reprint author), Univ Dodoma, Coll Hlth & Allied Sci, Sch Med & Dent, Dept Internal Med, Dodoma, Tanzania.
EM boniempondo@gmail.com
NR 14
TC 0
Z9 0
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD JUL 8
PY 2016
VL 17
AR 71
DI 10.1186/s12882-016-0276-9
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA DR3QZ
UT WOS:000379819000004
PM 27391318
ER
PT J
AU Morris, A
Paulson, JN
Talukder, H
Tipton, L
Kling, H
Cui, LJ
Fitch, A
Pop, M
Norris, KA
Ghedin, E
AF Morris, Alison
Paulson, Joseph N.
Talukder, Hisham
Tipton, Laura
Kling, Heather
Cui, Lijia
Fitch, Adam
Pop, Mihai
Norris, Karen A.
Ghedin, Elodie
TI Longitudinal analysis of the lung microbiota of cynomolgous macaques
during long-term SHIV infection
SO MICROBIOME
LA English
DT Article
DE SHIV; Microbiota; 16S rRNA; Time series
ID OBSTRUCTIVE PULMONARY-DISEASE; PREVOTELLA-INTERMEDIA; PRIMATE MODEL;
HIV-INFECTION; COLONIZATION
AB Background: Longitudinal studies of the lung microbiome are challenging due to the invasive nature of sample collection. In addition, studies of the lung microbiome in human disease are usually performed after disease onset, limiting the ability to determine early events in the lung. We used a non-human primate model to assess lung microbiome alterations over time in response to an HIV-like immunosuppression and determined impact of the lung microbiome on development of obstructive lung disease. Cynomolgous macaques were infected with the SIV-HIV chimeric virus SHIV89.6P. Bronchoalveolar lavage fluid samples were collected pre-infection and every 4 weeks for 53 weeks post-infection. The microbiota was characterized at each time point by 16S ribosomal RNA (rRNA) sequencing.
Results: We observed individual variation in the composition of the lung microbiota with a proportion of the macaques having Tropheryma whipplei as the dominant organism in their lungs. Bacterial communities varied over time both within and between animals, but there did not appear to be a systematic alteration due to SHIV infection. Development of obstructive lung disease in the SHIV-infected animals was characterized by a relative increase in abundance of oral anaerobes. Network analysis further identified a difference in community composition that accompanied the development of obstructive disease with negative correlations between members of the obstructed and non-obstructed groups. This emphasizes how species shifts can impact multiple other species, potentially resulting in disease.
Conclusions: This study is the first to investigate the dynamics of the lung microbiota over time and in response to immunosuppression in a non-human primate model. The persistence of oral bacteria in the lung and their association with obstruction suggest a potential role in pathogenesis. The lung microbiome in the non-human primate is a valuable tool for examining the impact of the lung microbiome in human health and disease.
C1 [Morris, Alison; Fitch, Adam] Univ Pittsburgh, Sch Med, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15213 USA.
[Morris, Alison; Kling, Heather; Norris, Karen A.] Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA.
[Paulson, Joseph N.; Talukder, Hisham; Pop, Mihai] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA.
[Tipton, Laura; Ghedin, Elodie] New York Univ, Dept Biol, Ctr Genom & Syst Biol, 12 Waverly Pl, New York, NY 10003 USA.
[Tipton, Laura; Ghedin, Elodie] New York Univ, Coll Global Publ Hlth, 12 Waverly Pl, New York, NY 10003 USA.
[Tipton, Laura; Ghedin, Elodie] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
[Cui, Lijia] Tsinghua Univ, Sch Med, Beijing, Peoples R China.
[Paulson, Joseph N.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Paulson, Joseph N.] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Ghedin, E (reprint author), New York Univ, Dept Biol, Ctr Genom & Syst Biol, 12 Waverly Pl, New York, NY 10003 USA.; Ghedin, E (reprint author), New York Univ, Coll Global Publ Hlth, 12 Waverly Pl, New York, NY 10003 USA.; Ghedin, E (reprint author), Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
EM elodie.ghedin@nyu.edu
FU US National Science Foundation [DGE0750616]; NIH/NHLBI [U01 HL098962,
K24 HL123342, R01 HL077095, R01 HL083462]; NIH/NIAID [R01 AI100947];
China Scholarship Council; [T32 AI49820]
FX JNP was supported by a US National Science Foundation Graduate Research
Fellowship (DGE0750616). EG, AM, MP, and LT were supported by NIH/NHLBI
U01 HL098962. AM was also supported by NIH/NHLBI K24 HL123342. KAN was
supported by NIH/NHLBI R01 HL077095 and R01 HL083462. MP was supported
by NIH/NIAID R01 AI100947. HK was supported by T32 AI49820. LC was a
visiting scholar from Tsinghua University and supported in part by the
China Scholarship Council.
NR 29
TC 1
Z9 1
U1 2
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 2049-2618
J9 MICROBIOME
JI Microbiome
PD JUL 8
PY 2016
VL 4
AR 38
DI 10.1186/s40168-016-0183-0
PG 11
WC Microbiology
SC Microbiology
GA DR4UI
UT WOS:000379898200001
PM 27391224
ER
PT J
AU Weiniger, CF
Lyell, DJ
Tsen, LC
Butwick, AJ
Shachar, B
Callaghan, WM
Creanga, AA
Bateman, BT
AF Weiniger, Carolyn F.
Lyell, Deirdre J.
Tsen, Lawrence C.
Butwick, Alexander J.
Shachar, BatZion
Callaghan, William M.
Creanga, Andreea A.
Bateman, Brian T.
TI Maternal outcomes of term breech presentation delivery: impact of
successful external cephalic version in a nationwide sample of delivery
admissions in the United States
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
DE Breech; Cesarean delivery; External cephalic version; Maternal morbidity
ID PRIMARY CESAREAN DELIVERY; VAGINAL BIRTH; RISK; MORBIDITY; RATES;
ASSOCIATION; PREDICTORS; MORTALITY; SECTION; WOMEN
AB Background: We aimed to define the frequency and predictors of successful external cephalic version in a nationally-representative cohort of women with breech presentations and to compare maternal outcomes associated with successful external cephalic version versus persistent breech presentation.
Methods: Using the Nationwide Inpatient Sample, a United States healthcare utilization database, we identified delivery admissions between 1998 and 2011 for women who had successful external cephalic version or persistent breech presentation (including unsuccessful or no external cephalic version attempt) at term. Multivariable logistic regression identified patient and hospital-level factors associated with successful external cephalic version. Maternal outcomes were compared between women who had successful external cephalic version versus persistent breech.
Results: Our study cohort comprised 1,079,576 delivery admissions with breech presentation; 56,409 (5.2 %) women underwent successful external cephalic version and 1,023,167 (94.8 %) women had persistent breech presentation at the time of delivery. The rate of cesarean delivery was lower among women who had successful external cephalic version compared to those with persistent breech (20.2 % vs. 94.9 %; p < 0.001). Compared to women with persistent breech at the time of delivery, women with successful external cephalic version were also less likely to experience several measures of significant maternal morbidity including endometritis (adjusted Odds Ratio (aOR) = 0.36, 95 % Confidence Interval (CI) 0.24-0.52), sepsis (aOR = 0.35, 95 % CI 0.24-0.51) and length of stay > 7 days (aOR = 0.53, 95 % CI 0.40-0.70), but had a higher risk of chorioamnionitis (aOR = 1.83, 95 % CI 1.54-2.17).
Conclusions: Overall a low proportion of women with breech presentation undergo successful external cephalic version, and it is associated with significant reduction in the frequency of cesarean delivery and a number of measures of maternal morbidity. Increased external cephalic version use may be an important approach to mitigate the high rate of cesarean delivery observed in the United States.
C1 [Weiniger, Carolyn F.] Hadassah Hebrew Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, POB 12000, Jerusalem, Israel.
[Lyell, Deirdre J.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Stanford, CA 94305 USA.
[Tsen, Lawrence C.] Harvard Med Sch, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA.
[Butwick, Alexander J.] Stanford Univ, Dept Anesthesiol Perioperat & Pain Med, Sch Med, Stanford, CA 94305 USA.
[Shachar, BatZion] Stanford Univ, Sch Med, Sheba Met & March Dimes Prematur Res Ctr, Maternal Fetal Med Unit,Dept Obstet & Gynecol, Stanford, CA 94305 USA.
[Callaghan, William M.] Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA.
[Creanga, Andreea A.] Johns Hopkins Bloomberg Sch Publ Hlth, Int Ctr Maternal & Newborn Hlth, Dept Int Hlth, 615 N Wolfe St, Baltimore, MD USA.
[Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Bateman, Brian T.] Harvard Med Sch, Boston, MA USA.
[Bateman, Brian T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA.
RP Weiniger, CF (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, POB 12000, Jerusalem, Israel.
EM carolynfweiniger@gmail.com
OI Butwick, Alexander/0000-0002-2048-0879
NR 34
TC 0
Z9 0
U1 1
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2393
J9 BMC PREGNANCY CHILDB
JI BMC Pregnancy Childbirth
PD JUL 8
PY 2016
VL 16
AR 150
DI 10.1186/s12884-016-0941-9
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DR0NX
UT WOS:000379605300001
PM 27392035
ER
PT J
AU Ortiz-Teran, L
Ortiz, T
Perez, DL
Aragon, JI
Diez, I
Pascual-Leone, A
Sepulcre, J
AF Ortiz-Teran, Laura
Ortiz, Tomas
Perez, David L.
Ignacio Aragon, Jose
Diez, Ibai
Pascual-Leone, Alvaro
Sepulcre, Jorge
TI Brain Plasticity in Blind Subjects Centralizes Beyond the Modal Cortices
SO FRONTIERS IN SYSTEMS NEUROSCIENCE
LA English
DT Article
DE congenital blind; fMRI; functional connectivity; late-onset blind;
multimodal integration network
ID INTRINSIC FUNCTIONAL CONNECTIVITY; HUMAN CEREBRAL-CORTEX; PRIMARY
VISUAL-CORTEX; OCCIPITAL CORTEX; MULTISENSORY INTEGRATION;
NEUROCOGNITIVE NETWORKS; ORGANIZATION; HUMANS; EXPERIENCE; LANGUAGE
AB It is well established that the human brain reorganizes following sensory deprivations. In blind individuals, visual processing regions including the lateral occipital cortex (LOC) are activated by auditory and tactile stimuli as demonstrated by neurophysiological and neuroimaging investigations. The mechanisms for such plasticity remain unclear, but shifts in connectivity across existing neural networks appear to play a critical role. The majority of research efforts to date have focused on neuroplastic changes within visual unimodal regions, however we hypothesized that neuroplastic alterations may also occur in brain networks beyond the visual cortices including involvement of multimodal integration regions and heteromodal cortices. In this study, two recently developed graph-theory based functional connectivity analyses, interconnector analyses and local and distant connectivity, were applied to investigate functional reorganization in regional and distributed neural-systems in late-onset blind (LB) and congenitally blind (CB) cohorts each compared to their own group of sighted controls. While functional network alterations as measured by the degree of differential links (DDL) occurred in sensory cortices, neuroplastic changes were most prominent within multimodal and association cortices. Subjects with LB showed enhanced multimodal integration connections in the parieto-opercular, temporoparietal junction (TPJ) and ventral premotor (vPM) regions, while CB individuals exhibited increased superior parietal cortex (SPC) connections. This study reveals the critical role of recipient multi-sensory integration areas in network reorganization and cross-modal plasticity in blind individuals. These findings suggest that aspects of cross-modal neuroplasticity and adaptive sensory-motor and auditory functions may potentially occur through reorganization in multimodal integration regions.
C1 [Ortiz-Teran, Laura; Pascual-Leone, Alvaro] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol,Div Cognit Neurol, Boston, MA USA.
[Ortiz-Teran, Laura; Diez, Ibai; Sepulcre, Jorge] Harvard Med Sch, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA USA.
[Ortiz-Teran, Laura; Diez, Ibai; Sepulcre, Jorge] Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02114 USA.
[Ortiz, Tomas] Univ Complutense Madrid, Fac Med, Dept Psiquiatria, Madrid, Spain.
[Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
[Perez, David L.; Sepulcre, Jorge] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed imaging, Boston, MA USA.
[Ignacio Aragon, Jose] Hosp Univ Puerta Hierro Majadahonda, Dept Radiodiagnost, Madrid, Spain.
[Diez, Ibai] Cruces Univ Hosp, BioCruces Hlth Res Inst, Baracaldo, Spain.
RP Sepulcre, J (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA USA.; Sepulcre, J (reprint author), Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02114 USA.; Sepulcre, J (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed imaging, Boston, MA USA.
EM sepulcre@nmr.mgh.harvard.edu
FU NIBIB NIH HHS [T32 EB013180]
NR 60
TC 0
Z9 0
U1 6
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5137
J9 FRONT SYST NEUROSCI
JI Front. Syst. Neurosci.
PD JUL 8
PY 2016
VL 10
AR 61
DI 10.3389/fnsys.2016.00061
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA DQ6JV
UT WOS:000379311700001
PM 27458350
ER
PT J
AU Weng, LD
Ziaei, S
Elliott, GD
AF Weng, Lindong
Ziaei, Shima
Elliott, Gloria D.
TI Effects of Water on Structure and Dynamics of Trehalose Glasses at Low
Water Contents and its Relationship to Preservation Outcomes
SO SCIENTIFIC REPORTS
LA English
DT Article
ID MOLECULAR-DYNAMICS; INTRACELLULAR GLASSES; MAMMALIAN-CELLS; TEMPERATURE;
CRYOPRESERVATION; VITRIFICATION; SIMULATION; GLYCEROL; SYSTEMS; STATE
AB Dry preservation of biologics in sugar glasses is regarded as a promising alternative to conventional cryopreservation. Evidence from various studies has suggested that there is a critical range of water content beyond which the viability of preserved biologics can be greatly compromised. In this study the viability of T-cells was determined as a function of end water content after microwave-assisted drying in trehalose solutions. Hydrogen-bonding and clustering phenomena in trehalose solutions of the same moisture content were also evaluated using molecular dynamics simulation. Post-rehydration viability decreased dramatically within the range of 0.1-1 gH(2)O/gdw. Molecular modeling revealed that as the water content approached 0.1 gH(2)O/gdw the matrix formed a large interconnected trehalose skeleton with a minimal number of bound water molecules scattered in the bulk. The diffusion coefficients of trehalose oxygen atoms most distant from the glycosidic linkage fluctuated around 7.5 x 10(-14) m(2)/s within the range of 0.02-0.1 gH(2)O/gdw and increased again to similar to 1.13 x 10(-13) m(2)/s at 0.01 gH(2)O/gdw and below due to the loss of water in the free volume between trehalose molecules. These insights can guide the optimal selection of final moisture contents to advance dry preservation methods.
C1 [Weng, Lindong; Ziaei, Shima; Elliott, Gloria D.] Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA.
[Weng, Lindong] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02129 USA.
RP Elliott, GD (reprint author), Univ N Carolina, Dept Mech Engn & Engn Sci, Charlotte, NC 28223 USA.
EM gdelliot@uncc.edu
RI Weng, Lindong/A-6041-2017
OI Weng, Lindong/0000-0003-4811-6531
FU National Institutes of Health [5R01GM101796]
FX This study was supported by grant # 5R01GM101796 from the National
Institutes of Health. The MD simulations were performed on the
University Research Computing (URC) High Performance Computing (HPC)
clusters at UNC Charlotte.
NR 33
TC 0
Z9 1
U1 18
U2 25
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 8
PY 2016
VL 6
AR 28795
DI 10.1038/srep28795
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ5HL
UT WOS:000379235700001
PM 27387435
ER
PT J
AU Harrington, D
Parmigiani, G
AF Harrington, David
Parmigiani, Giovanni
TI I-SPY 2-A Glimpse of the Future of Phase 2 Drug Development?
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID CLINICAL-TRIALS
C1 [Harrington, David] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Harrington, D (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
NR 5
TC 3
Z9 3
U1 1
U2 1
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 7
PY 2016
VL 375
IS 1
BP 7
EP 9
DI 10.1056/NEJMp1602256
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA EL8VA
UT WOS:000394897200003
PM 27406345
ER
PT J
AU Hotta, K
Aoyama, A
Oura, T
Yamada, Y
Tonsho, M
Huh, KH
Kawai, K
Schoenfeld, D
Allan, JS
Madsen, JC
Benichou, G
Smith, RN
Colvin, RB
Sachs, DH
Cosimi, AB
Kawai, T
AF Hotta, Kiyohiko
Aoyama, Akihiro
Oura, Tetsu
Yamada, Yohei
Tonsho, Makoto
Huh, Kyu Ha
Kawai, Kento
Schoenfeld, David
Allan, James S.
Madsen, Joren C.
Benichou, Gilles
Smith, Rex-Neal
Colvin, Robert B.
Sachs, David H.
Cosimi, A. Benedict
Kawai, Tatsuo
TI Induced regulatory T cells in allograft tolerance via transient mixed
chimerism
SO JCI INSIGHT
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; MHC CLASS-II; MISMATCHED
RENAL-TRANSPLANTATION; NONHUMAN-PRIMATES; MAINTENANCE IMMUNOSUPPRESSION;
HEMATOPOIETIC CHIMERISM; PERIPHERAL TOLERANCE; CYNOMOLGUS MACAQUES;
ENDOTHELIAL-CELLS; DONOR ANTIGEN
AB Successful induction of allograft tolerance has been achieved in nonhuman primates (NHPs) and humans via induction of transient hematopoietic chimerism. Since allograft tolerance was achieved in these recipients without durable chimerism, peripheral mechanisms are postulated to play a major role. Here, we report our studies of T cell immunity in NHP recipients that achieved long-term tolerance versus those that rejected the allograft (AR). All kidney, heart, and lung transplant recipients underwent simultaneous or delayed donor bone marrow transplantation (DBMT) following conditioning with a nonmyeloablative regimen. After DBMT, mixed lymphocyte culture with CFSE consistently revealed donor-specific loss of CD8(+) T cell responses in tolerant (TOL) recipients, while marked CD4(+) T cell proliferation in response to donor antigens was found to persist. Interestingly, a significant proportion of the proliferated CD4(+) cells were FOXP3(+) in TOL recipients, but not in AR or naive NHPs. In TOL recipients, CD4(+) FOXP3(+) cell proliferation against donor antigens was greater than that observed against third-party antigens. Finally, the expanded Tregs appeared to be induced Tregs (iTregs) that were converted from non-Tregs. These data provide support for the hypothesis that specific induction of iTregs by donor antigens is key to long-term allograft tolerance induced by transient mixed chimerism.
C1 [Hotta, Kiyohiko; Aoyama, Akihiro; Oura, Tetsu; Yamada, Yohei; Tonsho, Makoto; Huh, Kyu Ha; Kawai, Kento; Allan, James S.; Madsen, Joren C.; Benichou, Gilles; Sachs, David H.; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Ctr Transplantat Sci, Dept Surg, Boston, MA 02114 USA.
[Hotta, Kiyohiko; Aoyama, Akihiro; Oura, Tetsu; Yamada, Yohei; Tonsho, Makoto; Huh, Kyu Ha; Kawai, Kento; Allan, James S.; Madsen, Joren C.; Benichou, Gilles; Smith, Rex-Neal; Colvin, Robert B.; Sachs, David H.; Cosimi, A. Benedict; Kawai, Tatsuo] Harvard Med Sch, Boston, MA USA.
[Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
[Smith, Rex-Neal; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Kawai, T (reprint author), Harvard Med Sch, Ctr Transplantat Sci, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM TKAWAI@mgh.harvard.edu
NR 43
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD JUL 7
PY 2016
VL 1
IS 10
AR e86419
DI 10.1172/jci.insight.86419
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1LL
UT WOS:000387113300008
ER
PT J
AU Iwanicki, MP
Chen, HY
Iavarone, C
Zervantonakis, IK
Muranen, T
Novak, M
Ince, TA
Drapkin, R
Brugge, JS
AF Iwanicki, Marcin P.
Chen, Hsing-Yu
Iavarone, Claudia
Zervantonakis, Ioannis K.
Muranen, Taru
Novak, Marian
Ince, Tan A.
Drapkin, Ronny
Brugge, Joan S.
TI Mutant p53 regulates ovarian cancer transformed phenotypes through
autocrine matrix deposition
SO JCI INSIGHT
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; GRADE SEROUS CARCINOMA; TUBAL
INTRAEPITHELIAL CARCINOMA; DISTAL FALLOPIAN-TUBE; ANOIKIS RESISTANCE;
MESOTHELIAL CELLS; GENE-EXPRESSION; UP-REGULATION; TUMOR-CELLS; MOUSE
MODEL
AB High-grade serous ovarian carcinoma (HGS-OvCa) harbors p53 mutations and can originate from the epithelial cell compartment of the fallopian tube fimbriae. From this site, neoplastic cells detach, survive in the peritoneal cavity, and form cellular clusters that intercalate into the mesothelium to form ovarian and peritoneal masses. To examine the contribution of mutant p53 to phenotypic alterations associated with HGS-OvCA, we developed live-cell microscopy assays that recapitulate these early events in cultured fallopian tube nonciliated epithelial (FNE) cells. Expression of stabilizing mutant variants of p53, but not depletion of endogenous wild-type p53, in FNE cells promoted survival and cell-cell aggregation under conditions of cell detachment, leading to the formation of cell clusters with mesothelium-intercalation capacity. Mutant p53(R175H)-induced phenotypes were dependent on fibronectin production, alpha 5 beta 1 fibronectin receptor engagement, and TWIST1 expression. These results indicate that FNE cells expressing stabilizing p53 mutants acquire anchorage independence and subsequent mesothelial intercalation capacity through a mechanism involving mesenchymal transition and matrix production. These findings provide important new insights into activities of mutant p53 in the cells of origin of HGS-OvCa.
C1 [Iwanicki, Marcin P.; Chen, Hsing-Yu; Iavarone, Claudia; Zervantonakis, Ioannis K.; Muranen, Taru; Brugge, Joan S.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA.
[Novak, Marian; Drapkin, Ronny] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA.
[Ince, Tan A.] Univ Miami, Miller Sch Med, Stem Cell Inst, Miami, FL 33136 USA.
[Drapkin, Ronny] Univ Penn, Perelman Sch Med, Basser Ctr BRCA, Penn Ovarian Canc Res Ctr, 421 Curie Blvd, Philadelphia, PA 19104 USA.
RP Drapkin, R (reprint author), Univ Penn, Perelman Sch Med, Basser Ctr BRCA, Penn Ovarian Canc Res Ctr, 421 Curie Blvd, Philadelphia, PA 19104 USA.; Brugge, JS (reprint author), Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA.
EM rdrapkin@mail.med.upenn.edu; Joan_Brugge@hms.harvard.edu
NR 82
TC 4
Z9 4
U1 1
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 2379-3708
J9 JCI INSIGHT
JI JCI Insight
PD JUL 7
PY 2016
VL 1
IS 10
AR e86829
DI 10.1172/jci.insight.86829
PG 20
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1LL
UT WOS:000387113300011
ER
PT J
AU Liu, CT
Raghavan, S
Maruthur, N
Kabagambe, EK
Hong, J
Ng, MCY
Hivert, MF
Lu, YC
An, P
Bentley, AR
Drolet, AM
Gaulton, KJ
Guo, XQ
Armstrong, LL
Irvin, MR
Li, M
Lipovich, L
Rybin, DV
Taylor, KD
Agyemang, C
Palmer, ND
Cade, BE
Chen, WM
Dauriz, M
Delaney, JAC
Edwards, TL
Evans, DS
Evans, MK
Lange, LA
Leong, A
Liu, JM
Liu, YM
Nayak, U
Patel, SR
Porneala, BC
Rasmussen-Torvik, LJ
Snijder, MB
Stallings, SC
Tanaka, T
Yanek, LR
Zhao, W
Becker, DM
Bielak, LF
Biggs, ML
Bottinger, EP
Bowden, DW
Chen, GJ
Correa, A
Couper, DJ
Crawford, DC
Cushman, M
Eicher, JD
Fornage, M
Franceschini, N
Fu, YP
Goodarzi, MO
Gottesman, O
Hara, K
Harris, TB
Jensen, RA
Johnson, AD
Jhun, MA
Karter, AJ
Keller, MF
Kho, AN
Kizer, JR
Krauss, RM
Langefeld, CD
Li, XH
Liang, JL
Liu, SM
Lowe, WL
Mosley, TH
North, KE
Pacheco, JA
Peyser, PA
Patrick, AL
Rice, KM
Selvin, E
Sims, M
Smith, JA
Tajuddin, SM
Vaidya, D
Wren, MP
Yao, J
Zhu, XF
Ziegler, JT
Zmuda, JM
Zonderman, AB
Zwinderman, AH
Adeyemo, A
Boerwinkle, E
Ferrucci, L
Hayes, MG
Kardia, SLR
Miljkovic, I
Pankow, JS
Rotimi, CN
Sale, MM
Wagenknecht, LE
Arnett, DK
Chen, YDI
Nalls, MA
Province, MA
Kao, WHL
Siscovick, DS
Psaty, BM
Wilson, JG
Loos, RJF
Dupuis, J
Rich, SS
Florez, JC
Rotter, JI
Morris, AP
Meigs, JB
AF Liu, Ching-Ti
Raghavan, Sridharan
Maruthur, Nisa
Kabagambe, Edmond Kato
Hong, Jaeyoung
Ng, Maggie C. Y.
Hivert, Marie-France
Lu, Yingchang
An, Ping
Bentley, Amy R.
Drolet, Anne M.
Gaulton, Kyle J.
Guo, Xiuqing
Armstrong, Loren L.
Irvin, Marguerite R.
Li, Man
Lipovich, Leonard
Rybin, Denis V.
Taylor, Kent D.
Agyemang, Charles
Palmer, Nicholette D.
Cade, Brian E.
Chen, Wei-Min
Dauriz, Marco
Delaney, Joseph A. C.
Edwards, Todd L.
Evans, Daniel S.
Evans, Michele K.
Lange, Leslie A.
Leong, Aaron
Liu, Jingmin
Liu, Yongmei
Nayak, Uma
Patel, Sanjay R.
Porneala, Bianca C.
Rasmussen-Torvik, Laura J.
Snijder, Marieke B.
Stallings, Sarah C.
Tanaka, Toshiko
Yanek, Lisa R.
Zhao, Wei
Becker, Diane M.
Bielak, Lawrence F.
Biggs, Mary L.
Bottinger, Erwin P.
Bowden, Donald W.
Chen, Guanjie
Correa, Adolfo
Couper, David J.
Crawford, Dana C.
Cushman, Mary
Eicher, John D.
Fornage, Myriam
Franceschini, Nora
Fu, Yi-Ping
Goodarzi, Mark O.
Gottesman, Omri
Hara, Kazuo
Harris, Tamara B.
Jensen, Richard A.
Johnson, Andrew D.
Jhun, Min A.
Karter, Andrew J.
Keller, Margaux F.
Kho, Abel N.
Kizer, Jorge R.
Krauss, Ronald M.
Langefeld, Carl D.
Li, Xiaohui
Liang, Jingling
Liu, Simin
Lowe, William L., Jr.
Mosley, Thomas H.
North, Kari E.
Pacheco, Jennifer A.
Peyser, Patricia A.
Patrick, Alan L.
Rice, Kenneth M.
Selvin, Elizabeth
Sims, Mario
Smith, Jennifer A.
Tajuddin, Salman M.
Vaidya, Dhananjay
Wren, Mary P.
Yao, Jie
Zhu, Xiaofeng
Ziegler, Julie T.
Zmuda, Joseph M.
Zonderman, Alan B.
Zwinderman, Aeilko H.
Adeyemo, Adebowale
Boerwinkle, Eric
Ferrucci, Luigi
Hayes, M. Geoffrey
Kardia, Sharon L. R.
Miljkovic, Iva
Pankow, James S.
Rotimi, Charles N.
Sale, Michele M.
Wagenknecht, Lynne E.
Arnett, Donna K.
Chen, Yii-Der Ida
Nalls, Michael A.
Province, Michael A.
Kao, W. H. Linda
Siscovick, David S.
Psaty, Bruce M.
Wilson, James G.
Loos, Ruth J. F.
Dupuis, Josee
Rich, Stephen S.
Florez, Jose C.
Rotter, Jerome I.
Morris, Andrew P.
Meigs, James B.
CA AAAG Consortium
CARe Consortium
COGENT-BP Consortium
eMERGE Consortium
MEDIA Consortium
MAGIC Consortium
TI Trans-ethnic Meta-analysis and Functional Annotation Illuminates the
Genetic Architecture of Fasting Glucose and Insulin
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; TYPE-2 DIABETES RISK; GLUCOKINASE REGULATORY
PROTEIN; BETA-CELL FUNCTION; BODY-MASS INDEX; TRIGLYCERIDE LEVELS;
PLASMA-GLUCOSE; TRANSETHNIC METAANALYSIS; AFRICAN-ANCESTRY; GLYCEMIC
TRAITS
AB Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
C1 [Liu, Ching-Ti; Hong, Jaeyoung; Rybin, Denis V.; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Raghavan, Sridharan; Leong, Aaron; Porneala, Bianca C.; Meigs, James B.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Raghavan, Sridharan] Eastern Colorado Hlth Care Syst, Dept Vet Affairs Med Ctr, Denver, CO 80220 USA.
[Raghavan, Sridharan] Univ Colorado, Sch Med, Dept Med, Div Gen Internal Med, Denver, CO 80220 USA.
[Maruthur, Nisa] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21287 USA.
[Maruthur, Nisa; Selvin, Elizabeth] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21287 USA.
[Maruthur, Nisa; Li, Man; Selvin, Elizabeth; Vaidya, Dhananjay; Kao, W. H. Linda] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA.
[Kabagambe, Edmond Kato; Edwards, Todd L.] Vanderbilt Univ, Med Ctr, Sch Med, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
[Ng, Maggie C. Y.; Palmer, Nicholette D.; Bowden, Donald W.] Wake Forest Univ, Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.
[Ng, Maggie C. Y.; Bowden, Donald W.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.
[Hivert, Marie-France] Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA 02215 USA.
[Hivert, Marie-France; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ J1G 0A2, Canada.
[Lu, Yingchang; Bottinger, Erwin P.; Gottesman, Omri; Hara, Kazuo; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[An, Ping; Province, Michael A.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA.
[Bentley, Amy R.; Chen, Guanjie; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Drolet, Anne M.; Lipovich, Leonard] Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA.
[Gaulton, Kyle J.; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Guo, Xiuqing; Taylor, Kent D.; Li, Xiaohui; Yao, Jie; Chen, Yii-Der Ida; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
[Armstrong, Loren L.; Kho, Abel N.; Lowe, William L., Jr.; Pacheco, Jennifer A.; Hayes, M. Geoffrey] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Irvin, Marguerite R.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Lipovich, Leonard] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA.
[Agyemang, Charles; Snijder, Marieke B.; Zwinderman, Aeilko H.] Acad Med Ctr Amsterdam, Dept Publ Hlth, Meibergdreef 15, NL-1105 AZ Amsterdam, Netherlands.
[Palmer, Nicholette D.; Bowden, Donald W.; Wren, Mary P.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biochem, Winston Salem, NC 27157 USA.
[Cade, Brian E.] Harvard Med Sch, Brigham & Womens Hosp, Div Sleep & Circadian Disorders, Boston, MA 02115 USA.
[Chen, Wei-Min; Nayak, Uma; Sale, Michele M.; Rich, Stephen S.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Dauriz, Marco] Univ Verona, Dept Med, Div Endocrinol Diabet & Metab, I-37126 Verona, Italy.
[Delaney, Joseph A. C.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Evans, Daniel S.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA.
[Evans, Michele K.; Tajuddin, Salman M.] NIA, Hlth Dispar Res Sect, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27607 USA.
[Liu, Jingmin] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA.
[Patel, Sanjay R.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.
[Rasmussen-Torvik, Laura J.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Translat Gerontol Branch, Harbor Hosp, Baltimore, MD 21225 USA.
[Yanek, Lisa R.; Becker, Diane M.; Vaidya, Dhananjay] Johns Hopkins Univ, Dept Med, Div Gen Internal Med, GeneSTAR Res Program, Baltimore, MD 21287 USA.
[Zhao, Wei; Bielak, Lawrence F.; Jhun, Min A.; Peyser, Patricia A.; Smith, Jennifer A.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Becker, Diane M.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD 21287 USA.
[Biggs, Mary L.; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Biggs, Mary L.; Jensen, Richard A.; Siscovick, David S.; Psaty, Bruce M.] Univ Washington, Sch Med, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Correa, Adolfo; Sims, Mario] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Couper, David J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC 27514 USA.
[Crawford, Dana C.] Case Western Reserve Univ, Inst Computat Biol, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Cushman, Mary] Univ Vermont, Coll Med, Dept Pathol & Med, Burlington, VT 05405 USA.
[Eicher, John D.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Eicher, John D.; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Framingham, MA 01702 USA.
[Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Franceschini, Nora; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Fu, Yi-Ping] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, NIH, Framingham, MA 01702 USA.
[Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Hara, Kazuo] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo 1138655, Japan.
[Hara, Kazuo] Tokyo Med Univ, Dept Diabet Endocrinol & Metab, Tokyo 1630023, Japan.
[Harris, Tamara B.] NIH, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Karter, Andrew J.] Kaiser Permanente, Div Res, Oakland, CA 94612 USA.
[Keller, Margaux F.] Merck Res Labs, Dept Genet & Pharmacogen, 33 Ave Louis Pasteur, Boston, MA 02115 USA.
[Kizer, Jorge R.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Langefeld, Carl D.; Ziegler, Julie T.] Wake Forest Univ, Bowman Gray Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27157 USA.
[Langefeld, Carl D.; Ziegler, Julie T.] Wake Forest Univ, Bowman Gray Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.
[Liang, Jingling; Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Liu, Simin] Brown Univ, Dept Epidemiol, Providence, RI 02912 USA.
[Liu, Simin] Brown Univ, Dept Med, Providence, RI 02903 USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr Gerontol, Jackson, MS 39216 USA.
[Patrick, Alan L.] Tobago Hlth Studies Off, Scarborough, Trinid & Tobago.
[Zmuda, Joseph M.; Miljkovic, Iva] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Zonderman, Alan B.] NIA, Behav Epidemiol Sect, Lab Epidemiol & Populat Sci, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Pankow, James S.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Wagenknecht, Lynne E.] Wake Forest Univ, Bowman Gray Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA.
[Arnett, Donna K.] Univ Kentucky, Coll Publ Hlth, Lexington, KY 40563 USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Siscovick, David S.] New York Acad Med, New York, NY 10029 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Metab, Cambridge, MA 02142 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Florez, Jose C.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Inst Translat Med, Liverpool L69 3BX, Merseyside, England.
[Stallings, Sarah C.] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Clin & Translat Res, Nashville, TN 37203 USA.
RP Liu, CT (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.; Meigs, JB (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
EM ctliu@bu.edu; jmeigs@partners.org
RI Johnson, Andrew/G-6520-2013; Dauriz, Marco/S-5843-2016;
OI Dauriz, Marco/0000-0002-5542-5941; Tajuddin, Salman
M./0000-0002-7919-8528; Patel, Sanjay/0000-0002-9142-5172; Zonderman,
Alan B/0000-0002-6523-4778; Vaidya, Dhananjay/0000-0002-7164-1601;
Smith, Jennifer/0000-0002-3575-5468; Pankow, James/0000-0001-7076-483X
FU Johnson Johnson
FX B.M.P. serves on the DSMB of a clinical trial for the device
manufacturer Zoll LifeCor and on the Steering Committee for the Yale
Open Data Access Project funded by Johnson & Johnson. D.V. is a
consultant for Consumable Science, Inc. J.R.K. holds stock in Pfizer,
Inc., and Gilead Sciences, Inc.
NR 61
TC 1
Z9 1
U1 1
U2 2
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 7
PY 2016
VL 99
IS 1
BP 56
EP 75
DI 10.1016/j.ajhg.2016.05.006
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA DT6TI
UT WOS:000381616600005
PM 27321945
ER
PT J
AU Zhang, J
Ratanasirintrawoot, S
Chandrasekaran, S
Wu, ZT
Ficarro, SB
Yu, CX
Ross, CA
Cacchiarelli, D
Xia, Q
Seligson, M
Shinoda, G
Xie, W
Cahan, P
Wang, LF
Ng, SC
Tintara, S
Trapnell, C
Onder, T
Loh, YH
Mikkelsen, T
Sliz, P
Teitell, MA
Asara, JM
Marto, JA
Li, H
Collins, JJ
Daley, GQ
AF Zhang, Jin
Ratanasirintrawoot, Sutheera
Chandrasekaran, Sriram
Wu, Zhaoting
Ficarro, Scott B.
Yu, Chunxiao
Ross, Christian A.
Cacchiarelli, Davide
Xia, Qing
Seligson, Marc
Shinoda, Gen
Xie, Wen
Cahan, Patrick
Wang, Longfei
Ng, Shyh-Chang
Tintara, Supisara
Trapnell, Cole
Onder, Tamer
Loh, Yuin-Han
Mikkelsen, Tarjei
Sliz, Piotr
Teitell, Michael A.
Asara, John M.
Marto, Jarrod A.
Li, Hu
Collins, James J.
Daley, George Q.
TI LIN28 Regulates Stem Cell Metabolism and Conversion to Primed
Pluripotency
SO CELL STEM CELL
LA English
DT Article
ID GROUND-STATE PLURIPOTENCY; HUMAN SOMATIC-CELLS; MICRORNA BIOGENESIS;
SELF-RENEWAL; GLUCOSE-METABOLISM; DEFINED FACTORS; MESSENGER-RNAS;
LET-7; CANCER; PROLIFERATION
AB The RNA-binding proteins LIN28A and LIN28B play critical roles in embryonic development, tumorigenesis, and pluripotency, but their exact functions are poorly understood. Here, we show that, like LIN28A, LIN28B can function effectively with NANOG, OCT4, and SOX2 in reprogramming to pluripotency and that reactivation of both endogenous LIN28A and LIN28B loci are required for maximal reprogramming efficiency. In human fibroblasts, LIN28B is activated early during reprogramming, while LIN28A is activated later during the transition to bona fide induced pluripotent stem cells (iPSCs). In murine cells, LIN28A and LIN28B facilitate conversion from naive to primed pluripotency. Proteomic and metabolomic analysis highlighted roles for LIN28 in maintaining the low mitochondrial function associated with primed pluripotency and in regulating one-carbon metabolism, nucleotide metabolism, and histone methylation. LIN28 binds to mRNAs of proteins important for oxidative phosphorylation and modulates protein abundance. Thus, LIN28A and LIN28B play cooperative roles in regulating reprogramming, naive/primed pluripotency, and stem cell metabolism.
C1 [Zhang, Jin; Ratanasirintrawoot, Sutheera; Wu, Zhaoting; Xia, Qing; Seligson, Marc; Shinoda, Gen; Xie, Wen; Cahan, Patrick; Ng, Shyh-Chang; Tintara, Supisara; Onder, Tamer; Loh, Yuin-Han; Daley, George Q.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.
[Zhang, Jin; Ratanasirintrawoot, Sutheera; Wu, Zhaoting; Ficarro, Scott B.; Yu, Chunxiao; Xia, Qing; Seligson, Marc; Shinoda, Gen; Xie, Wen; Cahan, Patrick; Wang, Longfei; Ng, Shyh-Chang; Tintara, Supisara; Onder, Tamer; Loh, Yuin-Han; Sliz, Piotr; Marto, Jarrod A.; Daley, George Q.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Chandrasekaran, Sriram; Collins, James J.] MIT, Dept Biol Engn, Inst Med Engn & Sci, Cambridge, MA 02142 USA.
[Chandrasekaran, Sriram; Collins, James J.] MIT, Synthet Biol Ctr, Cambridge, MA 02142 USA.
[Chandrasekaran, Sriram; Cacchiarelli, Davide; Trapnell, Cole; Mikkelsen, Tarjei; Collins, James J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Chandrasekaran, Sriram; Collins, James J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Ficarro, Scott B.; Marto, Jarrod A.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yu, Chunxiao; Sliz, Piotr] Harvard Med Sch, Boston Childrens Hosp, Mol Med Lab, Boston, MA 02115 USA.
[Ross, Christian A.; Li, Hu] Mayo Clin, Ctr Individualized Med, Rochester, MN 55905 USA.
[Ross, Christian A.; Li, Hu] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN 55905 USA.
[Cacchiarelli, Davide; Trapnell, Cole; Mikkelsen, Tarjei] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Xia, Qing] Peking Univ, Sch Pharmaceut Sci, Dept Biol Chem, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China.
[Loh, Yuin-Han] A STAR Inst Mol & Cell Biol, Epigenet & Cell Fates Lab, Singapore 138673, Singapore.
[Loh, Yuin-Han] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
[Teitell, Michael A.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Broad Stem Cell Res Ctr, Los Angeles, CA 90095 USA.
[Teitell, Michael A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Asara, John M.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA.
[Asara, John M.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Ratanasirintrawoot, Sutheera] Chulalongkorn Univ, Fac Med, Bangkok 10330, Thailand.
RP Daley, GQ (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.; Daley, GQ (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM george.daley@childrens.harvard.edu
FU Howard Hughes Medical Institute; SysCODE (Systems-based Consortium for
Organ Design Engineering); NIH [RL1DE019021, CA196631-01A1,
1U54GM114838-01, R01GM107536, P50GM099117, U01 HL100001, P01CA120964,
S10RR032861, P30CA006516]; Mayo Clinic Foundation; Mayo Clinic Center
for Individualized Medicine; Ellison Medical Foundation
FX J.J.C. and H.L. were supported by the Howard Hughes Medical Institute,
SysCODE (Systems-based Consortium for Organ Design & Engineering), and
NIH grant RL1DE019021. H.L. was supported by NIH (grants CA196631-01A1
and 1U54GM114838-01), the Mayo Clinic Foundation, and the Mayo Clinic
Center for Individualized Medicine. G.Q.D. was supported by grants from
the NIH (R01GM107536, P50GM099117, and U01 HL100001) and by the Ellison
Medical Foundation and is an investigator of the Howard Hughes Medical
Institute. J.M.A. is supported by NIH grants P01CA120964, S10RR032861,
and P30CA006516. We thank Min Yuan and Susanne Breit-kopf for help with
mass spectrometry experiments; the Marcia Haigis laboratory for Seahorse
Analyzer facility; Lewis Cantley and Matthew Vander Heiden for
discussion; Michael Chen and the Brigham and Women's Hospital Transgenic
Core Facility for help with embryo analysis; The Boston Children's
Hospital Molecular Genetics Core Facility for microarray experiments;
and Thorsten Schlaeger and the Boston Children's Hospital hESC Core
Facility for support with stem cells.
NR 50
TC 11
Z9 11
U1 6
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD JUL 7
PY 2016
VL 19
IS 1
BP 66
EP 80
PG 15
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA DT6UT
UT WOS:000381620500012
PM 27320042
ER
PT J
AU Chami, N
Chen, MH
Slater, AJ
Eicher, JD
Evangelou, E
Tajuddin, SM
Love-Gregory, L
Kacprowski, T
Schick, UM
Nomura, A
Giri, A
Lessard, S
Brody, JA
Schurmann, C
Pankratz, N
Yanek, LR
Manichaikul, A
Pazoki, R
Mihailov, E
Hill, WD
Raffield, LM
Burt, A
Bartz, TM
Becker, DM
Becker, LC
Boerwinkle, E
Bork-Jensen, J
Bottinger, EP
O'Donoghue, ML
Crosslin, DR
de Denus, S
Dube, MP
Elliott, P
Engstrom, G
Evans, MK
Floyd, JS
Fornage, M
Gao, H
Greinacher, A
Gudnason, V
Hansen, T
Harris, TB
Hayward, C
Hernesniemi, J
Highland, HM
Hirschhorn, JN
Hofman, A
Irvin, MR
Kahonen, M
Lange, E
Launer, LJ
Lehtimaki, T
Li, J
Liewald, DCM
Linneberg, A
Liu, YM
Lu, YC
Lyytikainen, LP
Magi, R
Mathias, RA
Melander, O
Metspalu, A
Mononen, N
Nalls, MA
Nickerson, DA
Nikus, K
O'Donnell, CJ
Orho-Melander, M
Pedersen, O
Petersmann, A
Polfus, L
Psaty, BM
Raitakari, OT
Raitoharju, E
Richard, M
Rice, KM
Rivadeneira, F
Rotter, JI
Schmidt, F
Smith, AV
Starr, JM
Taylor, KD
Teumer, A
Thuesen, BH
Torstenson, ES
Tracy, RP
Tzoulaki, I
Zakai, NA
Vacchi-Suzzi, C
van Duijn, CM
van Rooij, FJA
Cushman, M
Deary, IJ
Edwards, DRV
Vergnaud, AC
Wallentin, L
Waterworth, DM
White, HD
Wilson, JG
Zonderman, AB
Kathiresan, S
Grarup, N
Esko, T
Loos, RJF
Lange, LA
Faraday, N
Abumrad, NA
Edwards, TL
Ganesh, SK
Auer, PL
Johnson, AD
Reiner, AP
Lettre, G
AF Chami, Nathalie
Chen, Ming-Huei
Slater, Andrew J.
Eicher, John D.
Evangelou, Evangelos
Tajuddin, Salman M.
Love-Gregory, Latisha
Kacprowski, Tim
Schick, Ursula M.
Nomura, Akihiro
Giri, Ayush
Lessard, Samuel
Brody, Jennifer A.
Schurmann, Claudia
Pankratz, Nathan
Yanek, Lisa R.
Manichaikul, Ani
Pazoki, Raha
Mihailov, Evelin
Hill, W. David
Raffield, Laura M.
Burt, Amber
Bartz, Traci M.
Becker, Diane M.
Becker, Lewis C.
Boerwinkle, Eric
Bork-Jensen, Jette
Bottinger, Erwin P.
O'Donoghue, Michelle L.
Crosslin, David R.
de Denus, Simon
Dube, Marie-Pierre
Elliott, Paul
Engstrom, Gunnar
Evans, Michele K.
Floyd, James S.
Fornage, Myriam
Gao, He
Greinacher, Andreas
Gudnason, Vilmundur
Hansen, Torben
Harris, Tamara B.
Hayward, Caroline
Hernesniemi, Jussi
Highland, Heather M.
Hirschhorn, Joel N.
Hofman, Albert
Irvin, Marguerite R.
Kahonen, Mika
Lange, Ethan
Launer, Lenore J.
Lehtimaki, Terho
Li, Jin
Liewald, David C. M.
Linneberg, Allan
Liu, Yongmei
Lu, Yingchang
Lyytikainen, Leo-Pekka
Magi, Reedik
Mathias, Rasika A.
Melander, Olle
Metspalu, Andres
Mononen, Nina
Nalls, Mike A.
Nickerson, Deborah A.
Nikus, Kjell
O'Donnell, Chris J.
Orho-Melander, Marju
Pedersen, Oluf
Petersmann, Astrid
Polfus, Linda
Psaty, Bruce M.
Raitakari, Olli T.
Raitoharju, Emma
Richard, Melissa
Rice, Kenneth M.
Rivadeneira, Fernando
Rotter, Jerome I.
Schmidt, Frank
Smith, Albert Vernon
Starr, John M.
Taylor, Kent D.
Teumer, Alexander
Thuesen, Betina H.
Torstenson, Eric S.
Tracy, Russell P.
Tzoulaki, Ioanna
Zakai, Neil A.
Vacchi-Suzzi, Caterina
van Duijn, Cornelia M.
van Rooij, Frank J. A.
Cushman, Mary
Deary, Ian J.
Edwards, Digna R. Velez
Vergnaud, Anne-Claire
Wallentin, Lars
Waterworth, Dawn M.
White, Harvey D.
Wilson, James G.
Zonderman, Alan B.
Kathiresan, Sekar
Grarup, Niels
Esko, Tonu
Loos, Ruth J. F.
Lange, Leslie A.
Faraday, Nauder
Abumrad, Nada A.
Edwards, Todd L.
Ganesh, Santhi K.
Auer, Paul L.
Johnson, Andrew D.
Reiner, Alexander P.
Lettre, Guillaume
TI Exome Genotyping Identifies Pleiotropic Variants Associated with Red
Blood Cell Traits
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; AFRICAN-AMERICANS;
DILATED CARDIOMYOPATHY; NATURAL-SELECTION; SEQUENCE VARIANTS;
PYRUVATE-KINASE; LOW-FREQUENCY; LOCI; GENE
AB Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.
C1 [Chami, Nathalie; Lessard, Samuel; Dube, Marie-Pierre; Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.
[Chami, Nathalie; Lessard, Samuel; de Denus, Simon; Dube, Marie-Pierre; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada.
[Chen, Ming-Huei; Eicher, John D.; O'Donnell, Chris J.; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.
[Slater, Andrew J.] GlaxoSmithKline, Genet Target Sci, Res Triangle Pk, Res Triangle Pk, NC 27709 USA.
[Slater, Andrew J.] OmicSoft Corp, Cary, NC 27513 USA.
[Evangelou, Evangelos; Elliott, Paul; Gao, He; Tzoulaki, Ioanna; Vergnaud, Anne-Claire] Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England.
[Evangelou, Evangelos; Tzoulaki, Ioanna] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina 45110, Greece.
[Tajuddin, Salman M.; Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA.
[Love-Gregory, Latisha; Abumrad, Nada A.] Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA.
[Kacprowski, Tim; Schmidt, Frank] Ernst Moritz Arndt Univ Greifswald, Dept Funct Gen, Interfaculty Inst Genet & Funct Gen, Univ Med, D-17475 Greifswald, Germany.
[Kacprowski, Tim] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
[Schick, Ursula M.; Schurmann, Claudia; Bottinger, Erwin P.; Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.
[Nomura, Akihiro; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Nomura, Akihiro; Hirschhorn, Joel N.; Kathiresan, Sekar; Esko, Tonu] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Nomura, Akihiro; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Nomura, Akihiro; Kathiresan, Sekar] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Nomura, Akihiro] Kanazawa Univ, Grad Sch Med Sci, Div Cardiovasc Med, Kanazawa, Ishikawa 9200942, Japan.
[Giri, Ayush; Torstenson, Eric S.; Edwards, Todd L.] Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA.
[Brody, Jennifer A.; Floyd, James S.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Schurmann, Claudia; Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.
[Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA.
[Yanek, Lisa R.; Becker, Diane M.] Johns Hopkins Univ, Sch Med, Dept Med Div Gen Internal Med icine, Div Gen Internal Med, Baltimore, MD 21205 USA.
[Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA.
[Pazoki, Raha; Hofman, Albert; Rivadeneira, Fernando; van Duijn, Cornelia M.; van Rooij, Frank J. A.] Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands.
[Mihailov, Evelin; Magi, Reedik; Metspalu, Andres; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Hill, W. David; Liewald, David C. M.; Starr, John M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Hill, W. David; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Raffield, Laura M.; Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
[Burt, Amber] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA.
[Bartz, Traci M.; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Becker, Lewis C.] Johns Hopkins Univ Sch Med, Dept Med, Div Cardiol & Gen Internal Med, Baltimore, MD 21205 USA.
[Boerwinkle, Eric; Highland, Heather M.; Polfus, Linda] Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Bork-Jensen, Jette; Hansen, Torben; Pedersen, Oluf; Grarup, Niels] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark.
[O'Donoghue, Michelle L.] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA.
[Crosslin, David R.] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA.
[de Denus, Simon] Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada.
[Engstrom, Gunnar; Melander, Olle; Orho-Melander, Marju] Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.
[Engstrom, Gunnar; Melander, Olle; Orho-Melander, Marju] Skane Univ Hosp, S-22241 Malmo, Sweden.
[Fornage, Myriam; Richard, Melissa] Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA.
[Greinacher, Andreas] Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany.
[Gudnason, Vilmundur; Smith, Albert Vernon] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Gudnason, Vilmundur; Smith, Albert Vernon] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Intramural Res Program, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Hayward, Caroline] Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Hernesniemi, Jussi; Lehtimaki, Terho; Lyytikainen, Leo-Pekka; Mononen, Nina; Raitoharju, Emma] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.
[Hernesniemi, Jussi; Lehtimaki, Terho; Lyytikainen, Leo-Pekka; Mononen, Nina; Raitoharju, Emma] Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland.
[Hernesniemi, Jussi; Nikus, Kjell] Univ Tampere, Sch Med, Tampere 33014, Finland.
[Highland, Heather M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Hirschhorn, Joel N.] Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Irvin, Marguerite R.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, Sch Med, Tampere 33014, Finland.
[Lange, Ethan] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Lange, Ethan] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Li, Jin] Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA.
[Linneberg, Allan; Thuesen, Betina H.] Capital Region Denmark, Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark.
[Linneberg, Allan] Rigshosp, Dept Clin Expt Res, DK-2100 Glostrup, Denmark.
[Linneberg, Allan] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA.
[Mathias, Rasika A.] Johns Hopkins Univ Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA.
[Mathias, Rasika A.] Johns Hopkins Univ Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA.
[Nalls, Mike A.] NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA.
[Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA.
[Nikus, Kjell] Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.
[O'Donnell, Chris J.] Boston Vet Adm VA Healthcare, Cardiol Sect, Boston, MA 02118 USA.
[O'Donnell, Chris J.] Boston Vet Adm VA Healthcare, Ctr Populat Gen, Boston, MA 02118 USA.
[Petersmann, Astrid] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany.
[Psaty, Bruce M.] Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland.
[Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.
[Rivadeneira, Fernando] NCHA, NL-3015 Rotterdam, Netherlands.
[Rotter, Jerome I.; Taylor, Kent D.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
[Rotter, Jerome I.; Taylor, Kent D.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
[Starr, John M.] Alzheimer Scotland Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Teumer, Alexander] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
[Tracy, Russell P.] Univ Vermont Coll Med, Dept Pathol, Colchester, VT 05446 USA.
[Tracy, Russell P.] Univ Vermont Coll Med, Dept Lab Med, Colchester, VT 05446 USA.
[Tracy, Russell P.] Univ Vermont Coll Med, Dept Biochem, Colchester, VT 05446 USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont Coll Med, Dept Med, Burlington, VT 05405 USA.
[Zakai, Neil A.; Cushman, Mary] Univ Vermont Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Vacchi-Suzzi, Caterina] SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN 37203 USA.
[Wallentin, Lars] Uppsala Univ, Dept Med Sci, Cardiol & Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden.
[Waterworth, Dawn M.] Genet Target Sci, GlaxoSmithKline, King Of Prussia, PA 19406 USA.
[White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.
[White, Harvey D.] Univ Auckland, Auckland 1142, New Zealand.
[Wilson, James G.] Univ Mississippi Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA.
[Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48108 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48108 USA.
[Auer, Paul L.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.
[Reiner, Alexander P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Reiner, Alexander P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
RP Lettre, G (reprint author), Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.; Lettre, G (reprint author), Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada.; Reiner, AP (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.; Reiner, AP (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
EM apreiner@u.washington.edu; guillaume.lettre@umontreal.ca
RI Schurmann, Claudia/L-1204-2016; Floyd, James/G-7563-2015; Johnson,
Andrew/G-6520-2013; Kacprowski, Tim/K-8650-2013; Dube,
Marie-Pierre/B-9364-2008; Grarup, Niels/K-2807-2015;
OI Schurmann, Claudia/0000-0003-4158-9192; Evangelou,
Evangelos/0000-0002-5488-2999; Linneberg, Allan/0000-0002-0994-0184;
Kacprowski, Tim/0000-0002-5393-2413; Dube,
Marie-Pierre/0000-0001-8442-4393; Grarup, Niels/0000-0001-5526-1070;
Manichaikul, Ani/0000-0002-5998-795X; Tajuddin, Salman
M./0000-0002-7919-8528; Zonderman, Alan B/0000-0002-6523-4778
FU Fonds de Recherche du Queebec-Santee (FRQS); Canadian Institute of
Health Research (Banting-CIHR); Canadian Institute of Health Research
(operating grant MOP) [123382]; Canada Research Chair program; NHLBI
[R21 HL121422-02]; NIH [DK060022]; Yoshida Scholarship Foundation;
Research Scholar award from the Massachusetts General Hospital (MGH);
Howard Goodman Fellowship from MGH; Donovan Family Foundation
[R01HL107816]; Fondation Leducq
FX We thank all participants, staff, and study coordinating centers. We
also thank Raymond Doty and Jan Abkowitz for discussion of the ALAS2
finding. We would like to thank Liling Warren for contributions to the
genetic analysis of the SOLID-TIMI-52 and STABILITY datasets. Young
Finns Study (YFS) acknowledges the expert technical assistance in the
statistical analyses by Ville Aalto and Irina Lisinen. Estonian Genome
Center, University of Tartu (EGCUT) thanks co-workers at the Estonian
Biobank, especially Mr. V. Soo, Mr. S. Smith, and Dr. L. Milani. Airwave
thanks Louisa Cavaliero who assisted in data collection and management
as well as Peter McFarlane and the Glasgow CARE, Patricia Munroe at
Queen Mary University of London, and Joanna Sarnecka and Ania Zawodniak
at Northwick Park for their contributions to the study. This work was
supported by the Fonds de Recherche du Queebec-Santee (FRQS, scholarship
to N.C.), the Canadian Institute of Health Research (Banting-CIHR,
scholarship to S.L. and operating grant MOP#123382 to G.L.), and the
Canada Research Chair program (to G.L.). P.L.A. was supported by NHLBI
R21 HL121422-02. N.A.A. is funded by NIH DK060022. A.N. was supported by
the Yoshida Scholarship Foundation. S.K. was supported by a Research
Scholar award from the Massachusetts General Hospital (MGH), the Howard
Goodman Fellowship from MGH, the Donovan Family Foundation, R01HL107816,
and a grant from Fondation Leducq. Additional acknowledgments and
funding information is provided in the Supplemental Data.
NR 65
TC 3
Z9 3
U1 5
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 7
PY 2016
VL 99
IS 1
BP 8
EP 21
DI 10.1016/j.ajhg.2016.05.007
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA DT6TI
UT WOS:000381616600002
PM 27346685
ER
PT J
AU Tajuddin, SM
Schick, UM
Eicher, JD
Chami, N
Giri, A
Brody, JA
Hill, WD
Kacprowski, T
Li, J
Lyytikainen, LP
Manichaikul, A
Mihailov, E
O'Donoghue, ML
Pankratz, N
Pazoki, R
Polfus, LM
Smith, AV
Schurmann, C
Vacchi-Suzzi, C
Waterworth, DM
Evangelou, E
Yanek, LR
Burt, A
Chen, MH
van Rooij, FJA
Floyd, JS
Greinacher, A
Harris, TB
Highland, HM
Lange, LA
Liu, Y
Magi, R
Nalls, MA
Mathias, RA
Nickerson, DA
Nikus, K
Starr, JM
Tardif, JC
Tzoulaki, I
Edwards, DRV
Wallentin, L
Bartz, TM
Becker, LC
Denny, JC
Raffield, LM
Rioux, JD
Friedrich, N
Fornage, M
Gao, H
Hirschhorn, JN
Liewald, DCM
Rich, SS
Uitterlinden, A
Bastarache, L
Becker, DM
Boerwinkle, E
de Denus, S
Bottinger, EP
Hayward, C
Hofman, A
Homuth, G
Lange, E
Launer, LJ
Lehtimaki, T
Lu, YC
Metspalu, A
O'Donnell, CJ
Quarells, RC
Richard, M
Torstenson, ES
Taylor, KD
Vergnaud, AC
Zonderman, AB
Crosslin, DR
Deary, IJ
Dorr, M
Elliott, P
Evans, MK
Gudnason, V
Kahonen, M
Psaty, BM
Rotter, JI
Slater, AJ
Dehghan, A
White, HD
Ganesh, SK
Loos, RJF
Esko, T
Faraday, N
Wilson, JG
Cushman, M
Johnson, AD
Edwards, TL
Zakai, NA
Lettre, G
Reiner, AP
Auer, PL
AF Tajuddin, Salman M.
Schick, Ursula M.
Eicher, John D.
Chami, Nathalie
Giri, Ayush
Brody, Jennifer A.
Hill, W. David
Kacprowski, Tim
Li, Jin
Lyytikainen, Leo-Pekka
Manichaikul, Ani
Mihailov, Evelin
O'Donoghue, Michelle L.
Pankratz, Nathan
Pazoki, Raha
Polfus, Linda M.
Smith, Albert Vernon
Schurmann, Claudia
Vacchi-Suzzi, Caterina
Waterworth, Dawn M.
Evangelou, Evangelos
Yanek, Lisa R.
Burt, Amber
Chen, Ming-Huei
van Rooij, Frank J. A.
Floyd, James S.
Greinacher, Andreas
Harris, Tamara B.
Highland, Heather M.
Lange, Leslie A.
Liu, Yongmei
Magi, Reedik
Nalls, Mike A.
Mathias, Rasika A.
Nickerson, Deborah A.
Nikus, Kjell
Starr, John M.
Tardif, Jean-Claude
Tzoulaki, Ioanna
Edwards, Digna R. Velez
Wallentin, Lars
Bartz, Traci M.
Becker, Lewis C.
Denny, Joshua C.
Raffield, Laura M.
Rioux, John D.
Friedrich, Nele
Fornage, Myriam
Gao, He
Hirschhorn, Joel N.
Liewald, David C. M.
Rich, Stephen S.
Uitterlinden, Andre
Bastarache, Lisa
Becker, Diane M.
Boerwinkle, Eric
de Denus, Simon
Bottinger, Erwin P.
Hayward, Caroline
Hofman, Albert
Homuth, Georg
Lange, Ethan
Launer, Lenore J.
Lehtimaki, Terho
Lu, Yingchang
Metspalu, Andres
O'Donnell, Chris J.
Quarells, Rakale C.
Richard, Melissa
Torstenson, Eric S.
Taylor, Kent D.
Vergnaud, Anne-Claire
Zonderman, Alan B.
Crosslin, David R.
Deary, Ian J.
Dorr, Marcus
Elliott, Paul
Evans, Michele K.
Gudnason, Vilmundur
Kahonen, Mika
Psaty, Bruce M.
Rotter, Jerome I.
Slater, Andrew J.
Dehghan, Abbas
White, Harvey D.
Ganesh, Santhi K.
Loos, Ruth J. F.
Esko, Tonu
Faraday, Nauder
Wilson, James G.
Cushman, Mary
Johnson, Andrew D.
Edwards, Todd L.
Zakai, Neil A.
Lettre, Guillaume
Reiner, Alex P.
Auer, Paul L.
TI Large-Scale Exome-wide Association Analysis Identifies Loci for White
Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; UROKINASE RECEPTOR; GENETIC-VARIANTS;
LYMPHOBLASTIC-LEUKEMIA; TRANSCRIPTION FACTORS; SUSCEPTIBILITY LOCI;
LYMPHOID ORGANS; EMERGE NETWORK; RISK LOCI; EXPRESSION
AB White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of similar to 157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3 ' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.
C1 [Tajuddin, Salman M.; Zonderman, Alan B.; Evans, Michele K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Schick, Ursula M.; Schurmann, Claudia; Bottinger, Erwin P.; Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Schick, Ursula M.; Schurmann, Claudia; Lu, Yingchang; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Eicher, John D.; Chen, Ming-Huei; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.
[Chami, Nathalie; Tardif, Jean-Claude; Rioux, John D.; Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.
[Chami, Nathalie; Tardif, Jean-Claude; Rioux, John D.; de Denus, Simon; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Giri, Ayush; Torstenson, Eric S.] Vanderbilt Univ, Div Epidemiol, Inst Med & Publ Hlth, Nashville, TN 37235 USA.
[Brody, Jennifer A.; Floyd, James S.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Hill, W. David; Starr, John M.; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Hill, W. David; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Kacprowski, Tim; Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, D-17475 Greifswald, Germany.
[Kacprowski, Tim; Homuth, Georg] Ernst Moritz Arndt Univ Greifswald, D-17475 Greifswald, Germany.
[Kacprowski, Tim; Friedrich, Nele; Dorr, Marcus] DZHK German Ctr Cardiovasc Res, Greifswald, Germany.
[Li, Jin] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94305 USA.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland.
[Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Mihailov, Evelin; Magi, Reedik; Metspalu, Andres; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA.
[Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA.
[Pazoki, Raha; van Rooij, Frank J. A.; Uitterlinden, Andre; Hofman, Albert; Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.
[Polfus, Linda M.; Highland, Heather M.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, IS-201 Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Vacchi-Suzzi, Caterina] SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA.
[Waterworth, Dawn M.] GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA 19406 USA.
[Evangelou, Evangelos; Tzoulaki, Ioanna; Gao, He; Vergnaud, Anne-Claire; Elliott, Paul] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
[Evangelou, Evangelos; Tzoulaki, Ioanna] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Yanek, Lisa R.; Becker, Diane M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA.
[Burt, Amber] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Greinacher, Andreas] Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Highland, Heather M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Lange, Leslie A.; Raffield, Laura M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA.
[Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA.
[Mathias, Rasika A.; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA.
[Nickerson, Deborah A.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98105 USA.
[Nikus, Kjell] Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.
[Nikus, Kjell] Univ Tampere, Sch Med, Tampere 33014, Finland.
[Starr, John M.] Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr,Dept Obstet & Gynecol, Nashville, TN 37203 USA.
[Wallentin, Lars] Uppsala Univ, Cardiol, Dept Med Sci, S-75185 Uppsala, Sweden.
[Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden.
[Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA.
[Denny, Joshua C.; Bastarache, Lisa] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37203 USA.
[Friedrich, Nele] Univ Med Greifswald, Inst Clin Chem & Lab Med, D-13347 Greifswald, Germany.
[Fornage, Myriam; Richard, Melissa] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Hirschhorn, Joel N.; Esko, Tonu] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Hirschhorn, Joel N.] Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Uitterlinden, Andre] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands.
[Uitterlinden, Andre] NCHA, NL-3015 GD Rotterdam, Netherlands.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[de Denus, Simon] Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada.
[Hayward, Caroline] Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Hofman, Albert] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lange, Ethan] Univ N Carolina, Dept Genet & Biostat, Chapel Hill, NC 27599 USA.
[O'Donnell, Chris J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Chris J.] Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA 02118 USA.
[O'Donnell, Chris J.] Boston Vet Adm Healthcare, Ctr Populat Genom, Boston, MA 02118 USA.
[Quarells, Rakale C.] Morehouse Sch Med, Social Epidemiol Res Ctr, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Taylor, Kent D.; Rotter, Jerome I.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
[Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
[Crosslin, David R.] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA.
[Dorr, Marcus] Univ Med Greifswald, Dept Cardiol, D-17475 Greifswald, Germany.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Slater, Andrew J.] OmicSoft Corp, Cary, NC 27513 USA.
[Slater, Andrew J.] GlaxoSmithKline, Genet Target Sci, Res Triangle Pk, NC 27709 USA.
[White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.
[White, Harvey D.] Univ Auckland, Auckland 1142, New Zealand.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48108 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48108 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Cushman, Mary; Zakai, Neil A.] Univ Vermont, Dept Med, Div Hematol Oncol, Colchester, VT 05446 USA.
[Edwards, Todd L.] Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Div Epidemiol,Dept Med, Nashville, TN 37203 USA.
[Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Auer, Paul L.] Univ Wisconsin Milwaukee, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.
RP Reiner, AP (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.; Reiner, AP (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.; Auer, PL (reprint author), Univ Wisconsin Milwaukee, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.
EM apreiner@u.washington.edu; pauer@uwm.edu
RI Schurmann, Claudia/L-1204-2016; Floyd, James/G-7563-2015; Rioux,
John/A-9599-2015; Johnson, Andrew/G-6520-2013; Kacprowski,
Tim/K-8650-2013;
OI Schurmann, Claudia/0000-0003-4158-9192; Rioux, John/0000-0001-7560-8326;
Kacprowski, Tim/0000-0002-5393-2413; Manichaikul,
Ani/0000-0002-5998-795X; Tajuddin, Salman M./0000-0002-7919-8528;
Zonderman, Alan B/0000-0002-6523-4778; Evangelou,
Evangelos/0000-0002-5488-2999; Dehghan, Abbas/0000-0001-6403-016X
FU NHLBI [R21 HL121422-02, R01 HL086694]; Canada Research Chair program;
Canadian Institute of Health Research MOP [123382]; National Institute
on Aging, NIH Intramural Research Program; a component of the NIH
Roadmap for Medical Research [UL1RR025005]
FX We thank all participants and study coordinating centers of the
participating studies and cohorts. P.L.A. was supported by NHLBI R21
HL121422-02. G.L. was supported by the Canada Research Chair program and
the Canadian Institute of Health Research MOP#123382. This work was
supported in part by the National Institute on Aging, NIH Intramural
Research Program. Data analyses utilized the computational resources of
the NIH HPC Biowulf cluster at the NIH. The Framingham Heart Study (FHS)
acknowledges the Shared Computing Cluster at Boston University.
Infrastructure and data analysis for the ARIC study was partly supported
by Grant Number UL1RR025005, a component of the NIH Roadmap for Medical
Research, and grant R01 HL086694 from the NHLBI. Airwave study thanks
Louisa Cavaliero who assisted in data collection and management, Peter
McFarlane and the Glasgow CARE, Patricia Munroe at Queen Mary University
of London, and Joanna Sarnecka and Ania Zawodniak at Northwick Park for
their contributions to the study. SOLID-TIMI-52 and STABILITY thank
Liling Warren for contributions to the genetic analysis of the study
datasets. Estonian Genome Center, University of Tartu (EGCUT) thanks Mr.
V. Soo, Mr. S. Smith, and Dr. L. Milani for their contribution. The
Rotterdam Study (RS) thanks Ms. Mila Jhamai, Ms. Sarah Higgins, and Mr.
Marijn Verkerk for their help in creating the Exomechip database, and
Ms. Carolina MedinaGomez, Mr. Lennard Karsten, and Dr. Linda Broer.
Additional acknowledgments and funding information are provided in the
Supplemental Data.
NR 96
TC 3
Z9 3
U1 7
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 7
PY 2016
VL 99
IS 1
BP 22
EP 39
DI 10.1016/j.ajhg.2016.05.003
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA DT6TI
UT WOS:000381616600003
PM 27346689
ER
PT J
AU Eicher, JD
Chami, N
Kacprowski, T
Nomura, A
Chen, MH
Yanek, LR
Tajuddin, SM
Schick, UM
Slater, AJ
Pankratz, N
Polfus, L
Schurmann, C
Giri, A
Brody, JA
Lange, LA
Manichaikul, A
Hill, WD
Pazoki, R
Elliot, P
Evangelou, E
Tzoulaki, I
Gao, H
Vergnaud, AC
Mathias, RA
Becker, DM
Becker, LC
Burt, A
Crosslin, DR
Lyytikainen, LP
Nikus, K
Hernesniemi, J
Kahonen, M
Raitoharju, E
Mononen, N
Raitakari, OT
Lehtimaki, T
Cushman, M
Zakai, NA
Nickerson, DA
Raffield, LM
Quarells, R
Willer, CJ
Peloso, GM
Abecasis, GR
Liu, DJJ
Deloukas, P
Samani, NJ
Schunkert, H
Erdmann, J
Fornage, M
Richard, M
Tardif, JC
Rioux, JD
Dube, MP
de Denus, S
Lu, YC
Bottinger, EP
Loos, RJF
Smith, AV
Harris, TB
Launer, LJ
Gudnason, V
Edwards, DRV
Torstenson, ES
Liu, YM
Tracy, RP
Rotter, JI
Rich, SS
Highland, HM
Boerwinkle, E
Li, J
Lange, E
Wilson, JG
Mihailov, E
Magi, R
Hirschhorn, J
Metspalu, A
Esko, T
Vacchi-Suzzi, C
Nalls, MA
Zonderman, AB
Evans, MK
Engstrom, G
Orho-Melander, M
Melander, O
O'Donoghue, ML
Waterworth, DM
Wallentin, L
White, HD
Floyd, JS
Bartz, TM
Rice, KM
Psaty, BM
Starr, JM
Liewald, DCM
Hayward, C
Deary, IJ
Greinacher, A
Volker, U
Thiele, T
Volzke, H
van Rooij, FJA
Uitterlinden, AG
Franco, OH
Dehghan, A
Edwards, TL
Ganesh, SK
Kathiresan, S
Faraday, N
Auer, PL
Reiner, AP
Lettre, G
Johnson, AD
AF Eicher, John D.
Chami, Nathalie
Kacprowski, Tim
Nomura, Akihiro
Chen, Ming-Huei
Yanek, Lisa R.
Tajuddin, Salman M.
Schick, Ursula M.
Slater, Andrew J.
Pankratz, Nathan
Polfus, Linda
Schurmann, Claudia
Giri, Ayush
Brody, Jennifer A.
Lange, Leslie A.
Manichaikul, Ani
Hill, W. David
Pazoki, Raha
Elliot, Paul
Evangelou, Evangelos
Tzoulaki, Ioanna
Gao, He
Vergnaud, Anne-Claire
Mathias, Rasika A.
Becker, Diane M.
Becker, Lewis C.
Burt, Amber
Crosslin, David R.
Lyytikainen, Leo-Pekka
Nikus, Kjell
Hernesniemi, Jussi
Kahonen, Mika
Raitoharju, Emma
Mononen, Nina
Raitakari, Olli T.
Lehtimaki, Terho
Cushman, Mary
Zakai, Neil A.
Nickerson, Deborah A.
Raffield, Laura M.
Quarells, Rakale
Willer, Cristen J.
Peloso, Gina M.
Abecasis, Goncalo R.
Liu, Dajiang J.
Deloukas, Panos
Samani, Nilesh J.
Schunkert, Heribert
Erdmann, Jeanette
Fornage, Myriam
Richard, Melissa
Tardif, Jean-Claude
Rioux, John D.
Dube, Marie-Pierre
de Denus, Simon
Lu, Yingchang
Bottinger, Erwin P.
Loos, Ruth J. F.
Smith, Albert Vernon
Harris, Tamara B.
Launer, Lenore J.
Gudnason, Vilmundur
Edwards, Digna R. Velez
Torstenson, Eric S.
Liu, Yongmei
Tracy, Russell P.
Rotter, Jerome I.
Rich, Stephen S.
Highland, Heather M.
Boerwinkle, Eric
Li, Jin
Lange, Ethan
Wilson, James G.
Mihailov, Evelin
Magi, Reedik
Hirschhorn, Joel
Metspalu, Andres
Esko, Tonu
Vacchi-Suzzi, Caterina
Nalls, Mike A.
Zonderman, Alan B.
Evans, Michele K.
Engstrom, Gunnar
Orho-Melander, Marju
Melander, Olle
O'Donoghue, Michelle L.
Waterworth, Dawn M.
Wallentin, Lars
White, Harvey D.
Floyd, James S.
Bartz, Traci M.
Rice, Kenneth M.
Psaty, Bruce M.
Starr, J. M.
Liewald, David C. M.
Hayward, Caroline
Deary, Ian J.
Greinacher, Andreas
Volker, Uwe
Thiele, Thomas
Volzke, Henry
van Rooij, Frank J. A.
Uitterlinden, Andre G.
Franco, Oscar H.
Dehghan, Abbas
Edwards, Todd L.
Ganesh, Santhi K.
Kathiresan, Sekar
Faraday, Nauder
Auer, Paul L.
Reiner, Alex P.
Lettre, Guillaume
Johnson, Andrew D.
CA Global Lipids Genetics Consortium
CARDIoGRAM Exome Consortium
Myocardial Infarction Genetics
TI Platelet-Related Variants Identified by Exomechip Meta-analysis in
157,293 Individuals
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; EPSILON-RI-ALPHA; PIAS-LIKE PROTEIN; IMMUNE
THROMBOCYTOPENIA; MYOCARDIAL-INFARCTION; AFRICAN-AMERICANS; SEQUENCE
VARIANTS; BLOOD-PRESSURE; BINDING-SITE; IGE BINDING
AB Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
C1 [Eicher, John D.; Chen, Ming-Huei; Johnson, Andrew D.] NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.
[Chami, Nathalie; Tardif, Jean-Claude; Rioux, John D.; Dube, Marie-Pierre; Lettre, Guillaume] Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.
[Chami, Nathalie; Tardif, Jean-Claude; Rioux, John D.; Dube, Marie-Pierre; de Denus, Simon; Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Kacprowski, Tim; Volker, Uwe] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, D-17475 Greifswald, Germany.
[Kacprowski, Tim; Volker, Uwe] Ernst Mortiz Arndt Univ Greifswald, D-17475 Greifswald, Germany.
[Kacprowski, Tim; Volker, Uwe; Volzke, Henry] DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany.
[Nomura, Akihiro; Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Nomura, Akihiro; Peloso, Gina M.; Hirschhorn, Joel; Esko, Tonu; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Nomura, Akihiro; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Nomura, Akihiro; Kathiresan, Sekar] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Nomura, Akihiro] Kanazawa Univ, Div Cardiovasc Med, Grad Sch Med Sci, Kanazawa, Ishikawa 9200942, Japan.
[Yanek, Lisa R.; Mathias, Rasika A.; Becker, Diane M.; Becker, Lewis C.] Johns Hopkins Univ, Div Gen Internal Med, Dept Med, Sch Med, Baltimore, MD 21205 USA.
[Tajuddin, Salman M.; Zonderman, Alan B.; Evans, Michele K.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Schick, Ursula M.; Schurmann, Claudia; Lu, Yingchang; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Schick, Ursula M.; Schurmann, Claudia] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Slater, Andrew J.] GlaxoSmithKline, Genet, Target Sci, Res Triangle Pk, NC 27709 USA.
[Slater, Andrew J.] OmicSoft Corp, Cary, NC 27513 USA.
[Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA.
[Polfus, Linda; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Giri, Ayush; Torstenson, Eric S.; Edwards, Todd L.] Vanderbilt Univ, Inst Med & Publ Hlth, Div Epidemiol, Nashville, TN 37235 USA.
[Brody, Jennifer A.; Floyd, James S.] Univ Washington, Dept Med, Seattle, WA 98101 USA.
[Lange, Leslie A.; Raffield, Laura M.; Lange, Ethan] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
[Manichaikul, Ani; Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA.
[Hill, W. David; Starr, J. M.; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Hill, W. David; Liewald, David C. M.; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Pazoki, Raha; van Rooij, Frank J. A.; Uitterlinden, Andre G.; Franco, Oscar H.; Dehghan, Abbas] Erasmus MC, Dept Epidemiol, NL-3000 Rotterdam, Netherlands.
[Elliot, Paul; Evangelou, Evangelos; Tzoulaki, Ioanna; Gao, He; Vergnaud, Anne-Claire] Univ London Imperial Coll Sci Technol & Med, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London W2 1PG, England.
[Evangelou, Evangelos; Tzoulaki, Ioanna] Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina 45110, Greece.
[Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy, Baltimore, MD 21205 USA.
[Mathias, Rasika A.] Johns Hopkins Univ, Sch Med, Dept Med, Div Immunol, Baltimore, MD 21205 USA.
[Becker, Lewis C.] Johns Hopkins Univ, Div Cardiol, Dept Med, Sch Med, Baltimore, MD 21205 USA.
[Burt, Amber] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA.
[Crosslin, David R.] Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98105 USA.
[Lyytikainen, Leo-Pekka; Hernesniemi, Jussi; Raitoharju, Emma; Mononen, Nina; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.
[Lyytikainen, Leo-Pekka; Hernesniemi, Jussi; Raitoharju, Emma; Mononen, Nina; Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33514, Finland.
[Nikus, Kjell; Hernesniemi, Jussi] Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.
[Nikus, Kjell] Univ Tampere, Sch Med, Tampere 33514, Finland.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, Tampere 33514, Finland.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland.
[Cushman, Mary; Zakai, Neil A.] Univ Vermont, Coll Med, Dept Med, Burlington, VT 05405 USA.
[Cushman, Mary; Zakai, Neil A.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA.
[Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA.
[Quarells, Rakale] Morehouse Sch Med, Social Epidemiol Res Ctr, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Willer, Cristen J.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48108 USA.
[Willer, Cristen J.] Univ Michigan, Dept Computat Med & Bioinformat, Dept Human Genet, Ann Arbor, MI 48108 USA.
[Willer, Cristen J.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48108 USA.
[Peloso, Gina M.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02118 USA.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48108 USA.
[Liu, Dajiang J.] Penn State Univ Hosp, Dept Publ Hlth Sci, Coll Med, Hershey, PA 17033 USA.
[Deloukas, Panos] Queen Mary Univ London, William Harvey Res Inst, London E1 4NS, England.
[Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
[Samani, Nilesh J.] Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Schunkert, Heribert] DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80333 Munich, Germany.
[Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80333 Munich, Germany.
[Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt Genom, D-23562 Lubeck, Germany.
[Erdmann, Jeanette] DZHK German Res Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, D-23562 Lubeck, Germany.
[Fornage, Myriam; Richard, Melissa] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[de Denus, Simon] Univ Montreal, Fac Pharm, Montreal H3T 1J4, PQ, Canada.
[Smith, Albert Vernon; Gudnason, Vilmundur] Icelandic Heart Assoc, IS-201 Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN 37203 USA.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Lab Med, Colchester, VT 05446 USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Biochem, Colchester, VT 05446 USA.
[Rotter, Jerome I.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA.
[Highland, Heather M.] Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Houston, TX 77030 USA.
[Highland, Heather M.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Li, Jin] Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94305 USA.
[Lange, Ethan] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27514 USA.
[Wilson, James G.] Univ Mississippi, Dept Physiol & Biophys, Med Ctr, Jackson, MS 39216 USA.
[Mihailov, Evelin; Magi, Reedik; Metspalu, Andres; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Hirschhorn, Joel] Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA.
[Vacchi-Suzzi, Caterina] SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA.
[Nalls, Mike A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 21224 USA.
[Engstrom, Gunnar; Orho-Melander, Marju; Melander, Olle] Lund Univ, Dept Clin Sci Malmo, S-22100 Malmo, Sweden.
[Engstrom, Gunnar; Orho-Melander, Marju; Melander, Olle] Skane Univ Hosp, S-22241 Malmo, Sweden.
[O'Donoghue, Michelle L.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA.
[Waterworth, Dawn M.] GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA 19406 USA.
[Wallentin, Lars] Uppsala Univ, Dept Med Sci, Cardiol, S-75185 Uppsala, Sweden.
[Wallentin, Lars] Uppsala Univ, Dept Med Sci, Uppsala Clin Res Ctr, S-75185 Uppsala, Sweden.
[White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.
[White, Harvey D.] Univ Auckland, Auckland 1142, New Zealand.
[Bartz, Traci M.; Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA.
[Starr, J. M.] Alzheimer Scotland Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Hayward, Caroline] Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Greinacher, Andreas; Thiele, Thomas] Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany.
[Volzke, Henry] Univ Med Greifswald, Inst Community Med, D-13347 Greifswald, Germany.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Netherlands Consortium Hlth Ageing, NL-3015 Rotterdam, Netherlands.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal & Human Genet, Ann Arbor, MI 48108 USA.
[Faraday, Nauder] Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA.
[Auer, Paul L.] Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA.
[Reiner, Alex P.] Univ Washington, Dept Epidemiol, Seattle, WA 98105 USA.
[Eicher, John D.; Chami, Nathalie; Kacprowski, Tim; Nomura, Akihiro; Faraday, Nauder; Auer, Paul L.; Reiner, Alex P.; Lettre, Guillaume; Johnson, Andrew D.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
RP Johnson, AD (reprint author), NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.; Johnson, AD (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
EM johnsonad2@nhlbi.nih.gov
RI Schurmann, Claudia/L-1204-2016; Floyd, James/G-7563-2015; Rioux,
John/A-9599-2015; Johnson, Andrew/G-6520-2013; Kacprowski,
Tim/K-8650-2013; Deloukas, Panos/B-2922-2013; Dube,
Marie-Pierre/B-9364-2008;
OI Evangelou, Evangelos/0000-0002-5488-2999; Dehghan,
Abbas/0000-0001-6403-016X; Schurmann, Claudia/0000-0003-4158-9192;
Rioux, John/0000-0001-7560-8326; Kacprowski, Tim/0000-0002-5393-2413;
Deloukas, Panos/0000-0001-9251-070X; Dube,
Marie-Pierre/0000-0001-8442-4393; Manichaikul, Ani/0000-0002-5998-795X;
Tajuddin, Salman M./0000-0002-7919-8528; Zonderman, Alan
B/0000-0002-6523-4778
FU British Heart Foundation [RG/14/5/30893]; Medical Research Council
[MC_PC_U127561128, MR/K026992/1]; NCATS NIH HHS [UL1 TR000124, UL1
TR000445]; NHGRI NIH HHS [U01 HG004402, U01 HG004603]; NHLBI NIH HHS
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, HHSN268201100037C,
HHSN268201300026C, HHSN268201300028C, N01 HC025195, N01 HC095159, N01
HC095160, R01 HL059367, R01 HL086694, R01 HL087641, R01 HL087698, R01
HL112064, R01 HL122684, R01 HL127564, RC2 HL102419, U01 HL072518]; NICHD
NIH HHS [R01 HD074711]; NIDDK NIH HHS [P30 DK063491]
NR 77
TC 4
Z9 4
U1 3
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD JUL 7
PY 2016
VL 99
IS 1
BP 40
EP 55
DI 10.1016/j.ajhg.2016.05.005
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA DT6TI
UT WOS:000381616600004
PM 27346686
ER
PT J
AU Kasenda, B
Loeffler, J
Illerhaus, G
Ferreri, AJM
Rubenstein, J
Batchelor, TT
AF Kasenda, Benjamin
Loeffler, Jay
Illerhaus, Gerald
Ferreri, Andres J. M.
Rubenstein, James
Batchelor, Tracy T.
TI The role of whole brain radiation in primary CNS lymphoma
SO BLOOD
LA English
DT Review
ID CENTRAL-NERVOUS-SYSTEM; STEM-CELL TRANSPLANTATION; HIGH-DOSE
CHEMOTHERAPY; NON-HODGKINS-LYMPHOMA; TERM-FOLLOW-UP; IMMUNOCOMPETENT
PATIENTS; 1ST-LINE TREATMENT; ELDERLY-PATIENTS; X-IRRADIATION; PHASE-II
C1 [Kasenda, Benjamin; Illerhaus, Gerald] Klinikum Stuttgart, Dept Hematol Oncol & Palliat Care, Stuttgart, Germany.
[Loeffler, Jay] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Ferreri, Andres J. M.] Ist Sci San Raffaele, Ist Ricovero & Cura Carattere Sci, Dept Oncohematol, Unit Lymphoid Malignancies, Milan, Italy.
[Rubenstein, James] Univ Calif San Francisco, San Francisco Helen Diller Family Comprehens Canc, Div Hematol Oncol, San Francisco, CA 94143 USA.
[Batchelor, Tracy T.] Harvard Med Sch, Partners Neurol Residency Program, Boston, MA USA.
[Batchelor, Tracy T.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA.
EM tbatchelor@mgh.harvard.edu
FU Genentech; Pfizer
FX J.R. receives research funding from Genentech; T.T.B. receives
consulting honoraria from Accerta, Cavion, Champions Biotechnology,
Merck, OXiGENE, Proximagen, Roche, UpToDate, and research funding from
Pfizer. The remaining authors declare no competing financial interests.
NR 37
TC 0
Z9 0
U1 4
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 7
PY 2016
VL 128
IS 1
BP 32
EP 36
DI 10.1182/blood-2016-01-650101
PG 5
WC Hematology
SC Hematology
GA DQ5MN
UT WOS:000379249600010
PM 27207798
ER
PT J
AU Usmani, SZ
Weiss, BM
Plesner, T
Bahlis, NJ
Belch, A
Lonial, S
Lokhorst, HM
Voorhees, PM
Richardson, PG
Chari, A
Sasser, AK
Axel, A
Feng, HB
Uhlar, CM
Wang, JP
Khan, I
Ahmadi, T
Nahi, H
AF Usmani, Saad Z.
Weiss, Brendan M.
Plesner, Torben
Bahlis, Nizar J.
Belch, Andrew
Lonial, Sagar
Lokhorst, Henk M.
Voorhees, Peter M.
Richardson, Paul G.
Chari, Ajai
Sasser, A. Kate
Axel, Amy
Feng, Huaibao
Uhlar, Clarissa M.
Wang, Jianping
Khan, Imran
Ahmadi, Tahamtan
Nahi, Hareth
TI Clinical efficacy of daratumumab monotherapy in patients with heavily
pretreated relapsed or refractory multiple myeloma
SO BLOOD
LA English
DT Article
ID SINGLE-AGENT; IMPROVED SURVIVAL; OPEN-LABEL; ANTIBODY; PHASE-2; CANCER;
SAFETY; BLOOD; INTERFERENCE; TRIAL
AB The efficacy and favorable safety profile of daratumumab monotherapy in multiple myeloma (MM) was previously reported. Here, we present an updated pooled analysis of 148 patients treated with daratumumab 16 mg/kg. Data were combined from part 2 of a first-in-human phase 1/2 study of patients who relapsed after or were refractory to >= 2 prior therapies and a phase 2 study of patients previously treated with >= 3 prior lines of therapy (including a proteasome inhibitor [PI] and an immunomodulatory drug [IMiD]) or were double refractory. Among the pooled population, patients received a median of 5 prior lines of therapy (range, 2 to 14 prior lines of therapy), and 86.5% were double refractory to a PI and an IMiD. Overall response rate was 31.1%, including 13 very good partial responses, 4 complete responses, and 3 stringent complete responses. The median duration of response was 7.6 months (95% confidence interval [CI], 5.6 to not evaluable [NE]). The median progression-free survival (PFS) and overall survival (OS) were 4.0 months (95% CI, 2.8-5.6 months) and 20.1 months (95% CI, 16.6 months to NE), respectively. When stratified by responders vs stable disease/minimal response vs progressive disease/NE, median PFS was 15.0 months (95% CI, 7.4 months to NE) vs 3.0 months(95% CI, 2.8-3.7months) vs 0.9 months (95% CI, 0.9-1.0 months), respectively, and median OS was NE(95% CI, NE to NE) vs 18.5 months (95% CI, 15.1-22.4 months) vs 3.7 months (95% CI, 1.7-7.6 months), respectively. No new safety signals were identified. In this pooled data set, daratumumab 16 mg/kg monotherapy demonstrated rapid, deep, and durable responses, with a clinical benefit that extended to patients with stable disease or better.
C1 [Usmani, Saad Z.] Carolinas HealthCare Syst, Levine Canc Inst, Charlotte, NC USA.
[Weiss, Brendan M.] Univ Penn, Abramson Canc Ctr, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA.
[Weiss, Brendan M.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Plesner, Torben] Vejle Hosp, Vejle, Denmark.
[Plesner, Torben] Univ Southern Denmark, Vejle, Denmark.
[Bahlis, Nizar J.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada.
[Belch, Andrew] Cross Canc Inst, Edmonton, AB, Canada.
[Lonial, Sagar] Emory Univ, Winship Canc Inst, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA.
[Lokhorst, Henk M.] Vrije Univ Amsterdam Med Ctr, Dept Hematol, Amsterdam, Netherlands.
[Voorhees, Peter M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol Oncol, Chapel Hill, NC USA.
[Richardson, Paul G.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[Chari, Ajai] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Sasser, A. Kate; Axel, Amy; Uhlar, Clarissa M.; Wang, Jianping; Ahmadi, Tahamtan] Janssen Res & Dev LLC, Spring House, PA USA.
[Feng, Huaibao; Khan, Imran] Janssen Res & Dev LLC, Raritan, NJ USA.
[Nahi, Hareth] Karolinska Univ Hosp Huddinge, Dept Med, Karolinska Inst, Div Hematol, Stockholm, Sweden.
RP Usmani, SZ (reprint author), Levine Canc Inst, 1021 Morehead Med Dr, Charlotte, NC 28204 USA.
EM saad.usmani@carolinashealthcare.org
RI Voorhees, Peter /B-6700-2009;
OI nahi, hareth/0000-0003-4711-5094
FU Janssen Research & Development, LLC.; Janssen Global Services, LLC.
FX This study was sponsored by Janssen Research & Development, LLC. Medical
writing and editorial support were provided by Erica Chevalier-Larsen of
MedErgy and were funded by Janssen Global Services, LLC.
NR 26
TC 12
Z9 12
U1 2
U2 4
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 7
PY 2016
VL 128
IS 1
BP 37
EP 44
DI 10.1182/blood-2016-03-705210
PG 8
WC Hematology
SC Hematology
GA DQ5MN
UT WOS:000379249600011
PM 27216216
ER
PT J
AU Lu, YZ
Hanada, T
Fujiwara, Y
Nwankwo, JO
Wieschhaus, AJ
Hartwig, J
Huang, S
Han, J
Chishti, AH
AF Lu, Yunzhe
Hanada, Toshihiko
Fujiwara, Yuko
Nwankwo, Jennifer O.
Wieschhaus, Adam J.
Hartwig, John
Huang, Sha
Han, Jongyoon
Chishti, Athar H.
TI Gene disruption of dematin causes precipitous loss of erythrocyte
membrane stability and severe hemolytic anemia
SO BLOOD
LA English
DT Article
ID RED-BLOOD-CELLS; HEADPIECE DOMAIN; TARGETED DISRUPTION; PROTEIN-KINASE;
GLYCOPHORIN-C; IN-VITRO; SKELETON; MICE; SPECTRIN; ADDUCIN
AB Dematin is a relatively low abundance actin binding and bundling protein associated with the spectrin-actin junctions of mature erythrocytes. Primary structure of dematin includes a loosely folded core domain and a compact headpiece domain that was originally identified in villin. Dematin's actin binding properties are regulated by phosphorylation of its headpiece domain by cyclic adenosine monophosphate-dependent protein kinase. Here, we used a novel gene disruption strategy to generate the whole body dematin gene knockout mouse model (FLKO). FLKO mice, while born at a normal Mendelian ratio, developed severe anemia and exhibited profound aberrations of erythrocyte morphology and membrane stability. Having no apparent effect on primitive erythropoiesis, FLKO mice show significant enhancement of erythroblast enucleation during definitive erythropoiesis. Using membrane protein analysis, domain mapping, electron microscopy, and dynamic deformability measurements, we investigated the mechanism of membrane instability in FLKO erythrocytes. Although many membrane and cytoskeletal proteins remained at their normal levels, the major peripheral membrane proteins spectrin, adducin, and actin were greatly reduced in FLKO erythrocytes. Our results demonstrate that dematin plays a critical role in maintaining the fundamental properties of the membrane cytoskeleton complex.
C1 [Lu, Yunzhe; Hanada, Toshihiko; Nwankwo, Jennifer O.; Wieschhaus, Adam J.; Chishti, Athar H.] Tufts Univ, Sch Med, Dept Dev Mol & Chem Biol, Jaharis Bldg,Room 714,150 Harrison Ave, Boston, MA 02111 USA.
[Fujiwara, Yuko] Harvard Med Sch, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA.
[Fujiwara, Yuko] Harvard Med Sch, Harvard Stem Cell Inst, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA.
[Nwankwo, Jennifer O.; Chishti, Athar H.] Tufts Univ, Sch Med, Pharmacol & Expt Therapeut, Jaharis Bldg,Room 714,150 Harrison Ave, Boston, MA 02111 USA.
[Hartwig, John] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA USA.
[Huang, Sha; Han, Jongyoon] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA USA.
[Han, Jongyoon] MIT, Dept Biol Engn, Cambridge, MA USA.
[Chishti, Athar H.] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Programs Cellular & Mol Physiol, Jaharis Bldg,Room 714,150 Harrison Ave, Boston, MA 02111 USA.
[Chishti, Athar H.] Tufts Univ, Sch Med, Dept Mol Microbiol, Jaharis Bldg,Room 714,150 Harrison Ave, Boston, MA 02111 USA.
RP Chishti, AH (reprint author), Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Program Cellular & Mol Physiol,Program Pharmacol, Jaharis Bldg,Room 714,150 Harrison Ave, Boston, MA 02111 USA.
EM athar.chishti@tufts.edu
FU National Institutes of Health, National Human Genome Research Institute
[U01HG004085]; CSD Consortium [U01HG004080]; National Heart, Lung, and
Blood Institute [HL095050, HL051445]; American Society of Hematology
Bridge grant award; Howard Hughes Medical Institute International
Student Research Fellowship; American Heart Association
FX National Institutes of Health, National Human Genome Research Institute
grants to Velocigene at Regeneron (U01HG004085) and the CSD Consortium
(U01HG004080) funded the generation of gene-targeted ES cells for 8500
genes in the KOMP Program and archived and distributed by the KOMP
Repository at University of California, Davis and Children's Hospital
Oakland Research Institute (U42RR024244). This work was supported in
part by National Heart, Lung, and Blood Institute grants HL095050 and
HL051445, an American Society of Hematology Bridge grant award, a Howard
Hughes Medical Institute International Student Research Fellowship
(J.O.N.), and a Grant-in-Aid from the American Heart Association.
NR 44
TC 1
Z9 1
U1 4
U2 5
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 7
PY 2016
VL 128
IS 1
BP 93
EP 103
DI 10.1182/blood-2016-01-692251
PG 11
WC Hematology
SC Hematology
GA DQ5MN
UT WOS:000379249600017
PM 27073223
ER
PT J
AU Koreth, J
Kim, HT
Jones, KT
Lange, PB
Reynolds, CG
Chammas, MJ
Dusenbury, K
Whangbo, J
Nikiforow, S
Alyea, EP
Armand, P
Cutler, CS
Ho, VT
Chen, YB
Avigan, D
Blazar, BR
Antin, JH
Ritz, J
Soiffer, RJ
AF Koreth, John
Kim, Haesook T.
Jones, Kyle T.
Lange, Paulina B.
Reynolds, Carol G.
Chammas, Marie J.
Dusenbury, Katherine
Whangbo, Jennifer
Nikiforow, Sarah
Alyea, Edwin P., III
Armand, Philippe
Cutler, Corey S.
Ho, Vincent T.
Chen, Yi-Bin
Avigan, David
Blazar, Bruce R.
Antin, Joseph H.
Ritz, Jerome
Soiffer, Robert J.
TI Efficacy, durability, and response predictors of low-dose interleukin-2
therapy for chronic graft-versus-host disease
SO BLOOD
LA English
DT Article
ID REGULATORY T-CELLS; CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT;
BONE-MARROW-TRANSPLANTATION; CLINICAL-TRIALS; CHRONIC GVHD; CRITERIA;
TOLERANCE; IL-2; VALIDATION
AB Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well tolerated, did not exacerbate alloimmunity, augmented Treg in vivo, and was associated with improvement of active cGVHD. In the current phase 2 study, 35 adults with steroid-refractory cGVHD received daily IL-2(1 x 10(6) IU/m(2)) for 12 weeks. Median time from transplantation and cGVHD onset was 616 days (range, 270-2145 days) and 317 days (range, 28-1880 days), respectively. Two patients withdrew and 5 required IL-2 dose reductions due to side effects. Twenty of 33 evaluable patients (61%) had clinical responses at multiple cGVHD sites (liver, skin, gastrointestinal tract, lung, joint/muscle/fascia). Three patients (9%) had progressive cGVHD. Compared with pretreatment levels, Treg and natural killer cell counts rose > fivefold (P < .001) and > fourfold (P < .001), respectively, without significant change in conventional CD4 T cells (Tcons) or CD8 T cells. The Treg: Tcon ratio rose > fivefold (P < .001). Clinical responders initiated IL-2 earlier (508 vs 917 days after transplantation, P = .005; 249 vs 461 days after cGVHD onset; P = .03). Treg: Tcon ratios >= 0.07 at baseline and >= 0.2 at week 1 also predicted clinical response (P = .003; P = .0003, respectively). After a 4-week treatment hiatus, clinical responders were eligible to continue IL-2 therapy indefinitely. During 2 years of extended IL-2 therapy, clinical and Treg immune responses persisted, while Tcon count and Treg: Tcon ratio gradually normalized. Low-dose IL-2 provides durable clinical improvement in active cGVHD and extended therapy is well-tolerated.
C1 [Koreth, John; Jones, Kyle T.; Lange, Paulina B.; Reynolds, Carol G.; Chammas, Marie J.; Dusenbury, Katherine; Whangbo, Jennifer; Nikiforow, Sarah; Alyea, Edwin P., III; Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.] Dana Farber Canc Inst, Div Hematol Malignancies, D2029,450 Brookline Ave, Boston, MA 02115 USA.
[Koreth, John; Kim, Haesook T.; Jones, Kyle T.; Lange, Paulina B.; Reynolds, Carol G.; Chammas, Marie J.; Dusenbury, Katherine; Whangbo, Jennifer; Nikiforow, Sarah; Alyea, Edwin P., III; Armand, Philippe; Cutler, Corey S.; Ho, Vincent T.; Chen, Yi-Bin; Avigan, David; Antin, Joseph H.; Ritz, Jerome; Soiffer, Robert J.] Harvard Med Sch, Boston, MA USA.
[Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Chen, Yi-Bin] Massachusetts Gen Hosp, Hematol Oncol Div, Boston, MA 02114 USA.
[Avigan, David] Beth Israel Deaconess Med Ctr, Hematol Oncol, Boston, MA 02215 USA.
[Blazar, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Blazar, Bruce R.] Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN USA.
RP Koreth, J (reprint author), Dana Farber Canc Inst, D2029,450 Brookline Ave, Boston, MA 02215 USA.
EM john_koreth@dfci.harvard.edu
FU National Institutes of Health National Cancer Institute [RO1CA183559,
RO1CA183560, PO1CA142106]; Leukemia & Lymphoma Society [6005-12];
Prometheus Laboratories Inc; Ted and Eileen Pasquarello Research Fund
FX This work was supported by National Institutes of Health National Cancer
Institute grants RO1CA183559, RO1CA183560, and PO1CA142106; Leukemia &
Lymphoma Society grant 6005-12; Prometheus Laboratories Inc; and the Ted
and Eileen Pasquarello Research Fund.
NR 41
TC 15
Z9 15
U1 2
U2 2
PU AMER SOC HEMATOLOGY
PI WASHINGTON
PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA
SN 0006-4971
EI 1528-0020
J9 BLOOD
JI Blood
PD JUL 7
PY 2016
VL 128
IS 1
BP 130
EP 137
DI 10.1182/blood-2016-02-702852
PG 8
WC Hematology
SC Hematology
GA DQ5MN
UT WOS:000379249600021
PM 27073224
ER
PT J
AU Kotani, H
Ebi, H
Kitai, H
Nanjo, S
Kita, K
Huynh, TG
Ooi, A
Faber, AC
Mino-Kenudson, M
Yano, S
AF Kotani, H.
Ebi, H.
Kitai, H.
Nanjo, S.
Kita, K.
Huynh, T. G.
Ooi, A.
Faber, A. C.
Mino-Kenudson, M.
Yano, S.
TI Co-active receptor tyrosine kinases mitigate the effect of FGFR
inhibitors in FGFR1-amplified lung cancers with low FGFR1 protein
expression
SO ONCOGENE
LA English
DT Article
ID IN-SITU HYBRIDIZATION; ACQUIRED-RESISTANCE; GENE AMPLIFICATION; TARGETED
THERAPIES; BREAST-CANCER; GROWTH; SENSITIVITY; ACTIVATION; GENOMICS;
AZD4547
AB Targeted therapies are effective in subsets of lung cancers with EGFR mutations and anaplastic lymphoma kinase (ALK) translocations. Large-scale genomics have recently expanded the lung cancer landscape with FGFR1 amplification found in 10-20% of squamous cell carcinomas (SCCs). However, the response rates have been low for biomarker-directed fibroblast growth factor receptor (FGFR) inhibitor therapy in SCC, which contrasts to the relatively high rates of response seen in EGFR mutant and ALK-translocated lung cancers treated with epidermal growth factor receptor (EGFR) inhibitors and ALK inhibitors, respectively. In order to better understand the low response rates of FGFR1-amplified lung cancers to FGFR inhibitors, relationships between gene copy number, mRNA expression and protein expression of FGFR1 were assessed in cell lines, tumor specimens and data from The Cancer Genome Atlas. The importance of these factors for the sensitivity to FGFR inhibitors was determined by analyzing drug screen data and conducting in vitro and in vivo experiments. We report that there was a discrepancy between FGFR1 amplification level and FGFR1 protein expression in a number of these cell lines, and the cancers with unexpectedly low FGFR1 expression were uniformly resistant to the different FGFR inhibitors. Further interrogation of the receptor tyrosine kinase activity in these discordant cell lines revealed co-activation of HER2 and platelet-derived growth factor receptor-a (PDGFRa) caused by gene amplification or ligand overexpression maintained phosphoinositide 3-kinase (PI3K) and MEK/ERK signaling even in the presence of FGFR inhibitor. Accordingly, co-inhibition of FGFR1 and HER2 or PDGFRa led to enhanced drug responses. In contrast, FGFR1-amplified high FGFR1 protein-expressing lung cancers are sensitive to FGFR inhibitor monotherapy by downregulating ERK signaling. Addition of a PI3K inhibitor to these high FGFR1 protein-expressing cancers further sensitized them to FGFR inhibitor. These data reveal that biomarker-directed trials for FGFR1-amplified SCC require assessment of FGFR1 protein expression and uncover novel therapeutic strategies for FGFR1-amplified SCC with low FGFR1 protein expression.
C1 [Kotani, H.; Ebi, H.; Kitai, H.; Nanjo, S.; Kita, K.; Yano, S.] Kanazawa Univ, Canc Res Inst, Div Med Oncol, 13-1 Takaramachi, Kanazawa, Ishikawa 9200934, Japan.
[Huynh, T. G.; Mino-Kenudson, M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Ooi, A.] Kanazawa Univ, Grad Sch Med Sci, Dept Mol & Cellular Pathol, Kanazawa, Ishikawa, Japan.
[Faber, A. C.] Virginia Commonwealth Univ, Sch Dent, VCU Philips Inst Oral Hlth Res, Richmond, VA USA.
[Faber, A. C.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA.
RP Ebi, H; Yano, S (reprint author), Kanazawa Univ, Canc Res Inst, Div Med Oncol, 13-1 Takaramachi, Kanazawa, Ishikawa 9200934, Japan.
EM hebi@staff.kanazawa-u.ac.jp; syano@staff.kanazawa-u.ac.jp
OI Ebi, Hiromichi/0000-0003-3155-7576
FU Ministry of Education, Culture, Sports, Science and Technology (MEXT) of
Japan [26830105, 22112010A01]
FX We thank Dr Shuta Tomida at Okayama University for his assistance with
the statistics. This work was supported by Grants-in-Aid for Scientific
Research (H Ebi, 26830105 and S Yano, 21390256), Scientific Research on
Innovative Areas 'Integrative Research on Cancer Microenvironment
Network' (H Ebi and S Yano, 22112010A01) and Grant-in-Aid for Project
for Development of Innovative Research on Cancer Therapeutics (P-Direct)
from the Ministry of Education, Culture, Sports, Science and Technology
(MEXT) of Japan.
NR 49
TC 5
Z9 5
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL 7
PY 2016
VL 35
IS 27
BP 3587
EP 3597
DI 10.1038/onc.2015.426
PG 11
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DR0UD
UT WOS:000379621500011
PM 26549034
ER
PT J
AU Wang, Q
Liu, P
Spangle, JM
Von, T
Roberts, TM
Lin, NU
Krop, IE
Winer, EP
Zhao, JJ
AF Wang, Q.
Liu, P.
Spangle, J. M.
Von, T.
Roberts, T. M.
Lin, N. U.
Krop, I. E.
Winer, E. P.
Zhao, J. J.
TI PI3K-p110 alpha mediates resistance to HER2-targeted therapy in HER2+,
PTEN-deficient breast cancers
SO ONCOGENE
LA English
DT Article
ID P110-ALPHA ISOFORM; PI3K; PIK3CA; TUMORIGENESIS; TRASTUZUMAB;
INHIBITION; RECEPTORS; P110-BETA; TUMORS; METASTASIS
AB Human epidermal growth factor receptor-2 (HER2) amplification/overexpression (HER2+) frequently co-occurs with PI3K pathway activation in breast tumors. PI3K signaling is most often activated by PIK3CA mutation or PTEN loss, which frequently results in sensitivity to p110 alpha or p110 beta inhibitors, respectively. To examine the p110 isoform dependence in HER2+, PTEN-deficient tumors, we generated genetic mouse models of breast tumors driven by concurrent Her2 activation and Pten loss coupled with deletion of p110 alpha or p110 beta. Ablation of p110 alpha, but not p110 beta, significantly impaired the development of Her2+/Pten-null tumors in mice. We further show that p110 alpha primarily mediates oncogenic signaling in HER2+/PTEN-deficient human cancers while p110 beta conditionally mediates PI3K/AKT signaling only upon HER2 inhibition. Combined HER2 and p110 alpha inhibition effectively reduced PI3K/AKT signaling and growth of cancer cells both in vitro and in vivo. Addition of the p110 beta inhibitor to dual HER2 and p110 alpha inhibition induced tumor regression in a xenograft model of HER2+/PTEN-deficient human cancers. Together, our data suggest that combined inhibition of HER2 and p110 alpha/beta may serve as a potent and durable therapeutic regimen for the treatment of HER2+, PTEN-deficient breast tumors.
C1 [Wang, Q.; Liu, P.; Spangle, J. M.; Von, T.; Roberts, T. M.; Zhao, J. J.] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 936B, Boston, MA 02115 USA.
[Wang, Q.; Spangle, J. M.; Von, T.; Roberts, T. M.; Zhao, J. J.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA.
[Liu, P.] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Ctr Canc, Wuhan, Peoples R China.
[Lin, N. U.; Krop, I. E.; Winer, E. P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Wang, Q.] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA.
RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,Smith 936B, Boston, MA 02115 USA.
EM jean_zhao@dfci.harvard.edu
FU Department of Pathology and Laboratory Medicine, Medical University of
South Carolina; Susan G. Komen Breast Cancer Foundation [CCR 12225834];
Breast Cancer Research Foundation; NIH grants [CA187918, CA172461-01,
1P50CA168504]
FX We thank Dr Roderick Bronson and the Dana-Farber/Harvard Cancer Center
Rodent Histopathology Core for histopathological analyses. MMTV-NIC mice
were provided by W Muller (McGill University). Floxed Pten mice were
provided by H Wu (UCLA). This work was supported by start-up fund from
Department of Pathology and Laboratory Medicine, Medical University of
South Carolina (QW), the Susan G. Komen Breast Cancer Foundation CCR
12225834 (IEK), the Breast Cancer Research Foundation (NUL, EPW, JJZ),
NIH grants CA187918 (TMR and JJZ), CA172461-01 (JJZ) and 1P50CA168504
(TMR, IEK, EPW, NUL and JJZ).
NR 27
TC 1
Z9 1
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD JUL 7
PY 2016
VL 35
IS 27
BP 3607
EP 3612
DI 10.1038/onc.2015.406
PG 6
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA DR0UD
UT WOS:000379621500013
PM 26500061
ER
PT J
AU Atwoli, L
Platt, JM
Basu, A
Williams, DR
Stein, DJ
Koenen, KC
AF Atwoli, Lukoye
Platt, Jonathan M.
Basu, Archana
Williams, David R.
Stein, Dan J.
Koenen, Karestan C.
TI Associations between lifetime potentially traumatic events and chronic
physical conditions in the South African Stress and Health Survey: a
cross-sectional study
SO BMC PSYCHIATRY
LA English
DT Article
DE Trauma; Physical health; South Africa; Posttraumatic stress disorder
ID ADVERSE CHILDHOOD EXPERIENCES; NATIONAL EPIDEMIOLOGIC SURVEY; INTIMATE
PARTNER VIOLENCE; CORONARY-HEART-DISEASE; MEDICAL CONDITIONS;
PRIMARY-CARE; PSYCHOLOGICAL TRAUMA; MENTAL-DISORDERS; INFORMED CARE;
PTSD SYMPTOMS
AB Background: This study examined the association between the type, and cumulative number of lifetime potentially traumatic events (PTEs), and chronic physical conditions, in a South African sample. PTE exposures have been associated with an increased risk for a wide range of chronic physical conditions, but it is unclear whether psychiatric disorders mediate this association. Given the established differences in trauma occurrence, and the epidemiology of posttraumatic stress disorder (PTSD) in South Africa relative to other countries, examining associations between PTEs and chronic physical conditions, particularly while accounting for psychiatric comorbidity is important.
Methods: Data were drawn from the South African Stress and Health Study, a cross-sectional population-representative study of psychological and physical health of South African adults. Twenty-seven PTEs, based on the World Health Organization Composite International Diagnostic Interview Version 3.0, DSM-IV PTSD module were grouped into seven PTE types (war events, physical violence, sexual violence, accidents, unexpected death of a loved one, network events, and witnessing PTEs). Five clusters of physical conditions (cardiovascular, arthritis, respiratory, chronic pain, and other health conditions) were examined. Logistic regressions assessed the odds of reporting a physical condition in relation to type and cumulative number of PTEs. Cochran-Armitage test for trend was used to examine dose-response effect of cumulative PTEs on physical conditions.
Results: After adjusting for sociodemographic variables and psychiatric disorders, respondents with any PTE had increased odds of all assessed physical conditions, ranging between 1.48 (95 % CI: 1.06-2.07) for arthritis and 2.07 (95 % CI: 1.57-2.73) for respiratory conditions, compared to those without PTE exposure. Sexual violence, physical violence, unexpected death of a loved one, and network PTEs significantly increased the odds of all or nearly all the physical conditions assessed. There was a dose-response relationship between number of PTEs and increased odds of all physical conditions.
Conclusions: Results from this study, the first in an African general population, are consistent with other population-based studies; PTEs confer a broad-spectrum risk for chronic physical conditions, independent of psychiatric disorders. These risks increase with each cumulative PTE exposure. Clinically, comprehensive evaluations for risk of mental and physical health morbidities should be considered among PTE survivors.
C1 [Atwoli, Lukoye] Moi Univ, Sch Med, Dept Mental Hlth, POB 1493, Eldoret 30100, Kenya.
[Atwoli, Lukoye; Stein, Dan J.] Univ Cape Town, Dept Psychiat & Mental Hlth, MRC, Unit Anxiety & Stress Disorders, Cape Town, South Africa.
[Platt, Jonathan M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Basu, Archana; Koenen, Karestan C.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Williams, David R.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
[Koenen, Karestan C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
RP Atwoli, L (reprint author), Moi Univ, Sch Med, Dept Mental Hlth, POB 1493, Eldoret 30100, Kenya.; Atwoli, L (reprint author), Univ Cape Town, Dept Psychiat & Mental Hlth, MRC, Unit Anxiety & Stress Disorders, Cape Town, South Africa.
EM Lukoye.atwoli@mu.ac.ke
RI Stein, Dan/A-1752-2008;
OI Stein, Dan/0000-0001-7218-7810; Atwoli, Lukoye/0000-0001-7710-9723
FU Medical Research Council of South Africa; National Institute of Mental
Health [5-T32-MH-13043-43]; [T32-MH 017119]; [R01-MH101269];
[R01-MH101227]; [R21-MH102570]; [R21TW009795]; [R01MH093612];
[U01OH010407]; [P51RR000165]
FX Dan J. Stein is supported by the Medical Research Council of South
Africa. Jonathan Platt is supported by the National Institute of Mental
Health [5-T32-MH-13043-43]. Archana Basu is supported by T32-MH 017119.
Karestan C. Koenen is supported by R01-MH101269, R01-MH101227,
R21-MH102570, R21TW009795, R01MH093612, U01OH010407 and P51RR000165.
NR 64
TC 0
Z9 0
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-244X
J9 BMC PSYCHIATRY
JI BMC Psychiatry
PD JUL 7
PY 2016
VL 16
AR 214
DI 10.1186/s12888-016-0929-z
PG 10
WC Psychiatry
SC Psychiatry
GA DQ5DS
UT WOS:000379225400005
PM 27389090
ER
PT J
AU Liu, X
Zhang, ZB
Ruan, JB
Pan, YD
Magupalli, VG
Wu, H
Lieberman, J
AF Liu, Xing
Zhang, Zhibin
Ruan, Jianbin
Pan, Youdong
Magupalli, Venkat Giri
Wu, Hao
Lieberman, Judy
TI Inflammasome-activated gasdermin D causes pyroptosis by forming membrane
pores
SO NATURE
LA English
DT Article
ID MIXED LINEAGE KINASE; LISTERIA-MONOCYTOGENES; INTRACELLULAR BACTERIA;
CASPASE-1 ACTIVATION; NLRP3 INFLAMMASOME; CELL-DEATH;
INTERLEUKIN-1-BETA; GRANULYSIN; GRANZYMES; PERFORIN
AB Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and Asp275, respectively, to generate an N-terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1 beta(1,2). Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined.
C1 [Liu, Xing; Zhang, Zhibin; Ruan, Jianbin; Magupalli, Venkat Giri; Wu, Hao; Lieberman, Judy] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Liu, Xing; Zhang, Zhibin; Lieberman, Judy] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Ruan, Jianbin; Magupalli, Venkat Giri; Wu, Hao] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Pan, Youdong] Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA.
[Pan, Youdong] Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, 75 Francis St, Boston, MA 02115 USA.
RP Wu, H; Lieberman, J (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Lieberman, J (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.; Wu, H (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM wu@crystal.harvard.edu; judy.lieberman@childrens.harvard.edu
FU US NIH [R01AI123265]
FX This work was supported by US NIH grant R01AI123265 (J.L.).
NR 29
TC 35
Z9 35
U1 14
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD JUL 7
PY 2016
VL 535
IS 7610
BP 153
EP +
DI 10.1038/nature18629
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2EU
UT WOS:000379015600043
PM 27383986
ER
PT J
AU Kellnberger, S
Assmann, W
Lehrack, S
Reinhardt, S
Thirolf, P
Queiros, D
Sergiadis, G
Dollinger, G
Parodi, K
Ntziachristos, V
AF Kellnberger, Stephan
Assmann, Walter
Lehrack, Sebastian
Reinhardt, Sabine
Thirolf, Peter
Queiros, Daniel
Sergiadis, George
Dollinger, Guenther
Parodi, Katia
Ntziachristos, Vasilis
TI Ionoacoustic tomography of the proton Bragg peak in combination with
ultrasound and optoacoustic imaging
SO SCIENTIFIC REPORTS
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; COMPUTED-TOMOGRAPHY; IN-VIVO;
PHOTOACOUSTIC MICROSCOPY; PLASMA ACCELERATORS; RANGE UNCERTAINTIES;
THERAPY; BEAM; SIMULATION; VERIFICATION
AB Ions provide a more advantageous dose distribution than photons for external beam radiotherapy, due to their so-called inverse depth dose deposition and, in particular a characteristic dose maximum at their end-of-range (Bragg peak). The favorable physical interaction properties enable selective treatment of tumors while sparing surrounding healthy tissue, but optimal clinical use requires accurate monitoring of Bragg peak positioning inside tissue. We introduce ionoacoustic tomography based on detection of ion induced ultrasound waves as a technique to provide feedback on the ion beam profile. We demonstrate for 20 MeV protons that ion range imaging is possible with submillimeter accuracy and can be combined with clinical ultrasound and optoacoustic tomography of similar precision. Our results indicate a simple and direct possibility to correlate, in-vivo and in real-time, the conventional ultrasound echo of the tumor region with ionoacoustic tomography. Combined with optoacoustic tomography it offers a well suited pre-clinical imaging system.
C1 [Kellnberger, Stephan; Queiros, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany.
[Kellnberger, Stephan; Queiros, Daniel; Ntziachristos, Vasilis] Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany.
[Kellnberger, Stephan] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Assmann, Walter; Lehrack, Sebastian; Reinhardt, Sabine; Thirolf, Peter; Parodi, Katia] Univ Munich, Dept Med Phys, D-85748 Garching, Germany.
[Sergiadis, George] Aristotle Univ Thessaloniki, Dept Elect & Comp Engn, Thessaloniki 54124, Greece.
[Dollinger, Guenther] Univ Bundeswehr, Inst Appl Phys & Measurement Technol, D-85577 Neubiberg, Germany.
RP Ntziachristos, V (reprint author), Tech Univ Munich, Inst Biol & Med Imaging, D-85764 Neuherberg, Germany.; Ntziachristos, V (reprint author), Helmholtz Zentrum Munchen, D-85764 Neuherberg, Germany.
EM v.ntziachristos@tum.de
FU Alexander von Humboldt-Stiftung; DFG Cluster of Excellence Munich Centre
for Advanced Photonics (MAP); DFG Reinhart Koselleck award 'High
resolution near-field thermoacoustic sensing and imaging' [NT 3/9-1]
FX We thank Murad Omar, Juan Sebastian Osorio Valencia, Christoph Gabisch,
Thomas Hellerer, and Marcus Moser for their experimental support, George
Dedes for his help in simulations. S. K. acknowledges financial support
from the Alexander von Humboldt-Stiftung though a Feodor Lynen Research
Fellowship. This work was funded by the DFG Cluster of Excellence Munich
Centre for Advanced Photonics (MAP) and the DFG Reinhart Koselleck award
'High resolution near-field thermoacoustic sensing and imaging' (NT
3/9-1).
NR 39
TC 0
Z9 0
U1 2
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 7
PY 2016
VL 6
AR 29305
DI 10.1038/srep29305
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ4AP
UT WOS:000379145700001
PM 27384505
ER
PT J
AU Carey, LA
Winer, EP
AF Carey, Lisa A.
Winer, Eric P.
TI I-SPY 2-Toward More Rapid Progress in Breast Cancer Treatment
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Editorial Material
ID TRASTUZUMAB; TRIAL; CARBOPLATIN
C1 [Carey, Lisa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol Oncol, Chapel Hill, NC 27599 USA.
[Winer, Eric P.] Dana Farber Canc Inst, Breast Oncol Program, Boston, MA 02115 USA.
RP Carey, LA (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Div Hematol Oncol, Chapel Hill, NC 27599 USA.
NR 9
TC 5
Z9 5
U1 0
U2 3
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 7
PY 2016
VL 375
IS 1
BP 83
EP 84
DI 10.1056/NEJMe1603691
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ1ZP
UT WOS:000379000200010
PM 27406352
ER
PT J
AU Bearnot, B
Schmitt, W
Nejad, S
AF Bearnot, Benjamin
Schmitt, William
Nejad, Shamim
TI Mitigation Strategies for Opioid Abuse
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Bearnot, Benjamin; Schmitt, William; Nejad, Shamim] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Bearnot, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM bbearnot@partners.org
NR 2
TC 0
Z9 0
U1 0
U2 0
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD JUL 7
PY 2016
VL 375
IS 1
BP 95
EP 95
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ1ZP
UT WOS:000379000200025
PM 27406368
ER
PT J
AU Yip, SSF
Aerts, HJWL
AF Yip, Stephen S. F.
Aerts, Hugo J. W. L.
TI Applications and limitations of radiomics
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Review
DE PET; quantitative imaging; radiomics
ID CELL LUNG-CANCER; TUMOR TEXTURE ANALYSIS; TRACER UPTAKE HETEROGENEITY;
STANDARDIZED UPTAKE VALUES; F-18-FDG PET/CT IMAGES; CONTRAST-ENHANCED
MRI; ESOPHAGEAL CANCER; FDG UPTAKE; PATHOLOGICAL RESPONSE; PULMONARY
NODULES
AB Radiomics is an emerging field in quantitative imaging that uses advanced imaging features to objectively and quantitatively describe tumour phenotypes. Radiomic features have recently drawn considerable interest due to its potential predictive power for treatment outcomes and cancer genetics, which may have important applications in personalized medicine. In this technical review, we describe applications and challenges of the radiomic field. We will review radiomic application areas and technical issues, as well as proper practices for the designs of radiomic studies.
C1 [Yip, Stephen S. F.; Aerts, Hugo J. W. L.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.
[Yip, Stephen S. F.; Aerts, Hugo J. W. L.] Harvard Univ, Sch Med, Boston, MA USA.
[Aerts, Hugo J. W. L.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
RP Aerts, HJWL (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA.; Aerts, HJWL (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Aerts, HJWL (reprint author), Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
EM Hugo_Aerts@dfci.harvard.edu
RI Aerts, Hugo/P-6350-2015
OI Aerts, Hugo/0000-0002-2122-2003
FU National Institute of Health [U01CA190234, U24CA194354]; American
Association of Physicists in Medicine
FX The authors would like to acknowledge the support from National
Institute of Health (Award Number U01CA190234 and U24CA194354) and
research seed funding grant from the American Association of Physicists
in Medicine. The authors would also like to thank Dr Elizabeth Huynh for
editorial assistance.
NR 119
TC 7
Z9 7
U1 16
U2 38
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0031-9155
EI 1361-6560
J9 PHYS MED BIOL
JI Phys. Med. Biol.
PD JUL 7
PY 2016
VL 61
IS 13
BP R150
EP R166
DI 10.1088/0031-9155/61/13/R150
PG 17
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA DO9GS
UT WOS:000378094000002
PM 27269645
ER
PT J
AU Lee, S
Shang, YL
Redmond, SA
Urisman, A
Tang, AA
Li, KH
Burlingame, AL
Pak, RA
Jovicic, A
Gitler, AD
Wang, JH
Gray, NS
Seeley, WW
Siddique, T
Bigio, EH
Lee, VMY
Trojanowski, JQ
Chan, JR
Huang, EJ
AF Lee, Sebum
Shang, Yulei
Redmond, Stephanie A.
Urisman, Anatoly
Tang, Amy A.
Li, Kathy H.
Burlingame, Alma L.
Pak, Ryan A.
Jovicic, Ana
Gitler, Aaron D.
Wang, Jinhua
Gray, Nathanael S.
Seeley, William W.
Siddique, Teepu
Bigio, Eileen H.
Lee, Virginia M. -Y.
Trojanowski, John Q.
Chan, Jonah R.
Huang, Eric J.
TI Activation of HIPK2 Promotes ER Stress-Mediated Neurodegeneration in
Amyotrophic Lateral Sclerosis
SO NEURON
LA English
DT Article
ID UNFOLDED PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; FRONTOTEMPORAL
LOBAR DEGENERATION; C9ORF72 REPEAT EXPANSION; MUTANT SOD1;
MOTOR-NEURONS; WILD-TYPE; NUCLEOCYTOPLASMIC TRANSPORT; KINASE
ACTIVATION; TDP-43 PATHOLOGY
AB Persistent accumulation of misfolded proteins causes endoplasmic reticulum (ER) stress, a prominent feature in many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). Here we report the identification of homeodomain interacting protein kinase 2 (HIPK2) as the essential link that promotes ER-stress-induced cell death via the IRE1 alpha-ASK1-JNK pathway. ER stress, induced by tunicamycin or SOD1(G93A), activates HIPK2 by phosphorylating highly conserved serine and threonine residues (S359/T360) within the activation loop of the HIPK2 kinase domain. In SOD1 G93A mice, loss of HIPK2 delays disease onset, reduces cell death in spinal motor neurons, mitigates glial pathology, and improves survival. Remarkably, HIPK2 activation positively correlates with TDP-43 proteinopathy in NEFH-tTA/tetO-hTDP-43DNLS mice, sporadic ALS and C9ORF72 ALS, and blocking HIPK2 kinase activity protects motor neurons from TDP-43 cytotoxicity. These results reveal a previously unrecognized role of HIPK2 activation in ER-stress-mediated neurodegeneration and its potential role as a biomarker and therapeutic target for ALS.
C1 [Lee, Sebum; Shang, Yulei; Urisman, Anatoly; Tang, Amy A.; Pak, Ryan A.; Seeley, William W.; Huang, Eric J.] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94158 USA.
[Redmond, Stephanie A.; Seeley, William W.; Chan, Jonah R.; Huang, Eric J.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.
[Redmond, Stephanie A.; Chan, Jonah R.; Huang, Eric J.] Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94158 USA.
[Li, Kathy H.; Burlingame, Alma L.] Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94158 USA.
[Jovicic, Ana; Gitler, Aaron D.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Wang, Jinhua; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Wang, Jinhua; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Div Neuromuscular Med, Chicago, IL 60611 USA.
[Siddique, Teepu] Northwestern Univ, Feinberg Sch Med, Davee Dept Neurol, Chicago, IL 60611 USA.
[Bigio, Eileen H.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Lee, Virginia M. -Y.; Trojanowski, John Q.] Univ Penn, Perelman Sch Med, Ctr Neurodegenerat Dis Res, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Huang, Eric J.] VA Med Ctr, Pathol Serv 113B, San Francisco, CA 94121 USA.
RP Huang, EJ (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94158 USA.; Huang, EJ (reprint author), Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94158 USA.; Huang, EJ (reprint author), Univ Calif San Francisco, Neurosci Grad Program, San Francisco, CA 94158 USA.; Huang, EJ (reprint author), VA Med Ctr, Pathol Serv 113B, San Francisco, CA 94121 USA.
EM eric.huang2@ucsf.edu
FU NIH [F31 NS081905-02, U54 HG006097-02, 8P41GM103481, 1S10OD016229-01,
P50 AG023501, P01 AG019724, OD010927, OD011915, AG017586, AG013854,
NS062796]; Les Turner ALS Foundation; Department of Veterans Affairs
Merit Review Awards [I01-BX001108, I01-RX002133]
FX We thank Linda Kwong, John Robinson, and Theresa Schuck from the Center
for Neurodegenerative Disease Research at the University of Pennsylvania
for their assistance with NEFH-tTA/tetO-hTDP-43 Delta NLS and human
samples; Dr. Kevan Shokat for advice on HIPK2 kinase characterization;
and members of the Huang lab for discussions. This work was supported by
NIH F31 NS081905-02 (S.A.R.), U54 HG006097-02 (N.S.G.), 8P41GM103481 and
1S10OD016229-01 (A.L.B.), P50 AG023501 and P01 AG019724 (W.W.S.),
OD010927 and OD011915 (E.J.H.), AG017586 (V.M.-Y.L.), AG013854 (E.H.B.),
NS062796 (J.R.C.), Les Turner ALS Foundation (T.S.), and the Department
of Veterans Affairs Merit Review Awards I01-BX001108 and I01-RX002133
(E.J.H.).
NR 48
TC 2
Z9 2
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD JUL 6
PY 2016
VL 91
IS 1
BP 41
EP 55
DI 10.1016/j.neuron.2016.05.021
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA DU7KY
UT WOS:000382394300010
PM 27321923
ER
PT J
AU Cheng, CY
Cheng, T
Xiao, H
Krzyaniak, MD
Wang, YP
McGonigal, PR
Frasconi, M
Barnes, JC
Fahrenbach, AC
Wasielewski, MR
Goddard, WA
Stoddart, JF
AF Cheng, Chuyang
Cheng, Tao
Xiao, Hai
Krzyaniak, Matthew D.
Wang, Yuping
McGonigal, Paul R.
Frasconi, Marco
Barnes, Jonathan C.
Fahrenbach, Albert C.
Wasielewski, Michael R.
Goddard, William A., III
Stoddart, J. Fraser
TI Influence of Constitution and Charge on Radical Pairing Interactions in
Tris-radical Tricationic Complexes
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID MECHANICALLY INTERLOCKED MOLECULES; FUNCTIONAL SUPRAMOLECULAR POLYMERS;
CONTINUUM DIELECTRIC THEORY; ELECTRON-TRANSFER REACTIONS; GAUSSIAN-BASIS
SETS; PI-PI INTERACTIONS; DONOR-ACCEPTOR; BIOMEDICAL APPLICATIONS;
DIMERIZATION EQUILIBRIUM; NONCOVALENT INTERACTIONS
AB The results of a systematic investigation of trisradical tricationic complexes formed between cyclobis(paraquat-p-phenylene) bisradical dicationic (CBPQT(2(center dot+))) rings and a series of 18 dumbbells, containing centrally located 4,4'-bipyridinium radical cationic (BIPY center dot+) units within oligomethylene chains terminated for the most part by charged 3,5-dimethylpyridinium (PY+) and/or neutral 3,5-dimethylphenyl (PH) groups, are reported. The complexes were obtained by treating equimolar amounts of the CBPQT(4+) ring and the dumbbells containing BIPY2+ units with zinc dust in acetonitrile solutions. Whereas UV-Vis-NIR spectra revealed absorption bands centered on ca. 1100 nm with quite different intensities for the 1:1 complexes depending on the constitutions and charges on the dumbbells, titration experiments showed that the association constants (K-a) for complex formation vary over a wide range, from 800 M-1 for the weakest to 180 000 M-1 for the strongest. While Coulombic repulsions emanating from PY+ groups located at the ends of some of the dumbbells undoubtedly contribute to the destabilization of the trisradical tricationic complexes, solid-state superstructures support the contention that those dumbbells with neutral PH groups at the ends of flexible and appropriately constituted links to the BIPY center dot+ units stand to gain some additional stabilization from C-H center dot center dot center dot pi interactions between the CBPQT(2(center dot+)) rings and the PH termini on the dumbbells. The findings reported in this Article demonstrate how structural changes implemented remotely from the BIPY center dot+ units influence their non-covalent bonding interactions with CBPQT(2(center dot+)) rings. Different secondary effects (Coulombic repulsions versus C-H center dot center dot center dot pi interactions) are uncovered, and their contributions to both binding strengths associated with trisradical interactions and the kinetics of associations and dissociations are discussed at some length, supported by extensive DFT calculations at the M06-D3 level. A fundamental understanding of molecular recognition in radical complexes has relevance when it comes to the design and synthesis of non-equilibrium systems.
C1 [Cheng, Chuyang; Krzyaniak, Matthew D.; Wang, Yuping; McGonigal, Paul R.; Frasconi, Marco; Barnes, Jonathan C.; Fahrenbach, Albert C.; Wasielewski, Michael R.; Stoddart, J. Fraser] Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
[Cheng, Tao; Xiao, Hai; Goddard, William A., III] CALTECH, Mat & Proc Simulat Ctr MC 139 74, Pasadena, CA 91125 USA.
[Krzyaniak, Matthew D.; Wasielewski, Michael R.] Northwestern Univ, Argonne Northwestern Solar Energy Res ANSER Ctr, 2145 Sheridan Rd, Evanston, IL 60208 USA.
[McGonigal, Paul R.] Univ Durham, Dept Chem, South Rd, Durham DH1 3LE, England.
[Frasconi, Marco] Univ Padua, Dept Chem Sci, Via Marzolo 1, I-35131 Padua, Italy.
[Barnes, Jonathan C.] MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Fahrenbach, Albert C.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Mol Biol, 185 Cambridge St, Boston, MA 02114 USA.
[Fahrenbach, Albert C.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA.
[Fahrenbach, Albert C.] Tokyo Inst Technol, Earth Life Sci Inst, Meguro Ku, 2-12-1-IE-1 Ookayama, Tokyo 1528550, Japan.
RP Stoddart, JF (reprint author), Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL 60208 USA.
EM stoddart@northwestern.edu
RI Wasielewski, Michael/K-5888-2016; McGonigal, Paul/J-8291-2012; Cheng,
Tao/B-3491-2016; Frasconi, Marco/C-4767-2014; Cheng,
Chuyang/B-6608-2014;
OI McGonigal, Paul/0000-0002-8538-7579; Cheng, Tao/0000-0003-4830-177X;
Frasconi, Marco/0000-0003-2010-175X; Cheng, Chuyang/0000-0002-3834-0479;
Xiao, Hai/0000-0001-9399-1584
FU National Science Foundation (NSF) [CHE-1308107]; Office of Science of
the U.S. Department of Energy [DE-SC0004993]; NSF [CHE-1565925]; Chinese
Scholarship Council; Foresight Institute; Earth-Life Science Institute;
Howard Hughes Medical Institute through the Life Sciences Research
Foundation
FX This research is supported by National Science Foundation (NSF) under
grant no. CHE-1308107. T.C., H.X., and W.A.G. thank the Joint Center for
Artificial Photosynthesis, a DOE Energy Innovation Hub, supported
through the Office of Science of the U.S. Department of Energy under
Award DE-SC0004993. This work was also supported by the NSF under grant
no. CHE-1565925 (M.R.W.). The authors acknowledge the Integrated
Molecular Structure Education and Research Center (IMSERC) at
Northwestern University for NMR and HRMS characterizations. We thank Dr.
Amy Sarjeant and Charlotte C. Stern for solving the single-crystal X-ray
structures. C.C. thanks the Chinese Scholarship Council for the Award
for Outstanding Self-Financed Students Abroad and Foresight Institute
for the Distinguished Student Award. A.C.F. acknowledges support from
the Earth-Life Science Institute. J.C.B. acknowledges postdoctoral
support from the Howard Hughes Medical Institute through the Life
Sciences Research Foundation.
NR 159
TC 2
Z9 2
U1 45
U2 75
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD JUL 6
PY 2016
VL 138
IS 26
BP 8288
EP 8300
DI 10.1021/jacs.6b04343
PG 13
WC Chemistry, Multidisciplinary
SC Chemistry
GA DQ8JA
UT WOS:000379455600036
PM 27264680
ER
PT J
AU Zheng, DF
Wang, R
Ye, T
Yu, S
Hu, HC
Shen, XX
Li, Y
Ji, HB
Sun, YH
Chen, HQ
AF Zheng, Difan
Wang, Rui
Ye, Ting
Yu, Su
Hu, Haichuan
Shen, Xuxia
Li, Yuan
Ji, Hongbin
Sun, Yihua
Chen, Haiquan
TI MET exon 14 skipping defines a unique molecular class of non-small cell
lung cancer
SO ONCOTARGET
LA English
DT Article
DE MET; non-small cell lung cancer; surgery; targeted therapy
ID DRIVER MUTATIONS; ADENOCARCINOMA; CRIZOTINIB; AMPLIFICATION; GEFITINIB;
RESPONSIVENESS; RESISTANCE; SURVIVAL; SMOKERS; GROWTH
AB Purpose: Recurrent MET exon 14 splicing has been revealed in lung cancers and is a promising therapeutic target. Because we have limited knowledge about the natural history of MET mutant tumors, the current study was aiming to determine the clinical and pathological characteristics in non-small cell lung cancers (NSCLC). Results: Twenty-three patients (1.3%) were positive for MET exon 14 skipping. Patients with MET exon 14 skipping displayed unique characteristics: female, nonsmokers, earlier pathology stage and older age. MET exon 14 skipping indicated an early event as other drivers in lung cancer, while MET copy number gain was more likely a late event in lung cancer. Overall survival (OS) of patients harboring MET exon 14 skipping was longer than patients with KRAS mutation. Almost four-fifths of the lung tumors with MET exon 14 skipping had EGFR and/or HER2 gene copy number gains. EGFR inhibitor showed moderate antitumor activity in treatment of a patient harboring MET exon 14 skipping. Patients and Methods: From October 2007 to June 2013, we screened 1770 patients with NSCLC and correlated MET status with clinical pathologic characteristics and mutations in EGFR, KRAS, BRAF, HER2, and ALK. Quantitative Real-Time PCR was used to detect MET gene copy number gain. Immunohistochemistry (IHC) was also performed to screen MET exon 14 skipping. Clinicopathological characteristics and survival information were analyzed. Conclusions: MET exon 14 skipping was detected in 1.3% (23/ 1770) of the Chinese patients with NSCLC. MET exon 14 skipping defined a new molecular subset of NSCLC with identifiable clinical characteristics. The therapeutic EGFR inhibitors might be an alternative treatment for patients with MET mutant NSCLC.
C1 [Zheng, Difan; Wang, Rui; Ye, Ting; Yu, Su; Hu, Haichuan; Sun, Yihua; Chen, Haiquan] Fudan Univ, Dept Thorac Surg, Shanghai Canc Ctr, Shanghai, Peoples R China.
[Zheng, Difan; Wang, Rui; Ye, Ting; Yu, Su; Hu, Haichuan; Shen, Xuxia; Li, Yuan; Sun, Yihua; Chen, Haiquan] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China.
[Shen, Xuxia; Li, Yuan] Fudan Univ, Dept Pathol, Shanghai Canc Ctr, Shanghai, Peoples R China.
[Chen, Haiquan] Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China.
[Yu, Su] Fudan Univ, Canc Res Lab, Shanghai Canc Ctr, Shanghai, Peoples R China.
[Ji, Hongbin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Innovat Ctr Cell Signaling Network, Shanghai, Peoples R China.
[Hu, Haichuan] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Sun, YH; Chen, HQ (reprint author), Fudan Univ, Dept Thorac Surg, Shanghai Canc Ctr, Shanghai, Peoples R China.; Sun, YH; Chen, HQ (reprint author), Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai, Peoples R China.; Chen, HQ (reprint author), Fudan Univ, Inst Biomed Sci, Shanghai, Peoples R China.
EM Sun_yihua76@hotmail.com; hqchen1@yahoo.com
FU National Natural Science Foundation of China [81330056, 81401886,
81401891, 81422029, 81472173, 81372525]; Science and Technology
Commission of Shanghai Municipality [JGGG1302]; Wu Jieping Medical
Foundation [320.6750.14317]; Shen-Kang Center Project [SKMB1201];
Shanghai rising star program [16QA1403500]
FX This work was supported by the National Natural Science Foundation of
China (81330056, 81401886, 81401891, 81422029, 81472173 and 81372525),
the Key Project of Science and Technology Commission of Shanghai
Municipality (JGGG1302), Wu Jieping Medical Foundation (320.6750.14317)
and Shen-Kang Center Project (SKMB1201), Shanghai rising star program
(16QA1403500).
NR 23
TC 1
Z9 1
U1 8
U2 8
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD JUL 5
PY 2016
VL 7
IS 27
BP 41691
EP 41702
DI 10.18632/oncotarget.9541
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DS7DI
UT WOS:000380942600058
PM 27223439
ER
PT J
AU Kim, S
Lee, JH
Kang, I
Hyun, S
Yu, J
Shin, C
AF Kim, Soyoung
Lee, Jung Hyun
Kang, Igojo
Hyun, Soonsil
Yu, Jaehoon
Shin, Chanseok
TI An Amphiphilic Peptide Induces Apoptosis Through the miR29b-p53 Pathway
in Cancer Cells
SO MOLECULAR THERAPY-NUCLEIC ACIDS
LA English
DT Article
DE apoptosis; cancer therapy; Dicer processing; miR29b-p53 pathway;
synthesized amphiphilic peptide
ID ANTICANCER ACTIVITY; P53; MICRORNA; RNA; TARGETS; MIRNAS; DRUGS; DICER;
OLIGONUCLEOTIDES; EXPRESSION
AB Peptides have been in the limelight, as therapeutic agents for cancer treatment through various applications due to their high target selectivity and exceptional ability to penetrate the cell membrane. Recent studies have revealed that synthesized peptides bind to hairpin structures of RNA that affect their activities such as changing the efficacy of microRNA maturation. MicroRNA-mediated p53 activation by the microRNA-29 (miR29) family is one of the most important regulatory pathways in cancer therapeutics. By targeting the suppressors of p53, a tumor suppressor protein, miR29 induces apoptosis of cancer cells through p53 stabilization. Here, we identify a novel synthesized amphiphilic peptide, LK-L1C/K6W/L8C, which enhances expression of miR29b and promotes p53 activity. In the presence of LK-L1C/K6W/L8C, pre-miR29b preferentially forms a complex with the Dicer protein through interaction of LK-L1C/K6W/L8C with the terminal loop region of pre-miR29b, leading to an increase in Dicer processing. Furthermore, LK-L1C/K6W/L8C stimulates apoptosis by improving p53 stability in miR29-inducible HeLa and MCF7 cells. Collectively, our study shows that a peptide can directly influence the miR29b-mediated p53 activation pathway in cancer cells. Therefore, our findings provide the basis for a new, potentially promising peptide-based drug for cancer therapy.
C1 [Kim, Soyoung; Kang, Igojo; Shin, Chanseok] Seoul Natl Univ, Dept Agr Biotechnol, Seoul, South Korea.
[Lee, Jung Hyun] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Lee, Jung Hyun] Harvard Med Sch, Charlestown, MA USA.
[Hyun, Soonsil; Yu, Jaehoon] Seoul Natl Univ, Dept Chem & Educ, Seoul, South Korea.
[Shin, Chanseok] Seoul Natl Univ, Res Inst Agr & Life Sci, Seoul, South Korea.
[Shin, Chanseok] Seoul Natl Univ, Plant Genom & Breeding Inst, 1 Gwanak Ro, Seoul 08826, South Korea.
RP Shin, C (reprint author), Seoul Natl Univ, Plant Genom & Breeding Inst, 1 Gwanak Ro, Seoul 08826, South Korea.; Shin, C (reprint author), Seoul Natl Univ, Dept Agr Biotechnol, Res Inst Agr & Life Sci, 1 Gwanak Ro, Seoul 08826, South Korea.
EM cshin@snu.ac.kr
FU Next-Generation BioGreen 21 Program [PJ01115601]; Rural Development
Administration, Republic of Korea; Seoul National University Research
Grant (Brain Fusion Program) [500-20120248]
FX We are grateful for helpful discussion with members of the Shin
laboratory. We also thank V. Narry Kim for providing pG 13-luciferase
plasmid and miR29-inducible HeLa cells. This work was supported by the
Next-Generation BioGreen 21 Program (No. PJ01115601), Rural Development
Administration, Republic of Korea and the Seoul National University
Research Grant (Brain Fusion Program: 500-20120248). The authors declare
that there are no conflicts of interest.
NR 49
TC 1
Z9 1
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2162-2531
J9 MOL THER-NUCL ACIDS
JI Mol. Ther.-Nucl. Acids
PD JUL 5
PY 2016
VL 5
AR e330
DI 10.1038/mtna.2016.45
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DU3PL
UT WOS:000382124300001
PM 27377134
ER
PT J
AU Pasnoor, M
He, JH
Herbelin, L
Burns, TM
Nations, S
Bril, V
Wang, AK
Elsheikh, BH
Kissel, JT
Saperstein, D
Shaibani, JA
Jackson, C
Swenson, A
Howard, JF
Goyal, N
David, W
Wicklund, M
Pulley, M
Becker, M
Mozaffar, T
Benatar, M
Pazcuzzi, R
Simpson, E
Rosenfeld, J
Dimachkie, MM
Statland, JM
Barohn, RJ
AF Pasnoor, Mamatha
He, Jianghua
Herbelin, Laura
Burns, Ted M.
Nations, Sharon
Bril, Vera
Wang, Annabel K.
Elsheikh, Bakri H.
Kissel, John T.
Saperstein, David
Shaibani, J. Aziz
Jackson, Carlayne
Swenson, Andrea
Howard, James F., Jr.
Goyal, Namita
David, William
Wicklund, Matthew
Pulley, Michael
Becker, Mara
Mozaffar, Tahseen
Benatar, Michael
Pazcuzzi, Robert
Simpson, Ericka
Rosenfeld, Jeffrey
Dimachkie, Mazen M.
Statland, Jeffrey M.
Barohn, Richard J.
CA Methotrexate MG Investigators Musc
TI A randomized controlled trial of methotrexate for patients with
generalized myasthenia gravis
SO NEUROLOGY
LA English
DT Article
ID DAILY LIVING PROFILE; MYCOPHENOLATE-MOFETIL; DOUBLE-BLIND;
RECOMMENDATIONS; AZATHIOPRINE; CYCLOSPORINE; PREDNISONE; SCORE
AB Objective:To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG).Methods:We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12. Secondary outcome measures included 12-month changes of the Quantitative Myasthenia Gravis Score, the Myasthenia Gravis Composite Score, Manual Muscle Testing, the Myasthenia Gravis Quality of Life, and the Myasthenia Gravis Activities of Daily Living.Results:Fifty-eight patients were screened and 50 enrolled. MTX did not reduce the month 4-12 prednisone AUDTC when compared to placebo (difference MTX - placebo: -488.0 mg, 95% confidence interval -2,443.4 to 1,467.3, p = 0.26); however, the average daily prednisone dose decreased in both groups. MTX did not improve secondary measures of MG compared to placebo over 12 months. Eight participants withdrew during the course of the study (1 MTX, 7 placebo). There were no serious MTX-related adverse events. The most common adverse event was nonspecific pain (19%).Conclusions:We found no steroid-sparing benefit of MTX in MG over 12 months of treatment, despite being well-tolerated. This study demonstrates the challenges of conducting clinical trials in MG, including difficulties with recruitment, participants improving on prednisone alone, and the need for a better understanding of outcome measure variability for future clinical trials.Classification of evidence:This study provides Class I evidence that for patients with generalized MG MTX does not significantly reduce the prednisone AUDTC over 12 months of therapy.
C1 [He, Jianghua] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS USA.
[Pasnoor, Mamatha; He, Jianghua; Herbelin, Laura; Dimachkie, Mazen M.; Statland, Jeffrey M.; Barohn, Richard J.] Univ Kansas, Med Ctr, Kansas City, KS 66160 USA.
[Burns, Ted M.] Univ Virginia, Charlottesville, VA USA.
[Nations, Sharon] Univ Texas Southwestern, Dallas, TX USA.
[Bril, Vera] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Wang, Annabel K.; Mozaffar, Tahseen] Univ Calif Irvine, Orange, CA 92668 USA.
[Elsheikh, Bakri H.; Kissel, John T.] Ohio State Univ, Columbus, OH 43210 USA.
[Saperstein, David] Phoenix Neurol Associates, Phoenix, AZ USA.
[Shaibani, J. Aziz] Nerve & Muscle Ctr Texas, Houston, TX USA.
[Jackson, Carlayne] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Swenson, Andrea] Univ Iowa, Iowa City, IA USA.
[Howard, James F., Jr.] Univ N Carolina, Chapel Hill, NC USA.
[Goyal, Namita; David, William] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wicklund, Matthew] Penn State Hershey Med Ctr, Hershey, PA USA.
Univ Florida Jacksonville, Jacksonville, FL USA.
[Becker, Mara] Childrens Mercy Hosp & Clin, Kansas City, MO USA.
[Benatar, Michael] Univ Miami, Coral Gables, FL 33124 USA.
[Pazcuzzi, Robert] Indiana Univ, Indianapolis, IN 46204 USA.
[Simpson, Ericka] Methodist Hosp Syst, Houston, TX USA.
[Rosenfeld, Jeffrey] Univ San Francisco, San Francisco, CA 94117 USA.
RP Pasnoor, M (reprint author), Univ Kansas, Med Ctr, Kansas City, KS 66160 USA.
EM mpasnoor@kumc.edu
OI Howard, James/0000-0002-7136-8617
FU Food and Drug Administration Orphan Products Division [RO1 FD 003538];
University of Kansas Medical Center Clinical and Translational Science
Awards (CTSA) [UL1 RR 033179, UL1 TR 000001]; NCATS grant [KL2TR000119]
FX This study was funded by Food and Drug Administration Orphan Products
Division RO1 FD 003538 (M.P.). Additional funding was provided in part
by grants UL1 RR 033179 (which is now UL1 TR 000001) from the University
of Kansas Medical Center Clinical and Translational Science Awards
(CTSA). Dr. Statland's work on this project was supported by a NCATS
grant awarded to the University of Kansas Medical Center for Frontiers:
The Heartland Institute for Clinical and Translational Research
#KL2TR000119.
NR 25
TC 8
Z9 9
U1 6
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0028-3878
EI 1526-632X
J9 NEUROLOGY
JI Neurology
PD JUL 5
PY 2016
VL 87
IS 1
BP 57
EP 64
DI 10.1212/WNL.0000000000002795
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DR7VH
UT WOS:000380107300015
PM 27306628
ER
PT J
AU Du, MM
Jiao, S
Bien, SA
Gala, M
Abecasis, G
Bezieau, S
Brenner, H
Butterbach, K
Caan, BJ
Carlson, CS
Casey, G
Chang-Claude, J
Conti, DV
Curtis, KR
Duggan, D
Gallinger, S
Haile, RW
Harrison, TA
Hayes, RB
Hoffmeister, M
Hopper, JL
Hudson, TJ
Jenkins, MA
Kury, S
Le Marchand, L
Leal, SM
Newcomb, PA
Nickerson, DA
Potter, JD
Schoen, RE
Schumacher, FR
Seminara, D
Slattery, ML
Hsu, L
Chan, AT
White, E
Berndt, SI
Peters, U
AF Du, Mengmeng
Jiao, Shuo
Bien, Stephanie A.
Gala, Manish
Abecasis, Goncalo
Bezieau, Stephane
Brenner, Hermann
Butterbach, Katja
Caan, Bette J.
Carlson, Christopher S.
Casey, Graham
Chang-Claude, Jenny
Conti, David V.
Curtis, Keith R.
Duggan, David
Gallinger, Steven
Haile, Robert W.
Harrison, Tabitha A.
Hayes, Richard B.
Hoffmeister, Michael
Hopper, John L.
Hudson, Thomas J.
Jenkins, Mark A.
Kury, Sebastien
Le Marchand, Loic
Leal, Suzanne M.
Newcomb, Polly A.
Nickerson, Deborah A.
Potter, John D.
Schoen, Robert E.
Schumacher, Fredrick R.
Seminara, Daniela
Slattery, Martha L.
Hsu, Li
Chan, Andrew T.
White, Emily
Berndt, Sonja I.
Peters, Ulrike
TI Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor
Risk Identified Potential Functional Variants
SO PLOS ONE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CANCER SUSCEPTIBILITY LOCI; PROSTATE-CANCER;
GENOTYPE IMPUTATION; CHROMOSOME 8Q24; COMPLEX TRAITS; SNP RS6983267;
TARGET GENES; METAANALYSIS; EXPRESSION
AB Genome-wide association studies (GWAS) have identified many common single nucleotide polymorphisms (SNPs) associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs). We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33). We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s).
C1 [Du, Mengmeng] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Du, Mengmeng; Jiao, Shuo; Bien, Stephanie A.; Carlson, Christopher S.; Curtis, Keith R.; Harrison, Tabitha A.; Newcomb, Polly A.; Hsu, Li; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
[Bien, Stephanie A.; Newcomb, Polly A.; Potter, John D.; White, Emily; Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Gala, Manish; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Gala, Manish; Chan, Andrew T.] Harvard Med Sch, Boston, MA USA.
[Abecasis, Goncalo] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Bezieau, Stephane; Kury, Sebastien] CHU Nantes, Serv Genet Med, Nantes, France.
[Brenner, Hermann; Butterbach, Katja; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany.
[Caan, Bette J.] Kaiser Permanente Med Care Program Northern Calif, Div Res, Oakland, CA USA.
[Casey, Graham; Conti, David V.; Haile, Robert W.; Schumacher, Fredrick R.] Univ Southern Calif, Keck Sch Med, Los Angeles, CA USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Duggan, David] Translat Genom Res Inst, Phoenix, AZ USA.
[Gallinger, Steven] Mt Sinai Hosp, Dept Surg, Toronto, ON, Canada.
[Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA.
[Hopper, John L.; Jenkins, Mark A.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
[Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON, Canada.
[Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Leal, Suzanne M.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Nickerson, Deborah A.] Univ Washington, Genome Sci, Seattle, WA 98195 USA.
[Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Dept Med & Epidemiol, Pittsburgh, PA USA.
[Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Du, MM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.; Du, MM; Peters, U (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.; Peters, U (reprint author), Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
EM dumeng@mskcc.org; upeters@fhcrc.org
RI Jenkins, Mark/P-7803-2015; Gallinger, Steven/E-4575-2013; Brenner,
Hermann/B-4627-2017;
OI Jenkins, Mark/0000-0002-8964-6160; Brenner, Hermann/0000-0002-6129-1572;
Hayes, Richard/0000-0002-0918-661X; Bien, Stephanie/0000-0002-8713-4583;
Hoffmeister, Michael/0000-0002-8307-3197
FU GECCO: National Cancer Institute; GECCO: National Institutes of Health;
GECCO: U.S. Department of Health and Human Services [U01 CA137088, R01
CA059045, U01 CA164930]; National Cancer Institute [R25 CA94880, P30
CA008748]; Regional Council of Pays de la Loire; Groupement des
Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC);
Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer
(LRCC); National Cancer Institute, National Institutes of Health [U01
CA122839]; National Institutes of Health: Australasian Colorectal Cancer
Family Registry [U01 CA097735]; National Institutes of Health: Ontario
Registry for Studies of Familial Colorectal Cancer [U01 CA074783];
National Institutes of Health: Seattle Colorectal Cancer Family Registry
[U01 CA074794]; DACHS: German Research Council (Deutsche
Forschungsgemeinschaft) [BR 1704/6-1, BR 1704/6-3, BR 1704/6-4, CH
117/1-1]; COLO2&3: National Institutes of Health [R01 CA60987]; CCFR:
National Institutes of Health (RFA) [CA-95-011]; German Federal Ministry
of Education and Research [01KH0404, 01ER0814]; DALS: National
Institutes of Health [R01 CA48998]; NHS; PHS: HPFS by National
Institutes of Health [P01 CA 055075, UM1 CA167552, R01 137178, P50 CA
127003]; NHS by the National Institutes of Health [P50 CA 127003, R01
CA137178, P01 CA 087969]; National Institutes of Health [CA42182]; Damon
Runyon Clinical investigator Award; MEC: National Institutes of Health
[R37 CA54281, P01 CA033619, R01 CA63464]; OFCCR: National Institutes of
Health [U01 CA074783]; GL2 grant from Ontario Research Fund; Canadian
Institutes of Health Research; Cancer Risk Evaluation (CaRE) Program
grant from Canadian Cancer Society Research Institute; Senior
Investigator Awards from Ontario Institute for Cancer Research; Ontario
Ministry of Research and Innovation; PLCO: Intramural Research Program
of the Division of Cancer Epidemiology and Genetics; Division of Cancer
Prevention, National Cancer Institute, NIH, DHHS; National Institutes of
Health (NIH), Genes, Environment and Health Initiative (GEI) [Z01 CP
010200]; NIH [U01 HG004446]; NIH GEI [U01 HG 004438]; PMH-CCFR: National
Institutes of Health [R01 CA076366]; VITAL: National Institutes of
Health [K05 CA154337]; National Heart, Lung, and Blood Institute,
National Institutes of Health, U.S. Department of Health and Human
Services [HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; CORECT:
National Cancer Institute, National Institutes of Health under RFA
[CA-09-002 (U19 CA148107)]; [K24 DK098311]
FX This work was supported by the following: GECCO: National Cancer
Institute, National Institutes of Health, U.S. Department of Health and
Human Services (U01 CA137088; R01 CA059045; U01 CA164930), M.D. is
supported by grants R25 CA94880 and P30 CA008748 from the National
Cancer Institute. ASTERISK: Hospital Clinical Research Program (PHRC)
and supported by the Regional Council of Pays de la Loire, the
Groupement des Entreprises Francaises dans la Lutte contre le Cancer
(GEFLUC), the Association Anne de Bretagne Genetique and the Ligue
Regionale Contre le Cancer (LRCC). COLO2&3: National Institutes of
Health (R01 CA60987). CCFR: National Institutes of Health (RFA #
CA-95-011) and through cooperative agreements with members of the Colon
Cancer Family Registry and P.I.s. This genome wide scan was supported by
the National Cancer Institute, National Institutes of Health by U01
CA122839. The content of this manuscript does not necessarily reflect
the views or policies of the National Cancer Institute or any of the
collaborating centers in the CFRs, nor does mention of trade names,
commercial products, or organizations imply endorsement by the US
Government or the CFR. The following Colon CFR centers contributed data
to this manuscript and were supported by National Institutes of Health:
Australasian Colorectal Cancer Family Registry (U01 CA097735), Ontario
Registry for Studies of Familial Colorectal Cancer (U01 CA074783), and
Seattle Colorectal Cancer Family Registry (U01 CA074794). DACHS: German
Research Council (Deutsche Forschungsgemeinschaft, BR 1704/6-1, BR
1704/6-3, BR 1704/6-4 and CH 117/1-1), and the German Federal Ministry
of Education and Research (01KH0404 and 01ER0814). DALS: National
Institutes of Health (R01 CA48998 to M.L.S.); HPFS, NHS, and PHS: HPFS
by the National Institutes of Health (P01 CA 055075, UM1 CA167552, R01
137178, and P50 CA 127003), NHS by the National Institutes of Health
(R01 CA137178, P01 CA 087969 and P50 CA 127003,) and PHS by the National
Institutes of Health (CA42182). A.T.C. is also supported by a Damon
Runyon Clinical investigator Award and K24 DK098311. MEC: National
Institutes of Health (R37 CA54281, P01 CA033619, and R01 CA63464).
OFCCR: National Institutes of Health, through funding allocated to the
Ontario Registry for Studies of Familial Colorectal Cancer (U01
CA074783); see CCFR section above. As subset of ARCTIC, OFCCR is
supported by a GL2 grant from the Ontario Research Fund, the Canadian
Institutes of Health Research, and the Cancer Risk Evaluation (CaRE)
Program grant from the Canadian Cancer Society Research Institute.
T.J.H. is a recipient of Senior Investigator Awards from the Ontario
Institute for Cancer Research, through generous support from the Ontario
Ministry of Research and Innovation. PLCO: Intramural Research Program
of the Division of Cancer Epidemiology and Genetics and supported by
contracts from the Division of Cancer Prevention, National Cancer
Institute, NIH, DHHS. Additionally, a subset of control samples were
genotyped as part of the Cancer Genetic Markers of Susceptibility
(CGEMS) Prostate Cancer GWAS (Yeager, M et al. Nat Genet 2007
May;39(5):645-9), Colon CGEMS pancreatic cancer scan (PanScan)
(Amundadottir, L et al. Nat Genet. 2009 Sep;41(9):986-90 and Petersen,
GM et al Nat Genet. 2010 Mar;42(3):2248), and the Lung Cancer and
Smoking study. The prostate and PanScan study datasets were accessed
with appropriate approval through the dbGaP online resource
(http://cgems.cancer.gov/data/) accession numbers phs000207v.1p1 and
phs000206.v3.; p2, respectively, and the lung datasets were accessed
from the dbGaP website (http://www.ncbi.nlm.nih.gov/gap) through
accession number phs000093v2.p2. Funding for the Lung Cancer and Smoking
study was provided by National Institutes of Health (NIH), Genes,
Environment and Health Initiative (GEI) Z01 CP 010200, NIH U01 HG004446,
and NIH GEI U01 HG 004438. For the lung study, the GENEVA Coordinating
Center provided assistance with genotype cleaning and general study
coordination, and the Johns Hopkins University Center for Inherited
Disease Research conducted genotyping. PMH-CCFR: National Institutes of
Health (R01 CA076366 to P.A.N.). VITAL: National Institutes of Health
(K05 CA154337). WHI: The WHI program is funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, U.S.
Department of Health and Human Services through contracts
HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. CORECT:
National Cancer Institute, National Institutes of Health under RFA
#CA-09-002 (U19 CA148107). The content of this manuscript does not
necessarily reflect the views or policies of the National Cancer
Institute or any of the collaborating centers in CORECT, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government or CORECT. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 75
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U1 3
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD JUL 5
PY 2016
VL 11
IS 7
AR e0157521
DI 10.1371/journal.pone.0157521
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR3JE
UT WOS:000379798700007
PM 27379672
ER
PT J
AU Walensky, RP
AF Walensky, Rochelle P.
TI Investing in People Who Inject Drugs: A PrEPonderance of Opportunities
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Editorial Material
ID USERS
C1 [Walensky, Rochelle P.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Walensky, RP (reprint author), Massachusetts Gen Hosp, Med Practice Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM rwalensky@partners.org
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER COLL PHYSICIANS
PI PHILADELPHIA
PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA
SN 0003-4819
EI 1539-3704
J9 ANN INTERN MED
JI Ann. Intern. Med.
PD JUL 5
PY 2016
VL 165
IS 1
BP 63
EP 64
DI 10.7326/M16-0788
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ5AD
UT WOS:000379215800013
ER
PT J
AU Samuel, BS
Rowedder, H
Braendle, C
Felix, MA
Ruvkun, G
AF Samuel, Buck S.
Rowedder, Holli
Braendle, Christian
Felix, Marie-Anne
Ruvkun, Gary
TI Caenorhabditis elegans responses to bacteria from its natural habitats
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE Caenorhabditis elegans; host-microbe interactions; ecology
ID C. ELEGANS; GUT MICROBIOTA; TRANSLATIONAL INHIBITION; PATHOGEN;
ASSOCIATIONS; DIVERSITY; SEQUENCES; HISTORY; MODELS; GENES
AB Most Caenorhabditis elegans studies have used laboratory Escherichia coli as diet and microbial environment. Here we characterize bacteria of C. elegans' natural habitats of rotting fruits and vegetation to provide greater context for its physiological responses. By the use of 16S ribosomal DNA (rDNA)-based sequencing, we identified a large variety of bacteria in C. elegans habitats, with phyla Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria being most abundant. From laboratory assays using isolated natural bacteria, C. elegans is able to forage on most bacteria (robust growth on similar to 80% of >550 isolates), although similar to 20% also impaired growth and arrested and/or stressed animals. Bacterial community composition can predict wild C. elegans population states in both rotting apples and reconstructed microbiomes: alpha-Proteobacteria-rich communities promote proliferation, whereas Bacteroidetes or pathogens correlate with non-proliferating dauers. Combinatorial mixtures of detrimental and beneficial bacteria indicate that bacterial influence is not simply nutritional. Together, these studies provide a foundation for interrogating how bacteria naturally influence C. elegans physiology.
C1 [Samuel, Buck S.; Rowedder, Holli; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Braendle, Christian] Univ Nice Sophia Antipolis, Inst Biol Valrose, INSERM, CNRS, Parc Valrose, F-06108 Nice, France.
[Felix, Marie-Anne] Ecole Normale Super, INSERM U1024, CNRS UMR8197, Inst Biol, F-75005 Paris, France.
[Samuel, Buck S.] Baylor Coll Med, Dept Mol Virol & Microbiol, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA.
RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Felix, MA (reprint author), Ecole Normale Super, INSERM U1024, CNRS UMR8197, Inst Biol, F-75005 Paris, France.
EM felix@biologie.ens.fr; ruvkun@molbio.mgh.harvard.edu
OI Samuel, Buck/0000-0002-4347-3997; Braendle,
Christian/0000-0003-0203-4581
FU NIH Office of Research Infrastructure Programs [P40 OD010440]; Charles
King Trust Senior Postdoctoral Fellowship; Ruth L. Kirchstein National
Research Service Award Postdoctoral Fellowship [DK838852]; NIH [AG16636]
FX We thank Tony Belicard for help during collection of apples that were
used to culture natural bacterial isolates; Isabelle Nuez for 16S
sequencing of some bacterial strains; Jonah Larkins-Ford and Annie
Conery for help with worm sorting experiments; Chris Carr for technical
help with the Ion Torrent sequencing; Fred Ausubel for strains and
helpful suggestions; Sarah Marsh for comments on the manuscript; members
of the G.R. laboratory, the F. Ausubel laboratory, and the J. Kaplan
laboratory for support and suggestions throughout the project; and C.
elegans Genetic Stock Center for strains, which is funded by NIH Office
of Research Infrastructure Programs (P40 OD010440). B.S.S. was funded by
a Charles King Trust Senior Postdoctoral Fellowship and Ruth L.
Kirchstein National Research Service Award Postdoctoral Fellowship
(DK838852). This work was also supported by NIH Grant AG16636 (to G.R.).
NR 52
TC 7
Z9 7
U1 8
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 5
PY 2016
VL 113
IS 27
BP E3941
EP E3949
DI 10.1073/pnas.1607183113
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2GW
UT WOS:000379021700018
PM 27317746
ER
PT J
AU Su, Y
Xia, W
Li, J
Walz, T
Humphries, MJ
Vestweber, D
Cabanas, C
Lu, CF
Springer, TA
AF Su, Yang
Xia, Wei
Li, Jing
Walz, Thomas
Humphries, Martin J.
Vestweber, Dietmar
Cabanas, Carlos
Lu, Chafen
Springer, Timothy A.
TI Relating conformation to function in integrin alpha(5)beta(1)
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
ID X-RAY-SCATTERING; CRYSTAL-STRUCTURE; MONOCLONAL-ANTIBODIES;
EXTRACELLULAR SEGMENT; FIBRONECTIN RECEPTOR; ELECTRON-MICROSCOPY;
LEUKOCYTE INTEGRIN; REGULATORY REGION; LIGAND-BINDING; HYBRID DOMAIN
AB Whether beta(1) integrin ectodomains visit conformational states similarly to beta(2) and beta(3) integrins has not been characterized. Furthermore, despite a wealth of activating and inhibitory antibodies to beta(1) integrins, the conformational states that these antibodies stabilize, and the relation of these conformations to function, remain incompletely characterized. Using negative-stain electron microscopy, we show that the integrin alpha(5)beta(1) ectodomain adopts extended-closed and extended-open conformations as well as a bent conformation. Antibodies SNAKA51, 8E3, N29, and 9EG7 bind to different domains in the alpha(5) or beta(1) legs, activate, and stabilize extended ectodomain conformations. Antibodies 12G10 and HUTS-4 bind to the beta(1) beta I domain and hybrid domains, respectively, activate, and stabilize the open headpiece conformation. Antibody TS2/16 binds a similar epitope as 12G10, activates, and appears to stabilize an open beta I domain conformation without requiring extension or hybrid domain swing-out. mAb13 and SG/19 bind to the beta I domain and beta I-hybrid domain interface, respectively, inhibit, and stabilize the closed conformation of the headpiece. The effects of the antibodies on cell adhesion to fibronectin substrates suggest that the extended-open conformation of alpha(5)beta(1) is adhesive and that the extended-closed and bent-closed conformations are nonadhesive. The functional effects and binding sites of antibodies and fibronectin were consistent with their ability in binding to alpha(5)beta(1) on cell surfaces to cross-enhance or inhibit one another by competitive or noncompetitive (allosteric) mechanisms.
C1 [Su, Yang; Xia, Wei; Li, Jing; Lu, Chafen; Springer, Timothy A.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.
[Su, Yang; Xia, Wei; Li, Jing; Lu, Chafen; Springer, Timothy A.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Walz, Thomas] Rockefeller Univ, New York, NY 10065 USA.
[Humphries, Martin J.] Univ Manchester, Fac Life Sci, Wellcome Trust Ctr Cell Matrix Res, Manchester M13 9PT, Lancs, England.
[Vestweber, Dietmar] Max Planck Inst Mol Biomed, D-48149 Munster, Germany.
[Cabanas, Carlos] Ctr Biol Mol Severo Ochoa CSIC UAM, Madrid 28049, Spain.
RP Springer, TA (reprint author), Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA.; Springer, TA (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
EM timothy.springer@childrens.harvard.edu
FU NIH [HL-108248]
FX We thank Li-Zhi Mi for help with EM data collection and processing. This
work was supported by NIH Grant HL-108248.
NR 45
TC 7
Z9 7
U1 4
U2 7
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD JUL 5
PY 2016
VL 113
IS 27
BP E3872
EP E3881
DI 10.1073/pnas.1605074113
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2GW
UT WOS:000379021700011
PM 27317747
ER
PT J
AU Takatani, T
Shirakawa, J
Roe, MW
Leech, CA
Maier, BF
Mirmira, RG
Kulkarni, RN
AF Takatani, Tomozumi
Shirakawa, Jun
Roe, Michael W.
Leech, Colin A.
Maier, Bernhard F.
Mirmira, Raghavendra G.
Kulkarni, Rohit N.
TI IRS1 deficiency protects beta-cells against ER stress-induced apoptosis
by modulating sXBP-1 stability and protein translation
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ENDOPLASMIC-RETICULUM STRESS; INSULIN-RECEPTOR; MESSENGER-RNA;
REGULATORY SUBUNITS; P38 MAPK; ELONGATION; ACTIVATION; AUTOPHAGY;
GROWTH; MICE
AB Endoplasmic reticulum (ER) stress is among several pathological features that underlie beta-cell failure in the development of type 1 and type 2 diabetes. Adaptor proteins in the insulin/insulin-like-growth factor-1 signaling pathways, such as insulin receptor substrate-1 (IRS1) and IRS2, differentially impact beta-cell survival but the underlying mechanisms remain unclear. Here we report that beta-cells deficient in IRS1 (IRS1KO) are resistant, while IRS2 deficiency (IRS2KO) makes them susceptible to ER stress-mediated apoptosis. IRS1KOs exhibited low nuclear accumulation of spliced XBP-1 due to its poor stability, in contrast to elevated accumulation in IRS2KO. The reduced nuclear accumulation in IRS1KO was due to protein instability of Xbp1 secondary to proteasomal degradation. IRS1KO also demonstrated an attenuation in their general translation status in response to ER stress revealed by polyribosomal profiling. Phosphorylation of eEF2 was dramatically increased in IRS1KO enabling the beta-cells to adapt to ER stress by blocking translation. Furthermore, significantly high ER calcium (Ca2+) was detected in IRS1KO beta-cells even upon induction of ER stress. These observations suggest that IRS1 could be a therapeutic target for beta-cell protection against ER stress-mediated cell death by modulating XBP-1 stability, protein synthesis, and Ca2+ storage in the ER.
C1 [Takatani, Tomozumi; Shirakawa, Jun; Kulkarni, Rohit N.] Harvard Med Sch, Islet Cell & Regenerat Biol, Joslin Diabet Ctr, Dept Med,Brigham & Womens Hosp,Harvard Stem Cell, Boston, MA USA.
[Roe, Michael W.; Leech, Colin A.] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA.
[Maier, Bernhard F.; Mirmira, Raghavendra G.] Indiana Univ Sch Med, Dept Pediat, Indianapolis, IN 46202 USA.
[Maier, Bernhard F.; Mirmira, Raghavendra G.] Indiana Univ Sch Med, Herman B Wells Ctr Pediat Res, Indianapolis, IN 46202 USA.
[Mirmira, Raghavendra G.] Indiana Univ Sch Med, Dept Cellular & Integrat Physiol, Dept Biochem & Mol Biol, Dept Med, Indianapolis, IN 46202 USA.
RP Kulkarni, RN (reprint author), Harvard Med Sch, Islet Cell & Regenerat Biol, Joslin Diabet Ctr, Dept Med,Brigham & Womens Hosp,Harvard Stem Cell, Boston, MA USA.
EM rohit.kulkarni@joslin.harvard.edu
OI Shirakawa, Jun/0000-0002-0822-8750
FU Manpei Suzuki Diabetes Foundation; Iacocca Foundation; Japan Society for
the Promotion of Science; National Institutes of Health [R01 DK60581,
R01 DK67536]; Indiana Diabetes Research Center Core service [P30
DK097512]; [R01 DK103215]
FX T.T. was supported by Manpei Suzuki Diabetes Foundation and the Iacocca
Foundation. J.S. is supported by the Japan Society for the Promotion of
Science. This work was supported by grants from from the National
Institutes of Health R01 DK60581 and Indiana Diabetes Research Center
Core service (P30 DK097512) (R.G.M), and by grants from the National
Institutes of Health R01 DK67536 and in part from R01 DK103215 (R.N.K.).
NR 59
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 5
PY 2016
VL 6
AR 28177
DI 10.1038/srep28177
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ2YI
UT WOS:000379069200001
PM 27378176
ER
PT J
AU Braunwald, E
AF Braunwald, Eugene
TI Circulation: The Beat Goes On
SO CIRCULATION
LA English
DT Article
DE cell therapy; editors; journal; PCSK9 inhibitors; science
C1 [Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp,Sch Med, Boston, MA 02115 USA.
[Braunwald, Eugene] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Braunwald, E (reprint author), Brigham & Womens Hosp, 350 Longwood Ave, Boston, MA 02115 USA.
EM ebraunwald@partners.org
NR 3
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 5
PY 2016
VL 134
IS 1
BP 6
EP 8
DI 10.1161/CIRCULATIONAHA.116.021747
PG 3
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DQ0OV
UT WOS:000378900300004
PM 27358431
ER
PT J
AU Bohula, EA
Giugliano, RP
Ruff, CT
Kuder, JF
Murphy, SA
Antman, EM
Braunwald, E
AF Bohula, Erin A.
Giugliano, Robert P.
Ruff, Christian T.
Kuder, Julia F.
Murphy, Sabina A.
Antman, Elliott M.
Braunwald, Eugene
TI Impact of Renal Function on Outcomes With Edoxaban in the ENGAGE AF-TIMI
48 Trial
SO CIRCULATION
LA English
DT Article
DE anticoagulants; atrial fibrillation; kidney; thromboembolism; warfarin
ID NONVALVULAR ATRIAL-FIBRILLATION; CHRONIC KIDNEY-DISEASE;
GLOMERULAR-FILTRATION-RATE; XA INHIBITOR EDOXABAN;
MYOCARDIAL-INFARCTION; SYSTEMIC EMBOLISM; WARFARIN; RISK;
ANTICOAGULATION; STROKE
AB Background: Edoxaban, an oral factor Xa inhibitor with 50% renal clearance, was noninferior to well-managed warfarin for stroke or systemic embolism (S/SE) prevention and reduced bleeding in patients with atrial fibrillation. We evaluated the efficacy and safety of edoxaban versus warfarin across the range of baseline creatinine clearance (CrCl) in the ENGAGE AF-TIMI 48 trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction Study 48) with a focus on the higher-dose edoxaban regimen (HDER) and the upper range of CrCl.
Methods: A total of 14 071 patients with atrial fibrillation at moderate to high risk for stroke were randomized to warfarin or HDER (60 mg daily or a 50% dose reduction to 30 mg daily for CrCl 30-50 mL/min, body weight of <= 60 kg, or use of a potent phosphorylated glycoprotein inhibitor). CrCl <30 mL/min was exclusionary. End points of S/SE, International Society on Thrombosis and Haemostasis major bleeding, and the net clinical outcome of S/SE/major bleeding or death were evaluated by intention-to-treat analysis using the prespecified CrCl cut point of 50 mL/min and additional exploratory cut points with the CockcroftGault formula. A sensitivity analysis was performed with the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula for estimating renal function.
Results: The relative risk of S/SE with HDER versus warfarin in patients with CrCl > 50 mL/min (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.72-1.04) was similar to that in patients with CrCl <= 50 mL/min (HR, 0.87; 95% CI, 0.65-1.18; P for interaction=0.94). Several exploratory analyses suggested lower relative efficacy for the prevention of S/SE with HDER compared with warfarin at higher levels of CrCl (CrCl <= 50 mL/min: HR, 0.87; 95% CI, 0.65-1.18; CrCl >50-95 mL/min: HR, 0.78; 95% CI, 0.64-0.96; CrCl > 95 mL/min: HR, 1.36; 95% CI, 0.88-2.10; P for interaction=0.08). Bleeding rates were lower at all levels of CrCl with HDER (P for interaction=0.11). Because of the preserved effect on bleeding, the net clinical outcome was more favorable with HDER across the range of CrCl (P for interaction=0.73). Similar findings were observed in the sensitivity analysis using the CKD-EPI formula.
Conclusions: Although there was an apparent decrease in relative efficacy to prevent arterial thromboembolism in the upper range of CrCl, the safety and net clinical benefit of HDER compared with warfarin are consistent across the range of renal function.
C1 [Bohula, Erin A.; Giugliano, Robert P.; Ruff, Christian T.; Kuder, Julia F.; Murphy, Sabina A.; Antman, Elliott M.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, Sch Med, TIMI Study Grp,Cardiovasc Div,Dept Med, Boston, MA 02115 USA.
RP Bohula, EA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,First Off Floor, Boston, MA 02115 USA.
EM ebohula@partners.org
FU Daiichi Sankyo
FX The ENGAGE AF-TIMI 48 study was sponsored by Daiichi Sankyo.
NR 27
TC 10
Z9 10
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 5
PY 2016
VL 134
IS 1
BP 24
EP +
DI 10.1161/CIRCULATIONAHA.116.022361
PG 25
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DQ0OV
UT WOS:000378900300007
PM 27358434
ER
PT J
AU Fordyce, CB
Hellkamp, AS
Lokhnygina, Y
Lindner, SM
Piccini, JP
Becker, RC
Berkowitz, SD
Breithardt, G
Fox, KAA
Mahaffey, KW
Nessel, CC
Singer, DE
Patel, MR
AF Fordyce, Christopher B.
Hellkamp, Anne S.
Lokhnygina, Yuliya
Lindner, Samuel M.
Piccini, Jonathan P.
Becker, Richard C.
Berkowitz, Scott D.
Breithardt, Guenter
Fox, Keith A. A.
Mahaffey, Kenneth W.
Nessel, Christopher C.
Singer, Daniel E.
Patel, Manesh R.
CA ROCKET AF Steering Comm
TI On-Treatment Outcomes in Patients With Worsening Renal Function With
Rivaroxaban Compared With Warfarin Insights From ROCKET AF
SO CIRCULATION
LA English
DT Article
DE anticoagulants; atrial fibrillation; kidney; renal insufficiency
ID NONVALVULAR ATRIAL-FIBRILLATION; GLOMERULAR-FILTRATION-RATE; LY
RANDOMIZED EVALUATION; FACTOR-XA INHIBITOR; HEART-FAILURE; SERUM
CREATININE; SYSTEMIC EMBOLISM; RISK-FACTORS; BASE-LINE; IMPAIRMENT
AB Background: Despite rapid clinical adoption of novel anticoagulants, it is unknown whether outcomes differ among patients with worsening renal function (WRF) taking these new drugs compared with warfarin. We aimed to determine whether the primary efficacy (stroke or systemic embolism) and safety (major bleeding and nonmajor clinically relevant bleeding) end points from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation trial) differed among participants with WRF taking rivaroxaban and those taking warfarin.
Methods: After excluding patients without at least 1 follow-up creatinine measurement (n=1624), we included all remaining patients (n=12 612) randomly assigned to either rivaroxaban or dose-adjusted warfarin. Ontreatment WRF (a decrease of > 20% from screening creatinine clearance measurement at any time point during the study) was evaluated as a timedependent covariate in Cox proportional hazards models.
Results: Baseline characteristics were generally similar between patients with stable renal function (n=9292) and WRF (n=3320). Rates of stroke or systemic embolism, myocardial infarction, and bleeding were also similar, but WRF patients experienced a higher incidence of vascular death versus stable renal function (2.21 versus 1.41 events per 100 patient-years; P=0.026). WRF patients who were randomized to receive rivaroxaban had a reduction in stroke or systemic embolism compared with those taking warfarin (1.54 versus 3.25 events per 100 patient-years) that was not seen in patients with stable renal function who were randomized to receive rivaroxaban (P=0.050 for interaction). There was no difference in major or nonmajor clinically relevant bleeding among WRF patients randomized to warfarin versus rivaroxaban.
Conclusions: Among patients with on-treatment WRF, rivaroxaban was associated with lower rates of stroke and systemic embolism compared with warfarin, without an increase in the composite bleeding end point.
C1 [Fordyce, Christopher B.; Hellkamp, Anne S.; Lokhnygina, Yuliya; Lindner, Samuel M.; Piccini, Jonathan P.; Patel, Manesh R.] Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.
[Becker, Richard C.] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA.
[Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA.
[Breithardt, Guenter] Univ Hosp Munster, Dept Cardiovasc Med, Div Electrophysiol, Munster, Germany.
[Fox, Keith A. A.] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh EH8 9YL, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
[Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA.
RP Fordyce, CB (reprint author), Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.
EM christopher.fordyce@duke.edu
FU Johnson & Johnson Pharmaceutical Research and Development; Bayer
HealthCare
FX This work and the ROCKET AF trial were supported by Johnson & Johnson
Pharmaceutical Research and Development and Bayer HealthCare. The Duke
Clinical Research Institute coordinated the trial, managed the database,
and undertook the primary analysis independent of the sponsors. The
authors had complete access to the data and were responsible for writing
and submitting the manuscript for publication.
NR 33
TC 7
Z9 7
U1 3
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 5
PY 2016
VL 134
IS 1
BP 37
EP +
DI 10.1161/CIRCULATIONAHA.116.021890
PG 20
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DQ0OV
UT WOS:000378900300008
PM 27358435
ER
PT J
AU El-Jawahri, A
Paasche-Orlow, MK
Matlock, D
Stevenson, LW
Lewis, EF
Stewart, G
Semigran, M
Chang, YC
Parks, K
Walker-Corkery, ES
Temel, JS
Bohossian, H
Ooi, H
Mann, E
Volandes, AE
AF El-Jawahri, Areej
Paasche-Orlow, Michael K.
Matlock, Dan
Stevenson, Lynne Warner
Lewis, Eldrin F.
Stewart, Garrick
Semigran, Marc
Chang, Yuchiao
Parks, Kimberly
Walker-Corkery, Elizabeth S.
Temel, Jennifer S.
Bohossian, Hacho
Ooi, Henry
Mann, Eileen
Volandes, Angelo E.
TI Randomized, Controlled Trial of an Advance Care Planning Video Decision
Support Tool for Patients With Advanced Heart Failure
SO CIRCULATION
LA English
DT Article
DE heart failure; quality of health care; quality of life
ID CANCER; RESUSCITATION; COMMUNICATION; HOSPICE
AB Background: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure.
Methods: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients >= 64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention.
Results: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001).
Conclusions: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only.
C1 [El-Jawahri, Areej; Semigran, Marc; Chang, Yuchiao; Parks, Kimberly; Walker-Corkery, Elizabeth S.; Temel, Jennifer S.; Mann, Eileen; Volandes, Angelo E.] Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02115 USA.
[El-Jawahri, Areej; Stevenson, Lynne Warner; Lewis, Eldrin F.; Stewart, Garrick; Semigran, Marc; Chang, Yuchiao; Parks, Kimberly; Walker-Corkery, Elizabeth S.; Temel, Jennifer S.; Volandes, Angelo E.] Harvard Univ, Sch Med, Boston, MA USA.
[Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Matlock, Dan] Univ Colorado, Sch Med, Aurora, CO USA.
[Stevenson, Lynne Warner; Lewis, Eldrin F.; Stewart, Garrick] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Bohossian, Hacho] Newton Wellesley Hosp, Newton, MA USA.
[Bohossian, Hacho] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Ooi, Henry] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Ooi, Henry] Nashville Vet Adm Med Ctr, Nashville, TN USA.
RP El-Jawahri, A (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Yawkey 9E, Boston, MA 02115 USA.
EM ael-jawahri@partners.org
FU National Heart, Lung, and Blood Institute [R01 HL 107268]
FX This work was supported by grant R01 HL 107268 from the National Heart,
Lung, and Blood Institute. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
National Heart, Lung, and Blood Institute. The sponsor did not have any
role in the design and conduct of the study; collection, management,
analysis, and interpretation of the data; and preparation or approval of
the manuscript.
NR 23
TC 2
Z9 2
U1 4
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD JUL 5
PY 2016
VL 134
IS 1
BP 52
EP +
DI 10.1161/CIRCULATIONAHA.116.021937
PG 21
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DQ0OV
UT WOS:000378900300010
PM 27358437
ER
PT J
AU Carson, SS
Cox, CE
Wallenstein, S
Hanson, LC
Danis, M
Tulsky, JA
Chai, E
Nelson, JE
AF Carson, Shannon S.
Cox, Christopher E.
Wallenstein, Sylvan
Hanson, Laura C.
Danis, Marion
Tulsky, James A.
Chai, Emily
Nelson, Judith E.
TI Effect of Palliative Care-Led Meetings for Families of Patients With
Chronic Critical Illness A Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID PROLONGED MECHANICAL VENTILATION; OF-LIFE CARE; COMMUNICATION-SKILLS;
RESOURCE UTILIZATION; DEPRESSION SCALE; HOSPITAL ANXIETY; UNITED-STATES;
ILL PATIENTS; ICU; VALIDATION
AB IMPORTANCE Family caregivers of patients with chronic critical illness experience significant psychological distress.
OBJECTIVE To determine whether family informational and emotional support meetings led by palliative care clinicians improve family anxiety and depression.
DESIGN, SETTING, AND PARTICIPANTS A multicenter randomized clinical trial conducted from October 2010 through November 2014 in 4 medical intensive care units (ICUs). Adult patients (aged >= 21 years) requiring 7 days of mechanical ventilation were randomized and their family surrogate decision makers were enrolled in the study. Observers were blinded to group allocation for the measurement of the primary outcomes.
INTERVENTIONS At least 2 structured family meetings led by palliative care specialists and provision of an informational brochure (intervention) compared with provision of an informational brochure and routine family meetings conducted by ICU teams (control). There were 130 patients with 184 family surrogate decision makers in the intervention group and 126 patients with 181 family surrogate decision makers in the control group.
MAIN OUTCOMES AND MEASURES The primary outcome was Hospital Anxiety and Depression Scale symptom score (HADS; score range, 0[best] to 42[worst]; minimal clinically important difference, 1.5) obtained during 3-month follow-up interviews with the surrogate decision makers. Secondary outcomes included posttraumatic stress disorder experienced by the family and measured by the Impact of Events Scale-Revised (IES-R; total score range, 0 [best] to 88 [worst]), discussion of patient preferences, hospital length of stay, and 90-day survival.
RESULTS Among 365 family surrogate decision makers (mean age, 51 years; 71% female), 312 completed the study. At 3 months, there was no significant difference in anxiety and depression symptoms between surrogate decision makers in the intervention group and the control group (adjusted mean HADS score, 12.2 vs 11.4, respectively; between-group difference, 0.8 [95% CI, -0.9 to 2.6]; P = .34). Posttraumatic stress disorder symptoms were higher in the intervention group (adjusted mean IES-R score, 25.9) compared with the control group (adjusted mean IES-R score, 21.3) (between-group difference, 4.60 [95% CI, 0.01 to 9.10]; P = .0495). There was no difference between groups regarding the discussion of patient preferences (intervention, 75%; control, 83%; odds ratio, 0.63[95% CI, 0.34 to 1.16; P = .14]). The median number of hospital days for patients in the intervention vs the control group (19 days vs 23 days, respectively; between-group difference, -4 days [95% CI, -6 to 3 days]; P = .51) and 90-day survival (hazard ratio, 0.95 [95% CI, 0.65 to 1.38], P = .96) were not significantly different.
CONCLUSIONS AND RELEVANCE Among families of patients with chronic critical illness, the use of palliative care-led informational and emotional support meetings compared with usual care did not reduce anxiety or depression symptoms and may have increased posttraumatic stress disorder symptoms. These findings do not support routine or mandatory palliative care-led discussion of goals of care for all families of patients with chronic critical illness.
C1 [Carson, Shannon S.; Hanson, Laura C.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Cox, Christopher E.] Duke Univ, Med Ctr, Durham, NC USA.
[Wallenstein, Sylvan; Chai, Emily] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Danis, Marion] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Tulsky, James A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
[Tulsky, James A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA.
[Nelson, Judith E.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Nelson, Judith E.] Weill Cornell Med Coll, New York, NY USA.
RP Carson, SS (reprint author), Univ N Carolina, Sch Med, Div Pulm & Crit Care Med, Marsico Lung Inst,Cecil B Sheps Ctr Hlth Serv Res, 4125 Bioinformat Bldg,CB 7020, Chapel Hill, NC 27599 USA.
EM scarson@med.unc.edu
FU National Institute of Nursing Research [R01-NR012413]
FX This project was funded by grant R01-NR012413 from the National
Institute of Nursing Research.
NR 36
TC 15
Z9 16
U1 13
U2 15
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 0098-7484
EI 1538-3598
J9 JAMA-J AM MED ASSOC
JI JAMA-J. Am. Med. Assoc.
PD JUL 5
PY 2016
VL 316
IS 1
BP 51
EP 62
DI 10.1001/jama.2016.8474
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DQ2MY
UT WOS:000379037600018
PM 27380343
ER
PT J
AU Blatter, C
Meijer, EFJ
Nam, AS
Jones, D
Bouma, BE
Padera, TP
Vakoc, BJ
AF Blatter, Cedric
Meijer, Eelco F. J.
Nam, Ahhyun S.
Jones, Dennis
Bouma, Brett E.
Padera, Timothy P.
Vakoc, Benjamin J.
TI In vivo label-free measurement of lymph flow velocity and volumetric
flow rates using Doppler optical coherence tomography
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RETINAL BLOOD-FLOW; VESSELS; MICE; MICROSCOPY; DISEASE; CANCER; NODES
AB Direct in vivo imaging of lymph flow is key to understanding lymphatic system function in normal and disease states. Optical microscopy techniques provide the resolution required for these measurements, but existing optical techniques for measuring lymph flow require complex protocols and provide limited temporal resolution. Here, we describe a Doppler optical coherence tomography platform that allows direct, label-free quantification of lymph velocity and volumetric flow rates. We overcome the challenge of very low scattering by employing a Doppler algorithm that operates on low signal-to-noise measurements. We show that this technique can measure lymph velocity at sufficiently high temporal resolution to resolve the dynamic pulsatile flow in collecting lymphatic vessels.
C1 [Blatter, Cedric; Nam, Ahhyun S.; Bouma, Brett E.; Vakoc, Benjamin J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Blatter, Cedric; Meijer, Eelco F. J.; Nam, Ahhyun S.; Jones, Dennis; Bouma, Brett E.; Padera, Timothy P.; Vakoc, Benjamin J.] Harvard Med Sch, Boston, MA 02115 USA.
[Meijer, Eelco F. J.; Jones, Dennis; Padera, Timothy P.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs Tumor Biol, Ctr Canc, Boston, MA 02114 USA.
[Nam, Ahhyun S.] MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RP Vakoc, BJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Vakoc, BJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM bvakoc@mgh.harvard.edu
OI Padera, Timothy/0000-0002-3453-9384
FU Center for Biomedical OCT Research and Translation [P41EB015903];
National Institutes of Health [R01CA163528, DP2OD008780, R21AI097745,
R01HL128168, F32CA183465]; National Cancer Institute Federal Share of
Proton Income; Swiss National Science Foundation early post-doctoral
mobility fellowship [P2SKP2_158640]; Burroughs Wellcome Fund
postdoctoral award; UNCF-Merck postdoctoral fellowship
FX Research reported in this publication was supported in part by the
Center for Biomedical OCT Research and Translation through Grant Number
P41EB015903, awarded by the National Institute of Biomedical Imaging and
Bioengineering of the National Institutes of Health, by the National
Institutes of Health under award numbers R01CA163528 (B.J.V.),
DP2OD008780 (T.P.P.), R21AI097745 (T.P.P.), R01HL128168 (T.P.P.) and
F32CA183465 (D.J.). The National Cancer Institute Federal Share of
Proton Income also supported this work (T.P.P., B.J.V.). Cedric Blatter
was supported by a Swiss National Science Foundation early post-doctoral
mobility fellowship (P2SKP2_158640). Dennis Jones was supported by a
Burroughs Wellcome Fund postdoctoral award and UNCF-Merck postdoctoral
fellowship. The authors acknowledge Matthias Geissbuehler for a modified
StackReg ImageJ plugin.
NR 43
TC 1
Z9 1
U1 4
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD JUL 5
PY 2016
VL 6
AR 29035
DI 10.1038/srep29035
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DQ3BI
UT WOS:000379077300001
PM 27377852
ER
PT J
AU Jaffer, FA
O'Gara, PT
AF Jaffer, Farouc A.
O'Gara, Patrick T.
TI Multivessel CAD in Nondiabetic Patients To Operate or to Dilate?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE coronary artery bypass grafting; multivessel disease; percutaneous
coronary intervention
ID PERCUTANEOUS CORONARY INTERVENTION; ISCHEMIC-HEART-DISEASE;
ARTERY-DISEASE; BYPASS-SURGERY; ELUTING STENTS; SYNTAX SCORE; LEFT MAIN;
MANAGEMENT; GUIDELINE; DIAGNOSIS
C1 [Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[O'Gara, Patrick T.] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, MGH CVRC, 185 Cambridge St, Boston, MA 02114 USA.; O'Gara, PT (reprint author), Brigham & Womens Hosp, BWH Cardiol, 75 Francis St, Boston, MA 02115 USA.
EM fjaffer@mgh.harvard.edu; pogara@partners.org
NR 11
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0735-1097
EI 1558-3597
J9 J AM COLL CARDIOL
JI J. Am. Coll. Cardiol.
PD JUL 5
PY 2016
VL 68
IS 1
BP 37
EP 39
DI 10.1016/j.jacc.2016.05.008
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DP5IB
UT WOS:000378528400006
PM 27364048
ER
PT J
AU English, L
Miller, JS
Mbusa, R
Matte, M
Kenney, J
Bwambale, S
Ntaro, M
Patel, P
Mulogo, E
Stone, GS
AF English, Lacey
Miller, James S.
Mbusa, Rapheal
Matte, Michael
Kenney, Jessica
Bwambale, Shem
Ntaro, Moses
Patel, Palka
Mulogo, Edgar
Stone, Geren S.
TI Monitoring iCCM referral systems: Bugoye Integrated Community Case
Management Initiative (BIMI) in Uganda (vol 15, pg 247, 2016)
SO MALARIA JOURNAL
LA English
DT Correction
C1 [English, Lacey] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Miller, James S.] Harvard Med Sch, Boston, MA USA.
[Mbusa, Rapheal; Bwambale, Shem] Bugoye Hlth Ctr III, Bugoye, Uganda.
[Matte, Michael; Ntaro, Moses; Mulogo, Edgar] Mbarara Univ Sci & Technol, Dept Community Hlth, Mbarara, Uganda.
[Kenney, Jessica; Patel, Palka; Stone, Geren S.] Massachusetts Gen Hosp, Global Primary Care Program, Boston, MA 02114 USA.
RP English, L (reprint author), Univ N Carolina, Sch Med, Chapel Hill, NC USA.
EM Lacey_English@med.unc.edu
NR 1
TC 1
Z9 1
U1 1
U2 1
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD JUL 4
PY 2016
VL 15
AR 343
DI 10.1186/s12936-016-1375-6
PG 1
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DQ1WC
UT WOS:000378990100003
ER
PT J
AU Kubzansky, LD
Kim, ES
Salinas, J
Huffman, JC
Kawachi, I
AF Kubzansky, Laura D.
Kim, Eric S.
Salinas, Joel
Huffman, Jeff C.
Kawachi, Ichiro
TI Happiness, health, and mortality Reply
SO LANCET
LA English
DT Letter
C1 [Kubzansky, Laura D.; Kim, Eric S.; Kawachi, Ichiro] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Salinas, Joel] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Huffman, Jeff C.] Massachusetts Gen Hosp, Cardiac Psychiat Res Program, Boston, MA 02114 USA.
[Huffman, Jeff C.] Massachusetts Gen Hosp, Inpatient Med Psychiat Serv, Boston, MA 02114 USA.
RP Kubzansky, LD (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
EM lkubzans@hsph.harvard.edu
NR 7
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD JUL 2
PY 2016
VL 388
IS 10039
BP 27
EP 27
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DP9PM
UT WOS:000378828400020
PM 27397787
ER
PT J
AU Djemie, T
Weckhuysen, S
von Spiczak, S
Carvill, GL
Jaehn, J
Anttonen, AK
Brilstra, E
Caglayan, HS
de Kovel, CG
Depienne, C
Gaily, E
Hamalainen, E
Giraldez, BG
Gormley, P
Guerrero-Lopez, R
Guerrini, R
Hamalainen, E
Hartmann, C
Hernandez-Hernandez, L
Hjalgrim, H
Koeleman, BPC
Leguern, E
Lehesjoki, AE
Lemke, JR
Leu, C
Marini, C
McMahon, JM
Mei, D
Moller, RS
Muhle, H
Myers, CT
Nava, C
Serratosa, JM
Sisodiya, SM
Stephani, U
Striano, P
van Kempen, MJA
Verbeek, NE
Usluer, S
Zara, F
Palotie, A
Mefford, HC
Scheffer, IE
De Jonghe, P
Helbig, I
Suls, A
AF Djemie, Tania
Weckhuysen, Sarah
von Spiczak, Sarah
Carvill, Gemma L.
Jaehn, Johanna
Anttonen, Anna-Kaisa
Brilstra, Eva
Caglayan, Hande S.
de Kovel, Carolien G.
Depienne, Christel
Gaily, Eija
Hamalainen, Eija
Giraldez, Beatriz G.
Gormley, Padhraig
Guerrero-Lopez, Rosa
Guerrini, Renzo
Hamalainen, Eija
Hartmann, Corinna
Hernandez-Hernandez, Laura
Hjalgrim, Helle
Koeleman, Bobby P. C.
Leguern, Eric
Lehesjoki, Anna-Elina
Lemke, Johannes R.
Leu, Costin
Marini, Carla
McMahon, Jacinta M.
Mei, Davide
Moller, Rikke S.
Muhle, Hiltrud
Myers, Candace T.
Nava, Caroline
Serratosa, Jose M.
Sisodiya, Sanjay M.
Stephani, Ulrich
Striano, Pasquale
van Kempen, Marjan J. A.
Verbeek, Nienke E.
Usluer, Sunay
Zara, Federico
Palotie, Aarno
Mefford, Heather C.
Scheffer, Ingrid E.
De Jonghe, Peter
Helbig, Ingo
Suls, Arvid
CA EuroEPINOMICS-RES Dravet Working
TI Pitfalls in genetic testing: the story of missed SCN1A mutations
SO MOLECULAR GENETICS & GENOMIC MEDICINE
LA English
DT Article
DE Dravet syndrome; epilepsy; genetic screening; next-generation
sequencing; Sanger sequencing
ID DE-NOVO MUTATIONS; DRAVET SYNDROME; EPILEPTIC ENCEPHALOPATHY; PHENOTYPE
AB Background
Sanger sequencing, still the standard technique for genetic testing in most diagnostic laboratories and until recently widely used in research, is gradually being complemented by next-generation sequencing (NGS). No single mutation detection technique is however perfect in identifying all mutations. Therefore, we wondered to what extent inconsistencies between Sanger sequencing and NGS affect the molecular diagnosis of patients. Since mutations in SCN1A, the major gene implicated in epilepsy, are found in the majority of Dravet syndrome (DS) patients, we focused on missed SCN1A mutations.
Methods
We sent out a survey to 16 genetic centers performing SCN1A testing.
Results
We collected data on 28 mutations initially missed using Sanger sequencing. All patients were falsely reported as SCN1A mutation-negative, both due to technical limitations and human errors.
Conclusion
We illustrate the pitfalls of Sanger sequencing and most importantly provide evidence that SCN1A mutations are an even more frequent cause of DS than already anticipated.
C1 [Djemie, Tania; Weckhuysen, Sarah; Brilstra, Eva; Serratosa, Jose M.; De Jonghe, Peter; Suls, Arvid] VIB, Dept Mol Genet, Neurogenet Grp, Antwerp, Belgium.
[Djemie, Tania; Weckhuysen, Sarah; De Jonghe, Peter; Suls, Arvid] Univ Antwerp, Inst Born Bunge, Neurogenet Lab, Antwerp, Belgium.
[Weckhuysen, Sarah; Depienne, Christel; Leguern, Eric; Nava, Caroline] UPMC Univ Paris 06, Sorbonne Univ, 91-105 Blvd Hop, F-75013 Paris, France.
[Weckhuysen, Sarah; Depienne, Christel; Leguern, Eric; Nava, Caroline] INSERM, CNRS, ICM, UMR 7225,U 1127, 47-83 Blvd Hop, F-75013 Paris, France.
[Weckhuysen, Sarah] Grp Hosp Pitie Salpetriere, AP HP, Ctr Reference Epilepsies Rares, Epilepsy Unit, F-75013 Paris, France.
[von Spiczak, Sarah; Jaehn, Johanna; Hartmann, Corinna; Muhle, Hiltrud; Stephani, Ulrich] Univ Med Ctr Schleswig Holstein, Dept Neuropediat, Kiel, Germany.
[Carvill, Gemma L.; Myers, Candace T.; Mefford, Heather C.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA.
[Anttonen, Anna-Kaisa; Lehesjoki, Anna-Elina] Folkhalsan Inst Genet, Helsinki, Finland.
[Anttonen, Anna-Kaisa] Univ Helsinki, Med & Clin Genet, Helsinki, Finland.
[Anttonen, Anna-Kaisa] Helsinki Univ Hosp, Helsinki, Finland.
[de Kovel, Carolien G.; Koeleman, Bobby P. C.; van Kempen, Marjan J. A.; Verbeek, Nienke E.] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands.
[Caglayan, Hande S.; Usluer, Sunay] Bogazici Univ, Dept Mol Biol & Genet, Istanbul, Turkey.
[Depienne, Christel; Leguern, Eric; Nava, Caroline] Hop La Pitie Salpetriere, AP HP, Dept Genet, 47-83 Blvd Hop, F-75013 Paris, France.
[Gaily, Eija] Helsinki Univ Hosp, Dept Pediat Neurol, Helsinki, Finland.
[Hamalainen, Eija] EO Osped Galliera, Genet Lab, Genoa, Italy.
[Giraldez, Beatriz G.; Serratosa, Jose M.] Univ Autonoma Madrid, Neurol Lab, Madrid, Spain.
[Giraldez, Beatriz G.; Serratosa, Jose M.] Univ Autonoma Madrid, Dept Neurol, Epilepsy Unit, Inst Invest Sanitaria,Fdn Jimenez Diaz, Madrid, Spain.
[Giraldez, Beatriz G.; Guerrero-Lopez, Rosa; Serratosa, Jose M.] IIS Fdn Jimenez Diaz, Madrid, Spain.
[Giraldez, Beatriz G.; Guerrero-Lopez, Rosa; Serratosa, Jose M.] Ctr Invest Biomed Red Enfermedades Raras CIBERER, Madrid, Spain.
[Gormley, Padhraig] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Gormley, Padhraig] Harvard Med Sch, Boston, MA 02114 USA.
[Gormley, Padhraig; Palotie, Aarno] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Gormley, Padhraig] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Gormley, Padhraig; Hamalainen, Eija] Wellcome Trust Sanger Inst, Hinxton, England.
[Guerrini, Renzo; Marini, Carla; Mei, Davide] Univ Florence, A Meyer Childrens Hosp, Pediat Neurol & Neurogenet Unit & Labs, Florence, Italy.
[Hamalainen, Eija; Palotie, Aarno] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Hernandez-Hernandez, Laura; Leu, Costin; Sisodiya, Sanjay M.] UCL Inst Neurol, Biomed Res Ctr, NIHR Univ Coll London Hosp, Dept Clin & Expt Epilepsy, London, England.
[Hernandez-Hernandez, Laura; Sisodiya, Sanjay M.] Epilepsy Soc, Gerrards Cross, Bucks, England.
[Hjalgrim, Helle; Moller, Rikke S.] Danish Epilepsy Ctr, Dept Neurol, Dianalund, Denmark.
[Hjalgrim, Helle; Moller, Rikke S.] Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark.
[Lehesjoki, Anna-Elina] Univ Helsinki, Res Programs Unit, Mol Neurol, Helsinki, Finland.
[Lemke, Johannes R.] Univ Leipzig, Inst Human Genet, Leipzig, Germany.
[McMahon, Jacinta M.; Scheffer, Ingrid E.] Univ Melbourne, Dept Med, Epilepsy Res Ctr, Austin Hlth, Melbourne, Vic, Australia.
[Striano, Pasquale] Univ Genoa, Pediat Neurol & Muscular Dis Unit, G Gaslini Inst, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, Genoa, Italy.
[Zara, Federico] Giannina Gaslini Inst, Dept Neurosci, Neurogenet Lab, Genoa, Italy.
[Scheffer, Ingrid E.] Univ Melbourne, Dept Paediat, Parkville, Vic 3052, Australia.
[Scheffer, Ingrid E.] Royal Childrens Hosp, Parkville, Vic 3052, Australia.
[Scheffer, Ingrid E.] Florey Inst Neurosci & Mental Hlth, Melbourne, Vic 3084, Australia.
[De Jonghe, Peter] Univ Antwerp Hosp, Div Neurol, Antwerp, Belgium.
[Helbig, Ingo] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA.
[Suls, Arvid] Univ Antwerp, Ctr Med Genet, GENOMED, Antwerp, Belgium.
RP Suls, A (reprint author), Univ Antwerp, Ctr Med Genet, Campus Drie Eiken,Prins Boudewijnlaan 43, B-2650 Edegem, Belgium.
EM arvid.suls@uantwerpen.be
FU Assistance Publique des Hopitaux de Paris (AP-HP); Dravet Syndrome UK;
Katy Baggott Foundation; Epilepsy Society; International Coordination
Action (ICA) [G0E8614N]; EpiPGX (European Union 7th Framework Programme
Grant) [279062]; UK Department of Health's NIHR Biomedical Research
Centres funding scheme; Folkhalsan Research Foundation; Eurocores
program of the European Science Foundation P.D.J. [G.A.136.11.N,
FWO/ESF-ECRP]; TUBITAK [110S518]; medical faculty of Kiel University,
Germany; French program "Investissements d'avenir" [ANR-10-IAIHU-06];
[HE5415/3-1]
FX This study was funded by the following sources: Assistance Publique des
Hopitaux de Paris (AP-HP), Dravet Syndrome UK, the Katy Baggott
Foundation, the Epilepsy Society, the International Coordination Action
(ICA, grant G0E8614N), and EpiPGX (European Union 7th Framework
Programme Grant 279062). This work was partly undertaken at UCLH/UCL,
which received a proportion of funding from the UK Department of
Health's NIHR Biomedical Research Centres funding scheme. This work was
supported by Folkhalsan Research Foundation (A-KA, A-EL). Within the
Eurocores program of the European Science Foundation P.D.J.
(G.A.136.11.N and FWO/ESF-ECRP) and I.H. (HE5415/3-1) received financial
support within the EuroEPINOMICS-RES network. H.C. is granted by the
TUBITAK project no 110S518. S.v.S, H.M., U.S. and I.H. received funding
from the medical faculty of Kiel University, Germany. T.D. is a PhD
fellow of the Institute of Science and Technology (IWT). A.S. was a
postdoctoral fellow of the Fund for Scientific Research Flanders (FWO).
S.W. is supported by French program "Investissements d'avenir"
(ANR-10-IAIHU-06).
NR 19
TC 3
Z9 3
U1 0
U2 0
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2324-9269
J9 MOL GENET GENOM MED
JI Mol. Genet. Genom. Med.
PD JUL
PY 2016
VL 4
IS 4
BP 457
EP 464
DI 10.1002/mgg3.217
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA EL2KX
UT WOS:000394449700009
PM 27465585
ER
PT J
AU Schoffski, P
Choy, E
Le Cesne, A
Camargo, V
Bauer, S
Rha, SY
Blay, JY
D'Adamo, DR
Guo, M
Maki, RG
AF Schoffski, Patrick
Choy, Edwin
Le Cesne, Axel
Camargo, Veridiana
Bauer, Sebastian
Rha, Sun Young
Blay, Jean-Yves
D'Adamo, David R.
Guo, Matthew
Maki, Robert G.
TI Phase (ph) 3 study of eribulin (ERI) vs dacarbazine (DTIC) in
leiomyosarcoma (LMS) and liposarcoma (LPS) patients (pts)
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Japanese-Society-of-Medical-Oncology
CY JUL 28-30, 2016
CL Kobe, JAPAN
SP Japanese Soc Med Oncol
C1 [Schoffski, Patrick] Univ Hosp Leuven, Dept Gen Med Oncol, Leuven, Belgium.
[Choy, Edwin] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Le Cesne, Axel] Gustave Roussy, Villejuif, France.
[Camargo, Veridiana] Hosp Sirio Libanes, Dept Med Oncol, Sau Paulo, Brazil.
[Bauer, Sebastian] West German Canc Ctr, Essen, Germany.
[Rha, Sun Young] Severance Hosp, Seoul, South Korea.
[Blay, Jean-Yves] Univ Claude Bernard, Lyon, France.
[Blay, Jean-Yves] Ctr Leon Berard, Lyon, France.
[D'Adamo, David R.; Guo, Matthew] Eisai Inc, Woodcliff Lake, NJ USA.
[Maki, Robert G.] Mt Sinai Med Ctr, Tisch Canc Inst, New York, NY 10029 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JUL 1
PY 2016
VL 27
SU 7
MA PS - 2
PG 1
WC Oncology
SC Oncology
GA EK4QK
UT WOS:000393911700128
ER
PT J
AU Suzuki, K
Kuss, I
Smith, MR
Fizazi, K
AF Suzuki, Kazuhiro
Kuss, Iris
Smith, Matthew R.
Fizazi, Karim
TI ARAMIS trial: Efficacy and safety of ODM-201 in men with high-risk
nonmetastatic castration-resistant prostate cancer
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Japanese-Society-of-Medical-Oncology
CY JUL 28-30, 2016
CL Kobe, JAPAN
SP Japanese Soc Med Oncol
C1 [Suzuki, Kazuhiro] Gunma Univ, Grad Sch Med, Gunma, Japan.
[Suzuki, Kazuhiro] Gunma Univ Hosp, Gunma, Japan.
[Kuss, Iris] Bayer Pharma AG, Global Clin Oncol, Berlin, Germany.
[Smith, Matthew R.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA.
[Fizazi, Karim] Inst Gustave Roussy, Dept Canc Med, Villejuif, France.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JUL 1
PY 2016
VL 27
SU 7
MA PF1-091
PG 1
WC Oncology
SC Oncology
GA EK4QK
UT WOS:000393911700257
ER
PT J
AU Florez, JC
AF Florez, Jose C.
TI Precision Medicine in Diabetes: Is It Time?
SO DIABETES CARE
LA English
DT Article
ID INSULIN-RESISTANCE; PREVENTION PROGRAM; GENOMIC MEDICINE; LIFE-STYLE;
METFORMIN; HYPERGLYCEMIA; PREDICTION; MANAGEMENT; MUTATIONS; VARIANTS
C1 [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Metab Program, Cambridge, MA 02142 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Florez, Jose C.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.; Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Florez, JC (reprint author), Broad Inst, Metab Program, Cambridge, MA 02142 USA.; Florez, JC (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Florez, JC (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
EM jcflorez@partners.org
FU Massachusetts General Hospital Scholars Award
FX J.C.F. is supported by a Massachusetts General Hospital Scholars Award.
NR 27
TC 4
Z9 4
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1085
EP 1088
DI 10.2337/dc16-0586
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500013
PM 27289125
ER
PT J
AU Pandharipande, PV
Herts, BR
Gore, RM
Mayo-Smith, WW
Harvey, HB
Megibow, AJ
Berland, LL
AF Pandharipande, Pari V.
Herts, Brian R.
Gore, Richard M.
Mayo-Smith, William W.
Harvey, H. Benjamin
Megibow, Alec J.
Berland, Lincoln L.
TI Rethinking Normal: Benefits and Risks of Not Reporting Harmless
Incidental Findings
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Incidental finding; health policy; medical decision making
ID WHITE PAPER; COMMITTEE II; PELVIC CT; RENAL CYSTS;
CLASSIFICATION-SYSTEM; MRI; RECOMMENDATIONS; DISEASE; BURDEN; MASSES
AB The authors explore the benefits and risks of not reporting imaging findings that do not have clinical relevance, with the goal of developing recommendations to reduce their reporting. The authors review the example of incidentally detected, simple renal cysts (Bosniak category I), including medicolegal conditions required for such a shift in reporting practices to be acceptable. The authors propose four potential criteria for not reporting clinically unimportant findings and recommend that these criteria be debated in other contexts, so that they can be refined and implemented.
C1 [Pandharipande, Pari V.; Harvey, H. Benjamin] Massachusetts Gen Hosp, Dept Radiol, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
[Pandharipande, Pari V.; Harvey, H. Benjamin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Herts, Brian R.] Cleveland Clin, Dept Radiol, Cleveland, OH 44106 USA.
[Gore, Richard M.] NorthShore Univ Hlth Syst, Dept Radiol, Evanston, IL USA.
[Mayo-Smith, William W.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
[Megibow, Alec J.] NYU, Dept Radiol, Langone Med Ctr, 560 1St Ave, New York, NY 10016 USA.
[Berland, Lincoln L.] Univ Alabama Birmingham, Dept Radiol, Birmingham, AL USA.
RP Pandharipande, PV (reprint author), Massachusetts Gen Hosp, Dept Radiol, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM pari@mgh-ita.org
NR 22
TC 7
Z9 7
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2016
VL 13
IS 7
BP 764
EP 767
DI 10.1016/j.jacr.2016.03.017
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DZ6SF
UT WOS:000385991500006
PM 27162042
ER
PT J
AU Smith, AK
Ritchie, CS
Miao, YH
Boscardin, WJ
Wallhagen, ML
AF Smith, Alexander K.
Ritchie, Christine S.
Miao, Yinghui
Boscardin, W. John
Wallhagen, Margaret L.
TI Self-Reported Hearing in the Last 2 Years of Life in Older Adults
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE hearing loss; end of life; population-based studies
ID LONGITUDINAL ANALYSIS; UNITED-STATES; AID USE; CARE; IMPAIRMENT;
PREVALENCE; COMMUNICATION; EPIDEMIOLOGY; QUALITY; PATIENT
AB OBJECTIVES: To assess the prevalence and correlates of self-reported hearing loss during the last 2 years of life.
DESIGN: Observational cohort study.
SETTING: The Health and Retirement Study (HRS), a longitudinal nationally representative cohort of adults aged 50 and older (2000-13).
PARTICIPANTS: Older adults (N = 5,895, mean age at death 78, 53% female, 20% nonwhite).
MEASUREMENTS: The HRS interview closest to death was used (mean 12.2 months before death). Participants rated their hearing (excellent, very good, good, fair, poor) and indicated whether they used hearing aids. The prevalence and correlates of fair and poor ratings are described, adjusted for age and sex.
RESULTS: Thirty-two percent (95% confidence interval (CI) = 31-34%) of all participants and 60% (95% CI = 57-64%) of the 7% of participants who used hearing aids rated their hearing as fair or poor. The prevalence of fair or poor hearing was highest in participants interviewed closest to death (29% 19-24 months before death, 36% 1-6 months before death, P for trend = .01). Correlates of fair or poor hearing during the last 2 years of life included age at death (50-59, 22%; 60-69, 21%; 70-79, 26%; 80-89, 38%; >= 90, 50%), sex (men 35%, women 30%), race and ethnicity (Hispanic 42%, white 33%), wealth (lowest quartile 38%, highest quartile 27%), history of heart disease (yes 38%, no 27%), activity of daily living dependence (yes 42%, no 26%), difficulty taking medications (yes 46%, no 29%), and probable dementia (yes 44%, no 24%).
CONCLUSION: Self-reported hearing loss increases during the last 2 years of life and is associated with physical and social vulnerability.
C1 [Smith, Alexander K.; Ritchie, Christine S.; Boscardin, W. John] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
[Smith, Alexander K.; Miao, Yinghui; Boscardin, W. John] Univ Calif San Francisco, Vet Affairs Med Ctr, Geriatr Palliat & Extended Care, San Francisco, CA 94143 USA.
[Ritchie, Christine S.] Univ Calif San Francisco, Jewish Home San Francisco, San Francisco, CA 94143 USA.
[Miao, Yinghui; Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Wallhagen, Margaret L.] Univ Calif San Francisco, Dept Physiol Nursing, San Francisco, CA USA.
RP Smith, AK (reprint author), UCSF, Div Geriatr, San Francisco VA Med Ctr, Med, 4150 Clement St 181G, San Francisco, CA 94121 USA.
EM aksmith@ucsf.edu
FU National Institute on Aging [1K23AG040772]; American Federation for
Aging Research
FX Dr. Wallhagen serves on the board of the Hearing Loss Association of
America. Dr. Smith was funded by a K23 Beeson award from the National
Institute on Aging (1K23AG040772) and the American Federation for Aging
Research.
NR 23
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-8614
EI 1532-5415
J9 J AM GERIATR SOC
JI J. Am. Geriatr. Soc.
PD JUL
PY 2016
VL 64
IS 7
BP 1486
EP 1491
DI 10.1111/jgs.14145
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DW3NN
UT WOS:000383548400015
ER
PT J
AU Pepke-Zaba, J
Jais, X
Channick, R
AF Pepke-Zaba, Joanna
Jais, Xavier
Channick, Richard
TI Medical Therapy in Chronic Thromboembolic Pulmonary Hypertension
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
DE pulmonary circulation; thromboembolism; vasodilator agents; riociguat;
pulmonary vascular resistance
AB Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but life-threatening condition resulting from unresolved thromboembolic obstructions. Pulmonary endarterectomy surgery is currently the standard of treatment, as it is potentially curative; however, not all cases are amenable to surgical intervention due to distal distribution of the organized thromboembolic material or the presence of comorbidities. Up to one-third of patients have persistent or recurrent pulmonary hypertension after pulmonary endarterectomy. In addition to the occlusive organized thromboembolic material, there is a small-vessel vasculopathy in nonoccluded parts of the pulmonary circulation that is histologically similar to that described in pulmonary arterial hypertension. This observation has led to frequent off-license use of approved pulmonary arterial hypertension therapies in CTEPH. Small uncontrolled trials have investigated prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors in CTEPH with mixed results. A phase III study of the endothelin receptor antagonist bosentan met only one of its two coprimary end points. The first large randomized controlled trial showing a positive treatment effect was the Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial (CHEST). This study led to the licensing of riociguat for use in inoperable or persistent recurrent CTEPH. Rigorous randomized controlled trials of medical therapy for CTEPH are needed, and several are underway or planned. In the future, outcomes research may be facilitated by identification of novel end points specific to CTEPH.
C1 [Pepke-Zaba, Joanna] Papworth Hosp, Pulm Vasc Dis Unit, Cambridge CB23 3RE, England.
[Jais, Xavier] Univ Paris Sud, Bicetre Hosp, Dept Pulmonol, Le Kremlin Bicetre, France.
[Channick, Richard] Massachusetts Gen Hosp, Pulm Hypertens & Thromboendarterect Program, Boston, MA 02114 USA.
RP Pepke-Zaba, J (reprint author), Papworth Hosp, Pulm Vasc Dis Unit, Cambridge CB23 3RE, England.
EM joanna.pepkezaba@papworth.nhs.uk
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD JUL
PY 2016
VL 13
SU 3
BP S248
EP S254
DI 10.1513/AnnalsATS.201512-802AS
PG 7
WC Respiratory System
SC Respiratory System
GA EJ2HU
UT WOS:000393031500007
PM 27571006
ER
PT J
AU Paulus, YM
Butler, NJ
AF Paulus, Yannis M.
Butler, Nicholas J.
TI Spectral-Domain Optical Coherence Tomography, Wide-Field Photography,
and Fundus Autofluorescence Correlation of Posterior Ophthalmomyiasis
Interna
SO OPHTHALMIC SURGERY LASERS & IMAGING RETINA
LA English
DT Article
AB Posterior ophthalmomyiasis interna is a rare, potentially devastating infestation of the posterior segment by fly larvae. The authors report the first demonstration of spectral-domain optical coherence tomography (SD-OCT) (Spectralis; Heidelberg Engineering, Heidelberg, Germany), wide-field angiography (Optos, Dunfermline, Scotland) and photography, and fundus autofluorescence with temporal progression during a period of 6 months. A 12-year-old white female presented with acute, painless vision loss with hand motions visual acuity. No larva was visible, so she was treated with oral ivermectin. Visual acuity improved to 20/80. OCT demonstrated hyporeflective spaces of the outer retina and retinal pigment epithelium, which resolved during 1-month period with improved ellipsoid layer by 6 months. Fundus autofluorescence demonstrated linear hypoautofluorescent tracks.
C1 [Paulus, Yannis M.] Univ Michigan, Kellogg Eye Ctr, Ann Arbor, MI 48109 USA.
[Butler, Nicholas J.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Butler, Nicholas J.] VA Boston Healthcare Syst, Boston, MA USA.
RP Paulus, YM (reprint author), 1000 Wall St, Ann Arbor, MI 48105 USA.
EM ypaulus@med.umich.edu
FU Heed Ophthalmic Foundation
FX Supported in part by the Heed Ophthalmic Foundation Fellows Grant (YMP).
NR 8
TC 0
Z9 0
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 2325-8160
EI 2325-8179
J9 OSLI RETINA
JI Ophthalmic Surg. Lasers Imag. Retin.
PD JUL
PY 2016
VL 47
IS 7
BP 682
EP 685
DI 10.3928/23258160-20160707-13
PG 4
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA EJ3FP
UT WOS:000393098300013
PM 27434903
ER
PT J
AU Yeung, CM
Lozano-Calderon, SA
Allar, B
Naqvi, M
Gebhardt, MC
Anderson, ME
AF Yeung, Caleb M.
Lozano-Calderon, Santiago A.
Allar, Benjamin
Naqvi, Manahil
Gebhardt, Mark C.
Anderson, Megan E.
TI Ipsilateral Nonvascularized Autograft and Periosteal Repair for the
Treatment of Pediatric Tumors of the Distal Fibula
SO ORTHOPEDICS
LA English
DT Article
ID RECONSTRUCTION; RESECTION; SURVIVAL; SARCOMA; GRAFT
AB Resection of the distal fibula is used to treat malignant or benign locally aggressive tumors involving this region. Current reconstructive techniques are limited by undesirable functional deficits. The authors present a partretrospective and part-prospective case-comparison of 2 patient groups (study and control) treated for malignant or benign locally aggressive primary bone tumors of the distal fibula. Patients in the study group underwent a novel surgical technique involving distal transportation of the ipsilateral proximal portion of the fibula after periosteal dissection and osteotomy with subsequent proximal periosteal reconstruction. Patients in the control group underwent other limb-salvage or amputation procedures. Patients were evaluated at follow-up appointments for oncologic, radiographic, and functional outcomes. The groups had similar demographic and perioperative data. Operative time was longer in the study group. Radiographic union occurred in 75% of the study group vs 50% of the control group. Musculoskeletal Tumor Society scores were similar between groups. According to American Foot and Ankle scores, activity limitations and support requirements were greater in the study group; according to Foot and Ankle Disability Index scores, patients in the control group reported more difficulty with squatting. All patients in the study group were without recurrence at follow-up. One patient in the control group had recurrence of disease. Complications occurred in 3 of 4 study group patients and in all control group patients. With the authors' technique for distal fibular reconstruction involving transporting the ipsilateral remaining proximal fibula as a nonvascularized autograft, the regenerative capability of the periosteum allows for restoration of the proximal fibula, preserving osseous stock.
C1 [Yeung, Caleb M.; Lozano-Calderon, Santiago A.; Allar, Benjamin; Naqvi, Manahil; Gebhardt, Mark C.; Anderson, Megan E.] Boston Childrens Hosp, Dept Orthopaed, Boston, MA USA.
[Lozano-Calderon, Santiago A.; Gebhardt, Mark C.; Anderson, Megan E.] Harvard MIT, Beth Israel Deaconess Med Ctr, Cambridge, MA USA.
[Yeung, Caleb M.] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA.
[Lozano-Calderon, Santiago A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA.
RP Lozano-Calderon, SA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA.
EM slozanocalderon@mgh.harvard.edu
NR 16
TC 1
Z9 1
U1 0
U2 0
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0147-7447
EI 1938-2367
J9 ORTHOPEDICS
JI Orthopedics
PD JUL-AUG
PY 2016
VL 39
IS 4
BP E687
EP E694
DI 10.3928/01477447-20160419-03
PG 8
WC Orthopedics
SC Orthopedics
GA EJ3IJ
UT WOS:000393105500015
PM 27111078
ER
PT J
AU Maison, S
Liberman, LD
Liberman, MC
AF Maison, Stephane
Liberman, Leslie D.
Liberman, M. Charles
TI Type II Cochlear Ganglion Neurons Do Not Drive the Olivocochlear Reflex:
Re-Examination of the Cochlear Phenotype in Peripherin Knock-Out Mice
SO ENEURO
LA English
DT Article
DE olivocochlear reflex; feedback; peripherin; hair cells; cochlea
ID GUINEA-PIG COCHLEA; AIDED 3-DIMENSIONAL RECONSTRUCTION; SPIRAL GANGLION;
HAIR-CELLS; EFFERENT INNERVATION; HORSERADISH-PEROXIDASE; RECIPROCAL
SYNAPSES; AFFERENT NEURONS; AUDITORY-NERVE; ADULT CATS
AB The cochlear nerve includes a small population of unmyelinated sensory fibers connecting outer hair cells to the brain. The functional role of these type II afferent neurons is controversial, because neurophysiological data are sparse. A recent study (Froud et al., 2015) reported that targeted deletion of peripherin, a type of neurofilament, eliminated type II afferents and inactivated efferent feedback to the outer hair cells, thereby suggesting that type II afferents were the sensory drive to this sound-evoked, negative-feedback reflex, the olivocochlear pathway. Here, we re-evaluated the cochlear phenotype in mice from the peripherin knock-out line and show that (1) type II afferent terminals are present in normal number and (2) olivocochlear suppression of cochlear responses is absent even when this efferent pathway is directly activated by shocks. We conclude that type II neurons are not the sensory drive for the efferent reflex and that peripherin deletion likely causes dysfunction of synaptic transmission between olivocochlear terminals and their peripheral targets.
C1 [Maison, Stephane; Liberman, M. Charles] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Maison, Stephane; Liberman, Leslie D.; Liberman, M. Charles] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA.
RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, 243 Charles St, Boston, MA 02114 USA.
EM Charles_Liberman@meei.harvard.edu
NR 46
TC 1
Z9 1
U1 0
U2 0
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 2373-2822
J9 ENEURO
JI eNeuro
PD JUL-AUG
PY 2016
VL 3
IS 4
AR UNSP e0207
DI 10.1523/ENEURO.0207-16.2016
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA EH7BV
UT WOS:000391928700041
ER
PT J
AU Sloas, DC
Zhuo, R
Xue, HB
Chambers, AR
Kolaczyk, E
Polley, DB
Sen, K
AF Sloas, David C.
Zhuo, Ran
Xue, Hongbo
Chambers, Anna R.
Kolaczyk, Eric
Polley, Daniel B.
Sen, Kamal
TI Interactions across Multiple Stimulus Dimensions in Primary Auditory
Cortex
SO ENEURO
LA English
DT Article
DE auditory; evolutionary algorithm; generalized additive model;
integration; sensory
ID MACAQUE INFEROTEMPORAL CORTEX; RECEPTIVE-FIELDS; NATURAL SOUNDS;
CORTICAL-NEURONS; CAT; RESPONSES; REPRESENTATION; OPTIMIZATION;
ORGANIZATION; SELECTIVITY
AB Although sensory cortex is thought to be important for the perception of complex objects, its specific role in representing complex stimuli remains unknown. Complex objects are rich in information along multiple stimulus dimensions. The position of cortex in the sensory hierarchy suggests that cortical neurons may integrate across these dimensions to form a more gestalt representation of auditory objects. Yet, studies of cortical neurons typically explore single or few dimensions due to the difficulty of determining optimal stimuli in a high dimensional stimulus space. Evolutionary algorithms (EAs) provide a potentially powerful approach for exploring multidimensional stimulus spaces based on real-time spike feedback, but two important issues arise in their application. First, it is unclear whether it is necessary to characterize cortical responses to multidimensional stimuli or whether it suffices to characterize cortical responses to a single dimension at a time. Second, quantitative methods for analyzing complex multidimensional data from an EA are lacking. Here, we apply a statistical method for nonlinear regression, the generalized additive model (GAM), to address these issues. The GAM quantitatively describes the dependence between neural response and all stimulus dimensions. We find that auditory cortical neurons in mice are sensitive to interactions across dimensions. These interactions are diverse across the population, indicating significant integration across stimulus dimensions in auditory cortex. This result strongly motivates using multidimensional stimuli in auditory cortex. Together, the EA and the GAM provide a novel quantitative paradigm for investigating neural coding of complex multidimensional stimuli in auditory and other sensory cortices.
C1 [Sloas, David C.; Sen, Kamal] Boston Univ, Hearing Res Ctr, Boston, MA 02215 USA.
[Sloas, David C.; Sen, Kamal] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Zhuo, Ran; Xue, Hongbo; Kolaczyk, Eric] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Chambers, Anna R.; Polley, Daniel B.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA.
[Polley, Daniel B.] Harvard Med Sch, Dept Otolaryngol, Boston, MA 02115 USA.
RP Sen, K (reprint author), Boston Univ, Hearing Res Ctr, Boston, MA 02215 USA.; Sen, K (reprint author), Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
EM kamalsen@bu.edu
NR 35
TC 0
Z9 0
U1 0
U2 0
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 2373-2822
J9 ENEURO
JI eNeuro
PD JUL-AUG
PY 2016
VL 3
IS 4
DI 10.1523/ENEURO.0124-16.2016
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA EH7BV
UT WOS:000391928700024
ER
PT J
AU Furie, R
Merrill, J
Werth, V
Khamashta, M
Kalunian, K
Brohawn, P
Illei, G
Drappa, J
Wang, L
Yoo, S
AF Furie, R.
Merrill, J.
Werth, V.
Khamashta, M.
Kalunian, K.
Brohawn, P.
Illei, G.
Drappa, J.
Wang, L.
Yoo, S.
TI ANIFROLUMAB, AN ANTI-INTERFERON-ALPHA RECEPTOR MONOCLONAL ANTIBODY, IN
MODERATE TO SEVERE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
DE Efficacy; Clinical trial; Low disease activity
C1 [Furie, R.] Northwell Hlth, Great Neck, NY USA.
[Merrill, J.] Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
[Werth, V.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Werth, V.] Univ Penn, Philadelphia, PA 19104 USA.
[Khamashta, M.] Graham Hughes Lupus Res Lab, Div Womens Hlth, London, England.
[Kalunian, K.] UCSD Sch Med, La Jolla, CA USA.
[Brohawn, P.; Illei, G.; Drappa, J.; Wang, L.] MedImmune, Gaithersburg, MD USA.
[Yoo, S.] Regenxbio, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
EI 1593-098X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2016
VL 34
IS 4
SU 99
MA S2:03
BP S4
EP S4
PG 1
WC Rheumatology
SC Rheumatology
GA EF4IT
UT WOS:000390289700005
ER
PT J
AU Merrill, J
Furie, R
Werth, V
Khamashta, M
Drappa, J
Wang, L
Illei, G
AF Merrill, J.
Furie, R.
Werth, V.
Khamashta, M.
Drappa, J.
Wang, L.
Illei, G.
TI ANIFROLUMAB REDUCES DISEASE ACTIVITY IN MULTIPLE ORGAN DOMAINS IN
MODERATE TO SEVERE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Meeting Abstract
DE novel therapy; interferon; efficacy
C1 [Merrill, J.] Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA.
[Furie, R.] Northwell Hlth, Great Neck, NY USA.
[Werth, V.] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Werth, V.] Univ Penn, Philadelphia, PA 19104 USA.
[Khamashta, M.] Graham Hughes Lupus Res Lab, Div Womens Hlth, London, England.
[Drappa, J.; Wang, L.; Illei, G.] MedImmune, Gaithersburg, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
EI 1593-098X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2016
VL 34
IS 4
SU 99
MA S2:04
BP S4
EP S4
PG 1
WC Rheumatology
SC Rheumatology
GA EF4IT
UT WOS:000390289700006
ER
PT J
AU Ogino, S
Nishihara, R
AF Ogino, Shuji
Nishihara, Reiko
TI All Biomedical and Health Science Researchers, Including Laboratory
Physicians and Scientists, Need Adequate Education and Training in Study
Design and Statistics
SO CLINICAL CHEMISTRY
LA English
DT News Item
C1 [Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,DFCI Rm M422, Boston, MA 02215 USA.
[Ogino, Shuji] Harvard Med Sch, Boston, MA USA.
[Ogino, Shuji; Nishihara, Reiko] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji; Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,DFCI Rm M422, Boston, MA 02215 USA.
EM shuji_ogino@dfci.harvard.edu
FU NCI NIH HHS [K07 CA190673, R35 CA197735]
NR 2
TC 1
Z9 1
U1 0
U2 0
PU AMER ASSOC CLINICAL CHEMISTRY
PI WASHINGTON
PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA
SN 0009-9147
EI 1530-8561
J9 CLIN CHEM
JI Clin. Chem.
PD JUL
PY 2016
VL 62
IS 7
BP 1039
EP 1040
DI 10.1373/clinchem.2016.257873
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA EF2CL
UT WOS:000390132000023
PM 27354573
ER
PT J
AU Boas, DA
Sakadzic, S
Selb, J
Farzam, P
Franceschini, MA
Carp, SA
AF Boas, David A.
Sakadzic, Sava
Selb, Juliette
Farzam, Parisa
Franceschini, Maria Angela
Carp, Stefan A.
TI Establishing the diffuse correlation spectroscopy signal relationship
with blood flow
SO NEUROPHOTONICS
LA English
DT Article
DE diffuse correlation spectroscopy; blood flow; Monte Carlo; photon
migration
ID OPTICAL-PROPERTIES; WAVE SPECTROSCOPY; RADIATIVE-TRANSFER; VALIDATION;
TISSUE; MEDIA; CELLS; SUSPENSIONS; SCATTERING; LIGHT
AB Diffuse correlation spectroscopy (DCS) measurements of blood flow rely on the sensitivity of the temporal autocorrelation function of diffusively scattered light to red blood cell (RBC) mean square displacement (MSD). For RBCs flowing with convective velocity v(RBC), the autocorrelation is expected to decay exponentially with (v(RBC)(tau))(2), where tau is the delay time. RBCs also experience shear-induced diffusion with a diffusion coefficient D-shear and an MSD of 6D(shear)tau. Surprisingly, experimental data primarily reflect diffusive behavior. To provide quantitative estimates of the relative contributions of convective and diffusive movements, we performed Monte Carlo simulations of light scattering through tissue of varying vessel densities. We assumed laminar vessel flow profiles and accounted for shear-induced diffusion effects. In agreement with experimental data, we found that diffusive motion dominates the correlation decay for typical DCS measurement parameters. Furthermore, our model offers a quantitative relationship between the RBC diffusion coefficient and absolute tissue blood flow. We thus offer, for the first time, theoretical support for the empirically accepted ability of the DCS blood flow index (BFi) to quantify tissue perfusion. We find BFi to be linearly proportional to blood flow, but with a proportionality modulated by the hemoglobin concentration and the average blood vessel diameter. (C) The Authors.
C1 [Boas, David A.; Sakadzic, Sava; Selb, Juliette; Farzam, Parisa; Franceschini, Maria Angela; Carp, Stefan A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Boas, DA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, MGH HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM dboas@nmr.mgh.harvard.edu
FU NCI NIH HHS [R01 CA187595]; NIBIB NIH HHS [P41 EB015896]; NINDS NIH HHS
[R01 NS091230, R21 NS093259]
NR 36
TC 3
Z9 3
U1 1
U2 1
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 2329-423X
EI 2329-4248
J9 NEUROPHOTONICS
JI Neurophotonics
PD JUL-SEP
PY 2016
VL 3
IS 3
AR 031412
DI 10.1117/1.NPh.3.3.031412
PG 9
WC Neurosciences; Optics
SC Neurosciences & Neurology; Optics
GA EF8MG
UT WOS:000390582600012
PM 27335889
ER
PT J
AU Cassano, P
Petrie, SR
Hamblin, MR
Henderson, TA
Iosifescu, DV
AF Cassano, Paolo
Petrie, Samuel R.
Hamblin, Michael R.
Henderson, Theodore A.
Iosifescu, Dan V.
TI Review of transcranial photobiomodulation for major depressive disorder:
targeting brain metabolism, inflammation, oxidative stress, and
neurogenesis
SO NEUROPHOTONICS
LA English
DT Review
DE near-infrared radiation; photobiomodulation; low-level laser therapy;
major depressive disorder; metabolism; inflammation; neurogenesis;
oxidative stress; near-infrared; NILT; low-level light therapy
ID LEVEL LASER THERAPY; NEAR-INFRARED LIGHT;
MAGNETIC-RESONANCE-SPECTROSCOPY; ADULT HIPPOCAMPAL NEUROGENESIS; TERM
NEUROLOGICAL DEFICITS; GLUCOSE-METABOLISM; NEUROTHERA EFFECTIVENESS;
ISCHEMIC-STROKE; EMBOLIC STROKES; NITRIC-OXIDE
AB We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD. (C) The Authors.
C1 [Cassano, Paolo; Petrie, Samuel R.] Massachusetts Gen Hosp, Depress Clin & Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA.
[Cassano, Paolo] Harvard Med Sch, Dept Psychiat, 401 Pk Dr, Boston, MA 02215 USA.
[Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St, Boston, MA 02114 USA.
[Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, 55 Fruit St, Boston, MA 02114 USA.
[Hamblin, Michael R.] Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Henderson, Theodore A.] Synapt Space, 3979 East Arapahoe Rd, Littleton, CO 80122 USA.
[Henderson, Theodore A.] Neurolaser Fdn, Suite 420,215 South Wadsworth, Lakewood, CO 80226 USA.
[Iosifescu, Dan V.] Mt Sinai Sch Med, Mood & Anxiety Disorders Program, 1428 Madison Ave, New York, NY 10029 USA.
[Iosifescu, Dan V.] Mt Sinai Sch Med, Dept Psychiat & Neurosci, 1 Gustave L Levy Pl, New York, NY 10029 USA.
RP Cassano, P (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA.; Cassano, P (reprint author), Harvard Med Sch, Dept Psychiat, 401 Pk Dr, Boston, MA 02215 USA.
EM pcassano@mgh.harvard.edu
NR 96
TC 3
Z9 3
U1 4
U2 21
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 2329-423X
EI 2329-4248
J9 NEUROPHOTONICS
JI Neurophotonics
PD JUL-SEP
PY 2016
VL 3
IS 3
AR 031404
DI 10.1117/1.NPh.3.3.031404
PG 10
WC Neurosciences; Optics
SC Neurosciences & Neurology; Optics
GA EF8MG
UT WOS:000390582600004
PM 26989758
ER
PT J
AU Maione, AG
Smith, A
Kashpur, O
Yanez, V
Knight, E
Mooney, DJ
Md, AV
Tomic-Canic, M
Garlick, JA
AF Maione, Anna G.
Smith, Avi
Kashpur, Olga
Yanez, Vanessa
Knight, Elana
Mooney, David J.
Veves, Aristidis
Tomic-Canic, Marjana
Garlick, Jonathan A.
TI Altered ECM deposition by diabetic foot ulcer-derived fibroblasts
implicates fibronectin in chronic wound repair
SO WOUND REPAIR AND REGENERATION
LA English
DT Article
ID VENOUS LEG ULCERS; EXTRACELLULAR-MATRIX; CELLULAR INFILTRATE;
REGENERATION; CONTRACTION; COLLAGEN
AB Current chronic wound treatments often fail to promote healing of diabetic foot ulcers (DFU), leading to amputation and increased patient morbidity. A critical mediator of proper wound healing is the production, assembly, and remodeling of the extracellular matrix (ECM) by fibroblasts. However, little is known about how these processes are altered in fibroblasts within the DFU microenvironment. Thus, we investigated the capacity of multiple, primary DFU-derived fibroblast strains to express, produce, and assemble ECM proteins compared to diabetic patient-derived fibroblasts and healthy donor-derived fibroblasts. Gene expression microarray analysis showed differential expression of ECM and ECM-regulatory genes by DFU-derived fibroblasts which translated to functional differences in a 3D in vitro ECM tissue model. DFU-derived fibroblasts produced thin, fibronectin-rich matrices, and responded abnormally when challenged with transforming growth factor-beta, a key regulator of matrix production during healing. These results provide novel evidence that DFU-derived fibroblasts contribute to the defective matrices of DFUs and chronic wound pathogenesis.
C1 [Maione, Anna G.; Smith, Avi; Kashpur, Olga; Yanez, Vanessa; Knight, Elana; Garlick, Jonathan A.] Tufts Univ, Sch Dent Med, Dept Oral & Maxillofacial Pathol Oral Med & Crani, 55 Kneeland St,South Cove,Room 116, Boston, MA 02111 USA.
[Mooney, David J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
[Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Veves, Aristidis] Harvard Med Sch, Microcirculat Lab, Boston, MA USA.
[Veves, Aristidis] Harvard Med Sch, Joslin Beth Israel Deaconess Foot Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Tomic-Canic, Marjana] Univ Miami, Miller Sch Med, Wound Healing & Regenerat Med Res Program, Dept Dermatol & Cutaneous Surg, Miami, FL 33136 USA.
RP Garlick, JA (reprint author), Tufts Univ, Sch Dent Med, Dept Oral & Maxillofacial Pathol Oral Med & Crani, 55 Kneeland St,South Cove,Room 116, Boston, MA 02111 USA.
EM jonathan.garlick@tufts.edu
FU National Institute of Health (NIH) [DK098055-06A1]
FX This work was supported by grant #DK098055-06A1 to Jonathan A. Garlick
from National Institute of Health (NIH).
NR 31
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1067-1927
EI 1524-475X
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD JUL-AUG
PY 2016
VL 24
IS 4
BP 630
EP 643
DI 10.1111/wrr.12437
PG 14
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA EE1SX
UT WOS:000389364500002
PM 27102877
ER
PT J
AU Bale, TA
Abedalthagafi, M
Bi, WL
Kang, YJ
Merrill, P
Dunn, IF
Dubuc, A
Charbonneau, SK
Brown, L
Ligon, AH
Ramkissoon, SH
Ligon, KL
AF Bale, Tejus A.
Abedalthagafi, Malak
Bi, Wenya Linda
Kang, Yun Jee
Merrill, Parker
Dunn, Ian F.
Dubuc, Adrian
Charbonneau, Sarah K.
Brown, Loreal
Ligon, Azra H.
Ramkissoon, Shakti H.
Ligon, Keith L.
TI Genomic characterization of recurrent high-grade astroblastoma
SO CANCER GENETICS
LA English
DT Article
DE Astroblastoma; aCGH; NGS; GBM; SETD2
ID GLIOMAS; GLIOBLASTOMA; EPENDYMOMA; FEATURES; TUMORS; MEDULLOBLASTOMA;
CLASSIFICATION; NEUROGENESIS; MUTATIONS; SURVIVAL
AB Astroblastomas are rare primary brain tumors, diagnosed based on histologic features. Not currently assigned a WHO grade, they typically display indolent behavior, with occasional variants taking a more aggressive course. We characterized the immunohistochemical characteristics, copy number (high-resolution array comparative genomic hybridization, OncoCopy) and mutational profile (targeted next-generation exome sequencing, OncoPanel) of a cohort of seven biopsies from four patients to identify recurrent genomic events that may help distinguish astroblastomas from other more common high-grade gliomas. We found that tumor histology was variable across patients and between primary and recurrent tumor samples. No common molecular features were identified among the four tumors. Mutations commonly observed in astrocytic tumors (IDH1/2, TP53, ATRX, and PTEN) or ependymoma were, not identified. However one case with rapid clinical progression displayed mutations more commonly associated with GBM (NF1(N1054H/K63 star), PIK3CA(R38H) and ERG(A403T)). Conversely, another case, originally classified as glioblastoma with nine-year survival before recurrence, lacked a GBM mutational profile. Other mutations frequently seen in lower grade gliomas (BCOR, BCORL1, ERBB3, MYB, ATM) were also present in several tumors. Copy number changes were variable across tumors. Our findings indicate that astroblastomas have variable growth patterns and morphologic features, posing significant challenges to accurate classification in the absence of diagnostically specific copy number alterations and molecular features. Their histopathologic overlap with glioblastoma will likely confound the observation of long-term GBM "survivors". Further genomic profiling is needed to determine whether these tumors represent a distinct entity and to guide management strategies.
C1 [Bale, Tejus A.; Abedalthagafi, Malak; Merrill, Parker; Dubuc, Adrian; Ligon, Azra H.; Ramkissoon, Shakti H.; Ligon, Keith L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.
[Abedalthagafi, Malak; Kang, Yun Jee; Charbonneau, Sarah K.; Brown, Loreal; Ramkissoon, Shakti H.; Ligon, Keith L.] Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
[Abedalthagafi, Malak] King Fahad Med City, Dept Pathol, Riyadh, Saudi Arabia.
[Bi, Wenya Linda; Dunn, Ian F.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA.
RP Ligon, KL (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA.; Ligon, KL (reprint author), Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA.
EM keith_ligon@dfci.harvard.edu
FU King Abdulaziz City for Science and Technology (KACST), Saudi Arabia
FX The authors would like to thank the members of the Ligon lab for helpful
discussions. The authors would like to thank Marian Slaney and Sebastian
Valentin for the technical assistance with tissue processing and the
Center for Advanced Molecular Diagnostic lab members for the genetic
testing. This study was supported by the King Abdulaziz City for Science
and Technology (KACST), Saudi Arabia (M.A.).
NR 39
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2210-7762
EI 2210-7770
J9 CANCER GENET-NY
JI Cancer Genet.
PD JUL-AUG
PY 2016
VL 209
IS 7-8
BP 321
EP 330
DI 10.1016/j.cancergen.2016.06.002
PG 10
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA EA8EF
UT WOS:000386867400003
PM 27425854
ER
PT J
AU Ruderman, L
Ehrlich, DB
Roy, A
Pietrzak, RH
Harpaz-Rotem, I
Levy, I
AF Ruderman, Lital
Ehrlich, Daniel B.
Roy, Alicia
Pietrzak, Robert H.
Harpaz-Rotem, Ilan
Levy, Ifat
TI POSTTRAUMATIC STRESS SYMPTOMS AND AVERSION TO AMBIGUOUS LOSSES IN COMBAT
VETERANS
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE PTSD; decision making; uncertainty; ambiguity; aversion; anxious arousal
ID DECISION-MAKING; PSYCHOLOGICAL DISTRESS; PREFRONTAL CORTEX; UNCERTAINTY;
DISORDER; RISK; RDOC; HYPERAROUSAL; FRAMEWORK; BEHAVIOR
AB Background: Psychiatric symptoms typically cut across traditional diagnostic categories. In order to devise individually tailored treatments, there is a need to identify the basic mechanisms that underlie these symptoms. Behavioral economics provides a framework for studying these mechanisms at the behavioral level. Here, we utilized this framework to examine a widely ignored aspect of trauma-related symptomatology-individual uncertainty attitudes-in combat veterans with and without posttraumatic stress disorder (PTSD). Methods: Fifty-seven combat veterans, including 30 with PTSD and 27 without PTSD, completed a risk and ambiguity decision-making task that characterizes individual uncertainty attitudes, distinguishing between attitudes toward uncertain outcomes with known ("risk") and unknown ("ambiguity") probabilities, and between attitudes toward uncertain gains and uncertain losses. Participants' choices were used to estimate risk and ambiguity attitudes in the gain and loss domains. Results: Veterans with PTSD were more averse to ambiguity, but not risk, compared to veterans without PTSD, when making choices between possible losses, but not gains. The degree of aversion was associated with anxious arousal (e.g., hypervigilance) symptoms, as well as with the degree of combat exposure. Moreover, ambiguity attitudes fully mediated the association between combat exposure and anxious arousal symptoms. Conclusions: These results provide a foundation for prospective studies of the causal association between ambiguity attitudes and trauma-related symptoms, as well as etiologic studies of the neural underpinnings of these behavioral outcomes. More generally, these results demonstrate the potential of neuroeconomic and behavioral economic techniques for devising objective and incentive-compatible diagnostic tools, and investigating the etiology of psychiatric disorders. (C) 2016 Wiley Periodicals, Inc.
C1 [Ruderman, Lital; Ehrlich, Daniel B.; Levy, Ifat] Yale Sch Med, Sect Comparat Med, POB 208016, New Haven, CT 06520 USA.
[Roy, Alicia; Pietrzak, Robert H.; Harpaz-Rotem, Ilan; Levy, Ifat] US Dept Vet Affairs, Natl Ctr PTSD, New Haven, CT USA.
[Roy, Alicia; Pietrzak, Robert H.; Harpaz-Rotem, Ilan] Yale Sch Med, Dept Psychiat, New Haven, CT USA.
[Levy, Ifat] Yale Sch Med, Dept Neurosci, New Haven, CT USA.
RP Levy, I (reprint author), Yale Sch Med, Sect Comparat Med, POB 208016, New Haven, CT 06520 USA.
EM ifat.levy@yale.edu
FU National Institute of Mental Health [R21MH102634]; Clinical
Neurosciences Division of the U.S. Department of Veterans Affairs
National Center for PTSD
FX Contract grant sponsor: National Institute of Mental Health (to I. L.
and I. H.-R.); Contract grant number: R21MH102634; Contract grant
sponsor: Clinical Neurosciences Division of the U.S. Department of
Veterans Affairs National Center for PTSD.
NR 39
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD JUL
PY 2016
VL 33
IS 7
BP 606
EP 613
DI 10.1002/da.22494
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DW5TD
UT WOS:000383708900005
PM 27000639
ER
PT J
AU Gordon, LB
Kieran, MW
Kleinman, ME
Misteli, T
AF Gordon, Leslie B.
Kieran, Mark W.
Kleinman, Monica E.
Misteli, Tom
TI The decision-making process and criteria in selecting candidate drugs
for progeria clinical trials
SO EMBO MOLECULAR MEDICINE
LA English
DT Editorial Material
ID HUTCHINSON-GILFORD PROGERIA
AB Hutchinson-Gilford progeria syndrome (progeria) is an extremely rare premature aging disease with a population prevalence of 1 in 20 million. Nevertheless, propelled by the discovery of a causal mutation in the lamin A/C gene (LMNA) (De Sandre-Giovannoli et al, 2003; Eriksson et al, 2003) and strong patient advocacy (Gordon & Gordon, 2014), progeria has rapidly become a vibrant field of study, attracting a wide range of researchers from basic cell biologists to clinicians.
C1 [Gordon, Leslie B.; Kleinman, Monica E.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
[Gordon, Leslie B.; Kleinman, Monica E.] Harvard Med Sch, Boston, MA 02115 USA.
[Gordon, Leslie B.] Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Providence, RI 02912 USA.
[Gordon, Leslie B.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Kieran, Mark W.] Dana Farber Canc Inst, Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA 02115 USA.
[Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
RP Gordon, LB (reprint author), Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.; Gordon, LB (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Gordon, LB (reprint author), Brown Univ, Dept Pediat, Hasbro Childrens Hosp, Providence, RI 02912 USA.; Gordon, LB (reprint author), Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
EM leslie_gordon@brown.edu
NR 8
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1757-4676
EI 1757-4684
J9 EMBO MOL MED
JI EMBO Mol. Med.
PD JUL
PY 2016
VL 8
IS 7
BP 685
EP 687
DI 10.15252/emmm.201606280
PG 3
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DW4SC
UT WOS:000383632300001
PM 27234439
ER
PT J
AU Boikos, SA
Pappo, AS
Killian, JK
LaQuaglia, MP
Weldon, CB
George, S
Trent, JC
von Mehren, M
Wright, JA
Schiffman, JD
Raygada, M
Pacak, K
Meltzer, PS
Miettinen, MM
Stratakis, C
Janeway, KA
Helman, LJ
AF Boikos, Sosipatros A.
Pappo, Alberto S.
Killian, J. Keith
LaQuaglia, Michael P.
Weldon, Chris B.
George, Suzanne
Trent, Jonathan C.
von Mehren, Margaret
Wright, Jennifer A.
Schiffman, Josh D.
Raygada, Margarita
Pacak, Karel
Meltzer, Paul S.
Miettinen, Markku M.
Stratakis, Constantine
Janeway, Katherine A.
Helman, Lee J.
TI Molecular Subtypes of KIT/PDGFRA Wild-Type Gastrointestinal Stromal
Tumors A Report From the National Institutes of Health Gastrointestinal
Stromal Tumor Clinic
SO JAMA ONCOLOGY
LA English
DT Article
ID SUCCINATE-DEHYDROGENASE; GERMLINE MUTATIONS; IDH2 MUTATIONS; KIT;
PDGFRA; GENES; GIST; GENETICS; IMATINIB; CANCER
AB IMPORTANCE Wild-type (WT) gastrointestinal stromal tumors (GISTs), which lack KIT and PDGFRA gene mutations, are the primary form of GIST in children and occasionally occur in adults. They respond poorly to standard targeted therapy. Better molecular and clinical characterization could improve management.
OBJECTIVE To evaluate the clinical and tumor genomic features of WT GIST.
DESIGN, SETTING, AND PARTICIPANTS Patients enrolled in an observational study at the National Institutes of Health starting in 2008 and were evaluated in a GIST clinic held once or twice yearly. Patients provided access to existing medical records and tumor specimens. Self-referred or physician-referred patients younger than 19 years with GIST or 19 years or older with known WT GIST (no mutations in KIT or PDGFRA) were recruited; 116 patients with WT GIST were enrolled, and 95 had adequate tumor specimen available. Tumors were characterized by immunohistochemical analysis (IHC) for succinate dehydrogenase (SDH) subunit B, sequencing of SDH genes, and determination of SDHC promoter methylation. Testing of germline SDH genes was offered to consenting patients and families.
MAIN OUTCOMES AND MEASURES For classification, tumors were characterized by SDHA, B, C, or D (SDHX) mutations and other genetic and epigenetic alterations, including presence of mutations in germline. Clinical characteristics were categorized.
RESULTS Wild-type GIST specimens from 95 patients (median age, 23 [range, 7-78] years; 70% female) were classified into 3 molecular subtypes: SDH-competent (n = 11), defined by detection of SDHB by IHC; and 2 types of SDH-deficient GIST (n = 84). Of SDH-deficient tumors, 63 (67%) had SDH mutations, and in 31 of 38 (82%), the SDHX mutation was also present in germline. Twenty-one (22%) SDH-deficient tumors had methylation of the SDHC promoter leading to silencing of expression. Mutations in known cancer-associated pathways were identified in 9 of 11 SDH-competent tumors. Among patients with SDH-mutant tumors, 62% were female (39 of 63), median (range) age was 23 (7-58) years, and approximately 30% presented with metastases (liver [12 of 58], peritoneal [6 of 58], lymph node [15 of 23]). SDHC-epimutant tumors mostly affected young females (20 of 21; median [range] age, 15 [8-50] years), and approximately 40% presented with metastases (liver [7 of 19], peritoneal [1 of 19], lymph node [3 of 8]). SDH-deficient tumors occurred only in the stomach and had an indolent course.
CONCLUSIONS AND RELEVANCE An observational study of WT GIST permitted the evaluation of a large number of patients with this rare disease. Three molecular subtypes with implications for prognosis and clinical management were identified.
C1 [Boikos, Sosipatros A.; Helman, Lee J.] NCI, Pediat Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 31,Room 3A11, Bethesda, MD 20892 USA.
[Boikos, Sosipatros A.] Virginia Commonwealth Univ, Massey Canc Ctr, Sarcoma & Rare Tumors Program, Div Hematol Oncol & Palliat Care, Richmond, VA 23284 USA.
[Pappo, Alberto S.] St Jude Childrens Res Hosp, Dept Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Killian, J. Keith; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[LaQuaglia, Michael P.] Mem Sloan Kettering Canc Ctr, Pediat Surg Serv, 1275 York Ave, New York, NY 10021 USA.
[Weldon, Chris B.] Boston Childrens Hosp, Dept Surg, Boston, MA USA.
[George, Suzanne] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
[Trent, Jonathan C.] Univ Miami, Div Hematol Oncol, Dept Med, Sylvester Comprehens Canc Ctr, Miami, FL USA.
[von Mehren, Margaret] Fox Chase Canc Ctr, Div Hematol Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Wright, Jennifer A.; Schiffman, Josh D.] Huntsman Canc Inst, Pediat Hematol & Oncol, Salt Lake City, UT USA.
[Raygada, Margarita] Natl Inst Child Hlth & Human Dev, Div Intramural Res, Bethesda, MD USA.
[Pacak, Karel] Natl Inst Child Hlth & Human Dev, Sect Med Neuroendocrinol, Bethesda, MD USA.
[Miettinen, Markku M.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Stratakis, Constantine] NICHHD, Sect Endocrinol & Genet, Bethesda, MD 20892 USA.
[Janeway, Katherine A.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
RP Helman, LJ (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 31,Room 3A11, Bethesda, MD 20892 USA.
EM helmanl@nih.gov
FU intramural National Cancer Institute (NCI), National Institutes of
Health (NIH)
FX The study was funded by the intramural National Cancer Institute (NCI),
National Institutes of Health (NIH).
NR 33
TC 8
Z9 8
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD JUL
PY 2016
VL 2
IS 7
BP 922
EP 928
DI 10.1001/jamaoncol.2016.0256
PG 7
WC Oncology
SC Oncology
GA DW5RK
UT WOS:000383704300016
PM 27011036
ER
PT J
AU Piotrowska, Z
Sequist, LV
AF Piotrowska, Zofia
Sequist, Lecia V.
TI Treatment of EGFR-Mutant Lung Cancers After Progression in Patients
Receiving First-Line EGFR Tyrosine Kinase Inhibitors A Review
SO JAMA ONCOLOGY
LA English
DT Review
ID RANDOMIZED PHASE-3 TRIAL; ACQUIRED-RESISTANCE; OPEN-LABEL;
NSCLC-PATIENTS; MET AMPLIFICATION; TARGETED THERAPY; T790M MUTATION;
ASIAN PATIENTS; NEVER-SMOKERS; TKI THERAPY
AB IMPORTANCE Patients with EGFR-mutant lung cancer benefit from treatment with EGFR inhibitors such as erlotinib, gefitinib, and afatinib, but outcomes are limited by the eventual development of resistance to these agents. Over half of patients acquire a secondary T790M mutation in EGFR at the time of progression and a substantial minority develops resistance through other mechanisms. Multiple treatment strategies are now available to patients whose disease has progressed on their initial EGFR inhibitor, including therapies targeting both T790M, and non-T790M-mediated resistance.
OBSERVATIONS This review summarizes information about and current treatment strategies for patients with EGFR-mutant lung cancer whose disease progresses on their initial EGFR inhibitor, including those with T790M and other types of acquired resistance. Postprogression therapy should be tailored based on identified resistance mechanisms, sites, and pace of disease progression, and patient preference. Biopsy and genotyping of resistant tissue or plasma are essential to identifying resistance mechanisms and selecting the most appropriate treatment when patients' disease progresses during treatment with an initial EGFR inhibitor. Third-generation EGFR inhibitors are generally preferred for patients with T790M-positive resistance, whereas standard chemotherapy and clinical trials are preferred for those without T790M. For select patients, treatment can be continued beyond progression and local ablative therapies can be used to target sites of oligoprogression.
CONCLUSIONS AND RELEVANCE Treatment for patients who progress on their initial EGFR inhibitor should be tailored to identified resistance mechanisms and sites of progression. Emerging reports about resistance to third-generation EGFR inhibitors will lay the groundwork for overcoming the next generation of resistance, and further research is needed to develop more effective therapies.
C1 [Piotrowska, Zofia; Sequist, Lecia V.] Harvard Med Sch, Boston, MA USA.
[Piotrowska, Zofia; Sequist, Lecia V.] Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
RP Piotrowska, Z (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM zpiotrowska@partners.org
NR 61
TC 2
Z9 2
U1 3
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD JUL
PY 2016
VL 2
IS 7
BP 948
EP 954
DI 10.1001/jamaoncol.2016.0333
PG 7
WC Oncology
SC Oncology
GA DW5RK
UT WOS:000383704300020
PM 27196961
ER
PT J
AU Shimizu, M
Joyashiki, E
Noda, H
Watanabe, T
Okazaki, M
Nagayasu, M
Adachi, K
Tamura, T
Potts, JT
Gardella, TJ
Kawabe, Y
AF Shimizu, Masaru
Joyashiki, Eri
Noda, Hiroshi
Watanabe, Tomoyuki
Okazaki, Makoto
Nagayasu, Miho
Adachi, Kenji
Tamura, Tatsuya
Potts, John T., Jr.
Gardella, Thomas J.
Kawabe, Yoshiki
TI Pharmacodynamic Actions of a Long-Acting PTH Analog (LA-PTH) in
Thyroparathyroidectomized (TPTX) Rats and Normal Monkeys
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE HYPOPARATHYROIDISM; LONG-ACTING PTH ANALOG; PTH RECEPTOR; HORMONE
REPLACEMENT THERAPY; THYROPARATHYROIDECTOMIZED RATS; CALCIUM HOMEOSTASIS
ID PARATHYROID-HORMONE RECEPTOR; RANDOMIZED CROSSOVER TRIAL; REPLACEMENT
THERAPY; FOLLOW-UP; HYPOPARATHYROIDISM; CONFORMATIONS; SELECTIVITY;
GENERATION; EFFICACY; BINDING
AB Hypoparathyroidism is a disease of chronic hypocalcemia and hyperphosphatemia due to a deficiency of parathyroid hormone (PTH). PTH and analogs of the hormone are of interest as potential therapies. Accordingly, we examined the pharmacological properties of a long-acting PTH analog, [Ala1,3,12,18,22, Gln10, Arg11, Trp14, Lys26]-PTH(1-14)/ PTHrP(15-36) (LA-PTH) in thyroparathyroidectomized (TPTX) rats, a model of HP, as well as in normal monkeys. In TPTX rats, a single intravenous administration of LA-PTH at a dose of 0.9 nmol/kg increased serum calcium (sCa) and decreased serum phosphate (sPi) to near-normal levels for longer than 48 hours, whereas PTH(1-34) and PTH(1-84), each injected at a dose 80-fold higher than that used for LA-PTH, increased sCa and decreased sPi only modestly and transiently (< 6 hours). LA-PTH also exhibited enhanced and prolonged efficacy versus PTH(1-34) and PTH(1-84) for elevating sCa when administered subcutaneously (s.c.) into monkeys. Daily s.c. administration of LA-PTH (1.8 nmol/kg) into TPTX rats for 28 days elevated sCa to near normal levels without causing hypercalciuria or increasing bone resorption markers, a desirable goal in the treatment of hypoparathyroidism. The results are supportive of further study of long-acting PTH analogs as potential therapies for patients with hypoparathyroidism. (C) 2016 American Society for Bone and Mineral Research.
C1 [Shimizu, Masaru; Joyashiki, Eri; Noda, Hiroshi; Watanabe, Tomoyuki; Okazaki, Makoto; Nagayasu, Miho; Adachi, Kenji; Tamura, Tatsuya; Kawabe, Yoshiki] Chugai Pharmaceut Co Ltd, Div Res, 1-135 Komakado, Shizuoka, Japan.
[Watanabe, Tomoyuki; Potts, John T., Jr.; Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
RP Shimizu, M (reprint author), Chugai Pharmaceut Co Ltd, Div Res, 1-135 Komakado, Shizuoka, Japan.
EM shimizumsr@chugai-pharm.co.jp
FU Chugai Pharmaceutical Co., Ltd.; NIH grant NIDDK [11794, AR066261]
FX This work was supported by Chugai Pharmaceutical Co., Ltd.; and was
partially supported by NIH grant NIDDK 11794 (to TJG and JTP), and
AR066261 (to TJG). We thank the staff of Chugai Research Institute for
Medical Science, Inc., for the technical assistance of in vivo studies.
NR 30
TC 4
Z9 4
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD JUL
PY 2016
VL 31
IS 7
BP 1405
EP 1412
DI 10.1002/jbmr.2811
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DW5VP
UT WOS:000383715800009
PM 26865415
ER
PT J
AU Petrillo, LA
Ritchie, CS
AF Petrillo, Laura A.
Ritchie, Christine S.
TI The challenges of symptom management for patients with multimorbidity in
research and practice: A thematic review
SO PROGRESS IN PALLIATIVE CARE
LA English
DT Review
DE Multimorbidity; Symptom management; Palliative care
ID MULTIPLE CHRONIC CONDITIONS; QUALITY-OF-LIFE; OLDER-ADULTS; PALLIATIVE
CARE; PHYSICAL FUNCTION; COMORBIDITY; PREVALENCE
AB Introduction: Multimorbidity, the presence of multiple coexisting diseases or conditions, afflicts the majority of older adults, and is associated with increased mortality and healthcare utilization. In addition, multimorbidity negatively impacts quality of life and increases symptom burden. Yet, there is a dearth of evidence on how to best manage symptoms in patients with multimorbidity.
Methods: We conducted a thematic review of approaches to symptom management in multimorbidity.
Results: Research in this area has been hampered by inconsistent definitions of multimorbidity and challenges in outcome measurement. Investigations of symptom management strategies in specific disease states, like cancer, typically exclude medically complex patients. In the absence of evidence, the American Geriatrics Society's recommendations for the care of adults with multimorbidity provide a useful starting point for clinicians. We present a case to demonstrate how the AGS recommendations can be tailored to the situation of symptom management in patients with multimorbidity. We also present suggestions for future research directions.
Discussion: Multimorbidity is an incredibly common and overlooked problem in our healthcare system, and only stands to increase in relevance as patients live longer and have the opportunity to accrue a greater burden of chronic illness. A comprehensive approach to patients with multimorbidity includes focusing on patient preferences, carefully interpreting the available evidence (including both the benefits and potential harms), and thinking critically about the burden of any treatment. Taking time to elicit patient goals and preferences, and apprise patients of their prognosis if they want to know, are especially important in symptom management discussions with patients with multimorbidity.
C1 [Petrillo, Laura A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
[Ritchie, Christine S.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
RP Petrillo, LA (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA.
EM laura.petrillo@ucsf.edu
NR 37
TC 0
Z9 0
U1 2
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 0969-9260
EI 1743-291X
J9 PROG PALLIAT CARE
JI Prog. Palliat. Care
PD JUL
PY 2016
VL 24
IS 5
BP 262
EP 267
DI 10.1080/09699260.2016.1192320
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DW4AE
UT WOS:000383583400002
ER
PT J
AU Rong, SS
Chen, LJ
Pang, CP
AF Rong, Shi Song
Chen, Li Jia
Pang, Chi Pui
TI Myopia Genetics-The Asia-Pacific Perspective
SO ASIA-PACIFIC JOURNAL OF OPHTHALMOLOGY
LA English
DT Review
DE myopia; refractive error; gene; genetics; ethnicity
ID GENOME-WIDE ASSOCIATION; HIGH-GRADE MYOPIA; STATIONARY NIGHT BLINDNESS;
RECESSIVE HIGH MYOPIA; DOMINANT HIGH MYOPIA; HAN CHINESE POPULATION;
TIME SPENT OUTDOORS; CHILDRENS EYE SIZE; REFRACTIVE ERROR;
SUSCEPTIBILITY LOCUS
AB Myopia is a major cause of visual impairment worldwide. In particular, high myopia is associated with serious blinding complications, including retinal detachment, chorioretinal degeneration, and choroidal neovascularization. Myopia is multifactorial in etiology, resulting from the interaction of environmental and genetic risk factors. During the past 2 decades, a large number of gene loci and variants have been identified for myopia. There are more than 20 myopia-associated loci spanning all chromosomes. Earlier findings were obtained mainly from family linkage analyses and candidate gene studies, and more recent results are principally from genome-wide association studies and exome sequencing. Some genetic associations have been successfully validated and replicated in populations of different geographic localities and ethnicities, but some have not. Compared with Whites, Asian populations-in particular Japanese, Korean, and Chinese-have a much higher prevalence of myopia, especially high myopia. Both genetic and environmental factors contribute to such ethnic variations. This review attempts to summarize and compare the allelic frequencies of gene variants known to be associated with myopia in different ethnic groups, especially in the Asia-Pacific region.
C1 [Rong, Shi Song; Chen, Li Jia; Pang, Chi Pui] Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147 K Argyle St, Kowloon, Hong Kong, Peoples R China.
[Rong, Shi Song] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA.
RP Pang, CP (reprint author), Chinese Univ Hong Kong, Hong Kong Eye Hosp, Dept Ophthalmol & Visual Sci, 147 K Argyle St, Kowloon, Hong Kong, Peoples R China.
EM cppang@cuhk.edu.hk
NR 105
TC 2
Z9 3
U1 7
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2162-0989
J9 ASIA-PAC J OPHTHALMO
JI Asia-Pac. J. Ophthalmol.
PD JUL-AUG
PY 2016
VL 5
IS 4
BP 236
EP 244
DI 10.1097/APO.0000000000000224
PG 9
WC Ophthalmology
SC Ophthalmology
GA ED6NQ
UT WOS:000388972700004
PM 27488065
ER
PT J
AU Mihos, CG
Pineda, AM
Horvath, SA
Santana, O
AF Mihos, Christos G.
Pineda, Andres M.
Horvath, Sofia A.
Santana, Orlando
TI Anterior Mitral Leaflet Augmentation for Ischemic Mitral Regurgitation
Performed Via a Right Thoracotomy Approach
SO INNOVATIONS-TECHNOLOGY AND TECHNIQUES IN CARDIOTHORACIC AND VASCULAR
SURGERY
LA English
DT Article
DE Anterior leaflet augmentation; Functional mitral regurgitation; Ischemic
cardiomyopathy; Ischemic mitral regurgitation; Pericardial patch
ID VALVE SURGERY; DYSFUNCTION; DISEASE
AB Ischemic mitral regurgitation (MR) after myocardial infarction is associated with poor long-term survival, and the optimal treatment strategy remains debated. The most common repair technique used is a restrictive annuloplasty. However, up to 15% to 30% of patients experience recurrent MR owing to progressive left ventricular remodeling and geometric distortion of the mitral valve apparatus. Anterior mitral leaflet augmentation using a pericardial patch, in combination with a true-sized mitral annuloplasty, has been proposed as an adjunctive technique to increase the durability of valve repair for ischemic MR. Herein, we describe 2 cases of anterior mitral leaflet augmentation with annuloplasty repair for severe ischemic MR via a minimally invasive right thoracotomy, and review the literature regarding patient selection and clinical outcomes of this technique.
C1 [Mihos, Christos G.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02140 USA.
[Pineda, Andres M.; Horvath, Sofia A.; Santana, Orlando] Columbia Univ, Div Cardiol, Mt Sinai Heart Inst, Miami Beach, FL USA.
RP Mihos, CG (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02140 USA.
EM cmihos@mgh.harvard.edu
NR 16
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1556-9845
EI 1559-0879
J9 INNOVATIONS
JI Innovations
PD JUL-AUG
PY 2016
VL 11
IS 4
BP 298
EP 300
PG 3
WC Surgery
SC Surgery
GA ED6CQ
UT WOS:000388942800013
PM 27612148
ER
PT J
AU Yeomans, PD
Ross, RJ
AF Yeomans, Peter D.
Ross, Richard J.
TI Removing Barriers in the Assessment of Combat-Related Post-traumatic
Stress Disorder
SO MILITARY MEDICINE
LA English
DT Editorial Material
ID VETERANS
AB While the Veterans Health Administration continues to treat Vietnam War Veterans, approximately two million service men and women have returned from Iraq and Afghanistan. However, our treatments can only be as effective as the quality of our clinical assessment. Disclosure of trauma is facilitated when the type of trauma is present in the sociocultural environment of patient and clinician. Topics that once were deemed too shameful for inquiry, specifically, childhood abuse, domestic violence, sexual abuse, and military sexual trauma are now part of a standard assessment. Similarly, the standard clinical assessment of combat Veterans should include specific queries that address the darkest underside of wartime experiences.
C1 [Yeomans, Peter D.; Ross, Richard J.] Philadelphia Vet Affairs Med, Behav Hlth Serv, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
[Ross, Richard J.] Univ Penn, Perelman Sch Med, Dept Psychiat, 3535 Market St, Philadelphia, PA 19104 USA.
RP Yeomans, PD (reprint author), Philadelphia Vet Affairs Med, Behav Hlth Serv, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
NR 8
TC 0
Z9 0
U1 1
U2 1
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2016
VL 181
IS 7
BP 625
EP 626
DI 10.7205/MILMED-D-15-00182
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW5LT
UT WOS:000383687400006
PM 27391614
ER
PT J
AU Heinz, AJ
Pennington, DL
Cohen, N
Schmeling, B
Lasher, BA
Schrodek, E
Batki, SL
AF Heinz, Adrienne J.
Pennington, David L.
Cohen, Nicole
Schmeling, Brandi
Lasher, Brooke A.
Schrodek, Emily
Batki, Steven L.
TI Relations Between Cognitive Functioning and Alcohol Use, Craving, and
Post-Traumatic Stress: An Examination Among Trauma-Exposed Military
Veterans With Alcohol Use Disorder
SO MILITARY MEDICINE
LA English
DT Article
ID SUBSTANCE USE DISORDERS; COMPULSIVE DRINKING SCALE; RANDOMIZED
CLINICAL-TRIAL; RISK TASK BART; EXECUTIVE FUNCTION; PREFRONTAL CORTEX;
PSYCHOMETRIC PROPERTIES; TREATMENT OUTCOMES; TREATMENT RESPONSE;
WORKING-MEMORY
AB Cognitive dysfunction is commonly observed among individuals with alcohol use disorder (AUD) and trauma exposure and is, in turn, associated with worse clinical outcomes. Accordingly, disruptions in cognitive functioning may be conceptualized as a trans-disease phenomenon representing a potential high-yield target for intervention. Less is known though about how different cognitive functions covary with alcohol use, craving, and post-traumatic stress symptom severity among trauma-exposed individuals with AUD. Sixty-eight male and female trauma-exposed military veterans with AUD, entering treatment trials to reduce alcohol use, completed measures assessing alcohol use and craving, post-traumatic stress symptom severity, and cognitive functioning. In multivariate models, after controlling for post-traumatic stress symptom severity, poorer learning and memory was associated with higher alcohol consumption and higher risk taking/impulsivity was associated with stronger preoccupations with alcohol and compulsions to drink. Alcohol consumption and craving, but not performance on cognitive tests, were positively associated with post-traumatic stress symptom severity. Findings suggest that interventions to strengthen cognitive functioning might be used as a preparatory step to augment treatments for AUD. Clinicians are encouraged to consider a standard assessment of cognitive functioning, in addition to post-traumatic stress symptom severity, in treatment planning and delivery for this vulnerable and high-risk population.
C1 [Heinz, Adrienne J.; Cohen, Nicole] Palo Alto Vet Affairs Hlth Care Syst, Ctr Innovat Implementat, Natl Ctr Posttraumat Stress Disorder, 795 Willow Rd, Menlo Pk, CA 94025 USA.
[Pennington, David L.; Lasher, Brooke A.; Schrodek, Emily; Batki, Steven L.] San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA.
[Pennington, David L.; Lasher, Brooke A.; Schrodek, Emily; Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, 500 Parnassus Ave, San Francisco, CA 94143 USA.
[Pennington, David L.] Northern Calif Inst Res & Educ, 4150 Clement St 151NC, San Francisco, CA 94121 USA.
[Schmeling, Brandi] Palo Alto Univ, 1791 Arastradero Rd, Palo Alto, CA 94304 USA.
RP Heinz, AJ (reprint author), Palo Alto Vet Affairs Hlth Care Syst, Ctr Innovat Implementat, Natl Ctr Posttraumat Stress Disorder, 795 Willow Rd, Menlo Pk, CA 94025 USA.
FU Department of Defense [W81XWH-05-2-0094, W81XWH-12-2-0137,
W81XWH-11-2-0245]; National Center for Research Resources; National
Center for Advancing Translational Sciences, National Institutes of
Health [UCSF-CTSI UL1 RR024131]; VA Rehabilitation Research and
Development (RR&D) Career Development Award-2 [1IK2RX001492-01A1]
FX This project was supported by Department of Defense W81XWH-05-2-0094,
W81XWH-12-2-0137, and W81XWH-11-2-0245 (SLB), the National Center for
Research Resources and the National Center for Advancing Translational
Sciences, National Institutes of Health UCSF-CTSI UL1 RR024131, which
were administered by the Northern California Institute for Research and
Education, and with resources of the Veterans Affairs Medical Center,
San Francisco, California. Support was also provided by a VA
Rehabilitation Research and Development (RR&D) Career Development
Award-2 (1IK2RX001492-01A1) granted to Dr. Heinz.
NR 97
TC 0
Z9 0
U1 10
U2 10
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2016
VL 181
IS 7
BP 663
EP 671
DI 10.7205/MILMED-D-15-00228
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW5LT
UT WOS:000383687400012
PM 27391620
ER
PT J
AU Edwards-Stewart, A
Smolenski, DJ
Reger, GM
Bush, N
Workman, DE
AF Edwards-Stewart, Amanda
Smolenski, Derek J.
Reger, Greg M.
Bush, Nigel
Workman, Don E.
TI An Analysis of Personal Technology Use by Service Members and Military
Behavioral Health Providers
SO MILITARY MEDICINE
LA English
DT Article
ID SMARTPHONE; SOLDIERS; IPHONE
AB Personal technology use is ubiquitous in the United States today and technology, in general, continues to change the face of health care. However, little is known about the personal technology use of military service members and the behavioral health care providers that treat them. This study reports the technology use of 1,101 active duty service members and 45 behavioral health care providers at a large military installation. Participants reported Internet usage; ownership of smartphones, tablets, and e-readers; usage of mobile applications (apps); and basic demographic information. Compared with providers, service members reported higher rates of smartphone ownership, were more likely to own Android smartphones than iPhones, and spent more time gaming. Both groups spent a comparable amount of time using social media. With the exception of gaming, however, differences between service members and providers were not statistically significant when demographics were matched and controlled. Among service members, younger respondents (18-34) were statistically more likely than older respondents (35-58) to own smartphones, spend time gaming, and engage in social media. Our findings can help inform provider's technology-based education and intervention of their patients and guide the development of new technologies to support the psychological health of service members.
C1 [Edwards-Stewart, Amanda; Smolenski, Derek J.; Bush, Nigel; Workman, Don E.] Natl Ctr Telehlth & Technol T2, 9933 West Hayes St, Tacoma, WA 98431 USA.
[Reger, Greg M.] VA Puget Sound, Dept Vet Affairs, 9600 Vet Dr, Tacoma, WA 98493 USA.
RP Edwards-Stewart, A (reprint author), Natl Ctr Telehlth & Technol T2, 9933 West Hayes St, Tacoma, WA 98431 USA.
NR 28
TC 1
Z9 1
U1 2
U2 2
PU ASSOC MILITARY SURG US
PI BETHESDA
PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA
SN 0026-4075
EI 1930-613X
J9 MIL MED
JI Milit. Med.
PD JUL
PY 2016
VL 181
IS 7
BP 701
EP 709
DI 10.7205/MILMED-D-15-00041
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW5LT
UT WOS:000383687400017
PM 27391625
ER
PT J
AU Athalye, PS
Sekeljic, NJ
Ilic, MM
Tonyushkin, AA
Notaros, BM
AF Athalye, Pranav S.
Sekeljic, Nada J.
Ilic, Milan M.
Tonyushkin, Alexey A.
Notaros, Branislav M.
TI Subject-loaded quadrifilar helical-antenna RF coil with high B-1(+)
field uniformity and large FOV for 3-T MRI
SO CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING
LA English
DT Article
DE B-1(+) field uniformity; high-field 3-T MRI systems; magnetic resonance
imaging (MRI); quadrifilar helical-antenna coil; RF body coils
ID COAXIAL WAVE-GUIDE; ULTRAHIGH FIELDS; HOMOGENEITY; EFFICIENCY; STRENGTH
AB A novel method for excitation of RF B-1 field in high-field (3-T) magnetic resonance imaging (MRI) systems using a subject-loaded quadrifilar helical antenna as an RF coil is proposed, evaluated, and demonstrated. Design, analysis, characterization, and evaluation of the novel coil when situated in a 3-T MRI bore and loaded with different phantoms are performed and cross-validated by extensive numerical simulations using multiple computational electromagnetics techniques. The results for the quadrifilar helical-antenna RF body coil show (a) strong field penetration in the entire phantoms; (b) excellent right-hand circular polarization (RCP); (c) high spatial uniformity of RCP RF magnetic field, B-1(+), throughout the phantoms; (d) large field of view (FOV); (e) good transmit efficiency; and (f) low local specific absorption rate (SAR). The examples show that the new RF coil provides substantially better B-1(+)-field uniformity and much larger FOV than any of the previously reported numerical and experimental results for the existing RF coil designs at 3 T in literature that enable comparison. In addition, helical RF body coils of different lengths can, for instance, easily provide an excellent RCP and highly uniform B-1(+)-field within the MRI maximum FOV length of 50cm, and even 100cm. The proposed MRI RF coil yields a remarkable improvement in the field uniformity in the longitudinal direction, for various phantoms, with comparable efficiency and SAR levels.
C1 [Athalye, Pranav S.; Sekeljic, Nada J.; Ilic, Milan M.; Notaros, Branislav M.] Colorado State Univ, Dept Elect & Comp Engn, Ft Collins, CO 80523 USA.
[Sekeljic, Nada J.] Intel Corp, Hillsboro, OR 97124 USA.
[Ilic, Milan M.] Univ Belgrade, Sch Elect Engn, Belgrade, Serbia.
[Tonyushkin, Alexey A.] Univ Massachusetts, Dept Phys, Boston, MA 02125 USA.
[Tonyushkin, Alexey A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
RP Notaros, BM (reprint author), Colorado State Univ, Dept Elect & Comp Engn, Ft Collins, CO 80523 USA.
EM notaros@colostate.edu
FU National Science Foundation [ECCS-1307863]; Serbian Ministry of
Education, Science, and Technological Development [TR-32005]
FX This work was supported by the National Science Foundation under grant
ECCS-1307863 and by the Serbian Ministry of Education, Science, and
Technological Development under grant TR-32005.
NR 39
TC 0
Z9 0
U1 7
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-5031
EI 1552-504X
J9 CONCEPT MAGN RESON B
JI Concepts Magn. Reson. Part B
PD JUL
PY 2016
VL 46
IS 3
BP 106
EP 117
DI 10.1002/cmr.b.21326
PG 12
WC Chemistry, Physical; Instruments & Instrumentation; Physics, Atomic,
Molecular & Chemical; Spectroscopy
SC Chemistry; Instruments & Instrumentation; Physics; Spectroscopy
GA EC0GP
UT WOS:000387777500001
ER
PT J
AU Ponte, PR
Somerville, JG
Adams, JM
AF Ponte, Patricia Reid
Somerville, Jackie G.
Adams, Jeffrey M.
TI Assuring the Capture of Standardized Nursing Data: A Call to Action for
Chief Nursing Officers
SO INTERNATIONAL JOURNAL OF NURSING KNOWLEDGE
LA English
DT Editorial Material
C1 [Ponte, Patricia Reid] Dana Farber Canc Inst, Patient Care Serv DFCI, Boston, MA 02115 USA.
[Ponte, Patricia Reid] Dana Farber Canc Inst, Oncol Nursing & Clin Serv BWH, Boston, MA 02115 USA.
[Somerville, Jackie G.] Brigham & Womens Hosp, Patient Care Serv, 75 Francis St, Boston, MA 02115 USA.
[Adams, Jeffrey M.] Workforce Outcomes Res & Leadership Dev Inst WORL, Boston, MA USA.
[Adams, Jeffrey M.] Robert Wood Johnson Fdn, AONE ASU Interprofess Fellowship Innovat Hlth Lea, Princeton, NJ 08543 USA.
RP Adams, JM (reprint author), Workforce Outcomes Res & Leadership Dev Inst WORL, Boston, MA USA.; Adams, JM (reprint author), Robert Wood Johnson Fdn, AONE ASU Interprofess Fellowship Innovat Hlth Lea, Princeton, NJ 08543 USA.
EM jeffrey.m.adams@asu.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-3087
EI 2047-3095
J9 INT J NURS KNOWL
JI Int. J. Nurs. Knowl.
PD JUL
PY 2016
VL 27
IS 3
BP 127
EP 128
DI 10.1111/2047-3095.12136
PG 2
WC Nursing
SC Nursing
GA EC7IP
UT WOS:000388310800001
ER
PT J
AU Christakopoulos, GE
Karmpaliotis, D
Alaswad, K
Yeh, RW
Jaffer, FA
Wyman, RM
Lombardi, W
Grantham, JA
Kandzari, DA
Lembo, N
Moses, JW
Kirtane, A
Parikh, M
Green, P
Finn, M
Garcia, S
Doing, A
Patel, M
Bahadorani, J
Christopoulos, G
Karatasakis, A
Thompson, CA
Banerjee, S
Brilakis, ES
AF Christakopoulos, Georgios E.
Karmpaliotis, Dimitri
Alaswad, Khaldoon
Yeh, Robert W.
Jaffer, Farouc A.
Wyman, R. Michael
Lombardi, William
Grantham, J. Aaron
Kandzari, David A.
Lembo, Nicholas
Moses, Jeffrey W.
Kirtane, Ajay
Parikh, Manish
Green, Philip
Finn, Matthew
Garcia, Santiago
Doing, Anthony
Patel, Mitul
Bahadorani, John
Christopoulos, Georgios
Karatasakis, Aris
Thompson, Craig A.
Banerjee, Subhash
Brilakis, Emmanouil S.
TI Contrast Utilization During Chronic Total Occlusion Percutaneous
Coronary Intervention: Insights From a Contemporary Multicenter Registry
SO JOURNAL OF INVASIVE CARDIOLOGY
LA English
DT Article
DE percutaneous coronary intervention; chronic total occlusion; contrast
volume; radiation; complications; air kerma; fluoroscopy
ID IN-STENT RESTENOSIS; ACUTE-RENAL-FAILURE; INDUCED NEPHROPATHY; US
REGISTRY; HYBRID APPROACH; PROCEDURAL OUTCOMES; SUCCESS; SCORE;
VALIDATION; PREVENTION
AB Background. Administration of a large amount of contrast volume during chronic total occlusion (CTO) percutaneous coronary intervention (PCI) may lead to contrast-induced nephropathy. Methods. We examined the association of clinical, angiographic and procedural variables with contrast volume administered during 1330 CTO-PCI procedures performed at 12 experienced United States centers. Results. Technical and procedural success was 90% and 88%, respectively, and mean contrast volume was 289 +/- 138 mL. Approximately 33% of patients received >320 mL of contrast (high contrast utilization group). On univariable analysis, male gender (P=.01), smoking (P=.01), prior coronary artery bypass graft surgery (P=.04), moderate or severe calcification (P=.01), moderate or severe tortuosity (P=.04), proximal cap ambiguity (P=.01), distal cap at a bifurcation (P<.001), side branch at the proximal cap (P<.001), blunt/no stump (P=.01), occlusion length (P<.001), higher J-CTO score (P=.02), use of antegrade dissection and reentry or retrograde approach (P<.001), ad hoc CTO-PCI (P=.04), dual arterial access (P<.001), and 8 Fr guide catheters (P<.001) were associated with higher contrast volume; conversely, diabetes mellitus (P=.01) and in-stent restenosis (P=.01) were associated with lower contrast volume. On multivariable analysis, moderate/severe calcification (P=.04), distal cap at a bifurcation (P<.001), ad hoc CTO-PCI (P<.001), dual arterial access (P=.01), 8 Fr guide catheters (P=.02), and use of antegrade dissection/reentry or the retrograde approach (P<.001) were independently associated with higher contrast use, whereas diabetes (P=.02), larger target vessel diameter (P=.03), and presence of "interventional" collaterals (P<.001) were associated with lower contrast utilization. Conclusions. Several baseline clinical, angiographic, and procedural characteristics are associated with higher contrast volume administration during CTO-PCI.
C1 [Christakopoulos, Georgios E.; Christopoulos, Georgios; Karatasakis, Aris; Banerjee, Subhash; Brilakis, Emmanouil S.] VA North Texas Healthcare Syst, Dallas, TX USA.
[Christakopoulos, Georgios E.; Christopoulos, Georgios; Karatasakis, Aris; Banerjee, Subhash; Brilakis, Emmanouil S.] UT Southwestern Med Ctr, Dallas, TX USA.
[Karmpaliotis, Dimitri; Moses, Jeffrey W.; Kirtane, Ajay; Parikh, Manish; Green, Philip; Finn, Matthew] Columbia Univ, New York, NY USA.
[Alaswad, Khaldoon] Henry Ford Hosp, Detroit, MI 48202 USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Yeh, Robert W.] Harvard Med Sch, Boston, MA USA.
[Jaffer, Farouc A.; Wyman, R. Michael] Torrance Mem Med Ctr, Torrance, CA USA.
[Lombardi, William] Univ Washington, Seattle, WA 98195 USA.
[Grantham, J. Aaron] Mid Amer Heart Inst, Kansas City, MO USA.
[Kandzari, David A.; Lembo, Nicholas] Piedmt Heart Inst, Atlanta, GA USA.
[Garcia, Santiago] Minneapolis VA Healthcare Syst, Minneapolis, MN USA.
[Garcia, Santiago] Univ Minnesota, Minneapolis, MN USA.
[Doing, Anthony] Med Ctr Rockies, Loveland, CO USA.
[Patel, Mitul; Bahadorani, John] VA San Diego Healthcare Syst, San Diego, CA USA.
[Patel, Mitul; Bahadorani, John] Univ Calif San Diego, San Diego, CA 92103 USA.
[Thompson, Craig A.] Boston Sci, Natick, MA USA.
RP Brilakis, ES (reprint author), Dallas VA Med Ctr 111A, 4500 South Lancaster Rd, Dallas, TX 75216 USA.
EM esbrilakis@gmail.com
FU National Center for Advancing Translational Sciences of the National
Institutes of Health [UL1TR001105]
FX Research reported in this publication was supported by the National
Center for Advancing Translational Sciences of the National Institutes
of Health under award number UL1TR001105. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH.
NR 33
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U2 1
PU H M P COMMUNICATIONS
PI MALVERN
PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA
SN 1042-3931
EI 1557-2501
J9 J INVASIVE CARDIOL
JI J. Invasive Cardiol.
PD JUL
PY 2016
VL 28
IS 7
BP 288
EP 294
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EC9EO
UT WOS:000388447300008
PM 27342206
ER
PT J
AU Lorsakul, A
El Fakhri, G
Worstell, W
Ouyang, JS
Rakvongthai, Y
Laine, AF
Li, QZ
AF Lorsakul, Auranuch
El Fakhri, Georges
Worstell, William
Ouyang, Jinsong
Rakvongthai, Yothin
Laine, Andrew F.
Li, Quanzheng
TI Numerical observer for atherosclerotic plaque classification in spectral
computed tomography
SO JOURNAL OF MEDICAL IMAGING
LA English
DT Article
DE numerical observer; channelized Hotelling observer; spectral computed
tomography; classification task; plaque imaging; image quality
assessment
ID DUAL-ENERGY CT; LESION DETECTION; IMAGE QUALITY; CAROTID
ATHEROSCLEROSIS; DETECTION PERFORMANCE; GOLD NANOPARTICLES;
HOTELLING-OBSERVER; DATA SETS; IN-VIVO; CORONARY
AB Spectral computed tomography (SCT) generates better image quality than conventional computed tomography (CT). It has overcome several limitations for imaging atherosclerotic plaque. However, the literature evaluating the performance of SCT based on objective image assessment is very limited for the task of discriminating plaques. We developed a numerical-observer method and used it to assess performance on discrimination vulnerable-plaque features and compared the performance among multienergy CT (MECT), dual-energy CT (DECT), and conventional CT methods. Our numerical observer was designed to incorporate all spectral information and comprised two-processing stages. First, each energy-window domain was preprocessed by a set of localized channelized Hotelling observers (CHO). In this step, the spectral image in each energy bin was decorrelated using localized prewhitening and matched filtering with a set of Laguerre-Gaussian channel functions. Second, the series of the intermediate scores computed from all the CHOs were integrated by a Hotelling observer with an additional prewhitening and matched filter. The overall signal-to-noise ratio (SNR) and the area under the receiver operating characteristic curve (AUC) were obtained, yielding an overall discrimination performance metric. The performance of our new observer was evaluated for the particular binary classification task of differentiating between alternative plaque characterizations in carotid arteries. A clinically realistic model of signal variability was also included in our simulation of the discrimination tasks. The inclusion of signal variation is a key to applying the proposed observer method to spectral CT data. Hence, the task-based approaches based on the signal-known-exactly/background-known-exactly (SKE/BKE) framework and the clinical-relevant signal-known-statistically/background-known-exactly (SKS/BKE) framework were applied for analytical computation of figures of merit (FOM). Simulated data of a carotid-atherosclerosis patient were used to validate our methods. We used an extended cardiac-torso anthropomorphic digital phantom and three simulated plaque types (i.e., calcified plaque, fatty-mixed plaque, and iodine-mixed blood). The images were reconstructed using a standard filtered backprojection (FBP) algorithm for all the acquisition methods and were applied to perform two different discrimination tasks of: (1) calcified plaque versus fatty-mixed plaque and (2) calcified plaque versus iodine-mixed blood. MECT outperformed DECT and conventional CT systems for all cases of the SKE/BKE and SKS/BKE tasks (all p < 0.01). On average of signal variability, MECT yielded the SNR improvements over other acquisition methods in the range of 46.8% to 65.3% (all p < 0.01) for FBP-Ramp images and 53.2% to 67.7% (all p < 0.01) for FBP-Hanning images for both identification tasks. This proposed numerical observer combined with our signal variability framework is promising for assessing material characterization obtained through the additional energy-dependent attenuation information of SCT. These methods can be further extended to other clinical tasks such as kidney or urinary stone identification applications. (C) 2016 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Lorsakul, Auranuch; El Fakhri, Georges; Ouyang, Jinsong; Rakvongthai, Yothin; Li, Quanzheng] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Gordon Ctr Med Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA.
[Lorsakul, Auranuch; Laine, Andrew F.] Columbia Univ, Dept Biomed Engn, 1210 Amsterdam Ave, New York, NY 10027 USA.
[El Fakhri, Georges; Ouyang, Jinsong; Li, Quanzheng] Harvard Med Sch, Dept Radiol, 25 Shattuck St, Boston, MA 02115 USA.
[Worstell, William] PhotoDiagnost Syst Inc, 85 Swanson Rd, Boxboro, MA 01719 USA.
[Rakvongthai, Yothin] Chulalongkorn Univ, Dept Radiol, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.
RP Li, QZ (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Gordon Ctr Med Imaging, 55 Fruit St,White 427, Boston, MA 02114 USA.; Li, QZ (reprint author), Harvard Med Sch, Dept Radiol, 25 Shattuck St, Boston, MA 02115 USA.
EM li.quanzheng@mgh.harvard.edu
NR 66
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U1 0
U2 0
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 2329-4302
EI 2329-4310
J9 J MED IMAGING
JI J. Med. Imaging
PD JUL-SEP
PY 2016
VL 3
IS 3
AR 035501
DI 10.1117/1.JMI.3.3.035501
PG 18
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EC6FO
UT WOS:000388232100013
ER
PT J
AU Shimada, SL
Allison, JJ
Rosen, AK
Feng, H
Houston, TK
AF Shimada, Stephanie L.
Allison, Jeroan J.
Rosen, Amy K.
Feng, Hua
Houston, Thomas K.
TI Sustained Use of Patient Portal Features and Improvements in Diabetes
Physiological Measures
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE personal health records; diabetes mellitus; type 2; self care; HbA1c;
cholesterol; LDL; blood pressure; veterans
ID PERSONAL HEALTH RECORDS; SHARED MEDICAL-RECORD; CROSS-SECTIONAL
ANALYSIS; ADHERENCE; SYSTEM; CARE; COMMUNICATION; MANAGEMENT
AB Background: Personal health records (PHRs) have the potential to improve patient self-management for chronic conditions such as diabetes. However, evidence is mixed as to whether there is an association between PHR use and improved health outcomes.
Objective: The aim of this study was to evaluate the association between sustained use of specific patient portal features (Web-based prescription refill and secure messaging-SM) and physiological measures important for the management of type 2 diabetes.
Methods: Using a retrospective cohort design, including Veterans with diabetes registered for the My Health e Vet patient portal who had not yet used the Web-based refill or SM features and who had at least one physiological measure (HbA1c, low-density lipoprotein (LDL) cholesterol, blood pressure) in 2009-2010 (baseline) that was above guideline recommendations (N=111,686), we assessed portal use between 2010 and 2014. We calculated the odds of achieving control of each measure by 2013 to 2014 (follow-up) by years of using each portal feature, adjusting for demographic and clinical characteristics associated with portal use.
Results: By 2013 to 2014, 34.13% (38,113/111,686) of the cohort was using Web-based refills, and 15.75% (17,592/111,686) of the cohort was using SM. Users were slightly younger (P<.001), less likely to be eligible for free care based on economic means (P<.001), and more likely to be women (P<.001). In models adjusting for both features, patients with uncontrolled HbA1c at baseline who used SM were significantly more likely than nonusers to achieve glycemic control by follow-up if they used SM for 2 years (odds ratio-OR=1.24, CI: 1.14-1.34) or 3 or more years (OR=1.28, CI: 1.12-1.45). However, there was no significant association between Web-based refill use and glycemic control. Those with uncontrolled blood pressure at baseline who used Web-based refills were significantly more likely than nonusers to achieve control at follow-up with 2 (OR=1.07, CI: 1.01-1.13) or 3 (OR=1.08, CI: 1.02-1.14) more years of Web-based refill use. Both features were significantly associated with improvements in LDL cholesterol levels at follow-up.
Conclusions: Although rates of use of the refill function were higher within the population, sustained SM use had a greater impact on HbA1c. Evaluations of patient portals should consider that individual components may have differential effects on health improvements.
C1 [Shimada, Stephanie L.; Feng, Hua; Houston, Thomas K.] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA.
[Shimada, Stephanie L.] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Boston, MA USA.
[Shimada, Stephanie L.; Allison, Jeroan J.; Feng, Hua; Houston, Thomas K.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Hlth Informat & Implementat Sci, Worcester, MA USA.
[Rosen, Amy K.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA.
[Rosen, Amy K.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA.
RP Shimada, SL (reprint author), Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA.
EM Stephanie.Shimada@va.gov
OI Shimada, Stephanie/0000-0002-6517-5122
FU Department of Veterans Affairs Health Services Research and Development
Service [CDA 10-210]; VA eHealth QUERI [EHQ 10-190]
FX Dr. Shimada was supported by a Career Development Award (CDA 10-210)
from the Department of Veterans Affairs Health Services Research and
Development Service and the VA eHealth QUERI (EHQ 10-190). The contents
do not represent the views of the US Department of Veterans Affairs or
the US Government.
NR 35
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U1 2
U2 2
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1438-8871
J9 J MED INTERNET RES
JI J. Med. Internet Res.
PD JUL
PY 2016
VL 18
IS 7
AR e179
DI 10.2196/jmir.5663
PG 13
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA EC9WS
UT WOS:000388495600017
PM 27369696
ER
PT J
AU Cauley, RP
Liao, EC
AF Cauley, Ryan P.
Liao, Eric C.
TI Deepithelialization and Extended Dermal Apposition: A Technique for
Closure of High-risk Incisions in Breast Reconstruction
SO PLASTIC AND RECONSTRUCTIVE SURGERY-GLOBAL OPEN
LA English
DT Editorial Material
C1 [Cauley, Ryan P.; Liao, Eric C.] Harvard Med Sch, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA USA.
RP Liao, EC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Surg & Genet, 15 Parkman St, Boston, MA 02114 USA.
EM cliao@partners.org
NR 5
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2169-7574
J9 PRS-GLOB OPEN
JI PRS-GLOB. OPEN
PD JUL
PY 2016
VL 4
IS 7
AR e802
DI 10.1097/GOX.0000000000000791
PG 2
WC Surgery
SC Surgery
GA EC7ZN
UT WOS:000388359800014
PM 27536481
ER
PT J
AU Kortlever, JTP
Janssen, SJ
Molleman, J
Hageman, MGJS
Ring, D
AF Kortlever, Joost T. P.
Janssen, Stein J.
Molleman, Jeroen
Hageman, Michiel G. J. S.
Ring, David
TI Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm
Pain
SO ARCHIVES OF BONE AND JOINT SURGERY-ABJS
LA English
DT Article
DE Arm; Discrete; Nonspecific; Pain; Pathophysiology
ID EXTREMITY MUSCULOSKELETAL DISORDERS; UPPER-LIMB DISORDERS; PSYCHOSOCIAL
FACTORS; GENERAL-POPULATION; CONTROLLED-TRIAL; FOREARM PAIN;
PRIMARY-CARE; RISK-FACTORS; FOLLOW-UP; PREVALENCE
AB Background: Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms?
Methods: We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain.
Results: There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms.
Conclusion: Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.
C1 [Kortlever, Joost T. P.; Janssen, Stein J.; Molleman, Jeroen; Hageman, Michiel G. J. S.; Ring, David] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, Austin, TX 78712 USA.
EM Dring@partners.org
NR 44
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U1 0
U2 0
PU MASHHAD UNIV MED SCIENCES
PI MASHHAD
PA VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 -
445, MASHHAD, 00000, IRAN
SN 2345-4644
EI 2345-461X
J9 ARCH BONE JT SURG-AB
JI Arch. Bone Jt. Surg.-ABJS
PD JUL
PY 2016
VL 4
IS 3
BP 213
EP 219
PG 7
WC Orthopedics
SC Orthopedics
GA EC4KU
UT WOS:000388098900003
PM 27517064
ER
PT J
AU ter Meulen, DP
Nota, SPFT
Hageman, MGJS
Ring, DC
AF ter Meulen, Dirk P.
Nota, Sjoerd P. F. T.
Hageman, Michiel G. J. S.
Ring, David C.
TI Progression of Heterotopic Ossification around the Elbow after Trauma
SO ARCHIVES OF BONE AND JOINT SURGERY-ABJS
LA English
DT Article
DE Disease progression; Elbow; Heterotopic; Injuries; Ossification
ID RADIATION-THERAPY; RISK-FACTORS
AB Background: This study addresses the null hypothesis that there is no expansion of heterotopic ossification (HO) in the elbow beyond what can be seen early on.
Methods: The area of HO was measured on lateral radiographs of 38 consecutive patients that had operative treatment of HO between 2000 and 2013. Measurements from radiographs obtained between 3 to 7 weeks were compared to measurements from radiographs made 3 months or more after injury.
Results: There was no significant difference between the average area of HO on the first (median 2.8 square centimeters, Q1: 1.5, Q3: 5.1) and later radiographs (median of 2.8 square centimeters, Q1: 1.4, Q3: 5.0) (P = 0.99).
Conclusion: According to our results the area of HO does not expand beyond what can be seen early in the disease process.
C1 [ter Meulen, Dirk P.; Nota, Sjoerd P. F. T.; Hageman, Michiel G. J. S.; Ring, David C.] Massachusetts Gen Hosp, Hand Surg Serv, Boston, MA 02114 USA.
RP Ring, DC (reprint author), 1400 Barbara Jordan Blvd 1-114, Austin, TX 78723 USA.
EM david.ring@austin.utexas.edu
NR 9
TC 0
Z9 0
U1 0
U2 0
PU MASHHAD UNIV MED SCIENCES
PI MASHHAD
PA VICE-CHANCELLOR FOR RES CTR OFF IJBMS, DANESHGAH ST, PO BOX 9138813944 -
445, MASHHAD, 00000, IRAN
SN 2345-4644
EI 2345-461X
J9 ARCH BONE JT SURG-AB
JI Arch. Bone Jt. Surg.-ABJS
PD JUL
PY 2016
VL 4
IS 3
BP 228
EP 230
PG 3
WC Orthopedics
SC Orthopedics
GA EC4KU
UT WOS:000388098900006
PM 27517067
ER
PT J
AU Hamilton, HK
Lilly, E
Arndt, KA
Dover, JS
AF Hamilton, Heather K.
Lilly, Evelyn
Arndt, Kenneth A.
Dover, Jeffrey S.
TI No Difference in Psychotropic Medication Use in Cosmetic and General
Dermatology Patients
SO JOURNAL OF DRUGS IN DERMATOLOGY
LA English
DT Article
ID PREVALENCE; DISORDERS; SURGERY
AB Background: Patients presenting for appearance-related concerns are often perceived as being more difficult (ie, more needy, more difficult to satisfy) than patients presenting for medical dermatologic problems. While the reasons for this perception are many, some hypothesize that this may be related to a higher rate of anxiety, depression, or body image issues among these patients.
Objective: To determine the prevalence of psychotropic medication use in cosmetic dermatology patients compared to the prevalence of such medication use in general dermatology patients.
Methods & Materials: The study was a retrospective chart review of female patients, 18 or older, new to a private practice. Exclusion criteria included dermatologic disorders with known psychosocial comorbidity. Psychotropic medication use was recorded.
Results:The percentage of subjects in the medical group (n=156) who reported using psychotropic medications was 22.2% compared to 26.8% in the cosmetic group (n=154; P=0.09).
Conclusion: The prevalence of psychotropic medication use among all dermatology patients in our practice was relatively high, but there was no statistically significant difference in the rate of psychotropic medication use in cosmetic dermatology patients compared to general dermatology patients.
C1 [Hamilton, Heather K.; Lilly, Evelyn; Arndt, Kenneth A.; Dover, Jeffrey S.] SkinCare Physicians, Chestnut Hill, MA 02467 USA.
[Hamilton, Heather K.; Lilly, Evelyn; Arndt, Kenneth A.; Dover, Jeffrey S.] Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA.
[Lilly, Evelyn] Harvard Med Sch, Boston, MA USA.
[Lilly, Evelyn] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Hamilton, HK (reprint author), SkinCare Physicians, Chestnut Hill, MA 02467 USA.; Hamilton, HK (reprint author), Yale Univ, Sch Med, 333 Cedar St, New Haven, CT 06520 USA.
EM heatheraklein@yahoo.com
NR 12
TC 0
Z9 0
U1 0
U2 0
PU JOURNAL OF DRUGS IN DERMATOLOGY
PI NEW YORK
PA 377 PARK AVE SOUTH, 6TH FLOOR, NEW YORK, NY 10016 USA
SN 1545-9616
J9 J DRUGS DERMATOL
JI J. Drugs Dermatol.
PD JUL
PY 2016
VL 15
IS 7
BP 858
EP 861
PG 4
WC Dermatology
SC Dermatology
GA EC2IQ
UT WOS:000387935800007
PM 27391636
ER
PT J
AU Maree, AO
Margey, RJ
Selzer, F
Bajrangee, A
Jneid, H
Marroquin, OC
Mulukutla, SR
Laskey, WK
Jacobs, AK
AF Maree, Andrew O.
Margey, Ronan J.
Selzer, Faith
Bajrangee, Amrit
Jneid, Hani
Marroquin, Oscar C.
Mulukutla, Suresh R.
Laskey, Warren K.
Jacobs, Alice K.
TI Renal insufficiency, bleeding and prescription of dischargemedication in
patients undergoing percutaneous coronary intervention in the National
Heart, Lung, and Blood Institute (NHLBI) Dynamic Registry
SO CARDIOVASCULAR REVASCULARIZATION MEDICINE
LA English
DT Article
DE Renal insufficiency; Percutaneous coronary intervention; Cardiovascular
medication; Antiplatelet
ID DRUG-ELUTING STENTS; CHRONIC KIDNEY-DISEASE; ST-SEGMENT ELEVATION;
GLOBAL REGISTRY; OUTCOMES; EVENTS; ERA; MORTALITY; GRACE
AB Aims: To establish the relationship between renal insufficiency, bleeding and prescription of cardiovascular medication.
Methods and results: This was a prospective, multi-center, cohort study of consecutive patients undergoing PCI during three NHLBI Dynamic Registry recruitment waves. Major and minor bleeding, access site bleeding and rates of prescription of cardiovascular medication at discharge were determined based on estimated glomerular filtration rate (eGFR). Renal insufficiency was an independent predictor of major adverse cardiovascular events (MACE). Bleeding events and access site bleeding requiring transfusion were significantly associated with degrees of renal insufficiency (p < 0.001). There was an incremental decline in prescription of cardiovascular medication at discharge proportionate to the degree of renal impairment (aspirin, thienopyridine, statin, coumadin (overall p < 0.001), beta blocker (overall p = 0.003), ACE inhibitor (overall p = 0.02). Bleeders were less likely to be discharged on a thienopyridine (95.4% versus 89.9% for bleeding, p < 0.001 and 95.3% versus 87.9% for access site bleeding, p= 0.005), but not aspirin (96.3% versus 96.2%, p= 0.97 and 96.3% versus 93.6%, p= 0.29 respectively). Failure to prescribe anti-platelet therapy at discharge was strongly associated with increased MACE at one year.
Conclusions: Renal insufficiency is associated with bleeding in patients undergoing PCI. Patients with renal insufficiency are less likely to receive recommended discharge pharmacotherapy. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Maree, Andrew O.; Jacobs, Alice K.] Boston Med Ctr, Div Cardiol, Boston, MA USA.
[Maree, Andrew O.; Jacobs, Alice K.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Margey, Ronan J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Margey, Ronan J.] Harvard Med Sch, Boston, MA USA.
[Selzer, Faith] Univ Pittsburgh, Div Cardiol, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Maree, Andrew O.; Bajrangee, Amrit] St James Hosp, Div Cardiol, Dublin, Ireland.
[Maree, Andrew O.; Bajrangee, Amrit] Trinity Coll Dublin, Dublin, Ireland.
[Jneid, Hani] Michael E DeBakey VA Med Ctr, Div Cardiol, Houston, TX USA.
[Jneid, Hani] Baylor Coll Med, Houston, TX 77030 USA.
[Marroquin, Oscar C.; Mulukutla, Suresh R.] Univ Pittsburgh, Med Ctr, Div Cardiol, Pittsburgh, PA 15260 USA.
[Laskey, Warren K.] Univ New Mexico, Sch Med, Div Cardiol, Albuquerque, NM 87131 USA.
RP Maree, AO (reprint author), St James Hosp, CREST Directorate, Div Cardiol, Dublin 8, Ireland.
EM andrew.maree@gmail.com
NR 14
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1553-8389
EI 1878-0938
J9 CARDIOVASC REVASCULA
JI Cardiovasc. Revascularization Med.
PD JUL-AUG
PY 2016
VL 17
IS 5
BP 302
EP 307
DI 10.1016/j.carrev.2016.03.002
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA9KS
UT WOS:000386963300003
PM 27053436
ER
PT J
AU Dallalzadeh, LO
Go, AS
Chang, YC
Borowsky, LH
Fang, MC
Singer, DE
AF Dallalzadeh, Liane O.
Go, Alan S.
Chang, Yuchiao
Borowsky, Leila H.
Fang, Margaret C.
Singer, Daniel E.
TI Stability of High-Quality Warfarin Anticoagulation in a Community-Based
Atrial Fibrillation Cohort: The Anticoagulation and Risk Factors in
Atrial Fibrillation (ATRIA) Study
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE anticoagulants; arrhythmia; embolism; prevention; risk factors
ID NORMALIZED RATIO CONTROL; STABLE INR CONTROL; STROKE PREVENTION; ORAL
ANTICOAGULANTS; RANDOMIZED-TRIALS; THERAPY; OUTCOMES; DABIGATRAN;
EDOXABAN; EFFICACY
AB Background-Warfarin reduces ischemic stroke risk in atrial fibrillation (AF) but increases bleeding risk. Novel anticoagulants challenge warfarin as stroke-preventive therapy for AF. They are available at fixed doses but are more costly. Warfarin anticoagulation at a time in therapeutic range (TTR) >= 70% is similarly as effective and safe as novel anticoagulants. It is unclear whether AF patients with TTR >= 70% will remain stably anticoagulated and avoid the need to switch to a novel anticoagulant. We assessed stability of warfarin anticoagulation in AF patients with an initial TTR >= 70%.
Methods and Results-Within the community-based Anticoagulation and Risk Factors in AF (ATRIA) cohort followed from 1996 to 2003, we identified 2841 new warfarin users who continued warfarin over 9 months. We excluded months 1 to 3 to achieve a stable dose. For the 987 patients with TTR >= 70% in an initial 6-month period (TTR1; months 4-9), we described the distribution of TTR2 (months 10-15) and assessed multivariable correlates of persistent TTR >= 70%. Of patients with TTR1 >= 70%, 57% persisted with TTR2 >= 70% and 16% deteriorated to TTR2 <50%. Only initial TTR1 >= 90% (adjusted odds ratio 1.47, 95% CI 1.07-2.01) independently predicted TTR2 >= 70%. Heart failure was moderately associated with marked deterioration (TTR2 <50%); adjusted odds ratio 1.45, 95% CI 1.00-2.10.
Conclusions-Nearly 60% of AF patients with high-quality TTR1 on warfarin maintained TTR >= 70% over the next 6 months. A minority deteriorated to very poor TTR. Patient features did not strongly predict TTR in the second 6-month period. Our analyses support watchful waiting for AF patients with initial high-quality warfarin anticoagulation before considering alternative anticoagulants.
C1 [Dallalzadeh, Liane O.; Chang, Yuchiao; Singer, Daniel E.] Harvard Med Sch, Boston, MA USA.
[Go, Alan S.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Go, Alan S.] Univ Calif San Francisco, Dept Med Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Fang, Margaret C.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA.
[Go, Alan S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
RP Singer, DE (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM desinger@mgh.harvard.edu
FU National Institute on Aging [R01 AG15478]; National Heart, Lung, and
Blood Institute [RC2HL101589, U19 HL091179]; Eliot B. and Edith C.
Shoolman Fund of the Massachusetts General Hospital (Boston, MA)
FX This study was supported by the National Institute on Aging (R01
AG15478), the National Heart, Lung, and Blood Institute (RC2HL101589 and
U19 HL091179) and the Eliot B. and Edith C. Shoolman Fund of the
Massachusetts General Hospital (Boston, MA). The funding sources had no
role in the design or conduct of the study; collection, management,
analysis, and interpretation of the data; or in preparation, review or
approval of the manuscript.
NR 37
TC 0
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e003482
DI 10.1161/JAHA.116.003482
PG 14
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800036
ER
PT J
AU Eisen, A
Ruff, CT
Braunwald, E
Nordio, F
Corbalan, R
Dalby, A
Dorobantu, M
Mercuri, M
Lanz, H
Rutman, H
Wiviott, SD
Antman, EM
Giugliano, RP
AF Eisen, Alon
Ruff, Christian T.
Braunwald, Eugene
Nordio, Francesco
Corbalan, Ramon
Dalby, Anthony
Dorobantu, Maria
Mercuri, Michele
Lanz, Hans
Rutman, Howard
Wiviott, Stephen D.
Antman, Elliott M.
Giugliano, Robert P.
TI Sudden Cardiac Death in Patients With Atrial Fibrillation: Insights From
the ENGAGE AF-TIMI 48 Trial
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE atrial fibrillation; sudden cardiac death
ID RISK STRATIFICATION; PREDICTING STROKE; COMPETING-RISK; DIGOXIN USE;
EPIDEMIOLOGY; WARFARIN; ASSOCIATION; VALIDATION; EDOXABAN; OUTCOMES
AB Background-Recent findings suggest that atrial fibrillation is associated with sudden cardiac death (SCD). We examined the incidence, characteristics, and factors associated with SCD in patients with atrial fibrillation.
Methods and Results-SCD was defined as witnessed death <= 60 minutes from the onset of new symptoms or unwitnessed death 1 to 24 hours after being observed alive, without another known cause of death. Predictors of SCD were examined using multivariate competing risks models. Over 2.8 years (median), 2349 patients died (40.5 per 1000 patient-years), of which 1668 (71%) were cardiovascular deaths. SCD was the most common cause of cardiovascular death (n=749; median age 73 years; 70.6% male). Most SCD events occurred out of hospital (92.8%) and without prior symptoms (66.0%). Predictors of SCD included low ejection fraction, heart failure, and prior myocardial infarction (P<0.001 for each). Additional significant baseline predictors of SCD, but not of other causes of death, included male sex, electrocardiographic left ventricular hypertrophy, higher heart rate, nonuse of beta blockers, and use of digitalis. The latter was associated with SCD in patients with or without heart failure (adjusted hazard ratio 1.55 [95% CI 1.29-1.86] and 1.56 [95% CI 1.14-2.11], respectively; P-interaction=0.73). The rate of SCD was numerically but not statistically lower with edoxaban (1.20% per year with lower dose edoxaban; 1.28% per year with higher dose edoxaban) compared with warfarin (1.40% per year).
Conclusion-SCD is the most common cause of cardiovascular death in patients with atrial fibrillation and has several distinct predictors, some of which are modifiable. These findings may be considered in planning research and treatment strategies for patients with atrial fibrillation.
C1 [Eisen, Alon; Ruff, Christian T.; Braunwald, Eugene; Nordio, Francesco; Wiviott, Stephen D.; Antman, Elliott M.; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, Boston, MA USA.
[Eisen, Alon; Ruff, Christian T.; Braunwald, Eugene; Nordio, Francesco; Wiviott, Stephen D.; Antman, Elliott M.; Giugliano, Robert P.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Corbalan, Ramon] Hosp Clin Pontificia Univ Catolica Chile, Santiago, Chile.
[Dalby, Anthony] Milpark Hosp, Johannesburg, South Africa.
[Dorobantu, Maria] Carol Davila Univ Med & Pharm, Emergency Clin Hosp, Bucharest, Romania.
[Mercuri, Michele; Lanz, Hans; Rutman, Howard] Daiichi Sankyo, Parsippany, NJ USA.
RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA.
EM rgiugliano@partners.org
FU AstraZeneca; Eisai; Intarcia; Johnson Johnson; Bristol Myers Squibb;
Merck amp; Co.; Daiichi Sankyo; Glaxo Smith Kline; Sanofi Aventis; Duke
University; Novartis; Amgen Daiichi Sankyo; Merck; Eli Lilly and
Company; Boehringer Ingelheim; Merck Co; Medicines Co.; Medscape; Bayer;
Menarini International; Sanofi; Boehringer Ingelheim Pharmaceuticals,
Inc; Sanofi-Aventis; Daiichi Sankyo Inc.; Daiichi Sankyo.; AngelMed;
Janssen Pharmaceuticals; Xoma; ICON Clinical Research; Boston Clinical
Research Institute; American College of Cardiology; Amgen;
Boehringer-Ingelheim; Bristol-Myers Squibb Company; CVS Caremark;
GlaxoSmithKline; Lexicon; Pfizer; Portola; St Jude Medical
FX Christian Ruff discloses consultant fees/honoraria: Boehringer
Ingelheim, Daiichi Sankyo; research/research grants: AstraZeneca, Eisai,
Intarcia. Eugene Braunwald discloses consultant fees/honoraria: Merck &
Co (no compensation), The Medicines Co., Medscape, Bayer, Daiichi
Sankyo, Menarini International, Sanofi, Novartis (uncompensated);
research/research grants: AstraZeneca, Johnson & Johnson, Bristol Myers
Squibb, Merck & amp; Co., Daiichi Sankyo, Glaxo Smith Kline, Sanofi
Aventis, Duke University and Novartis. Anthony Dalby discloses
consultant fees/honoraria: Boehringer Ingelheim Pharmaceuticals, Inc,
Sanofi-Aventis; speakers bureau: Bayer Healthcare Pharmaceuticals.
Michele Mercuri discloses salary: Daiichi Sankyo Inc. Hans Joachim Lanz
discloses salary: Daiichi Sankyo Inc. Howard Rutman discloses salary:
Daiichi Sankyo. Stephen Wiviott discloses consultant fees: AstraZeneca,
Bristol-Myers Squibb, Eisai, Arena Pharmaceuticals, Eli Lilly, Daiichi
Sankyo, Aegerion, AngelMed, Janssen Pharmaceuticals, Xoma, ICON Clinical
Research, and Boston Clinical Research Institute and grant support
through his institution from AstraZeneca, Bristol-Myers Squibb, Eisai,
Arena Pharmaceuticals, Merck, Eli Lilly, Daiichi Sankyo, and Sanofi.
Elliott Antman discloses research/research grants: AstraZeneca, Daiichi
Sankyo, Eli Lilly and Company. Robert Giugliano discloses consultant
fees/honoraria: American College of Cardiology, Amgen,
Boehringer-Ingelheim, Bristol-Myers Squibb Company, CVS Caremark,
Daiichi Sankyo, GlaxoSmithKline, Lexicon, Merck, Pfizer, Portola, St
Jude Medical; research/research grants: Amgen Daiichi Sankyo and Merck
to his institution. The remaining authors have no disclosures to report.
NR 26
TC 1
Z9 1
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e003735
DI 10.1161/JAHA.116.003735
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800059
ER
PT J
AU Guo, FJ
Garvey, WT
AF Guo, Fangjian
Garvey, W. Timothy
TI Trends in Cardiovascular Health Metrics in Obese Adults: National Health
and Nutrition Examination Survey (NHANES), 1988-2014
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE blood pressure; glucose; lipids; obesity; risk factor
ID BODY-MASS INDEX; WEIGHT-LOSS THERAPY; METABOLIC SYNDROME;
INSULIN-RESISTANCE; UNITED-STATES; US ADULTS; MYOCARDIAL-INFARCTION;
DISEASE RISK; PREVALENCE; OVERWEIGHT
AB Background-No study has quantified trends in the prevalence of cardiovascular disease risk factors and cardiovascular health metrics among obese people in the United States in recent years.
Methods and Results-We examined the secular changes in cardiovascular health metrics and key cardiovascular disease risk factors among obese adults (aged >= 20 years) in the United States. We included 18 626 obese adults (body mass index >= 30) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Among those obese adults, there were decreases in mean systolic blood pressure, diastolic blood pressure, and total cholesterol levels and increases in mean high-density lipoprotein cholesterol levels and mean hemoglobin A1c levels. Prevalence of blood pressure health and lipid health remained stable during the period 1988-2014, whereas prevalence of blood glucose health decreased significantly during this period. Prevalence of freedom from cardiovascular disease risk factors remained stable at approximate to 15% among the adult obese population during the period 1988-2014, whereas prevalence of presence of all 3 risk factors increased from 16.4% to 22.4% during this period, commensurate with a decline in those with 1 to 2 risk factors (from 69.6% to 62.4%).
Conclusions-During the past 3 decades, blood pressure health and blood lipid health remained stable or improved, whereas blood glucose health deteriorated among adult obese population. This resulted in an overall decrease in cardiovascular health status among obese adults and greater risk of type 2 diabetes mellitus. The data argue for interventions targeted to those obese persons who are metabolically unhealthy to stem rising rates of diabetes mellitus.
C1 [Guo, Fangjian] Univ Texas Med Branch, Dept Obstet & Gynecol, Galveston, TX 77555 USA.
[Guo, Fangjian] Univ Texas Med Branch, Ctr Interdisciplinary Res Womens Hlth, Galveston, TX 77555 USA.
[Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Guo, FJ (reprint author), Univ Texas Med Branch, Ctr Interdisciplinary Res Womens Hlth, Dept Obstet & Gynecol, 301 Univ Blvd, Galveston, TX 77555 USA.
EM guofangjian@gmail.com; garveyt@uab.edu
OI Guo, Fangjian/0000-0003-3729-2724
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD) at the National Institutes of Health (NIH)
[T32HD055163]; Merit Review program of the Department of Veterans
Affairs, National Institutes of Health [DK-038765, DK-083562]; UAB
Diabetes Research Center [P60-DK079626]; National Center for Health
Statistics Centers for Disease Control and Prevention
FX Dr Guo is currently a postdoctoral fellow supported by an institutional
training grant (National Research Service Award T32HD055163) from the
Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD) at the National Institutes of Health (NIH). This
study is supported by the Merit Review program of the Department of
Veterans Affairs, National Institutes of Health (DK-038765 and
DK-083562), and the UAB Diabetes Research Center (P60-DK079626). Role of
the Sponsors: All data from NHANES used in this study were collected by
the National Center for Health Statistics Centers for Disease Control
and Prevention.
NR 47
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e003619
DI 10.1161/JAHA.116.003619
PG 20
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800050
ER
PT J
AU Kidd, SK
Bonaca, MP
Braunwald, E
De Ferrari, GM
Lewis, BS
Merlini, PA
Murphy, SA
Scirica, BM
White, HD
Morrow, DA
AF Kidd, Stephen K.
Bonaca, Marc P.
Braunwald, Eugene
De Ferrari, Gaetano M.
Lewis, Basil S.
Merlini, Piera A.
Murphy, Sabina A.
Scirica, Benjamin M.
White, Harvey D.
Morrow, David A.
TI Universal Classification System Type of Incident Myocardial Infarction
in Patients With Stable Atherosclerosis: Observations From Thrombin
Receptor Antagonist in Secondary Prevention of Atherothrombotic Ischemic
Events (TRA 2 degrees P)-TIMI 50
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE atherosclerosis; cardiovascular disease; myocardial infarction; platelet
inhibitor
ID TRITON-TIMI 38; CARDIOVASCULAR DEATH; AMERICAN-COLLEGE; TRIAL; CORONARY;
DEFINITION; VORAPAXAR; REDUCTION; PRASUGREL; RISK
AB Background-Our dual aims were as follows: (1) to classify new or recurrent myocardial infarctions (MI) in patients with stable atherosclerosis using the Universal Definition of MI classification system; and (2) to characterize the effects of vorapaxar, a first-in-class platelet protease-activated receptor -1 antagonist, on new or recurrent MI.
Methods and Results-We analyzed data from TRA 2 degrees P-TIMI 50, a multinational, randomized, double-blind, placebo-controlled trial of vorapaxar. This analysis included 20 770 patients with previous MI or peripheral arterial disease without a history of transient ischemic attack or stroke. Each new or recurrent MI after randomization that met the trial end point definition was further categorized according to the European Society of Cardiology, American College of Cardiology, American Heart Association, World Heart Federation Universal Definition classification of type and size. Of 1095 incident MIs, 77% were spontaneous (Type 1), with a smaller number (9.8%) of secondary MIs (Type 2). Vorapaxar reduced Type 1 MI (hazard ratio [HR] 0.84, CI 0.73-0.98, P=0.024), with a similar pattern for Type 2 MI (HR 0.74, CI 0.49-1.10, P=0.13). Notably, vorapaxar showed a consistent pattern of reduction across size of MIs, including MIs in the highest Universal MI size class (>= 10x upper reference limit, HR 0.83, CI 0.70-0.98, P=0.025). As such, there was a significant reduction in larger, spontaneous MIs (Type 1, >= 10x upper reference limit, HR 0.81, CI 0.67-0.99, P=0.036), and a consistent pattern with respect to fatal MI (HR 0.66, CI 0.39-1.11, P=0.12).
Conclusions-Among stable patients with established atherosclerosis, the most common type of incident MI is spontaneous MI, and the reduction in MI with vorapaxar was consistent across MIs of varying type and size, including spontaneous infarctions >= 10x upper reference limit.
C1 [Bonaca, Marc P.; Braunwald, Eugene; Murphy, Sabina A.; Scirica, Benjamin M.; Morrow, David A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, TIMI Study Grp,Cardiovasc Div, Boston, MA USA.
[Kidd, Stephen K.; Bonaca, Marc P.; Braunwald, Eugene; Scirica, Benjamin M.; Morrow, David A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA.
[De Ferrari, Gaetano M.] Univ Pavia, Dept Mol Med, I-27100 Pavia, Italy.
[De Ferrari, Gaetano M.] Fdn IRCCS Policlin San Matteo, Dept Cardiol, Pavia, Italy.
[Lewis, Basil S.] Technion, Lady Davis Carmel Med Ctr, Haifa, Israel.
[Lewis, Basil S.] Technion, Ruth & Bruce Rappaport Sch Med, Haifa, Israel.
[Merlini, Piera A.] Azienda Osped Niguarda Ca Granda, Div Cardiol 4, Milan, Italy.
[White, Harvey D.] Auckland City Hosp, Green Lane Cardiovasc Serv, West Auckland, New Zealand.
RP Morrow, DA (reprint author), Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
FU Merck and Co.
FX The TRA 2 degrees P-TIMI 50 trial was funded by Merck and Co.
NR 16
TC 0
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e003237
DI 10.1161/JAHA.116.003237
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800021
ER
PT J
AU Menard, MT
Farber, A
Assmann, SF
Choudhry, NK
Conte, MS
Creager, MA
Dake, MD
Jaff, MR
Kaufman, JA
Powell, RJ
Reid, DM
Siami, FS
Sopko, G
White, CJ
Rosenfield, K
AF Menard, Matthew T.
Farber, Alik
Assmann, Susan F.
Choudhry, Niteesh K.
Conte, Michael S.
Creager, Mark A.
Dake, Michael D.
Jaff, Michael R.
Kaufman, John A.
Powell, Richard J.
Reid, Diane M.
Siami, Flora Sandra
Sopko, George
White, Christopher J.
Rosenfield, Kenneth
TI Design and Rationale of the Best Endovascular Versus Best Surgical
Therapy for Patients With Critical Limb Ischemia (BEST-CLI) Trial
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE atherosclerosis; cost-effectiveness; critical limb ischemia;
endovascular; outcome; quality; stent treatment; surgery
ID PERIPHERAL ARTERIAL-DISEASE; COST-EFFECTIVENESS ANALYSIS; LEG BASIL
TRIAL; LOWER-EXTREMITY; THREATENING ISCHEMIA; AMPUTATION-FREE;
SAPHENOUS-VEIN; TASK-FORCE; BYPASS; ANGIOPLASTY
AB Background-Critical limb ischemia (CLI) is increasing in prevalence, and remains a significant source of mortality and limb loss. The decision to recommend surgical or endovascular revascularization for patients who are candidates for both varies significantly among providers and is driven more by individual preference than scientific evidence.
Methods and Results-The Best Endovascular Versus Best Surgical Therapy for Patients With Critical Limb Ischemia (BEST-CLI) Trial is a prospective, randomized, multidisciplinary, controlled, superiority trial designed to compare treatment efficacy, functional outcomes, quality of life, and cost in patients undergoing best endovascular or best open surgical revascularization. Approximately 140 clinical sites in the United States and Canada will enroll 2100 patients with CLI who are candidates for both treatment options. A pragmatic trial design requires consensus on patient eligibility by at least 2 investigators, but leaves the choice of specific procedural strategy within the assigned revascularization approach to the individual treating investigator. Patients with suitable single-segment of saphenous vein available for potential bypass will be randomized within Cohort 1 (n=1620), while patients without will be randomized within Cohort 2 (n= 480). The primary efficacy end point of the trial is Major Adverse Limb Event-Free Survival. Key secondary end points include Re-intervention and Amputation-Free-Survival and Amputation Free-Survival.
Conclusions-The BEST-CLI trial is the first randomized controlled trial comparing endovascular therapy to open surgical bypass in patients with CLI to be carried out in North America. This landmark comparative effectiveness trial aims to provide Level I data to clarify the appropriate role for both treatment strategies and help define an evidence-based standard of care for this challenging patient population.
C1 [Menard, Matthew T.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA.
[Choudhry, Niteesh K.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Farber, Alik] Boston Med Ctr, Div Vasc & Endovasc Surg, Boston, MA USA.
[Assmann, Susan F.; Siami, Flora Sandra] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA.
[Conte, Michael S.] Univ Calif San Francisco, Med Ctr, Div Vasc & Endovasc Surg, San Francisco, CA USA.
[Creager, Mark A.] Dartmouth Hitchcock Med Ctr, Dartmouth Hitchcock Heart & Vasc Ctr, Lebanon, NH 03766 USA.
[Powell, Richard J.] Dartmouth Hitchcock Med Ctr, Div Vasc Surg, Lebanon, NH 03766 USA.
[Dake, Michael D.] Stanford Hosp & Clin, Dept Cardiothorac Surg, Stanford, CA USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Fireman Vasc Ctr, Boston, MA 02114 USA.
[Rosenfield, Kenneth] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Kaufman, John A.] Dotter Intervent Inst OHSU, Portland, OR USA.
[Reid, Diane M.; Sopko, George] NHLBI, Bldg 10, Bethesda, MD 20892 USA.
[White, Christopher J.] Ochsner Med Ctr, Dept Cardiol, New Orleans, LA USA.
RP Menard, MT (reprint author), Brigham & Womens Hosp, Dept Vasc Surg, 75 Francis St, Boston, MA 02115 USA.
EM mmenard@partners.org
FU National Heart, Lung, and Blood Institute [U01HL107407, U01HL107352,
U01HL115662]
FX This trial is funded by National Heart, Lung, and Blood Institute
through grant numbers U01HL107407, U01HL107352, and U01HL115662.
NR 42
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Z9 7
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e003219
DI 10.1161/JAHA.116.003219
PG 21
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800018
ER
PT J
AU van't Hof, FNG
Ruigrok, YM
Lee, CH
Ripke, S
Anderson, G
de Andrade, M
Baas, AF
Blankensteijn, JD
Bottinger, EP
Bown, MJ
Broderick, J
Bijlenga, P
Carrell, DS
Crawford, DC
Crosslin, DR
Ebeling, C
Eriksson, JG
Fornage, M
Foroud, T
von und zu Fraunberg, M
Friedrich, CM
Gaal, EI
Gottesman, O
Guo, DC
Harrison, SC
Hernesniemi, J
Hofman, A
Inoue, I
Jaaskelainen, JE
Jones, GT
Kiemeney, LALM
Kivisaari, R
Ko, N
Koskinen, S
Kubo, M
Kullo, IJ
Kuivaniemi, H
Kurki, MI
Laakso, A
Lai, D
Leal, SM
Lehto, H
LeMaire, SA
Low, SK
Malinowski, J
McCarty, CA
Milewicz, DM
Mosley, TH
Nakamura, Y
Nakaoka, H
Niemela, M
Pacheco, J
Peissig, PL
Pera, J
Rasmussen-Torvik, L
Ritchie, MD
Rivadeneira, F
van Rij, AM
Santos-Cortez, RLP
Saratzis, A
Slowik, A
Takahashi, A
Tromp, G
Uitterlinden, AG
Verma, SS
Vermeulen, SH
Wang, GT
Han, B
Rinkel, GJE
de Bakker, PIW
AF van't Hof, Femke N. G.
Ruigrok, Ynte M.
Lee, Cue Hyunkyu
Ripke, Stephan
Anderson, Graig
de Andrade, Mariza
Baas, Annette F.
Blankensteijn, Jan D.
Bottinger, Erwin P.
Bown, Matthew J.
Broderick, Joseph
Bijlenga, Philippe
Carrell, David S.
Crawford, Dana C.
Crosslin, David R.
Ebeling, Christian
Eriksson, Johan G.
Fornage, Myriam
Foroud, Tatiana
von und zu Fraunberg, Mikael
Friedrich, Christoph M.
Gaal, Emilia I.
Gottesman, Omri
Guo, Dong-Chuan
Harrison, Seamus C.
Hernesniemi, Juha
Hofman, Albert
Inoue, Ituro
Jaaskelainen, Juha E.
Jones, Gregory T.
Kiemeney, Lambertus A. L. M.
Kivisaari, Riku
Ko, Nerissa
Koskinen, Seppo
Kubo, Michiaki
Kullo, Iftikhar J.
Kuivaniemi, Helena
Kurki, Mitja I.
Laakso, Aki
Lai, Dongbing
Leal, Suzanne M.
Lehto, Hanna
LeMaire, Scott A.
Low, Siew-Kee
Malinowski, Jennifer
McCarty, Catherine A.
Milewicz, Dianna M.
Mosley, Thomas H.
Nakamura, Yusuke
Nakaoka, Hirofumi
Niemela, Mika
Pacheco, Jennifer
Peissig, Peggy L.
Pera, Joanna
Rasmussen-Torvik, Laura
Ritchie, Marylyn D.
Rivadeneira, Fernando
van Rij, Andre M.
Santos-Cortez, Regie Lyn P.
Saratzis, Athanasios
Slowik, Agnieszka
Takahashi, Atsushi
Tromp, Gerard
Uitterlinden, Andre G.
Verma, Shefali S.
Vermeulen, Sita H.
Wang, Gao T.
Han, Buhm
Rinkel, Gabriel J. E.
de Bakker, Paul I. W.
CA Aneurysm Consortium
Vasc Res Consortium New Zealand
TI Shared Genetic Risk Factors of Intracranial, Abdominal, and Thoracic
Aneurysms
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE abdominal aortic aneurysm; genome wide association study; intracranial
aneurysm; thoracic aortic aneurysm
ID GENOME-WIDE ASSOCIATION; AORTIC-ANEURYSMS; SEQUENCE VARIANT;
SUSCEPTIBILITY; LINKAGE; LOCI; PATHOGENESIS; METAANALYSIS; DISSECTIONS;
IMPUTATION
AB Background-Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs.
Methods and Results-We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]= 1.11; P=4.1 x 10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1 x 10(-3)).
Conclusions-Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.
C1 [van't Hof, Femke N. G.; Ruigrok, Ynte M.; Rinkel, Gabriel J. E.] Univ Med Ctr Utrecht, Utrecht Stroke Ctr, Dept Neurol & Neurosurg, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands.
[Baas, Annette F.] Univ Med Ctr Utrecht, Dept Med Genet, Ctr Mol Med, Utrecht, Netherlands.
[de Bakker, Paul I. W.] Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ripke, Stephan] Harvard Med Sch, Boston, MA USA.
[Lee, Cue Hyunkyu; Han, Buhm] Univ Ulsan, Coll Med, Dept Convergence Med, Seoul, South Korea.
[Lee, Cue Hyunkyu; Han, Buhm] Asan Med Ctr, Asan Inst Life Sci, Seoul, South Korea.
[Ripke, Stephan] Charite, Dept Psychiat & Psychotherapy, Berlin, Germany.
[Anderson, Graig] Univ Sydney, George Inst Int Hlth, Sydney, NSW 2006, Australia.
[de Andrade, Mariza; Kullo, Iftikhar J.] Mayo Clin, Rochester, NY USA.
[Blankensteijn, Jan D.] Vrije Univ Amsterdam Med Ctr, Dept Vasc Surg, Amsterdam, Netherlands.
[Bottinger, Erwin P.; Gottesman, Omri] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Bown, Matthew J.; Saratzis, Athanasios] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
[Bown, Matthew J.; Saratzis, Athanasios] Univ Leicester, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE1 7RH, Leics, England.
[Broderick, Joseph] Univ Cincinnati, Sch Med, Dept Neurol, Cincinnati, OH USA.
[Bijlenga, Philippe] Hop Univ Geneve, Geneva, Switzerland.
[Bijlenga, Philippe] Fac Med Geneva, Geneva, Switzerland.
[Carrell, David S.] Grp Hlth Res Inst, Seattle, WA USA.
[Crawford, Dana C.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Inst Computat Biol, Cleveland, OH 44106 USA.
[Crawford, Dana C.; Malinowski, Jennifer] Vanderbilt Univ, Ctr Human Genet Res, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Crosslin, David R.] Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA.
[Ebeling, Christian] Fraunhofer Inst Algorithmen & Wissensch Rechnen, St Augustin, Germany.
[Eriksson, Johan G.] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Helsinki Univ Hosp, Helsinki, Finland.
[Gaal, Emilia I.] FIMM, Helsinki, Finland.
Univ Helsinki, FIN-00014 Helsinki, Finland.
[von und zu Fraunberg, Mikael] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[von und zu Fraunberg, Mikael] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Foroud, Tatiana; Lai, Dongbing] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[von und zu Fraunberg, Mikael; Jaaskelainen, Juha E.; Kurki, Mitja I.] Kuopio Univ Hosp, Neurosurg NeuroCtr, Kuopio, Finland.
[Friedrich, Christoph M.] Univ Appl Sci & Arts, Dept Comp Sci, Dortmund, Germany.
[Gaal, Emilia I.; Laakso, Aki] Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland.
[Koskinen, Seppo] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Helsinki, Finland.
[Gaal, Emilia I.; Hernesniemi, Juha; Kivisaari, Riku; Lehto, Hanna; Niemela, Mika] Univ Helsinki, Cent Hosp, Dept Neurosurg, Helsinki, Finland.
[Harrison, Seamus C.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE1 7RH, Leics, England.
[Hofman, Albert; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Inoue, Ituro; Nakaoka, Hirofumi] Natl Inst Genet, Div Human Genet, Mishima, Shizuoka, Japan.
[Jones, Gregory T.; van Rij, Andre M.] Univ Otago, Dept Surg, Dunedin, New Zealand.
[Kiemeney, Lambertus A. L. M.; Vermeulen, Sita H.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.
[LeMaire, Scott A.] Baylor Coll Med, Michael E DeBakey Dept Surg, Houston, TX 77030 USA.
[LeMaire, Scott A.] Texas Heart Inst, Houston, TX 77025 USA.
[Guo, Dong-Chuan; Milewicz, Dianna M.] Univ Texas Med Sch Houston, Dept Internal Med, Houston, TX USA.
[Ko, Nerissa] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Kubo, Michiaki; Low, Siew-Kee; Takahashi, Atsushi] RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
[Kuivaniemi, Helena; Tromp, Gerard] Geisinger Hlth Syst, Sigfried & Janet Weis Ctr Res, Danville, PA USA.
[Kuivaniemi, Helena] Temple Univ, Dept Surg, Sch Med, Philadelphia, PA 19122 USA.
[Kurki, Mitja I.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kurki, Mitja I.] Broad Inst, Med & Populat Genet Program, Boston, MA USA.
[Leal, Suzanne M.; Santos-Cortez, Regie Lyn P.; Wang, Gao T.] Baylor Coll Med, Ctr Stat Genet, Houston, TX 77030 USA.
[Malinowski, Jennifer] Yale Sch Med, Dept Surg, New Haven, CT USA.
[McCarty, Catherine A.] Essentia Inst Rural Hlth, Div Res, Duluth, MN USA.
[Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Nakamura, Yusuke] Univ Chicago, Dept Med, Sect Hematol & Oncol, Chicago, IL 60637 USA.
[Pacheco, Jennifer] Northwestern Univ, Feinberg Sch Med, Ctr Genet Med, Chicago, IL 60611 USA.
[Rasmussen-Torvik, Laura] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Peissig, Peggy L.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA.
[Pera, Joanna; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, Krakow, Poland.
[Ritchie, Marylyn D.; Verma, Shefali S.] Penn State Univ, Ctr Syst Genom, University Pk, PA 16802 USA.
[Kuivaniemi, Helena; Tromp, Gerard] Univ Stellenbosch, Dept Biomed Sci, Tygerberg, South Africa.
RP de Bakker, PIW (reprint author), Univ Med Ctr Utrecht, Dept Med Genet, Univ Weg 100, NL-3584 CG Utrecht, Netherlands.; de Bakker, PIW (reprint author), Univ Med Ctr Utrecht, Dept Epidemiol, Univ Weg 100, NL-3584 CG Utrecht, Netherlands.
EM pdebakker@umcutrecht.nl
RI Bown, Matthew/P-1957-2016; Bijlenga, Philippe/S-1049-2016;
OI Bown, Matthew/0000-0002-6180-3611; Bijlenga,
Philippe/0000-0002-3586-2757; Deloukas, Panos/0000-0001-9251-070X;
Lindholt, Jes/0000-0001-9536-4488
FU Dutch Heart Foundation (NHS) [2008B004]; clinical fellowship grant of
the Netherlands Organization for Scientific Research (NWO)
[40-00703-98-13533]; Dr E. Dekker Program of the Netherlands Heart
Foundation [2009T001]; HEFCE Clinical Senior Lecturer Fellowship;
Familial Intracranial Aneurysm (FIA) [R01NS39512, R03NS083468];
Instrumentarium Science Foundation, Finland; Finnish Foundation for
Cardiovascular Research; University of Eastern Finland; National
Institutes of Health (NIH) [P50-HL083794]; Netherlands Organization of
Scientific Research NWO Investments [175.010.2005.011, 911-03-012];
Genetic Laboratory of the Department of Internal Medicine, Erasmus MC;
Research Institute for Diseases in the Elderly (RIDE2) [014-93-015];
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO); Netherlands Consortium for Healthy Aging
(NCHA) [050-060-810]; Erasmus Medical Center and Erasmus University,
Rotterdam; Netherlands Organization for the Health Research and
Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; Municipality of Rotterdam; Ministry of Education,
Culture, Sports, Sciences and Technology, Japan; National Health and
Medical Research Council (NHMRC), Australia; Health Research Council of
New Zealand [08-75, 14-155]; Jagiellonian University Medical College
[K/ZDS/001456]; National Heart, Lung, and Blood Institute [HHSN268
201100005C, HHSN268201100006C, HHSN26820110000 7C, HHSN268201100008C,
HHSN268201100009C, HHSN2 68201100010C, HHSN268201100011C, HHSN26820
110012C, R01HL087641, R01HL59367, R01HL086694]; National Human Genome
Research Institute [U01HG004402]; NIH [P50-HL083794, HHSN268200625226C,
R01-HL62594, UL1RR024148, K08-HL080085]; 6th framework program of the
European Commission [FP6-IST-2004-027703]; Wellcome Trust [084695,
076113, 085475]; Pennsylvania Commonwealth Universal Research
Enhancement Program; Geisinger Clinical Research Fund; American Heart
Association; Ben Franklin Technology Development Fund of Pennsylvania;
NHGRI; NIGMS [U01HG004438, U01HG004424, U01HG004610, U01HG006375, U01HG
004608, U01HG006389, U01HG04599, U01HG006379, U01HG004609, U01HG006388,
U01HG04603, U01HG006378, U01HG006385, U01HG006382, U01HG006380];
Vanderbilt University Medical Center's BioVU; National Center for
Research Resources at National Center for Advancing Translational
Sciences [UL1 RR024975-01, 2 UL1 TR000445-06]; Doris Duke Charitable
Trust; Vivian L. Smith Foundation; TexGen Foundation; Thoracic Surgery
Foundation for Research and Education; NIH [CTSA] [UL1RR025758];
[UL1RR025005]; [R01-HL70825]
FX van 't Hof is supported by a grant of the Dutch Heart Foundation (NHS;
Project No. 2008B004). Ruigrok is supported by a clinical fellowship
grant of the Netherlands Organization for Scientific Research (NWO;
Project No. 40-00703-98-13533). Baas is supported by a grant from the Dr
E. Dekker Program of the Netherlands Heart Foundation 2009T001). Bown is
supported by a HEFCE Clinical Senior Lecturer Fellowship. Broderick is
supported by a Familial Intracranial Aneurysm (FIA) grant (R01NS39512).
Foroud is supported by an FIA grant (R03NS083468). Kubo is funded by the
Instrumentarium Science Foundation, Finland, and by the Finnish
Foundation for Cardiovascular Research, University of Eastern Finland.
Saratzis is an NIHR Academic Clinical Lecturer. Milewicz is supported by
grants from the National Institutes of Health (NIH; P50-HL083794).; The
generation and management of GWAS genotype data for the Rotterdam Study
(RS I, RS II, and RS III) was executed by the Human Genotyping Facility
of the Genetic Laboratory of the Department of Internal Medicine,
Erasmus MC, Rotterdam, The Netherlands. The GWAS data sets are supported
by the Netherlands Organization of Scientific Research NWO Investments
(No. 175.010.2005.011, 911-03-012), the Genetic Laboratory of the
Department of Internal Medicine, Erasmus MC, the Research Institute for
Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics
Initiative (NGI)/Netherlands Organization for Scientific Research (NWO),
Netherlands Consortium for Healthy Aging (NCHA; Project No.
050-060-810). The Rotterdam Study is funded by Erasmus Medical Center
and Erasmus University, Rotterdam, Netherlands Organization for the
Health Research and Development (ZonMw), the Research Institute for
Diseases in the Elderly (RIDE), the Ministry of Education, Culture and
Science, the Ministry for Health, Welfare and Sports, the European
Commission (DG XII), and the Municipality of Rotterdam.; The Japanese IA
GWAS (named "Japan 2" in this study) was conducted as part of the
Biobank Japan Project that was supported by the Ministry of Education,
Culture, Sports, Sciences and Technology, Japan.; For the "USA+" IA
GWAS, infrastructure was partly supported by Grant No. UL1RR025005, a
component of the NIH and NIH Roadmap for Medical Research. This study
was also supported by the National Health and Medical Research Council
(NHMRC), Australia, and the Health Research Council of New Zealand.
Additional funding was provided by a grant from Jagiellonian University
Medical College K/ZDS/001456. The study also contains data from
Atherosclerosis Risk in Communities, which is performed as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN268 201100005C, HHSN268201100006C,
HHSN26820110000 7C, HHSN268201100008C, HHSN268201100009C, HHSN2
68201100010C, HHSN268201100011C, and HHSN26820 110012C), R01HL087641,
R01HL59367, and R01HL086694; National Human Genome Research Institute
contract U01HG004402; and NIH contract HHSN268200625226C. Neurocognitive
data were collected by U01 HL096812, HL096814, HL096899, HL096902, and
HL096917 with previous brain MRI examinations funded by R01-HL70825.;
The @neurIST project is supported by the 6th framework program of the
European Commission (www.aneurist.org) FP6-IST-2004-027703.; AAA GWAS
data provided by the Aneurysm Consortium were funded by the Wellcome
Trust (Award No. 084695) and makes use of data generated by the WTCCC. A
full list of the investigators who contributed to the generation of the
data is available from www.wtccc.org.uk. Funding for the WTCCC project
was provided by the Wellcome Trust under awards 076113 and 085475.
Funding for the New Zealand project was provided by the Health Research
Council of New Zealand (08-75, 14-155). The Geisinger project was
funded, in part, by the Pennsylvania Commonwealth Universal Research
Enhancement Program, the Geisinger Clinical Research Fund, the American
Heart Association, and the Ben Franklin Technology Development Fund of
Pennsylvania. The eMERGE Network is funded by the NHGRI, with additional
funding from the NIGMS through the following grants: U01HG004438 to
Johns Hopkins University; U01HG004424 to The Broad Institute;
U01HG004438 to CIDR; U01HG004610 and U01HG006375 to Group Health
Cooperative; U01HG 004608 to Marshfield Clinic; U01HG006389 to Essentia
Institute of Rural Health; U01HG04599 and U01HG006379 to Mayo Clinic;
U01HG004609 and U01HG006388 to Northwestern University; U01HG04603 and
U01HG006378 to Vanderbilt University; U01HG006385 to the Coordinating
Center; U01HG006382 to Geisinger Health System; and U01HG006380 to Icahn
School of Medicine Mount Sinai. Vanderbilt's data set(s) used for the
analyses described were obtained from Vanderbilt University Medical
Center's BioVU, which is supported by institutional funding and by the
National Center for Research Resources (Grant UL1 RR024975-01; which is
now at the National Center for Advancing Translational Sciences: Grant 2
UL1 TR000445-06).; The project that created the data regarding the TAA
cohort was supported by grants from the NIH (P50-HL083794 and
R01-HL62594; UL1RR024148 and UL1RR025758 [CTSA]; K08-HL080085), as well
as the Doris Duke Charitable Trust, the Vivian L. Smith Foundation, the
TexGen Foundation, and the Thoracic Surgery Foundation for Research and
Education.
NR 46
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e002603
DI 10.1161/JAHA.115.002603
PG 19
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800009
ER
PT J
AU Wu, C
Arora, P
AF Wu, Connie
Arora, Pankaj
TI Noncoding Genome-Wide Association Studies Variant for Obesity: Inroads
Into Mechanism An Overview From the AHA's Council on Functional Genomics
and Translational Biology
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Editorial Material
DE adipocyte; epigenetics; genome-wide association study; obesity
ID ADULT OBESITY; CHILDHOOD
C1 [Wu, Connie] Harvard Med Sch, Dept Med, Cardiovasc Res Ctr, Massachusetts Gen Hosp, Boston, MA USA.
[Wu, Connie] Harvard Med Sch, Dept Anesthesia, Anesthesia Ctr Crit Care Res Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA USA.
[Arora, Pankaj] Univ Alabama Birmingham, Dept Med, Div Cardiol, 1808 7th Ave S,BDB 201, Birmingham, AL 35294 USA.
RP Wu, C (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Anesthesia Ctr Crit Care Res, 55 Fruit St,GRB 444, Boston, MA 02114 USA.; Arora, P (reprint author), Univ Alabama Birmingham, Div Cardiol, 1808 7th Ave S,BDB 201, Birmingham, AL 35294 USA.
EM parora@uabmc.edu
NR 11
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD JUL
PY 2016
VL 5
IS 7
AR e003060
DI 10.1161/JAHA.115.003060
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6CT
UT WOS:000386713800012
ER
PT J
AU Kacmarek, RM
Vilar, J
Blanch, L
AF Kacmarek, Robert M.
Vilar, Jesus
Blanch, Lluis
TI Cycle asynchrony: always a concern during pressure ventilation!
SO MINERVA ANESTESIOLOGICA
LA English
DT Editorial Material
ID MECHANICAL VENTILATION
C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St, Boston, MA 01460 USA.
[Kacmarek, Robert M.] Harvard Univ, Dept Anesthesiol, Boston, MA 02115 USA.
[Vilar, Jesus; Blanch, Lluis] Inst Salud Carlos II, CIBER Enfermedades Resp, Madrid, Spain.
[Vilar, Jesus] Hosp Univ Dr Negrin, Res Unit, Multidisciplinary Organ Dysfunct Evaluat Res Netw, Las Palmas Gran Canaria, Spain.
[Blanch, Lluis] Univ Autonoma Barcelona, Crit Care Ctr, Corp Sanitaria Univ Parc Tauli, Inst Invest Innovacio Parc Tauli, Sabadell, Spain.
RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Dept Resp Care, 55 Fruit St, Boston, MA 01460 USA.
EM rkacmarek@partners.org
NR 10
TC 1
Z9 1
U1 0
U2 0
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 0375-9393
EI 1827-1596
J9 MINERVA ANESTESIOL
JI Minerva Anestesiol.
PD JUL
PY 2016
VL 82
IS 7
BP 728
EP 730
PG 3
WC Anesthesiology; Critical Care Medicine
SC Anesthesiology; General & Internal Medicine
GA EA8MK
UT WOS:000386888700002
PM 26859156
ER
PT J
AU Elgin, C
Nuhi, V
Johnson, RH
AF Elgin, Cristina
Nuhi, Veldana
Johnson, Ralph H.
TI Comparison of decentralized versus centralized pharmacist management of
patients with atrial fibrillation treated with direct oral
anticoagulants (DOACs).
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT American-College-of-Clinical-Pharmacy (ACCP) Virtual Poster Symposium
CY MAY 18-19, 2016
CL ELECTR NETWORK
SP Amer Coll Clin Pharm
C1 [Elgin, Cristina; Nuhi, Veldana; Johnson, Ralph H.] Ralph H Johnson VA Med Ctr, Dept Pharm, Charleston, SC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-0008
EI 1875-9114
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD JUL
PY 2016
VL 36
IS 7
MA 5
BP E85
EP E85
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DW4EP
UT WOS:000383595600008
ER
PT J
AU Gauthier, J
Griffith, J
AF Gauthier, Joshua
Griffith, June
TI Implementation and evaluation of an overdose education and naloxone
distribution (OEND) program.
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT American-College-of-Clinical-Pharmacy (ACCP) Virtual Poster Symposium
CY MAY 18-19, 2016
CL ELECTR NETWORK
SP Amer Coll Clin Pharm
C1 [Gauthier, Joshua] Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA.
[Griffith, June] Tuscaloosa VA Med Ctr, US Dept Vet Affairs, Tuscaloosa, AL USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-0008
EI 1875-9114
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD JUL
PY 2016
VL 36
IS 7
MA 148
BP E126
EP E126
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DW4EP
UT WOS:000383595600145
ER
PT J
AU Im, EP
Griffith, J
Hamilton, D
AF Im, Eun Pyung
Griffith, June
Hamilton, Debora
TI Opioid safety initiative: clinical pharmacy intervention.
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT American-College-of-Clinical-Pharmacy (ACCP) Virtual Poster Symposium
CY MAY 18-19, 2016
CL ELECTR NETWORK
SP Amer Coll Clin Pharm
C1 [Im, Eun Pyung; Griffith, June; Hamilton, Debora] US Dept Vet Affairs, Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-0008
EI 1875-9114
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD JUL
PY 2016
VL 36
IS 7
MA 138
BP E123
EP E124
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DW4EP
UT WOS:000383595600136
ER
PT J
AU Morgan, J
Griffith, J
AF Morgan, Joni
Griffith, June
TI Quality improvement project regarding posttraumatic stress disorder
(PTSD) and benzodiazepines as part of the Psychotropic Drug Safety
Initiative ( PDSI).
SO PHARMACOTHERAPY
LA English
DT Meeting Abstract
CT American-College-of-Clinical-Pharmacy (ACCP) Virtual Poster Symposium
CY MAY 18-19, 2016
CL ELECTR NETWORK
SP Amer Coll Clin Pharm
C1 [Morgan, Joni; Griffith, June] Tuscaloosa VA Med Ctr, US Dept Vet Affairs, Tuscaloosa, AL USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-0008
EI 1875-9114
J9 PHARMACOTHERAPY
JI Pharmacotherapy
PD JUL
PY 2016
VL 36
IS 7
MA 147
BP E126
EP E126
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DW4EP
UT WOS:000383595600144
ER
PT J
AU Garza-Mayers, AC
McClurkin, M
Smith, GP
AF Garza-Mayers, Anna Cristina
McClurkin, Michael
Smith, Gideon P.
TI Review of treatment for discoid lupus erythematosus
SO DERMATOLOGIC THERAPY
LA English
DT Review
DE discoid; lupus; chronic cutaneous; therapeutics
ID CUTANEOUS LUPUS; DOUBLE-BLIND; MYCOPHENOLATE-MOFETIL; CONTROLLED-TRIAL;
EFFICACY; THERAPY; SMOKING; SAFETY; HYDROXYCHLOROQUINE; INFLAMMATION
AB Discoid lupus erythematosus (DLE) is a chronic cutaneous disease characterized by inflammatory plaques that, in the absence of prompt diagnosis and treatment, may lead to disfiguring scarring and skin atrophy. However, there is limited evidence for which treatments are most effective. Currently, no medications have been approved specifically for the treatment of DLE. Many of the drugs described in the literature were developed for use in other immune disorders. This review will summarize current therapeutic options for DLE and their supporting evidence with discussion of prevention, topical measures, physical modalities, and systemic therapies, including newer potential therapies.
C1 [Garza-Mayers, Anna Cristina; McClurkin, Michael; Smith, Gideon P.] Harvard Med Sch, Boston, MA USA.
[Garza-Mayers, Anna Cristina; Smith, Gideon P.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
RP Smith, GP (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
EM gpsmith@mgh.harvard.edu
FU NIGMS NIH HHS [T32 GM007753]
NR 50
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1396-0296
EI 1529-8019
J9 DERMATOL THER
JI Dermatol. Ther.
PD JUL-AUG
PY 2016
VL 29
IS 4
BP 274
EP 283
DI 10.1111/dth.12358
PG 10
WC Dermatology
SC Dermatology
GA DZ8AW
UT WOS:000386091700015
PM 27073142
ER
PT J
AU Effing, TW
Vercoulen, JH
Bourbeau, J
Trappenburg, J
Lenferink, A
Cafarella, P
Coultas, D
Meek, P
van der Valk, P
Bischoff, EWMA
Bucknall, C
Dewan, NA
Early, F
Fan, V
Frith, P
Janssen, DJA
Mitchell, K
Morgan, M
Nici, L
Patel, I
Walters, H
Rice, KL
Singh, S
Zuwallack, R
Benzo, R
Goldstein, R
Partridge, MR
van der Palen, J
AF Effing, Tanja W.
Vercoulen, Jan H.
Bourbeau, Jean
Trappenburg, Jaap
Lenferink, Anke
Cafarella, Paul
Coultas, David
Meek, Paula
van der Valk, Paul
Bischoff, Erik W. M. A.
Bucknall, Christine
Dewan, Naresh A.
Early, Frances
Fan, Vincent
Frith, Peter
Janssen, Daisy J. A.
Mitchell, Katy
Morgan, Mike
Nici, Linda
Patel, Irem
Walters, Haydn
Rice, Kathryn L.
Singh, Sally
Zuwallack, Richard
Benzo, Roberto
Goldstein, Roger
Partridge, Martyn R.
van der Palen, Job
TI Definition of a COPD self-management intervention: International Expert
Group consensus
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; MOTIVATION
AB There is an urgent need for consensus on what defines a chronic obstructive pulmonary disease (COPD) self-management intervention. We aimed to obtain consensus regarding the conceptual definition of a COPD self-management intervention by engaging an international panel of COPD self-management experts using Delphi technique features and an additional group meeting.
In each consensus round the experts were asked to provide feedback on the proposed definition and to score their level of agreement (1=totally disagree; 5=totally agree). The information provided was used to modify the definition for the next consensus round. Thematic analysis was used for free text responses and descriptive statistics were used for agreement scores.
In total, 28 experts participated. The consensus round response rate varied randomly over the five rounds (ranging from 48% (n=13) to 85% (n=23)), and mean definition agreement scores increased from 3.8 (round 1) to 4.8 (round 5) with an increasing percentage of experts allocating the highest score of 5 (round 1: 14% (n=3); round 5: 83% (n=19)).
In this study we reached consensus regarding a conceptual definition of what should be a COPD self-management intervention, clarifying the requisites for such an intervention. Operationalisation of this conceptual definition in the near future will be an essential next step.
C1 [Effing, Tanja W.; Cafarella, Paul; Frith, Peter] Southern Adelaide Local Hlth Network, Dept Resp Med, Adelaide, SA, Australia.
[Effing, Tanja W.; Cafarella, Paul; Frith, Peter] Flinders Univ S Australia, Sch Med, Adelaide, SA 5001, Australia.
[Vercoulen, Jan H.] Radboud Univ Nijmegen, Med Ctr, Dept Med Psychol, NL-6525 ED Nijmegen, Netherlands.
[Vercoulen, Jan H.] Radboud Univ Nijmegen, Med Ctr, Dept Pulm Dis, NL-6525 ED Nijmegen, Netherlands.
[Bourbeau, Jean] McGill Univ, McGill Univ Hlth Ctr, Res Inst, Resp Epidemiol & Clin Res Unit, Montreal, PQ, Canada.
[Trappenburg, Jaap] Univ Med Ctr Utrecht, Dept Rehabil Nursing Sci & Sports, Utrecht, Netherlands.
[Lenferink, Anke; van der Valk, Paul; van der Palen, Job] Med Spectrum Twente, Dept Pulm Med, Enschede, Netherlands.
[Coultas, David] Oregon Hlth & Sci Univ, VA Portland Hlth Care Syst, Portland, OR 97201 USA.
[Coultas, David] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Meek, Paula] Univ Colorado, Coll Nursing, Aurora, CO USA.
[Bischoff, Erik W. M. A.] Radboud Univ Nijmegen, Med Ctr, Dept Primary & Community Care, Nijmegen, Netherlands.
[Bucknall, Christine] Glasgow Royal Infirm, Dept Resp Med, Glasgow G4 0SF, Lanark, Scotland.
[Dewan, Naresh A.] Creighton Univ, Div Pulm Crit Care & Sleep Med, Omaha, NE 68178 USA.
[Dewan, Naresh A.] Omaha Vet Affairs Med Ctr, Omaha, NE USA.
[Early, Frances] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Ctr Self Management Support, Cambridge, England.
[Fan, Vincent] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Fan, Vincent] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Janssen, Daisy J. A.] CIRO, Ctr Expertise Chron Organ Failure, Dept Res & Educ, Horn, Netherlands.
[Mitchell, Katy; Singh, Sally] Univ Hosp Leicester, Ctr Exercise & Rehabil Sci, Leicester, Leics, England.
[Morgan, Mike] Univ Hosp Leicester NHS Trust, Glenfield Hosp, Dept Resp Med, Leicester, Leics, England.
[Nici, Linda] Providence Vet Adm Med Ctr, Dept Pulm & Crit Care, Providence, RI USA.
[Patel, Irem] Kings Coll Hosp NHS Trust, Dept Resp Med, London, England.
[Walters, Haydn] Univ Tasmania, Sch Med, CRE Chron Resp Dis, Hobart, Tas, Australia.
[Rice, Kathryn L.] VA Med Ctr, Dept Med, Pulm Sect, Minneapolis, MN USA.
[Rice, Kathryn L.] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA.
[Zuwallack, Richard] St Francis Hosp & Med Ctr, Dept Pulm & Crit Care, Hartford, CT USA.
[Benzo, Roberto] Mayo Clin, Mindful Breathing Lab, Rochester, MN USA.
[Goldstein, Roger] Univ Toronto, West Pk Healthcare, Toronto, ON, Canada.
[Partridge, Martyn R.] Imperial Coll, Natl Heart & Lung Inst, London, England.
[van der Palen, Job] Univ Twente, Dept Res Methodol Measurement & Data Anal, POB 217, NL-7500 AE Enschede, Netherlands.
RP Effing, TW (reprint author), Repatriat Gen Hosp, Dept Resp Med, Daws Rd, Daw Pk, SA 5041, Australia.
EM tanja.effing@health.sa.gov.au
NR 23
TC 5
Z9 5
U1 2
U2 2
PU EUROPEAN RESPIRATORY SOC JOURNALS LTD
PI SHEFFIELD
PA 442 GLOSSOP RD, SHEFFIELD S10 2PX, ENGLAND
SN 0903-1936
EI 1399-3003
J9 EUR RESPIR J
JI Eur. Resp. J.
PD JUL
PY 2016
VL 48
IS 1
BP 46
EP 54
DI 10.1183/13993003.00025-2016
PG 9
WC Respiratory System
SC Respiratory System
GA DZ6FK
UT WOS:000385956800011
PM 27076595
ER
PT J
AU Brizzi, K
Deki, S
Tshering, L
Clark, SJ
Nirola, DK
Patenaude, BN
McKenzie, ED
McLane, HC
Cash, SS
Dorji, C
Mateen, FJ
AF Brizzi, Kate
Deki, Sonam
Tshering, Lhab
Clark, Sarah J.
Nirola, Damber K.
Patenaude, Bryan N.
McKenzie, Erica D.
McLane, Hannah C.
Cash, Sydney S.
Dorji, Chencho
Mateen, Farrah J.
TI Knowledge, attitudes and practices regarding epilepsy in the Kingdom of
Bhutan
SO INTERNATIONAL HEALTH
LA English
DT Article
DE Awareness; Bhutan; Epilepsy; Neurology; Social stigma; Traditional
medicine
ID STIGMA-SCALE; HEALTH; PERCEPTION; PEOPLE
AB To assess the knowledge, attitudes and practices of epilepsy among healthcare workers (HCWs) and people with epilepsy (PWE) living in Bhutan.
A survey with similar questions was distributed to HCWs and PWE (2014-2015). Responses were compared between the two groups. A Stigma Scale in Epilepsy Score was tested for an independent association with patient age, sex, years of education and presence of seizure freedom using regression models.
PWE (n=177), when compared to HCWs (n=75), were more likely to believe that epilepsy is contagious; epilepsy results from karma or past actions; PWE need help in school; and people with epilepsy have spiritual powers (p < 0.05 for each comparison). Among people with epilepsy, a higher stigma score was independently associated with lower educational attainment (p=0.006) and presence of a seizure in the prior year (p=0.013), but not age, sex or anti-epileptic drug side effects.
While knowledge of epilepsy was overall fairly high, PWE more often held certain stigmatizing beliefs, including theories of contagion and a relationship between seizures and spiritual powers. Higher educational level and seizure freedom were associated with lower stigma, underscoring their importance in stigma reduction.
C1 [Brizzi, Kate; Clark, Sarah J.; McKenzie, Erica D.; Cash, Sydney S.; Mateen, Farrah J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Deki, Sonam; Tshering, Lhab; Nirola, Damber K.; Dorji, Chencho] Jigme Dorji Wangchuck Natl Referral Hosp, Dept Psychiat, Thimphu, Bhutan.
[Patenaude, Bryan N.; McLane, Hannah C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Cash, Sydney S.; Mateen, Farrah J.] Harvard Med Sch, Boston, MA USA.
RP Mateen, FJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Mateen, FJ (reprint author), Harvard Med Sch, Boston, MA USA.
EM fmateen@partners.org
FU Grand Challenges Canada, Partners Center for Expertise in Global Health.
FX Grand Challenges Canada, Partners Center for Expertise in Global Health.
NR 16
TC 1
Z9 1
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1876-3413
EI 1876-3405
J9 INT HEALTH
JI Int. Health
PD JUL
PY 2016
VL 8
IS 4
BP 286
EP 291
DI 10.1093/inthealth/ihw017
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DZ7QG
UT WOS:000386060300010
PM 27160683
ER
PT J
AU Brink, JA
AF Brink, James A.
TI Providing Higher Value Care Through Population Health Management: What
Is the Radiologist's Role?
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Editorial Material
C1 [Brink, James A.] Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA.
RP Brink, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA.
EM jabrinke@partners.org
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2016
VL 13
IS 7
BP 759
EP 760
DI 10.1016/j.jacr.2016.06.001
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DZ6SF
UT WOS:000385991500001
PM 27378540
ER
PT J
AU Sheehan, SE
Coburn, JA
Singh, H
Vanness, DJ
Sittig, DF
Moberg, DP
Safdar, N
Lee, KS
Brunner, MC
AF Sheehan, Scott E.
Coburn, John A.
Singh, Hardeep
Vanness, David J.
Sittig, Dean F.
Moberg, D. Paul
Safdar, Nasia
Lee, Kenneth S.
Brunner, Michael C.
TI Reducing Unnecessary Shoulder MRI Examinations Within a Capitated Health
Care System: A Potential Role for Shoulder Ultrasound
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Shoulder; MRI; ultrasound; utilization; costs
ID CLINICAL DECISION-SUPPORT; ROTATOR CUFF TEARS; PHYSICIAN ORDER ENTRY;
LONG HEAD; UTILIZATION MANAGEMENT; METAANALYSIS; RADIOLOGY; ACCURACY;
JOINT; PAIN
AB Purpose: MRI is frequently overused. The aim of this study was to analyze shoulder MRI ordering practices within a capitated health care system and explore the potential effects of shoulder ultrasound substitution.
Methods: We reviewed medical records of 237 consecutive shoulder MRI examinations performed in 2013 at a Department of Veterans Affairs tertiary care hospital. Using advanced imaging guidelines, we assessed ordering appropriateness of shoulder MRI and estimated the proportion of examinations for which musculoskeletal ultrasound could have been an acceptable substitute, had it been available. We then reviewed MRI findings and assessed if ultrasound with preceding radiograph would have been adequate for diagnosis, based on literature reports of shoulder ultrasound diagnostic performance.
Results: Of the 237 examinations reviewed, 106 (45%) were deemed to be inappropriately ordered, most commonly because of an absent preceding radiograph (n = 98; 92%). Nonorthopedic providers had a higher frequency of inappropriate ordering (44%) relative to orthopedic specialists (17%) (P = .016; odds ratio = 3.15, 95% confidence interval = 1.24-8.01). In the 237 examinations, ultrasound could have been the indicated advanced imaging modality for 157 (66%), and most of these (133/157; 85%) could have had all relevant pathologies characterized when combined with radiographs. Regardless of indicated modality, ultrasound could have characterized 80% of all cases ordered by nonorthopedic providers and 50% of cases ordered by orthopedic specialists (P = .007).
Conclusions: Advanced shoulder imaging is often not ordered according to published appropriateness criteria. While nonorthopedic provider orders were more likely to be inappropriate, inappropriateness persisted among orthopedic providers. A combined ultrasound and radiograph evaluation strategy could accurately characterize shoulder pathologies for most cases.
C1 [Sheehan, Scott E.; Coburn, John A.; Vanness, David J.; Moberg, D. Paul; Safdar, Nasia; Lee, Kenneth S.; Brunner, Michael C.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA.
[Coburn, John A.; Vanness, David J.; Moberg, D. Paul; Lee, Kenneth S.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Singh, Hardeep] Michael E DeBakey VA Med Ctr, Houston VA Ctr Innovat Qual Effectiveness & Safet, Houston, TX USA.
[Singh, Hardeep] Baylor Coll Med, Houston, TX 77030 USA.
[Sittig, Dean F.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
RP Sheehan, SE (reprint author), William S Middleton Mem Vet Adm Med Ctr, Dept Radiol 114, 2500 Overlook Terrace, Madison, WI 53705 USA.
EM ssheehan@uwhealth.org
NR 52
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2016
VL 13
IS 7
BP 780
EP 787
DI 10.1016/j.jacr.2016.03.015
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DZ6SF
UT WOS:000385991500009
PM 27162045
ER
PT J
AU Rao, S
Rao, S
Rincon, S
Caruso, P
Ptak, T
Raja, AS
Prabhakar, AM
Harvey, HB
AF Rao, Sevith
Rao, Sishir
Rincon, Sandra
Caruso, Paul
Ptak, Thomas
Raja, Ali S.
Prabhakar, Anand M.
Harvey, H. Benjamin
TI Assessment of Pediatric Neurotrauma Imaging Appropriateness at a Level I
Pediatric Trauma Center
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Radiology; appropriateness criteria; CT; MRI; head trauma; TBI;
utilization; diagnostic radiation; Image Gently; pediatrics; concussion
ID BLUNT HEAD TRAUMA; COMPUTED-TOMOGRAPHY; EMERGENCY-DEPARTMENT;
RADIATION-EXPOSURE; CHILDREN; CRITERIA; INJURY; CHILDHOOD; QUICK; SCANS
AB Purpose: The aim of this study was to assess the prevalence of appropriate neuroimaging on the basis of the ACR Appropriateness Criteria among pediatric patients presenting after head trauma to a level I emergency department.
Methods: A retrospective emergency department record review was performed for patients <18 years of age undergoing head CT or MRI for the indication "head trauma" between January 2013 and December 2014. Clinical history and symptoms were compared with the ACR Appropriateness Criteria; the indication was deemed appropriate for ratings of >= 7. Patients were analyzed by age, gender, presentation, imaging obtained, follow-up, treatment, and outcomes.
Results: Among 207 patients, 120 (58%) were imaged with CT and 107 (52%) with MRI; 20 patients underwent both CT and MRI. One hundred eighty-seven patients (90.3%) were appropriately imaged, with 90.0% of CT studies (108 of 120) deemed appropriate and 91.6% of MRI studies (98 of 107) deemed appropriate. Younger patients were more likely to be inappropriately imaged with CT or MRI than older patients (P = .02 and P < .01, respectively). Patients undergoing CT were older (mean age 9.9 +/- 5.8 years) and more likely to be male (85.2%) than those undergoing MRI (5.6 +/- 5.6 years and 55.1%, respectively) (P < .01 and P < .001, respectively). The diagnostic yield of positive imaging findings for intracranial trauma was significantly lower in the MRI group (P < .01), and patients undergoing MRI were significantly more likely to return to baseline with conservative management (P < .01).
Conclusions: Most pediatric patients undergoing neuroimaging for head trauma did so appropriately per ACR guidelines and had symptom resolution with conservative management. The minority not imaged appropriately represent a target for quality improvement efforts.
C1 [Rao, Sevith; Rao, Sishir; Rincon, Sandra; Caruso, Paul; Ptak, Thomas; Prabhakar, Anand M.; Harvey, H. Benjamin] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Rao, Sevith; Rao, Sishir; Rincon, Sandra; Caruso, Paul; Ptak, Thomas; Raja, Ali S.; Prabhakar, Anand M.; Harvey, H. Benjamin] Harvard Med Sch, Boston, MA USA.
[Harvey, H. Benjamin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Harvey, H. Benjamin] ACR Appropriateness Criteria Expert Panel Neurol, Boston, MA USA.
RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, 101 Merrimac St,10th Floor, Boston, MA 02114 USA.
EM hbharvey@mgh.harvard.edu
NR 22
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2016
VL 13
IS 7
BP 788
EP 793
DI 10.1016/j.jacr.2016.02.022
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DZ6SF
UT WOS:000385991500010
PM 27084071
ER
PT J
AU Hanley, M
Ahmed, O
Chandra, A
Gage, KL
Gerhard-Herman, MD
Ginsburg, M
Gornik, HL
Johnson, PT
Oliva, IB
Ptak, T
Steigner, ML
Strax, R
Rybicki, FJ
Dill, KE
AF Hanley, Michael
Ahmed, Osmanuddin
Chandra, Ankur
Gage, Kenneth L.
Gerhard-Herman, Marie D.
Ginsburg, Michael
Gornik, Heather L.
Johnson, Pamela T.
Oliva, Isabel B.
Ptak, Thomas
Steigner, Michael L.
Strax, Richard
Rybicki, Frank J.
Dill, Karin E.
TI ACR Appropriateness Criteria Clinically Suspected Pulmonary
Arteriovenous Malformation
SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY
LA English
DT Article
DE Appropriateness Criteria; pulmonary arteriovenous malformations;
hereditary hemorrhagic telangiectasia; Osler-Weber-Rendu syndrome;
transthoracic echocardiography; chest CT
ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; TO-LEFT SHUNT; CONTRAST
ECHOCARDIOGRAPHY; MR-ANGIOGRAPHY; CT; EMBOLIZATION; UPDATE
AB Pulmonary arteriovenous malformations are often included in the differential diagnosis of common clinical presentations, including hypoxemia, hemoptysis, brain abscesses, and paradoxical stroke, as well as affecting 30% to 50% of patients with hereditary hemorrhagic telangiectasia (HHT). Various imaging studies are used in the diagnostic and screening settings, which have been reviewed by the ACR Appropriateness Criteria Vascular Imaging Panel. Pulmonary arteriovenous malformation screening in patients with HHT is commonly performed with transthoracic echocardiographic bubble study, followed by CT for positive cases. Although transthoracic echocardiographic bubble studies and radionuclide perfusion detect right-to-left shunts, they do not provide all of the information needed for treatment planning and may remain positive after embolization. Pulmonary angiography is appropriate for preintervention planning but not as an initial test. MR angiography has a potential role in younger patients with HHT who may require lifelong surveillance, despite lower spatial resolution compared with CT.
The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
C1 [Hanley, Michael] Univ Virginia Hlth Syst, POB 800170, Charlottesville, VA 22908 USA.
[Ahmed, Osmanuddin] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Chandra, Ankur] Scripps Green Hosp, La Jolla, CA USA.
[Chandra, Ankur] Soc Vasc Surg, San Diego, CA USA.
[Gage, Kenneth L.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Gerhard-Herman, Marie D.; Steigner, Michael L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Gerhard-Herman, Marie D.; Gornik, Heather L.; Steigner, Michael L.] Amer Coll Cardiol, Washington, DC USA.
[Ginsburg, Michael] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Gornik, Heather L.] Cleveland Clin, Inst Heart & Vasc, Cleveland, OH 44106 USA.
[Johnson, Pamela T.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Oliva, Isabel B.] Univ Arizona, Coll Med, Tucson, AZ USA.
[Ptak, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Strax, Richard] Baylor Coll Med, Houston, TX 77030 USA.
[Rybicki, Frank J.] Univ Ottawa, Ottawa Hosp, Res Inst, Ottawa, ON, Canada.
[Rybicki, Frank J.] Univ Ottawa, Dept Radiol, Ottawa, ON, Canada.
[Dill, Karin E.] Univ Chicago, Chicago, IL 60637 USA.
RP Hanley, M (reprint author), Univ Virginia Hlth Syst, POB 800170, Charlottesville, VA 22908 USA.
EM mhanley@virginia.edu
NR 22
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1546-1440
J9 J AM COLL RADIOL
JI J. Am. Coll. Radiol.
PD JUL
PY 2016
VL 13
IS 7
BP 796
EP 800
DI 10.1016/j.jacr.2016.03.020
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DZ6SF
UT WOS:000385991500012
PM 27209598
ER
PT J
AU Chang, SY
Lo, CS
Zhao, XP
Liao, MC
Chenier, I
Bouley, R
Ingelfinger, JR
Chan, JSD
Zhang, SL
AF Chang, Shiao-Ying
Lo, Chao-Sheng
Zhao, Xin-Ping
Liao, Min-Chun
Chenier, Isabelle
Bouley, Richard
Ingelfinger, Julie R.
Chan, John S. D.
Zhang, Shao-Ling
TI Overexpression of angiotensinogen downregulates aquaporin 1 expression
via modulation of Nrf2-HO-1 pathway in renal proximal tubular cells of
transgenic mice
SO JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM
LA English
DT Article
DE Aquaporin-1; Nrf2; intrarenal renin-angiotensin system; hypertension;
kidney injury
ID NA+/H+ EXCHANGER 3; WATER CHANNELS; BLOOD-PRESSURE; ENDOTHELIAL-CELLS;
HEME OXYGENASE; RAT; HYPERTENSION; APOPTOSIS; SYSTEM; KIDNEY
AB Introduction: We aimed to examine the regulation of aquaporin 1 expression in an angiotensinogen transgenic mouse model, focusing on underlying mechanisms.
Methods: Male transgenic mice overexpressing rat angiotensinogen in their renal proximal tubular cells (RPTCs) and rat immortalised RPTCs stably transfected with rat angiotensinogen cDNA were used.
Results: Angiotensinogen-transgenic mice developed hypertension and nephropathy, changes that were either partially or completely attenuated by treatment with losartan or dual renin-angiotensin system blockade (losartan and perindopril), respectively, while hydralazine prevented hypertension but not nephropathy. Decreased expression of aquaporin 1 and heme oxygenase-1 and increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and sodium-hydrogen exchanger 3 were observed in RPTCs of angiotensinogen-transgenic mice and in angiotensinogen-transfected immortalised RPTCs. These parameters were normalised by dual renin-angiotensin system blockade. Both in vivo and in vitro studies identified a novel mechanism in which angiotensinogen overexpression in RPTCs enhances the cytosolic accumulation of Nrf2 via the phosphorylation of pGSK3 beta Y216. Consequently, lower intranuclear Nrf2 levels are less efficient to trigger heme oxygenase-1 expression as a defence mechanism, which subsequently diminishes aquaporin 1 expression in RPTCs.
Conclusions: Angiotensinogen-mediated downregulation of aquaporin 1 and Nrf2 signalling may play an important role in intrarenal renin-angiotensin system-induced hypertension and kidney injury.
C1 [Chang, Shiao-Ying; Lo, Chao-Sheng; Zhao, Xin-Ping; Liao, Min-Chun; Chenier, Isabelle; Chan, John S. D.; Zhang, Shao-Ling] CRCHUM, Montreal, PQ, Canada.
[Bouley, Richard] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Bouley, Richard; Ingelfinger, Julie R.] Harvard Med Sch, Boston, MA USA.
[Ingelfinger, Julie R.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA.
RP Zhang, SL (reprint author), CRCHUM, Montreal, PQ, Canada.
EM shao.ling.zhang@umontreal.ca
FU Kidney Foundation of Canada [KFOC130032]; Canadian Diabetes Association
[OG-3-13-4073-SZ, DS-3-13-4408-SC]; Canadian Institutes of Health
Research [MOP-10688, MOP-84363, MOP-142378]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
project was supported by the grants to SLZ from the Kidney Foundation of
Canada (grant number KFOC130032) and Canadian Diabetes Association
(grant number OG-3-13-4073-SZ) as well as grants to JSDC and SLZ from
the Canadian Institutes of Health Research (grant numbers MOP-10688,
MOP-84363 and MOP-142378). SYC is the recipient of a Canadian Diabetes
Association doctoral research award (grant number DS-3-13-4408-SC).
NR 51
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PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1470-3203
EI 1752-8976
J9 J RENIN-ANGIO-ALDO S
JI J. Renin-Angiotensin-Aldosterone Syst.
PD JUL-SEP
PY 2016
VL 17
IS 3
AR UNSP 1470320316668737
DI 10.1177/1470320316668737
PG 12
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DZ4PY
UT WOS:000385842200017
ER
PT J
AU Mbanze, I
Moschovis, PP
Malhotra, A
AF Mbanze, Irina
Moschovis, Peter P.
Malhotra, Atul
TI The American Thoracic Society Global Scholars Program
SO JOURNAL OF THORACIC DISEASE
LA English
DT Editorial Material
ID CRITICAL-CARE MEDICINE; INCOME COUNTRIES; NEXT-GENERATION; PULMONARY;
EDUCATION
C1 [Mbanze, Irina] Maputo Cent Hosp, Dept Med, Div Cardiol, Maputo, Mozambique.
[Moschovis, Peter P.] Massachusetts Gen Hosp, Div Pulm, Boston, MA 02114 USA.
[Moschovis, Peter P.] Massachusetts Gen Hosp, Div Crit Care Med, Boston, MA 02114 USA.
[Moschovis, Peter P.] Massachusetts Gen Hosp, Div Pediat Global Hlth, Boston, MA 02114 USA.
[Malhotra, Atul] Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, La Jolla, CA 92093 USA.
RP Malhotra, A (reprint author), Univ Calif San Diego, Div Pulm Crit Care & Sleep Med, La Jolla, CA 92093 USA.
EM amalhotra@ucsd.edu
FU NHLBI NIH HHS [K24 HL132105, R01 HL085188, R01 HL081823, R21 HL121794,
R01 HL119201, F32 HL124951]
NR 10
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U1 0
U2 0
PU PIONEER BIOSCIENCE PUBL CO
PI HONG KONG
PA 9A GOLD SHINE TOWER, 346-348 QUEEN'S RD CENTRAL, SHEUNG WAN, HONG KONG,
00000, PEOPLES R CHINA
SN 2072-1439
EI 2077-6624
J9 J THORAC DIS
JI J. Thorac. Dis.
PD JUL
PY 2016
VL 8
SU 7
BP S586
EP S587
DI 10.21037/jtd.2016.07.46
PG 2
WC Respiratory System
SC Respiratory System
GA DY9FK
UT WOS:000385438900020
PM 27606102
ER
PT J
AU Rho, M
Camacho-Soto, A
Cheng, A
Havran, M
Morone, NE
Rodriguez, E
Shega, J
Weiner, DK
AF Rho, Monica
Camacho-Soto, Alejandra
Cheng, Abby
Havran, Mark
Morone, Natalia E.
Rodriguez, Eric
Shega, Joseph
Weiner, Debra K.
TI Deconstructing Chronic Low Back Pain in the Older Adult-Step by Step
Evidence and Expert-Based Recommendations for Evaluation and Treatment.
Part VIII: Lateral Hip and Thigh Pain
SO PAIN MEDICINE
LA English
DT Article
DE Lateral Hip Pain; Greater Trochanteric Pain Syndrome; Chronic Low Back
Pain; Thigh Pain; Iliotibial Band Pain; Lumbar Radiculopathy; Lumbar
Radiculitis; Hip Osteoarthritis; Lumbar Spinal Stenosis; Meralgia
Paresthetica; Diagnostic Algorithm; Elderly
ID LUMBAR DISC HERNIATION; NERVE STRETCH TEST; ILIOTIBIAL BAND;
NONOPERATIVE TREATMENT; MERALGIA-PARESTHETICA; OSTEOARTHRITIS; RUNNERS;
RADICULOPATHY; IMPINGEMENT; FLEXIBILITY
AB Objective. This article presents an evidence-based algorithm to assist primary care providers with the diagnosis and management of lateral hip and thigh pain in older adults. It is part of a series that focuses on coexisting pain patterns and contributors to chronic low back pain (CLBP) in the aging population. The objective of the series is to encourage clinicians to take a holistic approach when evaluating and treating CLBP in older adults.
Methods. A content expert panel and a primary care panel collaboratively used the modified Delphi approach to iteratively develop an evidence-based diagnostic and treatment algorithm. The panelists included physiatrists, geriatricians, internists, and physical therapists who treat both civilians and Veterans, and the algorithm was developed so that all required resources are available within the Veterans Health Administration system. An illustrative patient case was chosen from one of the author's clinical practices to demonstrate the reasoning behind principles presented in the algorithm.
Results. An algorithm was developed which logically outlines evidence-based diagnostic and therapeutic recommendations for lateral hip and thigh pain in older adults. A case is presented which highlights the potential complexities of identifying the true pain generator and the importance of implementing proper treatment.
Conclusions. Lateral hip and thigh pain in older adults can contribute to and coexist with CLBP. Distinguishing the true cause(s) of pain from potentially a myriad of asymptomatic degenerative changes can be challenging, but a systematic approach can assist in identifying and treating some of the most common causes.
C1 [Rho, Monica; Cheng, Abby] Northwestern Univ, McGaw Med Ctr, Rehabil Inst Chicago, Dept Phys Med & Rehabil, Chicago, IL 60611 USA.
[Camacho-Soto, Alejandra] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Havran, Mark] VA Cent Iowa Hlth Care Syst, Extended Care & Rehab, Des Moines, IA USA.
[Havran, Mark] Des Moines Univ, Des Moines, IA USA.
[Morone, Natalia E.; Weiner, Debra K.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Morone, Natalia E.] Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA USA.
[Morone, Natalia E.; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Clin & Translat Sci Inst, Pittsburgh, PA USA.
[Rodriguez, Eric; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA.
[Shega, Joseph] VITAS Healthcare, Miami, FL USA.
[Weiner, Debra K.] Dept Psychiat, Pittsburgh, PA USA.
[Weiner, Debra K.] Dept Anesthesiol, Pittsburgh, PA USA.
RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Univ Dr,Bldg 30,00GR, Pittsburgh, PA 15240 USA.
EM debra.weiner@va.gov
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development, Rehabilitation Research and Development
Service
FX This material is based on work supported by the Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Rehabilitation Research and Development Service. Drs.
Monica Rho and Alejandra Camacho-Soto are co-first authors.
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1526-2375
EI 1526-4637
J9 PAIN MED
JI Pain Med.
PD JUL
PY 2016
VL 17
IS 7
BP 1249
EP 1260
DI 10.1093/pm/pnw111
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DZ1WK
UT WOS:000385632100008
ER
PT J
AU Lampert, RC
Nesbitt, TR
Chuang, SK
Ziccardi, VB
AF Lampert, Robert C.
Nesbitt, Travis R.
Chuang, Sung-Kiang
Ziccardi, Vincent B.
TI Management of endodontic injuries to the inferior alveolar nerve
SO QUINTESSENCE INTERNATIONAL
LA English
DT Article
DE endodontic injuries; external neurolysis; inferior alveolar nerve
repair; internal neurolysis
ID MICROSURGERY; PARESTHESIA; REPAIR; CEMENT; DAMAGE
AB Objective: Functional sensory recovery from microsurgical intervention for inferior alveolar nerve (IAN) injuries resulting from endodontic treatment were evaluated using a retrospective chart review. Other variables assessed included time from injury to surgery as well as other factors which improved functional neurosensory recovery (FSR). Method and Materials: This case series of seven patients evaluated the outcome of IAN microsurgery following endodontic-related nerve injuries. All patients were referred, evaluated, and operated on by the primary investigator (VBZ). Surgical intervention consisted of external and/or internal neurolysis with irrigation of the mandibular canal and decompression of the affected IAN as well as allogeneic nerve graft in one patient. Preoperative and postoperative sensory levels were recorded and FSR was assessed using the Medical Research Council scale. Results: Seven subjects with a mean age of 35.57 years (range 22 to 55 years old) opted to undergo trigeminal nerve microsurgery for management of their IAN injury resulting from endodontic treatment of mandibular molar teeth. Six women and one man were included in this population. The majority of subjects presented with an initial chief complaint of dysesthesia and hypoesthesia. The mean interval between nerve injury and surgical treatment was 15 weeks (range 1 to 40 weeks). All patients had preoperative sensory level of S0, S1, or S2+, and achieved FSR following surgery. Two patients had postoperative sensory level of S3, four patients had a postoperative sensory level of S3+, and one had a postoperative sensory level of S4 (complete recovery). Conclusions: The results of this study suggest that trigeminal nerve microsurgery for the surgical treatment of endodontic injuries to the IAN can improve neurosensory function. Surgical intervention in this study was beneficial to alleviate neurosensory deficits and symptoms for those injuries to the IAN caused by endodontic treatment.
C1 [Lampert, Robert C.; Ziccardi, Vincent B.] Rutgers Sch Dent Med, Dept Oral & Maxillofacial Surg, Newark, NJ USA.
[Nesbitt, Travis R.] Brookdale Univ Hosp & Med Ctr, Dept Oral & Maxillofacial Surg, Brooklyn, NY USA.
[Chuang, Sung-Kiang] Harvard Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA USA.
[Chuang, Sung-Kiang] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA.
RP Ziccardi, VB (reprint author), Dept Oral & Maxillofacial Surg, 110 Bergen St,Room B854, Newark, NJ 07103 USA.
EM ziccarvb@sdm.rutgers.edu
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PU QUINTESSENCE PUBLISHING CO INC
PI HANOVER PARK
PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA
SN 0033-6572
EI 1936-7163
J9 QUINTESSENCE INT
JI Quintessence Int.
PD JUL-AUG
PY 2016
VL 47
IS 7
BP 581
EP 587
DI 10.3290/j.qi.a36176
PG 7
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DW0VV
UT WOS:000383362000005
PM 27319813
ER
PT J
AU Nigwekar, SU
Sprague, SM
AF Nigwekar, Sagar U.
Sprague, Stuart M.
TI We Do Too Many Parathyroidectomies for Calciphylaxis
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID HEMODIALYSIS; NECROSIS; OUTCOMES; DISEASE
AB Calciphylaxis, a disorder of dermal arteriolar calcification with a distinct predilection for patients with advanced kidney disease, remains an enigmatic condition that challenges clinicians. Observations regarding positive associations between levels of circulating parathyroid hormone (PTH) and the risk of calciphylaxis, combined with experimental data suggesting a pathogenic role of secondary hyperparathyroidism in vascular calcification, have led to the assumption that reducing PTH levels will improve the outcomes in patients with calciphylaxis. This editorial communicates the contemporary data regarding surgical parathyroidectomy as a treatment option for these patients. We raise concerns regarding the quality of available data and discuss the direction of future comparative effectiveness research in this field.
C1 [Nigwekar, Sagar U.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
[Sprague, Stuart M.] Univ Chicago, Pritzker Sch Med, NorthShore Univ HealthSyst, Div Nephrol & Hypertens, Evanston, IL USA.
RP Sprague, SM (reprint author), Div Nephrol & Hypertens, 2650 Ridge Ave, Evanston, IL 60201 USA.
EM stuartmsprague@gmail.com
NR 13
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-0959
EI 1525-139X
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD JUL-AUG
PY 2016
VL 29
IS 4
BP 312
EP 314
DI 10.1111/sdi.12502
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA DZ1QB
UT WOS:000385611800021
PM 27082830
ER
PT J
AU Patel, MS
Volpp, KG
Rosin, R
Bellamy, SL
Small, DS
Fletcher, MA
Osman-Koss, R
Brady, JL
Haff, N
Lee, SM
Wesby, L
Hoffer, K
Shuttleworth, D
Taylor, DH
Hilbert, V
Zhu, JS
Yang, L
Wang, XM
Asch, DA
AF Patel, Mitesh S.
Volpp, Kevin G.
Rosin, Roy
Bellamy, Scarlett L.
Small, Dylan S.
Fletcher, Michele A.
Osman-Koss, Rosemary
Brady, Jennifer L.
Haff, Nancy
Lee, Samantha M.
Wesby, Lisa
Hoffer, Karen
Shuttleworth, David
Taylor, Devon H.
Hilbert, Victoria
Zhu, Jingsan
Yang, Lin
Wang, Xingmei
Asch, David A.
TI A Randomized Trial of Social Comparison Feedback and Financial
Incentives to Increase Physical Activity
SO AMERICAN JOURNAL OF HEALTH PROMOTION
LA English
DT Article
DE physical activity; social comparison; performance feedback; teams;
financial incentives; behavioral economics; connected health
ID CORONARY-HEART-DISEASE; HEALTH BEHAVIOR-CHANGE; WEARABLE DEVICES;
IMPROVE HEALTH; WEIGHT-LOSS; US ADULTS; ALL-CAUSE; METAANALYSIS; RISK;
ECONOMICS
AB Purpose: To compare the effectiveness of different combinations of social comparison feedback and financial incentives to increase physical activity.
Design: Randomized trial (Clinicaltrials.gov number, NCT02030080).
Setting: Philadelphia, Pennsylvania.
Participants: Two hundred eighty-six adults.
Interventions: Twenty-six weeks of weekly feedback on team performance compared to the 50th percentile (n = 100) or the 75th percentile (n = 64) and 13 weeks of weekly lottery-based financial incentive plus feedback on team performance compared to the 50th percentile (n = 80) or the 75th percentile (n = 44) followed by 13 weeks of only performance feedback.
Measures: Mean proportion of participant-days achieving the 7000-step goal during the 13-week intervention.
Analysis: Generalized linear mixed models adjusting for repeated measures and clustering by team.
Results: Compared to the 75th percentile without incentives during the intervention period, the mean proportion achieving the 7000-step goal was significantly greater for the 50th percentile with incentives group (0.45 vs 0.27, difference: 0.18, 95% confidence interval [CI]: 0.04 to 0.32; P = .012) but not for the 75th percentile with incentives group (0.38 vs 0.27, difference: 0.11, 95% CI: -0.05 to 0.27; P = .19) or the 50th percentile without incentives group (0.30 vs 0.27, difference: 0.03, 95% CI: -0.10 to 0.16; P = .67).
Conclusion: Social comparison to the 50th percentile with financial incentives was most effective for increasing physical activity.
C1 [Patel, Mitesh S.; Volpp, Kevin G.; Bellamy, Scarlett L.; Yang, Lin; Wang, Xingmei; Asch, David A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Patel, Mitesh S.; Volpp, Kevin G.; Small, Dylan S.; Asch, David A.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
[Patel, Mitesh S.; Volpp, Kevin G.; Wesby, Lisa; Hoffer, Karen; Shuttleworth, David; Taylor, Devon H.; Hilbert, Victoria; Zhu, Jingsan; Asch, David A.] Univ Penn, LDI Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
[Patel, Mitesh S.; Volpp, Kevin G.; Rosin, Roy; Asch, David A.] Univ Penn Hlth Syst, Ctr Hlth Care Innovat, Philadelphia, PA USA.
[Patel, Mitesh S.; Volpp, Kevin G.; Asch, David A.] Crescenz Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Fletcher, Michele A.; Osman-Koss, Rosemary; Brady, Jennifer L.] Univ Penn, Univ Penn Hlth Syst, Philadelphia, PA 19104 USA.
[Haff, Nancy] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Lee, Samantha M.] Columbia Univ, Dept Med, Med Ctr, New York, NY USA.
RP Patel, MS (reprint author), 1312b Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA.
EM mpatel@upenn.edu
FU National Institute on Aging [RC4 AG039114]; Department of Veteran
Affairs; Robert Wood Johnson Foundation; CVS Caremark; Humana; Discovery
(South Africa); Merck
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This work
was funded by the National Institute on Aging (RC4 AG039114) to Drs Asch
and Volpp. Dr Patel was supported in part by the Department of Veteran
Affairs and the Robert Wood Johnson Foundation. Dr. Volpp also has
received consulting income from CVS Caremark and research funding from
Humana, CVS Caremark, Discovery (South Africa), and Merck, none of which
are related to the work described in this manuscript.
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U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0890-1171
EI 2168-6602
J9 AM J HEALTH PROMOT
JI Am. J. Health Promot.
PD JUL-AUG
PY 2016
VL 30
IS 6
BP 416
EP 424
DI 10.1177/0890117116658195
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DS7DY
UT WOS:000380944300002
PM 27422252
ER
PT J
AU Liu, J
Wang, PP
Douglas, SL
Tate, JM
Sham, S
Lloyd, SG
AF Liu, Jian
Wang, Peipei
Douglas, Samuel L.
Tate, Joshua M.
Sham, Simon
Lloyd, Steven G.
TI Impact of high-fat, low-carbohydrate diet on myocardial substrate
oxidation, insulin sensitivity, and cardiac function after
ischemia-reperfusion
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE diet; myocardial ischemia-reperfusion injury; insulin; metabolism
ID KETONE-BODY METABOLISM; PERFUSED RAT-HEART; LOW-FLOW ISCHEMIA; ACID
OXIDATION; MITOCHONDRIAL METABOLISM; GLUCOSE-TOLERANCE; KETOGENIC DIET;
OBESE RATS; INJURY; RESISTANCE
AB High-fat, low-carbohydrate Diet (HFLCD) impairs the myocardial response to ischemia-reperfusion, but the underlying mechanisms remain elusive. We sought to determine the magnitude of diet-induced alterations in intrinsic properties of the myocardium (including insulin sensitivity and substrate oxidation) and circulating substrate and insulin differences resulting from diet, leading to this impaired response. Rats were fed HFLCD (60% kcal from fat/30% protein/10% carbohydrate) or control diet (CONT) (16%/19%/65%) for 2 wk. Isolated hearts underwent global low-flow ischemia followed by reperfusion (I/R). Carbon-13 NMR spectroscopy was used to determine myocardial substrate TCA cycle entry. Myocardial insulin sensitivity was assessed as dose-response of Akt phosphorylation. There was a significant effect of HFLCD and I/R with both these factors leading to an increase in free fatty acid (FFA) oxidation and a decrease in carbohydrate or ketone oxidation. Following I/R, HFLCD led to decreased ketone and increased FFA oxidation; the recovery of left ventricular (LV) function was decreased in HFLCD and was negatively correlated with FFA oxidation and positively associated with ketone oxidation. HFLCD also resulted in reduced insulin sensitivity. Under physiologic ranges, there were no direct effects of buffer insulin and ketone levels on oxidation of any substrate and recovery of cardiac function after I/R. An insulinketone interaction exists for myocardial substrate oxidation characteristics. We conclude that the impaired recovery of function after ischemia-reperfusion with HFLCD is largely due to intrinsic diet effects on myocardial properties, rather than to diet effect on circulating insulin or substrate levels.
C1 [Liu, Jian; Douglas, Samuel L.; Tate, Joshua M.; Sham, Simon; Lloyd, Steven G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Wang, Peipei] Natl Univ Singapore, Natl Univ Hlth Syst, Cardiovasc Res Inst, Singapore, Singapore.
[Lloyd, Steven G.] Birmingham VA Med Ctr, Birmingham, AL USA.
RP Lloyd, SG (reprint author), Univ Alabama Birmingham, Div Cardiovasc Dis, Dept Med, D-101 Cardiac MRI,1808 7th Ave South, Birmingham, AL 35294 USA.
EM slloyd@uabmc.edu
FU American Heart Association [0735212N]; National Institute of Diabetes
and Digestive and Kidney Diseases [P30 DK-056336]
FX This work was supported in part by American Heart Association Scientist
Development Grant 0735212N and by National Institute of Diabetes and
Digestive and Kidney Diseases P30 DK-056336.
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2016
VL 311
IS 1
BP H1
EP H10
DI 10.1152/ajpheart.00809.2015
PG 10
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA DY3CZ
UT WOS:000384969700001
PM 27199129
ER
PT J
AU McClatchey, PM
Schafer, M
Hunter, KS
Reusch, JEB
AF McClatchey, P. Mason
Schafer, Michal
Hunter, Kendall S.
Reusch, Jane E. B.
TI The endothelial glycocalyx promotes homogenous blood flow distribution
within the microvasculature
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE glycocalyx; microvascular perfusion; perfusion heterogeneity; oxygen
delivery
ID CHRONIC HEART-FAILURE; TRANSIT-TIME HETEROGENEITY; SKELETAL-MUSCLE;
METABOLIC SYNDROME; PERFUSION HETEROGENEITY; EXERCISE CAPACITY; IN-VIVO;
CAPILLARY HEMODYNAMICS; INSULIN-RESISTANCE; BARRIER PROPERTIES
AB Many common diseases involve impaired tissue perfusion, and heterogeneous distribution of blood flow in the microvasculature contributes to this pathology. The physiological mechanisms regulating homogeneity/heterogeneity of microvascular perfusion are presently unknown. Using established empirical formulations for blood viscosity modeling in vivo (blood vessels) and in vitro (glass tubes), we showed that the in vivo formulation predicts more homogenous perfusion of microvascular networks at the arteriolar and capillary levels. Next, we showed that the more homogeneous blood flow under simulated in vivo conditions can be explained by changes in red blood cell interactions with the vessel wall. Finally, we demonstrated that the presence of a spacefilling, semipermeable layer (such as the endothelial glycocalyx) at the vessel wall can account for the changes of red blood cell interactions with the vessel wall that promote homogenous microvascular perfusion. Collectively, our results indicate that the mechanical properties of the endothelial glycocalyx promote homogeneous microvascular perfusion. Preservation or restoration of normal glycocalyx properties may be a viable strategy for improving tissue perfusion in a variety of diseases.
C1 [McClatchey, P. Mason; Reusch, Jane E. B.] Univ Colorado, Div Endocrinol, Anschutz Med Campus, Aurora, CO USA.
[McClatchey, P. Mason; Reusch, Jane E. B.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA.
[McClatchey, P. Mason; Schafer, Michal; Hunter, Kendall S.; Reusch, Jane E. B.] Univ Colorado, Dept Bioengn, Anschutz Med Campus, Aurora, CO USA.
[Schafer, Michal; Hunter, Kendall S.] Childrens Hosp Colorado, Div Cardiol, Dept Pediat, Aurora, CO USA.
[Reusch, Jane E. B.] Univ Colorado, Sch Med, Ctr Womens Hlth Res, Aurora, CO USA.
RP Reusch, JEB (reprint author), 12801 E 17th Ave,MS 8106, Aurora, CO 80045 USA.
EM jane.reusch@ucdenver.edu
FU Colorado Clinical and Translational Sciences Institute [UL1-RR-025780];
Center for Women's Health Research; Veterans Affairs Merit Review;
Department of Bioengineering
FX This work was supported by Colorado Clinical and Translational Sciences
Institute-UL1-RR-025780 (to J. E. B. Reusch, M. Schafer, K. S. Hunter,
and P. M. McClatchey), the Center for Women's Health Research (to J. E.
B. Reusch), Veterans Affairs Merit Review (to J. E. B. Reusch), and the
Department of Bioengineering (to P. M. McClatchey).
NR 63
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD JUL
PY 2016
VL 311
IS 1
BP H168
EP H176
DI 10.1152/ajpheart.00132.2016
PG 9
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA DY3CZ
UT WOS:000384969700017
PM 27199117
ER
PT J
AU Firth, PG
AF Firth, Paul G.
TI Of Penguins, Pinnipeds, and Poisons Anesthesia on Elephant Island
SO ANESTHESIOLOGY
LA English
DT Article
ID CHLOROFORM
AB Although Ernest Shackleton's Endurance Antarctic expedition of 1914 to 1916 is a famous epic of survival, the medical achievements of the two expedition doctors have received little formal examination. Marooned on Elephant Island after the expedition ship sank, Drs. Macklin and McIlroy administered a chloroform anesthetic to crew member Perce Blackborow to amputate his frostbitten toes. As the saturated vapor pressure of chloroform at 0 degrees C is 71.5 mmHg and the minimum alveolar concentration is 0.5% of sea-level atmospheric pressure (3.8 mmHg), it would have been feasible to induce anesthesia at a low temperature. However, given the potentially lethal hazards of a light chloroform anesthetic, an adequate and constant depth of anesthesia was essential. The pharmacokinetics of the volatile anesthetic, administered via the open-drop technique in the frigid environment, would have been unfamiliar to the occasional anesthetist. To facilitate vaporization of the chloroform, the team burned penguin skins and seal blubber under overturned lifeboats to increase the ambient temperature from -0.5 degrees to 26.6 degrees C. Chloroform degrades with heat to chlorine and phosgene, but buildup of these poisonous gases did not occur due to venting of the confined space by the stove chimney. The anesthetic went well, and the patient-and all the ship's crew-survived to return home.
C1 [Firth, Paul G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
RP Firth, PG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM pfirth@partners.org
NR 36
TC 1
Z9 1
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUL
PY 2016
VL 125
IS 1
BP 25
EP 33
DI 10.1097/ALN.0000000000001151
PG 9
WC Anesthesiology
SC Anesthesiology
GA DY2JO
UT WOS:000384919100014
PM 27148920
ER
PT J
AU Zaremba, S
Shin, CH
Hutter, MM
Malviya, SA
Grabitz, SD
MacDonald, T
Diaz-Gil, D
Ramachandran, SK
Hess, D
Malhotra, A
Eikermann, M
AF Zaremba, Sebastian
Shin, Christina H.
Hutter, Matthew M.
Malviya, Sanjana A.
Grabitz, Stephanie D.
MacDonald, Teresa
Diaz-Gil, Daniel
Ramachandran, Satya Krishna
Hess, Dean
Malhotra, Atul
Eikermann, Matthias
TI Continuous Positive Airway Pressure Mitigates Opioid-induced Worsening
of Sleep-disordered Breathing Early after Bariatric Surgery
SO ANESTHESIOLOGY
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; PREVENT PULMONARY COMPLICATIONS; INDUCED
RESPIRATORY DEPRESSION; NATIONWIDE INPATIENT SAMPLE; MORBIDLY
OBESE-PATIENTS; POWER SPECTRAL-ANALYSIS; Y GASTRIC BYPASS; WEIGHT-LOSS;
ADAPTIVE SERVOVENTILATION; POSTOPERATIVE HYPOXEMIA
AB Background: Bariatric surgery patients are vulnerable to sleep-disordered breathing (SDB) early after recovery from surgery and anesthesia. The authors hypothesized that continuous positive airway pressure (CPAP) improves postoperative oxygenation and SDB and mitigates opioid-induced respiratory depression.
Methods: In a randomized crossover trial, patients after bariatric surgery received 30% oxygen in the postanesthesia care unit (PACU) under two conditions: atmospheric pressure and CPAP (8 to 10 cm H2O). During 1 h of each treatment, breathing across cortical arousal states was analyzed using polysomnography and spirometry. Arousal state and respiratory events were scored in accordance with American Academy of Sleep Medicine guidelines. Data on opioid boluses in the PACU were collected. The primary and secondary outcomes were the apnea hypopnea index (AHI) and apnea after self-administration of opioids in the PACU. Linear mixed model analysis was used to compare physiologic measures of breathing.
Results: Sixty-four percent of the 33 patients with complete postoperative polysomnography data demonstrated SDB (AHI greater than 5/h) early after recovery from anesthesia. CPAP treatment decreased AHI (8 +/- 2/h vs. 25 +/- 5/h, P < 0.001), decreased oxygen desaturations (5 +/- 10/h vs. 16 +/- 20/h, P < 0.001), and increased the mean oxygen saturation by 3% (P = 0.003). CPAP significantly decreased the respiratory-depressant effects observed during wakefulness-sleep transitions without affecting hemodynamics. The interaction effects between CPAP treatment and opioid dose for the dependent variables AHI (P < 0.001), inspiratory flow (P = 0.002), and minute ventilation (P = 0.015) were significant.
Conclusions: This pharmacophysiologic interaction trial shows that supervised CPAP treatment early after surgery improves SDB and ameliorates the respiratory-depressant effects of opioids without undue hemodynamic effects.
C1 [Zaremba, Sebastian; Shin, Christina H.; Malviya, Sanjana A.; Grabitz, Stephanie D.; MacDonald, Teresa; Diaz-Gil, Daniel; Eikermann, Matthias] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Hutter, Matthew M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA.
[Hess, Dean] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Resp Care, Boston, MA USA.
[Zaremba, Sebastian] Univ Bonn, Dept Neurol, Sleep Med, Bonn, Germany.
[Zaremba, Sebastian] Helmholtz Assoc, German Ctr Neurodegenerat Dis DZNE, Bonn, Germany.
[Ramachandran, Satya Krishna] Univ Michigan, Sch Med, Dept Anesthesiol, Ann Arbor, MI USA.
[Malhotra, Atul] Univ Calif San Diego, Dept Med, Div Pulm & Crit Care Med, La Jolla, CA 92093 USA.
[Eikermann, Matthias] Univ Hosp Essen, Dept Anesthesia & Crit Care, Essen, Germany.
RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM meikermann@partners.org
RI Ramachandran, Satya Krishna/P-6636-2016
OI Ramachandran, Satya Krishna/0000-0002-7176-6375
FU ResMed Foundation, La Jolla, California; National Institutes of Health
(Bethesda, Maryland) [R01 HL085188, K24 HL093218]
FX Supported by a research grant titled "Consequences of Obstructive Sleep
Apnea on Respiratory Function following Weight-loss Surgery: A
Randomized Controlled Trial" from the ResMed Foundation, La Jolla,
California (to Dr. Eikermann); and the National Institutes of Health
(Bethesda, Maryland) grants R01 HL085188 and K24 HL093218 (to Dr.
Malhotra).
NR 67
TC 2
Z9 2
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUL
PY 2016
VL 125
IS 1
BP 92
EP 104
DI 10.1097/ALN.0000000000001160
PG 13
WC Anesthesiology
SC Anesthesiology
GA DY2JO
UT WOS:000384919100021
PM 27171827
ER
PT J
AU Turner, JA
Fitzsimons, MG
Pardo, MC
Hawkins, JL
Huang, YM
Rudolph, MDD
Keyes, MA
Howard-Quijano, KJ
Naim, NZ
Buckley, JC
Grogan, TR
Steadman, RH
AF Turner, Judi A.
Fitzsimons, Michael G.
Pardo, Manuel C., Jr.
Hawkins, Joy L.
Huang, Yue Ming
Rudolph, Maria D. D.
Keyes, Mary A.
Howard-Quijano, Kimberly J.
Naim, Natale Z.
Buckley, Jack C.
Grogan, Tristan R.
Steadman, Randolph H.
TI Effect of Performance Deficiencies on Graduation and Board Certification
Rates A 10-yr Multicenter Study of Anesthesiology Residents
SO ANESTHESIOLOGY
LA English
DT Article
ID RESIDENCY PROGRAM DIRECTORS; MEDICINE RESIDENCY; NATIONAL-SURVEY; RISK
RESIDENTS; REMEDIATION; EXPERIENCE; PROBATION; DISMISSAL; OUTCOMES;
LEARNER
AB Background: This multicenter, retrospective study was conducted to determine how resident performance deficiencies affect graduation and board certification.
Methods: Primary documents pertaining to resident performance were examined over a 10-yr period at four academic anesthesiology residencies. Residents entering training between 2000 and 2009 were included, with follow-up through February 2016. Residents receiving actions by the programs' Clinical Competency Committee were categorized by the area of deficiency and compared to peers without deficiencies.
Results: A total of 865 residents were studied (range: 127 to 275 per program). Of these, 215 residents received a total of 405 actions from their respective Clinical Competency Committee. Among those who received an action compared to those who did not, the proportion graduating differed (93 vs. 99%, respectively, P < 0.001), as did the proportion achieving board certification (89 vs. 99%, respectively, P < 0.001). When a single deficiency in an Essential Attribute (e.g., ethical, honest, respectful behavior; absence of impairment) was identified, the proportion graduating dropped to 55%. When more than three Accreditation Council for Graduate Medical Education Core Competencies were deficient, the proportion graduating also dropped significantly.
Conclusions: Overall graduation and board certification rates were consistently high in residents with no, or isolated, deficiencies. Residents deficient in an Essential Attribute, or multiple competencies, are at high risk of not graduating or achieving board certification. More research is needed on the effectiveness and selective deployment of remediation efforts, particularly for high-risk groups.
C1 [Turner, Judi A.; Huang, Yue Ming; Keyes, Mary A.; Howard-Quijano, Kimberly J.; Naim, Natale Z.; Buckley, Jack C.; Steadman, Randolph H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol & Perioperat Med, Los Angeles, CA 90095 USA.
[Grogan, Tristan R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med Stat Core, Los Angeles, CA 90095 USA.
[Rudolph, Maria D. D.] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Simulat Ctr, Los Angeles, CA 90095 USA.
[Fitzsimons, Michael G.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Pardo, Manuel C., Jr.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA.
[Hawkins, Joy L.] Univ Colorado, Sch Med, Dept Anesthesiol, Denver, CO USA.
RP Steadman, RH (reprint author), RRUMC, Dept Anesthesiol & Perioperat Med, Box 957403,757 Westwood Blvd,Suite 3325, Los Angeles, CA 90095 USA.
EM rsteadman@mednet.ucla.edu
FU Department of Anesthesiology and Perioperative Medicine, David Geffen
School of Medicine at University of California, Los Angeles, Los
Angeles, California; Department of Anesthesia, Critical Care and Pain
Medicine, Harvard Medical School, Massachusetts General Hospital,
Boston, Massachusetts; Department of Anesthesia and Perioperative Care,
University of California, San Francisco, San Francisco, California;
Department of Anesthesiology, University of Colorado School of Medicine,
Denver, Colorado; National Institutes of Health/National Center for
Advancing Translational Science UCLA Clinical and Translational Science
Institute [UL1TR000124]
FX This study was supported by the authors' institutions: Department of
Anesthesiology and Perioperative Medicine, David Geffen School of
Medicine at University of California, Los Angeles, Los Angeles,
California; Department of Anesthesia, Critical Care and Pain Medicine,
Harvard Medical School, Massachusetts General Hospital, Boston,
Massachusetts; Department of Anesthesia and Perioperative Care,
University of California, San Francisco, San Francisco, California; and
Department of Anesthesiology, University of Colorado School of Medicine,
Denver, Colorado. Statistical analyses described were partially
supported by National Institutes of Health/National Center for Advancing
Translational Science UCLA Clinical and Translational Science Institute
grant number UL1TR000124.
NR 23
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD JUL
PY 2016
VL 125
IS 1
BP 221
EP 229
DI 10.1097/ALN.0000000000001142
PG 9
WC Anesthesiology
SC Anesthesiology
GA DY2JO
UT WOS:000384919100034
PM 27119434
ER
PT J
AU Gerbaud, E
Weisz, G
Tanaka, A
Kashiwagi, M
Shimizu, T
Wang, L
Souza, C
Bouma, BE
Suter, MJ
Shishkov, M
Ughi, GJ
Halpern, EF
Rosenberg, M
Waxman, S
Moses, JW
Mintz, GS
Maehara, A
Tearney, GJ
AF Gerbaud, Edouard
Weisz, Giora
Tanaka, Atsushi
Kashiwagi, Manabu
Shimizu, Takehisa
Wang, Lin
Souza, Christiano
Bouma, Brett E.
Suter, Melissa J.
Shishkov, Milen
Ughi, Giovanni J.
Halpern, Elkan F.
Rosenberg, Mireille
Waxman, Sergio
Moses, Jeffrey W.
Mintz, Gary S.
Maehara, Akiko
Tearney, Guillermo J.
TI Multi-laboratory inter-institute reproducibility study of IVOCT and IVUS
assessments using published consensus document definitions
SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
LA English
DT Article
DE Reproducibility; Intravascular ultrasound imaging; Optical frequency
domain imaging; Optical coherence tomography
ID OPTICAL COHERENCE TOMOGRAPHY; INTRAVASCULAR ULTRASOUND; INTEROBSERVER
VARIABILITY; INTRACORONARY ULTRASOUND; OCT; INTRAOBSERVER; ACQUISITION;
STANDARDS; IMAGE
AB Aims The aim of this study was to investigate the reproducibility of intravascular optical coherence tomography (IVOCT) assessments, including a comparison to intravascular ultrasound (IVUS). Intra-observer and inter-observer variabilities of IVOCT have been previously described, whereas inter-institute reliability in multiple laboratories has never been systematically studied.
Methods and results In 2 independent laboratories with intravascular imaging expertise, 100 randomized matched data sets of IVOCT and IVUS images were analysed by 4 independent observers according to published consensus document definitions. Intraobserver, inter-observer, and inter-institute variabilities of IVOCT qualitative and quantitative measurements vs. IVUS measurements were assessed. Minor inter-and intra-observer variability of both imaging techniques was observed for detailed qualitative and geometric analysis, except for inter-observer mixed plaque identification on IVUS (kappa = 0.70) and for inter-observer fibrous cap thickness measurement reproducibility on IVOCT (ICC = 0.48). The magnitude of inter-institute measurement differences for IVOCT was statistically significantly less than that for IVUS concerning lumen cross-sectional area (CSA), maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters (P < 0.001, P < 0.001, P < 0.001, P = 0.02, P < 0.001, and P = 0.01, respectively). Minor interinstitute measurement variabilities using both techniques were also found for plaque identification.
Conclusion In the measurement of lumen CSA, maximum and minimum lumen diameters, stent CSA, and maximum and minimum stent diameters by analysts from two different laboratories, reproducibility of IVOCT was more consistent than that of IVUS.
C1 [Gerbaud, Edouard; Tanaka, Atsushi; Kashiwagi, Manabu; Bouma, Brett E.; Suter, Melissa J.; Shishkov, Milen; Ughi, Giovanni J.; Rosenberg, Mireille; Tearney, Guillermo J.] Massachusetts Gen Hosp, Harvard Med Sch, BHX604A, Boston, MA 02114 USA.
[Gerbaud, Edouard; Tanaka, Atsushi; Kashiwagi, Manabu; Bouma, Brett E.; Suter, Melissa J.; Shishkov, Milen; Ughi, Giovanni J.; Rosenberg, Mireille; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, BHX604A, Boston, MA 02114 USA.
[Weisz, Giora; Shimizu, Takehisa; Wang, Lin; Souza, Christiano; Moses, Jeffrey W.; Mintz, Gary S.; Maehara, Akiko] Columbia Univ, Med Ctr, New York, NY USA.
[Weisz, Giora; Shimizu, Takehisa; Wang, Lin; Souza, Christiano; Moses, Jeffrey W.; Mintz, Gary S.; Maehara, Akiko] Cardiovasc Res Fdn, New York, NY USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
[Waxman, Sergio] Lahey Clin Med Ctr, Dept Cardiol, Burlington, MA 01803 USA.
[Tearney, Guillermo J.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA.
[Tearney, Guillermo J.] Harvard Med Sch, Dept Pathol, Boston, MA USA.
[Tearney, Guillermo J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, BHX604A, Boston, MA 02114 USA.; Tearney, GJ (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BHX604A, Boston, MA 02114 USA.; Tearney, GJ (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA.; Tearney, GJ (reprint author), Harvard Med Sch, Dept Pathol, Boston, MA USA.; Tearney, GJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM gtearney@partners.org
OI Ughi, Giovanni J./0000-0003-3354-0698
FU NIH [R01HL076398]
FX The research was funded in part by NIH R01HL076398.
NR 21
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2047-2404
EI 2047-2412
J9 EUR HEART J-CARD IMG
JI Eur. Heart J.-Cardiovasc. Imaging
PD JUL 1
PY 2016
VL 17
IS 7
BP 756
EP 764
DI 10.1093/ehjci/jev229
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DX9OP
UT WOS:000384725300010
PM 26377904
ER
PT J
AU Schoenhagen, P
Ghoshhajra, B
Achenbach, S
Abbara, S
AF Schoenhagen, Paul
Ghoshhajra, Brian
Achenbach, Stephan
Abbara, Suhny
TI Interpretation of 'incidental' cardiovascular findings in standard chest
CTs impact of evolving scanner technology on educational requirements
SO JOURNAL OF CARDIOVASCULAR COMPUTED TOMOGRAPHY
LA English
DT Editorial Material
ID CARDIAC COMPUTED-TOMOGRAPHY; IMAGE QUALITY; ANGIOGRAPHY; IDENTIFICATION;
DISEASE; AORTA
C1 [Schoenhagen, Paul] Cleveland Clin, Cleveland, OH 44106 USA.
[Ghoshhajra, Brian] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Achenbach, Stephan] Univ Erlangen Nurnberg, Erlangen, Germany.
[Abbara, Suhny] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA.
RP Schoenhagen, P (reprint author), Cleveland Clin, Cardiovasc Imaging, Desk J1-4 24,9500 Euclid Ave, Cleveland, OH 44195 USA.
EM schoenp1@ccf.org
NR 20
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-5925
J9 J CARDIOVASC COMPUT
JI J. Cardiovasc. Comput. Tomogr.
PD JUL-AUG
PY 2016
VL 10
IS 4
BP 289
EP 290
DI 10.1016/j.jcct.2016.04.004
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DY3SN
UT WOS:000385014800004
PM 27145695
ER
PT J
AU Hoge, WS
Polimeni, JR
AF Hoge, W. Scott
Polimeni, Jonathan R.
TI Dual-Polarity GRAPPA for Simultaneous Reconstruction and Ghost
Correction of Echo Planar Imaging Data
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE Nyquist ghost correction; parallel imaging; fMRI; artifact correction;
oblique ghosts; GESTE
ID PARALLEL ACQUISITIONS GRAPPA; PHASE CORRECTION; FUNCTIONAL MRI; EPI;
ARTIFACTS
AB Purpose: The purpose of this study was to seek improved image quality from accelerated echo planar imaging (EPI) data, particularly at ultrahigh fields. Certain artifacts in EPI reconstructions can be attributed to nonlinear phase differences between data acquired using frequency-encoding gradients of alternating polarity. These errors appear near regions of local susceptibility gradients and typically cannot be corrected with conventional Nyquist ghost correction (NGC) methods.
Methods: We propose a new reconstruction method that integrates ghost correction into the parallel imaging data recovery process. This is achieved through a pair of generalized auto-calibrating partially parallel acquisitions (GRAPPA) kernels that operate directly on the measured EPI data. The proposed dual-polarity GRAPPA (DPG) method estimates missing k-space data while simultaneously correcting inherent EPI phase errors.
Results: Simulation results showed that standard NGC is incapable of correcting higher-order phase errors, whereas the DPG kernel approach successfully removed these errors. The presence of higher-order phase errors near regions of local susceptibility gradients was demonstrated with in vivo data. DPG reconstructions of in vivo 3T and 7T EPI data acquired near these regions showed a marked improvement over conventional methods.
Conclusion: This new parallel imaging method for reconstructing accelerated EPI data shows better resilience to inherent EPI phase errors, resulting in higher image quality in regions where higher-order EPI phase errors commonly occur. (C) 2015 Wiley Periodicals, Inc.
C1 [Hoge, W. Scott] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
[Hoge, W. Scott] Harvard Med Sch, Boston, MA USA.
[Polimeni, Jonathan R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Hoge, WS (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
EM shoge@bwh.harvard.edu
FU Functional Neuroimaging Laboratory, Brigham and Women's Hospital;
National Institute of Biomedical Imaging and Bioengineering
[K01-EB011498, R01-EB019437]; Athinoula A. Martinos Center for
Biomedical Imaging
FX Grant sponsor: Functional Neuroimaging Laboratory, Brigham and Women's
Hospital; Grant sponsor: National Institute of Biomedical Imaging and
Bioengineering; Grant number: K01-EB011498, R01-EB019437; Grant sponsor:
Athinoula A. Martinos Center for Biomedical Imaging.
NR 25
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2016
VL 76
IS 1
BP 32
EP 44
DI 10.1002/mrm.25839
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3MK
UT WOS:000384996900003
PM 26208304
ER
PT J
AU Han, F
Zhou, ZW
Rapacchi, S
Nguyen, KL
Finn, JP
Hu, P
AF Han, Fei
Zhou, Ziwu
Rapacchi, Stanislas
Nguyen, Kim-Lien
Finn, J. Paul
Hu, Peng
TI Segmented Golden Ratio Radial Reordering with Variable Temporal
Resolution for Dynamic Cardiac MRI
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE golden ratio; cardiac MRI; RF golden angle radial; segmented k-space
ID RETROSPECTIVE RECONSTRUCTION; CINE IMAGES; K-SPACE; ANGIOGRAPHY; MOTION
AB Purpose: Golden ratio (GR) radial reordering allows for retrospective choice of temporal resolution by providing a near-uniform k-space sampling within any reconstruction window. However, when applying GR to electrocardiogram (ECG)-gated cardiac imaging, the k-space coverage may not be as uniform because a single reconstruction window is broken into several temporally isolated ones. The goal of this study was to investigate the image artifacts caused by applying GR to ECG-gated cardiac imaging and to propose a segmented GR method to address this issue.
Methods: Computer simulation and phantom experiments were used to evaluate the image artifacts resulting from three k-space sampling patterns (ie, uniform radial, conventional GR, and segmented GR). Two-and three-dimensional cardiac cine images were acquired in seven healthy subjects. Imaging artifacts due to k-space sampling nonuniformity were graded on a 5-point scale by an experienced cardiac imaging reader.
Results: Segmented GR provides more uniform k-space sampling that is independent of heart-rate variation than conventional GR. Cardiac cine images using segmented GR have significantly higher and more reliable image quality than conventional GR.
Conclusion: Segmented GR successfully addresses the non-uniform sampling that occurs with combining conventional GR with ECG gating. This technique can potentially be applied to any ECG-gated cardiac imaging application to allow for retrospective selection of a reconstruction window. (C) 2015 Wiley Periodicals, Inc.
C1 [Han, Fei; Zhou, Ziwu; Rapacchi, Stanislas; Nguyen, Kim-Lien; Finn, J. Paul; Hu, Peng] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA.
[Han, Fei; Zhou, Ziwu] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA USA.
[Hu, Peng] Univ Calif Los Angeles, Biomed Phys Interdept Grad Program, Los Angeles, CA USA.
[Nguyen, Kim-Lien] VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA USA.
[Nguyen, Kim-Lien] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Hu, P (reprint author), Dept Radiol Sci, 300 UCLA Med Plaza Suite B119, Los Angeles, CA 90095 USA.
EM penghu@mednet.ucla.edu
OI Nguyen, Kim-Lien/0000-0002-8854-2976
FU National Institutes of Health [1R01HL127153]
FX Grant sponsor: National Institutes of Health; Grant number:
1R01HL127153.
NR 20
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2016
VL 76
IS 1
BP 94
EP 103
DI 10.1002/mrm.25861
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3MK
UT WOS:000384996900008
PM 26243442
ER
PT J
AU Farivar, R
Grigorov, F
van der Kouwe, AJ
Wald, LL
Keil, B
AF Farivar, Reza
Grigorov, Filip
van der Kouwe, Andre J.
Wald, Lawrence L.
Keil, Boris
TI Dense, Shape-Optimized Posterior 32-Channel Coil for Submillimeter
Functional Imaging of Visual Cortex at 3T
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE magnetic resonance imaging; phased-array; fMRI; parallel imaging; shape
optimization; ocular dominance columns; functional MRI; orientation
columns; accelerated EPI
ID OCULAR DOMINANCE COLUMNS; SURFACE-BASED ANALYSIS; PHASED-ARRAY; HEAD
COIL; BRAIN; MRI; NOISE; FMRI; DESIGN; TESLA
AB Purpose: Functional neuroimaging of small cortical patches such as columns is essential for testing computational models of vision, but imaging from cortical columns at conventional 3T fields is exceedingly difficult. By targeting the visual cortex exclusively, we tested whether combined optimization of shape, coil placement, and electronics would yield the necessary gains in signal-to-noise ratio (SNR) for submillimeter visual cortex functional MRI (fMRI).
Method: We optimized the shape of the housing to a population-averaged atlas. The shape was comfortable without cushions and resulted in the maximally proximal placement of the coil elements. By using small wire loops with the least number of solder joints, we were able to maximize the Q factor of the individual elements. Finally, by planning the placement of the coils using the brain atlas, we were able to target the arrangement of the coil elements to the extent of the visual cortex.
Results: The combined optimizations led to as much as two-fold SNR gain compared with a whole-head 32-channel coil. This gain was reflected in temporal SNR as well and enabled fMRI mapping at 0.75 mm resolutions using a conventional GRAPPA-accelerated gradient echo echo planar imaging.
Conclusion: Integrated optimization of shape, electronics, and element placement can lead to large gains in SNR and empower submillimeter fMRI at 3T. (C) 2015 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
C1 [Farivar, Reza; Grigorov, Filip] McGill Univ, Dept Ophthalmol, McGill Vis Res Unit, Montreal, PQ, Canada.
[van der Kouwe, Andre J.; Wald, Lawrence L.; Keil, Boris] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[van der Kouwe, Andre J.; Wald, Lawrence L.; Keil, Boris] Harvard Med Sch, Boston, MA USA.
[Wald, Lawrence L.] MIT, Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RP Farivar, R (reprint author), Royal Victoria Hosp, McGill Vis Res Unit, Room H4-14,687 Pine Ave West, Montreal, PQ H3A 1A1, Canada.
EM reza.farivar@mcgill.ca
FU National Institutes of Health [P41RR14075]; Research Institute of the
McGill University Health Centre
FX Grant sponsor: National Institutes of Health; Grant number: P41RR14075;
Grant sponsor: Research Institute of the McGill University Health Centre
(internal award to Reza Farivar).
NR 30
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2016
VL 76
IS 1
BP 321
EP 328
DI 10.1002/mrm.25815
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3MK
UT WOS:000384996900032
PM 26218835
ER
PT J
AU Mahmood, Z
McDaniel, P
Guerin, B
Keil, B
Vester, M
Adalsteinsson, E
Wald, LL
Daniel, L
AF Mahmood, Zohaib
McDaniel, Patrick
Guerin, Bastien
Keil, Boris
Vester, Markus
Adalsteinsson, Elfar
Wald, Lawrence L.
Daniel, Luca
TI General Design Approach and Practical Realization of Decoupling Matrices
for Parallel Transmission Coils
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE decoupling matrix; robust decoupling; parallel transmit coils; parallel
transmission; power efficiency
ID RF PULSE DESIGN; PHASED-ARRAY; SAR REDUCTION; GLOBAL SAR; 8 CHANNELS;
LOCAL SAR; EXCITATION; POWER; MRI; CONSTRAINTS
AB Purpose: In a coupled parallel transmit (pTx) array, the power delivered to a channel is partially distributed to other channels because of coupling. This power is dissipated in circulators resulting in a significant reduction in power efficiency. In this study, a technique for designing robust decoupling matrices interfaced between the RF amplifiers and the coils is proposed. The decoupling matrices ensure that most forward power is delivered to the load without loss of encoding capabilities of the pTx array.
Theory and Methods: The decoupling condition requires that the impedance matrix seen by the power amplifiers is a diagonal matrix whose entries match the characteristic impedance of the power amplifiers. In this work, the impedance matrix of the coupled coils is diagonalized by a successive multiplication by its eigenvectors. A general design procedure and software are developed to generate automatically the hardware that implements diagonalization using passive components.
Results: The general design method is demonstrated by decoupling two example parallel transmit arrays. Our decoupling matrices achieve better than -20 db decoupling in both cases.
Conclusion: A robust framework for designing decoupling matrices for pTx arrays is presented and validated. The proposed decoupling strategy theoretically scales to any arbitrary number of channels. (C) 2015 Wiley Periodicals, Inc.
C1 [Mahmood, Zohaib; McDaniel, Patrick; Adalsteinsson, Elfar; Daniel, Luca] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Guerin, Bastien; Keil, Boris; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Vester, Markus] Siemens AG, Healthcare Sect, Imaging & Therapy Div, Erlangen, Germany.
[Adalsteinsson, Elfar; Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA.
[Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RP Mahmood, Z (reprint author), MIT, Off 36-732,77 Massachusetts Ave, Cambridge, MA 02139 USA.
FU National Science Foundation [1227020-EEC]; Semiconductor Research
Corporation [TASK 2436.001]; NIH [R01EB0006847, R01EB007942,
P41EB015896]
FX Grant sponsor: National Science Foundation; Grant number: 1227020-EEC;
Grant sponsor: the Semiconductor Research Corporation; Grant number:
TASK 2436.001; Grant sponsor: NIH; Grant numbers: R01EB0006847,
R01EB007942, P41EB015896.
NR 55
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD JUL
PY 2016
VL 76
IS 1
BP 329
EP 339
DI 10.1002/mrm.25855
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3MK
UT WOS:000384996900033
PM 26228386
ER
PT J
AU Lemieux, JE
Tran, AD
Freimark, L
Schaffner, SF
Goethert, H
Andersen, KG
Bazner, S
Li, A
McGrath, G
Sloan, L
Vannier, E
Milner, D
Pritt, B
Rosenberg, E
Telford, S
Bailey, JA
Sabeti, PC
AF Lemieux, Jacob E.
Tran, Alice D.
Freimark, Lisa
Schaffner, Stephen F.
Goethert, Heidi
Andersen, Kristian G.
Bazner, Suzane
Li, Amy
McGrath, Graham
Sloan, Lynne
Vannier, Edouard
Milner, Dan
Pritt, Bobbi
Rosenberg, Eric
Telford, Sam, III
Bailey, Jeffrey A.
Sabeti, Pardis C.
TI A global map of genetic diversity in Babesia microti reveals strong
population structure and identifies variants associated with clinical
relapse
SO NATURE MICROBIOLOGY
LA English
DT Article
ID MULTIPLE SEQUENCE ALIGNMENT; CYTOCHROME-B; IMMUNOCOMPROMISED PATIENTS;
ATOVAQUONE-RESISTANCE; RIBOSOMAL MUTATIONS; HYBRID SELECTION;
UNITED-STATES; INFECTION; PARASITES; AZITHROMYCIN
AB Human babesiosis caused by Babesia microti is an emerging tick-borne zoonosis of increasing importance due to its rising incidence and expanding geographic range(1). Infection with this organism, an intraerythrocytic parasite of the phylum Apicomplexa, causes a febrile syndrome similar to malaria(2). Relapsing disease is common among immunocompromised and asplenic individuals(3,4) and drug resistance has recently been reported(5). To investigate the origin and genetic diversity of this parasite, we sequenced the complete genomes of 42 B. microti samples from around the world, including deep coverage of clinical infections at endemic sites in the continental USA. Samples from the continental USA segregate into a Northeast lineage and a Midwest lineage, with subsequent divergence of subpopulations along geographic lines. We identify parasite variants that associate with relapsing disease, including amino acid substitutions in the atovaquone-binding regions of cytochrome b (cytb) and the azithromycin-binding region of ribosomal protein subunit L4 (rpl4). Our results shed light on the origin, diversity and evolution of B. microti, suggest possible mechanisms for clinical relapse, and create the foundation for further research on this emerging pathogen.
C1 [Lemieux, Jacob E.; Freimark, Lisa; Schaffner, Stephen F.; Andersen, Kristian G.; Sabeti, Pardis C.] Broad Inst MIT Div Hlth Sci, Cambridge, MA 02142 USA.
[Lemieux, Jacob E.; Freimark, Lisa; Schaffner, Stephen F.; Andersen, Kristian G.; Sabeti, Pardis C.] MIT, Cambridge, MA 02142 USA.
[Lemieux, Jacob E.; Bazner, Suzane; McGrath, Graham; Rosenberg, Eric] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Tran, Alice D.; Bailey, Jeffrey A.] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Worcester, MA 01605 USA.
[Goethert, Heidi; Telford, Sam, III] Tufts Sch Vet Med, North Grafton, MA 01536 USA.
[Andersen, Kristian G.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Li, Amy] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02142 USA.
[Sloan, Lynne; Pritt, Bobbi] Mayo Clin, Dept Pathol, Rochester, MN 55905 USA.
[Vannier, Edouard] Tufts Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA.
[Milner, Dan] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Rosenberg, Eric] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bailey, Jeffrey A.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA.
[Sabeti, Pardis C.] MIT Div Hlth Sci & Univ, Dept Evolutionary & Organism Biol, Cambridge, MA 02138 USA.
RP Sabeti, PC (reprint author), Broad Inst MIT Div Hlth Sci, Cambridge, MA 02142 USA.; Sabeti, PC (reprint author), MIT, Cambridge, MA 02142 USA.; Sabeti, PC (reprint author), MIT Div Hlth Sci & Univ, Dept Evolutionary & Organism Biol, Cambridge, MA 02138 USA.
EM pardis@broadinstitute.org
RI Schaffner, Stephen/D-1189-2011
FU Broad Institute SPARC programme; Bill and Melinda Gates Foundation;
Howard Hughes Medical Institute; Infectious Disease Society of America;
MIT Division of Health Sciences and/MIT Division of Health Sciences and
Technology Research Assistantship; NIH MSTP [T32GM007753]; NIH
[U01AI109656, R41AI078631]; Evelyn Lilly Lutz Foundation; Dorothy
Harrison Egan Foundation; National Research Fund for Tick-Borne Diseases
FX The authors thank R. Tewhey, A. Piantadosi and J. Maguire for feedback
and advice, and J. Robbins, J. Katz, J. Gelfand and T. Wieczorek for
discussions and assistance with sample collection. The authors
acknowledge members of the parasitology and haematology laboratories at
Massachusetts General Hospital and Brigham and Women's Hospital for
assistance with case identification. P.C.S. and this work are supported
by the Broad Institute SPARC programme and the Bill and Melinda Gates
Foundation and the Howard Hughes Medical Institute. This work was
supported in part by an Infectious Disease Society of America Medical
Scholars award, a MIT Division of Health Sciences and/MIT Division of
Health Sciences and Technology Research Assistantship to J.E.L. and NIH
MSTP grants T32GM007753 to J.E.L. and A.L. S.T. and H.K.G. are supported
by NIH U01AI109656 and R41AI078631 and by grants from the Evelyn Lilly
Lutz Foundation, the Dorothy Harrison Egan Foundation and the Bill and
Melinda Gates Foundation. E.V. was supported by a grant from the
National Research Fund for Tick-Borne Diseases.
NR 50
TC 3
Z9 3
U1 6
U2 6
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
EI 2058-5276
J9 NAT MICROBIOL
JI NAT. MICROBIOL
PD JUL
PY 2016
VL 1
IS 7
AR 16079
DI 10.1038/NMICROBIOL.2016.79
PG 7
WC Microbiology
SC Microbiology
GA DW4IF
UT WOS:000383605700015
PM 27572973
ER
PT J
AU Nierenberg, AA
AF Nierenberg, Andrew A.
TI Why We Sleep
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Nierenberg, Andrew A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA.
[Nierenberg, Andrew A.] Massachusetts Gen Hosp, MGH Res Inst, Training & Educ, Boston, MA 02114 USA.
[Nierenberg, Andrew A.] Harvard Med Sch, Psychiat, Boston, MA 02115 USA.
RP Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA.; Nierenberg, AA (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA.; Nierenberg, AA (reprint author), Massachusetts Gen Hosp, MGH Res Inst, Training & Educ, Boston, MA 02114 USA.; Nierenberg, AA (reprint author), Harvard Med Sch, Psychiat, Boston, MA 02115 USA.
EM psyann@Healio.com
NR 2
TC 0
Z9 0
U1 2
U2 2
PU SLACK INC
PI THOROFARE
PA 6900 GROVE RD, THOROFARE, NJ 08086 USA
SN 0048-5713
EI 1938-2456
J9 PSYCHIAT ANN
JI Psychiatr. Ann.
PD JUL
PY 2016
VL 46
IS 7
BP 381
EP 381
DI 10.3928/00485713-20160520-01
PG 1
WC Psychiatry
SC Psychiatry
GA DY3VF
UT WOS:000385022600001
ER
PT J
AU Patino, M
Prochowski, A
Agrawal, MD
Simeone, FJ
Gupta, R
Hahn, PF
Sahani, DV
AF Patino, Manuel
Prochowski, Andrea
Agrawal, Mukta D.
Simeone, Frank J.
Gupta, Rajiv
Hahn, Peter F.
Sahani, Dushyant V.
TI Material Separation Using Dual-Energy CT: Current and Emerging
Applications
SO RADIOGRAPHICS
LA English
DT Article
ID VIRTUAL NONENHANCED IMAGES; ACUTE PULMONARY-EMBOLISM; ADDITIONAL
SPECTRAL FILTRATION; EFFECTIVE ATOMIC NUMBER; RENAL STONE COMPOSITION;
COMPUTED-TOMOGRAPHY; DIAGNOSTIC PERFORMANCE; MULTIDETECTOR CT; MATERIAL
DENSITY; LIVER FIBROSIS
AB Dual-energy (DE) computed tomography (CT) offers the opportunity to generate material-specific images on the basis of the atomic number Z and the unique mass attenuation coefficient of a particular material at different x-ray energies. Material-specific images provide qualitative and quantitative information about tissue composition and contrast media distribution. The most significant contribution of DE CT-based material characterization comes from the capability to assess iodine distribution through the creation of an image that exclusively shows iodine. These iodine-specific images increase tissue contrast and amplify subtle differences in attenuation between normal and abnormal tissues, improving lesion detection and characterization in the abdomen. In addition, DE CT enables computational removal of iodine influence from a CT image, generating virtual noncontrast images. Several additional materials, including calcium, fat, and uric acid, can be separated, permitting imaging assessment of metabolic imbalances, elemental deficiencies, and abnormal deposition of materials within tissues. The ability to obtain material-specific images from a single, contrast-enhanced CT acquisition can complement the anatomic knowledge with functional information, and may be used to reduce the radiation dose by decreasing the number of phases in a multiphasic CT examination. DE CT also enables generation of energy-specific and virtual monochromatic images. Clinical applications of DE CT leverage both material-specific images and virtual monochromatic images to expand the current role of CT and overcome several limitations of single-energy CT. (C) RSNA, 2016.
C1 [Patino, Manuel; Prochowski, Andrea; Agrawal, Mukta D.; Simeone, Frank J.; Gupta, Rajiv; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, 55 Fruit St, Boston, MA 02114 USA.
[Hahn, Peter F.] Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA.
Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA.
RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, 55 Fruit St, Boston, MA 02114 USA.
EM dsahani@mgh.harvard.edu
NR 99
TC 1
Z9 1
U1 1
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD JUL-AUG
PY 2016
VL 36
IS 4
BP 1087
EP 1105
DI 10.1148/rg.2016150220
PG 19
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3YG
UT WOS:000385033800011
PM 27399237
ER
PT J
AU Barnett, PG
Schmitt, SK
Yu, W
Goetz, MB
Ohl, ME
Asch, SM
AF Barnett, Paul G.
Schmitt, Susan K.
Yu, Wei
Goetz, Matthew Bidwell
Ohl, Michael E.
Asch, Steven M.
TI How Will New Guidelines Affect CD4 Testing in Veterans With HIV?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE HIV; CD4 testing; veterans; guidelines; cost
ID ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; CELL COUNT; SUPPRESSION
AB Background. Guidelines now recommend limited use of routine CD4 cell count testing in human immunodeficiency virus (HIV)-infected patients with successful viral control who are not immunocompromised.
Methods. CD4 and viral load tests for patients receiving HIV care from the US Department of Veterans Affairs during 2009-2013 were evaluated to determine trends in CD4 testing frequency and the number, cost, and results of CD4 tests considered optional under the guidelines.
Results. There were 28 530 individuals with sufficient testing to be included. At the time of the last CD4 test, 19.8% of the cohort was eligible for optional monitoring and 15.6% for minimal monitoring. CD4 testing frequency declined by 10.8% over 4 years, reducing the direct cost of testing by US$196 000 per year. Full implementation of new treatment guidelines could reduce CD4 testing a further 28.9%, an additional annual savings of US$600 000. CD4 tests conducted during periods of potentially reduced monitoring were rarely <200 cells/mu L: 1.1% of the tests conducted when minimal monitoring was recommended and just 0.3% of tests conducted when optional monitoring was recommended were less than this value.
Conclusions. Reduced CD4 monitoring of HIV-infected patients would result in modest cost savings and likely reduce patient anxiety, with little or no impact on the quality of care. Veterans Affairs has made substantial progress in reducing the frequency of optional CD4 testing, but further reductions may still be warranted.
C1 [Barnett, Paul G.; Schmitt, Susan K.; Yu, Wei] Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA.
[Barnett, Paul G.] Univ Calif San Francisco, Dept Psychiat, Treatment Res Ctr, San Francisco, CA USA.
[Barnett, Paul G.; Yu, Wei; Asch, Steven M.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA.
[Goetz, Matthew Bidwell] Univ Calif Los Angeles, Infect Dis Sect, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA.
[Goetz, Matthew Bidwell] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Ohl, Michael E.] Univ Iowa, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City Vet Affairs Med Ctr, Dept Internal Med,Carver Coll Med, Iowa City, IA 52242 USA.
[Asch, Steven M.] Stanford Univ, Sch Med, Dept Gen Med Disciplines, Stanford, CA 94305 USA.
RP Barnett, PG (reprint author), VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA.
EM paul.barnett@va.gov
FU Quality Enhancement Research Initiative; Health Services Research and
Development Service of the US Department of Veterans Affairs
FX This work was supported by the Quality Enhancement Research Initiative
and the Health Services Research and Development Service of the US
Department of Veterans Affairs.
NR 18
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1058-4838
EI 1537-6591
J9 CLIN INFECT DIS
JI Clin. Infect. Dis.
PD JUL 1
PY 2016
VL 63
IS 1
BP 96
EP 100
DI 10.1093/cid/ciw194
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DT1FH
UT WOS:000381226600019
PM 27045125
ER
PT J
AU Garvey, WT
Mechanick, JI
Brett, EM
Garber, AJ
Hurley, DL
Jastreboff, AM
Nadolsky, K
Pessah-Pollack, R
Plodkowski, R
AF Garvey, W. Timothy
Mechanick, Jeffrey I.
Brett, Elise M.
Garber, Alan J.
Hurley, Daniel L.
Jastreboff, Ania M.
Nadolsky, Karl
Pessah-Pollack, Rachel
Plodkowski, Raymond
CA AACE ACE Obesity Clinical Practice
TI AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE
OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL
CARE OF PATIENTS WITH OBESITY
SO ENDOCRINE PRACTICE
LA English
DT Article
ID BODY-MASS INDEX; POLYCYSTIC-OVARY-SYNDROME; NONALCOHOLIC FATTY-LIVER;
RANDOMIZED-CONTROLLED-TRIAL; TYPE-2 DIABETES-MELLITUS;
GASTROESOPHAGEAL-REFLUX DISEASE; BINGE-EATING DISORDER; OBSTRUCTIVE
SLEEP-APNEA; PLACEBO-CONTROLLED TRIAL; LIFE-STYLE INTERVENTION
AB Objective: Development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and the American College of Endocrinology (ACE) Board of Trustees and adheres to published AACE protocols for the standardized production of clinical practice guidelines (CPGs).
Methods: Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors.
Results: There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements (85 [53.1%] strong [Grade A]; 48 [30.0%] intermediate [Grade B], and 11 [6.9%] weak [Grade C], with 16 [10.0%] based on expert opinion [Grade D]) that build a comprehensive medical care plan for obesity. There were 133 (83.1%) statements based on strong (best evidence level [BEL] 1 = 79 [49.4%]) or intermediate (BEL 2 = 54 [33.7%]) levels of scientific substantiation. There were 34 (23.6%) evidence-based recommendation grades (Grades A-C = 144) that were adjusted based on subjective factors. Among the 1,790 reference citations used in this CPG, 524 (29.3%) were based on strong (evidence level [EL] 1), 605 (33.8%) were based on intermediate (EL 2), and 308 (17.2%) were based on weak (EL 3) scientific studies, with 353 (19.7%) based on reviews and opinions (EL 4).
Conclusion: The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety.
C1 [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] UAB Diabet Res Ctr, Birmingham, AL USA.
[Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL USA.
[Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Metab Support, New York, NY 10029 USA.
[Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, Med, New York, NY 10029 USA.
[Brett, Elise M.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
[Garber, Alan J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Garber, Alan J.] Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Garber, Alan J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Hurley, Daniel L.] Mayo Clin, Med, Rochester, MN USA.
[Jastreboff, Ania M.] Yale Univ, Sch Med, Internal Med, Endocrinol,Pediat,Pediat Endocrinol, New Haven, CT USA.
[Nadolsky, Karl] Walter Reed Natl Mil Med Ctr, Diabet Obes & Metab Inst, Bethesda, MD USA.
[Pessah-Pollack, Rachel] Mt Sinai Sch Med, ProHlth Care Associates, Div Endocrinol, Lake Success, NY USA.
[Plodkowski, Raymond] Scripps Clin, Ctr Weight Management, Div Endocrinol Diabet & Metab, San Diego, CA USA.
RP Garvey, WT (reprint author), Amer Assoc Clin Endocrinologists, 245 Riverside Ave,Suite 200, Jacksonville, FL 32202 USA.
EM publications@aace.com
NR 1790
TC 10
Z9 10
U1 26
U2 26
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD JUL
PY 2016
VL 22
SU 3
BP 1
EP 203
DI 10.4158/EP161365.GL
PG 203
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DX3NJ
UT WOS:000384279500001
PM 27219496
ER
PT J
AU Garvey, WT
Mechanick, JI
Brett, EM
Garber, AJ
Hurley, DL
Jastreboff, AM
Nadolsky, K
Pessah-Pollack, R
Plodkowski, R
AF Garvey, W. Timothy
Mechanick, Jeffrey I.
Brett, Elise M.
Garber, Alan J.
Hurley, Daniel L.
Jastreboff, Ania M.
Nadolsky, Karl
Pessah-Pollack, Rachel
Plodkowski, Raymond
CA AACE ACE Obesity Clinical Practice
TI AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE
OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL
CARE OF PATIENTS WITH OBESITY
SO ENDOCRINE PRACTICE
LA English
DT Article
ID CARDIOVASCULAR-DISEASE RISK; WEIGHT-LOSS DIETS; RANDOMIZED
CONTROLLED-TRIAL; IMPROVING PRIMARY-CARE; BODY-MASS INDEX; MEDITERRANEAN
DIET; METABOLIC SYNDROME; MACRONUTRIENT COMPOSITION; STANDARDIZED
PRODUCTION; INSULIN SENSITIVITY
AB Objective: Development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and the American College of Endocrinology (ACE) Board of Trustees and adheres to published AACE protocols for the standardized production of clinical practice guidelines (CPGs).
Methods: Recommendations are based on diligent review of clinical evidence with transparent incorporation of subjective factors.
Results: There are 9 broad clinical questions with 123 recommendation numbers that include 160 specific statements (85 [53.1%] strong [Grade A], 48 [30.0%] intermediate [Grade B], and 11 [6.9%] weak [Grade C], with 16 [10.0%] based on expert opinion [Grade D]) that build a comprehensive medical care plan for obesity. There were 133 (83.1%) statements based on strong (best evidence level [BEL] 1 = 79 [49.4%]) or intermediate (BEL 2 = 54 [33.7%]) levels of scientific substantiation. There were 34 (23.6%) evidence-based recommendation grades (Grades A-C = 144) that were adjusted based on subjective factors. Among the 1,788 reference citations used in this CPG, 524 (29.3%) were based on strong (evidence level [EL] 1), 605 (33.8%) were based on intermediate (EL 2), and 308 (17.2%) were based on weak (EL 3) scientific studies, with 351 (19.6%) based on reviews and opinions (EL 4).
Conclusion: The final recommendations recognize that obesity is a complex, adiposity-based chronic disease, where management targets both weight-related complications and adiposity to improve overall health and quality of life. The detailed evidence-based recommendations allow for nuanced clinical decision-making that addresses real-world medical care of patients with obesity, including screening, diagnosis, evaluation, selection of therapy, treatment goals, and individualization of care. The goal is to facilitate high-quality care of patients with obesity and provide a rational, scientific approach to management that optimizes health outcomes and safety.
C1 [Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] UAB Diabet Res Ctr, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham VA Med Ctr, Birmingham, AL 35233 USA.
[Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Metab Support, New York, NY 10029 USA.
[Mechanick, Jeffrey I.] Icahn Sch Med Mt Sinai, Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
[Brett, Elise M.] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
[Garber, Alan J.] Baylor Coll Med, Dept Med Biochem & Mol Biol, Houston, TX 77030 USA.
[Garber, Alan J.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Hurley, Daniel L.] Mayo Clin, Med, Rochester, MN USA.
[Jastreboff, Ania M.] Yale Univ, Sch Med, Internal Med Endocrinol Pediat Pediat Endocrinol, New Haven, CT USA.
[Nadolsky, Karl] Walter Reed Natl Mil Med Ctr, Diabet Obes & Metab Inst, Bethesda, MD USA.
[Pessah-Pollack, Rachel] Mt Sinai Sch Med, New York, NY USA.
[Pessah-Pollack, Rachel] ProHealth Care Associates, Div Endocrinol, Lake Success, NY USA.
[Plodkowski, Raymond] Scripps Clin, Div Endocrinol Diabet & Metab, Ctr Weight Management, San Diego, CA USA.
RP Garvey, WT (reprint author), Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.; Garvey, WT (reprint author), UAB Diabet Res Ctr, Birmingham, AL 35294 USA.; Garvey, WT (reprint author), Birmingham VA Med Ctr, Birmingham, AL 35233 USA.
EM publications@aace.com
NR 75
TC 5
Z9 5
U1 3
U2 3
PU AMER ASSOC CLINICAL ENDOCRINOLOGISTS
PI JACKSONVILLE
PA 245 RIVERSIDE AVENUE, STE 200, JACKSONVILLE, FL 32202 USA
SN 1530-891X
EI 1934-2403
J9 ENDOCR PRACT
JI Endocr. Pract.
PD JUL
PY 2016
VL 22
IS 7
BP 842
EP 884
DI 10.4158/EP161356.ESGL
PG 43
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DX3NI
UT WOS:000384279400011
PM 27472012
ER
PT J
AU Heidenreich, PA
Sahay, A
Oliva, N
Gholami, P
Lin, S
Mittman, BS
Rumsfeld, JS
AF Heidenreich, Paul A.
Sahay, Anju
Oliva, Nancy
Gholami, Parisa
Lin, Shoutzu
Mittman, Brian S.
Rumsfeld, John S.
TI Impact of the Hospital to Home Initiative on Readmissions in the VA
Health Care System
SO QUALITY MANAGEMENT IN HEALTH CARE
LA English
DT Article
DE heart failure; quality of care; readmission; transition of care
ID HEART-FAILURE; INTERVENTIONS; METAANALYSIS; RATES
AB Background: Hospital to Home (H2H) is a national quality improvement initiative sponsored by the Institute for Healthcare Improvement and the American College of Cardiology, with the goal of reducing readmission for patients hospitalized with heart disease. We sought to determine the impact of H2H within the Veterans Affairs (VA) health care system.
Methods: Using a controlled interrupted time series, we determined the association of VA hospital enrollment in H2H with the primary outcome of 30-day all-cause readmission following a heart failure hospitalization. VA heart failure providers were surveyed to determine quality improvement projects initiated in response to H2H. Secondary outcomes included initiation of recommended H2H projects, follow-up within 7 days, and total hospital days at 30 days and 1 year.
Results: Sixty-five of 104 VA hospitals (66%) enrolled in the national H2H initiative. Hospital characteristic associated with H2H enrollment included provision of tertiary care, academic affiliation, and greater use of home monitoring. There was no significant difference in mean 30-day readmission rates (20.0% 5.0% for H2H vs 19.3% +/- 5.9% for non-H2H hospitals; P = .48) The mean fraction of patients with a cardiology visit within 7 days was slightly higher for H2H hospitals (3.0% +/- 2.4% for H2H vs 2.0% +/- 1.9% for non-H2H hospitals; P = .05). Patients discharged from H2H hospitals had fewer mean hospitals days during the following year (7.6% +/- 2.6% for H2H vs 9.2% +/- 3.0 for non-H2H; P = .01) early after launch of H2H, but the effect did not persist.
Conclusions: VA hospitals enrolling in H2H had slightly more early follow-up in cardiology clinic but no difference in 30-day readmission rates compared with hospitals not enrolling in H2H.
C1 [Heidenreich, Paul A.; Sahay, Anju; Oliva, Nancy; Gholami, Parisa; Lin, Shoutzu] Vet Adm Palo Alto Hlth Care Syst, 111C,3801 Ave, Palo Alto, CA 94303 USA.
[Mittman, Brian S.] Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA.
[Rumsfeld, John S.] Eastern Colorado VA Hlth Care Syst, Denver, CO USA.
RP Heidenreich, PA (reprint author), Vet Adm Palo Alto Hlth Care Syst, 111C,3801 Ave, Palo Alto, CA 94303 USA.
EM heiden@stanford.edu
FU Veterans Administration's Quality Enhancement and Research Initiative
[04-326, SDP 09-160]
FX This study was supported by grants from the Veterans Administration's
Quality Enhancement and Research Initiative 04-326 and SDP 09-160.
NR 11
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1063-8628
EI 1550-5154
J9 QUAL MANAG HEALTH CA
JI Qual. Manag. Health Care
PD JUL-SEP
PY 2016
VL 25
IS 3
BP 129
EP 133
DI 10.1097/QMH.0000000000000105
PG 5
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DX1OI
UT WOS:000384136300002
PM 27367213
ER
PT J
AU Berretta, P
Patel, HJ
Gleason, TG
Sundt, TM
Myrmel, T
Desai, N
Korach, A
Panza, A
Bavaria, J
Khoynezhad, A
Woznicki, E
Montgomery, D
Isselbacher, EM
Di Bartolomeo, R
Fattori, R
Nienaber, CA
Eagle, KA
Trimarchi, S
Di Eusanio, M
AF Berretta, Paolo
Patel, Himanshu J.
Gleason, Thomas G.
Sundt, Thoralf M.
Myrmel, Truls
Desai, Nimesh
Korach, Amit
Panza, Antonello
Bavaria, Joe
Khoynezhad, Ali
Woznicki, Elise
Montgomery, Dan
Isselbacher, Eric M.
Di Bartolomeo, Roberto
Fattori, Rossella
Nienaber, Christoph A.
Eagle, Kim A.
Trimarchi, Santi
Di Eusanio, Marco
TI IRAD experience on surgical type A acute dissection patients: results
and predictors of mortality
SO ANNALS OF CARDIOTHORACIC SURGERY
LA English
DT Article
DE Type A aortic dissection; aorta; international registry of acute aortic
dissection (IRAD); aortic surgery
ID ACUTE-AORTIC-DISSECTION; INTERNATIONAL-REGISTRY; CLINICAL
CHARACTERISTICS; ROOT REPLACEMENT; RISK-FACTORS; MANAGEMENT; OUTCOMES;
REPAIR; MALPERFUSION; INSIGHTS
AB Type A acute aortic dissection (TAAD) is a disease that has a catastrophic impact on a patient's life and emergent surgery represents a key goal of early treatment. Despite continuous improvements in imaging techniques, medical therapy and surgical management, early mortality in patients undergoing TAAD repair still remains high, ranging from 17% to 26%. In this setting, the International Registry of Acute Aortic Dissection (IRAD), the largest worldwide registry for acute aortic dissection, was established to assess clinical characteristics, management and outcomes of TAAD patients. The present review aimed to evaluate and comment on outcomes of TAAD surgery as reported from IRAD series.
C1 [Berretta, Paolo; Di Eusanio, Marco] G Mazzini Hosp, Div Cardiac Surg, Teramo, Italy.
[Patel, Himanshu J.] Univ Michigan Hlth Syst, Cardiac Surg, Ann Arbor, MI USA.
[Gleason, Thomas G.] Univ Pittsburgh, Div Cardiothorac Surg, Pittsburgh, PA USA.
[Sundt, Thoralf M.; Isselbacher, Eric M.] Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA.
[Myrmel, Truls] Univ Tromso Hosp, Dept Thorac & Cardiovasc Surg, Tromso, Norway.
[Desai, Nimesh; Bavaria, Joe] Univ Penn, Sch Med, Div Cardiovasc Surg, Philadelphia, PA 19104 USA.
[Korach, Amit] Hadassah Hebrew Univ Med Ctr, Dept Cardiothorac Surg, Jerusalem, Israel.
[Panza, Antonello] Univ Hosp San Giovanni di Dio & Ruggi dAragona, Dept Cardiol & Cardiac Surg, Salerno, Italy.
[Khoynezhad, Ali] Cedars Sinai Med Ctr, Div Cardiothorac Surg, Los Angeles, CA 90048 USA.
[Woznicki, Elise; Montgomery, Dan; Eagle, Kim A.] Univ Michigan Hlth Syst, Cardiovasc Ctr, Ann Arbor, MI USA.
[Di Bartolomeo, Roberto] Univ Bologna, S Orsola Malpighi Hosp, Dept Cardiac Surg, I-40126 Bologna, Italy.
[Fattori, Rossella] San Salvatore Hosp, Intervent Cardiol Unit, Pesaro, Italy.
[Nienaber, Christoph A.] Royal Brompton & Harefield NHS Trust, Cardiol & Aort Ctr, London, England.
[Trimarchi, Santi] IRCCS Policlin San Donato, Thorac Aort Res Ctr, San Donato Milanese, Italy.
RP Di Eusanio, M (reprint author), G Mazzini Hosp, Dept Cardiac Surg, Piazza Italia, I-64100 Teramo, Italy.
EM marco.dieusanio@aslteramo.it
NR 38
TC 1
Z9 2
U1 0
U2 0
PU AME PUBL CO
PI SHEUNG WAN
PA ROOM 604 6-F HOLLYWOOD CENTER, 77-91, QUEENS ROAD, SHEUNG WAN, HONG KONG
00000, PEOPLES R CHINA
SN 2225-319X
EI 2304-1021
J9 ANN CARDIOTHORAC SUR
JI Ann. Cardiothorac. Surg.
PD JUL
PY 2016
VL 5
IS 4
BP 346
EP 351
DI 10.21037/acs.2016.05.10
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW0TX
UT WOS:000383356800009
PM 27563547
ER
PT J
AU Fussner, LA
Hummel, AM
Schroeder, DR
Silva, F
Cartin-Ceba, R
Snyder, MR
Hoffman, GS
Kallenberg, CGM
Langford, CA
Merkel, PA
Monach, PA
Seo, P
Spiera, RF
St Clair, EW
Tchao, NK
Stone, JH
Specks, U
AF Fussner, Lynn A.
Hummel, Amber M.
Schroeder, Darrell R.
Silva, Francisco
Cartin-Ceba, Rodrigo
Snyder, Melissa R.
Hoffman, Gary S.
Kallenberg, Cees G. M.
Langford, Carol A.
Merkel, Peter A.
Monach, Paul A.
Seo, Philip
Spiera, Robert F.
St Clair, E. William
Tchao, Nadia K.
Stone, John H.
Specks, Ulrich
CA Rituximab ANCA-Associated Vasculit
TI Factors Determining the Clinical Utility of Serial Measurements of
Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID ANCA-ASSOCIATED VASCULITIS; TERM-FOLLOW-UP; WEGENERS-GRANULOMATOSIS;
DISEASE-ACTIVITY; POLYANGIITIS WEGENERS; SYSTEMIC VASCULITIS; TREATMENT
RESISTANCE; REMISSION-INDUCTION; CAPTURE-ELISA; RELAPSE
AB Objective. Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse.
Methods. Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serialmeasurements by direct and capture enzyme-linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3-ANCA, using Cox proportional hazards regression.
Results. An increase in PR3-ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P50.002 for direct ELISA andHR 4.54; P50.007 for capture ELISA) but not the cyclophosphamide/azathioprine group (P=0.103 and P=0.197, respectively).
Conclusion. The association of an increase in PR3-ANCA level with the risk of subsequent relapse is partially affected by the PR3-ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3-ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3-ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.
C1 [Fussner, Lynn A.; Hummel, Amber M.; Schroeder, Darrell R.; Cartin-Ceba, Rodrigo; Snyder, Melissa R.; Specks, Ulrich] Mayo Clin, Rochester, MN USA.
[Fussner, Lynn A.; Hummel, Amber M.; Schroeder, Darrell R.; Cartin-Ceba, Rodrigo; Snyder, Melissa R.; Specks, Ulrich] Mayo Fdn Med Educ & Res, Rochester, MN USA.
[Silva, Francisco] Univ Desarrollo, Santiago, Chile.
[Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin Fdn, Cleveland, OH USA.
[Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA.
[Monach, Paul A.] Boston Univ, Med Ctr, Boston, MA USA.
[Monach, Paul A.] VA Boston Healthcare Syst, Boston, MA USA.
[Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA.
[Spiera, Robert F.] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
[St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA.
[Tchao, Nadia K.] Immune Tolerance Network, San Francisco, CA USA.
[Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Specks, U (reprint author), Mayo Clin, Div Pulm & Crit Care Med, 200 First St SW,Stabile Bldg 8-56, Rochester, MN 55905 USA.
EM specks.ulrich@mayo.edu
FU NIH (National Center for Advancing Translational Sciences Clinical and
Translational Science Award [CTSA]) [UL1-TR-000135]; Immune Tolerance
Network (NIH) [N01-AI-15416, ITN021AI]; National Institute of Allergy
and Infectious Diseases, NIH; Juvenile Diabetes Research Foundation;
Genentech; Biogen Idec; Arthritis Foundation; NIH [CTSA
1-UL1-RR-024150-01, CTSA UL1-RR-025005, K23-AR-052820, K24-AR-049185,
CTSA UL1-RR-025771, M01-RR-00533, K24-AR-02224, UL1-TR-000439]
FX Supported by the NIH (National Center for Advancing Translational
Sciences Clinical and Translational Science Award [CTSA] UL1-TR-000135).
Enzyme-linked immunosorbent assay kits for antineutrophil cytoplasmic
antibody (ANCA) testing were provided by Euroimmun (Lubeck, Germany).
Data for the current study were obtained from the Rituximab versus
Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial, which was
performed with the support of the Immune Tolerance Network (NIH contract
N01-AI-15416, protocol number ITN021AI), an international clinical
research consortium headquartered at the University of California and
supported by the National Institute of Allergy and Infectious Diseases,
NIH, and the Juvenile Diabetes Research Foundation. Genentech and Biogen
Idec provided the study medications and partial funding for the RAVE
trial. At the Mayo Clinic and Foundation, Johns Hopkins University,
Boston University, and the Cleveland Clinic, the RAVE trial was
supported by the NIH (Mayo Clinic: National Center for Research
Resources CTSA 1-UL1-RR-024150-01; Johns Hopkins University: National
Center for Research Resources CTSA UL1-RR-025005 and career development
awards K23-AR-052820 to Dr. Seo and K24-AR-049185 to Dr. Stone; Boston
University: National Center for Research Resources CTSA UL1-RR-025771,
grant M01-RR-00533, and career development award K24-AR-02224 to Dr.
Merkel; Cleveland Clinic: National Center for Advancing Translational
Sciences grant UL1-TR-000439). The RAVE trial at Boston University was
also supported by the Arthritis Foundation (Investigator Award to Dr.
Monach).
NR 52
TC 8
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2326-5191
EI 2326-5205
J9 ARTHRITIS RHEUMATOL
JI Arthritis Rheumatol.
PD JUL
PY 2016
VL 68
IS 7
BP 1700
EP 1710
DI 10.1002/art.39637
PG 11
WC Rheumatology
SC Rheumatology
GA DW2UO
UT WOS:000383497500018
PM 26882078
ER
PT J
AU Fenske, TS
Ahn, KW
Graff, TM
DiGilio, A
Bashir, Q
Kamble, RT
Ayala, E
Bacher, U
Brammer, JE
Cairo, M
Chen, A
Chen, YB
Chhabra, S
D'Souza, A
Farooq, U
Freytes, C
Ganguly, S
Hertzberg, M
Inwards, D
Jaglowski, S
Kharfan-Dabaja, MA
Lazarus, HM
Nathan, S
Pawarode, A
Perales, MA
Reddy, N
Seo, S
Sureda, A
Smith, SM
Hamadani, M
AF Fenske, Timothy S.
Ahn, Kwang W.
Graff, Tara M.
DiGilio, Alyssa
Bashir, Qaiser
Kamble, Rammurti T.
Ayala, Ernesto
Bacher, Ulrike
Brammer, Jonathan E.
Cairo, Mitchell
Chen, Andy
Chen, Yi-Bin
Chhabra, Saurabh
D'Souza, Anita
Farooq, Umar
Freytes, Cesar
Ganguly, Siddhartha
Hertzberg, Mark
Inwards, David
Jaglowski, Samantha
Kharfan-Dabaja, Mohamed A.
Lazarus, Hillard M.
Nathan, Sunita
Pawarode, Attaphol
Perales, Miguel-Angel
Reddy, Nishitha
Seo, Sachiko
Sureda, Anna
Smith, Sonali M.
Hamadani, Mehdi
TI Allogeneic transplantation provides durable remission in a subset of
DLBCL patients relapsing after autologous transplantation
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE DLBCL; prognostic score; allogeneic transplantation; prior autologous
transplan
ID B-CELL LYMPHOMA; CONDITIONING REGIMENS; REDUCED-INTENSITY; PREDICT
SURVIVAL; IMPACT; RITUXIMAB; GRAFT; OUTCOMES; ORIGIN
AB For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT.
C1 [Fenske, Timothy S.; Hamadani, Mehdi] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA.
[Ahn, Kwang W.; DiGilio, Alyssa; D'Souza, Anita; Hamadani, Mehdi] Med Coll Wisconsin, Dept Med, CIBMTR, Milwaukee, WI 53226 USA.
[Ahn, Kwang W.] Med Coll Wisconsin, Div Biostat, Inst Hlth & Soc, Milwaukee, WI 53226 USA.
[Graff, Tara M.] Med Oncol Hematol Associates, Des Moines, IA USA.
[Bashir, Qaiser; Brammer, Jonathan E.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Dept Stem Cell Transplantat, Houston, TX 77030 USA.
[Kamble, Rammurti T.] Baylor Coll Med, Div Hematol & Oncol, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Ayala, Ernesto; Kharfan-Dabaja, Mohamed A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Blood & Marrow Transplantat, Tampa, FL USA.
[Bacher, Ulrike] Univ Med Goettingen, Dept Haematol Oncol, Gottingen, Germany.
[Bacher, Ulrike] Univ Canc Ctr Hamburg, Interdisciplinary Clin Stem Cell Transplantat, Hamburg, Germany.
[Cairo, Mitchell] New York Med Coll, Dept Pediat, Div Pediat Hematol Oncol & Stem Cell Transplantat, Valhalla, NY 10595 USA.
[Chen, Andy] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA.
[Chen, Yi-Bin] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Chhabra, Saurabh] Med Univ South Carolina, Div Hematol Oncol, Charleston, SC USA.
[Farooq, Umar] Univ Iowa Hosp & Clin, Dept Oncol & Blood Marrow Transplantat, Iowa City, IA 52242 USA.
[Freytes, Cesar] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Freytes, Cesar] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Ganguly, Siddhartha] Univ Kansas, Med Ctr, Div Hematol Oncol, Blood & Marrow Transplantat, Kansas City, KS 66103 USA.
[Hertzberg, Mark] Prince Wales Hosp, Dept Haematol, Randwick, NSW, Australia.
[Inwards, David] Mayo Clin, Div Hematol, Rochester, MN USA.
[Jaglowski, Samantha] Ohio State Univ, Med Ctr, Div Hematol, Columbus, OH 43210 USA.
[Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Seidman Canc Ctr, Cleveland, OH USA.
[Nathan, Sunita] Rush Univ, Dept Hematol, Med Ctr, Chicago, IL 60612 USA.
[Pawarode, Attaphol] Univ Michigan, Sch Med, Dept Internal Med, Blood & Marrow Transplantat Program,Div Hematol O, Ann Arbor, MI USA.
[Perales, Miguel-Angel] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, 1275 York Ave, New York, NY 10021 USA.
[Reddy, Nishitha] Vanderbilt Univ, Med Ctr, Div Hematol Oncol, Nashville, TN USA.
[Seo, Sachiko] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Sureda, Anna] Hosp Duran I Reynals, Serv Hematol, Inst Catala Oncol, Barcelona, Spain.
[Sureda, Anna] European Grp Blood & Marrow Transplantat, Barcelona, Spain.
[Smith, Sonali M.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
RP Hamadani, M (reprint author), Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA.
EM mhamadani@mcw.edu
FU Public Health Service Grant/Cooperative Agreement from the National
Cancer Institute (NCI) [U24-CA076518]; National Heart, Lung and Blood
Institute (NHLBI); National Institute of Allergy and Infectious Diseases
(NIAID); NHLBI [5U10HL069294]; NCI; Health Resources and Services
Administration (HRSA/DHHS) [HHSH250201200016C]; Office of Naval Research
[N00014-13-1-0039, N00014-14-1-0028]; Actinium Pharmaceuticals; Allos
Therapeutics, Inc.; Amgen, Inc.; Ariad; Be the Match Foundation; Blue
Cross and Blue Shield Association; Celgene Corporation; Chimerix, Inc.;
Fred Hutchinson Cancer Research Center; Fresenius-Biotech North America,
Inc.; Gamida Cell Teva Joint Venture Ltd.; Genentech, Inc.; Gentium SpA;
Genzyme Corporation; GlaxoSmithKline; Health Research, Inc.; Roswell
Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jeff
Gordon Children's Foundation; Kiadis Pharma; The Leukemia & Lymphoma
Society; Medac GmbH; The Medical College of Wisconsin; Merck Co, Inc.;
Millennium: The Takeda Oncology Co.; Milliman USA, Inc.; Miltenyi
Biotec, Inc.; National Marrow Donor Program; Onyx Pharmaceuticals; Optum
Healthcare Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; Perkin Elmer, Inc.; Remedy Informatics; Sanofi US;
Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St.
Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.;
Stemsoft Software, Inc.; Swedish Orphan Biovitrum; Tarix
Pharmaceuticals; TerumoBCT; Teva Neuroscience, Inc.; THERAKOS, Inc.;
University of Minnesota; University of Utah; Wellpoint, Inc.
FX Morgan Geronime for administrative Support. The CIBMTR is supported by
Public Health Service Grant/Cooperative Agreement U24-CA076518 from the
National Cancer Institute (NCI), the National Heart, Lung and Blood
Institute (NHLBI) and the National Institute of Allergy and Infectious
Diseases (NIAID); a Grant/Cooperative Agreement 5U10HL069294 from NHLBI
and NCI; a contract HHSH250201200016C with Health Resources and Services
Administration (HRSA/DHHS); two Grants N00014-13-1-0039 and
N00014-14-1-0028 from the Office of Naval Research; and grants from
*Actinium Pharmaceuticals; Allos Therapeutics, Inc.; *Amgen, Inc.;
Anonymous donation to the Medical College of Wisconsin; Ariad; Be the
Match Foundation; *Blue Cross and Blue Shield Association; *Celgene
Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center;
Fresenius-Biotech North America, Inc.; *Gamida Cell Teva Joint Venture
Ltd.; Genentech, Inc.;*Gentium SpA; Genzyme Corporation;
GlaxoSmithKline; Health Research, Inc. Roswell Park Cancer Institute;
HistoGenetics, Inc.; Incyte Corporation; Jeff Gordon Children's
Foundation; Kiadis Pharma; The Leukemia & Lymphoma Society; Medac GmbH;
The Medical College of Wisconsin; Merck & Co, Inc.; Millennium: The
Takeda Oncology Co.; *Milliman USA, Inc.; *Miltenyi Biotec, Inc.;
National Marrow Donor Program; Onyx Pharmaceuticals; Optum Healthcare
Solutions, Inc.; Osiris Therapeutics, Inc.; Otsuka America
Pharmaceutical, Inc.; Perkin Elmer, Inc.; *Remedy Informatics; *Sanofi
US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Soligenix, Inc.; St.
Baldrick's Foundation; StemCyte, A Global Cord Blood Therapeutics Co.;
Stemsoft Software, Inc.; Swedish Orphan Biovitrum; *Tarix
Pharmaceuticals; *TerumoBCT; *Teva Neuroscience, Inc.; *THERAKOS, Inc.;
University of Minnesota; University of Utah; and *Wellpoint, Inc. The
views expressed in this article do not reflect the official policy or
position of the National Institute of Health, the Department of the
Navy, the Department of Defense, Health Resources and Services
Administration (HRSA) or any other agency of the U.S. Government.
*Corporate Members.
NR 26
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2016
VL 174
IS 2
BP 235
EP 248
DI 10.1111/bjh.14046
PG 14
WC Hematology
SC Hematology
GA DW6PP
UT WOS:000383773700006
PM 26989808
ER
PT J
AU Rosenthal, A
Kumar, S
Hofmeister, C
Laubach, J
Vij, R
Dueck, A
Gano, K
Stewart, AK
AF Rosenthal, Allison
Kumar, Shaji
Hofmeister, Craig
Laubach, Jacob
Vij, Ravi
Dueck, Amylou
Gano, Katherine
Stewart, A. Keith
TI A Phase Ib Study of the combination of the Aurora Kinase Inhibitor
Alisertib (MLN8237) and Bortezomib in Relapsed Multiple Myeloma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE multiple myeloma; alisertib; aurora kinase; bortezomib; relapse
ID ADVANCED SOLID TUMORS
C1 [Rosenthal, Allison; Dueck, Amylou; Gano, Katherine; Stewart, A. Keith] Mayo Clin, Scottsdale, AZ 85259 USA.
[Kumar, Shaji] Mayo Clin, Rochester, MN USA.
[Hofmeister, Craig] Ohio State, James Canc Ctr, Columbus, OH USA.
[Laubach, Jacob] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Vij, Ravi] Washington Univ, St Louis, MO USA.
RP Stewart, AK (reprint author), Mayo Clin, Scottsdale, AZ 85259 USA.
EM stewart.keith@mayo.edu
RI Hofmeister, Craig/E-3256-2011
OI Hofmeister, Craig/0000-0003-4816-1607
FU NCI NIH HHS [P30 CA016672, P30 CA016058]
NR 8
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD JUL
PY 2016
VL 174
IS 2
BP 323
EP 325
DI 10.1111/bjh.13765
PG 3
WC Hematology
SC Hematology
GA DW6PP
UT WOS:000383773700016
PM 26403323
ER
PT J
AU Balbach, ST
Orkin, SH
AF Balbach, Sebastian T.
Orkin, Stuart H.
TI An Achilles' Heel for MLL-Rearranged Leukemias: Writers and Readers of
H3 Lysine 36 Dimethylation
SO CANCER DISCOVERY
LA English
DT Editorial Material
ID HEMATOPOIETIC STEM-CELLS; MEDIATED TRANSFORMATION; DOT1L
AB Histone H3 lysine 36 dimethylation (H3K36me2), a modification associated with transcriptional activation, is required for mixed-lineage leukemia-dependent transcription and leukemic transformation. In this issue of Cancer Discovery, Zhu and colleagues map the network of readers, writers, and erasers of H3K36me2 and uncover the ASH1L histone methyltransferase as a novel target for therapeutic intervention. (C) 2016 AACR.
C1 [Balbach, Sebastian T.; Orkin, Stuart H.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA.
[Balbach, Sebastian T.; Orkin, Stuart H.] Harvard Med Sch, Boston, MA USA.
[Orkin, Stuart H.] Harvard Stem Cell Inst, Cambridge, MA USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Orkin, SH (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
EM Stuart_Orkin@dfci.harvard.edu
RI Balbach, Sebastian/A-1107-2009
OI Balbach, Sebastian/0000-0003-0212-5758
NR 11
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD JUL
PY 2016
VL 6
IS 7
BP 700
EP 702
DI 10.1158/2159-8290.CD-16-0564
PG 3
WC Oncology
SC Oncology
GA DW0TC
UT WOS:000383354500021
PM 27371576
ER
PT J
AU Kim, E
Ilic, N
Shrestha, Y
Zou, LH
Kamburov, A
Zhu, C
Yang, XP
Lubonja, R
Tran, N
Nguyen, C
Lawrence, MS
Piccioni, F
Bagul, M
Doench, JG
Chouinard, CR
Wu, XY
Hogstrom, L
Natoli, T
Tamayo, P
Horn, H
Corsello, SM
Lage, K
Root, DE
Subramanian, A
Golub, TR
Getz, G
Boehm, JS
Hahn, WC
AF Kim, Eejung
Ilic, Nina
Shrestha, Yashaswi
Zou, Lihua
Kamburov, Atanas
Zhu, Cong
Yang, Xiaoping
Lubonja, Rakela
Tran, Nancy
Nguyen, Cindy
Lawrence, Michael S.
Piccioni, Federica
Bagul, Mukta
Doench, John G.
Chouinard, Candace R.
Wu, Xiaoyun
Hogstrom, Larson
Natoli, Ted
Tamayo, Pablo
Horn, Heiko
Corsello, Steven M.
Lage, Kasper
Root, David E.
Subramanian, Aravind
Golub, Todd R.
Getz, Gad
Boehm, Jesse S.
Hahn, William C.
TI Systematic Functional Interrogation of Rare Cancer Variants Identifies
Oncogenic Alleles
SO CANCER DISCOVERY
LA English
DT Article
ID PROSTATE-CANCER; MISSENSE MUTATIONS; TUMOR-SUPPRESSOR; SOMATIC
MUTATIONS; LUNG-CANCER; PTEN; GENOME; GENES; SPOP; RAS
AB Cancer genome characterization efforts now provide an initial view of the somatic alterations in primary tumors. However, most point mutations occur at low frequency, and the function of these alleles remains undefined. We have developed a scalable systematic approach to interrogate the function of cancer-associated gene variants. We subjected 474 mutant alleles curated from 5,338 tumors to pooled in vivo tumor formation assays and gene expression profiling. We identified 12 transforming alleles, including two in genes (PIK3CB, POT1) that have not been shown to be tumorigenic. One rare KRAS allele, D33E, displayed tumorigenicity and constitutive activation of known RAS effector pathways. By comparing gene expression changes induced upon expression of wild-type and mutant alleles, we inferred the activity of specific alleles. Because alleles found to be mutated only once in 5,338 tumors rendered cells tumorigenic, these observations underscore the value of integrating genomic information with functional studies.
SIGNIFICANCE: Experimentally inferring the functional status of cancer-associated mutations facilitates the interpretation of genomic information in cancer. Pooled in vivo screen and gene expression profiling identified functional variants and demonstrated that expression of rare variants induced tumorigenesis. Variant phenotyping through functional studies will facilitate defining key somatic events in cancer. (C) 2016 AACR.
C1 [Kim, Eejung; Ilic, Nina; Shrestha, Yashaswi; Zou, Lihua; Kamburov, Atanas; Zhu, Cong; Yang, Xiaoping; Lubonja, Rakela; Tran, Nancy; Nguyen, Cindy; Lawrence, Michael S.; Piccioni, Federica; Bagul, Mukta; Doench, John G.; Chouinard, Candace R.; Wu, Xiaoyun; Hogstrom, Larson; Natoli, Ted; Tamayo, Pablo; Horn, Heiko; Corsello, Steven M.; Lage, Kasper; Root, David E.; Subramanian, Aravind; Golub, Todd R.; Getz, Gad; Boehm, Jesse S.; Hahn, William C.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Kim, Eejung; Ilic, Nina; Corsello, Steven M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Zou, Lihua; Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Zou, Lihua; Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Tamayo, Pablo] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Horn, Heiko; Lage, Kasper] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
RP Hahn, WC (reprint author), Dana Farber Canc Inst, Med Oncol, Dana 1538,450 Brookline Ave, Boston, MA 02215 USA.
EM william_hahn@dfci.harvard.edu
FU Samsung Scholarship; Susan G. Komen Postdoctoral Fellowship
[PDF12230602]; European Molecular Biology Laboratory; Conquer Cancer
Foundation of ASCO Young Investigator Award; U.S. NCI grant [U01
CA176058]; Carlos Slim Foundation in Mexico
FX This study was supported by a Samsung Scholarship (to E. Kim), Susan G.
Komen Postdoctoral Fellowship PDF12230602 (to N. Ilic), a long-term
postdoctoral fellowship from the European Molecular Biology Laboratory
(to A. Kamburov), a Conquer Cancer Foundation of ASCO Young Investigator
Award (to S.M. Corsello), and U.S. NCI grant U01 CA176058 (to W.C.
Hahn). This work was conducted as part of the Slim Initiative for
Genomic Medicine, a project funded by the Carlos Slim Foundation in
Mexico.
NR 58
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Z9 9
U1 1
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD JUL
PY 2016
VL 6
IS 7
BP 714
EP 726
DI 10.1158/2159-8290.CD-16-0160
PG 13
WC Oncology
SC Oncology
GA DW0TC
UT WOS:000383354500023
PM 27147599
ER
PT J
AU Saha, SK
Gordan, JD
Kleinstiver, BP
Vu, P
Najem, MS
Yeo, JC
Shi, L
Kato, Y
Levin, RS
Webber, JT
Damon, LJ
Egan, RK
Greninger, P
McDermott, U
Garnett, MJ
Jenkins, RL
Rieger-Christ, KM
Sullivan, TB
Hezel, AF
Liss, AS
Mizukami, Y
Goyal, L
Ferrone, CR
Zhu, AX
Joung, JK
Shokat, KM
Benes, CH
Bardeesy, N
AF Saha, Supriya K.
Gordan, John D.
Kleinstiver, Benjamin P.
Vu, Phuong
Najem, Mortada S.
Yeo, Jia-Chi
Shi, Lei
Kato, Yasutaka
Levin, Rebecca S.
Webber, James T.
Damon, Leah J.
Egan, Regina K.
Greninger, Patricia
McDermott, Ultan
Garnett, Mathew J.
Jenkins, Roger L.
Rieger-Christ, Kimberly M.
Sullivan, Travis B.
Hezel, Aram F.
Liss, Andrew S.
Mizukami, Yusuke
Goyal, Lipika
Ferrone, Cristina R.
Zhu, Andrew X.
Joung, J. Keith
Shokat, Kevan M.
Benes, Cyril H.
Bardeesy, Nabeel
TI Isocitrate Dehydrogenase Mutations Confer Dasatinib Hypersensitivity and
SRC Dependence in Intrahepatic Cholangiocarcinoma
SO CANCER DISCOVERY
LA English
DT Article
ID KINASE INHIBITOR SELECTIVITY; UNKNOWN PRIMARY SITE; MYELOID-LEUKEMIA;
TARGETED THERAPY; BILIARY CANCER; BCR-ABL; RESISTANCE; POTENT; CELLS;
IDH1
AB Intrahepatic cholangiocarcinoma (ICC) is an aggressive liver bile duct malignancy exhibiting frequent isocitrate dehydrogenase (IDH1/IDH2) mutations. Through a high-throughput drug screen of a large panel of cancer cell lines, including 17 biliary tract cancers, we found that IDH mutant (IDHm) ICC cells demonstrate a striking response to the multikinase inhibitor dasatinib, with the highest sensitivity among 682 solid tumor cell lines. Using unbiased proteomics to capture the activated kinome and CRISPR/Cas9-based genome editing to introduce dasatinib-resistant "gatekeeper" mutant kinases, we identified SRC as a critical dasatinib target in IDHm ICC. Importantly, dasatinib-treated IDHm xenografts exhibited pronounced apoptosis and tumor regression. Our results show that IDHm ICC cells have a unique dependency on SRC and suggest that dasatinib may have therapeutic benefit against IDHm ICC. Moreover, these proteomic and genome-editing strategies provide a systematic and broadly applicable approach to define targets of kinase inhibitors underlying drug responsiveness.
SIGNIFICANCE: IDH mutations define a distinct subtype of ICC, a malignancy that is largely refractory to current therapies. Our work demonstrates that IDHm ICC cells are hypersensitive to dasatinib and critically dependent on SRC activity for survival and proliferation, pointing to new therapeutic strategies against these cancers. (C) 2016 AACR.
C1 [Saha, Supriya K.; Vu, Phuong; Najem, Mortada S.; Yeo, Jia-Chi; Shi, Lei; Kato, Yasutaka; Damon, Leah J.; Egan, Regina K.; Greninger, Patricia; Mizukami, Yusuke; Goyal, Lipika; Ferrone, Cristina R.; Zhu, Andrew X.; Benes, Cyril H.; Bardeesy, Nabeel] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Gordan, John D.; Webber, James T.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Kleinstiver, Benjamin P.; Joung, J. Keith] Massachusetts Gen Hosp, Mol Pathol Unit, Ctr Canc Res, Charlestown, MA USA.
[Kleinstiver, Benjamin P.; Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Charlestown, MA USA.
[Kleinstiver, Benjamin P.; Joung, J. Keith] Harvard Med Sch, Dept Pathol, Boston, MA USA.
[Levin, Rebecca S.; Shokat, Kevan M.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[McDermott, Ultan; Garnett, Mathew J.] Wellcome Trust Sanger Inst, Hinxton, England.
[Jenkins, Roger L.] Lahey Hosp & Med Ctr, Dept Transplantat, Burlington, MA USA.
[Rieger-Christ, Kimberly M.; Sullivan, Travis B.] Lahey Hosp & Med Ctr, Dept Translat Res, Burlington, MA USA.
[Hezel, Aram F.] Univ Rochester, Sch Med, Rochester, NY USA.
[Liss, Andrew S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Liss, Andrew S.] Massachusetts Gen Hosp, Andrew L Warshaw MD Inst Pancreat Canc Res, Boston, MA 02114 USA.
[Liss, Andrew S.] Harvard Med Sch, Boston, MA 02114 USA.
[Mizukami, Yusuke] Sapporo Higashi Tokushukai Hosp, Ctr Clin & Biomed Res, Sapporo, Hokkaido, Japan.
[Shokat, Kevan M.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA.
RP Bardeesy, N (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,CPZN 4216, Boston, MA 02114 USA.; Benes, CH (reprint author), CNY 149 Room 7401,149 13th St, Charlestown, MA 02129 USA.
EM cbenes@mgh.harvard.edu; nelbardeesy@partners.org
OI McDermott, Ultan/0000-0001-9032-4700; Webber, James/0000-0001-8594-9888
FU Translational Research Award from the V Foundation; Target Cancer
Foundation; Gallagher Chair in Gastrointestinal Cancer Research at
Massachusetts General Hospital; NCI-Mentored Clinical Scientist Research
Career Development Award [1K08CA194268-01]; DF/HCC GI SPORE
[P50CA127003]; American Cancer Society Postdoctoral Grant; Natural
Sciences and Engineering Research Council of Canada Postdoctoral
Fellowship; Wellcome Trust [102696]; NIH Director's Pioneer Award [DP1
GM105378]; Editas Medicine; Hera Testing Laboratories; Poseida
Therapeutics; Transposagen Biopharmaceuticals
FX This work was supported by a Translational Research Award from the V
Foundation to N. Bardeesy, C.H. Benes, and A.X. Zhu, and by a grant from
Target Cancer Foundation to N. Bardeesy. N. Bardeesy is the holder of
the Gallagher Chair in Gastrointestinal Cancer Research at Massachusetts
General Hospital. S.K. Saha is supported by an NCI-Mentored Clinical
Scientist Research Career Development Award (1K08CA194268-01). N.
Bardeesy and S.K. Saha are supported by the DF/HCC GI SPORE
(P50CA127003). J.D. Gordan was supported by an American Cancer Society
Postdoctoral Grant. K.M. Shokat is a Howard Hughes Medical Institute
Investigator. B.P. Kleinstiver was supported by a Natural Sciences and
Engineering Research Council of Canada Postdoctoral Fellowship. C.H.
Benes, U. McDermott, and M.J. Garnett are supported by a grant from the
Wellcome Trust (102696). J.K. Joung is supported by an NIH Director's
Pioneer Award (DP1 GM105378) and is a consultant for Horizon Discovery.
J.K. Joung has financial interests in Editas Medicine, Hera Testing
Laboratories, Poseida Therapeutics, and Transposagen Biopharmaceuticals.
J.K. Joung's interests were reviewed and are managed by Massachusetts
General Hospital and Partners Health-Care in accordance with their
conflict of interest policies.
NR 45
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U1 4
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD JUL
PY 2016
VL 6
IS 7
BP 727
EP 739
DI 10.1158/2159-8290.CD-15-1442
PG 13
WC Oncology
SC Oncology
GA DW0TC
UT WOS:000383354500024
PM 27231123
ER
PT J
AU Patnaik, A
Rosen, LS
Tolaney, SM
Tolcher, AW
Goldman, JW
Gandhi, L
Papadopoulos, KP
Beeram, M
Rasco, DW
Hilton, JF
Nasir, A
Beckmann, RP
Schade, AE
Fulford, AD
Nguyen, TS
Martinez, R
Kulanthaivel, P
Li, LQ
Frenzel, M
Cronier, DM
Chan, EM
Flaherty, KT
Wen, PY
Shapiro, GI
AF Patnaik, Amita
Rosen, Lee S.
Tolaney, Sara M.
Tolcher, Anthony W.
Goldman, Jonathan W.
Gandhi, Leena
Papadopoulos, Kyriakos P.
Beeram, Muralidhar
Rasco, Drew W.
Hilton, John F.
Nasir, Aejaz
Beckmann, Richard P.
Schade, Andrew E.
Fulford, Angie D.
Nguyen, Tuan S.
Martinez, Ricardo
Kulanthaivel, Palaniappan
Li, Lily Q.
Frenzel, Martin
Cronier, Damien M.
Chan, Edward M.
Flaherty, Keith T.
Wen, Patrick Y.
Shapiro, Geoffrey I.
TI Efficacy and Safety of Abemaciclib, an Inhibitor of CDK4 and CDK6, for
Patients with Breast Cancer, Non-Small Cell Lung Cancer, and Other Solid
Tumors
SO CANCER DISCOVERY
LA English
DT Article
ID KINASE 4/6 INHIBITOR; CYCLIN-DEPENDENT KINASES; PD 0332991;
ANTITUMOR-ACTIVITY; DOSE-ESCALATION; OVARIAN-CANCER; PHASE-I;
PROLIFERATION; COMBINATION; PALBOCICLIB
AB We evaluated the safety, pharmacokinetic profile, pharmacodynamic effects, and antitumor activity of abemaciclib, an orally bioavailable inhibitor of cyclin-dependent kinases (CDK) 4 and 6, in a multicenter study including phase I dose escalation followed by tumorspecific cohorts for breast cancer, non-small cell lung cancer (NSCLC), glioblastoma, melanoma, and colorectal cancer. A total of 225 patients were enrolled: 33 in dose escalation and 192 in tumor-specific cohorts. Dose-limiting toxicity was grade 3 fatigue. The maximum tolerated dose was 200 mg every 12 hours. The most common possibly related treatment-emergent adverse events involved fatigue and the gastrointestinal, renal, or hematopoietic systems. Plasma concentrations increased with dose, and pharmacodynamic effects were observed in proliferating keratinocytes and tumors. Radiographic responses were achieved in previously treated patients with breast cancer, NSCLC, and melanoma. For hormone receptor-positive breast cancer, the overall response rate was 31%; moreover, 61% of patients achieved either response or stable disease lasting >= 6 months.
SIGNIFICANCE: Abemaciclib represents the first selective inhibitor of CDK4 and CDK6 with a safety profile allowing continuous dosing to achieve sustained target inhibition. This first-in-human experience demonstrates single-agent activity for patients with advanced breast cancer, NSCLC, and other solid tumors. (C) 2016 AACR.
C1 [Patnaik, Amita; Tolcher, Anthony W.; Papadopoulos, Kyriakos P.; Beeram, Muralidhar; Rasco, Drew W.] South Texas Accelerated Res Therapeut, 4383 Med Dr, San Antonio, TX 78229 USA.
[Rosen, Lee S.; Goldman, Jonathan W.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Tolaney, Sara M.; Gandhi, Leena; Hilton, John F.; Wen, Patrick Y.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Nasir, Aejaz; Beckmann, Richard P.; Schade, Andrew E.; Fulford, Angie D.; Nguyen, Tuan S.; Martinez, Ricardo; Kulanthaivel, Palaniappan; Li, Lily Q.; Frenzel, Martin; Cronier, Damien M.; Chan, Edward M.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hilton, John F.] Univ Ottawa, Ottawa, ON, Canada.
RP Patnaik, A (reprint author), South Texas Accelerated Res Therapeut, 4383 Med Dr, San Antonio, TX 78229 USA.; Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Early Drug Dev Ctr, Mayer 446,450 Brookline Ave, Boston, MA 02215 USA.
EM amita.patnaik@start.stoh.com; geoffrey_shapiro@dfci.harvard.edu
FU Eli Lilly and Company
FX All funding was provided by Eli Lilly and Company.
NR 47
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U1 5
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD JUL
PY 2016
VL 6
IS 7
BP 740
EP 753
DI 10.1158/2159-8290.CD-16-0095
PG 14
WC Oncology
SC Oncology
GA DW0TC
UT WOS:000383354500025
PM 27217383
ER
PT J
AU Stone, JH
AF Stone, J. H.
TI IgG4-related disease: pathophysiologic insights drive emerging treatment
approaches
SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
LA English
DT Article; Proceedings Paper
CT 18th International Symposium on Advances in Targeted Therapies
CY MAR 16-20, 2016
CL Palma de Mallorca, SPAIN
DE IgG4-related disease; cytotoxic T cell; SLAMF7; plasmablast
ID AUTOIMMUNE PANCREATITIS; RITUXIMAB THERAPY; SYSTEMIC-DISEASE; STATEMENT
AB IgG4-related disease (IgG4-RD) is a fibroinflammatory condition that can affect essentially any organ. The disease shows similar histopathology findings across organ systems, consisting of a lymphoplasmacytic infiltrate enriched in IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4 itself appears to be a reactive phenomenon rather than the primary disease driver. Recent investigations have focused on the interactions between cells of the B cell lineage and a novel CD4(+) SLAMF7(+) cytotoxic T cells capable of promoting fibrosis.
Plasmablasts appear to play a crucial role along with B cells in the presentation of antigen to this T cell. IgG4-RD is marked by responsiveness to glucocorticoids, but frequent disease relapse, the inability to taper glucocorticoids completely, and steroid toxicity are problematic. Targeted treatment approaches against the B cell lineage appear promising, and therapeutic efforts focused upon the CD4(+) SLAMF7(+) cytotoxic T cell may also be feasible.
C1 [Stone, J. H.] Massachusetts Gen Hosp, Rheumatol Clin Yawkey 2, 55 Fruit St, Boston, MA 02114 USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Clin Yawkey 2, 55 Fruit St, Boston, MA 02114 USA.
EM jhstone@partners.org
NR 21
TC 0
Z9 0
U1 2
U2 2
PU CLINICAL & EXPER RHEUMATOLOGY
PI PISA
PA VIA SANTA MARIA 31, 56126 PISA, ITALY
SN 0392-856X
EI 1593-098X
J9 CLIN EXP RHEUMATOL
JI Clin. Exp. Rheumatol.
PD JUL-AUG
PY 2016
VL 34
IS 4
SU 98
BP S66
EP S68
PG 3
WC Rheumatology
SC Rheumatology
GA DW8TI
UT WOS:000383928000016
ER
PT J
AU Cefalu, WT
Boulton, AJM
Tamborlane, WV
Moses, RG
LeRoith, D
Greene, EL
Hu, FB
Bakris, G
Wylie-Rosett, J
Rosenstock, J
Weinger, K
Blonde, L
de Groot, M
Rich, SS
D'Alessio, D
Riddle, MC
Reynolds, L
AF Cefalu, William T.
Boulton, Andrew J. M.
Tamborlane, William V.
Moses, Robert G.
LeRoith, Derek
Greene, Eddie L.
Hu, Frank B.
Bakris, George
Wylie-Rosett, Judith
Rosenstock, Julio
Weinger, Katie
Blonde, Lawrence
de Groot, Mary
Rich, Stephen S.
D'Alessio, David
Riddle, Matthew C.
Reynolds, Lyn
TI Diabetes Care: "Lagniappe" and "Seeing Is Believing"!
SO DIABETES CARE
LA English
DT Editorial Material
ID METABOLIC SURGERY; MANAGEMENT
C1 [Cefalu, William T.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Boulton, Andrew J. M.] Univ Manchester, Manchester Diabet Ctr, Manchester, Lancs, England.
[Tamborlane, William V.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Moses, Robert G.] ISLHD, Wollongong, NSW, Australia.
[LeRoith, Derek] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA.
[Greene, Eddie L.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA.
[Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Bakris, George] Univ Chicago Med, ASH Comprehens Hypertens Ctr, Dept Med, Div Endocrinol Diabet & Metab, Chicago, IL USA.
[Wylie-Rosett, Judith] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Rosenstock, Julio] Med City, Dallas Diabet & Endocrine Ctr, Dallas, TX USA.
[Weinger, Katie] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA.
[Blonde, Lawrence] Ochsner Med Ctr, Ochsner Diabet Clin Res Unit, Frank Riddick Diabet Inst, Dept Endocrinol, New Orleans, LA USA.
[de Groot, Mary] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Rich, Stephen S.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[D'Alessio, David] Duke Univ, Div Endocrinol Diabet & Metab, Durham, NC USA.
[Riddle, Matthew C.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA.
[Reynolds, Lyn] Amer Diabet Assoc, Indianapolis, IN USA.
RP Cefalu, WT (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
EM cefaluwt@pbrc.edu
FU NCCIH NIH HHS [P50 AT002776]; NIGMS NIH HHS [U54 GM104940]
NR 19
TC 1
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U1 4
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1069
EP 1071
DI 10.2337/dc16-0891
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500008
PM 27631957
ER
PT J
AU Russell, SJ
Beck, RW
AF Russell, Steven J.
Beck, Roy W.
TI Design Considerations for Artificial Pancreas Pivotal Studies
SO DIABETES CARE
LA English
DT Article
ID SEVERE HYPOGLYCEMIC EVENTS; EXCHANGE CLINIC REGISTRY; GLYCATED ALBUMIN;
GLYCEMIC CONTROL; GLUCOSE; TYPE-1; COMPLICATIONS; MANAGEMENT; IMPACT;
TRIAL
AB The development of artificial pancreas systems has evolved to the point that pivotal studies designed to assess efficacy and safety are in progress or soon to be initiated. These pivotal studies are intended to provide the necessary data to gain clearance from the U.S. Food and Drug Administration, coverage by payers, and adoption by patients and clinicians. Although there will not be one design that is appropriate for every system, there are certain aspects of protocol design that will be considerations in all pivotal studies designed to assess efficacy and safety. One key aspect of study design is the intervention to be used by the control group. A case can be made that the control group should use the currently available best technology, which is sensor-augmented pump therapy. However, an equally, if not more, compelling case can be made that the control intervention should be usual care. In this Perspective, we elaborate on this issue and provide a pragmatic approach to the design of clinical trials of artificial pancreas systems.
C1 [Russell, Steven J.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Beck, Roy W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
RP Beck, RW (reprint author), Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
EM rbeck@jaeb.org
FU Dexcom; Tandem Diabetes; Eli Lilly; Sanofi; Animas; Tandem; Bigfoot
Biomedical
FX S.J.R. reports pending patent applications for a blood glucose control
system assigned to Partners HealthCare and Massachusetts General
Hospital; reports receiving loaned equipment, support in kind, and/or
technical assistance from Dexcom, Tandem Diabetes, and Eli Lilly;
reports honoraria for lectures from Tandem Diabetes, Dexcom, Sanofi, and
Eli Lilly; reports consulting fees from Sanofi; and reports serving on
the scientific advisory boards for Tandem Diabetes and Companion
Medical. R.W.B. reports that his nonprofit employer has received
consultant payments on his behalf from Animas, Tandem, and Bigfoot
Biomedical with no personal compensation to him and grant funds from
Dexcom. No other potential conflicts of interest relevant to this
article were reported.
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PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1161
EP 1167
DI 10.2337/dc15-2449
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500023
PM 27330125
ER
PT J
AU Maahs, DM
Buckingham, BA
Castle, JR
Cinar, A
Damiano, ER
Dassau, E
DeVries, JH
Doyle, FJ
Griffen, SC
Haidar, A
Heinemann, L
Hovorka, R
Jones, TW
Kollman, C
Kovatchev, B
Levy, BL
Nimri, R
O'Neal, DN
Philip, M
Renard, E
Russell, SJ
Weinzimer, SA
Zisser, H
Lum, JW
AF Maahs, David M.
Buckingham, Bruce A.
Castle, Jessica R.
Cinar, Ali
Damiano, Edward R.
Dassau, Eyal
DeVries, J. Hans
Doyle, Francis J., III
Griffen, Steven C.
Haidar, Ahmad
Heinemann, Lutz
Hovorka, Roman
Jones, Timothy W.
Kollman, Craig
Kovatchev, Boris
Levy, Brian L.
Nimri, Revital
O'Neal, David N.
Philip, Moshe
Renard, Eric
Russell, Steven J.
Weinzimer, Stuart A.
Zisser, Howard
Lum, John W.
TI Outcome Measures for Artificial Pancreas Clinical Trials: A Consensus
Report
SO DIABETES CARE
LA English
DT Article
ID AMERICAN-DIABETES-ASSOCIATION; SEVERE HYPOGLYCEMIC EVENTS; CONTINUOUS
GLUCOSE MONITOR; FREE-LIVING CONDITIONS; LOOP INSULIN DELIVERY;
CLOSED-LOOP; POSITION STATEMENT; TYPE-1; ACCURACY; SYSTEMS
AB Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA(1c), and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.
C1 [Maahs, David M.] Univ Colorado, Sch Med, Barbara Davis Ctr Childhood Diabet, Aurora, CO USA.
[Buckingham, Bruce A.] Stanford Univ, Dept Pediat Endocrinol, Div Pediat Endocrinol & Diabet, Stanford, CA 94305 USA.
[Castle, Jessica R.] Oregon Hlth & Sci Univ, Dept Med, Harold Schnitzer Diabet Hlth Ctr, Div Endocrinol, Portland, OR 97201 USA.
[Cinar, Ali] IIT, Dept Chem & Biol Engn, Chicago, IL 60616 USA.
[Damiano, Edward R.; Russell, Steven J.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA.
[Dassau, Eyal; Doyle, Francis J., III; Zisser, Howard] Univ Calif Santa Barbara, Dept Chem Engn, Santa Barbara, CA 93106 USA.
[Dassau, Eyal; Doyle, Francis J., III] Harvard Univ, Harvard John A Paulson Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[DeVries, J. Hans] Univ Amsterdam, Acad Med Ctr, Dept Endocrinol, Amsterdam, Netherlands.
[Griffen, Steven C.] JDRF, New York, NY USA.
[Haidar, Ahmad] McGill Univ, Dept Biomed Engn, Montreal, PQ, Canada.
[Haidar, Ahmad] McGill Univ, Div Endocrinol, Montreal, PQ, Canada.
[Heinemann, Lutz] Profil Inst Metab Res, Neuss, Germany.
[Hovorka, Roman] Univ Cambridge, Wellcome Trust Med Res Clin Inst Metab Sci, Cambridge, England.
[Jones, Timothy W.] Univ Western Australia, Telethon Kids Inst, Perth, WA, Australia.
[Kollman, Craig; Lum, John W.] Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
[Kovatchev, Boris] Univ Virginia, Charlottesville, VA USA.
[Levy, Brian L.] Johnson & Johnson Diabet Care Co, Wayne, PA USA.
[Nimri, Revital; Philip, Moshe] Tel Aviv Univ, Jesse Z & Sara Lea Shafer Inst Endocrinol & Diabe, Schneider Childrens Med Ctr Israel, Natl Ctr Childhood Diabet,Sackler Fac Med, Petah Tiqwa, Israel.
[O'Neal, David N.] Univ Melbourne, St Vincents Hosp Melbourne, Dept Med, Fitzroy, Vic, Australia.
[Renard, Eric] Univ Montpellier, Dept Endocrinol Diabet & Nutr, Montpellier Univ Hosp,UMR 5203,U1191, Clin Invest Ctr 1411,INSERM,Inst Funct Genom,CNRS, Montpellier, France.
[Russell, Steven J.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Russell, Steven J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Russell, Steven J.] Harvard Med Sch, Boston, MA USA.
[Weinzimer, Stuart A.] Yale Univ, Sch Med, New Haven, CT USA.
RP Lum, JW (reprint author), Jaeb Ctr Hlth Res, Tampa, FL 33647 USA.
EM jlum@jaeb.org
RI Hovorka, Roman/J-4123-2016;
OI Hovorka, Roman/0000-0003-2901-461X; DeVries, J. Hans/0000-0001-9196-9906
FU Abbott; Insulet; Medtronic; Dexcom; Roche Diagnostics; JDRF; Sanofi;
Tandem Diabetes Care; Novo Nordisk; National Institutes of Health (NIH);
Automated Glucose Control LLC; Animas Corp.; Johnson Johnson; NIH; Eli
Lilly; B. Braun; Profil; Diabetes UK; Sanofi-Aventis; National Institute
of Diabetes and Digestive and Kidney Diseases; European Commission;
National Institute for Health Research Efficacy and Mechanism Evaluation
Programme; Becton, Dickson, and Co.; Merck; Andromeda; Bristol-Myers
Squibb; Kamada; Pfizer; AstraZeneca; NG Solutions Ltd.; Nutriteen
Professionals Ltd.; A. Menarini Diagnostics; Cellnovo; LifeScan
FX D.M.M. reports personal fees from Abbott and Insulet and research
support from Medtronic, Dexcom, and Roche Diagnostics. B.A.B. reports
grant support from JDRF, Medtronic, and Dexcom; personal fees from
Medtronic, Sanofi, Tandem Diabetes Care, and Novo Nordisk; and other
support from Roche Diagnostics, Dexcom, and Abbott. J.R.C. has a
significant financial interest in Pacific Diabetes Technologies, Inc., a
company that may have a commercial interest in the results of this
research and technology. This potential conflict of interest has been
reviewed and managed by Oregon Health & Science University. A.C. reports
personal fees from Medtronic and a patent "Automatic insulin pumps using
recursive multivariable models and adaptive control algorithms"
(#US8690820) issued. E.R.D. reports a patent "Fully automated control
system for type 1 diabetes" (#US7806854) issued, grants from JDRF and
the National Institutes of Health (NIH), and personal fees from
Automated Glucose Control LLC and Animas Corp. J.H.D. reports grants
from Medtronic and personal fees from Johnson & Johnson and Sanofi.
F.J.D. reports grants from JDRF and NIH and personal fees from Automated
Glucose Control LLC and Animas Corp. A.H. owns intellectual property in
the field of artificial pancreas (dosing algorithm). A.H. has received
consultant and speaker honoraria from SNELL Medical Communication and
the Diabetic Children's Foundation and research support from Medtronic.
R.H. reports personal fees from Medtronic, Eli Lilly, Novo Nordisk, B.
Braun, Sanofi, and Profil and grants from JDRF and Diabetes UK. In
addition, R.H. has a patent "Substance monitoring and control in human
R.H. reports personal fees from Medtronic, Eli Lilly, Novo Nordisk, B.
Braun, Sanofi-Aventis, and Profil, as well as grants from JDRF, Diabetes
UK, the National Institute of Diabetes and Digestive and Kidney
Diseases, European Commission 7th Framework Programme for Research and
Technological Development, and National Institute for Health Research
Efficacy and Mechanism Evaluation Programme. In addition, R.H. has a
patent "Substance monitoring and control in human or animal bodies"
(#US9089305) license, a patent "Overnight closed-loop insulin delivery
with model predictive control and glucose measurement error model"
(#US8585637) issued, a patent "A system for insulin delivery using
glucose regulation and measurement error models" (#US8062249) issued,
and a patent "Substance monitoring and control in human or animal
bodies" (#US8977504) licensed. T.W.J. reports personal fees and
nonfinancial support from Medtronic and personal fees from Novo Nordisk
and Animas Corp. B.K. reports grants from Becton, Dickson, and Co. and
Sanofi, personal fees from Sanofi, and nonfinancial support from Animas
Corp., Roche Diagnostics, and Tandem Diabetes Care. In addition, B.K.
has a patent "CGM-based prevention of hypoglycemia via hypoglycemia risk
assessment and smooth reduction of insulin delivery" (#US8562587), with
royalties paid to Animas Corp.; a patent "Method and apparatus for
modular power management and protection of critical services in
ambulatory medical devices" (PCT/US12/43883), licensed to TypeZero
Technologies; and a patent "Unified platform for monitoring and control
of blood glucose levels in diabetic patients" (PCT/US12/43910), licensed
to TypeZero Technologies. R.H. is a shareholder in TypeZero
Technologies. B.L.L. reports other support from LifeScan and Animas
Corp. R.N. reports grants from JDRF and other support from Novo Nordisk
and DreaMed Diabetes Ltd. D.N.O.; reports grants and personal fees from
Medtronic, Roche Diagnostics, Sanofi, and Novo Nordisk. M.P. report
grants from Medtronic, Novo Nordisk, Roche Diagnostics, Eli Lilly,
Merck, Andromeda, Sanofi, Bristol-Myers Squibb, Kamada, Pfizer,
AstraZeneca, NG Solutions Ltd., and Nutriteen Professionals Ltd.;
personal fees from Medtronic, Novo Nordisk, Eli Lilly, Sanofi, and
Pfizer; and other support from Medtronic, Novo Nordisk, Roche
Diagnostics, CGM3 Ltd., NG Solutions Ltd., DreaMed Diabetes Ltd., and
Nutriteen Professionals Ltd. M.P. has a patent "Method and system for
automatic monitoring of diabetes related treatments" (#US20120123234 A1)
pending. E.R. reports personal fees from A. Menarini Diagnostics,
Cellnovo, Eli Lilly, Johnson & Johnson, Animas Corp., LifeScan,
Medtronic, Novo Nordisk, Abbott, Roche Diagnostics, Dexcom, and Sanofi
and nonfinancial support from Abbott, Roche Diagnostics, Dexcom, and
Insulet. S.J.R. reports personal fees from Dexcom, Tandem Diabetes Care,
Sanofi, Eli Lilly, and Novo Nordisk; nonfinancial support from Eli
Lilly, SweetSpot Diabetes, International Biomedical, Abbott, Insulet,
and Medtronic; and other support from Companion Medical. S.J.R. has
patents pending on aspects of bionic pancreas. S.A.W. reports grants
from Medtronic and personal fees from Medtronic, Insulet, and Tandem
Diabetes Care. H.Z. reports grants from NIH and JDRF. No other potential
conflicts of interest relevant to this article were reported.
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PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1175
EP 1179
DI 10.2337/dc15-2716
PG 5
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500025
PM 27330126
ER
PT J
AU Cefalu, WT
Buse, JB
Tuomilehto, J
Fleming, GA
Ferrannini, E
Gerstein, HC
Bennett, PH
Ramachandran, A
Raz, I
Rosenstock, J
Kahn, SE
AF Cefalu, William T.
Buse, John B.
Tuomilehto, Jaakko
Fleming, G. Alexander
Ferrannini, Ele
Gerstein, Hertzel C.
Bennett, Peter H.
Ramachandran, Ambady
Raz, Itamar
Rosenstock, Julio
Kahn, Steven E.
TI Update and Next Steps for Real-World Translation of Interventions for
Type 2 Diabetes Prevention: Reflections From a Diabetes Care Editors'
Expert Forum
SO DIABETES CARE
LA English
DT Article
ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION;
RANDOMIZED-CONTROLLED-TRIAL; CORONARY-HEART-DISEASE; 10-YEAR FOLLOW-UP;
BETA-CELL FUNCTION; DA QING IGT; FASTING GLUCOSE; INSULIN-SECRETION;
PROGRAM OUTCOMES
AB The International Diabetes Federation estimates that 415 million adults worldwide now have diabetes and 318 million have impaired glucose tolerance. These numbers are expected to increase to 642 million and 482 million, respectively, by 2040. This burgeoning pandemic places an enormous burden on countries worldwide, particularly resource-poor regions. Numerous landmark trials evaluating both intensive lifestyle modification and pharmacological interventions have persuasively demonstrated that type 2 diabetes can be prevented or its onset can be delayed in high-risk individuals with impaired glucose tolerance. However, key challenges remain, including how to scale up such approaches for widespread translation and implementation, how to select appropriately from various interventions and tailor them for different populations and settings, and how to ensure that preventive interventions yield clinically meaningful, cost-effective outcomes. In June 2015, a Diabetes Care Editors' Expert Forum convened to discuss these issues. This article, an outgrowth of the forum, begins with a summary of seminal prevention trials, followed by a discussion of considerations for selecting appropriate populations for intervention and the clinical implications of the various diagnostic criteria for prediabetes. The authors outline knowledge gaps in need of elucidation and explore a possible new avenue for securing regulatory approval of a prevention-related indication for metformin, as well as specific considerations for future pharmacological interventions to delay the onset of type 2 diabetes. They conclude with descriptions of some innovative, pragmatic translational initiatives already under way around the world.
C1 [Cefalu, William T.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Buse, John B.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.
[Tuomilehto, Jaakko] Dasman Diabet Inst, Dasman, Kuwait.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Saudi Diabet Res Grp, Jeddah, Saudi Arabia.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Fleming, G. Alexander] Kinexum, Harpers Ferry, WV USA.
[Ferrannini, Ele] CNR, Inst Clin Physiol, Pisa, Italy.
[Gerstein, Hertzel C.] McMaster Univ, Hamilton, ON, Canada.
[Gerstein, Hertzel C.] Hamilton Hlth Sci, Hamilton, ON, Canada.
[Bennett, Peter H.] NIH, Phoenix, AZ USA.
[Ramachandran, Ambady] India Diabet Res Fdn, Madras, Tamil Nadu, India.
[Bennett, Peter H.] Dr A Ramachandrans Diabet Hosp, Madras, Tamil Nadu, India.
[Raz, Itamar] Hadassah Hebrew Univ Hosp, Dept Internal Med, Diabet Unit, Jerusalem, Israel.
[Rosenstock, Julio] Med City, Dallas Diabet & Endocrine Ctr, Dallas, TX USA.
[Rosenstock, Julio] Univ Texas Southwestern Med Ctr, Dallas, TX USA.
[Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Kahn, Steven E.] Univ Washington, Seattle, WA 98195 USA.
RP Cefalu, WT (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
EM william.cefalu@pbrc.edu
OI Kahn, Steven/0000-0001-7307-9002
FU National Institutes of Health (NIH) [1U54-GM-104940]; NIH
[P50-AT-002776]
FX Writing and editing support services for this article were provided by
Debbie Kendall of Kendall Editorial in Richmond, VA. The Editorial
Committee recognizes that the work of the journal and contributions such
as this Expert Forum would not be possible without the dedicated work
and continued support of many individuals. Specifically, the planning,
logistics, and funding of the meeting and the incredible editorial
support would not have been possible without the tireless efforts of
Chris Kohler and his staff at the ADA Publishing office. In addition,
the Editorial Committee thanks Lyn Reynolds and her staff in the ADA
editorial office for support and Anne Gooch at the Pennington Biomedical
Research Center for her valuable assistance in helping to organize the
Expert Forum. W.T.C. is supported in part by National Institutes of
Health (NIH) grant 1U54-GM-104940, which funds the Louisiana Clinical
and Translational Science Center, and NIH grant P50-AT-002776.
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PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1186
EP 1201
DI 10.2337/dc16-0873
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500027
PM 27631469
ER
PT J
AU Piccolo, RS
Subramanian, SV
Pearce, N
Florez, JC
McKinlay, JB
AF Piccolo, Rebecca S.
Subramanian, S. V.
Pearce, Neil
Florez, Jose C.
McKinlay, John B.
TI Relative Contributions of Socioeconomic, Local Environmental,
Psychosocial, Lifestyle/Behavioral, Biophysiological, and Ancestral
Factors to Racial/Ethnic Disparities in Type 2 Diabetes
SO DIABETES CARE
LA English
DT Article
ID HEALTH BACH SURVEY; GENETIC ANCESTRY; PHYSICAL-ACTIVITY;
AFRICAN-AMERICAN; HBA(1C) LEVELS; RISK; ACCELEROMETER; ASSOCIATION;
IMPUTATION; ADMIXTURE
AB OBJECTIVE
Racial/ethnic minorities in the U.S. have a higher prevalence of type 2 diabetes mellitus (T2DM) than white adults. While many independent risk factors for T2DM have been identified, these determinants are often viewed in isolation without considering the joint contributions of competing risk factors. The objective of this study was to assess the relative contributions of six domains of influence to racial/ethnic disparities in T2DM.
RESEARCH DESIGN AND METHODS
Cross-sectional analyses were conducted using the Boston Area Community Health III Survey (2010-2012), the third wave of a population-based sample of men and women from three racial/ethnic groups (black, Hispanic, white) living in Boston, Massachusetts (N = 2,764). Prevalent diabetes was defined by self-report of T2DM, fasting glucose >125mg/dL, or HbA(1c) >= 6.5%. Structural equation models were constructed to evaluate the direct effects of each conceptual domain of influence on T2DM prevalence, as well as their indirect effects on the race/ethnicity-T2DM relationship. All direct and indirect pathways were included.
RESULTS
The final model indicated that 38.9% and 21.8% of the total effect of black race and Hispanic ethnicity, respectively, on T2DM prevalence was mediated by the socioeconomic, environmental, psychosocial, and lifestyle/behavioral risk scores. The largest mediating influence was the socioeconomic risk score, which explained 21.8% and 26.2% of the total effect of black race and Hispanic ethnicity, respectively.
CONCLUSIONS
Our study found that socioeconomic factors had the greatest impact on explaining the excess prevalence of T2DM among racial/ethnic minorities.
C1 [Piccolo, Rebecca S.; Pearce, Neil] London Sch Hyg & Trop Med, London, England.
[Subramanian, S. V.] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Harvard Med Sch, Boston, MA USA.
[McKinlay, John B.] New England Res Inst, Dept Epidemiol, 9 Galen St, Watertown, MA 02172 USA.
RP Piccolo, RS (reprint author), London Sch Hyg & Trop Med, London, England.
EM rebecca.piccolo@lshtm.ac.uk
FU National Institutes of Diabetes and Digestive and Kidney Diseases
[DK056842, DK080786]
FX This study was supported by grants from the National Institutes of
Diabetes and Digestive and Kidney Diseases (DK056842 and DK080786).
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PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1208
EP 1217
DI 10.2337/dc15-2255
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500029
PM 27330127
ER
PT J
AU Hering, BJ
Clarke, WR
Bridges, ND
Eggerman, TL
Alejandro, R
Bellin, MD
Chaloner, K
Czarniecki, CW
Goldstein, JS
Hunsicker, LG
Kaufman, DB
Korsgren, O
Larsen, CP
Luo, XR
Markmann, JF
Naji, A
Oberholzer, J
Posselt, AM
Rickels, MR
Ricordi, C
Robien, MA
Senior, PA
Shapiro, AMJ
Stock, PG
Turgeon, NA
AF Hering, Bernhard J.
Clarke, William R.
Bridges, Nancy D.
Eggerman, Thomas L.
Alejandro, Rodolfo
Bellin, Melena D.
Chaloner, Kathryn
Czarniecki, Christine W.
Goldstein, Julia S.
Hunsicker, Lawrence G.
Kaufman, Dixon B.
Korsgren, Olle
Larsen, Christian P.
Luo, Xunrong
Markmann, James F.
Naji, Ali
Oberholzer, Jose
Posselt, Andrew M.
Rickels, Michael R.
Ricordi, Camillo
Robien, Mark A.
Senior, Peter A.
Shapiro, A. M. James
Stock, Peter G.
Turgeon, Nicole A.
CA Clinical Islet Transplantation Con
TI Phase 3 Trial of Transplantation of Human Islets in Type 1 Diabetes
Complicated by Severe Hypoglycemia
SO DIABETES CARE
LA English
DT Article
ID EXCHANGE CLINIC REGISTRY; INSULIN PUMP THERAPY; PANCREAS
TRANSPLANTATION; GLYCEMIC CONTROL; CURRENT STATE; AWARENESS; ADULTS;
MELLITUS; OUTCOMES; IDDM
AB OBJECTIVE
Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment.
RESEARCH DESIGN AND METHODS
This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA(1c) <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant.
RESULTS
The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA(1c) level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients.
CONCLUSIONS
Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
C1 [Hering, Bernhard J.; Bellin, Melena D.] Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA.
[Hering, Bernhard J.] Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA.
[Clarke, William R.; Chaloner, Kathryn; Hunsicker, Lawrence G.] Univ Iowa, Clin Trials Stat & Data Management Ctr, Iowa City, IA USA.
[Bridges, Nancy D.; Czarniecki, Christine W.; Goldstein, Julia S.; Robien, Mark A.] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Eggerman, Thomas L.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Alejandro, Rodolfo; Ricordi, Camillo] Univ Miami, Miller Sch Med, Diabet Res Inst, Miami, FL 33136 USA.
[Bellin, Melena D.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA.
[Kaufman, Dixon B.] Univ Wisconsin, Dept Surg, Div Transplantat, Madison, WI USA.
[Korsgren, Olle] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Larsen, Christian P.; Turgeon, Nicole A.] Emory Univ, Emory Transplant Ctr, Atlanta, GA 30322 USA.
[Luo, Xunrong] Northwestern Univ, Feinberg Sch Med, Comprehens Transplant Ctr, Chicago, IL 60611 USA.
[Markmann, James F.] Harvard Med Sch, Massachusetts Gen Hosp, Div Transplant Surg, Boston, MA USA.
[Naji, Ali; Rickels, Michael R.] Univ Penn, Perelman Sch Med, Inst Diabet Obes & Metab, Philadelphia, PA 19104 USA.
[Naji, Ali; Rickels, Michael R.] Univ Penn, Perelman Sch Med, Dept Surg, Philadelphia, PA 19104 USA.
[Naji, Ali; Rickels, Michael R.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Oberholzer, Jose] Univ Illinois Hosp & Hlth Sci Syst, Div Transplantat, Chicago, IL USA.
[Posselt, Andrew M.; Stock, Peter G.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Senior, Peter A.; Shapiro, A. M. James] Univ Alberta, Clin Islet Transplant Program, Edmonton, AB, Canada.
[Senior, Peter A.; Shapiro, A. M. James] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada.
RP Hering, BJ (reprint author), Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA.; Hering, BJ (reprint author), Univ Minnesota, Dept Surg, Box 242 UMHC, Minneapolis, MN 55455 USA.
EM bhering@umn.edu
OI Ricordi, Camillo/0000-0001-8092-7153
FU National Institute of Allergy and Infectious Diseases; National
Institute for Diabetes and Digestive and Kidney Diseases [U01-AI-089317,
U01-AI-089316, U01-AI-065191, U01-DK-085531, 5U01-DK-070431-10,
U01-DK-070431, U01-DK070460, U01-AI-065193, U01-DK-070430,
U01-AI-065192]; General Clinical Research Center Awards and Clinical and
Translational Science Awards [UL1-TR-000454, 5UL1-RR-025741,
8UL1-TR-000150, UL1-TR-000004, UL1-TR-000050, 1UL1-TR-000460,
5M01-RR-000400, UL1-TR-000114, M01-RR-00040, UL1-TR-000003]; National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health [NO1-AI-15416, UM1-AI-109565]
FX This research was supported by grants from the National Institute of
Allergy and Infectious Diseases and the National Institute for Diabetes
and Digestive and Kidney Diseases to the following institutions: Emory
University (Atlanta, GA), U01-AI-089317; Northwestern University
(Evanston, IL), U01-AI-089316; University of Alberta(Edmonton, Alberta,
Canada), U01-AI-065191; University of California, San Francisco (San
Francisco, CA) U01-DK-085531; University of Illinois, Chicago(Chicago,
IL), 5U01-DK-070431-10; University of Iowa (Iowa City, IA),
U01-DK-070431; University of Miami (Miami, FL), U01-DK070460; University
of Minnesota (Minneapolis, MN), U01-AI-065193; University of
Pennsylvania (Philadelphia, PA), U01-DK-070430; and Uppsala University
(Uppsala, Sweden), U01-AI-065192. In addition, the study was supported
by the following General Clinical Research Center Awards and Clinical
and Translational Science Awards: to Emory University, UL1-TR-000454;
Northwestern University, 5UL1-RR-025741 and 8UL1-TR-000150; University
of California, San Francisco, UL1-TR-000004; University of Illinois,
Chicago, UL1-TR-000050; University of Miami, 1UL1-TR-000460; University
of Minnesota, 5M01-RR-000400 and UL1-TR-000114; and University of
Pennsylvania, M01-RR-00040 and UL1-TR-000003. TrialShare, a public
database maintained by the Immune Tolerance Network, is supported by the
National Institute of Allergy and Infectious Diseases of the National
Institutes of Health under award numbers NO1-AI-15416 and UM1-AI-109565.
NR 40
TC 19
Z9 19
U1 3
U2 3
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1230
EP 1240
DI 10.2337/dc15-1988
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500032
PM 27208344
ER
PT J
AU Celeng, C
Maurovich-Horvat, P
Ghoshhajra, BB
Merkely, B
Leiner, T
Takx, RAP
AF Celeng, Csilla
Maurovich-Horvat, Pal
Ghoshhajra, Brian B.
Merkely, Bela
Leiner, Tim
Takx, Richard A. P.
TI Prognostic Value of Coronary Computed Tomography Angiography in Patients
With Diabetes: A Meta-analysis
SO DIABETES CARE
LA English
DT Article
ID AMERICAN-HEART-ASSOCIATION; ARTERY-DISEASE; CT ANGIOGRAPHY;
CARDIOVASCULAR-DISEASE; CARDIAC EVENTS; FOLLOW-UP; RISK; MELLITUS;
INDIVIDUALS; POPULATION
AB OBJECTIVE
The usefulness of coronary computed tomography angiography (CTA) for the evaluation of coronary artery disease (CAD) in patients with diabetes is ambiguous. We therefore performed a meta-analysis of studies reporting event rates and hazard ratios (HR) to determine the prognostic value of CTA in this patient population.
RESEARCH DESIGN AND METHODS
We searched PubMed and Embase up to November 2015. Study subjects' characteristics, events (all-cause mortality or cardiac death, nonfatal myocardial infarction, unstable angina pectoris, stroke, revascularization), and events excluding revascularization were collected. We calculated the prevalence of obstructive and nonobstructive CAD on CTA, annualized event rates, and pooled unadjusted and adjusted HR using a generic inverse random model.
RESULTS
Eight studies were eligible for inclusion into this meta-analysis, with 6,225 participants (56% male; weighted age, 61 years) with a follow-up period ranging from 20 to 66 months. The prevalence of obstructive CAD, nonobstructive CAD, and no CAD was 38%, 36%, and 25%, respectively. The annualized event rate was 17.1% for obstructive CAD, 4.5% for nonobstructive CAD, and 0.1% for no CAD. Obstructive and nonobstructive CAD were associated with an increased HR of 5.4 and 4.2, respectively. A higher HR for obstructive CAD was observed in studies including revascularization compared with those that did not (7.3 vs. 3.7, P = 0.124).
CONCLUSIONS
CTA in patients with diabetes allows for safely ruling out future events, and the detection of CAD could allow for the identification of high-risk patients in whom aggressive risk factor modification, medical surveillance, or elective revascularization could potentially improve survival.
C1 [Celeng, Csilla; Maurovich-Horvat, Pal; Merkely, Bela] Semmelweis Univ, Heart & Vasc Ctr, MTA SE Cardiovasc Imaging Res Grp, Budapest, Hungary.
[Ghoshhajra, Brian B.; Takx, Richard A. P.] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiovasc Imaging, Boston, MA 02114 USA.
[Ghoshhajra, Brian B.; Takx, Richard A. P.] Harvard Med Sch, Boston, MA 02115 USA.
[Leiner, Tim; Takx, Richard A. P.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
RP Takx, RAP (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Div Cardiovasc Imaging, Boston, MA 02114 USA.; Takx, RAP (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Takx, RAP (reprint author), Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
EM r.a.p.takx@umcutrecht.nl
FU Van Leersum Grant of the Royal Netherlands Academy of Arts and Sciences
FX R.A.P.T. is supported by Van Leersum Grant of the Royal Netherlands
Academy of Arts and Sciences.
NR 35
TC 0
Z9 1
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP 1274
EP 1280
DI 10.2337/dc16-0281
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500037
PM 27330128
ER
PT J
AU Arnold, SV
Inzucchi, SE
McGuire, DK
Mehta, SN
Goyal, A
Sperling, LS
Maddox, TM
Einhorn, D
Wong, ND
Ratner, RE
Hammar, N
Fenici, P
Sheehan, JJ
Wong, JL
Kosiborod, M
AF Arnold, Suzanne V.
Inzucchi, Silvio E.
McGuire, Darren K.
Mehta, Sanjeev N.
Goyal, Abhinav
Sperling, Laurence S.
Maddox, Thomas M.
Einhorn, Daniel
Wong, Nathan D.
Ratner, Robert E.
Hammar, Niklas
Fenici, Peter
Sheehan, John J.
Wong, Jennifer L.
Kosiborod, Mikhail
TI Evaluating the Quality of Comprehensive Cardiometabolic Care for
Patients With Type 2 Diabetes in the US: The Diabetes Collaborative
Registry
SO DIABETES CARE
LA English
DT Letter
ID CLINICAL-PRACTICE; ASSOCIATION; GUIDELINES; MORTALITY; MELLITUS; BURDEN
C1 [Arnold, Suzanne V.; Kosiborod, Mikhail] St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Arnold, Suzanne V.; Kosiborod, Mikhail] Univ Missouri, Kansas City, MO 64110 USA.
[Inzucchi, Silvio E.] Yale Univ, Sch Med, New Haven, CT USA.
[McGuire, Darren K.] Univ Texas Southwestern Med Ctr, Dallas, TX USA.
[Mehta, Sanjeev N.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Goyal, Abhinav; Sperling, Laurence S.] Emory Univ, Sch Med, Atlanta, GA USA.
[Maddox, Thomas M.] VA Eastern Colorado Hlth Care Syst, Denver, CO USA.
[Maddox, Thomas M.] Univ Colorado, Sch Med, Denver, CO USA.
[Einhorn, Daniel] Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA.
[Wong, Nathan D.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA.
[Ratner, Robert E.] Amer Diabet Assoc, Alexandria, VA USA.
[Hammar, Niklas] AstraZeneca, Molndal, Sweden.
[Fenici, Peter] AstraZeneca, Rome, Italy.
[Sheehan, John J.] AstraZeneca, Ft Washington, PA USA.
[Wong, Jennifer L.] Amer Coll Cardiol Fdn, Washington, DC USA.
RP Kosiborod, M (reprint author), St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA.; Kosiborod, M (reprint author), Univ Missouri, Kansas City, MO 64110 USA.
EM mkosiborod@saint-lukes.org
NR 20
TC 0
Z9 0
U1 0
U2 0
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD JUL
PY 2016
VL 39
IS 7
BP E99
EP E101
DI 10.2337/dc16-0585
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT3YG
UT WOS:000381416500005
PM 27222504
ER
PT J
AU Davis, M
Aviki, E
Rauh-Hain, JA
Worley, M
Berkowitz, R
Schorge, J
Muto, M
Sisodia, RC
Horowitz, N
del Carmen, M
AF Davis, Michelle
Aviki, Emeline
Rauh-Hain, J. Alejandro
Worley, Michael, Jr.
Berkowitz, Ross
Schorge, John
Muto, Michael
Sisodia, Rachel Clark
Horowitz, Neil
del Carmen, Marcela
TI Investigating the Impact of Body Mass Index on Intraperitoneal
Chemotherapy Outcomes in Ovarian and Fallopian Tube Cancer
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Article
DE Ovarian cancer; Intraperitoneal chemotherapy; Obesity
ID GYNECOLOGIC-ONCOLOGY-GROUP; CYTOREDUCTIVE SURGERY; OBESITY; WOMEN;
COMPLICATIONS; APPENDICEAL; MANAGEMENT; CISPLATIN; SURVIVAL; DISEASE
AB Objectives: The aim of this study was to investigate the impact of body mass index (BMI) on completion, complications, and clinical outcomes of intraperitoneal (IP) chemotherapy in patients with advanced-stage ovarian cancer.
Methods: Patients with optimally cytoreduced International Federation of Gynecology and Obstetrics stage IIIC ovarian cancer treated with IP chemotherapy were retrospectively identified using an institutional review boardYapproved database. Clinical data were abstracted from the longitudinal medical record. Survival estimates were calculated using the Kaplan-Meier method.
Results: Ninety-two patients (35.5%) completed at least one cycle of IP chemotherapy. For these patients, there was no difference in histology, surgical complexity, or degree of cytoreduction based on BMI. Sixty-five percent of normal weight, 70% of overweight, and 59.1% of obese women completed 6 cycles (P = 0.697). There was also no significant difference in IP chemotherapy complications (P = 0.303). Body mass index had no impact on disease-free survival (P = 0.44) or overall survival, with a median overall survival of 68.5 months for normal weight, 65.9 months for overweight, and 61.7 months for obese women (P = 0.25). However, on multivariate analysis, obesity had an odds ratio of 2.92 (P = 0.02) for mortality. There was a trend toward treatment with intravenous chemotherapy (84.2%) over IP (15.8%) in patients with class II obesity (P = 0.06).
Discussion: There was no difference in completion of IP chemotherapy or complications with respect to BMI; however, there was a trend away from treatment with IP therapy in extreme obesity. These data suggest that IP chemotherapy is feasible in obese patients without incurring increased morbidity.
C1 [Davis, Michelle; Aviki, Emeline; Berkowitz, Ross; Muto, Michael; Horowitz, Neil] Harvard Med Sch, Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA USA.
[Aviki, Emeline; Rauh-Hain, J. Alejandro; Schorge, John; Sisodia, Rachel Clark; del Carmen, Marcela] Harvard Med Sch, Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, Boston, MA USA.
[Worley, Michael, Jr.] St Peters Univ Hosp, New Brunswick, NJ USA.
RP del Carmen, M (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA.
EM mdelcarmen@partners.org
NR 28
TC 1
Z9 1
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1048-891X
EI 1525-1438
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD JUL
PY 2016
VL 26
IS 6
BP 1033
EP 1040
DI 10.1097/IGC.0000000000000729
PG 8
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DW9CV
UT WOS:000383953500008
PM 27206282
ER
PT J
AU Simmons, AR
Clarke, CH
Badgwell, DB
Lu, Z
Sokoll, LJ
Lu, KH
Zhang, Z
Bast, RC
Skates, SJ
AF Simmons, Archana R.
Clarke, Charlotte H.
Badgwell, Donna B.
Lu, Zhen
Sokoll, Lori J.
Lu, Karen H.
Zhang, Zhen
Bast, Robert C., Jr.
Skates, Steven J.
TI Validation of a Biomarker Panel and Longitudinal Biomarker Performance
for Early Detection of Ovarian Cancer
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Article
DE Ovarian cancer; Early detection; Multiple marker; Longitudinal biomarker
ID RANDOMIZED CONTROLLED-TRIAL; STATISTICS; MORTALITY; PROSTATE; LUNG
AB Objectives: Longitudinal multimarker combinations have the potential to improve sensitivity while maintaining the high specificity required for the early detection of ovarian cancer. The use of multiple markers to improve sensitivity over cancer antigen 125 (CA125) in longitudinal algorithms for early ovarian cancer detection requires the selection of markers with optimal discriminatory power and low longitudinal variance relative to disease-initiated changes. Our objective was to identify a multimarker panel suitable for ovarian cancer, where each individual marker has its own baseline, permitting longitudinal algorithm development.
Materials and Methods: In this retrospective study, we measured CA125, human epididymis protein 4 (HE4), matrix metalloproteinase-7 (MMP-7), CA72-4, CA19-9, CA15-3, carcinoembryonic antigen, and soluble vascular cell adhesion molecule (sVCAM) concentrations using immunoassays in pretreatment sera from 142 stage I ovarian cancer cases and 5 annual samples each from 217 healthy controls. After random division into training and validation sets, all possible biomarker combinations were explored exhaustively using linear classifiers to identify the panel with the greatest sensitivity for stage I disease at a high specificity of 98%. To evaluate longitudinal performance of the individual markers, the within-person over time and the between-person coefficient of variation (CV) were estimated. Hierarchical modeling across women of log-concentrations enabled the borrowing of information across subjects to moderate variance estimates given the small number of observations per subject.
Results: The 4-marker panel comprising CA125, HE4, MMP-7, and CA72-4 performed with the highest sensitivity (83.2%) at 98% specificity. The within-person CVs were lower for CA125, HE4, MMP-7, and CA72-4 (15%, 25%, 25%, and 21%, respectively) compared with their corresponding between-person CV (49%, 20%, 35%, and 84%, respectively) indicating baselines in healthy volunteers. After simple log-transformations, the within volunteer variation across volunteers was modeled with a normal distribution permitting parsimonious hierarchical modeling.
Conclusions: The multiplex panel chosen is suitable for the early detection of ovarian cancer and the individual markers have their own baseline permitting longitudinal algorithm development.
C1 [Simmons, Archana R.; Clarke, Charlotte H.; Badgwell, Donna B.; Lu, Zhen; Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Sokoll, Lori J.; Zhang, Zhen] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Lu, Karen H.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Skates, Steven J.] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA.
RP Bast, RC (reprint author), Univ Texas MD Anderson Canc Ctr, 1400 Pressler St,Unit 1439, Houston, TX 77230 USA.
EM rbast@mdanderson.org
RI Bast, Robert/E-6585-2011
OI Bast, Robert/0000-0003-4621-8462
FU MD Anderson SPORE in Ovarian Cancer NCI [P50 CA83639]; Shared Resources
of the MD Anderson CCSG NCI [P30 CA16672]; Cancer Prevention and
Research Institute of Texas [RP101382]; Ovarian Cancer Research Fund;
National Foundation for Cancer Research
FX This study was supported in part by a grant from the MD Anderson SPORE
in Ovarian Cancer NCI P50 CA83639 grant; the Shared Resources of the MD
Anderson CCSG NCI P30 CA16672 grant; the Cancer Prevention and Research
Institute of Texas grant RP101382; the Ovarian Cancer Research Fund; the
National Foundation for Cancer Research; and philanthropic support from
the Zarrow Foundation and Stuart and Gaye Lynn Zarrow, Golfers Against
Cancer, the Kaye Yow Foundation, and the Mossy Family Foundation. Cancer
antigen 72-4 reagents were provided by Roche Diagnostics.
NR 16
TC 2
Z9 2
U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1048-891X
EI 1525-1438
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD JUL
PY 2016
VL 26
IS 6
BP 1070
EP 1077
DI 10.1097/IGC.0000000000000737
PG 8
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DW9CV
UT WOS:000383953500013
PM 27206285
ER
PT J
AU Chuang, LT
Randall, TC
Denny, L
Johnston, CM
Schmeler, KM
Covens, AL
Cibula, D
Bookman, MA
Rawal, S
DePetrillo, D
Nam, JH
Goodman, A
Naik, R
Manchanda, R
Gaffney, DK
Small, W
Creutzberg, C
Rattray, C
Kesic, V
Paraja, R
Eiken, M
Belleson, K
Coleman, RL
Barakat, RR
Trimble, EL
Quinn, M
AF Chuang, Linus T.
Randall, Thomas C.
Denny, Lynette
Johnston, Carolyn M.
Schmeler, Kathleen M.
Covens, Allan L.
Cibula, David
Bookman, Michael A.
Rawal, Sudhir
DePetrillo, Denny
Nam, Joo-Hyun
Goodman, Annekathryn
Naik, Raj
Manchanda, Ranjit
Gaffney, David K.
Small, William, Jr.
Creutzberg, Carien
Rattray, Carole
Kesic, Vesna
Paraja, Rene
Eiken, Mary
Belleson, Kristin
Coleman, Robert L.
Barakat, Richard R.
Trimble, Edward L.
Quinn, Michael
TI Sister Society Meeting on Global Education Development and Collaboration
Meeting Report
SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER
LA English
DT Article
DE Sister society; Low- and middle-income countries; Global education;
Collaboration
ID GYNECOLOGIC ONCOLOGY; HEALTH; SURGERY
AB Objectives: To identify common barriers to teaching and training and to identify strategies that would be useful in developing future training programs in gynecologic oncology in low- and middle-income countries.
Methods: There is a lack of overall strategy to meet the needs of education and training in gynecologic oncology in low- and middle-income countries, the leaderships of sister societies and global health volunteers met at the European Society of Gynecologic Oncology in October 23, 2015. The challenges of the training programs supported by gynecologic oncology societies, major universities and individual efforts were presented and discussed. Strategies to improve education and training were identified.
Results: Major challenges include language barriers, limited surgical equipment, inadequate internet access, lack of local support for sustainability in training programs, inadequate pathology and radiation oncology, finance and a global deficiency in identifying sites and personnel in partnering or developing training programs. The leaderships identified various key components including consultation with the local Ministry of Health, local educational institutions; inclusion of the program into existing local programs, a needs assessment, and the development of curriculum and regional centers of excellence.
Conclusions: Proper preparation of training sites and trainers, the development of global curriculum, the establishment of centers of excellence, and the ability to measure outcomes are important to improve education and training in gynecologic oncology in low- and middle- income countries.
C1 [Chuang, Linus T.] Icahn Sch Med Mt Sinai, 1176 Fifth Ave,Box 1173, New York, NY 10029 USA.
[Randall, Thomas C.; Goodman, Annekathryn] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Denny, Lynette] Univ Cape Town, Schuur Hosp, ZA-7700 Rondebosch, South Africa.
[Johnston, Carolyn M.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Schmeler, Kathleen M.; Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Covens, Allan L.] Univ Toronto, Odette Canc Ctr, Toronto, ON M5S 1A1, Canada.
[Cibula, David] Charles Univ Prague, Prague, Czech Republic.
[Cibula, David] Gen Univ Hosp, Prague, Czech Republic.
[Bookman, Michael A.] US Oncol Network, The Woodlands, TX USA.
[Rawal, Sudhir] Rajiv Gandhi Canc Inst, New Delhi, India.
[DePetrillo, Denny] Univ Toronto, CAREpath Canada, Toronto, ON M5S 1A1, Canada.
[Nam, Joo-Hyun] Univ Ulsan, Coll Med, Seoul, South Korea.
[Naik, Raj] Queen Elizabeth Hosp, Gateshead, England.
[Manchanda, Ranjit] Queen Mary Univ London, Barts Canc Inst, London, England.
[Gaffney, David K.] Univ Utah, Huntsman Canc Hosp, Salt Lake City, UT 84112 USA.
[Small, William, Jr.] Loyola Univ, Stritch Sch Med, Chicago, IL 60611 USA.
[Creutzberg, Carien] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Rattray, Carole] Univ West Indies, Mona Campus, Kingston, Jamaica.
[Kesic, Vesna] Clin Ctr Serbia, Belgrade, Serbia.
[Paraja, Rene] Inst Cancerol Amer, Antioquia, Colombia.
[Eiken, Mary] Int Gynecol Canc Soc, Louisville, KY USA.
[Belleson, Kristin] Soc Gynecol Oncol, Chicago, IL USA.
[Barakat, Richard R.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Trimble, Edward L.] NCI, Bethesda, MD 20892 USA.
[Quinn, Michael] Royal Womens Hosp, Melbourne, Vic, Australia.
RP Chuang, LT (reprint author), Icahn Sch Med Mt Sinai, 1176 Fifth Ave,Box 1173, New York, NY 10029 USA.
EM linus.chuang@mssm.edu
OI Cibula, David/0000-0001-6387-9356
FU NCI NIH HHS [P30 CA008748]
NR 6
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1048-891X
EI 1525-1438
J9 INT J GYNECOL CANCER
JI Int. J. Gynecol. Cancer
PD JUL
PY 2016
VL 26
IS 6
BP 1186
EP 1188
DI 10.1097/IGC.0000000000000735
PG 3
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DW9CV
UT WOS:000383953500030
PM 27327155
ER
PT J
AU Wilens, T
Zulauf, C
Martelon, M
Morrison, NR
Simon, A
Carrellas, NW
Yule, A
Anselmo, R
AF Wilens, Timothy
Zulauf, Courtney
Martelon, MaryKate
Morrison, Nicholas R.
Simon, Andrew
Carrellas, Nicholas W.
Yule, Amy
Anselmo, Rayce
TI Nonmedical Stimulant Use in College Students: Association With
Attention-Deficit/Hyperactivity Disorder and Other Disorders
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
DE Attention-Deficit/Hyperactivity Disorder; Substance-Related Disorders
ID ADHD MEDICATION USE; PRESCRIPTION STIMULANTS; ILLICIT USE; DOUBLE-BLIND;
ADOLESCENTS; MOTIVES; PREVALENCE; DIVERSION; CHILDREN; MISUSE
AB Objective: The nonmedical use of stimulants (misuse) in the college setting remains of utmost public health and clinical concern. The objective of this study was to evaluate comprehensively the characteristics of college students who misused stimulants, attending to rates of attention-deficit/hyperactivity disorder (ADHD), other psychopathology, and substance use disorders.
Methods: The data presented are from a cross-sectional study of college students who misused prescription stimulant medications (not including cocaine or methamphetamine) and controls (college students without stimulant misuse). Between May 2010 and May 2013, college students were assessed blindly for psychopathology and substance use disorder by way of Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P) and completion of self-report questionnaires.
Results: The analysis included 198 controls (mean +/- SD age = 20.7 +/- 2.6 years) and 100 stimulant misusers (20.7 +/- 1.7 years). Misusers, when compared to controls, were more likely to endorse alcohol, drug, alcohol + drug, and any substance use disorder (all P values <.01). When a subset of stimulant misusers (n = 58) was examined, 67% had a full or subthreshold prescription stimulant use disorder. Misusers also had higher rates of conduct disorder (10% vs 3%; P = .02) and ADHD (including subthreshold cases; 27% vs 16%; P = .02) in addition to lower Global Assessment of Functioning score (P < .01). Higher rates of misuse of immediate-release-relative to extended-release-stimulants were reported.
Conclusions: Our data suggest that, compared to controls, college students who misuse stimulant medications are more likely to have ADHD, conduct disorder, stimulant and other substance use disorder, and overall dysfunction. (C) Copyright 2016 Physicians Postgraduate Press, Inc.
C1 [Wilens, Timothy; Zulauf, Courtney; Martelon, MaryKate; Morrison, Nicholas R.; Simon, Andrew; Carrellas, Nicholas W.; Yule, Amy] Massachusetts Gen Hosp, Div Child Psychiat, Pediat Psychopharmacol Program, Boston, MA 02114 USA.
[Wilens, Timothy; Yule, Amy; Anselmo, Rayce] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Wilens, Timothy; Yule, Amy; Anselmo, Rayce] Harvard Med Sch, Boston, MA USA.
RP Wilens, T (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, 55 Fruit St,YAW 6A, Boston, MA 02114 USA.
EM twilens@partners.org
FU NIH [K24 DA016264]
FX This work was supported by an NIH K24 DA016264 grant to Dr Wilens.
NR 40
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U1 4
U2 4
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUL
PY 2016
VL 77
IS 7
BP 940
EP 947
DI 10.4088/JCP.14m09559
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW6XY
UT WOS:000383795900021
PM 27464314
ER
PT J
AU Gracious, BL
Fontanella, CA
Phillips, GS
Bridge, JA
Marcus, SC
Campo, JV
AF Gracious, Barbara L.
Fontanella, Cynthia A.
Phillips, Gary S.
Bridge, Jeffrey A.
Marcus, Steven C.
Campo, John V.
TI Antidepressant Exposure and Risk of Fracture Among Medicaid-Covered
Youth
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
DE Antidepressants; Child and Adolescent Psychiatry
ID SEROTONIN-REUPTAKE INHIBITORS; BONE-MINERAL DENSITY; PEDIATRIC OFFICIAL
POSITIONS; DEPRESSIVE SYMPTOMS; ADOLESCENTS; CHILDREN; WOMEN; GROWTH;
RECOMMENDATIONS; OSTEOPOROSIS
AB Objective: This study examines the association between antidepressant use and risk of fracture in depressed youth and assesses whether fracture incidence varies over the course of antidepressant treatment.
Method: A retrospective cohort analysis of Ohio Medicaid claims data was conducted for youth ages 6-17 years with a new episode of ICD-9-diagnosed depression from 2001-2009. The primary outcome variable was time to fracture. Fracture rates were compared between depressed youth treated with antidepressant medication and untreated depressed youth. Time categories of no use, past use, and current use were compared.
Results: Of 50,673 depressed youths, 5,872 (11.6%) experienced a fracture. Of those who had a fracture, 2,228 (37.9%) were exposed to antidepressants, 80% of which were selective serotonin reuptake inhibitors. The adjusted hazard ratio (HR) was 3% higher in those currently prescribed antidepressants (HR = 1.03; 95% CI, 1.00-1.06; P = .03). The risk ratio (RR) for adjusted fracture rates per 10,000 persons was twice as high during the first 30 days of antidepressant use compared to the other time periods (RR = 2.0; 95% CI, 1.2-3.3; P = .007). The number of fractures for those with past antidepressant use did not differ from those with no history of antidepressant use.
Conclusions: Antidepressant use may be associated with a small but significant increase in fracture risk, particularly within the first 30 days of treatment. Findings underscore a need for additional prospective and mechanistic research. Prescribers should consider other risks for fracture in antidepressant-treated youth, particularly disability and the concomitant use of other medications that increase fracture risk. (C) Copyright 2016 Physicians Postgraduate Press, Inc.
C1 [Gracious, Barbara L.; Fontanella, Cynthia A.; Campo, John V.] Ohio State Univ, Dept Psychiat & Behav Hlth, Wexner Med Ctr, Columbus, OH 43210 USA.
[Gracious, Barbara L.; Bridge, Jeffrey A.] Nationwide Childrens Hosp, Res Inst, Ctr Innovat Pediat Practice, Columbus, OH USA.
[Phillips, Gary S.] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
[Bridge, Jeffrey A.] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA.
[Marcus, Steven C.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Marcus, Steven C.] Univ Penn, Sch Social Policy & Practice, Philadelphia, PA 19104 USA.
RP Gracious, BL (reprint author), Nationwide Childrens Hosp, 700 Childrens Dr,J West 4923, Columbus, OH 43205 USA.
EM Barbara.Gracious@nationwidechildrens.org
FU National Center for Research Resources [UL1RR025755]; Jeffrey Research
Fellowship at the Department of Psychiatry and Behavioral Health;
Nationwide Children's Hospital; Ohio State University
FX This project was supported by Award Number UL1RR025755 from the National
Center for Research Resources, for the statistical support by Mr
Phillips. Dr Gracious' salary for the project was supported by The
Jeffrey Research Fellowship at the Department of Psychiatry and
Behavioral Health, Nationwide Children's Hospital and The Ohio State
University.
NR 37
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Z9 0
U1 3
U2 3
PU PHYSICIANS POSTGRADUATE PRESS
PI MEMPHIS
PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA
SN 0160-6689
EI 1555-2101
J9 J CLIN PSYCHIAT
JI J. Clin. Psychiatry
PD JUL
PY 2016
VL 77
IS 7
BP 950
EP +
DI 10.4088/JCP.15m09828
PG 11
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW6XY
UT WOS:000383795900023
ER
PT J
AU Frey, LJ
Bernstam, EV
Denny, JC
AF Frey, Lewis J.
Bernstam, Elmer V.
Denny, Joshua C.
TI Precision medicine informatics
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Editorial Material
ID ELECTRONIC HEALTH RECORDS; GENOME-WIDE ASSOCIATION; GENOTYPE; DISEASE;
SYSTEMS; IMPLEMENTATION; MELANOMA; THERAPY; NETWORK; SUPPORT
C1 [Frey, Lewis J.] Med Univ South Carolina, Biomed Informat Ctr, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Frey, Lewis J.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC 29401 USA.
[Bernstam, Elmer V.] Univ Texas Hlth Sci Ctr Houston, Sch Biomed Informat, Houston, TX 77030 USA.
[Bernstam, Elmer V.] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Gen Internal Med, Sch Med, Houston, TX 77030 USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Denny, Joshua C.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
RP Frey, LJ (reprint author), Med Univ South Carolina, Biomed Informat Ctr, Dept Publ Hlth Sci, Charleston, SC 29425 USA.; Frey, LJ (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC 29401 USA.
FU National Institutes of Health (NIH) [1R01GM108346-01, U54-GM104941];
Health Equity and Rural Outreach Innovation Center [CIN 13-418];
Hollings Cancer Center at the Medical University of South Carolina [P30
CA138313]; National Cancer Institute (NCI) [U01 CA180964]; Sheikh Bin
Zayed Al Nahyan Foundation; Cancer Prevention Research Institute of
Texas Precision Oncology Decision Support Core [RP150535]; National
Center for Advancing Translational Sciences (NCATS) [UL1 TR000371];
Bosarge Foundation; MD Anderson Cancer Center [NCI P30 CA016672]; NIH
[R01 LM 010685, R01 GM 103859, R01 GM 105688]
FX The work of L.J.F. was supported in part by National Institutes of
Health (NIH) grants 1R01GM108346-01 and U54-GM104941, Health Equity and
Rural Outreach Innovation Center grant CIN 13-418, and funding from the
Hollings Cancer Center's support grant P30 CA138313 at the Medical
University of South Carolina. The work of E.V.B. was supported by
National Cancer Institute (NCI) U01 CA180964, the Sheikh Bin Zayed Al
Nahyan Foundation, the Cancer Prevention Research Institute of Texas
Precision Oncology Decision Support Core RP150535, National Center for
Advancing Translational Sciences (NCATS) grant UL1 TR000371 (Center for
Clinical and Translational Sciences), the Bosarge Foundation, and an MD
Anderson Cancer Center support grant (NCI P30 CA016672). The work of
J.C.D. was supported by R01 LM 010685, R01 GM 103859, and R01 GM 105688
from the NIH.
NR 72
TC 1
Z9 2
U1 5
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1067-5027
EI 1527-974X
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD JUL
PY 2016
VL 23
IS 4
BP 668
EP 670
DI 10.1093/jamia/ocw053
PG 3
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA DW6SS
UT WOS:000383782100002
PM 27274018
ER
PT J
AU Chavez, A
Tuttle, M
Pruitt, BW
Ewen-Campen, B
Chari, R
Ter-Ovanesyan, D
Haque, SJ
Cecchi, RJ
Kowal, EJK
Buchthal, J
Housden, BE
Perrimon, N
Collins, JJ
Church, G
AF Chavez, Alejandro
Tuttle, Marcelle
Pruitt, Benjamin W.
Ewen-Campen, Ben
Chari, Raj
Ter-Ovanesyan, Dmitry
Haque, Sabina J.
Cecchi, Ryan J.
Kowal, Emma J. K.
Buchthal, Joanna
Housden, Benjamin E.
Perrimon, Norbert
Collins, James J.
Church, George
TI Comparison of Cas9 activators in multiple species
SO NATURE METHODS
LA English
DT Article
ID TRANSCRIPTION FACTORS; GENE-EXPRESSION; GENOME; SYSTEM; DNA;
CRISPR-CAS9; COMPLEX; ENDONUCLEASE; TECHNOLOGIES; CRISPR/CAS9
AB Several programmable transcription factors exist based on the versatile Cas9 protein, yet their relative potency and effectiveness across various cell types and species remain unexplored. Here, we compare Cas9 activator systems and examine their ability to induce robust gene expression in several human, mouse, and fly cell lines. We also explore the potential for improved activation through the combination of the most potent activator systems, and we assess the role of cooperativity in maximizing gene expression.
C1 [Chavez, Alejandro; Tuttle, Marcelle; Pruitt, Benjamin W.; Ter-Ovanesyan, Dmitry; Cecchi, Ryan J.; Kowal, Emma J. K.; Buchthal, Joanna; Collins, James J.; Church, George] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
[Chavez, Alejandro] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Chavez, Alejandro; Ewen-Campen, Ben; Chari, Raj; Ter-Ovanesyan, Dmitry; Housden, Benjamin E.; Perrimon, Norbert; Church, George] Harvard Med Sch, Dept Genet, Boston, MA USA.
[Haque, Sabina J.] Middlebury Coll, Dept Mol Biol & Biochem, Middlebury, VT 05753 USA.
[Haque, Sabina J.] Middlebury Coll, Dept Math, Middlebury, VT 05753 USA.
[Perrimon, Norbert] Harvard Med Sch, Howard Hughes Med Inst, Boston, MA USA.
[Collins, James J.] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Collins, James J.] MIT, Synthet Biol Ctr, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Collins, James J.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Collins, James J.] Broad Inst & Harvard, Cambridge, MA USA.
RP Chavez, A; Church, G (reprint author), Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.; Chavez, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Chavez, A; Church, G (reprint author), Harvard Med Sch, Dept Genet, Boston, MA USA.
EM alex.chavez@wyss.harvard.edu; gchurch@genetics.med.harvard.edu
OI Pruitt, Benjamin/0000-0001-7532-7081; Kowal, Emma/0000-0002-8992-7608;
Housden, Benjamin/0000-0001-9134-4279; Ewen-Campen,
Ben/0000-0002-4326-3033
FU US National Institutes of Health (NIH) National Human Genome Research
Institute [P50 HG005550]; Wyss Institute for Biologically Inspired
Engineering; National Cancer Institute [5T32CA009216-34]; Banting
postdoctoral fellowship from the Canadian Institutes of Health Research;
Defense Threat Reduction Agency [HDTRA1-14-1-0006]; NIH under Ruth L.
Kirschstein National Research Service Award from the NIH General Medical
Sciences Division [F32GM113395]
FX We would like to thank S. Vora, A. Tung, M.K. Cromer, and all the
members of the Church and Collins labs for helpful discussions and
technical assistance. G.C. acknowledges support from US National
Institutes of Health (NIH) National Human Genome Research Institute
grant P50 HG005550 and from the Wyss Institute for Biologically Inspired
Engineering. In addition, A.C. was funded by National Cancer Institute
grant 5T32CA009216-34, R.C. was funded by a Banting postdoctoral
fellowship from the Canadian Institutes of Health Research, and J.J.C.
was supported by Defense Threat Reduction Agency grant HDTRA1-14-1-0006.
B.E.-C. acknowledges funding from the NIH under Ruth L. Kirschstein
National Research Service Award F32GM113395 from the NIH General Medical
Sciences Division. We would also like to thank J. Lee (Cold Spring
Harbor, Cold Spring Harbor, NY), P. Mali (UCSD, La Jolla, CA), and S.
Shipman (Harvard Medical School, Boston, MA) for gifting us cell lines.
NR 40
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U1 10
U2 12
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
EI 1548-7105
J9 NAT METHODS
JI Nat. Methods
PD JUL
PY 2016
VL 13
IS 7
BP 563
EP +
DI 10.1038/NMETH.3871
PG 7
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DW6XK
UT WOS:000383794500013
PM 27214048
ER
PT J
AU Essa, MM
Akbar, M
Khan, MAS
AF Essa, Musthafa Mohamed
Akbar, Mohammed
Khan, Mohammed Abdul Sattar
TI Beneficial effects of date palm fruits on neurodegenerative diseases
SO NEURAL REGENERATION RESEARCH
LA English
DT Editorial Material
ID DIETARY SUPPLEMENTATION; ANTIOXIDANT ACTIVITY; ALZHEIMERS-DISEASE;
AMYLOID-BETA
C1 [Essa, Musthafa Mohamed] Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Food Sci & Nutr, Muscat, Oman.
[Essa, Musthafa Mohamed] Sultan Qaboos Univ, Ageing & Dementia Res Grp, Muscat, Oman.
[Akbar, Mohammed] NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA.
[Khan, Mohammed Abdul Sattar] Massachusetts Gen Hosp, Shriners Hosp Children, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Khan, Mohammed Abdul Sattar] Harvard Med Sch, Boston, MA USA.
RP Essa, MM (reprint author), Sultan Qaboos Univ, Coll Agr & Marine Sci, Dept Food Sci & Nutr, Muscat, Oman.; Essa, MM (reprint author), Sultan Qaboos Univ, Ageing & Dementia Res Grp, Muscat, Oman.
EM drmdessa@gmail.com
NR 15
TC 0
Z9 0
U1 2
U2 2
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 1673-5374
EI 1876-7958
J9 NEURAL REGEN RES
JI Neural Regen. Res.
PD JUL
PY 2016
VL 11
IS 7
BP 1071
EP 1072
DI 10.4103/1673-5374.187032
PG 2
WC Cell Biology; Neurosciences
SC Cell Biology; Neurosciences & Neurology
GA DW6YW
UT WOS:000383798300015
PM 27630684
ER
PT J
AU Brugger, SD
Bomar, L
Lemon, KP
AF Brugger, Silvio D.
Bomar, Lindsey
Lemon, Katherine P.
TI Commensal-Pathogen Interactions along the Human Nasal Passages
SO PLOS PATHOGENS
LA English
DT Article
ID BIOSYNTHETIC GENE CLUSTERS; UPPER RESPIRATORY-TRACT; HUMAN SKIN
MICROBIOME; ACUTE OTITIS-MEDIA; STAPHYLOCOCCUS-AUREUS; COMMUNITIES;
DIVERSITY; CHILDREN; DISEASE; COLONIZATION
C1 [Brugger, Silvio D.; Bomar, Lindsey; Lemon, Katherine P.] Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA.
[Brugger, Silvio D.; Bomar, Lindsey] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA.
[Lemon, Katherine P.] Harvard Med Sch, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
RP Lemon, KP (reprint author), Forsyth Inst, Dept Microbiol, Cambridge, MA 02142 USA.; Lemon, KP (reprint author), Harvard Med Sch, Boston Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA.
EM klemon@forsyth.org
FU National Institutes of Health through the National Institute of Allergy
and Infectious Diseases [R01 AI101018]; National Institute of General
Medical Sciences [R01 GM117174]; McIntosh Foundation; Swiss National
Science Foundation; Swiss Foundation for Grants in Biology and Medicine
[P3SMP3_155315]
FX This work was supported by the National Institutes of Health through the
National Institute of Allergy and Infectious Diseases R01 AI101018 (KPL)
and the National Institute of General Medical Sciences R01 GM117174
(KPL), by the McIntosh Foundation (KPL), and by the Swiss National
Science Foundation and Swiss Foundation for Grants in Biology and
Medicine P3SMP3_155315 (SDB). Funders had no role in the preparation of
this manuscript or decision to publish.
NR 48
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U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD JUL
PY 2016
VL 12
IS 7
AR e1005633
DI 10.1371/journal.ppat.1005633
PG 9
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DW0XN
UT WOS:000383366400004
PM 27389401
ER
PT J
AU Williams, JS
Egede, LE
AF Williams, Joni S.
Egede, Leonard E.
TI The Association Between Multimorbidity and Quality of Life, Health
Status and Functional Disability
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Multimorbidity; Quality of life; Health status; Functional disability;
Chronic disease
ID MULTIPLE CHRONIC CONDITIONS; PRIMARY-CARE; COMMUNITY SETTINGS; MANAGING
PATIENTS; PREVALENCE; VALIDITY; RELIABILITY; MANAGEMENT; ADULTS; SCALES
AB Introduction: Approximately 50% of adults have multimorbidity (MM) that is associated with greater disability, poorer quality of life (QOL) and increased psychological distress. This study assessed the association between MM and QOL, health status and functional disability in U.S. adults.
Methods: Cross-sectional study of 23,789 patients from 2011 Medical Expenditure Panel Survey was conducted. Mean scores were calculated for QOL (physical component score [PCS] and mental component score [MCS]) and proportions for functional limitation (activities of daily living [ADL]; instrumental ADL [IADL] and physical functioning). Health status was assessed by depression and serious psychological distress. Regression models evaluated associations between MM and QOL, functional health status and functional limitations, while adjusting for confounders.
Results: Approximately 53% of 45-64-year-olds and 84% of those =65-years-old had MM. In adjusted models, =3 conditions were significantly associated with poorer outcomes-PCS QOL (b = -9.15; 95% CI: -9.69 to -8.61), MCS QOL ( = -1.98; 95% CI: -2.43 to -1.52), ADL (odds ratio [OR] = 5.80; 95% CI: 2.27-14.8), IADL (OR = 3.99; 95% CI: 2.31-6.88) and physical functioning (OR = 16.8; 95% CI: 12.0-23.6) compared with 1-2 conditions. Depression (PCS QOL: b = -4.02; 95% CI: -4.89 to -3.15; MCS QOL: b = -12.5; 95% CI: -13.2 to -10.9; ADL: OR = 2.49; 95% CI: 1.65-3.76; IADL: OR = 2.65; 95% CI: 1.88-3.72; physical functioning: OR = 2.44; 95% CI: 1.99-2.99) and serious psychological distress (PCS QOL: b = -3.16; 95% CI: -4.30 to -2.03; MCS QOL: b = -11.8; 95% CI: -12.8 to -10.8; ADL: OR = 1.57; 95% CI: 0.95-2.60; IADL: OR = 1.13; 95% CI: 0.80-1.59 and physical functioning: OR = 1.41; 95% CI: 1.11-1.78) were significantly associated with adverse outcomes.
Conclusions: In this nationally representative sample of U.S. adults, MM was significantly associated with poorer QOL, functional health status and physical functioning, when adjusting for relevant confounders. A holistic view of the complexities associated with MM must dictate comprehensive care.
C1 [Williams, Joni S.; Egede, Leonard E.] Med Univ South Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC USA.
[Williams, Joni S.; Egede, Leonard E.] Med Univ South Carolina, Div Gen Internal Med & Geriatr, Dept Med, Charleston, SC USA.
[Egede, Leonard E.] Ralph H Johnson Dept Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA.
RP Egede, LE (reprint author), Med Univ South Carolina, Hlth Equ & Rural Outreach Innovat Ctr, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA.
EM egedel@musc.edu
FU National Institute of Diabetes and Digestive and Kidney Disease
[K24DK093699]
FX This study was supported by Grant no. K24DK093699 from The National
Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard
Egede).
NR 22
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U1 7
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9629
EI 1538-2990
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD JUL
PY 2016
VL 352
IS 1
BP 45
EP 52
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DV1GB
UT WOS:000382667400006
PM 27432034
ER
PT J
AU Gabrielsen, JS
Tanrikut, C
AF Gabrielsen, J. S.
Tanrikut, C.
TI Chronic exposures and male fertility: the impacts of environment, diet,
and drug use on spermatogenesis
SO ANDROLOGY
LA English
DT Review
DE chronic exposures; diet; drug use; male infertility; pollution;
spermatogenesis
ID DISINFECTION BY-PRODUCTS; REPRODUCTIVE ENDOCRINE FUNCTION; PLASMA
ANTIOXIDANT CAPACITY; ETHYLENE-GLYCOL ETHERS; HUMAN SPERM MOTILITY; MALE
GERM-CELLS; ADULT MALE-RATS; SEMEN QUALITY; SEMINAL PLASMA; INFERTILE
MEN
AB Several recent studies have suggested that sperm concentrations and semen quality have been decreasing over the past several decades in many areas of the world. The etiology of these decreases is currently unknown. Acute events can have significant impacts on spermatogenesis and are often readily identified during the male fertility evaluation. The majority of male factor infertility, however, is idiopathic. Chronic, low-dose exposures to chemicals and nutrients are more difficult to identify, but are extremely prevalent. These exposures have been shown to have dramatic effects on both individual and community health and interest in the cumulative and synergistic impacts of such agents on spermatogenesis has been increasing. While our understanding of these potential hazards is evolving, it is clear that they may significantly influence male reproductive potential. This review explores the literature related to effects of chronic exposures from drug use, dietary intake, and the environment on spermatogenesis in humans and animals.
C1 [Gabrielsen, J. S.; Tanrikut, C.] Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,YAW-10A, Boston, MA 02114 USA.
RP Tanrikut, C (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,YAW-10A, Boston, MA 02114 USA.
EM ctanrikut@partners.org
NR 208
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U1 10
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-2919
EI 2047-2927
J9 ANDROLOGY-US
JI Andrology
PD JUL
PY 2016
VL 4
IS 4
SI SI
BP 648
EP 661
DI 10.1111/andr.12198
PG 14
WC Andrology
SC Endocrinology & Metabolism
GA DV9VT
UT WOS:000383291000013
PM 27230702
ER
PT J
AU Kannan, L
Ramos, M
Re, A
El-Hachem, N
Safikhani, Z
Gendoo, DMA
Davis, S
Gomez-Cabrero, D
Castelo, R
Hansen, KD
Carey, VJ
Morgan, M
Culhane, AC
Haibe-Kains, B
Waldron, L
AF Kannan, Lavanya
Ramos, Marcel
Re, Angela
El-Hachem, Nehme
Safikhani, Zhaleh
Gendoo, Deena M. A.
Davis, Sean
Gomez-Cabrero, David
Castelo, Robert
Hansen, Kasper D.
Carey, Vincent J.
Morgan, Martin
Culhane, Aedin C.
Haibe-Kains, Benjamin
Waldron, Levi
TI Public data and open source tools for multi-assay genomic investigation
of disease
SO BRIEFINGS IN BIOINFORMATICS
LA English
DT Article
DE multiple assays (multi-assays); public data; bioconductor; integrative
genomics; cancer; pharmacogenomics; omics
ID BRITISH BIRTH COHORT; CANONICAL CORRELATION-ANALYSIS; GENE-EXPRESSION
SIGNATURES; CANCER-CELL LINES; DRUG-SENSITIVITY; WIDE ASSOCIATION; SMALL
MOLECULES; COPY NUMBER; TUMOR TYPES; DATA SETS
AB Molecular interrogation of a biological sample through DNA sequencing, RNA and microRNA profiling, proteomics and other assays, has the potential to provide a systems level approach to predicting treatment response and disease progression, and to developing precision therapies. Large publicly funded projects have generated extensive and freely available multi-assay data resources; however, bioinformatic and statistical methods for the analysis of such experiments are still nascent. We review multi-assay genomic data resources in the areas of clinical oncology, pharmacogenomics and other perturbation experiments, population genomics and regulatory genomics and other areas, and tools for data acquisition. Finally, we review bioinformatic tools that are explicitly geared toward integrative genomic data visualization and analysis. This review provides starting points for accessing publicly available data and tools to support development of needed integrative methods.
C1 [Kannan, Lavanya; Ramos, Marcel] CUNY Hunter Coll, Sch Publ Hlth, New York, NY 10021 USA.
[Re, Angela] Univ Trento, Ctr Integrat Biol, Trento, Italy.
[El-Hachem, Nehme] Univ Montreal, Montreal, PQ H3C 3J7, Canada.
[Safikhani, Zhaleh; Gendoo, Deena M. A.; Haibe-Kains, Benjamin] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Davis, Sean] NCI, NIH, Bethesda, MD 20892 USA.
[Gomez-Cabrero, David] Karolinska Inst, Unit Computat Med, S-10401 Stockholm, Sweden.
[Castelo, Robert] Univ Pompeu Fabra, Bioinformat & Biostat, Barcelona, Spain.
[Hansen, Kasper D.] Johns Hopkins Univ, Biostat, Baltimore, MD 21218 USA.
[Carey, Vincent J.] Harvard Med Sch, Med Biostat, Boston, MA USA.
[Morgan, Martin] Roswell Pk Canc Inst, Biostat & Bioinformat, Buffalo, NY 14263 USA.
[Culhane, Aedin C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Waldron, Levi] CUNY Hunter Coll, Sch Publ Hlth, Biostat, New York, NY 10021 USA.
RP Waldron, L (reprint author), 2180 3rd Ave, New York, NY 10040 USA.
EM levi.waldron@hunter.cuny.edu
RI Castelo, Robert/A-4679-2010; Gasull, Martina/A-6630-2013;
OI Castelo, Robert/0000-0003-2229-4508; Haibe-Kains,
Benjamin/0000-0002-7684-0079; Waldron, Levi/0000-0003-2725-0694
FU National Cancer Institute [U24CA180996, 1U19 AI111224-01]; National
Institute on Minority Health and Health Disparities [MD007599]; NCI
Intramural Research Program of the National Institutes of Health;
Spanish MINECO [TIN2011-22826]; Gattuso Slaight Personalized Cancer
Medicine Fund at Princess Margaret Cancer Centre; Cancer Research
Society (Canada); Brain Canada-CIBC Brain Cancer Research Training
Award; University of Trento; Breast Cancer Research Program
[W81XWH-15-1-0013]
FX The authors' work was funded by the National Cancer Institute
[U24CA180996 to MM], the National Institute on Minority Health and
Health Disparities [MD007599 to LW] and the NCI Intramural Research
Program [SD] of the National Institutes of Health. Spanish MINECO grant
TIN2011-22826 to RC. BHK was supported by the Gattuso Slaight
Personalized Cancer Medicine Fund at Princess Margaret Cancer Centre. ZS
was supported by the Cancer Research Society (Canada). DMAG was
supported by the Brain Canada-CIBC Brain Cancer Research Training Award
AR was supported by the Biotechnology start-up project of the University
of Trento. AC was supported by National Cancer Institute 1U19
AI111224-01 and the Assistant Secretary of Defense Health Program,
through the Breast Cancer Research Program, Award No. W81XWH-15-1-0013.
NR 96
TC 2
Z9 2
U1 8
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1467-5463
EI 1477-4054
J9 BRIEF BIOINFORM
JI Brief. Bioinform.
PD JUL
PY 2016
VL 17
IS 4
SI SI
BP 603
EP 615
DI 10.1093/bib/bbv080
PG 13
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DV7XI
UT WOS:000383151200005
PM 26463000
ER
PT J
AU Meng, C
Zeleznik, OA
Thallinger, GG
Kuster, B
Gholami, AM
Culhane, AC
AF Meng, Chen
Zeleznik, Oana A.
Thallinger, Gerhard G.
Kuster, Bernhard
Gholami, Amin M.
Culhane, Aedin C.
TI Dimension reduction techniques for the integrative analysis of
multi-omics data
SO BRIEFINGS IN BIOINFORMATICS
LA English
DT Article
DE multivariate analysis; multi-omics data integration; dimension
reduction; integrative genomics; exploratory data analysis; multi-assay
ID CANONICAL CORRELATION-ANALYSIS; PRINCIPAL COMPONENT ANALYSIS; CO-INERTIA
ANALYSIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION DATA;
NONNEGATIVE MATRIX FACTORIZATION; GENOMIC DATA; CROSS-PLATFORM;
ONCOGENIC ROLE; R PACKAGE
AB State-of-the-art next-generation sequencing, transcriptomics, proteomics and other high-throughput 'omics' technologies enable the efficient generation of large experimental data sets. These data may yield unprecedented knowledge about molecular pathways in cells and their role in disease. Dimension reduction approaches have been widely used in exploratory analysis of single omics data sets. This review will focus on dimension reduction approaches for simultaneous exploratory analyses of multiple data sets. These methods extract the linear relationships that best explain the correlated structure across data sets, the variability both within and between variables (or observations) and may highlight data issues such as batch effects or outliers. We explore dimension reduction techniques as one of the emerging approaches for data integration, and how these can be applied to increase our understanding of biological systems in normal physiological function and disease.
C1 [Meng, Chen] Tech Univ Munich, Bernhard Kusters Grp, Applicat Multivariate Methods Integrat Anal Omics, D-80290 Munich, Germany.
[Zeleznik, Oana A.] Graz Univ Technol, Gerhard Thallingers Grp, Enhancement Existing Methods & Dev Novel Gene Set, A-8010 Graz, Austria.
[Thallinger, Gerhard G.] Graz Univ Technol, A-8010 Graz, Austria.
[Kuster, Bernhard] Tech Univ Munich, Prote & Bioanalyt, D-80290 Munich, Germany.
[Kuster, Bernhard] Bavarian Biomol Mass Spectrometry Ctr, Freising Weihenstephan, Germany.
[Gholami, Amin M.] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA USA.
[Culhane, Aedin C.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA.
[Culhane, Aedin C.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
RP Culhane, AC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM aedin@jimmy.harvard.edu
RI Kuster, Bernhard/Q-6031-2016;
OI Kuster, Bernhard/0000-0002-9094-1677; Thallinger, Gerhard
G./0000-0002-2864-5404
FU Austrian Ministry of Science, Research and Economics [OMICS Center HSRSM
initiative]; Dana-Farber Cancer Institute BCB Research Scientist
Developmental Funds; National Cancer Institute [2P50 CA101942-11];
Breast Cancer Research Program [W81XWH-15-1-0013]
FX GGT was supported by the Austrian Ministry of Science, Research and
Economics [OMICS Center HSRSM initiative]. AC was supported by
Dana-Farber Cancer Institute BCB Research Scientist Developmental Funds,
National Cancer Institute 2P50 CA101942-11 and the Assistant Secretary
of Defense Health Program, through the Breast Cancer Research Program
under Award No. W81XWH-15-1-0013. Opinions, interpretations, conclusions
and recommendations are those of the author and are not necessarily
endorsed by the Department of Defense.
NR 94
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U1 8
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1467-5463
EI 1477-4054
J9 BRIEF BIOINFORM
JI Brief. Bioinform.
PD JUL
PY 2016
VL 17
IS 4
SI SI
BP 628
EP 641
DI 10.1093/bib/bbv108
PG 14
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DV7XI
UT WOS:000383151200007
PM 26969681
ER
PT J
AU Alexander, EK
Faquin, WC
Krane, JF
AF Alexander, Erik K.
Faquin, William C.
Krane, Jeffrey F.
TI Highlights for the Cytology Community From the 2015 American Thyroid
Association Clinical Guidelines on the Management of Thyroid Nodules and
Well-Differentiated Thyroid Cancer
SO CANCER CYTOPATHOLOGY
LA English
DT Article
ID GENERATION SEQUENCING ASSAY; BETHESDA SYSTEM; DIAGNOSIS; IMPACT;
CYTOPATHOLOGY
C1 [Alexander, Erik K.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Thyroid Sect, Boston, MA USA.
[Faquin, William C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA.
[Krane, Jeffrey F.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
RP Krane, JF (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
EM jkrane@partners.org
FU Asuragen Inc; Veracyte Inc.; Asuragen; Veracyte
FX Erik K. Alexander has acted as a paid member of the Scientific Advisory
Board for Asuragen Inc and as a paid consultant for Veracyte Inc. In
addition, his institution has received research support from both
Asuragen and Veracyte.
NR 16
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
EI 1934-6638
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD JUL
PY 2016
VL 124
IS 7
BP 453
EP 456
DI 10.1002/cncy.21662
PG 4
WC Oncology; Pathology
SC Oncology; Pathology
GA DV3YM
UT WOS:000382861800003
PM 26618757
ER
PT J
AU Nishino, M
Hoang, MP
Della Pelle, P
Morales-Oyarvide, V
Huynh, TG
Mark, EJ
Mino-Kenudson, M
AF Nishino, Michiya
Hoang, Mai P.
Della Pelle, Patricia
Morales-Oyarvide, Vicente
Huynh, Tiffany G.
Mark, Eugene J.
Mino-Kenudson, Mari
TI Napsin A/p40 Antibody Cocktail for Subtyping Non-Small Cell Lung
Carcinoma on Cytology and Small Biopsy Specimens
SO CANCER CYTOPATHOLOGY
LA English
DT Article
DE adenocarcinoma; cytology; napsin A; non-small cell lung cancer; p40
(Delta Np63); small biopsy; squamous cell carcinoma
ID TRANSCRIPTION FACTOR-I; ASPARTIC PROTEINASE; DELTA-NP63 P40; USEFUL
MARKER; DOUBLE STAIN; ADENOCARCINOMA; CANCER; P63; DIAGNOSIS;
CLASSIFICATION
AB BACKGROUND: Subtyping non-small cell lung carcinomas (NSCLC) into adenocarcinoma (ACA) or squamous cell carcinoma (SQCC) is important for treatment and specimen triage for molecular studies. To preserve tissue for molecular studies in cytology/small biopsy specimens, a 2-antibody cocktail for NSCLC subtyping was developed. METHODS: Markers for lung ACA (thyroid transcription factor 1 and napsin A) and SQCC (cytokeratin 5/6 and p40) were evaluated on tissue microarrays (TMAs) with 143 ACA and 98 SQCC specimens. The napsin A/p40 combination was selected for NSCLC subtyping and validated on the TMA as well as on a cohort of cell block/small biopsy specimens from 80 poorly differentiated NSCLCs. RESULTS: Using TMA analysis, the napsin A-positive (1)/p40 +/- immunophenotype identified ACA with 94% sensitivity and 100% specificity, whereas the napsin A (negative)-/p40+ immunophenotype identified SQCC with 100% sensitivity and specificity. On the validation cohort of 80 cell block and small biopsy specimens, the napsin A/p40 cocktail accurately subtyped 63 of 70 NSCLC (90%) as ACA or SQCC using the subsequent surgical resection as reference histology. Of the remaining 17 cases, 15 were classified as NSCLC-not otherwise specified based on a napsin A-/p40- immunophenotype; their corresponding resections were diagnosed as ACA (7 cases), large cell carcinoma (7 cases), or pleomorphic carcinoma (1 case). Two additional large cell carcinoma cases showed a napsin A-/p40+ or napsin A+/p40+ profile in the preoperative cell block/small biopsy sample. CONCLUSIONS: A napsin A/p40 cocktail can accurately subtype NSCLC into ACA and SQCC in most cell block/small biopsy specimens of poorly differentiated NSCLC. In the minority of cases in which the napsin A/p40 immunophenotype is indeterminate, additional stains may be necessary for precise classification. (C) 2016 American Cancer Society.
C1 [Nishino, Michiya] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
[Hoang, Mai P.; Della Pelle, Patricia; Morales-Oyarvide, Vicente; Huynh, Tiffany G.; Mark, Eugene J.; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
RP Mino-Kenudson, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM mminokenudson@partners.org
NR 36
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
EI 1934-6638
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD JUL
PY 2016
VL 124
IS 7
BP 472
EP 484
DI 10.1002/cncy.21707
PG 13
WC Oncology; Pathology
SC Oncology; Pathology
GA DV3YM
UT WOS:000382861800006
PM 27412420
ER
PT J
AU Balassanian, R
Wool, GD
Ono, JC
Olejnik-Nave, J
Mah, MM
Sweeney, BJ
Liberman, H
Ljung, BM
Pitman, MB
AF Balassanian, Ronald
Wool, Geoffrey D.
Ono, Jill C.
Olejnik-Nave, Jolanta
Mah, Molinda M.
Sweeney, Brenda J.
Liberman, Hava
Ljung, Britt-Marie
Pitman, Martha B.
TI A Superior Method for Cell Block Preparation for Fine-Needle Aspiration
Biopsies
SO CANCER CYTOPATHOLOGY
LA English
DT Article; Proceedings Paper
CT Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology
CY MAY 01-12, 2014
CL San Diego, CA
SP US & Canadian Acad Pathol
DE cell block; collodion bag; fine-needle aspiration (FNA) biopsy;
HistoGel; saline plasma thrombin
AB BACKGROUND: Cell block (CB) techniques for fine-needle aspiration biopsies (FNABs) vary. A direct comparison of CB techniques with statistical validation was performed to identify the best method. METHODS: Three CB techniques were compared: 1) FNAB rinsed in saline and clotted with plasma and thrombin (SPT); 2) FNAB rinsed in formalin and clotted with HistoGel (HG); and 3) FNAB rinsed in formalin, centrifuged, and the pellet captured in a collodion bag (ColB). FNAB was performed on 35 random surgical specimens for smears and each CB technique. A randomized blinded review of hematoxylin and eosin-stained CB slides was performed and each case was scored on a scale of 1 to 3 for cellularity, preservation, and architecture and the overall best CB was identified. Significance was determined by the Mann-Whitney U test for nonparametric ordinal data. RESULTS: The mean cellularity score was 1.71 for SPT (standard deviation [SD], 0.89), 1.68 for HG (SD, 0.67), and 3.0 for ColB (SD, 0). The mean preservation score was 1.31 for SPT (SD, 0.58), 1.54 for HG (SD, 0.70), and 2.91 for ColB (SD, 0.37). The mean architecture score was 1.45 for SPT (SD, 0.70), 1.43 for HG (SD, 0.60), and 2.71 for ColB (SD, 0.57). There was no statistical significance noted between SPT or HG when compared for each category. ColB was found to be superior to both SPT and HG when compared for each category (P<.05). The overall best CB was obtained with ColB in 33 of 35 cases (94%), with SPT proving superior in 1 of 35 cases (3%) and HG superior in 1 of 35 cases (3%). CONCLUSIONS: ColB appears to be a superior technique for CB, yielding greater cellularity, preservation, and architecture in the majority of cases. (C) 2016 American Cancer Society.
C1 [Balassanian, Ronald; Mah, Molinda M.; Liberman, Hava; Ljung, Britt-Marie] Univ Calif San Francisco, Dept Pathol, 1825 4th St, San Francisco, CA 94143 USA.
[Wool, Geoffrey D.] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Ono, Jill C.] Lab Med Consultants, Las Vegas, NV USA.
[Olejnik-Nave, Jolanta; Sweeney, Brenda J.; Pitman, Martha B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA.
RP Balassanian, R (reprint author), Univ Calif San Francisco, Dept Pathol, 1825 4th St, San Francisco, CA 94143 USA.
EM ronald.balassanian@ucsf.edu
NR 14
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1934-662X
EI 1934-6638
J9 CANCER CYTOPATHOL
JI Cancer Cytopathol.
PD JUL
PY 2016
VL 124
IS 7
BP 508
EP 518
DI 10.1002/cncy.21722
PG 11
WC Oncology; Pathology
SC Oncology; Pathology
GA DV3YM
UT WOS:000382861800010
PM 27105161
ER
PT J
AU Hove, MJ
Stelzer, J
Nierhaus, T
Thiel, SD
Gundlach, C
Margulies, DS
Van Dijk, KRA
Turner, R
Keller, PE
Merker, B
AF Hove, Michael J.
Stelzer, Johannes
Nierhaus, Till
Thiel, Sabrina D.
Gundlach, Christopher
Margulies, Daniel S.
Van Dijk, Koene R. A.
Turner, Robert
Keller, Peter E.
Merker, Bjorn
TI Brain Network Reconfiguration and Perceptual Decoupling During an
Absorptive State of Consciousness
SO CEREBRAL CORTEX
LA English
DT Article
DE brain networks; eigenvector centrality; functional connectivity; shaman;
trance
ID INTRINSIC FUNCTIONAL CONNECTIVITY; DEFAULT NETWORK; VISUAL-CORTEX;
SYSTEM; MIND; ORGANIZATION; FMRI; MRI; FLUCTUATIONS; ARCHITECTURE
AB Trance is an absorptive state of consciousness characterized by narrowed awareness of external surroundings and has long been used-for example, by shamans-to gain insight. Shamans across cultures often induce trance by listening to rhythmic drumming. Using functional magnetic resonance imaging (fMRI), we examined the brain-network configuration associated with trance. Experienced shamanic practitioners (n = 15) listened to rhythmic drumming, and either entered a trance state or remained in a nontrance state during 8-min scans. We analyzed changes in network connectivity. Trance was associated with higher eigenvector centrality (i.e., stronger hubs) in 3 regions: posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (dACC), and left insula/operculum. Seed-based analysis revealed increased coactivation of the PCC (a default network hub involved in internally oriented cognitive states) with the dACC and insula (control-network regions involved in maintaining relevant neural streams). This coactivation suggests that an internally oriented neural stream was amplified by the modulatory control network. Additionally, during trance, seeds within the auditory pathway were less connected, possibly indicating perceptual decoupling and suppression of the repetitive auditory stimuli. In sum, trance involved coactive default and control networks, and decoupled sensory processing. This network reconfiguration may promote an extended internal train of thought wherein integration and insight can occur.
C1 [Hove, Michael J.; Stelzer, Johannes; Nierhaus, Till; Thiel, Sabrina D.; Gundlach, Christopher; Margulies, Daniel S.; Turner, Robert; Keller, Peter E.] Max Planck Inst Human Cognit & Brain Sci, Leipzig, Germany.
[Hove, Michael J.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Stelzer, Johannes] Max Planck Inst Biol Cybernet, Tubingen, Germany.
[Nierhaus, Till] Free Univ Berlin, Neurocomputat & Neuroimaging Unit, Berlin, Germany.
[Van Dijk, Koene R. A.] Harvard Univ, Cambridge, MA 02138 USA.
[Keller, Peter E.] Univ Western Sydney, MARCS Inst, Penrith, NSW 1797, Australia.
RP Hove, MJ (reprint author), Harvard Med Sch, Dept Psychiat, Room 2660,149 13th St, Charlestown, MA 02129 USA.
EM michaeljhove@gmail.com
RI Van Dijk, Koene/G-3317-2012; Margulies, Daniel/L-4719-2016;
OI Van Dijk, Koene/0000-0001-6137-4282; Margulies,
Daniel/0000-0002-8880-9204; Keller, Peter/0000-0001-7579-6515
FU Varela Award from the Mind and Life Institute; National Institute of
Mental Health Grant [T32-MH16259]; Max Planck Society
FX This work was supported partially by a Varela Award from the Mind and
Life Institute and a National Institute of Mental Health Grant (grant
number T32-MH16259) to M.J.H. and by the Max Planck Society.
NR 69
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U1 5
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1047-3211
EI 1460-2199
J9 CEREB CORTEX
JI Cereb. Cortex
PD JUL
PY 2016
VL 26
IS 7
BP 3116
EP 3124
DI 10.1093/cercor/bhv137
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DV8QC
UT WOS:000383200500014
PM 26108612
ER
PT J
AU Javorsky, E
Perkins, A
Scharf, MJ
AF Javorsky, Emilia
Perkins, Alexis
Scharf, Mark J.
TI Resolution of Disseminated Granuloma Annulare With Removal of Surgical
Hardware
SO CUTIS
LA English
DT Editorial Material
C1 [Javorsky, Emilia; Perkins, Alexis; Scharf, Mark J.] Univ Massachusetts, Med Ctr, Dept Dermatol, Worcester, MA USA.
[Javorsky, Emilia] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
RP Scharf, MJ (reprint author), UMMHC, Dept Dermatol, Hahnemann Campus,281 Lincoln St, Worcester, MA 01605 USA.
EM Mark.Scharf@umassmemorial.org
NR 5
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Z9 0
U1 0
U2 0
PU QUADRANT HEALTHCOM INC
PI PARSIPPANY
PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA
SN 0011-4162
EI 2326-6929
J9 CUTIS
JI Cutis
PD JUL
PY 2016
VL 98
IS 1
BP E10
EP E11
PG 2
WC Dermatology
SC Dermatology
GA DV8RD
UT WOS:000383203300005
PM 27529714
ER
PT J
AU Furtek, KJ
Kubiak, DW
Barra, M
Varughese, CA
Ashbaugh, CD
Koo, S
AF Furtek, Kari J.
Kubiak, David W.
Barra, Megan
Varughese, Christy A.
Ashbaugh, Cameron D.
Koo, Sophia
TI High incidence of neutropenia in patients with prolonged ceftaroline
exposure
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; ENDOCARDITIS; AGRANULOCYTOSIS;
INFECTIONS; THERAPY
AB Objectives: We sought to determine the rate of incident neutropenia and identify potential clinical factors associated with incident neutropenia among patients treated with long courses of ceftaroline.
Methods: We retrospectively identified adult patients who received ceftaroline for >= 7 days consecutively at two large academic medical centres in Boston, USA between November 2010 and March 2015. Clinical characteristics (age, gender, medication allergies, baseline renal function, duration of ceftaroline exposure, total daily ceftaroline dose, body mass-adjusted ceftaroline dose and development of rash and neutropenia) were recorded and the rate of incident neutropenia was calculated. The Naranjo probability scale was used to assess whether ceftaroline exposure was associated with neutropenia. We assessed whether clinical factors were associated with neutropenia.
Results: The overall rate of incident neutropenia was 10%-14% with >= 2 weeks and 21% with >= 3 weeks of ceftaroline exposure. The median duration of ceftaroline exposure [26 days (IQR 22-44; range 13-68) in patients who developed neutropenia and 15 days (IQR 9-29; range 7-64) in patients without neutropenia] was associated with incident neutropenia (P = 0.048). The median total number of ceftaroline doses received [63 (IQR 44-126; range 36-198) by neutropenic patients and 32 (IQR 22-63; range 14-180) by non-neutropenic patients] was also associated with incident neutropenia (P = 0.023).
Conclusions: The overall rate of neutropenia was high and associated with duration of ceftaroline exposure and total number of doses received. Close laboratory monitoring is warranted with long-term ceftaroline use.
C1 [Furtek, Kari J.] Northeastern Univ, Sch Pharm, Boston, MA 02115 USA.
[Furtek, Kari J.; Kubiak, David W.; Barra, Megan] Brigham & Womens Hosp, Dept Pharm, 75 Francis St, Boston, MA 02115 USA.
[Varughese, Christy A.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA.
[Ashbaugh, Cameron D.; Koo, Sophia] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
[Ashbaugh, Cameron D.; Koo, Sophia] Harvard Med Sch, Boston, MA USA.
RP Furtek, KJ (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
EM kfurtek@gmail.com
FU Brigham and Women's Physicians Organization; National Institutes of
Health [K23 AI097225]
FX This project was funded, in part, by a grant from the Brigham and
Women's Physicians Organization. S. K. is supported by a grant from the
National Institutes of Health (K23 AI097225).
NR 12
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U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-7453
EI 1460-2091
J9 J ANTIMICROB CHEMOTH
JI J. Antimicrob. Chemother.
PD JUL
PY 2016
VL 71
IS 7
BP 2010
EP 2013
DI 10.1093/jac/dkw062
PG 4
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA DV9FP
UT WOS:000383246000034
PM 27076105
ER
PT J
AU Rajagopal, M
Martin, MJ
Santiago, M
Lee, W
Kos, VN
Meredith, T
Gilmore, MS
Walker, S
AF Rajagopal, Mithila
Martin, Melissa J.
Santiago, Marina
Lee, Wonsik
Kos, Veronica N.
Meredith, Tim
Gilmore, Michael S.
Walker, Suzanne
TI Multidrug Intrinsic Resistance Factors in Staphylococcus aureus
Identified by Profiling Fitness within High-Diversity Transposon
Libraries
SO MBIO
LA English
DT Article
ID SMALL COLONY VARIANTS; PENICILLIN-BINDING PROTEIN; BETA-LACTAM
RESISTANCE; CELL-WALL BIOSYNTHESIS; METHICILLIN RESISTANCE;
TEICHOIC-ACIDS; FLUOROQUINOLONE RESISTANCE; PEPTIDOGLYCAN HYDROLASE;
ANTIMICROBIAL PEPTIDES; ANTIBIOTIC-RESISTANCE
AB Staphylococcus aureus is a leading cause of life-threatening infections worldwide. The MIC of an antibiotic against S. aureus, as well as other microbes, is determined by the affinity of the antibiotic for its target in addition to a complex interplay of many other cellular factors. Identifying nontarget factors impacting resistance to multiple antibiotics could inform the design of new compounds and lead to more-effective antimicrobial strategies. We examined large collections of transposon insertion mutants in S. aureus using transposon sequencing (Tn-Seq) to detect transposon mutants with reduced fitness in the presence of six clinically important antibiotics-ciprofloxacin, daptomycin, gentamicin, linezolid, oxacillin, and vancomycin. This approach allowed us to assess the relative fitness of many mutants simultaneously within these libraries. We identified pathways/genes previously known to be involved in resistance to individual antibiotics, including graRS and vraFG (graRS/vraFG), mprF, and fmtA, validating the approach, and found several to be important across multiple classes of antibiotics. We also identified two new, previously uncharacterized genes, SAOUHSC_01025 and SAOUHSC_01050, encoding polytopic membrane proteins, as important in limiting the effectiveness of multiple antibiotics. Machine learning identified similarities in the fitness profiles of graXRS/vraFG, SAOUHSC_01025, and SAOUHSC_01050 mutants upon antibiotic treatment, connecting these genes of unknown function to modulation of crucial cell envelope properties. Therapeutic strategies that combine a known antibiotic with a compound that targets these or other intrinsic resistance factors may be of value for enhancing the activity of existing antibiotics for treating otherwise-resistant S. aureus strains.
IMPORTANCE Bacterial resistance to every major class of antibiotics has emerged, and we are entering a "post-antibiotic era" where relatively minor infections can lead to serious complications or even death. The utility of an antibiotic for a specific pathogen is limited by both intrinsic and acquired factors. Identifying the repertoire of intrinsic resistance factors of an antibiotic for Staphylococcus aureus, a leading cause of community-and hospital-acquired infections, would inform the design of new drugs as well as the identification of compounds that enhance the activity of existing drugs. To identify factors that limit the activity of antibiotics against S. aureus, we used Tn-Seq to simultaneously assess fitness of transposon mutants in every nonessential gene in the presence of six clinically important antibiotics. This work provides an efficient approach for identifying promising targets for drugs that can enhance susceptibility or restore sensitivity to existing antibiotics.
C1 [Rajagopal, Mithila; Santiago, Marina; Lee, Wonsik; Meredith, Tim; Gilmore, Michael S.; Walker, Suzanne] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
[Rajagopal, Mithila] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Martin, Melissa J.; Kos, Veronica N.; Gilmore, Michael S.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
[Meredith, Tim] Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA.
RP Gilmore, MS; Walker, S (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.; Gilmore, MS (reprint author), Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA.
EM Michael_Gilmore@meei.harvard.edu; Suzanne_Walker@hms.harvard.edu
FU Institut Merieux; HHS \ National Institutes of Health (NIH) [P01
AI083214, U19 AI109764]
FX This work, including the efforts of Melissa J. Martin, Veronica Kos, and
Michael S. Gilmore, was funded by Institut Merieux. This work, including
the efforts of Mithila Rajagopal, Melissa J. Martin, Marina Santiago,
Wonsik Lee, Veronica Kos, Timothy C. Meredith, Michael S. Gilmore, and
Suzanne Walker, was funded by HHS vertical bar National Institutes of
Health (NIH) (P01 AI083214). This work, including the efforts of Mithila
Rajagopal, Marina Santiago, Wonsik Lee, Timothy C. Meredith, and Suzanne
Walker, was funded by HHS vertical bar National Institutes of Health
(NIH) (U19 AI109764).
NR 83
TC 0
Z9 0
U1 6
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2016
VL 7
IS 4
AR e00950-16
DI 10.1128/mBio.00950-16
PG 11
WC Microbiology
SC Microbiology
GA DW1YQ
UT WOS:000383440500039
ER
PT J
AU Selleck, EM
Gilmore, MS
AF Selleck, Elizabeth M.
Gilmore, Michael S.
TI Oxygen as a Virulence Determinant in Polymicrobial Infections
SO MBIO
LA English
DT Editorial Material
ID BACTERIAL; SALMONELLA; HOST
AB Infections caused by multiple organisms, or polymicrobial infections, are likely more common than is broadly appreciated. Interaction among microbial communities (and with their host) can change the infection landscape by subverting immunity, providing nutrients and inhibiting competing microbes. Stacy et al. (A. Stacy, D. Fleming, R. J. Lamont, K. P. Rumbaugh, and M. Whiteley, mBio 7: e00782-16, 2016, http://dx.doi.org/10.1128/mBio.00782-16) described a novel mechanism that results in synergistic growth of oral microbes Aggregatibacter actinomycetemcomitans and Streptococcus gordonii. The authors used whole-genome fitness profiling by transposon sequencing (Tn-seq) to identify genes differentially required for growth in vitro versus in a mono-or coinfection in a thigh abscess model. They found that coinfection with S. gordonii allowed A. actinomycetemcomitans to shift from an anaerobic to an aerobic mode of growth. This shift involved the production of a terminal electron acceptor H2O2 by S. gordonii and increased A. actinomycetemcomitans persistence-an interaction termed "crossrespiration."
C1 [Selleck, Elizabeth M.; Gilmore, Michael S.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
[Selleck, Elizabeth M.; Gilmore, Michael S.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
RP Gilmore, MS (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA.
EM Michael_Gilmore@meei.harvard.edu
NR 15
TC 0
Z9 0
U1 1
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2016
VL 7
IS 4
AR e01249
DI 10.1128/mBio.01249-16
PG 3
WC Microbiology
SC Microbiology
GA DW1YQ
UT WOS:000383440500076
ER
PT J
AU Sheehan, KB
Martin, M
Lesser, CF
Isberg, RR
Newton, ILG
AF Sheehan, Kathy B.
Martin, MaryAnn
Lesser, Cammie F.
Isberg, Ralph R.
Newton, Irene L. G.
TI Identification and Characterization of a Candidate Wolbachia pipientis
Type IV Effector That Interacts with the Actin Cytoskeleton
SO MBIO
LA English
DT Article
ID STEM-CELL NICHE; ADP-RIBOSYLATING TOXIN; SECRETION SYSTEMS;
BINDING-PROTEIN; ALPHA-SYNUCLEIN; SACCHAROMYCES-CEREVISIAE; INVASIVE
SALMONELLA; FILAMENT NUCLEATION; FILARIAL NEMATODES; VIRULENCE PROTEINS
AB Many bacteria live as intracellular symbionts, causing persistent infections within insects. One extraordinarily common infection is that of Wolbachia pipientis, which infects 40% of insect species and induces reproductive effects. The bacteria are passed from generation to generation both vertically (through the oocyte) and horizontally (by environmental transmission). Maintenance of the infection within Drosophila melanogaster is sensitive to the regulation of actin, as Wolbachia inefficiently colonizes strains hemizygous for the profilin or villin genes. Therefore, we hypothesized that Wolbachia must depend on the host actin cytoskeleton. In this study, we identify and characterize a Wolbachia protein (WD0830) that is predicted to be secreted by the bacterial parasite. Expression of WD0830 in a model eukaryote (the yeast Saccharomyces cerevisiae) induces a growth defect associated with the appearance of aberrant, filamentous structures which colocalize with rhodamine-phalloidin-stained actin. Purified WD0830 bundles actin in vitro and cosediments with actin filaments, suggesting a direct interaction of the two proteins. We characterized the expression of WD0830 throughout Drosophila development and found it to be upregulated in third-instar larvae, peaking in early pupation, during the critical formation of adult tissues, including the reproductive system. In transgenic flies, heterologously expressed WD0830 localizes to the developing oocyte. Additionally, overexpression of WD0830 results in increased Wolbachia titers in whole flies, in stage 9 and 10 oocytes, and in embryos, compared to controls, suggesting that the protein may facilitate Wolbachia's replication or transmission. Therefore, this candidate secreted effector may play a role in Wolbachia's infection of and persistence within host niches.
IMPORTANCE The obligate intracellular Wolbachia pipientis is a ubiquitous alphaproteobacterial symbiont of arthropods and nematodes and is related to the rickettsial pathogens Ehrlichia spp. and Anaplasma spp. Studies of Wolbachia cell biology suggest that this bacterium relies on host actin for efficient proliferation and transmission between generations. Here, we identified and characterized a Wolbachia protein that localizes to and manipulates the eukaryotic actin cytoskeleton, is expressed by Wolbachia during host development, and alters Wolbachia titers and localization in transgenic fruit flies. We hypothesize that WD0830 may be utilized by the bacterium to facilitate replication in or invasion of different niches during host development.
C1 [Sheehan, Kathy B.; Martin, MaryAnn; Newton, Irene L. G.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Lesser, Cammie F.] Harvard Med Sch, Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Cambridge, MA USA.
[Isberg, Ralph R.] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Newton, ILG (reprint author), Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
EM irnewton@indiana.edu
FU HHS \ National Institutes of Health (NIH) [R01AI064285]; National
Science Foundation (NSF) [1456545]
FX This work, including the efforts of Cammie F. Lesser, was funded by HHS
vertical bar National Institutes of Health (NIH) (R01AI064285). This
work, including the efforts of Irene L.G. Newton, was funded by National
Science Foundation (NSF) (1456545).
NR 79
TC 3
Z9 3
U1 8
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 2150-7511
J9 MBIO
JI mBio
PD JUL-AUG
PY 2016
VL 7
IS 4
AR e00622-16
DI 10.1128/mBio.00622-16
PG 12
WC Microbiology
SC Microbiology
GA DW1YQ
UT WOS:000383440500010
ER
PT J
AU de Gusmao, CM
Dy, M
Sharma, N
AF de Gusmao, Claudio M.
Dy, Marisela
Sharma, Nutan
TI Beyond Dystonia-Parkinsonism: Chorea and Ataxia with ATP1A3 Mutations
SO MOVEMENT DISORDERS CLINICAL PRACTICE
LA English
DT Article
DE rapid-onset dystonia; parkinsonism; dystonia; ataxia
ID DISORDERS; PHENOTYPE; GENE
AB Mutations in the ATP1A3 gene (the alpha-3 subunit of the Na+/K+ ATPase) are associated with rapid-onset dystonia-parkinsonism; alternating hemiplegia of childhood; and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS syndrome). The authors report 3 cases with pleiotropic movement disorders, including a novel mutation in a patient who presented with ataxia and dysphagia. Case 1 had a history of attention deficit hyperactivity disorder and developed dysphagia, chorea, and limb dystonia after a febrile illness at age 12 years. Case 2 presented with limb dystonia at age 26 years and dysarthia and dysphagia after a febrile illness. Case 3 had a history of learning disability and developed progressive ataxia with cerebellar atrophy at age 20 years. In all cases, deleterious mutations were identified in ATP1A3. They illustrate wide phenotypic variability, including chorea and ataxia. New cases are likely to be diagnosed as knowledge about the phenotypic spectrum expands.
C1 [de Gusmao, Claudio M.; Sharma, Nutan] Massachusetts Gen Hosp, Dept Neurol, 185 Cambridge St,Suite 820, Boston, MA 02115 USA.
[Dy, Marisela] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
RP de Gusmao, CM (reprint author), Massachusetts Gen Hosp, 185 Cambridge St,Suite 820, Boston, MA 02115 USA.
EM cdegusmao@partners.org
NR 14
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2330-1619
J9 MOV DISORD CLIN PRAC
JI MOV. DISORD. CLIN. PRACT.
PD JUL-AUG
PY 2016
VL 3
IS 4
BP 402
EP 404
DI 10.1002/mdc3.12317
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA DV9GS
UT WOS:000383249300012
ER
PT J
AU Florez, JC
AF Florez, Jose C.
TI Leveraging Genetics to Advance Type 2 Diabetes Prevention
SO PLOS MEDICINE
LA English
DT Editorial Material
ID IMPAIRED GLUCOSE-TOLERANCE; LIFE-STYLE INTERVENTION; WEIGHT-LOSS;
INSULIN-RESISTANCE; RISK-FACTORS; FOLLOW-UP; PROGRAM; METFORMIN;
PREDICTION; VARIANTS
C1 [Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.] Broad Inst, Program Metab, Cambridge, MA 02142 USA.
[Florez, Jose C.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Florez, Jose C.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
RP Florez, JC (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.; Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.; Florez, JC (reprint author), Broad Inst, Program Metab, Cambridge, MA 02142 USA.; Florez, JC (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Florez, JC (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
EM jcflorez@partners.org
NR 25
TC 1
Z9 1
U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD JUL
PY 2016
VL 13
IS 7
AR e1002102
DI 10.1371/journal.pmed.1002102
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW0TA
UT WOS:000383354300021
PM 27458973
ER
PT J
AU Mingrone, G
Cummings, DE
AF Mingrone, Geltrude
Cummings, David E.
TI Changes of insulin sensitivity and secretion after bariatric/metabolic
surgery
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Article
ID Y GASTRIC BYPASS; BETA-CELL FUNCTION; TYPE-2 DIABETES-MELLITUS; NORMAL
GLUCOSE-TOLERANCE; SEVERELY OBESE-PATIENTS; BARIATRIC SURGERY;
WEIGHT-LOSS; SLEEVE GASTRECTOMY; BILIOPANCREATIC DIVERSION; GLYCEMIC
CONTROL
AB Type 2 diabetes (T2D) is classically characterized by failure of pancreatic beta-cell function and insulin secretion to compensate for a prevailing level of insulin resistance, typically associated with visceral obesity. Although this is usually a chronic, progressive disease in which delay of end-organ complications is the primary therapeutic goal for medical and behavioral approaches, several types of bariatric surgery, especially those that include intestinal bypass components, exert powerful anti diabetes effects to yield remission of T2D in most cases. It has become increasingly clear that in addition to the known benefits of acute caloric restriction and chronic weight loss to ameliorate T2D, bariatric/metabolic operations also engage a variety of weight-independent mechanisms to improve glucose homeostasis, enhancing insulin sensitivity and secretion to varying degrees depending on the specific operation. In this paper, we review the effects of Roux-en-Y gastric bypass, biliopancreatic diversion, and vertical sleeve gastrectomy on the primary determinants of glucose homeostasis: insulin sensitivity, insulin secretion, and, to the lesser extent that it is known, insulin independent glucose disposal. A full understanding of these effects should help optimize surgical and device-based designs' to provide maximal antidiabetes impact, and it holds the promise to identify targets for possible novel diabetes pharmacotherapeutics. These insights also contribute to the conceptual rationale for use of bariatric operations as "metabolic surgery," employed primarily to treat T2D, including among patients not obese enough to qualify for surgery based on traditional criteria related to high body mass index. (C) 2016 American Society for Metabolic and Bariatric Surgery. All rights reserved.
C1 [Mingrone, Geltrude] Univ Cattolica Sacro Cuore, Dept Internal Med, Rome, Italy.
[Cummings, David E.] Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Cummings, David E.] Univ Washington, Diabet & Obes Ctr Excellence, Seattle, WA 98195 USA.
RP Cummings, DE (reprint author), Univ Washington, Dept Med, Box 358280,Mail Stop 111, Seattle, WA 98195 USA.
EM davidec@u.washington.edu
RI DE SOUZA, AGLECIO/Q-4056-2016
NR 68
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-7289
EI 1878-7533
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD JUL
PY 2016
VL 12
IS 6
BP 1199
EP 1205
DI 10.1016/j.soard.2016.05.013
PG 7
WC Surgery
SC Surgery
GA DV8VU
UT WOS:000383215600008
PM 27568471
ER
PT J
AU Greenwood-Ericksen, MB
Havens, JM
Ma, JM
Weissman, JS
Schuur, JD
AF Greenwood-Ericksen, Margaret B.
Havens, Joaquim M.
Ma, Jiemin
Weissman, Joel S.
Schuur, Jeremiah D.
TI Trends in Hospital Admission and Surgical Procedures Following ED visits
for Diverticulitis
SO WESTERN JOURNAL OF EMERGENCY MEDICINE
LA English
DT Article
DE Emergency Department; Health Services; Diverticulitis; Admission
ID INSURANCE STATUS; UNITED-STATES; DISEASE; YOUNG; PATHOGENESIS;
POPULATION; MANAGEMENT; VIRULENT; PATTERNS; PATIENT
AB Introduction: Diverticulitis is a common diagnosis in the emergency department (ED). Outpatient management of diverticulitis is safe in selected patients, yet the rates of admission and surgical procedures following ED visits for diverticulitis are unknown, as are the predictive patient characteristics. Our goal is to describe trends in admission and surgical procedures following ED visits for diverticulitis, and to determine which patient characteristics predict admission.
Methods: We performed a cross-sectional descriptive analysis using data on ED visits from 2006-2011 to determine change in admission and surgical patterns over time. The Nationwide Emergency Department Sample database, a nationally representative administrative claims dataset, was used to analyze ED visits for diverticulitis. We included patients with a principal diagnosis of diverticulitis (ICD-9 codes 562.11, 562.13). We analyzed the rate of admission and surgery in all admitted patients and in low-risk patients, defined as age <50 with no comorbidities (Elixhauser). We used hierarchical multivariate logistic regression to identify patient characteristics associated with admission for diverticulitis.
Results: From 2006 to 2011 ED visits for diverticulitis increased by 21.3% from 238,248 to 302,612, while the admission rate decreased from 55.7% to 48.5% (-7.2%, 95% CI [-7.78 to -6.62]; p<0.001 for trend). The admission rate among low-risk patients decreased from 35.2% in 2006 to 26.8% in 2011 (-8.4%, 95% CI [-9.6 to -7.2]; p<0.001 for trend). Admission for diverticulitis was independently associated with male gender, comorbid illnesses, higher income and commercial health insurance. The surgical rate decreased from 6.5% in 2006 to 4.7% in 2011 (-1.8%, 95% CI [-2.1 to -1.5]; p<0.001 for trend), and among low-risk patients decreased from 4.0% to 2.2% (-1.8%, 95% CI [-4.5 to -1.7]; p<0.001 for trend).
Conclusion: From 2006 to 2011 ED visits for diverticulitis increased, while ED admission rates and surgical rates declined, with comorbidity, sociodemographic factors predicting hospitalization. Future work should focus on determining if these differences reflect increased disease prevalence, increased diagnosis, or changes in management.
C1 [Greenwood-Ericksen, Margaret B.] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA.
[Greenwood-Ericksen, Margaret B.; Schuur, Jeremiah D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Greenwood-Ericksen, Margaret B.; Havens, Joaquim M.; Weissman, Joel S.; Schuur, Jeremiah D.] Harvard Med Sch, Boston, MA USA.
[Havens, Joaquim M.; Weissman, Joel S.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
[Havens, Joaquim M.] Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA.
[Ma, Jiemin] Amer Canc Soc, Surveillance & Hlth Serv Res Program, Atlanta, GA 30329 USA.
RP Greenwood-Ericksen, MB (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA.
EM mgreenwood-ericksen@partners.org
NR 40
TC 0
Z9 0
U1 1
U2 1
PU WESTJEM
PI ORANGE
PA C/O SHAHRAM LOTFIPOUR, MD, MPH, 333 CITY BLVD W STE 640, RT 128-01,
ORANGE, CA 92868 USA
SN 1936-900X
EI 1936-9018
J9 WEST J EMERG MED
JI West. J. Emerg. Med.
PD JUL
PY 2016
VL 17
IS 2
BP 409
EP 417
DI 10.5811/westjem.2016.4.29757
PG 9
WC Emergency Medicine
SC Emergency Medicine
GA DV3QJ
UT WOS:000382837600005
PM 27429691
ER
PT J
AU Pugh, TJ
Amr, SS
Bowser, MJ
Gowrisankar, S
Hynes, E
Mahanta, LM
Rehm, HL
Funke, B
Lebo, MS
AF Pugh, Trevor J.
Amr, Sami S.
Bowser, Mark J.
Gowrisankar, Sivakumar
Hynes, Elizabeth
Mahanta, Lisa M.
Rehm, Heidi L.
Funke, Birgit
Lebo, Matthew S.
TI VisCap: inference and visualization of germ-line copy-number variants
from targeted clinical sequencing data
SO GENETICS IN MEDICINE
LA English
DT Article
DE copy-number variation; germ-line; molecular genetics; targeted clinical
sequencing; visualization; VisCap
ID CARDIOMYOPATHY; CAPTURE
AB Purpose: To develop and validate VisCap, a software program targeted to clinical laboratories for inference and visualization of germ-line copy-number variants (CNVs) from targeted next-generation sequencing data.
Methods: VisCap calculates the fraction of overall sequence coverage assigned to genomic intervals and computes log2 ratios of these values to the median of reference samples profiled using the same test configuration. Candidate CNVs are called when log2 ratios exceed user-defined thresholds.
Results: We optimized VisCap using 14 cases with known CNVs, followed by prospective analysis of 1,104 cases referred for diagnostic DNA sequencing. To verify calls in the prospective cohort, we used droplet digital polymerase chain reaction (PCR) to confirm 10/27 candidate CNVs and 72/72 copy-neutral genomic regions scored by VisCap. We also used a genome-wide bead array to confirm the absence of CNV calls across panels applied to 10 cases. To improve specificity, we instituted a visual scoring system that enabled experienced reviewers to differentiate true-positive from false-positive calls with minimal impact on laboratory workflow.
Conclusions: VisCap is a sensitive method for inferring CNVs from targeted sequence data from targeted gene panels. Visual scoring of data underlying CNV calls is a critical step to reduce false-positive calls for follow-up testing.
C1 [Pugh, Trevor J.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Pugh, Trevor J.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
[Amr, Sami S.; Bowser, Mark J.; Gowrisankar, Sivakumar; Hynes, Elizabeth; Mahanta, Lisa M.; Rehm, Heidi L.; Funke, Birgit; Lebo, Matthew S.] Partners HealthCare Personalized Med, Mol Med Lab, Boston, MA USA.
[Amr, Sami S.; Rehm, Heidi L.; Funke, Birgit; Lebo, Matthew S.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Amr, Sami S.; Rehm, Heidi L.; Funke, Birgit; Lebo, Matthew S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Amr, Sami S.; Rehm, Heidi L.; Funke, Birgit; Lebo, Matthew S.] Harvard Med Sch, Dept Pathol, Boston, MA USA.
RP Pugh, TJ (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada.; Pugh, TJ (reprint author), Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
EM trevor.pugh@utoronto.ca
OI Duffy Hynes, Elizabeth/0000-0002-3817-2145; Lebo,
Matthew/0000-0002-9733-5207; Amr, Sami/0000-0003-0927-6057; Rehm,
Heidi/0000-0002-6025-0015
FU Princess Margaret Cancer Foundation
FX We thank the staff and fellows of the Laboratory for Molecular Medicine
and the Princess Margaret Genomics Centre for their technical assistance
in generating and interpreting these data. T.J.P. is supported by
funding from the Princess Margaret Cancer Foundation.
NR 21
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
EI 1530-0366
J9 GENET MED
JI Genet. Med.
PD JUL
PY 2016
VL 18
IS 7
BP 712
EP 719
DI 10.1038/gim.2015.156
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DS9XL
UT WOS:000381136700010
PM 26681316
ER
PT J
AU Kuntz, KM
Zauber, AG
Knudsen, AB
Rutter, CM
Lansdorp-Vogelaar, I
AF Kuntz, Karen M.
Zauber, Ann G.
Knudsen, Amy B.
Rutter, Carolyn M.
Lansdorp-Vogelaar, Iris
TI A Restricted Look at CRC Screening: Not Considering Annual Stool Testing
as an Option
SO AMERICAN JOURNAL OF MANAGED CARE
LA English
DT Letter
ID COLORECTAL-CANCER
C1 [Kuntz, Karen M.] Univ Minnesota, Minneapolis, MN USA.
[Zauber, Ann G.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Knudsen, Amy B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA.
[Lansdorp-Vogelaar, Iris] Erasmus MC, Rotterdam, Netherlands.
RP Kuntz, KM (reprint author), Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, 420 Delaware St SE, Minneapolis, MN 55455 USA.
EM kmkuntz@umn.edu
FU NCI NIH HHS [P30 CA008748]
NR 4
TC 0
Z9 0
U1 0
U2 0
PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC
PI PLAINSBORO
PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA
SN 1088-0224
J9 AM J MANAG CARE
JI Am. J. Manag. Care
PD JUL
PY 2016
VL 22
IS 7
BP E270
EP E271
PG 2
WC Health Care Sciences & Services; Health Policy & Services; Medicine,
General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DU9SQ
UT WOS:000382558400006
PM 27442311
ER
PT J
AU Nocera, AL
Meurer, AT
Singleton, A
Simons, C
BuSaba, J
Gass, NT
Han, X
Bleier, BS
AF Nocera, Angela L.
Meurer, Ana T.
Singleton, Amy
Simons, Christopher
BuSaba, Joseph
Gass, Nicole Tara
Han, Xue
Bleier, Benjamin S.
TI Intact soluble P-glycoprotein is secreted by sinonasal epithelial cells
SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
LA English
DT Article
ID NASAL POLYPS; CHRONIC RHINOSINUSITIS; CHRONIC SINUSITIS; MDR1
AB Background: P-glycoprotein (P-gp) is a 170 kDa transmembrane efflux pump, which is upregulated in chronic rhinosinusitis. Studies of leukemia demonstrated that P-gp may also be secreted in an intact soluble form. The purpose of this study was to explore whether sinonasal epithelial cells were capable of secreting soluble P-gp and whether P-gp has any functional role.
Methods: Soluble and cytoplasmic P-gp were quantified in vehicle and lipopolysaccharide exposed cultures by enzyme-linked immunosorbent assay. The molecular weight of the soluble P-gp was determined by Western blot. Naive cultures were exposed to recombinant human P-gp at 0-2000 ng/mL. The degree of membranous interpolation was determined by quantitative fluorescent immunocytochemistry and function was determined by a calcein acetoxymethyl ester assay.
Results: Soluble P-gp was secreted intact at 170 kDa. Mean (standard deviation) secretion was detected within vehicle wells at 55.43 +/- 26.26 ng/mL, which significantly increased to 333.27 +/- 305.98 ng/mL (p < 0.001) after lipopolysaccharide stimulation. Soluble P-gp strongly and significantly correlated with cytoplasmic P-gp (r = 0.57, p = 0.000001). Exposure to 2000 ng/mL of recombinant P-gp significantly increased corrected total cell fluorescence (1.34 +/- 1.85) relative to vehicle control 0.29 +/- 0.26 (p = 0.01) and significantly reduced calcein acetoxymethyl ester fluorescence (82.03 +/- 43.69) relative to 100 ng/mL recombinant P-gp exposed cells (123.11 +/- 42.16, p = 0.001).
Conclusion: Cultured sinonasal epithelial cells were able to both secrete intact P-gp and could functionally interpolate soluble P-gp into their cell membrane. These in vitro findings indicated that soluble P-gp may be present in nasal mucus as a biomarker and could participate in the maintenance of P-gp overexpression in chronic rhinosinusitis and associated inflammation.
C1 [Nocera, Angela L.; Meurer, Ana T.; BuSaba, Joseph; Gass, Nicole Tara; Bleier, Benjamin S.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Singleton, Amy; Simons, Christopher; Han, Xue] Boston Univ, Dept Biomed Engn, Boston, MA USA.
RP Bleier, BS (reprint author), 243 Charles St, Boston, MA 02114 USA.
EM benjamin_bleier@meei.harvard.edu
NR 14
TC 1
Z9 1
U1 2
U2 2
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1945-8924
EI 1945-8932
J9 AM J RHINOL ALLERGY
JI Am. J. Rhinol. Allergy
PD JUL-AUG
PY 2016
VL 30
IS 4
BP 246
EP 249
DI 10.2500/ajra.2016.30.4330
PG 4
WC Otorhinolaryngology
SC Otorhinolaryngology
GA DU3IN
UT WOS:000382104100011
PM 27456593
ER
PT J
AU Schlosser, RJ
Gage, SE
Kohli, P
Soler, ZM
AF Schlosser, Rodney J.
Gage, Selby E.
Kohli, Preeti
Soler, Zachary M.
TI Burden of illness: A systematic review of depression in chronic
rhinosinusitis
SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY
LA English
DT Review
ID QUALITY-OF-LIFE; ENDOSCOPIC SINUS SURGERY; DISEASE SEVERITY; OUTCOMES;
ANXIETY; HEALTH; IMPACT; SYMPTOMS; COHORT
AB Background: Depression has been reported in patients with chronic rhinosinusitis (CRS), but its prevalence varies across studies, and uncertainty remains regarding the association with baseline disease severity and treatment outcomes.
Objective: To systematically assess the prevalence of depression in CRS and to review its relationship to baseline disease severity and outcomes after treatment.
Methods: A systematic review of the prevalence of possible depression was performed by using the available methods to diagnose depression, and the results were pooled. Studies that examined the relationship of depression on baseline disease severity and treatment outcomes were organized and reported individually.
Results: Thirteen studies met inclusion criteria for prevalence analysis. The prevalence of possible or likely depression in patients with CRS ranged from 11.0 to 40.0%, depending on the method of diagnosis and sensitivity of various depression instruments. Positive depression screening was consistently associated with worse CRS-specific quality of life (QOL), medication usage, and health care utilization, but there were no reliable CRS-specific factors to predict the presence of depression. Patients with possible depression who underwent medical or surgical treatment for CRS tended to have improvements in CRS-specific QOL but did not achieve the same degree of QOL as patients who were not depressed. Depression-specific QOL seemed to improve after treatment for CRS.
Conclusion: Positive depression screening was common in patients with CRS and had a negative association on the entire spectrum of QOL, health care utilization, and productivity. CRS-specific treatments were still beneficial in patients who seemed to be depressed and improved both depression-specific and CRS-specific QOL.
C1 [Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, Dept Surg, Charleston, SC USA.
[Schlosser, Rodney J.; Gage, Selby E.; Kohli, Preeti; Soler, Zachary M.] Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA.
RP Soler, ZM (reprint author), Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA.
EM solerz@musc.edu
FU Flight Attendant Medical Research Institute [113042 CIA]; National
Institute on Deafness and Other Communication Disorders, the National
Institutes of Health, Bethesda, Maryland [R01 DC005805, R03 DC013651-01]
FX Supported by a grant from the Flight Attendant Medical Research
Institute (ID 113042 CIA). Z.M. Soler is also supported by grants from
the National Institute on Deafness and Other Communication Disorders,
the National Institutes of Health, Bethesda, Maryland (R01 DC005805; R03
DC013651-01)
NR 27
TC 1
Z9 1
U1 1
U2 1
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1945-8924
EI 1945-8932
J9 AM J RHINOL ALLERGY
JI Am. J. Rhinol. Allergy
PD JUL-AUG
PY 2016
VL 30
IS 4
BP 250
EP 256
DI 10.2500/ajra.2016.30.4343
PG 7
WC Otorhinolaryngology
SC Otorhinolaryngology
GA DU3IN
UT WOS:000382104100012
PM 28124650
ER
PT J
AU Newman, E
Thompson, WK
Bartsch, H
Hagler, DJ
Chen, CH
Brown, TT
Kuperman, JM
McCabe, C
Chung, Y
Libiger, O
Akshoomoff, N
Bloss, CS
Casey, BJ
Chang, LD
Ernst, TM
Frazier, JA
Gruen, JR
Kennedy, DN
Murray, SS
Sowell, ER
Schork, N
Kenet, T
Kaufmann, WE
Mostofsky, S
Amaral, DG
Dale, AM
Jernigan, TL
AF Newman, Erik
Thompson, Wesley K.
Bartsch, Hauke
Hagler, Donald J., Jr.
Chen, Chi-Hua
Brown, Timothy T.
Kuperman, Joshua M.
McCabe, Connor
Chung, Yoonho
Libiger, Ondrej
Akshoomoff, Natacha
Bloss, Cinnamon S.
Casey, B. J.
Chang, Linda
Ernst, Thomas M.
Frazier, Jean A.
Gruen, Jeffrey R.
Kennedy, David N.
Murray, Sarah S.
Sowell, Elizabeth R.
Schork, Nicholas
Kenet, Tal
Kaufmann, Walter E.
Mostofsky, Stewart
Amaral, David G.
Dale, Anders M.
Jernigan, Terry L.
TI Anxiety is related to indices of cortical maturation in typically
developing children and adolescents
SO BRAIN STRUCTURE & FUNCTION
LA English
DT Article
DE Anxiety; Brain development; Cortical surface area; Cortical thickness;
Magnetic resonance imaging; Ventromedial prefrontal cortex
ID VENTROMEDIAL PREFRONTAL CORTEX; DOMAIN CRITERIA RDOC; ORBITOFRONTAL
CORTEX; FUNCTIONAL-ANATOMY; FEAR EXTINCTION; TRAIT ANXIETY; SOURCE
MEMORY; SURFACE-AREA; FOLLOW-UP; DISORDERS
AB Anxiety is a risk factor for many adverse neuropsychiatric and socioeconomic outcomes, and has been linked to functional and structural changes in the ventromedial prefrontal cortex (VMPFC). However, the nature of these differences, as well as how they develop in children and adolescents, remains poorly understood. More effective interventions to minimize the negative consequences of anxiety require better understanding of its neurobiology in children. Recent research suggests that structural imaging studies may benefit from clearly delineating between cortical surface area and thickness when examining these associations, as these distinct cortical phenotypes are influenced by different cellular mechanisms and genetic factors. The present study examined relationships between cortical surface area and thickness of the VMPFC and a self-report measure of anxiety (SCARED-R) in 287 youths aged 7-20 years from the Pediatric Imaging, Neurocognition, and Genetics (PING) study. Age and gender interactions were examined for significant associations in order to test for developmental differences. Cortical surface area and thickness were also examined simultaneously to determine whether they contribute independently to the prediction of anxiety. Anxiety was negatively associated with relative cortical surface area of the VMPFC as well as with global cortical thickness, but these associations diminished with age. The two cortical phenotypes contributed additively to the prediction of anxiety. These findings suggest that higher anxiety in children may be characterized by both delayed expansion of the VMPFC and an altered trajectory of global cortical thinning. Further longitudinal studies will be needed to confirm these findings.
C1 [Newman, Erik; McCabe, Connor; Chung, Yoonho; Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Ctr Human Dev, 9500 Gilman Dr,MC 0115, San Diego, CA 92093 USA.
[Newman, Erik; Thompson, Wesley K.; Chen, Chi-Hua; Akshoomoff, Natacha; Jernigan, Terry L.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Thompson, Wesley K.] Univ Calif San Diego, Stein Inst Res Aging, San Diego, CA 92103 USA.
[Bartsch, Hauke; Hagler, Donald J., Jr.; Chen, Chi-Hua; Brown, Timothy T.; Kuperman, Joshua M.; Chung, Yoonho; Dale, Anders M.] Univ Calif San Diego, Multimodal Imaging Lab, San Diego, CA 92103 USA.
[Hagler, Donald J., Jr.; Kuperman, Joshua M.; Dale, Anders M.; Jernigan, Terry L.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.
[Brown, Timothy T.; Dale, Anders M.] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA.
[McCabe, Connor] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Chung, Yoonho] Yale Univ, Dept Psychol, New Haven, CT USA.
[Libiger, Ondrej; Bloss, Cinnamon S.] Scripps Translat Sci Inst, Scripps Genom Med, La Jolla, CA USA.
[Libiger, Ondrej; Bloss, Cinnamon S.] Scripps Hlth, La Jolla, CA USA.
[Casey, B. J.] Weill Cornell Med Coll, Sackler Inst Dev Psychobiol, New York, NY USA.
[Chang, Linda; Ernst, Thomas M.] Univ Hawaii, Dept Med, Honolulu, HI 96822 USA.
[Chang, Linda; Ernst, Thomas M.] Queens Med Ctr, Honolulu, HI USA.
[Frazier, Jean A.; Kennedy, David N.] Univ Massachusetts, Sch Med, Dept Psychiat, Boston, MA 02125 USA.
[Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Gruen, Jeffrey R.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Murray, Sarah S.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA.
[Sowell, Elizabeth R.] Univ Southern Calif, Dept Pediat, Los Angeles, CA USA.
[Sowell, Elizabeth R.] Childrens Hosp, Los Angeles, CA 90027 USA.
[Kenet, Tal] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Kenet, Tal] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Kaufmann, Walter E.] Boston Childrens Hosp, Boston, MA USA.
[Kaufmann, Walter E.] Harvard Med Sch, Boston, MA USA.
[Mostofsky, Stewart] Kennedy Krieger Inst, Baltimore, MD USA.
[Mostofsky, Stewart] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Amaral, David G.] Univ Calif Davis, Dept Psychiat & Behav Sci, Davis, CA 95616 USA.
[Dale, Anders M.; Jernigan, Terry L.] Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA.
RP Newman, E (reprint author), Univ Calif San Diego, Ctr Human Dev, 9500 Gilman Dr,MC 0115, San Diego, CA 92093 USA.; Newman, E (reprint author), Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
EM enewman@ucsd.edu
FU National Institute On Drug Abuse [RC2 DA029475]; Eunice Kennedy Shriver
National Institute Of Child Health & Human Development [R01 HD061414];
National Institute of General Medical Sciences of the National
Institutes of Health [R01 GM104400]
FX This work was supported by the National Institute On Drug Abuse (grant
number RC2 DA029475), the Eunice Kennedy Shriver National Institute Of
Child Health & Human Development (Grant Number R01 HD061414), and the
National Institute of General Medical Sciences (Grant Number R01
GM104400) of the National Institutes of Health. The content presented
herein is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. These data are freely available on the PING portal:
http://pingstudy.ucsd.edu.
NR 52
TC 1
Z9 1
U1 7
U2 7
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2653
EI 1863-2661
J9 BRAIN STRUCT FUNCT
JI Brain Struct. Funct.
PD JUL
PY 2016
VL 221
IS 6
BP 3013
EP 3025
DI 10.1007/s00429-015-1085-9
PG 13
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA DV1MD
UT WOS:000382684300009
PM 26183468
ER
PT J
AU Chalmers, JR
Simpson, E
Apfelbacher, CJ
Thomas, KS
von Kobyletzki, L
Schmitt, J
Singh, JA
Svensson, A
Williams, HC
Abuabara, K
Aoki, V
Ardeleanu, M
Awici-Rasmussen, M
Barbarot, S
Berents, TL
Block, J
Bragg, A
Burton, T
Clemmensen, KKB
Creswell-Melville, A
Dinesen, M
Drucker, A
Eckert, L
Flohr, C
Garg, M
Gerbens, LAA
Graff, ALB
Hanifin, J
Heinl, D
Humphreys, R
Ishii, HA
Kataoka, Y
Leshem, YA
Marquort, B
Massuel, MA
Merhand, S
Mizutani, H
Murota, H
Murrell, DF
Nakahara, T
Nasr, I
Nograles, K
Ohya, Y
Osterloh, I
Pander, J
Prinsen, C
Purkins, L
Ridd, M
Sach, T
Schuttelaar, MLA
Shindo, S
Smirnova, J
Sulzer, A
Gjerde, ES
Takaoka, R
Talmo, HV
Tauber, M
Torchet, F
Volke, A
Wahlgren, CF
Weidinger, S
Weisshaar, E
Wollenberg, A
Yamaga, K
Zhao, CY
Spuls, PI
AF Chalmers, J. R.
Simpson, E.
Apfelbacher, C. J.
Thomas, K. S.
von Kobyletzki, L.
Schmitt, J.
Singh, J. A.
Svensson, A.
Williams, H. C.
Abuabara, K.
Aoki, V.
Ardeleanu, M.
Awici-Rasmussen, M.
Barbarot, S.
Berents, T. L.
Block, J.
Bragg, A.
Burton, T.
Clemmensen, K. K. Bjerring
Creswell-Melville, A.
Dinesen, M.
Drucker, A.
Eckert, L.
Flohr, C.
Garg, M.
Gerbens, L. A. A.
Graff, A. L. B.
Hanifin, J.
Heinl, D.
Humphreys, R.
Ishii, H. A.
Kataoka, Y.
Leshem, Y. A.
Marquort, B.
Massuel, M. -A.
Merhand, S.
Mizutani, H.
Murota, H.
Murrell, D. F.
Nakahara, T.
Nasr, I.
Nograles, K.
Ohya, Y.
Osterloh, I.
Pander, J.
Prinsen, C.
Purkins, L.
Ridd, M.
Sach, T.
Schuttelaar, M. -L. A.
Shindo, S.
Smirnova, J.
Sulzer, A.
Gjerde, E. Synnove
Takaoka, R.
Talmo, H. Vestby
Tauber, M.
Torchet, F.
Volke, A.
Wahlgren, C. -F.
Weidinger, S.
Weisshaar, E.
Wollenberg, A.
Yamaga, K.
Zhao, C. Y.
Spuls, P. I.
TI Report from the fourth international consensus meeting to harmonize core
outcome measures for atopic eczema/dermatitis clinical trials (HOME
initiative)
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
ID MEASUREMENT INSTRUMENTS; ECZEMA; QUALITY; DELPHI; COSMIN; SIGNS
AB This article is a report of the fourth meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in Malmo, Sweden on 23-24 April 2015 (HOME IV). The aim of the meeting was to achieve consensus over the preferred outcome instruments for measuring patient-reported symptoms and quality of life for the HOME core outcome set for atopic eczema (AE). Following presentations, which included data from systematic reviews, consensus discussions were held in a mixture of whole group and small group discussions. Small groups were allocated a priori to ensure representation of different stakeholders and countries. Decisions were voted on using electronic keypads. For the patient-reported symptoms, the group agreed by vote that itch, sleep loss, dryness, redness/inflamed skin and irritated skin were all considered essential aspects of AE symptoms. Many instruments for capturing patient-reported symptoms were discussed [ including the Patient-Oriented SCOring Atopic Dermatitis index, Patient-Oriented Eczema Measure (POEM), Self-Administered Eczema Area and Severity Index, Itch Severity Scale, Atopic Dermatitis Quickscore and the Nottingham Eczema Severity Score] and, by consensus, POEM was selected as the preferred instrument to measure patient-reported symptoms. Further work is needed to determine the reliability and measurement error of POEM. Further work is also required to establish the importance of pain/soreness and the importance of collecting information regarding the intensity of symptoms in addition to their frequency. Much of the discussion on quality of life concerned the Dermatology Life Quality Index and Quality of Life Index for Atopic Dermatitis; however, consensus on a preferred instrument for measuring this domain could not be reached. In summary, POEM is recommended as the HOME core outcome instrument for measuring AE symptoms.
C1 [Chalmers, J. R.; Thomas, K. S.; Williams, H. C.] Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham, England.
[Simpson, E.; Hanifin, J.; Leshem, Y. A.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA.
[Apfelbacher, C. J.; Heinl, D.] Univ Regensburg, Inst Epidemiol & Prevent Med, Med Sociol, D-93053 Regensburg, Germany.
[von Kobyletzki, L.] Lund Univ, Skane Univ Hospital, Dept Dermatol, Malmo, Sweden.
[von Kobyletzki, L.; Smirnova, J.] Karlstad Univ, Dept Publ Hlth Sci, Karlstad, Sweden.
[Schmitt, J.] Univ Dresden, Ctr Lvidence Based Hlthcare, Dresden, Germany.
[Schmitt, J.] Tech Univ Dresden, Dept Occupat & Social Med, D-01062 Dresden, Germany.
[Singh, J. A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
[Singh, J. A.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Svensson, A.] Malmo Univ Hosp, Dept Dermatol & Venerol, Malmo, Sweden.
[Abuabara, K.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Aoki, V.; Takaoka, R.] Univ Sao Paulo, Sch Med, Dept Dermatol, Sao Paulo, Brazil.
[Ardeleanu, M.] Regeneron Pharmaceut Inc, Immunol & Inflammat, New York, NY USA.
[Awici-Rasmussen, M.; Gjerde, E. Synnove] Psoriasis & Eczema Assoc Norway, Oslo, Norway.
[Barbarot, S.] CHU Nantes, Dept Dermatol, F-44035 Nantes 01, France.
[Berents, T. L.] Univ Oslo, Inst Clin Med, Oslo 3, Norway.
[Berents, T. L.] Oslo Univ Hosp, Dept Dermatol, Oslo, Norway.
[Block, J.] Natl Eczema Assoc, Natl Eczema Org, San Rafael, CA USA.
[Bragg, A.] Chugai Pharma Europe Ltd, London, England.
[Clemmensen, K. K. Bjerring] Univ Copenhagen, Bispebjerg Hosp, Dept Dermatol, Copenhagen, Denmark.
[Creswell-Melville, A.] Soc Canadienne IEczema, Keswick, ON, Canada.
[Dinesen, M.] LEO Pharma AS, Industriparken 55, Ballerup, Denmark.
[Drucker, A.] Univ Hlth Nem ork, Div Dermatol, Toronto, ON, Canada.
[Eckert, L.] Hlth Econ & Outcomes Res, Sanofi, France.
[Flohr, C.] Guys & St Thomas Hosp NHS Fdn Trust, St Johns Inst Dermatol, London, England.
[Flohr, C.] Kings Coll London, London, England.
[Garg, M.] LEO Pharma, Copenhagen, Denmark.
[Gerbens, L. A. A.; Spuls, P. I.] Univ Amsterdam, Acad Med Ctr, Dept Dermatol, Amsterdam, Netherlands.
[Graff, A. L. B.; Humphreys, R.] Natl Eczema Soc, London, England.
[Ishii, H. A.] Brazilian Atop Dermatitis Assoc AADA, Sao Paulo, Brazil.
[Kataoka, Y.] Osaka Prefectural Med Ctr Resp & Allerg Dis, Osaka, Japan.
[Massuel, M. -A.] Sanofi Aventis, Paris, France.
[Merhand, S.] Assoc Francaise Eczema, Redon, France.
[Mizutani, H.; Torchet, F.] Mie Univ, Grad Sch Med, Tsu, Mie, Japan.
[Mizutani, H.; Torchet, F.] Mie Univ, Hosp Tsu, Tsu, Mie, Japan.
[Murota, H.; Shindo, S.; Yamaga, K.] Osaka Univ, Dept Dermatol, Osaka, Japan.
[Murrell, D. F.; Zhao, C. Y.] St George Hosp, Dept Dermatol, Sydney, NSW, Australia.
[Murrell, D. F.; Zhao, C. Y.] Univ New S Wales, Sydney, NSW, Australia.
[Nakahara, T.] Kyushu Univ, Grad Sch Med Sci, Dept Dermatol, Fukuoka, Japan.
[Nograles, K.] Greater New York City Area Pharmaceut, Celgene Corp, New York, NY USA.
[Ohya, Y.] Natl Ctr Child Hlth & Dev, Dept Med Subspecialties, Div Allergy, Tokyo, Japan.
[Osterloh, I.] Ostermed Ltd, Kent, OH USA.
[Pander, J.] Celgene BV, Utrecht, Netherlands.
[Prinsen, C.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Epidemiol & Biostat, Amsterdam, Netherlands.
[Purkins, L.] Ziarco Pharma Ltd, Canterbury, Kent, England.
[Ridd, M.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Sach, T.] Univ E Anglia, Hlth Econ Grp, Norwich, Norfolk, England.
[Schuttelaar, M. -L. A.] Univ Groningen, Univ Med Ctr Groningen, Dept Dermatol, Groningen, Netherlands.
[Sulzer, A.; Talmo, H. Vestby] Sanofi Aventis, Montpellier, France.
[Tauber, M.] Toulouse Univ, Toulouse, France.
[Volke, A.] Univ Tartu, Dept Dermatol, Tartu, Estonia.
[Wahlgren, C. -F.] Karolinska Inst, Dept Med, Dermatol Unit, Solna, Sweden.
[Wahlgren, C. -F.] Karolinska Univ Hosp, Stockholm, Sweden.
[Weidinger, S.] Venereol & Allergy Univ Hosp Schleswig Holstein, Dept Dermatol, Kiel, Germany.
[Weisshaar, E.] Heidelberg Univ, Dept Social Med, Occupat & Environm Dermatol, Heidelberg, Germany.
[Wollenberg, A.] Univ Munich, Dept Dermatol & Allergy, Munich, Germany.
RP Chalmers, JR (reprint author), Univ Nottingham, Ctr Evidence Based Dermatol, Nottingham, England.
RI Weidinger, Stephan/C-8461-2011; Aoki, Valeria/H-1415-2012;
OI Apfelbacher, Christian/0000-0003-3805-8219; Ridd,
Matthew/0000-0002-7954-8823; Schuttelaar,
Marie-Louise/0000-0002-0766-4382
FU Department of Health [CDF-2014-07-006]
NR 19
TC 3
Z9 3
U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD JUL
PY 2016
VL 175
IS 1
BP 69
EP 79
DI 10.1111/bjd.14773
PG 11
WC Dermatology
SC Dermatology
GA DS6UF
UT WOS:000380917600017
PM 27436240
ER
PT J
AU Kimball, AB
Naegeli, AN
Edson-Heredia, E
Lin, CY
Gaich, C
Nikai, E
Wyrwich, K
Yosipovitch, G
AF Kimball, A. B.
Naegeli, A. N.
Edson-Heredia, E.
Lin, C. -Y.
Gaich, C.
Nikai, E.
Wyrwich, K.
Yosipovitch, G.
TI Psychometric properties of the Itch Numeric Rating Scale in patients
with moderate-to-severe plaque psoriasis
SO BRITISH JOURNAL OF DERMATOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; DISEASE SEVERITY; PRURITUS; PREVALENCE; SYMPTOMS;
INDEX; ARTHRITIS; VALIDITY
AB Background Itching is a profoundly distressing symptom for many patients with psoriasis, but it has not been rigorously studied using validated tools for this condition.
Objectives This study investigated the psychometric properties of the Itch Numeric Rating Scale (Itch NRS), a single-item patient-reported outcome (PRO) measuring the worst itching severity due to psoriasis in the past 24 h.
Methods Using disease-specific clinician-rated and PRO data from one phase II and three phase III randomized clinical studies of subjects with moderate-to-severe plaque psoriasis, the Itch NRS was evaluated for test-retest reliability, construct validity and responsiveness. A responder definition was explored using anchor- and distribution-based methods.
Results Test-retest reliability analyses supported the reproducibility of the measure (intraclass correlation coefficient range 0.71-0.74). To support the construct validity of the Itch NRS, large cross-sectional correlations with the Dermatology Life Quality Index (DLQI) Symptoms and Feelings domain (r >= 0.60 at baseline and r >= 0.80 at week 12) supported a priori hypotheses, while large correlations (r >= 0.71) between changes in Itch NRS scores and changes in DLQI Symptoms and Feelings domain scores from baseline to week 12 established responsiveness. A 4-point change was optimal for demonstrating a level of clinically meaningful improvement in itch severity after 12 weeks of treatment, which corresponds with marked clinical improvements in plaque psoriasis.
Conclusions The Itch NRS demonstrated sufficient reliability, validity and responsiveness, and appropriate interpretation standards for evaluating change over time in itch severity among patients with moderate-to-severe plaque psoriasis when validated using clinical trial data for this condition.
C1 [Kimball, A. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kimball, A. B.] Harvard Med Sch, Boston, MA 02115 USA.
[Naegeli, A. N.; Edson-Heredia, E.; Lin, C. -Y.; Gaich, C.; Nikai, E.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Wyrwich, K.] Evidera Inc, Bethesda, MD USA.
[Yosipovitch, G.] Temple Univ, Philadelphia, PA 19122 USA.
RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Kimball, AB (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM harvardskinstudies@partners.org
NR 27
TC 4
Z9 4
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-0963
EI 1365-2133
J9 BRIT J DERMATOL
JI Br. J. Dermatol.
PD JUL
PY 2016
VL 175
IS 1
BP 157
EP 162
DI 10.1111/bjd.14464
PG 6
WC Dermatology
SC Dermatology
GA DS6UF
UT WOS:000380917600027
PM 26852717
ER
PT J
AU Eisen, A
Giugliano, RP
AF Eisen, Alon
Giugliano, Robert P.
TI Antiplatelet and Anticoagulation Treatment in Patients With
Non-ST-Segment Elevation Acute Coronary Syndrome Comparison of the
Updated North American and European Guidelines
SO CARDIOLOGY IN REVIEW
LA English
DT Review
DE non-ST-elevation acute coronary syndrome; ACC/AHA guidelines; ESC
guidelines; antiplatelet; anticoagulation
ID OPTIMIZING PLATELET INHIBITION; ASSOCIATION TASK-FORCE; BYPASS
GRAFT-SURGERY; MYOCARDIAL-INFARCTION; HEART-ASSOCIATION; UNFRACTIONATED
HEPARIN; PRASUGREL-THROMBOLYSIS; THERAPEUTIC OUTCOMES; SECONDARY
PREVENTION; ASSESS IMPROVEMENT
AB In 2014, the American Heart Association and the American College of Cardiology (AHA/ACC) published their guideline for the management of patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), whereas the European Society of Cardiology published their latest guideline for the management of patients with NSTE-ACS in 2011. In this article, we review the main updates in antiplatelet and anticoagulation therapy in the 2014 AHA/ACC guideline and compare them with the 2011 European guidelines. Key recommendations in the AHA/ACC guidelines include the addition of ticagrelor to a broad spectrum of patients with NSTE-ACS, narrowing of the role of prasugrel to patients who undergo coronary stenting, and limiting the use of glycoprotein IIb/IIIa receptor inhibitors mainly to high-risk patients during percutaneous coronary intervention. These modifications bring the North American and the European guidelines closer together. The recommendations regarding anticoagulants still differ between the 2 guidelines, although all 4 parenteral agents (unfractionated heparin, low-molecular-weight heparin, bivalirudin, and fondaparinux) are now considered acceptable by both guidelines. We also review new data from clinical trials that became available after the 2014 guidelines were finalized, including studies with cangrelor, rivaroxaban, vorapaxar, ticagrelor, and long-term use of dual antiplatelets that will be considered in future guidelines. As the 2014 guidelines represent the most comprehensive and authoritative document for the management of patients with NSTE-ACS, clinicians who manage these patients should be familiar with their recommendations to ensure optimal patient care.
C1 [Eisen, Alon; Giugliano, Robert P.] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.
RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA.
EM rgiugliano@partners.org
FU Brigham and Women's Hospital from Merck; Daiichi Sankyo
FX Dr. Giugliano received research grant support from the Brigham and
Women's Hospital from Merck and Daiichi Sankyo, and Honoraria for CME
lectures and/or consulting from Daiichi Sankyo, Sanofi, The Medicines
Company, Merck, Bristol Myers Squibb, Glaxo-Smith-Kline. The other
author has no conflicts of interest to report.
NR 35
TC 0
Z9 0
U1 5
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1061-5377
EI 1538-4683
J9 CARDIOL REV
JI Cardiol. Rev.
PD JUL-AUG
PY 2016
VL 24
IS 4
BP 170
EP 176
DI 10.1097/CRD.0000000000000080
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DT0GL
UT WOS:000381161100004
PM 26186386
ER
PT J
AU Wolpin, S
Halpenny, B
Sorrentino, E
Stewart, M
McReynolds, J
Cvitkovic, I
Chang, P
Berry, D
AF Wolpin, Seth
Halpenny, Barbara
Sorrentino, Erica
Stewart, Mark
McReynolds, Justin
Cvitkovic, Ivan
Chang, Peter
Berry, Donna
TI Usability Testing the "Personal Patient Profile-Prostate" in a Sample of
African American and Hispanic Men
SO CIN-COMPUTERS INFORMATICS NURSING
LA English
DT Article
DE Decision support; Health literacy; Infographics; nursing informatics;
Prostate cancer
ID DECISION-SUPPORT-SYSTEM; CANCER; LITERACY; GRAPHS
AB Shared treatment decision making in a cancer setting requires a patient's understanding of the potential benefits and risks of each treatment option. Graphical display of risk information is one approach to improving understanding. Little is known about how patients engage with infographics in the context of health education materials and whether interactions vary with health literacy levels. We conducted an observational study, using an eye tracker device, of how men with newly diagnosed localized prostate cancer visually engaged with an on-screen infographic depicting risk information in the Personal Patient Profile-Prostate. Health literacy was measured with the Short Assessment of Health Literacy-English. Gaze patterns on an exemplar screens containing infographics about survival were analyzed and explored with respect to sociodemographic and health literacy data. Acceptability of Personal Patient Profile-Prostate was measured with the Acceptability E-scale. Twenty-six English-speaking men participated, and eye tracking data were collected for 12 men on the exemplar page of risk information that we analyzed. We found preliminary evidence of visual scanning and of participants with lower literacy focusing sooner on infographics versus text. Acceptability for Personal Patient Profile-Prostate was high. These findings suggest that infographics may be of higher relative value to participants with low health literacy. Eye trackers may provide valuable information on how people visually engage with infographics and may inform development of health education materials, although care must be taken to minimize data loss.
C1 [Wolpin, Seth; Stewart, Mark; McReynolds, Justin; Cvitkovic, Ivan; Berry, Donna] Univ Washington, Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA.
[Halpenny, Barbara; Sorrentino, Erica; Berry, Donna] Dana Farber Canc Inst, Phyllis F Cantor Ctr, Boston, MA 02115 USA.
[Chang, Peter] Beth Israel Deaconess Med Ctr, Div Urol, Boston, MA 02215 USA.
RP Wolpin, S (reprint author), Univ Washington, Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA.
EM swolpin@uw.edu
FU A. David Mazzone Research Award at Dana-Farber/Harvard Cancer Center
FX This study was funded by an A. David Mazzone Research Award at
Dana-Farber/Harvard Cancer Center.
NR 23
TC 0
Z9 0
U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1538-2931
EI 1538-9774
J9 CIN-COMPUT INFORM NU
JI CIN-Comput. Inform. Nurs.
PD JUL
PY 2016
VL 34
IS 7
BP 288
EP 296
PG 9
WC Computer Science, Interdisciplinary Applications; Medical Informatics;
Nursing
SC Computer Science; Medical Informatics; Nursing
GA DU6LC
UT WOS:000382325100002
PM 27081755
ER
PT J
AU Tofthagen, C
Kip, KE
Passmore, D
Loy, I
Berry, DL
AF Tofthagen, Cindy
Kip, Kevin E.
Passmore, Denise
Loy, Ian
Berry, Donna L.
TI Usability and Acceptability of a Web-Based Program for
Chemotherapy-Induced Peripheral Neuropathy
SO CIN-COMPUTERS INFORMATICS NURSING
LA English
DT Article
DE Antineoplastic agents; Antitumor drugs; Neuropathy; Painful
ID SELF-REPORT ASSESSMENT; HEALTH COMMUNICATION; RANDOMIZED-TRIAL; CANCER;
INTERVENTIONS; CAREGIVERS; MANAGEMENT; SYMPTOMS; MESSAGES
AB Chemotherapy-induced neuropathy is a painful and debilitating adverse effect of certain chemotherapy drugs. There have not been any patient-centered, easily accessible Web-based interventions to assist with self-management of chemotherapy-induced neuropathy. The aims of this study were to evaluate usability and acceptability and to estimate an effect size of a Web-based intervention for assessing and managing chemotherapy-induced neuropathy. Participants (N = 14) were instructed to complete the Creativity, Optimism, Planning, and Expert Information for Chemotherapy-Induced Peripheral Neuropathy program and provide verbal responses to the program. Participants completed the Chemotherapy Induced Peripheral Neuropathy Assessment Tool and Post-Study System Usability Questionnaire. Iterative changes were made to the COPE-CIPN. Participants were asked to provide feedback on the revised COPECIPN, repeat the Chemotherapy Induced Peripheral Neuropathy Assessment Tool, and evaluate acceptability using the Acceptability e-Scale. The COPE-CIPN demonstrated high usability (mean, 1.98 [SD, 1.12]) and acceptability (mean, 4.40 [SD, 0.52]). Comments indicated that the interface was easy to use, and the information was helpful. While neuropathy symptoms continued to increase in this group of patients receiving neurotoxic chemotherapy, there was a decrease in mean level of interference with activities from 53.71 to 39.29 over 3 to 4 months, which indicated a moderate effect (d = 0.39) size. The COPE-CIPN may be a useful intervention to support self-management of chemotherapy-induced neuropathy.
C1 [Tofthagen, Cindy; Kip, Kevin E.; Passmore, Denise; Loy, Ian] Univ S Florida, Tampa, FL USA.
[Berry, Donna L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Berry, Donna L.] Harvard Med Sch, Boston, MA USA.
RP Tofthagen, C (reprint author), Univ S Florida, Coll Nursing, 12901 Bruce B Downs Blvd,MDC 22, Tampa, FL 33612 USA.
EM ctofthag@health.usf.edu
NR 38
TC 0
Z9 0
U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1538-2931
EI 1538-9774
J9 CIN-COMPUT INFORM NU
JI CIN-Comput. Inform. Nurs.
PD JUL
PY 2016
VL 34
IS 7
BP 322
EP 329
PG 8
WC Computer Science, Interdisciplinary Applications; Medical Informatics;
Nursing
SC Computer Science; Medical Informatics; Nursing
GA DU6LC
UT WOS:000382325100006
PM 27116414
ER
PT J
AU Oreskovic, NM
Fletcher, R
Sharifi, M
Knutsen, JD
Chilingirian, A
Taveras, EM
AF Oreskovic, Nicolas M.
Fletcher, Richard
Sharifi, Mona
Knutsen, John D.
Chilingirian, Ani
Taveras, Elsie M.
TI Design and rationale of the STRIVE trial to improve cardiometabolic
health among children and families
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE mHealth; Health behaviors; Technology; Obesity; Childhood;
Cardiometabolic
ID CARDIOVASCULAR RISK; PRIMARY-CARE; OBESITY; ADOLESCENTS; CHILDHOOD;
INTERVENTION; PARENTS; TOOL
AB Background: Many of the health behaviors known to contribute to cardiometabolic risk and disease (CMRD), including physical activity, diet, sleep, and screen time, begin during childhood. Given the population-wide burden of CMRD, novel ways of assessing risk and providing feedback to support behavior change are needed.
Purpose: This paper describes the design and rationale for the Study for using Technology to Reach Individual Excellence (STRIVE), a randomized controlled trial testing the use of an integrated, closed-loop feedback system that incorporates longitudinal, patient-generated, mobile health technology (mHealth) data on health behaviors and provides clinical recommendations to help manage CMRD among at-risk families.
Methods: STRIVE is a 6-month trial among 68 children, ages 6-12 year olds with a body mass index >= 85th percentile from Massachusetts with at least one parent with CMRD. Data on several health behaviors will be collected daily over 6 months. Children and parents will each wear wristbands that collect objective physical activity, sleep, and screen time data via accelerometry, noise, and infrared detection. Sugar sweetened beverage consumption will be assessed by self-report via a smartphone application. Weight will be collected using a wireless scale. Intervention group parents receive feedback on their child's health behaviors and personalized CMRD counseling via mobile messaging. Control parents receive standard of care recommendations and weekly health behavior reports for self-guided care.
Conclusion: The STRIVE trial will test the use of mHealth and closed-loop feedback systems to improve health behaviors among families at-risk for or with established CMRD. (C) 2016 Elsevier Inc All rights reserved.
C1 [Oreskovic, Nicolas M.; Sharifi, Mona; Knutsen, John D.; Taveras, Elsie M.] MassGen Hosp Children, Div Gen Acad Pediat, Dept Pediat, Boston, MA USA.
[Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA.
[Oreskovic, Nicolas M.; Sharifi, Mona; Knutsen, John D.; Taveras, Elsie M.] Harvard Med Sch, Boston, MA USA.
[Fletcher, Richard; Chilingirian, Ani] MIT, Media Lab, Cambridge, MA 02139 USA.
[Taveras, Elsie M.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
RP Oreskovic, NM (reprint author), Massachusetts Gen Hosp, Div Gen Acad Pediat, 125 Nashua St,8th Floor, Boston, MA 02114 USA.
EM noreskovic@mgh.harvard.edu; fletcher@media.mit.edu;
msharifi@mgh.harvard.edu; jknutsen@mgh.harvard.edu; anic@mit.edu;
etaveras@mgh.harvard.edu
RI Emchi, Karma/Q-1952-2016
FU Agency for Healthcare Research and Quality grant [1R21HS024001]; Agency
for Healthcare Research and Quality [K12HS022986]; National Institute of
Diabetes and Digestive and Kidney Diseases [K24DK10589]
FX The authors thank Michael P. Duggan for his outstanding research
assistance on this study. This trial is sponsored by the Agency for
Healthcare Research and Quality grant # 1R21HS024001 (PI, Oreskovic).
Dr. Sharifi is supported by a grant from the Agency for Healthcare
Research and Quality (K12HS022986). Dr. Taveras is supported by a grant
from the National Institute of Diabetes and Digestive and Kidney
Diseases (K24DK10589).
NR 28
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
EI 1559-2030
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD JUL
PY 2016
VL 49
BP 149
EP 154
DI 10.1016/j.cct.2016.07.012
PG 6
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA DT5SV
UT WOS:000381543800020
PM 27417980
ER
PT J
AU Bos, D
Dason, S
Matsumoto, E
Pinthus, J
Allard, C
AF Bos, Derek
Dason, Shawn
Matsumoto, Edward
Pinthus, Jehonathan
Allard, Christopher
TI A prospective evaluation of obesometric parameters associated with renal
stone recurrence
SO CUAJ-CANADIAN UROLOGICAL ASSOCIATION JOURNAL
LA English
DT Article
ID ALL-CAUSE MORTALITY; METABOLIC SYNDROME; KIDNEY-STONES;
CARDIOVASCULAR-DISEASE; CALCIUM; OBESITY; RISK; ADIPONECTIN; PREVALENCE;
ADIPOSITY
AB Introduction: Our aim was to evaluate whether obesometric serum hormones and body fat distribution are associated with renal stone recurrence.
Methods: We conducted a prospective cohort study of participants undergoing renal stone (RS) intervention at a single institution from November 2009-June 2010 and followed them for a median 62 months. Obesometric parameters were measured at baseline, including body mass index (BMI), fasting serum leptin and adiponectin, and proportion of visceral adipose tissue (%VAT) averaged from three fixed axial computed tomography (CT) slices. The primary study outcome was stone recurrence.
Results: A total of 110 participants were enrolled. Elevated %VAT was associated RS recurrence; participants with %VAT in the highest quartile had a five-year stone-free rate of 47.1% compared to 72.2% among other participants (p=0.004). Adjusting for gender, elevated %VAT was independently predictive of renal stone recurrence among initial stone formers (n=74; hazard ratio [HR] 4.53, 95% confidence interval [CI] 1.08. 19.02), but not among recurrent stone formers (n=19; HR 0.51, 95% CI 0.054-4.72). Other obesometric factors, including leptin, adiponectin, and BMI, were not significantly predictive of recurrence.
Conclusions: We report a novel association between an elevated %VAT and stone recurrence. These findings may inform patient counselling and followup regimens. The metabolic basis for these findings requires further investigation.
C1 [Bos, Derek; Dason, Shawn; Matsumoto, Edward; Pinthus, Jehonathan; Allard, Christopher] McMaster Univ, Hamilton, ON, Canada.
[Allard, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Allard, Christopher] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
RP Bos, D (reprint author), McMaster Univ, Hamilton, ON, Canada.
EM derek.bos@medportal.ca
NR 29
TC 1
Z9 1
U1 0
U2 0
PU CANADIAN UROLOGICAL ASSOCIATION
PI DORVAL
PA 185 DORVAL AVENUE, STE 401, DORVAL, QC H9S 5J9, CANADA
SN 1911-6470
EI 1920-1214
J9 CUAJ-CAN UROL ASSOC
JI CUAJ-Can. Urol. Assoc. J.
PD JUL-AUG
PY 2016
VL 10
IS 7-8
BP 234
EP 238
DI 10.5489/cuaj.3876
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA DU9IC
UT WOS:000382529100008
PM 27878041
ER
PT J
AU Nagarajan, S
Seddighzadeh, B
Baccarelli, A
Wise, LA
Williams, M
Shields, AE
AF Nagarajan, Sairaman
Seddighzadeh, Bobak
Baccarelli, Andrea
Wise, Lauren A.
Williams, Michelle
Shields, Alexandra E.
TI Adverse maternal exposures, methylation of glucocorticoid-related genes
and perinatal outcomes: a systematic review
SO EPIGENOMICS
LA English
DT Review
DE biomarker; epigenetic; hydroxysteroid 11beta dehydrogenases; infant;
glucocorticoid; methylation; pediatric; perinatal; smoking; stress
ID BORDERLINE PERSONALITY-DISORDER; ONE-CARBON METABOLISM; DNA METHYLATION;
RECEPTOR GENE; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; HUMAN PLACENTA;
BIRTH-WEIGHT; EPIGENETIC REGULATION; CHROMOSOMAL LOCALIZATION;
DEVELOPMENTAL ORIGINS
AB Aim: Maternal environmental exposures affect perinatal outcomes through epigenetic placental changes. We examine the literature addressing associations between adverse maternal exposures, perinatal outcomes and methylation of key genes regulating placental cortisol metabolism. Methods: We searched three databases for studies that examined NR3C1 and HSD11 beta 1/HSD11 beta 2 methylation with maternal exposures or perinatal outcomes. Nineteen studies remained after screening. We followed Cochrane's PRISMA reporting guidelines (2009). Results: NR3C1 and HSD11 beta methylation were associated with adverse infant neurobehavior, stress response, blood pressure and physical development. In utero exposure to maternal stress, nutrition, preeclampsia, smoking and diabetes were associated with altered NR3C1 and HSD11 beta methylation. Conclusion: NR3C1 and HSD11 beta methylation are useful biomarkers of specific environmental stressors associated with important perinatal outcomes that determine pediatric and adult disease risk.
C1 [Nagarajan, Sairaman; Seddighzadeh, Bobak; Shields, Alexandra E.] Massachusetts Gen Hosp, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Mongan Inst Hlth Policy, Boston, MA 02114 USA.
[Nagarajan, Sairaman; Seddighzadeh, Bobak; Shields, Alexandra E.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
[Baccarelli, Andrea] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Wise, Lauren A.; Williams, Michelle] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Williams, Michelle] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
RP Shields, AE (reprint author), Massachusetts Gen Hosp, Harvard MGH Ctr Genom Vulnerable Populat & Hlth D, Mongan Inst Hlth Policy, Boston, MA 02114 USA.; Shields, AE (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.
EM ashields@mgh.harvard.edu
FU John Templeton Foundation (AE Shields)
FX This study was supported by a grant received from the John Templeton
Foundation (AE Shields). The authors have no other relevant affiliations
or financial involvement with any organization or entity with a
financial interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those disclosed.
NR 92
TC 2
Z9 2
U1 6
U2 6
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1750-1911
EI 1750-192X
J9 EPIGENOMICS-UK
JI Epigenomics
PD JUL
PY 2016
VL 8
IS 7
BP 925
EP 944
DI 10.2217/epi.16.9
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA DS8LE
UT WOS:000381034100006
PM 27381417
ER
PT J
AU Vegh, EM
Engels, EB
van Deursen, CJM
Merkely, B
Vernooy, K
Singh, JP
Prinzen, FW
AF Vegh, Eszter M.
Engels, Elien B.
van Deursen, Caroline J. M.
Merkely, Bela
Vernooy, Kevin
Singh, Jagmeet P.
Prinzen, Frits W.
TI T-wave area as biomarker of clinical response to cardiac
resynchronization therapy
SO EUROPACE
LA English
DT Article
DE Cardiac resynchronization therapy; Long-term clinical outcome;
Vectorcardiography; Left bundle branch block; T wave area
ID BUNDLE-BRANCH BLOCK; HEART-FAILURE; VECTORCARDIOGRAM; WOMEN; SIZE; MEN
AB Aims There is increasing evidence that left bundle branch block (LBBB) morphology on the electrocardiogram is a positive predictor for response to cardiac resynchronization therapy (CRT). We previously demonstrated that the vectorcardiography (VCG)-derived T-wave area predicts echocardiographic CRT response in LBBB patients. In the present study, we investigate whether the T-wave area also predicts long-term clinical outcome to CRT.
Methods and results This is a retrospective study consisting of 335 CRT recipients. Primary endpoint were the composite of heart failure (HF) hospitalization, heart transplantation, left ventricular assist device implantation or death during a 3-year follow-up period. HF hospitalization and death alone were secondary endpoints. The patient subgroup with a large T-wave area and LBBB 36% reached the primary endpoint, which was considerably less (P < 0.01) than for patients with LBBB and a small T-wave area or non-LBBB patients with a small or large T-wave area (48, 57, and 51%, respectively). Similar differences were observed for the secondary endpoints, HF hospitalization (31 vs. 51, 51, and 38%, respectively, P < 0.01) and death (19 vs. 42, 34, and 42%, respectively, P < 0.01). In multivariate analysis, a large T-wave area and LBBB were the only independent predictors of the combined endpoint besides high creatinine levels and use of diuretics.
Conclusion T-wave area may be useful as an additional biomarker to stratify CRT candidates and improve selection of those most likely to benefit from CRT. A large T-wave area may derive its predictive value from reflecting good intrinsic myocardial properties and a substrate for CRT.
C1 [Vegh, Eszter M.; Singh, Jagmeet P.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA USA.
[Vegh, Eszter M.; Merkely, Bela] Semmelweis Univ, Heart & Vasc Ctr, Budapest, Hungary.
[Engels, Elien B.; van Deursen, Caroline J. M.; Prinzen, Frits W.] Maastricht Univ, Dept Physiol, Cardiovasc Res Inst Maastricht, POB 616, NL-6200 MD Maastricht, Netherlands.
[van Deursen, Caroline J. M.; Vernooy, Kevin] Maastricht Univ, Dept Cardiol, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands.
RP Prinzen, FW (reprint author), Maastricht Univ, Dept Physiol, Cardiovasc Res Inst Maastricht, POB 616, NL-6200 MD Maastricht, Netherlands.
EM frits.prinzen@maastrichtuniversity.nl
OI Engels, Elien/0000-0002-6300-0564
FU Center for Translational Molecular Medicine; Project COHFAR (Congestive
Heart Failure and Arrhythmia) [01C-203]; Dutch Heart Foundation
FX This work was supported within the framework of Center for Translational
Molecular Medicine (www.ctmm.nl), Project COHFAR (Congestive Heart
Failure and Arrhythmia) (Grant number 01C-203), and supported by the
Dutch Heart Foundation.
NR 21
TC 2
Z9 2
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1099-5129
EI 1532-2092
J9 EUROPACE
JI Europace
PD JUL
PY 2016
VL 18
IS 7
BP 1077
EP 1085
DI 10.1093/europace/euv259
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DU2QP
UT WOS:000382056100020
PM 26462704
ER
PT J
AU Sabbatino, F
Wang, YY
Scognamiglio, G
Favoino, E
Feldman, SA
Villani, V
Flaherty, KT
Nota, S
Giannarelli, D
Simeone, E
Anniciello, AM
Palmieri, G
Pepe, S
Botti, G
Ascierto, PA
Ferrone, CR
Ferrone, S
AF Sabbatino, Francesco
Wang, Yangyang
Scognamiglio, Giosue
Favoino, Elvira
Feldman, Steven A.
Villani, Vincenzo
Flaherty, Keith T.
Nota, Sjoerd
Giannarelli, Diana
Simeone, Ester
Anniciello, Anna M.
Palmieri, Giuseppe
Pepe, Stefano
Botti, Gerardo
Ascierto, Paolo A.
Ferrone, Cristina R.
Ferrone, Soldano
TI Antitumor Activity of BRAF Inhibitor and IFN alpha Combination in
BRAF-Mutant Melanoma
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID CELLS-IN-VITRO; INTERFERON-ALPHA; METASTATIC MELANOMA; HUMAN-LEUKOCYTE;
PRIMARY TUMORS; UP-REGULATION; OPEN-LABEL; EXPRESSION; ANTIGEN; RECEPTOR
AB Background: BRAF(V600E)-mediated MAPK pathway activation is associated in melanoma cells with IFNAR1 downregulation. IFNAR1 regulates melanoma cell sensitivity to IFN alpha, a cytokine used for the adjuvant treatment of melanoma. These findings and the limited therapeutic efficacy of BRAF-I prompted us to examine whether the efficacy of IFN alpha therapy of BRAF(V600E) melanoma can be increased by its combination with BRAF-I.
Methods: BRAF/NRAS genotype, ERK activation, IFNAR1, and HLA class I expression were tested in 60 primary melanoma tumors from treatment-naive patients. The effect of BRAF-I on IFNAR1 expression was assessed in three melanoma cell lines and in four biopsies of BRAF(V600E) metastases. The antiproliferative, pro-apoptotic and immunomodulatory activity of BRAF-I and IFN alpha combination was tested in vitro and in vivo utilizing three melanoma cell lines, HLA class I-MA peptide complex-specific T-cells and immunodeficient mice (5 per group for survival and 10 per group for tumor growth inhibition). All statistical tests were two-sided. Differences were considered statistically significant when the P value was less than .05.
Results: The IFNAR1 level was statistically significantly (P < .001) lower in BRAF(V600E) primary melanoma tumors than in BRAF wild-type tumors. IFNAR1 downregulation was reversed by BRAF-I treatment in the three melanoma cell lines (P <= .02) and in three out of four metastases. The IFNAR1 level in the melanoma tumors analyzed was increased as early as 10 to 14 days following the beginning of the treatment. These changes were associated with: 1) an increased susceptibility in vitro of melanoma cells to the antiproliferative (P <= .04), pro-apoptotic (P <= .009) and immunomodulatory activity, including upregulation of HLA class I antigen APM component (P <= .04) and MA expression as well as recognition by cognate T-cells (P < .001), of BRAF-I and IFN alpha combination and 2) an increased survival (P < .001) and inhibition of tumor growth of melanoma cells (P < .001) in vivo by BRAF-I and IFN alpha combination.
Conclusions: The described results provide a strong rationale for the clinical trials implemented in BRAFV600E melanoma patients with BRAF-I and IFN alpha combination.
C1 [Sabbatino, Francesco; Wang, Yangyang; Favoino, Elvira; Villani, Vincenzo; Ferrone, Cristina R.; Ferrone, Soldano] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
[Flaherty, Keith T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA.
[Nota, Sjoerd; Ferrone, Soldano] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA.
[Scognamiglio, Giosue; Anniciello, Anna M.; Botti, Gerardo] Fdn G Pascale, Ist Nazl Tumori, Unit Pathol, Naples, Italy.
[Simeone, Ester; Ascierto, Paolo A.] Fdn G Pascale, Ist Nazl Tumori, Unit Melanoma Canc Immunotherapy & Innovat Therap, Naples, Italy.
[Feldman, Steven A.] NCI, Surg Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
[Giannarelli, Diana] Regina Elena Inst Canc Res, Biostat Unit, Rome, Italy.
[Palmieri, Giuseppe] CNR, Inst Biomol Chem, Unit Canc Genet, Sassari, Italy.
[Sabbatino, Francesco; Pepe, Stefano] Univ Salerno, Dept Med & Surg, Salerno, Italy.
[Favoino, Elvira] IRCCS Saverio de Bellis, Natl Inst Digest Dis, Lab Cellular & Mol Biol, Castellana Grotte, BA, Italy.
RP Ferrone, S (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
EM sferrone@mgh.harvard.edu
OI Palmieri, Giuseppe/0000-0002-4350-2276
FU National Cancer Institute (PHS grants) [RO1CA138188, P50CA121973];
Fondazione Umberto Veronesi; Susan G. Komen for the Cure Foundation
[KG111486]; Centro per la Comunicazione e la Ricerca of the Collegio
Ghislieri of Pavia
FX This study was supported by the National Cancer Institute (PHS grants
RO1CA138188 and P50CA121973 to SF), by Fondazione Umberto Veronesi
(Fondazione Umberto Veronesi Post Doctoral Fellowship by FS), by the
Susan G. Komen for the Cure Foundation (Susan Komen Post Doctoral
Fellowship KG111486 by YW), and by Centro per la Comunicazione e la
Ricerca of the Collegio Ghislieri of Pavia (Research Fellowship by VV).
NR 38
TC 3
Z9 3
U1 5
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD JUL
PY 2016
VL 108
IS 7
AR djv435
DI 10.1093/jnci/djv435
PG 11
WC Oncology
SC Oncology
GA DU9FT
UT WOS:000382522500008
ER
PT J
AU Buzurovic, IM
Hansen, JL
Bhagwat, MS
O'Farrell, DA
Friesen, S
Harris, TC
Damato, AL
Cormack, RA
Martin, NE
Devlin, PM
AF Buzurovic, Ivan M.
Hansen, Jorgen L.
Bhagwat, Mandar S.
O'Farrell, Desmond A.
Friesen, Scott
Harris, Thomas C.
Damato, Antonio L.
Cormack, Robert A.
Martin, Neil E.
Devlin, Phillip M.
TI Clinical implementation of a novel applicator in high-dose-rate
brachytherapy treatment of esophageal cancer
SO JOURNAL OF CONTEMPORARY BRACHYTHERAPY
LA English
DT Article
DE brachytherapy; esophageal cancer; HDR; optimization
ID RATE INTRALUMINAL BRACHYTHERAPY; EXTERNAL-BEAM RADIATION; CONCURRENT
CHEMOTHERAPY; RANDOMIZED-TRIAL; PHASE I/II; PALLIATION; CARCINOMA;
RADIOTHERAPY; EXPERIENCE; DYSPHAGIA
AB Purpose: In this study, we present the clinical implementation of a novel transoral balloon centering esophageal applicator (BCEA) and the initial clinical experience in high-dose-rate (HDR) brachytherapy treatment of esophageal cancer, using this applicator.
Material and methods: Acceptance testing and commissioning of the BCEA were performed prior to clinical use. Full performance testing was conducted including measurements of the dimensions and the catheter diameter, evaluation of the inflatable balloon consistency, visibility of the radio -opaque markers, congruence of the markers, absolute and relative accuracy of the HDR source in the applicator using the radiochromic film and source position simulator, visibility and digitization of the applicator on the computed tomography (CT) images under the clinical conditions, and reproducibility of the offset. Clinical placement of the applicator, treatment planning, treatment delivery, and patient's response to the treatment were elaborated as well.
Results: The experiments showed sub -millimeter accuracy in the source positioning with distal position at 1270 mm. The digitization (catheter reconstruction) was uncomplicated due to the good visibility of markers. The treatment planning resulted in a favorable dose distribution. This finding was pronounced for the treatment of the curvy anatomy of the lesion due to the improved repeatability and consistency of the delivered fractional dose to the patient, since the radioactive source was placed centrally within the lumen with respect to the clinical target due to the five inflatable balloons.
Conclusions: The consistency of the BCEA positioning resulted in the possibility to deliver optimized non-uniform dose along the catheter, which resulted in an increase of the dose to the cancerous tissue and lower doses to healthy tissue. A larger number of patients and long-term follow-up will be required to investigate if the delivered optimized treatment can lead to improved clinical outcomes.
C1 [Buzurovic, Ivan M.; Hansen, Jorgen L.; Bhagwat, Mandar S.; O'Farrell, Desmond A.; Friesen, Scott; Harris, Thomas C.; Damato, Antonio L.; Cormack, Robert A.; Martin, Neil E.; Devlin, Phillip M.] Harvard Med Sch, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA.
RP Buzurovic, IM (reprint author), Harvard Med Sch, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Div Med Phys & Biophys, 75 Francis St,L2,CWL214, Boston, MA 02115 USA.
EM ibuzurovic@lroc.harvard.edu
OI /0000-0001-9632-3434
NR 27
TC 2
Z9 2
U1 0
U2 0
PU TERMEDIA PUBLISHING HOUSE LTD
PI POZNAN
PA KLEEBERGA ST 2, POZNAN, 61-615, POLAND
SN 1689-832X
EI 2081-2841
J9 J CONTEMP BRACHYTHER
JI J. Contemp. Brachytherapy
PD JUL-AUG
PY 2016
VL 8
IS 4
BP 319
EP 325
DI 10.5114/jcb.2016.61933
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DV3GD
UT WOS:000382808100006
PM 27648086
ER
PT J
AU Apelo, SIA
Lamming, DW
AF Apelo, Sebastian I. Arriola
Lamming, Dudley W.
TI Rapamycin: An InhibiTOR of Aging Emerges From the Soil of Easter Island
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Review
DE Intermittent rapamycin; Lifespan; Mouse; Rapamycin analogs
ID EXTENDS LIFE-SPAN; KIDNEY-TRANSPLANT RECIPIENTS; GENETICALLY
HETEROGENEOUS MICE; INDUCED INSULIN-RESISTANCE; STEM-CELL
TRANSPLANTATION; DIETARY RESTRICTION; ADIPOSE-TISSUE;
MYCOPHENOLATE-MOFETIL; GLUCOSE-HOMEOSTASIS; COGNITIVE DEFICITS
AB Rapamycin (sirolimus) is a macrolide immunosuppressant that inhibits the mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in model organisms including mice. Although rapamycin is an FDA-approved drug for select indications, a diverse set of negative side effects may preclude its wide-scale deployment as an antiaging therapy. mTOR forms two different protein complexes, mTORC1 and mTORC2; the former is acutely sensitive to rapamycin whereas the latter is only chronically sensitive to rapamycin in vivo. Over the past decade, it has become clear that although genetic and pharmacological inhibition of mTORC1 extends lifespan and delays aging, inhibition of mTORC2 has negative effects on mammalian health and longevity and is responsible for many of the negative side effects of rapamycin. In this review, we discuss recent advances in understanding the molecular and physiological effects of rapamycin treatment, and we discuss how the use of alternative rapamycin treatment regimens or rapamycin analogs has the potential to mitigate the deleterious side effects of rapamycin treatment by more specifically targeting mTORC1. Although the side effects of rapamycin are still of significant concern, rapid progress is being made in realizing the revolutionary potential of rapamycin-based therapies for the treatment of diseases of aging.
C1 Univ Wisconsin, Dept Med, Madison, WI USA.
[Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA.
RP Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA.
EM dlamming@medicine.wisc.edu
FU National Institute on Aging at the National Institutes of Health [R00
AG041765]; University of Wisconsin-Madison School of Medicine and Public
Health; University of Wisconsin-Madison Department of Medicine; American
Diabetes Association [1-16-PMF-001]; Glenn Award for Research in the
Biological Mechanisms of Aging; AFAR Research Grant from American
Federation for Aging Research; William S. Middleton Memorial Veterans
Hospital
FX This work was supported by the National Institute on Aging at the
National Institutes of Health (R00 AG041765 to D.W.L.); the University
of Wisconsin-Madison School of Medicine and Public Health; and the
University of Wisconsin-Madison Department of Medicine. S.I.A.A is
supported by a fellowship from the American Diabetes Association
(1-16-PMF-001). The Lamming Laboratory is supported in part by a Glenn
Award for Research in the Biological Mechanisms of Aging and an AFAR
Research Grant from the American Federation for Aging Research. This
work was supported using facilities and resources at the William S.
Middleton Memorial Veterans Hospital. This work does not represent the
views of the Department of Veterans Affairs or the United States
Government.
NR 126
TC 6
Z9 6
U1 6
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2016
VL 71
IS 7
BP 841
EP 849
DI 10.1093/gerona/glw090
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DT0YW
UT WOS:000381209900001
ER
PT J
AU Apelo, SIA
Pumper, CP
Baar, EL
Cummings, NE
Lamming, DW
AF Apelo, Sebastian I. Arriola
Pumper, Cassidy P.
Baar, Emma L.
Cummings, Nicole E.
Lamming, Dudley W.
TI Intermittent Administration of Rapamycin Extends the Life Span of Female
C57BL/6J Mice
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Anti-aging; Life span; Mice; mTOR; Rapamycin
ID INDUCED INSULIN-RESISTANCE; COGNITIVE DEFICITS; ALZHEIMERS-DISEASE;
MAMMALIAN TARGET; MTOR INHIBITION; RESTRICTION; ACTIVATION; LONGEVITY;
COMPLEX; DIET
AB Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2 mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.
C1 [Apelo, Sebastian I. Arriola; Pumper, Cassidy P.; Baar, Emma L.; Cummings, Nicole E.; Lamming, Dudley W.] Univ Wisconsin, Dept Med, Madison, WI USA.
[Apelo, Sebastian I. Arriola; Pumper, Cassidy P.; Baar, Emma L.; Cummings, Nicole E.; Lamming, Dudley W.] William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA.
[Cummings, Nicole E.; Lamming, Dudley W.] Univ Wisconsin, Endocrinol & Reprod Physiol Grad Training Program, Madison, WI 53706 USA.
RP Lamming, DW (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace,Room C3127 Res 151, Madison, WI 53705 USA.
EM dlamming@medicine.wisc.edu
FU National Institute on Aging at the National Institutes of Health [R00
AG041765]; UW-Madison School of Medicine and Public Health; UW-Madison
Department of Medicine; American Diabetes Association [1-16-PMF-001]
FX This work was supported by the National Institute on Aging at the
National Institutes of Health (R00 AG041765 to D.W.L.); the UW-Madison
School of Medicine and Public Health; and the UW-Madison Department of
Medicine. S.I.A.A is supported by a fellowship from the American
Diabetes Association (1-16-PMF-001). This work was supported using
facilities and resources at the William S. Middleton Memorial Veterans
Hospital. This work does not represent the views of the Department of
Veterans Affairs or the United States Government.
NR 44
TC 3
Z9 3
U1 3
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD JUL
PY 2016
VL 71
IS 7
BP 876
EP 881
DI 10.1093/gerona/glw064
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DT0YW
UT WOS:000381209900005
ER
PT J
AU Choudhury, SR
Fitzpatrick, Z
Harris, AF
Maitland, SA
Ferreira, JS
Zhang, YF
Ma, S
Sharma, RB
Gray-Edwards, HL
Johnson, JA
Johnson, AK
Alonso, LC
Punzo, C
Wagner, KR
Maguire, CA
Kotin, RM
Martin, DR
Sena-Esteves, M
AF Choudhury, Sourav R.
Fitzpatrick, Zachary
Harris, Anne F.
Maitland, Stacy A.
Ferreira, Jennifer S.
Zhang, Yuanfan
Ma, Shan
Sharma, Rohit B.
Gray-Edwards, Heather L.
Johnson, Jacob A.
Johnson, Aime K.
Alonso, Laura C.
Punzo, Claudio
Wagner, Kathryn R.
Maguire, Casey A.
Kotin, Robert M.
Martin, Douglas R.
Sena-Esteves, Miguel
TI In Vivo Selection Yields AAV-B1 Capsid for Central Nervous System and
Muscle Gene Therapy
SO MOLECULAR THERAPY
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; ADENOASSOCIATED VIRAL VECTOR; DIRECTED EVOLUTION;
ADULT MICE; PERIPHERAL-TISSUES; NONHUMAN-PRIMATES; HEMOPHILIA-B; VIRUS
VECTOR; PHASE-I; DELIVERY
AB Adeno-associated viral (AAV) vectors have shown promise as a platform for gene therapy of neurological disorders. Achieving global gene delivery to the central nervous system (CNS) is key for development of effective therapies for many of these diseases. Here we report the isolation of a novel CNS tropic AAV capsid, AAV-B1, after a single round of in vivo selection from an AAV capsid library. Systemic injection of AAV-B1 vector in adult mice and cat resulted in widespread gene transfer throughout the CNS with transduction of multiple neuronal subpopulations. In addition, AAV-B1 transduces muscle, beta-cells, pulmonary alveoli, and retinal vasculature at high efficiency. This vector is more efficient than AAV9 for gene delivery to mouse brain, spinal cord, muscle, pancreas, and lung. Together with reduced sensitivity to neutralization by antibodies in pooled human sera, the broad transduction profile of AAV-B1 represents an important improvement over AAV9 for CNS gene therapy.
C1 [Choudhury, Sourav R.; Harris, Anne F.; Maitland, Stacy A.; Ferreira, Jennifer S.; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA.
[Choudhury, Sourav R.; Harris, Anne F.; Maitland, Stacy A.; Ferreira, Jennifer S.; Ma, Shan; Punzo, Claudio; Kotin, Robert M.; Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Gene Therapy Ctr, 368 Plantat St,ASC6-2055, Worcester, MA 01605 USA.
[Fitzpatrick, Zachary; Maguire, Casey A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Fitzpatrick, Zachary; Maguire, Casey A.] Harvard Med Sch, Program Neurosci, Boston, MA USA.
[Zhang, Yuanfan; Wagner, Kathryn R.] Johns Hopkins Sch Med, Kennedy Krieger Inst, Hugo W Moser Res Inst, Baltimore, MD USA.
[Zhang, Yuanfan; Wagner, Kathryn R.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA.
[Zhang, Yuanfan; Wagner, Kathryn R.] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA.
[Ma, Shan; Punzo, Claudio] Univ Massachusetts, Sch Med, Dept Ophthalmol, Worcester, MA USA.
[Sharma, Rohit B.; Alonso, Laura C.] Univ Massachusetts, Sch Med, Diabet Ctr Excellence, Worcester, MA USA.
[Gray-Edwards, Heather L.; Martin, Douglas R.] Auburn Univ, Coll Vet Med, Scott Ritchey Res Ctr, Auburn, AL 36849 USA.
[Johnson, Jacob A.; Johnson, Aime K.] Auburn Univ, Coll Vet Med, Dept Clin Sci, Auburn, AL 36849 USA.
[Kotin, Robert M.] Voyager Therapeut, Cambridge, MA USA.
[Martin, Douglas R.] Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA.
RP Sena-Esteves, M (reprint author), Univ Massachusetts, Sch Med, Gene Therapy Ctr, 368 Plantat St,ASC6-2055, Worcester, MA 01605 USA.
EM miguel.esteves@umassmed.edu
FU [R01NS066310]
FX We thank Damien J. Cabral and Yves T. Falanga for technical assistance,
and Guangping Gao, Erica Mondo, and Christian Mueller for technical
advice. This work was supported by grant R01NS066310 (M.S.-E.). R.M.K.
is an employee of Voyager Therapeutics and holds equity in the company.
NR 65
TC 3
Z9 3
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD JUL
PY 2016
VL 24
IS 7
BP 1247
EP 1257
DI 10.1038/mt.2016.84
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA DT3YY
UT WOS:000381418300011
PM 27117222
ER
PT J
AU Klein, E
Solomon, AJ
Corboy, J
Bernat, J
AF Klein, E.
Solomon, A. J.
Corboy, J.
Bernat, J.
TI Physician compensation for industry-sponsored clinical trials in
multiple sclerosis influences patient trust
SO MULTIPLE SCLEROSIS AND RELATED DISORDERS
LA English
DT Article
DE Multiple sclerosis; Trust; Clinical trials; Conflict of interest;
Professional conduct and ethics; Industry-sponsored clinical trials
ID CONFLICTS-OF-INTEREST; POTENTIAL RESEARCH PARTICIPANTS; CARE; VIEWS
AB Background: Perceived physician financial conflicts of interest of can affect patient trust. Payment to physicians for industry sponsored clinical trials in multiple sclerosis is a relatively new potential source of physician conflict of interest. There is limited available data on how physician payment for trial involvement in multiple sclerosis clinical trials may influence patient trust.
Objective: To understand how patient trust is influenced by information about physician payment for multiple sclerosis clinical trials.
Methods: An anonymous online instrument was developed.
Results: 597 people with multiple sclerosis participated in the study. The study found that 61% of patients who had not previously participated in a clinical trial estimated that they would have lower levels of trust in their physician if the physician was paid for involvement in their clinical trial. Among former clinical trial participants, 38% self-reported a lower level of trust. Other potential physician-industry relationships, such as industry consulting or giving industry-sponsored talks, also adversely affected trust, though to a lesser extent than physician payment for subject participation in clinical trials.
Conclusions: Results of this study demonstrate that physician payment for study participation in multiple sclerosis clinical trials is a potential conflict that can adversely affect patient trust. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Klein, E.] Portland VA Med Ctr, Neurol Serv, POB 1034,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA.
[Klein, E.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Klein, E.] Univ Washington, Ctr Sensorimotor Neural Engn, Seattle, WA 98195 USA.
[Klein, E.] Univ Washington, Dept Philosophy, Seattle, WA 98195 USA.
[Solomon, A. J.] Univ Vermont, Dept Neurol Sci, Burlington, VT 05405 USA.
[Corboy, J.] Univ Colorado, Dept Neurol, Boulder, CO 80309 USA.
[Bernat, J.] Geisel Sch Med Dartmouth, Dept Neurol, Hanover, NH USA.
RP Klein, E (reprint author), Portland VA Med Ctr, Neurol Serv, POB 1034,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA.
EM kleine@ohsu.edu
NR 20
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2211-0348
EI 2211-0356
J9 MULT SCLER RELAT DIS
JI Mult. Scler. Relat. Disord.
PD JUL
PY 2016
VL 8
BP 4
EP 8
DI 10.1016/j.msard.2016.04.001
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6SP
UT WOS:000382345200004
PM 27456867
ER
PT J
AU Bove, R
Musallam, A
Xia, Z
Baruch, N
Messina, S
Healy, BC
Chitnis, T
AF Bove, R.
Musallam, A.
Xia, Z.
Baruch, N.
Messina, S.
Healy, B. C.
Chitnis, T.
TI Longitudinal BMI trajectories in multiple sclerosis: Sex differences in
association with disease severity
SO MULTIPLE SCLEROSIS AND RELATED DISORDERS
LA English
DT Article
DE Body mass index; Multiple sclerosis; Obesity; Sex differences
ID BODY-MASS INDEX; DISABILITY; RISK; MS; LEPTIN; ENCEPHALOMYELITIS;
COMORBIDITY; ADIPOSITY; WOMEN
AB Background: Adolescent obesity is a risk factor for multiple sclerosis (MS), but little is known about changes in body mass index (BMI) after MS onset. Objective: To assess the relationship between MS and longitudinal changes in BMI.
Methods: We analyzed prospectively collected BMIs in a cohort of patients with adult-onset MS and matched adult healthy controls (HC) gathered from the same hospital network central clinical data registry.
Results: We made three main observations. First, at baseline MS patients had a significantly higher BMI than HC (age- and sex-adjusted mean difference=0.57; 95% CI: 0.15, 0.99; p=0.008). Second, a significant age by MS status interaction was observed (p<0.0001), such that in MS, BMIs did not increase significantly higher in older individuals, whereas BMIs in HCs were higher with increasing age. Third, we observed sex-specific associations with disease severity: higher BMI was associated with higher cross-sectional EDSS in women, but with lower EDSS in men (p=0.003, N=758). There were no longitudinal associations between BMI and EDSS in either sex or in the entire cohort (p=0.65, N=772).
Conclusion: After MS onset, patients may not experience age-expected increases in BMI. BMI may have sex-specific associations with MS disability scores. More refined measures of body composition are warranted in future studies to distinguish adiposity from muscle mass. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Bove, R.; Musallam, A.; Xia, Z.; Baruch, N.; Messina, S.; Healy, B. C.; Chitnis, T.] Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Dept Neurol, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA.
[Bove, R.; Xia, Z.; Healy, B. C.; Chitnis, T.] Harvard Med Sch, Boston, MA 02115 USA.
[Baruch, N.; Chitnis, T.] Massachusetts Gen Hosp, Partners Pediat Multiple Sclerosis Ctr, Boston, MA 02114 USA.
[Messina, S.] Univ Catania, Dept GF Ingrassia, Sect Neurosci, I-95124 Catania, Italy.
[Healy, B. C.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA.
RP Chitnis, T (reprint author), Brigham & Womens Hosp, Partners Multiple Sclerosis Ctr, Dept Neurol, 1 Brookline Pl,Suite 602, Brookline, MA 02445 USA.
EM riley_bove@post.harvard.edu; ajmusallam@gmail.com;
zxia1@post.harvard.edu; baruch.natalie352@gmail.com;
silvia.messina@unict.it; bchealy@partners.org; tchitnis@partners.org
FU National Multiple Sclerosis Society [RG-4256A4/2]; National Multiple
Sclerosis Society/American Brain Foundation [FAN 1761-A-1]; American
Brain Foundation; NINDS [K08 NS079493]
FX This research was supported by the National Multiple Sclerosis Society
RG-4256A4/2 (TC), and the National Multiple Sclerosis Society/American
Brain Foundation Clinician Scientist Award FAN 1761-A-1 (RB). Dr. Xia
was a former recipient of the National Multiple Sclerosis Society and
American Brain Foundation Clinician Scientist Development Award, and is
supported in part by the NINDS K08 award (K08 NS079493).
NR 31
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U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2211-0348
EI 2211-0356
J9 MULT SCLER RELAT DIS
JI Mult. Scler. Relat. Disord.
PD JUL
PY 2016
VL 8
BP 136
EP 140
DI 10.1016/j.msard.2016.05.019
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6SP
UT WOS:000382345200026
PM 27456889
ER
PT J
AU Nagami, GT
AF Nagami, Glenn T.
TI Hyperchloremia - Why and how
SO NEFROLOGIA
LA English
DT Review
DE Hyperchloremia; Electrolyte disorder; Serum bicarbonate
ID CRITICALLY-ILL PATIENTS; THICK ASCENDING LIMB; RENAL BLOOD-FLOW;
PROXIMAL TUBULE; METABOLIC-ACIDOSIS; CHLORIDE; SODIUM; KIDNEY; NACL;
MORTALITY
AB Hyperchloremia is a common electrolyte disorder that is associated with a diverse group of clinical conditions. The kidney plays an important role in the regulation of chloride concentration through a variety of transporters that are present along the nephron. Nevertheless, hyperchloremia can occur when water losses exceed sodium and chloride losses, when the capacity to handle excessive chloride is overwhelmed, or when the serum bicarbonate is low with a concomitant rise in chloride as occurs with a normal anion gap metabolic acidosis or respiratory alkalosis. The varied nature of the underlying causes of the hyperchloremia will, to a large extent, determine how to treat this electrolyte disturbance. Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Nefrologia. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Nagami, Glenn T.] VA Greater Los Angeles Healthcare Syst, Dept Med, Nephrol Sect, Los Angeles, CA 90073 USA.
[Nagami, Glenn T.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
RP Nagami, GT (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Nephrol Sect, Los Angeles, CA 90073 USA.; Nagami, GT (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA.
EM glenn.nagami@va.gov
FU U.S. Department of Veterans Affairs
FX This work was supported, in part, by the U.S. Department of Veterans
Affairs.
NR 35
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U2 0
PU SOC ESPANOLA NEFROLOGIA DR RAFAEL MATESANZ
PI MADRID
PA HOSPITAL RAMON Y CAJAL CTR DE COLMENAR, KM 9,100, 28034 MADRID, SPAIN
SN 0211-6995
EI 1989-2284
J9 NEFROLOGIA
JI Nefrologia
PD JUL-AUG
PY 2016
VL 36
IS 4
BP 347
EP 353
DI 10.1016/j.nefro.2016.04.001
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DU1GU
UT WOS:000381957000003
PM 27267918
ER
PT J
AU Loupe, JM
Miller, PJ
Bonner, BP
Maggi, EC
Vijayaraghavan, J
Crabtree, JS
Taylor, CM
Zabaleta, J
Hollenbach, AD
AF Loupe, J. M.
Miller, P. J.
Bonner, B. P.
Maggi, E. C.
Vijayaraghavan, J.
Crabtree, J. S.
Taylor, C. M.
Zabaleta, J.
Hollenbach, A. D.
TI Comparative transcriptomic analysis reveals the oncogenic fusion protein
PAX3-FOXO1 globally alters mRNA and miRNA to enhance myoblast invasion
SO ONCOGENESIS
LA English
DT Article
ID CHILDRENS ONCOLOGY GROUP; REFRACTORY SOLID TUMORS; ALVEOLAR
RHABDOMYOSARCOMA; HEPATOCELLULAR-CARCINOMA; CELL-PROLIFERATION;
COLORECTAL-CANCER; CDNA MICROARRAYS; PHASE-2 TRIAL; YOUNG-ADULTS;
PAX3-FKHR
AB Rhabdomyosarcoma, one of the most common childhood sarcomas, is comprised of two main subtypes, embryonal and alveolar (ARMS). ARMS, the more aggressive subtype, is primarily characterized by the t(2;13)(p35;p14) chromosomal translocation, which fuses two transcription factors, PAX3 and FOXO1 to generate the oncogenic fusion protein PAX3-FOXO1. Patients with PAX3-FOXO1-postitive tumors have a poor prognosis, in part due to the enhanced local invasive capacity of these cells, which leads to the increased metastatic potential for this tumor. Despite this knowledge, little is known about the role that the oncogenic fusion protein has in this increased invasive potential. In this report we use large-scale comparative transcriptomic analyses in physiologically relevant primary myoblasts to demonstrate that the presence of PAX3-FOXO1 is sufficient to alter the expression of 70 mRNA and 27 miRNA in a manner predicted to promote cellular invasion. In contrast the expression of PAX3 alters 60 mRNA and 23 miRNA in a manner predicted to inhibit invasion. We demonstrate that these alterations in mRNA and miRNA translate into changes in the invasive potential of primary myoblasts with PAX3-FOXO1 increasing invasion nearly 2-fold while PAX3 decreases invasion nearly 4-fold. Taken together, these results allow us to build off of previous reports and develop a more expansive molecular model by which the presence of PAX3-FOXO1 alters global gene regulatory networks to enhance the local invasiveness of cells. Further, the global nature of our observed changes highlights the fact that instead of focusing on a single-gene target, we must develop multi-faceted treatment regimens targeting multiple genes of a single oncogenic phenotype or multiple genes that target different oncogenic phenotypes for tumor progression.
C1 [Loupe, J. M.; Miller, P. J.; Bonner, B. P.; Maggi, E. C.; Vijayaraghavan, J.; Crabtree, J. S.; Hollenbach, A. D.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, 533 Bolivar St,CSRB 6th Floor, New Orleans, LA 70112 USA.
[Taylor, C. M.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol Immunol & Parasitol, New Orleans, LA USA.
[Zabaleta, J.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA.
[Zabaleta, J.] Louisiana State Univ, Hlth Sci Ctr, Stanley S Scott Canc Ctr, New Orleans, LA USA.
[Loupe, J. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, Boston, MA 02114 USA.
[Miller, P. J.] Tulane Univ, New Orleans, LA 70112 USA.
RP Hollenbach, AD (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Genet, 533 Bolivar St,CSRB 6th Floor, New Orleans, LA 70112 USA.
EM aholle@lsuhsc.edu
FU National Cancer Institute [R01CA138656]; Louisiana State University
School of Medicine Research Enhancement Bridge Grant; Louisiana Cancer
Research Consortium (LCRC); National Institute of General Medicine
Sciences (NIGMS) [P20GM103501,, 30GM114732, U54GM104940-01]; National
Institute on Minority Health and Health Disparities (NIMHD)
[P20MD004817, U54MD006176-01]
FX Funding for this project is from the National Cancer Institute grant
R01CA138656, the Louisiana State University School of Medicine Research
Enhancement Bridge Grant and the Louisiana Cancer Research Consortium
(LCRC) (ADH). JZ has been partially supported by grants from the
National Institute of General Medicine Sciences (NIGMS) grants
P20GM103501, subproject #2, P30GM114732 and U54GM104940-01, and the
National Institute on Minority Health and Health Disparities (NIMHD)
grants P20MD004817 and U54MD006176-01. All deep sequencing was performed
in the LCRC Translational Genomics Core facility.
NR 54
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U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-9024
J9 ONCOGENESIS
JI Oncogenesis
PD JUL
PY 2016
VL 5
AR e246
DI 10.1038/oncsis.2016.53
PG 8
WC Oncology
SC Oncology
GA DU2DC
UT WOS:000382020200006
PM 27454080
ER
PT J
AU Burrows, CK
Kosova, G
Herman, C
Patterson, K
Hartmann, KE
Edwards, DRV
Stephenson, MD
Lynch, VJ
Ober, C
AF Burrows, Courtney K.
Kosova, Gulum
Herman, Catherine
Patterson, Kristen
Hartmann, Katherine E.
Edwards, Digna R. Velez
Stephenson, Mary D.
Lynch, Vincent J.
Ober, Carole
TI Expression Quantitative Trait Locus Mapping Studies in Mid-secretory
Phase Endometrial Cells Identifies HLA-F and TAP2 as
Fecundability-Associated Genes
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; EARLY-PREGNANCY LOSS; RECURRENT MISCARRIAGES;
3-UNTRANSLATED REGION; REPRODUCTIVE FITNESS; G GENOTYPES; PREECLAMPSIA;
RISK; MUTATION; SUSCEPTIBILITY
AB Fertility traits in humans are heritable, however, little is known about the genes that influence reproductive outcomes or the genetic variants that contribute to differences in these traits between individuals, particularly women. To address this gap in knowledge, we performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium. We identified 423 cis-eQTLs for 132 genes that were significant at a false discovery rate (FDR) of 1%. After pruning for strong LD (r(2) >0.95), we tested for associations between eSNPs and fecundability (the ability to get pregnant), measured as the length of the interval to pregnancy, in 117 women. Two eSNPs were associated with fecundability at a FDR of 5%; both were in the HLA region and were eQTLs for the TAP2 gene (P = 1.3x10(-4)) and the HLA-F gene (P = 4.0x10(-4)), respectively. The effects of these SNPs on fecundability were replicated in an independent sample. The two eSNPs reside within or near regulatory elements in decidualized human endometrial stromal cells. Our study integrating eQTL mapping in a primary tissue with association studies of a related phenotype revealed novel genes and associated alleles with independent effects on fecundability, and identified a central role for two HLA region genes in human implantation success.
C1 [Burrows, Courtney K.; Kosova, Gulum; Herman, Catherine; Patterson, Kristen; Lynch, Vincent J.; Ober, Carole] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Hartmann, Katherine E.; Edwards, Digna R. Velez] Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Hartmann, Katherine E.; Edwards, Digna R. Velez] Vanderbilt Univ, Med Ctr, Dept Obstet, Nashville, TN USA.
[Hartmann, Katherine E.; Edwards, Digna R. Velez] Vanderbilt Univ, Med Ctr, Dept Gynecol, Nashville, TN USA.
[Hartmann, Katherine E.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Genet Inst, Nashville, TN USA.
[Stephenson, Mary D.; Ober, Carole] Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA.
[Kosova, Gulum] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Stephenson, Mary D.] Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA.
RP Ober, C (reprint author), Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.; Ober, C (reprint author), Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA.
EM c-ober@genetics.uchicago.edu
OI Kagan, Courtney/0000-0003-1715-1123
FU National Institutes of Health [R01 HD21244, R01 HL085197, R01 HD043883,
R01 HD049675]; American Water Works Association Research Foundation
[2579]; Clinical and Translational Science Award from the National
Center for Advancing Translational Sciences [UL1TR000445]
FX This work was supported by the National Institutes of Health grants R01
HD21244 and R01 HL085197 to CO, and National Institutes of Health grants
R01 HD043883 and R01 HD049675 and the American Water Works Association
Research Foundation (2579) to KEH. Additional funds were provided by
Clinical and Translational Science Award UL1TR000445 to KEH from the
National Center for Advancing Translational Sciences. The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 71
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U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2016
VL 12
IS 7
AR e1005858
DI 10.1371/journal.pgen.1005858
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA DS8RI
UT WOS:000381050100001
PM 27447835
ER
PT J
AU Kuzu, G
Kaye, EG
Chery, J
Siggers, T
Yang, L
Dobson, JR
Boor, S
Bliss, J
Liu, W
Jogl, G
Rohs, R
Singh, ND
Bulyk, ML
Tolstorukov, MY
Larschan, E
AF Kuzu, Guray
Kaye, Emily G.
Chery, Jessica
Siggers, Trevor
Yang, Lin
Dobson, Jason R.
Boor, Sonia
Bliss, Jacob
Liu, Wei
Jogl, Gerwald
Rohs, Remo
Singh, Nadia D.
Bulyk, Martha L.
Tolstorukov, Michael Y.
Larschan, Erica
TI Expansion of GA Dinucleotide Repeats Increases the Density of CLAMP
Binding Sites on the X-Chromosome to Promote Drosophila Dosage
Compensation
SO PLOS GENETICS
LA English
DT Article
ID TRANSCRIPTION FACTORS; MSL COMPLEX; DNA SHAPE; CAENORHABDITIS-ELEGANS;
CXC DOMAIN; SEQUENCE; GENOME; MELANOGASTER; RECOGNITION; CHROMATIN
AB Dosage compensation is an essential process that equalizes transcript levels of X-linked genes between sexes by forming a domain of coordinated gene expression. Throughout the evolution of Diptera, many different X-chromosomes acquired the ability to be dosage compensated. Once each newly evolved X-chromosome is targeted for dosage compensation in XY males, its active genes are upregulated two-fold to equalize gene expression with XX females. In Drosophila melanogaster, the CLAMP zinc finger protein links the dosage compensation complex to the X-chromosome. However, the mechanism for X-chromosome identification has remained unknown. Here, we combine biochemical, genomic and evolutionary approaches to reveal that expansion of GA-dinucleotide repeats likely accumulated on the X-chromosome over evolutionary time to increase the density of CLAMP binding sites, thereby driving the evolution of dosage compensation. Overall, we present new insight into how subtle changes in genomic architecture, such as expansions of a simple sequence repeat, promote the evolution of coordinated gene expression.
C1 [Kuzu, Guray; Kaye, Emily G.; Boor, Sonia; Bliss, Jacob; Jogl, Gerwald; Larschan, Erica] Brown Univ, Dept Mol Biol Cellular Biol & Biochem, Providence, RI 02912 USA.
[Kuzu, Guray; Tolstorukov, Michael Y.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Chery, Jessica] Massachusetts Gen Hosp, Ctr Canc, Dept Cell Biol, Boston, MA USA.
[Siggers, Trevor] Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA.
[Yang, Lin; Rohs, Remo] Univ So Calif, Dept Biol Sci, Mol & Computat Biol Program, Los Angeles, CA 90089 USA.
[Dobson, Jason R.] Novartis Inst Biomed Res, Cambridge, MA USA.
[Liu, Wei] Zhejiang Acad Agr Sci, Inst Plant Protect & Microbiol, Hangzhou, Zhejiang, Peoples R China.
[Singh, Nadia D.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Bulyk, Martha L.] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
[Bulyk, Martha L.] Harvard Med Sch, Boston, MA USA.
[Bulyk, Martha L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
RP Larschan, E (reprint author), Brown Univ, Dept Mol Biol Cellular Biol & Biochem, Providence, RI 02912 USA.; Tolstorukov, MY (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
EM tolstorukov@molbio.mgh.harvard.edu; erica_larschan@brown.edu
FU US National Institutes of Health [R01GM098461-1, R01 HG005287,
U01GM103804, R01GM106056]; American Cancer Society
[123682-RSG-13-040-01-DMC]; Pew Biomedical Scholars program grant;
National Institute on Aging [T32 AG041688]
FX This research was supported by the following grants: 1) US National
Institutes of Health (nih.gov) R01GM098461-1, American Cancer Society
Research Scholar 123682-RSG-13-040-01-DMC (www.cancer.org) and Pew
Biomedical Scholars
(http://www.pewtrusts.org/en/projects/pew-biomedical-scholars) program
grant to EL; 2) the institutional predoctoral training grant T32
AG041688 from the National Institute on Aging to EGK; 3) R01 HG005287
from the US National Institutes of Health to MLB; 4) US National
Institutes of Health U01GM103804 and R01GM106056 to RR. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 62
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U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2016
VL 12
IS 7
AR e1006120
DI 10.1371/journal.pgen.1006120
PG 28
WC Genetics & Heredity
SC Genetics & Heredity
GA DS8RI
UT WOS:000381050100006
PM 27414415
ER
PT J
AU Lewis, WR
Malarkey, EB
Tritschler, D
Bower, R
Pasek, RC
Porath, JD
Birket, SE
Saunier, S
Antignac, C
Knowles, MR
Leigh, MW
Zariwala, MA
Challa, AK
Kesterson, RA
Rowe, SM
Drummond, IA
Parant, JM
Hildebrandt, F
Porter, ME
Yoder, BK
Berbari, NF
AF Lewis, Wesley R.
Malarkey, Erik B.
Tritschler, Douglas
Bower, Raqual
Pasek, Raymond C.
Porath, Jonathan D.
Birket, Susan E.
Saunier, Sophie
Antignac, Corinne
Knowles, Michael R.
Leigh, Margaret W.
Zariwala, Maimoona A.
Challa, Anil K.
Kesterson, Robert A.
Rowe, Steven M.
Drummond, Iain A.
Parant, John M.
Hildebrandt, Friedhelm
Porter, Mary E.
Yoder, Bradley K.
Berbari, Nicolas F.
TI Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia
Function and Human Disease
SO PLOS GENETICS
LA English
DT Article
ID DYNEIN-REGULATORY-COMPLEX; CHLAMYDOMONAS-FLAGELLA; RADIAL SPOKES; INNER;
DYSKINESIA; ARMS; DEFECTS; GAS11; CILIOPATHY; APPARATUS
AB Ciliopathies are genetic disorders arising from dysfunction of microtubule-based cellular appendages called cilia. Different cilia types possess distinct stereotypic microtubule doublet arrangements with non-motile or 'primary' cilia having a 9+0 and motile cilia have a 9+2 array of microtubule doublets. Primary cilia are critical sensory and signaling centers needed for normal mammalian development. Defects in their structure/function result in a spectrum of clinical and developmental pathologies including abnormal neural tube and limb patterning. Altered patterning phenotypes in the limb and neural tube are due to perturbations in the hedgehog (Hh) signaling pathway. Motile cilia are important in fluid movement and defects in motility result in chronic respiratory infections, altered left-right asymmetry, and infertility. These features are the hallmarks of Primary Ciliary Dyskinesia (PCD, OMIM 244400). While mutations in several genes are associated with PCD in patients and animal models, the genetic lesion in many cases is unknown. We assessed the in vivo functions of Growth Arrest Specific 8 (GAS8). GAS8 shares strong sequence similarity with the Chlamydomonas Nexin-Dynein Regulatory Complex (NDRC) protein 4 (DRC4) where it is needed for proper flagella motility. In mammalian cells, the GAS8 protein localizes not only to the microtubule axoneme of motile cilia, but also to the base of non-motile cilia. Gas8 was recently implicated in the Hh signaling pathway as a regulator of Smoothened trafficking into the cilium. Here, we generate the first mouse with a Gas8 mutation and show that it causes severe PCD phenotypes; however, there were no overt Hh pathway phenotypes. In addition, we identified two human patients with missense variants in Gas8. Rescue experiments in Chlamydomonas revealed a subtle defect in swim velocity compared to controls. Further experiments using CRISPR/Cas9 homology driven repair (HDR) to generate one of these human missense variants in mice demonstrated that this allele is likely pathogenic.
C1 [Lewis, Wesley R.; Malarkey, Erik B.; Yoder, Bradley K.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35233 USA.
[Tritschler, Douglas; Bower, Raqual; Porter, Mary E.] Univ Minnesota, Sch Med, Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
[Pasek, Raymond C.] Vanderbilt Univ, Cell & Dev Biol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Porath, Jonathan D.; Hildebrandt, Friedhelm] Harvard Med Sch, Boston Childrens Hosp, Dept Med, Div Nephrol, Boston, MA USA.
[Birket, Susan E.; Rowe, Steven M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Birket, Susan E.; Rowe, Steven M.] Univ Alabama Birmingham, Cyst Fibrosis Res Ctr, Birmingham, AL USA.
[Saunier, Sophie] Hop Necker Enfants Malad, INSERM, U983, Paris, France.
[Saunier, Sophie] Paris Descartes Univ, Sorbonne Paris Cite, Imagine Inst, Paris, France.
[Antignac, Corinne] INSERM, UMR 1163, Lab Hereditary Kidney Dis, Paris, France.
[Antignac, Corinne] Hop Necker Enfants Malad, AP HP, Dept Genet, Paris, France.
[Knowles, Michael R.] UNC Sch Med, Marisco Lung Inst, Dept Med, Chapel Hill, NC USA.
[Leigh, Margaret W.] UNC Sch Med, Marisco Lung Inst, Dept Pediat, Chapel Hill, NC USA.
[Zariwala, Maimoona A.] UNC Sch Med, Marisco Lung Inst, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Challa, Anil K.; Kesterson, Robert A.] Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA.
[Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA.
[Parant, John M.] Univ Alabama Birmingham, Dept Pharmacol & Toxicol, Birmingham, AL USA.
[Berbari, Nicolas F.] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46205 USA.
RP Yoder, BK (reprint author), Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35233 USA.; Berbari, NF (reprint author), Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46205 USA.
EM byoder@uab.edu; nberbari@iupui.edu
OI Pasek, Raymond/0000-0002-1817-8697
FU National Institutes of Health: National Institute of General Medical
Sciences [T32 GM811126]; National Institute of Child Health and Human
Development [R01 HD56030]; National Institute of Diabetes and Digestive
and Kidney Disease [P30 DK074038, R01 DK065655, R01 DK098306, F32
088404]
FX This work was funded by the following grants and institutes at the
National Institutes of Health (https://www.nih.gov/): National Institute
of General Medical Sciences (T32 GM811126), National Institute of Child
Health and Human Development (R01 HD56030, BKY), and the National
Institute of Diabetes and Digestive and Kidney Disease (P30 DK074038
BKY, R01 DK065655 BKY, R01 DK098306 FH, F32 088404 NFB). The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 38
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U1 4
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD JUL
PY 2016
VL 12
IS 7
AR e1006220
DI 10.1371/journal.pgen.1006220
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA DS8RI
UT WOS:000381050100060
PM 27472056
ER
PT J
AU Altawalbeh, SM
Thorpe, JM
Thorpe, CT
Smith, KJ
AF Altawalbeh, Shoroq M.
Thorpe, Joshua M.
Thorpe, Carolyn T.
Smith, Kenneth J.
TI Cost-Utility Analysis of Long-Acting Beta Agonists versus Leukotriene
Receptor Antagonists in Older Adults with Persistent Asthma Receiving
Concomitant Inhaled Corticosteroid Therapy
SO VALUE IN HEALTH
LA English
DT Article
DE asthma treatment; cost-utility analysis; hospitalization; older adults
ID QUALITY-OF-LIFE; ADD-ON THERAPY; ELDERLY-PATIENTS; PLUS SALMETEROL;
UNITED-STATES; MONTELUKAST; EXACERBATIONS; METAANALYSIS; MEDICATIONS;
MANAGEMENT
AB Background: Long-acting beta agonists (LABA) and leukotriene receptor antagonists (LTRA) are the major add-on treatments in older adults with persistent asthma when inhaled corticosteroids (ICS) fail to achieve adequate asthma control. Objectives: To evaluate the cost utility of ICS + LABA treatment compared with ICS + LTRA treatment in older adults with asthma. Methods: A Markov model was used to estimate the incremental costs and quality-adjusted life expectancy associated with ICS + LABA treatment versus ICS + LTRA treatment in older adults with asthma in the United States from the health system perspective. The HCUPnet 2010 national statistics were used to extract the costs associated with asthma and cardiovascular hospitalizations, and inpatient mortality associated with these events. Event probabilities were predicted using Medicare 2009-2010 claims for older adults with asthma. Treatment costs were estimated on the basis of average wholesale drug price listings, and utility estimates were extracted from the literature. To account for uncertainty, oneway sensitivity analysis and probabilistic sensitivity analysis were performed. Results: The model predicted that, compared with ICS + LTRA treatment, ICS + LABA treatment costs $5,823 more while gaining 0.03 quality-adjusted life-years (QALYs), resulting in an incremental cost-effectiveness ratio of $209,090 per QALY. Hospitalization probabilities and posthospitalization utilities were the most influential parameters in the one-way sensitivity analysis. Probabilistic uncertainty analysis using Monte-Carlo simulations showed that the probabilities that ICS + LTRA treatment is cost-effective compared with ICS + LABA treatment are 77% and 62% at $50,000 and $100,000 per QALY gained willingness-to-pay thresholds, respectively. Conclusions: The cost-effectiveness of ICS + LABA treatment is economically unfavorable in older adults when compared with LTRA as addon treatment.
C1 [Altawalbeh, Shoroq M.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Ctr Clin Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Altawalbeh, Shoroq M.] Jordan Univ Sci & Technol, Sch Pharm, Dept Clin Pharm, Irbid, Jordan.
[Thorpe, Joshua M.; Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA.
[Thorpe, Joshua M.; Thorpe, Carolyn T.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Smith, Kenneth J.] Univ Pittsburgh, Sch Med, Dept Med, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA.
RP Altawalbeh, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA.
EM sha55@pitt.edu
FU University of Pittsburgh School of Pharmacy; Pittsburgh Claude D. Pepper
Older Americans Independence Center [NIA P30 AGAG024827]
FX This study was supported by the University of Pittsburgh School of
Pharmacy and the Pittsburgh Claude D. Pepper Older Americans
Independence Center (NIA P30 AGAG024827).
NR 48
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1098-3015
EI 1524-4733
J9 VALUE HEALTH
JI Value Health
PD JUL-AUG
PY 2016
VL 19
IS 5
BP 537
EP 543
DI 10.1016/j.jval.2016.02.004
PG 7
WC Economics; Health Care Sciences & Services; Health Policy & Services
SC Business & Economics; Health Care Sciences & Services
GA DU5MA
UT WOS:000382254600007
PM 27565270
ER
PT J
AU Coleman, CN
Higgins, GS
Brown, JM
Baumann, M
Kirsch, DG
Willers, H
Prasanna, PGS
Dewhirst, MW
Bernhard, EJ
Ahmed, MM
AF Coleman, C. Norman
Higgins, Geoff S.
Brown, J. Martin
Baumann, Michael
Kirsch, David G.
Willers, Henning
Prasanna, Pataje G. S.
Dewhirst, Mark W.
Bernhard, Eric J.
Ahmed, Mansoor M.
TI Improving the Predictive Value of Preclinical Studies in Support of
Radiotherapy Clinical Trials
SO CLINICAL CANCER RESEARCH
LA English
DT Review
ID CANCER STEM-CELLS; RADIATION ONCOLOGY; TUMOR XENOGRAFTS; ANTICANCER
AGENTS; DRUG SCREEN; THERAPY; HETEROGENEITY; EXPRESSION;
RADIOSENSITIZERS; COMBINATIONS
AB There is an urgent need to improve reproducibility and translatability of preclinical data to fully exploit opportunities for molecular therapeutics involving radiation and radiochemotherapy. For in vitro research, the clonogenic assay remains the current state-of-the-art of preclinical assays, whereas newer moderate and high-throughput assays offer the potential for rapid initial screening. Studies of radiation response modification by molecularly targeted agents can be improved using more physiologic 3D culture models. Elucidating effects on the cancer stem cells (CSC, and CSC-like) and developing biomarkers for defining targets and measuring responses are also important. In vivo studies are necessary to confirm in vitro findings, further define mechanism of action, and address immunomodulation and treatment-induced modification of the microenvironment. Newer in vivo models include genetically engineered and patient-derived xenograft mouse models and spontaneously occurring cancers in domesticated animals. Selection of appropriate endpoints is important for in vivo studies; for example, regrowth delay measures bulk tumor killing, whereas local tumor control assesses effects on CSCs. The reliability of individual assays requires standardization of procedures and cross-laboratory validation. Radiation modifiers must be tested as part of clinical standard of care, which includes radiochemotherapy for most tumors. Radiation models are compatible with but also differ from those used for drug screening. Furthermore, the mechanism of a drug as a chemotherapeutic agent may be different from its interaction with radiation and/or radiochemotherapy. This provides an opportunity to expand the use of molecular-targeted agents. (C) 2016 AACR.
C1 [Coleman, C. Norman; Prasanna, Pataje G. S.; Bernhard, Eric J.; Ahmed, Mansoor M.] NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr,3W102, Bethesda, MD 20892 USA.
[Higgins, Geoff S.] Univ Oxford, Oxford Inst Radiat Oncol, MRC, Canc Res UK, Oxford OX1 2JD, England.
[Brown, J. Martin] Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA.
[Baumann, Michael] Tech Univ Dresden, Helmholtz Zenrtum Dresden Rossendorf, OncoRay Natl Ctr Radiat Res, Dresden, Germany.
[Baumann, Michael] Dresden German Canc Res Ctr DKFZ, German Canc Consortium, Dresden, Germany.
[Kirsch, David G.; Dewhirst, Mark W.] Duke Univ, Dept Radiat Oncol, Durham, NC USA.
[Kirsch, David G.] Duke Univ, Dept Pharmacol, Durham, NC USA.
[Kirsch, David G.] Duke Univ, Dept Canc Biol, Durham, NC USA.
[Willers, Henning] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA.
[Dewhirst, Mark W.] Duke Univ, Dept Pathol, Durham, NC 27706 USA.
[Dewhirst, Mark W.] Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA.
RP Coleman, CN (reprint author), NCI, Radiat Res Program, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr,3W102, Bethesda, MD 20892 USA.
EM ccoleman@mail.nih.gov
FU American Cancer Society [123420RSG-12-224-01-DMC]
FX H. Willers is supported by the American Cancer Society
(123420RSG-12-224-01-DMC).
NR 71
TC 4
Z9 4
U1 5
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD JUL 1
PY 2016
VL 22
IS 13
BP 3138
EP 3147
DI 10.1158/1078-0432.CCR-16-0069
PG 10
WC Oncology
SC Oncology
GA DS7AE
UT WOS:000380933900005
PM 27154913
ER
PT J
AU Bittner, JC
Hasegawa, K
Probst, BD
Mould-Millman, NK
Silverman, RA
Camargo, CA
AF Bittner, Jane C.
Hasegawa, Kohei
Probst, Beatrice D.
Mould-Millman, Nee-Kofi
Silverman, Robert A.
Camargo, Carlos A., Jr.
TI Smoking status and smoking cessation intervention among US adults
hospitalized for asthma exacerbation
SO ALLERGY AND ASTHMA PROCEEDINGS
LA English
DT Article
ID EMERGENCY-DEPARTMENT; CIGARETTE-SMOKING; MULTICENTER
AB Background: In a previous multicenter study during 1999-2000, we found a high prevalence of smoking among patients hospitalized for asthma exacerbations (35%) and suboptimal smoking cessation efforts. There have been no recent multicenter efforts to examine the smoking status and implementation of smoking cessation efforts among patients hospitalized for asthma exacerbation.
Objective: To investigate the prevalence of cigarette smoking and the proportion and characteristics of patients who received an inpatient smoking cessation intervention.
Methods: We conducted a secondary analysis of a 25-center observational study, which included 597 U.S. adults hospitalized for asthma exacerbation during 2012-2013.
Results: Among the analytic cohort, 215 (36%) were current smokers. In the multivariable model, compared with patients with private health insurance, those with public health insurance (odds ratio [OR] 1.71 [95% confidence interval {CI}, 1.06-2.77]) or no health insurance (OR 1.75 [95% CI, 1.02-2.99]) were more likely to be current smokers. By contrast, patients with a previous evaluation by an asthma specialist in the past 12 months (OR 0.49 [95% CI, 0.28-0.86]) and use of inhaled corticosteroids (OR 0.63 [95% CI, 0.43-0.93]) were less likely to be current smokers. Among current smokers, only 55% received smoking cessation interventions during their hospitalization. In the multivariable model, current smokers who had public health insurance (OR 0.25 [95% CI, 0.07-0.82]) or no health insurance (OR 0.26 [95% CI, 0.07-0.94]) were less likely to receive inpatient smoking cessation interventions compared with those with private health insurance.
Conclusion: Our findings showed a persistently high prevalence of smokers among U.S. patients hospitalized for asthma exacerbations and an underutilized opportunity to provide this at-risk population with smoking cessation interventions.
C1 [Bittner, Jane C.; Hasegawa, Kohei; Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA.
[Probst, Beatrice D.] Loyola Univ, Med Ctr, Dept Emergency Med, Maywood, IL USA.
[Mould-Millman, Nee-Kofi] Univ Colorado Hosp, Dept Emergency Med, Aurora, CO USA.
[Silverman, Robert A.] Long Isl Jewish Med Ctr, Dept Emergency Med, New Hyde Pk, NY USA.
RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Suite 920, Boston, MA 02114 USA.
EM ccamargo@partners.org
FU Novartis Pharmaceuticals Corporation
FX The study was supported by a grant from Novartis Pharmaceuticals
Corporation to Massachusetts General Hospital (PI: C. Camargo). The
sponsor had no role in the conduct of the study, or collection,
management, or analysis of the data.
NR 19
TC 3
Z9 3
U1 2
U2 2
PU OCEAN SIDE PUBLICATIONS INC
PI PROVIDENCE
PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA
SN 1088-5412
EI 1539-6304
J9 ALLERGY ASTHMA PROC
JI Allergy Asthma Proc.
PD JUL-AUG
PY 2016
VL 37
IS 4
BP 318
EP 323
DI 10.2500/aap.2016.37.3952
PG 6
WC Allergy
SC Allergy
GA DU3IM
UT WOS:000382104000014
PM 27401318
ER
PT J
AU Kohli, P
Soler, ZM
Nguyen, SA
Muus, JS
Schlosser, RJ
AF Kohli, Preeti
Soler, Zachary M.
Nguyen, Shaun A.
Muus, John S.
Schlosser, Rodney J.
TI The Association Between Olfaction and Depression: A Systematic Review
SO CHEMICAL SENSES
LA English
DT Review
DE anosmia; BDI; hyposmia; normosmia; SIT-40; Sniffin' Sticks
ID QUALITY-OF-LIFE; CHRONIC RHINOSINUSITIS; MAJOR DEPRESSION; ODOR
IDENTIFICATION; DISORDERS; DYSFUNCTION; SCHIZOPHRENIA; SENSITIVITY;
MEMORY; MOOD
AB Previous studies on the relationship between olfaction and depression have revealed mixed results. In addition, few have focused on the reciprocity of this association. The aim of this study is to combine depression and olfactory data in two separate patient populations to further understand their association. A systematic literature review was conducted using 3 online databases to identify studies correlating olfaction and depression in patients presenting with either primary depression or primary olfactory dysfunction. For the depressed population, weighted means and standard deviations for the Sniffin' Sticks Test and the 40-item Smell Identification Test were combined using 10 studies. For the olfactory dysfunction population, weighted means of Beck's Depression Inventory were combined using 3 studies. Independent t-tests were used to compare differences between groups. Comparing primary depressed patients with controls, depressed patients showed decreased scores in olfactory threshold (6.31 +/- 1.38 vs. 6.78 +/- 0.88, P = 0.0005), discrimination (12.05 +/- 1.44 vs. 12.66 +/- 1.36, P = 0.0073), identification (12.57 +/- 0.74 vs. 12.98 +/- 0.90, P < 0.0001), and 40-Item Smell Identification Test (35.31 +/- 1.91 vs. 37.41 +/- 1.45, P < 0.0001). In patients with primary olfactory dysfunction, Beck's Depression Inventory scores were significantly different between patients classified as normosmics, hyposmics and anosmics (5.21 +/- 4.73 vs. 10.93 +/- 9.25 vs. 14.15 +/- 5.39, P a parts per thousand currency sign 0.0274 for all 3 comparisons). In conclusion, patients with depression have reduced olfactory performance when compared with the healthy controls and conversely, patients with olfactory dysfunction, have symptoms of depression that worsen with severity of smell loss.
C1 [Kohli, Preeti; Soler, Zachary M.; Nguyen, Shaun A.; Muus, John S.; Schlosser, Rodney J.] Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA.
[Schlosser, Rodney J.] Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA.
RP Kohli, P (reprint author), Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,MSC 550, Charleston, SC 29425 USA.
EM pkohli89@gmail.com
NR 38
TC 2
Z9 2
U1 8
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0379-864X
EI 1464-3553
J9 CHEM SENSES
JI Chem. Senses
PD JUL
PY 2016
VL 41
IS 6
BP 479
EP 486
DI 10.1093/chemse/bjw061
PG 8
WC Behavioral Sciences; Food Science & Technology; Neurosciences;
Physiology
SC Behavioral Sciences; Food Science & Technology; Neurosciences &
Neurology; Physiology
GA DT1BE
UT WOS:000381215900001
PM 27170667
ER
PT J
AU Reijmer, YD
Fotiadis, P
Piantoni, G
Boulouis, G
Kelly, KE
Gurol, ME
Leemans, A
O'Sullivan, MJ
Greenberg, SM
Viswanathan, A
AF Reijmer, Yael D.
Fotiadis, Panagiotis
Piantoni, Giovanni
Boulouis, Gregoire
Kelly, Kathleen E.
Gurol, Mahmut E.
Leemans, Alexander
O'Sullivan, Michael J.
Greenberg, Steven M.
Viswanathan, Anand
TI Small Vessel Disease and Cognitive Impairment: The Relevance of Central
Network Connections
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE diffusion tensor imaging; vascular brain injury; cognition; white
matter; executive function
ID CEREBRAL AMYLOID ANGIOPATHY; SMALL-WORLD NETWORKS; SPHERICAL
DECONVOLUTION; ALZHEIMER-DISEASE; BRAIN NETWORKS; DIFFUSION MRI;
DEMENTIA; PROGRESSION; DISRUPTION; MODELS
AB Central brain network connections greatly contribute to overall network efficiency. Here we examined whether small vessel disease (SVD) related white matter alterations in central brain network connections have a greater impact on executive functioning than alterations in non-central brain network connections. Brain networks were reconstructed from diffusion-weighted MRI scans in 72 individuals (75 +/- 8 years) with cognitive impairment and SVD on MRI. The centrality of white matter connections in the network was defined using graph theory. The association between the fractional anisotropy (FA) of central versus non-central connections, executive functioning, and markers of SVD was evaluated with linear regression and mediation analysis. Lower FA in central network connections was more strongly associated with impairment in executive functioning than FA in non-central network connections (r = 0.41 vs. r = 0.27; P < 0.05). Results were consistent across varying thresholds to define the central subnetwork (>50%-10% connections). Higher SVD burden was associated with lower FA in central as well as non-central network connections. However, only central network FA mediated the relationship between white matter hyperintensity volume and executive functioning [change in regression coefficient after mediation (95% CI): -0.15 (-0.35 to -0.02)]. The mediation effect was not observed for FA alterations in non-central network connections [-0.03 (-0.19 to 0.04)]. These findings suggest that the centrality of network connections, and thus their contribution to global network efficiency, appears to be relevant for understanding the relationship between SVD and cognitive impairment. (C) 2016 Wiley Periodicals, Inc.
C1 [Reijmer, Yael D.; Fotiadis, Panagiotis; Boulouis, Gregoire; Gurol, Mahmut E.; Greenberg, Steven M.; Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Boston, MA 02115 USA.
[Piantoni, Giovanni] Harvard Med Sch, Massachusetts Gen Hosp, Cort Physiol Lab, Dept Neurol, Boston, MA 02115 USA.
[Kelly, Kathleen E.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Leemans, Alexander] Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands.
[O'Sullivan, Michael J.] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England.
RP Reijmer, YD (reprint author), JP Kistler Stroke Res Ctr, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM yaelreijmer@gmail.com
RI Leemans, Alexander/A-1784-2011; Gurol, Edip/J-2279-2014;
OI Gurol, Edip/0000-0002-2169-4457; Boulouis, Gregoire/0000-0001-8422-9205
FU National Institutes of Health [R01 AG047975, R01 AG026484, P50 AG005134,
K23 AG02872605, R01 AG26484, R01 NS070834]; American Heart Association
[14POST20010031]; BIAL Foundation [220/12]; VIDI from from the
Netherlands Organisation for Scientific Research (NWO) [639.072.411]
FX Contract grant sponsor: National Institutes of Health; Contract grant
number: R01 AG047975, R01 AG026484, P50 AG005134, K23 AG02872605 (to
Viswanthan); R01 AG26484 and R01 NS070834 (to Greenberg); Contract grant
sponsor: American Heart Association; Contract grant number:
14POST20010031; Contract grant sponsor: BIAL Foundation; Contract grant
number: 220/12 (to Piantoni); Contract grant sponsor: VIDI from from the
Netherlands Organisation for Scientific Research (NWO); Contract grant
number: 639.072.411
NR 39
TC 2
Z9 2
U1 4
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD JUL
PY 2016
VL 37
IS 7
BP 2446
EP 2454
DI 10.1002/hbm.23186
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DU8TV
UT WOS:000382488800007
PM 27004840
ER
PT J
AU Pinto, CB
Velez, FGS
Bolognini, N
Crandell, D
Merabet, LB
Fregni, F
AF Pinto, Camila Bonin
Velez, Faddi Ghassan Saleh
Bolognini, Nadia
Crandell, David
Merabet, Lotfi B.
Fregni, Felipe
TI Optimizing Rehabilitation for Phantom Limb Pain Using Mirror Therapy and
Transcranial Direct Current Stimulation: A Randomized, Double-Blind
Clinical Trial Study Protocol
SO JMIR RESEARCH PROTOCOLS
LA English
DT Article
DE cerebral cortex; clinical trial; electrical stimulation; electric
stimulation therapy; factorial design; mirror therapy; non-invasive
brain stimulation; transcranial electrical stimulation
ID UPPER EXTREMITY AMPUTEES; MOTOR CORTEX; CORTICAL REORGANIZATION;
MAGNETIC STIMULATION; SOMATOSENSORY CORTEX; PSYCHOMETRIC PROPERTIES;
NEUROPATHIC PAIN; STUMP PAIN; AMPUTATION; MODULATION
AB Background: Despite the multiple available pharmacological and behavioral therapies for the management of chronic phantom limb pain (PLP) in lower limb amputees, treatment for this condition is still a major challenge and the results are mixed. Given that PLP is associated with maladaptive brain plasticity, interventions that promote cortical reorganization such as non-invasive brain stimulation and behavioral methods including transcranial direct current stimulation (tDCS) and mirror therapy (MT), respectively, may prove to be beneficial to control pain in PLP. Due to its complementary effects, a combination of tDCS and MT may result in synergistic effects in PLP.
Objective: The objective of this study is to evaluate the efficacy of tDCS and MT as a rehabilitative tool for the management of PLP in unilateral lower limb amputees.
Methods: A prospective, randomized, placebo-controlled, double-blind, factorial, superiority clinical trial will be carried out. Participants will be eligible if they meet the following inclusion criteria: lower limb unilateral traumatic amputees that present PLP for at least 3 months after the amputated limb has completely healed. Participants (N=132) will be randomly allocated to the following groups: (1) active tDCS and active MT, (2) sham tDCS and active MT, (3) active tDCS and sham MT, and (4) sham tDCS and sham MT. tDCS will be applied with the anodal electrode placed over the primary motor cortex (M1) contralateral to the amputation side and the cathode over the contralateral supraorbital area. Stimulation will be applied at the same time of the MT protocol with the parameters 2 mA for 20 minutes. Pain outcome assessments will be performed at baseline, before and after each intervention session, at the end of MT, and in 2 follow-up visits. In order to assess cortical reorganization and correlate with clinical outcomes, participants will undergo functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) before and after the intervention.
Results: This clinical trial received institutional review board (IRB) approval in July of 2015 and enrollment started in December of 2015. To date 2 participants have been enrolled. The estimate enrollment rate is about 30 to 35 patients per year; thus we expect to complete enrollment in 4 years.
Conclusions: This factorial design will provide relevant data to evaluate whether tDCS combined with MT is more effective than each therapy alone, as well as with no intervention (sham/sham) in patients with chronic PLP after unilateral lower limb amputation. In addition, this randomized clinical trial will help to investigate the neurophysiological mechanisms underlying the disease, which could potentially provide relevant findings for further management of this chronic condition and also help to optimize the use of this novel intervention.
C1 [Pinto, Camila Bonin; Velez, Faddi Ghassan Saleh; Fregni, Felipe] Harvard Med Sch, Spaulding Rehabil Hosp, Lab Neuromodulat, 96 13th St, Boston, MA 02115 USA.
[Pinto, Camila Bonin; Velez, Faddi Ghassan Saleh; Fregni, Felipe] Harvard Med Sch, Spaulding Rehabil Hosp, Ctr Clin Res Learning, Phys & Rehabil Dept, 96 13th St, Boston, MA 02115 USA.
[Bolognini, Nadia] Univ Milano Bicocca, IRCSS Ist Auxol Italiano, Lab Neuropsychol, Milan, Italy.
[Bolognini, Nadia] Univ Milano Bicocca, Dept Psychol, NeuroMi Milan Ctr Neurosci, Milan, Italy.
[Crandell, David] Harvard Med Sch, Spaulding Rehabil Hosp, Boston, MA USA.
[Merabet, Lotfi B.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Lab Visual Neuroplast, Boston, MA USA.
RP Fregni, F (reprint author), Harvard Med Sch, Spaulding Rehabil Hosp, Lab Neuromodulat, 96 13th St, Boston, MA 02115 USA.; Fregni, F (reprint author), Harvard Med Sch, Spaulding Rehabil Hosp, Ctr Clin Res Learning, Phys & Rehabil Dept, 96 13th St, Boston, MA 02115 USA.
EM Fregni.Felipe@mgh.harvard.edu
OI BOLOGNINI, NADIA/0000-0002-2921-8658; merabet, lotfi/0000-0002-8094-9536
FU NICHD NIH HHS [R01 HD082302]
NR 62
TC 1
Z9 1
U1 16
U2 23
PU JMIR PUBLICATIONS, INC
PI TORONTO
PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA
SN 1929-0748
J9 JMIR RES PROTOC
JI JMIR RES. Protoc.
PD JUL-SEP
PY 2016
VL 5
IS 3
BP 104
EP 117
AR e138
DI 10.2196/resprot.5645
PG 14
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DT1AR
UT WOS:000381214600011
PM 27383993
ER
PT J
AU Radwin, LE
Castonguay, D
Keenan, CB
Hermann, C
AF Radwin, Laurel E.
Castonguay, Denise
Keenan, Carolyn B.
Hermann, Cherice
TI An Expanded Theoretical Framework of Care Coordination Across
Transitions in Care Settings
SO JOURNAL OF NURSING CARE QUALITY
LA English
DT Article
DE care coordination; continuity of care; patient-centered care;
theoretical framework; transitions
ID NURSING-CARE; PATIENTS PERCEPTIONS; PATIENT; QUALITY
AB For many patients, high-quality, patient-centered, and cost-effective health care requires coordination among multiple clinicians and settings. Ensuring optimal care coordination requires a clear understanding of how clinician activities and continuity during transitions affect patient-centeredness and quality outcomes. This article describes an expanded theoretical framework to better understand care coordination. The framework provides clear articulation of concepts. Examples are provided of ways to measure the concepts.
C1 [Radwin, Laurel E.] Vet Adm Ctr Healthcare Org & Implementat Res, Boston, MA USA.
[Castonguay, Denise; Keenan, Carolyn B.] Manchester VAMC, Manchester, NH USA.
RP Radwin, LE (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA 02130 USA.
EM laurel.radwin@va.gov
FU Department of Veteran Affairs, Veterans Health Administration, VISN 1
Research Enhancement Fund
FX The article reported here was supported by the Department of Veteran
Affairs, Veterans Health Administration, VISN 1 Research Enhancement
Fund to Dr Radwin. For the remaining authors, no conflict of interest
was declared.
NR 23
TC 0
Z9 0
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1057-3631
EI 1550-5065
J9 J NURS CARE QUAL
JI J. Nurs. Care Qual.
PD JUL-SEP
PY 2016
VL 31
IS 3
BP 269
EP 274
DI 10.1097/NCQ.0000000000000165
PG 6
WC Nursing
SC Nursing
GA DT4TR
UT WOS:000381474500012
PM 26595361
ER
PT J
AU Pandey, N
Herrera, HH
Johnson, CM
MacCarthy, AA
Copeland, LA
AF Pandey, Nivedita
Herrera, Henry H.
Johnson, Christopher M.
MacCarthy, Andrea A.
Copeland, Laurel A.
TI Preventative care for patients with inflammatory bowel disease in the
Veterans Health Administration
SO MEDICINE
LA English
DT Article
DE inflammatory bowel disease; preventative health; veterans health
administration
ID INCREASED RISK; METAANALYSIS; GUIDELINES; DIAGNOSES; THERAPY; AFFAIRS;
CANCER
AB Patients with inflammatory bowel disease (IBD) have underlying immune dysregulation. Immunosuppressive medications put them at risk of infection. This study assessed rates of recommended vaccinations and preventative screening in patients with IBD.
Nationwide data on patients diagnosed with IBD in the Veterans Health Administration (VHA) October 2004 to September 2014 were extracted. Variation in vaccination, screenings, and risk of death by demographic factors (age group, gender) were estimated in bivariate and multivariable analyses.
During the 10-year study period, 62,002 patients were treated for IBD. Nonmelanoma skin cancer was found in 2.6%, and these patients more commonly accessed dermatology clinic (22.5% vs 15.2%; chi-square = 66.6; df = 1; P < 0.0001). In total, 15% received DEXA scans, especially women (34.7% vs 13.2% men; chi-square = 1415.5; df = 1; P < 0.0001). Eye manifestations were noted in 38.3% yet only 31% were referred to ophthalmology. Abnormal Pap smears were found for 15% of women < 65 (compared to 5% among normal patient populations); 34% had no record of Pap smear in VHA data. Vaccination rates were modest: pneumococcal 39%; TDAP 23%; hepatitis B 3%; varicella and PPD <0.5%. In an adjusted logistic regression model, 5-year mortality was lower among those using primary care prior to IBD diagnosis (odds ratio [OR] = 0.61; 95% CI 0.55-0.68).
Despite the current IBD guidelines, vaccination and preventative screening rates were unacceptably low among patients diagnosed with IBD. Interventions such as education and increased awareness may be needed to improve these rates.
C1 [Pandey, Nivedita] Cent Texas Vet Hlth Care Syst, Gastroenterol Serv, Temple, TX USA.
[Herrera, Henry H.; Johnson, Christopher M.] Scott & White Mem Hosp & Clin, Dept Med, Div Gastroenterol, Temple, TX 76508 USA.
[MacCarthy, Andrea A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Copeland, Laurel A.] Scott & White Mem Hosp & Clin, Dept Med, Ctr Appl Hlth Res, Cent Texas Vet Hlth Care Syst, Temple, TX 76508 USA.
[Copeland, Laurel A.] UT Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA.
RP Pandey, N (reprint author), Vet Mem Dr, Temple, TX USA.
EM nainidel@gmail.com
OI Copeland, Laurel/0000-0002-9478-0209
FU Veterans Health Administration HSRD Award [09-335]; Gastroenterology
division of Central Texas Veterans Health Care System; Veterans Health
Administration; Scott & White Healthcare; NIMH
FX This study was supported by the Veterans Health Administration HSR&D
Award #09-335 with additional support from Gastroenterology division of
Central Texas Veterans Health Care System. LAC received grant funds from
Veterans Health Administration, Scott & White Healthcare, and NIMH.
NR 28
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD JUL
PY 2016
VL 95
IS 27
AR e4012
DI 10.1097/MD.0000000000004012
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS1QW
UT WOS:000380372400027
PM 27399081
ER
PT J
AU Pinello, L
Canver, MC
Hoban, MD
Orkin, SH
Kohn, DB
Bauer, DE
Yuan, GC
AF Pinello, Luca
Canver, Matthew C.
Hoban, Megan D.
Orkin, Stuart H.
Kohn, Donald B.
Bauer, Daniel E.
Yuan, Guo-Cheng
TI Analyzing CRISPR genome-editing experiments with CRISPResso
SO NATURE BIOTECHNOLOGY
LA English
DT Letter
ID CAS9; SPECIFICITY; NUCLEASES; SYSTEM; CELLS
C1 [Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Pinello, Luca; Yuan, Guo-Cheng] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Canver, Matthew C.; Orkin, Stuart H.; Bauer, Daniel E.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA.
[Canver, Matthew C.; Orkin, Stuart H.; Bauer, Daniel E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Canver, Matthew C.; Orkin, Stuart H.; Bauer, Daniel E.] Harvard Univ, Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
[Canver, Matthew C.; Orkin, Stuart H.; Bauer, Daniel E.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA.
[Hoban, Megan D.; Kohn, Donald B.] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, Los Angeles, CA USA.
[Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA.
RP Pinello, L (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.; Pinello, L (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
EM lpinello@jimmy.harvard.edu; daniel.bauer@childrens.harvard.edu;
gcyuan@jimmy.harvard.edu
OI Hoban, Megan/0000-0002-5011-9582
FU NHGRI NIH HHS [R01 HG005085, K99 HG008399]; NHLBI NIH HHS [P01 HL032262,
R01 HL032259, R01 HL119099, T32 HL007574]; NIDDK NIH HHS [F30 DK103359,
K08 DK093705, P30 DK049216]
NR 9
TC 7
Z9 7
U1 8
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2016
VL 34
IS 7
BP 695
EP 697
DI 10.1038/nbt.3583
PG 4
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DT2TT
UT WOS:000381335400017
PM 27404874
ER
PT J
AU Palchaudhuri, R
Saez, B
Hoggatt, J
Schajnovitz, A
Sykes, DB
Tate, TA
Czechowicz, A
Kfoury, Y
Ruchika, FNU
Rossi, DJ
Verdine, GL
Mansour, MK
Scadden, DT
AF Palchaudhuri, Rahul
Saez, Borja
Hoggatt, Jonathan
Schajnovitz, Amir
Sykes, David B.
Tate, Tiffany A.
Czechowicz, Agnieszka
Kfoury, Youmna
Ruchika, F. N. U.
Rossi, Derrick J.
Verdine, Gregory L.
Mansour, Michael K.
Scadden, David T.
TI Non-genotoxic conditioning for hematopoietic stem cell transplantation
using a hematopoietic-cell-specific internalizing immunotoxin
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; CHRONIC GRANULOMATOUS-DISEASE;
GENE-THERAPY; MONOCLONAL-ANTIBODIES; MIXED CHIMERISM; FANCONI-ANEMIA;
CANCER; MOUSE; CYCLOPHOSPHAMIDE; ENGRAFTMENT
AB Hematopoietic stem cell transplantation (HSCT) offers curative therapy for patients with hemoglobinopathies, congenital immunodeficiencies, and other conditions, possibly including AIDS. Autologous HSCT using genetically corrected cells would avoid the risk of graft-versus-host disease (GVHD), but the genotoxicity of conditioning remains a substantial barrier to the development of this approach. Here we report an internalizing immunotoxin targeting the hematopoietic-cell-restricted CD45 receptor that effectively conditions immunocompetent mice. A single dose of the immunotoxin, CD45-saporin (SAP), enabled efficient (>90%) engraftment of donor cells and full correction of a sickle-cell anemia model. In contrast to irradiation, CD45-SAP completely avoided neutropenia and anemia, spared bone marrow and thymic niches, enabling rapid recovery of T and B cells, preserved anti-fungal immunity, and had minimal overall toxicity. This non-genotoxic conditioning method may provide an attractive alternative to current conditioning regimens for HSCT in the treatment of non-malignant blood diseases.
C1 [Palchaudhuri, Rahul; Saez, Borja; Hoggatt, Jonathan; Schajnovitz, Amir; Sykes, David B.; Tate, Tiffany A.; Czechowicz, Agnieszka; Kfoury, Youmna; Ruchika, F. N. U.; Rossi, Derrick J.; Verdine, Gregory L.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Palchaudhuri, Rahul; Saez, Borja; Hoggatt, Jonathan; Schajnovitz, Amir; Sykes, David B.; Tate, Tiffany A.; Kfoury, Youmna; Ruchika, F. N. U.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Palchaudhuri, Rahul; Saez, Borja; Hoggatt, Jonathan; Schajnovitz, Amir; Sykes, David B.; Tate, Tiffany A.; Czechowicz, Agnieszka; Kfoury, Youmna; Ruchika, F. N. U.; Rossi, Derrick J.; Verdine, Gregory L.; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Palchaudhuri, Rahul; Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Czechowicz, Agnieszka; Rossi, Derrick J.] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA.
[Czechowicz, Agnieszka; Rossi, Derrick J.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
[Czechowicz, Agnieszka] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Mansour, Michael K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
RP Palchaudhuri, R; Scadden, DT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.; Palchaudhuri, R; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.; Palchaudhuri, R; Scadden, DT (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Palchaudhuri, R (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
EM rpalcha2@gmail.com; david_scadden@harvard.edu
FU Life Science Research Foundation fellowship - Jake Wetchler Foundation;
American Society of Hematology scholar award; NIH NHLBI [K99/R00
HL119559, HL44851, HL129903, HL107630]; NIAID NIH [1K08AI110655]; Gerald
and Darlene Jordan Chair of Medicine of Harvard University; Harvard
Blavatnik Biomedical Accelerator Fund
FX We would like to thank R.T. Bronson (Harvard Medical School) for
histology services, G. Sempowski (Duke University) for mouse sjTREC
plasmid, and the Harvard Stem Cell and Regenerative Biology flow
cytometry core. We would like to acknowledge N. Van Gastel and A.
Papazian for technical assistance. R.P. was supported by a Life Science
Research Foundation fellowship sponsored by the Jake Wetchler
Foundation. B.S. was supported by an American Society of Hematology
scholar award. J.H. was supported by an NIH NHLBI K99/R00 HL119559.
M.K.M. was supported by NIAID NIH 1K08AI110655. D.T.S. was supported by
the Gerald and Darlene Jordan Chair of Medicine of Harvard University.
Grants from the Harvard Blavatnik Biomedical Accelerator Fund (D.T.S.),
NIH NHLBI HL44851 (D.T.S.), HL129903 (D.T.S., D.J.R.), and HL107630
(D.J.R.) funded this work.
NR 69
TC 8
Z9 8
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD JUL
PY 2016
VL 34
IS 7
BP 738
EP +
DI 10.1038/nbt.3584
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DT2TT
UT WOS:000381335400028
PM 27272386
ER
PT J
AU Kaviani, S
Zeraatkar, N
Sajedi, S
Akbarzadeh, A
Gorjizadeh, N
Farahani, MH
Teimourian, B
Ghafarian, P
Sabet, H
Ay, MR
AF Kaviani, Sanaz
Zeraatkar, Navid
Sajedi, Salar
Akbarzadeh, Afshin
Gorjizadeh, Nahid
Farahani, Mohammad Hossein
Teimourian, Behnoosh
Ghafarian, Pardis
Sabet, Hamid
Ay, Mohammad Reza
TI Design and development of a dedicated portable gamma camera system for
intra-operative imaging
SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS
LA English
DT Article
DE Sentinel lymph node (SLN); Lymphoscintigraphy; SURGEOSIGHT-I; Breast
cancer; Intra-operative gamma camera
ID LYMPH-NODE BIOPSY; SCINTILLATION CAMERA; SENTINEL NODE; BREAST-CANCER;
SMALL-FIELD; MELANOMA; SURGERY; PROBES; TESTS
AB Purpose: We developed a high performance portable gamma camera platform dedicated to identification of sentinel lymph nodes (SLNs) and radio-guided surgery for cancer patients. In this work, we present the performance characteristics of SURGEOSIGHT-I, the first version of this platform that can intraoperatively provide high-resolution images of the surveyed areas.
Methods: At the heart of this camera, there is a 43 x 43 array of pixelated sodium-activated cesium iodide (CsI(Na)) scintillation crystal with 1 x 1mm(2) pixel size and 5 mm thickness coupled to a Hamamatsu H8500 flat-panel multi-anode (64 channels) photomultiplier tube. The probe is equipped with a hexagonal parallel-hole lead collimator with 1.2 mm holes. The detector, collimator, and the associated front-end electronics are encapsulated in a common housing referred to as head.
Results: Our results show a count rate of similar to 41 kcps for 20% count loss. The extrinsic energy resolution was measured as 20.6% at 140 keV. The spatial resolution and the sensitivity of the system on the collimator surface was measured as 2.2 mm and 142 cps/MBq, respectively. In addition, the integral and differential uniformity, after uniformity correction, in useful field-of-view (UFOV) were measured 4.5% and 4.6%, respectively.
Conclusions: This system can be used for a number of clinical applications including SLN biopsy and radiopharmaceutical-guided surgery. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
C1 [Kaviani, Sanaz; Zeraatkar, Navid; Sajedi, Salar; Akbarzadeh, Afshin; Gorjizadeh, Nahid; Farahani, Mohammad Hossein; Teimourian, Behnoosh; Ay, Mohammad Reza] Univ Tehran Med Sci, Res Ctr Mol & Cellular Imaging, Tehran, Iran.
[Gorjizadeh, Nahid; Ay, Mohammad Reza] Univ Tehran Med Sci, Dept Med Phys & Biomed Engn, Tehran, Iran.
[Ghafarian, Pardis] Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, Chron Resp Dis Res Ctr, NRITLD, Tehran, Iran.
[Ghafarian, Pardis] Shahid Beheshti Univ Med Sci, Masih Daneshvari Hosp, PET CT & Cyclotron Ctr, Tehran, Iran.
[Sabet, Hamid] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
RP Ay, MR (reprint author), Univ Tehran Med Sci, Dept Med Phys & Biomed Engn, Tehran, Iran.
EM mohammadreza_ay@tums.ac.ir
FU Tehran University of Medical Sciences, Tehran, Iran [20386]
FX This work was supported under Grant number 20386, Tehran University of
Medical Sciences, Tehran, Iran.
NR 39
TC 2
Z9 2
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1120-1797
EI 1724-191X
J9 PHYS MEDICA
JI Phys. Medica
PD JUL
PY 2016
VL 32
IS 7
BP 889
EP 897
DI 10.1016/j.ejmp.2016.06.004
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DT6IS
UT WOS:000381588500005
PM 27345258
ER
PT J
AU Ouyang, Z
Liu, B
Yasmin-Karim, S
Sajo, E
Ngwa, W
AF Ouyang, Zi
Liu, Bo
Yasmin-Karim, Sayeda
Sajo, Erno
Ngwa, Wilfred
TI Nanoparticle-aided external beam radiotherapy leveraging the Cerenkov
effect
SO PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS
LA English
DT Article
DE Cerenkov; Titania nanoparticles; EBRT; Tumor sensitization
ID BREAST IRRADIATION APBI; TARGETED RADIOTHERAPY; GOLD NANOPARTICLES;
RADIATION-THERAPY; TITANIUM-DIOXIDE; REAL-TIME; TISSUE; BRACHYTHERAPY;
SYSTEM
AB This study investigates the feasibility of exploiting the Cerenkov radiation (CR) present during external beam radiotherapy (EBRT) for significant therapeutic gain, using titanium dioxide (titania) nanoparticles (NPs) delivered via newly designed radiotherapy biomaterials. Using Monte Carlo radiation transport simulations, we calculated the total CR yield inside a tumor volume during EBRT compared to that of the radionuclides. We also considered a novel approach for intratumoral titania delivery using radiotherapy biomaterials (e.g. fiducials) loaded with NPs. The intratumoral distribution/diffusion of titania released from the fiducials was calculated. To confirm the CR induced enhancement in EBRT experimentally, we used 6 MV radiation to irradiate human lung cancer cells with or without titania NPs and performed clonogenic assays. For a radiotherapy biomaterial loaded with 20 mu g/g of 2-nm titania NPs, at least 1 mu g/g could be delivered throughout a tumor sub-volume of 2-cm diameter after 14 days. This concentration level could inflict substantial damage to cancer cells during EBRT. The Monte Carlo results showed the CR yield by 6 MV radiation was higher than by the radionuclides of interest and hence greater damage might be obtained during EBRT. In vitro study showed significant enhancement with 6 MV radiation and titania NPs. These preliminary findings demonstrate a potential new approach that can be used to take advantage of the CR present during megavoltage EBRT to boost damage to cancer cells. The results provide significant impetus for further experimental studies towards the development of nanoparticleaided EBRT powered by the Cerenkov effect. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
C1 [Ouyang, Zi; Yasmin-Karim, Sayeda; Ngwa, Wilfred] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02215 USA.
[Ouyang, Zi; Yasmin-Karim, Sayeda; Ngwa, Wilfred] Harvard Med Sch, 75 Francis St, Boston, MA 02215 USA.
[Ouyang, Zi; Liu, Bo; Sajo, Erno; Ngwa, Wilfred] Univ Massachusetts, Dept Phys & Appl Phys, Med Phys Program, Lowell, MA USA.
RP Ngwa, W (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 75 Francis St, Boston, MA 02215 USA.; Ngwa, W (reprint author), Harvard Med Sch, 75 Francis St, Boston, MA 02215 USA.
EM wngwa@lroc.harvard.edu
FU NCI NIH HHS [K01 CA172478]
NR 22
TC 4
Z9 4
U1 3
U2 3
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1120-1797
EI 1724-191X
J9 PHYS MEDICA
JI Phys. Medica
PD JUL
PY 2016
VL 32
IS 7
BP 944
EP 947
DI 10.1016/j.ejmp.2016.06.015
PG 4
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DT6IS
UT WOS:000381588500013
PM 27397906
ER
PT J
AU Merlino, G
Herlyn, M
Fisher, DE
Bastian, BC
Flaherty, KT
Davies, MA
Wargo, JA
Curiel-Lewandrowski, C
Weber, MJ
Leachman, SA
Soengas, MS
McMahon, M
Harbour, JW
Swetter, SM
Aplin, AE
Atkins, MB
Bosenberg, MW
Dummer, R
Gershenwald, JE
Halpern, AC
Herlyn, D
Karakousis, GC
Kirkwood, JM
Krauthammer, M
Lo, RS
Long, GV
McArthur, G
Ribas, A
Schuchter, L
Sosman, JA
Smalley, KS
Steeg, P
Thomas, NE
Tsao, H
Tueting, T
Weeraratna, A
Xu, G
Lomax, R
Martin, A
Silverstein, S
Turnham, T
Ronai, ZA
AF Merlino, Glenn
Herlyn, Meenhard
Fisher, David E.
Bastian, Boris C.
Flaherty, Keith T.
Davies, Michael A.
Wargo, Jennifer A.
Curiel-Lewandrowski, Clara
Weber, Michael J.
Leachman, Sancy A.
Soengas, Maria S.
McMahon, Martin
Harbour, J. William
Swetter, Susan M.
Aplin, Andrew E.
Atkins, Michael B.
Bosenberg, Marcus W.
Dummer, Reinhard
Gershenwald, Jeffrey E.
Halpern, Allan C.
Herlyn, Dorothee
Karakousis, Giorgos C.
Kirkwood, John M.
Krauthammer, Michael
Lo, Roger S.
Long, Georgina V.
McArthur, Grant
Ribas, Antoni
Schuchter, Lynn
Sosman, Jeffrey A.
Smalley, Keiran S.
Steeg, Patricia
Thomas, Nancy E.
Tsao, Hensin
Tueting, Thomas
Weeraratna, Ashani
Xu, George
Lomax, Randy
Martin, Alison
Silverstein, Steve
Turnham, Tim
Ronai, Ze'ev A.
TI The state of melanoma: challenges and opportunities
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE melanoma; prevention; early diagnosis; metastasis; dormancy; therapy
AB The Melanoma Research Foundation (MRF) has charted a comprehensive assessment of the current state of melanoma research and care. Intensive discussions among members of the MRF Scientific Advisory Council and Breakthrough Consortium, a group that included clinicians and scientists, focused on four thematic areas diagnosis/early detection, prevention, tumor cell dormancy (including metastasis), and therapy (response and resistance). These discussions extended over the course of 2015 and culminated at the Society of Melanoma Research 2015 International Congress in November. Each of the four groups has outlined their thoughts as per the current status, challenges, and opportunities in the four respective areas. The current state and immediate and longterm needs of the melanoma field, from basic research to clinical management, are presented in the following report.
C1 [Merlino, Glenn] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Herlyn, Meenhard; Herlyn, Dorothee; Weeraratna, Ashani] Wistar Inst Anat & Biol, Melanoma Res Ctr, 3601 Spruce St, Philadelphia, PA 19104 USA.
[Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA USA.
[Bastian, Boris C.] Univ Calif San Francisco, Dept Dermatol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Bastian, Boris C.] Univ Calif San Francisco, Dept Pathol, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94140 USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Dev Therapeut, Ctr Canc, Charlestown, MA USA.
[Davies, Michael A.; Wargo, Jennifer A.; Gershenwald, Jeffrey E.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med & Surg Oncol, Houston, TX 77030 USA.
[Curiel-Lewandrowski, Clara] Univ Arizona, Ctr Canc, Dept Med, Tucson, AZ USA.
[Curiel-Lewandrowski, Clara] Univ Arizona, Ctr Canc, Dept Dermatol, Tucson, AZ USA.
[Weber, Michael J.] Univ Virginia, Sch Med, Dept Microbiol Immunol & Canc Biol, Charlottesville, VA 22908 USA.
[Leachman, Sancy A.] Oregon Hlth & Sci Univ, Dept Dermatol, Knight Canc Inst, Melanoma & Skin Canc Program, Portland, OR USA.
[Soengas, Maria S.] CNIO, Mol Oncol Program, Melanoma Lab, Madrid, Spain.
[McMahon, Martin] Huntsman Canc Inst, Dept Dermatol, Salt Lake City, UT USA.
[Harbour, J. William] Univ Miami, Bascom Palmer Eye Inst, Miami, FL USA.
[Harbour, J. William] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
[Swetter, Susan M.] Stanford Univ, Med Ctr, Dept Dermatol, Palo Alto, CA 94304 USA.
[Swetter, Susan M.] VA Palo Alto Hlth Care Syst, Inst Canc, Palo Alto, CA USA.
[Aplin, Andrew E.] Thomas Jefferson Univ, Sidney Kimmel Canc Ctr, Philadelphia, PA 19107 USA.
[Atkins, Michael B.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Bosenberg, Marcus W.] Yale Univ, Ctr Canc, Dept Dermatol & Dermatopathol, New Haven, CT USA.
[Dummer, Reinhard] Univ Zurich, Dept Dermatol, Zurich, Switzerland.
[Halpern, Allan C.] Mem Sloan Kettering Canc Ctr, Dermatol, 1275 York Ave, New York, NY 10021 USA.
[Karakousis, Giorgos C.; Schuchter, Lynn; Xu, George] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Kirkwood, John M.] Univ Pittsburgh, Melanoma & Skin Canc Program, Pittsburgh, PA USA.
[Krauthammer, Michael] Yale Univ, Dept Pathol, Ctr Canc, New Haven, CT USA.
[Lo, Roger S.; Ribas, Antoni] Univ Calif Los Angeles, Dept Med Oncol & Dermatol, Los Angeles, CA USA.
[Long, Georgina V.] Univ Sydney, Melanoma Inst, Sydney, NSW, Australia.
[McArthur, Grant] Peter MacCallum Canc Ctr, Dept Canc Med, East Melbourne, Vic, Australia.
[Sosman, Jeffrey A.] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37212 USA.
[Smalley, Keiran S.] H Lee Moffitt Canc Ctr & Res Inst, Dept Tumor Biol, Tampa, FL USA.
[Steeg, Patricia] NCI, Women Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Thomas, Nancy E.] Univ N Carolina, Melanoma Program, Dept Dermatol, Lineberger Canc Ctr, Chapel Hill, NC USA.
[Tsao, Hensin] Massachusetts Gen Hosp, Melanoma & Pigmented Lesion Ctr, Charlestown, MA USA.
[Tueting, Thomas] Univ Bonn, Dept Dermatol, Bonn, Germany.
[Lomax, Randy; Martin, Alison; Silverstein, Steve; Turnham, Tim] Melanoma Res Fdn, Washington, DC USA.
[Ronai, Ze'ev A.] Sanford Burnham Prebys Med Discovery Inst, Tumor Initiat & Maintenance Program, La Jolla, CA 92037 USA.
RP Ronai, ZA (reprint author), Sanford Burnham Prebys Med Discovery Inst, Tumor Initiat & Maintenance Program, La Jolla, CA 92037 USA.
EM ronai@SBPdiscovery.org
FU NCI NIH HHS [P30 CA016672, P30 CA010815, P50 CA121973]; NIAMS NIH HHS
[R01 AR043369]
NR 0
TC 6
Z9 6
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD JUL
PY 2016
VL 29
IS 4
BP 404
EP 416
DI 10.1111/pcmr.12475
PG 13
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA DT2IC
UT WOS:000381303000005
PM 27087480
ER
PT J
AU Adams, JM
Natarajan, S
AF Adams, Jeffrey M.
Natarajan, Sudha
TI Understanding Influence within the Context of Nursing Development of the
Adams Influence Model Using Practice, Research, and Theory
SO ADVANCES IN NURSING SCIENCE
LA English
DT Article
DE AIM; Adams influence model; conceptual model; Imogene King; influence;
LIPPES; middle-range theory; power
ID INFLUENCE TACTICS; ORGANIZATIONS; LEADERSHIP; SCALE; POWER
AB Acquiring influence, and knowing how to use it, is a required competency for nurse leaders, yet the concept of influence and how it works is not well described in the nursing literature. In this article, the authors examine what is known about influence and present an influence model specific to nurse leaders. The Adams Influence Model was developed through an iterative process and is based on a comprehensive review of the influence literature, expert commentary, multiple pilot studies, evaluation of nursing theories, and validation by an external data source. Rather than defining "how to" influence, the model serves as a guide for personal reflection, helping nurse leaders understand and reflect on the influence process and factors, tactics, and strategies they can use when seeking to influence others.
C1 [Adams, Jeffrey M.] Arizona State Univ, Coll Nursing & Hlth Innovat, Workforce Outcomes Res & Leadership Dev WORLD Ins, Phoenix, AZ USA.
[Adams, Jeffrey M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Adams, Jeffrey M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Natarajan, Sudha] Massachusetts Gen Hosp, Palliat Care Div, Boston, MA 02114 USA.
RP Adams, JM (reprint author), Brigham & Womens Hosp, Ctr Nursing Excellence, Workforce Outcomes Res & Leadership Dev Inst WORL, BC 4-006A,1620 Tremont St, Boston, MA 02120 USA.
EM jeffrey.m.adams@asu.edu
FU MGH Connell Research Scholars Program; Yvonne L. Munn Pre and
Postdoctoral Fellowship Grants
FX This work completed through financial support from the MGH Connell
Research Scholars Program and Yvonne L. Munn Pre and Postdoctoral
Fellowship Grants. The authors thank Dorothy Jones, EdD, RNC, FAAN,
Jeanette Ives Erickson, DNP, RN, FAAN, Joyce C. Clifford, PhD, RN, FAAN,
Danny Willis, PhD, RN, Callista Roy, PhD, RN, FAAN, Ada Sue Hinshaw,
PhD, RN, FAAN, Barbara Therrien, PhD, RN, FAAN, and Gail Keenan, PhD,
RN, FAAN, and Beth Kantz, MS, RN for their assistance in development of
this work.
NR 61
TC 0
Z9 0
U1 3
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0161-9268
EI 1550-5014
J9 ADV NURS SCI
JI Adv. Nurs. Sci.
PD JUL-SEP
PY 2016
VL 39
IS 3
BP E40
EP E56
DI 10.1097/ANS.0000000000000134
PG 17
WC Nursing
SC Nursing
GA DT0GS
UT WOS:000381161900004
PM 27490886
ER
PT J
AU Gygli, PE
Chang, JC
Gokozan, HN
Catacutan, FP
Schmidt, TA
Kaya, B
Goksel, M
Baig, FS
Chen, SN
Griveau, A
Michowski, W
Wong, M
Palanichamy, K
Sicinski, P
Nelson, RJ
Czeisler, C
Otero, JJ
AF Gygli, Patrick E.
Chang, Joshua C.
Gokozan, Hamza N.
Catacutan, Fay P.
Schmidt, Theresa A.
Kaya, Behiye
Goksel, Mustafa
Baig, Faisal S.
Chen, Shannon
Griveau, Amelie
Michowski, Wojciech
Wong, Michael
Palanichamy, Kamalakannan
Sicinski, Piotr
Nelson, Randy J.
Czeisler, Catherine
Otero, Jose J.
TI Cyclin A2 promotes DNA repair in the brain during both development and
aging
SO AGING-US
LA English
DT Article
DE Cyclin A2; DNA repair; mathematical modeling; neural stem cells;
ventricular zone/subventricular zone
ID STRAND BREAK REPAIR; CEREBELLAR CORTICAL LAMINATION; PROGENITOR CELLS;
HOMOLOGOUS RECOMBINATION; NEURAL STEM; NEOCORTICAL NEURONOGENESIS;
DEPENDENT KINASE; STOCHASTIC-MODEL; MAMMALIAN-CELLS; DAMAGE RESPONSE
AB Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation in CCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.
C1 [Gygli, Patrick E.; Gokozan, Hamza N.; Catacutan, Fay P.; Schmidt, Theresa A.; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S.; Czeisler, Catherine; Otero, Jose J.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA.
[Chang, Joshua C.] Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA.
[Chen, Shannon; Nelson, Randy J.] Ohio State Univ, Coll Med, Dept Neurosci, Columbus, OH 43210 USA.
[Griveau, Amelie; Wong, Michael] Univ Calif San Francisco, Dept Pediat, San Francisco Sch Med, San Francisco, CA 94143 USA.
[Michowski, Wojciech; Sicinski, Piotr] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
[Michowski, Wojciech; Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Palanichamy, Kamalakannan] Ohio State Univ, Coll Med, Dept Radiat Oncol, Columbus, OH 43210 USA.
RP Otero, JJ (reprint author), Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43210 USA.; Chang, JC (reprint author), Ohio State Univ, Math Biosci Inst, Columbus, OH 43210 USA.
EM joshchang@ucla.edu; jose.otero@osumc.edu
FU National Science Foundation [0635561]; Army Research Office [58386MA];
National Cancer Institute at the National Institutes of Health
[R01CA132740]; California Institute of Regenerative Medicine
[TG2-01153]; National Institute of Neurological Disorders and Stroke at
the National Institutes of Health [P30 NS045758]; National Heart, Lung,
and Blood Institute at the National Institutes of Health [R01HL123355];
National Center for Advancing Translational Sciences at the National
Institutes of Health [8UL1TR000090-05]
FX This work was supported by the National Science Foundation (Agreement
No. 0635561 to JCC); the Army Research Office (Grant No. 58386MA to
JCC); the National Cancer Institute at the National Institutes of Health
(Grant No. R01CA132740 to PS); the California Institute of Regenerative
Medicine (Grant Number TG2-01153 to JJO); the National Institute of
Neurological Disorders and Stroke at the National Institutes of Health
(Grant No. P30 NS045758); the National Heart, Lung, and Blood Institute
at the National Institutes of Health (Grant no. R01HL123355 to JJO and
CC) and the National Center for Advancing Translational Sciences at the
National Institutes of Health (Grant No. 8UL1TR000090-05).
NR 89
TC 0
Z9 0
U1 2
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD JUL
PY 2016
VL 8
IS 7
BP 1540
EP 1570
DI 10.18632/aging.100990
PG 31
WC Cell Biology
SC Cell Biology
GA DU1DV
UT WOS:000381949300019
PM 27425845
ER
PT J
AU Yeh, D
Peev, MP
Quraishi, SA
Osler, P
Chang, YC
Rando, EG
Albano, C
Darak, S
Velmahos, GC
AF Yeh, Dante
Peev, Miroslav P.
Quraishi, Sadeq A.
Osler, Polina
Chang, Yuchiao
Rando, Erin Gillis
Albano, Caitlin
Darak, Sharon
Velmahos, George C.
TI CLINICAL OUTCOMES OF INADEQUATE CALORIE DELIVERY AND PROTEIN DEFICIT IN
SURGICAL INTENSIVE CARE PATIENTS
SO AMERICAN JOURNAL OF CRITICAL CARE
LA English
DT Article
ID CRITICALLY-ILL PATIENTS; ENTERAL NUTRITION; ENERGY PROVISION; ICU
PATIENTS; GUIDELINES; PROTOCOL; THERAPY; TRIAL; MALNUTRITION; SUPPORT
AB Background Adequate nutritional therapy in critically ill patients is integral to optimal outcome.
Objective To evaluate the association between cumulative macronutrient deficit and overall morbidity in surgical intensive care unit patients.
Methods Adult patients receiving enteral nutrition for more than 72 hours were included if they had no previous admission to the surgical intensive care unit, had received no enteral feedings before admission, had no intestinal obstruction or ileus, and survived 72 hours or more after admission. Data on demographics, outcomes, and nutritional intake during the unit stay were collected for up to 14 days until oral intake began, discharge, or death. Outcome variables included lengths of stay in the hospital and intensive care unit, days with no mechanical ventilation, complications, and mortality.
Results Of 94 participants, 71% were men, mean age was 63 years, and mean score on the Acute Physiology and Chronic Health Evaluation II was 14. Patients with high cumulative calorie deficit (>= 6000 cal) and high protein deficit (>= 300 g) had significantly fewer days with no mechanical ventilation (P < .001), longer unit stays (P < .001), longer hospital stays (P = .007), more total complications (P = .007), and more infectious complications (P = .009) than other participants. These associations remained significant in multivariable models after adjustments for age, sex, reason for admission, and propensity score of deficit. In-hospital and 30-day mortality did not differ.
Conclusions Cumulative macronutrient deficits have important clinical outcomes in surgical intensive care patients.
C1 [Yeh, Dante] Harvard Med Sch, Surg, Boston, MA USA.
[Yeh, Dante] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
[Peev, Miroslav P.] Tufts Univ, Boston, MA 02111 USA.
[Quraishi, Sadeq A.] Massachusetts Gen Hosp, Harvard Med Sch, Anesthesia, Boston, MA 02114 USA.
[Quraishi, Sadeq A.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Osler, Polina] Harvard Med Sch, Boston, MA USA.
[Chang, Yuchiao] Harvard Med Sch, Med, Boston, MA USA.
[Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA.
[Rando, Erin Gillis; Albano, Caitlin; Darak, Sharon] Massachusetts Gen Hosp, Dept Nutr & Food Serv, Boston, MA 02114 USA.
[Velmahos, George C.] Massachusetts Gen Hosp, Harvard Med Sch, Surg, Boston, MA 02114 USA.
[Velmahos, George C.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA.
RP Yeh, D (reprint author), 165 Cambridge St 810, Boston, MA 02114 USA.
EM dyeh2@partners.org
NR 26
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CRITICAL CARE NURSES
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 1062-3264
EI 1937-710X
J9 AM J CRIT CARE
JI Am. J. Crit. Care
PD JUL
PY 2016
VL 25
IS 4
BP 318
EP 326
DI 10.4037/ajcc2016584
PG 9
WC Critical Care Medicine; Nursing
SC General & Internal Medicine; Nursing
GA DU0BD
UT WOS:000381865400008
PM 27369030
ER
PT J
AU Juliano, AF
Ting, EY
Mingkwansook, V
Hamberg, LM
Curtin, HD
AF Juliano, A. F.
Ting, E. Y.
Mingkwansook, V.
Hamberg, L. M.
Curtin, H. D.
TI Vestibular Aqueduct Measurements in the 45 degrees Oblique (Poschl)
Plane
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID ENDOLYMPHATIC DUCT; COMPUTED-TOMOGRAPHY; MENIERES-DISEASE; TEMPORAL
BONE; SAC
AB BACKGROUND AND PURPOSE: The 45 degrees oblique (Poschl) plane allows reliable depiction of the vestibular aqueduct, with virtually its entire length often visible on 1 CT image. We measured its midpoint width in this plane, aiming to determine normal measurement values based on this plane.
MATERIALS AND METHODS: We retrospectively evaluated temporal bone CT studies of 96 pediatric patients without sensorineural hearing loss. Midvestibular aqueduct widths were measured in the 45 degrees oblique plane by 2 independent readers by visual assessment (subjective technique). The vestibular aqueducts in 4 human cadaver specimens were also measured in this plane. In addition, there was a specimen that had undergone CT scanning before sectioning, and measurements made on that CT scan and on the histologic section were compared. Measurements from the 96 patients' CT images were then repeated by using findings derived from the radiologic-histologic comparison (objective technique).
RESULTS: All vestibular aqueducts were clearly identifiable on 45 degrees oblique-plane CT images. The mean for subjective measurement was 0.526 0.08 mm (range, 0.337-0.947 mm). The 97.5th percentile value was 0.702 mm. The mean for objective measurement was 0.537 +/- 0.077 mm (range, 0.331-0.922 mm). The 97.5th percentile value was 0.717 mm.
CONCLUSIONS: Measurements of the vestibular aqueduct can be performed reliably and accurately in the 45 degrees oblique plane. The mean midpoint width was 0.5 mm, with a range of 0.3-0.9 mm. These may be considered normal measurement values for the vestibular aqueduct midpoint width when measured in the 45 degrees oblique plane.
C1 [Juliano, A. F.; Curtin, H. D.] Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA.
[Hamberg, L. M.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA.
[Ting, E. Y.] Natl Univ Hlth Syst, Dept Diagnost Imaging, Singapore, Singapore.
[Mingkwansook, V.] Thammasat Univ Hosp, Dept Radiol, Pathum Thani, Thailand.
RP Juliano, AF (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA.
EM amy_juliano@meei.harvard.edu
NR 24
TC 0
Z9 0
U1 2
U2 2
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD JUL
PY 2016
VL 37
IS 7
BP 1331
EP 1337
DI 10.3174/ajnr.A4735
PG 7
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DS1NL
UT WOS:000380362600022
PM 27012297
ER
PT J
AU Sanchez, DF
Rodriguez, IM
Piris, A
Canete, S
Lezcano, C
Velazquez, EF
Fernandez-Nestosa, MJ
Mendez-Pena, JE
Hoang, MP
Cubilla, AL
AF Sanchez, Diego F.
Rodriguez, Ingrid M.
Piris, Adriano
Canete, Sofia
Lezcano, Cecilia
Velazquez, Elsa F.
Fernandez-Nestosa, Maria J.
Mendez-Pena, Javier E.
Hoang, Mai P.
Cubilla, Antonio L.
TI Clear Cell Carcinoma of the Penis: An HPV-related Variant of Squamous
Cell Carcinoma: A Report of 3 Cases
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE clear cell carcinoma; penile carcinoma; HPV
ID HUMAN-PAPILLOMAVIRUS DNA; P16(INK4A) EXPRESSION; FEATURES;
ADENOCARCINOMA; ASSOCIATION; PREVALENCE; INFECTION; SURVIVAL; TRACT
AB Penile clear cell carcinoma originating in skin adnexal glands has been previously reported. Here, we present 3 morphologically distinctive penile tumors with prominent clear cell features originating not in the penile skin but in the mucosal tissues of the glans surface squamous epithelium. Clinical and pathologic features were evaluated. Immunohistochemical stains were GATA3 and p16. Human papilloma virus (HPV) detection by in situ hybridization was performed in 3 cases, and whole-tissue section-polymerase chain reaction was performed in 1 case. Patients' ages were 52, 88, and 95 years. Tumors were large and involved the glans and coronal sulcus in all cases. Microscopically, nonkeratinizing clear cells predominated. Growth was in solid nests with comedo-like or geographic necrosis. Focal areas of invasive warty or basaloid carcinomas showing in addition warty or basaloid penile intraepithelial neoplasia were present in 2 cases. There was invasion of corpora cavernosa, lymphatic vessels, veins, and perineural spaces in all cases. p16 was positive, and GATA3 stain was negative in the 3 cases. HPV was detected in 3 cases by in situ hybridization and in 1 case by polymerase chain reaction. Differential diagnoses included other HPV-related penile carcinomas, skin adnexal tumors, and metastatic renal cell carcinoma. Features that support primary penile carcinoma were tumor location, concomitant warty and/or basaloid penile intraepithelial neoplasia, and HPV positivity. Clinical groin metastases were present in all cases, pathologically confirmed in 1. Two patients died from tumor dissemination at 9 and 12 months after penectomy. Clear cell carcinoma, another morphologic variant related to HPV, originates in the penile mucosal surface and is probably related to warty carcinomas.
C1 [Sanchez, Diego F.; Rodriguez, Ingrid M.; Canete, Sofia; Cubilla, Antonio L.] Inst Patol & Invest, Cap Manuel Brizuela 325 & Ayala Velazquez, Asuncion 1584, Paraguay.
[Sanchez, Diego F.; Rodriguez, Ingrid M.; Cubilla, Antonio L.] Natl Univ Asuncion, Sch Med, Asuncion, Paraguay.
[Fernandez-Nestosa, Maria J.] Natl Univ Asuncion, Polytech Sch, San Lorenzo, Paraguay.
[Piris, Adriano] Harvard Med Sch, Mihm Cutaneous Pathol Consultat Serv, Brigham & Womens Hosp, Boston, MA USA.
[Velazquez, Elsa F.] Miraca Life Sci, Boston, MA USA.
[Velazquez, Elsa F.] Tuft Univ, Boston, MA USA.
[Mendez-Pena, Javier E.; Hoang, Mai P.] Harvard Med Sch, Dept Pathol, Boston, MA USA.
[Mendez-Pena, Javier E.; Hoang, Mai P.] Massachusetts Gen Hosp, Boston, MA USA.
[Lezcano, Cecilia] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
RP Cubilla, AL (reprint author), Inst Patol & Invest, Cap Manuel Brizuela 325 & Ayala Velazquez, Asuncion 1584, Paraguay.
EM antoniocubillaramos@gmail.com
NR 31
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD JUL
PY 2016
VL 40
IS 7
BP 917
EP 922
DI 10.1097/PAS.0000000000000607
PG 6
WC Pathology; Surgery
SC Pathology; Surgery
GA DR4AI
UT WOS:000379843400006
PM 26848799
ER
PT J
AU Phipps, JE
Hoyt, T
Vela, D
Wang, TY
Michalek, JE
Buja, LM
Jang, IK
Milner, TE
Feldman, MD
AF Phipps, Jennifer E.
Hoyt, Taylor
Vela, Deborah
Wang, Tianyi
Michalek, Joel E.
Buja, L. Maximilian
Jang, Ik-Kyung
Milner, Thomas E.
Feldman, Marc D.
TI Diagnosis of Thin-Capped Fibroatheromas in Intravascular Optical
Coherence Tomography Images Effects of Light Scattering
SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS
LA English
DT Article
DE atherosclerosis; lipids; myocytes, smooth muscle; plaque, amyloid;
tomography, optical coherence
ID NATIVE CORONARY-ARTERIES; EX-VIVO VALIDATION; IN-VIVO; TISSUE
CHARACTERIZATION; LESION MORPHOLOGY; RUPTURED PLAQUES; ULTRASOUND; OCT;
FREQUENCY; IVUS
AB Background-Intravascular optical coherence tomography (IVOCT) images are recorded by detecting light backscattered within coronary arteries. We hypothesize that non-thin-capped fibroatheroma (TCFA) causes may scatter light to create the false appearance of IVOCT TCFA.
Methods and Results-Ten human cadaver hearts were imaged with IVOCT (n=14 coronary arteries). IVOCT and histological TCFA images were coregistered and compared. Of 21 IVOCT TCFAs (fibrous cap <65 mu m, lipid arc > 1 quadrant), only 8 were true histological TCFA. Foam cell infiltration was responsible for 70% of false IVOCT TCFA and caused both thick-capped fibroatheromas to appear as TCFA, and the appearance of TCFAs when no lipid core was present. Other false IVOCT TCFA causes included smooth muscle cell-rich fibrous tissue (12%) and loose connective tissue (9%). If the lipid arc >1 quadrant (obtuse) criterion was disregarded, 45 IVOCT TCFAs were identified, and sensitivity of IVOCT TCFA detection increased from 63% to 87%, and specificity remained high at 92%.
Conclusions-We demonstrate that IVOCT can exhibit 87% (95% CI, 75%-93%) sensitivity and 92% specificity (95% CI, 86%-96%) to detect all lipid arcs (both obtuse and acute, <1 quadrant) TCFA, and we also propose new mechanisms involving light scattering that explain why other plaque components can masquerade as TCFA and cause low positive predictive value of IVOCT for TCFA detection (47% for obtuse lipid arcs). Disregarding the lipid arc > 1 quadrant requirement enhances the ability of IVOCT to detect TCFA.
C1 [Phipps, Jennifer E.; Hoyt, Taylor; Feldman, Marc D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,MSC 7872, San Antonio, TX 78229 USA.
[Michalek, Joel E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Vela, Deborah; Buja, L. Maximilian] Texas Heart Inst, Dept Cardiovasc Pathol, Houston, TX 77025 USA.
[Wang, Tianyi; Milner, Thomas E.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78712 USA.
[Jang, Ik-Kyung] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
[Feldman, Marc D.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA.
RP Feldman, MD (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr,MSC 7872, San Antonio, TX 78229 USA.
EM feldmanm@uthscsa.edu
FU Veterans Health Administration Merit Grant [I01 BX000397]; Clayton
Foundation, Houston, TX; Pathobiology of Occlusive Vascular Disease
NIH/NHLBI at the UT Health Science Center San Antonio (UTHSCSA);
American Heart Association [13POST17080074]; Biomedical Engineering
Advancement fund at the University of Texas at Austin
FX This study was supported by The Veterans Health Administration Merit
Grant I01 BX000397; The Clayton Foundation, Houston, TX; Pathobiology of
Occlusive Vascular Disease NIH/NHLBI T32 at the UT Health Science Center
San Antonio (UTHSCSA); American Heart Association 13POST17080074; The
Biomedical Engineering Advancement fund at the University of Texas at
Austin.
NR 32
TC 3
Z9 3
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-7640
EI 1941-7632
J9 CIRC-CARDIOVASC INTE
JI Circ.-Cardiovasc. Interv.
PD JUL
PY 2016
VL 9
IS 7
AR e003163
DI 10.1161/CIRCINTERVENTIONS.115.003163
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DS2MW
UT WOS:000380607800001
ER
PT J
AU Copes, LE
Pober, BR
Terilli, CA
AF Copes, L. E.
Pober, B. R.
Terilli, C. A.
TI Description of Common Musculoskeletal Findings in Williams Syndrome and
Implications for Therapies
SO CLINICAL ANATOMY
LA English
DT Review
DE Williams Syndrome; musculoskeletal; physical therapy
ID SUPRAVALVULAR AORTIC-STENOSIS; BEUREN-SYNDROME; ADULTS; CHILDREN;
HYPERCALCEMIA; MECHANISMS; HYPERTONIA; SCOLIOSIS
AB Williams syndrome (WS), also referred to as Williams-Beuren syndrome (WBS), is a relatively rare genetic disorder affecting similar to 1/10,000 persons. Since the disorder is caused by a micro-deletion of similar to 1.5 Mb, it is not surprising that the manifestations of WS are extremely broad, involving most body systems. In this paper, we primarily focus on the musculoskeletal aspects of WS as these findings have not been the subject of a comprehensive review. We review the MSK features commonly seen in individuals with WS, along with related sensory and neurological issues interacting with and compounding underlying MSK abnormalities. We end by providing perspective, particularly from the vantage point of a physical therapist, on therapeutic interventions to address the most common MSK and related features seen in WS. (C) 2016 Wiley Periodicals, Inc.
C1 [Copes, L. E.; Pober, B. R.] Quinnipiac Univ, Frank H Netter MD Sch Med, Dept Med Sci, Hamden, CT USA.
[Pober, B. R.] Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA.
[Pober, B. R.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
[Terilli, C. A.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA.
[Terilli, C. A.] Rose F Kennedy Childrens Evaluat & Rehabil Ctr Mo, Bronx, NY USA.
RP Copes, LE (reprint author), Quinnipiac Univ, Frank H Netter MD Sch Med, Dept Med Sci, NH MED, 275 Mt Carmel Ave, Hamden, CT 06518 USA.
EM lynn.copes@quinnipiac.edu
NR 28
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0897-3806
EI 1098-2353
J9 CLIN ANAT
JI Clin. Anat.
PD JUL
PY 2016
VL 29
IS 5
BP 578
EP 589
DI 10.1002/ca.22685
PG 12
WC Anatomy & Morphology
SC Anatomy & Morphology
GA DS7FD
UT WOS:000380947500007
PM 26749433
ER
PT J
AU Politei, JM
Bouhassira, D
Germain, DP
Goizet, C
Guerrero-Sola, A
Hilz, MJ
Hutton, EJ
Karaa, A
Liguori, R
Uceyler, N
Zeltzer, LK
Burlina, A
AF Politei, Juan M.
Bouhassira, Didier
Germain, Dominique P.
Goizet, Cyril
Guerrero-Sola, Antonio
Hilz, Max J.
Hutton, Elspeth J.
Karaa, Amel
Liguori, Rocco
Ueceyler, Nurcan
Zeltzer, Lonnie K.
Burlina, Alessandro
TI Pain in Fabry Disease: Practical Recommendations for Diagnosis and
Treatment
SO CNS NEUROSCIENCE & THERAPEUTICS
LA English
DT Article
DE Diagnosis; Enzyme replacement therapy; Fabry disease; Pain; Peripheral
nervous system
ID ENZYME REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; CHRONIC
NEUROPATHIC PAIN; SMALL FIBER DYSFUNCTION; AGALSIDASE-BETA; SCREENING
QUESTIONNAIRE; SYSTEM INVOLVEMENT; DOSE REDUCTION; ADULT PATIENTS;
OUTCOME SURVEY
AB Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Wurzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications.
C1 [Politei, Juan M.] Fdn Estudio Enfermedades Neurometab FESEN, Buenos Aires, DF, Argentina.
[Bouhassira, Didier] Hop Ambroise Pare, Ctr Evaluat & Traitement Douleur, INSERM, U987, Boulogne, France.
[Germain, Dominique P.] Paris Saclay Univ, Univ Versailles St Quentin Yvelines, Div Med Genet, Montigny, France.
[Goizet, Cyril] CHU Bordeaux, Hop Pellegrin, Serv Genet Med, Bordeaux, France.
[Goizet, Cyril] Univ Bordeaux, Lab Malad Rares Genet & Metab MRGM, EA4576, Bordeaux, France.
[Guerrero-Sola, Antonio] Hosp Clin San Carlos, Dept Neurol, Neuromuscular Unit, Madrid, Spain.
[Hilz, Max J.] Univ Erlangen Nurnberg, Dept Neurol, Erlangen, Germany.
[Hutton, Elspeth J.] Alfred Hosp, Dept Neurol, Melbourne, Vic, Australia.
[Karaa, Amel] Massachusetts Gen Hosp, Genet Unit, Boston, MA 02114 USA.
[Liguori, Rocco] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy.
[Liguori, Rocco] IRCCS Inst Neurol Sci, Bologna, Italy.
[Ueceyler, Nurcan] Univ Wurzburg, Dept Neurol, Wurzburg, Germany.
[Zeltzer, Lonnie K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Pediat Pain & Palliat Care Program, Los Angeles, CA 90095 USA.
[Burlina, Alessandro] St Bassiano Hosp, Neurol Unit, Via Lotti 40, I-36061 Bassano Del Grappa, Italy.
RP Burlina, A (reprint author), St Bassiano Hosp, Neurol Unit, Via Lotti 40, I-36061 Bassano Del Grappa, Italy.
EM alessandro.burlina@aslbassano.it
OI Zeltzer, Lonnie/0000-0001-9306-9450; Liguori, Rocco/0000-0002-1815-1013;
Uceyler, Nurcan/0000-0001-6973-6428
FU Genzyme, a Sanofi company; Genzyme
FX The Expert Panel on Peripheral Neuropathy in Fabry disease (Rome, Italy,
March 2014) was sponsored by Genzyme, a Sanofi company. The authors
received editorial/writing support in the preparation of this manuscript
from Alessia Piazza, PhD, of Excerpta Medica, funded by Genzyme. The
authors were responsible for all content and editorial decisions, and
received no honoraria related to the development of this publication.
NR 78
TC 2
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-5930
EI 1755-5949
J9 CNS NEUROSCI THER
JI CNS Neurosci. Ther.
PD JUL
PY 2016
VL 22
IS 7
BP 568
EP 576
DI 10.1111/cns.12542
PG 9
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA DS8EH
UT WOS:000381015600004
PM 27297686
ER
PT J
AU Biegus, J
Hillege, HL
Postmus, D
Valente, MAE
Bloomfield, DM
Cleland, JGF
Cotter, G
Davison, BA
Dittrich, HC
Fiuzat, M
Givertz, MM
Massie, BM
Metra, M
Teerlink, JR
Voors, AA
O'Connor, CM
Ponikowski, P
AF Biegus, Jan
Hillege, Hans L.
Postmus, Douwe
Valente, Mattia. A. E.
Bloomfield, Daniel M.
Cleland, John G. F.
Cotter, Gad
Davison, Beth A.
Dittrich, Howard C.
Fiuzat, Mona
Givertz, Michael M.
Massie, Barry M.
Metra, Marco
Teerlink, John R.
Voors, Adriaan A.
O'Connor, Christopher M.
Ponikowski, Piotr
TI Abnormal liver function tests in acute heart failure: relationship with
clinical characteristics and outcome in the PROTECT study
SO EUROPEAN JOURNAL OF HEART FAILURE
LA English
DT Article
DE Acute heart failure; Liver dysfunction; Prognosis; Liver function tests
ID LEVELS PREDICT SURVIVAL; EJECTION FRACTION; RENAL-FUNCTION; MORTALITY;
ADMISSION; TROPONIN; PROGRAM; TRIAL
AB Aims Episodes of acute heart failure (AHF) unfavourably affect multiple organs, which may have an adverse impact on the outcomes. We investigated the prevalence and clinical consequences of abnormal liver function tests (LFTs) in AHF patients enrolled in the PROTECT study.
Methods and results The LFTs comprised serial assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin at baseline and during follow-up (daily until discharge, on days 7 and 14). The prevalence of abnormal LFTs (above upper limit of normal for AST and ALT or below lower limit of normal for albumin) was: at baseline AST 20%, ALT 12%, albumin 40%; and at day 14: AST 15%, ALT 9%, albumin 26%. Abnormal LFTs at baseline were associated with a higher risk of in-hospital death with odds ratios [95% confidence interval (CI)] of 3.5 (1.7-7.3) for AST, 3.9 (1.8-8.4) for ALT, and 2.8 (1.3-5.9) for albumin (all P < 0.01). Abnormal baseline and discharge LFTs had an unfavourable impact on 180-day mortality with hazard ratios (95% CI) for baseline AST, ALT, and albumin of 1.3 (1.0-1.7), 1.1 (1.0-1.2), 1.4 (1.1-1.8), respectively, and 1.5 (1.1-2.0), 1.5 (1.0-2.2), and 1.6 (1.2-2.1), for discharge AST, ALT, albumin, respectively (all P < 0.05). Analysis of LFTs trajectories (calculated as changes in LFTs over time) revealed that increasing AST and ALT on day 3 as well as decreasing albumin on day 4 were independent prognosticators of 180-day outcome (all P < 0.05).
Conclusions Abnormal LFTs are frequent in AHF at baseline and during hospital stay and predict worse outcomes. Whether this association is causal and what are the underlying mechanisms involved require further study.
C1 [Biegus, Jan; Ponikowski, Piotr] Med Univ, Dept Heart Dis, Wroclaw, Poland.
[Biegus, Jan; Ponikowski, Piotr] Clin Mil Hosp, Dept Cardiol, Ctr Heart Dis, Wroclaw, Poland.
[Hillege, Hans L.; Postmus, Douwe; Valente, Mattia. A. E.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
[Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA.
[Cleland, John G. F.] Univ Hull, Castle Hill Hosp, Dept Cardiol, Natl Heart & Lung Inst,Imperial Coll London,Royal, Kingston Upon Hull HU6 7RX, N Humberside, England.
[Cotter, Gad; Davison, Beth A.] Momentum Res Inc, Durham, NC USA.
[Dittrich, Howard C.] Univ Iowa, Carver Coll Med, Cardiovasc Res Ctr, Iowa City, IA USA.
[Fiuzat, Mona; O'Connor, Christopher M.] Duke Univ, Med Ctr, Div Cardiovasc Med, Duke Clin Res Inst, Durham, NC USA.
[Givertz, Michael M.] Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA USA.
[Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Sect Cardiol, San Francisco, CA 94143 USA.
[Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
[Metra, Marco] Univ Brescia, Dept Med & Surg Specialties, Radiol Sci & Publ Hlth, Cardiol, Brescia, Italy.
RP Ponikowski, P (reprint author), Med Univ, Wroclaw Ctr Heart Dis, Dept Heart Dis, Clin Mil Hosp, Weigla 5, PL-53114 Wroclaw, Poland.
EM piotrponikowski@4wsk.pl
NR 21
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1388-9842
EI 1879-0844
J9 EUR J HEART FAIL
JI Eur. J. Heart Fail.
PD JUL
PY 2016
VL 18
IS 7
BP 830
EP 839
DI 10.1002/ejhf.532
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DS8DG
UT WOS:000381012700013
PM 27170455
ER
PT J
AU Chen, EJ
AF Chen, Eddy J.
TI Being an Oncology Hospitalist
SO HOSPITAL MEDICINE CLINICS
LA English
DT Review
DE Oncology hospitalists; Oncology hospital medicine; Hospitalists;
Oncologists; Patients with cancer; Hospital medicine
ID CARE; CANCER; PHYSICIANS; MEDICINE; CONSEQUENCES; CHALLENGES; WORK; COST
AB A continuing growth trend in the aging population will result in a corresponding increase in demand for oncologist hospitalists, because this demographic of individuals also has the highest incidence of cancer. To fulfill this need, it is anticipated that general hospitalists and oncologists will have to join the ranks of existing oncology hospitalists. This article introduces the role of oncology hospitalists and highlights the challenges that they face. Skills and concepts that are likely beneficial to oncology hospitalists are also discussed, including potential areas of research and innovation. In addition, current models of oncology hospitalist groups are outlined.
C1 [Chen, Eddy J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
RP Chen, EJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM ejchen@alum.mit.edu
NR 37
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2211-5943
J9 HOSP MED CLIN
JI Hosp. Med. Clin.
PD JUL
PY 2016
VL 5
IS 3
BP 335
EP +
DI 10.1016/j.ehmc.2016.02.002
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT5GV
UT WOS:000381510600002
ER
PT J
AU Yusuf, RZ
AF Yusuf, Rushdia Zareen
TI Acute Leukemia
SO HOSPITAL MEDICINE CLINICS
LA English
DT Review
DE Acute myeloid leukemia; Acute lymphoid leukemia; Acute promyelocytic
leukemia
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE
MYELOID-LEUKEMIA; TRANS-RETINOIC ACID; TERM-FOLLOW-UP; ARSENIC TRIOXIDE;
ADULTS; ANTHRACYCLINE; CHEMOTHERAPY; REMISSION
AB Acute leukemia is not a single disease. Traditionally classified into acute myeloid leukemia, acute lymphoid leukemia, and acute promyelocytic leukemia, it is now understood to be several molecularly distinct entities, each with a predictable course and its own prognosis. However, the basics of the in-hospital treatment of the three traditional entities have remained largely unchanged over the last two decades. Familiarity with how patients present, key points to be followed during their stabilization, and an understanding of the chemotherapy agents used in the initial treatment, together with a knowledge of their predictable side effects, are essential for hospitalist physicians.
C1 [Yusuf, Rushdia Zareen] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer Bldg,1B-22, Boston, MA 02115 USA.
RP Yusuf, RZ (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Mayer Bldg,1B-22, Boston, MA 02115 USA.
EM RYUSUF@PARTNERS.ORG
NR 25
TC 0
Z9 0
U1 8
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2211-5943
J9 HOSP MED CLIN
JI Hosp. Med. Clin.
PD JUL
PY 2016
VL 5
IS 3
BP 347
EP +
DI 10.1016/j.ehmc.2016.03.001
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT5GV
UT WOS:000381510600003
ER
PT J
AU Chen, EJ
AF Chen, Eddy J.
TI Preface
SO HOSPITAL MEDICINE CLINICS
LA English
DT Editorial Material
C1 [Chen, Eddy J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
RP Chen, EJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM ejchen@alum.mit.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2211-5943
J9 HOSP MED CLIN
JI Hosp. Med. Clin.
PD JUL
PY 2016
VL 5
IS 3
BP A7
EP A8
DI 10.1016/j.ehmc.2016.02.009
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT5GV
UT WOS:000381510600001
ER
PT J
AU Zhou, ES
Manley, PE
Marcus, KJ
Recklitis, CJ
AF Zhou, Eric S.
Manley, Peter E.
Marcus, Karen J.
Recklitis, Christopher J.
TI Medical and Psychosocial Correlates of Insomnia Symptoms in Adult
Survivors of Pediatric Brain Tumors
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Article
DE childhood cancer; insomnia; pediatric brain tumor; sleep efficiency;
survivorship
ID CHILDHOOD-CANCER SURVIVOR; ACUTE LYMPHOBLASTIC-LEUKEMIA;
CENTRAL-NERVOUS-SYSTEM; LONG-TERM SURVIVORS; SLEEP DISTURBANCES;
BREAST-CANCER; PROJECT REACH; CHILDREN; FATIGUE; PREVALENCE
AB ObjectiveaEuro integral Children diagnosed with brain tumors are at risk for insomnia. We evaluated insomnia symptoms, medical and psychosocial correlates, and medical documentation of sleep-related issues in a neuro-oncology clinic.aEuro integral MethodsaEuro integral 98 adult survivors of pediatric brain tumors provided data about sleep, psychological distress, and health-related quality of life. Medical records were reviewed for treatment-related information and for documentation of sleep-related issues.aEuro integral ResultsaEuro integral 26% of the sample reported insomnia symptoms as evidenced by poor sleep efficiency. Insomnia symptoms were associated with a migraine headache history, but not with other medical or psychosocial outcomes. Approximately one in three medical providers did not document discussing sleep during the survivorship visit.aEuro integral ConclusionsaEuro integral A sizeable number of pediatric brain tumor survivors experience insomnia symptoms. The survivorship visit is an ideal opportunity for providers to conduct a sleep evaluation for this at-risk population and to provide referrals for evidence-based insomnia treatment.
C1 [Zhou, Eric S.; Manley, Peter E.; Marcus, Karen J.; Recklitis, Christopher J.] Dana Farber Canc Inst, David B Perini Qual Life Clin, 450 Brookline Ave, Boston, MA 02215 USA.
[Zhou, Eric S.; Manley, Peter E.; Marcus, Karen J.; Recklitis, Christopher J.] Harvard Med Sch, Boston, MA USA.
[Manley, Peter E.; Marcus, Karen J.] Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
RP Zhou, ES (reprint author), Dana Farber Canc Inst, David B Perini Qual Life Clin, 450 Brookline Ave, Boston, MA 02215 USA.
EM eric_zhou@dfci.harvard.edu
FU Childhood Brain Tumor Foundation; Pedals for Pediatrics
FX Funding provided by the Childhood Brain Tumor Foundation and Pedals for
Pediatrics.
NR 46
TC 2
Z9 2
U1 2
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
EI 1465-735X
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD JUL
PY 2016
VL 41
IS 6
SI SI
BP 623
EP 630
DI 10.1093/jpepsy/jsv071
PG 8
WC Psychology, Developmental
SC Psychology
GA DT0GQ
UT WOS:000381161700005
PM 26275977
ER
PT J
AU Bates, CR
Bohnert, AM
Ward, AK
Burdette, KA
Kliethermes, SA
Welch, SB
Silton, RL
Dugas, LR
AF Bates, Carolyn R.
Bohnert, Amy M.
Ward, Amanda K.
Burdette, Kimberly A.
Kliethermes, Stephanie A.
Welch, Sarah B.
Silton, Rebecca L.
Dugas, Lara R.
TI Sleep is in for Summer: Patterns of Sleep and Physical Activity in Urban
Minority Girls
SO JOURNAL OF PEDIATRIC PSYCHOLOGY
LA English
DT Article
DE adolescents; health behavior; race; ethnicity; sleep
ID SCHOOL-AGED CHILDREN; BODY-MASS INDEX; NOCTURNAL SLEEP; UNITED-STATES;
WEIGHT-GAIN; ADOLESCENTS; DURATION; OBESITY; OVERWEIGHT; CHILDHOOD
AB ObjectiveaEuro integral Urban minority girls are at risk for summertime weight gain, and may also experience insufficient summertime sleep. Few studies have objectively measured sleep in this population or examined correlates, including physical activity (PA). This study is the first to objectively describe summertime sleep among urban minority girls.aEuro integral MethodsaEuro integral Data were collected at a community-based summer program that promoted PA (n = 60 girls, ages 10-14 years), at two time points: before beginning programming (T1; unstructured context) and during the final week of programming (T2; structured context).aEuro integral ResultsaEuro integral At both time points, participants experienced shorter nighttime sleep than the recommended amount for girls their age. African American girls recorded significantly less sleep than Latina girls in the unstructured context. Findings also suggest that sleep schedules have an influential role in youths' abilities to obtain adequate sleep.aEuro integral ConclusionaEuro integral Overall, summertime sleep is an understudied health behavior that may be important to consider among minority youth.
C1 [Bates, Carolyn R.; Bohnert, Amy M.; Burdette, Kimberly A.; Silton, Rebecca L.] Loyola Univ Chicago, Dept Psychol, 1032 W Sheridan Rd, Chicago, IL 60660 USA.
[Ward, Amanda K.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
[Kliethermes, Stephanie A.; Dugas, Lara R.] Loyola Univ Chicago, Stritch Sch Med, Dept Publ Hlth Sci, Chicago, IL USA.
[Welch, Sarah B.] Stanley Manne Childrens Res Inst, Consortium Lower Obes Chicago Children, Chicago, IL USA.
RP Bates, CR (reprint author), Loyola Univ Chicago, Dept Psychol, 1032 W Sheridan Rd, Chicago, IL 60660 USA.
EM cbates3@luc.edu
FU Loyola University Chicago's Provost Fellowship
FX This research was funded by Loyola University Chicago's Provost
Fellowship.
NR 56
TC 1
Z9 1
U1 7
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0146-8693
EI 1465-735X
J9 J PEDIATR PSYCHOL
JI J. Pediatr. Psychol.
PD JUL
PY 2016
VL 41
IS 6
SI SI
BP 692
EP 700
DI 10.1093/jpepsy/jsw009
PG 9
WC Psychology, Developmental
SC Psychology
GA DT0GQ
UT WOS:000381161700012
PM 26929098
ER
PT J
AU Bohnen, JD
Ramly, EP
Sangji, NF
de Moya, M
Yeh, DD
Lee, J
Velmahos, GC
Chang, DC
Kaafarani, HMA
AF Bohnen, Jordan D.
Ramly, Elie P.
Sangji, Naveen F.
de Moya, Marc
Yeh, D. Dante
Lee, Jarone
Velmahos, George C.
Chang, David C.
Kaafarani, Haytham M. A.
TI Perioperative risk factors impact outcomes in emergency versus
nonemergency surgery differently: Time to separate our national
risk-adjustment models?
SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
LA English
DT Article
DE Benchmarking; emergency surgery; perioperative risk factors; risk
adjustment; surgical quality
ID SURGICAL QUALITY IMPROVEMENT; GENERAL-SURGERY; AMERICAN-COLLEGE; PROGRAM
DATABASE; UNITED-STATES; CARE; MORBIDITY; BURDEN; TRAUMA
AB BACKGROUND: Emergency surgery (ES) is acknowledged to be riskier than nonemergency surgery (NES). Yet, little is known about the relative impact of individual perioperative risk factors on 30-day outcomes in ES versus NES.
METHODS: Using the 2011-2012 American College of Surgeons National Surgical Quality Improvement Program nationwide database, the 20 most common ES procedures were identified by Current Procedural Terminology code. Current Procedural Terminology codes with less than 300 observations in either ES or NES were excluded. Emergency surgery cases were defined as "emergent" and "nonelective" per American College of Surgeons National Surgical Quality Improvement Program criteria. Multivariable regression models were constructed to identify predictors of 30-day major morbidity and mortality (MMM) in each group, controlling for demographics, American Society of Anesthesiologists class, comorbidities, preoperative laboratory values, and procedure type. The odds ratios of independent predictors of MMM in ES and NES were derived then individually compared between the two groups; "effect modification" of procedure status (ES vs. NES) on each risk factor was subsequently calculated.
RESULTS: Of 986,034 patients, 170,131 met inclusion criteria (59,949 ES; 110,182 NES). The overall risk of MMM was significantly higher in ES versus NES (16.75% vs. 9.73%, p < 0.001; odds ratio, 1.18; 95% confidence interval, 1.12-1.24; p < 0.001). Of 40 ES-and 38 NES-identified independent risk factors, preoperative transfusion and white blood cell count of 4.5 Chi 10(3)/mu L or less carried significantly higher relative risk of MMM in ES versus NES. Conversely, ascites, preoperative anemia, and white blood cell count of 11 Chi 10(3)/mu L to 25 Chi 10(3)/mu L carried greater relative risk for MMM in NES. Four procedures (laparoscopic cholecystectomy, laparotomy, and umbilical and incisional herniorrhaphy) were inherently riskier in ES versus NES. The effect modification of ES (vs. NES) ranged between 0.68 (0.52-0.88) for ascites and 2.56 (1.67-3.92) for umbilical hernia repair.
CONCLUSIONS: Perioperative risk factors and procedure type impact postoperative morbidity and mortality differently in ES versus NES. Instead of using the same risk-adjustment model for both ES and NES, as currently practiced, our findings strongly suggest the need to benchmark emergent and elective surgeries separately. (J Trauma Acute Care Surg. 2016; 81: 122-130. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.)
C1 [Bohnen, Jordan D.; Sangji, Naveen F.; de Moya, Marc; Yeh, D. Dante; Lee, Jarone; Velmahos, George C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Emergency Surg & Surg Crit Care, Div Trauma, Boston, MA 02114 USA.
Harvard Med Sch, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
[Ramly, Elie P.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA.
[Sangji, Naveen F.; Lee, Jarone; Chang, David C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA.
RP Kaafarani, HMA (reprint author), Harvard Med Sch, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.; Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA USA.
EM hkaafarani@mgh.harvard.org
NR 20
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 2163-0755
EI 2163-0763
J9 J TRAUMA ACUTE CARE
JI J. Trauma Acute Care Surg.
PD JUL
PY 2016
VL 81
IS 1
BP 122
EP 130
DI 10.1097/TA.0000000000001015
PG 9
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA DS5BV
UT WOS:000380796400019
PM 26958792
ER
PT J
AU Liu, XZ
Gao, Y
Shen, JS
Yang, W
Choy, E
Mankin, H
Hornicek, FJ
Duan, ZF
AF Liu, Xianzhe
Gao, Yan
Shen, Jacson
Yang, Wen
Choy, Edwin
Mankin, Henry
Hornicek, Francis J.
Duan, Zhenfeng
TI Cyclin-Dependent Kinase 11 (CDK11) Is Required for Ovarian Cancer Cell
Growth In Vitro and In Vivo, and Its Inhibition Causes Apoptosis and
Sensitizes Cells to Paclitaxel
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID BREAST-CANCER; THERAPY; INTERFERENCE; FLAVOPIRIDOL; EXPRESSION; TARGETS;
PALBOCICLIB; RESISTANCE; COUNTRIES; APPROVAL
AB Ovarian cancer is currently the most lethal gynecologic malignancy with limited treatment options. Improved targeted therapies are needed to combat ovarian cancer. Here, we report the identification of cyclin-dependent kinase 11 (CDK11) as a mediator of tumor cell growth and proliferation in ovarian cancer cells. Although CDK11 has not been implicated previously in this disease, we have found that its expression is upregulated in human ovarian cancer tissues and associated with malignant progression. Metastatic and recurrent tumors have significantly higher CDK11 expression when compared with the matched, original primary tumors. RNA-imediated CDK11 silencing by synthetic siRNA or lentiviral shRNA decreased cell proliferation and induced apoptosis in ovarian cancer cells. Moreover, CDK11 knockdown enhances the cytotoxic effect of paclitaxel to inhibit cell growth in ovarian cancer cells. Systemic in vivo administration of CDK11 siRNA reduced the tumor growth in an ovarian cancer xenograft model. Our findings suggest that CDK11 may be a promising therapeutic target for the treatment of ovarian cancer patients. (C) 2016 AACR.
C1 [Liu, Xianzhe; Gao, Yan; Shen, Jacson; Yang, Wen; Choy, Edwin; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Massachusetts Gen Hosp, Sarcoma Biol Lab, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
[Liu, Xianzhe; Gao, Yan; Shen, Jacson; Yang, Wen; Choy, Edwin; Mankin, Henry; Hornicek, Francis J.; Duan, Zhenfeng] Harvard Med Sch, Boston, MA USA.
[Liu, Xianzhe] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Orthopaed Surg, Wuhan, Peoples R China.
[Yang, Wen] Huazhong Univ Sci & Technol, Tongji Med Coll, Union Hosp, Dept Anesthesiol, Wuhan, Peoples R China.
RP Duan, ZF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Jackson Bldg Room 1115, Boston, MA 02114 USA.; Duan, ZF (reprint author), Harvard Med Sch, 55 Fruit St,Jackson Bldg Room 1115, Boston, MA 02114 USA.
EM zduan@mgh.harvard.edu
FU Gattegno and Wechsler funds; Sarcoma Foundation of America (SFA);
Sarcoma SPORE/NIH; National Cancer Institute (NCI)/NIH [UO1, CA151452];
National Natural Science Foundation of China [81302344, 81401573];
Morning Project of Youth Science and Technology of Wuhan City
[2014070404010221]
FX This work was supported in part by grants from the Gattegno and Wechsler
funds. Z. Duan is supported, in part, through a grant from the Sarcoma
Foundation of America (SFA), a pilot grant from Sarcoma SPORE/NIH, and a
grant from the National Cancer Institute (NCI)/NIH, UO1, CA151452. XZ.
Liu and W. Yang are supported by grants from the National Natural
Science Foundation of China (no. 81302344, to XZ. Liu; no. 81401573, to
W. Yang), and by grants from the Morning Project of Youth Science and
Technology of Wuhan City (no. 2014070404010221, to XZ. Liu).
NR 45
TC 0
Z9 0
U1 4
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD JUL
PY 2016
VL 15
IS 7
BP 1691
EP 1701
DI 10.1158/1535-7163.MCT-16-0032
PG 11
WC Oncology
SC Oncology
GA DS9FC
UT WOS:000381087200025
PM 27207777
ER
PT J
AU Diego, LAD
Salman, FC
Silva, JH
Brandao, JC
de Oliveira, G
Carneiro, AF
Bagatini, A
de Moraes, JM
AF dos Santos Diego, Luis Antonio
Salman, Fabiane Cardia
Silva, Joao Henrique
Brandao, Julio Cezar
de Oliveira Filho, Getulio
Carneiro, Antonio Fernando
Bagatini, Airton
de Moraes, Jose Mariano
TI Construction of a tool to measure perceptions about the use of the World
Health Organization Safe Surgery Checklist Program
SO REVISTA BRASILEIRA DE ANESTESIOLOGIA
LA English
DT Article
DE Tool; Checklist; Safe surgery; Adverse events; World Health Organization
ID MORTALITY
AB Background: The World Health Organization (WHO) has recommended greater attention to patient safety, particularly regarding preventable adverse events. The Safe Surgery Saves Lives (CSSV) program was released recommending the application of a surgical checklist for items on the safety of procedures. The checklist implementation reduced the hospital mortality rate in the first 30 days. In Brazil, we found no studies of anesthesiologists' adherence to the practice of the checklist.
Objective: The main objective was to develop a tool to measure the attitude of anesthesiologists and residents regarding the use of checklist in the perioperative period.
Method: This was a cross-sectional study performed during the 59th CBA in BH/MG, whose participants were enrolled physicians who responded to the questionnaire with quantitative epidemiological approach.
Results: From the sample of 459 participants who answered the questionnaire, 55% were male, 44.2% under 10 years of practice, and 15.5% with over 30 years of medical school completion. Seven items with 78% reliability coefficient were selected. There was a statistically significant difference between the groups of anesthesiologists who reported using the instrument in lessor more than 70% of patients, indicating that the attitude questionnaire discriminates between these two groups of professionals.
Conclusions: The seven items questionnaire showed adequate internal consistency and a well-defined factor structure, and can be used as a tool to measure the anesthesiologists' perceptions about the checklist usefulness and applicability. (C) 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda.
C1 [dos Santos Diego, Luis Antonio; Salman, Fabiane Cardia; Silva, Joao Henrique; Brandao, Julio Cezar; de Oliveira Filho, Getulio; Carneiro, Antonio Fernando; Bagatini, Airton; de Moraes, Jose Mariano] SBA, Rio De Janeiro, RJ, Brazil.
[dos Santos Diego, Luis Antonio] Univ Fed Fluminense, Fac Med, Niteroi, RJ, Brazil.
[Salman, Fabiane Cardia] Fundacao Oswaldo Cruz, Rio De Janeiro, RJ, Brazil.
[Silva, Joao Henrique] Hosp Moinhos Vento, Porto Alegre, RS, Brazil.
[Brandao, Julio Cezar] Univ Fed Sergipe, Sao Cristovao, SE, Brazil.
[Brandao, Julio Cezar; de Oliveira Filho, Getulio] Univ Fed Sao Paulo Unifesp, Translat Med, Sao Paulo, SP, Brazil.
[Brandao, Julio Cezar] Harvard, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
[de Oliveira Filho, Getulio] Univ Fed Santa Catarina, Florianopolis, SC, Brazil.
RP Brandao, JC (reprint author), SBA, Rio De Janeiro, RJ, Brazil.; Brandao, JC (reprint author), Univ Fed Sergipe, Sao Cristovao, SE, Brazil.; Brandao, JC (reprint author), Univ Fed Sao Paulo Unifesp, Translat Med, Sao Paulo, SP, Brazil.; Brandao, JC (reprint author), Harvard, Massachusetts Gen Hosp, Cambridge, MA 02138 USA.
EM juliobrand@hotmail.com
NR 12
TC 0
Z9 0
U1 5
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0034-7094
EI 1806-907X
J9 REV BRAS ANESTESIOL
JI Rev. Bras. Anestesiol.
PD JUL-AUG
PY 2016
VL 66
IS 4
BP 351
EP 355
DI 10.1016/j.bjane.2014.11.011
PG 5
WC Anesthesiology
SC Anesthesiology
GA DS5SU
UT WOS:000380843400004
PM 26582388
ER
PT J
AU Ng, AK
van Leeuwen, FE
AF Ng, Andrea K.
van Leeuwen, Flora E.
TI Hodgkin lymphoma: Late effects of treatment and guidelines for
surveillance
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
DE Hodgkin lymphoma; Late effects; Second malignant neoplasms;
Cardiovascular disease
ID LONG-TERM SURVIVORS; CORONARY-ARTERY-DISEASE; COMPUTED-TOMOGRAPHY
ANGIOGRAPHY; COLLABORATIVE BRITISH COHORT; BREAST-CANCER RISK;
STUDY-GROUP GHSG; CHILDHOOD-CANCER; LUNG-CANCER; RADIATION-THERAPY;
ADULT SURVIVORS
AB Long-term survivors of Hodgkin lymphoma (HL) are at risk for a range of late effects, with second malignant neoplasm and cardiovascular diseases being the leading causes of death in these patients. The excess risks remain significantly elevated decades after treatment, and are clearly associated with extent of treatment exposures. Other late effects have also been identified, such as pulmonary dysfunction, endocrinopathies, muscle atrophy, and persistent fatigue. Systemic documentation of late effects and recognition of treatment- and patient-related risk factors are important, as they inform optimal surveillance and risk-reduction strategies, as well as guide therapeutic modifications in newly diagnosed patients to minimize treatment-related complications. As HL therapy evolves over time, with adoption of novel agents and contemporary treatment techniques, late effect risks and follow-up recommendations need to be continuously updated. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Ng, Andrea K.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA.
[Ng, Andrea K.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[van Leeuwen, Flora E.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Dept Epidemiol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
RP van Leeuwen, FE (reprint author), Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Dept Epidemiol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
EM f.v.leeuwen@nki.nl
NR 71
TC 0
Z9 0
U1 4
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD JUL
PY 2016
VL 53
IS 3
BP 209
EP 215
DI 10.1053/j.seminhematol.2016.05.008
PG 7
WC Hematology
SC Hematology
GA DT2PU
UT WOS:000381323700011
PM 27496313
ER
PT J
AU Barroso-Sousa, R
Metzger, O
AF Barroso-Sousa, Romualdo
Metzger-Filho, Otto
TI Differences between invasive lobular and invasive ductal carcinoma of
the breast: results and therapeutic implications
SO THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
LA English
DT Review
DE breast neoplasm; chemotherapy; invasive ductal carcinoma; invasive
lobular carcinoma; letrozole; tamoxifen; TCGA; trastuzumab
ID NEOADJUVANT CHEMOTHERAPY; RECURRENCE SCORE; CANCER; TAMOXIFEN; FOXA1;
TRASTUZUMAB; EXPRESSION; LETROZOLE; OUTCOMES; BINDING
AB Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer (BC): ILC differs from invasive ductal carcinoma (IDC) in its clinicopathological characteristics and responsiveness to systemic therapy. From the clinical standpoint, data suggest that ILC derives a distinct benefit from systemic therapy compared to IDC. In addition, comprehensive molecular analyses have been reported for ILCs, confirming that these tumors have specific genomic profiles compared to IDC. Despite these differences, clinical trials and practical clinical guidelines tend to treat BC as a single entity. Here we discuss these clinical and molecular data and their therapeutic implications.
C1 [Barroso-Sousa, Romualdo; Metzger-Filho, Otto] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 1238, Boston, MA 02215 USA.
RP Metzger, O (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave,Yawkey 1238, Boston, MA 02215 USA.
EM otto_metzger@dfci.harvard.edu
NR 31
TC 1
Z9 1
U1 3
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1758-8340
EI 1758-8359
J9 THER ADV MED ONCOL
JI Ther. Adv. Med. Oncol.
PD JUL
PY 2016
VL 8
IS 4
BP 261
EP 266
DI 10.1177/1758834016644156
PG 6
WC Oncology
SC Oncology
GA DT3LZ
UT WOS:000381384000002
PM 27482285
ER
PT J
AU Mallipattu, SK
He, JC
AF Mallipattu, Sandeep K.
He, John C.
TI The podocyte as a direct target for treatment of glomerular disease?
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE abatacept; calcineurin inhibitors; glucocorticoids; podocyte; rituximab
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; ENDOTHELIAL GROWTH-FACTOR;
TRANSGENIC REN2 RAT; END-ORGAN DAMAGE; NEPHROTIC-SYNDROME; RETINOIC
ACID; PUROMYCIN AMINONUCLEOSIDE; COSTIMULATORY BLOCKADE;
MOLECULAR-MECHANISMS; PROTECTS PODOCYTES
AB The Centers for Disease Control and Prevention estimates more than 10% of adults in the United States, over 20 million Americans, have chronic kidney disease (CKD). A failure to maintain the glomerular filtration barrier directly contributes to the onset of CKD. The visceral epithelial cells, podocytes, are integral to the maintenance of this renal filtration barrier. Direct podocyte injury contributes to the onset and progression of glomerular diseases such as minimal change disease (MCD), focal segmental glomerular sclerosis (FSGS), diabetic nephropathy, and HIV-associated nephropathy (HIVAN). Since podocytes are terminally differentiated with minimal capacity to self-replicate, they are extremely sensitive to cellular injury. In the past two decades, our understanding of the mechanism(s) by which podocyte injury occurs has greatly expanded. With this newfound knowledge, therapeutic strategies have shifted to identifying targets directed specifically at the podocyte. Although the systemic effects of these agents are important, their direct effect on the podocyte proves to be essential in ameliorating glomerular disease. In this review, we highlight the mechanisms by which these agents directly target the podocyte independent of its systemic effects.
C1 [Mallipattu, Sandeep K.] SUNY Stony Brook, Dept Med, Div Nephrol, Stony Brook, NY 11794 USA.
[He, John C.] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
[He, John C.] James J Peters VA Med Ctr, Renal Sect, New York, NY USA.
RP He, JC (reprint author), Icahn Sch Med Mt Sinai, Dept Med Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA.
EM cijiang.he@mssm.edu
FU National Institutes of Health (NIH) [1K08DK-102519]; NIH
[1R01DK-078897]; Chinese 973 Fund [2012CB51760]
FX S. K. Mallipattu is supported by National Institutes of Health (NIH)
Grant 1K08DK-102519. J. C. He is supported by NIH 1R01DK-078897, and
Chinese 973 Fund 2012CB51760.
NR 63
TC 2
Z9 2
U1 4
U2 5
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JUL 1
PY 2016
VL 311
IS 1
BP F46
EP F51
DI 10.1152/ajprenal.00184.2016
PG 6
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA DS5MS
UT WOS:000380826900006
PM 27097894
ER
PT J
AU Wagner, B
Drel, V
Gorin, Y
AF Wagner, Brent
Drel, Viktor
Gorin, Yves
TI Pathophysiology of gadolinium-associated systemic fibrosis
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Review
DE fibrosis; gadolinium; nephrogenic fibrosing dermopathy; NADPH oxidase;
skin diseases
ID RESONANCE-IMAGING CONTRAST; STAGE RENAL-DISEASE; IN-VIVO; MYOFIBROBLAST
DIFFERENTIATION; CIRCULATING FIBROCYTES; DIABETIC-NEPHROPATHY;
KIDNEY-DISEASE; LIVER FIBROSIS; NADPH OXIDASES; CASE SERIES
AB Systemic fibrosis from gadoliniumbased magnetic resonance imaging contrast is a scourge for the afflicted. Although gadolinium-associated systemic fibrosis is a rare condition, the threat of litigation has vastly altered clinical practice. Most theories concerning the etiology of the fibrosis are grounded in case reports rather than experiment. This has led to the widely accepted conjecture that the relative affinity of certain contrast agents for the gadolinium ion inversely correlates with the risk of succumbing to the disease. How gadolinium-containing contrast agents trigger widespread and site-specific systemic fibrosis and how chronicity is maintained are largely unknown. This review highlights experimentally-derived information from our laboratory and others that pertain to our understanding of the pathophysiology of gadolinium-associated systemic fibrosis.
C1 [Wagner, Brent] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Wagner, Brent; Drel, Viktor; Gorin, Yves] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA.
RP Wagner, B (reprint author), Univ Texas Hlth Sci Ctr, South Texas Vet Hlth Care Syst, Dept Med, Div Nephrol, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM wagnerb@uthscsa.edu
FU Veterans Administration Merit Award [I01 BX001958]; National Institutes
of Health [R01 DK-102085, UL1 TR-001120, R01 DK-079996, R01 DK-78971];
National Priorities Research Program [NPRP8-1750-3-360]; Qatar National
Research Fund
FX The research was funded by the Veterans Administration Merit Award (I01
BX001958, B. Wagner); the National Institutes of Health through Grants
R01 DK-102085 (B. Wagner), UL1 TR-001120 (Y. Gorin), R01 DK-079996 (Y.
Gorin), and R01 DK-78971 (Y. Gorin); and an award from the Qatar
National Research Fund, National Priorities Research Program
(NPRP8-1750-3-360) (Y. Gorin).
NR 105
TC 1
Z9 1
U1 1
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD JUL 1
PY 2016
VL 311
IS 1
BP F1
EP F11
DI 10.1152/ajprenal.00166.2016
PG 11
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA DS5MS
UT WOS:000380826900001
PM 27147669
ER
PT J
AU Funke, M
Knudsen, L
Lagares, D
Ebener, S
Probst, CK
Fontaine, BA
Franklin, A
Kellner, M
Kuhnel, M
Matthieu, S
Grothausmann, R
Chun, J
Roberts, JD
Ochs, M
Tager, AM
AF Funke, Manuela
Knudsen, Lars
Lagares, David
Ebener, Simone
Probst, Clemens K.
Fontaine, Benjamin A.
Franklin, Alicia
Kellner, Manuela
Kuehnel, Mark
Matthieu, Stephanie
Grothausmann, Roman
Chun, Jerold
Roberts, Jesse D., Jr.
Ochs, Matthias
Tager, Andrew M.
TI Lysophosphatidic Acid Signaling through the Lysophosphatidic Acid-1
Receptor Is Required for Alveolarization
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE alveolarization; lung development; LPA(1); elastin; matrix
metalloproteinase
ID PULMONARY-FIBROSIS; LUNG INJURY; MOUSE LUNG; BRONCHOPULMONARY DYSPLASIA;
MATRIX; EMPHYSEMA; ALVEOLI; DISEASE; CELLS; LPA
AB Lysophosphatidic acid (LPA) signaling through one of its receptors, LPA(1), contributes to both the development and the pathological remodeling after injury of many organs. Because we found previously that LPA-LPA(1) signaling contributes to pulmonary fibrosis, here we investigated whether this pathway is also involved in lung development. Quantitative assessment of lung architecture of LPA(1)-deficient knockout (KO) and wild-type (WT) mice at 3, 12, and 24 weeks of age using design-based stereology suggested the presence of an alveolarization defect in LPA(1) KO mice at 3 weeks, which persisted as alveolar numbers increased in WT mice into adulthood. Across the ages examined, the lungs of LPA(1) KO mice exhibited decreased alveolar numbers, septal tissue volumes, and surface areas, and increased volumes of the distal airspaces. Elastic fibers, critical to the development of alveolar septa, appeared less organized and condensed and more discontinuous in KO alveoli starting at P4. Tropoelastin messenger RNA expression was decreased in KO lungs, whereas expression of matrix metalloproteinases degrading elastic fibers was either decreased or unchanged. These results are consistent with the abnormal lung phenotype of LPA(1) KO mice, being attributable to reduced alveolar septal formation during development, rather than to increased septal destruction as occurs in the emphysema of chronic obstructive pulmonary disease. Peripheral septal fibroblasts and myofibroblasts, which direct septation in late alveolarization, demonstrated reduced production of tropoelastin and matrix metalloproteinases, and diminished LPA-induced migration, when isolated from LPA(1) KO mice. Taken together, our data suggest that LPA-LPA(1) signaling is critically required for septation during alveolarization.
C1 [Funke, Manuela; Ebener, Simone] Inselspital Bern, Dept Pulm Med, Bern, Switzerland.
[Funke, Manuela; Ebener, Simone] Univ Bern, Clin Res, Bern, Switzerland.
[Funke, Manuela; Lagares, David; Probst, Clemens K.; Fontaine, Benjamin A.; Franklin, Alicia; Tager, Andrew M.] Harvard Med Sch, Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA USA.
[Funke, Manuela; Lagares, David; Probst, Clemens K.; Fontaine, Benjamin A.; Franklin, Alicia; Tager, Andrew M.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Roberts, Jesse D., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA.
[Knudsen, Lars; Kellner, Manuela; Kuehnel, Mark; Matthieu, Stephanie; Grothausmann, Roman; Ochs, Matthias] Hannover Med Sch, Inst Funct & Appl Anat, Hannover, Germany.
[Knudsen, Lars; Kellner, Manuela; Kuehnel, Mark; Matthieu, Stephanie; Grothausmann, Roman; Ochs, Matthias] German Ctr Lung Res, REBIRTH Cluster Excellence, Biomed Res Endstage & Obstruct Lung Dis Hannover, Hannover, Germany.
[Chun, Jerold] Scripps Res Inst, Dorris Neurosci Ctr, Dept Mol & Cellular Neurosci, La Jolla, CA 92037 USA.
RP Funke, M (reprint author), Univ Hosp Berne, Inselspital, Dept Pulm Med, CH-3010 Bern, Switzerland.
EM manuela.funke-chambour@insel.ch
FU National Institutes of Health [R01HL095732, R01HL108975, R01HL125715,
R01NS084398]
FX This work was supported by National Institutes of Health grants
R01HL095732 and R01HL108975 (A.M.T.), R01HL125715 (J.D.R.), and
R01NS084398 (J.C.).
NR 50
TC 3
Z9 3
U1 1
U2 2
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD JUL 1
PY 2016
VL 55
IS 1
BP 105
EP 116
DI 10.1165/rcmb.2015-0152OC
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA DT7XS
UT WOS:000381702200011
PM 27082727
ER
PT J
AU McHale, KJ
Rozell, JC
Milby, AH
Carey, JL
Sennett, BJ
AF McHale, Kevin J.
Rozell, Joshua C.
Milby, Andrew H.
Carey, James L.
Sennett, Brian J.
TI Outcomes of Lisfranc Injuries in the National Football League
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article; Proceedings Paper
CT 41st Annual Meeting of the
American-Orthopaedic-Society-for-Sports-Medicine (AOSSM)
CY JUL, 2015
CL Orlando, FL
SP Amer Orthopaed Soc Sports Med
DE football; foot; Lisfranc; NFL; return to play
ID JOINT INJURIES; LIGAMENT INJURIES; INTERNAL-FIXATION; MIDFOOT SPRAINS;
SCREW FIXATION; OPEN REDUCTION; ATHLETE; MANAGEMENT
AB Background: Tarsometatarsal (Lisfranc) joint injuries commonly occur in National Football League (NFL) competition; however, the career effect of these injuries is unknown.
Purpose: To define the time to return to competition for NFL players who sustained Lisfranc injuries and to quantify the effect on athletic performance.
Study Design: Case-control study; Level of evidence, 3.
Methods: Data on NFL players who sustained a Lisfranc injury between 2000 and 2010 were collected for analysis. Outcomes data included time to return to competition, total games played after season of injury, yearly total yards and touchdowns for offensive players, and yearly total tackles, sacks, and interceptions for defensive players. Offensive power ratings (OPR = [total yards/10] + [total touchdowns x 6]) and defensive power ratings (DPR = total tackles + [total sacks x 2] + [total interceptions x 2]) were calculated for the injury season and for 3 seasons before and after the injury season. Offensive and defensive control groups consisted of all players without an identified Lisfranc injury who competed in the 2005 season.
Results: The study group was composed of 28 NFL athletes who sustained Lisfranc injuries during the study period, including 11 offensive and 17 defensive players. While 2 of 28 (7.1%) players never returned to the NFL, 26 (92.9%) athletes returned to competition at a median of 11.1 (interquartile range [IQR], 10.3-12.5) months from time of injury and missed a median of 8.5 (IQR, 6.3-13.0) regular-season games. Analysis of pre- and postinjury athletic performance revealed no statistically significant changes after return to sport after Lisfranc injury. The magnitude of change in median OPR and DPR observed in offensive and defensive Lisfranc-injured study groups, -34.8 (IQR, -64.4 to 1.4) and -13.5 (-30.9 to 4.3), respectively, was greater than that observed in offensive and defensive control groups, -18.8 (-52.9 to 31.5) and -5.0 (-22.0 to 14.0), respectively; however, these differences did not reach statistical significance (P = .33 and .21, respectively). Evaluation of the durability of injured players after the season of injury revealed no statistically significant difference in career length compared with controls.
Conclusion: More than 90% of NFL athletes who sustained Lisfranc injuries returned to play in the NFL at a median of 11.1 months from time of injury. Offensive and defensive players experienced a decrease in performance after return from injury that did not reach statistical significance compared with their respective control groups over a similar time period.
C1 [McHale, Kevin J.; Rozell, Joshua C.; Milby, Andrew H.; Carey, James L.; Sennett, Brian J.] Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA.
[McHale, Kevin J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP McHale, KJ (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sports Med, 175 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM kmchale44@gmail.com
NR 18
TC 2
Z9 2
U1 4
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
EI 1552-3365
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD JUL
PY 2016
VL 44
IS 7
BP 1810
EP 1817
DI 10.1177/0363546516645082
PG 8
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA DR6MY
UT WOS:000380017200025
PM 27166291
ER
PT J
AU Greenberg, JL
Mothi, SS
Wilhelm, S
AF Greenberg, Jennifer L.
Mothi, Suraj Sarvode
Wilhelm, Sabine
TI Cognitive-Behavioral Therapy for Body Dysmorphic Disorder by Proxy
SO BEHAVIOR THERAPY
LA English
DT Article
DE body dysmorphic disorder; cognitive behavioral therapy; relationship;
OCD; body dysmorphic disorder by proxy
ID RANDOMIZED CONTROLLED-TRIAL; OBJECTIFICATION; MAINTENANCE; RELIABILITY;
UNCERTAINTY; VALIDITY; SCALE
AB Body dysmorphic disorder (BDD) is a distressing or impairing preoccupation with a perceived defect in physical appearance. BDD by proxy (BDDBP) is a significant but understudied variant of BDD in which the primary preoccupation involves perceived imperfections of another person. Like BDD, individuals with BDDBP engage in time-consuming rituals to "fix" the other person's appearance or alleviate distress. Avoidance is common and the impact of BDDBP on social functioning is profound. Cognitive behavioral therapy (CBT) is the best-studied and most promising psychological treatment for BDD, but no studies have examined its generalizability to the BDDBP variant. We tested feasibility, acceptability, and treatment outcome of CBT modified for BDDBP in a sample of 6 adults with primary BDDBP. Treatment was delivered in weekly individual sessions over 12-20 weeks. Mean symptom severity (BDDBP-YBOCS) dropped from the moderately severe range at pretreatment to the subclinical range at posttreatment, t(6) = 10.7, p < .001, d = 3.3. One hundred percent of treatment completers were responders (>= 30% reduction in BDDBP-YBOCS). Insight also improved. Treatment gains were maintained at 3-month follow-up. To our knowledge, this represents the first treatment study for BDDBP.
C1 [Greenberg, Jennifer L.; Mothi, Suraj Sarvode; Wilhelm, Sabine] Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA.
[Greenberg, Jennifer L.; Mothi, Suraj Sarvode; Wilhelm, Sabine] Harvard Med Sch, Boston, MA USA.
RP Greenberg, JL (reprint author), Massachusetts Gen Hosp, Simches Res Bldg,185 Cambridge St,Suite 2200, Boston, MA 02114 USA.
EM jlgreenberg@mgh.harvard.edu
FU David and Ellen Rich Research Fund; Ken and Meredith Levine Research
Fund
FX This work was supported by the David and Ellen Rich Research Fund and
the Ken and Meredith Levine Research Fund. We would like to thank Amanda
Calkins, Lauren Hallion, Jennifer Ragan, Natasha Hansen, Katie
Limoncelli, and Lillian Reuman for their work on the current study.
NR 36
TC 1
Z9 1
U1 3
U2 3
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
EI 1878-1888
J9 BEHAV THER
JI Behav. Therapy
PD JUL
PY 2016
VL 47
IS 4
BP 515
EP 526
PG 12
WC Psychology, Clinical
SC Psychology
GA DS7NR
UT WOS:000380970700007
PM 27423167
ER
PT J
AU Meyer, JD
Koltyn, KF
Stegner, AJ
Kim, JS
Cook, DB
AF Meyer, Jacob D.
Koltyn, Kelli F.
Stegner, Aaron J.
Kim, Jee-Seon
Cook, Dane B.
TI Influence of Exercise Intensity for Improving Depressed Mood in
Depression: A Dose-Response Study
SO BEHAVIOR THERAPY
LA English
DT Article
DE depression; exercise; antidepressant response; exercise optimization;
symptom management
ID RANDOMIZED CONTROLLED-TRIALS; PHYSICAL-ACTIVITY; DSM-IV; ANXIETY;
VALIDATION; DISORDERS; VALIDITY; ADULTS; STATES
AB Introduction: Exercise effectively improves mood in major depressive disorder (MDD), but the optimal exercise stimulus to improve depressed mood is unknown.
Purpose: To determine the dose-response relationship of acute exercise intensity with depressed mood responses to exercise in MDD. We hypothesized that the acute response to exercise would differ between light, moderate, and hard intensity exercise with higher intensities yielding more beneficial responses.
Methods: Once weekly, 24 women (age: 38.6 +/- 14.0) diagnosed with MDD underwent a 30-minute session at one of three steady-state exercise intensities (light, moderate, hard; rating of perceived exertion 11, 13 or 15) or quiet rest on a stationary bicycle. Depressed mood was evaluated with the Profile of Mood States before, 10 and 30 minutes post-exercise.
Results: Exercise reduced depressed mood 10 and 30 minutes following exercise, but this effect was not influenced by exercise intensity. Participants not currently taking antidepressants (n = 10) had higher baseline depression scores, but did not demonstrate a different antidepressant response to exercise compared to those taking antidepressants.
Conclusions: To acutely improve depressed mood, exercise of any intensity significantly improved feelings of depression with no differential effect following light, moderate, or hard exercise. Pharmacological antidepressant usage did not limit the mood-enhancing effect of acute exercise. Acute exercise should be used as a symptom management tool to improve mood in depression, with even light exercise an effective recommendation. These results need to be replicated and extended to other components of exercise prescription (e.g., duration, frequency, mode) to optimize exercise guidelines for improving depression.
C1 [Meyer, Jacob D.; Koltyn, Kelli F.; Stegner, Aaron J.; Kim, Jee-Seon; Cook, Dane B.] Univ Wisconsin, Madison, WI 53706 USA.
[Stegner, Aaron J.; Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Meyer, JD (reprint author), 2000 Observ Dr, Madison, WI 53706 USA.
EM jdmeyer3@wisc.edu
FU Virginia Home Henry Gift Fund; University of Wisconsin-Madison Graduate
School; Wisconsin Center for Education Research; National Research
Service Award from the Health Resources and Services Administration
[T32HP10010]
FX This project was funded, in part, by the Virginia Home Henry Gift Fund,
the University of Wisconsin-Madison Graduate School and the Wisconsin
Center for Education Research. Jacob Meyer was partially supported by a
National Research Service Award from the Health Resources and Services
Administration T32HP10010 to the University of Wisconsin Department of
Family Medicine and Community Health. None of the funding sources were
involved in the study design, collection, analysis or interpretation of
the data. The authors would like to thank Lauren Schlapman, Hannah
Feinstein, Shawn Tipple, Matthew Patton, Caroline Wickler and Rachel
Prince for their contributions during data collection and processing.
NR 38
TC 2
Z9 2
U1 26
U2 30
PU ASSOC ADV BEHAVIOR THERAPY
PI NEW YORK
PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA
SN 0005-7894
EI 1878-1888
J9 BEHAV THER
JI Behav. Therapy
PD JUL
PY 2016
VL 47
IS 4
BP 527
EP 537
PG 11
WC Psychology, Clinical
SC Psychology
GA DS7NR
UT WOS:000380970700008
PM 27423168
ER
PT J
AU Styer, AK
Rueda, BR
AF Styer, Aaron K.
Rueda, Bo R.
TI The Epidemiology and Genetics of Uterine Leiomyoma
SO BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY
LA English
DT Article
DE fibroids; leiomyomata; epidemiology; genetic; epigenetic
ID PROLACTIN-RELEASING PEPTIDE; AFRICAN-AMERICAN WOMEN; EXPRESSION PROFILE;
DNA METHYLATION; CYTOGENETIC ABNORMALITIES; REPRODUCTIVE FACTORS;
RISK-FACTORS; BLACK-WOMEN; FIBROIDS; MYOMETRIUM
AB Uterine leiomyomas (fibroids) are the most common benign neoplasms in premenopausal women, which confer significant morbidity during the reproductive years and represent a significant public health issue. The incidence of fibroids has been associated with African-American race, early onset of menarche, early parity, and environmental/dietary exposures. These sex steroid responsive uterine tumors are characterized by de novo transformation of the myometrium into fibroids via excessive formation of the extracellular matrix (ECM). Cytogenic anomalies, mutations in mediator complex subunit 12 (MED 12), and aberrant DNA methylation/demethylation have been observed, but have not been reported as direct mediators of fibroid development. Recent advances in epigenetics have implied a functional role of G protein-coupled receptor 10 (GPR10) overexpression and irregular microRNA expression in the pathobiology of fibroids that require future investigation. Herein, the impact of epidemiologic and genetic factors on the incidence and development of fibroids is reviewed. (C) 2016 Published by Elsevier Ltd.
C1 [Styer, Aaron K.; Rueda, Bo R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Thier 9-901, Boston, MA 02114 USA.
[Styer, Aaron K.; Rueda, Bo R.] Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
RP Rueda, BR (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Dept Obstet & Gynecol, Thier 9-901, Boston, MA 02114 USA.
EM brueda@mgh.harvard.edu
NR 81
TC 3
Z9 3
U1 3
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6934
EI 1532-1932
J9 BEST PRACT RES CL OB
JI Best Pract. Res. Clin. Obstet. Gynaecol.
PD JUL
PY 2016
VL 34
BP 3
EP 12
DI 10.1016/j.bpobgyn.2015.11.018
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DT7ED
UT WOS:000381649000002
PM 26725703
ER
PT J
AU Jacobus, SJ
Rajkumar, SV
Weiss, M
Stewart, AK
Stadtmauer, EA
Callander, NS
Dreosti, LM
Lacy, MQ
Fonseca, R
AF Jacobus, S. J.
Rajkumar, S. V.
Weiss, M.
Stewart, A. K.
Stadtmauer, E. A.
Callander, N. S.
Dreosti, L. M.
Lacy, M. Q.
Fonseca, R.
TI Randomized phase III trial of consolidation therapy with
bortezomib-lenalidomide-Dexamethasone (VRd) vs bortezomib-dexamethasone
(Vd) for patients with multiple myeloma who have completed a
dexamethasone based induction regimen
SO BLOOD CANCER JOURNAL
LA English
DT Letter
C1 [Jacobus, S. J.] ECOG ACRIN Biostat Ctr, Dana Farber Canc Inst, Boston, MA USA.
[Rajkumar, S. V.; Lacy, M. Q.] Mayo Clin, Rochester, MN USA.
[Weiss, M.] ThedaCare, Appleton, WI USA.
[Stewart, A. K.; Fonseca, R.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Stadtmauer, E. A.] Univ Penn, Philadelphia, PA 19104 USA.
[Callander, N. S.] Univ Wisconsin, Madison, WI USA.
[Dreosti, L. M.] Univ Pretoria, Pretoria, South Africa.
RP Fonseca, R (reprint author), Mayo Clin Arizona, Scottsdale, AZ USA.
EM fonseca.rafael@mayo.edu
NR 15
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD JUL
PY 2016
VL 6
AR e448
DI 10.1038/bcj.2016.55
PG 3
WC Oncology
SC Oncology
GA DS5VU
UT WOS:000380851900009
PM 27471864
ER
PT J
AU Barnes, GD
Stanislawski, MA
Liu, WH
Baron, AE
Armstrong, EJ
Ho, PM
Klein, A
Maddox, TM
Nallamothu, BK
Rumsfeld, JS
Tsai, TT
Bradley, SM
AF Barnes, Geoffrey D.
Stanislawski, Maggie A.
Liu, Wenhui
Baron, Anna E.
Armstrong, Ehrin J.
Ho, P. Michael
Klein, Andrew
Maddox, Thomas M.
Nallamothu, Brahmajee K.
Rumsfeld, John S.
Tsai, Thomas T.
Bradley, Steven M.
TI Use of Contraindicated Antiplatelet Medications in the Setting of
Percutaneous Coronary Intervention Insights From the Veterans Affairs
Clinical Assessment, Reporting, and Tracking Program
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE abciximab; eptifibatide; mortality; medication errors; percutaneous
coronary intervention
ID DECISION-SUPPORT-SYSTEMS; CART PROGRAM; PRASUGREL; REGISTRY; RISK;
THROMBOCYTOPENIA; EPTIFIBATIDE; CLOPIDOGREL; ABCIXIMAB; QUALITY
AB Background-Several antiplatelet medications used during and after percutaneous coronary intervention (PCI) are contraindicated for specific patient groups. A broad assessment of contraindicated medication use and associated clinical outcomes is not well described.
Methods and Results-Using national Veterans Affairs Clinical Assessment, Reporting, and Tracking Program data for all PCI between 2007 and 2013, we evaluated patients with contraindications to commonly used antiplatelet medications during and after PCI, defined in accordance with package inserts. Adjusted association between contraindicated medication use and outcomes of periprocedural bleeding and 30-day mortality were assessed using Cox proportional hazards with inverse probability weighting. Among 64 294 patients undergoing PCI, 11 315(17.6%) had a contraindication to a common antiplatelet medication and 737 (6.5%) of these patients received a contraindicated medication. In unadjusted analyses, any contraindicated medication use was associated with both increased bleeding and 30-day mortality. In adjusted models, contraindicated abciximab use in patients with thrombocytopenia (hazard ratio, 2.23; 95% confidence interval, 1.58-3.16) and in patients with a previous stroke (hazard ratio, 1.93; 95% confidence interval, 1.37-2.71) remained significantly associated with increased bleeding. Contraindicated abciximab use was not significantly associated with 30-day mortality in adjusted models. Use of eptifibatide in dialysis patients was not significantly associated with an increased risk of bleeding or mortality.
Conclusions-In this national cohort, approximate to 18% of patients undergoing PCI had contraindications to common antiplatelet medications. Approximately 6% of those patients received a contraindicated medication with attendant bleeding risk, although this did not translate into significantly higher risk of 30-day mortality. Continued efforts to reduce contraindicated medication use may help avoid periprocedural complications.
C1 [Barnes, Geoffrey D.; Nallamothu, Brahmajee K.] Univ Michigan, Ann Arbor VA Med Ctr, Frankel Cardiovasc Ctr, Ann Arbor, MI 48109 USA.
[Stanislawski, Maggie A.; Liu, Wenhui; Armstrong, Ehrin J.; Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.; Bradley, Steven M.] Denver VA Med Ctr, Denver, CO USA.
[Baron, Anna E.] Univ Colorado, Sch Publ Hlth, Denver, CO 80202 USA.
[Klein, Andrew] St Louis VA Med Ctr, St Louis, MO USA.
[Tsai, Thomas T.] Kaiser Permanente Colorado, Inst Heath Res, Denver, CO USA.
RP Barnes, GD (reprint author), Univ Michigan, Frankel Cardiovasc Ctr, 2800 Plymouth Rd,Bldg 14 G101, Ann Arbor, MI 48109 USA.
EM gbarnes@umich.edu
FU National Heart, Lung, and Blood Institute [T32-HL007853]; Veterans
Affairs Health Services Research and Development [HSRD-CDA2 10-199,
HSRD-CDA2 08-021]
FX Dr Barnes is supported by National Heart, Lung, and Blood Institute
grant T32-HL007853. Drs Bradley and Maddox are supported by Career
Development Awards (HSR&D-CDA2 10-199 and HSR&D-CDA2 08-021,
respectively) from Veterans Affairs Health Services Research and
Development.
NR 27
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-7705
EI 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2016
VL 9
IS 4
BP 406
EP +
DI 10.1161/CIRCOUTCOMES.115.002043
PG 19
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DS2MY
UT WOS:000380609700010
PM 27245070
ER
PT J
AU Afilalo, J
Steele, R
Manning, WJ
Khabbaz, KR
Rudski, LG
Langlois, Y
Morin, JF
Picard, MH
AF Afilalo, Jonathan
Steele, Russell
Manning, Warren J.
Khabbaz, Kamal R.
Rudski, Lawrence G.
Langlois, Yves
Morin, Jean-Francois
Picard, Michael H.
TI Derivation and Validation of Prognosis-Based Age Cutoffs to Define
Elderly in Cardiac Surgery
SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES
LA English
DT Article
DE aging; cardiac surgery; elderly; mortality; outcomes research
ID ARTERY-BYPASS SURGERY; MAJOR MORBIDITY; OUTCOMES; DISEASE; FRAILTY;
RISK; MORTALITY; ASSOCIATION; DATABASE; PREDICT
AB Background-The age cutoff to define elderly is controversial in cardiac surgery, empirically ranging from >= 65 to >= 80 years. Beyond semantics, this has important implications as a starting point for clinical care pathways and inclusion in trials. We sought to characterize the relationship between age and adverse outcomes in patients undergoing cardiac surgery and to derive and validate prognosis-based age cutoffs.
Methods and Results-Six thousand five hundred seventy one consecutive adult patients undergoing cardiac surgery at 3 hospitals in the United States and Canada were included in the cohort. Logistic regression models and generalized additive models with thin-plate splines were fit to the data. The age distribution was 50 to 59 years in 1244 (18.9%), 60 to 69 years in 2144 (32.6%), 70 to 79 years in 2000 (30.4%), >= 80 years in 1183 (18.0%) patients. After controlling for sex and type of operation, the relationship between age and 30-day operative mortality was found to be nonlinear. Receiver operating characteristic analysis showed that the optimal cutoffs to identify older patients at higher risk of operative mortality were greater than 74, 78, and 75 years for isolated coronary bypass, isolated valve surgery, and coronary bypass plus valve surgery, respectively. These age cutoffs were validated in an independent cohort.
Conclusions-The relationship between age and operative mortality is not linear, manifesting a steeper rise after age 75 for coronary bypass and approaching octogenarian age for isolated valve surgery. Rather than using arbitrary age cutoffs to define elderly, the outcomes-based cutoff of >= 75 years should be used to identify the population of older adults that has higher risk and may benefit from preoperative geriatric evaluation and optimization.
C1 [Afilalo, Jonathan; Rudski, Lawrence G.] McGill Univ, Jewish Gen Hosp, Dept Med, Div Cardiol, Montreal, PQ, Canada.
[Steele, Russell] McGill Univ, Dept Math, Montreal, PQ, Canada.
[Afilalo, Jonathan; Steele, Russell] McGill Univ, Jewish Gen Hosp, Ctr Clin Epidemiol, Montreal, PQ, Canada.
[Manning, Warren J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, Boston, MA 02215 USA.
[Khabbaz, Kamal R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Div Cardiac Surg, Boston, MA 02215 USA.
[Langlois, Yves; Morin, Jean-Francois] McGill Univ, Jewish Gen Hosp, Dept Surg, Div Cardiac Surg, Montreal, PQ, Canada.
[Picard, Michael H.] Harvard Univ, Massachusetts Gen Hosp, Dept Cardiovasc Med, Boston, MA USA.
RP Afilalo, J (reprint author), 3755 Cote Ste Catherine Rd,E-222, Montreal, PQ H3T 1E2, Canada.
EM jonathan.afilalo@mcgill.ca
OI Picard, Michael/0000-0002-9264-3243
FU Fonds de la Recherche en Sante du Quebec Fellowship Grant
FX This work was supported by the Fonds de la Recherche en Sante du Quebec
Fellowship Grant (Dr Afilalo).
NR 25
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-7705
EI 1941-7713
J9 CIRC-CARDIOVASC QUAL
JI Circ.-Cardiovasc. Qual. Outcomes
PD JUL
PY 2016
VL 9
IS 4
BP 424
EP 431
DI 10.1161/CIRCOUTCOMES.115.002409
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DS2MY
UT WOS:000380609700012
PM 27407052
ER
PT J
AU Covert, KL
Fleming, JN
Staino, C
Casale, JP
Boyle, KM
Pilch, NA
Meadows, HB
Mardis, CR
McGillicuddy, JW
Nadig, S
Bratton, CF
Chavin, KD
Baliga, PK
Taber, DJ
AF Covert, Kelly L.
Fleming, James N.
Staino, Carmelina
Casale, Jillian P.
Boyle, Kimberly M.
Pilch, Nicole A.
Meadows, Holly B.
Mardis, Caitlin R.
McGillicuddy, John W.
Nadig, Satish
Bratton, Charles F.
Chavin, Kenneth D.
Baliga, Prabhakar K.
Taber, David J.
TI Predicting and preventing readmissions in kidney transplant recipients
SO CLINICAL TRANSPLANTATION
LA English
DT Article
DE healthcare quality; hospital readmission; kidney transplantation;
medication adherence; pharmacy
ID EARLY HOSPITAL READMISSION; PATIENT; REHOSPITALIZATION; CRITERIA;
OUTCOMES
AB A lack of research exploring post-transplant process optimization to reduce readmissions and increasing readmission rates at our center from 2009 to 2013 led to this study, aimed at assessing the effect of patient and process factors on 30-d readmission rates after kidney transplantation. This was a retrospective case-control study in adult kidney transplant recipients. Univariate and multivariate analyses were utilized to assess patient and process determinants of 30-d readmissions. 384 patients were included; 30-d readmissions were significantly associated with graft loss and death (p = 0.001). Diabetes (p = 0.049), pharmacist identification of poor understanding or adherence, and prolonged time on hemodialysis prior to transplant were associated with an increased risk of 30-d readmissions. After controlling for risk factors, readmission rates were only independently predicted by pharmacist identification of patient lack of understanding or adherence regarding post-transplant medications and dialysis exposure for more than three yr (OR 2.3, 95% CI 1.10-4.71, p = 0.026 and OR 2.1, 95% CI 1.22, 3.70, respectively), both of which were significantly modified by history of diabetes. Thirty-d readmissions are attributable to both patient and process-level factors. These data suggest that a lack of post-transplant medication knowledge in high-risk patients drives early hospital readmission.
C1 [Covert, Kelly L.; Fleming, James N.; Staino, Carmelina; Casale, Jillian P.; Boyle, Kimberly M.; Pilch, Nicole A.; Meadows, Holly B.; Mardis, Caitlin R.] Med Univ South Carolina, Dept Pharm Serv, 280 Calhoun St,MSC 132, Charleston, SC 29425 USA.
[McGillicuddy, John W.; Nadig, Satish; Bratton, Charles F.; Chavin, Kenneth D.; Baliga, Prabhakar K.; Taber, David J.] Med Univ South Carolina, Dept Surg, Charleston, SC USA.
[Taber, David J.] Ralph H Johnson VAMC, Dept Pharm, Charleston, SC USA.
RP Covert, KL (reprint author), Med Univ South Carolina, Dept Pharm Serv, 280 Calhoun St,MSC 132, Charleston, SC 29425 USA.
EM kelly.covert@outlook.com
NR 16
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0902-0063
EI 1399-0012
J9 CLIN TRANSPLANT
JI Clin. Transplant.
PD JUL
PY 2016
VL 30
IS 7
BP 779
EP 786
DI 10.1111/ctr.12748
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DR5PS
UT WOS:000379955500006
PM 27101090
ER
PT J
AU Hu, H
Luo, ML
Desmedt, C
Nabavi, S
Yadegarynia, S
Hong, A
Konstantinopoulos, PA
Gabrielson, E
Hines-Boykin, R
Pihan, G
Yuan, X
Sotirious, C
Dittmer, DP
Fingeroth, JD
Wulf, GM
AF Hu, Hai
Luo, Man-Li
Desmedt, Christine
Nabavi, Sheida
Yadegarynia, Sina
Hong, Alex
Konstantinopoulos, Panagiotis A.
Gabrielson, Edward
Hines-Boykin, Rebecca
Pihan, German
Yuan, Xin
Sotirious, Christos
Dittmer, Dirk P.
Fingeroth, Joyce D.
Wulf, Gerburg M.
TI Epstein-Barr Virus Infection of Mammary Epithelial Cells Promotes
Malignant Transformation
SO EBIOMEDICINE
LA English
DT Article
ID NF-KAPPA-B; GROWTH-FACTOR-RECEPTOR; BREAST-CANCER CELLS; MESENCHYMAL
TRANSITION; MUTATIONAL PROCESSES; DNA-REPAIR; IN-VITRO; EXPRESSION;
ACTIVATION; RISK
AB Whether the human tumor virus, Epstein-Barr Virus (EBV), promotes breast cancer remains controversial and a potential mechanism has remained elusive. Here we show that EBV can infect primary mammary epithelial cells (MECs) that express the receptor CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype, activates MET signaling and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, similar to nasopharyngeal carcinoma(NPC). A human gene expression signature for MECs infected with EBV, termed EBVness, was associated with high grade, estrogen-receptor-negative status, p53 mutation and poor survival. In 11/33 EBVness-positive tumors, EBV-DNA was detected by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes. In an analysis of the TCGA breast cancer data EBVness correlated with the presence of the APOBEC mutational signature. We conclude that a contribution of EBV to breast cancer etiology is plausible, through a mechanism in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is no longer required once malignant transformation has occurred. (C) 2016 Published by Elsevier B.V.
C1 [Hu, Hai; Luo, Man-Li; Yadegarynia, Sina; Yuan, Xin; Wulf, Gerburg M.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA.
[Desmedt, Christine; Sotirious, Christos] Inst Jules Bordet, 121 Blvd Waterloolaan, B-1000 Brussels, Belgium.
[Nabavi, Sheida] Univ Connecticut, Comp Sci & Engn, 371 Fairfield Way, Storrs, CT 06268 USA.
[Konstantinopoulos, Panagiotis A.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
[Gabrielson, Edward] Johns Hopkins Univ, Dept Pathol, 4940 Eastern Ave, Baltimore, MD 21224 USA.
[Hines-Boykin, Rebecca; Dittmer, Dirk P.] Univ N Carolina, Dept Microbiol & Immunol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Fingeroth, Joyce D.] Univ Massachusetts, Dept Med, Sch Med, 364 Plantat St, Worcester, MA 01605 USA.
[Hong, Alex] MIT, Dept Biol, Cambridge, MA 02139 USA.
[Luo, Man-Li] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou 510120, Guangdong, Peoples R China.
[Pihan, German] Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA.
RP Wulf, GM (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA.
EM gwulf@bidmc.harvard.edu
OI Desmedt, Christine/0000-0002-5223-5579
FU NCI NIH HHS [P30 CA016086]
NR 84
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD JUL
PY 2016
VL 9
BP 148
EP 160
DI 10.1016/j.ebiom.2016.05.025
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT6VL
UT WOS:000381622500027
PM 27333046
ER
PT J
AU Angsana, J
Chen, JX
Liu, LY
Haller, CA
Chaikof, EL
AF Angsana, Julianty
Chen, Jiaxuan
Liu, Liying
Haller, Carolyn A.
Chaikof, Elliot L.
TI Efferocytosis as a regulator of macrophage chemokine receptor expression
and polarization
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
DE Chemotaxis; Efferocytosis; Macrophage activation; Peritonitis;
Resolution of inflammation
ID APOPTOTIC CELLS; INFLAMMATION; ACTIVATION; RESOLUTION; ATHEROSCLEROSIS;
NOMENCLATURE; PLERIXAFOR; PLAQUES; BLOOD; MICE
AB Efferocytosis has been suggested to promote macrophage resolution programs that are dependent on motility and emigration, however, few studies have addressed directed migration in resolving macrophages. In this report, we hypothesized that efferocytosis would induce differential chemokine receptor expression. Polarized macrophage populations, including macrophages actively engaged in efferocytosis, were characterized by PCR array and traditional transwell motility assays. We identified specific up-regulation of chemokine receptor CXCR4 on both mouse and human macrophages and characterized in vivo expression of CXCR4 in a resolving model of murine peritonitis. Using adoptive transfer and AMD3100 blocking, we confirmed a role for CXCR4 in macrophage egress to draining lymphatics. Collectively these data provide an important mechanistic link between efferocytosis and macrophage emigration.
C1 [Angsana, Julianty; Chaikof, Elliot L.] Georgia Inst Technol, Coulter Dept Biomed Engn, Petit Inst Bioengn & Biosci, Atlanta, GA 30332 USA.
[Angsana, Julianty; Chen, Jiaxuan; Liu, Liying; Haller, Carolyn A.; Chaikof, Elliot L.] Harvard Med Sch, Dept Surg, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Chen, Jiaxuan; Haller, Carolyn A.; Chaikof, Elliot L.] Harvard Univ, Wyss Inst Biol Inspired Engn, Boston, MA 02115 USA.
RP Haller, CA (reprint author), Harvard Med Sch, Dept Surg, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.; Chaikof, EL (reprint author), BIDMC, 110 Francis St,Suite 9F, Boston, MA 02215 USA.
EM echaikof@bidmc.harvard.edu
FU NIH [HL060903]; American Heart Association
FX This work was funded by NIH grant HL060903 (E.L. Chaikof) and a
fellowship from the American Heart Association (J. Angsana).
NR 30
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD JUL
PY 2016
VL 46
IS 7
BP 1592
EP 1599
DI 10.1002/eji.201546262
PG 8
WC Immunology
SC Immunology
GA DS4LM
UT WOS:000380752600008
PM 27139187
ER
PT J
AU Subhash, SS
Baracco, G
Miller, SL
Eagan, A
Radonovich, LJ
AF Subhash, Shobha S.
Baracco, Gio
Miller, Shelly L.
Eagan, Aaron
Radonovich, Lewis J.
TI ESTIMATION OF NEEDED ISOLATION CAPACITY FOR AN AIRBORNE INFLUENZA
PANDEMIC
SO HEALTH SECURITY
LA English
DT Article
ID EXPEDIENT PATIENT ISOLATION; SARS; CONTAINMENT; EPIDEMIC; CARE
AB We estimated the number of isolation beds needed to care for a surge in patients during an airborne-transmissible influenza pandemic. Based on US health system data, the amount of available airborne isolation beds needed for ill patients will be exceeded early in the course of a moderate or severe influenza pandemic, requiring medical facilities to find ways to further expand isolation bed capacity. Rather than building large numbers of permanent airborne infection isolation rooms to increase surge capacity, an investment that would come at great financial cost, it may be more prudent to prepare for wide-scale creation of just-in-time temporary negative-pressure wards.
C1 [Subhash, Shobha S.; Eagan, Aaron; Radonovich, Lewis J.] US Dept Vet Affairs, VA Natl Ctr Occupat Hlth & Infect Control, Gainesville, FL USA.
[Baracco, Gio] Miami VA Healthcare Syst, Infect Dis, Miami, FL USA.
[Baracco, Gio] Miami VA Healthcare Syst, Infect Control Program, Miami, FL USA.
[Baracco, Gio] Univ Miami, Miller Sch Med, Div Infect Dis, Med Clin, Miami, FL 33136 USA.
[Miller, Shelly L.] Univ Colorado, Mech Engn, Boulder, CO 80309 USA.
RP Subhash, SS (reprint author), Natl Ctr Occupat Hlth & Infect Control, Vet Hlth Adm, Off Patient Care Serv Publ Hlth, 1601 SW Archer Rd 151E, Gainesville, FL 32608 USA.
EM Shobsubhash@gmail.com
NR 28
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2326-5094
EI 2326-5108
J9 HEALTH SECUR
JI Health Secur.
PD JUL-AUG
PY 2016
VL 14
IS 4
BP 258
EP 263
DI 10.1089/hs.2016.0015
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DS4SS
UT WOS:000380772200008
PM 27447336
ER
PT J
AU Batmanghelich, NK
Dalca, A
Quon, G
Sabuncu, M
Golland, P
AF Batmanghelich, Nematollah K.
Dalca, Adrian
Quon, Gerald
Sabuncu, Mert
Golland, Polina
CA Alzheimer's Dis Neuroimaging Initi
TI Probabilistic Modeling of Imaging, Genetics and Diagnosis
SO IEEE TRANSACTIONS ON MEDICAL IMAGING
LA English
DT Article
DE Bayesian models; imaging genetics; probabilistic graphical model;
variational inference
ID BAYESIAN VARIABLE SELECTION; GENOME-WIDE ASSOCIATION; SURFACE-BASED
ANALYSIS; HUMAN CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; LINEAR-REGRESSION;
HUMAN BRAIN; PHENOTYPES; APPROXIMATION; SEGMENTATION
AB We propose a unified Bayesian framework for detecting genetic variants associated with disease by exploiting image-based features as an intermediate phenotype. The use of imaging data for examining genetic associations promises new directions of analysis, but currently the most widely used methods make sub-optimal use of the richness that these data types can offer. Currently, image features are most commonly selected based on their relevance to the disease phenotype. Then, in a separate step, a set of genetic variants is identified to explain the selected features. In contrast, our method performs these tasks simultaneously in order to jointly exploit information in both data types. The analysis yields probabilistic measures of clinical relevance for both imaging and genetic markers. We derive an efficient approximate inference algorithm that handles the high dimensionality of image and genetic data. We evaluate the algorithm on synthetic data and demonstrate that it outperforms traditional models. We also illustrate our method on Alzheimer's Disease Neuroimaging Initiative data.
C1 [Batmanghelich, Nematollah K.; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Dalca, Adrian; Golland, Polina] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Quon, Gerald] Univ Calif Davis, Davis, CA 95616 USA.
[Sabuncu, Mert] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Batmanghelich, NK (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
EM batmanghelich@gmail.com
FU NIH NIBIB NAMIC [U54-EB005149]; NIH NCRR NAC [P41-RR13218]; NIH NIBIB
NAC [P41-EB-015902]; NIH K25 NIBIB [1K25EB013649-01]; AHAF pilot
research grant in Alzheimer's disease [A2012333]; NSERC CGS-D; Barbara
J. Weedon Fellowship; Wistron Corporation
FX This work was supported by NIH NIBIB NAMIC U54-EB005149, NIH NCRR NAC
P41-RR13218 and NIH NIBIB NAC P41-EB-015902, NIH K25 NIBIB
1K25EB013649-01, AHAF pilot research grant in Alzheimer's disease
A2012333, NSERC CGS-D, Barbara J. Weedon Fellowship, and Wistron
Corporation. Asterisk indicates corresponding author.
NR 52
TC 0
Z9 0
U1 82
U2 84
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 0278-0062
EI 1558-254X
J9 IEEE T MED IMAGING
JI IEEE Trans. Med. Imaging
PD JUL
PY 2016
VL 35
IS 7
BP 1765
EP 1779
DI 10.1109/TMI.2016.2527784
PG 15
WC Computer Science, Interdisciplinary Applications; Engineering,
Biomedical; Engineering, Electrical & Electronic; Imaging Science &
Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Imaging Science & Photographic
Technology; Radiology, Nuclear Medicine & Medical Imaging
GA DR5GN
UT WOS:000379931600017
PM 26886973
ER
PT J
AU Ellis, MKM
Sally, MB
Malinoski, D
AF Ellis, Margaret Kathleen Menzel
Sally, Mitchell Brett
Malinoski, Darren
TI The development and current status of Intensive Care Unit management of
prospective organ donors
SO INDIAN JOURNAL OF UROLOGY
LA English
DT Review
DE Critical care; donor management; kidney transplant; renal transplant
ID DELAYED GRAFT FUNCTION; HEART-BEATING DONORS; KIDNEY-TRANSPLANT
RECIPIENTS; RENAL-FUNCTION; DECEASED DONORS; POTENTIAL DONORS; GOALS
WORKGROUP; DONATION RATES; TRAUMA CENTER; HEPATITIS-B
AB Introduction: Despite continuous advances in transplant medicine, there is a persistent worldwide shortage of organs available for donation. There is a growing body of research that supports that optimal management of deceased organ donors in Intensive Care Unit can substantially increase the availability of organs for transplant and improve outcomes in transplant recipients.
Methods: A systematic literature review was performed, comprising a comprehensive search of the PubMed database for relevant terms, as well as individual assessment of references included in large original investigations, and comprehensive society guidelines.
Results: In addition to overall adherence to catastrophic brain injury guidelines, optimization of physiologic state in accordance with established donor management goals (DMGs), and establishment of system-wide processes for ensuring early referral to organ procurement organizations (OPOs), several specific critical care management strategies have been associated with improved rates and outcomes of renal transplantation from deceased donors. These include vasoactive medication selection, maintenance of euvolemia, avoidance of hydroxyethyl starch, glycemic control, targeted temperature management, and blood transfusions if indicated.
Conclusions: Management of deceased organ donors should focus first on maintaining adequate perfusion to all organ systems through adherence to standard critical care guidelines, early referral to OPOs, and family support. Furthermore, several specific DMGs and strategies have been recently shown to improve both the rates and outcomes of organ transplantation.
C1 [Ellis, Margaret Kathleen Menzel] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Anesthesiol, Sect Anesthesiol, Portland, OR 97201 USA.
[Ellis, Margaret Kathleen Menzel] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Dept Anesthesiol, Sect Surg Crit Care, Portland, OR 97201 USA.
[Sally, Mitchell Brett; Malinoski, Darren] Oregon Hlth & Sci Univ, Portland VA Med Ctr, Div Trauma Crit Care & Acute Care Surg, Sect Surg Crit Care, Portland, OR 97201 USA.
RP Ellis, MKM (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,Mail Code P3 Anes, Portland, OR 97239 USA.
EM menzel@ohsu.edu
NR 63
TC 0
Z9 0
U1 3
U2 3
PU MEDKNOW PUBLICATIONS & MEDIA PVT LTD
PI MUMBAI
PA B-9, KANARA BUSINESS CENTRE, OFF LINK RD, GHAKTOPAR-E, MUMBAI, 400075,
INDIA
SN 0970-1591
EI 1998-3824
J9 INDIAN J UROL
JI Indian J. Urol.
PD JUL-SEP
PY 2016
VL 32
IS 3
BP 178
EP 185
DI 10.4103/0970-1591.185103
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA DS9NZ
UT WOS:000381111500004
PM 27555674
ER
PT J
AU Nipp, RD
Yao, NL
Lowenstein, LM
Buckner, JC
Parker, IR
Gajra, A
Morrison, VA
Dale, W
Ballman, KV
AF Nipp, Ryan D.
Yao, Nengliang (Aaron)
Lowenstein, Lisa M.
Buckner, Jan C.
Parker, Ira R.
Gajra, Ajeet
Morrison, Vicki A.
Dale, William
Ballman, Karla V.
TI Pragmatic study designs for older adults with cancer: Report from the
U13 conference
SO JOURNAL OF GERIATRIC ONCOLOGY
LA English
DT Article
DE Pragmatic Clinical Trials; Geriatrics; Aging; Cancer; Clinical Trial;
Quality of Life; Frail Older Adults
ID CLUSTER-RANDOMIZED-TRIALS; QUALITY-OF-LIFE; MEMORY-CONCENTRATION TEST;
CELL-LUNG-CANCER; CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; BREAST-CANCER;
ELDERLY-PATIENTS; COGNITIVE IMPAIRMENT; DEPRESSION SCALE
AB Cancer is a disease occurring disproportionately in older adults. However, the evidence base regarding how best to care for these patients remains limited due to their underrepresentation in cancer clinical trials. Pragmatic clinical trials represent a promising approach for enhancing the evidence base in geriatric oncology by allowing investigators to enroll older, frailer patients onto cancer clinical trials. These trials are more accessible, less resource intensive, and place minimal additional burden on participating patients. Additionally, these trials can be designed to measure endpoints directly relevant to older adults, such as quality of life, functional independence and treatment tolerability which are often not addressed in standard clinical trials. Therefore, pragmatic clinical trials allow researchers to include patients for whom the treatment will ultimately be applied and to utilize meaningful endpoints. Examples of pragmatic studies include both large, simple trials and cluster randomized trials. These study designs allow investigators to conduct clinical trials within the context of everyday practice. Further, researchers can devise these studies to place minimal burden on the patient, the treating clinicians and the participating institutions. In order to be successful, pragmatic trials must efficiently utilize the electronic medical record for data capture while also maximizing patient recruitment, enrollment and retention. Additionally, by strategically utilizing pragmatic clinical trials to test therapies and interventions that have previously shown efficacy in younger, fitter patients, these trials represent a potential mechanism to improve the evidence base in geriatric oncology and enhance care for older adults with cancer. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Nipp, Ryan D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Nipp, Ryan D.] Harvard Med Sch, Dept Med, Div Hematol & Oncol, Boston, MA USA.
[Yao, Nengliang (Aaron)] Univ Virginia, Ctr Canc, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Lowenstein, Lisa M.] Univ Texas MD Anderson Canc Ctr, Dept Hlth Serv Res, Div OVP Canc Prevent & Populat Sci, Houston, TX 77030 USA.
[Buckner, Jan C.] Mayo Clin, Dept Oncol, Div Med Oncol, Rochester, MN USA.
[Parker, Ira R.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Gajra, Ajeet] SUNY Upstate Univ, Dept Med, Syracuse, NY USA.
[Gajra, Ajeet] VA Med Ctr, Syracuse, NY USA.
[Morrison, Vicki A.] Univ Minnesota, Vet Affairs Med Ctr, Minneapolis, MN USA.
[Dale, William] Univ Chicago, Sect Geriatr & Palliat Med, Chicago, IL 60637 USA.
[Ballman, Karla V.] Weill Cornell Med Coll, Div Biostat & Epidemiol, New York, NY 10065 USA.
RP Nipp, RD (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM RNipp@MGH.Harvard.edu
NR 63
TC 2
Z9 2
U1 3
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1879-4068
EI 1879-4076
J9 J GERIATR ONCOL
JI J. Geriatr. Oncol.
PD JUL
PY 2016
VL 7
IS 4
SI SI
BP 234
EP 241
DI 10.1016/j.jgo.2016.02.005
PG 8
WC Oncology; Geriatrics & Gerontology
SC Oncology; Geriatrics & Gerontology
GA DS7NP
UT WOS:000380970500003
PM 27197914
ER
PT J
AU Jang, JH
Lee, JH
Chand, HS
Lee, JS
Lin, Y
Weathington, N
Mallampalli, R
Jeon, YJ
Nyunoya, T
AF Jang, Jun-Ho
Lee, Ji-Hyeok
Chand, Hitendra S.
Lee, Jong-Soo
Lin, Yong
Weathington, Nathaniel
Mallampalli, Rama
Jeon, You-Jin
Nyunoya, Toru
TI APO-9 '-Fucoxanthinone Extracted from Undariopsis peteseniana Protects
Oxidative Stress-Mediated Apoptosis in Cigarette Smoke-Exposed Human
Airway Epithelial Cells
SO MARINE DRUGS
LA English
DT Article
DE brown algae; apo-9 '-fucoxanthinone; cigarette smoke; airway epithelial
cells; DNA damage; apoptosis; oxidative stress
ID WERNERS-SYNDROME PROTEIN; HUMAN LUNG FIBROBLASTS; ALGA EISENIA-BICYCLIS;
ECKLONIA-CAVA; BROWN ALGA; DNA-DAMAGE; CELLULAR SENESCENCE;
MARINE-ALGAE; PELVETIA-SILIQUOSA; SARGASSUM-MUTICUM
AB Long-term cigarette smoking increases the risk for chronic obstructive pulmonary disease (COPD), characterized by irreversible expiratory airflow limitation. The pathogenesis of COPD involves oxidative stress and chronic inflammation. Various natural marine compounds possess both anti-oxidant and anti-inflammatory properties, but few have been tested for their efficacy in COPD models. In this study, we conducted an in vitro screening test to identify natural compounds isolated from various brown algae species that might provide protection against cigarette smoke extract (CSE)-induced cytotoxicity. Among nine selected natural compounds, apo-9'-fucoxanthinone (Apo9F) exhibited the highest protection against CSE-induced cytotoxicity in immortalized human bronchial epithelial cells (HBEC2). Furthermore, the protective effects of Apo9F were observed to be associated with a significant reduction in apoptotic cell death, DNA damage, and the levels of mitochondrial reactive oxygen species (ROS) released from CSE-exposed HBEC2 cells. These results suggest that Apo9F protects against CSE-induced DNA damage and apoptosis by regulating mitochondrial ROS production.
C1 [Jang, Jun-Ho; Weathington, Nathaniel; Mallampalli, Rama; Nyunoya, Toru] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.
[Jang, Jun-Ho; Mallampalli, Rama; Nyunoya, Toru] VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA.
[Lee, Ji-Hyeok; Jeon, You-Jin] Jeju Natl Univ, Dept Marine Sci, Jeju 690756, South Korea.
[Chand, Hitendra S.; Lin, Yong] Lovelace Resp Res Inst, Albuquerque, NM 87108 USA.
[Lee, Jong-Soo] Gyeongsang Natl Univ, Inst Marine Ind, Dept Seafood Sci & Technol, Tongyeong 650160, South Korea.
RP Nyunoya, T (reprint author), Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA.; Nyunoya, T (reprint author), VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Pittsburgh, PA 15240 USA.
EM jangj2@upmc.edu; lee198186@daum.net; hchand@lrri.org; legs@gnu.ac.kr;
ylin@lrri.org; weathingtonnm@upmc.edu; mallampallir@upmc.edu;
youjin2014@gmail.com; nyunoyat@upmc.edu
OI Chand, Hitendra/0000-0002-0574-9307
FU US Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Biomedical Laboratory Research and
the Development; US Department of Veterans Affairs [CX001048]; Flight
Attendant Medical Research Institute; National Institute of Health
[AI117560]; American Lung Association [RG306208]
FX This manuscript was supported, in part, by the US Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development, Biomedical Laboratory Research and the Development. This
work was supported by a Merit Review Award from the US Department of
Veterans Affairs (CX001048) to T.N.; Flight Attendant Medical Research
Institute to R.M.; National Institute of Health (AI117560) and American
Lung Association (RG306208) to H.C.
NR 54
TC 0
Z9 0
U1 1
U2 2
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1660-3397
J9 MAR DRUGS
JI Mar. Drugs
PD JUL
PY 2016
VL 14
IS 7
AR 140
DI 10.3390/md14070140
PG 14
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA DS4PJ
UT WOS:000380762700019
ER
PT J
AU Hong, JX
Qian, TT
Wei, AJ
Sun, ZM
Wu, D
Chen, YH
Marmalidou, A
Lu, Y
Sun, XH
Liu, ZG
Amparo, F
Xu, JJ
AF Hong, Jiaxu
Qian, Tingting
Wei, Anji
Sun, Zhongmou
Wu, Dan
Chen, Yihe
Marmalidou, Anna
Lu, Yi
Sun, Xinghuai
Liu, Zuguo
Amparo, Francisco
Xu, Jianjiang
TI Nasolacrimal recanalization as an alternative to external
dacryocystorhinostomy for treating failed nasolacrimal duct intubation
SO MEDICINE
LA English
DT Article
DE external dacryocystorhinostomy; failed silicon nasolacrimal duct
intubation; nasolacrimal duct obstruction; nasolacrimal recanalization
ID ENDONASAL DACRYOCYSTORHINOSTOMY; MITOMYCIN-C; OBSTRUCTION; OUTCOMES;
ADULTS
AB To compare the surgical duration and clinical outcomes of nasolacrimal recanalization versus external dacryocystorhinostomy (DCR) in the treatment of failed nasolacrimal duct intubation.
This is a retrospective, comparative, and interventional study. We evaluated the outcomes of 66 consecutive patients undergoing either nasolacrimal recanalization (n=32) or DCR (n=34) in a tertiary lacrimal disease referral center. Length of surgical duration, clinical outcomes, and rate of recurrence at 18 months postoperatively were compared.
The mean surgical duration was 18.5 minutes (range, 15-25 minutes) for nasolacrimal recanalization and 48.2 minutes (range, 45-61 minutes) for DCR, respectively (P<0.001). The rate of success was 84.4% in the recanalization group and 85.3% in the DCR group, respectively (P=0.91). The time to recurrence was 2.6 +/- 1.1 months in the recanalization group and 5.6 +/- 2.1 months in the DCR group (P<0.001). Five failed cases in each group received a secondary DCR surgery with the same resolution rate (40%). The absence of ocular discharge at baseline was a significant predictor for a successful outcome in the recanalization group (P=0.04) but not in the DCR group (P=0.63).
Nasolacrimal recanalization is an effective, safe, and time-saving alternative to DCR for the treatment of failed nasolacrimal duct intubation. Clinicians should be cautious in patients with discharge.
C1 [Hong, Jiaxu; Wei, Anji; Wu, Dan; Lu, Yi; Sun, Xinghuai; Xu, Jianjiang] Fudan Univ, Shanghai Med Coll, Eye & ENT Hosp, Dept Ophthalmol & Visual Sci, Shanghai, Peoples R China.
[Hong, Jiaxu; Liu, Zuguo] Xiamen Univ, Inst Eye, Fujian Prov Key Lab Ophthalmol & Visual Sci, Xiamen, Fujian, Peoples R China.
[Qian, Tingting] Fudan Univ, Shanghai Med Coll, Sch Basic Med Sci, Dept Immunol, Shanghai, Peoples R China.
[Sun, Zhongmou; Chen, Yihe; Marmalidou, Anna; Amparo, Francisco] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Sun, Xinghuai] Natl Hlth & Family Planning Commiss, Key Lab Myopia, Shanghai, Peoples R China.
[Liu, Zuguo] Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China.
RP Liu, ZG (reprint author), Cent S Univ, Xiangya Hosp 2, Dept Ophthalmol, Changsha, Hunan, Peoples R China.; Xu, JJ (reprint author), Fudan Univ, Sch Shanghai Med, Eye Ear Nose & Throat Hosp, Dept Ophthalmol & Visual Sci, Shanghai 200031, Peoples R China.
EM zuguoliu@126.com; jianjiangxu@126.com
FU Key Clinic Medicine Research Program, the Ministry of Health, China
[201302015]; National Natural Science Foundation of China [81170817,
81200658, 81300735, 81270978, U1205025, 81330022]; Young Scientist
Excellence Program, Fudan University; Chinese Postdoctoral Fund
[XMU135890]; New Technology Joint Research Project in Shanghai Hospitals
[SHDC12014114]
FX The authors were supported by grants from the Key Clinic Medicine
Research Program, the Ministry of Health, China (201302015); the
National Natural Science Foundation of China (81170817, 81200658,
81300735, 81270978, U1205025, and 81330022); the Young Scientist
Excellence Program, Fudan University (2015); the Chinese Postdoctoral
Fund (XMU135890); and the New Technology Joint Research Project in
Shanghai Hospitals (SHDC12014114).
NR 20
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD JUL
PY 2016
VL 95
IS 30
AR e4350
DI 10.1097/MD.0000000000004350
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS4RO
UT WOS:000380768900059
PM 27472722
ER
PT J
AU Perugino, CA
Wallace, ZS
Meyersohn, N
Oliveira, G
Stone, JR
Stone, JH
AF Perugino, Cory A.
Wallace, Zachary S.
Meyersohn, Nandini
Oliveira, George
Stone, James R.
Stone, John H.
TI Large vessel involvement by IgG4-related disease
SO MEDICINE
LA English
DT Article
DE aortitis; coronary artery aneurysm; IgG4-related disease (IgG4-RD);
inflammatory aortic aneurysm; large vessel vasculitis; periaortitis;
pulmonary artery aneurysm; retroperitoneal fibrosis
ID ABDOMINAL AORTIC-ANEURYSM; CONSENSUS STATEMENT; CORONARY-ARTERY;
PERIARTERITIS; MANIFESTATIONS; PERIAORTITIS; PANCREATITIS; NOMENCLATURE;
PATHOLOGY
AB Objectives: IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition that can affect multiple organs and lead to tumefactive, tissue-destructive lesions. Reports have described inflammatory aortitis and periaortitis, the latter in the setting of retroperitoneal fibrosis (RPF), but have not distinguished adequately between these 2 manifestations. The frequency, radiologic features, and response of vascular complications to B cell depletion remain poorly defined. We describe the clinical features, radiology findings, and treatment response in a cohort of 36 patients with IgG4-RD affecting large blood vessels.
Methods: Clinical records of all patients diagnosed with IgG4-RD in our center were reviewed. All radiologic studies were reviewed. We distinguished between primary large blood vessel inflammation and secondary vascular involvement. Primary involvement was defined as inflammation in the blood vessel wall as a principal focus of disease. Secondary vascular involvement was defined as disease caused by the effects of adjacent inflammation on the blood vessel wall.
Results: Of the 160 IgG4-RD patients in this cohort, 36 (22.5%) had large-vessel involvement. The mean age at disease onset of the patients with large-vessel IgG4-RD was 54.6 years. Twenty-eight patients (78%) were male and 8 (22%) were female. Thirteen patients (36%) had primary IgG4-related vasculitis and aortitis with aneurysm formation comprised the most common manifestation. This affected 5.6% of the entire IgG4-RD cohort and was observed in the thoracic aorta in 8 patients, the abdominal aorta in 4, and both the thoracic and abdominal aorta in 3. Three of these aneurysms were complicated by aortic dissection or contained perforation. Periaortitis secondary to RPF accounted for 27 of 29 patients (93%) of secondary vascular involvement by IgG4-RD. Only 5 patients demonstrated evidence of both primary and secondary blood vessel involvement. Of those treated with rituximab, a majority responded positively.
Conclusions: IgG4-RD is a distinctive, unique, and treatable cause of large-vessel vasculitis. It can also involve blood vessels secondary to perivascular tumefactive lesions. The most common manifestation of IgG4-related vasculitis is aortitis with aneurysm formation. The most common secondary vascular manifestation is periaortitis with relative sparing of the aortic wall. Both primary vasculitis and secondary vascular involvement respond well to B cell depletion therapy.
C1 [Perugino, Cory A.; Wallace, Zachary S.; Meyersohn, Nandini; Oliveira, George; Stone, James R.; Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Stone, JH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM jhstone@mgh.harvard.edu
NR 24
TC 2
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD JUL
PY 2016
VL 95
IS 28
AR e3344
DI 10.1097/MD.0000000000003344
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS4QZ
UT WOS:000380767200004
PM 27428181
ER
PT J
AU Mottalib, A
Mohd-Yusof, BN
Shehabeldin, M
Pober, DM
Mitri, J
Hamdy, O
AF Mottalib, Adham
Mohd-Yusof, Barakatun-Nisak
Shehabeldin, Mohamed
Pober, David M.
Mitri, Joanna
Hamdy, Osama
TI Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on
Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia
SO NUTRIENTS
LA English
DT Article
DE clinical nutrition; nutritional formula; meal replacement; medical food;
diabetes; obesity
ID GLUCAGON-LIKE PEPTIDE-1; PLASMA-GLUCOSE; WEIGHT LOSSES; RESPONSES;
HYPERGLYCEMIA; SECRETION; INGESTION; MELLITUS; COMPLICATIONS;
METAANALYSIS
AB Diabetes-specific nutritional formulas (DSNFs) are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP) effects of 2 DSNFs; Glucerna (GL) and Ultra Glucose Control (UGC) versus oatmeal (OM) on glucose, insulin, glucagon-like peptide-1 (GLP-1), free fatty acids (FFA) and triglycerides (TG). After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC(0-240)) after GL and UGC was lower than OM (p < 0.001 for both). Insulin positive AUC(0-120) after UGC was higher than after OM (p = 0.02). GLP-1 AUC(0-120) and AUC(0-240) after GL and UGC was higher than after OM (p < 0.001 for both). FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat.
C1 [Mottalib, Adham; Mohd-Yusof, Barakatun-Nisak; Shehabeldin, Mohamed; Pober, David M.; Mitri, Joanna; Hamdy, Osama] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Mohd-Yusof, Barakatun-Nisak] Univ Putra Malaysia, Fac Med & Hlth Sci, Dept Nutr & Dietet, Serdang 43400, Malaysia.
RP Mottalib, A; Hamdy, O (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA.
EM adham.mottalib@joslin.harvard.edu;
Barakatun.Nisak-Mohd-Yusof@joslin.harvard.edu; moshehabeldin@gmail.com;
david.pober@joslin.harvard.edu; joanna.mitri@joslin.harvard.edu;
osama.hamdy@joslin.harvard.edu
FU Metagenics, Inc.
FX This was supported by a grant from Metagenics, Inc.; however, Metagenics
had no role in the study design, conduct, analysis or presentation. Data
from this study were presented at the 75th American Diabetes Association
Meeting. We would like to thank staff of the Joslin Clinical Research
Center for their efforts, Harvard Catalyst for statistical consultation,
Haya Raef and Rani Polak for their assistance in conducting study visits
and data entry.
NR 32
TC 0
Z9 0
U1 3
U2 3
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 2072-6643
J9 NUTRIENTS
JI Nutrients
PD JUL
PY 2016
VL 8
IS 7
AR 443
DI 10.3390/nu8070443
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DS4QP
UT WOS:000380766200060
ER
PT J
AU Kessel, D
Evans, CL
AF Kessel, David
Evans, Conor L.
TI Promotion of Proapoptotic Signals by Lysosomal Photodamage: Mechanistic
Aspects and Influence of Autophagy
SO PHOTOCHEMISTRY AND PHOTOBIOLOGY
LA English
DT Article
ID PHOTODYNAMIC THERAPY; CELLS; APOPTOSIS; CANCER
AB Prior studies demonstrated that a low level (LD10-15) of lysosomal photodamage can sensitize cells to the apoptotic death that results from subsequent mitochondrial photodamage. We have proposed that this process occurs via a calpain-catalyzed cleavage of the autophagy-associated protein ATG5 to form a proapoptotic fragment. In this report, we provide evidence for the postulated ATG5 cleavage and show that the sequential photodynamic therapy (PDT) protocol can also partly overcome the adverse effect of hypoxia on the initiation of apoptosis. While autophagy can offer cytoprotection after mitochondrial photodamage, this does not appear to apply when lysosomes are the target. This may account for the ability of very low PDT doses directed at lysosomes to evoke ATG5 cleavage. The resulting proapoptotic effect overcomes intrinsic cytoprotection from mitochondrial photodamage along with a further stimulation of phototoxicity.
C1 [Kessel, David] Wayne State Univ, Dept Pharmacol, Detroit, MI 48201 USA.
[Evans, Conor L.] Harvard Med Sch, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA USA.
RP Kessel, D (reprint author), Wayne State Univ, Dept Pharmacol, Detroit, MI 48201 USA.
EM dhkessel@med.wayne.edu
FU National Cancer Institute, National Institutes of Health [CA23378]; NIH
Director's New Innovator Award [DP2 OD007096]
FX This study was partly supported by grant CA23378 from the National
Cancer Institute, National Institutes of Health. CLE was supported by
the NIH Director's New Innovator Award, grant DP2 OD007096. Information
on the New Innovator Award program is at
http://nihroadmap.nih.gov/newinnovator/.. We thank Ann Marie Santiago
for excellent technical assistance.
NR 23
TC 2
Z9 2
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0031-8655
EI 1751-1097
J9 PHOTOCHEM PHOTOBIOL
JI Photochem. Photobiol.
PD JUL-AUG
PY 2016
VL 92
IS 4
BP 620
EP 623
DI 10.1111/php.12592
PG 4
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DS6RX
UT WOS:000380911200016
PM 27096545
ER
PT J
AU Kales, HC
Kavanagh, J
Chiang, C
Kim, HM
Bishop, T
Valenstein, M
Blow, FC
AF Kales, Helen C.
Kavanagh, Janet
Chiang, Claire
Kim, H. Myra
Bishop, Tiffany
Valenstein, Marcia
Blow, Frederic C.
TI Predictors of Antidepressant Nonadherence Among Older Veterans With
Depression
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID PRIMARY-CARE; PERCEIVED STIGMA; ADHERENCE; PATIENT; SEVERITY; SERVICES;
RECEIPT; ANXIETY; RISK; RACE
AB Objective: Most depression among older adults is treated in primary care, and many patients do not adhere to medication treatment. The U.S. Department of Veterans Affairs (VA) has recently introduced initiatives to address such treatment gaps. This study examined patient-reported antidepressant nonadherence during the acute treatment period (first four months after a prescription) and identified predictors of nonadherence in a sample of older veterans.
Methods: This was a prospective, observational study of 311 participants ages 60 and older who received care at three VA medical centers and who had a diagnosis of clinically significant depression and were given a new outpatient antidepressant prescription. Participants completed an initial interview and a follow-up interview at four months after treatment recommendation. Antidepressant adherence was measured with a well-validated self-report measure.
Results: At four months, 29% of participants reported nonadherence to their antidepressant medication. In unadjusted analyses, nonadherence was significantly associated with being African American, having no spouse or significant other, having greater general medical comorbidity, and receiving the prescription in a primary care setting (versus a specialty mental health setting). In logistic regression models controlling for several variables (demographic, illness, and functional status variables; type of antidepressant; contact with a therapist; medical setting; and site of recruitment), two predictors remained significantly associated with nonadherence: African-American race (odds ratio [OR] = 4.23, p < .001) and general medical comorbidity (OR = 1.33, p = .002).
Conclusions: The two main predictors of nonadherence among older adults with depression were African-American race and general medical comorbidity. Results suggest that significant needs remain for important patient subgroups to improve antidepressant adherence.
C1 [Kales, Helen C.; Kavanagh, Janet; Bishop, Tiffany; Valenstein, Marcia; Blow, Frederic C.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Kim, H. Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI 48109 USA.
[Kales, Helen C.; Chiang, Claire; Valenstein, Marcia; Blow, Frederic C.] US Dept Vet Affairs, Ctr Clin Management Res Hlth Serv Res & Dev, Ann Arbor, MI USA.
RP Kales, HC (reprint author), Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
EM kales@med.umich.edu
FU Health Services Research and Development, U.S. Department of Veterans
Affairs [IIR 04-104-2]
FX This research was supported by grant IIR 04-104-2 from Health Services
Research and Development, U.S. Department of Veterans Affairs. The
funding organization had no role in the design and conduct of the study;
collection, management, analysis, and interpretation of the data; and
preparation, review, or approval of the manuscript.
NR 28
TC 0
Z9 0
U1 7
U2 7
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL 1
PY 2016
VL 67
IS 7
BP 728
EP 734
DI 10.1176/appi.ps.201500120
PG 7
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DT7NA
UT WOS:000381672300006
PM 27032656
ER
PT J
AU Coleman, KJ
Stewart, C
Waitzfelder, BE
Zeber, JE
Morales, LS
Ahmed, AT
Ahmedani, BK
Beck, A
Copeland, LA
Cummings, JR
Hunkeler, EM
Lindberg, NM
Lynch, F
Lu, CY
Owen-Smith, AA
Trinacty, CM
Whitebird, RR
Simon, GE
AF Coleman, Karen J.
Stewart, Christine
Waitzfelder, Beth E.
Zeber, John E.
Morales, Leo S.
Ahmed, Ameena T.
Ahmedani, Brian K.
Beck, Arne
Copeland, Laurel A.
Cummings, Janet R.
Hunkeler, Enid M.
Lindberg, Nangel M.
Lynch, Frances
Lu, Christine Y.
Owen-Smith, Ashli A.
Trinacty, Connie Mah
Whitebird, Robin R.
Simon, Gregory E.
TI Racial-Ethnic Differences in Psychiatric Diagnoses and Treatment Across
11 Health Care Systems in the Mental Health Research Network
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID AFFECTIVE-DISORDERS; UNITED-STATES; ANTIPSYCHOTIC MEDICATIONS;
ANTIDEPRESSANT TREATMENT; MEDICAID POPULATION; DEPRESSION CARE; NATIONAL
TRENDS; CHART AUDIT; SELF-REPORT; SCHIZOPHRENIA
AB Objective: The objective of this study was to characterize racial-ethnic variation in diagnoses and treatment of mental disorders in large not-for-profit health care systems.
Methods: Participating systems were 11 private, not-forprofit health care organizations constituting the Mental Health Research Network, with a combined 7,523,956 patients age 18 or older who received care during 2011. Rates of diagnoses, prescription of psychotropic medications, and total formal psychotherapy sessions received were obtained from insurance claims and electronic medical record databases across all health care settings.
Results: Of the 7.5 million patients in the study, 1.2 million (15.6%) received a psychiatric diagnosis in 2011. This varied significantly by race-ethnicity, with Native American/Alaskan Native patients having the highest rates of any diagnosis (20.6%) and Asians having the lowest rates (7.5%). Among patients with a psychiatric diagnosis, 73% (N = 850,585) received a psychotropic medication. Non-Hispanic white patients were significantly more likely (77.8%) than other racial-ethnic groups (odds ratio [OR] range.48-.81) to receive medication. In contrast, only 34% of patients with a psychiatric diagnosis (N=548,837) received formal psychotherapy. Racial-ethnic differences were most pronounced for depression and schizophrenia; compared with whites, non-Hispanic blacks were more likely to receive formal psychotherapy for their depression (OR=1.20) or for their schizophrenia (OR=2.64).
Conclusions: There were significant racial-ethnic differences in diagnosis and treatment of psychiatric conditions across 11 U.S. health care systems. Further study is needed to understand underlying causes of these observed differences and whether processes and outcomes of care are equitable across these diverse patient populations.
C1 [Coleman, Karen J.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Stewart, Christine; Simon, Gregory E.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Waitzfelder, Beth E.; Trinacty, Connie Mah] Kaiser Permanente Hawaii, Ctr Hlth Res, Honolulu, HI USA.
[Zeber, John E.; Copeland, Laurel A.] US Dept Vet Affairs, Hlth Serv Res & Dev, Temple, TX USA.
[Zeber, John E.; Copeland, Laurel A.] Baylor Scott & White Hlth, Ctr Appl Hlth Res, Temple, TX USA.
[Morales, Leo S.] Univ Washington, Ctr Hlth Equ Divers & Inclus, Seattle, WA 98195 USA.
[Ahmed, Ameena T.] Kaiser Permanente Northern Calif, Permanente Med Grp, San Francisco, CA USA.
[Ahmedani, Brian K.] Henry Ford Hlth Syst, Ctr Hlth Policy & Hlth Serv Res, Detroit, MI USA.
[Beck, Arne] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA.
[Cummings, Janet R.] Emory Univ, Dept Hlth Policy & Management, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Hunkeler, Enid M.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA.
[Lindberg, Nangel M.; Lynch, Frances] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
[Lu, Christine Y.] Harvard Med Sch, Boston, MA USA.
[Lu, Christine Y.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Owen-Smith, Ashli A.] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA.
[Whitebird, Robin R.] St Catherine Univ, Univ St Thomas, Sch Social Work, St Paul, MN USA.
RP Coleman, KJ (reprint author), Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
EM karen.j.coleman@kp.org
OI Copeland, Laurel/0000-0002-9478-0209
FU National Institute of Mental Health award - Mental Health Research
Network [U19MH092201]
FX Funding was provided by National Institute of Mental Health award
U19MH092201 in support of the Mental Health Research Network.
NR 47
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Z9 1
U1 2
U2 3
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL 1
PY 2016
VL 67
IS 7
BP 749
EP 757
DI 10.1176/appi.ps.201500217
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DT7NA
UT WOS:000381672300009
PM 27079987
ER
PT J
AU Leggett, A
Ganoczy, D
Zivin, K
Valenstein, M
AF Leggett, Amanda
Ganoczy, Dara
Zivin, Kara
Valenstein, Marcia
TI Predictors of Pharmacy-Based Measurement and Self-Report of
Antidepressant Adherence: Are Individuals Overestimating Adherence?
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID PATIENT ADHERENCE; DEPRESSION; PHARMACOTHERAPY; QUALITY; RISK
AB Objective: This study considered various factors as predictors of antidepressant adherence over time as assessed by self-report and medication possession ratios (MPRs) derived from administrative pharmacy data.
Methods: Adherence was assessed at six and 12 months among 443 veterans in ongoing treatment for depression in a trial of peer support. Logistic regression models were utilized to consider predictors of adequate adherence.
Results: At six and 12 months, respectively, 36% and 35% of patients had poor adherence on the basis of MPRs and 24% and 18% had poor adherence on the basis of self-report. MPRs indicating poor adherence were more likely among men, members of racial groups other than white, and patients with Hispanic ethnicity. Poor self-reported adherence was associated with increased depressive symptoms and unemployment.
Conclusions: These adherence measures may be complementary. Strategies to improve adherence might target specific demographic groups, unemployed persons, and persons with higher levels of depressive symptoms.
C1 [Leggett, Amanda; Zivin, Kara; Valenstein, Marcia] Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Ganoczy, Dara; Zivin, Kara; Valenstein, Marcia] US Dept Vet Affairs, Ctr Clin Management Res, Ann Arbor, MI USA.
RP Leggett, A (reprint author), Univ Michigan, Sch Med, Dept Psychiat, Ann Arbor, MI 48109 USA.
EM leggetta@med.umich.edu
FU Health Services Research and Development Service, U.S. Department of
Veterans Affairs [IIR-08-325]; National Institute of Mental Health
geriatric mental health services fellowship [T32 MH073553]
FX Support for this work was provided by the Health Services Research and
Development Service, U.S. Department of Veterans Affairs (IIR-08-325).
Dr. Leggett is funded by a National Institute of Mental Health geriatric
mental health services fellowship (T32 MH073553).
NR 15
TC 0
Z9 0
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL 1
PY 2016
VL 67
IS 7
BP 803
EP 806
DI 10.1176/appi.ps.201400568
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DT7NA
UT WOS:000381672300019
PM 26876656
ER
PT J
AU Kopacz, MS
Kane, CP
Stephens, B
Pigeon, WR
AF Kopacz, Marek S.
Kane, Cathleen P.
Stephens, Brady
Pigeon, Wilfred R.
TI Use of ICD-9-CM Diagnosis Code V62.89 (Other Psychological or Physical
Stress, Not Elsewhere Classified) Following a Suicide Attempt
SO PSYCHIATRIC SERVICES
LA English
DT Article
ID RISK
AB Objective: This study examined the demographic, diagnostic, and service characteristics of veterans who received services for "other psychological or physical stress, not elsewhere classified" (ICD-9-CM V62.89) in the month following a suicide attempt.
Methods: An electronic search of a Veterans Health Administration (VHA) suicide event reporting system identified 22,701 veterans who were survivors of a suicide attempt. Their clinical service encounter records were extracted from a VHA administrative database to identify those who received services related to V62.89.
Results: Services related to V62.89 were provided to N=2,173 (9.6%) of the sample. Chaplains were the predominant service provider, identified in N=1,745 (80%) of the service encounters. Differences were noted between those who received services related to V62.89 from a chaplain or from another service provider.
Conclusions: V62.89 appears to be a focus of clinical concern for some veteran suicide attempt survivors. Additional research is needed to better understand any implications for suicide "postvention."
C1 [Kopacz, Marek S.; Kane, Cathleen P.; Stephens, Brady; Pigeon, Wilfred R.] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA.
[Pigeon, Wilfred R.] Univ Rochester, Med Ctr, Dept Psychiat, Rochester, NY 14642 USA.
RP Kopacz, MS (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, Canandaigua, NY 14424 USA.
EM marek.kopacz@va.gov
FU U.S. Department of Veterans Affairs (VA) VISN 2 Center of Excellence for
Suicide Prevention, Canandaigua, New York; Merck; Sharp; Dohme
FX This work was funded in part by the U.S. Department of Veterans Affairs
(VA) VISN 2 Center of Excellence for Suicide Prevention, Canandaigua,
New York. The views expressed are those of the authors and do not
reflect the official policy or position of the VA or the U.S.
government.; Dr. Pigeon reports receipt of speaker fees from Merck,
Sharp, and Dohme. The other authors report no financial relationships
with commercial interests.
NR 15
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Z9 0
U1 0
U2 0
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1075-2730
EI 1557-9700
J9 PSYCHIAT SERV
JI Psychiatr. Serv.
PD JUL 1
PY 2016
VL 67
IS 7
BP 807
EP 810
DI 10.1176/appi.ps.201500302
PG 4
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychiatry
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychiatry
GA DT7NA
UT WOS:000381672300020
PM 26876664
ER
PT J
AU Mitchell, MA
Hedayati, DO
Rodriguez, KL
Gordon, AJ
Broyles, LM
True, G
Balbale, SN
Conley, JW
AF Mitchell, Michael A.
Hedayati, Daniel O.
Rodriguez, Keri L.
Gordon, Adam J.
Broyles, Lauren M.
True, Gala
Balbale, Salva N.
Conley, James W.
TI Logistical Lessons Learned in Designing and Executing a
Photo-Elicitation Study in the Veterans Health Administration
SO QUALITATIVE REPORT
LA English
DT Article
DE Homeless Persons; Photography; Qualitative Research; Veterans; Veterans'
Health
ID PATIENT-CENTERED CARE; ILLNESS
AB Participatory photography research methods have been used to successfully engage and collect in-depth information from individuals whose voices have been traditionally marginalized in clinical or research arenas. However, participatory photography methods can introduce unique challenges and considerations regarding study design, human subject protections, and other regulatory barriers, particularly with vulnerable patient populations and in highly regulated institutions. Practical guidance on navigating these complex, interrelated methodological, logistical, and ethical issues is limited. Using a case exemplar, we describe our experiences with the planning, refinement, and initiation of a research study that used photo-elicitation interviews to assess the healthcare experiences of homeless and marginally housed United States Veterans. We discuss practical issues and recommendations related to study design, logistical "pitfalls" during study execution, and ensuring human subjects protections in the context of a study with a highly vulnerable patient population taking place in a highly risk-averse research environment.
C1 [Mitchell, Michael A.] Allegheny Cty Dept Human Serv, Off Data Anal Res & Evaluat, Pittsburgh, PA 15222 USA.
[Mitchell, Michael A.; Gordon, Adam J.; Broyles, Lauren M.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.
[Hedayati, Daniel O.; Rodriguez, Keri L.; Gordon, Adam J.; Broyles, Lauren M.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
[Rodriguez, Keri L.; Conley, James W.] VA Pittsburgh Healthcare System, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15261 USA.
[Rodriguez, Keri L.] VA Pittsburgh Healthcare System, Vet Engn Resource Ctr, Pittsburgh, PA USA.
[True, Gala] Southeast Louisiana Vet Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 16, New Orleans, LA USA.
[True, Gala] Tulane Univ, Sch Med, 1430 Tulane Ave, New Orleans, LA 70112 USA.
[Balbale, Salva N.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Balbale, Salva N.] Dept Vet Affairs, Washington, DC USA.
[Conley, James W.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA 15261 USA.
RP Mitchell, MA (reprint author), Allegheny Cty Dept Human Serv, Off Data Anal Res & Evaluat, Pittsburgh, PA 15222 USA.; Mitchell, MA; Broyles, LM (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.; Hedayati, DO; Broyles, LM (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.; Conley, JW (reprint author), VA Pittsburgh Healthcare System, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15261 USA.; Conley, JW (reprint author), VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA 15261 USA.
EM mike.mitchell@alleghenycounty.us; daniel@medstudent.pitt.edu;
lauren.broyles@va.gov; james.conley@va.gov
NR 25
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Z9 0
U1 2
U2 2
PU NOVA SOUTHEASTERN UNIV
PI FORT LAUDERDALE-DAVIE
PA 3301 COLLEGE AVE, FORT LAUDERDALE-DAVIE, FL 33314 USA
SN 2160-3715
J9 QUAL REP
JI Qual. Rep.
PD JUL
PY 2016
VL 21
IS 7
BP 1303
EP 1315
PG 13
WC Social Sciences, Interdisciplinary
SC Social Sciences - Other Topics
GA DT6VQ
UT WOS:000381623100008
ER
PT J
AU Manchikanti, L
Hirsch, JA
AF Manchikanti, Laxmaiah
Hirsch, Joshua A.
TI Introduction of a predictive model for epidural steroid injections leads
to inappropriate and inaccurate conclusions
SO SPINE JOURNAL
LA English
DT Letter
ID CENTRAL SPINAL STENOSIS; LUMBAR SURGERY SYNDROME; 2-YEAR FOLLOW-UP;
DOUBLE-BLIND; CONTROLLED-TRIAL; DISC HERNIATION; FUSION SURGERY;
OLDER-ADULTS; COMPLICATIONS; CHARGES
C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA.
[Hirsch, Joshua A.] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, 55 Blossom St,Gray 241B, Boston, MA 02114 USA.
RP Manchikanti, L (reprint author), Pain Management Ctr Paducah, 2831 Lone Oak Rd, Paducah, KY 42003 USA.
NR 21
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1529-9430
EI 1878-1632
J9 SPINE J
JI Spine Journal
PD JUL
PY 2016
VL 16
IS 7
BP 905
EP 906
DI 10.1016/j.spinee.2016.02.028
PG 2
WC Clinical Neurology; Orthopedics
SC Neurosciences & Neurology; Orthopedics
GA DT8BJ
UT WOS:000381713100051
PM 27480023
ER
PT J
AU Meppelink, AM
Zhao, X
Griffin, DJ
Erali, R
Gill, TJ
Bonassar, LJ
Redmond, RW
Randolph, MA
AF Meppelink, Amanda M.
Zhao, Xing
Griffin, Darvin J.
Erali, Richard
Gill, Thomas J.
Bonassar, Lawrence J.
Redmond, Robert W.
Randolph, Mark A.
TI Hyaline Articular Matrix Formed by Dynamic Self-Regenerating Cartilage
and Hydrogels
SO TISSUE ENGINEERING PART A
LA English
DT Article
ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; TISSUE-ENGINEERED CARTILAGE;
SUSPENSION-CULTURE; STEM-CELLS; REPAIR; DEFECTS; KNEE; TRANSPLANTATION;
INTEGRATION; SCAFFOLDS
AB Injuries to the articular cartilage surface are challenging to repair because cartilage possesses a limited capacity for self-repair. The outcomes of current clinical procedures aimed to address these injuries are inconsistent and unsatisfactory. We have developed a novel method for generating hyaline articular cartilage to improve the outcome of joint surface repair. A suspension of 10(7) swine chondrocytes was cultured under reciprocating motion for 14 days. The resulting dynamic self-regenerating cartilage (dSRC) was placed in a cartilage ring and capped with fibrin and collagen gel. A control group consisted of chondrocytes encapsulated in fibrin gel. Constructs were implanted subcutaneously in nude mice and harvested after 6 weeks. Gross, histological, immunohistochemical, biochemical, and biomechanical analyses were performed. In swine patellar groove, dSRC was implanted into osteochondral defects capped with collagen gel and compared to defects filled with osteochondral plugs, collagen gel, or left empty after 6 weeks. In mice, the fibrin-and collagen-capped dSRC constructs showed enhanced contiguous cartilage matrix formation over the control of cells encapsulated in fibrin gel. Biochemically, the fibrin and collagen gel dSRC groups were statistically improved in glycosaminoglycan and hydroxyproline content compared to the control. There was no statistical difference in the biomechanical data between the dSRC groups and the control. The swine model also showed contiguous cartilage matrix in the dSRC group but not in the collagen gel and empty defects. These data demonstrate the survivability and successful matrix formation of dSRC under the mechanical forces experienced by normal hyaline cartilage in the knee joint. The results from this study demonstrate that dSRC capped with hydrogels successfully engineers contiguous articular cartilage matrix in both nonload-bearing and load-bearing environments.
C1 [Meppelink, Amanda M.; Zhao, Xing] Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, Boston, MA 02114 USA.
[Griffin, Darvin J.; Bonassar, Lawrence J.] Cornell Univ, Meinig Sch Biomed Engn, Ithaca, NY USA.
[Erali, Richard; Randolph, Mark A.] Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Boston, MA 02114 USA.
[Gill, Thomas J.] Boston Sports Med & Res Inst, Dedham, MA USA.
[Redmond, Robert W.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.
RP Randolph, MA (reprint author), Massachusetts Gen Hosp, Plast Surg Res Lab, 15 Parkman St,WAC 435, Boston, MA 02114 USA.
EM marandolph@mgh.harvard.edu
FU Department of Defense [W81XWH-10-1-0791]
FX This study was supported by a grant from the Department of Defense
(Award Number W81XWH-10-1-0791). The content of the articles does not
necessarily reflect the position or the policy of the Government, and no
official endorsement should be inferred. Special thanks to Tricia Della
Pelle and Nicole Brousides for their work in histological processing as
well as Jie Zhao, MD, PhD, for her help with the immunohistochemical
staining. The authors also thank Joseph Locascio, PhD, for assistance on
the statistical analysis.
NR 30
TC 0
Z9 0
U1 5
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3341
EI 1937-335X
J9 TISSUE ENG PT A
JI Tissue Eng. Part A
PD JUL
PY 2016
VL 22
IS 13-14
BP 962
EP 970
DI 10.1089/ten.tea.2015.0577
PG 9
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA DS2NE
UT WOS:000380614400006
PM 27324118
ER
PT J
AU Geerts, S
Ozer, S
Jaramillo, M
Yarmush, ML
Uygun, BE
AF Geerts, Sharon
Ozer, Sinan
Jaramillo, Maria
Yarmush, Martin L.
Uygun, Basak E.
TI Nondestructive Methods for Monitoring Cell Removal During Rat Liver
Decellularization
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID PORCINE LIVER; ORGAN; SCAFFOLDS; MATRIX
AB Whole liver engineering holds the promise to create transplantable liver grafts that may serve as substitutes for donor organs, addressing the donor shortage in liver transplantation. While decellularization and recellularization of livers in animal models have been successfully achieved, scale up to human livers has been slow. There are a number of donor human livers that are discarded because they are not found suitable for transplantation, but are available for engineering liver grafts. These livers are rejected due to a variety of reasons, which in turn may affect the decellularization outcome. Hence, a one-size-fit-for all decellularization protocol may not result in scaffolds with consistent matrix quality, subsequently influencing downstream recellularization and transplantation outcomes. There is a need for a noninvasive monitoring method to evaluate the extent of cell removal, while ensuring preservation of matrix components during decellularization. In this study, we decellularized rat livers using a protocol previously established by our group, and we monitored decellularization through traditional destructive techniques, including evaluation of DNA, collagen, and glycosaminoglycan (GAG) content in decellularized scaffolds, as well as histology. In addition, we used computed tomography and perfusate analysis as alternative nondestructive decellularization monitoring methods. We found that DNA removal correlates well with the Hounsfield unit of the liver, and perfusate analysis revealed that significant amount of GAG is removed during perfusion with 0.1% sodium dodecyl sulfate. This allowed for optimization of our decellularization protocol leading to scaffolds that have significantly higher GAG content, while maintaining appropriate removal of cellular contents. The significance of this is the creation of a nondestructive monitoring strategy that can be used for optimization of decellularization protocols for individual human livers available for liver engineering.
C1 [Geerts, Sharon; Ozer, Sinan; Jaramillo, Maria; Yarmush, Martin L.; Uygun, Basak E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med,Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
RP Uygun, BE (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Ctr Engn Med,Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
EM buygun@mgh.harvard.edu
FU National Institutes of Health [R01DK084053, R00DK088962]; Shriners
Hospitals for Children
FX Funding was received from the National Institutes of Health (R01DK084053
M.L.Y., R00DK088962 B.E.U.), Shriners Hospitals for Children (M.L.Y.).
NR 22
TC 0
Z9 1
U1 3
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
EI 1937-3392
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD JUL
PY 2016
VL 22
IS 7
BP 671
EP 678
DI 10.1089/ten.tec.2015.0571
PG 8
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA DS5EG
UT WOS:000380803200006
PM 27169332
ER
PT J
AU Campos-Neto, A
AF Campos-Neto, Antonio
TI Mycobacterium tuberculosis strain 18b, a useful non-virulent
streptomycin dependent mutant to study latent tuberculosis as well as
for in vivo and in vitro testing of anti-tuberculosis drugs
SO TUBERCULOSIS
LA English
DT Letter
ID MODEL; INFECTION
C1 [Campos-Neto, Antonio] Forsyth Inst, Cambridge, MA 02142 USA.
RP Campos-Neto, A (reprint author), Forsyth Inst, Cambridge, MA 02142 USA.
EM acampos@forsyth.org
NR 11
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD JUL
PY 2016
VL 99
BP 54
EP 55
DI 10.1016/j.tube.2016.04.006
PG 2
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA DS4MV
UT WOS:000380756100008
PM 27450005
ER
PT J
AU Goodwin, CR
Yanamadala, V
Ruiz-Valls, A
Abu-Bonsrah, N
Shankar, G
Sankey, EW
Boone, C
Clarke, MJ
Bilsky, M
Laufer, I
Fisher, C
Shin, JH
Sciubba, DM
AF Goodwin, C. Rory
Yanamadala, Vijay
Ruiz-Valls, Alejandro
Abu-Bonsrah, Nancy
Shankar, Ganesh
Sankey, Eric W.
Boone, Christine
Clarke, Michelle J.
Bilsky, Mark
Laufer, Ilya
Fisher, Charles
Shin, John H.
Sciubba, Daniel M.
TI A Systematic Review of Metastatic Hepatocellular Carcinoma to the Spine
SO WORLD NEUROSURGERY
LA English
DT Review
DE Hepatocellular carcinoma; Liver cancer; Spine metastasis; Surgery;
Survival; Tumor
ID CORD COMPRESSION; PROGNOSTIC-FACTORS; BONE METASTASES; FREE SURVIVAL;
RADIOSURGERY; EPIDEMIOLOGY; SACROPLASTY; COMBINATION; SORAFENIB;
OUTCOMES
AB BACKGROUND: Hepatocellular carcinoma (HCC) frequently metastasizes to the spine. The impact of medical and/or surgical intervention on overall survival has been examined in a limited number of clinical studies, and herein we systematically review these data.
METHODS: We performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles that reported survival, clinical outcomes, and/or prognostic factors associated with patients diagnosed with spinal metastases. The methodologic quality of each review was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses tool.
RESULTS: There were 26 articles (152 patients) that met the inclusion criteria and were treated with either surgery, radiotherapy, chemotherapy, and/or observation. There were 3 retrospective cohort studies, 17 case reports, 5 case series, and 1 longitudinal observational study. Of the patients with known overall survival after diagnosis of spinal metastasis, survival at 3 months, 6 months, 1 year, 2 years, and 5 years was 95.2%, 83.0%, 28.6%, 2.0%, and 1.4%, respectively. The median survival after diagnosis of the metastasis was 0.7 months in the patients who received no treatment, 7 months in the patients treated with surgical intervention alone, 6 months for patients who received chemotherapy and/or radiation, and 13.5 months in the patients treated with a combination of surgery and medical management. All other clinical or prognostic parameters were of low or insufficient strength.
CONCLUSIONS: Patients diagnosed with HCC spinal metastasis have a 10.6-month overall survival. Further analysis of patients in prospective controlled trials will be essential to the development of treatment algorithms for these patients in the future.
C1 [Goodwin, C. Rory; Ruiz-Valls, Alejandro; Abu-Bonsrah, Nancy; Sankey, Eric W.; Boone, Christine; Sciubba, Daniel M.] Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA.
[Yanamadala, Vijay; Shankar, Ganesh; Shin, John H.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Clarke, Michelle J.] Mayo Clin, Dept Neurosurg, Rochester, MN USA.
[Bilsky, Mark; Laufer, Ilya] Mem Sloan Kettering Canc Ctr, Dept Neurol Surg, 1275 York Ave, New York, NY 10021 USA.
[Fisher, Charles] Univ British Columbia, Dept Orthopaed, Div Spine, Vancouver, BC, Canada.
[Fisher, Charles] Vancouver Gen Hosp, Vancouver, BC, Canada.
RP Sciubba, DM (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USA.
EM dsciubb1@jhmi.edu
OI Goodwin, C. Rory/0000-0002-6540-2751
FU Burroughs Wellcome Fund; Johns Hopkins Neurosurgery Pain Research
Institute; OREF; AOSpine; Medtronic
FX C.R. Goodwin is supported by a UNCF Merck Postdoctoral Fellow and has
received awards from the Burroughs Wellcome Fund and the Johns Hopkins
Neurosurgery Pain Research Institute. I. Laufer is a consultant for
Depuy Globus and SpineWave. C. Fisher receives royalties from Medtronic,
is a consultant for Medtronic and Nuvasive, and receives research
support from OREF, AOSpine, and Medtronic. D.M. Sciubba is a consultant
for Medtronic.
NR 52
TC 2
Z9 2
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1878-8750
EI 1878-8769
J9 WORLD NEUROSURG
JI World Neurosurg.
PD JUL
PY 2016
VL 91
BP 510
EP +
DI 10.1016/J.WNEU.2016.04.026
PG 12
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA DS1OH
UT WOS:000380365000070
PM 27090971
ER
PT J
AU Wimalasena, NK
Le, VQ
Wimalasena, K
Schreiber, SL
Karmacharya, R
AF Wimalasena, Nivanthika K.
Le, Viet Q.
Wimalasena, Kandatege
Schreiber, Stuart L.
Karmacharya, Rakesh
TI Gene Expression-Based Screen for Parkinson's Disease Identifies GW8510
as a Neuroprotective Agent
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE GW8510; Parkinson's disease; neuroprotection; induced pluripotent stem
cells; iPSC; neural progenitor cells
ID PLURIPOTENT STEM-CELLS; SIGNALING PATHWAYS; CONNECTIVITY MAP;
INHIBITION; MECHANISM; MPP+; MITOCHONDRIA; METAANALYSIS; SELECTIVITY;
SIGNATURES
AB We carried out a gene expression-based in silico screen in order to identify small molecules with gene-expression profiles that are anticorrelated with a gene-expression profile for Parkinson's disease (PD). We identified the cyclin-dependent kinase 2/5 (CDK2/5) inhibitor GW8510 as our most significant hit and characterized its effects in rodent MN9D cells and in human neuronal cells derived from induced pluripotent stem cells. GW8510 demonstrated neuroprotective ability in MN9D cells in the presence of 1-methyl-4-phenylpyridium (MPP+), a widely used neurotoxin model for Parkinson's disease. In order to delineate the nature and extent of GW8510's neuroprotective properties, we studied GW8510 in human neuronal cells in the context of various mechanisms of cellular stress. We found that GW8510 was protective against small-molecule mitochondrial and endoplasmic reticulum stressors. Our findings illustrate an approach to using small-molecule gene expression libraries to identify compounds with therapeutic potential in human diseases.
C1 [Wimalasena, Nivanthika K.; Schreiber, Stuart L.; Karmacharya, Rakesh] Broad Inst Harvard, Ctr Sci Therapeut, Cambridge, MA 02142 USA.
[Wimalasena, Nivanthika K.; Schreiber, Stuart L.; Karmacharya, Rakesh] MIT, Cambridge, MA 02142 USA.
[Wimalasena, Nivanthika K.; Karmacharya, Rakesh] Harvard Med Sch, Ctr Human Genet Res, Ctr Expt Drugs & Diagnost, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Wimalasena, Nivanthika K.; Karmacharya, Rakesh] Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA.
[Wimalasena, Nivanthika K.] Harvard Med Sch, Program Neurosci, Boston, MA 02115 USA.
[Le, Viet Q.] Rochester Inst Technol, Dept Sci & Math, Natl Tech Inst Deaf, Rochester, NY 14623 USA.
[Wimalasena, Kandatege] Wichita State Univ, Dept Chem, Wichita, KS 67260 USA.
[Karmacharya, Rakesh] Harvard Med Sch, Schizophrenia & Bipolar Disorder Program, Belmont, MA 02478 USA.
[Karmacharya, Rakesh] McLean Hosp, Belmont, MA 02478 USA.
[Schreiber, Stuart L.] Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
RP Karmacharya, R (reprint author), Massachusetts Gen Hosp, 185 Cambridge St, Boston, MA 02114 USA.; Karmacharya, R (reprint author), Harvard Med Sch, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA.
EM karmacharya@mgh.harvard.edu
OI Karmacharya, Rakesh/0000-0002-0565-5482
FU National Institute of Mental Health Award [MH086846]; National Institute
of General Medical Sciences Award [GM038627]
FX This work was supported by the National Institute of Mental Health Award
MH086846 (to RK.), by Steve Willis and Elissa Freud (to RK.), and by the
National Institute of General Medical Sciences Award GM038627 (to
S.L.S.).
NR 38
TC 0
Z9 0
U1 7
U2 11
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD JUL
PY 2016
VL 7
IS 7
BP 857
EP 863
DI 10.1021/acschemneuro.6b00076
PG 7
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA DS0OV
UT WOS:000380297500003
PM 27270122
ER
PT J
AU Ojikutu, BO
Mazzola, E
Fullem, A
Vega, R
Landers, S
Gelman, RS
Bogart, LM
AF Ojikutu, Bisola O.
Mazzola, Emanuele
Fullem, Andrew
Vega, Rodolfo
Landers, Stewart
Gelman, Rebecca S.
Bogart, Laura M.
TI HIV Testing Among Black and Hispanic Immigrants in the United States
SO AIDS PATIENT CARE AND STDS
LA English
DT Article
ID HEALTH INTERVIEW SURVEY; LATE DIAGNOSIS; NATIVE-BORN; BARRIERS; CARE;
US; INFECTION; RECOMMENDATIONS; CONSEQUENCES; KNOWLEDGE
AB Late presentation is common among black and Hispanic US immigrants living with HIV. Little is known about HIV testing in this population because data are aggregated into racial and ethnic categories without regard to nativity. This study was undertaken to determine HIV testing patterns in these populations. We used data from the National Health Interview Survey (2007-2010), a nationally representative source of HIV testing data dis-aggregated by nativity. The sample consisted of 10,397 immigrants (83.9% Hispanic white, 13.1% non-Hispanic black, and 3.0% Hispanic black). The majority of participants were from the Caribbean, Central America, and Mexico (81.5%). Hispanic white immigrants were least likely to have undergone testing compared with non-Hispanic and Hispanic black immigrants (46.7% vs. 70.5% and 65.8%). Among immigrants with known risk factors or prior STDs, 59.2% and 74.8% reported previous HIV testing. Immigrants who had not recently talked to a healthcare provider were less likely to report testing: Hispanic white (AOR 0.65, 95% CI 0.58-0.72), non-Hispanic black (AOR 0.64, 95% CI 0.48-0.85), and Hispanic black (AOR 0.26, 95% CI 0.14-0.48). Only 17.2% of all immigrants intended to undergo HIV testing in the 12 months following participation in the survey. Among all three racial and ethnic groups, immigrants who reported a history of prior STDs were more likely to intend to test for HIV in the future. Many black and Hispanic immigrants to the United States have not undergone HIV testing. Interventions to increase access to HIV testing and awareness of transmission risk should be developed.
C1 [Ojikutu, Bisola O.] Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA.
[Ojikutu, Bisola O.; Fullem, Andrew; Vega, Rodolfo; Landers, Stewart] John Snow Res & Training Inst, Boston, MA USA.
[Ojikutu, Bisola O.; Gelman, Rebecca S.; Bogart, Laura M.] Harvard Med Sch, Boston, MA USA.
[Mazzola, Emanuele; Gelman, Rebecca S.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Bogart, Laura M.] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA.
[Bogart, Laura M.] RAND Corp, Santa Monica, CA USA.
RP Ojikutu, BO (reprint author), Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA.
EM bojikutu@partners.org
FU Harvard University Center for AIDS Research (CFAR), an NIH [P30
AI060354]
FX This publication was made possible with help from the Harvard University
Center for AIDS Research (CFAR), an NIH funded program (P30 AI060354).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 31
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Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1087-2914
EI 1557-7449
J9 AIDS PATIENT CARE ST
JI Aids Patient Care STDS
PD JUL
PY 2016
VL 30
IS 7
BP 307
EP 314
DI 10.1089/apc.2016.0120
PG 8
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA DS1QT
UT WOS:000380372100002
PM 27410494
ER
PT J
AU Koyama, AK
Tworoger, SS
Eliassen, AH
Okereke, OI
Weisskopf, MG
Rosner, B
Yaffe, K
Grodstein, F
AF Koyama, Alain K.
Tworoger, Shelley S.
Eliassen, A. Heather
Okereke, Olivia I.
Weisskopf, Marc G.
Rosner, Bernard
Yaffe, Kristine
Grodstein, Francine
TI Endogenous sex hormones and cognitive function in older women
SO Alzheimers & Dementia
LA English
DT Article
DE Hormones; Subjective cognitive complaints; Cognition; Dementia;
Alzheimer's disease
ID SUBJECTIVE MEMORY COMPLAINTS; ALZHEIMERS-DISEASE; POSTMENOPAUSAL WOMEN;
RISK; INDIVIDUALS; HIPPOCAMPUS; IMPAIRMENT; COMMUNITY; DEMENTIA; THERAPY
AB Introduction: We examined the association between endogenous sex hormones and both objective and subjective measures of cognitive function.
Methods: We followed 3044 women up to 23 years in a prospective cohort study. We measured plasma levels of estrone, estrone sulfate, estradiol, androstenedione, testosterone, dehydroepiandrosterone (DHEA), and dehydroepiandrosterone sulfate (DHEA-S) in 1989-1990, conducted neuropsychologic testing in 1999-2008, and inquired about subjective cognition in 2012.
Results: Overall, we observed little relation between plasma levels of hormones and either neuropsychologic test performance or subjective cognition. However, after adjustment for age and education, we observed a borderline significant association of higher levels of plasma estrone with higher scores for both overall cognition (P trend = .10) and verbal memory (P trend = .08).
Discussion: There were no clear associations of endogenous hormone levels at midlife and cognition in later life, although a suggested finding of higher levels of plasma estrone associated with better cognitive function merits further research. (C) 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
C1 [Koyama, Alain K.; Tworoger, Shelley S.; Eliassen, A. Heather; Okereke, Olivia I.; Rosner, Bernard; Grodstein, Francine] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Koyama, Alain K.; Tworoger, Shelley S.; Eliassen, A. Heather; Okereke, Olivia I.; Rosner, Bernard; Grodstein, Francine] Harvard Med Sch, Boston, MA 02115 USA.
[Koyama, Alain K.; Tworoger, Shelley S.; Eliassen, A. Heather; Okereke, Olivia I.; Weisskopf, Marc G.; Grodstein, Francine] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Weisskopf, Marc G.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Rosner, Bernard] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Koyama, AK (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.; Koyama, AK (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Koyama, AK (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM akoyama@post.harvard.edu
RI Okereke, Olivia/R-9934-2016
FU National Institute of Health [UM1 CA186107, R01 CA49449, T32 MH017119]
FX This work was supported by the National Institute of Health (UM1
CA186107, R01 CA49449, T32 MH017119).
NR 37
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Z9 0
U1 3
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD JUL
PY 2016
VL 12
IS 7
BP 758
EP 765
DI 10.1016/j.jalz.2015.12.010
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DS2EL
UT WOS:000380561100002
PM 26806389
ER
PT J
AU Walton, RG
Zhu, XL
Tian, L
Heywood, EB
Liu, J
Hill, HS
Liu, JR
Bruemmer, D
Yang, QL
Fu, YC
Garvey, WT
AF Walton, R. Grace
Zhu, Xiaolin
Tian, Ling
Heywood, Elizabeth B.
Liu, Jian
Hill, Helliner S.
Liu, Jiarong
Bruemmer, Dennis
Yang, Qinglin
Fu, Yuchang
Garvey, W. Timothy
TI AP2-NR4A3 transgenic mice display reduced serum epinephrine because of
increased catecholamine catabolism in adipose tissue
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE nuclear receptor 4A3 transgenic mice; nuclear receptor 4A3; type 2
diabetes; lipolysis; monoamine oxidase
ID GLUCOSE-TRANSPORT SYSTEM; LOW-DENSITY-LIPOPROTEIN; INSULIN-RESISTANCE;
CAROTID ARTERIES; LIPID-METABOLISM; GENE-EXPRESSION; ADIPOCYTES;
SECRETION; NOREPINEPHRINE; NORADRENALINE
AB The NR4A orphan nuclear receptors function as early response genes to numerous stimuli. Our laboratory has previously demonstrated that overexpression of NR4A3 (NOR-1, MINOR) in 3T3-L1 adipocytes enhances insulin-stimulated glucose uptake. To assess the in vivo effect of NR4A3 on adipocytes, we generated transgenic mice with NR4A3 overexpression driven by the adipocyte fatty acid-binding protein (AP2) promoter (AP2-NR4A3 mice). We hypothesized that AP2-NR4A3 mice would display enhanced glucose tolerance and insulin sensitivity. However, AP2-NR4A3 mice exhibit metabolic impairment, including increased fasting glucose and insulin, impaired glucose tolerance, insulin resistance, decreased serum free fatty acids, and increased low-density lipoprotein-cholesterol. AP2-NR4A3 mice also display a significant reduction in serum epinephrine due to increased expression of catecholamine-catabolizing enzymes in adipose tissue, including monoamine oxidase-A. Furthermore, enhanced expression of monoamine oxidase-A is due to direct transcriptional activation by NR4A3. Finally, AP2-NR4A3 mice display cardiac and behavioral alterations consistent with chronically low circulating epinephrine levels. In conclusion, overexpression of NR4A3 in adipocytes produces a complex phenotype characterized by impaired glucose metabolism and low serum catecholamines due to enhanced degradation by adipose tissue.
C1 [Walton, R. Grace; Zhu, Xiaolin; Tian, Ling; Liu, Jian; Hill, Helliner S.; Yang, Qinglin; Fu, Yuchang; Garvey, W. Timothy] Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.
[Heywood, Elizabeth B.; Bruemmer, Dennis] Univ Kentucky, Saha Cardiovasc Res Ctr, Lexington, KY USA.
[Heywood, Elizabeth B.; Bruemmer, Dennis] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA.
[Liu, Jiarong] Univ Alabama Birmingham, Dept Pathol, Div Mol & Cellular Pathol, Birmingham, AL 35294 USA.
[Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Walton, RG (reprint author), Univ Kentucky, Coll Hlth Sci, 900 S Limestone,CTW 433, Lexington, KY 40536 USA.
EM r.grace.walton@uky.edu
FU National Institutes of Health (NIH) [RO1-DK-083562]; Department of
Veterans Affairs Merit Review research award; UAB Diabetes Research
Center [P60-DK-079626]; NIH [RO1-HL-084611, RO1-HL-084611-S1]; UAB core
facilities
FX We received research support from a number of UAB core facilities. As
such, we would like to thank Dr. David Allison (UAB Nutrition Obesity
Research Center), Dr. Barbara A. Gower and Maryellen Williams (UAB
Diabetes Research and Treatment Center Human Physiology Core), Dr. Maria
Johnson and Dr. Timothy R. Nagy (UAB Diabetes Research and Treatment
Center Animal Physiology Core), Dr. Kevin A. Roth and Dr. Terry Lewis
(UAB Neuroscience Molecular Detection Core, P30 NS47466), Dr. Elliot J.
Lefkowitz (Molecular and Genetic Bioinformatics Facility,
5UL1-RR-025777), and Dr. Thomas Van Groen (UAB Small Animal Behavioral
Core, P30-NS-47466). This work was funded by National Institutes of
Health (NIH) Grant RO1-DK-083562 (W. T. Garvey), a Department of
Veterans Affairs Merit Review research award (W. T. Garvey), the UAB
Diabetes Research Center, P60-DK-079626 (W. T. Garvey), and NIH Grants
RO1-HL-084611 (D. Bruemmer) and RO1-HL-084611-S1 (D. Bruemmer).
NR 42
TC 0
Z9 0
U1 2
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD JUL 1
PY 2016
VL 311
IS 1
BP E69
EP E81
DI 10.1152/ajpendo.00330.2015
PG 13
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA DS1QS
UT WOS:000380372000005
PM 27166283
ER
PT J
AU McCubbrey, AL
Barthel, L
Mould, KJ
Mohning, MP
Redente, EF
Janssen, WJ
AF McCubbrey, Alexandra L.
Barthel, Lea
Mould, Kara J.
Mohning, Michael P.
Redente, Elizabeth F.
Janssen, William J.
TI Selective and inducible targeting of CD11b(+) mononuclear phagocytes in
the murine lung with hCD68-rtTA transgenic systems
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE CD11b(+) macrophages; hCD68-rtTA; mouse model; recruited macrophages;
transgenic mice
ID MACROPHAGES IN-VITRO; ALVEOLAR MACROPHAGES; TISSUE MACROPHAGES;
INTERSTITIAL MACROPHAGES; CIRCULATING MONOCYTES; EXUDATE MACROPHAGES;
GENE-EXPRESSION; DENDRITIC CELLS; LYMPH-NODES; MOUSE
AB Selective and inducible targeting of CD11b(+) mononuclear phagocytes in the murine lung with hCD68-rtTA transgenic systems. Am J Physiol Lung Cell Mol Physiol 311:L87-L100, 2016. First published May 17, 2016; doi:10.1152/ajplung.00141.2016.-During homeostasis two distinct macrophage (Mo) populations inhabit the lungs: tissue Mo (often called interstitial Mo) and resident alveolar Mo (re-sAMo). During acute lung inflammation, monocytes from the circulation migrate to areas of injury where they mature into a third Mo population: recruited Mo. Resident AMo uniquely express low levels of CD11b and high levels of CD11c. In comparison, recruited Mo and tissue Mo express high levels of CD11b and low levels of CD11c. It is likely that these three Mo subpopulations play distinct roles in injury and disease states; however, tools with which to individually target or track these populations are lacking. Here we demonstrate the utility of an hCD68-rtTA transgenic system for specific, robust, and inducible targeting of CD11b(+) recruited Mo and tissue Mo in the murine lung with negligible activation in resAMo. Using hCD68rtTA-GFP reporter mice, we show both during homeostasis and inflammation that administration of doxycycline induces tet-On reporter expression in recruited Mo and tissue Mo but not in resident AMo. We further demonstrate how hCD68-rtTA can be effectively combined with tet-On Cre to target these same recMo and tissue Mo. Accordingly, the hCD68-rtTA system is a powerful new tool that can be used for lineage tracing, fate mapping, and gene deletion in a variety of murine models, thereby enabling sophisticated investigation of the unique role of these CD11b(+) Mo during lung heath and disease.
C1 [McCubbrey, Alexandra L.; Barthel, Lea; Mould, Kara J.; Mohning, Michael P.; Janssen, William J.] Natl Jewish Hlth, Dept Med, 1400 Jackson St, Denver, CO 80206 USA.
[Redente, Elizabeth F.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA.
[Mould, Kara J.; Mohning, Michael P.; Janssen, William J.] Univ Colorado Denver, Dept Med, Aurora, CO USA.
[Redente, Elizabeth F.] Denver Vet Affairs Med Ctr, Dept Res, Denver, CO USA.
RP McCubbrey, AL (reprint author), Natl Jewish Hlth, Dept Med, 1400 Jackson St, Denver, CO 80206 USA.
EM mccubbreya@njhealth.org
FU National Heart, Lung, and Blood Institute [HL-109517, HL-114381,
HL-126333, HL-007085-41]; Parker B. Francis Foundation Fellowship;
Pulmonary Fibrosis Foundation Fellowship
FX This work was supported by National Heart, Lung, and Blood Institute
Grants HL-109517 (to W. Janssen), HL-114381 (to W. Janssen), HL-126333
(to M. Mohning), HL-007085-41 (to K. Mould), a Parker B. Francis
Foundation Fellowship (to E. Redente), and a Pulmonary Fibrosis
Foundation Fellowship (to Redente).
NR 52
TC 0
Z9 0
U1 2
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD JUL 1
PY 2016
VL 311
IS 1
BP L87
EP L100
DI 10.1152/ajplung.00141.2016
PG 14
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA DS4RE
UT WOS:000380767700009
PM 27190063
ER
PT J
AU Peters, AT
Shesler, LW
Sylvia, L
Magalhaes, PVD
Miklowitz, DJ
Otto, MW
Frank, E
Berk, M
Dougherty, DD
Nierenberg, AA
Deckersbach, T
AF Peters, Amy T.
Shesler, Leah W.
Sylvia, Louisa
da Silva Magalhaes, Pedro Vieira
Miklowitz, David J.
Otto, Michael W.
Frank, Ellen
Berk, Michael
Dougherty, Darin D.
Nierenberg, Andrew A.
Deckersbach, Thilo
TI Medical burden, body mass index and the outcome of psychosocial
interventions for bipolar depression
SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
LA English
DT Article
DE Bipolar disorder; psychotherapy; medical burden; body mass index
ID TREATMENT ENHANCEMENT PROGRAM; DISORDER STEP-BD; INTERNATIONAL
NEUROPSYCHIATRIC INTERVIEW; SOCIAL RHYTHM THERAPY; I-DISORDER;
RANDOMIZED-TRIAL; MENTAL-HEALTH; DSM-IV; DISEASE; EXERCISE
AB Objective: Individuals with bipolar disorder experience a disproportionately high incidence of medical co-morbidity and obesity. These health-related problems are a barrier to recovery from mood episodes and have been linked with unfavorable responses to pharmacological treatment. However, little is known about whether and how these characteristics affect responses to adjunctive psychotherapy.
Method: Embedded in the Systematic Treatment Enhancement Program for Bipolar Disorder was a randomized controlled trial of psychotherapy for bipolar depression comparing the efficacy of intensive psychotherapy plus pharmacotherapy with collaborative care (a three-session psycho-educational intervention) plus pharmacotherapy. We conducted a post-hoc analysis to evaluate whether medical burden and body mass index predicted and/or moderated the likelihood of recovery and time until recovery from a depressive episode among patients in the two treatments.
Results: Participants who had medical co-morbidity and body mass index data constituted 199 of the 293 patients in the original Systematic Treatment Enhancement Program for Bipolar Disorder trial. Higher medical burden predicted a lower likelihood of recovery from depression in both treatment conditions (odds ratio=0.89), but did not moderate responses to intensive psychotherapy vs collaborative care. Intensive psychotherapy yielded superior recovery rates for individuals of normal body mass index (odds ratio=2.39) compared with collaborative care, but not among individuals who were overweight or obese.
Conclusion: Medical co-morbidity and body weight impacts symptom improvement and attention to this co-morbidity may inform the development of more personalized treatments for bipolar disorder.
C1 [Peters, Amy T.] Univ Illinois, Chicago, IL USA.
[Shesler, Leah W.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Sylvia, Louisa; Dougherty, Darin D.; Nierenberg, Andrew A.; Deckersbach, Thilo] Massachusetts Gen Hosp, Dept Psychiat, 149-2628,Bldg 149,13th St,2nd Floor, Boston, MA 02129 USA.
[Sylvia, Louisa; Dougherty, Darin D.; Nierenberg, Andrew A.; Deckersbach, Thilo] Harvard Med Sch, Boston, MA USA.
[da Silva Magalhaes, Pedro Vieira] Univ Fed Rio Grande do Sul, Porto Alegre, Brazil.
[Miklowitz, David J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[Otto, Michael W.] Boston Univ, Boston, MA 02215 USA.
[Frank, Ellen] Univ Pittsburgh, Pittsburgh, PA USA.
[Berk, Michael] Deakin Univ, Melbourne, Vic, Australia.
[Berk, Michael] Univ Melbourne, Melbourne, Vic, Australia.
RP Deckersbach, T (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149-2628,Bldg 149,13th St,2nd Floor, Boston, MA 02129 USA.
EM tdeckersbach@partners.org
FU National Institute of Mental Health [N01MH80001, MH29618, MH43931,
MH55101]; National Alliance for Research on Schizophrenia and Depression
FX STEP-BD was funded in part by contract N01MH80001 from the National
Institute of Mental Health (Gary Sachs). Support for the development of
the psychosocial treatments was provided by grants MH29618 (Ellen
Frank), MH43931 (David Miklowitz) and MH55101 (David Miklowitz) from the
National Institute of Mental Health and by the National Alliance for
Research on Schizophrenia and Depression (David Miklowitz).
NR 52
TC 0
Z9 0
U1 4
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0004-8674
EI 1440-1614
J9 AUST NZ J PSYCHIAT
JI Aust. N. Z. J. Psych.
PD JUL
PY 2016
VL 50
IS 7
BP 667
EP 677
DI 10.1177/0004867415616694
PG 11
WC Psychiatry
SC Psychiatry
GA DR8BR
UT WOS:000380123900010
PM 26590023
ER
PT J
AU Dal-Bianco, JP
Bartko, PE
Levine, RA
AF Dal-Bianco, Jacob P.
Bartko, Philipp E.
Levine, Robert A.
TI Anticipating the Vicious Circle of Postinfarction Mitral Regurgitation
Imaging Insights
SO Circulation-Cardiovascular Imaging
LA English
DT Editorial Material
DE Editorials; adaptation; echocardiography; ischemia; mitral
regurgitation; prognosis
ID LEFT-VENTRICULAR DYSFUNCTION; COLOR DOPPLER-ECHOCARDIOGRAPHY;
MYOCARDIAL-PERFUSION PATTERN; ISOVELOCITY SURFACE-AREA; IN-VITRO;
TRANSTHORACIC ECHOCARDIOGRAPHY; INFARCTION; MECHANISM; VALVE; ADAPTATION
C1 [Dal-Bianco, Jacob P.; Bartko, Philipp E.; Levine, Robert A.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
RP Levine, RA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.
EM rlevine@partners.org
NR 29
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JUL
PY 2016
VL 9
IS 7
AR e005070
DI 10.1161/CIRCIMAGING.116.005070
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DS2MX
UT WOS:000380608900010
ER
PT J
AU Shah, RV
Semigran, MJ
AF Shah, Ravi V.
Semigran, Marc J.
TI Targeting the Heart for Risk Assessment in Myotonic Dystrophy An
Application for Cardiac Magnetic Resonance
SO Circulation-Cardiovascular Imaging
LA English
DT Editorial Material
DE Editorials; biomarkers; cardiomyopathy; heart failure; myalgia
C1 [Shah, Ravi V.; Semigran, Marc J.] Harvard Med Sch, Massachusetts Gen Hosp, Heart Failure & Cardiac Transplant Sect, Div Cardiol,Dept Med, Boston, MA USA.
[Shah, Ravi V.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Cardiac MR,PET,CT Program, Boston, MA USA.
RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplant Sect, Div Cardiol, Dept Med, Bigelow 800, Boston, MA 02114 USA.
EM msemigran@mgh.harvard.edu
NR 10
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD JUL
PY 2016
VL 9
IS 7
AR e005092
DI 10.1161/CIRCIMAGING.116.005092
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DS2MX
UT WOS:000380608900011
ER
PT J
AU Pectasides, E
AF Pectasides, Eirini
TI Genomic Alterations and Targeted Therapy in Gastric and Esophageal
Adenocarcinoma
SO CLINICAL THERAPEUTICS
LA English
DT Review
DE Gastric adenocarcinoma; esophageal adenocarcinoma; genomics; targeted
therapy
ID PHASE-III TRIAL; ADVANCED ESOPHAGOGASTRIC CANCER; GROWTH-FACTOR
RECEPTOR; GASTROESOPHAGEAL JUNCTION; PROGNOSTIC-SIGNIFICANCE; 1ST-LINE
THERAPY; DOUBLE-BLIND; BREAST-CANCER; OPEN-LABEL; GENE AMPLIFICATION
AB Purpose: Gastric and esophageal adenocarcinomas are common and aggressive malignancies. Systemic therapy for these tumors is based primarily on cytotoxic chemotherapy, but outcomes remain poor. Precision medicine, where treatments are tailored to specific molecular abnormalities of tumors, holds great promise for improving outcomes in this disease.
Methods: A search was performed in PubMed to identify studies that have characterized the molecular basis of gastric and esophageal adenocarcinoma, as well as clinical trials exploring targeted therapies in this disease.
Findings: Recent genomic studies have identified potentially targetable genomic alterations in gastroesophageal adenocarcinoma. Specifically, The Cancer Genome Atlas study defined 4 subgroups of gastric cancer, each harboring distinct genomic features. However, development of targeted therapies for gastroesophageal cancer has been challenging. The only biomarker-driven therapy in clinical practice, trastuzumab for the similar to 15% of patients with human epidermal growth factor receptor 2-positive disease, is modestly effective, extending median overall survival by 2.7 months. Clinical trials of other targeted therapies, including epidermal growth factor receptor, fibroblast growth factor receptor 2, and MET inhibitors, have had disappointing results so far. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.
C1 [Pectasides, Eirini] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Pectasides, E (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM eirini_pectasides@dfci.harvard.edu
FU Conquer Cancer Foundation American Society of Clinical Oncology Young
Investigator Award; Debbie's Dream Foundation-AACR Gastric Cancer
Research Fellowship; Claudia Adams Barr Program for Innovative Cancer
Research
FX Dr. Pectasides' research is financially supported by the Conquer Cancer
Foundation American Society of Clinical Oncology Young Investigator
Award, the Debbie's Dream Foundation-AACR Gastric Cancer Research
Fellowship and the Claudia Adams Barr Program for Innovative Cancer
Research.
NR 49
TC 4
Z9 4
U1 0
U2 1
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0149-2918
EI 1879-114X
J9 CLIN THER
JI Clin. Ther.
PD JUL
PY 2016
VL 38
IS 7
BP 1589
EP 1599
DI 10.1016/j.clinthera.2016.03.016
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS2PN
UT WOS:000380626100006
PM 27041412
ER
PT J
AU Underhill, ML
Germansky, KA
Yurgelun, MB
AF Underhill, Meghan L.
Germansky, Katharine A.
Yurgelun, Matthew B.
TI Advances in Hereditary Colorectal and Pancreatic Cancers
SO CLINICAL THERAPEUTICS
LA English
DT Review
DE familial gastrointestinal cancer; genetic testing; Lynch syndrome;
multigene panel testing
ID FAMILIAL ADENOMATOUS POLYPOSIS; LI-FRAUMENI-SYNDROME; MUTYH-ASSOCIATED
POLYPOSIS; PEUTZ-JEGHERS SYNDROME; MISMATCH REPAIR DEFICIENCY;
LYNCH-SYNDROME; GERMLINE MUTATIONS; MICROSATELLITE-INSTABILITY;
ENDOMETRIAL CANCER; JUVENILE POLYPOSIS
AB Purpose: Innovations in genetic medicine have led to improvements in the early detection, prevention, and treatment of cancer for patients with inherited risks of gastrointestinal cancer, particularly hereditary colorectal cancer and hereditary pancreatic cancer.
Methods: This review provides an update on recent data and key advances that have improved the identification, understanding, and management of patients with hereditary colorectal cancer and hereditary pancreatic cancer.
Findings: This review details recent and emerging data that highlight the developing landscape of genetics in hereditary colorectal and pancreatic cancer risk. A summary is provided of the current state-of-the-art practices for identifying, evaluating, and managing patients with suspected hereditary colorectal cancer and pancreatic cancer risk. The impact of next-generation sequencing technologies in the clinical diagnosis of hereditary gastrointestinal cancer and also in discovery efforts of new genes linked to familial cancer risk are discussed. Emerging targeted therapies that may play a particularly important role in the treatment of patients with hereditary forms of colorectal cancer and pancreatic cancer are also reviewed. Current approaches for pancreatic cancer screening and the psychosocial impact of such procedures are also detailed. (C) 2016 Elsevier HS Journals, Inc. All rights reserved.
C1 [Underhill, Meghan L.; Yurgelun, Matthew B.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Underhill, Meghan L.; Yurgelun, Matthew B.] Harvard Med Sch, Boston, MA USA.
[Germansky, Katharine A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Yurgelun, Matthew B.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
RP Yurgelun, MB (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Gastrointestinal Canc Ctr, 450 Brookline Ave, Boston, MA 02216 USA.
EM matthew_yurgelun@dfci.harvard.edu
OI Underhill, Meghan/0000-0002-1433-5915
FU Harvard Clinical and Translational Science Center (National Center for
Advancing Trangational Sciences, National Institutes of Health Award)
[KL2 TR001100]
FX Drs. Underhill and Germansky contributed equally to this manuscript. The
Harvard Clinical and Translational Science Center (National Center for
Research Resources and the National Center for Advancing Translational
Sciences, National Institutes of Health Award KL2 TR001100 (Dr.
Underhill).
NR 151
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Z9 3
U1 3
U2 4
PU ELSEVIER
PI BRIDGEWATER
PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA
SN 0149-2918
EI 1879-114X
J9 CLIN THER
JI Clin. Ther.
PD JUL
PY 2016
VL 38
IS 7
BP 1600
EP 1621
DI 10.1016/j.clinthera.2016.03.017
PG 22
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DS2PN
UT WOS:000380626100007
PM 27045993
ER
PT J
AU Galtier, M
De Sordi, L
Maura, D
Arachchi, H
Volant, S
Dillies, MA
Debarbieux, L
AF Galtier, Matthieu
De Sordi, Luisa
Maura, Damien
Arachchi, Harindra
Volant, Stevenn
Dillies, Marie-Agnes
Debarbieux, Laurent
TI Bacteriophages to reduce gut carriage of antibiotic resistant
uropathogens with low impact on microbiota composition
SO ENVIRONMENTAL MICROBIOLOGY
LA English
DT Article
ID URINARY-TRACT-INFECTION; ESCHERICHIA-COLI; PSEUDOMONAS-AERUGINOSA; PHAGE
COCKTAIL; CLINICAL-TRIAL; THERAPY; DISEASE; PATHOGENS; VIROME; WOMEN
AB Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) worldwide, causing over 150 million clinical cases annually. There is currently no specific treatment addressing the asymptomatic carriage in the gut of UPEC before they initiate UTIs. This study investigates the efficacy of virulent bacteriophages to decrease carriage of gut pathogens. Three virulent bacteriophages infecting an antibiotic-resistant UPEC strain were isolated and characterized both in vitro and in vivo. A new experimental murine model of gut carriage of E. coli was elaborated and the impact of virulent bacteriophages on colonization levels and microbiota diversity was assessed. A single dose of a cocktail of the three bacteriophages led to a sharp decrease in E. coli levels throughout the gut. We also observed that microbiota diversity was much less affected by bacteriophages than by antibiotics. Therefore, virulent bacteriophages can efficiently target UPEC strains residing in the gut, with potentially profound public health and economic impacts. These results open a new area with the possibility to manipulate specifically the microbiota using virulent bacteriophages, which could have broad applications in many gut-related disorders/diseases and beyond.
C1 [Galtier, Matthieu; De Sordi, Luisa; Maura, Damien] Inst Pasteur, Dept Microbiol, Paris, France.
[Galtier, Matthieu; Maura, Damien] Univ Paris Diderot, Sorbonne Paris Cite, Cellule Pasteur, Paris, France.
[Arachchi, Harindra; Volant, Stevenn; Dillies, Marie-Agnes; Debarbieux, Laurent] USR 3756 IP CNRS, Inst Pasteur Hub Bioinformat & Biostat C3BI, Paris, France.
[Maura, Damien] Harvard Med Sch, Boston, MA USA.
[Maura, Damien] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Debarbieux, L (reprint author), USR 3756 IP CNRS, Inst Pasteur Hub Bioinformat & Biostat C3BI, Paris, France.
EM laurent.debar-bieux@pasteur.fr
FU DigestScience Fundation (Lille, France); Institut Pasteur; Ministere de
l'Enseignement Superieur et de la Recherche [516 B3MI]
FX We thank Chantal Le Bouguenec, who provided the UPEC collection and
strongly supported this project, Laurence Fiette (Histopathology Unit,
Institut Pasteur, Paris, France), Thierry Pedron, Celine Mulet
(Molecular Microbial Pathogenesis Unit, Institut Pasteur, Paris, France)
and Jean-Philippe Nougayrede (CPTP INRA USC 1360 INSERM UMR 1043,
Toulouse, France) for assistance with histochemical and FISH analyses,
as well as Erick Denamur (Paris Diderot University, IAME, UMR 1137,
Sorbonne Paris Cite, Paris, France) for critical reading of this
manuscript. We thank France Genomique and the LABGeM team (Genoscope,
Evry, France) of Claudine Medigue, and Valerie Barbe and Sophie Layac in
particular, for assembly of the genome of strain AL505. We thank Marie
Touchon (Microbial Evolutionary Genomics, Institut Pasteur, Paris,
France) for core genome analysis and Camille Caplain for technical
assistance with 16S rDNA sample preparation. This work was supported by
DigestScience Fundation (Lille, France) and Institut Pasteur. D. Maura
and M. Galtier were supported by PhD fellowships from the Ministere de
l'Enseignement Superieur et de la Recherche (ED No516 B3MI Paris Diderot
University). The funders had no role in study design, data collection
and interpretation, or the decision to submit the work for publication.
Authors declare no conflict of interest.
NR 40
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U1 13
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-2912
EI 1462-2920
J9 ENVIRON MICROBIOL
JI Environ. Microbiol.
PD JUL
PY 2016
VL 18
IS 7
SI SI
BP 2237
EP 2245
DI 10.1111/1462-2920.13284
PG 9
WC Microbiology
SC Microbiology
GA DS1SA
UT WOS:000380376900014
PM 26971586
ER
PT J
AU Zhao, ZH
Azad, R
Yang, JH
Siroky, MB
Azadzoi, KM
AF Zhao, Zuohui
Azad, Roya
Yang, Jing-Hua
Siroky, Mike B.
Azadzoi, Kazem M.
TI Progressive changes in detrusor function and micturition patterns with
chroinc bladder ischemia
SO Investigative and Clinical Urology
LA English
DT Article
DE Contraction; Ischemia; Urinary bladder; Urination
ID URINARY-TRACT SYMPTOMS; MUSCARINIC RECEPTOR; CLINICAL-FEATURES;
SMOOTH-MUSCLE; LIVER-INJURY; UNDERACTIVITY; RAT; M-2; CONTRACTILITY;
SUBTYPES
AB Purpose: Lower urinary tract symptoms (LUTS) are bothersome constellation of voiding symptoms in men and women as they age. Multiple factors and comorbidities are attributed to this problem but underlying mechanisms of nonobstructive nonneurogenic detrusor overactivity, detrusor underactivity and LUTS remain largely unknown. Our goal was to characterize detrusor function and voiding patterns in relation to muscarinic receptors expression, nerve fiber density, and neural ultrastructure in chronic bladder ischemia.
Materials and Methods: Iliac artery atherosclerosis and bladder ischemia were produced in male Sprague-Dawley rats. At 8 and 16 weeks after ischemia, micturition patterns and cystometrograms were recorded in conscious rats then bladder blood flow and nonvoiding spontaneous contractions were measured under general anesthesia. Bladder tissues were processed for Western blotting, immunostaining, and transmission electron microscopy.
Results: Bladder responses to ischemic insult depended on the duration of ischemia. Micturition patterns and cystometric changes at 8-week ischemia suggested detrusor overactivity, while voiding behavior and cystometrograms at 16-week ischemia implied abnormal detrusor function resembling underactivity. Upregulation of muscarinic M2 receptor was found after 8- and 16 weeks of ischemia. Downregulation of M3 and upregulation of M1 were detected at 16-week ischemia. Neural structural damage and marked neurodegeneration were found after 8 and 16 weeks of ischemia, respectively.
Conclusions: Prolonged ischemia may be a mediating variable in progression of overactive bladder to dysfunctional patterns similar to detrusor underactivity. The mechanism appears to involve differential expression of M1, M2, and M3 receptors, neural structural injury, and progressive loss of nerve fibers.
C1 [Azadzoi, Kazem M.] VA Boston Healthcare Syst, Dept Urol, 150 South Huntington Ave, Boston, MA 02130 USA.
[Azadzoi, Kazem M.] Boston Univ, Sch Med, 150 South Huntington Ave, Boston, MA 02130 USA.
RP Azadzoi, KM (reprint author), VA Boston Healthcare Syst, Dept Urol, 150 South Huntington Ave, Boston, MA 02130 USA.; Azadzoi, KM (reprint author), Boston Univ, Sch Med, 150 South Huntington Ave, Boston, MA 02130 USA.
EM kazadzoi@bu.edu
FU BLRD VA [I01 BX001428]
NR 30
TC 2
Z9 2
U1 0
U2 0
PU KOREAN UROLOGICAL ASSOC
PI SEOUL
PA RM 103-1102, PARK TOWER OFFICETEL 5-19, YONGSAN-DONG, YONGSAN-GU, SEOUL,
140-904, SOUTH KOREA
SN 2466-0493
EI 2466-054X
J9 INVESTIG CLIN UROL
JI Investig. Clin. Urol.
PD JUL
PY 2016
VL 57
IS 4
BP 249
EP 259
DI 10.4111/icu.2016.57.4.249
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA DS2HJ
UT WOS:000380588300004
PM 27437534
ER
PT J
AU Leder, BZ
Tsai, JN
Neer, RM
Uihlein, AV
Wallace, PM
Burnett-Bowie, SAM
AF Leder, Benjamin Z.
Tsai, Joy N.
Neer, Robert M.
Uihlein, Alexander V.
Wallace, Paul M.
Burnett-Bowie, Sherri-Ann M.
TI Response to Therapy With Teriparatide, Denosumab, or Both in
Postmenopausal Women in the DATA (Denosumab and Teriparatide
Administration) Study Randomized Controlled Trial
SO JOURNAL OF CLINICAL DENSITOMETRY
LA English
DT Article
DE Bone mineral density; combination therapy; denosumab; postmenopausal
osteoporosis; teriparatide
ID BONE-MINERAL DENSITY; PARATHYROID-HORMONE; RISK REDUCTION; FRACTURE
RISK; OSTEOPOROSIS; ALENDRONATE; RISEDRONATE; PREVENTION; COMBINATION
AB Both antiresorptive and anabolic osteoporosis medications increase bone mineral density (BMD), but no single agent can restore normal bone strength in most osteoporotic patients. Moreover, the magnitude and consistency of the patient response to each individual agent vary depending on the anatomic site. In the DATA study, we reported that in postmenopausal osteoporotic women, 2 years of combined denosumab and teriparatide increase mean BMD at the hip and spine more than either drug alone. In the current analysis, we wished to determine if the individual rates of BMD response were also greater among women treated with both drugs. In DATA, 94 postmenopausal osteoporotic women (ages 51-91) were randomized to receive teriparatide (20 mcg subcutaneously daily), denosumab (60 mg subcutaneously every 6 mo), or both medications for 24 mo. The BMD of the total hip (TH), femoral neck (FN), and lumbar spine (LS) were assessed by dual-energy X-ray absorptiometry. The 82 subjects who completed all 2-yr treatments were analyzed. Responders were defined as experiencing BMD increases of >3%. An "excellent response" was defined as an increase of >6%. Over 24 mo, TH BMD increased by >3% in 36%, 53%, and 92% of women in the teriparatide, denosumab, and combination groups, respectively, and by >6% in 11%, 17%, and 50% in the teriparatide, denosumab, and combination groups, respectively (p < 0.01 for all comparisons vs combination). FN response rates were similar to TH. In the LS, BMD increased by >3% in 85%, 93%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (p = nonsignificant for all comparisons) and by >6% in 63%, 78%, and 100% of women in the teriparatide, denosumab, and combination groups, respectively (combination vs teriparatide, p = 0.001; combination vs denosumab, p = 0.016). In summary, more women treated with 24 mo of combined denosumab and teriparatide achieved a significant response at the TH and FN than those treated with either drug alone. All women treated with both agents together experienced an excellent response at the LS. These results support the continued investigation of combined denosumab and teriparatide therapy in postmenopausal osteoporotic women utilizing clinical endpoints such as fracture reduction.
C1 [Leder, Benjamin Z.; Tsai, Joy N.; Neer, Robert M.; Uihlein, Alexander V.; Wallace, Paul M.; Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Dept Med, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA.
RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, 50 Blossom St,Thier 1051, Boston, MA 02114 USA.
EM bzleder@partners.org
FU Eli Lilly Inc.; Amgen Inc. [1 UL1 RR025758-04]
FX This study was supported by Eli Lilly Inc. and Amgen Inc. (Grant Number
1 UL1 RR025758-04). Neither Eli Lilly nor Amgen had any role in the
study design or data analysis, or data interpretation.
NR 24
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1094-6950
EI 1559-0747
J9 J CLIN DENSITOM
JI J. Clin. Densitom.
PD JUL-SEP
PY 2016
VL 19
IS 3
BP 346
EP 351
DI 10.1016/j.jocd.2016.01.004
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DS2OG
UT WOS:000380622800014
PM 26900146
ER
PT J
AU Roberts, AL
Johnson, NJ
Cudkowicz, ME
Eum, KD
Weisskopf, MG
AF Roberts, Andrea L.
Johnson, Norman J.
Cudkowicz, Merit E.
Eum, Ki-Do
Weisskopf, Marc G.
TI Job-related formaldehyde exposure and ALS mortality in the USA
SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
LA English
DT Letter
C1 [Roberts, Andrea L.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
[Johnson, Norman J.] US Bur Census, Washington, DC 20233 USA.
[Cudkowicz, Merit E.] Harvard Med Sch, Boston, MA USA.
[Cudkowicz, Merit E.] Massachusetts Gen Hosp, Dept Neurol, MGH MDA ALS Clin, Boston, MA 02114 USA.
[Eum, Ki-Do; Weisskopf, Marc G.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Weisskopf, Marc G.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Roberts, AL (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Social & Behav Sci, 677 Huntington Ave, Boston, MA 02115 USA.
EM aroberts@hsph.harvard.edu
OI Roberts, Andrea/0000-0001-5023-4399
FU NIEHS NIH HHS [P30 ES000002]; NINDS NIH HHS [R56 NS082105]
NR 6
TC 2
Z9 2
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-3050
EI 1468-330X
J9 J NEUROL NEUROSUR PS
JI J. Neurol. Neurosurg. Psychiatry
PD JUL
PY 2016
VL 87
IS 7
BP 786
EP U151
DI 10.1136/jnnp-2015-310750
PG 3
WC Clinical Neurology; Psychiatry; Surgery
SC Neurosciences & Neurology; Psychiatry; Surgery
GA DS1VN
UT WOS:000380391900018
PM 26169306
ER
PT J
AU Xu, YZ
Navarro-Alvarez, N
Yang, C
Markmann, JF
Dong, JH
Yeh, HD
AF Xu, Yinzhe
Navarro-Alvarez, Nalu
Yang, Chao
Markmann, James F.
Dong, Jiahong
Yeh, Heidi
TI A reliable scoring system after major liver resection in mice
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Animal model; Posthepatectomy liver failure; Liver regeneration; Body
condition scoring system
ID PARTIAL-HEPATECTOMY; MOUSE; MODEL; REGENERATION; REFINEMENT; MARKERS;
WELFARE; DEATH
AB Background: Posthepatectomy liver failure and its transplant counterpart, small-for-size syndrome, remain significant limitations for liver resections and segmental liver transplantation. Partial hepatectomy in mice is one of the most commonly used models to study liver regeneration, but blood and tissue sampling necessary to collect data can affect outcomes or even require euthanasia. We therefore developed a quantitative observational system to predict death from hepatectomy during the first 24 postoperative hours.
Materials and methods: A total of 100 female, 10 to 12-week-old C57BL/6 mice underwent two-thirds hepatectomy and were monitored for up to 7 d. Our scoring system was based on five categories, each assigned 0-2 points: activity level, body posture, fur condition, respiratory status, and eye appearance. Seventy-five mice were scored 6 h, 12 h, 24 h, 2 d, 3 d, 5 d, and 7 d after surgery. The remaining 25 mice were scored similarly, but underwent, in addition, blood sampling for serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, or euthanasia with liver sampling for conventional hematoxylin-eosin and Ki-67 staining.
Results: Retrospective analysis indicated that body condition scores <= 5 on two consecutive time points within the first 24 postoperative hours accurately predicted eventual death. Animals in the low scoring group also had significantly higher serum alanine aminotransferase, total bilirubin, interleukin-6, tumor necrosis factor-alpha, more hepatocyte necrosis in hematoxylin-eosin, and fewer Ki-67 positive hepatocytes.
Conclusions: Our scoring system accurately predicts survival, hepatocyte damage, liver regeneration, and systemic inflammation in a mouse hepatectomy model, within the first 24 hours of surgery. This could be useful in evaluating posthepatectomy interventions for their effect on survival and liver regeneration. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Xu, Yinzhe; Dong, Jiahong] Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, 28 Fuxing Rd, Beijing 100853, Peoples R China.
[Xu, Yinzhe; Navarro-Alvarez, Nalu; Yang, Chao; Markmann, James F.; Yeh, Heidi] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Div Transplantat, Boston, MA USA.
RP Dong, JH (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Hepatobiliary Surg, 28 Fuxing Rd, Beijing 100853, Peoples R China.; Yeh, HD (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplant, 55 Fruit St,WHT 516, Boston, MA 02114 USA.
EM dongjh301@163.com; hyeh@mgh.harvard.edu
FU National Institute of Health, USA [5K08DK094965-04]; National Key
Technology R&D Program of China [2012BAI06B01]; National S&T Major
Project for Infectious Diseases of China [2012ZX10002-017]
FX The authors are grateful to Britany Merrick from Center for Comparative
Medicine in Massachusetts General Hospital for sharing her veterinary
experience in animal monitoring and care. The work is supported by the
National Institute of Health (ID: 5K08DK094965-04), USA, the National
Key Technology R&D Program of China (No. 2012BAI06B01), and the National
S&T Major Project for Infectious Diseases of China (No.
2012ZX10002-017).
NR 20
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD JUL
PY 2016
VL 204
IS 1
BP 75
EP 82
DI 10.1016/j.jss.2016.03.066
PG 8
WC Surgery
SC Surgery
GA DS4KM
UT WOS:000380750000013
PM 27451871
ER
PT J
AU Soh, BS
Ng, SY
Wu, H
Buac, K
Park, JHC
Lian, XJ
Xu, JJ
Foo, KS
Felldin, U
He, XB
Nichane, M
Yang, H
Bu, L
Li, RA
Lim, B
Chien, KR
AF Soh, Boon-Seng
Ng, Shi-Yan
Wu, Hao
Buac, Kristina
Park, Joo-Hye C.
Lian, Xiaojun
Xu, Jiejia
Foo, Kylie S.
Felldin, Ulrika
He, Xiaobing
Nichane, Massimo
Yang, Henry
Bu, Lie
Li, Ronald A.
Lim, Bing
Chien, Kenneth R.
TI Endothelin-1 supports clonal derivation and expansion of cardiovascular
progenitors derived from human embryonic stem cells (vol 7, 10774, 2016)
SO Nature Communications
LA English
DT Correction
C1 [Soh, Boon-Seng] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.
[Soh, Boon-Seng] Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA.
[Soh, Boon-Seng; Li, Ronald A.] Univ Hong Kong, HKU Karolinska Inst Collaborat Regenerat Med, Li Dak Sum Res Ctr, Hong Kong, Hong Kong, Peoples R China.
[Soh, Boon-Seng] Karolinska Inst, Dept Cell & Mol Biol & Med, S-17177 Stockholm, Sweden.
RP Soh, BS (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.; Soh, BS (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA.; Soh, BS (reprint author), Univ Hong Kong, HKU Karolinska Inst Collaborat Regenerat Med, Li Dak Sum Res Ctr, Hong Kong, Hong Kong, Peoples R China.; Soh, BS (reprint author), Karolinska Inst, Dept Cell & Mol Biol & Med, S-17177 Stockholm, Sweden.
FU NHLBI NIH HHS [T32 HL007208]
NR 1
TC 0
Z9 0
U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2016
VL 7
AR 12118
DI 10.1038/ncomms12118
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS5GO
UT WOS:000380809800001
PM 27431579
ER
PT J
AU Skorin, L
Dailey, KH
AF Skorin, Leonid, Jr.
Dailey, Kathryn H.
TI Clicking Eyelids: A New Finding of Prostaglandin-Associated
Periorbitopathy
SO OPTOMETRY AND VISION SCIENCE
LA English
DT Article
DE prostaglandin-associated periorbitopathy; prostaglandin; eyelids;
bimatoprost; clicking; orbital fat atrophy; tight orbits
ID TOPICAL BIMATOPROST; CILIARY MUSCLE; IN-VITRO; LATANOPROST; TRAVOPROST;
THERAPY; SULCUS
AB Purpose To present and discuss a case representing both a new sign and symptom of prostaglandin-associated periorbitopathy.
Case Report An 83-year-old female patient presented for a 6-month glaucoma follow-up in July 2013 with no specific visual or comfort complaints. The patient had a 14-year history of bilateral primary open angle glaucoma and a 13-year history of once daily bimatoprost use in both eyes. Evaluation at previous examinations revealed long eyelashes, tight eyelids, small palpebral fissures, and deepening of the upper eyelid sulcus. During slit-lamp examination of the anterior segment, it was noted that the patient's eyelids clicked intermittently when she blinked. The patient had not previously noticed the clicking and it was determined to be present in each eye individually. The eyelid clicking has been noted to be present in every follow-up examination since it was discovered in July 2013.
Conclusions Prostaglandin-associated periorbitopathy and the resulting cosmetic effects noticed visually by patients are well documented. Our case represents a new audible sign and symptom that may be found with prostaglandin-associated periorbitopathy but has not to our knowledge been reported in the literature.
C1 [Skorin, Leonid, Jr.] Mayo Clin Hlth Syst, Dept Ophthalmol, Albert Lea, MN USA.
[Dailey, Kathryn H.] VA Puget Sound Hlth Care Syst, Amer Lake Div, Tacoma, WA USA.
RP Skorin, L (reprint author), Mayo Clin Hlth Syst, 404 W Fountain St, Albert Lea, MN 56007 USA.
EM skorin.leonid@mayo.edu
NR 13
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-5488
EI 1538-9235
J9 OPTOMETRY VISION SCI
JI Optom. Vis. Sci.
PD JUL
PY 2016
VL 93
IS 7
BP 779
EP 781
DI 10.1097/OPX.0000000000000862
PG 3
WC Ophthalmology
SC Ophthalmology
GA DR9UJ
UT WOS:000380241300016
PM 27055061
ER
PT J
AU Kittiskulnam, P
Sheshadri, A
Johansen, KL
AF Kittiskulnam, Piyawan
Sheshadri, Anoop
Johansen, Kirsten L.
TI Consequences of CKD on Functioning
SO SEMINARS IN NEPHROLOGY
LA English
DT Review
DE Chronic kidney disease; physical function; frailty; cognitive function;
depression; health-related quality of life
ID CHRONIC KIDNEY-DISEASE; QUALITY-OF-LIFE; STAGE RENAL-DISEASE;
PERITONEAL-DIALYSIS PATIENTS; COMORBIDITY SURVEY REPLICATION; RECEIVING
CHRONIC-HEMODIALYSIS; BLOOD-PRESSURE VARIABILITY; IN-CENTER
HEMODIALYSIS; MINI-MENTAL-STATE; COGNITIVE IMPAIRMENT
AB Chronic kidney disease (CKD) is highly prevalent in the United States and throughout the world,(1) with approximately 13% of adults affected.(2) In addition, according to recent estimates, almost half of patients with CKD stages 3 to 5 are 70 years of age and older.(2) In the United States, the number of prevalent end-stage renal disease cases continues to increase in patients older than age 65. In light of the demographic characteristics of patients with CKD and ESRD, there has been considerable focus on associations between CKD and cardiovascular outcomes.(3) Until recently, less attention had been paid to other consequences of CKD in general and among older individuals with CKD in particular, but there is now solid evidence linking CKD with impairments of physical function, cognitive function, and emotional function and quality of life. This review summarizes available literature on these topics, focusing specifically on physical functioning and frailty, cognitive function, emotional health, including depression and anxiety, and health-related quality of life. Published by Elsevier Inc.
C1 [Kittiskulnam, Piyawan; Sheshadri, Anoop; Johansen, Kirsten L.] Univ Calif San Francisco, Div Nephrol, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
[Kittiskulnam, Piyawan] Chulalongkorn Univ, King Chulalongkorn Mem Hosp, Dept Med, Thai Red Cross Soc, Bangkok, Thailand.
RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Box 111J,4150 Clement St, San Francisco, CA 94121 USA.
EM kirsten.johansen@ucsf.edu
FU International Society of Nephrology Fellowship; National Institute of
Diabetes and Digestive and Kidney Diseases [K24 DK085153]; Veterans
Health Administration
FX This work was supported in part by an International Society of
Nephrology Fellowship (P.K.), by a grant (K24 DK085153) from the
National Institute of Diabetes and Digestive and Kidney Diseases
(K.L.J.), and by fellowship funding from the Veterans Health
Administration (A.S.).
NR 151
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U1 9
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0270-9295
EI 1558-4488
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD JUL
PY 2016
VL 36
IS 4
BP 305
EP 318
DI 10.1016/j.semnephrol.2016.05.007
PG 14
WC Urology & Nephrology
SC Urology & Nephrology
GA DT1IG
UT WOS:000381234300007
PM 27475661
ER
PT J
AU Pena-Polanco, JE
Fried, LF
AF Pena-Polanco, Julio E.
Fried, Linda F.
TI Established and Emerging Strategies in the Treatment of Chronic Kidney
Disease
SO SEMINARS IN NEPHROLOGY
LA English
DT Review
DE Chronic kidney disease; progression; renin-angiotensin system
ID CHRONIC RENAL-INSUFFICIENCY; RANDOMIZED CLINICAL-TRIAL; BLOOD-PRESSURE
CONTROL; CONVERTING ENZYME-INHIBITION; TYPE-2 DIABETIC-NEPHROPATHY;
DOUBLE-BLIND; URIC-ACID; RECEPTOR ANTAGONIST; CARDIOVASCULAR OUTCOMES;
MICROVASCULAR OUTCOMES
AB Chronic kidney disease (CKD) is a common condition that has become a significant public health concern. The mainstay therapeutic approach to CKD is based on renin-angiotensin system blockade as well as blood pressure and glycemic control. Despite these interventions, the management of CKD remains suboptimal, with a large proportion of the CKD population progressing to end-stage renal disease. Newer strategies for the treatment of CKD have emerged over the past years focusing on decreasing inflammation and delaying the development of fibrosis. Despite promising results in experimental models and small randomized studies, adequately powered randomized trials are required to evaluate the benefits and risks of these therapies in the CKD population. In this review, we discuss the evidence behind, and gaps in our knowledge of, established therapies as well as newer potential strategies for managing CKD, concentrating on interventions that currently are being evaluated in randomized studies. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Pena-Polanco, Julio E.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA.
[Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Fried, Linda F.] Univ Pittsburgh, Epidemiol & Clin & Translat Sci, Pittsburgh, PA USA.
RP Pena-Polanco, JE (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA.
NR 95
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U1 1
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0270-9295
EI 1558-4488
J9 SEMIN NEPHROL
JI Semin. Nephrol.
PD JUL
PY 2016
VL 36
IS 4
BP 331
EP 342
DI 10.1016/j.semnephrol.2016.05.009
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA DT1IG
UT WOS:000381234300009
PM 27475663
ER
PT J
AU Bendapudi, P
AF Bendapudi, Pavan
TI Bench to bedside: the challenge and promise of translating basic
research discoveries in thrombotic microangiopathies
SO TRANSFUSION
LA English
DT Editorial Material
ID THROMBOCYTOPENIC PURPURA; ADAMTS13; DEFICIENCY
C1 [Bendapudi, Pavan] Massachusetts Gen Hosp, Div Hematol & Blood Transfus Serv, Boston, MA 02114 USA.
RP Bendapudi, P (reprint author), Massachusetts Gen Hosp, Div Hematol & Blood Transfus Serv, Boston, MA 02114 USA.
EM pkbendapudi@partners.org
NR 8
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD JUL
PY 2016
VL 56
IS 7
BP 1675
EP 1677
DI 10.1111/trf.13651
PG 3
WC Hematology
SC Hematology
GA DS1NG
UT WOS:000380362100003
PM 27389992
ER
PT J
AU Levin, AE
Williamson, PC
Bloch, EM
Clifford, J
Cyrus, S
Shaz, BH
Kessler, D
Gorlin, J
Erwin, JL
Krueger, NX
Williams, GV
Penezina, O
Telford, SR
Branda, JA
Krause, PJ
Wormser, GP
Schotthoefer, AM
Fritsche, TR
Busch, MP
AF Levin, Andrew E.
Williamson, Phillip C.
Bloch, Evan M.
Clifford, Joan
Cyrus, Sherri
Shaz, Beth H.
Kessler, Debra
Gorlin, Jed
Erwin, James L.
Krueger, Neil X.
Williams, Greg V.
Penezina, Oksana
Telford, Sam R.
Branda, John A.
Krause, Peter J.
Wormser, Gary P.
Schotthoefer, Anna M.
Fritsche, Thomas R.
Busch, Michael P.
TI Serologic screening of United States blood donors for Babesia microti
using an investigational enzyme immunoassay
SO TRANSFUSION
LA English
DT Article
ID COST-EFFECTIVENESS; LYME-DISEASE; DIAGNOSIS; ANTIBODY; ASSAY; INFECTION;
SEROPREVALENCE; EHRLICHIOSIS; PARASITEMIA; ANTIGENS
AB BACKGROUNDThe tick-borne pathogen Babesia microti has become recognized as the leading infectious risk associated with blood transfusion in the United States, yet no Food and Drug Administration-licensed screening tests are currently available to mitigate this risk. The aim of this study was to evaluate the performance of an investigational enzyme immunoassay (EIA) for B. microti as a screening test applied to endemic and nonendemic blood donor populations.
STUDY DESIGN AND METHODSThe study aimed to test 20,000 blood donors from areas of the United States considered endemic for B. microti and 10,000 donors from a nonendemic area with the investigational B. microti EIA. Repeat-reactive samples were retested by polymerase chain reaction (PCR), blood smear, immunofluorescent assay (IFA), and immunoblot assay. In parallel, serum samples from symptomatic patients with confirmed babesiosis were tested by EIA, IFA, and immunoblot assays.
RESULTSA total of 38 of 13,757 (0.28%) of the donors from New York, 7 of 4583 (0.15%) from Minnesota, and 11 of 8363 (0.13%) from New Mexico were found repeat reactive by EIA. Nine of the 56 EIA repeat-reactive donors (eight from New York and one from Minnesota) were positive by PCR. The specificity of the assay in a nonendemic population was 99.93%. Among IFA-positive clinical babesiosis patients, the sensitivity of the assay was 91.1%.
CONCLUSIONThe B. microti EIA detected PCR-positive, potentially infectious blood donors in an endemic population and exhibited high specificity among uninfected and unexposed individuals. The EIA promises to provide an effective tool for blood donor screening for B. microti in a format amenable to high-throughput and cost-effective screening.
C1 [Levin, Andrew E.; Clifford, Joan; Erwin, James L.; Krueger, Neil X.; Williams, Greg V.; Penezina, Oksana] Immunetics Inc, 27 Drydock Ave, Boston, MA 02210 USA.
[Williamson, Phillip C.; Cyrus, Sherri] Creat Testing Solut, Tempe, AZ USA.
[Bloch, Evan M.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA USA.
[Bloch, Evan M.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Shaz, Beth H.; Kessler, Debra] New York Blood Ctr, New York, NY USA.
[Gorlin, Jed] Innovat Blood Resources Mem Blood Ctr, St Paul, MN USA.
[Telford, Sam R.] Tufts Univ, Cummings Sch Vet Med, North Grafton, MA USA.
[Branda, John A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Krause, Peter J.] Yale Sch Publ Hlth, New Haven, CT USA.
[Krause, Peter J.] Yale Sch Med, New Haven, CT USA.
[Wormser, Gary P.] New York Med Coll, Valhalla, NY USA.
[Schotthoefer, Anna M.; Fritsche, Thomas R.] Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA.
RP Levin, AE (reprint author), Immunetics Inc, 27 Drydock Ave, Boston, MA 02210 USA.
EM alevin@immunetics.com
FU National Heart Lung and Blood Institute at the National Institutes of
Health through SBIR [HHSN268201000047C]; Blood Systems Research
Institute [10734]
FX This project was supported by the National Heart Lung and Blood
Institute at the National Institutes of Health through SBIR Phase I and
Phase II Contract HHSN268201000047C, and by Blood Systems Research
Institute Contract 10734.
NR 40
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U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD JUL
PY 2016
VL 56
IS 7
BP 1866
EP 1874
DI 10.1111/trf.13618
PG 9
WC Hematology
SC Hematology
GA DS1NG
UT WOS:000380362100029
PM 27224258
ER
PT J
AU Carter, A
Borrero, S
Wessel, C
Washington, DL
Bean-Mayberry, B
Corbelli, J
AF Carter, Andrea
Borrero, Sonya
Wessel, Charles
Washington, Donna L.
Bean-Mayberry, Bevanne
Corbelli, Jennifer
CA VA Women's Hlth Disparities Res Wo
TI Racial and Ethnic Health Care Disparities Among Women in the Veterans
Affairs Healthcare System: A Systematic Review
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID UNITED-STATES; SATISFACTION; MILITARY; TRAUMA; RATES
AB Background: Women are a rapidly growing segment of patients who seek care in the Veterans Affairs (VA) Healthcare System, yet many questions regarding their health care experiences and outcomes remain unanswered. Racial and ethnic disparities have been well-documented in the general population and among veterans; however, prior disparities research conducted in the VA focused primarily on male veterans. We sought to characterize the findings and gaps in the literature on racial and ethnic disparities among women using the VA.
Methods: We systematically reviewed the literature on racial and ethnic health care disparities exclusively among women using the VA Healthcare System. We included studies that examined health care use, satisfaction, and/or quality, and stratified data by race or ethnicity.
Results: Nine studies of the 2,591 searched met our inclusion criteria. The included studies examined contraception provision/access (n = 3), treatment of low bone mass (n = 1), hormone therapy (n = 1), use of mental health or substance abuse-related services (n = 2), trauma exposure and use of various services (n = 1), and satisfaction with primary care (n = 1). Five of nine studies showed evidence of a significant racial or ethnic difference.
Conclusion: In contrast with the wealth of literature examining disparities both among the male veterans and women in non VA settings, only nine studies examine racial and ethnic disparities specifically among women in the VA Healthcare System. These results demonstrate that there is an unmet need to further assess health care disparities among female VA users. Published by Elsevier Inc. on behalf of Jacobs Institute of Women's Health.
C1 [Carter, Andrea; Borrero, Sonya; Corbelli, Jennifer] Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA USA.
[Borrero, Sonya] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Wessel, Charles] Univ Pittsburgh, Hlth Sci Lib Syst, Pittsburgh, PA USA.
[Washington, Donna L.; Bean-Mayberry, Bevanne] Vet Affairs Greater Los Angeles Healthcare Syst, Vet Affairs Hlth Serv Res & Dev, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA.
[Washington, Donna L.; Bean-Mayberry, Bevanne] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
RP Borrero, S (reprint author), 230 McKee Pl,Suite 600, Pittsburgh, PA 15213 USA.
EM borrerosp@upmc.edu
RI Wessel, Charles/B-2318-2013
OI Wessel, Charles/0000-0002-5018-0156
FU VA Women's Health Research Network [VA HSRD SDR 10-012]
FX This work was supported in part by the VA Women's Health Research
Network (VA HSR&D SDR 10-012). The contents of this manuscript do not
represent the views of the Department of Veterans Affairs or the United
States Government. To the best of our knowledge, there are no conflicts
of interest.
NR 38
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U1 3
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JUL-AUG
PY 2016
VL 26
IS 4
BP 401
EP 409
DI 10.1016/j.whi.2016.03.009
PG 9
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA DS4KB
UT WOS:000380748900007
PM 27138241
ER
PT J
AU Goodrich, DE
Klingaman, EA
Verchinina, L
Goldberg, RW
Littman, AJ
Janney, CA
Kim, HM
Maguen, S
Hoerster, KD
Owen, RR
Holleman, RG
Roman, P
Lai, ZS
Bowersox, NW
AF Goodrich, David E.
Klingaman, Elizabeth A.
Verchinina, Lilia
Goldberg, Richard W.
Littman, Alyson J.
Janney, Carol A.
Kim, Hyungjin Myra
Maguen, Shira
Hoerster, Katherine D.
Owen, Richard R.
Holleman, Robert G.
Roman, Pia
Lai, Zongshan
Bowersox, Nicholas W.
TI Sex Differences in Weight Loss among Veterans with Serious Mental
Illness: Observational Study of a National Weight Management Program
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; LIFE-STYLE INTERVENTIONS; BODY-MASS
INDEX; BIPOLAR DISORDER; HEALTH-CARE; RISK-FACTORS; CARDIOMETABOLIC
RISK; CARDIOVASCULAR RISK; GENDER-DIFFERENCES; WOMEN VETERANS
AB Purpose: Obesity disproportionately burdens individuals with serious mental illness (SMI), especially women. This observational study investigated whether there were sex differences in weight loss and program participation among veterans with SMI enrolled in the Veterans Health Administration's (VHA) MOVE! weight management program.
Procedures: Participants were identified from a national cohort of 148,254 veterans enrolled in MOVE! during fiscal years 2008 through 2012 who attended two or more sessions within 12 months of enrollment. The cohort included those with International Classification of Disease, 9th Edition, Clinical Modification (ICD-9-CM) diagnoses for SMI, age less than 70 years, and weight data at baseline and one or more follow-up timepoints within approximately 1 year of enrollment (n = 8,943 men; n = 2,245 women). Linear mixed models assessed associations of sex with 6-and 12-month weight change from baseline, adjusting for demographic-and site-level variables.
Findings: Both sexes averaged 6.4 (standard deviation, 4.6) sessions within 12 months; however, women with and without SMI participated at rates double their respective proportion rates among all VHA users. Participants averaged statistically significant weight loss at 6 months (men, -2.5 lb [95% CI, - 2.8 to -2.1]; women, -2.4 lb [95% CI, -3.1 to -1.7]) and 12 months (men, -2.5 lb [95% CI, -2.8 to -2.2]; women, -2.9 lb [95% CI, -3.6 to -2.2]), but no sex-based difference in absolute weight loss at either timepoint. Slightly more women achieved 5% or greater (clinically significant) weight loss at the 12-month follow-up than did men (25.7% vs. 23.0%; p < .05).
Conclusions: Women with SMI participated in MOVE! at rates equivalent to or greater than men with SMI, with comparable weight loss. More women were Black, single, had bipolar and posttraumatic stress disorder, and higher service-connected disability, suggesting areas for program customization. Published by Elsevier Inc. on behalf of Jacobs Institute of Women's Health. Published by Elsevier Inc. on behalf of Jacobs Institute of Women's Health.
C1 [Goodrich, David E.; Verchinina, Lilia; Janney, Carol A.; Kim, Hyungjin Myra; Holleman, Robert G.; Roman, Pia; Lai, Zongshan; Bowersox, Nicholas W.] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Ann Arbor, MI USA.
[Klingaman, Elizabeth A.; Goldberg, Richard W.] VA Maryland Hlth Care Syst, Baltimore VA Med Ctr, 10 North Greene St,Annex Suite 720, Baltimore, MD 21201 USA.
[Klingaman, Elizabeth A.; Goldberg, Richard W.] Univ Maryland, Sch Med, Div Psychiat Serv Res, Dept Psychiat, Baltimore, MD USA.
[Littman, Alyson J.] VA Puget Sound Med Ctr, Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Littman, Alyson J.] Univ Washington, Dept Epidemiol, Seattle, WA USA.
[Kim, Hyungjin Myra] Univ Michigan, Ctr Stat Consultat & Res, Ann Arbor, MI USA.
[Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA USA.
[Maguen, Shira] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Hoerster, Katherine D.] VA Puget Sound Healthcare Syst, Mental Hlth Serv, Seattle, WA USA.
[Hoerster, Katherine D.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Owen, Richard R.] Cent Arkansas Vet Healthcare Syst, VA Ctr Mental Healthcare & Outcomes Res, North Little Rock, AR USA.
[Owen, Richard R.] Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Inst Psychiat Res, Little Rock, AR 72205 USA.
[Bowersox, Nicholas W.] VA Serious Mental Illness Treatment Resource & Ev, Ann Arbor, MI USA.
RP Klingaman, EA (reprint author), VA Maryland Hlth Care Syst, Baltimore VA Med Ctr, 10 North Greene St,Annex Suite 720, Baltimore, MD 21201 USA.
EM Elizabeth.klingaman@va.gov
OI Goodrich, David/0000-0003-3232-2189
FU VA Health Services Research and Development Quality Enhancement Research
Initiative (QUERI) programs for Diabetes and Mental Health research as a
locally initiated project [QLP 55-017]; Department of Veterans Affairs
Office of Academic Affiliations Advanced Fellowship Program in Mental
Illness Research and Treatment; VA Rehabilitation R&D Career Development
Award [6982]
FX Funding was provided by the VA Health Services Research and Development
Quality Enhancement Research Initiative (QUERI) programs for Diabetes
and Mental Health research as a locally initiated project (QLP 55-017).
Dr. Klingaman's time was supported by the Department of Veterans Affairs
Office of Academic Affiliations Advanced Fellowship Program in Mental
Illness Research and Treatment and is the result of work supported with
resources and the use of facilities at the VA Capitol Health Care
Network (VISN 5) Mental Illness Research, Education, and Clinical Center
(MIRECC). Dr. Littman's time was supported by a VA Rehabilitation R&D
Career Development Award (#6982).
NR 74
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JUL-AUG
PY 2016
VL 26
IS 4
BP 410
EP 419
DI 10.1016/j.whi.2016.05.001
PG 10
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA DS4KB
UT WOS:000380748900008
PM 27365284
ER
PT J
AU Rosenbaum, DL
Kimerling, R
Pomernacki, A
Goldstein, KM
Yano, EM
Sadler, AG
Carney, D
Bastian, LA
Bean-Mayberry, BA
Frayne, SM
AF Rosenbaum, Diane L.
Kimerling, Rachel
Pomernacki, Alyssa
Goldstein, Karen M.
Yano, Elizabeth M.
Sadler, Anne G.
Carney, Diane
Bastian, Lori A.
Bean-Mayberry, Bevanne A.
Frayne, Susan M.
TI Binge Eating among Women Veterans in Primary Care: Comorbidities and
Treatment Priorities
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID MENTAL-HEALTH-SERVICES; DIALECTICAL BEHAVIOR-THERAPY; FEMALE VETERANS;
OBESE-PATIENTS; PSYCHIATRIC COMORBIDITY; AFGHANISTAN VETERANS; SURVEY
REPLICATION; COMMUNITY SAMPLE; UNITED-STATES; WEIGHT-GAIN
AB Background: Little is known about the clinical profile and treatment priorities of women with binge eating disorder (BED), a diagnosis new to the fifth edition of Diagnostic and Statistical Manual of Mental Disorders. We identified comorbidities and patients' treatment priorities, because these may inform implementation of clinical services.
Methods: Data were collected from women veteran primary care patients. Analyses compared those who screened positive for BED (BED+), and those without any binge eating symptoms (BED-).
Results: Frequencies of comorbid medical and psychological disorders were high in the BED+ group. The BED+ group's self-identified most common treatment priorities were mood concerns (72.2%), weight loss (66.7%), and body image/food issues (50%). Among those with obesity, a greater proportion of the BED+ group indicated body image/food issues was their top treatment priority (12.9% vs. 2.8%; p < .01), suggesting that these patients may be more apt to seek treatment beyond weight management for their problematic eating patterns.
Conclusions: Women primary care patients with BED demonstrate high medical and psychological complexity; their subjective treatment priorities often match objective needs. These findings may inform the development of targeted BED screening practices for women with obesity in primary care settings, and the eventual adoption of patient-centered BED treatment resources. Published by Elsevier Inc. on behalf of Jacobs Institute of Women's Health.
C1 [Rosenbaum, Diane L.; Kimerling, Rachel; Pomernacki, Alyssa; Carney, Diane; Frayne, Susan M.] VA Palo Alto Hlth Care Syst, Hlth Serv Res & Dev, Ctr Innovat Implementat, Palo Alto, CA USA.
[Rosenbaum, Diane L.] Drexel Univ, Dept Psychol, 3141 Chestnut St, Philadelphia, PA 19104 USA.
[Kimerling, Rachel] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Palo Alto, CA USA.
[Goldstein, Karen M.] Durham VA Med Ctr, Hlth Serv Res & Dev, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Goldstein, Karen M.] Duke Univ, Dept Med, Durham, NC USA.
[Yano, Elizabeth M.; Bean-Mayberry, Bevanne A.] VA Greater Los Angeles Healthcare Syst, Hlth Serv Res & Dev, Ctr Study Healthcare Innovat Implementat & Policy, Los Angeles, CA USA.
[Yano, Elizabeth M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA.
[Sadler, Anne G.] Iowa City VA Hlth Care Syst, Hlth Serv Res & Dev, Ctr Comprehens Access & Delivery Res & Evaluat, Iowa City, IA USA.
[Sadler, Anne G.] Univ Iowa Hosp & Clin, Dept Psychiat, Iowa City, IA 52242 USA.
[Bastian, Lori A.] VA Connecticut Healthcare Syst, Hlth Serv Res & Dev, Pain Res Informat Multimorbid & Educ Ctr, West Haven, CT USA.
[Bastian, Lori A.] Yale Sch Med, Internal Med, New Haven, CT USA.
[Bean-Mayberry, Bevanne A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Frayne, Susan M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA.
RP Rosenbaum, DL (reprint author), Drexel Univ, Dept Psychol, 3141 Chestnut St, Philadelphia, PA 19104 USA.
EM diane.rosenbaum@drexel.edu
FU VA HSRD [SDR 10-012]; VA HSR&D Service Senior Research Career Scientist
Award [RCS 05-195]
FX This study was funded by the VA HSR&D (Project SDR 10-012). Dr. Yano's
effort was funded by a VA HSR&D Service Senior Research Career Scientist
Award (RCS 05-195). The views expressed in this article are those of the
authors and do not necessarily reflect the position or policy of the
Department of Veterans Affairs or the United States Government.
NR 74
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U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JUL-AUG
PY 2016
VL 26
IS 4
BP 420
EP 428
DI 10.1016/j.whi.2016.02.004
PG 9
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA DS4KB
UT WOS:000380748900009
PM 26972486
ER
PT J
AU Breland, JY
Donalson, R
Dinh, J
Nevedal, A
Maguen, S
AF Breland, Jessica Y.
Donalson, Rosemary
Dinh, Julie
Nevedal, Andrea
Maguen, Shira
TI Women Veterans' Treatment Preferences for Disordered Eating
SO WOMENS HEALTH ISSUES
LA English
DT Article
ID WEIGHT-LOSS; BINGE; MILITARY; PREVALENCE; SYMPTOMS; OUTCOMES; PTSD; MEN
AB Objective: Disordered eating, which includes subclinical and clinical maladaptive eating behaviors, is common among women, including those served by the Veterans Health Administration (VA). We used qualitative methods to determine whether and how women veterans want to receive treatment for disordered eating.
Method: Women veterans participated in one of seven focus groups/interviews and completed in-person demographic and psychological questionnaires. We used thematic analysis of focus groups/interviews to understand preferences for disordered eating treatment.
Results: Participants (n = 20) were mostly women of color (55%); mean age was 48 (SD = 15) and 65% had significant psychological symptoms. Few participants described being assessed for disordered eating, but all thought VA should provide treatment for disordered eating. Through thematic analysis, we identified six preferences: 1) treatment for disordered eating should be provided in groups, 2) treatment for disordered eating should provide concrete skills to facilitate the transition out of structured military environments, 3) treatment for disordered eating should address the relationship between eating and mental health, 4) disordered eating can be treated with mindfulness and cognitive-behavioral therapy, 5) disordered eating treatment providers should be experienced and take an interactive approach to care, but can come from diverse disciplines, and 6) referrals to treatment for disordered eating should be open ended, occur early, and allow for ongoing, flexible access to treatment.
Conclusions: Women veterans are interested in treatment for disordered eating. Preferred treatments align with existing treatments, could be offered in conjunction with weight loss or primary care services, and should provide social support and interactive learning. Published by Elsevier Inc. on behalf of Jacobs Institute of Women's Health.
C1 [Breland, Jessica Y.; Nevedal, Andrea] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd,MPD-152, Menlo Pk, CA 94025 USA.
[Breland, Jessica Y.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Donalson, Rosemary; Dinh, Julie; Maguen, Shira] San Francisco VA Med Ctr, San Francisco, CA USA.
[Maguen, Shira] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Dinh, Julie] Rice Univ, Dept Psychol, Houston, TX 77251 USA.
RP Breland, JY (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd,MPD-152, Menlo Pk, CA 94025 USA.
EM breland@stanford.edu
OI Breland, Jessica/0000-0003-0024-3478
FU Veterans Health and Integration Program (VHIP); VA Office of Academic
Affiliations; VA Health Services Research and Development Service; VA
HSR&D Advanced Fellowship Program
FX This research was supported by the Veterans Health and Integration
Program (VHIP; PI: Maguen). Dr. Breland is supported by the VA Office of
Academic Affiliations and VA Health Services Research and Development
Service in conjunction with a VA HSR&D Advanced Fellowship Program.
Sponsors had no role in study design; in the collection, analysis and
interpretation of data; in the writing of the report; or in the decision
to submit the article for publication. The authors report no conflicts
of interest.
NR 29
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U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JUL-AUG
PY 2016
VL 26
IS 4
BP 429
EP 436
DI 10.1016/j.whi.2016.04.006
PG 8
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA DS4KB
UT WOS:000380748900010
PM 27264912
ER
PT J
AU Pascale, A
Beal, M
AF Pascale, Alisa
Beal, Margaret
TI Women's Urological Health as a Priority to the Woman Well Visit Reply
SO WOMENS HEALTH ISSUES
LA English
DT Letter
C1 [Pascale, Alisa] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Beal, Margaret] MGH Inst Hlth Profess, Boston, MA USA.
RP Pascale, A (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
OI Pascale, Alisa/0000-0002-3927-4258
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1049-3867
EI 1878-4321
J9 WOMEN HEALTH ISS
JI Womens Health Iss.
PD JUL-AUG
PY 2016
VL 26
IS 4
BP 478
EP 478
DI 10.1016/j.whi.2016.04.005
PG 1
WC Public, Environmental & Occupational Health; Women's Studies
SC Public, Environmental & Occupational Health; Women's Studies
GA DS4KB
UT WOS:000380748900017
PM 27448752
ER
PT J
AU Wagner, FF
Bishop, JA
Gale, JP
Shi, X
Walk, M
Ketterman, J
Patnaik, D
Barker, D
Walpita, D
Campbell, AJ
Nguyen, S
Lewis, M
Ross, L
Weiwer, M
An, WF
Germain, AR
Nag, PP
Metkar, S
Kaya, T
Dandapani, S
Olson, DE
Barbe, AL
Lazzaro, F
Sacher, JR
Cheah, JH
Fei, D
Perez, J
Munoz, B
Palmer, M
Stegmaier, K
Schreiber, SL
Scolnick, E
Zhang, YL
Haggarty, SJ
Holson, EB
Pan, JQ
AF Wagner, Florence F.
Bishop, Joshua A.
Gale, Jennifer P.
Shi, Xi
Walk, Michelle
Ketterman, Joshua
Patnaik, Debasis
Barker, Doug
Walpita, Deepika
Campbell, Arthur J.
Nguyen, Shannon
Lewis, Michael
Ross, Linda
Weiwer, Michel
An, W. Frank
Germain, Andrew R.
Nag, Partha P.
Metkar, Shailesh
Kaya, Taner
Dandapani, Sivaraman
Olson, David E.
Barbe, Anne-Laure
Lazzaro, Fanny
Sacher, Joshua R.
Cheah, Jaime H.
Fei, David
Perez, Jose
Munoz, Benito
Palmer, Michelle
Stegmaier, Kimberly
Schreiber, Stuart L.
Scolnick, Edward
Zhang, Yan-Ling
Haggarty, Stephen J.
Holson, Edward B.
Pan, Jen Q.
TI Inhibitors of Glycogen Synthase Kinase 3 with Exquisite Kinome-Wide
Selectivity and Their Functional Effects
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID FRAGILE-X-SYNDROME; ALZHEIMERS-DISEASE; TYROSINE PHOSPHORYLATION;
THERAPEUTIC TARGET; SIGNALING PATHWAY; GSK-3 INHIBITORS; MOUSE MODEL;
LITHIUM; KINASE-3-BETA; GSK-3-ALPHA
AB The mood stabilizer lithium, the first-line treatment for bipolar disorder, is hypothesized to exert its effects through direct inhibition of glycogen synthase kinase 3 (GSK3) and indirectly by increasing GSK3's inhibitory serine phosphorylation. GSK3 comprises two highly similar paralogs, GSK3 alpha and GSK3 beta, which are key regulatory kinases in the canonical Wnt pathway. GSK3 stands as a nodal target within this pathway and is an attractive therapeutic target for multiple indications. Despite being an active field of research for the past 20 years, many GSK3 inhibitors demonstrate either poor to moderate selectivity versus the broader human kinome or physicochemical properties unsuitable for use in in vitro systems or in vivo models. A nonconventional analysis of data from a GSK3 beta inhibitor high-throughput screening campaign, which excluded known GSK3 inhibitor chemotypes, led to the discovery of a novel pyrazolo-tetrahydroquinolinone scaffold with unparalleled kinome-wide selectivity for the GSK3 kinases. Taking advantage of an uncommon tridentate interaction with the hinge region of GSK3, we developed highly selective and potent GSK3 inhibitors, BRD1652 and BRD0209, which demonstrated in vivo efficacy in a dopaminergic signaling paradigm modeling mood-related disorders. These new chemical probes open the way for exclusive analyses of the function of GSK3 kinases in multiple signaling pathways involved in many prevalent disorders.
C1 [Wagner, Florence F.; Gale, Jennifer P.; Shi, Xi; Walk, Michelle; Ketterman, Joshua; Barker, Doug; Campbell, Arthur J.; Nguyen, Shannon; Lewis, Michael; Weiwer, Michel; Kaya, Taner; Olson, David E.; Barbe, Anne-Laure; Lazzaro, Fanny; Sacher, Joshua R.; Scolnick, Edward; Zhang, Yan-Ling; Haggarty, Stephen J.; Holson, Edward B.; Pan, Jen Q.] Broad Inst MIT Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
[Walpita, Deepika; An, W. Frank; Germain, Andrew R.; Nag, Partha P.; Metkar, Shailesh; Dandapani, Sivaraman; Cheah, Jaime H.; Munoz, Benito; Schreiber, Stuart L.] Broad Inst MIT Harvard, Ctr Sci Therapeut, Cambridge, MA 02142 USA.
[Fei, David; Perez, Jose; Palmer, Michelle] Broad Inst MIT Harvard, Therapeut Platform, Cambridge, MA 02142 USA.
[Bishop, Joshua A.; Patnaik, Debasis; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Chem Neurobiol Lab, Boston, MA 02215 USA.
[Bishop, Joshua A.; Patnaik, Debasis; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Chem Neurobiol Lab, Boston, MA 02215 USA.
[Ross, Linda; Stegmaier, Kimberly] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
[Ross, Linda; Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA 02215 USA.
RP Wagner, FF; Pan, JQ (reprint author), Broad Inst MIT Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA.
EM fwagner@broadinstitute.org; jpan@broadinstitute.org
OI Patnaik, Debasis/0000-0002-9829-3352; Haggarty, Stephen
J./0000-0002-7872-168X
FU Stanley Medical Research Institute; [R21MH099448-01]; [R03MH08744];
[5R01MH095088]; [1 U54 HG005032-1]
FX This work was supported by the Stanley Medical Research Institute and by
R21MH099448-01 (J.Q.P.), R03MH08744 (J.Q.P. and S.J.H.), 5R01MH095088
(S.J.H.), and 1 U54 HG005032-1 (S.L.S.).
NR 65
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U1 5
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD JUL
PY 2016
VL 11
IS 7
BP 1952
EP 1963
DI 10.1021/acschembio.6b00306
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR8XO
UT WOS:000380181900023
PM 27128528
ER
PT J
AU Gudrunardottir, T
Morgan, AT
Lux, AL
Walker, DA
Walsh, KS
Wells, EM
Wisoff, JH
Juhler, M
Schmahmann, JD
Keating, RF
Catsman-Berrevoets, C
AF Gudrunardottir, Thora
Morgan, Angela T.
Lux, Andrew L.
Walker, David A.
Walsh, Karin S.
Wells, Elizabeth M.
Wisoff, Jeffrey H.
Juhler, Marianne
Schmahmann, Jeremy D.
Keating, Robert F.
Catsman-Berrevoets, Coriene
CA Iceland Delphi Grp
TI Consensus paper on post-operative pediatric cerebellar mutism syndrome:
the Iceland Delphi results
SO CHILDS NERVOUS SYSTEM
LA English
DT Review
DE Cerebellar mutism; Posterior fossa syndrome; Cerebellar cognitive
affective syndrome; Children; Cerebellar tumor surgery; Consensus
ID POSTERIOR-FOSSA SYNDROME; COGNITIVE-AFFECTIVE SYNDROME;
OF-THE-LITERATURE; SUBSEQUENT DYSARTHRIA; TELOVELAR APPROACH; TUMOR
RESECTION; RISK-FACTORS; NEUROLOGIC COMPLICATIONS; SPEECH PRODUCTION;
CHILDREN
AB Introduction Confusion has surrounded the description of post-operative mutism and associated morbidity in pediatric patients with cerebellar tumors for years. The heterogeneity of definitions and diagnostic features has hampered research progress within the field, and to date, no international guidelines exist on diagnosis, prevention, treatment, or follow-up of this debilitating condition. An international group of clinicians and researchers from multiple relevant disciplines recently formed a cohesive panel to formulate a new working definition and agree upon standardized methods for diagnosis and follow-up.
Consensus was obtained using the modified nominal group technique, involving four rounds of online Delphi questionnaires interspersed with a structured consensus conference with lectures, group work, and open discussion sessions.
A new, proposed definition of "post-operative pediatric CMS" was formed, preliminary recommendations for diagnostic and follow-up procedures were created, two working groups on a new scoring scale and risk prediction and prevention were established, and areas were identified where further information is needed.
The consensus process was motivated by desire to further research and improve quality of life for pediatric brain tumor patients. The Delphi rounds identified relevant topics and established basic agreement, while face-to-face engagement helped resolve matters of conflict and refine terminology. The new definition is intended to provide a more solid foundation for future clinical and research work. It is thought as a consensus for moving forward and hopefully paves the way to developing a standard approach to this challenging problem with the advent of better scoring methods and ultimate goal of reducing the risk of CMS.
C1 [Gudrunardottir, Thora] North Zealand Hosp, Dept Oncol & Palliat, Dyrehavevej 29, DK-3400 Hillerod, Denmark.
[Morgan, Angela T.] Univ Melbourne, Ctr Neurosci Speech, Melbourne, Vic, Australia.
[Morgan, Angela T.] Murdoch Childrens Res Inst, Neurosci Speech, Melbourne, Vic, Australia.
[Lux, Andrew L.] Bristol Royal Hosp Children, Dept Paediat Neurol, Bristol, Avon, England.
[Walker, David A.] Queens Med Ctr, Dept Oncol, Nottingham, England.
[Walker, David A.] Univ Nottingham, Childrens Brain Tumour Res Ctr, Nottingham, England.
[Walsh, Karin S.] Childrens Natl Hlth Syst, Brain Tumor Inst, Neurofibromatosis Inst, Div Neuropsychol, Washington, DC USA.
[Wells, Elizabeth M.] Childrens Natl Hlth Syst, Brain Tumor Inst, Div Neurol, Washington, DC USA.
[Wisoff, Jeffrey H.] New York Univ Langone Med Ctr, Div Pediat Neurosurg, New York, NY USA.
[Juhler, Marianne] Rigshosp, Copenhagen Univ Hosp, Dept Neurosurg, Copenhagen, Denmark.
[Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Lab Neuroanat & Cerebellar Neurobiol,Ataxia Unit, Boston, MA 02114 USA.
[Schmahmann, Jeremy D.] Harvard Med Sch, Boston, MA USA.
[Keating, Robert F.] Childrens Natl Hlth Syst, Dept Pediat Neurosurg, Washington, DC USA.
[Catsman-Berrevoets, Coriene] Sophia Childrens Univ Hosp, Dept Pediat Neurol, Erasmus MC, Rotterdam, Netherlands.
RP Gudrunardottir, T (reprint author), North Zealand Hosp, Dept Oncol & Palliat, Dyrehavevej 29, DK-3400 Hillerod, Denmark.
EM info@posteriorfossa.org
OI Wisoff, Jeffrey/0000-0003-3303-2220
FU Children's Brain Tumor Research Centre, Nottingham, UK
FX David Walker is affiliated with the Children's Brain Tumor Research
Centre, Nottingham, UK, which provided partial funding for the consensus
conference. The other authors have no financial relationships relevant
to this article to disclose.
NR 89
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U1 4
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0256-7040
EI 1433-0350
J9 CHILD NERV SYST
JI Childs Nerv. Syst.
PD JUL
PY 2016
VL 32
IS 7
BP 1195
EP 1203
DI 10.1007/s00381-016-3093-3
PG 9
WC Clinical Neurology; Pediatrics; Surgery
SC Neurosciences & Neurology; Pediatrics; Surgery
GA DR7CC
UT WOS:000380056600006
PM 27142103
ER
PT J
AU Eisele, SC
Wen, PY
Lee, EQ
AF Eisele, Sylvia C.
Wen, Patrick Y.
Lee, Eudocia Q.
TI Assessment of Brain Tumor Response: RANO and Its Offspring
SO CURRENT TREATMENT OPTIONS IN ONCOLOGY
LA English
DT Review
DE Response criteria; Response assessment; RANO criteria; Brain tumor;
High-grade glioma; Glioblastoma; Low-grade glioma; Meningioma; Brain
metastases; Spine metastases; Leptomeningeal disease; Temozolomide;
Bevacizumab; Immunotherapy; Pseudoprogression; Pseudoresponse
ID NEWLY-DIAGNOSED GLIOBLASTOMA; HIGH-GRADE GLIOMAS; NERVOUS-SYSTEM
METASTASES; PROGRESSION-FREE SURVIVAL; PHASE-II TRIALS; CLINICAL-TRIALS;
MALIGNANT GLIOMA; SOLID TUMORS; LEPTOMENINGEAL METASTASIS; NEOPLASTIC
MENINGITIS
AB Treatment options for most nervous system tumors remain limited and patients are often confronted with significant morbidity and reduced life expectancy. However, significant efforts are underway to find more effective therapies for patients with primary and secondary brain tumors. As more and more clinical trials for nervous system tumors are being conducted, it is increasingly important to optimize the conduct of clinical trials in neuro-oncology. One of the key aspects in this regard is the development of objective and standardized criteria that allow for accurate response assessment in clinical trials and prevent the misclassification of responders and non-responders. Such misclassification may lead to premature discontinuation of an actually effective agent, thereby withholding a potentially active treatment from the patient. Conversely, patients may be inappropriately continued on an inactive treatment. Moreover, such misclassification may confound the data obtained in such studies and may lead to false conclusions with regards to the efficacy of the investigated drug. Therefore, reliable response assessment criteria are necessary that not only accurately capture radiographic changes but also account for treatment-related changes and incorporate the assessment of clinical status and quality of life (QoL). The Response Assessment in Neuro-Oncology (RANO) working group is an international collaboration of neuro-oncologists, medical oncologists, radiation oncologists, neurosurgeons, neuroradiologists, and regulatory groups (among others) commissioned to develop objective and tumor-specific response criteria for various tumor subtypes. This article reviews the currently available response criteria for high-grade glioma, low-grade glioma, and brain metastases and discusses some of the barriers to accurate assessment of treatment response in neuro-oncology.
C1 [Eisele, Sylvia C.; Wen, Patrick Y.; Lee, Eudocia Q.] Dana Farber Canc Inst, Dept Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA.
RP Lee, EQ (reprint author), Dana Farber Canc Inst, Dept Neurooncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM EQLEE@PARTNERS.ORG
FU Agios; Angiochem; AstraZeneca; Exelixis; Genentech/Roche;
GlaxoSmithKline; Karyopharm; Novartis; Sanofi-Aventis; Regeneron
Pharmaceuticals Inc.; Vascular Biogenics
FX Patrick Y. Wen receives research support from Agios, Angiochem,
AstraZeneca, Exelixis, Genentech/Roche, GlaxoSmithKline, Karyopharm,
Novartis, Sanofi-Aventis, Regeneron Pharmaceuticals Inc., and Vascular
Biogenics; he is on the advisory board for AbbVie, Cavion, Celldex,
Genentech/Roche, Midatech, Momenta, Novartis, Novocure, SigmaTau, and
Vascular Biogenics and is part of the Speakers Bureau for Merck.
NR 70
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Z9 4
U1 2
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2729
EI 1534-6277
J9 CURR TREAT OPTION ON
JI Curr. Treat. Options Oncol.
PD JUL
PY 2016
VL 17
IS 7
AR 35
DI 10.1007/s11864-016-0413-5
PG 13
WC Oncology
SC Oncology
GA DR8RI
UT WOS:000380164600006
PM 27262709
ER
PT J
AU Thirumalai, A
Cooper, LA
Rubinow, KB
Amory, JK
Lin, DW
Wright, JL
Marck, BT
Matsumoto, AM
Page, ST
AF Thirumalai, Arthi
Cooper, Lori A.
Rubinow, Katya B.
Amory, John K.
Lin, Daniel W.
Wright, Jonathan L.
Marck, Brett T.
Matsumoto, Alvin M.
Page, Stephanie T.
TI Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate
Men Treated With Exogenous Testosterone
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PROSTATE-CANCER; HYPOGONADAL MEN; OLDER MEN; SERUM TESTOSTERONE; SEXUAL
FUNCTION; REPLACEMENT THERAPY; BODY-COMPOSITION; CONTROLLED-TRIAL; YOUNG
MEN; ANDROGENS
AB Context: Concern exists that T replacement therapy (TRT) might increase the risk of prostate disease. There are limited data regarding the impact of TRT on prostate androgen concentrations.
Objective: Determine the dose-dependent effects of exogenous T administration on intraprostatic androgen concentrations.
Design: Twelve-week, double-blinded, randomized, placebo-controlled trial.
Setting: Academic medical center.
Participants: Sixty-two healthy eugonadal men, aged 25-55 years.
Interventions: Subjects were randomly assigned to receive injections of acyline, a GnRH antagonist (used to achieve medical castration), every 2 weeks plus transdermal T gel (1.25 g, 2.5 g, 5.0 g, 10 g, or 15 g daily), or placebo injections and transdermal gel for 12 weeks.
Main Outcomes: Serum T and dihydrotestosterone (DHT) were measured at baseline and every 2 weeks during treatment. Intraprostatic T and DHT concentrations were assessed from tissue obtained through ultrasound-guided prostate needle biopsies at week 12. Androgens were quantified by liquid chromatography-tandem mass spectrometry.
Results: 51 men completed the study and were included in the analysis. There were no significant adverse events. Exogenous T resulted in a dose-dependent increase in serum T and DHT concentrations (190-770 and 60-180 ng/dL, respectively). Although intraprostatic T differed among dose groups (P = .01), intraprostatic DHT was comparable regardless of T dose (P = .11) and was 10- to 20-fold greater than intraprostatic T.
Conclusions: In healthy, medically castrate men receiving exogenous T, the total intraprostatic androgen concentration (predominantly DHT) remained stable across serum T concentrations within the physiological range. These findings further our knowledge of the relationship between serum and intraprostatic androgens and suggest that physiological serum T achieved by TRT is unlikely to alter the prostate hormonal milieu.
C1 [Thirumalai, Arthi; Rubinow, Katya B.; Amory, John K.; Matsumoto, Alvin M.; Page, Stephanie T.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Cooper, Lori A.] Polyclinic, Endocrinol, Seattle, WA 98122 USA.
[Lin, Daniel W.; Wright, Jonathan L.] Univ Washington, Dept Urol, Seattle, WA 98195 USA.
[Lin, Daniel W.; Wright, Jonathan L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Marck, Brett T.; Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, Seattle, WA 98108 USA.
[Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA.
RP Thirumalai, A (reprint author), Univ Washington, Sch Med, Div Metab Endocrinol & Nutr, Box 357138,1959 NE Pacific St, Seattle, WA 98195 USA.
EM arthidoc@u.washington.edu
FU National Institute of Aging, National Institutes of Health (NIH)
[RO1AG037603]; NIH [5T32DK007247-37]; Robert B. McMillen Professorship;
University of Washington Nutrition Obesity Research Center [P30
DK035816]; American Heart Association Clinical Research Program; Eunice
Kennedy Shriver National Institute of Child Health and Development Grant
[6K12 HD053984]; VA Advanced Fellowship in Geriatrics
FX This work was supported by the National Institute of Aging, National
Institutes of Health (NIH) through Grant RO1AG037603 (to S.T.P.).
Additional support was received as follows: NIH Grant 5T32DK007247-37
(to A.T.), the Robert B. McMillen Professorship (to S.T.P.), University
of Washington Nutrition Obesity Research Center Pilot and Feasibility
Award P30 DK035816, the American Heart Association Clinical Research
Program, and the Eunice Kennedy Shriver National Institute of Child
Health and Development Grant 6K12 HD053984(all to K.B.R.). The work was
also supported by a VA Advanced Fellowship in Geriatrics (to L.A.C.) and
resource and facilities use at VA Puget Sound Health Care System in
Seattle, Washington (to B.T.M. and A.M.M.).
NR 40
TC 0
Z9 0
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD JUL
PY 2016
VL 101
IS 7
BP 2937
EP 2944
DI 10.1210/jc.2016-1483
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DR9OA
UT WOS:000380224800039
PM 27172434
ER
PT J
AU Zhang, CS
Li, CT
Pirrone, M
Sun, L
Mi, WD
AF Zhang, Changsheng
Li, Changtian
Pirrone, Massimiliano
Sun, Li
Mi, Weidong
TI Comparison of Dexmedetomidine and Clonidine as Adjuvants to Local
Anesthetics for Intrathecal Anesthesia: A Meta-Analysis of Randomized
Controlled Trials
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE clonidine; dexmedetomidine; local anesthetic; intrathecal anesthesia
ID HUMAN SPINAL-CORD; ALPHA(2)-ADRENERGIC AGONISTS; REGIONAL ANESTHESIA;
BUPIVACAINE; ANALGESIA; MORPHINE; QUALITY; BLOCK
AB The authors performed a meta-analysis to compare the characteristics of clonidine and dexmedetomidine as adjuvants to local anesthetic in intravertebral anesthesia. Four investigators independently searched electronic databases for randomized trials comparing the characteristics of clonidine vs dexmedetomidine as adjuvants to local anesthetic on adults. The endpoints were onset of analgesia, sensory and motor block, and duration of analgesia. A random-effects model was used to perform quantitative analysis. Seven studies comprising 354 subjects were included in this meta-analysis. The onset of sensory block was significantly 40 seconds shorter when dexmedetomidine was added as an adjuvant in the intrathecal injection. The duration of stable sensory block, duration of overall sensory block, and the time before the need for analgesic requirements were significantly extended, 10.8 minutes, 22.3 minutes, and 38.6 minutes, respectively, when dexmedetomidine was used as an adjuvant to local anesthetics (bupivacaine or ropivacaine). No significant differences were detected in the motor block characteristics and the time to achieve peak sensory level between dexmedetomidine and clonidine as adjuvants to local anesthetics. Compared to clonidine, the addition of dexmedetomidine as an adjuvant to local anesthetics is associated with earlier, prolonged sensory block characteristics and later need for analgesic requirements.
C1 [Zhang, Changsheng; Mi, Weidong] Chinese Peoples Liberat Army Gen Hosp, Anesthesia & Operat Ctr, Beijing 100853, Peoples R China.
[Li, Changtian] Chinese Peoples Liberat Army Gen Hosp, Dept Ultrasound, Beijing, Peoples R China.
[Pirrone, Massimiliano] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Sun, Li] Beijing Mil Region Gen Hosp, Dept Anesthesiol, Beijing, Peoples R China.
RP Mi, WD (reprint author), Chinese Peoples Liberat Army Gen Hosp, Anesthesia & Operat Ctr, Beijing 100853, Peoples R China.; Mi, WD (reprint author), Chinese PLA Med Sch, Anesthesia, Beijing 100853, Peoples R China.
EM plamzk@126.com
NR 27
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0091-2700
EI 1552-4604
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD JUL
PY 2016
VL 56
IS 7
BP 827
EP 834
DI 10.1002/jcph.666
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DR7AB
UT WOS:000380051300006
PM 26510095
ER
PT J
AU Fay, AP
de Velasco, G
Ho, TH
Van Allen, EM
Murray, B
Albiges, L
Signoretti, S
Hakimi, AA
Stanton, ML
Bellmunt, J
McDermott, DF
Atkins, MB
Garraway, LA
Kwiatkowski, DJ
Choueiri, TK
AF Fay, Andre P.
de Velasco, Guillermo
Ho, Thai H.
Van Allen, Eliezer M.
Murray, Bradley
Albiges, Laurence
Signoretti, Sabina
Hakimi, A. Ari
Stanton, Melissa L.
Bellmunt, Joaquim
McDermott, David F.
Atkins, Michael B.
Garraway, Levi A.
Kwiatkowski, David J.
Choueiri, Toni K.
TI Whole-Exome Sequencing in Two Extreme Phenotypes of Response to
VEGF-Targeted Therapies in Patients With Metastatic Clear Cell Renal
Cell Carcinoma
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
ID IMPACT; PBRM1
AB Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC). Patients with mRCC who had received first-line sunitinib or pazopanib and were in 2 extreme phenotypes of response were identified. Extreme responders (ERs) were defined as those with partial response or complete response for 3 or more years (n=13) and primary refractory patients (PRPs) were defined as those with progressive disease within the first 3 months of therapy (n=14). International Metastatic RCC Database Consortium prognostic scores were not significantly different between the groups (P=. 67). Considering the genes known to be mutated in RCC at significant frequency, PBRM1 mutations were identified in 7 ERs (54%) versus 1 PRP (7%) (P=.01). In addition, mutations in TP53 (n=4) were found only in PRPs (P=.09). Our data suggest that mutations in some genes in RCC may impact response to VEGF-TT.
C1 [Fay, Andre P.; de Velasco, Guillermo; Van Allen, Eliezer M.; Albiges, Laurence; Bellmunt, Joaquim; Garraway, Levi A.; Choueiri, Toni K.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ho, Thai H.] Mayo Clin, Div Hematol & Oncol, Scottsdale, AZ USA.
[Van Allen, Eliezer M.; Murray, Bradley; Garraway, Levi A.] MIT & Harvard, Broad Inst, Cambridge, MA USA.
[Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Hakimi, A. Ari] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA.
[Stanton, Melissa L.] Mayo Clin, Dept Lab Med Pathol, Scottsdale, AZ USA.
[McDermott, David F.; Atkins, Michael B.] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA.
[Atkins, Michael B.] Georgetown Lombardi Comprehens Canc Ctr, Dept Med Oncol, Washington, DC USA.
[Kwiatkowski, David J.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
RP Choueiri, TK (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 450 Brookline Ave, Boston, MA 02215 USA.; Choueiri, TK (reprint author), Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA.
EM Toni_Choueiri@dfci.harvard.edu
FU GlaxoSmithKline; Roche; Ventana; Syapse; Novartis; Pfizer; Astellas
Pharma; Pierre-Fabre; Millennium; Sanofi; Prometheus; Genentech;
Bristol-Myers Squibb; Merck; Foundation Medicine; Exelixis; TRACON
Pharma; Trust family at Dana-Farber Cancer Institute; Loker Pinard at
Dana-Farber Cancer Institute; Michael Brigham Funds for Kidney Cancer
Research at Dana-Farber Cancer Institute; Dana-Farber/Harvard Cancer
Center Kidney Cancer Program; Dana-Farber/Harvard Cancer Center Kidney
Cancer SPORE [P50 CA101942-01]; Kidney Cancer Association
FX Dr. de Velasco has disclosed that his spouse receives salary from
GlaxoSmithKline. Dr. Van Allen has disclosed that he receives consulting
fees from or is a scientific advisor for Roche Ventana and Syapse. Dr.
Albiges has disclosed that she is a scientific advisor for Novartis,
Pfizer, Bayer, Sanofi, and Amgen, and receives research support from
Novartis and Pfizer. Dr. Bellmunt has disclosed that he receives
consulting fees from or is a scientific advisor for Astellas Pharma,
Pfizer, and Pierre-Fabre; receives research support from Millennium and
Sanofi; and has received compensation for travel, accommodations,
expenses from MSD Oncology and Pfizer. Dr. McDermott has disclosed that
he is on the data safety monitoring board for Pfizer; is a consultant
for Bristol-Myers Squibb, Genentech BioOncology, Merck, Pfizer,
Novartis, Eisai, Excelixis, and Array BioPharm; and receives research
support from Prometheus. Dr. Atkins has disclosed that he receives
consulting fees from or is a scientific advisor for Novartis, Pfizer,
Genentech, Bristol-Myers Squibb, Merck, and GlaxoSmithKline. Dr.
Garraway has disclosed that he receives consulting fees from and has
equity interest in Foundation Medicine. Dr. Kwiatkowski has disclosed
that he receives consulting fees from Novartis. Dr. Choueiri has
disclosed that he receives institutional funding from Bristol-Myers
Squibb, Exelixis, GlaxoSmithKline, Merck, Novartis, Pfizer, and TRACON
Pharma, and is a scientific advisor for Bayer, GlaxoSmithKline, Merck,
Novartis, and Pfizer. The remaining authors have disclosed that they
have no financial interests, arrangements, affiliations, or commercial
interests with the manufacturers of any products discussed in this
article or their competitors.; This work was supported by the Trust
family, Loker Pinard, and Michael Brigham Funds for Kidney Cancer
Research (to Dr. Choueiri) at Dana-Farber Cancer Institute, the
Dana-Farber/Harvard Cancer Center Kidney Cancer Program, the
Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE P50 CA101942-01,
and by a grant from the Kidney Cancer Association. The authors declare
that the research was conducted in the absence of any commercial or
financial relationships that could be construed as a potential conflict
of interest.
NR 10
TC 4
Z9 4
U1 1
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUL 1
PY 2016
VL 14
IS 7
BP 820
EP +
PG 8
WC Oncology
SC Oncology
GA DR8VG
UT WOS:000380175200003
PM 27407122
ER
PT J
AU Ettinger, DS
Wood, DE
Akerley, W
Bazhenova, LA
Borghaei, H
Camidge, DR
Cheney, RT
Chirieac, LR
D'Amico, TA
Dilling, T
Dobelbower, M
Govindan, R
Hennon, M
Horn, L
Jahan, TM
Komaki, R
Lackner, RP
Lanuti, M
Lilenbaum, R
Lin, J
Loo, BW
Martins, R
Otterson, GA
Patel, JD
Pisters, KM
Reckamp, K
Riely, GJ
Schild, SE
Shapiro, TA
Sharma, N
Swanson, SJ
Stevenson, J
Tauer, K
Yang, SC
Gregory, K
Hughes, M
AF Ettinger, David S.
Wood, Douglas E.
Akerley, Wallace
Bazhenova, Lyudmila A.
Borghaei, Hossein
Camidge, David Ross
Cheney, Richard T.
Chirieac, Lucian R.
D'Amico, Thomas A.
Dilling, Thomas
Dobelbower, Michael
Govindan, Ramaswamy
Hennon, Mark
Horn, Leora
Jahan, Thierry M.
Komaki, Ritsuko
Lackner, Rudy P.
Lanuti, Michael
Lilenbaum, Rogerio
Lin, Jules
Loo, Billy W., Jr.
Martins, Renato
Otterson, Gregory A.
Patel, Jyoti D.
Pisters, Katherine M.
Reckamp, Karen
Riely, Gregory J.
Schild, Steven E.
Shapiro, Theresa A.
Sharma, Neelesh
Swanson, Scott J.
Stevenson, James
Tauer, Kurt
Yang, Stephen C.
Gregory, Kristina
Hughes, Miranda
TI NCCN Guidelines (R) Insights Malignant Pleural Mesothelioma, Version
3.2016 Featured Updates to the NCCN Guidelines
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
ID PEMETREXED PLUS CISPLATIN; EXPANDED ACCESS PROGRAM; MULTICENTER
PHASE-II; RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SURVIVAL; EXTRAPLEURAL
PNEUMONECTOMY; TRIMODALITY THERAPY; TALC PLEURODESIS;
PLEURECTOMY-DECORTICATION; NEOADJUVANT CHEMOTHERAPY
AB These NCCN Guidelines Insights focus on recent updates to the NCCN Guidelines for Malignant Pleural Mesothelioma (MPM). These NCCN Guidelines Insights discuss systemic therapy regimens and surgical controversies for MPM. The NCCN panel recommends cisplatin/pemetrexed (category1) for patients with MPM. The NCCN panel also now recommends bevacizumab/cisplatin/pemetrexed as a first-line therapy option for patients with unresectable MPM who are candidates for bevacizumab. The complete version of the NCCN Guidelines for MPM, available at NCCN. org, addresses all aspects of management for MPM including diagnosis, evaluation, staging, treatment, surveillance, and therapy for recurrence and metastasis; NCCN Guidelines are intended to assist with clinical decision-making.
C1 [Ettinger, David S.; Shapiro, Theresa A.; Yang, Stephen C.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
[Wood, Douglas E.; Martins, Renato] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA.
[Akerley, Wallace] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Bazhenova, Lyudmila A.] UC San Diego Moores Canc Ctr, La Jolla, CA USA.
[Borghaei, Hossein] Fox Chase Canc Ctr, Philadelphia, PA USA.
[Camidge, David Ross] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA.
[Cheney, Richard T.; Hennon, Mark] Roswell Pk Canc Inst, Buffalo, NY USA.
[Chirieac, Lucian R.; Swanson, Scott J.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[D'Amico, Thomas A.] Duke Canc Inst, Durham, NC USA.
[Dilling, Thomas] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Dobelbower, Michael] Univ Alabama, Birmingham Comprehens Canc Ctr, Tuscaloosa, AL 35487 USA.
[Govindan, Ramaswamy] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA.
[Govindan, Ramaswamy] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Jahan, Thierry M.] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
[Komaki, Ritsuko; Pisters, Katherine M.] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Lackner, Rudy P.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA.
[Lanuti, Michael] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Lilenbaum, Rogerio] Yale Canc Ctr, Smilow Canc Hosp, New Haven, CT USA.
[Lin, Jules] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Loo, Billy W., Jr.] Stanford Canc Inst, Stanford, CA USA.
[Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
[Otterson, Gregory A.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA.
[Patel, Jyoti D.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Reckamp, Karen] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA USA.
[Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Schild, Steven E.] Mayo Clin, Ctr Canc, Rochester, MN USA.
[Sharma, Neelesh; Stevenson, James] Case Comprehens Canc Ctr, Cleveland, OH USA.
[Sharma, Neelesh; Stevenson, James] Univ Hosp Seidman Canc Ctr, Cleveland, OH USA.
[Sharma, Neelesh; Stevenson, James] Cleveland Clin Taussig Canc Inst, Cleveland, OH USA.
[Tauer, Kurt] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA.
[Gregory, Kristina; Hughes, Miranda] Natl Comprehens Canc Network, Ft Washington, MD USA.
RP Ettinger, DS (reprint author), Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
FU AstraZeneca; Bayer Healthcare Pharmaceuticals Inc.; Bristol-Myers
Squibb; Clovis Oncology; Foundation Medicine; Genentech; Novartis
Oncology; Otsuka America Pharmaceutical, Inc.; Seattle Genetics, Inc.;
Takeda Oncology; Actelion Pharmaceuticals US, Inc.; Astellas;
Medivation, Inc.
FX This activity is supported by educational grants from AstraZeneca, Bayer
Healthcare Pharmaceuticals Inc., Bristol-Myers Squibb, Clovis Oncology,
Foundation Medicine, Genentech, Novartis Oncology, Otsuka America
Pharmaceutical, Inc., Seattle Genetics, Inc., and Takeda Oncology;
support provided by Actelion Pharmaceuticals US, Inc.; and by an
independent educational grant from Astellas and Medivation, Inc.
NR 101
TC 0
Z9 0
U1 0
U2 0
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUL 1
PY 2016
VL 14
IS 7
BP 825
EP 836
PG 12
WC Oncology
SC Oncology
GA DR8VG
UT WOS:000380175200004
PM 27407123
ER
PT J
AU Nardi, EA
Wolfson, JA
Rosen, ST
Diasio, RB
Gerson, SL
Parker, BA
Alvarnas, JC
Levine, HA
Fong, Y
Weisenburger, DD
Fitzgerald, CL
Egan, M
Stranford, S
Carlson, RW
Benz, EJ
AF Nardi, Elizabeth A.
Wolfson, Julie A.
Rosen, Steven T.
Diasio, Robert B.
Gerson, Stanton L.
Parker, Barbara A.
Alvarnas, Joseph C.
Levine, Harlan A.
Fong, Yuman
Weisenburger, Dennis D.
Fitzgerald, C. Lyn
Egan, Maggie
Stranford, Sharon
Carlson, Robert W.
Benz, Edward J., Jr.
TI Value, Access, and Cost of Cancer Care Delivery at Academic Cancer
Centers
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
ID IMPACT; VOLUME
AB Key challenges facing the oncology community today include access to appropriate, high quality, patient-centered cancer care; defining and delivering high-value care; and rising costs. The National Comprehensive Cancer Network convened a Work Group composed of NCCN Member Institution cancer center directors and their delegates to examine the challenges of access, high costs, and defining and demonstrating value at the academic cancer centers. The group identified key challenges and possible solutions to addressing these issues. The findings and recommendations of the Work Group were then presented at the Value, Access, and Cost of Cancer Care Policy Summit in September 2015 and multi-stakeholder roundtable panel discussions explored these findings and recommendations along with additional items.
C1 [Nardi, Elizabeth A.; Fitzgerald, C. Lyn; Carlson, Robert W.] Natl Comprehens Canc Network, 275 Commerce Dr,Suite 300, Ft Washington, PA 19473 USA.
[Wolfson, Julie A.] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA.
[Rosen, Steven T.; Alvarnas, Joseph C.; Levine, Harlan A.; Fong, Yuman; Weisenburger, Dennis D.] City Hope Natl Med Ctr, Ctr Comprehens Canc, Los Angeles, CA USA.
[Diasio, Robert B.] Mayo Clin, Ctr Canc, Rochester, MN USA.
[Gerson, Stanton L.] Case Comprehens Canc Ctr, Cleveland, OH USA.
[Gerson, Stanton L.] Univ Hosp Seidman Canc Ctr, Cleveland, OH USA.
[Gerson, Stanton L.] Cleveland Clin Taussig Canc Inst, Cleveland, OH USA.
[Parker, Barbara A.] UC San Diego Moores Canc Ctr, La Jolla, CA USA.
[Egan, Maggie; Stranford, Sharon] City Hope Natl Med Ctr, Ctr Comprehens Canc, Los Angeles, CA USA.
[Benz, Edward J., Jr.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nardi, EA (reprint author), Natl Comprehens Canc Network, 275 Commerce Dr,Suite 300, Ft Washington, PA 19473 USA.
EM nardi@nccn.org
FU Genentech
FX Dr. Parker has disclosed that she has received clinical research support
from Genentech. Ms. Nardi, Ms. Fitzgerald, and Dr. Carlson are employees
of NCCN. The remaining authors have disclosed that they have no
financial interests, arrangements, or affiliations with the
manufacturers of any products discussed in this article or their
competitors.
NR 42
TC 2
Z9 2
U1 1
U2 1
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUL 1
PY 2016
VL 14
IS 7
BP 837
EP 847
PG 11
WC Oncology
SC Oncology
GA DR8VG
UT WOS:000380175200005
PM 27407124
ER
PT J
AU Baden, LR
Swaminathan, S
Angarone, M
Blouin, G
Camins, BC
Casper, C
Cooper, B
Dubberke, ER
Engemann, AM
Freifeld, AG
Greene, JN
Ito, JI
Kaul, DR
Lustberg, ME
Montoya, JG
Rolston, K
Satyanarayana, G
Segal, B
Seo, SK
Shoham, S
Taplitz, R
Topal, J
Wilson, JW
Hoffmann, KG
Smith, C
AF Baden, Lindsey Robert
Swaminathan, Sankar
Angarone, Michael
Blouin, Gayle
Camins, Bernard C.
Casper, Corey
Cooper, Brenda
Dubberke, Erik R.
Engemann, Ashley Morris
Freifeld, Alison G.
Greene, John N.
Ito, James I.
Kaul, Daniel R.
Lustberg, Mark E.
Montoya, Jose G.
Rolston, Ken
Satyanarayana, Gowri
Segal, Brahm
Seo, Susan K.
Shoham, Shmuel
Taplitz, Randy
Topal, Jeffrey
Wilson, John W.
Hoffmann, Karin G.
Smith, Courtney
TI Prevention and Treatment of Cancer-Related Infections, Version 2.2016
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; HEPATITIS-B-VIRUS; CHRONIC
LYMPHOCYTIC-LEUKEMIA; RESPIRATORY SYNCYTIAL VIRUS;
BONE-MARROW-TRANSPLANTATION; INVASIVE FUNGAL-INFECTIONS; TENOFOVIR
DISOPROXIL FUMARATE; IMMUNIZATION PRACTICES ACIP; MINIMAL RESIDUAL
DISEASE; PLACEBO-CONTROLLED TRIAL
AB Infectious diseases are important causes of morbidity and mortality in patients with cancer. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prevention and Treatment of Cancer-Related Infections characterize the major pathogens to which patients with cancer are susceptible, with a focus on the prevention, diagnosis, and treatment of major common and opportunistic infections. This portion of the guidelines highlights the sections on antifungal and antiviral prophylaxis. Antifungal and antiviral prophylaxis recommendations have expanded over the past few years. New agents for the treatment of fungal infections and incorporation of therapeutic drug monitoring are presented. Antiviral prophylaxis for hepatitis B and management considerations for hepatitis C and HIV have been further developed.
C1 [Baden, Lindsey Robert] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA.
[Swaminathan, Sankar] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA.
[Angarone, Michael] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Blouin, Gayle] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Camins, Bernard C.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA.
[Casper, Corey] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA.
[Cooper, Brenda] Case Comprehens Canc Ctr, Cleveland, OH USA.
[Cooper, Brenda] Univ Hosp Seidman Canc Ctr, Cleveland, OH USA.
[Cooper, Brenda] Cleveland Clin Taussig Canc Inst, Cleveland, OH USA.
[Dubberke, Erik R.] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO USA.
[Dubberke, Erik R.] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Engemann, Ashley Morris] Duke Canc Inst, Durham, NC USA.
[Freifeld, Alison G.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA.
[Greene, John N.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Ito, James I.] City Hope Natl Med Ctr, Ctr Comprehens Canc, Duarte, CA USA.
[Kaul, Daniel R.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Lustberg, Mark E.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA.
[Lustberg, Mark E.] Solove Res Inst, Columbus, OH USA.
[Montoya, Jose G.] Stanford Canc Inst, Stanford, CA USA.
[Rolston, Ken] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Satyanarayana, Gowri] Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Segal, Brahm] Roswell Pk Canc Inst, Buffalo, NY USA.
[Seo, Susan K.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Shoham, Shmuel] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Taplitz, Randy] UC San Diego Moores Canc Ctr, La Jolla, CA USA.
[Topal, Jeffrey] Yale Canc Ctr, Smilow Canc Hosp, New Haven, CT USA.
[Wilson, John W.] Mayo Clin, Ctr Canc, Rochester, MN USA.
RP Baden, LR (reprint author), Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA.
FU Crucell; NIH; Janssen Pharmaceutical Products, LP; Roche Laboratories,
Inc.; Merck Co., Inc.; Rebiotix; sanofi pasteur; Astellas; City of Hope;
Chimerix; Gilead; NeuralStem; ViroPharma; K-PAX Pharmaceuticals;
Allergan; JMI Laboratories; Ventrus; Ansun; HHS/ASPR; NIAID Influenza
Research Collaboration Social & Scientific Systems, Inc.; Pfizer Inc.;
scynexis; World Health Information Science Consultants; GLG
FX Lindsey Robert Baden, MD Crucell; and NIH-funded research None None
7/3/15; Corey Casper, MD, MPH Janssen Pharmaceutical Products, LP; and
Roche Laboratories, Inc. GlaxoSmithKline; and TempTime None 6/16/16;
Erik R. Dubberke, MD Merck & Co., Inc.; Rebiotix; and sanofi pasteur
Merck & Co., Inc.; Rebiotix; and sanofi pasteur None 10/23/15; Alison G.
Freifeld, MD Astellas; and Merck & Co., Inc. None None 5/20/15; James I.
Ito, MD City of Hope Astellas; Merck & Co., Inc.; and Vical Astellas
Merck & Co., Inc. 5/20/15; Daniel R. Kaul, MD Chimerix; Gilead;
NeuralStem; and ViroPharma None None 6/7/16; Jose G. Montoya, MD K-PAX
Pharmaceuticals Cubist Pharmaceuticals None 9/11/15; Ken Rolston, MD
Allergan; JMI Laboratories; and Merck & Co., Inc. Allergan None 7/4/16;
Brahm Segal, MD Astellas; Merck & Co., Inc.; and Ventrus Astellas; and
Merck & Co., Inc. None 5/21/15; Shmuel Shoham, MD Ansun; Astellas;
Chimerix; HHS/ASPR; Gilead; Merck & Co., Inc.; NIAID Influenza Research
Collaboration Social & Scientific Systems, Inc.; Pfizer Inc.; scynexis;
Viropharma; and World Health Information Science Consultants Biota
Pharmaceuticals; LEK Consulting; Medical legal consultation to law
firms; Mycoses Study Group Education and Research Consortium; SunTrust
Robinson Humphrey, Inc; and Theravance None 3/30/16; Sankar Swaminathan,
MDa GLG None None 9/2/15
NR 276
TC 6
Z9 6
U1 2
U2 3
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD JUL 1
PY 2016
VL 14
IS 7
BP 882
EP 913
PG 32
WC Oncology
SC Oncology
GA DR8VG
UT WOS:000380175200010
PM 27407129
ER
PT J
AU Rajbhandari, R
Barton, K
Juncadella, AC
Rubin, AK
Ajayi, T
Wu, Y
Ananthakrishnan, AN
Chung, RT
AF Rajbhandari, R.
Barton, K.
Juncadella, A. C.
Rubin, A. K.
Ajayi, T.
Wu, Y.
Ananthakrishnan, A. N.
Chung, R. T.
TI Discontinuity of care for mothers with chronic hepatitis B diagnosed
during pregnancy
SO JOURNAL OF VIRAL HEPATITIS
LA English
DT Article
DE chronic Hepatitis B; pregnancy; quality improvement
ID HEPATOCELLULAR-CARCINOMA; PREVENTION; VIRUS; INFECTION; UPDATE
AB Assiduous measures are taken to prevent perinatal transmission of hepatitis B virus (HBV) to infants; it is unclear whether the mothers receive appropriate care for their chronic HBV. We sought to assess the quality of HBV care in hepatitis B surface antigen (HBsAg)-positive mothers following pregnancy. HBsAg-positive women (n = 243) who had sought prenatal care at Massachusetts General Hospital were retrospectively identified and charts reviewed. The primary outcome was adherence to the American Association for the Study of Liver Diseases (AASLD) and American College of Obstetricians and Gynecologists guidelines. Over one-third (37%) of women were first diagnosed with HBV infection at a prenatal visit. One-third (32%) did not undergo timely liver function test measurements. HBV DNA was never measured in 26% and was untimely in 34% of patients. One-third (34%) of the women were at high-risk for HCC based on AASLD criteria, yet only 33% of these women underwent timely imaging. Nearly half (49%) never saw a liver specialist for their HBV care. In multivariate analysis, women were 3.7 times more likely to have a timely ALT and 8.1 times more likely to have a timely HBV DNA if they were followed by a liver specialist (P = 0.001, < 0.001). We demonstrate remarkably inadequate and discontinuous HBV care for chronically infected mothers following pregnancy. As HBV infection is already being identified prenatally, quality improvement measures encompassing obstetricians, primary care providers and hepatologists are needed to ensure that HBV-infected women are linked to care postpregnancy.
C1 [Rajbhandari, R.; Wu, Y.; Ananthakrishnan, A. N.; Chung, R. T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Rajbhandari, R.; Juncadella, A. C.; Rubin, A. K.; Wu, Y.; Ananthakrishnan, A. N.; Chung, R. T.] Harvard Med Sch, Boston, MA USA.
[Rajbhandari, R.; Juncadella, A. C.; Rubin, A. K.; Wu, Y.; Ananthakrishnan, A. N.; Chung, R. T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Barton, K.] Hinton State Lab Inst, Bur Infect Dis, Massachusetts Dept Publ Hlth, Jamaica, NY USA.
[Ajayi, T.] Salem Hosp, Dept Med, Salem, MA USA.
RP Chung, RT (reprint author), Massachusetts Gen Hosp, Hepatol, GI Div, Boston, MA 02114 USA.
EM rtchung@partners.org
FU National Institutes of Health [T32 DK007191, K24 DK078772, K23 DK097142]
FX Financial support: Dr. Ruma Rajbhandari is supported by a grant from the
National Institutes of Health (T32 DK007191). Dr. Raymond Chung is
supported in part by a grant from the National Institutes of Health (K24
DK078772). Dr. Ananthakrishnan is supported in part by a grant from the
National Institutes of Health (K23 DK097142).
NR 19
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1352-0504
EI 1365-2893
J9 J VIRAL HEPATITIS
JI J. Viral Hepatitis
PD JUL
PY 2016
VL 23
IS 7
BP 561
EP 568
DI 10.1111/jvh.12524
PG 8
WC Gastroenterology & Hepatology; Infectious Diseases; Virology
SC Gastroenterology & Hepatology; Infectious Diseases; Virology
GA DR7IF
UT WOS:000380072500009
PM 26940754
ER
PT J
AU Aryal, B
Rotllan, N
Araldi, E
Ramirez, CM
He, S
Chousterman, BG
Fenn, AM
Wanschel, A
Madrigal-Matute, J
Warrier, N
Martin-Ventura, JL
Swirski, FK
Suarez, Y
Fernandez-Hernando, C
AF Aryal, Binod
Rotllan, Noemi
Araldi, Elisa
Ramirez, Cristina M.
He, Shun
Chousterman, Benjamin G.
Fenn, Ashley M.
Wanschel, Amarylis
Madrigal-Matute, Julio
Warrier, Nikhil
Martin-Ventura, Jose L.
Swirski, Filip K.
Suarez, Yajaira
Fernandez-Hernando, Carlos
TI ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion
and atherosclerosis progression
SO NATURE COMMUNICATIONS
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; ANGIOPOIETIN-LIKE PROTEIN-4; EX-VIVO EXPANSION;
KNOCKOUT MICE; STEM-CELLS; IN-VIVO; CHOLESTEROL ACCUMULATION; SCAVENGER
RECEPTORS; CORONARY PLAQUE; TARGET GENE
AB Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population. ANGPTL4-deficient CMPs have higher lipid raft content, are more proliferative and less apoptotic compared with the wild-type (WT) CMPs. Finally, we observe that ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 localization in the cell surface. Altogether, these findings demonstrate that haematopoietic ANGPTL4 deficiency increases atherogenesis through regulating myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.
C1 [Aryal, Binod; Rotllan, Noemi; Araldi, Elisa; Ramirez, Cristina M.; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, 333 Cedar St, New Haven, CT 06520 USA.
[Aryal, Binod; Rotllan, Noemi; Araldi, Elisa; Ramirez, Cristina M.; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Integrat Cell Signaling & Neurobiol Metab Program, Comparat Med Sect, 333 Cedar St, New Haven, CT 06520 USA.
[Aryal, Binod; Rotllan, Noemi; Araldi, Elisa; Ramirez, Cristina M.; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06520 USA.
[Aryal, Binod; Wanschel, Amarylis; Madrigal-Matute, Julio; Warrier, Nikhil] Yale Univ, Sch Med, Leon H Charney Div Cardiol & Cell Biol, Dept Med, 333 Cedar St, New Haven, CT 06520 USA.
[Aryal, Binod; Wanschel, Amarylis; Madrigal-Matute, Julio; Warrier, Nikhil] Yale Univ, Sch Med, Leon H Charney Div Cardiol & Cell Biol, Dept Cell Biol, 333 Cedar St, New Haven, CT 06520 USA.
[He, Shun; Chousterman, Benjamin G.; Fenn, Ashley M.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[He, Shun; Chousterman, Benjamin G.; Fenn, Ashley M.; Swirski, Filip K.] Harvard Med Sch, Boston, MA 02114 USA.
[Martin-Ventura, Jose L.] Univ Autonoma Madrid, Vasc Res Lab, IIS Fdn Jimenez Diaz, Madrid 28040, Spain.
RP Suarez, Y; Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Vasc Biol & Therapeut Program, 333 Cedar St, New Haven, CT 06520 USA.; Suarez, Y; Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Integrat Cell Signaling & Neurobiol Metab Program, Comparat Med Sect, 333 Cedar St, New Haven, CT 06520 USA.; Suarez, Y; Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Dept Pathol, 333 Cedar St, New Haven, CT 06520 USA.
EM yajaira.suarez@yale.edu; carlos.fernandez@yale.edu
FU National Institutes of Health [R01HL107953, R01HL106063, R01HL105945];
American Heart Association [12POST9780016, 16GRNT26420047]; Howard
Hughes Medical Institute International Student Research Fellowship;
Foundation Leducq Transatlantic Network of Excellence in Cardiovascular
Research
FX We thank Dr. Sander Kersten for generously providing the ANGPTL4 PPRE
plasmid, Dr Kathryn Moore for providing Cd36-/- mice and Dr
Jordan Pober for providing the human peripheral blood mononuclear cells
(PBMCs). We thank Leigh Goedeke and Juan Francisco Aranda for technical
assistance and Leigh Goedeke and Nathan Price for editing the
manuscript. Yale Keck Biotechnology Microarray Resource Laboratory. This
work was supported by grants from the National Institutes of Health
(R01HL107953 and R01HL106063 to CF-H; R01HL105945 to Y.S.), the American
Heart Association (12POST9780016 to C.M.R.; 16GRNT26420047 to Y.S.), the
Howard Hughes Medical Institute International Student Research
Fellowship (to E.A.), and the Foundation Leducq Transatlantic Network of
Excellence in Cardiovascular Research (to C.F.-H.).
NR 68
TC 4
Z9 4
U1 4
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2016
VL 7
AR 12313
DI 10.1038/ncomms12313
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS2DN
UT WOS:000380538000001
PM 27460411
ER
PT J
AU Rhee, EP
Yang, Q
Yu, B
Liu, X
Cheng, S
Deik, A
Pierce, KA
Bullock, K
Ho, JE
Levy, D
Florez, JC
Kathiresan, S
Larson, MG
Vasan, RS
Clish, CB
Wang, TJ
Boerwinkle, E
O'Donnell, CJ
Gerszten, RE
AF Rhee, Eugene P.
Yang, Qiong
Yu, Bing
Liu, Xuan
Cheng, Susan
Deik, Amy
Pierce, Kerry A.
Bullock, Kevin
Ho, Jennifer E.
Levy, Daniel
Florez, Jose C.
Kathiresan, Sek
Larson, Martin G.
Vasan, Ramachandran S.
Clish, Clary B.
Wang, Thomas J.
Boerwinkle, Eric
O'Donnell, Christopher J.
Gerszten, Robert E.
TI An exome array study of the plasma metabolome
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; VARIANTS;
CYSTATHIONINURIA; IDENTIFICATION; HERITABILITY; MUTATIONS; PROFILES;
FAMILIES; RISK
AB The study of rare variants may enhance our understanding of the genetic determinants of the metabolome. Here, we analyze the association between 217 plasma metabolites and exome variants on the Illumina HumanExome Beadchip in 2,076 participants in the Framingham Heart Study, with replication in 1,528 participants of the Atherosclerosis Risk in Communities Study. We identify an association between GMPS and xanthosine using single variant analysis and associations between HAL and histidine, PAH and phenylalanine, and UPB1 and ureidopropionate using gene-based tests (P < 5 x 10(-8) in meta-analysis), highlighting novel coding variants that may underlie inborn errors of metabolism. Further, we show how an examination of variants across the spectrum of allele frequency highlights independent association signals at select loci and generates a more integrated view of metabolite heritability. These studies build on prior metabolomics genome wide association studies to provide a more complete picture of the genetic architecture of the plasma metabolome.
C1 [Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St, Boston, MA 02114 USA.
[Rhee, Eugene P.] Massachusetts Gen Hosp, Div Endocrinol, 55 Fruit St, Boston, MA 02114 USA.
[Rhee, Eugene P.; Deik, Amy; Pierce, Kerry A.; Bullock, Kevin; Clish, Clary B.] Broad Inst MIT & Harvard, Metabolite Profiling, 415 Main St, Cambridge, MA 02142 USA.
[Yang, Qiong; Liu, Xuan; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, 801 Massachusetts Ave, Boston, MA 02118 USA.
[Yu, Bing; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Pressler St, Houston, TX 77030 USA.
[Cheng, Susan; Levy, Daniel; Larson, Martin G.; Vasan, Ramachandran S.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA.
[Cheng, Susan] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.
[Ho, Jennifer E.] Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA.
[Levy, Daniel] NHLBI, Populat Sci Branch, Bethesda, MD 20892 USA.
[Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, 55 Fruit St, Boston, MA 02114 USA.
[Florez, Jose C.; Kathiresan, Sek] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA.
[Florez, Jose C.; Kathiresan, Sek] Broad Inst MIT & Harvard, Program Med & Populat Genet, 415 Main St, Boston, MA 02114 USA.
[Kathiresan, Sek] Massachusetts Gen Hosp, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, 111 Cummington Mall, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med & Epidemiol, 801 Massachusetts Ave, Boston, MA 02118 USA.
[Wang, Thomas J.] Vanderbilt Univ, Med Ctr, Div Cardiovasc Med, 1211 Med Ctr Dr, Nashville, TN 37232 USA.
[Wang, Thomas J.] Vanderbilt Heart & Vasc Inst, 1211 Med Ctr Dr, Nashville, TN 37232 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, 1 Baylor Plaza, Houston, TX 77030 USA.
[O'Donnell, Christopher J.] Boston Vet Adm Healthcare, Cardiol Sect, 1400 VFW Pkwy, Boston, MA 02132 USA.
[Gerszten, Robert E.] Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 185 Pilgrim Rd, Boston, MA 02215 USA.
RP Rhee, EP (reprint author), Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St, Boston, MA 02114 USA.; Rhee, EP (reprint author), Massachusetts Gen Hosp, Div Endocrinol, 55 Fruit St, Boston, MA 02114 USA.; Rhee, EP (reprint author), Broad Inst MIT & Harvard, Metabolite Profiling, 415 Main St, Cambridge, MA 02142 USA.; Gerszten, RE (reprint author), Beth Israel Deaconess Med Ctr, Div Cardiovasc Med, 185 Pilgrim Rd, Boston, MA 02215 USA.
EM eprhee@partners.org; rgerszte@bidmc.harvard.edu
OI Ramachandran, Vasan/0000-0001-7357-5970
FU NIH [N01-HC-25195, R01-DK-HL-081572, R01-DK-108159, R01-HL-098280,
R-01-HL-093328, K08-DK-090142]; Division of Intramural Research of the
National Heart, Lung and Blood Institute; National Heart, Lung and Blood
Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; NIH through
the American Recovery and Reinvestment Act (ARRA) [5RC2HL102419];
National Genome Research Institute [HG004402]
FX This work was supported by NIH contracts N01-HC-25195, R01-DK-HL-081572,
R01-DK-108159 (R.E.G. and T.J.W.), R01-HL-098280 (R.E.G.),
R-01-HL-093328 (R.S.V.) and K08-DK-090142 (E.P.R.); funding for the
exome array genotyping in the Framingham Heart Study was provided by the
Division of Intramural Research of the National Heart, Lung and Blood
Institute (D.L., C.J.O.). The Atherosclerosis Risk in Communities (ARIC)
study is carried out as a collaborative study supported by the National
Heart, Lung and Blood Institute (NHLBI) contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C and
HHSN268201100012C). Funding support for 'Building on GWAS for
NHLBI-diseases: the US CHARGE consortium' was provided by the NIH
through the American Recovery and Reinvestment Act of 2009 (ARRA)
(5RC2HL102419). Metabolomic profiling in ARIC was supported by the
National Genome Research Institute (HG004402). We thank the staff and
participants of the FHS and ARIC study for their important
contributions.
NR 31
TC 4
Z9 4
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD JUL
PY 2016
VL 7
AR 12360
DI 10.1038/ncomms12360
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DR9GD
UT WOS:000380204200001
PM 27453504
ER
PT J
AU Bass, JK
Knight, KR
Yock, TI
Chang, KW
Cipkala, D
Grewal, SS
AF Bass, Johnnie K.
Knight, Kristin R.
Yock, Torunn I.
Chang, Kay W.
Cipkala, Douglas
Grewal, Satkiran S.
TI Evaluation and Management of Hearing Loss in Survivors of Childhood and
Adolescent Cancers: A Report From the Children's Oncology Group
SO PEDIATRIC BLOOD & CANCER
LA English
DT Review
DE cancer survivor; hearing loss; late effects; ototoxicity
ID TERM-FOLLOW-UP; PRIOR CRANIAL IRRADIATION; PEDIATRIC MEDULLOBLASTOMA;
RECEIVING CARBOPLATIN; BRAIN-TUMORS; OTOACOUSTIC EMISSIONS;
RADIATION-THERAPY; GRADING SCALES; RISK-FACTORS; OTOTOXICITY
AB Hearing loss (HL) is common in childhood cancer survivors exposed to platinum chemotherapy and/or cranial radiation and can severely impact quality of life. Early detection and appropriate management can mitigate academic, speech, language, social, and psychological morbidity resulting from hearing deficits. This review is targeted as a resource for providers involved in aftercare of child-hood cancers. The goal is to promote early identification of survivors at-risk for HL, appropriate evaluation and interpretation of diagnostic tests, timely referral to an audiologist when indicated, and to increase knowledge of current therapeutic options. (C) 2016 Wiley Periodicals, Inc.
C1 [Bass, Johnnie K.] St Jude Childrens Res Hosp, Rehabil Serv, 332 N Lauderdale St, Memphis, TN 38105 USA.
[Knight, Kristin R.] Oregon Hlth & Sci Univ, Child Dev & Rehabil Ctr, Portland, OR 97201 USA.
[Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Chang, Kay W.] Stanford Univ, Dept Otolaryngol, Stanford, CA 94305 USA.
[Cipkala, Douglas] Peyton Manning Childrens Hosp St Vincent, Ctr Canc & Blood Dis, Indianapolis, IN USA.
[Grewal, Satkiran S.] Baystate Med Ctr, Pediat Hematol Oncol, 376 Birnie Ave, Springfield, MA 01199 USA.
RP Grewal, SS (reprint author), Baystate Med Ctr, Pediat Hematol Oncol, 376 Birnie Ave, Springfield, MA 01199 USA.
EM satkiran.grewal@baystatehealth.org
NR 52
TC 2
Z9 2
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2016
VL 63
IS 7
BP 1152
EP 1162
DI 10.1002/pbc.25951
PG 11
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DR7UO
UT WOS:000380105400003
PM 26928933
ER
PT J
AU Patenaude, AF
Pelletier, W
Bingen, K
AF Patenaude, Andrea Farkas
Pelletier, Wendy
Bingen, Kristin
TI Response: A Call for Psychosocial and Palliative Care Training Standards
for Pediatric Hematology-Oncology Physicians, A Reply To: Communication,
Documentation, and Training Standards in Pediatric Psychosocial Oncology
SO PEDIATRIC BLOOD & CANCER
LA English
DT Letter
C1 [Patenaude, Andrea Farkas] Harvard Med Sch, Dana Farber Canc Ctr, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA.
[Pelletier, Wendy] Alberta Childrens Prov Gen Hosp, Calgary, AB, Canada.
[Bingen, Kristin] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA.
RP Patenaude, AF (reprint author), Harvard Med Sch, Dana Farber Canc Ctr, Dept Psychosocial Oncol & Palliat Care, 450 Brookline Ave, Boston, MA 02215 USA.
EM andrea_patenaude@dfci.harvard.edu
NR 7
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD JUL
PY 2016
VL 63
IS 7
BP 1315
EP 1315
DI 10.1002/pbc.26015
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DR7UO
UT WOS:000380105400035
PM 27082206
ER
PT J
AU Wittenberg, E
Bharel, M
Bridges, JFP
Ward, Z
Weinreb, L
AF Wittenberg, Eve
Bharel, Monica
Bridges, John F. P.
Ward, Zachary
Weinreb, Linda
TI Using Best-Worst Scaling to Understand Patient Priorities: A Case
Example of Papanicolaou Tests for Homeless Women
SO ANNALS OF FAMILY MEDICINE
LA English
DT Article
DE stated preferences; conjoint analysis; methods; best-worst scaling;
homeless; cervical cancer; vulnerable populations
ID DISCRETE-CHOICE EXPERIMENTS; HEALTH-CARE; PREVENTIVE SERVICES;
CONJOINT-ANALYSIS; DECISION-MAKING; PREFERENCES; INTERVENTIONS;
DISPARITIES; BEHAVIORS
AB PURPOSE Best-worst scaling (BWS) is a survey method for assessing individuals' priorities. It identifies the extremes-best and worst items, most and least important factors, biggest and smallest influences-among sets. In this article, we demonstrate an application of BWS in a primary care setting to illustrate its use in identifying patient priorities for services.
METHODS We conducted a BWS survey in 2014 in Boston, Massachusetts, to assess the relative importance of 10 previously identified attributes of Papanicolaou (Pap) testing services among women experiencing homelessness. Women were asked to evaluate 11 sets of 5 attributes of Pap services, and identify which attribute among each set would have the biggest and smallest influence on promoting uptake. We show how frequency analysis can be used to analyze results.
RESULTS In all, 165 women participated, a response rate of 72%. We identified the most and least salient influences on encouraging Pap screening based on their frequency of report among our sample, with possible standardized scores ranging from+1.0 (biggest influence) to -1.0 (smallest influence). Most important was the availability of support for issues beyond health (+0.39), while least important was the availability of accommodations for personal hygiene (-0.27).
CONCLUSIONS BWS quantifies patient priorities in a manner that is transparent and accessible. It is easily comprehendible by patients and relatively easy to administer. Our application illustrates its use in a vulnerable population, showing that factors beyond those typically provided in health care settings are highly important to women in seeking Pap screening. This approach can be applied to other health care services where prioritization is helpful to guide decisions.
C1 [Wittenberg, Eve; Ward, Zachary] Harvard TH Chan Sch Publ Hlth, Ctr Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA.
[Bharel, Monica] Massachusetts Gen Hosp, Boston Hlth Care Homeless Program, Boston, MA 02114 USA.
[Bharel, Monica] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Bharel, Monica] Boston Med Ctr, Boston, MA USA.
[Bharel, Monica] Commonwealth Massachusetts, Dept Publ Hlth, Boston, MA USA.
[Bridges, John F. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA.
[Weinreb, Linda] Univ Massachusetts, Sch Med, Dept Family Med & Community Hlth, Worcester, MA USA.
RP Wittenberg, E (reprint author), Harvard TH Chan Sch Publ Hlth, Ctr Hlth Decis Sci, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA.
EM ewittenb@hsph.harvard.edu
FU National Cancer Institute of the National Institutes of Health
[R21CA164712]
FX Research reported in this publication was supported by the National
Cancer Institute of the National Institutes of Health under award number
R21CA164712.
NR 40
TC 1
Z9 1
U1 4
U2 4
PU ANNALS FAMILY MEDICINE
PI LEAWOOD
PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA
SN 1544-1709
EI 1544-1717
J9 ANN FAM MED
JI Ann. Fam. Med.
PD JUL-AUG
PY 2016
VL 14
IS 4
BP 359
EP 364
DI 10.1370/afm.1937
PG 6
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA DR8KA
UT WOS:000380145600012
PM 27401425
ER
PT J
AU Nadal, R
Amin, A
Geynisman, DM
Voss, MH
Weinstock, M
Doyle, J
Zhang, Z
Viudez, A
Plimack, ER
McDermott, DF
Motzer, R
Rini, B
Hammers, HJ
AF Nadal, R.
Amin, A.
Geynisman, D. M.
Voss, M. H.
Weinstock, M.
Doyle, J.
Zhang, Z.
Viudez, A.
Plimack, E. R.
McDermott, D. F.
Motzer, R.
Rini, B.
Hammers, H. J.
TI Safety and clinical activity of vascular endothelial growth factor
receptor (VEGFR)-tyrosine kinase inhibitors after programmed cell death
1 inhibitor treatment in patients with metastatic clear cell renal cell
carcinoma
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE renal cell carcinoma; PD-1 inhibitor; nivolumab; ipilimumab; vascular
endothelial growth factor receptor-tyrosine kinase inhibitor
ID RANDOMIZED PHASE-3 TRIAL; SURVIVAL; EVEROLIMUS; SORAFENIB; NIVOLUMAB;
EFFICACY; AXITINIB
AB There are limited data on the efficacy and safety of vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) after programmed cell death (PD-1) inhibition. This study revealed that treatment with VEGFR-TKIs after PD-1 inhibition is safe and retains clinical activity in patients with mRCC.Emerging agents blocking the programmed cell death 1 (PD-1) pathway show activity in metastatic clear cell renal cell carcinoma (mRCC). The aim of this study was to evaluate the efficacy and safety of vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI) therapy after PD-1 inhibition.
Patients with mRCC treated with anti-PD-1 antibody (aPD-1) monotherapy or in combination (with VEGFR-TKI or ipilimumab) that subsequently received VEGFR-TKI were retrospectively reviewed. The efficacy end points were objective response rate (ORR) and progression-free survival (PFS) stratified by the type of prior PD-1 regimen. Safety by the type and PD-1 exposure was also evaluated.
Seventy patients were included. Forty-nine patients received prior therapy with immune checkpoint inhibitors (CPIs) alone and 21 had combination therapy of aPD-1 and VEGFR-TKI. Overall, ORR to VEGFR-TKI after PD-1 inhibition was 28% (19/68) and the median PFS was 6.4 months (mo) (4.3-9.5). ORR to VEGFR-TKI after aPD-1 in combination with VEGFR-TKI was lower than that in patients treated with VEGFR-TKI after CPI alone (ORR 10% versus 36%, P = 0.039). In the multivariable analysis, patients treated with prior CPI alone were more likely to achieve an objective response than those treated with aPD-1 in combination with VEGFR-TKI (OR = 5.38; 95% CI 1.12-26.0, P = 0.03). There was a trend toward numerically longer median PFS in the VEGFR-TKI after the CPI alone group, 8.4 mo (3.2-12.4) compared with 5.5 mo (2.9-8.3) for those who had VEGFR-TKI after aPD-1 in combination with VEGFR-TKI (P = 0.15). The most common adverse events (AEs) were asthenia, hypertension, and diarrhea.
The efficacy and safety of VEGFR-TKIs after PD-1 inhibition were demonstrated in this retrospective study. The response rate was lower and the median progression-free survival was shorter in those patients who received prior PD-1 in combination with VEGFR-TKI. PD-1 exposure does not seem to significantly influence the safety of subsequent VEGFR-TKI treatment.
C1 [Nadal, R.; Zhang, Z.; Viudez, A.; Hammers, H. J.] Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Amin, A.] Levine Canc Inst, Dept Oncol, Charlotte, NC USA.
[Geynisman, D. M.; Doyle, J.; Plimack, E. R.] Temple Univ Hlth Syst, Fox Chase Canc Ctr, Philadelphia, PA USA.
[Voss, M. H.; Motzer, R.] Mem Sloan Kettering Canc Ctr, Dept Oncol, 1275 York Ave, New York, NY 10021 USA.
[Weinstock, M.; McDermott, D. F.] Dana Farber Harvard Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Rini, B.] Cleveland Clin Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH USA.
RP Hammers, HJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Bunting Blaustein Canc Res Bldg,1650 Orleans St, Baltimore, MD 21231 USA.
EM hhammer2@jhmi.edu
FU Pfizer [11103561]; Bristol-Myers Squibb [DOD CA140917]; Acceleron;
GlaxoSmithKline; AstraZeneca; Pfizer
FX DMG has received research funding from Pfizer (grant number 11103561).
ERP has received research funding from Pfizer, Bristol-Myers Squibb,
Acceleron, GlaxoSmithKline, and AstraZeneca (no grant numbers applied).
MHV has research funding from Pfizer and Bristol-Myers Squibb (no grant
numbers applied). HJH has received clinical trial funding from
Bristol-Myers Squibb (grant number DOD CA140917).
NR 18
TC 0
Z9 0
U1 2
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JUL
PY 2016
VL 27
IS 7
BP 1304
EP 1311
DI 10.1093/annonc/mdw160
PG 8
WC Oncology
SC Oncology
GA DR2UZ
UT WOS:000379760700017
PM 27059553
ER
PT J
AU Chung, JH
Sanford, E
Johnson, A
Klempner, SJ
Schrock, AB
Palma, NA
Erlich, RL
Frampton, GM
Chalmers, ZR
Vergilio, J
Rubinson, DA
Sun, JX
Chmielecki, J
Yelensky, R
Suh, JH
Lipson, D
George, TJ
Elvin, JA
Stephens, PJ
Miller, VA
Ross, JS
Ali, SM
AF Chung, J. H.
Sanford, E.
Johnson, A.
Klempner, S. J.
Schrock, A. B.
Palma, N. A.
Erlich, R. L.
Frampton, G. M.
Chalmers, Z. R.
Vergilio, J.
Rubinson, D. A.
Sun, J. X.
Chmielecki, J.
Yelensky, R.
Suh, J. H.
Lipson, D.
George, T. J., Jr.
Elvin, J. A.
Stephens, P. J.
Miller, V. A.
Ross, J. S.
Ali, S. M.
TI Comprehensive genomic profiling of anal squamous cell carcinoma reveals
distinct genomically defined classes
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE anal squamous cell carcinoma; comprehensive genomic profiling; HPV;
PI3KCA; targeted therapy
ID COLORECTAL-CANCER; GENE; HEAD; EGFR; CHEMOTHERAPY; MUTATIONS; SURVIVAL;
TUMORS
AB Treatment of advanced anal squamous cell carcinoma (ASCC) with cisplatin-based chemotherapy, which is recommended by the National Comprehensive Cancer Network, provides limited benefit. An improved genomic understanding could guide therapeutic approaches. In this comprehensive genomic analysis of human papilloma-virus-positive and negative ASCC, we identify clinically relevant genomic alterations.Squamous cell cancers of the anal canal (ASCC) are increasing in frequency and lack effective therapies for advanced disease. Although an association with human papillomavirus (HPV) has been established, little is known about the molecular characterization of ASCC. A comprehensive genomic analysis of ASCC was undertaken to identify novel genomic alterations (GAs) that will inform therapeutic choices for patients with advanced disease.
Hybrid-capture-based next-generation sequencing of exons from 236 cancer-related genes and intronic regions from 19 genes commonly rearranged in cancer was performed on 70 patients with ASCC. HPV status was assessed by aligning tumor sequencing reads to HPV viral genomes. GAs were identified using an established algorithm and correlated with HPV status.
Sixty-one samples (87%) were HPV-positive. A mean of 3.5 GAs per sample was identified. Recurrent alterations in phosphoinositol-3-kinase pathway (PI3K/AKT/mTOR) genes including amplifications and homozygous deletions were present in 63% of cases. Clinically relevant GAs in genes involved in DNA repair, chromatin remodeling, or receptor tyrosine kinase signaling were observed in 30% of cases. Loss-of-function mutations in TP53 and CDKN2A were significantly enhanced in HPV-negative cases (P < 0.0001).
This is the first comprehensive genomic analysis of ASCC, and the results suggest new therapeutic approaches. Differing genomic profiles between HPV-associated and HPV-negative ASCC warrants further investigation and may require novel therapeutic and preventive strategies.
C1 [Chung, J. H.; Sanford, E.; Johnson, A.; Schrock, A. B.; Palma, N. A.; Erlich, R. L.; Frampton, G. M.; Chalmers, Z. R.; Vergilio, J.; Sun, J. X.; Chmielecki, J.; Yelensky, R.; Suh, J. H.; Lipson, D.; Elvin, J. A.; Stephens, P. J.; Miller, V. A.; Ross, J. S.; Ali, S. M.] Fdn Med, Cambridge, MA USA.
[Klempner, S. J.] Univ Calif Irvine, Div Hematol Oncol, Irvine, CA USA.
[Rubinson, D. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[George, T. J., Jr.] Univ Florida, Div Hematol Oncol, Gainesville, FL USA.
[Ross, J. S.] Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA.
RP Chung, JH (reprint author), Fdn Med Inc, 150 Second St,1st Floor, Cambridge, MA 02141 USA.
EM jchung@foundationmedicine.com
OI Chung, Jon/0000-0003-0526-3670
NR 31
TC 8
Z9 8
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD JUL
PY 2016
VL 27
IS 7
BP 1336
EP 1341
DI 10.1093/annonc/mdw152
PG 6
WC Oncology
SC Oncology
GA DR2UZ
UT WOS:000379760700022
PM 27052656
ER
PT J
AU Holmes, B
Lee, J
Landon, KA
Benavides-Serrato, A
Bashir, T
Jung, ME
Lichtenstein, A
Gera, J
AF Holmes, Brent
Lee, Jihye
Landon, Kenna A.
Benavides-Serrato, Angelica
Bashir, Tariq
Jung, Michael E.
Lichtenstein, Alan
Gera, Joseph
TI Mechanistic Target of Rapamycin (mTOR) Inhibition Synergizes with
Reduced Internal Ribosome Entry Site (IRES)-mediated Translation of
Cyclin D1 and c-MYC mRNAs to Treat Glioblastoma
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
DE cyclin D1; glioblastoma; heterogeneous nuclear ribonucleoprotein
(hnRNP); mechanistic target of rapamycin (mTOR); Myc (c-Myc);
translation; IRES; ITAF; mRNA translation
ID NUCLEAR RIBONUCLEOPROTEIN A1; TRANS-ACTING FACTOR; HNRNP A1; MAMMALIAN
TARGET; GROWTH; IRES; RESISTANCE; SENSITIVITY; MULTIFORME; INITIATION
AB Our previous work has demonstrated an intrinsic mRNA-specific protein synthesis salvage pathway operative in glioblastoma (GBM) tumor cells that is resistant to mechanistic target of rapamycin (mTOR) inhibitors. The activation of this internal ribosome entry site (IRES)-dependent mRNA translation initiation pathway results in continued translation of critical transcripts involved in cell cycle progression in the face of global eIF-4E-mediated translation inhibition. Recently we identified compound 11 (C11), a small molecule capable of inhibiting c-MYC IRES translation as a consequence of blocking the interaction of a requisite c-MYC IRES trans-acting factor, heterogeneous nuclear ribonucleoprotein A1, with its IRES. Here we demonstrate that C11 also blocks cyclin D1 IRES-dependent initiation and demonstrates synergistic anti-GBM properties when combined with the mechanistic target of rapamycin kinase inhibitor PP242. The structure-activity relationship of C11 was investigated and resulted in the identification of IRES-J007, which displayed improved IRES-dependent initiation blockade and synergistic anti-GBM effects with PP242. Mechanistic studies with C11 and IRES-J007 revealed binding of the inhibitors within the UP1 fragment of heterogeneous nuclear ribonucleoprotein A1, and docking analysis suggested a small pocket within close proximity to RRM2 as the potential binding site. We further demonstrate that co-therapy with IRES-J007 and PP242 significantly reduces tumor growth of GBM xenografts in mice and that combined inhibitor treatments markedly reduce the mRNA translational state of cyclin D1 and c-MYC transcripts in these tumors. These data support the combined use of IRES-J007 and PP242 to achieve synergistic antitumor responses in GBM.
C1 [Holmes, Brent; Lichtenstein, Alan; Gera, Joseph] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90048 USA.
[Jung, Michael E.; Lichtenstein, Alan; Gera, Joseph] Univ Calif Los Angeles, Jonnson Comprehens Canc Ctr, Los Angeles, CA 90048 USA.
[Jung, Michael E.; Gera, Joseph] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90048 USA.
[Lee, Jihye; Jung, Michael E.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90048 USA.
[Holmes, Brent; Landon, Kenna A.; Benavides-Serrato, Angelica; Bashir, Tariq; Lichtenstein, Alan; Gera, Joseph] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Res & Dev, Los Angeles, CA 91343 USA.
RP Gera, J (reprint author), 16111 Plummer St 151,Bldg 1,Rm C111A, Los Angeles, CA 91343 USA.
EM jgera@mednet.ucla.edu
FU National Institutes of Health [R01CA168700]; Department of Veterans
Affairs MERIT Grant [I01BX002665]
FX This work was supported by National Institutes of Health Grant
R01CA168700 and by Department of Veterans Affairs MERIT Grant
I01BX002665. The authors declare that they have no conflicts of interest
with the contents of this article. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health.
NR 39
TC 0
Z9 0
U1 6
U2 7
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD JUL 1
PY 2016
VL 291
IS 27
BP 14146
EP 14159
DI 10.1074/jbc.M116.726927
PG 14
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DR5XG
UT WOS:000379975100022
PM 27226604
ER
PT J
AU Griffiths, CE
Fava, M
Mrowietz, U
Miller, A
Russell, J
Ball, S
Zhang, L
Acharya, N
Rapaport, M
AF Griffiths, C. E.
Fava, M.
Mrowietz, U.
Miller, A.
Russell, J.
Ball, S.
Zhang, L.
Acharya, N.
Rapaport, M.
TI Short and long-term response and remission of depressive symptoms in
psoriasis patients treated continuously with ixekizumab in UNCOVER-3
SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY
LA English
DT Meeting Abstract
DE None
C1 [Griffiths, C. E.] Univ Manchester, Dermatol Ctr, Manchester, Lancs, England.
[Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Mrowietz, U.] Univ Med Ctr Schleswig Holstein, Schittenhelmstr, Germany.
[Miller, A.; Rapaport, M.] Emory Univ, Sch Med, Atlanta, GA USA.
[Russell, J.; Ball, S.; Zhang, L.; Acharya, N.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0926-9959
EI 1468-3083
J9 J EUR ACAD DERMATOL
JI J. Eur. Acad. Dermatol. Venereol.
PD JUL
PY 2016
VL 30
SU 6
SI SI
MA P069
BP 39
EP 40
PG 2
WC Dermatology
SC Dermatology
GA DR3CQ
UT WOS:000379780600070
ER
PT J
AU Brody, AA
Edelman, L
Siegel, EO
Foster, V
Bailey, DE
Bryant, AL
Bond, SM
AF Brody, Abraham A.
Edelman, Linda
Siegel, Elena O.
Foster, Victoria
Bailey, Donald E., Jr.
Bryant, Ashley Leak
Bond, Stewart M.
TI Evaluation of a peer mentoring program for early career gerontological
nursing faculty and its potential for application to other fields in
nursing and health sciences
SO NURSING OUTLOOK
LA English
DT Article
DE Mentoring; Peer mentorship; Gerontological nursing; Leadership;
Professional development; Faculty
ID JUNIOR FACULTY; EDUCATION; MODEL
AB Background: As the retirement rate of senior nursing faculty increases, the need to implement new models for providing mentorship to early career academics will become key to developing and maintaining an experienced faculty.
Purpose: This evaluation of a peer mentorship program for predoctoral and postdoctoral gerontological nurses examined its efficacy, utility, and potential for improvement.
Methods: A web-based survey was developed, implemented, and completed by 22 mentees and 17 mentors (71% and 61% response rates, respectively) as part of the evaluation.
Discussion: The peer mentorship program was found to be valuable by both mentors (64.7%) and mentees (72.7%) in helping mentees further develop their careers and networks and providing mentors with supported mentorship experience.
Conclusion: The peer mentorship program could serve as a model for other professional organizations, academic institutions:and consortiums to enhance and extend the formal vertical mentorship provided to early academic career individuals.
C1 [Brody, Abraham A.] NYU, Coll Nursing, Hartford Inst Geriatr Nursing, 433 First Ave,Room 504, New York, NY 10010 USA.
[Brody, Abraham A.] James J Peters Bronx VA Med Ctr, Bronx, NY USA.
[Edelman, Linda] Univ Utah, Sch Nursing, Hartford Ctr Geriatr Nursing Excellence, Salt Lake City, UT USA.
[Siegel, Elena O.] Univ Calif Davis, Betty Irene Moore Sch Nursing, Sacramento, CA 95817 USA.
[Foster, Victoria] Clayton State Univ, Sch Nursing, Morrow, GA USA.
[Bailey, Donald E., Jr.] Duke Univ, Sch Nursing, Durham, NC USA.
[Bryant, Ashley Leak] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA.
[Bond, Stewart M.] Boston Coll, Connell Sch Nursing, Chestnut Hill, MA 02167 USA.
RP Brody, AA (reprint author), NYU, Coll Nursing, Hartford Inst Geriatr Nursing, 433 First Ave,Room 504, New York, NY 10010 USA.
EM Ab.Brody@nyu.edu
OI Brody, Abraham/0000-0002-3405-7043
FU John A Hartford Foundation
FX The authors would like to acknowledge the John A Hartford Foundation for
its generous funding of this program, and the administrative support
provided by the National Hartford Center of Gerontological Nursing
Excellence.
NR 26
TC 0
Z9 0
U1 7
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0029-6554
EI 1528-3968
J9 NURS OUTLOOK
JI Nurs. Outlook
PD JUL-AUG
PY 2016
VL 64
IS 4
BP 332
EP 338
DI 10.1016/j.outlook.2016.03.004
PG 7
WC Nursing
SC Nursing
GA DR8YB
UT WOS:000380183200008
PM 27156778
ER
PT J
AU Cunningham, FE
Hur, K
Dong, DA
Miller, DR
Zhang, RP
Wei, XM
McCarren, M
Mosholder, AD
Graham, DJ
Aspinall, SL
Good, CB
AF Cunningham, Francesca E.
Hur, Kwan
Dong, Diane
Miller, Donald R.
Zhang, Rongping
Wei, Xiangming
McCarren, Madeline
Mosholder, Andrew D.
Graham, David J.
Aspinall, Sherrie L.
Good, Chester B.
TI A comparison of neuropsychiatric adverse events during early treatment
with varenicline or a nicotine patch
SO ADDICTION
LA English
DT Article
DE Adverse drug events; mental health disorder; nicotine replacement
therapy; varenicline
ID RECEPTOR PARTIAL AGONIST; RANDOMIZED CONTROLLED-TRIAL; SUSTAINED-RELEASE
BUPROPION; SMOKING-CESSATION; DOUBLE-BLIND; SCHIZOAFFECTIVE DISORDER;
PROSPECTIVE COHORT; SUICIDAL-BEHAVIOR; BIPOLAR DISORDER; MAJOR
DEPRESSION
AB Aims We compared the risk of mental health episodes requiring hospitalization (primary aim) or out-patient clinic visits (secondary aim) associated with varenicline versus the nicotine patch (NP) in an era prior to psychiatric boxed warnings. Design Retrospective cohort. Setting Department of Veterans Affairs (VA), USA. Participants VA patients with or without psychiatric comorbidities and a new prescription for varenicline (15 255) were propensity score-matched (1 : 2) to new users of NP (123 054) between 1 May 2006 and 30 September 2007, resulting in 11 774 and 23 548 patients in the varenicline and NP groups, respectively. Measurements The primary outcomes were hospitalizations with a primary discharge diagnosis of a range of mental health disorders: depression, schizophrenia, bipolar disorder, suicide attempt, post-traumatic stress disorder, other psychosis and drug-induced mental disorders. Secondary outcomes were out-patient clinic visits with a primary diagnosis of the above list of mental health disorders. Findings Background characteristics of the treatment groups were similar after matching. There was no statistically significant difference in risk of hospitalization for any of the studied mental health disorders with varenicline compared with NP. Among secondary outcomes there was an increased risk of out-patient clinic visits for schizophrenia among patients who received varenicline [hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.07, 1.51], this increase being evident only in those with a pre-existing mental health disorder. Conclusion In US VA patients studied prior to the boxed warning being implemented, use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. There was an increased rate of out-patient attendances with a primary diagnosis of schizophrenia amounting to five per 100 person years of treatment. This increase was found only in patients with a pre-existing mental health disorder.
C1 [Cunningham, Francesca E.; Hur, Kwan; Dong, Diane; Zhang, Rongping; Wei, Xiangming; McCarren, Madeline; Aspinall, Sherrie L.; Good, Chester B.] VA Ctr Medicat Safety, Hines, IL USA.
[Miller, Donald R.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Miller, Donald R.] Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA.
[Mosholder, Andrew D.; Graham, David J.] US FDA, Silver Spring, MD USA.
[Aspinall, Sherrie L.; Good, Chester B.] VA Pittsburgh Healthcare Syst, VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA.
[Good, Chester B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Aspinall, Sherrie L.; Good, Chester B.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA.
RP Cunningham, FE (reprint author), Ctr Medicat Safety, PBM Serv, Dept Vet Affairs, 1st Ave,1 Block,N Cermak Rd,Bldg 37,Room 139, Hines, IL 60141 USA.
EM fran.cunningham@va.gov
FU FDA
FX Funds from the FDA were used to support this study under an interagency
agreement between the FDA and the Veterans Health Administration. The
authors do not have a relevant financial interest in this paper or any
connections with the tobacco, alcohol, pharmaceutical or gaming
industries. The views expressed in this paper are those of the authors,
and no official endorsement by the United States Food and Drug
Administration, Department of Veteran Affairs or the United States
Government is intended or should be inferred.
NR 65
TC 1
Z9 1
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD JUL
PY 2016
VL 111
IS 7
BP 1283
EP 1292
DI 10.1111/add.13329
PG 10
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DR5OG
UT WOS:000379951700026
PM 26826702
ER
PT J
AU Jacobs, J
Schwartz, A
McDougle, CJ
Skotko, BG
AF Jacobs, Julia
Schwartz, Alison
McDougle, Christopher J.
Skotko, Brian G.
TI Rapid Clinical Deterioration in an Individual with Down Syndrome
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Down syndrome; catatonia; regression; psychosis
ID REGRESSION
AB A small percentage of adolescents and young adults with Down syndrome experience a rapid and unexplained deterioration in cognitive, adaptive, and behavioral functioning. Currently, there is no standardized work-up available to evaluate these patients or treat them. Their decline typically involves intellectual deterioration, a loss of skills of daily living, and prominent behavioral changes. Certain cases follow significant life events such as completion of secondary school with friends who proceed on to college or employment beyond the individual with DS. Others develop this condition seemingly unprovoked. Increased attention in the medical community to clinical deterioration in adolescents and young adults with Down syndrome could provide a framework for improved diagnosis, evaluation, and treatment. This report presents a young adult male with Down syndrome who experienced severe and unexplained clinical deterioration, highlighting specific challenges in the systematic evaluation and treatment of these patients. (C) 2016 Wiley Periodicals, Inc.
C1 [Jacobs, Julia] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Schwartz, Alison; Skotko, Brian G.] Massachusetts Gen Hosp, Dept Pediat, Div Med Genet, Syndrome Program, 185 Cambridge St,Room 2-222, Boston, MA 02114 USA.
[Schwartz, Alison; McDougle, Christopher J.; Skotko, Brian G.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
[McDougle, Christopher J.] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
RP Skotko, BG (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Med Genet, Syndrome Program, 185 Cambridge St,Room 2-222, Boston, MA 02114 USA.
EM bskotko@mgh.harvard.edu
NR 7
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U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD JUL
PY 2016
VL 170
IS 7
BP 1899
EP 1902
DI 10.1002/ajmg.a.37674
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA DR5MV
UT WOS:000379948000028
PM 27149638
ER
PT J
AU Hatoun, J
Suen, W
Liu, C
Shea, S
Patts, G
Weinberg, J
Eng, J
AF Hatoun, Jonathan
Suen, Winnie
Liu, Constance
Shea, Sandy
Patts, Gregory
Weinberg, Janice
Eng, Jessica
TI Elucidating Reasons for Resident Underutilization of Electronic Adverse
Event Reporting
SO AMERICAN JOURNAL OF MEDICAL QUALITY
LA English
DT Article
DE adverse event reporting; near miss reporting; residents and trainees;
risk management; medical quality
AB Reasons for resident underutilization of adverse event (AE) reporting systems are unclear, particularly given frequent resident exposure to AEs and near misses (NMs). Residents at an academic medical center were surveyed about AEs/NMs, barriers to reporting, patient safety climate, and educational interventions. A total of 350 of 527 eligible residents (66%) completed the survey; 77% of respondents reported involvement in an AE/NM, though only 43% had used the reporting system. Top barriers to reporting were not knowing what or how to report. Surgeons reported more than other residents (surgery, 61%; medical, 38%; hospital-based, 15%; P < .01), yet more often felt that systems were unlikely to change after reporting (surgery, 49%; medical, 28%; hospital-based. 18%; P < .01). Residents preferred discussions with supervisors (52%) and department-led conferences (46%) to increased reporting. Efforts to increase resident reporting should address common barriers to reporting as well as department-specific differences in resident knowledge, perceptions of system effectiveness, and educational preferences.
C1 [Hatoun, Jonathan] Boston Med Ctr, 88 East Newton St,Vose Hall 3rd Floor, Boston, MA 02118 USA.
[Suen, Winnie] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Suen, Winnie] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA.
[Liu, Constance] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Shea, Sandy] Comm Interns & Residents, Boston, MA USA.
[Patts, Gregory; Weinberg, Janice] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Eng, Jessica] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Eng, Jessica] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Hatoun, J (reprint author), Boston Med Ctr, 88 East Newton St,Vose Hall 3rd Floor, Boston, MA 02118 USA.
EM jonathan.hatoun@bmc.org
FU Boston Medical Center
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: The material
presented in this research report was funded by an institutional grant
from Boston Medical Center to promote patient safety.
NR 10
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U1 1
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1062-8606
EI 1555-824X
J9 AM J MED QUAL
JI Am. J. Med. Qual.
PD JUL-AUG
PY 2016
VL 31
IS 4
BP 308
EP 314
DI 10.1177/1062860615574504
PG 7
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DR6OH
UT WOS:000380020700003
PM 25753451
ER
PT J
AU Sanchez-Fueyo, A
Markmann, JF
AF Sanchez-Fueyo, A.
Markmann, J. F.
TI Immune Exhaustion and Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Review
DE translational research; science; immunobiology; immunosuppression;
immune modulation; tolerance; tolerance: mechanisms; T cell biology
ID T-CELL EXHAUSTION; CHRONIC HEPATITIS-C; LCMV INFECTION; PERSISTENCE;
ACCEPTANCE; RECIPIENTS; TOLERANCE; REJECTION; DIFFERENTIATION;
DYSFUNCTION
AB Exhaustion of lymphocyte function through chronic exposure to a high load of foreign antigen is well established for chronic viral infection and antitumor immunity and has been found to be associated with a distinct molecular program and characteristic cell surface phenotype. Although exhaustion has most commonly been studied in the context of CD8 viral responses, recent studies indicate that chronic antigen exposure may affect B cells, NK cells and CD4 T cells in a parallel manner. Limited information is available regarding the extent of lymphocyte exhaustion development in the transplant setting and its impact on anti-graft alloreactivity. By analogy to the persistence of a foreign virus, the large mass of alloantigen presented by an allograft in chronic residence could provide an ideal setting for exhausting donor-reactive T cells. The extent of T cell exhaustion occurring with various allografts, the kinetics of its development, whether exhaustion is influenced positively or negatively by different immunosuppressants, and the impact of exhaustion on graft survival and tolerance development remains a fertile area for investigation. Harnessing or encouraging the natural processes of exhaustion may provide a novel means to promote graft survival and transplantation tolerance.
T cell exhaustion, a general mechanism to prevent immunopathology in situations of high antigen load and persistent inflammation, may play a role in the long-term effects of immunosuppression and tolerance-promoting strategies.
C1 [Sanchez-Fueyo, A.] Kings Coll London Univ, Kings Coll Hosp, Fac Life Sci & Med,Inst Liver Studies, Div Transplantat Immunol & Mucosal Biol,Med Res C, London, England.
[Markmann, J. F.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Div Transplant Surg, Boston, MA 02114 USA.
RP Sanchez-Fueyo, A (reprint author), Kings Coll London Univ, Kings Coll Hosp, Fac Life Sci & Med,Inst Liver Studies, Div Transplantat Immunol & Mucosal Biol,Med Res C, London, England.
EM sanchez_fueyo@kcl.ac.uk
FU Medical Research Council UK (MRC) [MR/L008890/1]; MRC Centre for
Transplantation (MRC) [MR/J006742/1]; National Institute for Health
Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas'
NHS Foundation Trust and King's College London
FX A.S.-F. is supported by the Medical Research Council UK (MRC) grant no.
MR/L008890/1, the MRC Centre for Transplantation (MRC grant no.
MR/J006742/1) and the National Institute for Health Research (NIHR)
Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation
Trust and King's College London.
NR 34
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U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUL
PY 2016
VL 16
IS 7
BP 1953
EP 1957
DI 10.1111/ajt.13702
PG 5
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DR2II
UT WOS:000379727800006
PM 26729653
ER
PT J
AU Guinan, EC
Cole, GA
Wylie, WH
Kelner, RH
Janec, KJ
Yuan, H
Oppatt, J
Brennan, LL
Turka, LA
Markmann, J
AF Guinan, E. C.
Cole, G. A.
Wylie, W. H.
Kelner, R. H.
Janec, K. J.
Yuan, H.
Oppatt, J.
Brennan, L. L.
Turka, L. A.
Markmann, J.
TI Ex Vivo Costimulatory Blockade to Generate Regulatory T Cells From
Patients Awaiting Kidney Transplantation
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE translational research; science; basic (laboratory) research; science;
cellular transplantation (non-islet); kidney transplantation;
nephrology; organ transplantation in general; kidney transplantation:
living donor; tolerance: costimulation blockade; tolerance: experimental
ID THERAPY; BELATACEPT; UREMIA; FOXP3; INDUCTION; EXPANSION; SYSTEM;
TRIALS; BLOOD
AB Short-term outcomes of kidney transplantation have improved dramatically, but chronic rejection and regimen-related toxicity continue to compromise overall patient outcomes. Development of regulatory T cells (Tregs) as a means to decrease alloresponsiveness and limit the need for pharmacologic immunosuppression is an active area of preclinical and clinical investigation. Nevertheless, the immunomodulatory effects of end-stage renal disease on the efficacy of various strategies to generate and expand recipient Tregs for kidney transplantation are incompletely characterized. In this study, we show that Tregs can be successfully generated from either freshly isolated or previously cryopreserved uremic recipient (responder) and healthy donor (stimulator) peripheral blood mononuclear cells using the strategy of exvivo costimulatory blockade with belatacept during mixed lymphocyte culture. Moreover, these Tregs maintain a CD3(+)CD4(+)CD25(+)CD127(lo) surface phenotype, high levels of intracellular FOXP3 and significant demethylation of the FOXP3 Treg-specific demethylation region on allorestimulation with donor stimulator cells. These data support evaluation of this simple, brief Treg production strategy in clinical trials of mismatched kidney transplantation.
The authors demonstrate that the peripheral blood of uremic patients can generate donor antigen-specific T regulatory cells via an established in vitro costimulation blockade protocol, thereby setting the stage for use of these T regulatory cells as an immunotherapeutic treatment in renal transplantation.
C1 [Guinan, E. C.; Kelner, R. H.; Janec, K. J.; Yuan, H.; Brennan, L. L.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Guinan, E. C.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Cole, G. A.; Wylie, W. H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Oppatt, J.] Epiontis GmbH, Berlin, Germany.
[Turka, L. A.] Massachusetts Gen Hosp, Ctr Transplantat Sci, Boston, MA 02114 USA.
[Turka, L. A.; Markmann, J.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.; Guinan, EC (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
EM eva_guinan@dfci.harvard.edu
OI Guinan, Eva/0000-0003-3874-0007
FU Pfizer [WS2319657]
FX This work was supported by in part by Pfizer (grant WS2319657). We would
like to acknowledge Al Ozonoff, PhD, for helpful discussion regarding
statistics; the technical contributions of Annie Voskerchian and
Christine Barbon; the support of our research nurses Sandra L.
Debronkart, Kerry A. Crisalli and the floor nursing staff; and the
generous participation of patients and families, without whom this study
could not have been successfully undertaken.
NR 29
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD JUL
PY 2016
VL 16
IS 7
BP 2187
EP 2195
DI 10.1111/ajt.13725
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DR2II
UT WOS:000379727800027
PM 26790369
ER
PT J
AU Wurzman, R
Hamilton, RH
Pascual-Leone, A
Fox, MD
AF Wurzman, Rachel
Hamilton, Roy H.
Pascual-Leone, Alvaro
Fox, Michael D.
TI An Open Letter Concerning Do-It-Yourself Users of Transcranial Direct
Current Stimulation
SO ANNALS OF NEUROLOGY
LA English
DT Editorial Material
ID DORSOLATERAL PREFRONTAL CORTEX; BRAIN-STIMULATION; MOTOR CORTEX;
COGNITIVE ENHANCEMENT; ELECTRIC-FIELDS; WORKING-MEMORY; TDCS;
EXCITABILITY; HUMANS; MECHANISMS
C1 [Wurzman, Rachel] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Hamilton, Roy H.] Univ Penn, Dept Neurol & Phys Med & Rehabil, Philadelphia, PA 19104 USA.
[Pascual-Leone, Alvaro; Fox, Michael D.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Fox, Michael D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Fox, Michael D.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
RP Fox, MD (reprint author), Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.; Fox, MD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.; Fox, MD (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
EM foxmdphd@gmail.com
NR 54
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U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD JUL
PY 2016
VL 80
IS 1
BP 1
EP 4
DI 10.1002/ana.24689
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DR5JM
UT WOS:000379939300001
PM 27216434
ER
PT J
AU O'Grady, GL
Lek, M
Lamande, SR
Waddell, L
Oates, EC
Punetha, J
Ghaoui, R
Sandaradura, SA
Best, H
Kaur, S
Davis, M
Laing, NG
Muntoni, F
Hoffman, E
MacArthur, DG
Clarke, NF
Cooper, S
North, K
AF O'Grady, Gina L.
Lek, Monkol
Lamande, Shireen R.
Waddell, Leigh
Oates, Emily C.
Punetha, Jaya
Ghaoui, Roula
Sandaradura, Sarah A.
Best, Heather
Kaur, Simranpreet
Davis, Mark
Laing, Nigel G.
Muntoni, Francesco
Hoffman, Eric
MacArthur, Daniel G.
Clarke, Nigel F.
Cooper, Sandra
North, Kathryn
TI Diagnosis and Etiology of Congenital Muscular Dystrophy: We Are Halfway
There
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID FIBER-TYPE DISPROPORTION; CENTRONUCLEAR MYOPATHY; MUTATIONS; PHENOTYPE;
DYSTROGLYCAN; DISORDERS; GENE
AB Objective: To evaluate the diagnostic outcomes in a large cohort of congenital muscular dystrophy (CMD) patients using traditional and next generation sequencing (NGS) technologies.
Methods: A total of 123 CMD patients were investigated using the traditional approaches of histology, immunohistochemical analysis of muscle biopsy, and candidate gene sequencing. Undiagnosed patients available for further testing were investigated using NGS.
Results: Muscle biopsy and immunohistochemical analysis found deficiencies of laminin alpha 2, alpha-dystroglycan, or collagen VI in 50% of patients. Candidate gene sequencing and chromosomal microarray established a genetic diagnosis in 32% (39 of 123). Of 85 patients presenting in the past 20 years, 28 of 51 who lacked a confirmed genetic diagnosis (55%) consented to NGS studies, leading to confirmed diagnoses in a further 11 patients. Using the combination of approaches, a confirmed genetic diagnosis was achieved in 51% (43 of 85). The diagnoses within the cohort were heterogeneous. Forty-five of 59 probands with confirmed or probable diagnoses had variants in genes known to cause CMD (76%), and 11 of 59 (19%) had variants in genes associated with congenital myopathies, reflecting overlapping features of these conditions. One patient had a congenital myasthenic syndrome, and 2 had microdeletions. Within the cohort, 5 patients had variants in novel (PIGY and GMPPB) or recently published genes (GFPT1 and MICU1), and 7 had variants in TTN or RYR1, large genes that are technically difficult to Sanger sequence.
Interpretation: These data support NGS as a first-line tool for genetic evaluation of patients with a clinical phenotype suggestive of CMD, with muscle biopsy reserved as a second-tier investigation.
C1 [Lamande, Shireen R.; North, Kathryn] Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
[O'Grady, Gina L.; Lek, Monkol; Waddell, Leigh; Oates, Emily C.; Ghaoui, Roula; Sandaradura, Sarah A.; Best, Heather; Kaur, Simranpreet; Clarke, Nigel F.; Cooper, Sandra; North, Kathryn] Childrens Hosp Westmead, Kids Res Inst, Inst Neurosci & Muscle Res, Westmead, NSW, Australia.
[O'Grady, Gina L.; Oates, Emily C.; Ghaoui, Roula; Sandaradura, Sarah A.; Best, Heather; Clarke, Nigel F.; Cooper, Sandra] Univ Sydney, Fac Med, Discipline Paediat & Child Hlth, Sydney, NSW, Australia.
[Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Lamande, Shireen R.] Univ Melbourne, Dept Paediat, Parkville, Vic, Australia.
[Punetha, Jaya; Hoffman, Eric] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA.
[Davis, Mark; Laing, Nigel G.] QEII Med Ctr, PathWest Lab Med, Dept Diagnost Genom, Nedlands, WA, Australia.
[Laing, Nigel G.] Univ Western Australia, Med Res Ctr, Perth, WA, Australia.
[Laing, Nigel G.] Harry Perkins Inst Med Res, Neurogenet Unit, Nedlands, WA, Australia.
[Muntoni, Francesco] UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England.
[Muntoni, Francesco] Great Ormond St Hosp Sick Children, London, England.
[North, Kathryn] Univ Melbourne, Dept Paediat, Fac Med, Melbourne, Vic, Australia.
RP North, K (reprint author), Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
EM kathryn.north@mcri.edu.au
RI North, Kathryn/K-6476-2012
OI North, Kathryn/0000-0003-0841-8009
FU National Health and Medical Research Council of Australia [1022707,
1031893, APP1002147, 1056285, 633194]; Victorian Government; Muscular
Dystrophy NSW; Royal Australasian College of Physicians; National Human
Genome Research Institute (NIH) [U54 HG003067]; Muscular Dystrophy UK;
Biomedical Research Centre; National Specialist Commissioning Team
FX Supported by the National Health and Medical Research Council of
Australia (1022707, 1031893, N.F.C, N.G.L., K.N.; APP1002147, N.G.L.;
1056285, G.L.O.; 633194, E.C.O.) and the Victorian Government's
Operational Infrastructure Support Program. G.L.O. received funding from
Muscular Dystrophy NSW and the Royal Australasian College of Physicians.
Exome sequencing was supported by grants from the National Human Genome
Research Institute (NIH) (Medical Sequencing Program grant U54 HG003067
to the Broad Institute principal investigator, E.L.). Targeted
sequencing was supported by the NIH (3R01NS29525, E.H.).; We thank
Muscular Dystrophy UK, the Biomedical Research Centre, and the National
Specialist Commissioning Team for the support of the Dubowitz
Neuromuscular Centre at Great Ormond Street Hospital.
NR 28
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U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD JUL
PY 2016
VL 80
IS 1
BP 101
EP 111
DI 10.1002/ana.24687
PG 11
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DR5JM
UT WOS:000379939300010
PM 27159402
ER
PT J
AU Michaud, GC
Channick, CL
Law, AC
McCannon, JB
Antkowiak, M
Garrison, G
Sayah, D
Huynh, RH
Brady, AK
Adamson, R
DuBrock, H
Akuthota, P
Marion, C
Dela Cruz, C
Town, JA
Coruh, B
Thomson, CC
AF Michaud, Gaetane C.
Channick, Colleen L.
Law, Anica C.
McCannon, Jessica B.
Antkowiak, MaryEllen
Garrison, Garth
Sayah, David
Huynh, Richard H.
Brady, Anna K.
Adamson, Rosemary
DuBrock, Hilary
Akuthota, Praveen
Marion, Chad
Dela Cruz, Charles
Town, James A.
Coruh, Basak
Thomson, Carey C.
TI ATS Core Curriculum 2016 Part IV. Adult Pulmonary Medicine Core
Curriculum
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
C1 [Michaud, Gaetane C.] NYU, Sch Med, Pulm Crit Care & Sleep Med, New York, NY USA.
[Channick, Colleen L.; Law, Anica C.; McCannon, Jessica B.] Harvard Med Sch, Massachusetts Gen Hosp, Pulm & Crit Care Med, Boston, MA USA.
[Antkowiak, MaryEllen; Garrison, Garth] Univ Vermont, Coll Med, Pulm & Crit Care Med, Burlington, VT USA.
[Sayah, David; Huynh, Richard H.] Univ Calif Los Angeles, Pulm & Crit Care Med, Los Angeles, CA USA.
[Brady, Anna K.; Adamson, Rosemary; Town, James A.; Coruh, Basak] Univ Washington, Pulm & Crit Care Med, Seattle, WA 98195 USA.
[DuBrock, Hilary; Akuthota, Praveen] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Pulm Crit Care & Sleep Med, Boston, MA USA.
[Marion, Chad; Dela Cruz, Charles] Yale Univ, Sch Med, Pulm Crit Care & Sleep Med, New Haven, CT USA.
[Thomson, Carey C.] Harvard Med Sch, Mt Auburn Hosp, Pulm & Crit Care Med, Boston, MA USA.
RP Michaud, GC (reprint author), 531 First Ave,Suite 5D, New York, NY 10016 USA.
EM gaetanemichaud@yahoo.ca
OI Sayah, David/0000-0001-7021-8273
FU PneumRx; Allegro Diagnostics; Consulting Olympus; Medtronic; Olympus;
NIH; GlaxoSmithKline; Sanofi Pasteur; Cempra
FX Supported by PneumRx, Allegro Diagnostics, and Consulting Olympus
(G.C.M.); Medtronic and Olympus (C.L.C.); the NIH and GlaxoSmithKline
(P.A.); and Sanofi Pasteur and Cempra (C.D.C.).
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1546-3222
EI 2325-6621
J9 ANN AM THORAC SOC
JI Ann. Am. Thoracic Society
PD JUL
PY 2016
VL 13
IS 7
BP 1160
EP 1169
DI 10.1513/AnnalsATS.201601-060CME
PG 10
WC Respiratory System
SC Respiratory System
GA DR7YP
UT WOS:000380115900028
PM 27388404
ER
PT J
AU Post, RM
Altshuler, LL
Kupka, RW
McElroy, SL
Frye, MA
Rowe, M
Grunze, H
Suppes, T
Keck, PE
Leverich, GS
Nolen, WA
AF Post, R. M.
Altshuler, L. L.
Kupka, R. W.
McElroy, S. L.
Frye, M. A.
Rowe, M.
Grunze, H.
Suppes, T.
Keck, P. E., Jr.
Leverich, G. S.
Nolen, W. A.
TI Offspring of parents with bipolar illness from the US are more ill than
those from the Netherlands and Germany
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 18th Annual Conference of the
International-Society-for-Bipolar-Disorders / 8th Biennial Conference of
the International-Society-for-Affective-Disorders
CY JUL 13-16, 2016
CL Amsterdam, NETHERLANDS
SP Int Soc Bipolar Disorders, Int Soc Affect Disorders
C1 [Post, R. M.; Rowe, M.; Leverich, G. S.] Bipolar Collaborat Network, Bethesda, MD USA.
[Post, R. M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA.
[Altshuler, L. L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Altshuler, L. L.] VA Greater Los Angeles Healthcare Syst, West Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA.
[Kupka, R. W.; Keck, P. E., Jr.] VU Med Ctr Amsterdam, Dept Psychiat, Amsterdam, Netherlands.
[McElroy, S. L.; Keck, P. E., Jr.] Lindner Ctr HOPE, Mason, OH USA.
[McElroy, S. L.] Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA.
[Frye, M. A.] Mayo Clin, Dept Psychiat, Rochester, MN USA.
[Grunze, H.] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England.
[Suppes, T.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Suppes, T.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Nolen, W. A.] Univ Groningen, Univ Med Ctr, Dept Psychiat, Groningen, Netherlands.
NR 0
TC 0
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUL
PY 2016
VL 18
SU 1
SI SI
MA S-058
BP 35
EP 35
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5KI
UT WOS:000379941500066
ER
PT J
AU Sylvia, L
Hearing, C
Gold, A
Deckersbach, T
Nierenberg, A
AF Sylvia, L.
Hearing, C.
Gold, A.
Deckersbach, T.
Nierenberg, A.
TI Moodnetwork: a platform for patient-centered, comparative effectiveness
research
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 18th Annual Conference of the
International-Society-for-Bipolar-Disorders / 8th Biennial Conference of
the International-Society-for-Affective-Disorders
CY JUL 13-16, 2016
CL Amsterdam, NETHERLANDS
SP Int Soc Bipolar Disorders, Int Soc Affect Disorders
C1 [Sylvia, L.; Hearing, C.; Gold, A.; Deckersbach, T.; Nierenberg, A.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUL
PY 2016
VL 18
SU 1
SI SI
MA P-003
BP 70
EP 71
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5KI
UT WOS:000379941500167
ER
PT J
AU Dias, R
Salvini, R
Nierenberg, A
Lafer, B
AF Dias, R.
Salvini, R.
Nierenberg, A.
Lafer, B.
TI Machine learning approach with baseline clinical data forecasting
depression relapse in bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 18th Annual Conference of the
International-Society-for-Bipolar-Disorders / 8th Biennial Conference of
the International-Society-for-Affective-Disorders
CY JUL 13-16, 2016
CL Amsterdam, NETHERLANDS
SP Int Soc Bipolar Disorders, Int Soc Affect Disorders
C1 [Salvini, R.] Univ Fed Goias, Informat, Goiania, Go, Brazil.
[Nierenberg, A.] Harvard Med Sch, Massachussets Gen Hosp, Psychiat Bipolar Clin & Res Program, Boston, MA USA.
[Lafer, B.] Univ Sao Paulo, Fac Med, Psychiat Bipolar Disorder Res Program, Sao Paulo, Brazil.
OI Lafer, Beny/0000-0002-6132-9999
NR 0
TC 0
Z9 0
U1 7
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUL
PY 2016
VL 18
SU 1
SI SI
MA P-108
BP 103
EP 103
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5KI
UT WOS:000379941500272
ER
PT J
AU Kohler, O
Sylvia, L
Nierenberg, AA
AF Kohler, O.
Sylvia, L.
Nierenberg, A. A.
TI White blood cell count correlates with mood symptom severity and
specific mood symptoms in bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 18th Annual Conference of the
International-Society-for-Bipolar-Disorders / 8th Biennial Conference of
the International-Society-for-Affective-Disorders
CY JUL 13-16, 2016
CL Amsterdam, NETHERLANDS
SP Int Soc Bipolar Disorders, Int Soc Affect Disorders
C1 [Kohler, O.] Ctr Register Based Res, Aarhus V, Denmark.
[Sylvia, L.; Nierenberg, A. A.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUL
PY 2016
VL 18
SU 1
SI SI
MA P-176
BP 124
EP 125
PG 2
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5KI
UT WOS:000379941500340
ER
PT J
AU Sylvia, L
Gold, A
Chang, W
Bernstein, E
Nierenberg, A
Deckersbach, T
AF Sylvia, L.
Gold, A.
Chang, W.
Bernstein, E.
Nierenberg, A.
Deckersbach, T.
TI Examining biomarkers of a lifestyle intervention for bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 18th Annual Conference of the
International-Society-for-Bipolar-Disorders / 8th Biennial Conference of
the International-Society-for-Affective-Disorders
CY JUL 13-16, 2016
CL Amsterdam, NETHERLANDS
SP Int Soc Bipolar Disorders, Int Soc Affect Disorders
C1 [Sylvia, L.; Gold, A.; Chang, W.; Nierenberg, A.; Deckersbach, T.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA.
[Bernstein, E.] Harvard Univ, Psychol, Cambridge, MA 02138 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUL
PY 2016
VL 18
SU 1
SI SI
MA P-255
BP 150
EP 150
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5KI
UT WOS:000379941500419
ER
PT J
AU Weinstock, LM
Uebelacker, LA
Hearing, C
Deckersbach, T
Nierenberg, AA
Sylvia, LG
AF Weinstock, L. M.
Uebelacker, L. A.
Hearing, C.
Deckersbach, T.
Nierenberg, A. A.
Sylvia, L. G.
TI The acceptability and feasibility of an online yoga intervention for
individuals with mood disorders: a moodnetwork study
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 18th Annual Conference of the
International-Society-for-Bipolar-Disorders / 8th Biennial Conference of
the International-Society-for-Affective-Disorders
CY JUL 13-16, 2016
CL Amsterdam, NETHERLANDS
SP Int Soc Bipolar Disorders, Int Soc Affect Disorders
C1 [Weinstock, L. M.; Uebelacker, L. A.] Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Weinstock, L. M.; Uebelacker, L. A.] Butler Hosp, Psychosocial Res Program, Providence, RI 02906 USA.
[Hearing, C.; Deckersbach, T.; Nierenberg, A. A.; Sylvia, L. G.] Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA.
[Hearing, C.; Deckersbach, T.; Nierenberg, A. A.; Sylvia, L. G.] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD JUL
PY 2016
VL 18
SU 1
SI SI
MA P-327
BP 172
EP 172
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5KI
UT WOS:000379941500491
ER
PT J
AU Wilkinson, M
Wang, RP
van der Kouwe, A
Takahashi, E
AF Wilkinson, Molly
Wang, Rongpin
van der Kouwe, Andre
Takahashi, Emi
TI White and gray matter fiber pathways in autism spectrum disorder
revealed by ex vivo diffusion MR tractography
SO BRAIN AND BEHAVIOR
LA English
DT Article
DE Brain; callosal pathways; corticopontine pathways; development; ex vivo
imaging; high-angular resolution diffusion imaging; tractography
ID CORPUS-CALLOSUM; IMAGING TRACTOGRAPHY; YOUNG-CHILDREN; BRAIN;
CONNECTIVITY; SIZE; METAANALYSIS; ADOLESCENTS; CEREBELLUM; ADULTS
AB Introduction: The goal of this project was to study the white and gray matter brain pathways of young children with autism spectrum disorder (ASD) and investigate how ASD brains differ from those of typically developing children of the same age. Methods: High angular resolution resolution diffusion imaging tractography and diffusion tensor imaging tractography were used to analyze the brains of two 3-year-old children with ASD and two age-matched controls. Results: In the ASD brains, the callosal and corticopontine pathways were thinner overall and terminal areas in the cortical gray matter were significantly smaller. The ASD brains had more short-range u-fibers in the frontal lobe compared to the control brains. Gray matter pathways were found disorganized with less coherency in the ASD brain, specifically the lateral aspects of the middle part of the brain including motor areas, and both medial and lateral surfaces of the anterior frontal brain regions. Conclusion: These findings show our tractography technique is useful for identifying differences in brain pathways between the ASD and control groups. Given that scanning the brain of 3-year-old children with or even without ASD is challenging, postmortem scanning may offer valuable insights into the connectivity in the brain of young children with ASD.
C1 [Wilkinson, Molly] Northeastern Univ, Dept Behav Neurosci, Boston, MA 02115 USA.
[Wilkinson, Molly; Wang, Rongpin; Takahashi, Emi] Harvard Med Sch, Boston Childrens Hosp, Dept Med, Div Newborn Med, Boston, MA USA.
[van der Kouwe, Andre] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Takahashi, Emi] Harvard Med Sch, Fetal Neonatal Neuroimaging & Dev Sci Ctr, Boston Childrens Hosp, Boston, MA USA.
RP Takahashi, E (reprint author), Harvard Med Sch, Boston Childrens Hosp, Div Newborn Med, 1 Autumn St 456, Boston, MA 02215 USA.
EM emi@nmr.mgh.harvard.edu
FU National Institutes of Health [R01HD078561, R21HD069001, R03NS091587]
FX National Institutes of Health (Grant/Award Number: "R01HD078561,
R21HD069001, R03NS091587").
NR 35
TC 0
Z9 0
U1 1
U2 1
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2162-3279
J9 BRAIN BEHAV
JI Brain Behav.
PD JUL
PY 2016
VL 6
IS 7
AR e00483
DI 10.1002/brb3.483
PG 12
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA DR6VP
UT WOS:000380039700013
PM 27247853
ER
PT J
AU Chan, JM
Darke, AK
Penney, KL
Tangen, CM
Goodman, PJ
Lee, GSM
Sun, T
Peisch, S
Tinianow, AM
Rae, JM
Klein, EA
Thompson, IM
Kantoff, PW
Mucci, LA
AF Chan, June M.
Darke, Amy K.
Penney, Kathryn L.
Tangen, Catherine M.
Goodman, Phyllis J.
Lee, Gwo-Shu Mary
Sun, Tong
Peisch, Sam
Tinianow, Alex M.
Rae, James M.
Klein, Eric A.
Thompson, Ian M., Jr.
Kantoff, Philip W.
Mucci, Lorelei A.
TI Selenium- or Vitamin E-Related Gene Variants, Interaction with
Supplementation, and Risk of High-Grade Prostate Cancer in SELECT
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MANGANESE SUPEROXIDE-DISMUTASE;
PREVENTION TRIAL SELECT; E TRANSPORT GENES; DNA-REPAIR GENES; OXIDATIVE
STRESS; ALPHA-TOCOPHEROL; PLASMA SELENIUM; ANTIOXIDANT DEFENSE; ANDROGEN
RECEPTOR
AB Background: Epidemiologic studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E.
Methods: We undertook a case-cohort study of SELECT participants randomized to placebo, selenium, or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N = 278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics.
Results: We noted statistically significant (P < 0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2, and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA. In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome.
Conclusion: Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man's response to vitamin E or selenium supplementation with regards to these risks.
Impact: The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. (C)2016 AACR.
C1 [Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Chan, June M.] Univ Calif San Francisco, Dept Urol, 1450 3rd St,MC 3110, San Francisco, CA 94158 USA.
[Darke, Amy K.; Tangen, Catherine M.; Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Penney, Kathryn L.; Tinianow, Alex M.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Penney, Kathryn L.; Peisch, Sam; Mucci, Lorelei A.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA.
[Lee, Gwo-Shu Mary; Sun, Tong; Kantoff, Philip W.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Rae, James M.] Univ Michigan, Dept Internal Med, Ctr Canc, Div Hematol Oncol, Ann Arbor, MI 48109 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Thompson, Ian M., Jr.] Univ Texas Hlth Sci Ctr San Antonio, Canc Therapy & Res Ctr, San Antonio, TX 78229 USA.
[Kantoff, Philip W.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
RP Chan, JM (reprint author), Univ Calif San Francisco, Dept Urol, 1450 3rd St,MC 3110, San Francisco, CA 94158 USA.
EM June.chan@ucsf.edu
FU NIH [R01 CA106947-01A1]; Public Health Service grant from the National
Cancer Institute [U10 CA37429, UM1 CA182883]
FX The trial was funded by NIH R01 CA106947-01A1 (to J.M. Chan) and in part
by Public Health Service grants U10 CA37429 (to A.K. Darke, E.A. Klein,
I.M. Thompson, C.M. Tangen, J.M. Rae, and P.J. Goodman) and UM1 CA182883
(to I.M. Thompson, C.M. Tangen, A.K. Darke, P.J. Goodman) from the
National Cancer Institute.
NR 62
TC 1
Z9 1
U1 8
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2016
VL 25
IS 7
BP 1050
EP 1058
DI 10.1158/1055-9965.EPI-16-0104
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DR7IH
UT WOS:000380072700006
PM 27197287
ER
PT J
AU Childs, EJ
Chaffee, KG
Gallinger, S
Syngal, S
Schwartz, AG
Cote, ML
Bondy, ML
Hruban, RH
Chanock, SJ
Hoover, RN
Fuchs, CS
Rider, DN
Amundadottir, LT
Stolzenberg-Solomon, R
Wolpin, BM
Risch, HA
Goggins, MG
Petersen, GM
Klein, AP
AF Childs, Erica J.
Chaffee, Kari G.
Gallinger, Steven
Syngal, Sapna
Schwartz, Ann G.
Cote, Michele L.
Bondy, Melissa L.
Hruban, Ralph H.
Chanock, Stephen J.
Hoover, Robert N.
Fuchs, Charles S.
Rider, David N.
Amundadottir, Laufey T.
Stolzenberg-Solomon, Rachael
Wolpin, Brian M.
Risch, Harvey A.
Goggins, Michael G.
Petersen, Gloria M.
Klein, Alison P.
TI Association of Common Susceptibility Variants of Pancreatic Cancer in
Higher-Risk Patients: A PACGENE Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; FAMILY-HISTORY; ONSET; LOCI; EPIDEMIOLOGY;
CONSORTIUM; MUTATIONS; KINDREDS; GENE
AB Individuals from pancreatic cancer families are at increased risk, not only of pancreatic cancer, but also of melanoma, breast, ovarian, and colon cancers. While some of the increased risk may be due to mutations in high-penetrance genes (i.e., BRCA2, PALB2, ATM, p16/CDKN2A or DNA mismatch repair genes), common genetic variants may also be involved. In a high-risk population of cases with either a family history of pancreatic cancer or early-onset pancreatic cancer (diagnosis before the age of 50 years), we examined the role of genetic variants previously associated with risk of pancreatic, breast, ovarian, or prostate cancer. We genotyped 985 cases (79 early-onset cases, 906 cases with a family history of pancreatic cancer) and 877 controls for 215,389 SNPs using the iSelect Collaborative Oncological Gene-Environment Study (iCOGS) array with custom content. Logistic regression was performed using a log-linear additive model. We replicated several previously reported pancreatic cancer susceptibility loci, including recently identified variants on 2p13.3 and 7p13 (2p13.3, rs1486134: OR = 1.36; 95% CI, 1.13-1.63; P = 9.29 x 10(-4); 7p13, rs17688601: OR = 0.76; 95% CI, 0.63-0.93; P = 6.59 x 10(-3)). For the replicated loci, the magnitude of association observed in these high-risk patients was similar to that observed in studies of unselected patients. In addition to the established pancreatic cancer loci, we also found suggestive evidence of association (P < 5 < 10(-5)) to pancreatic cancer for SNPs atHDAC9(7p21.1) and COL6A2 (21q22.3). Even in high-risk populations, common variants influence pancreatic cancer susceptibility. (C) 2016 AACR.
C1 [Childs, Erica J.; Hruban, Ralph H.] Johns Hopkins Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Chaffee, Kari G.; Rider, David N.; Petersen, Gloria M.] Mayo Clin, Dept Hlth Sci Res, Coll Med, Rochester, MN USA.
[Gallinger, Steven] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Populat Sci, 75 Francis St, Boston, MA 02115 USA.
[Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Schwartz, Ann G.; Cote, Michele L.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
[Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Detroit, MI USA.
[Bondy, Melissa L.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Hruban, Ralph H.; Goggins, Michael G.; Klein, Alison P.] Johns Hopkins Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA.
[Chanock, Stephen J.; Hoover, Robert N.; Amundadottir, Laufey T.; Stolzenberg-Solomon, Rachael] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Fuchs, Charles S.; Wolpin, Brian M.] Harvard Med Sch, Boston, MA USA.
[Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Risch, Harvey A.] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
RP Klein, AP (reprint author), Johns Hopkins Sch Med, 354 CRB2,1550 Orleans St, Baltimore, MD 21231 USA.
EM aklein1@jhmi.edu
RI Gallinger, Steven/E-4575-2013
FU NIH [R01 CA97075, R01 CA154823, K07 CA140790]; NIH Specialized Programs
of Research Excellence [P50 CA062924, P50 CA102701]; Lustgarten
Foundation for Pancreatic Cancer Research; Michael Rolfe Foundation; Sol
Goldman Pancreatic Cancer Research Center; European Community [223175
(HEALTHF22009223175)]; Cancer Research UK [C1287/A10710]
FX This work was supported by NIH grants R01 CA97075 (to K.G. Chaffee, S.
Gallinger, S. Syngal, A.G. Schwartz, M.L. Cote, R.H. Hruban, D.N. Rider,
M.G. Goggins, G.M. Petersen, and A.P. Klein) and R01 CA154823 (to E.J.
Childs, K.G. Chaffee, S. Gallinger, H.A. Risch, M.G. Goggins, G.M.
Petersen, and A.P. Klein) and NIH Specialized Programs of Research
Excellence P50 CA062924 (to R.H. Hruban, M.G. Goggins, A.P. Klein) and
P50 CA102701 (K.G. Chaffee, D.N. Rider, G.M. Petersen), the Lustgarten
Foundation for Pancreatic Cancer Research (to R.H. Hruban, M.G. Goggins,
A.P. Klein), the Michael Rolfe Foundation (to R.H. Hruban, M.G.
Goggins), Susan Wojcicki and Dennis Troper (to R.H. Hruban, M.G.
Goggins, A.P. Klein), and the Sol Goldman Pancreatic Cancer Research
Center (to R.H. Hruban, M.G. Goggins, A.P. Klein). B.M. Wolpin was
supported by NIH under grant no. K07 CA140790. The development of the
iCOGS array was supported by the European Community's Seventh Framework
Programme under grant agreement 223175 (HEALTHF22009223175) and Cancer
Research UK (C1287/A10710).
NR 25
TC 1
Z9 1
U1 1
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD JUL
PY 2016
VL 25
IS 7
BP 1185
EP 1191
DI 10.1158/1055-9965.EPI-15-1217
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DR7IH
UT WOS:000380072700022
PM 27197284
ER
PT J
AU Tariman, JD
Gleason, C
Faiman, B
Doss, D
Catamero, D
Bishop-Royse, J
Katz, M
Kurtin, S
Moran, D
Lonial, S
AF Tariman, Joseph D.
Gleason, Charise
Faiman, Beth
Doss, Deborah
Catamero, Donna
Bishop-Royse, Jessica
Katz, Mike
Kurtin, Sandra
Moran, Diane
Lonial, Sagar
CA IMF Nurse Leadership Board
TI Lack of health maintenance examinations and risk in myeloma patients
SO CANCER MEDICINE
LA English
DT Article
DE Cancer; health maintenance; health promotion; multiple myeloma;
preventive health services; survivors
ID STEM-CELL TRANSPLANTATION; MULTIPLE-MYELOMA; CANCER SURVIVORS;
PROSTATE-CANCER; PREVENTIVE CARE; HEART-DISEASE; OLDER-ADULTS;
BEHAVIORS; MORTALITY; WOMEN
AB Health maintenance (HM) practices are essential to prevent illness, promote well-being, and maximize health. Patients with multiple myeloma (MM) are at increased risk for cardiovascular disease and cancers, yet, research on HM practices and preventative care of MM survivors has limited report. The study comprised a descriptive, correlational, and cross-sectional online survey design. Survey of patients with MM was carried out through the International Myeloma Foundation (IMF) and the Association of Cancer Online Resources (ACOR) e-mail list services. The members of the IMF and ACOR e-mail list services were surveyed, of which 237 patients responded. The modified Medical Expenditure Preventive Survey-Preventive Care questionnaire was used; it included items that ask patients regarding their healthcare practices that relate to dental care, cancer prevention, addiction, lifestyles, sensory screening, immunizations, cardiovascular, endocrine, psychosocial, and bone health. Descriptive statistics, Pearson's chi-square, and Spearman's rho correlation coefficient were obtained. In this study, men had statistically significant inferior global health maintenance scores than women (P = 0.002). Being employed (P = 0.054) and married or partnered (P = 0.017) were significantly correlated with better health maintenance patterns among male respondents. In contrast, no statistically significant correlations between sociodemographic factors and health maintenance patterns were found in women. Patients with MM, particularly men, require continued education and close monitoring of health maintenance practices. These findings are consistent with publications looking at gender disparities in healthcare utilization in the United States. Studies show that men, in general, are less likely to seek preventative healthcare screenings. Healthcare providers must incorporate health maintenance promotion during clinic visits.
C1 [Tariman, Joseph D.] Depaul Univ, Coll Sci & Hlth, Chicago, IL 60604 USA.
[Gleason, Charise; Lonial, Sagar] Emory Univ, Myeloma Program, Atlanta, GA 30322 USA.
[Faiman, Beth] Cleveland Clin Fdn, Myeloma Program, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Doss, Deborah] Dana Farber Canc Inst, Jerome Lipper Inst Myeloma, Boston, MA 02115 USA.
[Catamero, Donna] Mt Sinai Hosp, New York, NY 10029 USA.
[Bishop-Royse, Jessica] Depaul Univ, Social Sci Res Ctr, Chicago, IL 60604 USA.
[Katz, Mike; Moran, Diane; IMF Nurse Leadership Board] Int Myeloma Fdn, Los Angeles, CA USA.
[Katz, Mike; Moran, Diane] Int Myeloma Fdn Nurse Leadership Board, Los Angeles, CA USA.
[Kurtin, Sandra] Univ Arizona, Dept Hematol Oncol, Tucson, AZ USA.
RP Tariman, JD (reprint author), Depaul Univ, Coll Sci & Hlth, Chicago, IL 60604 USA.
EM jtariman@depaul.edu
NR 35
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD JUL
PY 2016
VL 5
IS 7
BP 1425
EP 1435
DI 10.1002/cam4.716
PG 11
WC Oncology
SC Oncology
GA DR6ZD
UT WOS:000380048900008
PM 27119422
ER
PT J
AU Key, NS
Khorana, AA
Mackman, N
McCarty, OJT
White, GC
Francis, CW
McCrae, KR
Palumbo, JS
Raskob, GE
Chan, AT
Sood, AK
AF Key, Nigel S.
Khorana, Alok A.
Mackman, Nigel
McCarty, Owen J. T.
White, Gilbert C.
Francis, Charles W.
McCrae, Keith R.
Palumbo, Joseph S.
Raskob, Gary E.
Chan, Andrew T.
Sood, Anil K.
TI Thrombosis in Cancer: Research Priorities Identified by a National
Cancer Institute/National Heart, Lung, and Blood Institute Strategic
Working Group
SO CANCER RESEARCH
LA English
DT Editorial Material
ID HOSPITALIZED MEDICAL PATIENTS; ACUTE VENOUS THROMBOEMBOLISM; TISSUE
FACTOR; ORAL RIVAROXABAN; TUMOR-CELLS; MICROPARTICLES; SURGERY;
THROMBOPROPHYLAXIS; COAGULATION; PROPHYLAXIS
AB The risk for venous thromboembolism (VTE) is increased in cancer and particularly with chemotherapy, and it portends poorer survival among patients with cancer. However, many fundamental questions about cancer-associated VTE, or Trousseau syndrome, remain unanswered. This report summarizes the proceedings of a working group assembled by the NCI and NHLBI in August 2014 to explore the state of the science in cancer-associated VTE, identify clinically important research gaps, and develop consensus on priorities for future research. Representing a convergence of research priorities between the two NIH Institutes, the workshop addressed epidemiologic, basic science, clinical, and translational issues in cancer-associated VTE. (C) 2016 AACR.
C1 [Key, Nigel S.; Mackman, Nigel] Univ North Carolina Chapel Hill, Div Hematol Oncol, Chapel Hill, NC 27599 USA.
[Khorana, Alok A.; McCrae, Keith R.] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Oncol, Cleveland, OH USA.
[McCarty, Owen J. T.] Oregon Hlth & Sci Univ, Dept Biomed Engn & Cell & Dev Biol, Portland, OR USA.
[White, Gilbert C.] Med Coll Wisconsin, Blood Res Inst, Blood Ctr Wisconsin, Dept Med Biochem & Pharmacol, Milwaukee, WI 53226 USA.
[Francis, Charles W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA.
[Francis, Charles W.] Univ Rochester, Dept Med, Rochester, NY USA.
[McCrae, Keith R.] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.
[Palumbo, Joseph S.] Cincinnati Childrens Hosp Med Ctr, Div Hematol, Cincinnati, OH 45229 USA.
[Raskob, Gary E.] Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Biostat & Epidemiol, Oklahoma City, OK USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA.
[Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA.
RP Key, NS (reprint author), Univ North Carolina Chapel Hill, 1079 Genet Med Bldg,Campus Box 7035, Chapel Hill, NC 27599 USA.
EM nigel_key@med.unc.edu
FU NCATS NIH HHS [UL1 TR001425]
NR 36
TC 2
Z9 2
U1 1
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD JUL 1
PY 2016
VL 76
IS 13
BP 3671
EP 3675
DI 10.1158/0008-5472.CAN-15-3100
PG 5
WC Oncology
SC Oncology
GA DR7HU
UT WOS:000380071400004
PM 27527638
ER
PT J
AU Sampaio, A
Moreira, PS
Osorio, A
Magalhaes, R
Vasconcelos, C
Fernandez, M
Carracedo, A
Alegria, J
Goncalves, OF
Soares, JM
AF Sampaio, Adriana
Moreira, Pedro Silva
Osorio, Ana
Magalhaes, Ricardo
Vasconcelos, Cristiana
Fernandez, Montse
Carracedo, Angel
Alegria, Joana
Goncalves, Oscar F.
Soares, Jose Miguel
TI Altered functional connectivity of the default mode network in Williams
syndrome: a multimodal approach
SO DEVELOPMENTAL SCIENCE
LA English
DT Article
ID RESTING-STATE NETWORKS; POSTERIOR CINGULATE CORTEX; SOCIAL COGNITION;
VISUOSPATIAL COGNITION; BRAIN; MRI; AUTISM; ABNORMALITIES; ANATOMY; TASK
AB Resting state brain networks are implicated in a variety of relevant brain functions. Importantly, abnormal patterns of functional connectivity (FC) have been reported in several neurodevelopmental disorders. In particular, the Default Mode Network (DMN) has been found to be associated with social cognition. We hypothesize that the DMN may be altered in Williams syndrome (WS), a neurodevelopmental genetic disorder characterized by an unique cognitive and behavioral phenotype. In this study, we assessed the architecture of the DMN using fMRI in WS patients and typically developing matched controls (sex and age) in terms of FC and volumetry of the DMN. Moreover, we complemented the analysis with a functional connectome approach. After excluding participants due to movement artifacts (n=3), seven participants with WS and their respective matched controls were included in the analyses. A decreased FC between the DMN regions was observed in the WS group when compared with the typically developing group. Specifically, we found a decreased FC in a posterior hub of the DMN including the precuneus, calcarine and the posterior cingulate of the left hemisphere. The functional connectome approach showed a focalized and global increased FC connectome in the WS group. The reduced FC of the posterior hub of the DMN in the WS group is consistent with immaturity of the brain FC patterns and may be associated with the singularity of their visual spatial phenotype.
C1 [Sampaio, Adriana; Osorio, Ana; Alegria, Joana; Goncalves, Oscar F.] Univ Minho, Sch Psychol, Neuropsychophysiol Lab, CIPsi, Braga, Portugal.
[Moreira, Pedro Silva; Magalhaes, Ricardo; Soares, Jose Miguel] Univ Minho, Sch Hlth Sci, Life & Hlth Sci Res Inst ICVS, Braga, Portugal.
[Moreira, Pedro Silva; Magalhaes, Ricardo; Soares, Jose Miguel] ICVS 3Bs PT Govt Associate Lab, Braga, Portugal.
[Osorio, Ana] Univ Prebiteriana Mackenzie, Social & Cognit Neurosci Lab, Postgrad Program Dev Disorders, Ctr Biol & Hlth Sci, Sao Paulo, Brazil.
[Fernandez, Montse; Carracedo, Angel] Univ Santiago de Compostela, Mol Genet Unit, Galician Publ Fdn Genom Med, Santiago De Compostela, Spain.
[Vasconcelos, Cristiana] Hosp Santo Antonio, Dept Neuroradiol, CHP, Oporto, Portugal.
[Goncalves, Oscar F.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr, Boston, MA USA.
[Goncalves, Oscar F.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Goncalves, Oscar F.] Northeastern Univ, Dept Appl Psychol, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
RP Sampaio, A (reprint author), Univ Minho, Sch Psychol, P-4710057 Braga, Portugal.
EM adriana.sampaio@psi.uminho.pt
RI Goncalves, Oscar/G-5278-2010
OI Goncalves, Oscar/0000-0003-2735-9155
FU FEDER funds through the Competitive Factors Operational Programme -
COMPETE; Portuguese Foundation for Science and Technology
[PTDC/PSI-PCL/115316/2009]; Portuguese Foundation for Science and
Technology; Portuguese Ministry of Education and Science; FEDER under
the PT2020 Partnership Agreement [UID/PSI/01662/2013]
FX We are thankful to all study participants. This research was supported
by FEDER funds through the Competitive Factors Operational Programme -
COMPETE, by national funds from the Portuguese Foundation for Science
and Technology (grant PTDC/PSI-PCL/115316/2009). This study was
partially conducted at the Psychology Research Centre, University of
Minho, and supported by the Portuguese Foundation for Science and
Technology and the Portuguese Ministry of Education and Science through
national funds and when applicable co-financed by FEDER under the PT2020
Partnership Agreement (UID/PSI/01662/2013).
NR 68
TC 0
Z9 0
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1363-755X
EI 1467-7687
J9 DEVELOPMENTAL SCI
JI Dev. Sci.
PD JUL
PY 2016
VL 19
IS 4
SI SI
BP 686
EP 695
DI 10.1111/desc.12443
PG 10
WC Psychology, Developmental; Psychology, Experimental
SC Psychology
GA DR5OK
UT WOS:000379952100011
PM 27412230
ER
PT J
AU Ogino, S
Nishihara, R
Vander Weele, TJ
Wang, ML
Nishi, A
Lochhead, P
Qian, ZR
Zhang, XH
Wu, KN
Nan, HM
Yoshida, K
Milner, DA
Chan, AT
Field, AE
Camargo, CA
Williams, MA
Giovannucci, EL
AF Ogino, Shuji
Nishihara, Reiko
Vander Weele, Tyler J.
Wang, Molin
Nishi, Akihiro
Lochhead, Paul
Qian, Zhi Rong
Zhang, Xuehong
Wu, Kana
Nan, Hongmei
Yoshida, Kazuki
Milner, Danny A., Jr.
Chan, Andrew T.
Field, Alison E.
Camargo, Carlos A., Jr.
Williams, Michelle A.
Giovannucci, Edward L.
TI The Role of Molecular Pathological Epidemiology in the Study of
Neoplastic and Non-neoplastic Diseases in the Era of Precision Medicine
SO EPIDEMIOLOGY
LA English
DT Review
ID ISLAND METHYLATOR PHENOTYPE; COLORECTAL-CANCER RISK; UNIQUE TUMOR
PRINCIPLE; LIFE-STYLE FACTORS; BODY-MASS INDEX;
MICROSATELLITE-INSTABILITY; FAMILY-HISTORY; CLINICOPATHOLOGICAL FACTORS;
PERSONALIZED MEDICINE; CELLULAR-METABOLISM
AB Molecular pathology diagnostics to subclassify diseases based on pathogenesis are increasingly common in clinical translational medicine. Molecular pathological epidemiology (MPE) is an integrative transdisciplinary science based on the unique disease principle and the disease continuum theory. While it has been most commonly applied to research on breast, lung, and colorectal cancers, MPE can investigate etiologic heterogeneity in non-neoplastic diseases, such as cardiovascular diseases, obesity, diabetes mellitus, drug toxicity, and immunity-related and infectious diseases. This science can enhance causal inference by linking putative etiologic factors to specific molecular biomarkers as outcomes. Technological advances increasingly enable analyses of various -omics, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, metagenomics, microbiome, immunomics, interactomics, etc. Challenges in MPE include sample size limitations (depending on availability of biospecimens or biomedical/radiological imaging), need for rigorous validation of molecular assays and study findings, and paucities of interdisciplinary experts, education programs, international forums, and standardized guidelines. To address these challenges, there are ongoing efforts such as multidisciplinary consortium pooling projects, the International Molecular Pathological Epidemiology Meeting Series, and the Strengthening the Reporting of Observational Studies in Epidemiology-MPE guideline project. Efforts should be made to build biorepository and biobank networks, and worldwide population-based MPE databases. These activities match with the purposes of the Big Data to Knowledge (BD2K), Genetic Associations and Mechanisms in Oncology (GAME-ON), and Precision Medicine Initiatives of the United States National Institute of Health. Given advances in biotechnology, bioinformatics, and computational/systems biology, there are wide open opportunities in MPE to contribute to public health.
C1 [Ogino, Shuji; Nishihara, Reiko; Vander Weele, Tyler J.; Wang, Molin; Yoshida, Kazuki; Field, Alison E.; Camargo, Carlos A., Jr.; Williams, Michelle A.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA.
[Ogino, Shuji; Milner, Danny A., Jr.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Ogino, Shuji; Nishihara, Reiko; Qian, Zhi Rong; Zhang, Xuehong; Yoshida, Kazuki; Milner, Danny A., Jr.; Chan, Andrew T.; Field, Alison E.; Camargo, Carlos A., Jr.; Giovannucci, Edward L.] Harvard Med Sch, Boston, MA USA.
[Ogino, Shuji; Nishihara, Reiko; Qian, Zhi Rong] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Nishihara, Reiko; Wu, Kana; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Nishihara, Reiko; Vander Weele, Tyler J.; Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Nishi, Akihiro] Yale Univ, Yale Inst Network Sci, New Haven, CT USA.
[Lochhead, Paul] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland.
[Lochhead, Paul; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Zhang, Xuehong; Chan, Andrew T.; Field, Alison E.; Camargo, Carlos A., Jr.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Nan, Hongmei] Indiana Univ, Melvin & Bren Simon Canc Ctr, Richard M Fairbanks Sch Publ, Dept Epidemiol, Indianapolis, IN 46204 USA.
[Yoshida, Kazuki] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA.
[Milner, Danny A., Jr.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA.
[Field, Alison E.] Boston Childrens Hosp, Div Adolescent Young Adult Med, Boston, MA USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Ogino, S (reprint author), Brigham & Womens Hosp, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,Room M422, Boston, MA 02215 USA.
EM shuji_ogino@dfci.harvard.edu
FU USA National Institute of Health (NIH) [R35 CA197735, R01 CA151993, K07
CA190673, R01 CA137178, K24 DK098311]; Japan Society for Promotion of
Science
FX Supported by grants from the USA National Institute of Health (NIH) (R35
CA197735 [to SO], R01 CA151993 [to SO], K07 CA190673 [to RN], R01
CA137178 [to ATC], and K24 DK098311 [to ATC]). AN was supported by a
Fellowship Grant from Japan Society for Promotion of Science. PL is a
Scottish Government Clinical Academic Fellow. ATC is Damon Runyon
Clinical Investigator. The content is solely the responsibility of the
authors and does not necessarily represent the official views of NIH.
Funding agencies did not have any role in the decision to submit the
manuscript for publication, or the writing of the manuscript.
NR 100
TC 18
Z9 18
U1 17
U2 28
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD JUL
PY 2016
VL 27
IS 4
BP 602
EP 611
DI 10.1097/EDE.0000000000000471
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DR4BX
UT WOS:000379847600026
PM 26928707
ER
PT J
AU Styer, AK
Luke, B
Vitek, W
Christianson, MS
Baker, VL
Christy, AY
Polotsky, AJ
AF Styer, Aaron K.
Luke, Barbara
Vitek, Wendy
Christianson, Mindy S.
Baker, Valerie L.
Christy, Alicia Y.
Polotsky, Alex J.
TI Factors associated with the use of elective single-embryo transfer and
pregnancy outcomes in the United States, 2004-2012
SO FERTILITY AND STERILITY
LA English
DT Article; Proceedings Paper
CT 71st Annual Meeting of the American-Society-for-Reproductive-Medicine
CY OCT 17-21, 2015
CL Baltimore, MD
SP Amer Soc Reprod Med
DE Assisted reproductive technology; elective single-embryo transfer; in
vitro fertilization; multiple pregnancy
ID IN-VITRO FERTILIZATION; ASSISTED REPRODUCTIVE TECHNOLOGY; MULTIPLE
BIRTHS; PERINATAL OUTCOMES; LIVE-BIRTH; TRANSFER POLICY; TRANSFER ESET;
NUMBER; RATES; CRYOPRESERVATION
AB Objective: To evaluate factors associated with elective single-embryo transfer (eSET) utilization and its effect on assisted reproductive technology outcomes in the United States.
Design: Historical cohort.
Setting: Not applicable.
Patient(s): Fresh IVF cycles of women aged 18-37 years using autologous oocytes with either one (SET) or two (double-embryo transfer [DET]) embryos transferred and reported to the Society for Assisted Reproductive Technology Clinic Outcome Reporting System between 2004 and 2012. Cycles were categorized into four groups with ([+]) or without ([-]) supernumerary embryos cryopreserved. The SET group with embryos cryopreserved was designated as eSET.
Intervention(s): None.
Main Outcomes Measure(s): The likelihood of eSET utilization, live birth, and singleton non-low birth weight term live birth, modeled using logistic regression. Presented as adjusted odds ratios (aORs) and 95% confidence intervals (CIs).
Result(s): The study included 263,375 cycles (21,917 SET[-] cryopreservation, 20,996 SET[+] cryopreservation, 103,371 DET[-] cryopreservation, and 117,091 DET[+] cryopreservation). The utilization of eSET (SET[+] cryopreservation) increased from 1.8% in 2004 to 14.9% in 2012 (aOR 7.66, 95% CI 6.87-8.53) and was more likely with assisted reproductive technology insurance coverage (aOR 1.60, 95% CI 1.54-1.66), Asian race (aOR 1.26, 95% CI 1.20-1.33), uterine factor diagnosis (aOR 1.48, 95% CI 1.37-1.59), retrieval of >= 16 oocytes (aOR 2.85, 95% CI 2.55-3.19), and the transfer of day 5-6 embryos (aOR 4.23, 95% CI 4.06-4.40); eSET was less likely in women aged 35-37 years (aOR 0.76, 95% CI 0.73-0.80). Compared with DET cycles, the likelihood of the ideal outcome, term non-low birth weight singleton live birth, was increased 45%-52% with eSET.
Conclusion(s): Expanding insurance coverage for IVF would facilitate the broader use of eSET and may reduce the morbidity and healthcare costs associated with multiple pregnancies. (C) 2016 by American Society for Reproductive Medicine.
C1 [Styer, Aaron K.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA 02114 USA.
[Styer, Aaron K.] Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA USA.
[Luke, Barbara] Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, E Lansing, MI 48824 USA.
[Vitek, Wendy] Univ Rochester, Dept Obstet & Gynecol, Sch Med, Rochester, NY USA.
[Christianson, Mindy S.] Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA.
[Baker, Valerie L.] Stanford Univ, Sch Med, Dept Obstet & Gynecol, Palo Alto, CA 94304 USA.
[Christy, Alicia Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Polotsky, Alex J.] Univ Colorado, Sch Med, Dept Obstet & Gynecol, Aurora, CO USA.
RP Styer, AK (reprint author), Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Reprod Med, Yaw 10A,55 Fruit St, Boston, MA 02114 USA.; Styer, AK (reprint author), Massachusetts Gen Hosp, IVF, Yaw 10A,55 Fruit St, Boston, MA 02114 USA.
EM astyer@mgh.harvard.edu
OI Luke, Barbara/0000-0002-0405-8133
FU NICHD NIH HHS [R25 HD075737]
NR 48
TC 1
Z9 1
U1 3
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2016
VL 106
IS 1
BP 80
EP 89
DI 10.1016/j.fertnstert.2016.02.034
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DR7HY
UT WOS:000380071800016
PM 26997248
ER
PT J
AU Lee, MS
Evans, BT
Stern, AD
Hornstein, MD
AF Lee, Malinda S.
Evans, Brady T.
Stern, Ariel D.
Hornstein, Mark D.
TI Economic implications of the Society for Assisted Reproductive
Technology embryo transfer guidelines: healthcare dollars saved by
reducing iatrogenic triplets
SO FERTILITY AND STERILITY
LA English
DT Article
DE Economic; embryo transfer; healthcare spending; in vitro fertilization;
multiple gestation
ID MULTIPLE BIRTHS; UNITED-STATES; PREGNANCY; COVERAGE; COST
AB Objective: To estimate the national cost savings resulting from reductions in higher-order multiple (HOM) live births (defined as three or more fetuses), following the initial publication of the Society for Assisted Reproductive Technology (SART) guidelines on ET in 1998.
Design: Descriptive use and cost analysis.
Setting: Not applicable.
Patient(s): Not applicable.
Intervention(s): Not applicable.
Main Outcome Measure(s): Estimates of the total number of HOM deliveries prevented (from 1998-2012) following the publication of SART guidelines; the associated healthcare savings (2014 US dollars).
Result(s): A singleton live birth was estimated to cost $17,100-$ 24,200. A twin live birth was estimated at $66,000-$117,500. A triplet live birth was estimated at $190,800-$456,300. The percentage of HOM gestations among all ART pregnancies decreased from 11.4% in 1997 to 2.0% in 2012, with the sharpest year-over-year decline of 20.3% occurring in the year following the publication of the guidelines. The number of prevented HOM deliveries from 1998 through 2012 was estimated to be between 13,500 and 16,300, corresponding to cost savings of $6.02B (billion) (range, $2.35B-$7.03B, 2014 US dollars).
Conclusion(s): Iatrogenic HOM gestations represent a substantial economic burden to our healthcare system. The introduction of guidelines for ET in 1998 coincided with a dramatic decrease in the HOM rate in subsequent years and an associated cumulative cost savings of more than $6B. Further reductions in HOM gestations could save up to an additional $2B annually. (C) 2016 by American Society for Reproductive Medicine.
C1 [Lee, Malinda S.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Integrated Residency Program Obstet & Gynecol, Boston, MA 02114 USA.
[Lee, Malinda S.; Evans, Brady T.; Hornstein, Mark D.] Harvard Med Sch, Boston, MA USA.
[Evans, Brady T.] Harvard Combined Orthopaed Residency Program, Boston, MA USA.
[Stern, Ariel D.] Harvard Sch Business, Boston, MA USA.
[Hornstein, Mark D.] Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA.
RP Hornstein, MD (reprint author), Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA.
EM mhornstein@partners.org
OI Stern, Ariel Dora/0000-0002-3586-1041
FU National Institute on Aging; Genetics; IVF Institute
FX A.D.S. reports grants from the National Institute on Aging. M.D.H. is on
the Medical Advisory Board of WINFertility; is a paid author for
UpToDate; and has received speaker fees from the Genetics and IVF
Institute. M.S.L. has nothing to disclose. B.T.E. has nothing to
disclose.
NR 25
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD JUL
PY 2016
VL 106
IS 1
BP 189
EP +
DI 10.1016/j.fertnstert.2016.03.014
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DR7HY
UT WOS:000380071800031
PM 27037461
ER
PT J
AU Dyson, NJ
AF Dyson, Nicholas J.
TI RB1: a prototype tumor suppressor and an enigma
SO GENES & DEVELOPMENT
LA English
DT Review
DE cell proliferation; E2F; tumor suppressor; pRB
ID KINASE 4/6 INHIBITOR; RETINOBLASTOMA GENE-PRODUCT; ADVANCED
BREAST-CANCER; CELL-CYCLE INHIBITION; PROMOTES GENOMIC INSTABILITY;
PRB-DEFICIENT CELLS; CHROMOSOMAL INSTABILITY; MITOCHONDRIAL-FUNCTION;
THERAPEUTIC RESPONSE; SUSCEPTIBILITY GENE
AB The retinoblastoma susceptibility gene (RB1) was the first tumor suppressor gene to be molecularly defined. RB1 mutations occur in almost all familial and sporadic forms of retinoblastoma, and this gene is mutated at variable frequencies in a variety of other human cancers. Because of its early discovery, the recessive nature of RB1 mutations, and its frequency of inactivation, RB1 is often described as a prototype for the class of tumor suppressor genes. Its gene product (pRB) regulates transcription and is a negative regulator of cell proliferation. Although these general features are well established, a precise description of pRB's mechanism of action has remained elusive. Indeed, in many regards, pRB remains an enigma. This review summarizes some recent developments in pRB research and focuses on progress toward answers for the three fundamental questions that sit at the heart of the pRB literature: What does pRB do? How does the inactivation of RB change the cell? How can our knowledge of RB function be exploited to provide better treatment for cancer patients?
C1 [Dyson, Nicholas J.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
RP Dyson, NJ (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA.
EM dyson@helix.mgh.harvard.edu
FU National Institutes of Health [R01 CA163698, R01 GM117413]; Ricbac
Foundation; Massachusetts General Hospital Executive Committee on
Research scholar's program
FX I thank Maxim Frolov, Elizaveta Benevolenskaya, Fred Dick, Benjamin
Drapkin, Ioannis Sanidas, and Wayne Miles for their insights and helpful
advice with this review. I am especially grateful to Ed Harlow for
inspiring an enduring fascination in RB, and Alan Dyson, Ann Dyson, and
Sue Lucas for their unwavering trust in the value of research, even as
they lost their lives to cancer. RB research in my laboratory is
supported by grants from the National Institutes of Health (R01 CA163698
and R01 GM117413), by The Ricbac Foundation, and by sponsorship from
James and Shirley Curvey through the Massachusetts General Hospital
Executive Committee on Research scholar's program.
NR 150
TC 4
Z9 4
U1 16
U2 17
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD JUL 1
PY 2016
VL 30
IS 13
BP 1492
EP 1502
DI 10.1101/gad.282145.116
PG 11
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DR8VW
UT WOS:000380177300003
PM 27401552
ER
PT J
AU Dowen, RH
Breen, PC
Tullius, T
Conery, AL
Ruvkun, G
AF Dowen, Robert H.
Breen, Peter C.
Tullius, Thomas
Conery, Annie L.
Ruvkun, Gary
TI A microRNA program in the C-elegans hypodermis couples to intestinal
mTORC2/PQM-1 signaling to modulate fat transport
SO GENES & DEVELOPMENT
LA English
DT Article
DE vitellogenesis; fat metabolism; microRNAs; insulin; mTORC2; pqm-1
ID MESSENGER-RNA TRANSLATION; CAENORHABDITIS-ELEGANS; LIFE-SPAN; TERMINAL
DIFFERENTIATION; DEVELOPMENTAL SWITCH; TRANSCRIPTION FACTOR; REGULATORY
GENES; BINDING PARTNER; STRESS-RESPONSE; PROTEIN
AB Animals integrate metabolic, developmental, and environmental information before committing key resources to reproduction. In Caenorhabditis elegans, adult animals transport fat from intestinal cells to the germline to promote reproduction. We identified a microRNA (miRNA)-regulated developmental timing pathway that functions in the hypodermis to nonautonomously coordinate the mobilization of intestinal fat stores to the germline upon initiation of adulthood. This developmental timing pathway, which is controlled by the lin-4 and let-7 miRNAs, engages mTOR signaling in the intestine. The intestinal signaling component is specific to mTORC2 and functions in parallel to the insulin pathway to modulate the activity of the serum/glucocorticoid-regulated kinase (SGK-1). Surprisingly, SGK-1 functions independently of DAF-16/FoxO; instead, SGK-1 promotes the cytoplasmic localization of the PQM-1 transcription factor, which antagonizes intestinal fat mobilization at the transcriptional level when localized to the nucleus. These results revealed that a non-cell-autonomous developmental input regulates intestinal fat metabolism by engaging mTORC2 signaling to promote the intertissue transport of fat reserves from the soma to the germline.
C1 [Dowen, Robert H.; Breen, Peter C.; Tullius, Thomas; Conery, Annie L.; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Dowen, Robert H.; Breen, Peter C.; Tullius, Thomas; Conery, Annie L.; Ruvkun, Gary] Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Ruvkun, G (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.
EM ruvkun@molbio.mgh.harvard.edu
FU National Institutes of Health Office of Research Infrastructure Programs
[P40 OD010440]; National Institute of Health [GM44619]
FX Some of the strains used in this work were provided by the
Caenorhabditis Genetics Center, which is supported by the National
Institutes of Health Office of Research Infrastructure Programs (P40
OD010440). The Pvit-3::GFP reporter strain (GR2122) was generated by
Justine Melo (Massachusetts General Hospital), and the
intestinal-specific RNAi strain (MGH171) was generously provided by Alex
Soukas (Massachusetts General Hospital). The transcription factor RNAi
sublibrary was constructed by Sean Curran (University of Southern
California) and Dave Simon (Josh Kaplan Laboratory, Massachusetts
General Hospital), the nuclear hormone receptor RNAi sublibrary was
constructed by Ho Yi Mak (Hong Kong University of Science and
Technology), the kinase RNAi sublibrary was constructed by Javier
Irazoqui (Massachusetts General Hospital), the RNA metabolism RNAi
sublibrary was constructed by Sylvia Fischer (Massachusetts General
Hospital) and John Kim (Johns Hopkins), and the gfp RNAi clone was
generated by Dorian Anderson (Josh Kaplan laboratory, Massachusetts
General Hospital). This work was funded in part by a grant to G.R. from
the National Institute of Health (GM44619). R.H.D. is an American Cancer
Society Postdoctoral Fellow (122240-PF-12-078-01-RMC).
NR 60
TC 1
Z9 1
U1 2
U2 7
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD JUL 1
PY 2016
VL 30
IS 13
BP 1515
EP 1528
DI 10.1101/gad.283895.116
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DR8VW
UT WOS:000380177300006
PM 27401555
ER
PT J
AU Saba, NF
Salama, JK
Beitler, JJ
Busse, PM
Cooper, JS
Jones, CU
Koyfman, S
Quon, H
Ridge, JA
Siddiqui, F
Worden, F
Yao, M
Yom, SS
AF Saba, Nabil F.
Salama, Joseph K.
Beitler, Jonathan J.
Busse, Paul M.
Cooper, Jay S.
Jones, Christopher U.
Koyfman, Shlomo
Quon, Harry
Ridge, John A.
Siddiqui, Farzan
Worden, Francis
Yao, Min
Yom, Sue S.
CA Expert Panel Radiation Oncology-He
TI ACR Appropriateness Criteria (R) for nasopharyngeal carcinoma
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE nasopharyngeal carcinoma (NPC); cancer of the nasopharynx; squamous cell
carcinoma of the nasopharynx; Appropriateness criteria for
nasopharyngeal cancer
ID INTENSITY-MODULATED RADIOTHERAPY; EPSTEIN-BARR-VIRUS; PROGRESSION-FREE
SURVIVAL; CONCURRENT CISPLATIN-RADIOTHERAPY; PLATINUM-BASED
CHEMOTHERAPY; SQUAMOUS-CELL-CARCINOMA; III RANDOMIZED-TRIAL; LOW-RISK
POPULATION; QUALITY-OF-LIFE; PHASE-II
AB Background. Nasopharyngeal carcinoma (NPC) presents mostly with locally advanced disease and is treated with multimodal therapy; however, consensus is lacking for different clinical scenarios.
Methods. The American College of Radiology (ACR) Appropriateness Criteria (R) are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
Results. The ACR Expert Panel on Radiation Oncology - Head and Neck Cancer developed consensus recommendations for guiding management of nasopharyngeal carcinoma.
Conclusion. Multidisciplinary evaluation is essential to guiding the optimal use of surgery, radiation, and systemic therapy in this disease. (C) 2015 American College of Radiology
C1 [Saba, Nabil F.] Emory Univ, Atlanta, GA 30322 USA.
[Saba, Nabil F.; Worden, Francis] Amer Soc Clin Oncol, Alexandria, VA 22314 USA.
[Salama, Joseph K.] Duke Univ, Durham, NC USA.
[Beitler, Jonathan J.] Emory Univ, Sch Med, 1365 Clifton Rd NE,Suite C2110, Atlanta, GA 30322 USA.
[Busse, Paul M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Cooper, Jay S.] Maimonides Canc Ctr, Brooklyn, NY USA.
[Jones, Christopher U.] Radiol Associates Sacramento, Sacramento, CA USA.
[Koyfman, Shlomo] Cleveland Clin, Cleveland, OH 44106 USA.
[Quon, Harry] Johns Hopkins Univ, Baltimore, MD USA.
[Ridge, John A.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Ridge, John A.] Amer Coll Surg, Chicago, IL USA.
[Siddiqui, Farzan] Henry Ford Hlth Syst, Detroit, MI USA.
[Worden, Francis] Univ Michigan, Ann Arbor, MI 48109 USA.
[Yao, Min] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Yom, Sue S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Saba, NF (reprint author), Emory Univ, Sch Med, 1365 Clifton Rd NE,Suite C2110, Atlanta, GA 30322 USA.
EM nabil.saba@emory.edu
FU Genentech
FX Sue S. Yom, MD. PhD, is affiliated with Genentech for research support
and is the principal investigator of a supported clinical trial.
Christopher U. Jones, MD, is employed by Bristol Myers Squibb in the
role speaking and teaching.
NR 69
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U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
EI 1097-0347
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD JUL
PY 2016
VL 38
IS 7
BP 979
EP 986
DI 10.1002/hed.24423
PG 8
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DR5JV
UT WOS:000379940200005
PM 27131050
ER
PT J
AU Veit, JA
Heine, D
Thierauf, J
Lennerz, J
Shetty, S
Schuler, PJ
Whiteside, T
Beutner, D
Meyer, M
Grunewald, I
Ritter, G
Gnjatic, S
Sikora, AG
Hoffmann, TK
Laban, S
AF Veit, Johannes A.
Heine, Daniela
Thierauf, Julia
Lennerz, Jochen
Shetty, Subasch
Schuler, Patrick J.
Whiteside, Theresa
Beutner, Dirk
Meyer, Moritz
Gruenewald, Inga
Ritter, Gerd
Gnjatic, Sacha
Sikora, Andrew G.
Hoffmann, Thomas K.
Laban, Simon
TI Expression and clinical significance of MAGE and NY-ESO-1 cancer-testis
antigens in adenoid cystic carcinoma of the head and neck
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE adenoid cystic carcinoma; head and neck cancer; cancer-testis antigens;
Melanoma antigen; New York esophageal squamous cell carcinoma (NY-ESO-1)
ID SQUAMOUS-CELL CARCINOMA; TUMOR-INFILTRATING LYMPHOCYTES; MELANOMA
PATIENTS; OROPHARYNGEAL CANCER; METASTATIC MELANOMA; PROTEIN
VACCINATION; CTLA-4 BLOCKADE; MYELOMA CELLS; IMMUNE-SYSTEM; LUNG-CANCER
AB Background. Adenoid cystic carcinoma (ACC) of the head and neck is a rare but highly malignant tumor. Cancer-testis antigens (CTAs) represent an immunogenic family of cancer-specific proteins and thus represent an attractive target for immunotherapy.
Methods. Eighty-four cases of ACC were identified, the CTAs pan-Melanoma antigen (pan-MAGE; M3H67) and New York esophageal squamous cell carcinoma (NY-ESO-1; E978) were detected immunohistochemically (IHC) and correlated with clinical data.
Results. Expression of NY-ESO-1 was found in 48 of 84 patients (57.1%) and of pan-MAGE in 28 of 84 patients (31.2%). Median overall survival (OS) in NY-ESO-1 positive versus negative patients was 130.8 and 282.0 months (p = .223), respectively. OS in pan-MAGE positive versus negative patients was 105.3 and 190.5 months, respectively (p=.096). Patients expressing both NY-ESO-1 and pan-MAGE simultaneously had significantly reduced OS with a median of 90.5 months compared with 282.0 months in negative patients (p=.047).
Conclusion. A significant fraction of patients with ACC show expression of the CTAs NY-ESO-1 and/or pan-MAGE with promising immunotherapeutic implications. (C) 2016 Wiley Periodicals, Inc.
C1 [Veit, Johannes A.; Heine, Daniela; Thierauf, Julia; Schuler, Patrick J.; Hoffmann, Thomas K.; Laban, Simon] Univ Med Ctr Ulm, Dept Otorhinolaryngol & Head & Neck Surg, Frauensteige 12, D-89070 Ulm, Germany.
[Lennerz, Jochen] Massachusetts Gen Hosp, Dept Pathol, Ctr Integrated Diagnost, Boston, MA 02114 USA.
[Shetty, Subasch] Kensington Hosp, Dept Ear Nose & Throat Surg, Whangarei, New Zealand.
[Whiteside, Theresa] Univ Pittsburgh, Dept Pathol, Hillman Canc Ctr, Pittsburgh, PA USA.
[Beutner, Dirk; Meyer, Moritz] Univ Cologne, Dept Otorhinolaryngol, Cologne, Germany.
[Gruenewald, Inga] Univ Cologne, Inst Pathol, Cologne, Germany.
[Ritter, Gerd] Ludwig Inst Canc Res, New York, NY USA.
[Ritter, Gerd] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Gnjatic, Sacha] Mt Sinai Hosp, Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Sikora, Andrew G.] Baylor Coll Med, Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA.
RP Laban, S (reprint author), Univ Med Ctr Ulm, Dept Otorhinolaryngol & Head & Neck Surg, Frauensteige 12, D-89070 Ulm, Germany.
EM simon.laban@gmail.com
FU NCI NIH HHS [R01 CA168628]
NR 60
TC 1
Z9 1
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
EI 1097-0347
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD JUL
PY 2016
VL 38
IS 7
BP 1008
EP 1016
DI 10.1002/hed.24403
PG 9
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DR5JV
UT WOS:000379940200009
PM 26874246
ER
PT J
AU Hussaini, AS
Dombrowski, JJ
Bolesta, ES
Walker, RJ
Varvares, MA
AF Hussaini, Adnan S.
Dombrowski, John J.
Bolesta, E. Stephen
Walker, Ronald J.
Varvares, Mark A.
TI Esthesioneuroblastoma with bilateral metastases to the parotid glands
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE esthesioneuroblastoma; olfactory neuroblastoma; parotid gland;
chemoradiation; craniofacial resection
ID OLFACTORY NEUROBLASTOMA; EXPERIENCE; NECK
AB Background. Esthesioneuroblastoma (ENB) is a rare, poorly characterized, intranasal cancer arising from olfactory neuroepithelium.
Methods. This case report reviews the underlying pathophysiology, clinical presentation, and diagnosis of primary ENB and parotid metastases.
Results. We present the case of a 43-year-old man who was referred to our practice with radiographically and biopsy confirmed ENB. After neoadjuvant chemotherapy, radiation, and open surgical resection, he returned to the clinic 30 months postoperatively with a right parotid mass, which was found to be a recurrence of his primary cancer. A parotidectomy was performed; however, he returned 10 months later with a new left parotid mass. Subsequent imaging and biopsy confirmed recurrence of ENB and a second parotidectomy was performed.
Conclusion. This case illustrates that delayed metastases in the setting of ENB are not limited to the cervical lymph nodes and, in rare instances, may involve the parotid glands. Surveillance should include the parotid lymph node basin with a high clinical index of suspicion in the setting of parotid lymphadenopathy after primary surgical therapy. (C) 2016 Wiley Periodicals, Inc.
C1 [Hussaini, Adnan S.] St Louis Univ, Sch Med, 1402 South Grand Blvd, St Louis, MO 63104 USA.
[Dombrowski, John J.] St Louis Univ, Sch Med, Dept Radiat Oncol, St Louis, MO USA.
[Bolesta, E. Stephen] St Louis Univ, Sch Med, Dept Pathol, St Louis, MO 63104 USA.
[Walker, Ronald J.] St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, St Louis, MO USA.
[Varvares, Mark A.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA.
[Varvares, Mark A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
RP Hussaini, AS (reprint author), St Louis Univ, Sch Med, 1402 South Grand Blvd, St Louis, MO 63104 USA.
EM ahussani@slu.edu
NR 17
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
EI 1097-0347
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD JUL
PY 2016
VL 38
IS 7
BP E2457
EP E2460
DI 10.1002/hed.24425
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DR5JV
UT WOS:000379940200003
ER
PT J
AU Shrime, MG
Verguet, S
Johansson, KA
Desalegn, D
Jamison, DT
Kruk, ME
AF Shrime, Mark G.
Verguet, Stephane
Johansson, Kjell Arne
Desalegn, Dawit
Jamison, Dean T.
Kruk, Margaret E.
TI Task-sharing or public finance for the expansion of surgical access in
rural Ethiopia: an extended cost-effectiveness analysis
SO HEALTH POLICY AND PLANNING
LA English
DT Article
DE Equity; extended cost-effectiveness analysis; impoverishment; surgery;
universal health care
ID EMERGENCY OBSTETRIC CARE; ANESTHESIA INFRASTRUCTURE;
HEALTH-PROFESSIONALS; DEVELOPING-COUNTRIES; ECTOPIC PREGNANCY;
INDUCED-ABORTION; SITE INFECTIONS; NATURAL-HISTORY; ADDIS-ABABA; SURGERY
AB Despite a high burden of surgical disease, access to surgical services in low- and middle-income countries is often limited. In line with the World Health Organization's current focus on universal health coverage and equitable access to care, we examined how policies to expand access to surgery in rural Ethiopia would impact health, impoverishment and equity. An extended cost-effectiveness analysis was performed. Deterministic and stochastic models of surgery in rural Ethiopia were constructed, utilizing pooled estimates of costs and probabilities from national surveys and published literature. Model calibration and validation were performed against published estimates, with sensitivity analyses on model assumptions to check for robustness. Outcomes of interest were the number of deaths averted, the number of cases of poverty averted and the number of cases of catastrophic expenditure averted for each policy, divided across wealth quintiles. Health benefits, financial risk protection and equity appear to be in tension in the expansion of access to surgical care in rural Ethiopia. Health benefits from each of the examined policies accrued primarily to the poor. However, without travel vouchers, many policies also induced impoverishment in the poor while providing financial risk protection to the rich, calling into question the equitable distribution of benefits by these policies. Adding travel vouchers removed the impoverishing effects of a policy but decreased the health benefit that could be bought per dollar spent. These results were robust to sensitivity analyses.
C1 [Shrime, Mark G.] Harvard Med Sch, Dept Global Hlth & Social Med, Program Global Surg & Social Change, Boston, MA 02115 USA.
[Shrime, Mark G.] Massachusetts Eye & Ear Infirm, Off Global Surg, Boston, MA 02114 USA.
[Verguet, Stephane; Kruk, Margaret E.] Harvard Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA.
[Johansson, Kjell Arne] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Desalegn, Dawit] Univ Addis Ababa, Sch Med, Dept Obstet & Gynaecol, Addis Ababa, Ethiopia.
[Jamison, Dean T.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
RP Shrime, MG (reprint author), Emergency Dept, 243 Charles St, Boston, MA 02114 USA.
EM shrime@gmail.com
NR 86
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Z9 0
U1 5
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1080
EI 1460-2237
J9 HEALTH POLICY PLANN
JI Health Policy Plan.
PD JUL
PY 2016
VL 31
IS 6
BP 706
EP 716
DI 10.1093/heapol/czv121
PG 11
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DR2ZQ
UT WOS:000379772800004
PM 26719347
ER
PT J
AU Chait, Y
Kalim, S
Horowitz, J
Hollot, CV
Ankers, ED
Germain, MJ
Thadhani, RI
AF Chait, Yossi
Kalim, Sahir
Horowitz, Joseph
Hollot, Christopher V.
Ankers, Elizabeth D.
Germain, Michael J.
Thadhani, Ravi I.
TI The greatly misunderstood erythropoietin resistance index and the case
for a new responsiveness measure
SO HEMODIALYSIS INTERNATIONAL
LA English
DT Article
DE Anemia; mathematical models; biostatistics
ID CHRONIC KIDNEY-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN;
HEMODIALYSIS-PATIENTS; EPOETIN-ALPHA; STIMULATING AGENTS; ANEMIA;
HYPORESPONSIVENESS; HEMATOCRIT; SURVIVAL; OUTCOMES
AB Introduction The optimal use of erythropoiesis stimulating agents (ESAs) to treat anemia in end stage renal disease remains controversial due to reported associations with adverse events. In analyzing these associations, studies often utilize ESA resistance indices (ERIs), to characterize a patient's response to ESA. In this study, we examine whether ERI is an adequate measure of ESA resistance. Methods We used retrospective data from a nonconcurrent cohort study of incident hemodialysis patients in the United States (n=9386). ERI is defined as average weekly erythropoietin (EPO) dose per kg body weight (wt) per average hemoglobin (Hgb), over a 3-month period (ERI=(EPO/wt)/Hgb). Linear regression was used to demonstrate the relationship between ERI and weight-adjusted EPO. The coefficient of variation was used to compare the variability of Hgb with that of weight-adjusted EPO to explain this relationship. This analysis was done for each quarter during the first year of dialysis. Findings ERI is strongly linearly related with weight-adjusted EPO dose in each of the four quarters by the equation ERI=0.0899*(EPO/wt) (range of R-2=0.97-0.98) and weakly linearly related to 1/Hgb (range of R-2=0.06-0.16). These correlations hold independent of age, sex, hgb level, ERI level, and epo-naive stratifications. Discussion ERI is strongly linearly related to weight-adjusted (and nonweight-adjusted) EPO dose by a universal, not patient-specific formula, and thus is a surrogate of EPO dose. Therefore, associations between ERI and clinical outcomes are associations between a confounded EPO dose and those outcomes.
C1 [Chait, Yossi] Univ Massachusetts, Dept Mech & Ind Engn, 160 Governors Dr, Amherst, MA 01003 USA.
[Kalim, Sahir; Ankers, Elizabeth D.; Thadhani, Ravi I.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Kalim, Sahir; Ankers, Elizabeth D.; Thadhani, Ravi I.] Harvard Med Sch, Boston, MA USA.
[Horowitz, Joseph] Univ Massachusetts, Dept Math & Stat, 160 Governors Dr, Amherst, MA 01003 USA.
[Hollot, Christopher V.] Univ Massachusetts, Dept Elect & Comp Engn, 160 Governors Dr, Amherst, MA 01003 USA.
[Germain, Michael J.] Baystate Med Ctr, Springfield, MA 01199 USA.
[Germain, Michael J.] Tufts Univ, Sch Med, Medford, MA 02155 USA.
RP Chait, Y (reprint author), Univ Massachusetts, Dept Mech & Ind Engn, 160 Governors Dr, Amherst, MA 01003 USA.
EM ychait@umass.edu
FU National Institutes of Health, National Institute of Diabetes and
Digestive and Kidney Diseases [K25 DK096006, K23 DK106479,
5K24DK094872-04]
FX This work was supported in part by grants from National Institutes of
Health, National Institute of Diabetes and Digestive and Kidney Diseases
(K25 DK096006 to YC, K23 DK106479 to SK, and 5K24DK094872-04 to RIT).
NR 32
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1492-7535
EI 1542-4758
J9 HEMODIAL INT
JI Hemodial. Int.
PD JUL
PY 2016
VL 20
IS 3
BP 392
EP 398
DI 10.1111/hdi.12407
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DR3TP
UT WOS:000379825800012
PM 26843352
ER
PT J
AU Valenza, G
Carli, V
Lanata, A
Chen, W
Jafari, R
Scilingo, EP
AF Valenza, Gaetano
Carli, Vladimir
Lanata, Antonio
Chen, Wei
Jafari, Roozbeh
Scilingo, Enzo Pasquale
TI Sensor Informatics for Managing Mental Health
SO IEEE JOURNAL OF BIOMEDICAL AND HEALTH INFORMATICS
LA English
DT Editorial Material
C1 [Valenza, Gaetano; Lanata, Antonio; Scilingo, Enzo Pasquale] Univ Pisa, Pisa, Italy.
[Valenza, Gaetano] Harvard Med Sch, Mass Gen Hosp, Boston, MA USA.
[Carli, Vladimir] Karolinska Inst, Stockholm, Sweden.
[Chen, Wei] Fudan Univ, Shanghai, Peoples R China.
[Jafari, Roozbeh] Texas A&M Univ, College Stn, TX USA.
RP Valenza, G (reprint author), Univ Pisa, Pisa, Italy.; Valenza, G (reprint author), Harvard Med Sch, Mass Gen Hosp, Boston, MA USA.
EM g.valenza@ieee.org; vladimir.carli@ki.se;
a.lanata@centropiaggio.unipi.it; w_chen@fudan.edu.cn; rjafari@tamu.edu;
e.scilingo@ing.unipi.it
NR 8
TC 0
Z9 0
U1 1
U2 2
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2194
J9 IEEE J BIOMED HEALTH
JI IEEE J. Biomed. Health Inform.
PD JUL
PY 2016
VL 20
IS 4
BP 975
EP 976
DI 10.1109/JBHI.2016.2565758
PG 2
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Mathematical & Computational Biology;
Medical Informatics
SC Computer Science; Mathematical & Computational Biology; Medical
Informatics
GA DR8DJ
UT WOS:000380128300001
ER
PT J
AU Nobles, CJ
Thomas, JJ
Valentine, SE
Gerber, MW
Vaewsorn, AS
Marques, L
AF Nobles, Carrie J.
Thomas, Jennifer J.
Valentine, Sarah E.
Gerber, Monica W.
Vaewsorn, Adin S.
Marques, Luana
TI Association of premenstrual syndrome and premenstrual dysphoric disorder
with bulimia nervosa and binge-eating disorder in a nationally
representative epidemiological sample
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE bulimia nervosa; binge-eating disorder; premenstrual dysphoric disorder
ID MENSTRUAL-CYCLE; COMORBIDITY SURVEY; OVARIAN HORMONES; MORTALITY-RATES;
AMERICAN LIFE; MENTAL-HEALTH; LATE-LUTEAL; WOMEN; EXACERBATION;
PREVALENCE
AB ObjectiveBulimia nervosa (BN) and binge-eating disorder (BED) are associated with significant health impairment. Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) comprise both psychological (disturbances in mood and affect) and physiological (bloating and changes in appetite) symptoms that may trigger binge-eating and/or purging.
MethodFemale participants were drawn from the Collaborative Psychiatric Epidemiological Surveys, conducted from 2001 to 2003. Weighted multivariable logistic regression modeled the association between lifetime PMS and PMDD and lifetime odds of BN or BED.
ResultsAmong 8,694 participants, 133 (1.0%) had BN and 185 (1.8%) BED. Additionally, 366 (4.2%) had PMDD and 3,489 (42.4%) had PMS. Prevalence of PMDD and PMS were 17.4 and 55.4% among those with BN, 10.7 and 48.9% among those with BED and 3.4 and 59.1% among those with subthreshold BED. After adjustment for age, race/ethnicity, income, education, body mass index, age at menarche, birth control use, and comorbid mental health conditions, PMDD was associated with seven times the odds of BN (OR 7.2, 95% CI 2.3, 22.4) and PMS with two times the odds of BN (OR 2.5, 95% CI 1.1, 5.7). Neither PMDD nor PMS were significantly associated with BED.
DiscussionWomen with PMS and PMDD have a higher odds of BN, independent of comorbid mental health conditions. PMS and PMDD may be important comorbidities to BN to consider in clinical settings, and future research should investigate whether PMS and PMDD affect the onset and duration of bulimic symptoms as well as the potential for shared risk factors across disorders. (c) 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:641-650)
C1 [Nobles, Carrie J.; Valentine, Sarah E.; Gerber, Monica W.; Vaewsorn, Adin S.; Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Community Psychiat PRIDE, 70 Everett Ave Suite 516, Chelsea, MA 02150 USA.
[Nobles, Carrie J.; Thomas, Jennifer J.; Valentine, Sarah E.; Marques, Luana] Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA.
[Thomas, Jennifer J.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, 2 Longfellow Pl Suite 200, Boston, MA 02114 USA.
RP Nobles, CJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Community Psychiat PRIDE, 70 Everett Ave Suite 516, Chelsea, MA 02150 USA.; Nobles, CJ (reprint author), Harvard Med Sch, Dept Psychiat, Boston, MA 02115 USA.
EM cnobles@mgh.harvard.edu
OI Nobles, Carrie/0000-0002-2182-8486
FU NIMH from National Institute of Health [K23 MH096029-01A1]
FX Supported by NIMH K23 MH096029-01A1 from National Institute of Health
(to L.M.).
NR 40
TC 1
Z9 1
U1 5
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0276-3478
EI 1098-108X
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD JUL
PY 2016
VL 49
IS 7
BP 641
EP 650
DI 10.1002/eat.22539
PG 10
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA DR5WF
UT WOS:000379972400001
PM 27206163
ER
PT J
AU Gaudin, RA
Robinson, M
Banks, CA
Baiungo, J
Jowett, N
Hadlock, TA
AF Gaudin, Robert A.
Robinson, Mara
Banks, Caroline A.
Baiungo, Jennifer
Jowett, Nate
Hadlock, Tessa A.
TI Emerging vs Time-Tested Methods of Facial Grading Among Patients With
Facial Paralysis
SO JAMA FACIAL PLASTIC SURGERY
LA English
DT Article
ID NERVE FUNCTION; HOUSE-BRACKMANN; SYSTEM; RELIABILITY; REANIMATION;
SUNNYBROOK
AB IMPORTANCE Most rehabilitation specialists and many facial reanimation surgeons use the Sunnybrook Facial Grading System (FGS) to measure and detect changes in facial function. The eFACE, an electronic and digitally graded facial measurement scale, was recently created to provide similar information to the Sunnybrook FGS, but with scaling uniformity across all categories of facial function, graphical outputs, and easy-to-use visual analog scales.
OBJECTIVES To establish the correlation between the scores on the eFACE and the Sunnybrook FGS among patients with facial paralysis and to compare the reliability of the 2 scales.
DESIGN, SETTING, AND PARTICIPANTS A retrospective review of medical records identified 109 patients who were evaluated at a facial nerve center by physical therapists using the eFACE and the Sunnybrook FGS on the same day, between November 1, 2014, and May 31, 2015. The level of facial function predicted using the 2 scales was compared to study correlation between the scales. Data analysis was conducted from June 1 to September 1, 2015.
MAIN OUTCOMES AND MEASURES Correlation between the Sunnybrook FGS and the eFACE grading scale.
METHODS Two independent physical therapists evaluated patients using both the eFACE and the Sunnybrook FGS. Scores were compared and the Spearman rank correlation coefficient was calculated between the total scores and each of the 3 subscores, including static, dynamic, and synkinesis scores. The total Sunnybrook FGS synkinesis score (worst score, 15; perfect score, 0) and static score (worst score, 20; perfect score, 0) were normalized to a 100-point scale with the eFACE (perfect score, 100; worst score, 1).
RESULTS eFACE scores ranged from 48 to 100, and Sunnybrook FGS scores ranged from 0 to 100. Among 109 patients, there was a moderately strong correlation between eFACE and Sunnybrook FGS scores in both total and subcategory scores. The Spearman rank correlation coefficient of the total eFACE and Sunnybrook FGS was 0.75 (r < 0.0001). For the static scores, the correlation coefficient was -0.71 (r < 0.0001). The correlation coefficients for the dynamic and synkinesis scores were 0.77 (r < 0.0001) and -0.78 (r < 0.0001), respectively.
CONCLUSIONS AND RELEVANCE There is moderately good agreement between the Sunnybrook FGS and the eFACE. Given the ease of using the eFACE on mobile devices, as well as its additional functionality, it may represent a reasonable facial grading option across disciplines in the future.
C1 [Gaudin, Robert A.; Robinson, Mara; Banks, Caroline A.; Baiungo, Jennifer; Jowett, Nate; Hadlock, Tessa A.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
RP Hadlock, TA (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM tessa_hadlock@meei.harvard.edu
NR 27
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6076
EI 2168-6092
J9 JAMA FACIAL PLAST SU
JI JAMA Facial Plast. Surg.
PD JUL-AUG
PY 2016
VL 18
IS 4
BP 251
EP 257
DI 10.1001/jamafacial.2016.0025
PG 7
WC Surgery
SC Surgery
GA DR7JB
UT WOS:000380074800003
PM 27101446
ER
PT J
AU Manuel, CT
Tjoa, T
Nguyen, T
Su, E
Wong, BJF
AF Manuel, Cyrus T.
Tjoa, Tjoson
Nguyen, Tony
Su, Erica
Wong, Brian J. F.
TI Optimal Electromechanical Reshaping of the Auricular Ear and Long-term
Outcomes in an In Vivo Rabbit Model
SO JAMA FACIAL PLASTIC SURGERY
LA English
DT Article
ID SEPTAL CARTILAGE; COSTAL CARTILAGE; PROTRUDING EARS; OTOPLASTY;
PROTRUSIONS; SUTURES; LACR
AB IMPORTANCE The prominent ear is a common external ear anomaly that is usually corrected through surgery. Electromechanical reshaping (EMR) may provide the means to reshape cartilage through the use of direct current (in milliamperes) applied percutaneously with needle electrodes and thus to reduce reliance on open surgery.
OBJECTIVE To determine the long-term outcomes (shape change, cell viability, and histology) of a more refined EMR voltage and time settings for reshaping rabbit auricle.
DESIGN, SETTING, AND SUBJECTS The intact ears of 14 New Zealand white rabbits were divided into 2 groups. Group 1 received 4 V for 5 minutes (5 ears), 5 V for 4 minutes (5 ears), or no voltage for 5 minutes (control; 4 ears). Group 2 received an adjusted treatment of 4 V for 4 minutes (7 ears) or 5 V for 3 minutes (7 ears). A custom mold with platinum electrodes was used to bend the pinna and to perform EMR. Pinnae were splinted for 6 months along the region of the bend. Rabbits were killed humanely and the ears were harvested the day after splint removal. Data were collected from March 14, 2013, to July 8, 2014, and analyzed from August 29, 2013, to March 1, 2015.
MAIN OUTCOMES AND MEASURES Bend angle and mechanical behavior via palpation were recorded through photography and videography. Tissue was sectioned for histologic examination and confocal microscopy to assess changes to microscopic structure and cell viability.
RESULTS Rabbits ranged in age from 6 to 8 months and weighed 3.8 to 4.0 g. The mean (SD) bend angles were 81 degrees (45 degrees) for the controls and, in the 5 EMR groups, 72 degrees (29 degrees) for 4 V for 4 minutes, 101 degrees (19 degrees) for 4 V for 5 minutes, 78 degrees (18 degrees) for 5 V for 3 minutes, and 126 degrees (21 degrees) for 5 V for 4 minutes. At 5 V, an increase in application time from 3 to 4 minutes provided significant shape change (78 degrees [18 degrees] and 126 degrees [21 degrees], respectively; P = .003). Pinnae stained with hematoxylin-eosin displayed localized areas of cell injury and fibrosis in and around electrode insertion sites. This circumferential zone of injury (range, 1.3-2.1 mm) corresponded to absence of red florescence on the cell viability assay.
CONCLUSIONS AND RELEVANCE In this in vivo study, EMR produces shape changes in the intact pinnae of rabbits. A short application of 4 V or 5 V can achieve adequate reshaping of the pinnae. Tissue injury around the electrodes is modest in spatial distribution. This study provides a more optimal set of EMR variables and a critical step toward evaluation of EMR in clinical trials.
C1 [Manuel, Cyrus T.; Nguyen, Tony; Su, Erica; Wong, Brian J. F.] Univ Calif Irvine, Beckman Laser Inst, 1002 Hlth Sci Rd, Irvine, CA 92617 USA.
[Tjoa, Tjoson; Wong, Brian J. F.] Univ Calif Irvine, Dept Otolaryngol, Irvine, CA USA.
[Tjoa, Tjoson] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Wong, BJF (reprint author), Univ Calif Irvine, Beckman Laser Inst, 1002 Hlth Sci Rd, Irvine, CA 92617 USA.
EM bjwong@uci.edu
FU Deployment-Related Medical Research Program from the US Department of
Defense [W81XWH-09-1-0602]; National Institutes of Health [DE019026,
HL103764, HL105215, EB015890]
FX This study was supported by Deployment-Related Medical Research Program
W81XWH-09-1-0602 from the US Department of Defense and by grants
DE019026, HL103764, HL105215, and EB015890 from the National Institutes
of Health.
NR 28
TC 0
Z9 0
U1 3
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6076
EI 2168-6092
J9 JAMA FACIAL PLAST SU
JI JAMA Facial Plast. Surg.
PD JUL-AUG
PY 2016
VL 18
IS 4
BP 277
EP 284
DI 10.1001/jamafacial.2016.0166
PG 8
WC Surgery
SC Surgery
GA DR7JB
UT WOS:000380074800008
PM 27101542
ER
PT J
AU Banks, CA
Jowett, N
Hadlock, CR
Hadlock, TA
AF Banks, Caroline A.
Jowett, Nate
Hadlock, Charles R.
Hadlock, Tessa A.
TI Weighting of Facial Grading Variables to Disfigurement in Facial Palsy
SO JAMA FACIAL PLASTIC SURGERY
LA English
DT Article
ID REANIMATION SURGERY; PERCEPTION; PARALYSIS; ATTRACTIVENESS; VALIDATION;
MANAGEMENT; ASYMMETRY; THRESHOLD; SOCIETY; SYSTEM
AB IMPORTANCE A universal, health care professional-graded scale for facial assessment would be a useful tool for reporting, comparing, and assessing facial function among patients with facial paralysis.
OBJECTIVES To correlate scores of an assessment tool, the eFACE scale, with expert-rated facial disfigurement and to determine the relative contributions of facial features to facial palsy-related disfigurement.
DESIGN, SETTING, AND PARTICIPANTS The eFACE scale yields 15 individual variable scores, in addition to subscores for static, dynamic, and synkinesis elements, and a total score that is based on 100-point scales. Two hundred patients with varying degrees of unilateral facial palsy underwent independent eFACE assessment and assignment of a disfigurement score by 2 facial nerve surgeons. The mean scores were determined, and multivariate regression analysis was performed to fit eFACE subset scores (static, dynamic, and synkinesis) to disfigurement ratings. A hybrid regression model was then used to weight each of the 15 eFACE variables, using stepwise regression to control for the effect of the other variables. Scoring was performed during an 8-week period from March 16 to May 8, 2015.
MAIN OUTCOME AND MEASURE Use of the 100-point eFACE variables, together with a 100-point visual analog scale of disfigurement, with 0 representing the most extreme disfigurement possible from a facial nerve disorder and 100 representing no discernible facial disfigurement.
RESULTS In the 200 patients included in analysis (126 [63.0% female]; mean [SD] age, 46.5 [16.4] years]), predicted disfigurement scores based on eFACE subset scores demonstrated excellent agreement with surgeon-graded disfigurement severity (r(2) = 0.79). Variable weighting demonstrated that the 6 key contributors to overall disfigurement were (in order of importance) nasolabial fold depth at rest (normalized coefficient [NC], 0.18; P < .001), oral commissure position at rest (NC, 0.15; P < .001), lower lip asymmetry while pronouncing the long /(e) over bar/ (NC, 0.09; P < .001), palpebral fissure width at rest (NC, 0.09; P < .001), nasolabial fold orientation with smiling (NC, 0.08; P = .001), and palpebral fissure width during attempts at full eye closure (NC, 0.06; P = .03).
CONCLUSIONS AND RELEVANCE A mathematical association between eFACE-measured facial features and overall expert-graded disfigurement in facial paralysis has been established. For those using the eFACE grading scale, predictions of the specific effects of various interventions on expert-rated disfigurement are now possible and may guide therapy.
C1 [Banks, Caroline A.; Jowett, Nate; Hadlock, Tessa A.] Harvard Med School, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
[Hadlock, Charles R.] Bentley Univ, Dept Math Sci, Waltham, MA USA.
RP Jowett, N (reprint author), Harvard Med School, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM nathan_jowett@meei.harvard.edu
NR 21
TC 0
Z9 0
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6076
EI 2168-6092
J9 JAMA FACIAL PLAST SU
JI JAMA Facial Plast. Surg.
PD JUL-AUG
PY 2016
VL 18
IS 4
BP 292
EP 298
DI 10.1001/jamafacial.2016.0226
PG 7
WC Surgery
SC Surgery
GA DR7JB
UT WOS:000380074800010
PM 27124886
ER
PT J
AU Cragg, JJ
Cudkowicz, ME
Weisskopf, MG
AF Cragg, Jacquelyn J.
Cudkowicz, Merit E.
Weisskopf, Marc G.
TI The Role of Environmental Toxins in Amyotrophic Lateral Sclerosis Risk
SO JAMA NEUROLOGY
LA English
DT Editorial Material
ID MILITARY SERVICE; ALS; EPIDEMIOLOGY
C1 [Cragg, Jacquelyn J.; Weisskopf, Marc G.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr, Boston, MA 02215 USA.
[Cudkowicz, Merit E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Weisskopf, Marc G.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Cragg, JJ (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, 401 Pk Dr, Boston, MA 02215 USA.
EM craggj@interchange.ubc.ca
NR 15
TC 0
Z9 0
U1 19
U2 19
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUL
PY 2016
VL 73
IS 7
BP 779
EP 780
DI 10.1001/jamaneurol.2016.1038
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DQ7XC
UT WOS:000379420500004
PM 27158795
ER
PT J
AU Wills, AM
Boyd, J
Perez, A
AF Wills, Anne-Marie
Boyd, James
Perez, Adriana
TI Association Between Body Mass Index and Parkinson Disease Reply
SO JAMA NEUROLOGY
LA English
DT Letter
ID SURVIVAL
C1 [Wills, Anne-Marie] Harvard Med Sch, Dept Neurol, Boston, MA 02114 USA.
[Wills, Anne-Marie] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Boyd, James] Univ Vermont, Coll Med, Dept Neurol Sci, Burlington, VT 05405 USA.
[Perez, Adriana] Univ Texas Hlth Sci Ctr Houston UT Hlth, Dept Biostat, Houston, TX 77030 USA.
RP Wills, AM (reprint author), Harvard Med Sch, 55 Fruit St,WACC Room 715, Boston, MA 02114 USA.
EM awills@partners.org
NR 2
TC 0
Z9 0
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD JUL
PY 2016
VL 73
IS 7
BP 892
EP 892
DI 10.1001/jamaneurol.2016.1245
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA DQ7XC
UT WOS:000379420500031
PM 27214659
ER
PT J
AU Adler, JT
Chang, DC
AF Adler, Joel T.
Chang, David C.
TI Implications of Market Competition, Technology Adoption, and Cost for
Surgical Patients
SO JAMA SURGERY
LA English
DT Editorial Material
ID SURGERY
C1 [Adler, Joel T.; Chang, David C.] Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 403, Boston, MA 02114 USA.
RP Chang, DC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Ste 403, Boston, MA 02114 USA.
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD JUL
PY 2016
VL 151
IS 7
BP 621
EP 621
DI 10.1001/jamasurg.2015.5554
PG 1
WC Surgery
SC Surgery
GA DR5MB
UT WOS:000379946000006
PM 26886881
ER
PT J
AU Berry, W
Haynes, A
Lagoo, J
AF Berry, William
Haynes, Alex
Lagoo, Janaka
TI The Surgical Checklist It CannotWork If You Do Not Use It
SO JAMA SURGERY
LA English
DT Editorial Material
C1 [Berry, William] Harvard Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
[Haynes, Alex] Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA.
[Lagoo, Janaka] Harvard Sch Publ Hlth, Ariadne Labs, Boston, MA USA.
[Lagoo, Janaka] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
RP Berry, W (reprint author), Harvard Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA.
EM wberry@ariadnelabs.org
NR 6
TC 0
Z9 0
U1 5
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD JUL
PY 2016
VL 151
IS 7
BP 647
EP 647
DI 10.1001/jamasurg.2015.5551
PG 1
WC Surgery
SC Surgery
GA DR5MB
UT WOS:000379946000011
PM 26842306
ER
PT J
AU Fiedler, AG
Song, TH
D'Alessandro, DA
AF Fiedler, Amy G.
Song, Tae H.
D'Alessandro, David A.
TI Redesigning Care for Patients With Acute Myocardial Infarction
Complicated by Cardiogenic Shock: The "Shock Team"
SO JAMA SURGERY
LA English
DT Letter
C1 [Fiedler, Amy G.; Song, Tae H.; D'Alessandro, David A.] Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
RP Fiedler, AG (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
EM afiedler@partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD JUL
PY 2016
VL 151
IS 7
BP 685
EP 685
DI 10.1001/jamasurg.2015.5517
PG 1
WC Surgery
SC Surgery
GA DR5MB
UT WOS:000379946000024
PM 26863918
ER
PT J
AU Wu, JH
Li, B
Wu, MX
AF Wu, Jeffrey H.
Li, Bo
Wu, Mei X.
TI Laser-induced capillary leakage for blood biomarker detection and
vaccine delivery via the skin
SO JOURNAL OF BIOPHOTONICS
LA English
DT Review
DE Laser; biomarkers; vessel leakage; skin
ID SELECTIVE PHOTOTHERMOLYSIS; PLASMA SEPARATION; MALARIA; IMMUNIZATION;
COLLECTION; MOSQUITO; MICRONEEDLES; TECHNOLOGY; INFLUENZA; STEPHENSI
AB Circulation system is the center for coordination and communication of all organs in our body. Examination of any change in its analytes or delivery of therapeutic drugs into the system consists of important medical practice in today's medicine. Two recent studies prove that brief illumination of skin with a low powered laser, at wavelengths preferentially absorbed by hemoglobin, increases the amount of circulating biomarkers in the epidermis and upper dermis by more than 1,000-fold. When probe-coated microneedle arrays are applied into laser-treated skin, plasma blood biomarkers can be reliably, accurately, and sufficiently quantified in 15 similar to 30 min assays, with a maximal detection in one hr in a manner independent of penetration depth or a molecular mass of the biomarker. Moreover, the laser treatment permits a high efficient delivery of radiation-attenuated malarial sporozoites (RAS) into the circulation, leading to robust immunity against malaria infections, whereas similar immunization at sham-treated skin elicits poor immune responses. Thus this technology can potentially instruct designs of small, portable devices for onsite, in mobile clinics, or at home for point-of-care diagnosis and drug/vaccine delivery via the skin. Laser-induced capillary leakage (a) to induce extravasation of circualing molecules only (b) or facilitate entry of attenuated malaria sporozoites into the capillary (c). Skin illumination with a laser preferably absorbed by hemoglobin causes dilation of the capillary beneath the skin. The extravasated molecules can be sufficiently measured in the skin or guide sporozoites to enter the vessel.
C1 [Wu, Mei X.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,Edwards 222, Boston, MA 02114 USA.
Harvard Med Sch, Dept Dermatol, 50 Blossom St,Edwards 222, Boston, MA 02114 USA.
RP Wu, MX (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, 50 Blossom St,Edwards 222, Boston, MA 02114 USA.
EM mwu5@mgh.harvard.edu
FU National Institutes of Health [AI089779, AI070785, AI097696]
FX This work was supported by the National Institutes of Health grants
AI089779, AI070785, and AI097696 (to M.X.W.).
NR 39
TC 0
Z9 0
U1 29
U2 32
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1864-063X
EI 1864-0648
J9 J BIOPHOTONICS
JI J. Biophotonics
PD JUL
PY 2016
VL 9
IS 7
BP 676
EP 682
DI 10.1002/jbio.201500226
PG 7
WC Biochemical Research Methods; Biophysics; Optics
SC Biochemistry & Molecular Biology; Biophysics; Optics
GA DR4FA
UT WOS:000379855700001
PM 26776718
ER
PT J
AU Fernandes, JR
Driscoll, DN
AF Fernandes, Justin R.
Driscoll, Daniel N.
TI Burn Ear Reconstruction Using Porous Polyethylene Implants and Tissue
Expansion
SO JOURNAL OF BURN CARE & RESEARCH
LA English
DT Article
ID TEMPOROPARIETAL FASCIA; CARTILAGE GRAFTS; EXPERIENCE; FRAMEWORK; FLAP
AB Reconstruction of the external ear after a burn is particularly challenging. The nature of the injury poses many problems including excessive scar tissue, poor blood supply, and the lack of adequate and appropriate materials for a framework. The use of costochondral grafts often leads to marginal outcomes which do not justify the morbidity. Children under the age of 10 years commonly have insufficient cartilage for a graft. Medpor (R) (Stryker, Kalamazoo, MI) offers minimal morbidity and a very effective result. In this series, the authors describe the experience using Medpor (R) and scalp tissue expansion to reconstruct severely burned ears. A total of 16 pediatric patients underwent 18 reconstructions, with two patients receiving bilateral procedures. All patients received Medpor (R) implants. Thirteen patients were tissue expanded under the subgaleal plane before reconstruction, for concomitant scalp alopecia reconstruction. Eleven temporoparietal fascial flaps were performed. In the remaining patients, coverage of the implant was achieved by local advancement flaps. Only two patients had complications, with exposure of the construct after several years. In these two cases, the implants were removed. The experience has shown porous polyethylene reconstruction to be very efficient, with low morbidity and good cosmetic outcomes. Medpor (R) is an excellent option for the reconstruction of both fully and partially burned ears as you may implant only the helical rim, base, or both pieces. The best results were achieved after tissue expansion and the use of the alopecic skin overlying a temporoparietal fascial flap. This has become the preferred method.
C1 [Fernandes, Justin R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Driscoll, Daniel N.] Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
RP Driscoll, DN (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA.
NR 14
TC 0
Z9 0
U1 4
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1559-047X
EI 1559-0488
J9 J BURN CARE RES
JI J. Burn Care Res.
PD JUL-AUG
PY 2016
VL 37
IS 4
BP E348
EP E352
DI 10.1097/BCR.0000000000000294
PG 5
WC Emergency Medicine; Dermatology; Surgery
SC Emergency Medicine; Dermatology; Surgery
GA DR1MM
UT WOS:000379669600007
PM 26284635
ER
PT J
AU Wrape, ER
Jenkins, SR
Callahan, JL
Nowlin, RB
AF Wrape, Elizabeth R.
Jenkins, Sharon Rae
Callahan, Jennifer L.
Nowlin, Rachel B.
TI Emotional and Cognitive Coping in Relationship Dissolution
SO JOURNAL OF COLLEGE COUNSELING
LA English
DT Article
DE relationship dissolution; repetitive negative thinking; avoidance
ID POSTTRAUMATIC STRESS-SYMPTOMS; COLLEGE-STUDENTS; ROMANTIC RELATIONSHIPS;
MENTAL-HEALTH; EXPERIENTIAL AVOIDANCE; RELATIONSHIP BREAKUP; DATING
COUPLES; DEPRESSED MOOD; EVENT SCALE; RUMINATION
AB Dissolution of a romantic relationship can adversely affect functioning among college students and represents one primary reason for seeking campus counseling. This study examined the associations among common coping strategies and distress following relationship dissolution. Avoidance and repetitive negative thinking (RNT) were significantly associated with distress, and gender was found to moderate the relationship between RNT and distress. Findings suggest that college counselors should consider emotional coping strategies following relationship dissolutions.
C1 [Wrape, Elizabeth R.; Jenkins, Sharon Rae; Callahan, Jennifer L.; Nowlin, Rachel B.] Univ North Texas, Dept Psychol, Denton, TX USA.
[Wrape, Elizabeth R.] Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, 1660 South Columbian Way, Seattle, WA 98108 USA.
RP Wrape, ER (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, 1660 South Columbian Way, Seattle, WA 98108 USA.
EM elizabeth.wrape2@va.gov
NR 62
TC 0
Z9 0
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1099-0399
EI 2161-1882
J9 J COLL COUNS
JI J. Coll. Couns.
PD JUL
PY 2016
VL 19
IS 2
BP 110
EP 123
DI 10.1002/jocc.12035
PG 14
WC Psychology, Applied
SC Psychology
GA DR4KV
UT WOS:000379871300002
ER
PT J
AU Devine, KA
Bukowski, WM
Sahler, OJZ
Ohman-Strickland, P
Smith, TH
Lown, EA
Patenaude, AF
Korones, DN
Noll, RB
AF Devine, Katie A.
Bukowski, William M.
Sahler, Olle Jane Z.
Ohman-Strickland, Pamela
Smith, Tristram H.
Lown, E. Anne
Patenaude, Andrea Farkas
Korones, David N.
Noll, Robert B.
TI Social Competence in Childhood Brain Tumor Survivors: Feasibility and
Preliminary Outcomes of a Peer- Mediated Intervention
SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
LA English
DT Article
DE social competence; brain tumor survivors; peer-mediated; childhood
cancer; pediatric oncology
ID DEVELOPMENTAL-PSYCHOLOGY; SKILLS INTERVENTION; CHILDREN; ADJUSTMENT;
TEACHER; NEUROSCIENCE; PERFORMANCE; FRIENDSHIP; DISORDER; BEHAVIOR
AB Objective: Evaluate the acceptability, feasibility, and preliminary outcomes of a peer-mediated intervention to improve social competence of brain tumor survivors and classmates. Method: Twelve childhood brain tumor survivors and 217 classroom peers in intervention (n = 8) or comparison (n = 4) classrooms completed measures of social acceptance and reputation at 2 time points in the year. The intervention (5-8 sessions over 4-6 weeks) taught peer leaders skills for engaging classmates. Individual and classroom outcomes were analyzed with analysis of covariance. Results: Recruitment rates of families of brain tumor survivors (81%) and schools (100%) were adequate. Peer leaders reported satisfaction with the intervention. Preliminary outcome data trended toward some benefit in increasing the number of friend nominations for survivors of brain tumors but no changes in other peer-reported metrics. Preliminary results also suggested some positive effects on classroom levels of victimization and rejection. Conclusion: A peer-mediated intervention was acceptable to families of brain tumor survivors and feasible to implement in schools. Findings warrant a larger trial to evaluate improvements for children with brain tumors and their peers.
C1 [Devine, Katie A.] Rutgers State Univ, Rutgers Canc Inst New Jersey, Dept Med, New Brunswick, NJ USA.
[Bukowski, William M.] Concordia Univ, Dept Psychol, Montreal, PQ, Canada.
[Sahler, Olle Jane Z.; Smith, Tristram H.; Korones, David N.] Univ Rochester, Med Ctr, Dept Pediat, Rochester, NY 14642 USA.
[Ohman-Strickland, Pamela] Rutgers State Univ, Sch Publ Hlth, Piscataway, NJ USA.
[Lown, E. Anne] Univ Calif San Francisco, Dept Social Behav Sci, San Francisco, CA 94143 USA.
[Patenaude, Andrea Farkas] Dana Farber Canc Inst, Dept Psychiat, Boston, MA 02115 USA.
[Noll, Robert B.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
RP Noll, RB (reprint author), Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA.
EM robert.noll@chp.edu
FU St. Baldrick's Foundation; National Cancer Institute at the National
Institutes of Health [K07CA174728, P30CA072720]
FX This work was funded by St. Baldrick's Foundation. The first author was
also supported by grants from the National Cancer Institute at the
National Institutes of Health (K07CA174728 & P30CA072720). The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 38
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0196-206X
EI 1536-7312
J9 J DEV BEHAV PEDIATR
JI J. Dev. Behav. Pediatr.
PD JUL-AUG
PY 2016
VL 37
IS 6
BP 475
EP 482
PG 8
WC Behavioral Sciences; Psychology, Developmental; Pediatrics
SC Behavioral Sciences; Psychology; Pediatrics
GA DR3DR
UT WOS:000379783300006
PM 27355881
ER
PT J
AU Wallace, ER
Collett, BR
Kapp-Simon, K
Starr, JR
Birgfeld, C
Speltz, ML
AF Wallace, Erin R.
Collett, Brent R.
Kapp-Simon, Kathleen
Starr, Jacqueline R.
Birgfeld, Craig
Speltz, Matthew L.
TI Visuomotor Function in School-Age Children with Single-Suture
Craniosynostosis
SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
LA English
DT Article
DE visuomotor function; craniosynostosis; visual function; motor function
ID FINE MOTOR-SKILLS; SAGITTAL CRANIOSYNOSTOSIS; PERFORMANCE; KINDERGARTEN;
INTELLIGENCE; INTEGRATION; PRESSURE; SIZE
AB Objective: Previous studies have shown that infants and young children with single-suture craniosynostosis (SSC) perform more poorly on tests of visuomotor function than children without SSC. However, previous studies are limited by small sample sizes and little is known about the persistence of visuomotor problems into the school-age years. The aim of this study was to compare visuomotor function in children with and without SSC at the beginning of elementary school. Methods: The study included 179 children with SSC (cases) and 183 children without SSC (controls). Visuomotor function was measured by the NEPSY-II Arrows, the Purdue Pegboard Test, and the Beery-Buktenica Developmental Test of visual-motor integration. Case-control differences were estimated using linear regression, adjusted for age, sex, socioeconomic status, and maternal IQ. Results: Cases scored more poorly on all measures of visuomotor function, although the magnitude of case-control differences varied across measures. The greatest differences were observed for the Purdue Pegboard Test, with an average adjusted difference of -0.2 to -0.4 SD points (p-values ranged from .008 to .05). Case-control differences were small in magnitude for other measures of visuomotor function, ranging from -0.01 to -0.1 SD points (p-values ranged from .22 to .88). Conclusion: Children with SSC experienced deficits in manual dexterity into the school-age years but were similar to children without SSC on measures of visual processing. These findings advocate for the assessment of fine-motor function as part of school readiness evaluations in children with SSC.
C1 [Wallace, Erin R.; Collett, Brent R.; Speltz, Matthew L.] Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, 2001 8th Ave,Suite 400,Mailstop CW8-6, Seattle, WA 98121 USA.
[Collett, Brent R.; Speltz, Matthew L.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Kapp-Simon, Kathleen] Shriners Hosp Children, Cleft Craniofacial Ctr, Chicago, IL USA.
[Kapp-Simon, Kathleen] Univ Illinois, Dept Surg, Craniofacial Ctr, Chicago, IL 60680 USA.
[Starr, Jacqueline R.] Forsyth Inst, Dept Clin & Translat Res, Cambridge, MA USA.
[Starr, Jacqueline R.] Harvard Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA USA.
[Birgfeld, Craig] Seattle Childrens Hosp, Seattle, WA USA.
RP Wallace, ER (reprint author), Seattle Childrens Res Inst, Ctr Child Hlth Behav & Dev, 2001 8th Ave,Suite 400,Mailstop CW8-6, Seattle, WA 98121 USA.
EM wallace@seattlechildrens.org
FU NIH from the National Institute of Dental and Craniofacial Research [R01
DE 13813]
FX All phases of this study were supported by NIH grant R01 DE 13813 from
the National Institute of Dental and Craniofacial Research to Dr.
Speltz.
NR 32
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U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0196-206X
EI 1536-7312
J9 J DEV BEHAV PEDIATR
JI J. Dev. Behav. Pediatr.
PD JUL-AUG
PY 2016
VL 37
IS 6
BP 483
EP 490
PG 8
WC Behavioral Sciences; Psychology, Developmental; Pediatrics
SC Behavioral Sciences; Psychology; Pediatrics
GA DR3DR
UT WOS:000379783300007
PM 27355879
ER
PT J
AU Bachhuber, MA
Bradley, KA
AF Bachhuber, Marcus A.
Bradley, Katharine A.
TI Evidence-Based Care for People with Unhealthy Alcohol Use-Still Elusive
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
ID INTERVENTION; METAANALYSIS; MISUSE
C1 [Bachhuber, Marcus A.] Montefiore Med Ctr, Albert Einstein Coll Med, Div Gen Internal Med, 3300 Kossuth Ave, Bronx, NY 10467 USA.
[Bradley, Katharine A.] Grp Hlth Res Inst, Seattle, WA USA.
[Bradley, Katharine A.] Univ Washington, Dept Med, Seattle, WA USA.
[Bradley, Katharine A.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Bradley, Katharine A.] VA Puget Sound, HSR&D Ctr Innovat, Seattle, WA USA.
RP Bachhuber, MA (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Div Gen Internal Med, 3300 Kossuth Ave, Bronx, NY 10467 USA.
EM mbachhub@montefiore.org
OI Bachhuber, Marcus/0000-0002-5610-8382
FU NCATS NIH HHS [UL1 TR001073]; NIAAA NIH HHS [K24 AA022128]
NR 10
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2016
VL 31
IS 7
BP 710
EP 711
DI 10.1007/s11606-016-3695-1
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4KS
UT WOS:000379871000004
PM 27071398
ER
PT J
AU Martsolf, GR
Kandrack, R
Gabbay, RA
Friedberg, MW
AF Martsolf, Grant R.
Kandrack, Ryan
Gabbay, Robert A.
Friedberg, Mark W.
TI Cost of Transformation among Primary Care Practices Participating in a
Medical Home Pilot
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE patient-centered medical home; primary care; costs
ID HEALTH-CARE; QUALITY; PAYMENT; ASSOCIATION
AB BACKGROUND: Medical home initiatives encourage primary care practices to invest in new structural capabilities such as patient registries and information technology, but little is known about the costs of these investments.
OBJECTIVES: To estimate costs of transformation incurred by primary care practices participating in a medical home pilot.
DESIGN: We interviewed practice leaders in order to identify changes practices had undertaken due to medical home transformation. Based on the principles of activity-based costing, we estimated the costs of additional personnel and other investments associated with these changes.
SETTING: The Pennsylvania Chronic Care Initiative (PACCI), a statewide multi-payer medical home pilot.
PARTICIPANTS: Twelve practices that participated in the PACCI.
MEASUREMENTS: One-time and ongoing yearly costs attributed to medical home transformation.
RESULTS: Practices incurred median one-time transformation-associated costs of $30,991 per practice (range, $7694 to $117,810), equivalent to $9814 per clinician ($1497 to $57,476) and $8 per patient ($1 to $30). Median ongoing yearly costs associated with transformation were $147,573 per practice (range, $83,829 to $346,603), equivalent to $64,768 per clinician ($18,585 to $93,856) and $30 per patient ($8 to $136). Care management activities accounted for over 60% of practices' transformation-associated costs. Per-clinician and per-patient transformation costs were greater for small and independent practices than for large and system-affiliated practices.
LIMITATIONS: Error in interviewee recall could affect estimates. Transformation costs in other medical home interventions may be different.
CONCLUSIONS: The costs of medical home transformation vary widely, creating potential financial challenges for primary care practices-especially those that are small and independent. Tailored subsidies from payers may help practices make these investments.
PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality
C1 [Martsolf, Grant R.; Kandrack, Ryan] RAND Corp, 20 Pk Plaza, Boston, MA 02116 USA.
[Gabbay, Robert A.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Gabbay, Robert A.; Friedberg, Mark W.] Harvard Med Sch, Boston, MA USA.
[Friedberg, Mark W.] RAND Corp, Boston, MA USA.
[Friedberg, Mark W.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
RP Martsolf, GR (reprint author), RAND Corp, 20 Pk Plaza, Boston, MA 02116 USA.
EM martsolf@rand.org
FU Agency for Healthcare Research and Quality [1R03HS002616-01]
FX This study was sponsored by the Agency for Healthcare Research and
Quality (1R03HS002616-01). No sponsor had a role in the design or
conduct of the study; collection, management, analysis, or
interpretation of the data; or preparation, review, or approval of the
manuscript. This paper was presented at the Academy Health Annual
Research Meeting in 2015.
NR 24
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2016
VL 31
IS 7
BP 723
EP 731
DI 10.1007/s11606-015-3553-6
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4KS
UT WOS:000379871000009
PM 26714484
ER
PT J
AU Patel, MS
Asch, DA
Rosin, R
Small, DS
Bellamy, SL
Eberbach, K
Walters, KJ
Haff, N
Lee, SM
Wesby, L
Hoffer, K
Shuttleworth, D
Taylor, DH
Hilbert, V
Zhu, JS
Yang, L
Wang, XM
Volpp, KG
AF Patel, Mitesh S.
Asch, David A.
Rosin, Roy
Small, Dylan S.
Bellamy, Scarlett L.
Eberbach, Kimberly
Walters, Karen J.
Haff, Nancy
Lee, Samantha M.
Wesby, Lisa
Hoffer, Karen
Shuttleworth, David
Taylor, Devon H.
Hilbert, Victoria
Zhu, Jingsan
Yang, Lin
Wang, Xingmei
Volpp, Kevin G.
TI Individual Versus Team-Based Financial Incentives to Increase Physical
Activity: A Randomized, Controlled Trial
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE behavioral economics; financial incentives; physical activity; step
counts; connected health; smartphones; teams
ID AMERICAN-HEART-ASSOCIATION; HEALTH BEHAVIOR-CHANGE; ACTIVITY
INTERVENTIONS; SCIENTIFIC STATEMENT; EXERCISE ADHERENCE; WEARABLE
DEVICES; IMPROVE HEALTH; OLDER-ADULTS; US ADULTS; METAANALYSIS
AB BACKGROUND: More than half of adults in the United States do not attain the minimum recommended level of physical activity to achieve health benefits. The optimal design of financial incentives to promote physical activity is unknown.
OBJECTIVE: To compare the effectiveness of individual versus team-based financial incentives to increase physical activity.
DESIGN: Randomized, controlled trial comparing three interventions to control.
PARTICIPANTS: Three hundred and four adult employees from an organization in Philadelphia formed 76 four-member teams.
INTERVENTIONS: All participants received daily feedback on performance towards achieving a daily 7000 step goal during the intervention (weeks 113) and follow-up (weeks 14-26) periods. The control arm received no other intervention. In the three financial incentive arms, drawings were held in which one team was selected as the winner every other day during the 13-week intervention. A participant on a winning team was eligible as follows: $50 if he or she met the goal (individual incentive), $50 only if all four team members met the goal (team incentive), or $20 if he or she met the goal individually and $10 more for each of three teammates that also met the goal (combined incentive).
MAIN MEASURES: Mean proportion of participant-days achieving the 7000 step goal during the intervention.
KEY RESULTS: Compared to the control group during the intervention period, the mean proportion achieving the 7000 step goal was significantly greater for the combined incentive (0.35 vs. 0.18, difference: 0.17, 95 % confidence interval [CI]: 0.07-0.28, p < 0.001) but not for the individual incentive (0.25 vs 0.18, difference: 0.08, 95 % CI: -0.02-0.18, p = 0.13) or the team incentive (0.17 vs 0.18, difference: -0.003, 95 % CI: -0.11-0.10, p = 0.96). The combined incentive arm participants also achieved the goal at significantly greater rates than the team incentive (0.35 vs. 0.17, difference: 0.18, 95 % CI: 0.08-0.28, p < 0.001), but not the individual incentive (0.35 vs. 0.25, difference: 0.10, 95 % CI: -0.001-0.19, p = 0.05). Only the combined incentive had greater mean daily steps than control (difference: 1446, 95 % CI: 448-2444, p = 0.005). There were no significant differences between arms during the follow-up period (weeks 14-26).
CONCLUSIONS: Financial incentives rewarded for a combination of individual and team performance were most effective for increasing physical activity.
C1 [Patel, Mitesh S.; Asch, David A.; Bellamy, Scarlett L.; Volpp, Kevin G.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Patel, Mitesh S.; Asch, David A.; Small, Dylan S.; Volpp, Kevin G.] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA.
[Patel, Mitesh S.; Asch, David A.; Wesby, Lisa; Hoffer, Karen; Shuttleworth, David; Taylor, Devon H.; Hilbert, Victoria; Zhu, Jingsan; Yang, Lin; Wang, Xingmei; Volpp, Kevin G.] Univ Penn, LDI Ctr Hlth Incent & Behav Econ, Philadelphia, PA 19104 USA.
[Patel, Mitesh S.; Asch, David A.; Rosin, Roy; Volpp, Kevin G.] Penn Med Ctr Hlth Care Innovat, Philadelphia, PA USA.
[Patel, Mitesh S.; Asch, David A.; Volpp, Kevin G.] Crescenz Vet Affairs Med Ctr, Philadelphia, PA USA.
[Eberbach, Kimberly; Walters, Karen J.] Independence Blue Cross, Philadelphia, PA USA.
[Haff, Nancy] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Lee, Samantha M.] Columbia Univ, Med Ctr, New York, NY USA.
RP Patel, MS (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM mpatel@upenn.edu
RI Emchi, Karma/Q-1952-2016
FU National Institute on Aging [RC4 AG039114]; Department of Veteran
Affairs; Robert Wood Johnson Foundation
FX This work was funded by the National Institute on Aging (RC4 AG039114)
to Drs. Asch and Volpp. Drs. Patel, Asch and Volpp were supported in
part by the Department of Veteran Affairs and Drs. Patel and Asch were
supported in part by the Robert Wood Johnson Foundation. The funding
sources had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; and preparation,
review, or approval of the manuscript; and decision to submit the
manuscript for publication. Dr. Patel had full access to all the data in
the study and takes responsibility for the integrity of the data and the
accuracy of the data analysis.
NR 57
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U1 7
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2016
VL 31
IS 7
BP 746
EP 754
DI 10.1007/s11606-016-3627-0
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4KS
UT WOS:000379871000012
PM 26976287
ER
PT J
AU Al-Helou, G
Anklesaria, Z
Kohlwes, J
Ahari, J
Dhaliwal, G
AF Al-Helou, Georges
Anklesaria, Zafia
Kohlwes, Jeffrey
Ahari, Jalil
Dhaliwal, Gurpreet
TI When the Illness Goes Off Script-An Exercise in Clinical Reasoning
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
DE systemic inflammatory response; sepsis; illness scripts
ID LANGERHANS CELL HISTIOCYTOSIS; HEMOPHAGOCYTIC SYNDROME; ABDOMINAL-PAIN;
WOMAN
C1 [Al-Helou, Georges; Ahari, Jalil] George Washington Univ Hosp, Pulm & Crit Care Div, Washington, DC 20037 USA.
[Anklesaria, Zafia] Univ Calif Los Angeles, Pulm & Crit Care Div, Los Angeles, CA USA.
[Kohlwes, Jeffrey; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kohlwes, Jeffrey; Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA.
RP Al-Helou, G (reprint author), George Washington Univ Hosp, Pulm & Crit Care Div, Washington, DC 20037 USA.
EM gre05@email.gwu.edu
NR 9
TC 0
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2016
VL 31
IS 7
BP 803
EP 807
DI 10.1007/s11606-016-3632-3
PG 5
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4KS
UT WOS:000379871000021
PM 26976289
ER
PT J
AU Rigotti, NA
AF Rigotti, Nancy A.
TI The Question that I Could Not Answer
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
[Rigotti, Nancy A.] Harvard Med Sch, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA.; Rigotti, NA (reprint author), Harvard Med Sch, 50 Staniford St,9th Floor, Boston, MA 02114 USA.
EM nrigotti@partners.org
NR 0
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD JUL
PY 2016
VL 31
IS 7
BP 816
EP 817
DI 10.1007/s11606-016-3622-5
PG 2
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DR4KS
UT WOS:000379871000026
PM 26921154
ER
PT J
AU Tsan, JY
Stock, EM
Greenawalt, DS
Zeber, JE
Copeland, LA
AF Tsan, Jack Y.
Stock, Eileen M.
Greenawalt, David S.
Zeber, John E.
Copeland, Laurel A.
TI Mental health treatment after major surgery among Vietnam-era Veterans
with posttraumatic stress disorder
SO JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE mental health treatment; posttraumatic stress disorder; surgery;
Veterans
ID QUALITY-OF-LIFE; ADMINISTRATIVE DATA; PHYSICAL HEALTH; OLDER-ADULTS;
MILITARY; AFFAIRS; PTSD
AB The purpose of this study was to examine mental health treatment use among Vietnam Veterans with posttraumatic stress disorder and determine whether undergoing major surgery interrupted mental health treatment or increased the risk of psychiatric hospitalization. Using retrospective data from Veterans Health Administration's electronic medical record system, a total of 3320 Vietnam-era surgery patients with preoperative posttraumatic stress disorder were identified and matched 1:4 with non-surgical patients with posttraumatic stress disorder. The receipt of surgery was associated with a decline in overall mental health treatment and posttraumatic stress disorder-specific treatment 1month following surgery but not during any subsequent month thereafter. Additionally, surgery was not associated with psychiatric admission.
C1 [Tsan, Jack Y.; Zeber, John E.; Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst, Austin, TX USA.
[Tsan, Jack Y.; Stock, Eileen M.; Zeber, John E.; Copeland, Laurel A.] Cent Texas Vet Hlth Care Syst Jointly Scott & Whi, Ctr Appl Hlth Res, Temple, TX USA.
[Greenawalt, David S.] Albany Stratton VA Med Ctr, Albany, NY USA.
RP Tsan, JY (reprint author), US Dept Vet Affairs, Cent Texas Vet Hlth Care Syst, Austin Outpatient Clin, 7901 Metropolis Dr,O11A-2, Austin, TX 78744 USA.
EM jack.tsan@va.gov
OI Copeland, Laurel/0000-0002-9478-0209
FU Veterans Health Administration [HSRD IIR-09-335]; VISN 17 Center of
Excellence for Research on Returning War Veterans; Center for Applied
Health Research; Central Texas Veterans Health Care System; Scott &
White Healthcare
FX This study was supported by the Veterans Health Administration including
HSR&D IIR-09-335 (Copeland-PI), the VISN 17 Center of Excellence for
Research on Returning War Veterans, and the Center for Applied Health
Research, jointly sponsored by Central Texas Veterans Health Care System
and Scott & White Healthcare.
NR 25
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Z9 0
U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1359-1053
EI 1461-7277
J9 J HEALTH PSYCHOL
JI J. Health Psychol.
PD JUL
PY 2016
VL 21
IS 7
BP 1249
EP 1260
DI 10.1177/1359105314551620
PG 12
WC Psychology, Clinical
SC Psychology
GA DR3SX
UT WOS:000379824000006
PM 25305191
ER
PT J
AU Dale, SK
Bogart, LM
Wagner, GJ
Galvan, FH
Klein, DJ
AF Dale, Sannisha K.
Bogart, Laura M.
Wagner, Glenn J.
Galvan, Frank H.
Klein, David J.
TI Medical mistrust is related to lower longitudinal medication adherence
among African-American males with HIV
SO JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE African-American males; beliefs; HIV; medical mistrust; medication
adherence
ID ANTIRETROVIRAL THERAPY ADHERENCE; RANDOMIZED CONTROLLED-TRIAL; LESS-THAN
95-PERCENT; HEALTH-CARE; INFECTED PATIENTS; RACIAL/ETHNIC DISPARITIES;
VIRAL SUPPRESSION; UNITED-STATES; DRUG-USERS; MEN
AB African-Americans living with HIV show worse health behaviors (e.g. medication adherence) and outcomes (e.g. viral suppression) than do their White counterparts. In a 6-month longitudinal study, we investigated whether medical mistrust among African-American males with HIV (214 enrolled, 140 with longitudinal data) predicted lower electronically monitored antiretroviral medication adherence. General medical mistrust (e.g. suspicion toward providers), but not racism-related mistrust (e.g. belief that providers treat African-Americans poorly due to race), predicted lower continuous medication adherence over time (b=-.08, standard error=.04, p=.03). Medical mistrust may contribute to poor health outcomes. Intervention efforts that address mistrust may improve adherence among African-Americans with HIV.
C1 [Dale, Sannisha K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dale, Sannisha K.; Bogart, Laura M.; Klein, David J.] Harvard Med Sch, Boston, MA USA.
[Dale, Sannisha K.; Bogart, Laura M.; Klein, David J.] Boston Childrens Hosp, Boston, MA USA.
[Wagner, Glenn J.] RAND Corp, Santa Monica, CA USA.
[Galvan, Frank H.] Bienestar Human Serv, San Diego, CA USA.
RP Dale, SK (reprint author), Massachusetts Gen Hosp, Behav Med Serv, One Bowdoin Sq,Suite 701, Boston, MA 02114 USA.
EM skdale@mgh.harvard.edu
FU National Institute of Mental Health [R01MH072351]; National Institute of
Minority Health and Health Disparities [R01MD003964]
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This
research was funded by the National Institute of Mental Health
(R01MH072351, PI: Laura M Bogart) and the National Institute of Minority
Health and Health Disparities (R01MD003964, PI: Laura M Bogart). The
authors of this publication are solely responsible for the content,
which does not necessarily represent the views of the National Institute
of Mental Health.
NR 37
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U1 1
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1359-1053
EI 1461-7277
J9 J HEALTH PSYCHOL
JI J. Health Psychol.
PD JUL
PY 2016
VL 21
IS 7
BP 1311
EP 1321
DI 10.1177/1359105314551950
PG 11
WC Psychology, Clinical
SC Psychology
GA DR3SX
UT WOS:000379824000012
PM 25293970
ER
PT J
AU Higgins, DM
Buta, E
Dorflinger, L
Heapy, AA
Ruser, CB
Goulet, JL
Masheb, RM
AF Higgins, Diana M.
Buta, Eugenia
Dorflinger, Lindsey
Heapy, Alicia A.
Ruser, Christopher B.
Goulet, Joseph L.
Masheb, Robin M.
TI Psychometric properties of a MOVE!23 subscale: Perceived Contributors to
Weight Change in a national sample of veterans
SO JOURNAL OF HEALTH PSYCHOLOGY
LA English
DT Article
DE body mass index; eating behavior; gender; illness; obesity;
psychological distress
ID HEALTH-CARE-SYSTEM; BODY-MASS; OBESITY; ADULTS; PREVALENCE; MORTALITY
AB The MOVE!23, a questionnaire to assess weight-related domains in veterans, was examined. Factor analysis of Perceived Contributors to Weight Change revealed three factors (psychosocial, eating behavior, and medical) that were positively correlated with body mass index, and psychiatric and medical comorbidity (p's<0.001). Multivariable cumulative logit models modeling the factor scores indicated that women were more likely than men to endorse psychosocial (odds ratio=2.15, confidence interval=2.04-2.27) and medical (odds ratio=1.69, confidence interval=1.59-1.79) items. The MOVE!23 Perceived Contributors to Weight Change subscale is a reliable and valid measure that is associated with body mass index and may assist in tailoring treatments according to gender and comorbidity.
C1 [Higgins, Diana M.] VA Boston Healthcare Syst, 150 South Huntington Ave,116B, Boston, MA USA.
[Higgins, Diana M.] Boston Univ, Boston, MA 02215 USA.
[Buta, Eugenia; Dorflinger, Lindsey; Heapy, Alicia A.; Ruser, Christopher B.; Goulet, Joseph L.; Masheb, Robin M.] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Buta, Eugenia; Dorflinger, Lindsey; Heapy, Alicia A.; Ruser, Christopher B.; Goulet, Joseph L.; Masheb, Robin M.] Yale Univ, New Haven, CT 06520 USA.
RP Higgins, DM (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave,116B, Boston, MA USA.
EM diana.higgins2@va.gov
OI Higgins, Diana/0000-0002-6885-266X; Goulet, Joseph/0000-0002-0842-804X
NR 15
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1359-1053
EI 1461-7277
J9 J HEALTH PSYCHOL
JI J. Health Psychol.
PD JUL
PY 2016
VL 21
IS 7
BP 1394
EP 1403
DI 10.1177/1359105314554530
PG 10
WC Psychology, Clinical
SC Psychology
GA DR3SX
UT WOS:000379824000020
PM 25293969
ER
PT J
AU Doyle, BJ
Ettner, SL
Nuckols, TK
AF Doyle, Brian J.
Ettner, Susan L.
Nuckols, Teryl K.
TI Supplemental insurance reduces out-of-pocket costs in medicare
observation services
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Letter
C1 [Doyle, Brian J.; Ettner, Susan L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Doyle, Brian J.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Ettner, Susan L.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA USA.
[Nuckols, Teryl K.] Cedar Sinai Med Ctr, Dept Med, Div Gen Internal Med, Los Angeles, CA USA.
[Nuckols, Teryl K.] RAND Corp, Santa Monica, CA USA.
RP Doyle, BJ (reprint author), 911 Broxton Plaza, Los Angeles, CA 90024 USA.
EM bdoyle@mednet.ucla.edu
OI Doyle, Brian/0000-0003-2782-2306
NR 11
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1553-5592
EI 1553-5606
J9 J HOSP MED
JI J. Hosp. Med.
PD JUL
PY 2016
VL 11
IS 7
BP 502
EP 504
DI 10.1002/jhm.2588
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA DR6VI
UT WOS:000380039000008
PM 27373701
ER
PT J
AU Prahl, M
Dhaliwal, G
Shulman, ST
Doshi, N
Monash, B
AF Prahl, Mary
Dhaliwal, Gurpreet
Shulman, Stanford T.
Doshi, Neeti
Monash, Bradley
TI Another spin
SO JOURNAL OF HOSPITAL MEDICINE
LA English
DT Editorial Material
ID TOXIC-SHOCK-SYNDROME; STAPHYLOCOCCUS-AUREUS
C1 [Prahl, Mary; Doshi, Neeti; Monash, Bradley] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA.
[Dhaliwal, Gurpreet; Monash, Bradley] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Shulman, Stanford T.] Northwestern Univ, Dept Pediat, Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
RP Monash, B (reprint author), 505 Parnassus Ave,Box 0131, San Francisco, CA 94143 USA.
EM bradley.monash@ucsf.edu
NR 7
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1553-5592
EI 1553-5606
J9 J HOSP MED
JI J. Hosp. Med.
PD JUL
PY 2016
VL 11
IS 7
BP 509
EP 512
DI 10.1002/jhm.2574
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DR6VI
UT WOS:000380039000010
PM 27018991
ER
PT J
AU Liao, YF
Feng, Y
Shen, J
Gao, Y
Cote, G
Choy, E
Harmon, D
Mankin, H
Hornicek, F
Duan, ZF
AF Liao, Yunfei
Feng, Yong
Shen, Jacson
Gao, Yan
Cote, Gregory
Choy, Edwin
Harmon, David
Mankin, Henry
Hornicek, Francis
Duan, Zhenfeng
TI Clinical and biological significance of PIM1 kinase in osteosarcoma
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE osteosarcoma; PIM1 kinase; tissue microarray; Bcl-2
ID PROSTATE-CANCER CELLS; POTENTIAL THERAPEUTIC TARGET; PROTEIN-KINASES;
GASTRIC-CANCER; STAT3 PATHWAY; EXPRESSION; APOPTOSIS; GROWTH;
PROLIFERATION; INHIBITOR
AB Osteosarcoma is the most prevalent histological form of primary malignant bone tumor. The majority of osteosarcoma patients have limited alternative therapeutic options and metastatic patients generally have a poor prognosis. Proto-oncogene serine/threonine-protein kinase PIM1 is associated with growth and survival of many kinds of tumor cells. However, the role of PIM1 in osteosarcoma remains largely unknown. In this study, we investigated the functional and therapeutic relevance of PIM1 as a putative target in osteosarcoma. We found PIM1 was highly expressed in various osteosarcoma cell lines and in tumor tissues from osteosarcoma patients. Tissue microarray and immunohistochemistry analysis showed that the overall and disease-free survival rate of patients with high levels of PIM1 protein expression were significantly shorter than patients with low levels. High levels of PIM1 were also associated with present metastasis and can be considered as an independent prognostic factor in osteosarcoma patients. Knockdown of PIM1 expression by synthetic siRNA or shRNA greatly inhibited cell growth, migration, and invasion. Moreover, these changes accompanied with down-regulation of anti-apoptotic protein Bcl-2. The similar results were obtained in osteosarcoma cells treated with PIM1 specific inhibitor (SMI-4a). These results suggest that PIM1 kinase is critical for the growth and metastasis of osteosarcoma cells and can be a potential therapeutic target for osteosarcoma treatment. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1185-1194, 2016.
C1 [Liao, Yunfei; Feng, Yong; Shen, Jacson; Gao, Yan; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA.
[Liao, Yunfei; Feng, Yong; Shen, Jacson; Gao, Yan; Cote, Gregory; Choy, Edwin; Harmon, David; Mankin, Henry; Hornicek, Francis; Duan, Zhenfeng] Harvard Med Sch, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA.
[Liao, Yunfei] Huazhong Univ Sci & Technol, Dept Endocrine, Wuhan Union Hosp, Tongji Med Coll, 1277 Jie Fang Ave, Wuhan 430022, Peoples R China.
[Feng, Yong] Huazhong Univ Sci & Technol, Dept Orthopaed Surg, Wuhan Union Hosp, Tongji Med Coll, 1277 Jie Fang Ave, Wuhan 430022, Peoples R China.
[Cote, Gregory; Choy, Edwin; Harmon, David] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA.
RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Sarcoma Biol Lab, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA.; Duan, ZF (reprint author), Harvard Med Sch, 55 Fruit St,Jackson 1115, Boston, MA 02114 USA.
EM zduan@mgh.harvard.edu
OI Cote, Gregory/0000-0003-0181-886X
FU Gattegno and Wechsler; Kenneth Stanton; Sarcoma Foundation of America
(SFA); National Cancer Institute (NCI)/National Institutes of Health
(NIH) [CA 151452-01]; Sarcoma SPORE/NIH; Academic Enrichment Fund of MGH
Orthopaedics
FX Grant sponsor: Gattegno and Wechsler; Grant sponsor: Kenneth Stanton;
Grant sponsor: Sarcoma Foundation of America (SFA); Grant sponsor:
National Cancer Institute (NCI)/National Institutes of Health (NIH);
Grant numbers: UO1, CA 151452-01; Grant sponsor: Sarcoma SPORE/NIH;
Grant sponsor: Academic Enrichment Fund of MGH Orthopaedics.
NR 44
TC 2
Z9 2
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD JUL
PY 2016
VL 34
IS 7
BP 1185
EP 1194
DI 10.1002/jor.23134
PG 10
WC Orthopedics
SC Orthopedics
GA DR6OT
UT WOS:000380021900010
PM 26687194
ER
PT J
AU Liang, T
Hu, XX
Zhu, L
Pan, XL
Zhou, YS
Liu, JZ
AF Liang, Tian
Hu, Xingxue
Zhu, Lin
Pan, Xueliang
Zhou, Yongsheng
Liu, Jianzhang
TI Comparative in vitro study of cementing techniques for implant-supported
restorations
SO JOURNAL OF PROSTHETIC DENTISTRY
LA English
DT Article
ID RETAINED PROSTHESES; EXCESS CEMENT; BOND STRENGTH; SCREW ACCESS; LUTING
AGENT; CROWNS; RETENTION; METAL; COMPLICATIONS; RESISTANCE
AB Statement of problem. Various techniques are used to cement implant-supported restorations. Excess residual cement is a concern.
Purpose. The purpose of this in vitro study was to evaluate 3 techniques for cementing implant supported restorations.
Material and methods. Twelve crowns and implant-abutment complexes (IAC) were cemented with 3 techniques: technique 1, a certain amount of cement evenly placed and excess cement removed with an explorer; technique 2, a smaller amount of cement without removal of excess cement; technique 3, a resin abutment replica used for excess cement removal after using a large amount of cement. Each specimen was treated with each technique 3 times. Precementing discrepancies (predis) and postcementing discrepancies (postdis) between IACs and crowns and the postcementing linear roughness (Ra and Rz) on designated junction areas of each specimen were measured. Tensile strength of the specimens was recorded with a universal testing machine at a crosshead speed of 0.5 mm/min. Repeated measures analysis with mixed models was used for differences among the 3 cementing techniques (alpha=.05).
Results. Compared with techniques 1 and 2, the specimens with technique 3 showed significantly lower mean differences between postdis and predis and Ra and Rz and higher mean tensile strength (P<.05).
Conclusions. The application of a resin abutment replica for the cementation of implant-supported restorations decreased the discrepancy between the restoration and abutment, reduced cement residue, and increased restoration retention.
C1 [Liang, Tian; Zhu, Lin; Zhou, Yongsheng; Liu, Jianzhang] Peking Univ, Dept Prosthodont, Sch & Hosp Stomatol, 22 Zhongguancun Nandajie, Beijing 100081, Peoples R China.
[Hu, Xingxue] Forsyth Inst, Cambridge, MA USA.
[Hu, Xingxue] Ohio State Univ, Coll Dent, Div Gen Practice & Mat Sci, Columbus, OH 43210 USA.
[Pan, Xueliang] Ohio State Univ, Coll Med, Ctr Biostat, Columbus, OH 43210 USA.
RP Liu, JZ (reprint author), Peking Univ, Dept Prosthodont, Sch & Hosp Stomatol, 22 Zhongguancun Nandajie, Beijing 100081, Peoples R China.
EM liujianzhangdr@163.com
FU National Key Clinical Specialty Construction Project of China
FX Supported by the National Key Clinical Specialty Construction Project of
China (2011).
NR 34
TC 0
Z9 0
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3913
EI 1097-6841
J9 J PROSTHET DENT
JI J. Prosthet. Dent.
PD JUL
PY 2016
VL 116
IS 1
BP 59
EP 66
PG 8
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DR4RG
UT WOS:000379889300013
PM 26946915
ER
PT J
AU Herwald, SE
Chen, JH
Arellano, RS
AF Herwald, Sauna E.
Chen, Jonathan H.
Arellano, Ronald S.
TI Irreversible Electroporation for Treatment of Hepatocellular Carcinoma
Adjacent to the Gallbladder
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Letter
ID HEPATIC-TUMORS ADJACENT; RADIOFREQUENCY ABLATION; SAFETY
C1 [Herwald, Sauna E.] Tufts Univ, Sch Med, 145 Harrison Ave, Boston, MA 02111 USA.
[Chen, Jonathan H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
RP Herwald, SE (reprint author), Tufts Univ, Sch Med, 145 Harrison Ave, Boston, MA 02111 USA.
NR 4
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1051-0443
EI 1535-7732
J9 J VASC INTERV RADIOL
JI J. Vasc. Interv. Radiol.
PD JUL
PY 2016
VL 27
IS 7
BP 1093
EP 1094
DI 10.1016/j.jvir.2016.03.008
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA DR3II
UT WOS:000379796500023
PM 27338501
ER
PT J
AU Zizic, M
Faquin, W
Stephen, AE
Kamani, D
Nehme, R
Slough, CM
Randolph, GW
AF Zizic, Marica
Faquin, William
Stephen, Antonia E.
Kamani, Dipti
Nehme, Romy
Slough, Cristian M.
Randolph, Gregory W.
TI Upper Neck Papillary Thyroid Cancer (UPTC): A New Proposed Term for the
Composite of Thyroglossal Duct Cyst-Associated Papillary Thyroid Cancer,
Pyramidal Lobe Papillary Thyroid Cancer, and Delphian Node Papillary
Thyroid Cancer Metastasis
SO LARYNGOSCOPE
LA English
DT Article
DE Thyroglossal duct cyst cancer; pyramidal lobe PTC; Delphian node
metastasis; midline neck mass
ID CASE SERIES; TUMOR SIZE; CARCINOMA; MANAGEMENT; CT; SURGERY; REMNANT
AB Objectives/Hypothesis: Thyroglossal duct cyst (TGDC) is a common congenital anomaly, but TGDC carcinoma is rare. Thyroglossal duct cyst carcinoma management is controversial, especially that of the orthotopic thyroid gland. We aim to provide an insight into the pathologic basis of this management controversy through the review of 28 TGDC cancer cases, thus far the largest such series to our knowledge.
Study Design: Retrospective.
Methods: Twenty-eight cases recorded as TGDC cancer in the hospital database were reviewed; their initial clinical diagnosis from medical chart review (DX1) and final pathological review diagnosis (DX2) through pathology slides review by our pathologist (blinded to DX1) were compared. The thyroid gland management and pathology were evaluated.
Results: In the 28 TGDC carcinoma (hospital-recorded diagnosis) patients, DX1 and DX2 were respectively reported as 53% and 14% TGDC carcinoma, 11% and 29% as pyramidal lobe primary, and 4% and 25% as metastatic Delphian node. Thirty-two percent of cases were in the indeterminate category, in both DX1 and DX2, but included different patients. Thyroidectomy was performed in 54% of the cases, papillary thyroid cancer (PTC) was reported in 37% of these thyroid glands. Concurrent thyroid gland malignancy was reported in all Delphian node and pyramidal lobe PTC patients.
Conclusion: The diagnosis of TGDC cancer comprises a heterogeneous group that includes true TGDC cancer, pyramidal lobe primary, Delphian node metastasis, and indeterminate cases. We propose a new terminology of upper neck papillary thyroid carcinoma (UPTC) to denote this heterogeneous group and recommend a rational algorithm for management. Correct pathologic subcategory and thyroid ultrasonography are essential for optimal management of thyroid gland in UPTC cases.
C1 [Zizic, Marica; Kamani, Dipti; Nehme, Romy; Slough, Cristian M.; Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA.
[Zizic, Marica; Faquin, William; Stephen, Antonia E.; Kamani, Dipti; Nehme, Romy; Slough, Cristian M.; Randolph, Gregory W.] Harvard Med Sch, Boston, MA USA.
[Faquin, William] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.
RP Randolph, GW (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA.
EM gregory_randolph@meei.harvard.edu
FU John and Claire Bertucci Thyroid Research fund
FX This work was funded by the John and Claire Bertucci Thyroid Research
fund. The authors have no other funding, financial relationships, or
conflicts of interest to disclose.
NR 28
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD JUL
PY 2016
VL 126
IS 7
BP 1709
EP 1714
DI 10.1002/lary.25824
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA DR6AP
UT WOS:000379983800046
PM 26691539
ER
PT J
AU Papp, KV
Mormino, EC
Amariglio, RE
Munro, C
Dagley, A
Schultz, AP
Johnson, KA
Sperling, RA
Rentz, DM
AF Papp, Kathryn V.
Mormino, Elizabeth C.
Amariglio, Rebecca E.
Munro, Catherine
Dagley, Alex
Schultz, Aaron P.
Johnson, Keith A.
Sperling, Reisa A.
Rentz, Dorene M.
TI Biomarker Validation of a Decline in Semantic Processing in Preclinical
Alzheimer's Disease
SO NEUROPSYCHOLOGY
LA English
DT Article
DE preclinical Alzheimer's disease; verbal fluency; semantic processing;
amyloid
ID MILD COGNITIVE IMPAIRMENT; MENTAL-STATE-EXAMINATION; VERBAL FLUENCY;
CATEGORY FLUENCY; OLDER-ADULTS; MEMORY; BETA; DEMENTIA; BRAIN;
PERFORMANCE
AB Objective: Differentially worse performance on category versus letter fluency suggests greater semantic versus retrieval difficulties. This discrepancy, combined with reduced episodic memory, has widespread clinical utility in diagnosing Alzheimer's disease (AD). Our objective was to investigate whether changes in semantic processing, as measured by the discrepancy between category and letter fluency, was detectable in preclinical AD: in clinically normal older adults with abnormal beta-amyloid (A beta) deposition on positron emission tomography (PET) neuroimaging. Method: Clinically normal older adults (mean Mini Mental State Exam (MMSE) score = 29) were classified as A beta+ (n = 70) or A beta- (n = 205) using Pittsburgh Compound B-(PET) imaging. Participants completed letter fluency (FAS; word generation to letters F-A-S) and category fluency (CAT; word generation to animals, vegetables, fruits) annually (mean follow-up = 2.42 years). The effect of A beta status on fluency over time was examined using linear mixed models controlling for age, sex, and education. To dissociate effects related to semantic (CAT) versus retrieval processes (CAT and FAS), we repeated models predicting CAT over time, controlling for FAS and likewise for CAT controlling for FAS. Results: At baseline, the A beta+ group performed better on FAS compared with the A beta- group but comparably on CAT. Longitudinally, the A beta+ group demonstrated greater decline on CAT compared with the A beta- group (p = .0011). This finding remained significant even when covarying for FAS (p = .0107). A beta+ participants similarly declined compared with A beta- participants on FAS (p = .0112), but this effect became insignificant when covarying for CAT (p = .1607). Conclusion: These findings provide biomarker validation for the greater specificity of declines in category versus letter fluency to underlying AD pathology. Our results also suggest that changes in semantic processing occur earlier in the AD trajectory than previously hypothesized.
C1 [Papp, Kathryn V.; Amariglio, Rebecca E.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Med Sch, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA USA.
[Mormino, Elizabeth C.; Munro, Catherine; Dagley, Alex; Schultz, Aaron P.; Johnson, Keith A.; Sperling, Reisa A.; Rentz, Dorene M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Johnson, Keith A.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA.
[Johnson, Keith A.] Harvard Med Sch, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA USA.
RP Papp, KV (reprint author), Brigham & Womens Hosp, Ctr Alzheimers Res & Treatment, 221 Longwood Ave, Boston, MA 02115 USA.
EM kpapp@partners.org
FU NIA grant [T32AG023480-08]; Health Resources in Action/Charles King
Trust; [P01 AG036694]; [K24 AG035007]; [R01AG027435]; [F32AG044054];
[K23AG044431]
FX This work was supported by NIA grant T32AG023480-08 and by the Health
Resources in Action/Charles King Trust (KVP) as well as: P01 AG036694
(RAS, KAJ), K24 AG035007 (RAS), R01AG027435 (RAS, KAJ), F32AG044054
(ECM), and K23AG044431 (REA).
NR 37
TC 1
Z9 1
U1 5
U2 5
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0894-4105
EI 1931-1559
J9 NEUROPSYCHOLOGY
JI Neuropsychology
PD JUL
PY 2016
VL 30
IS 5
SI SI
BP 624
EP 630
DI 10.1037/neu0000246
PG 7
WC Psychology, Clinical; Neurosciences; Psychology
SC Psychology; Neurosciences & Neurology
GA DR2XE
UT WOS:000379766400011
PM 26595826
ER
PT J
AU Teo, L
Lagler, CP
Mannor, G
Glass, LD
Freitag, SK
AF Teo, Livia
Lagler, Christine P.
Mannor, Geva
Glass, Lora D.
Freitag, Suzanne K.
TI Mullers Muscle Conjunctival Resection for Treatment of Contact
Lens-Associated Ptosis
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID UPPER EYELID PTOSIS; BLEPHAROPTOSIS; WEAR; SECONDARY; SURGERY
AB Purpose: The aim of this study was to look at the surgical outcomes of posterior approach Mullers muscle conjunctival resection surgery for contact lens-related ptosis.
Methods: This was a retrospective, comparative interventional case series. All patients and controls underwent phenylephrine 10% testing and had a positive response prior to surgical intervention.
Results: Thirty-one eyelids with ptosis were identified in 20 contact lens wearing patients, which were matched with 27 eyelids in 15 controls. The contact lens wearing patients wore contact lenses for a mean of 20.6 +/- 12.1 years. More than half (60%) wore soft contact lenses, as opposed to rigid gas-permeable contact lenses. Preoperative margin-to-reflex distance-1 was lower in patients who wore rigid contact lenses (0.8 +/- 0.7 mm) as compared with patients with soft contact lenses (1.7 +/- 1.1 mm) (p = 0.01). Surgical success, as defined by margin-to-reflex distance-1 >= 3 mm or symmetry of upper eyelid height (within 1 mm), was achieved in 93.5% in the contact lens group and 92.6% of controls. Postoperative margin-to-reflex distance-1 was significantly higher in the contact lens wearers (3.9 +/- 1.3 mm) compared with the controls (3.2 +/- 1.1 mm; p = 0.01). There was a significant correlation between the amount of tissue resected intraoperatively and the improvement in margin-to-reflex distance-1 (Pearsons correlation coefficient, r = 0.36; p = 0.006). There were no surgical complications of any patients in the study.
Conclusion: Mullers muscle conjunctival resection surgery is an effective surgical correction for contact lens-associated ptosis. Patients can achieve excellent results with minimal risk of residual ptosis or asymmetry.
C1 [Teo, Livia; Glass, Lora D.; Freitag, Suzanne K.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Teo, Livia] Singapore Natl Eye Ctr, Singapore, Singapore.
[Lagler, Christine P.] Boston Med Ctr, Boston, MA USA.
[Mannor, Geva] Scripps Clin, La Jolla, CA 92037 USA.
RP Freitag, SK (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, 243 Charles St, Boston, MA 02114 USA.
EM Suzanne_Freitag@MEEI.HARVARD.EDU
NR 22
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0740-9303
EI 1537-2677
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD JUL-AUG
PY 2016
VL 32
IS 4
BP 257
EP 260
DI 10.1097/IOP.0000000000000479
PG 4
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA DR2WU
UT WOS:000379765400016
PM 25906332
ER
PT J
AU Campbell, AA
Jakobiec, FA
Rashid, A
Dana, R
Yoon, MK
AF Campbell, Ashley A.
Jakobiec, Frederick A.
Rashid, Alia
Dana, Reza
Yoon, Michael K.
TI Bilateral Sequential Dacryocystitis in a Patient With Graft-Versus-Host
Disease
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; DRY EYE
AB A 29-year-old woman with a history of 2 bone marrow transplants for acute myelogenous leukemia developed bilateral sequential dacryocystitis in the context of known ocular graft-versus-host disease. With each infection, the patient underwent uneventful dacryocystorhinostomy. Postoperatively, she developed severe dry eye disease requiring replacement of punctal plugs and use of a prosthetic replacement of the ocular surface ecosystem lens. Histopathologic and immunohistochemical examination of the lacrimal sac showed a dense diffuse nonfollicular lymphocytic subepithelial infiltrate in the lacrimal sac that contained moderately more T-cells than B-cells. This is the first report of acute dacryocystitis associated with graft-versus-host disease. The authors caution that similar patients may develop worsening of ocular surface dryness due to restoration of normal lacrimal outflow.
C1 [Campbell, Ashley A.; Yoon, Michael K.] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA.
[Campbell, Ashley A.; Jakobiec, Frederick A.; Rashid, Alia; Dana, Reza; Yoon, Michael K.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA.
[Jakobiec, Frederick A.; Rashid, Alia] Massachusetts Eye & Ear Infirm, David G Cogan Ophthalm Pathol Lab, Boston, MA 02114 USA.
[Dana, Reza] Massachusetts Eye & Ear Infirm, Corneal & External Dis, Boston, MA 02114 USA.
RP Yoon, MK (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM michael_yoon@meei.harvard.edu
NR 15
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0740-9303
EI 1537-2677
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD JUL-AUG
PY 2016
VL 32
IS 4
BP E89
EP E92
DI 10.1097/IOP.0000000000000267
PG 5
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA DR2WU
UT WOS:000379765400007
PM 25192327
ER
PT J
AU Talcott, KE
Lee, NG
Freitag, SK
AF Talcott, Katherine E.
Lee, Nahyoung Grace
Freitag, Suzanne K.
TI Vascular Engorgement of Lacrimal Gland Associated With Port-Wine Stain
SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Article
ID STURGE-WEBER-SYNDROME; LESIONS; RISK
AB Port-wine stains are congenital dermal capillary malformations that typically involve the head and neck. While most of them are isolated malformations, they have been associated with other vascular findings, including conjunctival, episcleral, and choroidal hemangiomas. They have also been associated with the phakomatosis Sturge-Weber syndrome, characterized by parietooccipital, leptomeningeal, and ocular choroidal vascular malformations. However, vascular engorgement of the lacrimal gland has not been previously reported in association with port-wine stains. The authors present a case of a 52-year-old man with a long-standing and isolated right periorbital port-wine stain referred for lacrimal gland enlargement on CT scan. He was found to have asymptomatic right lacrimal gland vascular engorgement, which was radiographically stable over a period of 5 years.
C1 [Talcott, Katherine E.; Lee, Nahyoung Grace; Freitag, Suzanne K.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
RP Freitag, SK (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg Serv, 243 Charles St, Boston, MA 02114 USA.
EM Suzanne_Freitag@meei.harvard.edu
NR 8
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0740-9303
EI 1537-2677
J9 OPHTHAL PLAST RECONS
JI Ophthalmic Plast. Reconstr. Surg.
PD JUL-AUG
PY 2016
VL 32
IS 4
BP E92
EP E94
DI 10.1097/IOP.0000000000000271
PG 4
WC Ophthalmology; Surgery
SC Ophthalmology; Surgery
GA DR2WU
UT WOS:000379765400008
PM 25198395
ER
PT J
AU Puram, SV
Barber, SR
Kozin, ED
Shah, P
Remenschneider, A
Herrmann, BS
Duhaime, AC
Barker, FG
Lee, DJ
AF Puram, Sidharth V.
Barber, Samuel R.
Kozin, Elliott D.
Shah, Parth
Remenschneider, Aaron
Herrmann, Barbara S.
Duhaime, Ann-Christine
Barker, Fred G., II
Lee, Daniel J.
TI Outcomes following Pediatric Auditory Brainstem Implant Surgery: Early
Experiences in a North American Center
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT AAO-HNSF Annual Meeting and OTO EXPO
CY SEP 27-30, 2015
CL Dallas, TX
SP AAO, HNSF
DE auditory brainstem implant; ABI; pediatric; clinical trial; deafness;
hearing loss; nonneurofibromatosis type II
ID COCHLEAR NERVE; CHILDREN; ABI
AB There are no approved Food and Drug Administration indications for pediatric auditory brainstem implant (ABI) surgery in the United States. Our prospective case series aims to determine the safety and feasibility of ABI surgery in pediatric patients <5 years old with congenital deafness at a tertiary North American center. The inclusion criterion was pre- or postlinguistic deafness in children not eligible for cochlear implantation. Seventeen candidates were evaluated (mean +/- SD: age, 2.52 +/- 0.39 years). Four patients underwent ABI surgery (age, 19.2 +/- 3.43 months), including 4 primary procedures and 1 revision for device failure. Spontaneous device failure occurred in another subject postoperatively. No major/minor complications occurred, including cerebrospinal fluid leak, facial nerve injury, hematoma, and nonauditory stimulation. All subjects detected sound with environmental awareness, and several demonstrated babbling and mimicry. Poor durability of older implants underscores need for updated technology.
C1 [Puram, Sidharth V.; Barber, Samuel R.; Kozin, Elliott D.; Shah, Parth; Remenschneider, Aaron; Lee, Daniel J.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
[Puram, Sidharth V.; Kozin, Elliott D.; Remenschneider, Aaron; Lee, Daniel J.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA.
[Herrmann, Barbara S.] Massachusetts Eye & Ear Infirm, Dept Audiol, Boston, MA 02114 USA.
[Duhaime, Ann-Christine] Massachusetts Gen Hosp, Dept Pediat Neurosurg, Boston, MA 02114 USA.
[Duhaime, Ann-Christine; Barker, Fred G., II] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Duhaime, Ann-Christine; Barker, Fred G., II] Harvard Med Sch, Dept Surg Neurosurg, Boston, MA USA.
RP Lee, DJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM Daniel_lee@meei.harvard.edu
NR 18
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
EI 1097-6817
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD JUL
PY 2016
VL 155
IS 1
BP 133
EP 138
DI 10.1177/0194599816637599
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DR6NR
UT WOS:000380019100024
PM 27095049
ER
PT J
AU Naqvi, M
Goldfarb, IT
Hanmer, KJ
Bryant, A
AF Naqvi, Mariam
Goldfarb, Ilona T.
Hanmer, Kaitlin J.
Bryant, Allison
TI Chromosomal microarray use among women undergoing invasive prenatal
diagnosis
SO PRENATAL DIAGNOSIS
LA English
DT Article
ID DETECTED FETAL ANOMALIES; CONGENITAL-ANOMALIES; EXPERIENCES; ISSUES
AB ObjectiveTo study the offer and uptake of chromosomal microarray analysis (CMA) among women undergoing invasive prenatal testing.
MethodsThis is a retrospective cohort study of women who underwent chorionic villus sampling (CVS) or amniocentesis. Charts were reviewed for CMA offer and uptake, in additional to clinical and demographic variables.
ResultsOne hundred forty-one women underwent CVS (n=53) or amniocentesis (n=91) over the study period. Overall, 41% of women underwent CMA. Women who underwent invasive testing for a fetal structural abnormality were more likely to undergo CMA than women who underwent invasive testing for all other indications (aOR 43.18, 95% CI 4.64 - 401.58). Chromosomal microarray was offered more often to women who primarily spoke English (p<0.001), self-identified as white (p=0.046) and did not receive prenatal care in a community health center (p=0.044). Statistically significant differences in CMA uptake by race/ethnicity, language, insurance or provider type were not noted. Multiparous women were less likely to accept this test than nulliparas (aOR 0.39, 95% CI 0.17 - 0.86).
ConclusionWomen who undergo invasive fetal testing are more likely to undergo CMA if the indication is for a fetal structural anomaly. There may be important demographic disparities in the offering of CMA which bear further exploration. (c) 2016 John Wiley & Sons, Ltd.
C1 [Naqvi, Mariam; Goldfarb, Ilona T.; Hanmer, Kaitlin J.; Bryant, Allison] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA.
RP Naqvi, M (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02114 USA.
EM mnaqvi@partners.org
NR 20
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0197-3851
EI 1097-0223
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD JUL
PY 2016
VL 36
IS 7
BP 656
EP 661
DI 10.1002/pd.4835
PG 6
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA DR5BU
UT WOS:000379918800009
PM 27130707
ER
PT J
AU Yoshimi, A
Suda, A
Hayano, F
Nakamura, M
Aoyama-Uehara, K
Konishi, J
Asami, T
Kishida, I
Kawanishi, C
Inoue, T
McCarley, RW
Shenton, ME
Hirayasu, Y
AF Yoshimi, Asuka
Suda, Akira
Hayano, Fumi
Nakamura, Motoaki
Aoyama-Uehara, Kumi
Konishi, Jun
Asami, Takeshi
Kishida, Ikuko
Kawanishi, Chiaki
Inoue, Tomio
McCarley, Robert W.
Shenton, Martha E.
Hirayasu, Yoshio
TI Effects of NRG1 genotypes on orbitofrontal sulcogyral patterns in
Japanese patients diagnosed with schizophrenia
SO PSYCHIATRY AND CLINICAL NEUROSCIENCES
LA English
DT Article
DE magnetic resonance imaging; neuregulin-1; orbitofrontal gyrus;
schizophrenia; single nucleotide polymorphisms
ID HEALTHY-SUBJECTS; BRAIN; NEUREGULIN-1; GENE; SUSCEPTIBILITY;
POLYMORPHISM; CORTEX
AB AimNumerous reports have described differences in the distribution of orbitofrontal cortex (OFC) sulcogyral patterns between patients with schizophrenia (SZ patients) and healthy controls (HC). Alterations in OFC morphology are also observed in those at high risk for developing SZ and in first-episode SZ, suggesting that genetic associations may be extant in determining OFC sulcogyral patterns. We investigated the association between single nucleotide polymorphisms (SNP) in NRG1 and OFC sulcogyral patterns.
MethodsA total of 59 Japanese patients diagnosed with SZ and 60 HC were scanned on a 1.5-T magnet. Patients were also assessed clinically. OFC sulcogyral patterns were evaluated for each participant, and genotyping was performed for four SNP in NRG1(SNP8NRG243177, SNP8NRG221533, SNP8NRG241930, and rs1081062).
ResultsThere were significant differences in the distribution of OFC sulcogyral patterns between SZ patients and HC ((2) = 6.52, P = 0.038). SZ patients showed an increase in the frequency of Type III expression, which was associated with an earlier age of disease onset ( = -0.302, F = 4.948, P = 0.030). Although no difference was found in genotype frequencies between SZ patients and HC, an NRG1SNP, SNP8NRG243177, was associated with Type II expression in SZ patients ( = 0.237, F = 4.120, P = 0.047).
ConclusionOur results suggest that OFC sulcogyral pattern formation in schizophrenia may be associated with NRG1 allele frequency, which is closely related to neurodevelopment.
C1 [Yoshimi, Asuka; Suda, Akira; Hayano, Fumi; Nakamura, Motoaki; Konishi, Jun; Asami, Takeshi; Kishida, Ikuko; Hirayasu, Yoshio] Yokohama City Univ, Sch Med, Dept Psychiat, Yokohama, Kanagawa, Japan.
[Aoyama-Uehara, Kumi] Yokohama City Univ, Sch Med, Dept Psychiat Child Psychiat, Yokohama, Kanagawa, Japan.
[Inoue, Tomio] Yokohama City Univ, Sch Med, Dept Radiol, Yokohama, Kanagawa, Japan.
[Nakamura, Motoaki] Kanagawa Psychiat Ctr, Yokohama, Kanagawa, Japan.
[Kawanishi, Chiaki] Sapporo Med Univ, Sch Med, Dept Psychiat, Sapporo, Hokkaido, Japan.
[McCarley, Robert W.] Boston VA Healthcare Syst, Brockton Div, Clin Neurosci Div, Lab Neurosci, Boston, MA USA.
[Shenton, Martha E.] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
[Shenton, Martha E.] Harvard Med Sch, Dept Radiol, Boston, MA USA.
[Shenton, Martha E.] VA Boston Healthcare Syst, Boston, MA USA.
RP Hirayasu, Y (reprint author), Yokohama City Univ, Sch Med, Dept Psychiat, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan.
EM hirayasu@yokohama-cu.ac.jp
FU Intramural Research Grant for Neurological and Psychiatric Disorders of
the National Center of Neurology and Psychiatry [24-1]
FX This work was supported by an Intramural Research Grant (24-1) for
Neurological and Psychiatric Disorders of the National Center of
Neurology and Psychiatry.
NR 24
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1323-1316
EI 1440-1819
J9 PSYCHIAT CLIN NEUROS
JI Psychiatry Clin. Neurosci.
PD JUL
PY 2016
VL 70
IS 7
SI SI
BP 261
EP 268
DI 10.1111/pcn.12384
PG 8
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DR5JQ
UT WOS:000379939700002
PM 26909665
ER
PT J
AU LaMotte, AD
Taft, CT
Weatherill, RP
AF LaMotte, Adam D.
Taft, Casey T.
Weatherill, Robin P.
TI Mistrust of Others as a Mediator of the Relationship Between Trauma
Exposure and Use of Partner Aggression
SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY
LA English
DT Article
DE partner violence; abuse; trauma; mistrust; schema
ID POSTTRAUMATIC-STRESS-DISORDER; VIOLENCE PERPETRATION; LIFE EVENTS;
SYMPTOMS
AB Objective: Prior research indicates a connection between the experience of trauma and use of intimate partner aggression (IPA), but little work has focused on core cognitive schemas that can be influenced by trauma. In the current study, we examine the cognitive schema of mistrust in others as a mediator of the relationship between trauma exposure and IPA use. This schema may lead to IPA through distorted social information processing that can escalate relationship conflict. Method: The sample consisted of 83 heterosexual community couples. All variables were assessed via written questionnaires, and IPA frequency was calculated by incorporating both partners' reports on each member of the couple. Results: For males, mistrust significantly mediated the relationships between trauma exposure and both physical and psychological IPA use. For females, mistrust did not mediate the significant relationship between trauma exposure and IPA use. In analyses using the actor-partner interdependence model, both actor and partner mistrust uniquely predicted physical and psychological IPA use. Conclusions: The findings of the study suggest the importance of examining core schemas that may underlie trauma reactions and use of IPA.
C1 [LaMotte, Adam D.; Taft, Casey T.; Weatherill, Robin P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA.
[Taft, Casey T.; Weatherill, Robin P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
RP Taft, CT (reprint author), VA Boston Healthcare Syst 116B 4, 150 South Huntington Ave, Boston, MA 02130 USA.
EM casey.taft@va.gov
FU National Institute of Mental Health Award [K08 MH73117 01A2]
FX Funding for this study was provided by National Institute of Mental
Health Award K08 MH73117 01A2 to Casey T. Taft.
NR 20
TC 0
Z9 0
U1 4
U2 4
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1942-9681
EI 1942-969X
J9 PSYCHOL TRAUMA-US
JI Psychol. Trauma
PD JUL
PY 2016
VL 8
IS 4
BP 535
EP 540
DI 10.1037/tra0000157
PG 6
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DR2XO
UT WOS:000379767400016
PM 27348070
ER
PT J
AU Topcuoglu, MA
Singhal, AB
AF Topcuoglu, Mehmet A.
Singhal, Aneesh B.
TI Hemorrhagic Reversible Cerebral Vasoconstriction Syndrome Features and
Mechanisms
SO STROKE
LA English
DT Article
DE cerebral arterial diseases; headache; stroke; subarachnoid hemorrhage;
vasoconstriction
ID HYPERINTENSE VESSELS; ANGIOGRAPHY; NIMODIPINE; ANGIOPATHY; SERIES
AB Background and Purpose-To compare hemorrhagic and nonhemorrhagic reversible cerebral vasoconstriction syndromes (RCVS) with a view to understand mechanisms.
Methods-This single-center retrospective study included 162 patients with RCVS. Clinical, brain imaging, and angiography data were analyzed.
Results-The mean age was 44 +/- 13 years, 78% women. Hemorrhages occurred in 43% including 21 patients with intracerebral hemorrhage (ICH) and 62 with convexal subarachnoid hemorrhage (cSAH). The frequency of triggers (eg, vasoconstrictive drugs) and risk factors (eg, migraine) were not significantly different between hemorrhagic and nonhemorrhagic RCVS or between subgroups (ICH versus non-ICH, isolated cSAH versus normal scan). Hemorrhagic lesions occurred within the first week, whereas infarcts and vasogenic edema accumulated during 2 to 3 weeks (P<0.001). Although all ICHs occurred before cSAH, their time course was not significantly different (P=0.11). ICH and cSAH occurred earlier than infarcts (P <= 0.001), and ICH earlier than vasogenic edema (P=0.009). Angiogram analysis showed more severe vasoconstriction in distal versus proximal segments in all lesion types (ICH, cSAH, infarction, vasogenic edema, and normal scan). The isolated infarction group had more severe proximal vasoconstriction, and those with normal imaging had significantly less vasoconstriction. Multivariable analysis failed to uncover independent predictors of hemorrhagic RCVS; however, female sex predicted ICH (P=0.048), and angiographic severity predicted infarction (P=0.043).
Conclusions-ICH and cSAH are common complications of RCVS. Triggers and risk factors do not predict lesion subtype but may alter central vasomotor control mechanisms resulting in centripetal angiographic evolution. Early distal vasoconstriction is associated with lobar ICH and cSAH, and delayed proximal vasoconstriction with infarction.
C1 [Topcuoglu, Mehmet A.; Singhal, Aneesh B.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Topcuoglu, Mehmet A.] Hacettepe Univ Hosp, Dept Neurol, Ankara, Turkey.
RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA.
EM asinghal@partners.org
NR 19
TC 4
Z9 4
U1 2
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUL
PY 2016
VL 47
IS 7
BP 1742
EP 1747
DI 10.1161/STROKEAHA.116.013136
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DR4AX
UT WOS:000379844900023
PM 27272485
ER
PT J
AU Berntsson, J
Ostling, G
Persson, M
Smith, JG
Hedblad, B
Engstrom, G
AF Berntsson, John
Ostling, Gerd
Persson, Margaretha
Smith, J. Gustav
Hedblad, Bo
Engstrom, Gunnar
TI Orosomucoid, Carotid Plaque, and Incidence of Stroke
SO STROKE
LA English
DT Article
DE acute-phase reaction; carotid artery disease; cytokines; risk factor;
stroke
ID SENSITIVE PLASMA-PROTEINS; ACUTE-PHASE PROTEINS; C-REACTIVE PROTEIN;
ALPHA(1)-ACID GLYCOPROTEIN; ALPHA-1-ACID GLYCOPROTEIN; CEREBRAL
INFARCTION; CYSTATIN-C; MYOCARDIAL-INFARCTION; SERUM GLYCOPROTEINS;
ARTERY PLAQUE
AB Background and Purpose-Orosomucoid (alpha-1-acid glycoprotein) is an acute-phase protein that has been implicated in anti-inflammatory, immunomodulating, and angiogenic pathways. Orosomucoid has also been associated with coronary disease and stroke. The relationship between orosomucoid, carotid plaque, and stroke incidence were explored in this study.
Methods-Plasma levels of orosomucoid were assessed in 4285 subjects (39.8% men; mean age 57.5 +/- 5.9 years) without cardiovascular disease, who participated in the Malmo Diet and Cancer Study, between 1991 and 1994. The right carotid artery was examined for plaque using B-mode ultrasound examination. Incidence of stroke was followed up during a median follow-up time of 17.7 years.
Results-Carotid plaque was present in 43.5% at baseline. Orosomucoid was significantly higher in subjects with carotid plaque (mean +/- SD: 0.72 +/- 0.22 versus 0.69 +/- 0.20 g/L; P<0.001). A total of 234 subjects were diagnosed with ischemic stroke during follow-up. Orosomucoid was associated with ischemic stroke after adjustment for risk factors, with hazard ratio 1.48 (95% confidence interval, 1.02-2.16) comparing the third versus first tertile. In subjects with plaque and belonging to the top tertile of orosomucoid, the hazard ratio was 2.07 (95% confidence interval, 1.38-3.11) compared with those without plaque and with orosomucoid in the first and second tertiles, after adjustment for C-reactive protein and other risk factors.
Conclusions-Elevated levels of orosomucoid are associated with increased occurrence of carotid plaque and increased incidence of ischemic stroke. The combination of high orosomucoid and carotid plaque substantially increase the risk of stroke.
C1 [Berntsson, John; Ostling, Gerd; Persson, Margaretha; Smith, J. Gustav; Hedblad, Bo; Engstrom, Gunnar] Lund Univ, Dept Clin Sci Malmo, Lund, Sweden.
[Smith, J. Gustav] Lund Univ, Dept Cardiol, Lund, Sweden.
[Smith, J. Gustav] Skane Univ Hosp, Dept Heart Failure & Valvular Dis, Lund, Sweden.
[Smith, J. Gustav] Harvard & MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Smith, J. Gustav] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA.
[Smith, J. Gustav] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.
[Smith, J. Gustav] Harvard Med Sch, Boston, MA USA.
RP Berntsson, J (reprint author), Lund Univ, CRC, House 60,Level 13,Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden.
EM john.berntsson@med.lu.se
FU Swedish Heart-Lung Foundation; Swedish Research Council; Swedish Stroke
Foundation; Ernhold Lundstroms Foundation; Skane University Hospital;
European Research Council; Crafoord Foundation; clinical research within
the Swedish National Health Service
FX The study was supported by the Swedish Heart-Lung Foundation (G.
Engstrom and J.G. Smith), the Swedish Research Council (G. Engstrom and
J.G. Smith), the Swedish Stroke Foundation (G. Engstrom), the Ernhold
Lundstroms Foundation (G. Engstrom), and funds from Skane University
Hospital (G. Engstrom and J.G. Smith). J.G. Smith was supported by the
European Research Council, the Crafoord Foundation, and governmental
funding of clinical research within the Swedish National Health Service.
NR 38
TC 1
Z9 1
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUL
PY 2016
VL 47
IS 7
BP 1858
EP 1863
DI 10.1161/STROKEAHA.116.013374
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DR4AX
UT WOS:000379844900041
PM 27301938
ER
PT J
AU Arai, K
AF Arai, Ken
TI Third European Stroke Science Workshop
SO STROKE
LA English
DT Editorial Material
C1 [Arai, Ken] Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
[Arai, Ken] Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA.
[Arai, Ken] Harvard Med Sch, Charlestown, MA USA.
RP Arai, K (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, East 149-2401, Charlestown, MA 02129 USA.
EM karai@mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD JUL
PY 2016
VL 47
IS 7
BP e187
EP e187
DI 10.1161/STROKEAHA.116.013426
PG 1
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DR4AX
UT WOS:000379844900002
PM 28163337
ER
PT J
AU Boatin, AA
Wylie, BJ
Goldfarb, I
Azevedo, R
Pittel, E
Ng, C
Haberer, JE
AF Boatin, Adeline Adwoa
Wylie, Blair Johnson
Goldfarb, Ilona
Azevedo, Robin
Pittel, Elena
Ng, Courtney
Haberer, Jessica Elizabeth
TI Wireless Vital Sign Monitoring in Pregnant Women: A Functionality and
Acceptability Study
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE wireless monitoring; vital sign; wireless device; pregnant women;
maternal care; obstetrics
ID BLOOD-PRESSURE MONITOR; PROTOCOL REVISION 2010; EUROPEAN-SOCIETY; HOME;
HYPERTENSION; TEMPERATURE; VALIDATION; AGREEMENT; RESPONSES; NURSES
AB Objective: To test the functionality and acceptability of a wireless vital sign monitor in an inpatient obstetric unit. Materials and Methods: Pregnant women at a U.S. tertiary-care hospital wore a wireless vital sign sensor that captures heart rate, respiratory rate, and temperature. Measurements were compared with vital signs obtained by standard devices. We defined continuous capture of vital signs for 30 min with wireless data transfer to a central monitor as functional success. Acceptability was assessed per the pregnant women and nurses observing the device. Bland-Altman plots were constructed to assess agreement between the wireless sensor and standard measurements. Results: Thirty of 32 enrolled pregnant women had successful monitoring; 2 cases were stopped early for non-study-related reasons. Comparing wireless sensor and standard measurements, the mean difference (limits of agreement) values at the 25th and 75th percentiles were 1.6 (+/- 13.2) and 4.2 (+/- 18.6) heartbeats/min, 4.2 (+/- 6.1) and 0.7 (+/- 5.4) respirations/min, and 0.02 degrees C (+/- 1.5) and 0.5 degrees C (+/- 1.8), respectively. Most pregnant women found the device comfortable, likeable, and useful (78%, 81%, and 97%, respectively); 80% of nurses found the monitor easy to use, and 84% would recommend it to a patient. Conclusions: We successfully obtained maternal vital signs using a simple wireless monitor with high acceptability. Well-validated monitors of this nature could significantly alleviate the human resource burden of monitoring during labor and confer greatly desired mobility to laboring pregnant women, although incorporation of blood pressure monitoring will be critical.
C1 [Boatin, Adeline Adwoa] Harvard Med Sch, Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St,Founders 5, Boston, MA 02114 USA.
[Wylie, Blair Johnson; Goldfarb, Ilona] Harvard Med Sch, Massachusetts Gen Hosp, Div Maternal Fetal Med, 55 Fruit St,Founders 5, Boston, MA 02114 USA.
[Azevedo, Robin; Pittel, Elena] Massachusetts Gen Hosp, Dept Nursing, Boston, MA 02114 USA.
[Ng, Courtney] Harvard Sch Publ Hlth, Boston, MA USA.
[Haberer, Jessica Elizabeth] Harvard Med Sch, Ctr Global Hlth, Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Boatin, AA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Obstet & Gynecol, 55 Fruit St,Founders 5, Boston, MA 02114 USA.
EM aboatin@partners.org
FU Gary and Mary West Health Institute
FX This study was conducted at the Massachusetts General Hospital with
support provided by the Gary and Mary West Health Institute, an
independent, not-for-profit medical research organization that works
with healthcare providers and research institutions to create new, more
effective ways of delivering care.
NR 30
TC 0
Z9 0
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD JUL
PY 2016
VL 22
IS 7
BP 564
EP 571
DI 10.1089/tmj.2015.0173
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DQ8GU
UT WOS:000379447900004
PM 27172448
ER
PT J
AU Dorsey, ER
Achey, MA
Beck, CA
Beran, DB
Biglan, KM
Boyd, CM
Schmidt, PN
Simone, R
Willis, AW
Galifianakis, NB
Katz, M
Tanner, CM
Dodenhoff, K
Ziman, N
Aldred, J
Carter, J
Jimenez-Shahed, J
Hunter, C
Spindler, M
Mari, Z
Morgan, JC
McLane, D
Hickey, P
Gauger, L
Richard, IH
Bull, MT
Mejia, NI
Bwala, G
Nance, M
Shih, L
Anderson, L
Singer, C
Zadikoff, C
Okon, N
Feigin, A
Ayan, J
Vaughan, C
Pahwa, R
Cooper, J
Webb, S
Dhall, R
Hassan, A
Weis, D
DeMello, S
Riggare, SS
Wicks, P
Smith, J
Keenan, HT
Korn, R
Schwarz, H
Sharma, S
Stevenson, EA
Zhu, W
AF Dorsey, E. Ray
Achey, Meredith A.
Beck, Christopher A.
Beran, Denise B.
Biglan, Kevin M.
Boyd, Cynthia M.
Schmidt, Peter N.
Simone, Richard
Willis, Allison W.
Galifianakis, Nicholas B.
Katz, Maya
Tanner, Caroline M.
Dodenhoff, Kristen
Ziman, Nathan
Aldred, Jason
Carter, Julie
Jimenez-Shahed, Joohi
Hunter, Christine
Spindler, Meredith
Mari, Zoltan
Morgan, John C.
McLane, Dedi
Hickey, Patrick
Gauger, Lisa
Richard, Irene Hegeman
Bull, Michael T.
Mejia, Nicte I.
Bwala, Grace
Nance, Martha
Shih, Ludy
Anderson, Lauren
Singer, Carlos
Zadikoff, Cindy
Okon, Natalia
Feigin, Andrew
Ayan, Jean
Vaughan, Christina
Pahwa, Rajesh
Cooper, Jessica
Webb, Sydney
Dhall, Rohit
Hassan, Anhar
Weis, Delana
DeMello, Steven
Riggare, Sara S.
Wicks, Paul
Smith, Joseph
Keenan, H. Tait
Korn, Ryan
Schwarz, Heidi
Sharma, Saloni
Stevenson, E. Anna
Zhu, William
TI National Randomized Controlled Trial of Virtual House Calls for People
with Parkinson's Disease: Interest and Barriers
SO TELEMEDICINE AND E-HEALTH
LA English
DT Article
DE chronic conditions; home healthcare; Parkinson's disease; randomized
controlled trial; specialists; telemedicine; videoconferencing; access
to care
ID NURSING-HOME PLACEMENT; CLINICAL-TRIAL; SYSTEMATIC ANALYSIS; ECONOMIC
BURDEN; GLOBAL BURDEN; HEALTH-CARE; TELEMEDICINE; INTERNET; BOARD;
VALIDATION
AB Background: Delivering specialty care remotely directly into people's homes can enhance access for and improve the healthcare of individuals with chronic conditions. However, evidence supporting this approach is limited. Materials and Methods: Connect. Parkinson is a randomized comparative effectiveness study that compares usual care of individuals with Parkinson's disease in the community with usual care augmented by virtual house calls with a Parkinson's disease specialist from 1 of 18 centers nationally. Individuals in the intervention arm receive four virtual visits from a Parkinson's disease specialist over 1 year via secure, Web-based video-conferencing directly into their homes. All study activities, including recruitment, enrollment, and assessments, are conducted remotely. Here we report on interest, feasibility, and barriers to enrollment in this ongoing study. Results: During recruitment, 11,734 individuals visited the study's Web site, and 927 unique individuals submitted electronic interest forms. Two hundred ten individuals from 18 states enrolled in the study from March 2014 to June 2015, and 195 were randomized. Most participants were white (96%) and college educated (73%). Of the randomized participants, 73% had seen a Parkinson's disease specialist within the previous year. Conclusions: Among individuals with Parkinson's disease, national interest in receiving remote specialty care directly into the home is high. Remote enrollment in this care model is feasible but is likely affected by differential access to the Internet.
C1 [Dorsey, E. Ray; Biglan, Kevin M.; Richard, Irene Hegeman; Schwarz, Heidi] Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
[Dorsey, E. Ray; Keenan, H. Tait; Korn, Ryan; Sharma, Saloni; Stevenson, E. Anna; Zhu, William] Univ Rochester, Med Ctr, CHET, Rochester, NY 14642 USA.
[Achey, Meredith A.] Duke Univ, Sch Med, Durham, NC USA.
[Beck, Christopher A.; Bull, Michael T.] Univ Rochester, Dept Biostat, Rochester, NY USA.
[Beran, Denise B.; Schmidt, Peter N.] Natl Parkinson Fdn, Miami, FL USA.
[Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21205 USA.
[Simone, Richard] Simone Consulting, Sunnyvale, CA USA.
[Willis, Allison W.; Spindler, Meredith] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA.
[Willis, Allison W.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Galifianakis, Nicholas B.; Katz, Maya; Tanner, Caroline M.; Dodenhoff, Kristen; Ziman, Nathan] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Aldred, Jason] PLLC, Northwest Neurol, Spokane, WA USA.
[Carter, Julie] Oregon Hlth & Sci Univ, Parkinson Ctr, Portland, OR 97201 USA.
[Carter, Julie] Oregon Hlth & Sci Univ, Movement Disorders Program, Portland, OR 97201 USA.
[Jimenez-Shahed, Joohi; Hunter, Christine] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Mari, Zoltan] Johns Hopkins Univ, Dept Neurol & Neurosurg, Baltimore, MD USA.
[Morgan, John C.; McLane, Dedi] Georgia Regents Univ, Dept Neurol, Augusta, GA USA.
[Hickey, Patrick; Gauger, Lisa] Duke Med Ctr, Dept Neurol, Durham, NC USA.
[Mejia, Nicte I.; Bwala, Grace; Anderson, Lauren] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Nance, Martha; Singer, Carlos] Struthers Parkinsons Ctr, Golden Valley, MN USA.
[Shih, Ludy] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Singer, Carlos] Univ Miami, Dept Neurol, Miami, FL USA.
[Zadikoff, Cindy; Okon, Natalia] Northwestern Univ, Dept Neurol, Evanston, IL USA.
[Feigin, Andrew; Ayan, Jean] North Shore LIJ Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.
[Vaughan, Christina] Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA.
[Pahwa, Rajesh; Cooper, Jessica; Webb, Sydney] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA.
[Dhall, Rohit] Parkinsons Inst, Sunnyvale, CA USA.
[Hassan, Anhar; Weis, Delana] Mayo Clin, Dept Neurol, Rochester, MN USA.
[DeMello, Steven] Univ Calif Berkeley, Ctr Informat Technol Res Interest Soc, Berkeley, CA 94720 USA.
[Riggare, Sara S.] Karolinska Inst, Hlth Informat Ctr, Stockholm, Sweden.
[Wicks, Paul] PatientsLikeMe, Cambridge, MA USA.
[Smith, Joseph] West Hlth Inst, La Jolla, CA USA.
RP Dorsey, ER (reprint author), Univ Rochester, Med Ctr, Dept Neurol, Rochester, NY 14642 USA.
EM ray.dorsey@chet.rochester.edu
FU Patient-Centered Outcomes Research Institute [AD-12-11-4701]; National
Parkinson Foundation; University of Rochester CTSA award from the
National Center for Advancing Translational Sciences of the National
Institutes of Health [UL1 TR000042]
FX This research is supported by an award (AD-12-11-4701) from the
Patient-Centered Outcomes Research Institute, and the National Parkinson
Foundation is collaborating in the conduct of the study. Software used
in the study is provided and supported by SBR Health (Cambridge, MA),
Vidyo (Hackensack, NJ), and ID Solutions (Indianapolis, IN). The project
described in this publication was supported by the University of
Rochester CTSA award number UL1 TR000042 from the National Center for
Advancing Translational Sciences of the National Institutes of Health.
We would also like to thank Dr. David Brailer (Health Evolution
Partners), Dr. Robert Kolodner (ViTel Net), Dr. Ruth Schneider
(University of Rochester Medical Center), Ms. Kathryn Duderstadt
(Struthers Parkinson's Center), Ms. Silvia Vargas-Parra (University of
Miami), and Ms. Catherine Wielinski (Struthers Parkinson's Center) for
their contributions to the study.
NR 66
TC 3
Z9 3
U1 7
U2 10
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-5627
EI 1556-3669
J9 TELEMED E-HEALTH
JI Telemed. e-Health
PD JUL
PY 2016
VL 22
IS 7
BP 590
EP 598
DI 10.1089/tmj.2015.0191
PG 9
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DQ8GU
UT WOS:000379447900008
PM 26886406
ER
PT J
AU Stevenson, MD
Mansbach, JM
Mowad, E
Dunn, M
Clark, S
Piedra, PA
Sullivan, AF
Camargo, CA
AF Stevenson, Michelle D.
Mansbach, Jonathan M.
Mowad, Eugene
Dunn, Michelle
Clark, Sunday
Piedra, Pedro A.
Sullivan, Ashley F.
Camargo, Carlos A., Jr.
TI Prenatal Versus Postnatal Tobacco Smoke Exposure and Intensive Care Use
in Children Hospitalized With Bronchiolitis
SO ACADEMIC PEDIATRICS
LA English
DT Article
DE bronchiolitis; cigarette smoking; intensive care unit; respiratory
syncytial virus; tobacco
ID REAL-TIME PCR; MATERNAL SMOKING; LUNG-FUNCTION; CIGARETTE-SMOKE;
PROSPECTIVE MULTICENTER; PARENTAL SMOKING; CONTROLLED-TRIAL; INCREASED
RISK; ASTHMA; PREGNANCY
AB OBJECTIVE: Among children hospitalized with bronchiolitis, we examined the associations between in utero exposure to maternal cigarette smoking, postnatal tobacco smoke exposure, and risk of admission to the intensive care unit (ICU).
METHODS: We performed a 16-center, prospective cohort study of hospitalized children aged <2 years with a physician admitting diagnosis of bronchiolitis. For 3 consecutive years, from November 1, 2007 until March 31, 2010, site teams collected data from participating families, including information about prenatal maternal smoking and postnatal tobacco exposure. Analyses used chi-square, Fisher's exact, and Kruskal-Wallis tests and multivariable logistic regression.
RESULTS: Among 2207 enrolled children, 216 (10%) had isolated in utero exposure to maternal smoking, 168 (8%) had isolated postnatal tobacco exposure, and 115 (5%) experienced both. Adjusting for age, sex, race, birth weight, viral etiology, apnea, initial severity of retractions, initial oxygen saturation, oral intake, and postnatal tobacco exposure, children with in utero exposure to maternal smoking had greater odds of being admitted to the ICU (adjusted odds ratio [aOR] 1.51, 95% confidence interval [CI] 1.14-2.00). Among children with in utero exposure to maternal smoking, those with additional postnatal tobacco exposure had a greater likelihood of ICU admission (aOR 1.95, 95% CI 1.13-3.37) compared to children without postnatal tobacco smoke exposure (aOR 1.47, 95% CI 1.05-2.04).
CONCLUSIONS: Maternal cigarette smoking during pregnancy puts children hospitalized with bronchiolitis at significantly higher risk of intensive care use. Postnatal tobacco smoke exposure may exacerbate this risk. Health care providers should incorporate this information into counseling messages.
C1 [Stevenson, Michelle D.] Univ Louisville, Dept Pediat, Louisville, KY 40292 USA.
[Mansbach, Jonathan M.] Harvard Med Sch, Boston Childrens Hosp, Dept Med, Boston, MA USA.
[Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA.
[Mowad, Eugene] Akron Childrens Hosp, Dept Pediat, Akron, OH USA.
[Dunn, Michelle] Univ Penn, Perelman Sch Med, Dept Pediat, Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA.
[Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
RP Stevenson, MD (reprint author), 571 S Floyd St Suite 300, Louisville, KY 40202 USA.
EM michelle.stevenson@louisville.edu
FU National Institutes of Health (Bethesda, Md) [U01 AI-67693, K23
AI-77801]
FX We thank the MARC-30 investigators, whose names are listed in the
Appendix, for their continuing dedication to bronchiolitis research, and
Janice A. Espinola, MPH (Department of Emergency Medicine, Massachusetts
General Hospital, Harvard Medical School, Boston, Mass), for assistance
with data analysis and review of the article. Supported by grants U01
AI-67693 and K23 AI-77801 from the National Institutes of Health
(Bethesda, Md). The content of this article is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institute of Allergy and Infectious Diseases or the
National Institutes of Health.
NR 34
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1876-2859
EI 1876-2867
J9 ACAD PEDIATR
JI Acad. Pediatr.
PD JUL
PY 2016
VL 16
IS 5
BP 446
EP 452
PG 7
WC Pediatrics
SC Pediatrics
GA DQ7DI
UT WOS:000379366700006
PM 26555856
ER
PT J
AU Foss, MH
Pou, S
Davidson, PM
Dunaj, JL
Winter, RW
Pou, S
Licon, MH
Doh, JK
Li, YX
Kelly, JX
Dodean, RA
Koop, DR
Riscoe, MK
Purdy, GE
AF Foss, Marie H.
Pou, Sovitj
Davidson, Patrick M.
Dunaj, Jennifer L.
Winter, Rolf W.
Pou, Sovijja
Licon, Meredith H.
Doh, Julia K.
Li, Yuexin
Kelly, Jane X.
Dodean, Rozalia A.
Koop, Dennis R.
Riscoe, Michael K.
Purdy, Georgiana E.
TI Diphenylether-Modified 1,2-Diamines with Improved Drug Properties for
Development against Mycobacterium tuberculosis
SO ACS INFECTIOUS DISEASES
LA English
DT Article
DE antibiotic; drug development; tuberculosis; proton motive force; MmpL3
ID SPONTANEOUS MUTATION; ANTITUBERCULAR DRUG; TRANSPORTER ACRB; SQ109;
DISCOVERY; OPTIMIZATION; INHIBITION; MECHANISM; BINDING; MMPL3
AB New treatments for tuberculosis infection are critical to combat the emergence of multidrug- and extensively drug-resistant Mycobacterium tuberculosis (Mtb). We report the characterization of a diphenylether-modified adamantyl 1,2-diamine that we refer to as TBL-140, which has a minimal inhibitory concentration (MIC99) of 1.2 mu g/mL. TBL-140 is effective against drug-resistant Mtb and nonreplicating bacteria. In addition, TBL-140 eliminates expansion of Mtb in cell culture infection assays at its MIC. To define the mechanism of action of this compound, we performed a spontaneous mutant screen and biochemical assays. We determined that TBL-140 treatment affects the proton motive force (PMF) by perturbing the transmembrane potential (Delta Psi), consistent with a target in the electron transport chain (ETC). As a result, treated bacteria have reduced intracellular ATP levels. We show that TBL-140 exhibits greater metabolic stability than SQ109, a structurally similar compound in clinical trials for treatment of MDR-TB infections. Combined, these results suggest that TBL-140 should be investigated further to assess its potential as an improved therapeutic lead against Mtb.
C1 [Foss, Marie H.; Davidson, Patrick M.; Dunaj, Jennifer L.; Licon, Meredith H.; Doh, Julia K.; Riscoe, Michael K.; Purdy, Georgiana E.] Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
[Pou, Sovitj; Winter, Rolf W.; Pou, Sovijja; Li, Yuexin; Kelly, Jane X.; Dodean, Rozalia A.; Riscoe, Michael K.] Portland VA Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
[Koop, Dennis R.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
RP Purdy, GE (reprint author), Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM purdyg@ohsu.edu
FU Medical Research Foundation of Oregon Early Clinical Investigator grant;
NIH [T32 AI 007472]; U.S. Department of Veterans Affairs; National
Science Foundation [0741993]
FX M.H.F. was supported by a Medical Research Foundation of Oregon Early
Clinical Investigator grant and NIH T32 AI 007472. This project was
supported with funds from the U.S. Department of Veterans Affairs (MKR).
The National Science Foundation (Grant 0741993) supported the purchase
of the LTQ-Orbitrap Discovery MS system used for analysis of our
samples. We thank Dr. Karen Dobos at Colorado State University for
sharing the clinical susceptible and monoresistant Mtb pairs.
NR 29
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U1 3
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2373-8227
J9 ACS INFECT DIS
JI ACS Infect. Dis.
PD JUL
PY 2016
VL 2
IS 7
BP 500
EP 508
DI 10.1021/acsinfecdis.6b00052
PG 9
WC Chemistry, Medicinal; Infectious Diseases
SC Pharmacology & Pharmacy; Infectious Diseases
GA DR1AP
UT WOS:000379638600008
PM 27626102
ER
PT J
AU Petersen, T
Lee, YJ
Osinusi, A
Amorosa, VK
Wang, C
Kang, M
Matining, R
Zhang, X
Dou, DN
Umbleja, T
Kottilil, S
Peters, MG
AF Petersen, Tess
Lee, Yu-Jin
Osinusi, Anu
Amorosa, Valerianna K.
Wang, Crystal
Kang, Minhee
Matining, Roy
Zhang, Xiao
Dou, Diana
Umbleja, Triin
Kottilil, Shyam
Peters, Marion G.
TI Interferon Stimulated Gene Expression in HIV/HCV Coinfected Patients
Treated with Nitazoxanide/Peginterferon-Alfa-2a and Ribavirin
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HEPATITIS-C VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; NITAZOXANIDE;
TIZOXANIDE; PHARMACOKINETICS; INFECTION; HCV
AB A combination of nitazoxanide (NTZ), peginterferon (PegIFN), and ribavirin (RBV) may result in higher sustained virologic response (SVR) rates in hepatitis C virus (HCV) monoinfected patients. This study evaluated the effect of NTZ on interferon-stimulated gene (ISG) expression in vitro and in vivo among HIV/HCV genotype-1 (GT-1) treatment-naive patients. The ability of NTZ to enhance host response to interferon (IFN) signaling using the HCV cell culture system was initially evaluated. Second, ISG expression in 53 patients with treatment outcomes [21 SVR and 32 nonresponders (NR)] in the ACTG A5269 trial, a phase-II study (4-week lead in of NTZ 500mg daily followed by 48 weeks of NTZ, PegIFN, and weight-based RBV), was assessed. The relative expression of 48 ISGs in peripheral blood mononuclear cells (PBMCs) was measured at baseline, week 4, and week 8 of treatment in a blinded manner. In vitro NTZ produced a direct and additive antiviral effect with IFN-alfa, with pretreatment of NTZ resulting in maximal HCV suppression. NTZ augmented IFN-mediated ISG induction in PBMCs from relapsers and SVRs (p < 0.05), but not NR. In ACTG A5269, baseline expression of most ISGs was similar between NR and SVR. NTZ minimally induced 17 genes in NR and 13 genes in SVR after 4 weeks of therapy. However, after initiation of PegIFN and RBV, ISG induction was predominantly observed in the SVR group and not NR group. NTZ treatment facilitates IFN-induced suppression of HCV replication. Inability to achieve SVR with IFN-based therapy in this clinical trial is associated with diminished ISG response to therapy that is refractory to NTZ.
C1 [Petersen, Tess; Lee, Yu-Jin; Osinusi, Anu; Wang, Crystal; Zhang, Xiao; Dou, Diana; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Osinusi, Anu; Kottilil, Shyam] Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, 725 West Lombard St,Room S222, Baltimore, MD 21201 USA.
[Osinusi, Anu] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA.
[Amorosa, Valerianna K.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Amorosa, Valerianna K.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kang, Minhee; Matining, Roy; Umbleja, Triin] Harvard Sch Publ Hlth, Boston, MA USA.
[Peters, Marion G.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Kottilil, S (reprint author), Univ Maryland, Sch Med, Inst Human Virol, Div Clin Care & Res, 725 West Lombard St,Room S222, Baltimore, MD 21201 USA.
EM Skottilil@ihv.umaryland.edu
FU ACTG Network Leadership Grant [1U01AI068636]; ACTG Statistical and Data
Management Center Grant [1U01AI068634]; UAB VSL grant [NIH/NIAID
7UM1AI068636]; Intramural Research Program of the NIAID, National
Institutes of Health [AI000390]
FX ACTG A5269 members and funding: ACTG Network Leadership Grant
1U01AI068636. ACTG Statistical and Data Management Center Grant
1U01AI068634. For HCV RNA and HCV genotyping efforts performed at Dr.
Victoria A. Johnson's UAB Virology Laboratory 54: James Darren
Hazelwood. UAB VSL grant (NIH/NIAID 7UM1AI068636).; This research was
supported in part with federal funds from the Intramural Research
Program of the NIAID, National Institutes of Health (AI000390).
NR 21
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Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD JUL
PY 2016
VL 32
IS 7
BP 660
EP 667
DI 10.1089/aid.2015.0236
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA DR0PJ
UT WOS:000379609100007
PM 26974581
ER
PT J
AU Arout, CA
Perrino, AC
Ralevski, E
Acampora, G
Koretski, J
Limoncelli, D
Newcomb, J
Petrakis, IL
AF Arout, Caroline A.
Perrino, Albert C.
Ralevski, Elizabeth
Acampora, Gregory
Koretski, Julia
Limoncelli, Diana
Newcomb, Jenelle
Petrakis, Ismene L.
TI Effect of Intravenous Ethanol on Capsaicin-Induced Hyperalgesia in Human
Subjects
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Ethanol; Hyperalgesia; Capsaicin; Pain; Analgesia
ID EXPERIMENTAL PAIN MODELS; FEELING NO PAIN; CENTRAL SENSITIZATION;
HEALTHY-VOLUNTEERS; INTRADERMAL CAPSAICIN; ETHYL-ALCOHOL; ANALGESICS;
ALFENTANIL; MECHANISMS; DEPENDENCE
AB BackgroundThe objective of this study was to assess ethanol's (EtOH's) effects on capsaicin-induced hyperalgesia in healthy participants. Specifically, we investigated the change in area of capsaicin-induced hyperalgesia following 3 interventions: intravenous EtOH at 2 targeted breath alcohol concentrations (BrAC), or placebo.
MethodsEighteen participants participated in 3 test days in a randomized order. Each test day, participants received an intradermal capsaicin injection on the volar surface of the forearm, followed by either infusion of high concentration EtOH (targeted BrAC=0.100g/dl), low concentration EtOH (targeted BrAC=0.040g/dl), or placebo. The area of hyperalgesia was determined by von Frey technique at 2 time points, prior to EtOH infusion, and again when target BrAC was reached. The primary outcome was the percent change in the area of capsaicin-induced hyperalgesia. Additional outcome measures included the visual analogue scale of mood states (VAS), which was administered at each time point.
ResultsThere was a marked 30% reduction in the area of capsaicin-induced hyperalgesia with infusion of a high concentration of EtOH (p<0.05). Low concentration EtOH produced a 10% reduction in hyperalgesia area, although this finding did not reach significance. Further, participants reported significant feelings of euphoria and drowsiness at high concentrations of EtOH (p<0.05), as measured by the VAS.
ConclusionsIn a human model examining pain phenomena related to central sensitization, this study is the first to demonstrate that capsaicin-induced hyperalgesia is markedly attenuated by EtOH. The capsaicin experimental pain paradigm employed provides a novel approach to evaluate EtOH's effects on pain processing. The antihyperalgesic effects of EtOH observed have important clinical implications for the converging fields of substance abuse and pain medicine and may inform why patients with chronic pain often report alcohol use as a form of self-medication.
C1 [Arout, Caroline A.; Ralevski, Elizabeth; Koretski, Julia; Limoncelli, Diana; Newcomb, Jenelle; Petrakis, Ismene L.] Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA.
[Arout, Caroline A.; Ralevski, Elizabeth; Koretski, Julia; Limoncelli, Diana; Newcomb, Jenelle; Petrakis, Ismene L.] Yale Univ, Sch Med, Ctr Translat Neurosci Alcoholism, West Haven, CT 06516 USA.
[Arout, Caroline A.; Ralevski, Elizabeth; Koretski, Julia; Limoncelli, Diana; Newcomb, Jenelle; Petrakis, Ismene L.] Yale Univ, Sch Med, VA Alcohol Res Ctr, West Haven, CT 06516 USA.
[Perrino, Albert C.] Yale Univ, Sch Med, VA Connecticut Healthcare Syst, Dept Anesthesiol, West Haven, CT 06516 USA.
[Acampora, Gregory] Massachusetts Gen Hosp, Dept Psychiat, Harvard Ctr Addict Med, Boston, MA 02114 USA.
RP Arout, CA (reprint author), Yale Univ, Sch Med, Dept Psychiat, VA Connecticut Healthcare Syst, 950 Campbell Ave 116A, West Haven, CT 06516 USA.
EM caroline.arout@yale.edu
OI Arout, Caroline/0000-0003-0444-6432
FU Alcohol Beverage Medical Research Foundation; Veterans Administration
Merit Grant; VA Alcohol Research Center; Center for the Translational
Neuroscience of Alcoholism grant (NIAAA) [2P50-AA012870-07)]; [NIDA T32
DA007238]
FX Alcohol Beverage Medical Research Foundation, Veterans Administration
Merit Grant, VA Alcohol Research Center and Center for the Translational
Neuroscience of Alcoholism grant (NIAAA, 2P50-AA012870-07). This
manuscript was prepared for publication during C.A. Arout's postdoctoral
fellowship (grant # NIDA T32 DA007238; Principal Investigator: I. L.
Petrakis).
NR 36
TC 0
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U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD JUL
PY 2016
VL 40
IS 7
BP 1425
EP 1429
DI 10.1111/acer.13095
PG 5
WC Substance Abuse
SC Substance Abuse
GA DR3OG
UT WOS:000379811900007
PM 27218476
ER
PT J
AU Ptaszek, LM
White, B
Lubitz, SA
Carnicelli, AP
Heist, EK
Ellinor, PT
Machado, M
Wasfy, JH
Ruskin, JN
Armstrong, K
Brown, DF
Biddinger, PD
Mansour, M
AF Ptaszek, Leon M.
White, Benjamin
Lubitz, Steven A.
Carnicelli, Anthony P.
Heist, E. Kevin
Ellinor, Patrick T.
Machado, Monique
Wasfy, Jason H.
Ruskin, Jeremy N.
Armstrong, Katrina
Brown, David F.
Biddinger, Paul D.
Mansour, Moussa
TI Effect of a Multidisciplinary Approach for the Management of Patients
With Atrial Fibrillation in the Emergency Department on Hospital
Admission Rate and Length of Stay
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID UNITED-STATES; GUIDELINES; FLUTTER; DISCHARGE; COSTS
AB Management of atrial fibrillation (AF) in the emergency department (ED) is variable because of the absence of universally adopted treatment guidelines. To address potentially preventable hospital admissions and prolonged length of stay, an AF treatment pathway was co-developed by physicians from the cardiac electrophysiology service and the department of emergency medicine at our institution. The impact of this AF pathway on patient outcomes was evaluated with a prospective, observational study conducted in a single tertiary care center from July 1, 2013, to June 30, 2014. The primary study outcome was the rate of hospital admission. The secondary outcomes were duration of ED visit and inpatient length of stay. The 94 patients treated according to the AF pathway during the study period were less likely to be admitted than the 265 patients who received routine care (16% vs 80%, p <0.001). For admitted patients, the mean length of stay was shorter for patients treated according to the AF pathway (32 vs 85 hours, p = 0.002). The time spent in the ED was longer for patients in the AF pathway (16 vs 85 hours, p <0.001). Utilization of a multidisciplinary pathway for management of AF in the ED led to a significant reduction in the rate of hospital admission. Patients who were admitted after receiving care according to the AF pathway had a shorter length of stay. In conclusion, utilization of a multidisciplinary AF pathway resulted in a 5-fold reduction in admission rate and >2-fold reduction length of stay for admitted patients. (C) 2016 Elsevier Inc. All rights reserved. (Am J Cardiol 2016;118:64-71)
C1 [Ptaszek, Leon M.; Lubitz, Steven A.; Heist, E. Kevin; Ellinor, Patrick T.; Machado, Monique; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Ptaszek, Leon M.; Lubitz, Steven A.; Heist, E. Kevin; Ellinor, Patrick T.; Machado, Monique; Wasfy, Jason H.; Ruskin, Jeremy N.; Mansour, Moussa] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Ptaszek, Leon M.; Lubitz, Steven A.; Heist, E. Kevin; Ellinor, Patrick T.; Machado, Monique; Wasfy, Jason H.; Ruskin, Jeremy N.; Armstrong, Katrina; Mansour, Moussa] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[White, Benjamin; Brown, David F.; Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Carnicelli, Anthony P.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
RP Mansour, M (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.; Mansour, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.; Mansour, M (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
EM mmansour@mgh.harvard.edu
FU Deane Institute for Integrative Research in Atrial Fibrillation and
Stroke at the Massachusetts General Hospital
FX This work was supported by a research grant, awarded to Dr. Ptaszek, by
the Deane Institute for Integrative Research in Atrial Fibrillation and
Stroke at the Massachusetts General Hospital.
NR 23
TC 0
Z9 0
U1 1
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD JUL 1
PY 2016
VL 118
IS 1
BP 64
EP 71
DI 10.1016/j.amjcard.2016.04.014
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DR0YF
UT WOS:000379632100010
PM 27206910
ER
PT J
AU Mitchell, KS
Porter, B
Boyko, EJ
Field, AE
AF Mitchell, K. S.
Porter, B.
Boyko, E. J.
Field, A. E.
TI Longitudinal Associations Among Posttraumatic Stress Disorder,
Disordered Eating, and Weight Gain in Military Men and Women
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE binge eating; eating disorders; military; obesity
ID COMORBIDITY SURVEY-REPLICATION; MILLENNIUM COHORT; ADULT OBESITY; US
MILITARY; HEALTH; PREVALENCE; QUESTIONNAIRE; PREDICTORS; ENROLLMENT;
VETERANS
AB Obesity is a major health problem in the United States and a growing concern among members of the military. Posttraumatic stress disorder (PTSD) has been associated with overweight and obesity and may increase the risk of those conditions among military service members. Disordered eating behaviors have also been associated with PTSD and weight gain. However, eating disorders remain understudied in military samples. We investigated longitudinal associations among PTSD, disordered eating, and weight gain in the Millennium Cohort Study, which includes a nationally representative sample of male (italic toggle="yes"n = 27,741) and female (italic toggle="yes"n = 6,196) service members. PTSD at baseline (time 1; 2001-2003) was associated with disordered eating behaviors at time 2 (2004-2006), as well as weight change from time 2 to time 3 (2007-2008). Structural equation modeling results revealed that the association between PTSD and weight change from time 2 to time 3 was mediated by disordered eating symptoms. The association between PTSD and weight gain resulting from compensatory behaviors (vomiting, laxative use, fasting, overexercise) was significant for white participants only and for men but not women. PTSD was both directly and indirectly (through disordered eating) associated with weight change. These results highlight potentially important demographic differences in these associations and emphasize the need for further investigation of eating disorders in military service members.
C1 [Mitchell, K. S.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Mitchell, K. S.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Porter, B.] Naval Hlth Res Ctr, Deployment Hlth Res Dept, San Diego, CA USA.
[Porter, B.] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD USA.
[Boyko, E. J.] VA Puget Sound Healthcare Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
[Field, A. E.] Boston Childrens Hosp, Div Adolescent Med, Boston, MA USA.
[Field, A. E.] Harvard Med Sch, Boston, MA USA.
[Field, A. E.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Field, A. E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
RP Mitchell, KS (reprint author), Boston Univ, Natl Ctr PTSD, VA Boston Healthcare Syst, Dept Psychiat,Sch Med, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA.
EM Karen.Mitchell5@va.gov
FU Bureau of Medicine and Surgery [60002]; Military Operational Medicine
Research Program, United States Army Medical Research and Materiel
Command (Fort Detrick, Maryland); National Institutes of Health
[K01MH093750, P30DK017047]
FX This work represents report 15-25 supported by the Bureau of Medicine
and Surgery, under Work Unit No. 60002. The Millennium Cohort Study is
funded through the Military Operational Medicine Research Program,
United States Army Medical Research and Materiel Command (Fort Detrick,
Maryland). National Institutes of Health grants K01MH093750 (to K.S.M.)
and P30DK017047 (E.J.B.) supported the work of individual authors.
NR 43
TC 0
Z9 0
U1 9
U2 10
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD JUL 1
PY 2016
VL 184
IS 1
BP 33
EP 47
DI 10.1093/aje/kwv291
PG 15
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DR2UV
UT WOS:000379760300005
PM 27283146
ER
PT J
AU Wala, J
Zhang, CZ
Meyerson, M
Beroukhim, R
AF Wala, Jeremiah
Zhang, Cheng-Zhong
Meyerson, Matthew
Beroukhim, Rameen
TI VariantBam: filtering and profiling of next-generational sequencing data
using region-specific rules
SO BIOINFORMATICS
LA English
DT Article
AB We developed VariantBam, a C++ read filtering and profiling tool for use with BAM, CRAM and SAM sequencing files. VariantBam provides a flexible framework for extracting sequencing reads or read-pairs that satisfy combinations of rules, defined by any number of genomic intervals or variant sites. We have implemented filters based on alignment data, sequence motifs, regional coverage and base quality. For example, VariantBam achieved a median size reduction ratio of 3.1:1 when applied to 10 lung cancer whole genome BAMs by removing large tags and selecting for only high-quality variant-supporting reads and reads matching a large dictionary of sequence motifs. Thus VariantBam enables efficient storage of sequencing data while preserving the most relevant information for downstream analysis.
C1 [Wala, Jeremiah; Zhang, Cheng-Zhong; Meyerson, Matthew; Beroukhim, Rameen] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Wala, Jeremiah] Harvard Univ, Bioinformat & Integrat Genom, Cambridge, MA 02138 USA.
[Wala, Jeremiah; Meyerson, Matthew; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Beroukhim, R (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.; Beroukhim, R (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
EM rameen@broadinstitute.org
FU National Institutes of Health [T32 HG002295/HG/NHGRI, U54CA143798];
DFCI-Novartis Drug Discovery Program; Pediatric Low-Grade Astrocytoma
Foundation; Sontag Foundation
FX JW receives support from the National Institutes of Health (T32
HG002295/HG/NHGRI, U54CA143798) and the DFCI-Novartis Drug Discovery
Program. JW and RB receive support from the Pediatric Low-Grade
Astrocytoma Foundation. RB is also supported by the Sontag Foundation.
NR 7
TC 1
Z9 1
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD JUL 1
PY 2016
VL 32
IS 13
BP 2029
EP 2031
DI 10.1093/bioinformatics/btw111
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA DR2VH
UT WOS:000379761500016
PM 27153727
ER
PT J
AU Chu, KK
Unglert, C
Ford, TN
Cui, DY
Carruth, RW
Singh, K
Liu, LB
Birket, SE
Solomon, GM
Rowe, SM
Tearney, GJ
AF Chu, Kengyeh K.
Unglert, Carolin
Ford, Tim N.
Cui, Dongyao
Carruth, Robert W.
Singh, Kanwarpal
Liu, Linbo
Birket, Susan E.
Solomon, George M.
Rowe, Steven M.
Tearney, Guillermo J.
TI In vivo imaging of airway cilia and mucus clearance with micro-optical
coherence tomography
SO BIOMEDICAL OPTICS EXPRESS
LA English
DT Article
ID CYSTIC-FIBROSIS; ATHEROSCLEROSIS; RESOLUTION; MECHANISM
AB We have designed and fabricated a 4 mm diameter rigid endoscopic probe to obtain high resolution micro-optical coherence tomography (mu OCT) images from the tracheal epithelium of living swine. Our common-path fiber-optic probe used gradient-index focusing optics, a selectively coated prism reflector to implement a circular-obscuration apodization for depth-of-focus enhancement, and a common-path reference arm and an ultra-broadbrand supercontinuum laser to achieve high axial resolution. Benchtop characterization demonstrated lateral and axial resolutions of 3.4 mu m and 1.7 mu m, respectively (in tissue). Mechanical standoff rails flanking the imaging window allowed the epithelial surface to be maintained in focus without disrupting mucus flow. During in vivo imaging, relative motion was mitigated by inflating an airway balloon to hold the standoff rails on the epithelium. Software implemented image stabilization was also implemented during post-processing. The resulting image sequences yielded co-registered quantitative outputs of airway surface liquid and periciliary liquid layer thicknesses, ciliary beat frequency, and mucociliary transport rate, metrics that directly indicate airway epithelial function that have dominated in vitro research in diseases such as cystic fibrosis, but have not been available in vivo. (C) 2016 Optical Society of America
C1 [Chu, Kengyeh K.; Unglert, Carolin; Ford, Tim N.; Cui, Dongyao; Carruth, Robert W.; Singh, Kanwarpal; Liu, Linbo; Tearney, Guillermo J.] Massachusetts Gen Hosp, Dept Determatol, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA.
[Chu, Kengyeh K.; Unglert, Carolin; Ford, Tim N.; Cui, Dongyao; Carruth, Robert W.; Singh, Kanwarpal; Liu, Linbo; Tearney, Guillermo J.] Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA.
[Birket, Susan E.; Solomon, George M.; Rowe, Steven M.] Univ Alabama Birmingham, MCLM 706, Dept Med, 1918 Univ Blvd, Birmingham, AL 35294 USA.
[Birket, Susan E.; Solomon, George M.; Rowe, Steven M.] Univ Alabama Birmingham, MCLM 706, Gregory Fleming James Cyst Fibrosis Res Ctr, 1918 Univ Blvd, Birmingham, AL 35294 USA.
RP Tearney, GJ (reprint author), Massachusetts Gen Hosp, Dept Determatol, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA.; Tearney, GJ (reprint author), Harvard Med Sch, 55 Fruit St, Boston, MA 02114 USA.
EM gtearney@partners.org
FU National Institutes of Health [R01 HL116213]; Cystic Fibrosis
Foundation/Mucociliary Clearance Consortium [ROWE10XX0, TEARNE07XX0]
FX The authors gratefully acknowledge funding support from the National
Institutes of Health (R01 HL116213) and the Cystic Fibrosis
Foundation/Mucociliary Clearance Consortium (ROWE10XX0, TEARNE07XX0).
NR 23
TC 6
Z9 6
U1 3
U2 6
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 2156-7085
J9 BIOMED OPT EXPRESS
JI Biomed. Opt. Express
PD JUL 1
PY 2016
VL 7
IS 7
BP 2494
EP 2505
DI 10.1364/BOE.7.002494
PG 12
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA DR2UC
UT WOS:000379758400007
PM 27446685
ER
PT J
AU Mohty, M
Malard, F
Abecassis, M
Aerts, E
Alaskar, AS
Aljurf, M
Arat, M
Bader, P
Baron, F
Bazarbachi, A
Blaise, D
Ciceri, F
Corbacioglu, S
Dalle, JH
Dignan, F
Fukuda, T
Huynh, A
Masszi, T
Michallet, M
Nagler, A
NiChonghaile, M
Okamoto, S
Pagliuca, A
Peters, C
Petersen, FB
Richardson, PG
Ruutu, T
Savani, BN
Wallhult, E
Yakoub-Agha, I
Duarte, RF
Carreras, E
AF Mohty, M.
Malard, F.
Abecassis, M.
Aerts, E.
Alaskar, A. S.
Aljurf, M.
Arat, M.
Bader, P.
Baron, F.
Bazarbachi, A.
Blaise, D.
Ciceri, F.
Corbacioglu, S.
Dalle, J-H
Dignan, F.
Fukuda, T.
Huynh, A.
Masszi, T.
Michallet, M.
Nagler, A.
NiChonghaile, M.
Okamoto, S.
Pagliuca, A.
Peters, C.
Petersen, F. B.
Richardson, P. G.
Ruutu, T.
Savani, B. N.
Wallhult, E.
Yakoub-Agha, I.
Duarte, R. F.
Carreras, E.
TI Revised diagnosis and severity criteria for sinusoidal obstruction
syndrome/veno-occlusive disease in adult patients: a new classification
from the European Society for Blood and Marrow Transplantation
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
ID HEPATIC VENOOCCLUSIVE-DISEASE; STEM-CELL TRANSPLANTATION;
TISSUE-PLASMINOGEN ACTIVATOR; HIGH-RISK POPULATION; VERSUS-HOST-DISEASE;
MR-IMAGING FINDINGS; CONDITIONING REGIMEN; VENOCCLUSIVE DISEASE;
SIGNIFICANT TOXICITY; MULTIORGAN FAILURE
AB Sinusoidal obstruction syndrome, also known as veno-occlusive disease (SOS/VOD), is a potentially life threatening complication that can develop after hematopoietic cell transplantation. Although SOS/VOD progressively resolves within a few weeks in most patients, the most severe forms result in multi-organ dysfunction and are associated with a high mortality rate (480%). Therefore, careful attention must be paid to allow an early detection of SOS/VOD, particularly as drugs have now proven to be effective and licensed for its treatment. Unfortunately, current criteria lack sensitivity and specificity, making early identification and severity assessment of SOS/VOD difficult. The aim of this work is to propose a new definition for diagnosis, and a severity-grading system for SOS/VOD in adult patients, on behalf of the European Society for Blood and Marrow Transplantation.
C1 [Mohty, M.; Malard, F.] Hop St Antoine, Hematol Dept, Paris, France.
[Mohty, M.; Malard, F.] Univ Paris 06, Paris, France.
[Abecassis, M.] Inst Portugues Oncol Francisco Gentil, Lisbon, Portugal.
[Aerts, E.] Univ Zurich Hosp, Dept Haematol, Zurich, Switzerland.
[Alaskar, A. S.] King Saud Bin Abdulaziz Univ Hlth Sci, King Abdulaziz Med City, Dept Oncol, Minist Natl Guard Hlth Affairs,King Abdullah Int, Riyadh, Saudi Arabia.
[Aljurf, M.] King Faisal Specialist Hosp & Res Ctr, Riyadh, Saudi Arabia.
[Arat, M.] Sisli Florence Nightingale Hosp, HSCT Unit, Istanbul, Turkey.
[Bader, P.] Goethe Univ Frankfurt, Univ Hosp, Dept Children & Adolescents, Div Stem Cell Transplantat & Immunol, Frankfurt, Germany.
[Baron, F.] Univ Liege, Dept Hematol, Liege, Belgium.
[Bazarbachi, A.] Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon.
[Blaise, D.] Inst Paoli Calmettes, Dept Hematol, Blood & Marrow Transplantat Program, Marseille, France.
[Ciceri, F.] IRCCS San Raffaele Sci Inst, Hematol & Bone Marrow Transplantat Unit, Milan, Italy.
[Corbacioglu, S.] Univ Regensburg, Dept Pediat Hematol Oncol & Stem Cell Transplanta, Regensburg, Germany.
[Dignan, F.] Paris 7 Paris Diderot Univ, Hosp Robert Debre, Dept Hematol & Immunol, Paris, France.
Cent Manchester Fdn Trust, Dept Clin Haematol, Manchester, Lancs, England.
[Fukuda, T.] Natl Canc Ctr, HSCT Div, Tokyo, Japan.
[Huynh, A.] Inst Univ Canc Toulouse Oncopole, Hematol Dept, Toulouse, France.
[Masszi, T.] Semmelweis Univ, Budapest Dept Internal Med 3, St Istvan & St Laszlo Hosp, Dept Hematol & Stem Cell Transplantat, Budapest, Hungary.
[Michallet, M.] Univ Claude Bernard Lyon EST, Hospices Civils Lyon, Grp Hosp Sud, Hematol Dept, Pierre Benite, France.
[Nagler, A.] Chaim Sheba Med Ctr, Hematol & Bone Marrow Transplantat, Tel Hashomer, Israel.
[NiChonghaile, M.] Trinitiy Coll Dublin, Dept Haematol, St Jamess Hosp & Acad, Natl Stem Cell Transplant Unit Adults, Dublin, Ireland.
[Okamoto, S.] Keio Univ, Sch Med, Dept Med, Div Hematol, Tokyo, Japan.
[Pagliuca, A.] Kings Coll Hosp London, Dept Haematol, London, England.
[Peters, C.] St Anna Childrens Hosp, Dept Pediat, Vienna, Austria.
[Petersen, F. B.] LDS Hosp, Salt Lake City, UT USA.
[Richardson, P. G.] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancy, Boston, MA USA.
[Ruutu, T.] Helsinki Univ Hosp, Comprehens Canc Ctr, Helsinki, Finland.
[Savani, B. N.] Vanderbilt Univ, Med Ctr, Dept Med, Hematol & Stem Cell Transplantat Sect,Div Hematol, Nashville, TN USA.
[Savani, B. N.] Vet Affairs Med Ctr, Nashville, TN USA.
[Wallhult, E.] Sahlgrens Univ Hosp, Dept Internal Med, Sect Haematol & Coagulat, Gothenburg, Sweden.
[Yakoub-Agha, I.] Univ Lille 2, LIRIC INSERM U995, CHU Lille, F-59800 Lille, France.
[Duarte, R. F.] Hosp Univ Puerta Hierro Majadahonda, Dept Hematol, Madrid, Spain.
[Carreras, E.] Hosp Clin Barcelona, Dept Hematol, Josep Carreras Fdn & Leukemia Res Inst, Barcelona, Spain.
RP Mohty, M (reprint author), Hop St Antoine, Dept Clin Hematol & Cellular Therapy, 184 Rue Faubourg St Antoine, F-75571 Paris 12, France.
EM mohamad.mohty@inserm.fr
FU 'Association for Training, Education and Research in Hematology,
Immunology and Transplantation' (ATERHIT, Nantes, France)
FX MM thanks Prof JV Melo (University of Adelaide, Australia) for critical
reading of the manuscript. FM was supported by educational grants from
the 'Association for Training, Education and Research in Hematology,
Immunology and Transplantation' (ATERHIT, Nantes, France).
NR 77
TC 4
Z9 4
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUL
PY 2016
VL 51
IS 7
BP 906
EP 912
DI 10.1038/bmt.2016.130
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA DQ9OW
UT WOS:000379540200003
PM 27183098
ER
PT J
AU Espina, C
Jenkins, I
Taylor, L
Farah, R
Cho, E
Epworth, J
Coleman, K
Pinelli, J
Mentzer, S
Jarrett, L
Gooley, T
O'Donnell, P
Hirsch, IB
Bar, M
AF Espina, C.
Jenkins, I.
Taylor, L.
Farah, R.
Cho, E.
Epworth, J.
Coleman, K.
Pinelli, J.
Mentzer, S.
Jarrett, L.
Gooley, T.
O'Donnell, P.
Hirsch, I. B.
Bar, M.
TI Blood glucose control using a computer-guided glucose management system
in allogeneic hematopoietic cell transplant recipients
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
ID CRITICALLY-ILL PATIENTS; INTENSIVE INSULIN THERAPY; RANDOMIZED
CONTROLLED-TRIAL; NON-RELAPSE MORTALITY; FACTOR-KAPPA-B; GLYCEMIC
CONTROL; CARE-UNIT; MYOCARDIAL-INFARCTION; ADULT PATIENTS; HYPERGLYCEMIA
AB Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for patients with hematological malignancies. However, is associated with substantial rates of morbidity and mortality. We and others have shown that malglycemia is associated with adverse transplant outcome. Therefore, improving glycemic control may improve transplant outcome. In this prospective study we evaluated the feasibility of using Glucommander (a Computer-Guided Glucose Management System; CGGM) in order to achieve improved glucose control in hospitalized HCT patients. Nineteen adult patients contributed 21 separate instances on CGGM. Patients were on CGGM for a median of 43 h. Median initial blood glucose (BG) on CGGM was 244 mg/dL, and patients on 20 study instances reached the study BG target of 100-140 mg/dL after a median of 6 h. After BG reached the target range, the median average BG level per patient was 124 mg/dL. Six patients had a total of 10 events of BG <70 mg/dL (0.9% of BG measurements), and no patients experienced BG level <40 mg/dL. The total estimated duration of BG <70 mg/dL was 3 h (0.2% of the total CGGM time). In conclusion, our study demonstrates that stringent BG control in HCT patients using CGGM is feasible.
C1 [Espina, C.; Taylor, L.; Cho, E.; Epworth, J.; Coleman, K.; Pinelli, J.; Mentzer, S.; O'Donnell, P.; Hirsch, I. B.; Bar, M.] Univ Washington, Internal Med, Seattle, WA 98195 USA.
[Jenkins, I.; Taylor, L.; Cho, E.; Coleman, K.; Pinelli, J.; Mentzer, S.; Jarrett, L.; Gooley, T.; O'Donnell, P.; Bar, M.] Fred Hutchinson Canc Res Ctr, Clin Res Div, 1100 Fairview Ave N, Seattle, WA 98109 USA.
[Farah, R.] UPMC Canc Ctr, Pittsburgh, PA USA.
[O'Donnell, P.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Bar, M (reprint author), Fred Hutchinson Canc Res Ctr, Clin Res Div, 1100 Fairview Ave N, Seattle, WA 98109 USA.
EM mbar@u.washington.edu
FU NCI NIH HHS [T32 CA009515]
NR 51
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUL
PY 2016
VL 51
IS 7
BP 973
EP 979
DI 10.1038/bmt.2016.78
PG 7
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA DQ9OW
UT WOS:000379540200016
PM 27042836
ER
PT J
AU Hobbs, GS
Kaur, N
Hilden, P
Ponce, D
Cho, C
Castro-Malaspina, HR
Giralt, S
Goldberg, JD
Jakubowski, AA
Papadopoulos, EB
Sauter, C
Koehne, G
Yahalom, J
Delvin, S
Barker, JN
Perales, MA
AF Hobbs, G. S.
Kaur, N.
Hilden, P.
Ponce, D.
Cho, C.
Castro-Malaspina, H. R.
Giralt, S.
Goldberg, J. D.
Jakubowski, A. A.
Papadopoulos, E. B.
Sauter, C.
Koehne, G.
Yahalom, J.
Delvin, S.
Barker, J. N.
Perales, M-A
TI A novel reduced intensity conditioning regimen for patients with
high-risk hematological malignancies undergoing allogeneic stem cell
transplantation
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
ID CORD BLOOD TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; VERSUS-HOST-DISEASE;
MARROW TRANSPLANTATION; LYMPHOMA; INDEX
C1 [Hobbs, G. S.; Kaur, N.; Ponce, D.; Cho, C.; Castro-Malaspina, H. R.; Giralt, S.; Goldberg, J. D.; Jakubowski, A. A.; Papadopoulos, E. B.; Sauter, C.; Koehne, G.; Barker, J. N.; Perales, M-A] Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, 1275 York Ave, New York, NY 10021 USA.
[Hobbs, G. S.; Ponce, D.; Cho, C.; Castro-Malaspina, H. R.; Giralt, S.; Goldberg, J. D.; Jakubowski, A. A.; Papadopoulos, E. B.; Sauter, C.; Koehne, G.; Yahalom, J.; Delvin, S.; Barker, J. N.; Perales, M-A] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Hobbs, G. S.] Harvard Med Sch, Boston, MA USA.
[Hilden, P.; Delvin, S.] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, 1275 York Ave, New York, NY 10021 USA.
[Yahalom, J.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA.
[Hobbs, G. S.] Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA.
RP Perales, MA (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med, Adult Bone Marrow Transplantat Serv, 1275 York Ave, New York, NY 10021 USA.; Perales, MA (reprint author), Weill Cornell Med Coll, Dept Med, New York, NY USA.
EM peralesm@mskcc.org
OI Hobbs, Gabriela/0000-0002-0199-9333
FU NCI NIH HHS [P01 CA023766, P30 CA008748]
NR 15
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUL
PY 2016
VL 51
IS 7
BP 1010
EP 1012
DI 10.1038/bmt.2016.36
PG 3
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA DQ9OW
UT WOS:000379540200027
PM 26974271
ER
PT J
AU Watts, JM
Wang, XV
Swords, RT
Paietta, E
Douer, D
Lugar, SM
Fernandez, HF
Rowe, JM
Lazarus, HM
Tallman, MS
Litzow, MR
AF Watts, J. M.
Wang, X. V.
Swords, R. T.
Paietta, E.
Douer, D.
Lugar, S. M.
Fernandez, H. F.
Rowe, J. M.
Lazarus, H. M.
Tallman, M. S.
Litzow, M. R.
TI Very late relapse of AML after allogeneic hematopoietic cell
transplantation is often extramedullary
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW
C1 [Watts, J. M.; Swords, R. T.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Wang, X. V.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wang, X. V.] Harvard Sch Publ Hlth, Boston, MA USA.
[Paietta, E.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Douer, D.; Tallman, M. S.] Weill Cornell Med Coll, Mem Sloan Kettering Canc Ctr, Leukemia Serv, New York, NY USA.
[Lugar, S. M.] Univ Penn, Philadelphia, PA 19104 USA.
[Fernandez, H. F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Rowe, J. M.] Shaare Zedek Med Ctr, Jerusalem, Israel.
[Lazarus, H. M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Litzow, M. R.] Mayo Clin, Rochester, MN USA.
RP Watts, JM (reprint author), Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
EM jwatts@med.miami.edu
NR 13
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD JUL
PY 2016
VL 51
IS 7
BP 1013
EP 1015
DI 10.1038/bmt.2016.44
PG 3
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA DQ9OW
UT WOS:000379540200028
PM 26974275
ER
PT J
AU Kara, E
Tucci, A
Manzoni, C
Lynch, DS
Elpidorou, M
Bettencourt, C
Chelban, V
Manole, A
Hamed, SA
Haridy, NA
Federoff, M
Preza, E
Hughes, D
Pittman, A
Jaunmuktane, Z
Brandner, S
Xiromerisiou, G
Wiethoff, S
Schottlaender, L
Proukakis, C
Morris, H
Warner, T
Bhatia, KP
Korlipara, LVP
Singleton, AB
Hardy, J
Wood, NW
Lewis, PA
Houlden, H
AF Kara, Eleanna
Tucci, Arianna
Manzoni, Claudia
Lynch, David S.
Elpidorou, Marilena
Bettencourt, Conceicao
Chelban, Viorica
Manole, Andreea
Hamed, Sherifa A.
Haridy, Nourelhoda A.
Federoff, Monica
Preza, Elisavet
Hughes, Deborah
Pittman, Alan
Jaunmuktane, Zane
Brandner, Sebastian
Xiromerisiou, Georgia
Wiethoff, Sarah
Schottlaender, Lucia
Proukakis, Christos
Morris, Huw
Warner, Tom
Bhatia, Kailash P.
Korlipara, L. V. Prasad
Singleton, Andrew B.
Hardy, John
Wood, Nicholas W.
Lewis, Patrick A.
Houlden, Henry
TI Genetic and phenotypic characterization of complex hereditary spastic
paraplegia
SO BRAIN
LA English
DT Article
DE hereditary spastic paraplegia; SPG11; gene; mutation; Parkinson's
disease
ID THIN CORPUS-CALLOSUM; LEVODOPA-RESPONSIVE PARKINSONISM; NEURONAL
CEROID-LIPOFUSCINOSIS; SPATACSIN MUTATIONS; SPG11 MUTATIONS;
AUTOSOMAL-DOMINANT; CLINICAL-FEATURES; LYSOSOMAL PROTEIN; MASA SYNDROME;
DISEASE
AB High-throughput next-generation sequencing can identify disease-causing mutations in extremely heterogeneous disorders. Kara et al. investigate a series of 97 index cases with complex hereditary spastic paraplegia (HSP). They identify SPG11 defects in 30 families, as well as mutations in other HSP genes and genes associated with disorders including Parkinson's disease.High-throughput next-generation sequencing can identify disease-causing mutations in extremely heterogeneous disorders. Kara et al. investigate a series of 97 index cases with complex hereditary spastic paraplegia (HSP). They identify SPG11 defects in 30 families, as well as mutations in other HSP genes and genes associated with disorders including Parkinson's disease.The hereditary spastic paraplegias are a heterogeneous group of degenerative disorders that are clinically classified as either pure with predominant lower limb spasticity, or complex where spastic paraplegia is complicated with additional neurological features, and are inherited in autosomal dominant, autosomal recessive or X-linked patterns. Genetic defects have been identified in over 40 different genes, with more than 70 loci in total. Complex recessive spastic paraplegias have in the past been frequently associated with mutations in SPG11 (spatacsin), ZFYVE26/SPG15, SPG7 (paraplegin) and a handful of other rare genes, but many cases remain genetically undefined. The overlap with other neurodegenerative disorders has been implied in a small number of reports, but not in larger disease series. This deficiency has been largely due to the lack of suitable high throughput techniques to investigate the genetic basis of disease, but the recent availability of next generation sequencing can facilitate the identification of disease-causing mutations even in extremely heterogeneous disorders. We investigated a series of 97 index cases with complex spastic paraplegia referred to a tertiary referral neurology centre in London for diagnosis or management. The mean age of onset was 16 years (range 3 to 39). The SPG11 gene was first analysed, revealing homozygous or compound heterozygous mutations in 30/97 (30.9%) of probands, the largest SPG11 series reported to date, and by far the most common cause of complex spastic paraplegia in the UK, with severe and progressive clinical features and other neurological manifestations, linked with magnetic resonance imaging defects. Given the high frequency of SPG11 mutations, we studied the autophagic response to starvation in eight affected SPG11 cases and control fibroblast cell lines, but in our restricted study we did not observe correlations between disease status and autophagic or lysosomal markers. In the remaining cases, next generation sequencing was carried out revealing variants in a number of other known complex spastic paraplegia genes, including five in SPG7 (5/97), four in FA2H (also known as SPG35) (4/97) and two in ZFYVE26/SPG15. Variants were identified in genes usually associated with pure spastic paraplegia and also in the Parkinson's disease-associated gene ATP13A2, neuronal ceroid lipofuscinosis gene TPP1 and the hereditary motor and sensory neuropathy DNMT1 gene, highlighting the genetic heterogeneity of spastic paraplegia. No plausible genetic cause was identified in 51% of probands, likely indicating the existence of as yet unidentified genes.
C1 [Kara, Eleanna; Tucci, Arianna; Manzoni, Claudia; Lynch, David S.; Elpidorou, Marilena; Bettencourt, Conceicao; Chelban, Viorica; Manole, Andreea; Haridy, Nourelhoda A.; Preza, Elisavet; Hughes, Deborah; Pittman, Alan; Xiromerisiou, Georgia; Wiethoff, Sarah; Schottlaender, Lucia; Morris, Huw; Warner, Tom; Hardy, John; Wood, Nicholas W.; Lewis, Patrick A.; Houlden, Henry] UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England.
[Kara, Eleanna; Houlden, Henry] Harvard Med Sch, Dept Neurol, Alzheimers Dis Res Ctr, 114 16th St, Charlestown, MA 02129 USA.
[Kara, Eleanna; Houlden, Henry] Massachusetts Gen Hosp, 114 16th St, Charlestown, MA 02129 USA.
[Tucci, Arianna] Univ Milan, Dept Pathophysiol & Transplantat, Milan, Italy.
[Manzoni, Claudia; Lewis, Patrick A.] Univ Reading, Sch Pharm, Reading RG6 6AP, Berks, England.
[Hamed, Sherifa A.; Haridy, Nourelhoda A.] Assiut Univ Hosp, Fac Med, Dept Neurol & Psychiat, Assiut, Egypt.
[Federoff, Monica; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Jaunmuktane, Zane; Brandner, Sebastian] UCL, Inst Neurol, Natl Hosp Neurol & Neurosurg, Div Neuropathol, Queen Sq, London WC1N 3BG, England.
[Jaunmuktane, Zane; Brandner, Sebastian] UCL, Inst Neurol, Natl Hosp Neurol & Neurosurg, Dept Neurodegenerat Dis, Queen Sq, London WC1N 3BG, England.
[Xiromerisiou, Georgia] Papageorgiou Hosp, Dept Neurol, Thessaloniki, Greece.
[Proukakis, Christos; Morris, Huw] UCL, Inst Neurol, Dept Clin Neurosci, Royal Free Campus, London, England.
[Warner, Tom] UCL, Inst Neurol, Reta Lila Weston Inst Neurol Studies, Queen Sq, London WC1N 3BG, England.
[Warner, Tom] UCL, Inst Neurol, Brain Bank Neurol Disorders, Queen Sq, London WC1N 3BG, England.
[Bhatia, Kailash P.; Korlipara, L. V. Prasad] UCL, Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, Queen Sq, London WC1N 3BG, England.
[Wood, Nicholas W.] Natl Hosp Neurol & Neurosurg, Neurogenet Lab, Queen Sq, London WC1N 3BG, England.
RP Houlden, H (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England.
EM h.houlden@ucl.ac.uk
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Pittman,
Alan/D-6231-2012; Morris, Huw/B-8527-2008; Warner, Thomas/A-1454-2013;
Wood, Nicholas/C-2505-2009; Houlden, Henry/C-1532-2008;
OI Morris, Huw/0000-0002-5473-3774; Warner, Thomas/0000-0001-6195-6995;
Wood, Nicholas/0000-0002-9500-3348; Houlden, Henry/0000-0002-2866-7777;
Chelban, Viorica/0000-0002-5817-6290; Lewis, Patrick/0000-0003-4537-0489
FU Medical Research Council (MRC UK); Rosetrees Trust; Wellcome Trust
[104033]; Brain Research Trust (BRT); Muscular Dystrophy Association
(MDA); Muscular Dystrophy UK; UK HSP Society; EU [2012-305121]; HSP
society UK; MRC Centre for Neuromuscular Diseases [G0601943]; EMBO
[ATLF-815-2014]; National Brain Appeal Small Acorns Fund; Parkinson's UK
fellowship [F1002]; MRC [MR/L010933/1]; National Institute for Health
Research (NIHR) University College London Hospitals (UCLH) Biomedical
Research Centre (BRC)
FX This study was supported by the Medical Research Council (MRC UK), The
Rosetrees Trust, The Wellcome Trust [equipment and the Synaptopathies
strategic award (104033)] and The Brain Research Trust (BRT) The
Muscular Dystrophy Association (MDA), Muscular Dystrophy UK, The UK HSP
Society and the EU FP7/2007-2013 under grant agreement number
2012-305121 (NEUROMICS). We are also supported by the HSP society UK,
The MRC Centre for Neuromuscular Diseases (G0601943), EMBO Long term
fellowship ATLF-815-2014 (EK), The National Brain Appeal Small Acorns
Fund, Parkinson's UK fellowship F1002 (PAL), MRC grant MR/L010933/1
(PAL) and we are also supported by the National Institute for Health
Research (NIHR) University College London Hospitals (UCLH) Biomedical
Research Centre (BRC).
NR 77
TC 4
Z9 5
U1 5
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD JUL
PY 2016
VL 139
BP 1904
EP 1918
DI 10.1093/brain/aww111
PN 7
PG 15
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DR2VW
UT WOS:000379763000014
PM 27217339
ER
PT J
AU Noseda, R
Bernstein, CA
Nir, RR
Lee, AJ
Fulton, AB
Bertisch, SM
Hovaguimian, A
Cestari, DM
Saavedra-Walker, R
Borsook, D
Doran, BL
Buettner, C
Burstein, R
AF Noseda, Rodrigo
Bernstein, Carolyn A.
Nir, Rony-Reuven
Lee, Alice J.
Fulton, Anne B.
Bertisch, Suzanne M.
Hovaguimian, Alexandra
Cestari, Dean M.
Saavedra-Walker, Rodrigo
Borsook, David
Doran, Bruce L.
Buettner, Catherine
Burstein, Rami
TI Migraine photophobia originating in cone-driven retinal pathways
SO BRAIN
LA English
DT Article
DE headache; thalamus; electroretinography; visual evoked potential; pain
ID BENIGN ESSENTIAL BLEPHAROSPASM; INTACT CAT EYE; LIGHT SENSITIVITY;
B-WAVE; COLOR PREFERENCE; HEADACHE; ELECTRORETINOGRAM; CORTEX; MICE; ROD
AB Migraine headache is uniquely exacerbated by light. Using psychophysical assessments in patients with normal eyesight we found that green light exacerbates migraine headache significantly less than white, blue, amber or red lights. To delineate mechanisms, we used electroretinography and visual evoked potential recording in patients, and multi-unit recording of dura- and light-sensitive thalamic neurons in rats to show that green activates cone-driven retinal pathways to a lesser extent than white, blue and red; that thalamic neurons are most responsive to blue and least responsive to green; and that cortical responses to green are significantly smaller than those generated by blue, amber and red lights. These findings suggest that patients' experience with colour and migraine photophobia could originate in cone-driven retinal pathways, fine-tuned in relay thalamic neurons outside the main visual pathway, and preserved by the cortex. Additionally, the findings provide substrate for the soothing effects of green light.
C1 [Noseda, Rodrigo; Bernstein, Carolyn A.; Saavedra-Walker, Rodrigo; Burstein, Rami] Beth Israel Deaconess Med Ctr, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02215 USA.
[Noseda, Rodrigo; Bernstein, Carolyn A.; Fulton, Anne B.; Bertisch, Suzanne M.; Hovaguimian, Alexandra; Cestari, Dean M.; Borsook, David; Buettner, Catherine; Burstein, Rami] Harvard Med Sch, Boston, MA 02115 USA.
[Nir, Rony-Reuven] Rambam Hlth Care Campus, Dept Neurol, IL-31096 Haifa, Israel.
[Nir, Rony-Reuven] Technion Israel Inst Technol, Clin Neurophysiol Lab, Fac Med, IL-31096 Haifa, Israel.
[Lee, Alice J.] Beth Israel Deaconess Med Ctr, Harvard Catalyst Clin Res Ctr, Boston, MA 02215 USA.
[Fulton, Anne B.] Childrens Hosp Boston, Dept Ophthalmol, Boston, MA 02115 USA.
[Bertisch, Suzanne M.; Buettner, Catherine] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Hovaguimian, Alexandra] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Cestari, Dean M.] Massachusetts Eye & Ear Infirm, Dept Neuroophthalmol, Boston, MA 02114 USA.
[Borsook, David] Boston Childrens Hosp, Ctr Pain & Brain, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02115 USA.
[Doran, Bruce L.] Diagnosys LLC, Lowell, MA 01854 USA.
RP Burstein, R (reprint author), CLS 649,330 Brookline Ave, Boston, MA 02215 USA.
EM rburstei@bidmc.harvard.edu
FU NIH [R37 NS079678, RO1 NS069847, R21 NS090254-02, K24 NS77895]; Harvard
Catalyst, The Harvard Clinical and Translational Science Center
(National Center for Research Resources); Harvard Catalyst, The Harvard
Clinical and Translational Science Center (National Center for Advancing
Translational Sciences, National Institutes of Health) [UL1 TR001102];
Harvard University
FX This research was supported by NIH grants R37 NS079678, RO1 NS069847
(R.B.), R21 NS090254-02 (R.N.) and K24 NS77895 (D.B.). This work was
conducted with support from Harvard Catalyst, The Harvard Clinical and
Translational Science Center (National Center for Research Resources and
the National Center for Advancing Translational Sciences, National
Institutes of Health Award UL1 TR001102) and financial contributions
from Harvard University and its affiliated academic healthcare centres.
The funding sources had no involvement in the study design; collection,
analysis, and interpretation of data; the writing of the report; and the
decision to submit the article for publication. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of Harvard Catalyst, Harvard University and its
affiliated academic health care centres, or the National Institutes of
Health.
NR 48
TC 4
Z9 4
U1 2
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD JUL
PY 2016
VL 139
BP 1971
EP 1986
DI 10.1093/brain/aww119
PN 7
PG 16
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DR2VW
UT WOS:000379763000018
PM 27190022
ER
PT J
AU Bright, EE
Petrie, KJ
Partridge, AH
Stanton, AL
AF Bright, Emma E.
Petrie, Keith J.
Partridge, Ann H.
Stanton, Annette L.
TI Barriers to and facilitative processes of endocrine therapy adherence
among women with breast cancer
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Adherence; Tamoxifen; Aromatase inhibitor; Compliance;
Barriers
ID WORKING ALLIANCE INVENTORY; MEDICATION ADHERENCE; PATIENT-ADHERENCE;
CLINICAL-PRACTICE; NONADHERENCE; TAMOXIFEN; METAANALYSIS; COHORT;
PREDICTORS; DEPRESSION
AB The treatment of chronic illness, and the prevention of disease progression and recurrence, often involve long-term adherence to prescription medications in breast cancer. Despite the survival benefit of endocrine therapies, nonadherence remains high. In this study, we examined barriers to and facilitators of endocrine therapy adherence among women with breast cancer (n = 1371). Participants currently taking tamoxifen or aromatase inhibitors were recruited from Dr. Susan Love Research Foundation's Army of Women(A (R)) Registry. Participants responded online to open-ended and close-ended questions about thoughts, feelings, and behaviors relevant to endocrine therapy. Two weeks later, women were invited to complete a second online questionnaire regarding current endocrine therapy adherence. Approximately one-third (36 %) of participants reported the presence of factors that make endocrine therapy difficult; reporting any barrier to medication adherence was significantly associated with nonadherence (P < 0.001). In addition, 31 % of women used one or more strategies to maintain their motivation to adhere and the use of cognitive self-talk (e.g., thoughts regarding endocrine therapy efficacy) was related to higher adherence. Hierarchical linear regressions revealed a significant behavioral barrier x behavioral facilitator interaction (P < 0.05); participants who endorsed a behavioral barrier in the absence of a behavioral facilitator reported the lowest adherence. Findings suggest that a sizeable minority of women face barriers to taking endocrine therapy, which are associated with nonadherence.
C1 [Bright, Emma E.; Stanton, Annette L.] Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 90095-1563, Los Angeles, CA 90095 USA.
[Petrie, Keith J.] Univ Auckland, Dept Psychol Med, Auckland, New Zealand.
[Partridge, Ann H.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA USA.
[Stanton, Annette L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychol, Los Angeles, CA 90095 USA.
[Stanton, Annette L.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychiat Biobehav Sci, Los Angeles, CA 90095 USA.
RP Bright, EE; Stanton, AL (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 90095-1563, Los Angeles, CA 90095 USA.; Stanton, AL (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychol, Los Angeles, CA 90095 USA.; Stanton, AL (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Ctr Canc Prevent & Control Res, Dept Psychiat Biobehav Sci, Los Angeles, CA 90095 USA.
EM ebright@ucla.edu; astanton@ucla.edu
FU Breast Cancer Research Foundation
FX This research was supported by funding from the Breast Cancer Research
Foundation (Stanton).
NR 39
TC 0
Z9 0
U1 4
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2016
VL 158
IS 2
BP 243
EP 251
DI 10.1007/s10549-016-3871-3
PG 9
WC Oncology
SC Oncology
GA DQ8XA
UT WOS:000379493800004
PM 27342455
ER
PT J
AU Dong, JY
Ly, A
Arpin, R
Ahmed, Q
Brachtel, E
AF Dong, Jianyu
Ly, Amy
Arpin, Ronald
Ahmed, Quratulain
Brachtel, Elena
TI Breast fine needle aspiration continues to be relevant in a large
academic medical center: experience from Massachusetts General Hospital
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast; Fine needle aspiration; Diagnostic accuracy; Cell block;
Fluorescence in situ hybridization
ID FACTOR RECEPTOR 2; TISSUE BLOCK PREPARATIONS; IN-SITU HYBRIDIZATION;
PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; CELL BLOCK;
IMMUNOHISTOCHEMICAL DETECTION; DIAGNOSTIC-ACCURACY; TRIPLE-TEST; CANCER
AB Fine needle aspiration (FNA) is increasingly being supplanted by core needle biopsy. However, breast surgeons continue to rely on FNA at our institution. This retrospective study evaluated breast FNA for its diagnostic accuracy and breast cancer biomarker testing utility. All breast FNAs performed at Massachusetts General Hospital 2009-2015 were reviewed. Cytology diagnoses were compared with subsequent tissue or clinical diagnoses. Immunohistochemistry and fluorescence in situ hybridization (FISH) results using formalin-fixed paraffin-embedded (FFPE) cell blocks and histologic tissue blocks were compared. 1654 consecutive breast FNAs were included. Breast FNA demonstrated the following diagnostic performance: positive predictive value of malignant cytology diagnosis 100 %, negative predictive value of benign cytology diagnosis 97.5 %, complete sensitivity 91.6 %, and specificity 95.5 %. Concordance rates for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) immunohistochemistry, and HER2 FISH were 98.2 % (kappa = 0.95, p < 0.001), 100.0 % (kappa = 1.000, p < 0.001), 83.1 % (kappa = 0.69, p < 0.001), and 93.5 % (kappa = 0.785, p < 0.001), respectively. Review of consecutive breast FNAs in a large cohort confirmed the excellent accuracy of this biopsy technique for breast lesion diagnosis. FNA FFPE cell blocks collected in the course of routine clinical care are adequate, practical, and reliable for breast cancer biomarker testing.
C1 [Dong, Jianyu; Ly, Amy; Arpin, Ronald; Brachtel, Elena] Massachusetts Gen Hosp, Dept Pathol, Div Cytol, 55 Fruit St WRN 2, Boston, MA 02114 USA.
[Dong, Jianyu; Ly, Amy; Arpin, Ronald; Brachtel, Elena] Harvard Med Sch, 55 Fruit St WRN 2, Boston, MA 02114 USA.
[Dong, Jianyu] Southern Med Univ, Nanfang Hosp, Breast Ctr, Guangzhou 510515, Guangdong, Peoples R China.
[Ahmed, Quratulain] St John Providence Hlth Syst, 16001 W Nine Mile Rd, Southfield, MI 48075 USA.
RP Brachtel, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Cytol, 55 Fruit St WRN 2, Boston, MA 02114 USA.; Brachtel, E (reprint author), Harvard Med Sch, 55 Fruit St WRN 2, Boston, MA 02114 USA.
EM ebrachtel@mgh.harvard.edu
NR 41
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2016
VL 158
IS 2
BP 297
EP 305
DI 10.1007/s10549-016-3886-9
PG 9
WC Oncology
SC Oncology
GA DQ8XA
UT WOS:000379493800009
PM 27383478
ER
PT J
AU Pruneri, G
Gray, KP
Vingiani, A
Viale, G
Curigliano, G
Criscitiello, C
Lang, I
Ruhstaller, T
Gianni, L
Goldhirsch, A
Kammler, R
Price, KN
Cancello, G
Munzone, E
Gelber, RD
Regan, MM
Colleoni, M
AF Pruneri, Giancarlo
Gray, Kathryn P.
Vingiani, Andrea
Viale, Giuseppe
Curigliano, Giuseppe
Criscitiello, Carmen
Lang, Istvan
Ruhstaller, Thomas
Gianni, Lorenzo
Goldhirsch, Aron
Kammler, Roswitha
Price, Karen N.
Cancello, Giuseppe
Munzone, Elisabetta
Gelber, Richard D.
Regan, Meredith M.
Colleoni, Marco
TI Tumor-infiltrating lymphocytes (TILs) are a powerful prognostic marker
in patients with triple-negative breast cancer enrolled in the IBCSG
phase III randomized clinical trial 22-00
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Tumor-infiltrating lymphocytes; Triple negative; Low-dose maintenance
chemotherapy; Breast cancer; Prognosis
ID METRONOMIC CHEMOTHERAPY; RECOMMENDATIONS; DOXORUBICIN; EFFICACY;
BENEFIT; CELLS
AB The purpose of this study was to assess the prognostic and predictive value of tumor-infiltrating lymphocytes (TILs) in the triple-negative breast cancer (TNBC) cohort of the phase III IBCSG trial 22-00, comparing low-dose oral 'metronomic' cyclophosphamide-methotrexate maintenance chemotherapy (CM-maintenance) to no-CM-maintenance in early breast cancer. TILs were evaluated in full-face hematoxylin-and-eosin-stained sections of tumor samples confirmed centrally as TNBC (< 1 % of ER and PgR immunoreactivity and absence of HER2 overexpression or amplification). Mononuclear cells were evaluated in the stromal area within the borders of the invasive tumor. The primary endpoint was breast cancer-free interval (BCFI). Cox proportional hazards regression model assessed the association of BCFI and secondary endpoints with TILs score. In the 647 tumor samples, the median percentage of TILs was 18 % (IQR = 8-40 %), with 18 % having TILs a parts per thousand yen 50 % (lymphocyte-predominant breast cancer, LPBC). At a median follow-up of 6.9 years, TILs were associated with better prognosis. For every 10 % increase of TILs, BCFI risk reduction was 13 % (HR 0.87, 95 % CI 0.79-0.95,P = 0.003). DFS, DRFI, and OS risk reductions were 11 % (P = 0.005), 16 % (P = 0.003), and 17 % (P < 0.001), respectively. Multivariable analysis confirmed the independent prognostic value of TILs. No significant TILs-by-treatment interaction was observed (P = 0.39) for associations of TILs with BCFI, although patients with LPBC receiving CM-maintenance had a greater breast cancer risk reduction (HR 0.64,95 % CI 0.23-1.78) than those with non-LPBC (TILs < 50 %) (HR 0.96, 95 % CI 0.67-1.40). TILs score is a potent prognostic factor in patients with TNBC. Low-dose chemotherapy confers a greater (not statistically significant) clinical benefit in patients with LPBC.
C1 [Pruneri, Giancarlo; Vingiani, Andrea; Viale, Giuseppe] European Inst Oncol, Dept Pathol & Lab Med, IBCSG Cent Pathol Lab, Via Ripamonti 435, I-20141 Milan, Italy.
[Pruneri, Giancarlo; Vingiani, Andrea; Viale, Giuseppe] Univ Milan, Milan, Italy.
[Gelber, Richard D.; Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, 450 Brookline Ave, Boston, MA 02215 USA.
[Gray, Kathryn P.; Price, Karen N.; Gelber, Richard D.; Regan, Meredith M.] Int Breast Canc Study Grp IBCSG Stat Ctr, Boston, MA USA.
[Gray, Kathryn P.; Gelber, Richard D.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Curigliano, Giuseppe; Criscitiello, Carmen] European Inst Oncol, Div Expt Therapeut, Via Ripamonti 435, I-20141 Milan, Italy.
[Lang, Istvan] Natl Inst Oncol, Rath Gyorgy U 7-9, H-1122 Budapest, Hungary.
[Ruhstaller, Thomas] Kantonsspital, Breast Ctr St Gallen, St Gallen, Switzerland.
[Ruhstaller, Thomas] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland.
[Gianni, Lorenzo] Osped Infermi, Div Oncol, Viale Settembrini 2, I-47923 Rimini, Italy.
[Goldhirsch, Aron] European Inst Oncol, Program Breast Hlth, Via Ripamonti 435, I-20141 Milan, Italy.
[Kammler, Roswitha] IBCSG Coordinating Ctr, Translat Res Coordinat & Cent Pathol Off, Int Breast Canc Study Grp, Effingerstr 40, CH-3008 Bern, Switzerland.
[Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA.
[Cancello, Giuseppe; Munzone, Elisabetta; Colleoni, Marco] European Inst Oncol, Div Med Senol, Via Ripamonti 435, I-20141 Milan, Italy.
[Gelber, Richard D.; Regan, Meredith M.] Harvard Med Sch, Boston, MA USA.
RP Pruneri, G (reprint author), European Inst Oncol, Dept Pathol & Lab Med, IBCSG Cent Pathol Lab, Via Ripamonti 435, I-20141 Milan, Italy.; Pruneri, G (reprint author), Univ Milan, Milan, Italy.
EM giancarlo.pruneri@ieo.it; pkruan@jimmy.harvard.edu;
andrea.vingiani@unimi.it; giuseppe.viale@ieo.it;
giuseppe.curigliano@ieo.it; carmen.criscitiello@ieo.it; lang@oncol.hu;
thomas.ruhstaller@kssg.ch; lorenzo.gianni@auslromagna.it;
aron.goldhirsch@ibcsg.org; Rosita.Kammler@ibcsg.org;
price@jimmy.harvard.edu; giuseppe.cancello@ieo.it;
elisabetta.munzone@ieo.it; gelber@jimmy.harvard.edu;
mregan@jimmy.harvard.edu; marco.colleoni@ieo.it
OI Vingiani, Andrea/0000-0002-9827-3976
FU International Breast Cancer Study Group
FX This work was supported by the International Breast Cancer Study Group
and participating centers. Support for central coordination, data
management and statistics were provided by the Swedish Cancer League;
The Cancer Council Australia; Australia & New Zealand Breast Cancer
Trials Group; The Frontier Science and Technology Research Foundation;
The Swiss Group for Clinical Cancer Research; the Swiss Cancer
League/Oncosuisse; and the United States National Institutes of Health
(CA-75362 to MMR).
NR 27
TC 5
Z9 5
U1 5
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2016
VL 158
IS 2
BP 323
EP 331
DI 10.1007/s10549-016-3863-3
PG 9
WC Oncology
SC Oncology
GA DQ8XA
UT WOS:000379493800011
PM 27372069
ER
PT J
AU Freedman, RA
Viswanath, K
Vaz-Luis, I
Keating, NL
AF Freedman, Rachel A.
Viswanath, Kasisomayajula
Vaz-Luis, Ines
Keating, Nancy L.
TI Learning from social media: utilizing advanced data extraction
techniques to understand barriers to breast cancer treatment
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Underserved populations; Race and ethnicity; Adherence;
Qualitative research
ID OLDER WOMEN; ADJUVANT CHEMOTHERAPY; SOCIOECONOMIC-STATUS; RACIAL
DISPARITIES; UNITED-STATES; LOW-INCOME; THERAPY; RACE; INSURANCE; CARE
AB Past examinations of breast cancer treatment barriers have typically included registry, claims-based, and smaller survey studies. We examined treatment barriers using a novel, comprehensive, social media analysis of online, candid discussions about breast cancer. Using an innovative toolset to search postings on social networks, message boards, patient communities, and topical sites, we performed a large-scale qualitative analysis. We examined the sentiments and barriers expressed about breast cancer treatments by Internet users during 1 year (2/1/14-1/31/15). We categorized posts based on thematic patterns and examined trends in discussions by race/ethnicity (white/black/Hispanic) when this information was available. We identified 1,024,041 unique posts related to breast cancer treatment. Overall, 57 % of posts expressed negative sentiments. Using machine learning software, we assigned treatment barriers for 387,238 posts (38 %). Barriers included emotional (23 % of posts), preferences and spiritual/religious beliefs (21 %), physical (18 %), resource (15 %), healthcare perceptions (9 %), treatment processes/duration (7 %), and relationships (7 %). Black and Hispanic (vs. white) users more frequently reported barriers related to healthcare perceptions, beliefs, and pre-diagnosis/diagnosis organizational challenges and fewer emotional barriers. Using a novel analysis of diverse social media users, we observed numerous breast cancer treatment barriers that differed by race/ethnicity. Social media is a powerful tool, allowing use of real-world data for qualitative research, capitalizing on the rich discussions occurring spontaneously online. Future research should focus on how to further employ and learn from this type of social intelligence research across all medical disciplines.
C1 [Freedman, Rachel A.; Vaz-Luis, Ines] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Viswanath, Kasisomayajula] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Viswanath, Kasisomayajula] Harvard Sch Publ Hlth, Dept Soc & Behav Sci, Boston, MA USA.
[Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM rafreedman@partners.org
FU American Cancer Society; Susan G. Komen; National Cancer Institute
[K24CA181510]; Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011]
FX The funders for this study are American Cancer Society (RAF), Susan G.
Komen (RAF), K24CA181510 (NLK) from the National Cancer Institute,
Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011, Career
Development Award, (IVL)].
NR 40
TC 1
Z9 1
U1 2
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD JUL
PY 2016
VL 158
IS 2
BP 395
EP 405
DI 10.1007/s10549-016-3872-2
PG 11
WC Oncology
SC Oncology
GA DQ8XA
UT WOS:000379493800018
PM 27339067
ER
PT J
AU Sun, GB
Zacharias, J
Ma, B
Oreskovic, NM
AF Sun, Guibo
Zacharias, John
Ma, Ben
Oreskovic, Nicolas M.
TI How do metro stations integrate with walking environments? Results from
walking access within three types of built environment in Beijing
SO CITIES
LA English
DT Article
DE Walking environment; Transit-oriented development; Tracking method;
Geographic information system; Beijing
ID TRANSIT-ORIENTED DEVELOPMENT; PHYSICAL-ACTIVITY; PUBLIC-TRANSIT;
LAND-USE; TRAVEL; DENSITY; OBESITY; DESIGN; CITIES; RAIL
AB China is in a period of rapid metro system development. However, there are few empirical evaluations of the complex interactions between the local built environment and metro ridership in the Chinese context. In this study, we collected empirical data on the influence of local environmental characteristics on walking access in Beijing. Walking behaviors and built environment perceptions among commuters (N = 495) were collected at six metro stations in three distinctly different physical settings in Beijing two in hutong, two in danwei, and two in xiaoqu. Participants recorded walking routes from the metro stations until they arrived at their destinations. Evaluations of the built environment were collected using a questionnaire after the participants arrived. Geographic information system was used to map walking routes and code built environment variables. Walking behavior outcomes were measured as walked time from metro exit to participant's destination. ANOVA compared differences between perceived and measured built environment characteristics and walking behaviors among selected neighborhoods. Multiple regression was used to test for associations between the built environment and metro station routes. We found that mean walking time from the metro station to a destination was 8 min. Recreational and office destinations had similar walking times to the metro station as residential destinations. Metro riders in xiaoqu and danwei walked longer distances to their destinations compared to metro riders in hutong. Physical obstacles to crossing streets made walking times longer. Greater connectivity, both perceived and measured, predicted shorter walking times. Local land use is not well integrated into metro station placement in Beijing. Better connectivity, pedestrian-friendly designs and higher building coverage ratio around the metro station might promote easier walking access and have the potential to capture more metro riders. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Sun, Guibo] Univ Hong Kong, Fac Architecture, Pokfulam Rd, Hong Kong, Hong Kong, Peoples R China.
[Zacharias, John] Peking Univ, Coll Architecture & Landscape, Beijing, Peoples R China.
[Ma, Ben] Chinese Univ Hong Kong, Dept Geog & Resource Management, Shatin, Hong Kong, Peoples R China.
[Oreskovic, Nicolas M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Oreskovic, Nicolas M.] Harvard Med Sch, Boston, MA USA.
RP Zacharias, J (reprint author), Peking Univ, Coll Architecture & Landscape Architecture, R206,Hongsi Bldg, Beijing, Peoples R China.
EM johnzacharias@pku.edu.cn
FU State Administration for Foreign Experts Affairs, People's Republic of
China; NSFC [41561035, 51478300]
FX The authors gratefully acknowledge the funding support from the State
Administration for Foreign Experts Affairs, People's Republic of China.
Guibo Sun is supported by NSFC 41561035 and NSFC 51478300.
NR 47
TC 0
Z9 0
U1 11
U2 15
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0264-2751
EI 1873-6084
J9 CITIES
JI Cities
PD JUL
PY 2016
VL 56
SI SI
BP 91
EP 98
DI 10.1016/j.cities.2016.03.001
PG 8
WC Urban Studies
SC Urban Studies
GA DR1AM
UT WOS:000379638300011
ER
PT J
AU Robert, MC
Arafat, SN
Spurr-Michaud, S
Chodosh, J
Dohlman, CH
Gipson, IK
AF Robert, Marie-Claude
Arafat, Samer N.
Spurr-Michaud, Sandra
Chodosh, James
Dohlman, Claes H.
Gipson, Ilene K.
TI Tear Matrix Metalloproteinases and Myeloperoxidase Levels in Patients
With Boston Keratoprosthesis Type I
SO CORNEA
LA English
DT Article
DE Boston keratoprosthesis type 1; matrix metalloproteinase; chemical burn;
Stevens-Johnson syndrome; keratolysis; tears
ID CORNEAL EPITHELIAL-CELLS; MMP-9; GELATINASE; CYTOKINES;
MATRIX-METALLOPROTEINASE-9; EXPRESSION; ULCERATION; MECHANISM; FLUID
AB Purpose:To investigate the tear levels of matrix metalloproteinases (MMPs), myeloperoxidase (MPO), and tissue inhibitor of metalloproteinase-1 in eyes after Boston keratoprosthesis type I (B-KPro) implantation and to correlate these markers with the established B-KPro prognostic categories.Methods:Tear washes were collected from 40 patients (7 with autoimmune disease, 2 with chemical burn, and 31 with other noncicatrizing diagnoses). Tear levels of MMPs, MPO, and tissue inhibitor of metalloproteinase-1 were quantified using multianalyte bead-based enzyme-linked immunosorbent assays. The total MMP activity was determined using a fluorimetric assay. The analytes were compared to the underlying diagnosis and other clinical factors.Results:The MMP-8, MMP-9, and MPO levels were markedly elevated in the eyes with B-KPro (80 31, 291 +/- 77, and 244 +/- 33 pg/g, respectively). Chemical burn was associated with significantly higher tear MMP-8 (474 +/- 376 pg/g) and MMP-9 levels (1300 +/- 635 pg/g) compared with noncicatrizing diseases (MMP-8: 41 +/- 15 pg/g, P = 0.02 and MMP-9: 196 +/- 57 pg/g, P = 0.02) and higher MMP-9 levels compared with autoimmune diseases (MMP-8: 96 +/- 65 pg/g, P = 0.21 and MMP-9: 306 +/- 196 pg/g, P = 0.04). Similar analyte levels were observed in the B-KPro eye and the contralateral non-B-KPro eye of patients with bilateral diseases. MMP-8, MMP-9, and total MMP activities correlated strongly with each other.Conclusions:In the eyes with B-KPro, tear MMP-8 and MMP-9 levels seem to be related to the underlying ocular surface pathology and not significantly influenced by the presence of the prosthesis.
C1 [Robert, Marie-Claude; Arafat, Samer N.; Spurr-Michaud, Sandra; Gipson, Ilene K.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA USA.
[Robert, Marie-Claude; Arafat, Samer N.; Chodosh, James; Dohlman, Claes H.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Robert, Marie-Claude] Univ Montreal, Dept Ophthalmol, Ctr Hosp Univ Montreal, 3rd Floor,Deschamps Pavill,1560 Sherbrooke East, Montreal, PQ H2L 4M1, Canada.
RP Robert, MC (reprint author), Univ Montreal, Dept Ophthalmol, Ctr Hosp Univ Montreal, 3rd Floor,Deschamps Pavill,1560 Sherbrooke East, Montreal, PQ H2L 4M1, Canada.
EM marie-claude.robert.2@umontreal.ca
FU Boston Keratoprosthesis Foundation; Centre Hospitalier de l'Universite
de Montreal Fellowship Fund; NIH NEI grant [EY 03306]
FX This project was funded by the Boston Keratoprosthesis Foundation, the
Centre Hospitalier de l'Universite de Montreal Fellowship Fund (M-C.R.),
and NIH NEI grant EY 03306 (I.K.G.).
NR 25
TC 0
Z9 0
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0277-3740
EI 1536-4798
J9 CORNEA
JI Cornea
PD JUL
PY 2016
VL 35
IS 7
BP 1008
EP 1014
DI 10.1097/ICO.0000000000000893
PG 7
WC Ophthalmology
SC Ophthalmology
GA DR0RG
UT WOS:000379614000019
PM 27191670
ER
PT J
AU Lin, H
Yeh, DD
Levine, AR
AF Lin, Hsin
Yeh, Daniel Dante
Levine, Alexander R.
TI Daily vancomycin dose requirements as a continuous infusion in obese
versus non-obese SICU patients
SO CRITICAL CARE
LA English
DT Article
DE Vancomycin continuous infusion; Obesity; Pharmacokinetic and
pharmacodynamic; Infectious disease
ID CRITICALLY-ILL PATIENTS; INTERMITTENT INFUSION; GLOMERULAR-FILTRATION;
SEPTIC SHOCK; PHARMACOKINETICS; INFECTIONS; METAANALYSIS; POPULATION;
CLEARANCE; SURVIVAL
AB Background: Limited data are available assessing vancomycin concentrations in obese critically ill patients. Currently, there are no studies evaluating dosing requirements in this population who receive vancomycin administered as a continuous infusion (CI). The aim of this study was to assess whether there was a difference in the weight-based maintenance dose required to reach a therapeutic vancomycin concentration at 24 hours when given as a CI in obese versus non-obese critically ill patients.
Methods: A retrospective cohort study of adult obese patients admitted to the SICU between 2013 and 2015 receiving a vancomycin CI (CIV), and with 24-hour serum measurements were included. Obese patients (body mass index (BMI) >= 35 kg/m(2)) were matched with non-obese patients (BMI < 30 kg/m(2)) based on renal function, age and acute physiology and chronic health evaluation (APACHE)-II score at admission. All patients in this study received a loading dose of 25 mg/kg then a maintenance dose based on renal function according to the protocol. The study was approved by the Institutional Review Board. The primary outcome was the weight-based total daily maintenance dose required to achieve a vancomycin level of 20 mg/L. The secondary endpoints included the achievement of a therapeutic level at 24 hours.
Results: Twenty-six matched pairs of patients met the inclusion criteria. Of these, 17 pairs had preserved renal function and 9 pairs required continuous venovenous hemofiltration. Mean BMI was 40.9 kg/m(2) in obese and 24.8 kg/m(2) in non-obese patients. To achieve a vancomycin concentration of 20 mg/L, the weight-based daily maintenance dose in obese patients was 25.6 mg/kg versus 43.8 mg/kg in non-obese patients (p < 0.01). Therapeutic 24-hour levels were achieved in 24/26 obese versus 23/26 no-obese patients (p = 0.63). Mean 24-hour vancomycin level was 20.3 +/- 3.81 mcg/ml in obese compared to 20.03 +/- 3.79 mcg/ml in non-obese patients (p = 0.77). Mean daily maintenance doses required to achieve a level of 20 mcg/ml were 2961 +/- 1670 mg in obese compared to 3189 +/- 1600.69 mg in non-obese (p = 0.61).
Conclusions: The results of our study suggest that critically ill obese patients treated with CIV required a significantly lower maintenance dose per unit of body weight than non-obese patients to achieve the same target level.
C1 [Lin, Hsin] Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA.
[Yeh, Daniel Dante] Massachusetts Gen Hosp, Dept Surg, 55 Fruit St, Boston, MA 02114 USA.
[Levine, Alexander R.] Univ St Joseph, Sch Pharm, Dept Pharm Practice & Adm, 229 Trumbull St, Hartford, CT USA.
RP Lin, H (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA.
EM hlin13@partners.org
NR 20
TC 1
Z9 2
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1466-609X
EI 1364-8535
J9 CRIT CARE
JI Crit. Care
PD JUL 1
PY 2016
VL 20
AR 205
DI 10.1186/s13054-016-1363-9
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA DR0HQ
UT WOS:000379589000001
PM 27363312
ER
PT J
AU Nguyen, HB
Jaehne, AK
Jayaprakash, N
Semler, MW
Hegab, S
Yataco, AC
Tatem, G
Salem, D
Moore, S
Boka, K
Gill, JK
Gardner-Gray, J
Pflaum, J
Domecq, JP
Hurst, G
Belsky, JB
Fowkes, R
Elkin, RB
Simpson, SQ
Falk, JL
Singer, DJ
Rivers, EP
AF Nguyen, H. Bryant
Jaehne, Anja Kathrin
Jayaprakash, Namita
Semler, Matthew W.
Hegab, Sara
Yataco, Angel Coz
Tatem, Geneva
Salem, Dhafer
Moore, Steven
Boka, Kamran
Gill, Jasreen Kaur
Gardner-Gray, Jayna
Pflaum, Jacqueline
Domecq, Juan Pablo
Hurst, Gina
Belsky, Justin B.
Fowkes, Raymond
Elkin, Ronald B.
Simpson, Steven Q.
Falk, Jay L.
Singer, Daniel J.
Rivers, Emanuel P.
TI Early goal-directed therapy in severe sepsis and septic shock: insights
and comparisons to ProCESS, ProMISe, and ARISE
SO CRITICAL CARE
LA English
DT Review
ID VENOUS OXYGEN-SATURATION; INTENSIVE-CARE-UNIT; EMERGENCY-DEPARTMENT
PATIENTS; SEVERE SEPSIS/SEPTIC SHOCK; ACUTE LUNG INJURY; RANDOMIZED
CONTROLLED-TRIALS; QUALITY IMPROVEMENT PROJECT; ACUTE CIRCULATORY
FAILURE; CRITICALLY-ILL PATIENTS; IN-HOSPITAL MORTALITY
AB Prior to 2001 there was no standard for early management of severe sepsis and septic shock in the emergency department. In the presence of standard or usual care, the prevailing mortality was over 40-50 %. In response, a systems-based approach, similar to that in acute myocardial infarction, stroke and trauma, called early goal-directed therapy was compared to standard care and this clinical trial resulted in a significant mortality reduction. Since the publication of that trial, similar outcome benefits have been reported in over 70 observational and randomized controlled studies comprising over 70,000 patients. As a result, early goal-directed therapy was largely incorporated into the first 6 hours of sepsis management (resuscitation bundle) adopted by the Surviving Sepsis Campaign and disseminated internationally as the standard of care for early sepsis management. Recently a trio of trials (ProCESS, ARISE, and ProMISe), while reporting an all-time low sepsis mortality, question the continued need for all of the elements of early goal-directed therapy or the need for protocolized care for patients with severe and septic shock. A review of the early hemodynamic pathogenesis, historical development, and definition of early goal-directed therapy, comparing trial conduction methodology and the changing landscape of sepsis mortality, are essential for an appropriate interpretation of these trials and their conclusions.
C1 [Nguyen, H. Bryant] Loma Linda Univ, Dept Med Pulm & Crit Care Med, Loma Linda, CA 92350 USA.
[Nguyen, H. Bryant] Loma Linda Univ, Dept Emergency Med, Loma Linda, CA 92350 USA.
[Jaehne, Anja Kathrin; Moore, Steven; Gill, Jasreen Kaur; Gardner-Gray, Jayna; Pflaum, Jacqueline; Hurst, Gina; Fowkes, Raymond; Rivers, Emanuel P.] Wayne State Univ, Henry Ford Hosp, Dept Emergency Med, Detroit, MI USA.
[Jayaprakash, Namita] Mayo Clin Rochester, Div Pulm & Crit Care Med, Rochester, MN USA.
[Semler, Matthew W.] Vanderbilt Univ, Dept Med Pulm & Crit Care Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Hegab, Sara; Tatem, Geneva; Gardner-Gray, Jayna; Pflaum, Jacqueline; Hurst, Gina] Wayne State Univ, Henry Ford Hosp, Dept Med Pulm & Crit Care Med, Detroit, MI USA.
[Yataco, Angel Coz] Univ Kentucky, Lexington, KY USA.
[Salem, Dhafer] Mercy Hosp Med Ctr Chicago, Dept Internal Med, Chicago, IL USA.
[Boka, Kamran] Univ Texas Hlth Sci Ctr Houston, Dept Internal Med, Div Crit Care Med, Houston, TX 77030 USA.
[Domecq, Juan Pablo] Wayne State Univ, Dept Internal Med, Henry Ford Hosp, Detroit, MI 48202 USA.
[Domecq, Juan Pablo] Univ Peruana Cayetano Heredia, Conocimiento & Evidencia Res Unit, CONEVID, Lima, Peru.
[Belsky, Justin B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA.
[Elkin, Ronald B.] Calif Pacific Med Ctr, Pulm & Crit Care Med, San Francisco, CA USA.
[Simpson, Steven Q.] Univ Kansas, Pulm & Crit Care Med, Kansas City, KS USA.
[Falk, Jay L.] Orlando Reg Med Ctr Inc, Dept Emergency Med, Orlando, FL USA.
[Falk, Jay L.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA.
[Falk, Jay L.] Univ Florida, Coll Med, Orlando, FL USA.
[Falk, Jay L.] Univ S Florida, Coll Med, Orlando, FL USA.
[Falk, Jay L.] Florida State Univ, Coll Med, Orlando, FL USA.
[Singer, Daniel J.] Mt Sinai Hosp, Icahn Sch Med, Div Surg Crit Care, Dept Surg, New York, NY 10029 USA.
[Rivers, Emanuel P.] Wayne State Univ, Dept Surg, Henry Ford Hosp, Detroit, MI USA.
[Jaehne, Anja Kathrin] Aspirus Hosp, Dept Qual Assurance, Iron River, MI USA.
RP Rivers, EP (reprint author), Wayne State Univ, Henry Ford Hosp, Dept Emergency Med, Detroit, MI USA.; Rivers, EP (reprint author), Wayne State Univ, Dept Surg, Henry Ford Hosp, Detroit, MI USA.
EM erivers1@hfhs.org
NR 204
TC 11
Z9 12
U1 4
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1466-609X
EI 1364-8535
J9 CRIT CARE
JI Crit. Care
PD JUL 1
PY 2016
VL 20
AR 160
DI 10.1186/s13054-016-1288-3
PG 16
WC Critical Care Medicine
SC General & Internal Medicine
GA DR3GH
UT WOS:000379790100001
PM 27364620
ER
PT J
AU Graham, JR
West, LM
Martinez, J
Roemer, L
AF Graham, Jessica R.
West, Lindsey M.
Martinez, Jennifer
Roemer, Lizabeth
TI The Mediating Role of Internalized Racism in the Relationship Between
Racist Experiences and Anxiety Symptoms in a Black American Sample
SO CULTURAL DIVERSITY & ETHNIC MINORITY PSYCHOLOGY
LA English
DT Article
DE racism; anxiety; Black; African American
ID ETHNIC-IDENTITY; MENTAL-HEALTH; SOCIAL PHOBIA; PERCEIVED DISCRIMINATION;
AFRICAN-AMERICANS; SELF-ESTEEM; STRESS; DEPRESSION; DISORDER; STUDENTS
AB Objectives: The current study explores the potential mediating role of internalized racism in the relationship between racist experiences and anxiety symptomology in a Black American sample. Method: One hundred and 73 Black American participants, between 18 and 62 years of age, completed a questionnaire packet containing measures of anxious arousal and stress symptoms, internalized racism, and experiences of racist events. Results: Results indicated that internalized racism mediated the relationship between past-year frequency of racist events and anxious arousal as well as past-year frequency of racist events and stress symptoms. Conclusions: Internalized racism may be 1 mechanism that underlies the relationship between racism and anxious symptomology for Black Americans. These preliminary findings suggest that internalized racism may be an avenue through which clinicians can target the anxiety elicited by racist experiences. The clinical implications of these findings and future research directions are discussed.
C1 [Graham, Jessica R.] Natl Ctr PTSD, Boston, MA USA.
[West, Lindsey M.] Georgia Hlth Sci Univ, Dept Psychol, Augusta, GA USA.
[Martinez, Jennifer; Roemer, Lizabeth] Univ Massachusetts Boston, Dept Psychol, Boston, MA USA.
RP Graham, JR (reprint author), Salem State Univ, Dept Psychol, 352 Lafayette St, Salem, MA 01970 USA.
EM jessica.rose.graham@gmail.com
OI Roemer, Lizabeth/0000-0002-2453-5435
NR 49
TC 1
Z9 1
U1 7
U2 16
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1099-9809
EI 1939-0106
J9 CULT DIVERS ETHN MIN
JI Cult. Divers. Ethn. Minor. Psychol.
PD JUL
PY 2016
VL 22
IS 3
BP 369
EP 376
DI 10.1037/cdp0000073
PG 8
WC Ethnic Studies; Psychology, Social
SC Ethnic Studies; Psychology
GA DR2WZ
UT WOS:000379765900008
PM 26750994
ER
PT J
AU Segar, ML
Guerin, E
Phillips, E
Fortier, M
AF Segar, Michelle L.
Guerin, Eva
Phillips, Edward
Fortier, Michelle
TI From a Vital Sign to Vitality: Selling Exercise So Patients Want to Buy
It
SO CURRENT SPORTS MEDICINE REPORTS
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; SELF-DETERMINATION THEORY;
PHYSICAL-ACTIVITY; PRIMARY-CARE; DECISION-MAKING; BEHAVIOR; HEALTH;
MEDICINE; CALL; PARTICIPATION
AB Exercise is MedicineA (EIM) and physical activity as a vital sign are based on health-focused research and reflect ideal frames and messages for clinicians. However, they are nonoptimal for patients because they do not address what drives patients' decision-making and motivation. With the growing national emphasis on patient-centered and value-based care, it is the perfect time for EIM to evolve and advance a second-level consumer-oriented exercise prescription and communication strategy. Through research on decision-making, motivation, consumer behavior, andmeaningful goal pursuit, this article features six evidence-based issues to help clinicians make physical activity more relevant and compelling for patients to sustain in ways that concurrently support patient-centered care. Physical activity prescriptions and counseling can evolve to reflect affective and behavioral science and sell exercise so patients want to buy it.
C1 [Segar, Michelle L.] Univ Michigan, Sport Hlth & Act Res & Policy SHARP Ctr, 1122 Lane Hall 1109, Ann Arbor, MI 48109 USA.
[Guerin, Eva; Fortier, Michelle] Hop Montfort, Inst Rech, Ottawa, ON, Canada.
[Phillips, Edward] Boston VA Healthcare Syst, West Roxbury, MA USA.
RP Segar, ML (reprint author), Univ Michigan, Sport Hlth & Act Res & Policy SHARP Ctr, 1122 Lane Hall 1109, Ann Arbor, MI 48109 USA.
EM fitness@umich.edu
NR 59
TC 1
Z9 1
U1 6
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1537-890X
EI 1537-8918
J9 CURR SPORT MED REP
JI Curr. Sport. Med. Rep.
PD JUL-AUG
PY 2016
VL 15
IS 4
BP 276
EP 281
PG 6
WC Sport Sciences
SC Sport Sciences
GA DR2SH
UT WOS:000379753700011
PM 27399825
ER
PT J
AU Dang, M
Henderson, RE
Garraway, LA
Zon, LI
AF Dang, Michelle
Henderson, Rachel E.
Garraway, Levi A.
Zon, Leonard I.
TI Long-term drug administration in the adult zebrafish using oral gavage
for cancer preclinical studies
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE Adult zebrafish; Oral gavage; Melanoma; Vemurafenib
ID GUIDELINE VERSION 1.1; MELANOMA; TRANSPLANTATION; SYSTEM
AB Zebrafish are a major model for chemical genetics, and most studies use embryos when investigating small molecules that cause interesting phenotypes or that can rescue disease models. Limited studies have dosed adults with small molecules by means of water-borne exposure or injection techniques. Challenges in the form of drug delivery-related trauma and anesthesia-related toxicity have excluded the adult zebrafish from long-term drug efficacy studies. Here, we introduce a novel anesthetic combination of MS-222 and isoflurane to an oral gavage technique for a non-toxic, non-invasive and long-term drug administration platform. As a proof of principle, we established drug efficacy of the FDA-approved BRAF(V600E) inhibitor, Vemurafenib, in adult zebrafish harboring BRAF(V600E) melanoma tumors. In the model, adult casper zebrafish intraperitoneally transplanted with a zebrafish melanoma cell line (ZMEL1) and exposed to daily sub-lethal dosing at 100 mg/kg of Vemurafenib for 2 weeks via oral gavage resulted in an average 65% decrease in tumor burden and a 15% mortality rate. In contrast, Vemurafenib-resistant ZMEL1 cell lines, generated in culture from low-dose drug exposure for 4 months, did not respond to the oral gavage treatment regimen. Similarly, this drug treatment regimen can be applied for treatment of primary melanoma tumors in the zebrafish. Taken together, we developed an effective long-term drug treatment system that will allow the adult zebrafish to be used to identify more effective anti-melanoma combination therapies and opens up possibilities for treating adult models of other diseases.
C1 [Dang, Michelle; Henderson, Rachel E.; Zon, Leonard I.] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.
[Dang, Michelle; Henderson, Rachel E.; Zon, Leonard I.] Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.
[Dang, Michelle; Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA.
[Dang, Michelle; Garraway, Levi A.; Zon, Leonard I.] Harvard Med Sch, Boston, MA 02138 USA.
[Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Garraway, Levi A.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Dang, M; Zon, LI (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.; Dang, M; Zon, LI (reprint author), Boston Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA.; Dang, M; Zon, LI (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA.; Dang, M; Zon, LI (reprint author), Harvard Med Sch, Boston, MA 02138 USA.
EM mdang@fas.harvard.edu; zon@enders.tch.harvard.edu
FU National Institutes of Health; National Cancer Institute RO1
[CA103846-13]; Melanoma Research Alliance; Ellison Medical Foundation
FX This research was supported by the National Institutes of Health and
National Cancer Institute RO1 [grant CA103846-13], Melanoma Research
Alliance and Ellison Medical Foundation.
NR 24
TC 0
Z9 0
U1 1
U2 1
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD JUL 1
PY 2016
VL 9
IS 7
BP 811
EP 820
DI 10.1242/dmm.024166
PG 10
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA DQ9UW
UT WOS:000379555800009
PM 27482819
ER
PT J
AU Sirany, AME
Chow, CJ
Kunitake, H
Madoff, RD
Rothenberger, DA
Kwaan, MR
AF Sirany, Anne-Marie E.
Chow, Christopher J.
Kunitake, Hiroko
Madoff, Robert D.
Rothenberger, David A.
Kwaan, Mary R.
TI Colorectal Surgery Outcomes in Chronic Dialysis Patients: An American
College of Surgeons National Surgical Quality Improvement Program Study
SO DISEASES OF THE COLON & RECTUM
LA English
DT Article
DE Colorectal surgery; Dialysis; National Surgical Quality Improvement
Program; Postoperative mortality; Postoperative outcomes
ID ABDOMINAL-SURGERY; RENAL-FAILURE; ACS-NSQIP; POPULATION; RESCUE; RISK;
CARE; COMPLICATIONS; HEMODIALYSIS; RESECTION
AB BACKGROUND: More than 450,000 US patients with end-stage renal disease currently dialyze. The risk of morbidity and mortality for these patients after colorectal surgery has been incompletely described.
OBJECTIVE: We analyzed the 30-day morbidity and mortality rates of chronic dialysis patients who underwent colorectal surgery.
DESIGN: This was a retrospective analysis.
SETTINGS: Hospitals that participate in the American College of Surgeons National Surgical Quality Improvement Program were included.
PATIENTS: The study included adult patients who underwent emergency or elective colon or rectal resection between 2009 and 2014.
MAIN OUTCOME MEASURES: Baseline characteristics were compared by dialysis status. The impact of chronic dialysis on 30-day mortality and serious postoperative morbidity was examined using multivariate logistic regression.
RESULTS: We identified 128,757 patients who underwent colorectal surgery in the American College of Surgeons National Surgical Quality Improvement Program database. Chronic dialysis patients accounted for 1% (n = 1285) and were more likely to be older (65.4 vs 63.2 years; p < 0.0001), black (27.2% vs 8.7%; p < 0.0001), preoperatively septic (22.1% vs 7.1%; p < 0.0001), require emergency surgery (52.0% vs 14.7%; p < 0.0001), have ischemic bowel (15.7% vs 1.6%; p < 0.0001), or have perforation/peritonitis (15.5% vs 4.2%; p < 0.0001). Chronic dialysis patients were also less likely to have a laparoscopic procedure (17.3% vs 45.0%; p < 0.0001). Chronic dialysis patients had higher unadjusted mortality (22.4% vs 3.3%; p < 0.0001), serious postoperative morbidity (47.9% vs 18.8%; p < 0.0001), and median length of stay (9 vs 6 days; p < 0.0001). In emergent cases (n = 19,375), multivariate logistic regression models demonstrated a higher risk of mortality for dialysis patients (OR = 1.73 (95% CI, 1.38-2.16)) but not for serious morbidity. Models for elective surgery demonstrated a similar effect on mortality (OR = 2.47 (95% CI, 1.75-3.50)) but also demonstrated a higher risk of serious morbidity (OR = 1.28 (95% CI, 1.04-1.56)).
LIMITATIONS: The postoperative 30-day window may underestimate the true incidence of serious morbidity and mortality.
CONCLUSIONS: Chronic dialysis patients undergoing elective or emergent colorectal procedures have a higher risk-adjusted mortality.
C1 [Sirany, Anne-Marie E.] Hennepin Cty Med Ctr, Dept Surg, Minneapolis, MN 55415 USA.
[Chow, Christopher J.; Madoff, Robert D.; Rothenberger, David A.; Kwaan, Mary R.] Univ Minnesota, Dept Surg, 420 Delaware St SE, Minneapolis, MN 55455 USA.
[Kunitake, Hiroko] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Kwaan, MR (reprint author), Univ Minnesota, Dept Surg, 420 Delaware St SE, Minneapolis, MN 55455 USA.
EM mkwaan@umn.edu
FU National Institutes of Health [T32 CA132715]
FX Dr Chow was supported by National Institutes of Health training grant
T32 CA132715.
NR 18
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0012-3706
EI 1530-0358
J9 DIS COLON RECTUM
JI Dis. Colon Rectum
PD JUL
PY 2016
VL 59
IS 7
BP 662
EP 669
DI 10.1097/DCR.0000000000000609
PG 8
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA DR2TT
UT WOS:000379757500014
PM 27270519
ER
PT J
AU Taher, M
Nakao, S
Zandi, S
Melhorn, MI
Hayes, KC
Hafezi-Moghadam, A
AF Taher, Mahdi
Nakao, Shintaro
Zandi, Souska
Melhorn, Mark I.
Hayes, K. C.
Hafezi-Moghadam, Ali
TI Phenotypic transformation of intimal and adventitial lymphatics in
atherosclerosis: a regulatory role for soluble VEGF receptor 2
SO FASEB JOURNAL
LA English
DT Article
DE lymphangiogenesis; LYVE-1; podoplanin; macrophages; VEGF-C
ID E-DEFICIENT MICE; VASA VASORUM NEOVASCULARIZATION; LYMPHANGIOGENIC
FACTORS; PLAQUE PROGRESSION; ANGIOGENESIS; INFLAMMATION; ATHEROGENESIS;
MECHANISMS; EXPRESSION; ARTERIES
AB The role of lymphatics in atherosclerosis is not yet understood. Here, we investigate lymphatic growth dynamics and marker expression in atherosclerosis in apolipoprotein E-deficient (apoE(-/-)) mice. The prolymphangiogenic growth factor, VEGF-C, was elevated in atherosclerotic aortic walls. Despite increased VEGF-C, we found that adventitial lymphatics regress during the course of formation of atherosclerosis (P < 0.01). Similar to lymphatic regression, the number of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1(+)) macrophages decreased in the aortic adventitia of apoE(-/-) mice with atherosclerosis (P < 0.01). Intimal lymphatics in the atherosclerotic lesions exhibited an atypical phenotype, with the expression of podoplanin and VEGF receptor 3 (VEGFR-3) but not of LYVE-1 and prospero homeobox protein 1. In the aortas of atherosclerotic animals, we found markedly increased soluble VEGFR-2. We hypothesized that the elevated soluble VEGFR-2 that was found in the aortas of apoE(-/-) mice with atherosclerosis binds to and diminishes the activity of VEGF-C. This trapping mechanism explains, despite increased VEGF-C in the atherosclerotic aortas, how adventitial lymphatics regress. Lymphatic regression impedes the drainage of lipids, growth factors, inflammatory cytokines, and immune cells. Insufficient lymphatic drainage could thus exacerbate atherosclerosis formation. Our study contributes new insights to previously unknown dynamic changes of adventitial lymphatics. Targeting soluble VEGFR-2 in atherosclerosis may provide a new strategy for the liberation of endogenous VEGF-C and the prevention of lymphatic regression.
C1 [Taher, Mahdi; Nakao, Shintaro; Zandi, Souska; Melhorn, Mark I.; Hafezi-Moghadam, Ali] Brigham & Womens Hosp, Ctr Excellence Funct & Mol Imaging, 75 Francis St, Boston, MA 02115 USA.
[Taher, Mahdi; Nakao, Shintaro; Zandi, Souska; Melhorn, Mark I.; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA.
[Taher, Mahdi; Nakao, Shintaro; Zandi, Souska; Melhorn, Mark I.; Hafezi-Moghadam, Ali] Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA.
[Taher, Mahdi; Nakao, Shintaro; Zandi, Souska; Melhorn, Mark I.; Hafezi-Moghadam, Ali] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA.
[Taher, Mahdi] Charite, Med Ctr, Inst Biochem, Berlin, Germany.
[Hayes, K. C.] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA.
RP Hafezi-Moghadam, A (reprint author), Brigham & Womens Hosp, 45 Francis St, Boston, MA 02115 USA.
EM ahm@bwh.harvard.edu
FU DP3 IMPACT award from U.S. National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases Grant
[DK108238]; DiaComp award; German Academic Exchange Service-DAAD; Bausch
Lomb; Japan Eye Bank Association; Tear Film and Ocular Surface Society
Young Investigator Fellowship
FX The authors thank the Malaysian Palm Oil Board. This work was supported
by a DP3 IMPACT award from U.S. National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases Grant DK108238;
a DiaComp award (to A.H.-M.); an overseas doctoral fellowship from the
German Academic Exchange Service-DAAD (to M.T.); an overseas Research
Fellowship Award from Bausch & Lomb; a fellowship award from the Japan
Eye Bank Association; and a Tear Film and Ocular Surface Society Young
Investigator Fellowship (to S.N.).
NR 30
TC 1
Z9 1
U1 1
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD JUL
PY 2016
VL 30
IS 7
BP 2490
EP 2499
DI 10.1096/fj.201500112
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA DQ5MM
UT WOS:000379249500005
PM 27006449
ER
PT J
AU Abejuela, HR
Osser, DN
AF Abejuela, Harmony Raylen
Osser, David N.
TI The Psychopharmacology Algorithm Project at the Harvard South Shore
Program: An Algorithm for Generalized Anxiety Disorder
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Review
DE algorithms; anxiety disorders; evidence-based practice; generalized
anxiety disorder; psychopharmacology
ID PLACEBO-CONTROLLED TRIAL; SEROTONIN REUPTAKE INHIBITORS; FUMARATE
QUETIAPINE XR; RANDOMIZED CONTROLLED-TRIAL; MAJOR DEPRESSIVE DISORDER;
LONG-TERM TREATMENT; OPEN-LABEL TRIAL; POSTTRAUMATIC-STRESS-DISORDER;
OBSESSIVE-COMPULSIVE DISORDER; VENLAFAXINE EXTENDED-RELEASE
AB This revision of previous algorithms for the pharmacotherapy of generalized anxiety disorder was developed by the Psychopharmacology Algorithm Project at the Harvard South Shore Program. Algorithms from 1999 and 2010 and associated references were reevaluated. Newer studies and reviews published from 2008-14 were obtained from PubMed and analyzed with a focus on their potential to justify changes in the recommendations. Exceptions to the main algorithm for special patient populations, such as women of childbearing potential, pregnant women, the elderly, and those with common medical and psychiatric comorbidities, were considered. Selective serotonin reuptake inhibitors (SSRIs) are still the basic first-line medication. Early alternatives include duloxetine, buspirone, hydroxyzine, pregabalin, or bupropion, in that order. If response is inadequate, then the second recommendation is to try a different SSRI. Additional alternatives now include benzodiazepines, venlafaxine, kava, and agomelatine. If the response to the second SSRI is unsatisfactory, then the recommendation is to try a serotonin-norepinephrine reuptake inhibitor (SNRI). Other alternatives to SSRIs and SNRIs for treatment-resistant or treatment-intolerant patients include tricyclic antidepressants, second-generation antipsychotics, and valproate. This revision of the GAD algorithm responds to issues raised by new treatments under development (such as pregabalin) and organizes the evidence systematically for practical clinical application.
C1 [Abejuela, Harmony Raylen] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA.
[Osser, David N.] VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA.
RP Osser, DN (reprint author), VA Boston Healthcare Syst, Brockton Div, 940 Belmont St, Brockton, MA 02301 USA.
EM David.Osser@va.gov
NR 139
TC 1
Z9 1
U1 18
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1067-3229
EI 1465-7309
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD JUL-AUG
PY 2016
VL 24
IS 4
BP 243
EP 256
DI 10.1097/HRP.0000000000000098
PG 14
WC Psychiatry
SC Psychiatry
GA DR2TI
UT WOS:000379756400001
PM 27384395
ER
PT J
AU Lizano, P
Popat-Jain, A
Scharf, JM
Berman, NC
Widge, A
Dougherty, DD
Eskandar, E
AF Lizano, Paulo
Popat-Jain, Ami
Scharf, Jeremiah M.
Berman, Noah C.
Widge, Alik
Dougherty, Darin D.
Eskandar, Emad
TI Challenges in Managing Treatment-Refractory Obsessive-Compulsive
Disorder and Tourette's Syndrome
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Article
DE cognitive-behavioral therapy; deep brain stimulation; exposure response
prevention; memantine; obsessive-compulsive disorder; Tourtette's
syndrome
ID DEEP-BRAIN-STIMULATION; RANDOMIZED CONTROLLED-TRIAL; BEHAVIOR-THERAPY;
FAMILY ACCOMMODATION; DISRUPTIVE BEHAVIOR; CHILDREN; METAANALYSIS;
INVOLVEMENT; PREVALENCE; SYMPTOMS
C1 [Lizano, Paulo; Scharf, Jeremiah M.; Berman, Noah C.; Widge, Alik; Dougherty, Darin D.; Eskandar, Emad] Harvard Med Sch, Boston, MA USA.
[Lizano, Paulo] Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA.
[Popat-Jain, Ami] Northeastern Univ, Dept Counseling & Appl Educ, Boston, MA 02115 USA.
[Scharf, Jeremiah M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Dept Neurol, Boston, MA 02114 USA.
[Scharf, Jeremiah M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Dept Psychiat, Boston, MA 02114 USA.
[Scharf, Jeremiah M.] Massachusetts Gen Hosp, Div Movement Disorders, Dept Neurol, Boston, MA 02114 USA.
[Berman, Noah C.] Massachusetts Gen Hosp, OCD & Related Disorders Program, Boston, MA 02114 USA.
[Widge, Alik] Massachusetts Gen Hosp, TranslationalNeuroengn Lab, Boston, MA 02114 USA.
[Widge, Alik; Dougherty, Darin D.] Massachusetts Gen Hosp, Div Neurotherapeut, Boston, MA 02114 USA.
[Eskandar, Emad] Massachusetts Gen Hosp, Dept Psychiat & Funct Neurosurg, Boston, MA 02114 USA.
[Scharf, Jeremiah M.] Brigham & Womens Hosp, Div Neurol, Div Cognit & Behav Neurol, Boston, MA 02115 USA.
RP Lizano, P (reprint author), 221 Longwood Ave, Boston, MA 02115 USA.
EM lizanopl@gmail.com
NR 60
TC 0
Z9 0
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1067-3229
EI 1465-7309
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD JUL-AUG
PY 2016
VL 24
IS 4
BP 294
EP 301
DI 10.1097/HRP.0000000000000121
PG 8
WC Psychiatry
SC Psychiatry
GA DR2TI
UT WOS:000379756400004
PM 27384398
ER
PT J
AU Kontos, N
Querques, J
Freudenreich, O
AF Kontos, Nicholas
Querques, John
Freudenreich, Oliver
TI Psychological Symptom Amplification: Are Psychological Symptoms Subject
to "Somatization''-Like Processes?
SO HARVARD REVIEW OF PSYCHIATRY
LA English
DT Article
DE dualism; illness behavior; medicalization; psychiatric diagnosis;
somatoform disorders
ID MEDICALLY UNEXPLAINED SYMPTOMS; COMORBIDITY SURVEY REPLICATION; ABNORMAL
ILLNESS BEHAVIOR; PRIMARY-CARE; AMERICANS ATTITUDES; DISTRESS TOLERANCE;
GOOD HEALTH; DEPRESSION; DISORDERS; SEVERITY
AB Many patients demonstrate amplified somatic symptomexperiences that are felt by providers to cause excessive distress and functional impairment, and that can be diagnostically misleading. Terms attached to these presentations include somatization, medically unexplained symptoms, and, most recently, somatic symptomdisorder. The analogous amplification of psychological symptoms has not been considered. Accordingly, this column makes a case for discussion and investigation of psychological symptom amplification (PSA), a process made possible by the medical legitimization of certain types of human suffering. As various forms of psychological suffering gain greater medical legitimacy, PSA becomes increasingly relevant. Circumstantial evidence suggests that unrecognized PSA may distort research findings and clinical efficacy in psychiatry. The largely symptom-based nature of psychiatric diagnosis makes PSA a challenging, but necessary, object of further scientific and clinical scrutiny.
C1 Harvard Med Sch, Boston, MA USA.
[Kontos, Nicholas] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA.
RP Kontos, N (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 605, Boston, MA 02114 USA.
EM nkontos@partners.org
NR 47
TC 0
Z9 0
U1 3
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1067-3229
EI 1465-7309
J9 HARVARD REV PSYCHIAT
JI Harv. Rev. Psychiatr.
PD JUL-AUG
PY 2016
VL 24
IS 4
BP 302
EP 307
DI 10.1097/HRP.0000000000000104
PG 6
WC Psychiatry
SC Psychiatry
GA DR2TI
UT WOS:000379756400005
PM 27384399
ER
PT J
AU Horste, MMZ
Pateronis, K
Walz, MK
Alesina, P
Mann, K
Schott, M
Esser, J
Eckstein, AK
AF Horste, M. Meyer Zu
Pateronis, K.
Walz, M. K.
Alesina, P.
Mann, K.
Schott, M.
Esser, J.
Eckstein, A. K.
TI The Effect of Early Thyroidectomy on the Course of Active Graves'
Orbitopathy (GO): A Retrospective Case Study
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Article
DE thyroid treatment; thyroidectomy; ATD; course of GO
ID THYROTROPIN RECEPTOR ANTIBODIES; NEAR-TOTAL THYROIDECTOMY; SUBTOTAL
THYROIDECTOMY; RADIOIODINE THERAPY; ANTITHYROID DRUGS; CLINICAL-TRIAL;
DISEASE; OPHTHALMOPATHY; HYPERTHYROIDISM; AUTOANTIBODIES
AB he aim of the work was to investigate the effect of early thyroidectomy on the course of active Graves' orbitopathy (GO) in patients with low probability of remission [high TSH receptor antibody (TRAb) serum levels, severe GO] compared to that of continued therapy with antithyroid drugs. Two cohorts were evaluated retrospectively (total n = 92 patients with active GO, CAS >= 4). Forty-six patients underwent early thyroidectomy (Tx-group) 6 +/- 2 months after initiation of antithyroid drug (ATD) therapy, while ATD was continued for another 6 +/- 2 months in the ATD-group (n = 46). These controls were consecutively chosen from a database and matched to the Tx-group. GO was evaluated (activity, severity, TRAb) at baseline and at 6 month follow-up. At baseline, both cohorts were virtually identical as to disease severity, activity and duration, as well as prior anti-inflammatory treatment, age, gender, and smoking behavior. At 6 month follow-up, NOSPECS severity score was significantly decreased within each group, but did not differ between both groups. However, significantly more patients of the Tx-group presented with inactive GO (89.1 vs. 67.4 %, *p = 0.02), and mean CAS score was significantly lower in Tx-group (2.1) than in ADT-group (2.8; *p = 0.02) at the end of follow-up. TRAb levels declined in both groups (Tx-group: from 18.6 to 5.2 vs. ATD-group: 12.8-3.2 IU/l, p(0) = 0.07, p(6months) = 0.32). Residual GO activity was lower in Tx-group, associated with a higher rate of inactivation of GO. This allows an earlier initiation of ophthalmosurgical rehabilitation in patients with severe GO, which may positively influence quality of life of the patients.
C1 [Horste, M. Meyer Zu; Pateronis, K.; Esser, J.; Eckstein, A. K.] Univ Duisburg Essen, Dept Neuroophthalmol & Strabismus, Ctr Ophthalmol, Essen, Germany.
[Horste, M. Meyer Zu] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA.
[Walz, M. K.; Alesina, P.] Huyssen Stift Essen, Dept Surg, Essen, Germany.
[Walz, M. K.; Alesina, P.] Huyssen Stift Essen, Ctr Minimal Invas Surg, Essen, Germany.
[Mann, K.] Univ Essen Gesamthsch, Dept Endocrinol, Ctr Internal Med, Essen, Germany.
[Schott, M.] Univ Dusseldorf, Dept Endocrinol Diabetol & Rheumatol, Ctr Internal Med, Dusseldorf, Germany.
RP Eckstein, AK (reprint author), Univ Clin, Ctr Ophthalmol, Hufelandstr 55, D-45122 Essen, Germany.
EM anja.eckstein@uk-essen.de
FU DFG [ME 4162/1-1]
FX This project has partly been supported by DFG Grant ME 4162/1-1To MMzH.
NR 48
TC 0
Z9 0
U1 2
U2 4
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
EI 1439-4286
J9 HORM METAB RES
JI Horm. Metab. Res.
PD JUL
PY 2016
VL 48
IS 7
BP 433
EP 439
DI 10.1055/s-0042-108855
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DQ9YR
UT WOS:000379565700003
ER
PT J
AU Tom, MR
Li, J
Ueno, A
Gasia, MF
Chan, R
Hung, DY
Chenoo, S
Iacucci, M
Jijon, HB
Kaplan, GG
Beck, PL
Panaccione, R
Barkema, HW
Buret, AG
Yajnik, V
Ghosh, S
AF Tom, Michael R.
Li, Ji
Ueno, Aito
Gasia, Miriam Fort
Chan, Ronald
Hung, Daniel Y.
Chenoo, Shem
Iacucci, Marietta
Jijon, Humberto B.
Kaplan, Gilaad G.
Beck, Paul L.
Panaccione, Remo
Barkema, Herman W.
Buret, Andre G.
Yajnik, Vijay
Ghosh, Subrata
TI Novel CD8+T-Cell Subsets Demonstrating Plasticity in Patients with
Inflammatory Bowel Disease
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE Crohn's disease; ulcerative colitis; CD8+T cells; T-cell plasticity
ID CD8(+) T-CELLS; CROHNS-DISEASE; VITAMIN-D; ULCERATIVE-COLITIS; TH17
CELLS; TC17 CELLS; EXPRESSION; PATHOGENESIS; CYTOKINES; MUCOSA
AB Background:Distinct CD8+ T-cell subsets such as interleukin-17-expressing Tc17 and Foxp3-expressing Tcreg are functionally similar to CD4+ T cells. Though CD4+ T cells are dysregulated in patients with inflammatory bowel disease (IBD), CD8+ T cells are not well investigated. Vitamin D is an environmental factor which influences T-cell subsets. We assessed the prevalence of CD8+ T-cell subsets among peripheral blood mononuclear cells (PBMC) and lamina propria mononuclear cells (LPMC) of patients with Crohn's disease, patients with ulcerative colitis, and healthy controls. We then tested the effect of 1,25-dihydroxyvitamin D3 on CD8+ T-cell subsets.Methods:A total of 73 patients with Crohn's disease, 49 patients with ulcerative colitis, and 47 healthy controls were studied. LPMC or PBMC were isolated and flow cytometry was performed. CD3+ T cells, isolated from PBMC, were cultured with or without 1,25-dihydroxyvitamin D3, before flow cytometry.Results:In LPMC, the prevalence of Tcreg was higher in patients with IBD (P < 0.05), whereas Tc17 were higher in patients with ulcerative colitis compared with patients with Crohn's disease and healthy controls (P < 0.05). In PBMC, both Tcreg and Tc17 were higher in patients with IBD (P < 0.01). Double-expressing interferon-+ interleukin-17+ and Foxp3+ interleukin-17+ CD8+ T cells were also identified indicating possible CD8+ plasticity. 1,25-dihydroxyvitamin D3 decreased interferon--expressing Tc1 (P < 0.05), but had no effect on Tc17 or Tcreg.Conclusions:The prevalence of novel CD8+ T-cell subsets is altered in patients with IBD. Double-expressing cells indicate plasticity and were identified in patients with IBD. Vitamin D may have a limited effect on CD8+ T cells by decreasing interferon- expression.
C1 [Tom, Michael R.; Li, Ji; Ueno, Aito; Gasia, Miriam Fort; Chan, Ronald; Hung, Daniel Y.; Chenoo, Shem; Iacucci, Marietta; Jijon, Humberto B.; Kaplan, Gilaad G.; Beck, Paul L.; Panaccione, Remo; Barkema, Herman W.; Ghosh, Subrata] Univ Calgary, Dept Med, Calgary, AB, Canada.
[Tom, Michael R.; Buret, Andre G.] Univ Calgary, Dept Biol Sci, Calgary, AB, Canada.
[Li, Ji] Beijing Union Med Coll Hosp, Dept Gastroenterol, Beijing, Peoples R China.
[Kaplan, Gilaad G.; Barkema, Herman W.; Ghosh, Subrata] Univ Calgary, Dept Prod Anim Hlth, Calgary, AB, Canada.
[Yajnik, Vijay] Massachusetts Gen Hosp, Dept Gastroenterol & Hepatol, Boston, MA 02114 USA.
RP Tom, MR (reprint author), Hlth Sci Ctr, 1703,3330 Hosp Dr NW, Calgary, AB T2N 4Z5, Canada.
EM mrtom@ucalgary.ca
RI Barkema, Herman/B-9583-2008;
OI Barkema, Herman/0000-0002-9678-8378; Kaplan, Gilaad/0000-0003-2719-0556;
Tom, Michael/0000-0002-8748-4612
FU Alberta Innovates-Health Solutions; University of Calgary
FX Supported by grants from Alberta Innovates-Health Solutions and the
University of Calgary PURE and Markin USRP programs.
NR 67
TC 1
Z9 2
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD JUL
PY 2016
VL 22
IS 7
BP 1596
EP 1608
DI 10.1097/MIB.0000000000000848
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DR0RO
UT WOS:000379614800013
PM 27306067
ER
PT J
AU Cohen, BL
Ha, C
Ananthakrishnan, AN
Rieder, F
Bewtra, M
AF Cohen, Benjamin L.
Ha, Christina
Ananthakrishnan, Ashwin N.
Rieder, Florian
Bewtra, Meenakshi
CA REACH-IBD Grp
TI State of Adult Trainee Inflammatory Bowel Disease Education in the
United States: A National Survey
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE inflammatory bowel disease; fellowship; trainee; competency
ID QUALITY-OF-CARE; ULCERATIVE-COLITIS; HOSPITAL VOLUME;
GASTROENTEROLOGISTS; MANAGEMENT; OUTCOMES; IMPACT
AB Background:The fundamentals of inflammatory bowel disease (IBD) education begin during gastroenterology fellowship training. We performed a survey of gastroenterology fellowship program directors (PDs) and trainees with the aim to further examine the current state of IBD training in the United States.Methods:A 15-question PD survey and 19-question trainee survey was performed using an online platform.Results:Surveys were completed by 43/161 (27%) PDs and 160 trainees. All trainee years were equally represented. A significant proportion of trainees was unsure or believed that their inpatient (32%) or outpatient (43%) training was inadequate. Only 28% of trainees were satisfied with their current level of IBD exposure during training. Fewer than half the trainees reported comfort in the management of pouch or stoma issues, pregnant patients with IBD, or postoperative management. The proportion of PDs viewing a competency as essential for trainee education strongly correlated with trainee comfort in that area (Pearson's rho = 0.793; P < 0.01). In multivariate logistic regression, monthly IBD didactics was the only variable independently associated with satisfaction with the current level of training (odds ratio, 4.1 95% CI, 1.9-9.0).Conclusions:Over one-third of participating gastroenterology trainees did not feel confident or mostly comfortable with their level of IBD training, with varying comfort regarding different competencies in IBD management. These findings suggest that specific areas of IBD training may require additional focus during training and can provide the basis for the development of an IBD core competency curriculum.
C1 [Cohen, Benjamin L.] Icahn Sch Med Mt Sinai, Div Gastroenterol, 1 Gustave L Levy Pl,Box 1069, New York, NY 10029 USA.
[Ha, Christina] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Inflammatory Bowel Dis, Div Digest Dis, Los Angeles, CA 90095 USA.
[Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA USA.
[Rieder, Florian] Cleveland Clin Fdn, Dept Gastroenterol & Hepatol, Inst Digest Dis, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Bewtra, Meenakshi] Univ Penn, Dept Gastroenterol, Philadelphia, PA 19104 USA.
[Bewtra, Meenakshi] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
RP Cohen, BL (reprint author), Icahn Sch Med Mt Sinai, Div Gastroenterol, 1 Gustave L Levy Pl,Box 1069, New York, NY 10029 USA.
EM Benjamin.cohen@mssm.edu
FU AGA Academy of Educators Grant; NIH [1 K08 DK084347 to 01, T32DK083251,
P30DK097948]; Merck; Amgen; Janssen; AbbVie
FX This study was funded in part from an AGA Academy of Educators Grant and
NIH K08 grant # 1 K08 DK084347 to 01, T32DK083251 and P30DK097948.;
Benjamin Cohen serves on the advisory boards for AbbVie and Janssen.
Christina Ha serves on the advisory board, as a consultant, and on the
speaker's bureau for Abbive and as a consultant for Takeda. Ashwin
Ananthakrishnan serves on the advisory boards for AbbVie, Exact
Sciences, Merck and as research support for Merck and Amgen. Florian
Rieder serves on the advisory board for AbbVie. Meenakshi Bewtra has
received a research grant from Janssen, has served as a consultant for
GlaxoSmithKline and RMEI, and has received a research grant from AbbVie.
NR 18
TC 1
Z9 1
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD JUL
PY 2016
VL 22
IS 7
BP 1609
EP 1615
DI 10.1097/MIB.0000000000000766
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DR0RO
UT WOS:000379614800014
PM 27306068
ER
PT J
AU Frigault, MJ
Maus, MV
AF Frigault, Matthew J.
Maus, Marcela V.
TI Chimeric antigen receptor-modified T cells strike back
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Review
DE cellular immunotherapy; chimeric antigen receptor; clinical immunology;
gene therapy; T-cell therapy
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CYTOKINE RELEASE SYNDROME; ZETA-CHAIN;
ACTIVATION; THERAPY; IMMUNOTHERAPY; MALIGNANCIES; LYMPHOCYTES; DOMAINS;
CD19
AB CAR-T cells strike back.Chimeric antigen receptors (CARs) are engineered molecules designed to endow a polyclonal T-cell population with the ability to recognize tumor-associated surface antigens. In their simplest form, CARs comprise a targeting moiety in the form of a single-chain variable fragment from an antibody connected to various intracellular signaling domains allowing for T-cell activation. This powerful approach combines the specificity of an antibody with the cytotoxic ability of a T cell. There has been much excitement since early phase trials of CAR-T cells targeting CD19 expressed on B-cell malignancies demonstrated remarkable efficacy in inducing long-term, stable remissions in otherwise relapsed/refractory disease. Despite these successes, we have just begun to understand the intricacies of CAR biology with efforts underway to utilize this platform in the treatment of other, previously refractory malignancies. Challenges currently include identification of viable cancer targets, management strategies for potentially severe and irreversible toxicities and overcoming the immunosuppressive nature of the tumor microenvironment. This review will focus on basic CAR structure and function, previous success and new approaches aimed at the broader application of CAR-T-cell therapy.
C1 [Frigault, Matthew J.; Maus, Marcela V.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St,Room 7-219, Boston, MA 02129 USA.
RP Maus, MV (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St,Room 7-219, Boston, MA 02129 USA.
EM mvmaus@mgh.harvard.edu
FU NCI grant [K08CA166039]
FX M. V. M. was supported by the NCI grant K08CA166039.
NR 70
TC 2
Z9 2
U1 13
U2 27
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
EI 1460-2377
J9 INT IMMUNOL
JI Int. Immunol.
PD JUL
PY 2016
VL 28
IS 7
BP 355
EP 363
DI 10.1093/intimm/dxw018
PG 9
WC Immunology
SC Immunology
GA DR3AO
UT WOS:000379775200006
PM 27021308
ER
PT J
AU Natarajan, A
Kamara, J
Ahn, R
Nelson, BD
Eckardt, MJ
Williams, AM
Kargbo, SA
Burke, TF
AF Natarajan, Abirami
Kamara, Jennifer
Ahn, Roy
Nelson, Brett D.
Eckardt, Melody J.
Williams, Anne Marie
Kargbo, Samuel A.
Burke, Thomas F.
TI Provider experience of uterine balloon tamponade for the management of
postpartum hemorrhage in Sierra Leone
SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS
LA English
DT Article
DE Clinical pathway; Feasibility studies; Maternal mortality; Postpartum
hemorrhage; Sierra Leone; Uterine balloon tamponade
ID COUNTRIES
AB Objective: To understand healthcare providers' experience of incorporating uterine balloon tamponade (UBT) into the national postpartum hemorrhage (PPH) clinical pathway after UBT training. Methods: In a qualitative study, semi-structured interviews were undertaken with healthcare providers from 50 centers in Freetown, Sierra Leone, between May and June 2014. All eligible healthcare providers (undergone UBT training, actively conducted deliveries, and treated cases of PPH since UBT training) on duty at the time of center visit were interviewed. Results: Sixty-one providers at 47 facilities were interviewed. Bleeding was controlled in 28 (93%) of 30 cases of UBT device placement. Participants reported that UBT devices were easy to insert with only minor challenges, and enabled providers to manage most cases of uncontrolled PPH at their own facility and to refer others in a stable condition. Reported barriers to optimal UBT use included insufficient training and practical experience, and a scarcity of preassembled UBT devices. Facilitators of UBT use included widespread acceptance of UBT, comprehensive and enthusiastic training, and ready availability of UBT devices. Conclusion: UBT-used either as a primary endpoint or en route to obtaining advanced care-has been well accepted and integrated into the national PPH pathway by providers in health facilities in Freetown. (C) 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Natarajan, Abirami; Kamara, Jennifer; Ahn, Roy; Nelson, Brett D.; Eckardt, Melody J.; Williams, Anne Marie; Burke, Thomas F.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Boston, MA 02114 USA.
[Natarajan, Abirami; Ahn, Roy; Nelson, Brett D.; Williams, Anne Marie; Burke, Thomas F.] Harvard Med Sch, Boston, MA USA.
[Kargbo, Samuel A.] Minist Hlth & Sanitat, Div Reprod Hlth, Freetown, Sierra Leone.
RP Natarajan, A (reprint author), 125 Nashua St,Suite 910, Boston, MA 02114 USA.
EM abirami_natarajan@hms.harvard.edu
OI Nelson, Brett/0000-0002-5049-1798
FU Saving Lives at Birth (Washington, DC, USA); IZUMI Foundation (Boston,
MA, USA); Harvard Medical School (Boston, MA, USA)
FX Funding was provided by Saving Lives at Birth (Washington, DC, USA), the
IZUMI Foundation (Boston, MA, USA), and Harvard Medical School (Boston,
MA, USA).
NR 15
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0020-7292
EI 1879-3479
J9 INT J GYNECOL OBSTET
JI Int. J. Gynecol. Obstet.
PD JUL
PY 2016
VL 134
IS 1
BP 83
EP 86
DI 10.1016/j.ijgo.2015.10.026
PG 4
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DQ9VU
UT WOS:000379558200020
PM 27085981
ER
PT J
AU Abramowicz, S
Kim, S
Prahalad, S
Chouinard, AF
Kaban, LB
AF Abramowicz, S.
Kim, S.
Prahalad, S.
Chouinard, A. F.
Kaban, L. B.
TI Juvenile arthritis: current concepts in terminology, etiopathogenesis,
diagnosis, and management
SO INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY
LA English
DT Review
DE juvenile idiopathic arthritis; temporomandibular joint; children
ID IDIOPATHIC CONDYLAR RESORPTION; INTRAARTICULAR TRIAMCINOLONE
HEXACETONIDE; TEMPOROMANDIBULAR-JOINT ARTHRITIS; REPLACE MANDIBULAR
CONDYLES; TERM-FOLLOW-UP; RHEUMATOID-ARTHRITIS; CORTICOSTEROID
INJECTIONS; DISTRACTION OSTEOGENESIS; CLINICAL EXAMINATION; SKELETAL
SCINTIGRAPHY
AB The latest change in terminology from juvenile rheumatoid arthritis (JRA) to juvenile idiopathic arthritis (JIA), established by the International League of Associations for Rheumatology (ILAR), has resulted in some confusion for OMFS and other treating clinicians. JIA comprises a group of systemic inflammatory diseases that result in the destruction of hard and soft tissues in a single or multiple joints. In a significant number of patients, one or both temporomandibular joints (TMJ) are also involved. TMJ disease may be accompanied by pain, swelling, and limitation of motion, as well as mandibular retrognathism, open bite, and asymmetry. The purpose of this article is to provide a review, for the oral and maxillofacial surgeon, of the terminology, etiopathogenesis, diagnosis, and management of children with JIA.
C1 [Abramowicz, S.] Emory Univ, Childrens Healthcare Atlanta, Sect Dent Oral & Maxillofacial Surg, Dept Surg,Div Oral & Maxillofacial Surg,Sch Med, 1365 Clifton Rd NE Bldg B Suite 2300, Atlanta, GA 30306 USA.
[Kim, S.] Harvard Med Sch, Boston Childrens Hosp, Rheumatol Program, Boston, MA USA.
[Prahalad, S.] Emory Univ, Sch Med, Dept Pediat, 1365 Clifton Rd NE Bldg B Suite 2300, Atlanta, GA 30306 USA.
[Prahalad, S.] Emory Univ, Sch Med, Dept Human Genet, 1365 Clifton Rd NE Bldg B Suite 2300, Atlanta, GA 30306 USA.
[Prahalad, S.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Chouinard, A. F.; Kaban, L. B.] Harvard Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA USA.
RP Abramowicz, S (reprint author), Emory Univ, Dept Surg, Div Oral & Maxillofacial Surg, 1365 Clifton Rd NE Bldg B Suite 2300, Atlanta, GA 30306 USA.
EM sabram5@emory.edu
OI Chouinard, Anne-Frederique/0000-0002-1048-6177
FU Oral and Maxillofacial Surgery Foundation/American Association of Oral
and Maxillofacial Surgeons Faculty Educator Development Award;
Massachusetts General Hospital Oral and Maxillofacial Surgery Education
and Research Fund; Marcus Foundation Inc.
FX This project was supported in part by Oral and Maxillofacial Surgery
Foundation/American Association of Oral and Maxillofacial Surgeons
Faculty Educator Development Award (SA), the Massachusetts General
Hospital Oral and Maxillofacial Surgery Education and Research Fund, and
the Marcus Foundation Inc. (SP).
NR 108
TC 2
Z9 2
U1 6
U2 15
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0901-5027
EI 1399-0020
J9 INT J ORAL MAX SURG
JI Int. J. Oral Maxillofac. Surg.
PD JUL
PY 2016
VL 45
IS 7
BP 801
EP 812
DI 10.1016/j.ijom.2016.03.013
PG 12
WC Dentistry, Oral Surgery & Medicine; Surgery
SC Dentistry, Oral Surgery & Medicine; Surgery
GA DQ7FT
UT WOS:000379373000001
PM 27160609
ER
PT J
AU Yoon, J
Fonarow, GC
Groeneveld, PW
Teerlink, JR
Whooley, MA
Sahay, A
Heidenreich, PA
AF Yoon, Jean
Fonarow, Gregg C.
Groeneveld, Peter W.
Teerlink, John R.
Whooley, Mary A.
Sahay, Anju
Heidenreich, Paul A.
TI Patient and Facility Variation in Costs of VA Heart Failure Patients
SO JACC-HEART FAILURE
LA English
DT Article
DE costs; heart failure; veterans
ID MEDICARE BENEFICIARIES; ELDERLY-PATIENTS; OLDER PATIENTS; UNITED-STATES;
AVERAGE COST; HEALTH-CARE; RISK; READMISSION; VETERANS; HOSPITALIZATION
AB OBJECTIVES This study sought to determine the variation in annual health care costs among patients with heart failure in the Veterans Affairs (VA) system.
BACKGROUND Heart failure is associated with considerable use of health care resources, but Little is known about patterns in patient characteristics related to higher costs.
METHODS We obtained VA utilization and cost records for all patients with a diagnosis of heart failure in fiscal year 2010. We compared total VA costs by patient demographic factors, comorbid conditions, and facility where they were treated in bivariate analyses. We regressed total costs on patient factors alone, VA facility alone, and all factors combined to determine the relative contribution of patient factors and facility to explaining cost differences.
RESULTS There were 117,870 patients with heart failure, and their mean annual VA costs were $30,719 (SD 49,180) with more than one-half of their costs from inpatient care. Patients at younger ages, of Hispanic or black race/ethnicity, diagnosed with comorbid drug use disorders, or who died during the year had the highest costs (all p < 0.01). There was variation in costs by facility as mean adjusted costs ranged from approximately $15,000 to $48,000. In adjusted analyses, patient factors atone explained more of the variation in health care costs (R-2=0.116) compared with the facility where the patient was treated (R-2=0.018).
CONCLUSIONS A large variation in costs of heart failure patients was observed across facilities, although this was explained largely by patient factors. Improving the efficiency of VA resource utilization may require increased scrutiny of high-cost patients to determine if adequate value is being delivered to those patients. (C) 2016 by the American College of Cardiology Foundation.
C1 [Yoon, Jean] Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA.
[Groeneveld, Peter W.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Groeneveld, Peter W.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Teerlink, John R.; Whooley, Mary A.] San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA.
[Teerlink, John R.; Whooley, Mary A.] Univ Calif San Francisco, Dept Med, Div Cardiol, San Francisco, CA 94143 USA.
[Sahay, Anju; Heidenreich, Paul A.] Vet Affairs Palo Alto Hlth Care Syst, Ctr Innovat Implementat, Menlo Pk, CA USA.
[Heidenreich, Paul A.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
RP Yoon, J (reprint author), Vet Affairs Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, 795 Willow Rd 152 MPD, Menlo Pk, CA 94025 USA.
EM jean.yoon@va.gov
NR 30
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD JUL
PY 2016
VL 4
IS 7
BP 551
EP 558
DI 10.1016/j.jchf.2016.01.003
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DQ5YY
UT WOS:000379282400005
PM 26970829
ER
PT J
AU Pang, PS
Teerlink, JR
Voors, AA
Ponikowski, P
Greenberg, BH
Filippatos, G
Felker, GM
Davison, BA
Cotter, G
Kriger, J
Prescott, MF
Hua, TA
Severin, T
Metra, M
AF Pang, Peter S.
Teerlink, John R.
Voors, Adriaan A.
Ponikowski, Piotr
Greenberg, Barry H.
Filippatos, Gerasimos
Felker, G. Michael
Davison, Beth A.
Cotter, Gad
Kriger, Joshua
Prescott, Margaret F.
Hua, Tsushung A.
Severin, Thomas
Metra, Marco
TI Use of High-Sensitivity Troponin T to Identify Patients With Acute Heart
Failure at Lower Risk for Adverse Outcomes An Exploratory Analysis From
the RELAX-AHF Trial
SO JACC-HEART FAILURE
LA English
DT Article
DE acute heart failure; emergency department; risk stratification;
serelaxin
ID EMERGENCY-DEPARTMENT; CARDIAC TROPONIN; MORTALITY; HOSPITALIZATION;
STRATIFICATION; PREDICTION; DESIGN; VALIDATION; BIOMARKERS; ADMISSIONS
AB OBJECTIVES The aim of this study was to determine if a baseline high-sensitivity troponin T (hsTnT) value <= 99th percentile upper reference limit (0.014 mu g/l ["low hsTnT"]) identifies patients at tow risk for adverse outcomes.
BACKGROUND Approximately 85% of patients who present to emergency departments with acute heart failure are admitted. Identification of patients at low risk might decrease unnecessary admissions.
METHODS A post-hoc analysis was conducted from the RELAX-AHF (Serelaxin, Recombinant Human Relaxin-2, for Treatment of Acute Heart Failure) trial, which randomized patients within 16 h of presentation who had systolic blood pressure >125 mm Hg, mild to moderate renal impairment, and N-terminal pro-brain natriuretic peptide >= 1,600 ng/l to serelaxin versus placebo. Linear regression models for continuous endpoints and Cox models for time-to-event endpoints were used.
RESULTS Of the 1,076 patients with available baseline hsTnT values, 107 (9.9%) had low hsTnT. No cardiovascular (CV) deaths through day 180 were observed in the low-hsTnT group compared with 79 CV deaths (7.3%) in patients with higher hsTnT. By univariate analyses, low hsTnT was associated with lower risk for all 5 primary outcomes: 1) days alive and out of the hospital by day 60; 2) CV death or rehospitalization for heart failure or renal failure by day 60; 3) length of stay; 4) worsening heart failure through day 5; and 5) CV death through day 180. After multivariate adjustment, only 180-day CV mortality remained significant (hazard ratio: 0.0; 95% confidence interval: 0.0 to 0.736; p = 0.0234; C-index = 0.838 [95% confidence interval: 0.798 to 0.878]).
CONCLUSIONS No CV deaths through day 180 were observed in patients with hsTnT levels <= 0.014 mu g/l despite high N-terminal pro-brain natriuretic peptide levels. Low baseline hsTnT may identify patients with acute heart faiLure at very Low risk for CV mortality. (C) 2016 by the American College of Cardiology Foundation.
C1 [Pang, Peter S.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Pang, Peter S.] Regenstrief Inst Hlth Care, Indianapolis, IN USA.
[Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland.
[Greenberg, Barry H.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Filippatos, Gerasimos] Athens Univ Hosp, Athens, Greece.
[Felker, G. Michael] Duke Univ, Sch Med, Durham, NC USA.
[Felker, G. Michael] Duke Clin Res Inst, Durham, NC USA.
[Davison, Beth A.; Cotter, Gad] Momentum Res, Durham, NC USA.
[Kriger, Joshua] Columbia Univ, New York, NY USA.
[Prescott, Margaret F.; Hua, Tsushung A.] Novartis Pharmaceut, New Hanover, NJ USA.
[Severin, Thomas] Novartis Pharmaceut, Basel, Switzerland.
[Metra, Marco] Univ Brescia, Brescia, Italy.
RP Pang, PS (reprint author), Indiana Univ, Dept Emergency Med, 640 Eskenazi Ave,FOB 3rd Floor, Indianapolis, IN 46202 USA.
EM ppang@iu.edu
RI Ponikowski, Piotr/O-6454-2015
OI Ponikowski, Piotr/0000-0002-3391-7064
NR 36
TC 3
Z9 3
U1 2
U2 4
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD JUL
PY 2016
VL 4
IS 7
BP 591
EP 599
DI 10.1016/j.jchf.2016.02.009
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DQ5YY
UT WOS:000379282400012
PM 27039129
ER
PT J
AU Jaffe, AS
Morrow, DA
Scirica, BM
AF Jaffe, Allan S.
Morrow, David A.
Scirica, Benjamin M.
TI High-Sensitivity Troponin in the Triage of Acute Decompensated Heart
Failure
SO JACC-HEART FAILURE
LA English
DT Editorial Material
DE acute decompensated heart failure; biomarkers; emergency care
ID CARDIAC TROPONIN; INSIGHTS
C1 [Jaffe, Allan S.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA.
[Morrow, David A.; Scirica, Benjamin M.] Harvard Med Sch, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA.
RP Morrow, DA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.
EM dmorrow@partners.org
NR 13
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD JUL
PY 2016
VL 4
IS 7
BP 600
EP 602
DI 10.1016/j.jchf.2016.04.008
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DQ5YY
UT WOS:000379282400013
PM 27289402
ER
PT J
AU Roider, EM
Fisher, DE
AF Roider, Elisabeth M.
Fisher, David E.
TI Red Hair, Light Skin, and UV-Independent Risk for Melanoma Development
in Humans
SO JAMA DERMATOLOGY
LA English
DT Editorial Material
ID OXIDATIVE STRESS; PHEOMELANIN; MECHANISMS; PATHWAY
C1 [Roider, Elisabeth M.; Fisher, David E.] Harvard Med Sch, Dept Dermatol, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, Charlestown, MA USA.
RP Fisher, DE (reprint author), Harvard Med Sch, Dept Dermatol, Cutaneous Biol Res Ctr, Massachusetts Gen Hosp, 55 Fruit St,Bartlett 6, Boston, MA 02114 USA.
EM dfisher3@mgh.harvard.edu
FU NCI NIH HHS [P01 CA163222]; NIAMS NIH HHS [R01 AR043369]
NR 16
TC 1
Z9 1
U1 5
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6068
EI 2168-6084
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD JUL
PY 2016
VL 152
IS 7
BP 751
EP 753
DI 10.1001/jamadermatol.2016.0524
PG 3
WC Dermatology
SC Dermatology
GA DR0IB
UT WOS:000379590100002
PM 27050924
ER
PT J
AU Rengit, AC
McKowen, JW
O'Brien, J
Howe, YJ
McDougle, CJ
AF Rengit, Ashy C.
McKowen, James W.
O'Brien, Julie
Howe, Yamini J.
McDougle, Christopher J.
TI Brief Report: Autism Spectrum Disorder and Substance Use Disorder: A
Review and Case Study
SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
LA English
DT Article
DE Autism; Autism spectrum disorder; Substance use disorder; Alcohol
dependence
ID CHILDREN; ALCOHOL; ADOLESCENTS; TRIAL; DRUG
AB There is limited literature available on the comorbidity between autism spectrum disorder (ASD) and substance use disorder (SUD). This paper reviews existing literature and exemplifies the challenges of treating this population with a case report of an adult male with ASD and DSM-5 alcohol use disorder. This review and case study seeks to illustrate risk factors which predispose individuals with ASD to developing SUD and discuss the obstacles to and modifications of evidence-based treatments for SUD. A review of the therapeutic interventions implemented in the treatment of this young male are described to highlight potential recommendations for the general management of SUD in those with ASD.
C1 [Rengit, Ashy C.] Univ Sheffield, Sheffield, S Yorkshire, England.
[McKowen, James W.] Massachusetts Gen Hosp, Addict Recovery Management Serv, Boston, MA 02114 USA.
[O'Brien, Julie; Howe, Yamini J.; McDougle, Christopher J.] Massachusetts Gen Hosp, Lurie Ctr Autism, One Maguire Rd, Lexington, MA 02421 USA.
RP McDougle, CJ (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, One Maguire Rd, Lexington, MA 02421 USA.
EM cmcdougle@mgh.harvard.edu
FU Nancy Lurie Marks Family Foundation
FX The authors thank the Nancy Lurie Marks Family Foundation for their
support.
NR 18
TC 2
Z9 2
U1 2
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0162-3257
EI 1573-3432
J9 J AUTISM DEV DISORD
JI J. Autism Dev. Disord.
PD JUL
PY 2016
VL 46
IS 7
BP 2514
EP 2519
DI 10.1007/s10803-016-2763-z
PG 6
WC Psychology, Developmental
SC Psychology
GA DQ9RT
UT WOS:000379547700022
PM 26944591
ER
PT J
AU Tuepker, A
Zickmund, SL
Nicolajski, CE
Hahm, B
Butler, J
Weir, C
Post, L
Hickam, DH
AF Tuepker, Anais
Zickmund, Susan L.
Nicolajski, Cara E.
Hahm, Bridget
Butler, Jorie
Weir, Charlene
Post, Lori
Hickam, David H.
TI Providers' Note-Writing Practices for Post-traumatic Stress Disorder at
Five United States Veterans Affairs Facilities
SO JOURNAL OF BEHAVIORAL HEALTH SERVICES & RESEARCH
LA English
DT Article
ID ELECTRONIC HEALTH RECORDS; MEDICAL-RECORD; PTSD; INFORMATION;
EXPERIENCES; THERAPY; DOCTORS; PATIENT
AB The capacity of electronic health records (EHRs) to capture desired information depends on the practices of health care providers. These practices have not been well studied in relation to post-traumatic stress disorder (PTSD). This qualitative study investigated how providers write EHR notes on PTSD through 38 interviews with providers working at five Veterans Affairs (VA) hospitals across the United States of America. Two overarching themes were prominent in the results. Providers used progress notes primarily to remember and access details for direct patient care, but only rarely for care coordination. Providers infrequently recorded information not judged to directly contribute to improved care, sometimes deliberately omitting information perceived to jeopardize patients' access to, or quality of, care. Omitted information frequently included sexual or non-military trauma. Understanding providers' thought processes can help clinicians be aware of the limitations of EHR notes as a tool for learning the histories of new patients. Similarly, researchers relying on EHR data for PTSD research should be aware of likely areas of missing data.
C1 [Tuepker, Anais] VA Portland Hlth Care Syst, CIVIC, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
[Tuepker, Anais] Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97201 USA.
[Zickmund, Susan L.] VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA.
[Zickmund, Susan L.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Nicolajski, Cara E.] UPMC Ctr High Value Hlth Care, Pittsburgh, PA USA.
[Hahm, Bridget] James A Haley Vet Hosp, Tampa, FL USA.
[Butler, Jorie; Weir, Charlene] VA Salt Lake City Healthcare Syst, Consortium Healthcare Informat Res, Salt Lake City, UT USA.
[Post, Lori] Yale Univ, Dept Emergency Med, New Haven, CT USA.
[Hickam, David H.] PCORI, Washington, DC USA.
RP Tuepker, A (reprint author), VA Portland Hlth Care Syst, CIVIC, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.; Tuepker, A (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med, Portland, OR 97201 USA.
EM tuepker@ohsu.edu
FU VA's Health Services Research and Development Service through its
Consortium for Health Informatics Research (CHIR)
FX Funding for this research was provided by the VA's Health Services
Research and Development Service through its Consortium for Health
Informatics Research (CHIR). The views expressed are those of the
authors and do not necessarily represent the views of the Department of
Veterans Affairs. The authors would like to thank all members of the
Consortium for Health Informatics Research (CHIR) PTSD research team,
with particular thanks to Jessica Robb for project coordination.
NR 26
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1094-3412
EI 1556-3308
J9 J BEHAV HEALTH SER R
JI J. Behav. Health Serv. Res.
PD JUL
PY 2016
VL 43
IS 3
BP 428
EP 442
DI 10.1007/s11414-015-9472-9
PG 15
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA DQ2NZ
UT WOS:000379040600007
PM 26228929
ER
EF