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 ho