FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Bellad, RM
Bang, A
Carlo, WA
McClure, EM
Meleth, S
Goco, N
Goudar, SS
Derman, RJ
Hibberd, PL
Patel, A
Esamai, F
Bucher, S
Gisore, P
Wright, LL
AF Bellad, Roopa M.
Bang, Akash
Carlo, Waldemar A.
McClure, Elizabeth M.
Meleth, Sreelatha
Goco, Norman
Goudar, Shivaprasad S.
Derman, Richard J.
Hibberd, Patricia L.
Patel, Archana
Esamai, Fabian
Bucher, Sherri
Gisore, Peter
Wright, Linda L.
CA HBB Study Grp
TI A pre-post study of a multi-country scale up of resuscitation training
of facility birth attendants: does Helping Babies Breathe training save
lives?
SO BMC PREGNANCY AND CHILDBIRTH
LA English
DT Article
ID MIDDLE-INCOME COUNTRIES; MORTALITY; ETHIOPIA; WOMEN
AB Background: Whether facility-based implementation of Helping Babies Breathe (HBB) reduces neonatal mortality at a population level in low and middle income countries (LMIC) has not been studied. Therefore, we evaluated HBB implementation in this context where our study team has ongoing prospective outcome data on all pregnancies regardless of place of delivery.
Methods: We compared outcomes of birth cohorts in three sites in India and Kenya pre-post implementation of a facility-based intervention, using a prospective, population-based registry in 52 geographic clusters. Our hypothesis was that HBB implementation would result in a 20 % decrease in the perinatal mortality rate (PMR) among births >= 1500 g.
Results: We enrolled 70,704 births during two 12-month study periods. Births within each site did not differ pre-post intervention, except for an increased proportion of <2500 g newborns and deliveries by caesarean section in the post period. There were no significant differences in PMR among all registry births; however, a post-hoc analysis stratified by birthweight documented improvement in <2500 g mortality in Belgaum in both registry and in HBB-trained facility births. No improvement in <2500 g mortality measures was noted in Nagpur or Kenya and there was no improvement in normal birth weight survival.
Conclusions: Rapid scale up of HBB training of facility birth attendants in three diverse sites in India and Kenya was not associated with consistent improvements in mortality among all neonates >= 1500 g; however, differential improvements in <2500 g survival in Belgaum suggest the need for careful implementation of HBB training with attention to the target population, data collection, and ongoing quality monitoring activities.
C1 [Bellad, Roopa M.; Goudar, Shivaprasad S.] KLE Univ Jawaharlal Nehru Med Coll, Belgaum, Karnataka, India.
[Bang, Akash] Mahatma Gandhi Inst Med Sci, Sevagram, Maharashtra, India.
[Carlo, Waldemar A.] Univ Alabama Birmingham, Birmingham, AL USA.
[McClure, Elizabeth M.; Meleth, Sreelatha; Goco, Norman] RTI Int, Durham, NC USA.
[Derman, Richard J.] Christiana Care Hlth Syst, Dept Obstet & Gynecol, Newark, DE USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Patel, Archana] Lata Med Res Fdn, Nagpur, Maharashtra, India.
[Patel, Archana] Indira Gandhi Govt Med Coll, Nagpur, Maharashtra, India.
[Esamai, Fabian; Gisore, Peter] Moi Univ Sch Med, Dept Child Hlth & Paediat, Eldoret, Kenya.
[Bucher, Sherri] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Wright, Linda L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Wright, Linda L.] 5800 Nicholson Lane,1206, Rockville, MD 20852 USA.
RP Wright, LL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.; Wright, LL (reprint author), 5800 Nicholson Lane,1206, Rockville, MD 20852 USA.
EM lindawright.md@gmail.com
OI Somannavar, Manjunath/0000-0002-8871-5072
FU Norad; Laerdal Foundation; Eunice Kennedy Shriver National Institute of
Child Health and Human Development (NICHD)
FX The study was funded by grants from Norad, Laerdal Foundation and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD). NICHD staff had input into the study design, data
interpretation and writing of the report. RTI staff had access to all
the study data. The corresponding author wrote the first draft of the
manuscript and had final responsibility for the decision to submit for
publication.
NR 17
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Z9 1
U1 6
U2 6
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 AUG 15
PY 2016
VL 16
AR 222
DI 10.1186/s12884-016-0997-6
PG 10
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DT4UL
UT WOS:000381476500001
PM 27527831
ER
PT J
AU Figlewicz, DP
AF Figlewicz, Dianne P.
TI Expression of receptors for insulin and leptin in the ventral tegmental
area/substantia nigra (VTA/SN) of the rat: Historical perspective
SO BRAIN RESEARCH
LA English
DT Review
DE Dopamine; Fluorescence immunocytochemistry; Reward; Ingestive behavior
ID HIGH-FAT DIET; INTRAVENTRICULAR INSULIN; FOOD-DEPRIVATION;
MESSENGER-RNA; DOPAMINE TRANSPORTER; PLACE PREFERENCE; ENERGY-BALANCE;
BRAIN; INCREASES; REWARD
AB Since the publication of the observation that dopaminergic neurons in the ventral tegmental area/substantia nigra of the rat express receptors for insulin and leptin, numerous studies have extended and validated these findings. Thus, these major metabolic hormones have effects on synaptic and cell signaling function of the midbrain dopamine neurons, across a range of concentrations that reflect physiologic (fasting vs. fed) and pathophysiologic (diabetes) circumstances. The capacity of metabolic hormones to alter reward behaviors, including palatability-related food intake; motivation for food; and the conditioning of place preference by food, is now appreciated as an integral part of the larger actions of these hormones to regulate caloric homeostasis. Finally, the delineation of metabolic hormone effects on the CNS reward circuitry of normal animals provides the rationale and experimental basis for evaluating dysfunction of reward circuitry in obesity and diabetes.
This article is part-of a Special Issue entitled SI:50th Anniversary Issue. Published by Elsevier B.V.
C1 [Figlewicz, Dianne P.] VA Puget Sound Hlth Care Syst, BSLRD, Seattle, WA 98108 USA.
[Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Figlewicz, DP (reprint author), VAPSHCS 151, 1660 So Columbian Way, Seattle, WA 98108 USA.
EM latte@uw.edu
FU VA Puget Sound Health Care System, Seattle, Washington; NIH [DK40963];
American Recovery and Reinvestment Act (ARRA) [NIH DK 40963]
FX I particularly thank my colleagues of many years, Dr. Patti Szot and Dr.
Al Sipols. Their assistance and advice made the completion of all the
studies described here possible. I thank again the coauthors of the
original study, Dr. Scott Ng-Evans, a postdoctoral fellow in the lab;
Dr. Denis Baskin, a long-time colleague and collaborator; and Marcy Hoen
and Joyce Murphy, who provided expert technical assistance. Dianne
Figlewicz Lattemann is a Senior Research Career Scientist, Biomedical
Laboratory Research Program, Department of Veterans Affairs Puget Sound
Health Care System, Seattle, Washington. The author's research described
in this article is the result of work supported by resources from the VA
Puget Sound Health Care System, Seattle, Washington, and was supported
by NIH grant DK40963 and by the American Recovery and Reinvestment Act
(ARRA) (Grant No. NIH DK 40963).
NR 29
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Z9 1
U1 4
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD AUG 15
PY 2016
VL 1645
SI SI
BP 68
EP 70
DI 10.1016/j.brainres.2015.12.041
PG 3
WC Neurosciences
SC Neurosciences & Neurology
GA DT5QJ
UT WOS:000381537400021
PM 26731335
ER
PT J
AU Stopsack, KH
Gerke, TA
Sinnott, JA
Penney, KL
Tyekucheva, S
Sesso, HD
Andersson, SO
Andren, O
Cerhan, JR
Giovannucci, EL
Mucci, LA
Rider, JR
AF Stopsack, Konrad H.
Gerke, Travis A.
Sinnott, Jennifer A.
Penney, Kathryn L.
Tyekucheva, Svitlana
Sesso, Howard D.
Andersson, Swen-Olof
Andren, Ove
Cerhan, James R.
Giovannucci, Edward L.
Mucci, Lorelei A.
Rider, Jennifer R.
TI Cholesterol Metabolism and Prostate Cancer Lethality
SO CANCER RESEARCH
LA English
DT Article
ID INTRATUMORAL ANDROGENS; CARDIOVASCULAR-DISEASE; SQUALENE EPOXIDASE;
GENE-EXPRESSION; BETA-CAROTENE; RISK; PROGRESSION; HYPERCHOLESTEROLEMIA;
ANGIOGENESIS; ASSOCIATION
AB Cholesterol metabolism has been implicated in prostate cancer pathogenesis. Here, we assessed the association of intratumoral mRNA expression of cholesterol synthesis enzymes, transporters, and regulators in tumor specimen at diagnosis and lethal prostate cancer, defined as mortality or metastases from prostate cancer in contrast to nonlethal disease without evidence of metastases after at least 8 years of follow-up. We analyzed the prospective prostate cancer cohorts within the Health Professionals Follow-up Study (n = 249) and the Physicians' Health Study (n = 153) as well as expectantly managed patients in the Swedish Watchful Waiting Study (n = 338). The expression of squalene monooxygenase (SQLE) was associated with lethal cancer in all three cohorts. Men with high SQLE expression (>1 standard deviation above the mean) were 8.3 times (95% confidence interval, 3.5 to 19.7) more likely to have lethal cancer despite therapy compared with men with the mean level of SQLE expression. Absolute SQLE expression was associated with lethal cancer independently from Gleason grade and stage, as was a SQLE expression ratio in tumor versus surrounding benign prostate tissue. Higher SQLE expression was tightly associated with increased histologic markers of angiogenesis. Collectively, this study establishes the prognostic value of intratumoral cholesterol synthesis as measured via SQLE, its second rate-limiting enzyme. SQLE expression at cancer diagnosis is prognostic for lethal prostate cancer both after curative-intent prostatectomy and in a watchful waiting setting, possibly by facilitating micrometastatic disease. (C) 2016 AACR.
C1 [Stopsack, Konrad H.; Gerke, Travis A.; Sinnott, Jennifer A.; Penney, Kathryn L.; Sesso, Howard D.; Giovannucci, Edward L.; Mucci, Lorelei A.; Rider, Jennifer R.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Stopsack, Konrad H.] Mayo Clin, Dept Internal Med, 200 1st St SW, Rochester, MN 55905 USA.
[Gerke, Travis A.] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA.
[Gerke, Travis A.] Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA.
[Sinnott, Jennifer A.] Ohio State Univ, Dept Stat, Columbus, OH 43210 USA.
[Penney, Kathryn L.; Giovannucci, Edward L.; Mucci, Lorelei A.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Penney, Kathryn L.; Giovannucci, Edward L.; Mucci, Lorelei A.] Harvard Med Sch, Boston, MA USA.
[Tyekucheva, Svitlana] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA.
[Andersson, Swen-Olof; Andren, Ove] Univ Orebro, Sch Hlth & Med Sci, Dept Urol, Orebro, Sweden.
[Cerhan, James R.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Rider, Jennifer R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
RP Stopsack, KH (reprint author), Mayo Clin, Dept Internal Med, 200 1st St SW, Rochester, MN 55905 USA.
EM stopsack@post.harvard.edu
FU NCI NIH HHS [R01 CA097193, P01 CA055075, P50 CA090381, R01 CA034944, R01
CA034944-03, R01 CA040360, R01 CA133891, R01 CA141298, T32 CA009001, UM1
CA167552]; NHLBI NIH HHS [R01 HL026490, R01 HL026490-03, R01 HL034595,
R01 HL034595-07]
NR 32
TC 1
Z9 1
U1 3
U2 3
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 AUG 15
PY 2016
VL 76
IS 16
BP 4785
EP 4790
DI 10.1158/0008-5472.CAN-16-0903
PG 6
WC Oncology
SC Oncology
GA DU6BI
UT WOS:000382297700020
PM 27325648
ER
PT J
AU Li, J
Shin, S
Sun, Y
Yoon, SO
Li, CG
Zhang, E
Yu, J
Zhang, JM
Blenis, J
AF Li, Jing
Shin, Sejeong
Sun, Yang
Yoon, Sang-Oh
Li, Chenggang
Zhang, Erik
Yu, Jane
Zhang, Jianming
Blenis, John
TI mTORC1-Driven Tumor Cells Are Highly Sensitive to Therapeutic Targeting
by Antagonists of Oxidative Stress
SO CANCER RESEARCH
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; BUTHIONINE SULFOXIMINE; GLUTATHIONE
SYNTHESIS; CANCER-CELLS; NULL-CELLS; METABOLISM; AUTOPHAGY; ACTIVATION;
MECHANISMS; SURVIVAL
AB mTORC1 is a central signaling node in controlling cell growth, proliferation, and metabolism that is aberrantly activated in cancers and certain cancer-associated genetic disorders, such as tuberous sclerosis complex (TSC) and sporadic lymphangioleiomyomatosis. However, while mTORC1-inhibitory compounds (rapamycin and rapalogs) attracted interest as candidate therapeutics, clinical trials have not replicated the promising findings in preclinical models, perhaps because these compounds tend to limit cell proliferation without inducing cell death. In seeking to address this issue, we performed a high-throughput screen for small molecules that could heighten the cytotoxicity of mTORC1 inhibitors. Here we report the discovery that combining inhibitors of mTORC1 and glutamate cysteine ligase (GCLC) can selectively and efficiently trigger apoptosis in Tsc2-deficient cells but not wild-type cells. Mechanistic investigations revealed that coinhibition of mTORC1 and GCLC decreased the level of the intracellular thiol antioxidant glutathione (GSH), thereby increasing levels of reactive oxygen species, which we determined to mediate cell death in Tsc2-deficient cells. Our findings offer preclinical proof of concept for a strategy to selectively increase the cytotoxicity of mTORC1 inhibitors as a therapy to eradicate tumor cells marked by high mTORC1 signaling, based on cotargeting a GSH-controlled oxidative stress pathway. (C) 2016 AACR.
C1 [Li, Jing; Blenis, John] Harvard Med Sch, Dept Cell Biol, Boston, MA USA.
[Shin, Sejeong; Yoon, Sang-Oh; Blenis, John] Weill Cornell Med, Dept Pharmacol, Meyer Canc Ctr, New York, NY USA.
[Li, Chenggang; Zhang, Erik; Yu, Jane] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
[Sun, Yang; Li, Chenggang; Zhang, Erik; Yu, Jane] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Zhang, Jianming] Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA USA.
RP Blenis, J (reprint author), Weill Cornell Med, Meyer Canc Ctr, 413 East 69th St, New York, NY 10021 USA.
EM job2064@med.cornell.edu
FU NHLBI NIH HHS [R01 HL121266, R01 HL098216]; NIDDK NIH HHS [R01
DK098331]; NIGMS NIH HHS [R01 GM051405]
NR 39
TC 3
Z9 3
U1 6
U2 6
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 AUG 15
PY 2016
VL 76
IS 16
BP 4816
EP 4827
DI 10.1158/0008-5472.CAN-15-2629
PG 12
WC Oncology
SC Oncology
GA DU6BI
UT WOS:000382297700023
PM 27197195
ER
PT J
AU Menard, JA
Christianson, HC
Kucharzewska, P
Bourseau-Guilmain, E
Svensson, KJ
Lindqvist, E
Chandran, VI
Kjellen, L
Welinder, C
Bengzon, J
Johansson, MC
Belting, M
AF Menard, Julien A.
Christianson, Helena C.
Kucharzewska, Paulina
Bourseau-Guilmain, Erika
Svensson, Katrin J.
Lindqvist, Eva
Chandran, Vineesh Indira
Kjellen, Lena
Welinder, Charlotte
Bengzon, Johan
Johansson, Maria C.
Belting, Mattias
TI Metastasis Stimulation by Hypoxia and Acidosis-Induced Extracellular
Lipid Uptake Is Mediated by Proteoglycan-Dependent Endocytosis
SO CANCER RESEARCH
LA English
DT Article
ID HEPARAN-SULFATE PROTEOGLYCANS; TUMOR MICROENVIRONMENT; CANCER
METABOLISM; CELLS; LIPOPROTEINS; MACROPHAGES; RECEPTOR; SITES; LDL;
PHENOTYPE
AB Hypoxia and acidosis are inherent stress factors of the tumor microenvironment and have been linked to increased tumor aggressiveness and treatment resistance. Molecules involved in the adaptive mechanisms that drive stress-induced disease progression constitute interesting candidates of therapeutic intervention. Here, we provide evidence of a novel role of heparan sulfate proteoglycans (HSPG) in the adaptive response of tumor cells to hypoxia and acidosis through increased internalization of lipoproteins, resulting in a lipid-storing phenotype and enhanced tumor-forming capacity. Patient glioblastoma tumors and cells under hypoxic and acidic stress acquired a lipid droplet (LD)-loaded phenotype, and showed an increased recruitment of all major lipoproteins, HDL, LDL, and VLDL. Stress-induced LD accumulation was associated with increased spheroid-forming capacity during reoxygenation in vitro and lung metastatic potential in vivo. On a mechanistic level, we found no apparent effect of hypoxia on HSPGs, whereas lipoprotein receptors (VLDLR and SR-B1) were transiently upregulated by hypoxia. Importantly, however, using pharmacologic and genetic approaches, we show that stress-mediated lipoprotein uptake is highly dependent on intact HSPG expression. The functional relevance of HSPG in the context of tumor cell stress was evidenced by HSPG-dependent lipoprotein cell signaling activation through the ERK/MAPK pathway and by reversal of the LD-loaded phenotype by targeting of HSPGs. We conclude that HSPGs may have an important role in the adaptive response to major stress factors of the tumor microenvironment, with functional consequences on tumor cell signaling and metastatic potential. (C) 2016 AACR.
C1 [Menard, Julien A.; Christianson, Helena C.; Kucharzewska, Paulina; Bourseau-Guilmain, Erika; Lindqvist, Eva; Chandran, Vineesh Indira; Welinder, Charlotte; Johansson, Maria C.; Belting, Mattias] Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2B, SE-22185 Lund, Sweden.
[Svensson, Katrin J.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[Svensson, Katrin J.] Harvard Med Sch, Dept Cell Biol, Boston, MA USA.
[Kjellen, Lena] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, Uppsala, Sweden.
[Welinder, Charlotte] Lund Univ, Ctr Excellence Biol & Med Mass Spectrometry CEBMM, Biomed Ctr D13, Lund, Sweden.
[Bengzon, Johan] Lund Univ, Lund Stem Cell Ctr, Lund, Sweden.
[Bengzon, Johan] Lund Univ, Sect Neurosurg, Dept Clin Sci, Lund, Sweden.
[Belting, Mattias] Skane Univ Hosp, Lund, Sweden.
RP Belting, M (reprint author), Lund Univ, Sect Oncol & Pathol, Dept Clin Sci, Barngatan 2B, SE-22185 Lund, Sweden.
EM Mattias.Belting@med.lu.se
OI Welinder, Charlotte/0000-0001-9626-0576
NR 50
TC 0
Z9 0
U1 7
U2 7
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 AUG 15
PY 2016
VL 76
IS 16
BP 4828
EP 4840
DI 10.1158/0008-5472.CAN-15-2831
PG 13
WC Oncology
SC Oncology
GA DU6BI
UT WOS:000382297700024
PM 27199348
ER
PT J
AU Choi, JW
Yoon, KH
Yun, SH
AF Choi, Jin Woo
Yoon, Kwon-Ha
Yun, Seok Hyun
TI Antimetastatic Effect by Targeting CTC Cluster-Response
SO CANCER RESEARCH
LA English
DT Letter
ID PLASMINOGEN-ACTIVATOR SYSTEM; CIRCULATING TUMOR-CELLS; INVASION
C1 [Choi, Jin Woo] Wonkwang Univ, Sch Dent, Wonkwang Inst Integrat Biomed Sci, Iksan, Jeonbuk, South Korea.
[Choi, Jin Woo] Wonkwang Univ, Sch Dent, Dent Res Inst, Iksan, Jeonbuk, South Korea.
[Yoon, Kwon-Ha] Wonkwang Univ, Sch Med, Dept Radiol, Iksan, Jeonbuk, South Korea.
[Yun, Seok Hyun] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.
RP Yoon, KH (reprint author), Wonkwang Univ, Sch Med, Dept Radiol, Iksan, Jeonbuk, South Korea.; Yun, SH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.; Choi, JW (reprint author), Wonkwang Univ, Iksan 54538, Chonbuk, South Korea.
EM jinwoochoi@wku.ac.kr; khy1646@wonkwang.ac.kr; syun@hms.harvard.edu
FU NCI NIH HHS [R01 CA192878]; NIBIB NIH HHS [P41 EB015903]
NR 4
TC 0
Z9 0
U1 8
U2 8
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 AUG 15
PY 2016
VL 76
IS 16
BP 4910
EP 4910
DI 10.1158/0008-5472.CAN-16-0974
PG 1
WC Oncology
SC Oncology
GA DU6BI
UT WOS:000382297700033
PM 27528582
ER
PT J
AU John, MD
Greene, M
Hessol, NA
Zepf, R
Parrott, AH
Foreman, C
Bourgeois, J
Gandhi, M
Hare, CB
AF John, Malcolm D.
Greene, Meredith
Hessol, Nancy A.
Zepf, Roland
Parrott, Amanda Hutton
Foreman, Cameron
Bourgeois, James
Gandhi, Monica
Hare, C. Bradley
TI Geriatric Assessments and Association With VACS Index Among HIV-Infected
Older Adults in San Francisco
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE functional status; geriatrics; HIV; mental health; and social support
ID VETERANS AGING COHORT; HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL
THERAPY; AIDS; FRAILTY; AGE; DISEASE; RISK; PERFORMANCE; IMPAIRMENT
AB Objectives:To perform geriatric assessments in older HIV-infected adults in San Francisco and examine the association with age and the Veterans Aging Cohort Study (VACS) index scores.Methods:A cross-sectional study was conducted from 2012 to 2014 among HIV-infected patients 50 years at 2 San Francisco-based HIV clinics. We evaluated 4 health domains: (1) physical health and function (activities of daily living), instrumental activities of daily living (IADL), falls, gait speed, (2) social support (physical and perceived support, loneliness), (3) mental health (depression, anxiety, posttraumatic stress disorder) and cognition, and (4) behavioral and general health (antiretroviral adherence and quality of life). Contingency table and rank-sum analyses examined associations between these domains with age and VACS index scores.Results:Three hundred fifty-nine patients completed assessments (median age 57; 85% male; 57% white; 72% >high school education). On functional assessment, 39% reported dependence with 1 IADL, and 40% reported falls in the previous year. Fifty-eight percent experienced loneliness, 60% the lowest levels of perceived social support, 55% depression, and 12% posttraumatic stress disorder. Forty percent had possible mild cognitive impairment. Thirty percent reported poor or fair quality of life. Older age was associated with lower CD4 counts, balance problems, slower gait, lower anxiety, poorer general health, and higher antiretroviral adherence. VACS Index score was associated with dependence in 1 IADL and antiretroviral adherence.Conclusion:In a large sample of older HIV-infected adults, multiple significant aging-related conditions were identified. Integrating geriatric assessment tools into HIV/AIDS clinical care may help target interventions to optimize clinical care and quality of life for older HIV-infected individuals.
C1 [John, Malcolm D.; Hessol, Nancy A.; Zepf, Roland; Parrott, Amanda Hutton; Foreman, Cameron; Gandhi, Monica; Hare, C. Bradley] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA.
[Greene, Meredith] Univ Calif San Francisco, Div Geriatr, Dept Med, San Francisco, CA USA.
[Greene, Meredith] San Francisco VA Med Ctr, Sect Geriatr & Palliat Med, San Francisco, CA USA.
[Hessol, Nancy A.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Bourgeois, James] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Hare, C. Bradley] Kaiser Permanente Med Grp San Francisco Med Ctr, Div Infect Dis, San Francisco, CA USA.
RP John, MD (reprint author), 350 Parnassus Ave,Suite 908 Box 0378, San Francisco, CA 94143 USA.
EM Malcolm.John@ucsf.edu
FU University of California HIV/AIDS Research Program (CHRP) [A116894];
National Institutes of Health [5-T32-AG000212]; NIA at the NIH
[P30AG044281]
FX This research was funded by grant number A116894 from the University of
California HIV/AIDS Research Program (CHRP). M.G. received salary
support from the National Institutes of Health (5-T32-AG000212) during
this project and receives support from the P30AG044281 from the NIA at
the NIH.
NR 37
TC 1
Z9 1
U1 4
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2016
VL 72
IS 5
BP 534
EP 541
DI 10.1097/QAI.0000000000001009
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DT3KC
UT WOS:000381378700011
PM 27028497
ER
PT J
AU Chan, BT
Tsai, AC
AF Chan, Brian T.
Tsai, Alexander C.
TI HIV stigma trends in the general population during antiretroviral
treatment expansion: analysis of 31 countries in sub-Saharan Africa,
2003-2013
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article; Proceedings Paper
CT IDWeek
CY OCT 08, 2015
CL San Diego, CA
DE stigma; Africa; trends
ID CLUSTER-RANDOMIZED TRIAL; AIDS-RELATED STIGMA; RURAL UGANDA;
INTERNALIZED STIGMA; SOUTH-AFRICA; CAPE-TOWN; SCALE-UP; HIV/AIDS;
PEOPLE; ATTITUDES
AB Background:HIV-related stigma is associated with increased risk-taking behavior, reduced uptake of HIV testing, and decreased adherence to antiretroviral therapy (ART). Although ART scale-up may reduce HIV-related stigma, the extent to which levels of stigma in the general population have changed during the era of ART scale-up in sub-Saharan Africa is unknown.Methods:Social distance and anticipated stigma were operationalized using standard HIV-related stigma questions contained in the Demographic and Health Surveys and AIDS Indicator Surveys of 31 African countries between 2003 and 2013. We fitted multivariable linear regression models with cluster-correlated robust standard errors and country fixed effects, specifying social distance or anticipated stigma as the dependent variable and year as the primary explanatory variable of interest.Results:We estimated a statistically significant negative association between year and desires for social distance (b = -0.020; P < 0.001; 95% confidence interval: -0.026 to -0.015) but a statistically significant positive association between year and anticipated stigma (b = 0.023; P < 0.001; 95% confidence interval: 0.018 to 0.027). In analyses stratified by HIV prevalence above or below the sample median, declines in social distancing over time were more pronounced among countries with a higher HIV prevalence.Conclusions:Concomitant with ART scale-up in sub-Saharan Africa, anticipated stigma in the general population increased despite a decrease in social distancing toward people living with HIV. Although ART scale-up may help reduce social distancing toward people living with HIV, particularly in high-prevalence countries, other interventions targeting symbolic or instrumental concerns about HIV may be needed.
C1 [Chan, Brian T.] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
[Chan, Brian T.; Tsai, Alexander C.] Harvard Med Sch, Boston, MA USA.
[Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Tsai, Alexander C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda.
RP Chan, BT (reprint author), Brigham & Womens Hosp, 15 Francis St,PBBA 4, Boston, MA 02115 USA.
EM bchan@partners.org
FU NCATS NIH HHS [KL2 TR001100]; NIMH NIH HHS [K23 MH096620]
NR 63
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 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 15
PY 2016
VL 72
IS 5
BP 558
EP 564
DI 10.1097/QAI.0000000000001011
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DT3KC
UT WOS:000381378700015
PM 27035888
ER
PT J
AU Hensley, K
Poteshkina, A
Johnson, MF
Eslami, P
Gabbita, SP
Hristov, AM
Venkova-Hristova, KM
Harris-White, ME
AF Hensley, Kenneth
Poteshkina, Aleksandra
Johnson, Ming F.
Eslami, Pirooz
Gabbita, S. Prasad
Hristov, Alexandar M.
Venkova-Hristova, Kalina M.
Harris-White, Marni E.
TI Autophagy Modulation by Lanthionine Ketimine Ethyl Ester Improves
Long-Term Outcome after Central Fluid Percussion Injury in the Mouse
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE autophagy; behavior; diffuse axon injury; pathology
ID TRAUMATIC BRAIN-INJURY; DIFFUSE AXONAL INJURY; NEURONAL CELL-DEATH;
CLOSED-HEAD INJURY; CAENORHABDITIS-ELEGANS; ALZHEIMERS-DISEASE;
NEUROFILAMENT COMPACTION; MAMMALIAN TARGET; RAPAMYCIN MTOR; NERVE-FIBERS
AB Diffuse axonal injury is recognized as a progressive and long-term consequence of traumatic brain injury. Axonal injury can have sustained negative consequences on neuronal functions such as anterograde and retrograde transport and cellular processes such as autophagy that depend on cytoarchitecture and axon integrity. These changes can lead to somatic atrophy and an inability to repair and promote plasticity. Obstruction of the autophagic process has been noted after brain injury, and rapamycin, a drug used to stimulate autophagy, has demonstrated positive effects in brain injury models. The optimization of drugs to promote beneficial autophagy without negative side effects could be used to attenuate traumatic brain injury and promote improved outcome. Lanthionine ketimine ethyl ester, a bioavailable derivative of a natural sulfur amino acid metabolite, has demonstrated effects on autophagy both in vitro and in vivo. Thirty minutes after a moderate central fluid percussion injury and throughout the survival period, lanthionine ketimine ethyl ester was administered, and mice were subsequently evaluated for learning and memory impairments and biochemical and histological changes over a 5-week period. Lanthionine ketimine ethyl ester, which we have shown previously to modulate autophagy markers and alleviate pathology and slow cognitive decline in the 3 x TgAD mouse model, spared cognition and pathology after central fluid percussion injury through a mechanism involving autophagy modulation.
C1 [Hensley, Kenneth; Hristov, Alexandar M.; Venkova-Hristova, Kalina M.] Univ Toledo, Dept Pathol, Hlth Sci Campus, Toledo, OH USA.
[Hensley, Kenneth] Univ Toledo, Dept Neurosci, Hlth Sci Campus, Toledo, OH USA.
[Gabbita, S. Prasad] P2D Biosci Inc, Cincinnati, OH USA.
[Poteshkina, Aleksandra; Johnson, Ming F.; Eslami, Pirooz; Harris-White, Marni E.] Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Harris-White, Marni E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 11301 Wilshire Blvd 151, Los Angeles, CA 90073 USA.
RP Harris-White, ME (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 11301 Wilshire Blvd 151, Los Angeles, CA 90073 USA.
EM marni@ucla.edu
NR 90
TC 2
Z9 2
U1 3
U2 3
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 AUG 15
PY 2016
VL 33
IS 16
BP 1501
EP +
DI 10.1089/neu.2015.4196
PG 14
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA DU6ED
UT WOS:000382305900004
PM 26530250
ER
PT J
AU Cohen, P
Spiegelman, BM
AF Cohen, Paul
Spiegelman, Bruce M.
TI Cell biology of fat storage
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID BROWN ADIPOSE-TISSUE; ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA;
BEIGE FAT; ENERGY-EXPENDITURE; INSULIN-RESISTANCE; ADAPTIVE
THERMOGENESIS; GENE-EXPRESSION; OBESITY; ADIPOCYTES
AB The worldwide epidemic of obesity and type 2 diabetes has greatly increased interest in the biology and physiology of adipose tissues. Adipose (fat) cells are specialized for the storage of energy in the form of triglycerides, but research in the last few decades has shown that fat cells also play a critical role in sensing and responding to changes in systemic energy balance. White fat cells secrete important hormone-like molecules such as leptin, adiponectin, and adipsin to influence processes such as food intake, insulin sensitivity, and insulin secretion. Brown fat, on the other hand, dissipates chemical energy in the form of heat, thereby defending against hypothermia, obesity, and diabetes. It is now appreciated that there are two distinct types of thermogenic fat cells, termed brown and beige adipocytes. In addition to these distinct properties of fat cells, adipocytes exist within adipose tissue, where they are in dynamic communication with immune cells and closely influenced by innervation and blood supply. This review is intended to serve as an introduction to adipose cell biology and to familiarize the reader with how these cell types play a role in metabolic disease and, perhaps, as targets for therapeutic development.
C1 [Cohen, Paul] Rockefeller Univ, Lab Mol Metab, New York, NY 10065 USA.
[Spiegelman, Bruce M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Spiegelman, Bruce M.] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
RP Cohen, P (reprint author), Rockefeller Univ, Lab Mol Metab, New York, NY 10065 USA.; Spiegelman, BM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.; Spiegelman, BM (reprint author), Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA.
EM pcohen@rockefeller.edu; bruce_spiegelman@dfci.harvard.edu
FU NIDDK NIH HHS [P30 DK020541]
NR 57
TC 2
Z9 2
U1 11
U2 13
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD AUG 15
PY 2016
VL 27
IS 16
BP 2523
EP 2527
DI 10.1091/mbc.E15-10-0749
PG 5
WC Cell Biology
SC Cell Biology
GA DU6OZ
UT WOS:000382335800002
PM 27528697
ER
PT J
AU Liu, YJ
Lee, IJ
Sun, MZ
Lower, CA
Runge, KW
Ma, JJ
Wu, JQ
AF Liu, Yajun
Lee, I-Ju
Sun, Mingzhai
Lower, Casey A.
Runge, Kurt W.
Ma, Jianjie
Wu, Jian-Qiu
TI Roles of the novel coiled-coil protein Rng10 in septum formation during
fission yeast cytokinesis
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID GTPASE-ACTIVATING PROTEIN; PHOTOACTIVATABLE FLUORESCENT PROTEINS;
ALPHA-GLUCAN BIOSYNTHESIS; SCHIZOSACCHAROMYCES-POMBE; CELL-INTEGRITY;
SACCHAROMYCES-CEREVISIAE; CONTRACTILE-RING; SYNTHASE SUBUNIT; POLARIZED
GROWTH; TURGOR PRESSURE
AB Rho GAPs are important regulators of Rho GTPases, which are involved in various steps of cytokinesis and other processes. However, regulation of Rho-GAP cellular localization and function is not fully understood. Here we report the characterization of a novel coiled-coil protein Rng10 and its relationship with the Rho-GAP Rga7 in fission yeast. Both rng10 Delta and rga7 Delta result in defective septum and cell lysis during cytokinesis. Rng10 and Rga7 colocalize on the plasma membrane at the cell tips during interphase and at the division site during cell division. Rng10 physically interacts with Rga7 in affinity purification and coimmunoprecipitation. Of interest, Rga7 localization is nearly abolished without Rng10. Moreover, Rng10 and Rga7 work together to regulate the accumulation and dynamics of glucan synthases for successful septum formation in cytokinesis. Our results show that cellular localization and function of the Rho-GAP Rga7 are regulated by a novel protein, Rng10, during cytokinesis in fission yeast.
C1 [Liu, Yajun; Lee, I-Ju; Lower, Casey A.; Wu, Jian-Qiu] Ohio State Univ, Davis Heart & Lung Res Inst, Dept Mol Genet, Columbus, OH 43210 USA.
[Sun, Mingzhai; Ma, Jianjie] Ohio State Univ, Davis Heart & Lung Res Inst, Dept Surg, Columbus, OH 43210 USA.
[Wu, Jian-Qiu] Ohio State Univ, Dept Biol Chem & Pharmacol, Columbus, OH 43210 USA.
[Runge, Kurt W.] Cleveland Clin Lerner Coll Med, Dept Mol Genet, Cleveland, OH 44195 USA.
[Lee, I-Ju] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA.
RP Wu, JQ (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, Dept Mol Genet, Columbus, OH 43210 USA.; Wu, JQ (reprint author), Ohio State Univ, Dept Biol Chem & Pharmacol, Columbus, OH 43210 USA.
EM wu.620@osu.edu
OI Runge, Kurt/0000-0001-8492-0530
FU National Institute of General Medical Sciences of the National
Institutes of Health Grant [GM118746]; American Cancer Society Grant
[RSG-13-005-01-CCG]
FX We thank Mohan Balasubramanian, Takayoshi Kuno, Dannel McCollum, Stephen
Osmani, Pilar Perez, Thomas Pollard, Juan Carlos Ribas, Shelley Sazer,
and Ning Wang for strains and plasmids; the Anita Hopper, James Hopper,
and Stephen Osmani laboratories, the Mass Spectrometry and Proteomics
Facility at The Ohio State University, and Mary Morphew and Thomas
Giddings, Jr., at the University of Colorado at Boulder for technical
support; and members of the Wu laboratory for helpful discussions and
suggestions. This work was supported by National Institute of General
Medical Sciences of the National Institutes of Health Grant GM118746 and
American Cancer Society Grant RSG-13-005-01-CCG to J.-Q.W.
NR 86
TC 1
Z9 1
U1 0
U2 0
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
EI 1939-4586
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD AUG 15
PY 2016
VL 27
IS 16
BP 2528
EP 2541
DI 10.1091/mbc.E16-03-0156
PG 14
WC Cell Biology
SC Cell Biology
GA DU6OZ
UT WOS:000382335800003
PM 27385337
ER
PT J
AU Otto, MW
Kredlow, MA
Smits, JAJ
Hofmann, SG
Tolin, DF
de Kleine, RA
van Minnen, A
Evins, AE
Pollack, MH
AF Otto, Michael W.
Kredlow, M. Alexandra
Smits, Jasper A. J.
Hofmann, Stefan G.
Tolin, David F.
de Kleine, Rianne A.
van Minnen, Agnes
Evins, A. Eden
Pollack, Mark H.
TI Enhancement of Psychosocial Treatment With D-Cycloserine: Models,
Moderators, and Future Directions
SO BIOLOGICAL PSYCHIATRY
LA English
DT Review
DE Addiction; Anxiety; DCS; d-cycloserine; Depression; Extinction
ID OBSESSIVE-COMPULSIVE DISORDER; COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED
CONTROLLED-TRIAL; SOCIAL ANXIETY DISORDER; PLACEBO-CONTROLLED TRIAL;
POSTTRAUMATIC-STRESS-DISORDER; FEAR-POTENTIATED STARTLE; D-ASPARTATE
RECEPTOR; EXPOSURE THERAPY; RESPONSE PREVENTION
AB Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).
C1 [Otto, Michael W.; Kredlow, M. Alexandra; Hofmann, Stefan G.] Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,Floor 6, Boston, MA 02215 USA.
[Smits, Jasper A. J.] Univ Texas Austin, Mental Hlth Res Inst, Austin, TX 78712 USA.
[Smits, Jasper A. J.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
[Tolin, David F.] Inst Living, Anxiety Disorders Ctr, Hartford, CT USA.
Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[de Kleine, Rianne A.; van Minnen, Agnes] Radboud Univ Nijmegen, Overwaal Ctr Anxiety Disorders, Pro Persona, Inst Behav Sci, Nijmegen, Netherlands.
[Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
Harvard Med Sch, Boston, MA USA.
[Pollack, Mark H.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA.
RP Otto, MW (reprint author), Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,Floor 6, Boston, MA 02215 USA.
EM mwotto@bu.edu
RI Hofmann, Stefan/B-8769-2014
OI Hofmann, Stefan/0000-0002-3548-9681
FU National Institutes of Health (NIH)/National Institute of Mental Health
(NIMH) [R21MH102646]; NIH/NIMH [1F31MH103969, R34MH099318, R34MH086668,
5R34MH099309-02]; NIDA [K24 DA030443]; MicroTransponder Inc.; Concert
Pharmaceuticals; ProPhase; Palo Alto Health Sciences, Inc.; Forum
Pharmaceuticals; GlaxoSmithKline; Pfizer
FX Dr. Otto's effort on this manuscript was supported by National
Institutes of Health (NIH)/National Institute of Mental Health (NIMH)
Grant No. R21MH102646. Ms. Kredlow's effort on this manuscript was
supported by NIH/NIMH Grant No. 1F31MH103969. Dr. Smits' effort on this
grant was supported by NIH/NIMH Grant No. R34MH099318. Dr. Hofmann's
effort on this manuscript was supported by NIH/NIMH Grant No.
R34MH086668. Dr. Evins' work on this manuscript was supported by NIDA
Grant No. K24 DA030443. Dr. Pollack's effort on this manuscript was
supported by NIH/NIMH Grant No. 5R34MH099309-02. The National Institutes
of Health had no role in the writing of the report or in the decision to
submit the manuscript for publication. The National Institutes of Health
had no role other than financial support.; Dr. Otto reports serving, in
the last 3 years, as a paid consultant for MicroTransponder Inc.,
Concert Pharmaceuticals, and ProPhase; providing expert consensus
opinion for Otsuka Pharmaceuticals; receiving royalty support for use of
the SIGH-A from ProPhase; and receiving book royalties from Oxford
University Press, Routledge, and Springer. Dr. Hofmann reports serving
on the Advisory Board of Palo Alto Health Sciences and Otsuka America
Pharmaceutical, Inc. and receiving financial compensation for his
participation as an advisor and receiving royalties from various book
publishers and financial compensation for his editorial work from
Springer Publications and the American Psychological Association. Dr.
Tolin reports receiving research funding from Palo Alto Health Sciences,
Inc. Dr. Evins has received grant support to her institution from Forum
Pharmaceuticals (formerly Envivo pharmaceuticals), GlaxoSmithKline, and
Pfizer. She has provided consultation on behalf of her institution to
Reckitt Benckiser and Pfizer. Dr. Pollack reports serving on the
advisory board or consulting for Clintara, Concert Pharmaceuticals,
Corcept Therapeutics, Edgemont Pharmaceuticals, Eli Lilly, Ironwood
Pharmaceuticals, Medavante, Merck, Palo Alto Health Sciences, and
Project Plus; receiving equity from Doyen Medical, Medavante, Mensante
Corporation, Mindsite, and Targia Pharmaceuticals; and receiving
royalties/patents for SIGH-A and SAFER interviews. All other authors
report no biomedical financial interests or potential conflicts of
interest.
NR 89
TC 2
Z9 2
U1 16
U2 17
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 AUG 15
PY 2016
VL 80
IS 4
BP 274
EP 283
DI 10.1016/j.biopsych.2015.09.007
PG 10
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA DS5QT
UT WOS:000380838100009
PM 26520240
ER
PT J
AU Cooper, TM
Cassar, J
Eckroth, E
Malvar, J
Sposto, R
Gaynon, P
Chang, BH
Gore, L
August, K
Pollard, JA
DuBois, SG
Silverman, LB
Oesterheld, J
Gammon, G
Magoon, D
Annesley, C
Brown, PA
AF Cooper, Todd M.
Cassar, Jeannette
Eckroth, Elena
Malvar, Jemily
Sposto, Richard
Gaynon, Paul
Chang, Bill H.
Gore, Lia
August, Keith
Pollard, Jessica A.
DuBois, Steven G.
Silverman, Lewis B.
Oesterheld, Javier
Gammon, Guy
Magoon, Daniel
Annesley, Colleen
Brown, Patrick A.
TI A Phase I Study of Quizartinib Combined with Chemotherapy in Relapsed
Childhood Leukemia: A Therapeutic Advances in Childhood Leukemia &
Lymphoma (TACL) Study
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; INTERNAL TANDEM
DUPLICATION; TYROSINE KINASE INHIBITOR; PROGNOSTIC-SIGNIFICANCE; FLT3
INHIBITORS; EXPRESSION; GENE; MLL; MUTATIONS
AB Purpose: To determine a safe and biologically active dose of quizartinib (AC220), a potent and selective class III receptor tyrosine kinase (RTK) FLT3 inhibitor, in combination with salvage chemotherapy in children with relapsed acute leukemia.
Experimental Design: Quizartinib was administered orally to children with relapsed AML or MLL-rearranged ALL following 5 days of high-dose cytarabine and etoposide (AE). A 3+3 dose escalation design was used to identify a safe and biologically active dose. Plasma inhibitory assay (PIA) testing was performed weekly to determine biologic activity.
Results: Toxicities were consistent with intensive relapsed leukemia regimens. One of 6 patients experienced a dose-limiting toxicity (DLT) at 40 mg/m(2)/day (elevated lipase) and 1 of 9 had a DLT (hyperbilirubinemia) at the highest tested dose of 60 mg/m(2)/day. Of 17 response evaluable patients, 2 had complete response (CR), 1 complete response without platelet recovery (CRp), 1 complete response with incomplete neutrophil and platelet recovery (CRi), 10 stable disease (SD), and 3 progressive disease (PD). Of 7 FLT3-ITD patients, 1 achieved CR, 1 CRp, 1 Cri, and 4 SD. FLT3-ITD patients, but not FLT3 wild-type (WT) patients, had significantly lower blast counts post-quizartinib. FLT3 phosphorylation was completely inhibited in all patients.
Conclusions: Quizartinib plus intensive chemotherapy is well tolerated at 60 mg/m(2)/day with near complete inhibition of FLT3 phosphorylation in all patients. The favorable toxicity profile, pharmacodynamic activity, and encouraging response rates warrant further testing of quizartinib in children with FLT3-ITD AML. (C) 2016 AACR.
C1 [Cooper, Todd M.] Seattle Childrens Hosp, Canc & Blood Disorders Ctr, 4800 Sand Point Way NE,M-S MB8-501, Seattle, WA 98105 USA.
[Cassar, Jeannette; Eckroth, Elena; Malvar, Jemily; Sposto, Richard; Gaynon, Paul] Childrens Hosp Los Angeles, Childrens Ctr Canc & Blood Dis, Los Angeles, CA 90027 USA.
[Sposto, Richard; Gaynon, Paul] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Chang, Bill H.] Oregon Hlth & Sci Univ, Doernbecher Childrens Hosp, Portland, OR 97201 USA.
[Gore, Lia] Childrens Hosp Colorado, Aurora, CO USA.
[August, Keith] Childrens Mercy Hosp & Clin, Kansas City, MO USA.
[Pollard, Jessica A.] Maine Childrens Canc Program, Scarborough, ME USA.
[DuBois, Steven G.; Silverman, Lewis B.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
[Oesterheld, Javier] Levine Childrens Hosp, Charlotte, NC USA.
[Gammon, Guy] Ambit Biosci Corp, Clin Res & Dev, San Diego, CA USA.
[Magoon, Daniel; Annesley, Colleen; Brown, Patrick A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Cooper, TM (reprint author), Seattle Childrens Hosp, Canc & Blood Disorders Ctr, 4800 Sand Point Way NE,M-S MB8-501, Seattle, WA 98105 USA.
EM todd.cooper@seattlechildrens.org
FU Phase One Foundation; TACL Consortium; Leukemia and Lymphoma Society
(LLS Scholar in Clinical Research Grant) [2365-12]; American Cancer
Society [120237]
FX This work was financially supported by grants from the Phase One
Foundation to Children's Hospital of Los Angeles, TACL Consortium.
Quizartinib was provided by Ambit Biosciences Corporation. The
correlative laboratory assays were funded by grants (to P. Brown) from
the Leukemia and Lymphoma Society (LLS Scholar in Clinical Research
Grant #2365-12) and the American Cancer Society (ACS Research Scholar
Grant #120237).
NR 26
TC 4
Z9 4
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 AUG 15
PY 2016
VL 22
IS 16
BP 4014
EP 4022
DI 10.1158/1078-0432.CCR-15-1998
PG 9
WC Oncology
SC Oncology
GA DU5QH
UT WOS:000382265900006
PM 26920889
ER
PT J
AU Wu, SP
Pfeiffer, RM
Ahn, IE
Mailankody, S
Sonneveld, P
van Duin, M
Munshi, NC
Walker, BA
Morgan, G
Landgren, O
AF Wu, S. Peter
Pfeiffer, Ruth M.
Ahn, Inhye E.
Mailankody, Sham
Sonneveld, Pieter
van Duin, Mark
Munshi, Nikhil C.
Walker, Brian A.
Morgan, Gareth
Landgren, Ola
TI Impact of Genes Highly Correlated with MMSET Myeloma on the Survival of
Non-MMSET Myeloma Patients
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RISK MULTIPLE-MYELOMA; BREAST-CANCER RISK; T(4/14) MYELOMA; CELL-CYCLE;
C-MYC; PLASMA-CELLS; EXPRESSION; PREDICTION; TRANSLOCATION; TRANSCRIPTS
AB Purpose: The poor prognosis of multiple myeloma with t(4;14) is driven by the fusion of genes encoding multiple myeloma SET domain (MMSET) and immunoglobulin heavy chain. Specific genes affected by MMSET and their clinical implications in non-MMSET myeloma remain undetermined.
Experimental Design: We obtained gene expression profiles of 1,032 newly diagnosed myeloma patients enrolled in Total Therapy 2, Total Therapy 3, Myeloma IX, and HOVON65-GMMGHD4 trials and 156 patients from Multiple Myeloma Resource Collection. Probes that correlated most with MMSET myeloma were selected on the basis of a multivariable linear regression and Bonferroni correction and refined on the basis of the strength of association with survival in non-MMSET patients.
Results: Ten MMSET-like probes were associated with poor survival in non-MMSET myeloma. Non-MMSET myeloma patients in the highest quartile of the 10-gene signature (MMSET-like myeloma) had 5-year overall survival similar to that of MMSET myeloma [highest quartile vs. lowest quartile HR = 2.0; 95% confidence interval (CI), 1.5-2.8 in MMSET-like myeloma; HR = 2.3; 95% CI, 1.6-3.3 in MMSET myeloma]. Analyses of MMSET-like gene signature suggested the involvement of p53 and MYC pathways.
Conclusions: MMSET-like gene signature captures a subset of high-risk myeloma patients underrepresented by conventional risk stratification platforms and defines a distinct biologic subtype. (C) 2016 AACR.
C1 [Wu, S. Peter; Ahn, Inhye E.] NCI, Multiple Myeloma Sect, NIH, Bethesda, MD 20892 USA.
[Pfeiffer, Ruth M.] NCI, Dept Canc Epidemiol & Genet, Biostat Branch, NIH, Rockville, MD USA.
[Mailankody, Sham; Landgren, Ola] Mem Sloan Kettering Canc Ctr, Myeloma Serv, New York, NY 10021 USA.
[Sonneveld, Pieter; van Duin, Mark] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands.
[Munshi, Nikhil C.] Harvard Med Sch, Lebow Inst Myeloma Therapeut, Boston, MA USA.
[Munshi, Nikhil C.] Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA.
[Walker, Brian A.] Inst Canc Res, Sect Haematooncol, London, England.
[Morgan, Gareth] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA.
RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
EM landgrec@mskcc.org
OI Walker, Brian/0000-0002-8615-6254
FU NIH; NIH Medical Research Scholars Program
FX This work was supported by the intramural research program of the NIH.
Research support for S.P. Wu was made possible through the NIH Medical
Research Scholars Program, a public-private partnership supported
jointly by the NIH and generous contributions to the Foundation for the
NIH from Pfizer Inc., The Leona M. and Harry B. Helmsley Charitable
Trust, and the Howard Hughes Medical Institute, as well as other private
donors. For a complete list, please visit the Foundation website at
http://www.fnih.org/work/programs-development/medical-research-scholars-
program.
NR 35
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U1 0
U2 0
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 AUG 15
PY 2016
VL 22
IS 16
BP 4039
EP 4044
DI 10.1158/1078-0432.CCR-15-2366
PG 6
WC Oncology
SC Oncology
GA DU5QH
UT WOS:000382265900009
PM 26847058
ER
PT J
AU Tang, M
Zhao, R
de Velde, HV
Tross, JG
Mitsiades, C
Viselli, S
Neuwirth, R
Esseltine, DL
Anderson, K
Ghobrial, IM
San Miguel, JF
Richardson, PG
Tomasson, MH
Michor, F
AF Tang, Min
Zhao, Rui
de Velde, Helgi van
Tross, Jennifer G.
Mitsiades, Constantine
Viselli, Suzanne
Neuwirth, Rachel
Esseltine, Dixie-Lee
Anderson, Kenneth
Ghobrial, Irene M.
San Miguel, Jesus F.
Richardson, Paul G.
Tomasson, Michael H.
Michor, Franziska
TI Myeloma Cell Dynamics in Response to Treatment Supports a Model of
Hierarchical Differentiation and Clonal Evolution
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RELAPSED MULTIPLE-MYELOMA; BORTEZOMIB-MELPHALAN-PREDNISONE;
DRUG-RESISTANCE; STAGING SYSTEM; TUMOR-GROWTH; FOLLOW-UP; DEXAMETHASONE;
CHEMOTHERAPY; MALIGNANCIES; PROGENITORS
AB Purpose: Since the pioneering work of Salmon and Durie, quantitative measures of tumor burden in multiple myeloma have been used to make clinical predictions and model tumor growth. However, such quantitative analyses have not yet been performed on large datasets from trials using modern chemotherapy regimens.
Experimental Design: We analyzed a large set of tumor response data from three randomized controlled trials of bortezomib-based chemotherapy regimens (total sample size n = 1,469 patients) to establish and validate a novel mathematical model of multiple myeloma cell dynamics.
Results: Treatment dynamics in newly diagnosed patients were most consistent with a model postulating two tumor cell subpopulations, "progenitor cells" and "differentiated cells." Differential treatment responses were observed with significant tumoricidal effects on differentiated cells and less clear effects on progenitor cells. We validated this model using a second trial of newly diagnosed patients and a third trial of refractory patients. When applying our model to data of relapsed patients, we found that a hybrid model incorporating both a differentiation hierarchy and clonal evolution best explains the response patterns.
Conclusions: The clinical data, together with mathematical modeling, suggest that bortezomib-based therapy exerts a selection pressure on myeloma cells that can shape the disease phenotype, thereby generating further inter-patient variability. This model may be a useful tool for improving our understanding of disease biology and the response to chemotherapy regimens. 14. (C) 2016 AACR.
C1 [Tang, Min; Zhao, Rui; Tross, Jennifer G.; Michor, Franziska] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Tang, Min; Zhao, Rui; Michor, Franziska] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[de Velde, Helgi van; Neuwirth, Rachel; Esseltine, Dixie-Lee] Takeda Pharmaceut Inc, Cambridge, MA USA.
[Tross, Jennifer G.] Harvard Med Sch, Harvard Mit Div Hlth Sci & Technol, Boston, MA USA.
[Mitsiades, Constantine; Anderson, Kenneth; Ghobrial, Irene M.; Richardson, Paul G.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
[Viselli, Suzanne] Janssen Res & Dev LLC, Oncol R&D, Raritan, NJ USA.
[San Miguel, Jesus F.] USAL, CSIC, IBMCC, Hosp Univ Salamanca,CIC, Salamanca, Spain.
[Tomasson, Michael H.] Washington Univ, Sch Med, Div Oncol, St Louis, MO USA.
RP Michor, F (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM michor@jimmy.harvard.edu
FU Dana-Farber Cancer Institute Physical Sciences-Oncology Center
[U54CA193461]
FX The authors thank the Michor lab, Mithat Gonen, Katherine Weilbaecher,
Rameen Beroukhim, Victor DeGruttola, and Paul Catalano for helpful
discussions, especially thank all the participating patients, their
families, the research teams and the clinical investigators in the
VISTA, MMY-2001, and APEX studies, and acknowledge the support from the
Dana-Farber Cancer Institute Physical Sciences-Oncology Center
(U54CA193461).
NR 33
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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 AUG 15
PY 2016
VL 22
IS 16
BP 4206
EP 4214
DI 10.1158/1078-0432.CCR-15-2793
PG 9
WC Oncology
SC Oncology
GA DU5QH
UT WOS:000382265900024
PM 27006493
ER
PT J
AU Huang, YS
Nahar, S
Nakagawa, A
Fernandez-Barrena, MG
Mertz, JA
Bryant, BM
Adams, CE
Mino-Kenudson, M
Von Alt, KN
Chang, K
Conery, AR
Hatton, C
Sims, RJ
Fernandez-Zapico, ME
Wang, XP
Lillemoe, KD
Fernandez-del Castillo, C
Warshaw, AL
Thayer, SP
Liss, AS
AF Huang, Yinshi
Nahar, Sabikun
Nakagawa, Akifumi
Fernandez-Barrena, Maite G.
Mertz, Jennifer A.
Bryant, Barbara M.
Adams, Curtis E.
Mino-Kenudson, Mari
Von Alt, Kate N.
Chang, Kevin
Conery, Andrew R.
Hatton, Charlie
Sims, Robert J., III
Fernandez-Zapico, Martin E.
Wang, Xingpeng
Lillemoe, Keith D.
Fernandez-del Castillo, Carlos
Warshaw, Andrew L.
Thayer, Sarah P.
Liss, Andrew S.
TI Regulation of GLI Underlies a Role for BET Bromodomains in Pancreatic
Cancer Growth and the Tumor Microenvironment
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID PROSTATE-CANCER; ONCOGENIC KRAS; MOUSE MODEL; INHIBITION; HEDGEHOG;
PROGRESSION; PATHWAY; TARGET; BRD4; MYC
AB Purpose: The initiation, progression, and maintenance of pancreatic ductal adenocarcinoma (PDAC) results from the interplay of genetic and epigenetic events. While the genetic alterations of PDAC have been well characterized, epigenetic pathways regulating PDAC remain, for the most part, elusive. The goal of this study was to identify novel epigenetic regulators contributing to the biology of PDAC.
Experimental Design: In vivo pooled shRNA screens targeting 118 epigenetic proteins were performed in two orthotopic PDAC xenograft models. Candidate genes were characterized in 19 human PDAC cell lines, heterotopic xenograft tumor models, and a genetically engineered mouse (GEM) model of PDAC. Gene expression, IHC, and immunoprecipitation experiments were performed to analyze the pathways by which candidate genes contribute to PDAC.
Results: In vivo shRNA screens identified BRD2 and BRD3, members of the BET family of chromatin adaptors, as key regulators of PDAC tumor growth. Pharmacologic inhibition of BET bromodomains enhanced survival in a PDAC GEM model and inhibited growth of hum an-derived xenograft tumors. BET proteins contribute to PDAC cell growth through direct interaction with members of the GLI family of transcription factors and modulating their activity. Within cancer cells, BET bromodomain inhibition results in down regulation of SHH, a key mediator of the tumor microenvironrnent and canonical activator of GLI. Consistent with this, inhibition of BET bromodomains decreases cancer-associated fibroblast content of tumors in both GEM and xenograft tumor models.
Conclusions: Therapeutic inhibition of BET proteins offers a novel mechanism to target both the neoplastic and stromal components of PDAC. (C) 2016 AACR.
C1 [Huang, Yinshi; Wang, Xingpeng] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gastroenterol, Shanghai, Peoples R China.
[Huang, Yinshi; Nahar, Sabikun; Nakagawa, Akifumi; Adams, Curtis E.; Von Alt, Kate N.; Chang, Kevin; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.; Liss, Andrew S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Huang, Yinshi; Nahar, Sabikun; Nakagawa, Akifumi; Adams, Curtis E.; Von Alt, Kate N.; Chang, Kevin; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.; Liss, Andrew S.] Massachusetts Gen Hosp, Andrew L Warshaw MD Inst Pancreat Canc Res, Boston, MA 02114 USA.
[Huang, Yinshi; Nahar, Sabikun; Nakagawa, Akifumi; Adams, Curtis E.; Mino-Kenudson, Mari; Von Alt, Kate N.; Chang, Kevin; Lillemoe, Keith D.; Fernandez-del Castillo, Carlos; Warshaw, Andrew L.; Thayer, Sarah P.; Liss, Andrew S.] Harvard Med Sch, Boston, MA USA.
[Fernandez-Barrena, Maite G.; Fernandez-Zapico, Martin E.] Mayo Clin, Schulze Ctr Novel Therapeut, Div Oncol Res, Rochester, MN USA.
[Mertz, Jennifer A.; Bryant, Barbara M.; Conery, Andrew R.; Hatton, Charlie; Sims, Robert J., III] Constellat Pharmaceut, Cambridge, MA USA.
[Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Wang, Xingpeng] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 1, Dept Gastroenterol, Shanghai, Peoples R China.
RP Liss, AS (reprint author), Massachusetts Gen Hosp, 55 Blossom St,Thier 623, Boston, MA 02114 USA.; Thayer, SP (reprint author), Univ Nebraska Med Ctr, 986345 Nebraska Med Ctr, Omaha, NE 68198 USA.
EM sarah.thayer@unmc.edu; aliss@mgh.harvard.edu
FU Institute for Pancreatic Cancer Research; NIH [P01CA117969]
FX This work was supported by a grant from The Andrew L. Warshaw, MD
Institute for Pancreatic Cancer Research (awarded to A.S. Liss) and a
grant from the NIH(P01CA117969; awarded to S.P. Thayer).
NR 43
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U1 4
U2 5
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 AUG 15
PY 2016
VL 22
IS 16
BP 4259
EP 4270
DI 10.1158/1078-0432.CCR-15-2068
PG 12
WC Oncology
SC Oncology
GA DU5QH
UT WOS:000382265900029
PM 27169995
ER
PT J
AU Uribe-Patarroyo, N
Bouma, BE
AF Uribe-Patarroyo, Nestor
Bouma, Brett E.
TI Velocity gradients in spatially resolved laser Doppler flowmetry and
dynamic light scattering with confocal and coherence gating
SO PHYSICAL REVIEW E
LA English
DT Article
ID SPECKLE DECORRELATION; FLOW-VELOCITY; TOMOGRAPHY; RESOLUTION; SPECTRUM;
SPEED
AB Dynamic light scattering (DLS) is widely used to characterize diffusive motion to obtain precise information on colloidal suspensions by calculating the autocorrelation function of the signal from a heterodyne optical system. DLS can also be used to determine the flow velocity field in systems that exhibit mass transport by incorporating the effects of the deterministic motion of scatterers on the autocorrelation function, a technique commonly known as laser Doppler flowmetry. DLS measurements can be localized with confocal and coherence gating techniques such as confocal microscopy and optical coherence tomography, thereby enabling the determination of the spatially resolved velocity field in three dimensions. It has been thought that spatially resolved DLS can determine the axial velocity as well as the lateral speed in a single measurement. We demonstrate, however, that gradients in the axial velocity of scatterers exert a fundamental influence on the autocorrelation function even in well-behaved, nonturbulent flow. By obtaining the explicit functional relation between axial-velocity gradients and the autocorrelation function, we show that the velocity field and its derivatives are intimately related and their contributions cannot be separated. Therefore, a single DLS measurement cannot univocally determine the velocity field. Our extended theoretical model was found to be in good agreement with experimental measurements.
C1 [Uribe-Patarroyo, Nestor; Bouma, Brett E.] Harvard Med Sch, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.
[Uribe-Patarroyo, Nestor; Bouma, Brett E.] Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA.
RP Uribe-Patarroyo, N (reprint author), Harvard Med Sch, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA.; Uribe-Patarroyo, N (reprint author), Massachusetts Gen Hosp, 40 Blossom St, Boston, MA 02114 USA.
EM uribepatarroyo.nestor@mgh.harvard.edu
FU National Institute of Biomedical Imaging and Bioengineering of the
National Institutes of Health [P41 EB015903]; Terumo Corporation
FX Research in this publication was supported in part by the National
Institute of Biomedical Imaging and Bioengineering of the National
Institutes of Health, Grant No. P41 EB015903, and by Terumo Corporation.
NR 31
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U1 9
U2 9
PU AMER PHYSICAL SOC
PI COLLEGE PK
PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA
SN 2470-0045
EI 2470-0053
J9 PHYS REV E
JI Phys. Rev. E
PD AUG 15
PY 2016
VL 94
IS 2
AR 022604
DI 10.1103/PhysRevE.94.022604
PG 11
WC Physics, Fluids & Plasmas; Physics, Mathematical
SC Physics
GA DT5AF
UT WOS:000381492200011
PM 27627357
ER
PT J
AU Mowafy, S
Galanis, A
Doctor, ZM
Paranal, RM
Lasheen, DS
Farag, NA
Janne, PA
Abouzid, KAM
AF Mowafy, Samar
Galanis, A.
Doctor, Zainab M.
Paranal, Raymond M.
Lasheen, Deena S.
Farag, Nahla A.
Janne, Pasi A.
Abouzid, Khaled A. M.
TI Toward discovery of mutant EGFR inhibitors; Design, synthesis and in
vitro biological evaluation of potent 4-arylamino-6-ureido and
thioureido-quinazoline derivatives
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE EGFR inhibitors; Quinazolines; Urea derivatives; Synthesis; EGFR-Her2
dual inhibitors; EGFR L858R/T790 mutant; EGFR Del19/T790M mutant
ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; LUNG-CANCER;
CELL-LINES; RESISTANCE; MUTATION; 4-ANILINOQUINAZOLINES; AMPLIFICATION;
MECHANISM
AB A new series of w4-anilinoquinazolines with C-6 ureido and thioureido side chains and various sub-stituents at the C-4 anilino moiety was designed, synthesized and evaluated as wild type (WT) and mutant EGFR inhibitors. Most of the compounds inhibited EGFR kinase wild type (EGFR WT) with IC50 values in the low nanomolar range (<0.495-9.05 nM) and displayed more potent cytotoxic effect in BaF/3 expressing EGFR WT than reference compound gefitinib. The anti-proliferative effect of all synthesized compounds against gefitinib insensitive double mutant cell lines Ba/F3 expressing Del19/T790M and Ba/F3 expressing L858R/T790M were assayed. Compounds 4d, 6f, 7e showed significant inhibition (IC50 = 1.76-2.38 mu M) in these mutant lines and significant Her2 enzyme inhibition (IC50 = 19.2-40.6 nM) compared to lapatinib (60.1 nM). The Binding mode of compounds 6d, 6f, 7a, 7b and 8b were demonstrated. Furthermore, growth inhibition against gefitinib insensitive cell lines PC9-GR4 (Del19/T790M) were tested, compounds 6f and 7e showed about eight and three folds respectively greater potency than gefitinib. Our structure-activity relationships (SAR) studies suggested that presence of ethyl piperidino urea/thiourea at 6-position and bulky group of (3-chloro-4-(3-fluorobenzyloxy) phenyl) amino at 4-position of quinazoline may serve as promising scaffold for developing inhibitors against wild type and mutant EGFR. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Mowafy, Samar; Doctor, Zainab M.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Mowafy, Samar; Doctor, Zainab M.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA.
[Mowafy, Samar; Farag, Nahla A.] Misr Int Univ, Fac Pharm, Dept Pharmaceut Chem, Km 28 Cairo Ismailia Rd, Cairo, Egypt.
[Galanis, A.; Paranal, Raymond M.; Janne, Pasi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lasheen, Deena S.; Abouzid, Khaled A. M.] Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt.
RP Mowafy, S (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Mowafy, S (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, 250 Longwood Ave,SGM 628, Boston, MA 02115 USA.; Mowafy, S (reprint author), Misr Int Univ, Fac Pharm, Dept Pharmaceut Chem, Km 28 Cairo Ismailia Rd, Cairo, Egypt.; Abouzid, KAM (reprint author), Ain Shams Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11566, Egypt.
EM samarmowafy@gmail.com; khaled.abouzid@pharma.asu.edu.eg
FU Fulbright commission
FX I am grateful to the Fulbright commission for the scholarship
opportunity, Professor Nathanael Gray for his continuous support and Dr
Jaebong Jang in Gray lab for providing guidance and help during this
research. I would like to thank Dr Ciric in Pasi lab for sharing
thoughts on running double mutant cell line experiments.
NR 22
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Z9 0
U1 8
U2 10
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD AUG 15
PY 2016
VL 24
IS 16
BP 3501
EP 3512
DI 10.1016/j.bmc.2016.05.063
PG 12
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA DS2AF
UT WOS:000380515700019
PM 27288180
ER
PT J
AU Rynearson, KD
Buckle, RN
Barnes, KD
Herr, RJ
Mayhew, NJ
Paquette, WD
Sakwa, SA
Nguyen, PD
Johnson, G
Tanzi, RE
Wagner, SL
AF Rynearson, Kevin D.
Buckle, Ronald N.
Barnes, Keith D.
Herr, R. Jason
Mayhew, Nicholas J.
Paquette, William D.
Sakwa, Samuel A.
Nguyen, Phuong D.
Johnson, Graham
Tanzi, Rudolph E.
Wagner, Steven L.
TI Design and synthesis of aminothiazole modulators of the gamma-secretase
enzyme
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Alzheimer's disease; gamma-Secretase modulators; Aminothiazoles
ID ALZHEIMERS-DISEASE; AMYLOID HYPOTHESIS; THERAPEUTIC TARGET; SENILE
PLAQUES; MOUSE MODEL; DISCOVERY; PROGRESS; PROTEIN; PERSPECTIVE;
INHIBITORS
AB The design and construction of a series of novel aminothiazole-derived gamma-secretase modulators is described. The incorporation of heterocyclic replacements of the terminal phenyl D-ring of lead compound 1 was conducted in order to align potency with favorable drug-like properties. gamma-Secretase modulator 28 displayed good activity for in vitro inhibition of A beta 42, as well as substantial improvement in ADME and physicochemical properties, including aqueous solubility. Pharmacokinetic evaluation of compound 28 in mice revealed good brain penetration, as well as good clearance, half-life, and volume of distribution which collectively support the continued development of this class of compounds. (C) 2016 Published by Elsevier Ltd.
C1 [Rynearson, Kevin D.; Nguyen, Phuong D.; Wagner, Steven L.] Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr MC 0624, La Jolla, CA 92093 USA.
[Buckle, Ronald N.; Barnes, Keith D.; Herr, R. Jason; Mayhew, Nicholas J.; Paquette, William D.; Sakwa, Samuel A.] AMRI, Dept Med Chem, East Campus,3 Univ Pl, Rensselaer, NY 12144 USA.
[Johnson, Graham] NuPharmAdvise, 3 Lakeside Dr, Sanbornton, NH 03269 USA.
[Tanzi, Rudolph E.] Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Charlestown, MA 02129 USA.
RP Wagner, SL (reprint author), Univ Calif San Diego, Dept Neurosci, 9500 Gilman Dr MC 0624, La Jolla, CA 92093 USA.
EM slwagner@ucsd.edu
NR 44
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U1 5
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD AUG 15
PY 2016
VL 26
IS 16
BP 3928
EP 3937
DI 10.1016/j.bmcl.2016.07.011
PG 10
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA DS2FB
UT WOS:000380574400018
PM 27426299
ER
PT J
AU Wang, X
Beste, LA
Maier, MM
Zhou, XH
AF Wang, Xuan
Beste, Lauren A.
Maier, Marissa M.
Zhou, Xiao-Hua
TI Double robust estimator of average causal treatment effect for censored
medical cost data
SO STATISTICS IN MEDICINE
LA English
DT Article
DE average causal treatment effect; censored data; double robust estimator;
inverse probability weighted; lifetime medical cost data
ID DEPENDENT TERMINAL EVENT; PROPENSITY SCORE; LONGITUDINAL DATA;
REGRESSION; TIMES; MODEL
AB In observational studies, estimation of average causal treatment effect on a patient's response should adjust for confounders that are associated with both treatment exposure and response. In addition, the response, such as medical cost, may have incomplete follow-up. In this article, a double robust estimator is proposed for average causal treatment effect for right censored medical cost data. The estimator is double robust in the sense that it remains consistent when either the model for the treatment assignment or the regression model for the response is correctly specified. Double robust estimators increase the likelihood the results will represent a valid inference. Asymptotic normality is obtained for the proposed estimator, and an estimator for the asymptotic variance is also derived. Simulation studies show good finite sample performance of the proposed estimator and a real data analysis using the proposed method is provided as illustration. Copyright (c) 2016 John Wiley & Sons, Ltd.
C1 [Wang, Xuan; Zhou, Xiao-Hua] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Beste, Lauren A.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Gen Internal Med, VA Natl Liver Dis Database,Sch Med, Seattle, WA USA.
[Maier, Marissa M.] Oregon Hlth & Sci Univ, HIV Hepatitis & Publ Hlth Pathogens Program, VA Portland Hlth Care Syst,Div Infect Dis, Infect Dis Sect,Off Patient Care Serv,VHA, Portland, OR 97201 USA.
[Zhou, Xiao-Hua] Seattle HSR Ctr Innovat Veteran Cr & Value Driven, Dept Vet Affairs Med Ctr, Seattle, WA USA.
RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
EM azhou@u.washington.edu
FU US Department of Veterans Affairs, Veterans Affairs Health
Administration Research Career Scientist Award [RCS 05-196]
FX Xiao-Hua (Andrew) Zhou, PhD, is presently the Core Investigator and
Biostatistics Unit Director at the Seattle HSR&D Center of Innovation
for Veteran-Centered and Value-Driven Care, Department of Veterans
Affairs Medical Center, Seattle, WA. The views expressed in this article
are those of the authors and do not necessarily represent the views of
the Department of Veterans Affairs. Dr. Zhou's work was supported in
part by US Department of Veterans Affairs, Veterans Affairs Health
Administration Research Career Scientist Award (RCS 05-196),
NR 23
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U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD AUG 15
PY 2016
VL 35
IS 18
BP 3101
EP 3116
DI 10.1002/sim.6876
PG 16
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DR6PZ
UT WOS:000380025100005
PM 26818601
ER
PT J
AU Lee, D
Ganna, A
Pawitan, Y
Lee, W
AF Lee, Donghwan
Ganna, Andrea
Pawitan, Yudi
Lee, Woojoo
TI Nonparametric estimation of the rediscovery rate
SO STATISTICS IN MEDICINE
LA English
DT Article
DE rediscovery rate; multiple testing; false discovery rate; validation
study
ID GENOME-WIDE ASSOCIATION
AB Validation studies have been used to increase the reliability of the statistical conclusions for scientific discoveries; such studies improve the reproducibility of the findings and reduce the possibility of false positives. Here, one of the important roles of statistics is to quantify reproducibility rigorously. Two concepts were recently defined for this purpose: (i) rediscovery rate (RDR), which is the expected proportion of statistically significant findings in a study that can be replicated in the validation study and (ii) false discovery rate in the validation study (vFDR). In this paper, we aim to develop a nonparametric approach to estimate the RDR and vFDR and show an explicit link between the RDR and the FDR. Among other things, the link explains why reproducing statistically significant results even with low FDR level may be difficult. Two metabolomics datasets are considered to illustrate the application of the RDR and vFDR concepts in high-throughput data analysis. Copyright (c) 2016 John Wiley & Sons, Ltd.
C1 [Lee, Donghwan] Ewha Womans Univ, Dept Stat, Seoul, South Korea.
[Ganna, Andrea; Pawitan, Yudi] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Ganna, Andrea] Broad Inst & MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Ganna, Andrea] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ganna, Andrea] Harvard Med Sch, Boston, MA USA.
[Lee, Woojoo] Inha Univ, Dept Stat, Inchon, South Korea.
RP Lee, W (reprint author), Inha Univ, Dept Stat, Inchon, South Korea.
EM lwj221@gmail.com
OI Ganna, Andrea/0000-0002-8147-240X
FU Basic Science Research Program through the National Research Foundation
of Korea (NRF) - Ministry of Science, ICTFuture Planning
[NRF-2013R1A1A1061332]; Basic Science Research Program through the
National Research Foundation of Korea (NRF) - Ministry of Science, ICT &
Future Planning [NRF-2015R1C1A1A01055524]; Ewha Womans University
Research Grant
FX Woojoo Lee was supported by Basic Science Research Program through the
National Research Foundation of Korea (NRF) funded by the Ministry of
Science, ICT&Future Planning (NRF-2013R1A1A1061332). Donghwan Leewas
supported by Basic Science Research Program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Science,
ICT & Future Planning (NRF-2015R1C1A1A01055524) and also supported by
the 2014 Ewha Womans University Research Grant.
NR 14
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0277-6715
EI 1097-0258
J9 STAT MED
JI Stat. Med.
PD AUG 15
PY 2016
VL 35
IS 18
BP 3203
EP 3212
DI 10.1002/sim.6915
PG 10
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA DR6PZ
UT WOS:000380025100012
PM 26910365
ER
PT J
AU Hanyuda, A
Ogino, S
Qian, ZR
Nishihara, R
Song, MY
Mima, K
Inamura, K
Masugi, Y
Wu, KN
Meyerhardt, JA
Chan, AT
Fuchs, CS
Giovannucci, EL
Cao, Y
AF Hanyuda, Akiko
Ogino, Shuji
Qian, Zhi Rong
Nishihara, Reiko
Song, Mingyang
Mima, Kosuke
Inamura, Kentaro
Masugi, Yohei
Wu, Kana
Meyerhardt, Jeffrey A.
Chan, Andrew T.
Fuchs, Charles S.
Giovannucci, Edward L.
Cao, Yin
TI Body mass index and risk of colorectal cancer according to tumor
lymphocytic infiltrate
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE body mass index; colorectal carcinoma; lymphocytic reaction; molecular
pathological epidemiology
ID MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; ISLAND METHYLATOR PHENOTYPE;
C-REACTIVE PROTEIN; MICROSATELLITE INSTABILITY; LIFE-STYLE;
COLON-CANCER; DISEASE; OBESITY; FEATURES; ASSOCIATIONS
AB Higher body mass index (BMI), higher body adiposity and obesity have been associated with increased risk of colorectal cancer. Evidence suggests that excess energy balance may influence systemic immune and inflammatory status. Thus, we hypothesized that the positive association between BMI and colorectal cancer risk might differ according to colorectal carcinoma subtypes according to levels of histopathological lymphocytic reaction to tumor. We collected biennial questionnaire data on weight and baseline height information in two prospective cohort studies, the Nurses' Health Study (1980-2010) and the Health Professionals Follow-up Study (1986-2010). Utilizing duplication-method Cox proportional hazards regression models, we prospectively assessed the association between BMI and risk of colorectal cancer subtypes according to the degree of Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, the overall lymphocytic reaction score, or T-cell [CD3(+), CD8(+), CD45RO (PTPRC)(+) or FOXP3(+)] density in tumor tissue. Statistical significance level was adjusted for multiple hypotheses testing by Bonferroni correction. During follow up of 1,708,029 men and women (over 3,346,752 person-years), we documented 1,436 incident rectal and colon cancer cases with available formalin-fixed paraffin-embedded tumor tissue materials and pathological immunity data. BMI was significantly associated with higher risk of overall colorectal cancer (P-trend < 0.001); however, the association of BMI with colorectal carcinoma risk did not significantly differ by the level of lymphocytic reaction or T-cell infiltration in tumor tissue status (P-heterogeneity > 0.10). BMI may be associated with risk of colorectal cancer regardless of levels of lymphocytic response to tumor.
C1 [Hanyuda, Akiko; Nishihara, Reiko; Song, Mingyang; Wu, Kana; Giovannucci, Edward L.; Cao, Yin] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA.
[Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.; Cao, Yin] Harvard Univ, Sch Med, Boston, MA USA.
[Ogino, Shuji; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Ogino, Shuji; Qian, Zhi Rong; Nishihara, Reiko; Song, Mingyang; Mima, Kosuke; Inamura, Kentaro; Masugi, Yohei; Meyerhardt, Jeffrey A.; Chan, Andrew T.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji; Nishihara, Reiko; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Song, Mingyang; Chan, Andrew T.; Cao, Yin] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Song, Mingyang; Chan, Andrew T.; Cao, Yin] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St, Boston, MA 02115 USA.
[Inamura, Kentaro] JFCR, Inst Canc, Div Pathol, Tokyo, Japan.
[Chan, Andrew T.; Fuchs, Charles S.; Giovannucci, Edward L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
RP Cao, Y (reprint author), Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St, Boston, MA 02115 USA.; Giovannucci, EL (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr & Epidemiol, 655 Huntington Ave, Boston, MA 02215 USA.
EM egiovann@hsph.harvard.edu; yic576@mail.harvard.edu
FU U.S. National Institutes of Health (NIH) [K07 CA190673, R01 CA137178,
K24 DK098311, P50 CA127003, R01 CA151993, R35 CA197735, UM1 CA186107,
P01 CA87969, P01 CA55075, UM1 CA167552]; Project P Fund, the Friends of
the Dana-Farber Cancer Institute; Bennett Family Fund; Entertainment
Industry Foundation through National Colorectal Cancer Research
Alliance; Japan-United States Educational Exchange Promotion Foundation
(Fulbright Foundation), Japan; Japan Society for the Promotion of
Science Postdoctoral Fellowship for Research Abroad; Takashi Tsuruo
Memorial Fund, Japan; Program for Advancing Strategic International
Networks to Accelerate the Circulation of Talented Researchers from
Japanese Society for the Promotion of Science; Keio Gijuku Fukuzawa
Memorial Fund for the Advancement of Education and Research
FX Grant sponsor: U.S. National Institutes of Health (NIH); Grant number:
K07 CA190673, R01 CA137178, K24 DK098311, P50 CA127003, R01 CA151993,
R35 CA197735, UM1 CA186107, P01 CA87969, P01 CA55075, UM1 CA167552;
Grant sponsors: Project P Fund, the Friends of the Dana-Farber Cancer
Institute, the Bennett Family Fund and the Entertainment Industry
Foundation through National Colorectal Cancer Research Alliance.
Japan-United States Educational Exchange Promotion Foundation (Fulbright
Foundation), Japan; Japan Society for the Promotion of Science
Postdoctoral Fellowship for Research Abroad, Takashi Tsuruo Memorial
Fund, Japan, Program for Advancing Strategic International Networks to
Accelerate the Circulation of Talented Researchers from Japanese Society
for the Promotion of Science, Keio Gijuku Fukuzawa Memorial Fund for the
Advancement of Education and Research
NR 50
TC 4
Z9 4
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD AUG 15
PY 2016
VL 139
IS 4
BP 854
EP 868
DI 10.1002/ijc.30122
PG 15
WC Oncology
SC Oncology
GA DP3TM
UT WOS:000378418300021
PM 27037951
ER
PT J
AU Yu, YJ
Wu, TB
Johnson-Buck, A
Li, LD
Su, X
AF Yu, Yingjie
Wu, Tongbo
Johnson-Buck, Alexander
Li, Lidan
Su, Xin
TI A two-layer assay for single-nucleotide variants utilizing strand
displacement and selective digestion
SO BIOSENSORS & BIOELECTRONICS
LA English
DT Article
DE Single nucleotide variant; Toehold strand displacement; Lambda
exonuclease; Fluorescent probe
ID DNA; HYBRIDIZATION; MUTATIONS; MEDICINE; PLASMA
AB Point mutations have emerged as prominent biomarkers for disease diagnosis, particularly in the case of cancer. Discovering single-nucleotide variants (SNVs) is also of great importance for the identification of single-nucleotide polymorphisms within the population. The competing requirements of thermodynamic stability and specificity in conventional nucleic acid hybridization probes make it challenging to achieve highly precise detection of point mutants. Here, we present a fluorescence-based assay for low abundance mutation detection based on toehold-mediated strand displacement and nuclease-mediated strand digestion that enables highly precise detection of point mutations. We demonstrate that this combined assay provides 50-1000-fold discrimination (mean value: 255) between all possible single nucleotide mutations and their corresponding wild-type sequence for a model DNA target. Using experiments and kinetic modeling, we investigate probe properties that obtain additive benefits from both strand displacement and nucleolytic digestion, thus providing guidance for the design of enzyme mediated nucleic acid assays in the future. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Yu, Yingjie; Li, Lidan; Su, Xin] Beijing Univ Chem Technol, Coll Life Sci & Technol, Beijing 100029, Peoples R China.
[Yu, Yingjie] SUNY Stony Brook, Mat Sci & Engn, Stony Brook, NY 11790 USA.
[Wu, Tongbo] Peking Univ, Beijing Natl Lab Mol Sci, Coll Chem & Mol Engn, MOE Key Lab Bioorgan Chem & Mol Engn, Beijing 100871, Peoples R China.
[Johnson-Buck, Alexander] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
RP Su, X (reprint author), 15 North Third Ring Rd, Beijing 100029, Peoples R China.
EM xinsu@mail.buct.edu.cn
FU National Natural Science Foundation of China [81273631]; subject
promotion plan of Beijing University of Chemical Technology
[ys12060026025]
FX We thank Prof. Meiping Zhao at Peking University for her kindly
providing instruments. This work was supported by the National Natural
Science Foundation of China (81273631) and subject promotion plan of
Beijing University of Chemical Technology (ys12060026025).
NR 18
TC 0
Z9 0
U1 10
U2 39
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 AUG 15
PY 2016
VL 82
BP 248
EP 254
DI 10.1016/j.bios.2016.03.070
PG 7
WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical;
Electrochemistry; Nanoscience & Nanotechnology
SC Biophysics; Biotechnology & Applied Microbiology; Chemistry;
Electrochemistry; Science & Technology - Other Topics
GA DM7MT
UT WOS:000376545400036
ER
PT J
AU Murias, G
Montanya, J
Chacon, E
Estruga, A
Subira, C
Fernandez, R
Sales, B
de Haro, C
Lopez-Aguilar, J
Lucangelo, U
Villar, J
Kacmarek, RM
Blanch, L
AF Murias, Gaston
Montanya, Jaume
Chacon, Encarna
Estruga, Anna
Subira, Carles
Fernandez, Rafael
Sales, Bernat
de Haro, Candelaria
Lopez-Aguilar, Josefina
Lucangelo, Umberto
Villar, Jesus
Kacmarek, Robert M.
Blanch, Lluis
TI Automatic detection of ventilatory modes during invasive mechanical
ventilation
SO CRITICAL CARE
LA English
DT Article
DE Mechanical ventilation; Automatic detection; Ventilatory mode;
Information systems in critical care
ID PULSE PRESSURE VARIATION; STROKE VOLUME; FLUID RESPONSIVENESS;
INTENSIVE-CARE; TIME; MORTALITY; TAXONOMY; SURGERY; ICU
AB Background: Expert systems can help alleviate problems related to the shortage of human resources in critical care, offering expert advice in complex situations. Expert systems use contextual information to provide advice to staff. In mechanical ventilation, it is crucial for an expert system to be able to determine the ventilatory mode in use. Different manufacturers have assigned different names to similar or even identical ventilatory modes so an expert system should be able to detect the ventilatory mode. The aim of this study is to evaluate the accuracy of an algorithm to detect the ventilatory mode in use.
Methods: We compared the results of a two-step algorithm designed to identify seven ventilatory modes. The algorithm was built into a software platform (BetterCare (R) system, Better Care SL; Barcelona, Spain) that acquires ventilatory signals through the data port of mechanical ventilators. The sample analyzed compared data from consecutive adult patients who underwent > 24 h of mechanical ventilation in intensive care units (ICUs) at two hospitals. We used Cohen's kappa statistics to analyze the agreement between the results obtained with the algorithm and those recorded by ICU staff.
Results: We analyzed 486 records from 73 patients. The algorithm correctly labeled the ventilatory mode in 433 (89 %). We found an unweighted Cohen's kappa index of 84.5 % [CI (95 %) = (80.5 %: 88.4 %)].
Conclusions: The computerized algorithm can reliably identify ventilatory mode.
C1 [Murias, Gaston] Univ Favaloro, Fac Med, Dept Ciencias Fisiol Farmacol & Bioquim, Clin Bazterr & Clin Santa Isabel, Buenos Aires, DF, Argentina.
[Montanya, Jaume; Fernandez, Rafael; Lopez-Aguilar, Josefina; Villar, Jesus; Blanch, Lluis] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.
[Montanya, Jaume; Chacon, Encarna; Estruga, Anna; de Haro, Candelaria; Lopez-Aguilar, Josefina; Blanch, Lluis] Univ Autonoma Barcelona, I3PT, Parc Tauli Hosp Univ, C ParcTauli 1, Sabadell 08208, Spain.
[Subira, Carles; Fernandez, Rafael] Univ Int Catalunya, Hosp St Joan de Deu, Fundacio Althaia, Serv Med Intens, Manresa, Spain.
[Sales, Bernat] Better Care, Barcelona, Spain.
[Lucangelo, Umberto] Univ Trieste, Cattinara Hosp, Dept Perioperat Med Intens Care & Emergency, Trieste, Italy.
[Villar, Jesus] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain.
[Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Kacmarek, Robert M.] Harvard Med Sch, Dept Anesthesiol, Boston, MA USA.
RP Blanch, L (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.; Blanch, L (reprint author), Univ Autonoma Barcelona, I3PT, Parc Tauli Hosp Univ, C ParcTauli 1, Sabadell 08208, Spain.
EM lblanch@tauli.cat
RI Fernandez, Rafael/A-9586-2010
OI Fernandez, Rafael/0000-0001-5711-5317
FU Plan Nacional de R+D+I [PI09/91074, PI13/02204]; ISCIII- Subdireccion
General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER);
CIBER Enfermedades Respiratorias; Fundacion Mapfre; Fundacio Parc Tauli;
Plan Avanza [TSI-020302-2008-38]; MCYIN; MITYC (Spain)
FX This work was funded by projects PI09/91074 and PI13/02204, integrated
in the Plan Nacional de R+D+I and co-funded by the ISCIII- Subdireccion
General de Evaluacion y el Fondo Europeo de Desarrollo Regional (FEDER).
CIBER Enfermedades Respiratorias, Fundacion Mapfre, Fundacio Parc Tauli,
Plan Avanza TSI-020302-2008-38, MCYIN and MITYC (Spain).
NR 18
TC 0
Z9 0
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1466-609X
EI 1364-8535
J9 CRIT CARE
JI Crit. Care
PD AUG 14
PY 2016
VL 20
AR 258
DI 10.1186/s13054-016-1436-9
PG 7
WC Critical Care Medicine
SC General & Internal Medicine
GA DT6TJ
UT WOS:000381616700001
PM 27522580
ER
PT J
AU Bennett, J
Wellman, J
Marshall, KA
McCague, S
Ashtari, M
DiStefano-Pappas, J
Elci, OU
Chung, DC
Sun, JW
Wright, JF
Cross, DR
Aravand, P
Cyckowski, LL
Bennicelli, JL
Mingozzi, F
Auricchio, A
Pierce, EA
Ruggiero, J
Leroy, BP
Simonelli, F
High, KA
Maguire, AM
AF Bennett, Jean
Wellman, Jennifer
Marshall, Kathleen A.
McCague, Sarah
Ashtari, Manzar
DiStefano-Pappas, Julie
Elci, Okan U.
Chung, Daniel C.
Sun, Junwei
Wright, J. Fraser
Cross, Dominique R.
Aravand, Puya
Cyckowski, Laura L.
Bennicelli, Jeannette L.
Mingozzi, Federico
Auricchio, Alberto
Pierce, Eric A.
Ruggiero, Jason
Leroy, Bart P.
Simonelli, Francesca
High, Katherine A.
Maguire, Albert M.
TI Safety and durability of effect of contralateral-eye administration of
AAV2 gene therapy in patients with childhood-onset blindness caused by
RPE65 mutations: a follow-on phase 1 trial
SO LANCET
LA English
DT Article
ID LEBER CONGENITAL AMAUROSIS; ADENOASSOCIATED VIRUS; RETINAL DEGENERATION;
CANINE MODEL; VISUAL CYCLE; VISION; IMPROVEMENT; ROD
AB Background Safety and efficacy have been shown in a phase 1 dose-escalation study involving a unilateral subretinal injection of a recombinant adeno-associated virus (AAV) vector containing the RPE65 gene (AAV2-hRPE65v2) in individuals with inherited retinal dystrophy caused by RPE65 mutations. This finding, along with the bilateral nature of the disease and intended use in treatment, prompted us to determine the safety of administration of AAV2-hRPE65v2 to the contralateral eye in patients enrolled in the phase 1 study.
Methods In this follow-on phase 1 trial, one dose of AAV2-hRPE65v2 (1.5 x 10(11) vector genomes) in a total volume of 300 mu L was subretinally injected into the contralateral, previously uninjected, eyes of 11 children and adults (aged 11-46 years at second administration) with inherited retinal dystrophy caused by RPE65 mutations, 1.71-4.58 years after the initial subretinal injection. We assessed safety, immune response, retinal and visual function, functional vision, and activation of the visual cortex from baseline until 3 year follow-up, with observations ongoing. This study is registered with ClinicalTrials.gov, number NCT01208389.
Findings No adverse events related to the AAV were reported, and those related to the procedure were mostly mild (dellen formation in three patients and cataracts in two). One patient developed bacterial endophthalmitis and was excluded from analyses. We noted improvements in efficacy outcomes in most patients without significant immunogenicity. Compared with baseline, pooled analysis of ten participants showed improvements in mean mobility and full-field light sensitivity in the injected eye by day 30 that persisted to year 3 (mobility p=0.0003, white light full-field sensitivity p<0.0001), but no significant change was seen in the previously injected eyes over the same time period (mobility p=0.7398, white light full-field sensitivity p=0.6709). Changes in visual acuity from baseline to year 3 were not significant in pooled analysis in the second eyes or the previously injected eyes (p>0.49 for all time-points compared with baseline).
Interpretation To our knowledge, AAV2-hRPE65v2 is the first successful gene therapy administered to the contralateral eye. The results highlight the use of several outcome measures and help to delineate the variables that contribute to maximal benefit from gene augmentation therapy in this disease.
C1 [Bennett, Jean; Ashtari, Manzar; Chung, Daniel C.; Sun, Junwei; Aravand, Puya; Bennicelli, Jeannette L.; Maguire, Albert M.] Univ Penn, Ctr Adv Retinal & Ocular Therapeut, Philadelphia, PA 19104 USA.
[Bennett, Jean; Ashtari, Manzar; Chung, Daniel C.; Bennicelli, Jeannette L.; Pierce, Eric A.; Maguire, Albert M.] Univ Penn, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA.
[Pierce, Eric A.; Ruggiero, Jason; Maguire, Albert M.] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
Univ Penn, Scheie Eye Inst, Philadelphia, PA 19104 USA.
[Bennett, Jean; Wellman, Jennifer; Marshall, Kathleen A.; McCague, Sarah; Sun, Junwei; Wright, J. Fraser; Cross, Dominique R.; Mingozzi, Federico; Leroy, Bart P.; High, Katherine A.; Maguire, Albert M.] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA.
[Ashtari, Manzar; Cyckowski, Laura L.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA.
[DiStefano-Pappas, Julie; Elci, Okan U.] Childrens Hosp Philadelphia, Westat Biostat & Data Management Core, Philadelphia, PA 19104 USA.
[Pierce, Eric A.; Leroy, Bart P.; Maguire, Albert M.] Childrens Hosp Philadelphia, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Wellman, Jennifer; Chung, Daniel C.; Wright, J. Fraser; High, Katherine A.] Spark Therapeut, Philadelphia, PA USA.
[Mingozzi, Federico] Genethon, Immunol & Liver Gene Therapy, Evry, France.
[Auricchio, Alberto] Telethon Inst Genet & Med, Naples, Italy.
[Auricchio, Alberto] Univ Naples Federico II, Med Genet, Dept Pediat, Naples, Italy.
[Pierce, Eric A.] Harvard Med Sch, Ocular Genom Inst, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Leroy, Bart P.] Ghent Univ Hosp, Dept Ophthalmol, Ghent, Belgium.
[Leroy, Bart P.] Ghent Univ Hosp, Ctr Med Genet, Ghent, Belgium.
[Leroy, Bart P.] Univ Ghent, Ghent, Belgium.
[Simonelli, Francesca] Univ Naples 2, Eye Clin, Multidisciplinary Dept Med Surg & Dent Sci, Naples, Italy.
[High, Katherine A.] Howard Hughes Med Inst, Philadelphia, PA USA.
RP Bennett, J (reprint author), Univ Penn, Ctr Adv Retinal & Ocular Therapeut, Stellar Chance Labs 309c, 422 Curie Blvd, Philadelphia, PA 19104 USA.
EM jebennet@mail.med.upenn.edu
OI Pierce, Eric/0000-0002-2354-4102
FU Center for Cellular and Molecular Therapeutics at The Children's
Hospital of Philadelphia; Spark Therapeutics; US National Institutes of
Health; Foundation Fighting Blindness; Institute for Translational
Medicine and Therapeutics; Research to Prevent Blindness; Center for
Advanced Retinal and Ocular Therapeutics; Mackall Foundation Trust; F M
Kirby Foundation; Research Foundation-Flanders
FX Center for Cellular and Molecular Therapeutics at The Children's
Hospital of Philadelphia, Spark Therapeutics, US National Institutes of
Health, Foundation Fighting Blindness, Institute for Translational
Medicine and Therapeutics, Research to Prevent Blindness, Center for
Advanced Retinal and Ocular Therapeutics, Mackall Foundation Trust, F M
Kirby Foundation, and The Research Foundation-Flanders.
NR 30
TC 8
Z9 9
U1 9
U2 11
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 AUG 13
PY 2016
VL 388
IS 10045
BP 661
EP 672
DI 10.1016/S0140-6736(16)30371-3
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT1UX
UT WOS:000381268700026
PM 27375040
ER
PT J
AU Levey, EJ
Oppenheim, CE
Lange, BCL
Plasky, NS
Harris, BL
Lekpeh, GG
Kekulah, I
Henderson, DC
Borba, CPC
AF Levey, Elizabeth J.
Oppenheim, Claire E.
Lange, Brittany C. L.
Plasky, Naomi S.
Harris, Benjamin L.
Lekpeh, G. Gondah
Kekulah, Isaac
Henderson, David C.
Borba, Christina P. C.
TI A qualitative analysis of factors impacting resilience among youth in
post-conflict Liberia
SO CHILD AND ADOLESCENT PSYCHIATRY AND MENTAL HEALTH
LA English
DT Article
DE Liberia; Post-conflict; Qualitative analysis; Youth; Adolescent;
Resilience
ID PROTECTIVE PROCESSES; CHILDREN; STRESS; PATHWAYS; DISASTER; HEALTH; RISK
AB Background: In 2008, 5 years after the Liberian civil war ended, there were an estimated 340,000 orphans in Liberia, 18 % of the total child population of the country. Given that children make up half the population and that these children experienced significant trauma and loss both through direct exposure to the war and then to the Ebola epidemic, and indirectly as a result of the trauma experienced by their parents, the recovery of these children is essential to the recovery of the nation as a whole. The goal of this research was to identify factors contributing to resilience among youth in post-conflict Liberia. Resilience was defined as evidence of adaptive functioning and psychological health.
Methods: Seventy-five young people (age 13-18) in the capital city of Monrovia, Liberia were recruited in 2012. Semi-structured interviews were conducted, and demographic data were collected. Interviews were then transcribed and coded thematically.
Results: Forty-six of the participants were attending school, and 29 were not enrolled in school. Youth enrolled in school demonstrated greater adaptive functioning. This was particularly true for boys in any school setting and girls attending private school. Youth not attending school were more likely to have lost family members or become estranged from them, and many were also engaging in substance use. Emotion regulation, cognitive flexibility, agency, social intelligence and, in some cases, meaning-making were found in participants who showed resilient outcomes.
Conclusions: Caregiver relationships mediate the development of psychological capacities that impact resilience. These findings suggest that youth who have lost a caregiver, many of whom are not attending school, are experiencing a significant ongoing burden in terms of their daily functioning and psychological health in the post-war period and should be the focus of further study and intervention targeting substance use and community reintegration.
C1 [Levey, Elizabeth J.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, 5 Longfellow Pl, Boston, MA 02114 USA.
[Levey, Elizabeth J.] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA.
[Levey, Elizabeth J.] Univ Illinois, Coll Med, 1853 West Polk St, Chicago, IL 60612 USA.
[Oppenheim, Claire E.; Henderson, David C.; Borba, Christina P. C.] Boston Med Ctr, Dept Psychiat, 840 Harrison Ave, Boston, MA 02118 USA.
[Lange, Brittany C. L.] Univ Oxford, Dept Social Policy & Intervent, Barnett House,32-37 Wellington Sq, Oxford, England.
[Plasky, Naomi S.] Johns Hopkins Bloomberg Sch Publ Hlth, 615 North Wolfe St, Baltimore, MD 21205 USA.
[Harris, Benjamin L.; Lekpeh, G. Gondah; Kekulah, Isaac] Univ Liberia, AM Dogliotti Coll Med, Monrovia, Liberia.
[Henderson, David C.; Borba, Christina P. C.] Boston Univ, Sch Med, 72 East Concord St, Boston, MA 02118 USA.
RP Levey, EJ (reprint author), Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, 5 Longfellow Pl, Boston, MA 02114 USA.; Levey, EJ (reprint author), Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA.; Levey, EJ (reprint author), Univ Illinois, Coll Med, 1853 West Polk St, Chicago, IL 60612 USA.
EM elevey@partners.org
FU National Institutes of Health [T32-MH-093310]; Massachusetts General
Hospital Chester M. Pierce, MD Division of Global Psychiatry and
Partners Healthcare Center of Expertise in Global Health Travel Award
FX This research was supported by an award from the National Institutes of
Health (T32-MH-093310). Funding for travel expenses to conduct this
project was provided by the Massachusetts General Hospital Chester M.
Pierce, MD Division of Global Psychiatry and Partners Healthcare Center
of Expertise in Global Health Travel Award. Funding bodies had no role
in the design of the study, collection, analysis, interpretation of data
or in writing the manuscript.
NR 27
TC 1
Z9 1
U1 9
U2 9
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1753-2000
J9 CHILD ADOL PSYCH MEN
JI Child Adolesc. Psychiatry Ment. Health
PD AUG 12
PY 2016
VL 10
AR 26
DI 10.1186/s13034-016-0114-7
PG 11
WC Pediatrics; Psychiatry
SC Pediatrics; Psychiatry
GA EF2PH
UT WOS:000390166300001
PM 27525038
ER
PT J
AU Yaghjyan, L
Ghita, GL
Rosner, B
Farvid, M
Bertrand, KA
Tamimi, RM
AF Yaghjyan, Lusine
Ghita, Gabriela L.
Rosner, Bernard
Farvid, Maryam
Bertrand, Kimberly A.
Tamimi, Rulla M.
TI Adolescent fiber intake and mammographic breast density in premenopausal
women
SO BREAST CANCER RESEARCH
LA English
DT Article
DE Adolescent diet; Breast density; Fiber intake
ID CANCER RISK; POSTMENOPAUSAL WOMEN; DIETARY INTERVENTION; MULTIETHNIC
COHORT; SUBSEQUENT RISK; NURSES HEALTH; LIFE-STYLE; LOW-FAT;
ASSOCIATION; MENOPAUSE
AB Background: To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent fiber intake with mammographic density in premenopausal women.
Methods: This study included 743 cancer-free premenopausal women (mean age, 44.9 years) within the Nurses' Health Study II cohort. Percent breast density, absolute dense and non-dense areas were measured from digitized film mammograms using a computer-assisted thresholding technique. Adolescent and adult diet were assessed with a food frequency questionnaire; energy-adjusted nutrient intakes were estimated for each food item. Information regarding breast cancer risk factors was obtained from baseline or biennial questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations between quartiles of adolescent fiber intake and each of the breast density measures, adjusted for potential confounders. Associations were examined separately for total fiber intake; fiber from fruits, vegetables, legumes, and cereal; and food sources of fiber (fruits, vegetables, and nuts).
Results: In multivariable analyses, total fiber intake during adolescence was not associated with percent breast density (p for trend = 0.64), absolute dense area (p for trend = 0.80), or non-dense area (p for trend = 0.75). Similarly, neither consumption of fiber from fruits, vegetables, legumes, or cereal nor specific sources of fiber intake (fruits, vegetables, or nuts) during adolescence were associated with any of the mammographic density phenotypes.
Conclusions: Our findings do not support the hypothesis that adolescent fiber intake is associated with premenopausal mammographic breast density.
C1 [Yaghjyan, Lusine] Univ Florida, Dept Epidemiol, Coll Publ Hlth & Hlth Profess, 2004 Mowry Rd, Gainesville, FL 32610 USA.
[Yaghjyan, Lusine; Ghita, Gabriela L.] Univ Florida, Coll Med, 2004 Mowry Rd, Gainesville, FL 32610 USA.
[Ghita, Gabriela L.] Univ Florida, Dept Biostat, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA.
[Rosner, Bernard] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Rosner, Bernard] Harvard Med Sch, Boston, MA USA.
[Farvid, Maryam] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Farvid, Maryam] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, Harvard Massachusetts Gen Hosp, Ctr Genom Vulnerable Populat & Hlth Dispar, Boston, MA 02114 USA.
[Bertrand, Kimberly A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
RP Yaghjyan, L (reprint author), Univ Florida, Dept Epidemiol, Coll Publ Hlth & Hlth Profess, 2004 Mowry Rd, Gainesville, FL 32610 USA.; Yaghjyan, L (reprint author), Univ Florida, Coll Med, 2004 Mowry Rd, Gainesville, FL 32610 USA.
EM lyaghjyan@ufl.edu
FU National Cancer Institute at the National Institutes of Health
[CA131332, CA087969, CA175080, UM1 CA186107, UM1 CA176726]; Avon
Foundation for Women; Susan G. Komen for the Cure(R); Breast Cancer
Research Foundation; Simeon J. Fortin Charitable Foundation, Bank of
America, NA, Co-Trustee
FX This work was supported by the National Cancer Institute at the National
Institutes of Health [CA131332, CA087969, CA175080 to RMT, UM1 CA186107
to MS, UM1 CA176726 to WW], Avon Foundation for Women, Susan G. Komen
for the Cure (R), and Breast Cancer Research Foundation. KAB is
supported in part by the Simeon J. Fortin Charitable Foundation, Bank of
America, NA, Co-Trustee.
NR 56
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PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD AUG 12
PY 2016
VL 18
AR 85
DI 10.1186/s13058-016-0747-8
PG 8
WC Oncology
SC Oncology
GA DW1VI
UT WOS:000383430600001
PM 27520794
ER
PT J
AU Lee, CJ
Ahn, H
Lee, SB
Shin, JY
Park, WY
Kim, JI
Lee, J
Ryu, H
Kim, S
AF Lee, Chai-Jin
Ahn, Hongryul
Lee, Sean Bong
Shin, Jong-Yeon
Park, Woong-Yang
Kim, Jong-Il
Lee, Junghee
Ryu, Hoon
Kim, Sun
TI Integrated analysis of omics data using microRNA-target mRNA network and
PPI network reveals regulation of Gnai1 function in the spinal cord of
Ews/Ewsr1 KO mice
SO BMC MEDICAL GENOMICS
LA English
DT Article; Proceedings Paper
CT 5th Translational Bioinformatics Conference (TBC)
CY NOV 07-09, 2015
CL Tokyo, JAPAN
DE EWS; Ewsr1; Gnai1; MMIA; PPI; Network analysis
ID SARCOMA GENE EWS; EWINGS-SARCOMA; TUMORS; PROTEIN
AB Background: Multifunctional transcription factor (TF) gene EWS/EWSR1 is involved in various cellular processes such as transcription regulation, noncoding RNA regulation, splicing regulation, genotoxic stress response, and cancer generation. Role of a TF gene can be effectively studied by measuring genome-wide gene expression, i.e., transcriptome, in an animal model of Ews/Ewsr1 knockout (KO). However, when a TF gene has complex multi-functions, conventional approaches such as differentially expressed genes (DEGs) analysis are not successful to characterize the role of the EWS gene. In this regard, network-based analyses that consider associations among genes are the most promising approach.
Methods: Networks are constructed and used to show associations among biological entities at various levels, thus different networks represent association at different levels. Taken together, in this paper, we report contributions on both computational and biological sides.
Results: Contribution on the computational side is to develop a novel computational framework that combines miRNA-gene network and protein-protein interaction network information to characterize the multifunctional role of EWS gene. On the biological side, we report that EWS regulates G-protein, Gnai1, in the spinal cord of Ews/Ewsr1 KO mice using the two biological network integrated analysis method. Neighbor proteins of Gnai1, G-protein complex subunits Gnb1, Gnb2 and Gnb4 were also down-regulated at their gene expression level. Interestingly, up-regulated genes, such as Rgs1 and Rgs19, are linked to the inhibition of Gnai1 activities. We further verified the altered expression of Gnai1 by qRT-PCR in Ews/Ewsr1 KO mice.
Conclusions: Our integrated analysis of miRNA-transcriptome network and PPI network combined with qRT-PCR verifies that Gnai1 function is impaired in the spinal cord of Ews/Ewsr1 KO mice.
C1 [Lee, Chai-Jin; Kim, Sun] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151747, South Korea.
[Ahn, Hongryul; Kim, Sun] Seoul Natl Univ, Dept Comp Sci & Engn, Seoul 151744, South Korea.
[Kim, Sun] Seoul Natl Univ, Bioinformat Inst, Seoul 151747, South Korea.
[Lee, Sean Bong] Tulane Univ, Sch Med, Dept Pathol & Lab Med, 1430 Tulane Ave, New Orleans, LA 70112 USA.
[Shin, Jong-Yeon; Kim, Jong-Il] Seoul Natl Univ, Coll Med, Genome Med Inst, Seoul 110799, South Korea.
[Shin, Jong-Yeon; Kim, Jong-Il] Seoul Natl Univ, Coll Med, Dept Biochem, Seoul 110799, South Korea.
[Park, Woong-Yang] Sungkyunkwan Univ, Samsung Med Ctr, Samsung Genome Inst, Seoul 135710, South Korea.
[Park, Woong-Yang] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Dept Hlth Sci & Technol, Seoul 135710, South Korea.
[Lee, Junghee; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Lee, Junghee; Ryu, Hoon] Boston Univ, Alzheimers Dis Ctr, Boston, MA 02118 USA.
[Lee, Junghee; Ryu, Hoon] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Ryu, Hoon] Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neuromed, Seoul 136791, South Korea.
RP Kim, S (reprint author), Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul 151747, South Korea.; Ryu, H (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA.
EM hoonryu@bu.edu; sunkim.bioinfo@snu.ac.kr
RI KIM, JONG-IL/D-1019-2011
OI KIM, JONG-IL/0000-0002-7240-3744
FU NINDS NIH HHS [R01 NS067283]
NR 29
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Z9 0
U1 2
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1755-8794
J9 BMC MED GENOMICS
JI BMC Med. Genomics
PD AUG 12
PY 2016
VL 9
SU 1
AR 33
DI 10.1186/s12920-016-0195-4
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA DT2OH
UT WOS:000381319300006
PM 27534535
ER
PT J
AU Sanders-Jackson, A
Tan, ASL
Bigman, CA
Mello, S
Niederdeppe, J
AF Sanders-Jackson, Ashley
Tan, Andy S. L.
Bigman, Cabral A.
Mello, Susan
Niederdeppe, Jeff
TI To Regulate or Not to Regulate? Views on Electronic Cigarette
Regulations and Beliefs about the Reasons for and against Regulation
SO PLOS ONE
LA English
DT Article
ID ADOLESCENTS; EXPOSURE; RISK
AB Background
Policies designed to restrict marketing, access to, and public use of electronic cigarettes (e-cigarettes) are increasingly under debate in various jurisdictions in the US. Little is known about public perceptions of these policies and factors that predict their support or opposition.
Methods
Using a sample of US adults from Amazon Mechanical Turk in May 2015, this paper identifies beliefs about the benefits and costs of regulating e-cigarettes and identifies which of these beliefs predict support for e-cigarette restricting policies.
Results
A higher proportion of respondents agreed with 8 different reasons to regulate e-cigarettes (48.5% to 83.3% agreement) versus 7 reasons not to regulate e-cigarettes (11.5% to 18.9%). The majority of participants agreed with 7 out of 8 reasons for regulation. When all reasons to regulate or not were included in a final multivariable model, beliefs about protecting people from secondhand vapor and protecting youth from trying e-cigarettes significantly predicted stronger support for e-cigarette restricting policies, whereas concern about government intrusion into individual choices was associated with reduced support.
Discussion
This research identifies key beliefs that may underlie public support or opposition to policies designed to regulate the marketing and use of e-cigarettes. Advocates on both sides of the issue may find this research valuable in developing strategic campaigns related to the issue.
Implications
Specific beliefs of potential benefits and costs of e-cigarette regulation (protecting youth, preventing exposure to secondhand vapor, and government intrusion into individual choices) may be effectively deployed by policy makers or health advocates in communicating with the public.
C1 [Sanders-Jackson, Ashley] Michigan State Univ, Dept Advertising & Publ Relat, Coll Commun Arts & Sci, 404 Wilson Rd, Lansing, MI 48824 USA.
[Tan, Andy S. L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Kresge Bldg,677 Huntington Ave, Boston, MA 02115 USA.
[Bigman, Cabral A.] Univ Illinois, Coll Liberal Arts & Sci, Dept Commun, 3001 Lincoln Hall,702 S Wright St, Urbana, IL USA.
[Mello, Susan] Northeastern Univ, Dept Commun Studies, Coll Arts Media & Design, 360 Huntington Ave, Boston, MA 02115 USA.
[Niederdeppe, Jeff] Cornell Univ, Coll Agr & Life Sci, Dept Commun, 476 Mann Lib Bldg, Ithaca, NY 14853 USA.
[Tan, Andy S. L.] Dana Farber Canc Inst, Div Populat Sci, Ctr Community Based Res, 450 Brookline Ave LW662, Boston, MA 02115 USA.
RP Sanders-Jackson, A (reprint author), Michigan State Univ, Dept Advertising & Publ Relat, Coll Commun Arts & Sci, 404 Wilson Rd, Lansing, MI 48824 USA.
EM sande411@msu.edu
FU NHLBI of the National Institutes of Health [T32HL00703440]
FX Research reported in this paper was supported by NHLBI of the National
Institutes of Health under award number T32HL00703440. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health.
NR 31
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U1 2
U2 2
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 AUG 12
PY 2016
VL 11
IS 8
AR e0161124
DI 10.1371/journal.pone.0161124
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3LI
UT WOS:000381382100052
ER
PT J
AU Tan-Shalaby, JL
Carrick, J
Edinger, K
Genovese, D
Liman, AD
Passero, VA
Shah, RB
AF Tan-Shalaby, Jocelyn L.
Carrick, Jennifer
Edinger, Krystal
Genovese, Dana
Liman, Andrew D.
Passero, Vida A.
Shah, Rashmikant B.
TI Modified Atkins diet in advanced malignancies - final results of a
safety and feasibility trial within the Veterans Affairs Pittsburgh
Healthcare System
SO NUTRITION & METABOLISM
LA English
DT Article
ID KETOGENIC DIET; METABOLIC MANAGEMENT; ADVANCED CANCER; KETONE-BODIES;
EXPRESSION; THERAPY; LEPTIN; CELLS; GLIOBLASTOMA; EPILEPSY
AB Background: Dysfunctional mitochondrial processes limit malignant cells ability to use energy from fatty acids and ketones. Animal studies using ketogenic diets for cancer show encouraging results. We tested the diet's safety and feasibility in cancer patients across a broad variety of solid tumors.
Methods: We recruited 17 advanced cancer patients who were not on chemotherapy. They consumed 20 to 40 g of carbohydrates daily with evaluations performed weekly until week 4, then every 4 weeks until 16 weeks. Quality of life questionnaires monitored for tolerability and compliance. Positron emission/computerized tomography was ordered at baseline, 4,8 and 16 weeks. Student t-testing evaluated differences between baseline and last visit scores for quality of life, weight, body mass index, and serum parameters. Correlations between weight loss and serum ketones, glucose, lipids and creatinine were done. Two-tailed unpaired t-testing of the mean weight loss compared responders against non-responders.
Results: Eleven out of seventeen enrolled patients were evaluable. Mean age was 65+/- 11.7 years, weight 203 +/- 4.98 lbs. (92 +/- 2.3 kgs.) and previous treatment failures was 1.7, +/- 0.97. All lost significant weight with hematologic, biochemical and lipid tests remaining stable. Quality of life scores slightly improved. At 4,8 and 16 weeks, six (54.5 %), five (45.4 %) and four (36 %) patients were stable or improved. We observed no correlations between serum glucose, ketones or lipids. Clinical response did not correlate with ketosis or glycemia. Responders (stable disease or partial responders) lost statistically more weight than non-responders. Dietary compliance was difficult. Only three patients continued dieting past 16 weeks. Out of these, two patients developed brain metastases and were on steroids. They survived 80 and 116 weeks respectively. The third patient underwent residual tumor resection and has no disease at 131 weeks.
Conclusions: Modified Atkins diets are safe and feasible in advanced cancer. Quality of life was preserved. Patients who lost at least 10 % of their body weight responded the best. Steroid intake affected optimal ketone and glucose levels. Despite this, survival improved in some melanoma and lung cancer patients. Further studies are recommended.
C1 [Tan-Shalaby, Jocelyn L.; Carrick, Jennifer; Edinger, Krystal; Genovese, Dana; Liman, Andrew D.; Passero, Vida A.; Shah, Rashmikant B.] Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.
[Tan-Shalaby, Jocelyn L.; Edinger, Krystal; Genovese, Dana; Liman, Andrew D.; Passero, Vida A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
RP Tan-Shalaby, JL (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA.; Tan-Shalaby, JL (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
EM jocelyn.tan@va.gov
FU Veterans Research Foundation of Pittsburgh
FX Tammy Cobaugh for her help in drafting the initial trial protocol;
Samantha Bonant, Alanna Caffas and and Sharlene Wylie for research
assistance Becky Englert RN, Lynn Marmarelli RN and Pamela Malicki RN
for patient recruitment and followup; Mary Kay Winkelman for her
secretarial contribution; Joseph Mikolic for statistical analysis;
Mariam Shalaby for proofreading and technical support. I am grateful to
the Veterans Research Foundation of Pittsburgh for their overall support
and confidence in this project. I would like to thank Dr. Thomas
Seyfried, Professor of Biology at Boston College, for his critical
comments and valuable feedback during the editing and revision of the
final manuscript.
NR 28
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U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1743-7075
J9 NUTR METAB
JI Nutr. Metab.
PD AUG 12
PY 2016
VL 13
AR 52
DI 10.1186/s12986-016-0113-y
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DT9CY
UT WOS:000381794300001
PM 27525031
ER
PT J
AU Bazari, H
Palmer, WE
Baron, JM
Armstrong, K
AF Bazari, Hasan
Palmer, William E.
Baron, Jason M.
Armstrong, Katrina
TI Case 24-2016: A 66-Year-Old Man with Malaise, Weakness, and
Hypercalcemia
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ALKALI SYNDROME; MANAGEMENT
C1 [Bazari, Hasan; Armstrong, Katrina] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Palmer, William E.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA.
[Baron, Jason M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Bazari, Hasan; Armstrong, Katrina] Harvard Med Sch, Dept Med, Boston, MA USA.
[Palmer, William E.] Harvard Med Sch, Dept Radiol, Boston, MA USA.
[Baron, Jason M.] Harvard Med Sch, Dept Pathol, Boston, MA USA.
RP Bazari, H (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
FU International Business Machines; GlaxoSmithKline
FX Dr. Bazari reports holding stock in Pfizer; Dr. Baron, receiving grant
support to his institution from International Business Machines; and Dr.
Armstrong, receiving consulting fees from GlaxoSmithKline. No other
potential conflict of interest relevant to this article was reported.
NR 14
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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 AUG 11
PY 2016
VL 375
IS 6
BP 567
EP 577
DI 10.1056/NEJMcpc1503829
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DU4OT
UT WOS:000382193100011
PM 27509105
ER
PT J
AU Ghogawala, Z
Barker, FG
Benzel, EC
AF Ghogawala, Zoher
Barker, Fred G., II
Benzel, Edward C.
TI Fusion Surgery for Lumbar Spinal Stenosis REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID SPONDYLOLISTHESIS
C1 [Ghogawala, Zoher] Lahey Hosp & Med Ctr, Burlington, MA USA.
[Barker, Fred G., II] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Benzel, Edward C.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
RP Ghogawala, Z (reprint author), Lahey Hosp & Med Ctr, Burlington, MA USA.
EM zoher.ghogawala@lahey.org
NR 2
TC 1
Z9 1
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 AUG 11
PY 2016
VL 375
IS 6
BP 600
EP 601
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DU4OT
UT WOS:000382193100021
PM 27517105
ER
PT J
AU Matsumura, J
Monteleone, P
Rosenfield, K
AF Matsumura, Jon
Monteleone, Peter
Rosenfield, Kenneth
TI Stenting versus Surgery for Carotid Stenosis REPLY
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
C1 [Matsumura, Jon] Univ Wisconsin, Madison, WI 53706 USA.
[Monteleone, Peter; Rosenfield, Kenneth] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Matsumura, J (reprint author), Univ Wisconsin, Madison, WI 53706 USA.
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 AUG 11
PY 2016
VL 375
IS 6
BP 603
EP 604
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DU4OT
UT WOS:000382193100027
PM 27509114
ER
PT J
AU Hunter, ZR
Xu, L
Yang, G
Tsakmaklis, N
Vos, JM
Liu, X
Chen, J
Manning, RJ
Chen, JJG
Brodsky, P
Patterson, CJ
Gustine, J
Dubeau, T
Castillo, JJ
Anderson, KC
Munshi, NM
Treon, SP
AF Hunter, Zachary R.
Xu, Lian
Yang, Guang
Tsakmaklis, Nicholas
Vos, Josephine M.
Liu, Xia
Chen, Jie
Manning, Robert J.
Chen, Jiaji G.
Brodsky, Philip
Patterson, Christopher J.
Gustine, Joshua
Dubeau, Toni
Castillo, Jorge J.
Anderson, Kenneth C.
Munshi, Nikhil M.
Treon, Steven P.
TI Transcriptome sequencing reveals a profile that corresponds to genomic
variants in Waldenstrom macroglobulinemia
SO BLOOD
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL; MYD88 L265P; SOMATIC MUTATION;
TUMOR-SUPPRESSOR; MONOCLONAL GAMMOPATHY; NEGATIVE REGULATOR;
MULTIPLE-MYELOMA; DNA METHYLATION; CXCR4 MUTATIONS
AB Whole-genome sequencing has identified highly prevalent somatic mutations including MYD88, CXCR4, and ARID1A in Waldenstrom macroglobulinemia (WM). The impact of these and other somatic mutations on transcriptional regulation in WM remains to be clarified. We performed next-generation transcriptional profiling in 57 WM patients and compared findings to healthy donor B cells. Compared with healthy donors, WM patient samples showed greatly enhanced expression of the VDJ recombination genes DNTT, RAG1, and RAG2, but not AICDA. Genes related to CXCR4 signaling were also upregulated and included CXCR4, CXCL12, and VCAM1 regardless of CXCR4 mutation status, indicating a potential role for CXCR4 signaling in all WM patients. The WM transcriptional profile was equally dissimilar to healthy memory B cells and circulating B cells likely due increased differentiation rather than cellular origin. The profile for CXCR4 mutations corresponded to diminished B-cell differentiation and suppression of tumor suppressors upregulated by MYD88 mutations in a manner associated with the suppression of TLR4 signaling relative to those mutated for MYD88 alone. Promoter methylation studies of top findings failed to explain this suppressive effect but identified aberrant methylation patterns in MYD88 wild-type patients. CXCR4 and MYD88 transcription were negatively correlated, demonstrated allele-specific transcription bias, and, along with CXCL13, were associated with bone marrow disease involvement. Distinct gene expression profiles for patients with wild-type MYD88, mutated ARID1A, familial predisposition to WM, chr6q deletions, chr3q amplifications, and trisomy 4 are also described. The findings provide novel insights into the molecular pathogenesis and opportunities for targeted therapeutic strategies for WM. (Blood. 2016;128(6):827-838)
C1 [Hunter, Zachary R.; Xu, Lian; Yang, Guang; Tsakmaklis, Nicholas; Vos, Josephine M.; Liu, Xia; Chen, Jie; Manning, Robert J.; Chen, Jiaji G.; Brodsky, Philip; Patterson, Christopher J.; Gustine, Joshua; Dubeau, Toni; Castillo, Jorge J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,450 Brookline Ave, Boston, MA 02215 USA.
[Hunter, Zachary R.; Yang, Guang; Castillo, Jorge J.; Anderson, Kenneth C.; Munshi, Nikhil M.; Treon, Steven P.] Harvard Med Sch, Dept Med, Boston, MA 02215 USA.
[Anderson, Kenneth C.; Munshi, Nikhil M.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA.
[Munshi, Nikhil M.] Boston VA Healthcare Syst, Dept Med, West Roxbury, MA USA.
RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, M547,450 Brookline Ave, Boston, MA 02215 USA.
EM steven_treon@dfci.harvard.edu
OI Hunter, Zachary/0000-0002-1689-1691; Castillo, Jorge/0000-0001-9490-7532
FU Leukemia & Lymphoma Society; International Waldenstrom's
Macroglobulinemia Foundation; National Institutes of Health; National
Cancer Institute [5P50CA100707-12]; Orzag Family Fund for WM Research
FX This work was supported by Peter S. Bing, a Translational Research grant
from the Leukemia & Lymphoma Society, a grant from the International
Waldenstrom's Macroglobulinemia Foundation, a National Institutes of
Health, National Cancer Institute Spore 5P50CA100707-12 Research
Development Award, and the Orzag Family Fund for WM Research.
NR 71
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Z9 5
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 AUG 11
PY 2016
VL 128
IS 6
BP 827
EP 838
DI 10.1182/blood-2016-03-708263
PG 12
WC Hematology
SC Hematology
GA DW7KV
UT WOS:000383830500014
PM 27301862
ER
PT J
AU Horvath, S
Gurven, M
Levine, ME
Trumble, BC
Kaplan, H
Allayee, H
Ritz, BR
Chen, B
Lu, AT
Rickabaugh, TM
Jamieson, BD
Sun, D
Li, SX
Chen, W
Quintana-Murci, L
Fagny, M
Kobor, MS
Tsao, PS
Reiner, AP
Edlefsen, KL
Absher, D
Assimes, TL
AF Horvath, Steve
Gurven, Michael
Levine, Morgan E.
Trumble, Benjamin C.
Kaplan, Hillard
Allayee, Hooman
Ritz, Beate R.
Chen, Brian
Lu, Ake T.
Rickabaugh, Tammy M.
Jamieson, Beth D.
Sun, Dianjianyi
Li, Shengxu
Chen, Wei
Quintana-Murci, Lluis
Fagny, Maud
Kobor, Michael S.
Tsao, Philip S.
Reiner, Alexander P.
Edlefsen, Kerstin L.
Absher, Devin
Assimes, Themistocles L.
TI An epigenetic clock analysis of race/ethnicity, sex, and coronary heart
disease
SO GENOME BIOLOGY
LA English
DT Article
DE DNA methylation; Epigenetic clock; Race; Gender; Aging; Coronary heart
disease; Hispanic paradox; Black/white mortality cross-over
ID DNA METHYLATION AGE; HUMAN BRAIN; ALZHEIMERS-DISEASE; TELOMERE LENGTH;
PARKINSONS-DISEASE; AFRICAN-AMERICANS; UNITED-STATES; HUMAN TISSUES;
ALL-CAUSE; T-CELLS
AB Background: Epigenetic biomarkers of aging (the "epigenetic clock") have the potential to address puzzling findings surrounding mortality rates and incidence of cardio-metabolic disease such as: (1) women consistently exhibiting lower mortality than men despite having higher levels of morbidity; (2) racial/ethnic groups having different mortality rates even after adjusting for socioeconomic differences; (3) the black/white mortality cross-over effect in late adulthood; and (4) Hispanics in the United States having a longer life expectancy than Caucasians despite having a higher burden of traditional cardio-metabolic risk factors.
Results: We analyzed blood, saliva, and brain samples from seven different racial/ethnic groups. We assessed the intrinsic epigenetic age acceleration of blood (independent of blood cell counts) and the extrinsic epigenetic aging rates of blood (dependent on blood cell counts and tracks the age of the immune system). In blood, Hispanics and Tsimane Amerindians have lower intrinsic but higher extrinsic epigenetic aging rates than Caucasians. African-Americans have lower extrinsic epigenetic aging rates than Caucasians and Hispanics but no differences were found for the intrinsic measure. Men have higher epigenetic aging rates than women in blood, saliva, and brain tissue.
Conclusions: Epigenetic aging rates are significantly associated with sex, race/ethnicity, and to a lesser extent with CHD risk factors, but not with incident CHD outcomes. These results may help elucidate lower than expected mortality rates observed in Hispanics, older African-Americans, and women.
C1 [Horvath, Steve; Levine, Morgan E.; Lu, Ake T.] Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.
[Horvath, Steve] Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA.
[Gurven, Michael; Trumble, Benjamin C.] Univ Calif Santa Barbara, Dept Anthropol, Santa Barbara, CA 93106 USA.
[Kaplan, Hillard] Univ New Mexico, Dept Anthropol, Albuquerque, NM 87131 USA.
[Allayee, Hooman] Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Allayee, Hooman] Univ Southern Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA.
[Ritz, Beate R.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Chen, Brian] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Rickabaugh, Tammy M.; Jamieson, Beth D.] Univ Calif Los Angeles, AIDS Inst, Dept Med, Div Hematol Oncol, Los Angeles, CA USA.
[Sun, Dianjianyi; Li, Shengxu; Chen, Wei] Tulane Univ, Dept Epidemiol, New Orleans, LA 70112 USA.
[Quintana-Murci, Lluis] CNRS, Inst Pasteur, URA3012, URA3012,Unit Human Evolutionary Genet, F-75015 Paris, France.
[Fagny, Maud] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Fagny, Maud] Dana Farber Canc Inst, Dept Computat Biol & Biostat, Boston, MA 02115 USA.
[Kobor, Michael S.] Univ British Columbia, Ctr Mol Med & Therapeut, Child & Family Res Inst, Vancouver, BC V5Z 4H4, Canada.
[Kobor, Michael S.] Univ British Columbia, Dept Med Genet, Vancouver, BC V5Z 4H4, Canada.
[Tsao, Philip S.; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Tsao, Philip S.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Reiner, Alexander P.] Univ Washington, Fred Hutchinson Canc Res Ctr, Dept Epidemiol, Seattle, WA 98109 USA.
[Edlefsen, Kerstin L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL 35806 USA.
RP Horvath, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Human Genet, Los Angeles, CA 90095 USA.; Horvath, S (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Biostat, Los Angeles, CA 90095 USA.
EM shorvath@mednet.ucla.edu
RI Assimes, Themistocles/D-9696-2015;
OI Assimes, Themistocles/0000-0003-2349-0009; Horvath,
Steve/0000-0002-4110-3589; Fagny, Maud/0000-0002-7740-2521
FU NIH/NHLBI [60442456 BAA23]; National Institutes of Health NIH/NIA
[1U34AG051425-01]; National Heart, Lung, and Blood Institute, National
Institutes of Health, U.S. Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; NIEHS
[RO1ES10544, R21 ES024356]; NIH/NIA [R01AG024119, R56AG02411];
[P30AG10161]; [R01AG17917]; [RF1AG15819]; [R01AG36042]
FX This study was supported by NIH/NHLBI 60442456 BAA23 (Assimes, Absher,
Horvath), National Institutes of Health NIH/NIA 1U34AG051425-01
(Horvath). 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. The PEG data were supported by
NIEHS RO1ES10544 (Ritz) and NIEHS R21 ES024356 (Horvath, Ritz). Gurven
and Trumble were funded by NIH/NIA R01AG024119 and R56AG02411. The
Religious Order study and Rush Memory and Aging Project (brain dataset
6) were funded by P30AG10161, R01AG17917, RF1AG15819, and R01AG36042.
NR 89
TC 4
Z9 4
U1 18
U2 27
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD AUG 11
PY 2016
VL 17
AR 171
DI 10.1186/s13059-016-1030-0
PG 22
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DT8EH
UT WOS:000381721400001
PM 27511193
ER
PT J
AU Garcia-Caceres, C
Quarta, C
Varela, L
Gao, YQ
Gruber, T
Legutko, B
Jastroch, M
Johansson, P
Ninkovic, J
Yi, CX
Thuc, OL
Szigeti-Buck, K
Cai, WK
Meyer, CW
Pfluger, PT
Fernandez, AM
Luquet, S
Woods, SC
Torres-Aleman, I
Kahn, CR
Gotz, M
Horvath, TL
Tschop, MH
AF Garcia-Caceres, Cristina
Quarta, Carmelo
Varela, Luis
Gao, Yuanqing
Gruber, Tim
Legutko, Beata
Jastroch, Martin
Johansson, Pia
Ninkovic, Jovica
Yi, Chun-Xia
Thuc, Ophelia Le
Szigeti-Buck, Klara
Cai, Weikang
Meyer, Carola W.
Pfluger, Paul T.
Fernandez, Ana M.
Luquet, Serge
Woods, Stephen C.
Torres-Aleman, Ignacio
Kahn, C. Ronald
Goetz, Magdalena
Horvath, Tamas L.
Tschoep, Matthias H.
TI Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient
Availability
SO CELL
LA English
DT Article
ID BODY-WEIGHT; NEURONAL DYSFUNCTION; ALZHEIMERS-DISEASE;
ENERGY-METABOLISM; BARRIER; LEPTIN; CELLS; TRANSPORTER; CIRCUITS; MICE
AB We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic proopio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB.
C1 [Garcia-Caceres, Cristina; Quarta, Carmelo; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Yi, Chun-Xia; Thuc, Ophelia Le; Meyer, Carola W.; Pfluger, Paul T.; Tschoep, Matthias H.] Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr HDC, D-85764 Neuherberg, Germany.
[Garcia-Caceres, Cristina; Quarta, Carmelo; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Yi, Chun-Xia; Thuc, Ophelia Le; Meyer, Carola W.; Pfluger, Paul T.; Tschoep, Matthias H.] Helmholtz Zentrum Munchen, German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.
[Garcia-Caceres, Cristina; Quarta, Carmelo; Gao, Yuanqing; Gruber, Tim; Legutko, Beata; Jastroch, Martin; Yi, Chun-Xia; Thuc, Ophelia Le; Meyer, Carola W.; Pfluger, Paul T.; Tschoep, Matthias H.] Tech Univ Munich, Div Metab Dis, D-80333 Munich, Germany.
[Varela, Luis; Szigeti-Buck, Klara; Horvath, Tamas L.] Yale Univ, Sch Med, Comparat Med Sect, Program Integrat Cell Signaling & Neurobiol Metab, New Haven, CT 06520 USA.
[Johansson, Pia; Ninkovic, Jovica; Goetz, Magdalena] Helmholtz Zentrum Munchen, Inst Stem Cell Res Ctr, D-85764 Neuherberg, Germany.
[Johansson, Pia; Ninkovic, Jovica; Goetz, Magdalena] Ludwigs Maximilians Univ, Biomed Ctr, Physiol Genom, D-80336 Munich, Germany.
[Johansson, Pia; Ninkovic, Jovica; Goetz, Magdalena] Ludwigs Maximilians Univ, Biomed Ctr, 7SYNERGY, Excellence Cluster Syst Neurol, D-80336 Munich, Germany.
[Cai, Weikang; Kahn, C. Ronald] Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Integrat Physiol & Metab, Boston, MA 02115 USA.
[Cai, Weikang; Kahn, C. Ronald] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Cai, Weikang; Kahn, C. Ronald] Harvard Med Sch, Boston, MA 02115 USA.
[Fernandez, Ana M.; Torres-Aleman, Ignacio] CSIC, Inst Cajal, E-28002 Madrid, Spain.
[Luquet, Serge] Univ Paris Diderot, Sorbonne Paris Cite, Unite Biol Fonct & Adaptat, CNRS UMR 8251, F-75205 Paris, France.
[Woods, Stephen C.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, 2170 Galbraith Ave, Cincinnati, OH 45237 USA.
RP Tschop, MH (reprint author), Helmholtz Zentrum Munchen, Helmholtz Diabet Ctr HDC, D-85764 Neuherberg, Germany.; Tschop, MH (reprint author), Helmholtz Zentrum Munchen, German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany.; Tschop, MH (reprint author), Tech Univ Munich, Div Metab Dis, D-80333 Munich, Germany.
EM tschoep@helmholtz-muenchen.de
RI Garcia-Caceres, Cristina/O-6601-2016; Yi, Chun-Xia/J-4068-2016;
OI Garcia-Caceres, Cristina/0000-0001-6376-9448; Yi,
Chun-Xia/0000-0003-1184-4615; Torres Aleman,
Ignacio/0000-0001-8107-7947; luquet, serge/0000-0001-8668-6645
FU Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic
Diseases; Humboldt Foundation; Initiative and Networking Fund of the
Helmholtz Association; Deutsches Zentrum fur DiabetesForschung (DZD);
Institute of Advanced Studies of Technische Universitat Munchen (IAS-TUM
Hans-Fischer); DFG [SFB 1123, SFB 870, SFB 1757]
FX The authors thank Heicko Lickert and Silke Morin for helpful discussion
and support and Lewis Norris, Clarita Mergen, Veronica Casquero Garcia,
Olavi Jarvinen, and Nicole Wiegert for excellent technical assistance.
This work was funded, in part, by the Helmholtz Alliance ICEMED -
Imaging and Curing Environmental Metabolic Diseases, the Humboldt
Foundation (to M.H.T.), through the Initiative and Networking Fund of
the Helmholtz Association and Deutsches Zentrum fur DiabetesForschung
(DZD). This work also received funding from the Institute of Advanced
Studies of Technische Universitat Munchen (IAS-TUM Hans-Fischer Senior
Fellowship to T.L.H.) and from DFG funding (SFB 1123 to M.H.T; SFB 870
and SPP 1757 to M.G.).
NR 40
TC 12
Z9 12
U1 22
U2 25
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 AUG 11
PY 2016
VL 166
IS 4
BP 867
EP 880
DI 10.1016/j.cell.2016.07.028
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU5NO
UT WOS:000382258700011
PM 27518562
ER
PT J
AU Goncalves, KA
Silberstein, L
Li, SP
Severe, N
Hu, MFG
Yang, HL
Scadden, DT
Hu, GF
AF Goncalves, Kevin A.
Silberstein, Lev
Li, Shuping
Severe, Nicolas
Hu, Miaofen G.
Yang, Hailing
Scadden, David T.
Hu, Guo-fu
TI Angiogenin Promotes Hematopoietic Regeneration by Dichotomously
Regulating Quiescence of Stem and Progenitor Cells
SO CELL
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSFER-RNA HALVES; SELF-RENEWAL;
GENE-EXPRESSION; CORD BLOOD; PROLIFERATION; MAINTENANCE; STRESS;
IDENTIFICATION; EXPANSION
AB Regulation of stem and progenitor cell populations is critical in the development, maintenance, and regeneration of tissues. Here, we define a novelmechanism by which a niche-secreted RNase, angiogenin (ANG), distinctively alters the functional characteristics of primitive hematopoietic stem/progenitor cells (HSPCs) compared with lineage-committed myeloid-restricted progenitor (MyePro) cells. Specifically, ANG reduces the proliferative capacity of HSPC while simultaneously increasing proliferation of MyePro cells. Mechanistically, ANG induces cell-type-specific RNA-processing events: tRNAderived stress-induced small RNA (tiRNA) generation in HSPCs and rRNA induction in MyePro cells, leading to respective reduction andincrease inprotein synthesis. Recombinant ANG protein improves survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPCs in transplantation. Thus, ANG plays a non-cell-autonomous role in regulation of hematopoiesis by simultaneously preserving HSPC stemness and promoting MyePro proliferation. These cell-type-specific functions of ANG suggest considerable therapeutic potential.
C1 [Goncalves, Kevin A.; Li, Shuping; Hu, Miaofen G.; Yang, Hailing; Hu, Guo-fu] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA.
[Goncalves, Kevin A.; Yang, Hailing; Hu, Guo-fu] Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Cellular & Mol Physiol, Boston, MA 02111 USA.
[Silberstein, Lev; Severe, Nicolas; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02445 USA.
[Silberstein, Lev; Severe, Nicolas; Scadden, David T.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Silberstein, Lev; Severe, Nicolas; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
RP Hu, GF (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA.; Hu, GF (reprint author), Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Cellular & Mol Physiol, Boston, MA 02111 USA.; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02445 USA.; Scadden, DT (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Scadden, DT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
EM david_scadden@harvard.edu; guo-fu.hu@tufts.edu
FU NIH [F31HL128127, R01DK107784, R01HL096372, R01CA105241, R01NS065237];
Sackler Dean's Fellow award; Sackler Families Collaborative Cancer
Biology award; Leukemia & Lymphoma Research UK/Leukemia & Lymphoma
Society fellowships; NSFC [81272674]; DoD [W81XWH-15-1-0207]
FX We thank Kathryn Folz-Donahue, Steven Kwok, Allen Parmalee, Laura
Prickett-Rice, and Meredith Weglarz for assistance with cell sorting and
Dr. Alenka Lovy for assistance with microscopy. Aged WT mice were kindly
provided by NIH/NIA, and Osx and Ocn cDNA were gifts kindly provided by
Dr. Deepak Balani and Dr. Henry Kronenberg. This work was supported by
NIH fellowship F31HL128127 (to K.A.G.), a Sackler Dean's Fellow award
(to K.A.G.), a Sackler Families Collaborative Cancer Biology award (to
K.A.G. and G.H.), Leukemia & Lymphoma Research UK/Leukemia & Lymphoma
Society fellowships (to L.S.), NSFC grant #81272674 (to S.L.), NIH
grants R01DK107784 and R01HL096372 (to D.T.S.), DoD Award
W81XWH-15-1-0207 (to G.H.), and NIH grants R01CA105241 and R01NS065237
(to G.H.). D.T.S. is a consultant and stockholder for Magenta
Therapeutics and Fate Therapeutics and a consultant for Bone
Therapeutics, Teva Pharmaceutical Industries, Dr. Reddy's Laboratories,
and Apotex. G.H. is a consultant and stockholder of Fuyuan
Biopharmaceuticals and Karma Pharmaceuticals.
NR 45
TC 4
Z9 4
U1 9
U2 11
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 AUG 11
PY 2016
VL 166
IS 4
BP 894
EP 906
DI 10.1016/j.cell.2016.06.042
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DU5NO
UT WOS:000382258700013
PM 27518564
ER
PT J
AU Yagyu, S
Iehara, T
Tanaka, S
Gotoh, T
Misawa-Furihata, A
Sugimoto, T
London, WB
Hogarty, MD
Teramukai, S
Nakagawara, A
Hiyama, E
Maris, JM
Hosoi, H
AF Yagyu, Shigeki
Iehara, Tomoko
Tanaka, Shiro
Gotoh, Takahiro
Misawa-Furihata, Akiko
Sugimoto, Tohru
London, Wendy B.
Hogarty, Michael D.
Teramukai, Satoshi
Nakagawara, Akira
Hiyama, Eiso
Maris, John M.
Hosoi, Hajime
TI Serum-Based Quantification of MYCN Gene Amplification in Young Patients
with Neuroblastoma: Potential Utility as a Surrogate Biomarker for
Neuroblastoma
SO PLOS ONE
LA English
DT Article
ID CHILDRENS-ONCOLOGY-GROUP; LOCALIZED NEUROBLASTOMA; SPONTANEOUS
REGRESSION; CANCER PATIENTS; RISK GROUP; PROGNOSIS; INFANTS; DNA;
STRATIFICATION; CLASSIFICATION
AB We previously developed a method for determining MYCN gene amplification status using cell-free DNA fragments released from cancer cells into the blood of patients with neuroblastoma (NB). Here, we analyzed the relationship between MYCN amplification (MNA) status and neuroblastoma prognosis. We screened serum samples from 151 patients with NB for MNA, using real-time quantitative PCR, and compared the results with MYCN status determined using paired tumor samples. We additionally investigated whether MNA status correlates with patient survival. When a cut-off value of 5 was used, serum-based MNA analysis was found to show good sensitivity (86%) and very high specificity (95%). The sensitivities for stage 1 and 2 might be acceptable, even though it is not as good as for stage 3 and 4 (67% for stage 1 and 2, 92% for stage 3, and 87% for stage 4). MNA status correlated with overall survival in our cohort of 82 patients, with survival data available (p < 0.01). The hazard ratio of MNA status was 4.98 in patients diagnosed at less than 18 months of age (95% confidence interval, 1.00-24.78), and 1.41 (95% confidence interval, 0.63-3.14) for those diagnosed at 18 months of age or older. Serum-based MNA analysis is rapid and non-invasive compared with tumor-based MNA analysis, and has potential to predict tumor MNA status. There is still a room to improve the sensitivity of the test for tumors of stages 1 and 2, nonetheless this assay might help to determine therapeutic strategies prior to tumor biopsy, especially for patients with a life-threatening condition, as well as for patients of less than 18 months of age whose risk-grouping and treatment allocation depends on their MNA status.
C1 [Yagyu, Shigeki; Iehara, Tomoko; Gotoh, Takahiro; Misawa-Furihata, Akiko; Sugimoto, Tohru; Hosoi, Hajime] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Pediat, Kyoto, Japan.
[Tanaka, Shiro] Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Kyoto, Japan.
[London, Wendy B.] Harvard Med Sch, Dana Farber Canc Inst, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA.
[Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Hogarty, Michael D.; Maris, John M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
[Hogarty, Michael D.; Maris, John M.] Univ Penn, Philadelphia, PA 19104 USA.
[Teramukai, Satoshi] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Biostat, Kyoto, Japan.
[Nakagawara, Akira] Chiba Canc Ctr, Div Biochem & Innovat Canc Therapeut, Chiba, Japan.
[Nakagawara, Akira] Saga Med Canc KOSEIKAN, Saga, Japan.
[Hiyama, Eiso] Hiroshima Univ, Hiroshima Univ Hosp, Nat Sci Ctr Basic Res & Dev, Dept Pediat Surg, Hiroshima, Japan.
RP Hosoi, H (reprint author), Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Pediat, Kyoto, Japan.
EM hhosoi@koto.kpu-m.ac.jp
FU Japan Society for the Promotion of Science (JSPS) KAKENHI [25253095];
Practical Research for Innovative Cancer Control from Japan Agency for
Medical Research and development (AMED); Kyoto-Funding for Innovation in
Health-related RD Fields Grant [88]; Adaptable and Seamless Technology
Transfer Program through Target-driven RD [AS221Z03404F]
FX This work was supported by the Japan Society for the Promotion of
Science (JSPS) KAKENHI, Grant Number 25253095,
(https://www.jsps.go.jp/english/e-grants/); the Practical Research for
Innovative Cancer Control from Japan Agency for Medical Research and
development (AMED), (http://www.amed.go.jp/en/); Kyoto-Funding for
Innovation in Health-related R&D Fields Grant Number 88,
(http://www.astem.or.jp/english/); Adaptable and Seamless Technology
Transfer Program through Target-driven R&D, Grant Number AS221Z03404F,
(http://www.jst.go.jp/tt/EN/univ-ip/a-step.html). The funders had no
role in study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 32
TC 0
Z9 0
U1 0
U2 0
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 AUG 11
PY 2016
VL 11
IS 8
AR e0161039
DI 10.1371/journal.pone.0161039
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3KY
UT WOS:000381381100114
PM 27513929
ER
PT J
AU Batalha, VL
Ferreira, DG
Coelho, JE
Valadas, JS
Gomes, R
Temido-Ferreira, M
Shmidt, T
Baqi, Y
Buee, L
Muller, CE
Hamdane, M
Outeiro, TF
Bader, M
Meijsing, SH
Sadri-Vakili, G
Blum, D
Lopes, LV
AF Batalha, Vania L.
Ferreira, Diana G.
Coelho, Joana E.
Valadas, Jorge S.
Gomes, Rui
Temido-Ferreira, Mariana
Shmidt, Tatiana
Baqi, Younis
Buee, Luc
Mueller, Christa E.
Hamdane, Malika
Outeiro, Tiago F.
Bader, Michael
Meijsing, Sebastiaan H.
Sadri-Vakili, Ghazaleh
Blum, David
Lopes, Luisa V.
TI The caffeine-binding adenosine A(2A) receptor induces age-like HPA-axis
dysfunction by targeting glucocorticoid receptor function
SO SCIENTIFIC REPORTS
LA English
DT Article
ID LONG-TERM-POTENTIATION; PROTEIN-KINASE-A; ALZHEIMERS-DISEASE;
GENE-EXPRESSION; SYNAPTIC-TRANSMISSION; SALIVARY CORTISOL; RESPONSE
ELEMENTS; MEMORY DEFICITS; TAU PATHOLOGY; UP-REGULATION
AB Caffeine is associated with procognitive effects in humans by counteracting overactivation of the adenosine A(2A) receptor (A(2A)R), which is upregulated in the human forebrain of aged and Alzheimer's disease (AD) patients. We have previously shown that an anti-A(2A)R therapy reverts age-like memory deficits, by reestablishment of the hypothalamic-pituitary-adrenal (HPA) axis feedback and corticosterone circadian levels. These observations suggest that A(2A)R over-activation and glucocorticoid dysfunction are key events in age-related hippocampal deficits; but their direct connection has never been explored. We now show that inducing A(2A)R overexpression in an aging-like profile is sufficient to trigger HPA-axis dysfunction, namely loss of plasmatic corticosterone circadian oscillation, and promotes reduction of GR hippocampal levels. The synaptic plasticity and memory deficits triggered by finally, we demonstrate that A(2A)R act on GR nuclear translocation and GR-dependent transcriptional regulation. We provide the first demonstration that A(2A)R is a major regulator of GR function and that this functional interconnection may be a trigger to age-related memory deficits. This supports the idea that the procognitive effects of A(2A)R antagonists, namely caffeine, on Alzheimer's and age-related cognitive impairments may rely on its ability to modulate GR actions.
C1 [Batalha, Vania L.; Ferreira, Diana G.; Coelho, Joana E.; Valadas, Jorge S.; Gomes, Rui; Temido-Ferreira, Mariana; Lopes, Luisa V.] Univ Lisbon, Fac Med Lisboa, Inst Mol Med, Lisbon, Portugal.
[Batalha, Vania L.; Meijsing, Sebastiaan H.] Max Planck Inst Mol Genet, Berlin, Germany.
[Ferreira, Diana G.; Outeiro, Tiago F.] Univ Med Ctr Goettingen, Dept NeuroDegenerat & Restorat Res, Waldweg 33, D-37073 Gottingen, Germany.
[Ferreira, Diana G.] Univ Porto, Fac Med Porto, Inst Farmacol & Terapeut, Oporto, Portugal.
[Gomes, Rui] Univ Lisbon, Fac Ciencias Lisboa, Lisbon, Portugal.
[Shmidt, Tatiana] Max Delbrck Ctr Mol Med MDC, Berlin, Germany.
[Baqi, Younis; Mueller, Christa E.] Univ Bonn, PharmaCtr Bonn, Inst Pharmazeut, Pharmazeut Chem 1, Bonn, Germany.
[Baqi, Younis] Sultan Qaboos Univ, Fac Sci, Dept Chem, Muscat, Oman.
[Buee, Luc; Hamdane, Malika; Blum, David] Univ Lille, CHU Lille, INSERM, Alzheimer & Tauopathies,UMR S 1172, Lille, France.
[Outeiro, Tiago F.] Max Planck Inst Expt Med, Gottingen, Germany.
[Outeiro, Tiago F.] CEDOC, Ctr Estudos Doencas Cronicas, Lisbon, Portugal.
[Bader, Michael] Charite, Berlin, Germany.
[Bader, Michael] Univ Lubeck, Inst Biol, Lubeck, Germany.
[Sadri-Vakili, Ghazaleh] Massachusetts Gen Hosp, MassGeneral Inst Neurodegenerat Dis, Boston, MA USA.
[Valadas, Jorge S.] VIB, Ctr Biol Dis, Leuven, Belgium.
[Valadas, Jorge S.] Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium.
[Valadas, Jorge S.] Leuven Res Inst Neurosci & Dis LIND, Leuven, Belgium.
RP Lopes, LV (reprint author), Univ Lisbon, Fac Med Lisboa, Inst Mol Med, Lisbon, Portugal.; Blum, D (reprint author), Univ Lille, CHU Lille, INSERM, Alzheimer & Tauopathies,UMR S 1172, Lille, France.
EM david.blum@inserm.fr; lvlopes@medicina.ulisboa.pt
RI Gomes, Rui /M-1803-2015; Blum, David/E-9901-2016; Muller,
Christa/C-7748-2014;
OI Gomes, Rui /0000-0002-7242-6540; Blum, David/0000-0001-5691-431X;
Muller, Christa/0000-0002-0013-6624; Baqi, Younis/0000-0002-9659-8419
FU Fundacao para a Ciencia e Tecnologia [PTDC-099853/2009]; EMBO fellowship
(Harvard Medical School-GSV lab-exchange period); DFG Center for
Nanoscale Microscopy and Molecular Physiology of the Brain; LabEx
(excellence laboratory) DISTALZ (Development of Innovative Strategies
for a Transdisciplinary approach to Alzheimer's disease); Inserm; CNRS;
Universite Lille 2; Region Nord/Pas-de-Calais; DN2M; ANR (ADORATAU); FUI
MEDIALZ; LECMA/Alzheimer Forschung Initiative (AFI); PHC FCT/Pessoa
program; international exchange program (AAP Internationalisation / LIA)
- University of Lille
FX The authors acknowledge J. Baiao for technical assistance in the animal
house and C. Batalha for the figures layout. VLB and DGF were supported
by a grant from Fundacao para a Ciencia e Tecnologia and an EMBO
fellowship (Harvard Medical School-GSV lab-exchange period); LVL is an
Investigator FCT, funded by Fundacao para a Ciencia e Tecnologia
(PTDC-099853/2009). TFO is supported by the DFG Center for Nanoscale
Microscopy and Molecular Physiology of the Brain. MH, LB and DB thank
the following supports: LabEx (excellence laboratory) DISTALZ
(Development of Innovative Strategies for a Transdisciplinary approach
to Alzheimer's disease), Inserm, CNRS, Universite Lille 2, Region
Nord/Pas-de-Calais, DN2M, ANR (ADORATAU) and FUI MEDIALZ. DB, CEM and YB
are grateful for support by the LECMA/Alzheimer Forschung Initiative
(AFI). DB and LVL were recipients of PHC FCT/Pessoa program and are
currently recipients of an international exchange program (AAP
Internationalisation / LIA) funded by the University of Lille.
NR 68
TC 0
Z9 0
U1 6
U2 12
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 AUG 11
PY 2016
VL 6
AR 31493
DI 10.1038/srep31493
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT0QW
UT WOS:000381189100001
PM 27510168
ER
PT J
AU Kiesewetter, I
Schulz, C
Bausewein, C
Fountain, R
Schmitz, A
AF Kiesewetter, Isabel
Schulz, Christian
Bausewein, Claudia
Fountain, Rita
Schmitz, Andrea
TI Patients' perception of types of errors in palliative care - results
from a qualitative interview study
SO BMC PALLIATIVE CARE
LA English
DT Article
DE Error; Medical error; Palliative care; Patient's perspective
ID MEDICAL ERRORS; ADVERSE EVENTS; HEALTH-CARE; HOSPITALIZED-PATIENTS;
SAFETY; PHYSICIANS; ATTITUDES; CRITERIA
AB Background: Medical errors have been recognized as a relevant public health concern and research efforts to improve patient safety have increased. In palliative care, however, studies on errors are rare and mainly focus on quantitative measures. We aimed to explore how palliative care patients perceive and think about errors in palliative care and to generate an understanding of patients' perception of errors in that specialty.
Methods: A semistructured qualitative interview study was conducted with patients who had received at least 1 week of palliative care in an inpatient or outpatient setting. All interviews were transcribed verbatim and analysed according to qualitative content analysis.
Results: Twelve patients from two centers were interviewed (7 women, median age 63.5 years, range 22-90 years). Eleven patients suffered from a malignancy. Days in palliative care ranged from 10 to 180 days (median 28 days). 96 categories emerged which were summed up under 11 umbrella terms definition, difference, type, cause, consequence, meaning, recognition, handling, prevention, person causing and affected person. A deductive model was developed assigning umbrella terms to error-theory-based factor levels (definition, type and process-related factors). 23 categories for type of error were identified, including 12 categories that can be considered as palliative care specific. On the level of process-related factors 3 palliative care specific categories emerged (recognition, meaning and consequence of errors).
Conclusion: From the patients' perspective, there are some aspects of errors that could be considered as specific to palliative care. As the results of our study suggest, these palliative care-specific aspects seem to be very important from the patients' point of view and should receive further investigation. Moreover, the findings of this study can serve as a guide to further assess single aspects or categories of errors in palliative care in future research.
C1 [Kiesewetter, Isabel] Univ Munich, Dept Anaesthesiol, Munich Univ Hosp, Munich, Germany.
[Kiesewetter, Isabel; Bausewein, Claudia] Univ Munich, Dept Palliat Med, Munich Univ Hosp, Munich, Germany.
[Schulz, Christian] Kings Coll London, Inst Psychiat Psychol & Neurosci, Maudsley Training Programme, London, England.
[Fountain, Rita] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Schmitz, Andrea] Heinrich Heine Univ Hosp Dsseldorf, Interdisciplinary Ctr Palliat Med, Dusseldorf, Germany.
[Schmitz, Andrea] LVR Clin Psychiat Psychosomat & Psychotherapy Chi, Viersen, Germany.
RP Kiesewetter, I (reprint author), Univ Munich, Dept Anaesthesiol, Munich Univ Hosp, Munich, Germany.; Kiesewetter, I (reprint author), Univ Munich, Dept Palliat Med, Munich Univ Hosp, Munich, Germany.
EM Isabel.Kiesewetter@med.uni-muenchen.de
FU Dr. Werner Jackstadt Foundation
FX Many thanks to the Dr. Werner Jackstadt Foundation, that supported the
first author in her master studies of which the present project was part
of.
NR 34
TC 0
Z9 0
U1 5
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1472-684X
J9 BMC PALLIAT CARE
JI BMC Palliat. Care
PD AUG 11
PY 2016
VL 15
AR 75
DI 10.1186/s12904-016-0141-4
PG 12
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DT6DB
UT WOS:000381572100001
PM 27515997
ER
PT J
AU Nierhaus, T
Pach, D
Huang, WJ
Long, XY
Napadow, V
Roll, S
Liang, FR
Pleger, B
Villringer, A
Witt, CM
AF Nierhaus, Till
Pach, Daniel
Huang, Wenjing
Long, Xiangyu
Napadow, Vitaly
Roll, Stephanie
Liang, Fanrong
Pleger, Burkhard
Villringer, Arno
Witt, Claudia M.
TI Difficulties Choosing Control Points in Acupuncture Research. Response:
Commentary: Differential Cerebral Response, Measured with Both an EEG
and fMRI, to Somatosensory Stimulation of a Single Acupuncture Point vs.
Two Non-Acupuncture Points
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Editorial Material
DE somatosensory stimulation; functional magnetic resonance imaging (fMRI);
electroencephalography (EEG); acupuncture; background rhythm; functional
connectivity
C1 [Nierhaus, Till; Villringer, Arno] Charite Univ Med Berlin, Mind Brain Inst, Berlin Sch Mind & Brain, Berlin, Germany.
[Nierhaus, Till; Villringer, Arno] Humboldt Univ, Berlin, Germany.
[Nierhaus, Till; Long, Xiangyu; Pleger, Burkhard; Villringer, Arno] Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany.
[Pach, Daniel; Huang, Wenjing; Roll, Stephanie; Witt, Claudia M.] Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany.
[Huang, Wenjing; Liang, Fanrong] Chengdu Univ Tradit Chinese Med, Acupuncture Moxibust & Tuina Sch, Chengdu, Peoples R China.
[Napadow, Vitaly] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[Napadow, Vitaly] Logan Univ, Dept Radiol, Chesterfield, MO USA.
[Witt, Claudia M.] Univ Zurich Hosp, Inst Complementary & Integrat Med, Zurich, Switzerland.
RP Nierhaus, T (reprint author), Charite Univ Med Berlin, Mind Brain Inst, Berlin Sch Mind & Brain, Berlin, Germany.; Nierhaus, T (reprint author), Humboldt Univ, Berlin, Germany.; Nierhaus, T (reprint author), Max Planck Inst Human Cognit & Brain Sci, Dept Neurol, Leipzig, Germany.
EM till.nierhaus@fu-berlin.de
NR 14
TC 1
Z9 1
U1 7
U2 7
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD AUG 11
PY 2016
VL 10
AR 404
DI 10.3389/fnhum.2016.00404
PG 3
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA DT2ZZ
UT WOS:000381351600001
PM 27562659
ER
PT J
AU Roemer, MGM
Advani, RH
Ligon, AH
Natkunam, Y
Redd, RA
Homer, H
Connelly, CF
Sun, HH
Daadi, SE
Freeman, GJ
Armand, P
Chapuy, B
de Jong, D
Hoppe, RT
Neuberg, DS
Rodig, SJ
Shipp, MA
AF Roemer, Margaretha G. M.
Advani, Ranjana H.
Ligon, Azra H.
Natkunam, Yasodha
Redd, Robert A.
Homer, Heather
Connelly, Courtney F.
Sun, Heather H.
Daadi, Sarah E.
Freeman, Gordon J.
Armand, Philippe
Chapuy, Bjoern
de Jong, Daphne
Hoppe, Richard T.
Neuberg, Donna S.
Rodig, Scott J.
Shipp, Margaret A.
TI PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma
and Predict Outcome
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID B-CELL LYMPHOMA; REED-STERNBERG CELLS; PHASE-III TRIAL; STANFORD-V;
EXPRESSION; RADIOTHERAPY; IMBALANCES; INTERGROUP; RECURRENT; BLOCKADE
AB Purpose
Classical Hodgkin lymphomas (cHLs) include small numbers of malignant Reed-Sternberg cells within an extensive but ineffective inflammatory/immune cell infiltrate. In cHL, chromosome 9p24.1/PD-L1/PD-L2 alterations increase the abundance of the PD-1 ligands, PD-L1 and PD-L2, and their further induction through Janus kinase 2-signal transducers and activators of transcription signaling. The unique composition of cHL limits its analysis with high-throughput genomic assays. Therefore, the precise incidence, nature, and prognostic significance of PD-L1/PD-L2 alterations in cHL remain undefined.
Methods
We used a fluorescent in situ hybridization assay to evaluate CD274/PD-L1 and PDCD1LG2/PD-L2 alterations in 108 biopsy specimens from patients with newly diagnosed cHL who were treated with the Stanford V regimen and had long-term follow-up. In each case, the frequency and magnitude of 9p24.1 alterations-polysomy, copy gain, and amplification-were determined, and the expression of PD-L1 and PD-L2 was evaluated by immunohistochemistry. We also assessed the association of 9p24.1 alterations with clinical parameters, which included stage (early stage I/II favorable risk, early stage unfavorable risk, advanced stage [AS] III/IV) and progression-free survival (PFS).
Results
Ninety-seven percent of all evaluated cHLs had concordant alterations of the PD-L1 and PD-L2 loci (polysomy, 5% [five of 108]; copy gain, 56% [61 of 108]; amplification, 36% [39 of 108]). There was an association between PD-L1 protein expression and relative genetic alterations in this series. PFS was significantly shorter for patients with 9p24.1 amplification, and the incidence of 9p24.1 amplification was increased in patients with AS cHL.
Conclusion
PD-L1/PD-L2 alterations are a defining feature of cHL. Amplification of 9p24.1 is more common in patients with AS disease and associated with shorter PFS in this series. Further analyses of 9p24.1 alterations in patients treated with standard cHL induction regimens or checkpoint blockade are warranted. (C) 2016 by American Society of Clinical Oncology
C1 [Roemer, Margaretha G. M.; Redd, Robert A.; Homer, Heather; Connelly, Courtney F.; Freeman, Gordon J.; Armand, Philippe; Chapuy, Bjoern; Neuberg, Donna S.; Shipp, Margaret A.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
[Ligon, Azra H.; Homer, Heather; Rodig, Scott J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Roemer, Margaretha G. M.; de Jong, Daphne] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Advani, Ranjana H.; Natkunam, Yasodha; Daadi, Sarah E.; Hoppe, Richard T.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA.
RP Shipp, MA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA.
EM margaret_shipp@dfci.harvard.edu
FU National Institutes of Health [R01 CA161026]; Miller Family Fund
FX Supported by National Institutes of Health Grant No. R01 CA161026 and
the Miller Family Fund (M.A.S.).
NR 26
TC 23
Z9 23
U1 4
U2 4
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 AUG 10
PY 2016
VL 34
IS 23
BP 2690
EP +
DI 10.1200/JCO.2016.66.4482
PG 15
WC Oncology
SC Oncology
GA DU8MF
UT WOS:000382467000004
PM 27069084
ER
PT J
AU Lesokhin, AM
Ansell, SM
Armand, P
Scott, EC
Halwani, A
Gutierrez, M
Millenson, MM
Cohen, AD
Schuster, SJ
Lebovic, D
Dhodapkar, M
Avigan, D
Chapuy, B
Ligon, AH
Freeman, GJ
Rodig, SJ
Cattry, D
Zhu, LL
Grosso, JF
Garelik, MBB
Shipp, MA
Borrello, I
Timmerman, J
AF Lesokhin, Alexander M.
Ansell, Stephen M.
Armand, Philippe
Scott, Emma C.
Halwani, Ahmad
Gutierrez, Martin
Millenson, Michael M.
Cohen, Adam D.
Schuster, Stephen J.
Lebovic, Daniel
Dhodapkar, Madhav
Avigan, David
Chapuy, Bjoern
Ligon, Azra H.
Freeman, Gordon J.
Rodig, Scott J.
Cattry, Deepika
Zhu, Lili
Grosso, Joseph F.
Garelik, M. Brigid Bradley
Shipp, Margaret A.
Borrello, Ivan
Timmerman, John
TI Nivolumab in Patients With Relapsed or Refractory Hematologic
Malignancy: Preliminary Results of a Phase Ib Study
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID B-CELL LYMPHOMA; RESPONSE CRITERIA; ADVANCED MELANOMA; MULTIPLE-MYELOMA;
B7-H1 PD-L1; EXPRESSION; CANCER; BLOCKADE; IPILIMUMAB; ANTIBODY
AB Purpose
Cancer cells can exploit the programmed death-1 (PD-1) immune checkpoint pathway to avoid immune surveillance by modulating T-lymphocyte activity. In part, this may occur through overexpression of PD-1 and PD-1 pathway ligands (PD-L1 and PD-L2) in the tumor microenvironment. PD-1 blockade has produced significant antitumor activity in solid tumors, and similar evidence has emerged in hematologic malignancies.
Methods
In this phase I, open-label, dose-escalation, cohort-expansion study, patients with relapsed or refractory B-cell lymphoma, T-cell lymphoma, and multiple myeloma received the anti-PD-1 monoclonal antibody nivolumab at doses of 1 or 3 mg/kg every 2 weeks. This study aimed to evaluate the safety and efficacy of nivolumab and to assess PD-L1/PD-L2 locus integrity and protein expression.
Results
Eighty-one patients were treated (follicular lymphoma, n = 10; diffuse large B-cell lymphoma, n = 11; other B-cell lymphomas, n = 10; mycosis fungoides, n = 13; peripheral T-cell lymphoma, n = 5; other T-cell lymphomas, n = 5; multiple myeloma, n = 27). Patients had received a median of three (range, one to 12) prior systemic treatments. Drug-related adverse events occurred in 51 (63%) patients, and most were grade 1 or 2. Objective response rates were 40%, 36%, 15%, and 40% among patients with follicular lymphoma, diffuse large B-cell lymphoma, mycosis fungoides, and peripheral T-cell lymphoma, respectively. Median time of follow-up observation was 66.6 weeks (range, 1.6 to 132.0+ weeks). Durations of response in individual patients ranged from 6.0 to 81.6+ weeks.
Conclusion
Nivolumab was well tolerated and exhibited antitumor activity in extensively pretreated patients with relapsed or refractory B-and T-cell lymphomas. Additional studies of nivolumab in these diseases are ongoing. (C) 2016 by American Society of Clinical Oncology
C1 [Lesokhin, Alexander M.; Cattry, Deepika] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
[Lesokhin, Alexander M.] Weill Cornell Med Coll, New York, NY USA.
[Ansell, Stephen M.] Mayo Clin, Rochester, MN USA.
[Armand, Philippe; Chapuy, Bjoern; Freeman, Gordon J.; Rodig, Scott J.; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Ligon, Azra H.; Rodig, Scott J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Scott, Emma C.] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Halwani, Ahmad] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA.
[Gutierrez, Martin] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Zhu, Lili; Grosso, Joseph F.; Garelik, M. Brigid Bradley] Bristol Myers Squibb, Princeton, NJ USA.
[Millenson, Michael M.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Cohen, Adam D.; Schuster, Stephen J.] Univ Penn, Philadelphia, PA 19104 USA.
[Lebovic, Daniel] Univ Michigan, Ann Arbor, MI 48109 USA.
[Dhodapkar, Madhav] Yale Canc Ctr, New Haven, CT USA.
[Borrello, Ivan] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Timmerman, John] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Lesokhin, AM (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
EM lesokhia@mskcc.org
FU National Institutes of Health [U54CA163125, P01AI056299, R01CA161026];
Miller Fund
FX Supported by Bristol-Myers Squibb, grants from the National Institutes
of Health (U54CA163125 and P01AI056299 to G.J.F. and R01CA161026 to
M.A.S.), and a grant from the Miller Fund (to M.A.S.).
NR 25
TC 35
Z9 36
U1 12
U2 13
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 AUG 10
PY 2016
VL 34
IS 23
BP 2698
EP +
DI 10.1200/JCO.2015.65.9789
PG 10
WC Oncology
SC Oncology
GA DU8MF
UT WOS:000382467000005
PM 27269947
ER
PT J
AU Preston, MA
Batista, JL
Wilson, KM
Carlsson, SV
Gerke, T
Sjoberg, DD
Dahl, DM
Sesso, HD
Feldman, AS
Gann, PH
Kibel, AS
Vickers, AJ
Mucci, LA
AF Preston, Mark A.
Batista, Julie L.
Wilson, Kathryn M.
Carlsson, Sigrid V.
Gerke, Travis
Sjoberg, Daniel D.
Dahl, Douglas M.
Sesso, Howard D.
Feldman, Adam S.
Gann, Peter H.
Kibel, Adam S.
Vickers, Andrew J.
Mucci, Lorelei A.
TI Baseline Prostate-Specific Antigen Levels in Midlife Predict Lethal
Prostate Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID LONG-TERM RISK; UNITED-STATES; BLACK-MEN; FOLLOW-UP; AGE; MORTALITY;
OVERDIAGNOSIS; WHITE; OLD; PSA
AB Purpose
Prostate-specific antigen (PSA) level in midlife predicted future prostate cancer (PCa) mortality in an unscreened Swedish population. Our purpose was to determine if a baseline PSA level during midlife predicts lethal PCa in a US population with opportunistic screening.
Materials and Methods
We conducted a nested case-control study among men age 40 to 59 years who gave blood before random assignment in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene among 22,071 US male physicians initiated in 1982 and then transitioned into a prospective cohort with 30 years of follow-up. Baseline PSA levels were available for 234 patients with PCa and 711 age-matched controls. Seventy-one participants who developed lethal PCa were rematched to 213 controls. Conditional logistic regression was used to estimate odds ratios and the area under the receiver operating characteristic curve, with 95% CIs, of the association between baseline PSA and risk of lethal PCa.
Results
Median PSA among controls was 0.68, 0.88, and 0.96 ng/mL for men age 40 to 49, 50 to 54, and 55 to 59 years, respectively. Risk of lethal PCa was strongly associated with baseline PSA in midlife: odds ratios (95% CIs) comparing PSA in the >90th percentile versus less than or equal to median were 8.7 (1.0 to 78.2) at 40 to 49 years, 12.6 (1.4 to 110.4) at 50 to 54 years, and 6.9 (2.5 to 19.1) at 55 to 59 years. A total of 82%, 71%, and 86% of lethal cases occurred in men with PSA above the median at ages 40 to 49, 50 to 54, and 55 to 59 years, respectively.
Conclusion
PSA levels in midlife strongly predict future lethal PCa in a US cohort subject to opportunistic screening. Risk-stratified screening on the basis of midlife PSA should be considered in men age 45 to 59 years. (C) 2016 by American Society of Clinical Oncology
C1 [Preston, Mark A.; Batista, Julie L.; Sesso, Howard D.; Kibel, Adam S.] Brigham & Womens Hosp, 45 Francis St, Boston, MA 02115 USA.
[Batista, Julie L.; Wilson, Kathryn M.; Gerke, Travis; Sesso, Howard D.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
[Batista, Julie L.] Harvard Med Sch, Boston, MA USA.
[Dahl, Douglas M.; Feldman, Adam S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Carlsson, Sigrid V.; Sjoberg, Daniel D.; Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Carlsson, Sigrid V.] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden.
[Gann, Peter H.] Univ Illinois, Chicago, IL USA.
RP Preston, MA (reprint author), Brigham & Womens Hosp, 45 Francis St, Boston, MA 02115 USA.
EM mpreston@bwh.harvard.edu
FU National Institutes of Health [CA-097193, CA-34944, CA-40360, HL-26490,
HL-34595]; Department of Defense Prostate Cancer Research Program
[W81XWH-12-1-0072]; Dana-Farber Cancer Institute Mazzone Awards Program;
Prostate Cancer Foundation Young Investigator Award; American Urological
Association Urology Care Foundation Scholar; National Cancer Institute
[R33 CA127768-02, P50-CA92629, P50-CA090381]; Swedish Cancer Society
[3455]; Fundacion Federico; Sidney Kimmel Center for Prostate and
Urologic Cancers; Prostate Cancer Foundation; National Cancer Institute
made to Memorial Sloan Kettering Cancer Center [P30-CA008748]
FX The Physicians' Health Study was supported by the National Institutes of
Health Grants No. CA-097193, CA-34944, CA-40360, HL-26490, and HL-34595.
This work was also supported by the Department of Defense Prostate
Cancer Research Program Grant No. W81XWH-12-1-0072 (J.L.B.), Dana-Farber
Cancer Institute Mazzone Awards Program (J.L.B. and M.A.P.), and the
Prostate Cancer Foundation Young Investigator Award (L.A.M.); M.A.P. is
an American Urological Association Urology Care Foundation Scholar.
Additional funding support provided from the National Cancer Institute
Grants No. R33 CA127768-02, P50-CA92629, and P50-CA090381; Swedish
Cancer Society Grant No. 3455; Fundacion Federico; the Sidney Kimmel
Center for Prostate and Urologic Cancers; David H. Koch through the
Prostate Cancer Foundation; and a Cancer Center Support Grant from the
National Cancer Institute made to Memorial Sloan Kettering Cancer Center
Grant No. P30-CA008748 (S.C., D.S., and A.V.; PI: Craig B. Thompson).
NR 28
TC 3
Z9 3
U1 5
U2 5
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 AUG 10
PY 2016
VL 34
IS 23
BP 2705
EP +
DI 10.1200/JCO.2016.66.7527
PG 9
WC Oncology
SC Oncology
GA DU8MF
UT WOS:000382467000006
PM 27298404
ER
PT J
AU Frisina, RD
Wheeler, HE
Fossa, SD
Kerns, SL
Fung, C
Sesso, HD
Monahan, PO
Feldman, DR
Hamilton, R
Vaughn, DJ
Beard, CJ
Budnick, A
Johnson, EM
Ardeshir-Rouhani-Fard, S
Einhorn, LH
Lipshultz, SE
Dolan, ME
Travis, LB
AF Frisina, Robert D.
Wheeler, Heather E.
Fossa, Sophie D.
Kerns, Sarah L.
Fung, Chunkit
Sesso, Howard D.
Monahan, Patrick O.
Feldman, Darren R.
Hamilton, Robert
Vaughn, David J.
Beard, Clair J.
Budnick, Amy
Johnson, Eileen M.
Ardeshir-Rouhani-Fard, Shirin
Einhorn, Lawrence H.
Lipshultz, Steven E.
Dolan, M. Eileen
Travis, Lois B.
TI Comprehensive Audiometric Analysis of Hearing Impairment and Tinnitus
After Cisplatin-Based Chemotherapy in Survivors of Adult-Onset Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID HIGH-FREQUENCY AUDIOMETRY; TERM-FOLLOW-UP; TESTICULAR CANCER; INDUCED
OTOTOXICITY; PLATINUM CHEMOTHERAPY; RISK-FACTORS; CHILDREN;
EPIDEMIOLOGY; POPULATION; PRESBYCUSIS
AB Purpose
Cisplatin is widely used but highly ototoxic. Effects of cumulative cisplatin dose on hearing loss have not been comprehensively evaluated in survivors of adult-onset cancer.
Patients and Methods
Comprehensive audiological measures were conducted on 488 North American male germ cell tumor (GCT) survivors in relation to cumulative cisplatin dose, including audiograms (0.25 to 12 kHz), tests of middle ear function, and tinnitus. American Speech-Language-Hearing Association criteria defined hearing loss severity. The geometric mean of hearing thresholds (0.25 to 12 kHz) summarized overall hearing status consistent with audiometric guidelines. Patients were sorted into quartiles of hearing thresholds of age-and sex-matched controls.
Results
Increasing cumulative cisplatin dose (median, 400 mg/m(2); range, 200 to 800 mg/m(2)) was significantly related to hearing loss at 4, 6, 8, 10, and 12 kHz (P trends, .021 to < .001): every 100 mg/m(2) increase resulted in a 3.2-dB impairment in age-adjusted overall hearing threshold (4 to 12 kHz; P < .001). Cumulative cisplatin doses > 300 mg/m(2) were associated with greater American Speech-Language-Hearing Association-defined hearing loss severity (odds ratio, 1.59; P = .0066) and worse normative-matched quartiles (odds ratio, 1.33; P = .093) compared with smaller doses. Almost one in five (18%) patients had severe to profound hearing loss. Tinnitus (40% patients) was significantly correlated with reduced hearing at each frequency (P < .001). Noise-induced damage (10% patients) was unaffected by cisplatin dose (P = .59). Hypertension was significantly related (P = .0066) to overall hearing threshold (4 to 12 kHz) in age- and cisplatin dose-adjusted analyses. Middle ear deficits occurred in 22.3% of patients but, as expected, were not related to cytotoxic drug dosage.
Conclusion
Follow-up of adult-onset cancer survivors given cisplatin should include routine inquiry for hearing status and tinnitus, referral to audiologists as clinically indicated, and hypertension control. Patients should be urged to avoid noise exposure, ototoxic drugs, and other factors that further damage hearing. (C) 2016 by American Society of Clinical Oncology
C1 [Frisina, Robert D.] Univ S Florida, Tampa, FL USA.
[Wheeler, Heather E.] Loyola Univ, Chicago, IL 60611 USA.
[Dolan, M. Eileen] Univ Chicago, Chicago, IL 60637 USA.
[Fossa, Sophie D.] Oslo Univ Hosp, Radiumhosp, Oslo, Norway.
[Kerns, Sarah L.; Fung, Chunkit; Johnson, Eileen M.] Univ Rochester, Med Ctr, JP Wilmot Canc Inst, Rochester, NY 14627 USA.
[Feldman, Darren R.; Budnick, Amy] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Sesso, Howard D.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Beard, Clair J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Monahan, Patrick O.; Ardeshir-Rouhani-Fard, Shirin; Einhorn, Lawrence H.; Travis, Lois B.] Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,RT432, Indianapolis, IN 46204 USA.
[Hamilton, Robert] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Vaughn, David J.] Univ Penn, Philadelphia, PA 19104 USA.
[Lipshultz, Steven E.] Wayne State Univ, Sch Med, Childrens Hosp Michigan, Detroit, MI USA.
RP Einhorn, LH (reprint author), Indiana Univ, Melvin & Bren Simon Canc Ctr, 535 Barnhill Dr,RT432, Indianapolis, IN 46204 USA.
EM leinhorn@iupui.edu
FU NCATS NIH HHS [UL1 TR001108]; NCI NIH HHS [K07 CA187546, R01 CA157823]
NR 59
TC 3
Z9 3
U1 7
U2 7
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 AUG 10
PY 2016
VL 34
IS 23
BP 2712
EP +
DI 10.1200/JCO.2016.66.8822
PG 12
WC Oncology
SC Oncology
GA DU8MF
UT WOS:000382467000007
PM 27354478
ER
PT J
AU Enzinger, PC
Burtness, BA
Niedzwiecki, D
Ye, X
Douglas, K
Ilson, DH
Villaflor, VM
Cohen, SJ
Mayer, RJ
Venook, A
Benson, A
Goldberg, RM
AF Enzinger, Peter C.
Burtness, Barbara Ann
Niedzwiecki, Donna
Ye, Xing
Douglas, Kathe
Ilson, David H.
Villaflor, Victoria Meucci
Cohen, Steven J.
Mayer, Robert J.
Venook, Alan
Benson, Al Bowen, III
Goldberg, Richard M.
TI CALGB 80403 (Alliance)/E1206: A Randomized Phase II Study of Three
Chemotherapy Regimens Plus Cetuximab in Metastatic Esophageal and
Gastroesophageal Junction Cancers
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ADVANCED GASTRIC-CANCER; GROWTH-FACTOR RECEPTOR; ADVANCED
ESOPHAGOGASTRIC CANCER; FOLINIC ACID; 1ST-LINE TREATMENT; INFUSIONAL
FLUOROURACIL; WEEKLY OXALIPLATIN; COLORECTAL-CANCER; CLINICAL-TRIALS;
CISPLATIN
AB Purpose
To determine the optimal chemotherapy backbone for testing in future US cooperative group studies for metastatic esophageal and gastroesophageal junction cancers. Cetuximab was added to each treatment arm based on promising preclinical data.
Patients and Methods
Patients with previously untreated metastatic esophageal or gastroesophageal junction cancer were randomly assigned at a one-to-one-to-one ratio to epirubicin, cisplatin, and continuous-infusion fluorouracil (ECF), irinotecan plus cisplatin (IC), or FOLFOX (oxaliplatin, leucovorin, and bolus and infusional fluorouracil). All treatment programs included cetuximab once per week. The primary end point was response rate. Secondary outcomes included overall survival, progression-free survival, time to treatment failure, and safety. As prespecified, primary and secondary analyses were conducted only among patients with adenocarcinoma.
Results
This study randomly assigned 245 patients, including 222 with adenocarcinoma. Among patients with adenocarcinoma, response rate was 60.9% (95% CI, 47.9 to 72.8) for ECF plus cetuximab, 45.0% (95% CI, 33.0 to 57.0) for IC plus cetuximab, and 54.3% (95% CI, 42.0 to 66.2) for FOLFOX plus cetuximab. Median overall survival was 11.6, 8.6, and 11.8 months; median progression-free survival was 7.1, 4.9, and 6.8 months; and median time to treatment failure was 5.6, 4.3, and 6.7 months for each of these arms, respectively. FOLFOX plus cetuximab required fewer treatment modifications compared with ECF plus cetuximab and IC plus cetuximab (P = .013), and fewer patients were removed from treatment because of an adverse event or experienced treatment-related death.
Conclusion
In combination with cetuximab, ECF and FOLFOX had similar efficacy, but FOLFOX was better tolerated. Although differences were nonsignificant, IC plus cetuximab seemed to be the least effective and most toxic of the three regimens tested. (C) 2016 by American Society of Clinical Oncology
C1 [Enzinger, Peter C.; Mayer, Robert J.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[Enzinger, Peter C.; Mayer, Robert J.] Alliance Clin Trials Oncol, Boston, MA USA.
[Burtness, Barbara Ann; Cohen, Steven J.] Fox Chase Canc Ctr, Philadelphia, PA USA.
[Burtness, Barbara Ann; Cohen, Steven J.; Benson, Al Bowen, III] Eastern Cooperat Oncol Grp, Amer Coll Radiol, Imaging Network Canc Res Grp, Philadelphia, PA USA.
[Niedzwiecki, Donna; Ye, Xing; Douglas, Kathe] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA.
[Ilson, David H.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Ilson, David H.] Alliance Clin Trials Oncol, New York, NY USA.
[Villaflor, Victoria Meucci] Univ Chicago, Med & Alliance Clin Trials Oncol, Chicago, IL 60637 USA.
[Benson, Al Bowen, III] Northwestern Univ, Sch Med, Chicago, IL 60611 USA.
[Venook, Alan] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA.
[Venook, Alan] Alliance Clin Trials Oncol, San Francisco, CA USA.
[Goldberg, Richard M.] Ohio State Univ, James Comprehens Canc Ctr, Columbus, OH 43210 USA.
[Goldberg, Richard M.] Alliance Clin Trials Oncol, Columbus, OH USA.
RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM peter_enzinger@dfci.harvard.edu
FU National Cancer Institute of the National Institutes of Health (NIH)
[U10CA180821, U10CA180882]; NIH [5U10CA031946-31, 5U10CA021115-38];
ImClone Systems/Bristol-Myers Squibb, Pfizer Oncology, and Sanofi
FX Supported by the National Cancer Institute of the National Institutes of
Health (NIH) under Awards No. U10CA180821 and U10CA180882; in part by
NIH Grants No. 5U10CA031946-31 and 5U10CA021115-38; and in part by
ImClone Systems/Bristol-Myers Squibb, Pfizer Oncology, and Sanofi.
NR 37
TC 5
Z9 5
U1 4
U2 4
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 AUG 10
PY 2016
VL 34
IS 23
BP 2736
EP +
DI 10.1200/JCO.2015.65.5092
PG 11
WC Oncology
SC Oncology
GA DU8MF
UT WOS:000382467000010
PM 27382098
ER
PT J
AU Wey, HY
Gilbert, TM
Zurcher, NR
She, A
Bhanot, A
Taillon, BD
Schroeder, FA
Wang, CG
Haggarty, SJ
Hooker, JM
AF Wey, Hsiao-Ying
Gilbert, Tonya M.
Zurcher, Nicole R.
She, Angela
Bhanot, Anisha
Taillon, Brendan D.
Schroeder, Fredrick A.
Wang, Changing
Haggarty, Stephen J.
Hooker, Jacob M.
TI Insights into neuroepigenetics through human histone deacetylase PET
imaging
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID ALZHEIMERS-DISEASE; MOTION CORRECTION; MESSENGER-RNA; MEMORY; BRAIN;
HIPPOCAMPUS; INHIBITORS; BDNF; SEGMENTATION; EXPRESSION
AB Epigenetic dysfunction is implicated in many neurological and psychiatric diseases, including Alzheimer's disease and schizophrenia. Consequently, histone deacetylases (HDACs) are being aggressively pursued as therapeutic targets. However, a fundamental knowledge gap exists regarding the expression and distribution of HDACs in healthy individuals for comparison to disease states. Here, we report the first-in-human evaluation of neuroepigenetic regulation in vivo. Using positron emission tomography with [C-11] Martinostat, an imaging probe selective for class I HDACs (isoforms 1, 2, and 3), we found that HDAC expression is higher in cortical gray matter than in white matter, with conserved regional distribution patterns within and between healthy individuals. Among gray matter regions, HDAC expression was lowest in the hippocampus and amygdala. Through biochemical profiling of postmortem human brain tissue, we confirmed that [C-11] Martinostat selectively binds HDAC isoforms 1, 2, and 3, the HDAC subtypes most implicated in regulating neuroplasticity and cognitive function. In human stem cellderived neural progenitor cells, pharmacologic-level doses of Martinostat induced changes in genes closely associated with synaptic plasticity, including BDNF (brain-derived neurotrophic factor) and SYP (synaptophysin), as well as genes implicated in neurodegeneration, including GRN (progranulin), at the transcript level, in concert with increased acetylation at both histone H3 lysine 9 and histone H4 lysine 12. This study quantifies HDAC expression in the living human brain and provides the foundation for gaining unprecedented in vivo epigenetic information in health and disease.
C1 [Wey, Hsiao-Ying; Gilbert, Tonya M.; Zurcher, Nicole R.; Bhanot, Anisha; Taillon, Brendan D.; Schroeder, Fredrick A.; Wang, Changing; Hooker, Jacob M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
[She, Angela; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Chem Neurobiol Lab, Dept Neurol, Boston, MA 02114 USA.
[She, Angela; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Chem Neurobiol Lab, Dept Psychiat, Boston, MA 02114 USA.
RP Hooker, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
EM hooker@nmr.mgh.harvard.edu
FU National Institute on Drug Abuse of the NIH [R01DA030321, K99DA037928];
Harvard/MGH Nuclear Medicine Training Program from the Department of
Energy [DE-SC0008430, HHSN-271-2013-00030C]; National Institute of
Biomedical Imaging and Bioengineering, NIH [P41EB015896]; Harvard
Catalyst; Harvard Clinical and Translational Science Center (National
Center for Research Resources and the National Center for Advancing
Translational Sciences, NIH) [UL1 TR001102]; Harvard University;
Bluefield Project to Cure Frontotemporal Dementia; NIH Shared
Instrumentation Grant Program [S10RR017208, S10RR026666, S10RR022976,
S10RR019933, S10RR023401]
FX This research received funding from the National Institute on Drug Abuse
of the NIH under grant numbers R01DA030321 (to J.M.H.) and K99DA037928
(to H-Y.W.). This research was also supported by the Harvard/MGH Nuclear
Medicine Training Program from the Department of Energy under grants
DE-SC0008430 (to H-Y.W., T.M.G., and C.W.) and HHSN-271-2013-00030C (to
the Harvard Brain Tissue Resource Center). This research was carried out
at the Athinoula A. Martinos Center for Biomedical Imaging at
Massachusetts General Hospital, using resources provided by the Center
for Functional Neuroimaging Technologies, P41EB015896, a P41
Biotechnology Resource Grant supported by the National Institute of
Biomedical Imaging and Bioengineering, NIH. This work was conducted with
support from Harvard Catalyst and the Harvard Clinical and Translational
Science Center (National Center for Research Resources and the National
Center for Advancing Translational Sciences, NIH Award UL1 TR001102) and
financial contributions from Harvard University and its affiliated
academic healthcare centers. Additional support was provided by the
Bluefield Project to Cure Frontotemporal Dementia. This work also
involved the use of instrumentation supported by the NIH Shared
Instrumentation Grant Program, specifically grants S10RR017208,
S10RR026666, S10RR022976, S10RR019933, and S10RR023401.
NR 40
TC 5
Z9 5
U1 16
U2 16
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 AUG 10
PY 2016
VL 8
IS 351
AR 351ra106
DI 10.1126/scitranslmed.aaf7551
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DT3MB
UT WOS:000381384200003
ER
PT J
AU Abed, J
Emgard, JEM
Zamir, G
Faroja, M
Almogy, G
Grenov, A
Sol, A
Naor, R
Pikarsky, E
Atlan, KA
Mellul, A
Chaushu, S
Manson, AL
Earl, AM
Ou, N
Brennan, CA
Garrett, WS
Bachrach, G
AF Abed, Jawad
Emgard, Johanna E. M.
Zamir, Gideon
Faroja, Mouhammad
Almogy, Gideon
Grenov, Amalie
Sol, Asaf
Naor, Ronit
Pikarsky, Eli
Atlan, Karine A.
Mellul, Anna
Chaushu, Stella
Manson, Abigail L.
Earl, Ashlee M.
Ou, Nora
Brennan, Caitlin A.
Garrett, Wendy S.
Bachrach, Gilad
TI Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma
Enrichment by Binding to Tumor-Expressed Gal-GalNAc
SO CELL HOST & MICROBE
LA English
DT Article
ID PORPHYROMONAS-GINGIVALIS; MOLECULAR-FEATURES; HUMAN-LYMPHOCYTES;
CELL-ADHESION; E-CADHERIN; CANCER; MICROBIOTA; CARCINOMA; DISEASE;
CARCINOGENESIS
AB Fusobacterium nucleatum is associated with colorectal cancer and promotes colonic tumor formation in preclinical models. However, fusobacteria are core members of the human oral microbiome and less prevalent in the healthy gut, raising questions about how fusobacteria localize to CRC. We identify a host polysaccharide and fusobacterial lectin that explicates fusobacteria abundance in CRC. Gal-GalNAc, which is overexpressed in CRC, is recognized by fusobacterial Fap2, which functions as a Gal-GalNAc lectin. F. nucleatum binding to clinical adenocarcinomas correlates with Gal-GalNAc expression and is reduced upon O-glycanase treatment. Clinical fusobacteria strains naturally lacking Fap2 or inactivated Fap2 mutants show reduced binding to Gal-GalNAc-expressing CRC cells and established CRCs in mice. Additionally, intravenously injected F. nucleatum localizes to mouse tumor tissues in a Fap2-dependent manner, suggesting that fusobacteria use a hematogenous route to reach colon adenocarcinomas. Thus, targeting F. nucleatum Fap2 or host epithelial Gal-GalNAc may reduce fusobacteria potentiation of CRC.
C1 [Abed, Jawad; Emgard, Johanna E. M.; Grenov, Amalie; Sol, Asaf; Naor, Ronit; Bachrach, Gilad] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel.
[Zamir, Gideon; Faroja, Mouhammad; Almogy, Gideon] Hadassah Hebrew Univ, Med Ctr, Dept Gen Surg, IL-91120 Jerusalem, Israel.
[Pikarsky, Eli] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Immunol & Canc Res, Inst Med Res Israel Canada, IL-91120 Jerusalem, Israel.
[Pikarsky, Eli; Atlan, Karine A.; Mellul, Anna] Hadassah Hebrew Univ, Med Ctr, Dept Pathol, IL-91120 Jerusalem, Israel.
[Chaushu, Stella] Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Dept Orthodont, IL-91120 Jerusalem, Israel.
[Manson, Abigail L.; Earl, Ashlee M.; Garrett, Wendy S.] Broad Inst MIT & Harvard Univ, Cambridge, MA 02141 USA.
[Ou, Nora; Brennan, Caitlin A.; Garrett, Wendy S.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[Ou, Nora; Brennan, Caitlin A.; Garrett, Wendy S.] Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.
[Garrett, Wendy S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Bachrach, G (reprint author), Hebrew Univ Jerusalem, Hadassah Sch Dent Med, Inst Dent Sci, IL-91120 Jerusalem, Israel.; Garrett, WS (reprint author), Broad Inst MIT & Harvard Univ, Cambridge, MA 02141 USA.; Garrett, WS (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.; Garrett, WS (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA.; Garrett, WS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM wgarrett@hsph.harvard.edu; giladba@ekmd.huji.ac.il
FU Israel Cancer Research Fund Project grant; Israel Science Foundation
[201/15]; Hoffman-LaRoche; [RO1 CA154426]
FX We thank Professor Lawrence A. Tabak for useful discussions, Professor
Norman Grover for valuable assistance in statistics, and Carey Ann
Gallini for proofreading. This work was supported by the Israel Cancer
Research Fund Project grant and Israel Science Foundation grant 201/15
to G.B. and grant RO1 CA154426 and a Hoffman-LaRoche research grant to
W.S.G. W.S.G. is a SAB member of Evelo Therapeutics and Synlogic, has
received research funds from Hoffman-LaRoche, and consults for Janssen
Pharmaceuticals.
NR 49
TC 4
Z9 4
U1 6
U2 7
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1931-3128
EI 1934-6069
J9 CELL HOST MICROBE
JI Cell Host Microbe
PD AUG 10
PY 2016
VL 20
IS 2
BP 215
EP 225
DI 10.1016/j.chom.2016.07.006
PG 11
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DT6II
UT WOS:000381587500013
PM 27512904
ER
PT J
AU Kumar, MNK
Zhou, C
Wu, MX
AF Kumar, Mudnakudu Nagaraju Kiran
Zhou, Chang
Wu, Mei X.
TI Laser-facilitated epicutaneous immunotherapy to IgE-mediated allergy
SO JOURNAL OF CONTROLLED RELEASE
LA English
DT Article
DE Allergic asthma; Adjuvant; Epicutaneous immunotherapy (EPIT);
Immunoglobulin E (IgE); Laser and micro-fractional epicutaneous (mu EP)
delivery
ID CELLS; ASTHMA; VACCINATION; SAFETY; MODEL
AB Allergen specific immunotherapy has been shown to be the only effective treatment for long-lasting clinical benefit to IgE-mediated allergic diseases, but a fewer than 5% of patients choose the treatment because of inconvenience and a high risk of anaphylaxis. Recently, epicutaneous allergen-specific immunotherapy (EPIT) has proven effective, yet with limitations owing to strong skin reactions. We demonstrate here safer and faster EPIT, named mu EPIT, by delivering powdered allergen and adjuvants into many micropores in the epidermis. We fabricated a microarray patch fractionally coated with a powder mixture of ovalbumin (OVA) model allergen, CpG, and 1,25-dihydroxyvitamin D-3 (VD3). Topical application of the patch onto laser-microperforated skin resulted in a high level of epidermal delivery while greatly minimizing allergen leakage into circulation system as compared to current subcutaneous immunotherapy (SCIT). Moreover, only three times of mu EPIT over two weeks could sufficiently inhibit allergen-specific IgE responses in mice suffering OVA-induced airway hyperresponsivness (AHR), which was unattainable by eight times of SCIT over three weeks. Mechanistically, mu EPIT preferably enhanced IgG2a production suggesting T(H)1-biased immune responses and induced a high level of T-regulatory (Treg) cells against repeated allergen sensitization. The immune tolerance was confirmed by marked reduction in airway wall thickness as well as eosinophil and neutrophil infiltration into the respiratory airway. The mu EPIT represents a novel and painless technology to treat IgE-mediated allergic diseases with little local skin reaction and a minimal risk of anaphylaxis. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Kumar, Mudnakudu Nagaraju Kiran; Zhou, Chang; Wu, Mei X.] Harvard Med Sch, Dept Dermatol, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.
RP Wu, MX (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Edwards 222,50 Blossom St, Boston, MA 02114 USA.
EM mwu5@mgh.harvard.edu
FU National Institute of Health [AI113458-01, AI089779]
FX We thank the Pantec Biosolutions AG, Liechtenstein for the gift of
P.L.E.A.S.E. Laser device and the Photopathology Core, Wellman center
for their excellent technical support in obtaining tissue sections and
flow cytometry analyses. This work is supported by the National
Institute of Health grants AI113458-01 and AI089779 and department fund
to M.X.W.
NR 30
TC 0
Z9 0
U1 12
U2 12
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 AUG 10
PY 2016
VL 235
BP 82
EP 90
DI 10.1016/j.jconrel.2016.05.057
PG 9
WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy
SC Chemistry; Pharmacology & Pharmacy
GA DR1ZF
UT WOS:000379702700008
PM 27235977
ER
PT J
AU Melchardt, T
Hufnagl, C
Weinstock, DM
Kopp, N
Neureiter, D
Trankenschuh, W
Hackl, H
Weiss, L
Rinnerthaler, G
Hartmann, TN
Greil, R
Weigert, O
Egle, A
AF Melchardt, Thomas
Hufnagl, Clemens
Weinstock, David M.
Kopp, Nadja
Neureiter, Daniel
Traenkenschuh, Wolfgang
Hackl, Hubert
Weiss, Lukas
Rinnerthaler, Gabriel
Hartmann, Tanja N.
Greil, Richard
Weigert, Oliver
Egle, Alexander
TI Clonal evolution in relapsed and refractory diffuse large B-cell
lymphoma is characterized by high dynamics of subclones
SO ONCOTARGET
LA English
DT Article
DE DLBCL; clonal evolution; TP53; tumor heterogeneity; subclonal selection
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER GENES; MUTATIONS; PATTERNS; GENOME;
EXPRESSION; LANDSCAPE; PROGNOSIS; DISCOVERY; IMPACT
AB Little information is available about the role of certain mutations for clonal evolution and the clinical outcome during relapse in diffuse large B-cell lymphoma (DLBCL). Therefore, we analyzed formalin-fixed-paraffin-embedded tumor samples from first diagnosis, relapsed or refractory disease from 28 patients using next-generation sequencing of the exons of 104 coding genes. Non-synonymous mutations were present in 74 of the 104 genes tested. Primary tumor samples showed a median of 8 non-synonymous mutations (range: 0-24) with the used gene set. Lower numbers of non-synonymous mutations in the primary tumor were associated with a better median OS compared with higher numbers (28 versus 15 months, p=0.031). We observed three patterns of clonal evolution during relapse of disease: large global change, subclonal selection and no or minimal change possibly suggesting preprogrammed resistance. We conclude that targeted re-sequencing is a feasible and informative approach to characterize the molecular pattern of relapse and it creates novel insights into the role of dynamics of individual genes.
C1 [Melchardt, Thomas; Hufnagl, Clemens; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N.; Greil, Richard; Egle, Alexander] Paracelsus Med Univ Salzburg, Med Dept 3, Salzburg, Austria.
[Melchardt, Thomas; Hufnagl, Clemens; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N.; Greil, Richard; Egle, Alexander] Salzburg Canc Res Inst SCRI, Salzburg, Austria.
[Melchardt, Thomas; Hufnagl, Clemens; Weiss, Lukas; Rinnerthaler, Gabriel; Hartmann, Tanja N.; Greil, Richard; Egle, Alexander] Cancer Cluster Salzburg CCS, Salzburg, Austria.
[Weinstock, David M.; Kopp, Nadja] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Neureiter, Daniel; Traenkenschuh, Wolfgang] Paracelsus Med Univ Salzburg, Inst Pathol, Salzburg, Austria.
[Hackl, Hubert] Med Univ Innsbruck, Bioctr, Div Bioinformat, Innsbruck, Austria.
[Weigert, Oliver] Univ Munich, Univ Hosp, Med Dept 3, Lab Expt Leukemia & Lymphoma Res ELLF, Munich, Germany.
[Weigert, Oliver] German Canc Consortium DKTK, Heidelberg, Germany.
[Weigert, Oliver] German Canc Res Ctr, Heidelberg, Germany.
RP Egle, A (reprint author), Paracelsus Med Univ Salzburg, Med Dept 3, Salzburg, Austria.; Egle, A (reprint author), Salzburg Canc Res Inst SCRI, Salzburg, Austria.; Egle, A (reprint author), Cancer Cluster Salzburg CCS, Salzburg, Austria.
EM a.egle@salk.at
RI Hartmann, Tanja Nicole/C-9345-2017; Greil, Richard/C-7673-2017;
OI Hartmann, Tanja Nicole/0000-0002-2633-7301; Greil,
Richard/0000-0002-4462-3694; Egle, Alexander/0000-0003-0648-4416; Hackl,
Hubert/0000-0003-4055-3841
FU Paracelsus Medical University (PMU Grant) [E-13/17/089-MEG,
R-15/03/069-MEL, E-13/18/091-EGF]
FX The authors thank Paul van Hummelen and his team for assistance with
sequencing. This work was supported by the Paracelsus Medical University
(PMU Grant: E-13/17/089-MEG, R-15/03/069-MEL and E-13/18/091-EGF).
NR 29
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U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD AUG 9
PY 2016
VL 7
IS 32
BP 51494
EP 51502
DI 10.18632/oncotarget.9860
PG 9
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9CC
UT WOS:000385429100058
PM 27285986
ER
PT J
AU Laidlaw, KME
Berhan, S
Liu, SH
Silvestri, G
Holyoake, TL
Frank, DA
Aggarwal, B
Bonner, MY
Perrotti, D
Jorgensen, HG
Arbiser, JL
AF Laidlaw, Kamilla M. E.
Berhan, Samuel
Liu, Suhu
Silvestri, Giovannino
Holyoake, Tessa L.
Frank, David A.
Aggarwal, Bharat
Bonner, Michael Y.
Perrotti, Danilo
Jorgensen, Heather G.
Arbiser, Jack L.
TI Cooperation of imipramine blue and tyrosine kinase blockade demonstrates
activity against chronic myeloid leukemia
SO ONCOTARGET
LA English
DT Article
DE chronic myeloid leukemia; tyrosine kinase inhibitor; imipramine blue;
nilotinib; NADPH oxidase
ID CHRONIC MYELOGENOUS LEUKEMIA; HEMATOPOIETIC STEM-CELLS; PROTEIN
PHOSPHATASE 2A; IN-VITRO; PHILADELPHIA-CHROMOSOME; LYMPHOCYTIC-LEUKEMIA;
GENOMIC INSTABILITY; IMATINIB; METASTASIS; CML
AB The use of tyrosine kinase inhibitors (TKI), including nilotinib, has revolutionized the treatment of chronic myeloid leukemia (CML). However current unmet clinical needs include combating activation of additional survival signaling pathways in persistent leukemia stem cells after long-term TKI therapy. A ubiquitous signaling alteration in cancer, including CML, is activation of reactive oxygen species (ROS) signaling, which may potentiate stem cell activity and mediate resistance to both conventional chemotherapy and targeted inhibitors. We have developed a novel nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor, imipramine blue (IB) that targets ROS generation. ROS levels are known to be elevated in CML with respect to normal hematopoietic stem/progenitor cells and not corrected by TKI. We demonstrate that IB has additive benefit with nilotinib in inhibiting proliferation, viability, and clonogenic function of TKI-insensitive quiescent CD34(+) CML chronic phase (CP) cells while normal CD34(+) cells retained their clonogenic capacity in response to this combination therapy in vitro. Mechanistically, the pro-apoptotic activity of IB likely resides in part through its dual ability to block NF-kappa B and re-activate the tumor suppressor protein phosphatase 2A (PP2A). Combining BCR-ABL1 kinase inhibition with NADPH oxidase blockade may be beneficial in eradication of CML and worthy of further investigation.
C1 [Laidlaw, Kamilla M. E.; Berhan, Samuel; Holyoake, Tessa L.; Jorgensen, Heather G.] Univ Glasgow, Gartnavel Gen Hosp, Coll Med Vet & Life Sci, Paul OGorman Leukemia Res Ctr,Inst Canc Sci, Glasgow G12 0ZD, Lanark, Scotland.
[Liu, Suhu; Frank, David A.] Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Mayer 522B, Boston, MA 02215 USA.
[Aggarwal, Bharat] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Bonner, Michael Y.; Arbiser, Jack L.] Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA.
[Bonner, Michael Y.; Arbiser, Jack L.] Atlanta Vet Adm Hosp, Atlanta, GA 30322 USA.
[Silvestri, Giovannino; Perrotti, Danilo] Univ Maryland, Sch Med, Dept Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
RP Jorgensen, HG (reprint author), Univ Glasgow, Gartnavel Gen Hosp, Coll Med Vet & Life Sci, Paul OGorman Leukemia Res Ctr,Inst Canc Sci, Glasgow G12 0ZD, Lanark, Scotland.; Arbiser, JL (reprint author), Emory Univ, Sch Med, Dept Dermatol, Atlanta, GA 30322 USA.; Arbiser, JL (reprint author), Atlanta Vet Adm Hosp, Atlanta, GA 30322 USA.
EM heather.jorgensen@glasgow.ac.uk; jarbise@emory.edu
FU NIH-NCI [CA163800]; National Institutes of Health; Veterans
Administration Hospital Merit Award; Margolis Foundation;
Rabinowitch-Davis Foundation for Melanoma Research; Betty Minsk
Foundation for Melanoma Research; Friends of Paul O'Gorman in Glasgow;
Glasgow Experimental Cancer Medicine Centre (ECMC) - Cancer Research UK;
Chief Scientist's Office, Scotland; Kay Kendall Leukaemia Fund [KKL501];
Howat Foundation; [RO1 AR47901]; [P30 AR42687]
FX J.L.A. was supported by the grant RO1 AR47901and P30 AR42687, and
NIH-NCI grant CA163800 (D.P.). Emory Skin Disease Research Core Center
Grant from the National Institutes of Health, a Veterans Administration
Hospital Merit Award, as well as funds from the Margolis Foundation,
Rabinowitch-Davis Foundation for Melanoma Research and the Betty Minsk
Foundation for Melanoma Research. H.G.J. was supported by Friends of
Paul O'Gorman in Glasgow; the study was further supported by Glasgow
Experimental Cancer Medicine Centre (ECMC) funded by Cancer Research UK
and by the Chief Scientist's Office, Scotland; cell sorting facilities
were funded by the Kay Kendall Leukaemia Fund (KKL501) and the Howat
Foundation.
NR 48
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U1 2
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD AUG 9
PY 2016
VL 7
IS 32
BP 51651
EP 51664
DI 10.18632/oncotarget.10541
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY9CC
UT WOS:000385429100071
PM 27438151
ER
PT J
AU Berkovic, SF
Staropoli, JF
Carpenter, S
Oliver, KL
Kmoch, S
Anderson, GW
Damiano, JA
Hildebrand, MS
Sims, KB
Cotman, SL
Bahlo, M
Smith, KR
Cadieux-Dion, M
Cossette, P
Jedlickova, I
Pristoupilova, A
Mole, SE
AF Berkovic, Samuel F.
Staropoli, John F.
Carpenter, Stirling
Oliver, Karen L.
Kmoch, Stanislav
Anderson, Glenn W.
Damiano, John A.
Hildebrand, Michael S.
Sims, Katherine B.
Cotman, Susan L.
Bahlo, Melanie
Smith, Katherine R.
Cadieux-Dion, Maxime
Cossette, Patrick
Jedlickova, Ivana
Pristoupilova, Anna
Mole, Sara E.
CA ANCL Gene Discovery Consortium
TI Diagnosis and misdiagnosis of adult neuronal ceroid lipofuscinosis (Kufs
disease)
SO NEUROLOGY
LA English
DT Article
ID DOMINANT INHERITANCE; MUTATIONS; CLN6; NCL; DEFICIENCY; PHENOTYPES;
EPILEPSY; JUVENILE; SPECTRUM; DNAJC5
AB Objective: To critically re-evaluate cases diagnosed as adult neuronal ceroid lipofuscinosis (ANCL) in order to aid clinicopathologic diagnosis as a route to further gene discovery.
Methods: Through establishment of an international consortium we pooled 47 unsolved cases regarded by referring centers as ANCL. Clinical and neuropathologic experts within the Consortium established diagnostic criteria for ANCL based on the literature to assess each case. A panel of 3 neuropathologists independently reviewed source pathologic data. Cases were given a final clinicopathologic classification of definite ANCL, probable ANCL, possible ANCL, or not ANCL.
Results: Of the 47 cases, only 16 fulfilled the Consortium's criteria of ANCL (5 definite, 2 probable, 9 possible). Definitive alternate diagnoses were made in 10, including Huntington disease, early-onset Alzheimer disease, Niemann-Pick disease, neuroserpinopathy, prion disease, and neurodegeneration with brain iron accumulation. Six cases had features suggesting an alternate diagnosis, but no specific condition was identified; in 15, the data were inadequate for classification. Misinterpretation of normal lipofuscin as abnormal storage material was the commonest cause of misdiagnosis.
Conclusions: Diagnosis of ANCL remains challenging; expert pathologic analysis and recent molecular genetic advances revealed misdiagnoses in >1/3 of cases. We now have a refined group of cases that will facilitate identification of new causative genes.
C1 [Berkovic, Samuel F.; Oliver, Karen L.; Damiano, John A.; Hildebrand, Michael S.] Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic, Australia.
[Staropoli, John F.] Biogen Inc, 14 Cambridge Ctr, Cambridge, MA 02142 USA.
[Carpenter, Stirling] Ctr Hosp Sao Joao, Dept Pathol, Oporto, Portugal.
[Kmoch, Stanislav; Jedlickova, Ivana; Pristoupilova, Anna] Charles Univ Prague, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic.
[Kmoch, Stanislav] Gen Univ Hosp, Prague, Czech Republic.
[Anderson, Glenn W.] Great Ormond St Hosp Children NHS Fdn Trust, London, England.
[Sims, Katherine B.; Cotman, Susan L.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.
[Sims, Katherine B.; Cotman, Susan L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Bahlo, Melanie; Smith, Katherine R.] Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Parkville, Vic, Australia.
[Bahlo, Melanie] Univ Melbourne, Dept Math & Stat, Melbourne, Vic 3010, Australia.
[Bahlo, Melanie] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3010, Australia.
[Cadieux-Dion, Maxime; Cossette, Patrick] Univ Montreal, Ctr Hosp Univ Montreal, Ctr Rech, Montreal, PQ H3C 3J7, Canada.
[Mole, Sara E.] UCL, MRC Lab Cell Biol, Dept Genet Evolut & Environm, London WC1E 6BT, England.
UCL, UCL Inst Child Hlth, London WC1E 6BT, England.
RP Berkovic, SF (reprint author), Univ Melbourne, Austin Hlth, Dept Med, Epilepsy Res Ctr, Heidelberg, Vic, Australia.
EM s.berkovic@unimelb.edu.au
RI Pristoupilova, Anna/F-4990-2017;
OI Pristoupilova, Anna/0000-0003-0047-9405; Mole, Sara/0000-0003-4385-4957
FU National Health and Medical Research Council Program [628952]; Charles
University institutional programs [PRVOUK-P24/LF1/3, UNCE 204011,
SVV2016/260148]; NPU II from the Ministry of Education of the Czech
Republic [LQ1604]; Ministry of Health of the Czech Republic [15-28208A];
GA UK [269615, 1402213]; Genomic facility in Motol University Hospital
in Prague [OPPK.CZ.2.16/3.100/24022]; Rare NCL Gene Consortium; USA
Batten Disease Support and Research Association; National Institutes of
Health: National Institute of Neurologic Disorders Stroke [R01NS073813];
Fonds de Recherche du Quebec-Sante (FRQS)
FX S.F.B. was supported by a National Health and Medical Research Council
Program Grant (ID: 628952). S.K., I.J., and A.P. are funded by Charles
University institutional programs PRVOUK-P24/LF1/3, UNCE 204011, and
SVV2016/260148 and by the project LQ1604 NPU II from the Ministry of
Education of the Czech Republic. This work was specifically supported by
grant 15-28208A from the Ministry of Health of the Czech Republic and GA
UK No. 269615 (I.J.) and No. 1402213 (A.P.). Instrumental support for
exome and gene panel sequencing was provided by the Genomic facility in
Motol University Hospital in Prague (OPPK.CZ.2.16/3.100/24022). S.E.M.
received specific funding towards the work of the Rare NCL Gene
Consortium and Kufs disease from the USA Batten Disease Support and
Research Association. S.L.C. is funded by the National Institutes of
Health: National Institute of Neurologic Disorders & Stroke
(R01NS073813). M.C.-D. is supported by the Fonds de Recherche du
Quebec-Sante (FRQS).
NR 37
TC 0
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U1 4
U2 4
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 AUG 9
PY 2016
VL 87
IS 6
BP 579
EP 584
DI 10.1212/WNL.0000000000002943
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6LT
UT WOS:000382327000011
PM 27412140
ER
PT J
AU Shefner, JM
Liu, DW
Leitner, ML
Schoenfeld, D
Johns, DR
Ferguson, T
Cudkowicz, M
AF Shefner, Jeremy M.
Liu, Dawei
Leitner, Melanie L.
Schoenfeld, David
Johns, Donald R.
Ferguson, Toby
Cudkowicz, Merit
TI Quantitative strength testing in ALS clinical trials
SO NEUROLOGY
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; DISEASE
PROGRESSION; DOUBLE-BLIND; EFFICACY; SAFETY
AB Objective: To study the attributes of quantitative strength testing using hand-held dynamometry (HHD) as an efficacy measure in 2 large phase 3 amyotrophic lateral sclerosis (ALS) trials.
Methods: In the phase 3 trials of ceftriaxone and dexpramipexole, 513 and 943 patients, respectively, were enrolled in double-blind, randomized, placebo-controlled trials with planned follow-up of at least 1 year. Patients were studied every 3 months in the ceftriaxone study and every 2 months in the dexpramipexole study. Evaluators of HHD were trained and had to show evidence of adequate performance of strength testing; the testing paradigm involved testing 9 muscle groups in the upper and lower extremity bilaterally. Neither drug significantly affected any outcome measure. Strength measurements were evaluated by individual muscle and by megascores, which averaged scaled strength measures to produce an overall measure of muscle strength.
Results: A measure combining rate of decline with both within-and between-patient variabilities of measurement, the coefficient of variation for rate of change, was calculated, and showed that HHD overall performed slightly less well than Amyotrophic Lateral Sclerosis Functional Rating Scale-revised (ALSFRS-R) but better than vital capacity. Individual muscles were highly correlated to the identical muscles on the contralateral side, as well as to other muscles in the same body region. Strength decline was correlated both with ALSFRS-R and vital capacity.
Conclusion: Quantitative strength testing using HHD is a reliable and reproducible measure of decline in ALS.
C1 [Shefner, Jeremy M.] Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA.
[Liu, Dawei; Leitner, Melanie L.; Johns, Donald R.; Ferguson, Toby] Biogen, Cambridge, MA USA.
[Schoenfeld, David; Cudkowicz, Merit] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Shefner, JM (reprint author), Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA.
EM Jeremy.Shefner@DignityHealth.org
FU NIH/National Institute of Neurological Disorders and Stroke
[U01NS077179]; Biogen-Idec
FX The dexpramipexole clinical trial was funded entirely by Biogen-Idec.
The ceftriaxone clinical trial was funded by NIH/National Institute of
Neurological Disorders and Stroke (U01NS077179, PI Dr. Merit Cudkowicz).
NR 16
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Z9 4
U1 0
U2 0
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 AUG 9
PY 2016
VL 87
IS 6
BP 617
EP 624
DI 10.1212/WNL.0000000000002941
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6LT
UT WOS:000382327000016
PM 27385750
ER
PT J
AU Chen, KJ
Shanmugam, NKN
Pazos, MA
Hurley, BP
Cherayil, BJ
AF Chen, Kejie
Shanmugam, Nanda Kumar N.
Pazos, Michael A.
Hurley, Bryan P.
Cherayil, Bobby J.
TI Commensal Bacteria-Induced Inflammasome Activation in Mouse and Human
Macrophages Is Dependent on Potassium Efflux but Does Not Require
Phagocytosis or Bacterial Viability
SO PLOS ONE
LA English
DT Article
ID NLRP3 INFLAMMASOME; INTESTINAL INFLAMMATION; IL-1-BETA PRODUCTION;
CROHNS-DISEASE; RECEPTOR; AUTOPHAGY; PROTEIN; INFECTION; DECTIN-1; CELLS
AB Gut commensal bacteria contribute to the pathogenesis of inflammatory bowel disease, in part by activating the inflammasome and inducing secretion of interleukin-1 beta (IL-1 beta). Although much has been learned about inflammasome activation by bacterial pathogens, little is known about how commensals carry out this process. Accordingly, we investigated the mechanism of inflammasome activation by representative commensal bacteria, the Gram-positive Bifidobacterium longum subspecies infantis and the Gram-negative Bacteroides fragilis. B. infantis and B. fragilis induced IL-1 beta secretion by primary mouse bone marrow-derived macrophages after overnight incubation. IL-1 beta secretion also occurred in response to heat-killed bacteria and was only partly reduced when phagocytosis was inhibited with cytochalasin D. Similar results were obtained with a wild-type immortalized mouse macrophage cell line but neither B. infantis nor B. fragilis induced IL-1 beta secretion in a mouse macrophage line lacking the nucleotide-binding/leucine-rich repeat pyrin domain containing 3 (NLRP3) inflammasome. IL-1 beta secretion in response to B. infantis and B. fragilis was significantly reduced when the wild-type macrophage line was treated with inhibitors of potassium efflux, either increased extracellular potassium concentrations or the channel blocker ruthenium red. Both live and heat-killed B. infantis and B. fragilis also induced IL-1 beta secretion by human macrophages (differentiated THP-1 cells or primary monocyte-derived macrophages) after 4 hours of infection, and the secretion was inhibited by raised extracellular potassium and ruthenium red but not by cytochalasin D. Taken together, our findings indicate that the commensal bacteria B. infantis and B. fragilis activate the NLRP3 inflammasome in both mouse and human macrophages by a mechanism that involves potassium efflux and that does not require bacterial viability or phagocytosis.
C1 [Chen, Kejie; Shanmugam, Nanda Kumar N.; Pazos, Michael A.; Hurley, Bryan P.; Cherayil, Bobby J.] Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA.
[Chen, Kejie; Shanmugam, Nanda Kumar N.; Pazos, Michael A.; Hurley, Bryan P.; Cherayil, Bobby J.] Harvard Med Sch, Boston, MA 02115 USA.
[Chen, Kejie] Sichuan Agr Univ, Coll Vet Med, Yaan, Sichuan, Peoples R China.
RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Dept Pediat, Mucosal Immunol & Biol Res Ctr, Boston, MA 02114 USA.; Cherayil, BJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM cherayil@helix.mgh.harvard.edu
FU National Institute of Allergy and Infectious Diseases [R01AI089700,
R01AI095338]; China Scholarship Council; Cystic Fibrosis Foundation
[PAZOS13F0]
FX This work was supported by grant numbers R01AI089700 and R01AI095338
from the National Institute of Allergy and Infectious Diseases to BJC
and BPH, respectively. KC was supported by funding from the China
Scholarship Council and MAP by fellowship number PAZOS13F0 from the
Cystic Fibrosis Foundation. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 45
TC 0
Z9 0
U1 8
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 AUG 9
PY 2016
VL 11
IS 8
AR e0160937
DI 10.1371/journal.pone.0160937
PG 20
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3IK
UT WOS:000381374200082
PM 27505062
ER
PT J
AU O'Donnell, PE
Ye, XZ
DeChellis, MA
Davis, VM
Duan, SZ
Mortensen, RM
Milstone, DS
AF O'Donnell, Peter E.
Ye, Xiu Zhen
DeChellis, Melissa A.
Davis, Vannessa M.
Duan, Sheng Zhong
Mortensen, Richard M.
Milstone, David S.
TI Lipodystrophy, Diabetes and Normal Serum Insulin in PPAR gamma-Deficient
Neonatal Mice
SO PLOS ONE
LA English
DT Article
ID ACTIVATED-RECEPTOR-GAMMA; ADIPOSE-TISSUE; ADIPOCYTE DIFFERENTIATION;
BETA-CELLS; RESISTANCE; FAT; DISRUPTION; EXPRESSION; KNOCKOUT; MUSCLE
AB Peroxisome proliferator activated receptor gamma (PPAR gamma) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPAR gamma also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPAR gamma in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPAR gamma. PPAR gamma-rescued placentas support development of PPAR gamma-deficient embryos that are viable and born in near normal numbers. However, PPAR gamma-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPAR gamma 2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPAR gamma 1 in the neonatal period either alone or in combination with PPAR gamma 2 in lipid metabolism, glucose homeostasis and insulin sensitivity.
C1 [O'Donnell, Peter E.; Ye, Xiu Zhen; DeChellis, Melissa A.; Davis, Vannessa M.; Milstone, David S.] Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA.
[O'Donnell, Peter E.; Ye, Xiu Zhen; DeChellis, Melissa A.; Davis, Vannessa M.; Milstone, David S.] Harvard Med Sch, Boston, MA 02115 USA.
[Duan, Sheng Zhong; Mortensen, Richard M.] Univ Michigan, Sch Med, Dept Physiol, Ann Arbor, MI USA.
[O'Donnell, Peter E.] Novartis Inst Biomed Res, Cambridge, MA USA.
[DeChellis, Melissa A.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Duan, Sheng Zhong] Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai, Peoples R China.
RP Milstone, DS (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA.; Milstone, DS (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM milstone@rics.bwh.harvard.edu
FU National Institute of Child Health and Human Development [R01HD40895];
National Heart, Lung and Blood Institute [P01HL36028]; pilot project and
cores of the Michigan Diabetes Research and Training Center from the
National Institute of Diabetes & Digestive & Kidney Diseases (RMM)
[NIH5P60 DK20572]; Tissue Microarray and Imaging Core Facility of the
Dana-Farber/Harvard Cancer Center [P30 CA06516]; Department of
Pathology, Brigham and Women's Hospital
FX This work was supported by grants from the National Institute of Child
Health and Human Development R01HD40895 (DSM), the National Heart, Lung
and Blood Institute P01HL36028 (DSM), a pilot project and cores of the
Michigan Diabetes Research and Training Center (NIH5P60 DK20572) from
the National Institute of Diabetes & Digestive & Kidney Diseases (RMM),
the Tissue Microarray and Imaging Core Facility of the
Dana-Farber/Harvard Cancer Center (P30 CA06516) and by the Department of
Pathology, Brigham and Women's Hospital (DSM). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 40
TC 0
Z9 0
U1 2
U2 2
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 AUG 9
PY 2016
VL 11
IS 8
AR e0160636
DI 10.1371/journal.pone.0160636
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3IK
UT WOS:000381374200049
PM 27505464
ER
PT J
AU Tian, B
Maidana, DE
Dib, B
Miller, JB
Bouzika, P
Miller, JW
Vavvas, DG
Lin, HJ
AF Tian, Bo
Maidana, Daniel E.
Dib, Bernard
Miller, John B.
Bouzika, Peggy
Miller, Joan W.
Vavvas, Demetrios G.
Lin, Haijiang
TI miR-17-3p Exacerbates Oxidative Damage in Human Retinal Pigment
Epithelial Cells
SO PLOS ONE
LA English
DT Article
ID MITOCHONDRIAL SUPEROXIDE-DISMUTASE; MACULAR DEGENERATION; ARPE-19 CELLS;
ENDOTHELIAL-CELLS; GENE-EXPRESSION; DOWN-REGULATION; MOUSE MODEL; RPE
CELLS; STRESS; THIOREDOXIN
AB Oxidative stress has been shown to contribute to the development of age-related macular degeneration (AMD). MicroRNAs (miRNA) are small non-coding RNA molecules that function in RNA silencing and post-transcriptional regulation of gene expression. We showed miR-17-3p to be elevated in macular RPE cells from AMD patients and in ARPE-19 cells under oxidative stress. Transfection of miR-17-3p mimic in ARPE-19 induced cell death and exacerbated oxidative lethality that was alleviated by miR-17-3p inhibitor. The expression of antioxidant enzymes manganese superoxide dismutase (MnSOD) and thioredoxin reductase-2 (TrxR(2)) were suppressed by miR-17-3p mimic and reversed by miR-17-3p inhibitor. These results suggest miR-17-3p aggravates oxidative damage-induced cell death in human RPE cells, while miR-17-3p inhibitor acts as a potential protector against oxidative stress by regulating the expression of antioxidant enzymes.
C1 [Tian, Bo; Maidana, Daniel E.; Dib, Bernard; Miller, John B.; Bouzika, Peggy; Miller, Joan W.; Vavvas, Demetrios G.; Lin, Haijiang] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA.
[Tian, Bo] Zhengzhou Univ, Affiliated Hosp 1, Dept Ophthalmol, Zhengzhou, Henan, Peoples R China.
RP Vavvas, DG; Lin, HJ (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis Lab,Dept Ophthalmol, Boston, MA 02115 USA.
EM Demetrios_Vavvas@meei.harvard.edu; Haijiang_Lin@meei.harvard.edu
FU NEI [R21EY023079-01A1, EY014104]; Yeatts Family Foundation; Loefflers
Family Fund; Macula Society Research Grant award; Physician Scientist
Award; research to prevent blindness foundation; Bayer Healthcare Global
Ophthalmology Award
FX This work was supported by: NEI R21EY023079-01A1 (DGV); the Yeatts
Family Foundation (DGV, JWM); the Loefflers Family Fund (DGV, JWM); the
2013 Macula Society Research Grant award (DGV); a Physician Scientist
Award (DGV), an unrestricted grant (JWM) from the research to prevent
blindness foundation; NEI grant EY014104 (Meei Core Grant); and Bayer
Healthcare Global Ophthalmology Award (DEM). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.; This work was supported by: NEI
R21EY023079-01A1 (DGV); the Yeatts Family Foundation (DGV, JWM); the
Loefflers Family Fund (DGV, JWM); the 2013 Macula Society Research Grant
award (DGV); a Physician Scientist Award (DGV), an unrestricted grant
(JWM) from the research to prevent blindness foundation; NEI grant
EY014104 (Meei Core Grant); and Bayer Healthcare Global Ophthalmology
Award (DEM). The authors would like to thank Kassandra Kosmidou for
proofreading this manuscript.
NR 75
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U1 2
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD AUG 9
PY 2016
VL 11
IS 8
AR e0160887
DI 10.1371/journal.pone.0160887
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT3IK
UT WOS:000381374200073
PM 27505139
ER
PT J
AU Chen, KY
Cypess, AM
Laughlin, MR
Haft, CR
Hu, HH
Bredella, MA
Enerback, S
Kinahan, PE
Lichtenbelt, WV
Lin, FI
Sunderland, JJ
Virtanen, KA
Wahl, RL
AF Chen, Kong Y.
Cypess, Aaron M.
Laughlin, Maren R.
Haft, Carol R.
Hu, Houchun Harry
Bredella, Miriam A.
Enerback, Sven
Kinahan, Paul E.
Lichtenbelt, Wouter van Marken
Lin, Frank I.
Sunderland, John J.
Virtanen, Kirsi A.
Wahl, Richard L.
TI Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0):
Recommendations for Standardized FDG-PET/CT Experiments in Humans
SO CELL METABOLISM
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; TYPE-2 DIABETES-MELLITUS; ADULT HUMANS;
F-18-FDG PET/CT; ENERGY-EXPENDITURE; OXIDATIVE-METABOLISM; INSULIN
SENSITIVITY; COMPUTED-TOMOGRAPHY; TISSUE ACTIVITY; COLD-EXPOSURE
AB Human brown adipose tissue (BAT) presence, metabolic activity, and estimated mass are typically measured by imaging [18F]fluorodeoxyglucose (FDG) uptake in response to cold exposure in regions of the body expected to contain BAT, using positron emission tomography combined with X-ray computed tomography (FDG-PET/CT). Efforts to describe the epidemiology and biology of human BAT are hampered by diverse experimental practices, making it difficult to directly compare results among laboratories. An expert panel was assembled by the National Institute of Diabetes and Digestive and Kidney Diseases on November 4, 2014 to discuss minimal requirements for conducting FDG-PET/CT experiments of human BAT, data analysis, and publication of results. This resulted in Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0). Since there are no fully validated best practices at this time, panel recommendations are meant to enhance comparability across experiments, but not to constrain experimental design or the questions that can be asked.
C1 [Chen, Kong Y.; Cypess, Aaron M.; Laughlin, Maren R.; Haft, Carol R.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Hu, Houchun Harry] Phoenix Childrens Hosp, Phoenix, AZ 85016 USA.
[Bredella, Miriam A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bredella, Miriam A.] Harvard Med Sch, Boston, MA 02114 USA.
[Enerback, Sven] Univ Gothenburg, S-40530 Gothenburg, Sweden.
[Kinahan, Paul E.] Univ Washington, Seattle, WA 98105 USA.
[Lichtenbelt, Wouter van Marken] Maastricht Univ, NL-6211 LK Maastricht, Netherlands.
[Lin, Frank I.] NCI, NIH, Bethesda, MD 20892 USA.
[Sunderland, John J.] Univ Iowa, Iowa City, IA 52242 USA.
[Virtanen, Kirsi A.] Turku Univ Hosp, Turku 20500, Finland.
[Virtanen, Kirsi A.] Univ Turku, SF-20500 Turku, Finland.
[Wahl, Richard L.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
RP Chen, KY; Cypess, AM; Laughlin, MR (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA.
EM kong.chen@nih.gov; aaron.cypess@nih.gov; maren.laughlin@nih.gov
OI Chen, Kong/0000-0002-0306-1904
FU Intramural Research Program of the NIH; National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK); National Cancer Institute
(NCI)
FX This research was supported in part by the Intramural Research Program
of the NIH, The National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK), and the National Cancer Institute (NCI).
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U1 3
U2 3
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 AUG 9
PY 2016
VL 24
IS 2
BP 210
EP 222
DI 10.1016/j.cmet.2016.07.014
PG 13
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DT3PH
UT WOS:000381392800010
PM 27508870
ER
PT J
AU Khetarpal, SA
Schjoldager, KT
Christoffersen, C
Raghavan, A
Edmondson, AC
Reutter, HM
Ahmed, B
Ouazzani, R
Peloso, GM
Vitali, C
Zhao, W
Somasundara, AVH
Millar, JS
Park, Y
Fernando, G
Livanov, V
Choi, S
Noe, E
Patel, P
Ho, SP
Kirchgessner, TG
Wandall, HH
Hansen, L
Bennett, EP
Vakhrushev, SY
Saleheen, D
Kathiresan, S
Brown, CD
Abou Jamra, R
LeGuern, E
Clausen, H
Rader, DJ
AF Khetarpal, Sumeet A.
Schjoldager, Katrine T.
Christoffersen, Christina
Raghavan, Avanthi
Edmondson, Andrew C.
Reutter, Heiko M.
Ahmed, Bouhouche
Ouazzani, Reda
Peloso, Gina M.
Vitali, Cecilia
Zhao, Wei
Somasundara, Amritha Varshini Hanasoge
Millar, John S.
Park, YoSon
Fernando, Gayani
Livanov, Valentin
Choi, Seungbum
Noe, Eric
Patel, Pritesh
Ho, Siew Peng
Kirchgessner, Todd G.
Wandall, Hans H.
Hansen, Lars
Bennett, Eric P.
Vakhrushev, Sergey Y.
Saleheen, Danish
Kathiresan, Sekar
Brown, Christopher D.
Abou Jamra, Rami
LeGuern, Eric
Clausen, Henrik
Rader, Daniel J.
CA Myocardial Infarction Exome
TI Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans,
Nonhuman Primates, and Rodents
SO CELL METABOLISM
LA English
DT Article
ID PHOSPHOLIPID-TRANSFER PROTEIN; O-GLYCOSYLATION; CHOLESTEROL HOMEOSTASIS;
PLASMA; LOCI; SECRETION; VARIANTS; MUTATION; GLYCOPROTEOME; ASSOCIATION
AB Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian models. We identified two humans homozygous for loss-of-function mutations in GALNT2 who demonstrated low HDL-C. We also found that GALNT2 loss of function in mice, rats, and nonhuman primates decreased HDL-C. O-glycoproteomics studies of a human GALNT2-deficient subject validated ANGPTL3 and ApoC-III as GalNAc-T2 targets. Additional glycoproteomics in rodents identified targets influencing HDL-C, including phospholipid transfer protein (PLTP). GALNT2 deficiency reduced plasma PLTP activity in humans and rodents, and in mice this was rescued by reconstitution of hepatic Galnt2. We also found that GALNT2 GWAS SNPs associated with reduced HDL-C also correlate with lower hepatic GALNT2 expression. These results posit GALNT2 as a direct modulator of HDL metabolism across mammals.
C1 [Khetarpal, Sumeet A.; Raghavan, Avanthi; Edmondson, Andrew C.; Vitali, Cecilia; Zhao, Wei; Somasundara, Amritha Varshini Hanasoge; Millar, John S.; Park, YoSon; Brown, Christopher D.; Rader, Daniel J.] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Khetarpal, Sumeet A.; Raghavan, Avanthi; Edmondson, Andrew C.; Vitali, Cecilia; Zhao, Wei; Somasundara, Amritha Varshini Hanasoge; Millar, John S.; Rader, Daniel J.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Schjoldager, Katrine T.; Wandall, Hans H.; Hansen, Lars; Bennett, Eric P.; Vakhrushev, Sergey Y.; Clausen, Henrik] Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Cellular & Mol Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
[Schjoldager, Katrine T.; Wandall, Hans H.; Hansen, Lars; Bennett, Eric P.; Vakhrushev, Sergey Y.; Clausen, Henrik] Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Odontol, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
[Christoffersen, Christina] Univ Copenhagen, Rigshosp, Dept Clin Biochem, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
[Christoffersen, Christina] Univ Copenhagen, Dept Biomed Sci, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
[Reutter, Heiko M.] Univ Bonn, Inst Human Genet, D-53012 Bonn, Germany.
[Reutter, Heiko M.] Univ Bonn, Dept Neonatol & Pediat Intens Care, D-53012 Bonn, Germany.
[Ahmed, Bouhouche] Mohammed V Univ, Sch Med, Res Team Neurodegenerat Dis, Rabat 10100, Morocco.
[Ahmed, Bouhouche] Mohammed V Univ, Pharm, Rabat 10100, Morocco.
[Ouazzani, Reda] CHIS Ibn Sina, Hosp Special, Neurophysiol Div, Rabat 6402, Morocco.
[Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Peloso, Gina M.; Kathiresan, Sekar; Myocardial Infarction Exome] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Fernando, Gayani; Kirchgessner, Todd G.] Bristol Myers Squibb, Dept Cardiovasc Drug Discovery, Pennington, NJ 08534 USA.
[Livanov, Valentin; Patel, Pritesh; Ho, Siew Peng] Bristol Myers Squibb, Dept Appl Genom, Pennington, NJ 08534 USA.
[Choi, Seungbum] Gachon Univ, Gacheon Cardiovasc Res Inst, Inchon 21565, South Korea.
[Noe, Eric; LeGuern, Eric] Univ Paris 06, INSERM, Sorbonne Univ, UMR S 1127,U1127,CNRS,UMR 7225,ICM, F-75013 Paris, France.
[Noe, Eric; LeGuern, Eric] Pitie La Salpetriere Hosp, AP HP, Dept Genet, F-75013 Paris, France.
[Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.
[Saleheen, Danish] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Saleheen, Danish] Ctr Noncommunicable Dis, Karachi 75300, Pakistan.
[Kathiresan, Sekar] Harvard Med Sch, Dept Med, Boston, MA 02114 USA.
[Abou Jamra, Rami] Univ Leipzig, Hosp & Clin, Inst Human Genet, D-04103 Leipzig, Germany.
[Abou Jamra, Rami] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
RP Rader, DJ (reprint author), Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.; Rader, DJ (reprint author), Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.; Schjoldager, KT (reprint author), Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Cellular & Mol Med, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.; Schjoldager, KT (reprint author), Univ Copenhagen, Inst Hlth Sci, Copenhagen Ctr Glyc, Dept Odontol, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
EM schjoldager@sund.ku.dk; rader@mail.med.upenn.edu
OI Wandall, Hans H./0000-0003-0240-9232; Brown,
Christopher/0000-0002-3785-5008
FU Danish Research Councils; Kirsten og Freddy Johansen Fonden; A.P. Moller
og Hustru Chastine Mc-Kinney Mollers Fond til Almene Formaal; Novo
Nordisk Foundation; University of Copenhagen [CDO2016]; Danish National
Research Foundation [DNRF107]; NIH [R01 HL111398, R01 HL089309];
Foundation Leducq [10CVD03]; German Research Foundation (DFG)
[AB393/2-2]; Mizutani Foundation
FX We acknowledge Thomas F. Vogt, John S. Mudgett, and Merck Research
Laboratories for providing Galnt2 KO mice. We thank the UPenn Functional
Genomics Core at DRC (P30-DK19525) for RNA sequencing and the University
of Pennsylvania Preclinical Vector Core supported by the NHLBI Gene
Therapy Resource Program (GTRP) for providing gene vectors used in this
study. This work was supported by The Danish Research Councils (Sapere
Aude Research Talent Grant to K.T.S.), Kirsten og Freddy Johansen
Fonden, A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond til Almene
Formaal, The Novo Nordisk Foundation, a program of excellence from the
University of Copenhagen (CDO2016), the Danish National Research
Foundation (DNRF107), NIH grants R01 HL111398 and R01 HL089309, and
grant 10CVD03 from the Foundation Leducq to D.J.R; the German Research
Foundation (DFG) with funding AB393/2-2 to R.A.J.; and the Mizutani
Foundation to S.Y.V. We also thank Pr. El Fahime El Mostafa for hosting
K.T.S. in his laboratory.
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U1 3
U2 3
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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 AUG 9
PY 2016
VL 24
IS 2
BP 234
EP 245
DI 10.1016/j.cmet.2016.07.012
PG 12
WC Cell Biology; Endocrinology & Metabolism
SC Cell Biology; Endocrinology & Metabolism
GA DT3PH
UT WOS:000381392800012
PM 27508872
ER
PT J
AU Yu, VWC
Lymperi, S
Oki, T
Jones, A
Swiatek, P
Vasic, R
Ferraro, F
Scadden, DT
AF Yu, Vionnie W. C.
Lymperi, Stefania
Oki, Toshihiko
Jones, Alexandra
Swiatek, Peter
Vasic, Radovan
Ferraro, Francesca
Scadden, David T.
TI Distinctive Mesenchymal-Parenchymal Cell Pairings Govern B Cell
Differentiation in the Bone Marrow
SO STEM CELL REPORTS
LA English
DT Article
ID HEMATOPOIETIC STEM-CELL; GROWTH-FACTOR-I; OSTEOBLAST DIFFERENTIATION;
NICHE; PROGENITORS; MAINTENANCE; LINEAGE; OSTERIX; MICE; IDENTIFICATION
AB Bone marrow niches for hematopoietic progenitor cells are not well defined despite their critical role in blood homeostasis. We previously found that cells expressing osteocalcin, a marker of mature osteolineage cells, regulate the production of thymic-seeding T lymphoid progenitors. Here, using a selective cell deletion strategy, we demonstrate that a subset of mesenchymal cells expressing osterix, a marker of bone precursors in the adult, serve to regulate the maturation of early B lymphoid precursors by promoting pro-B to pre-B cell transition through insulin-like growth factor 1 (IGF-1) production. Loss of Osx(+) cells or Osx-specific deletion of IGF-1 led to a failure of B cell maturation and the impaired adaptive immune response. These data highlight the notion that bone marrow is a composite of specialized niches formed by pairings of specific mesenchymal cells with parenchymal stem or lineage committed progenitor cells, thereby providing distinctive functional units to regulate hematopoiesis.
C1 [Yu, Vionnie W. C.; Lymperi, Stefania; Oki, Toshihiko; Jones, Alexandra; Swiatek, Peter; Vasic, Radovan; Ferraro, Francesca; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Yu, Vionnie W. C.; Lymperi, Stefania; Oki, Toshihiko; Jones, Alexandra; Swiatek, Peter; Vasic, Radovan; Ferraro, Francesca; Scadden, David T.] Harvard Stem Cell Inst, Boston, MA 02114 USA.
[Yu, Vionnie W. C.; Lymperi, Stefania; Oki, Toshihiko; Jones, Alexandra; Swiatek, Peter; Vasic, Radovan; Ferraro, Francesca; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA.
[Ferraro, Francesca] Univ Penn Hlth Syst, Penn Hosp, Dept Med, 800 Spruce St, Philadelphia, PA 19107 USA.
[Scadden, David T.] Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02115 USA.
RP Ferraro, F; Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.; Ferraro, F; Scadden, DT (reprint author), Harvard Stem Cell Inst, Boston, MA 02114 USA.; Ferraro, F; Scadden, DT (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02139 USA.; Ferraro, F (reprint author), Univ Penn Hlth Syst, Penn Hosp, Dept Med, 800 Spruce St, Philadelphia, PA 19107 USA.; Scadden, DT (reprint author), Massachusetts Gen Hosp, Harvard Stem Cell Inst, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02115 USA.
EM f.ferraro.mgh@gmail.com; david_scadden@harvard.edu
FU NIH - Gerald and Darlene Jordan Chair of Medicine [HL044851, HL096372,
EB014703]
FX We thank Dr. Andrew P. McMahon at Harvard University for his generosity
in providing the Osx1-GFP::Cre mouse strain. We are thankful to Dr. Rene
Maher who provided the Rosa 26-loxP-STOP-loxP-membrane Cherry (Rosa-mCh)
mouse. We thank the Harvard Stem Cell Institute Flow Cytometry Core for
assistance in flow cytometry. This work was supported by NIH HL044851,
HL096372, EB014703 to D.T.S. who was also supported by the Gerald and
Darlene Jordan Chair of Medicine.
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U1 0
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PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2213-6711
J9 STEM CELL REP
JI Stem Cell Rep.
PD AUG 9
PY 2016
VL 7
IS 2
BP 220
EP 235
DI 10.1016/j.stemcr.2016.06.009
PG 16
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA DT3KW
UT WOS:000381380900008
PM 27453006
ER
PT J
AU Jourdain, G
Ngo-Giang-Huong, N
Cressey, TR
Hua, L
Harrison, L
Tierney, C
Salvadori, N
Decker, L
Traisathit, P
Sirirungsi, W
Khamduang, W
Bowonwatanuwong, C
Puthanakit, T
Siberry, GK
Watts, DH
Murphy, TV
Achalapong, J
Hongsiriwon, S
Klinbuayaem, V
Thongsawat, S
Chung, RT
Pol, S
Chotivanich, N
AF Jourdain, Gonzague
Ngo-Giang-Huong, Nicole
Cressey, Tim R.
Hua, Lei
Harrison, Linda
Tierney, Camlin
Salvadori, Nicolas
Decker, Luc
Traisathit, Patrinee
Sirirungsi, Wasna
Khamduang, Woottichai
Bowonwatanuwong, Chureeratana
Puthanakit, Thanyawee
Siberry, George K.
Watts, Diane Heather
Murphy, Trudy V.
Achalapong, Jullapong
Hongsiriwon, Suchat
Klinbuayaem, Virat
Thongsawat, Satawat
Chung, Raymond T.
Pol, Stanislas
Chotivanich, Nantasak
TI Prevention of mother-to-child transmission of hepatitis B virus: a phase
III, placebo-controlled, double-blind, randomized clinical trial to
assess the efficacy and safety of a short course of tenofovir disoproxil
fumarate in women with hepatitis B virus e-antigen
SO BMC INFECTIOUS DISEASES
LA English
DT Article
ID PERINATAL TRANSMISSION; INFANT TRANSMISSION; SURFACE-ANTIGEN; INFECTION;
PREGNANCY; METAANALYSIS
AB Background: Chronic hepatitis B virus (HBV) infection is complicated by cirrhosis and liver cancer. In Thailand, 6-7 % of adults are chronically infected with HBV. The risk of mother-to-child transmission (MTCT) of HBV has been estimated to be about 12 % when mothers have a high hepatitis B viral load, even if infants receive passive-active prophylaxis with HBV immunoglobulin (HBIg) and initiate the hepatitis B vaccine series at birth. We designed a study to assess the efficacy and safety of a short course of maternal tenofovir disoproxil fumarate (TDF) among women with a marker of high viral load for the prevention of MTCT of HBV.
Methods: The study is a phase III, multicenter (17 sites in Thailand), placebo-controlled, double-blind, randomized 1: 1, two-arm clinical trial of TDF 300 mg once daily versus placebo among pregnant women from 28 weeks' gestation through 2-month post-partum. All infants receive HBIg at birth, and a hepatitis B (HB) vaccination series according to Thai guidelines: birth, and age 1, 2, 4 and 6 months. Participant women at study entry must be age >= 18 years, hepatitis B surface antigen (HBsAg) and e-antigen (HBeAg) positive, have alanine aminotransferase (ALT) level < 30 IU/L at screening (confirmed < 60 IU/L pre-entry), negative hepatitis C serology, creatinine clearance > 50 mL/min, and no history of anti-HBV antiviral treatment.
The target sample size of 328 mother/infant pairs assumed 156 evaluable cases per arm to detect a >= 9 % difference in MTCT transmission (3 % experimental arm versus 12 % placebo arm) with 90 % power. Mothers and infants are followed until 12 months after delivery. The primary infant endpoint is detection of HBsAg, confirmed by detection of HBV DNA at six months of age. Secondary endpoints are maternal and infant adverse events, acute exacerbations of maternal hepatitis B disease (ALT > 300 IU/ L, defined as a "flare") following discontinuation of study treatment, infant HBV infection status and growth up to 12 months of age.
Discussion: The results of this randomized trial will clarify the efficacy and safety of a short course of antiviral treatment to prevent mother-to-child transmission of HBV and inform international guidelines.
C1 [Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.; Salvadori, Nicolas; Decker, Luc] Inst Rech Dev IRD France, PHPT, UMI 174, 187-10 Changklan Rd, Chiang Mai 50100, Thailand.
[Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.; Salvadori, Nicolas; Decker, Luc; Sirirungsi, Wasna; Khamduang, Woottichai] Chiang Mai Univ, Fac Associated Med Sci, 110 Intawaroroj Rd, Chiang Mai 50200, Thailand.
[Jourdain, Gonzague; Ngo-Giang-Huong, Nicole; Cressey, Tim R.] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, 677 Huntington Ave, Boston, MA 02115 USA.
[Cressey, Tim R.] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England.
[Hua, Lei; Harrison, Linda; Tierney, Camlin] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res CBAR, 677 Huntington Ave, Boston, MA 02115 USA.
[Bowonwatanuwong, Chureeratana; Chotivanich, Nantasak] Chonburi Hosp, 69 M-2,Sukhumvit Rd, Muang 20000, Chonburi, Thailand.
[Puthanakit, Thanyawee] Chulalongkorn Univ, Fac Med, 1873 Rama 4 Rd, Bangkok 10330, Thailand.
[Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 6100 Execut Blvd, Bethesda, MD 20892 USA.
[Watts, Diane Heather] US Dept State, Off Global AIDS Coordinator, SA-22,2201 C St NW, Washington, DC 20522 USA.
[Murphy, Trudy V.] Ctr Dis Control & Prevent, DHHS CDC NCHHSTP DVH Vaccine Unit, Bldg Corp SQ 12,Room 3111, Atlanta, GA 30329 USA.
[Achalapong, Jullapong] Chiangrai Prachanukroh Hosp, Dept Obstet & Gynecol, 1039 Sathan Phayaban Rd, Muang 57000, Chiang Rai, Thailand.
[Hongsiriwon, Suchat] Chonburi Hosp, Dept Pediat, 69 M-2,Sukhumvit Rd, Muang 20000, Chonburi, Thailand.
[Klinbuayaem, Virat] Sanpatong Hosp, Dept Med, 149 M-15 Yuhwa, Chiang Mai 50120, Thailand.
[Traisathit, Patrinee] Chiang Mai Univ, Dept Stat, Fac Sci, 239 Huaykaew Rd, Chiang Mai 50200, Thailand.
[Thongsawat, Satawat] Chiang Mai Univ, Dept Internal Med, Fac Med, Chiang Mai 50200, Thailand.
[Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, GI Unit, WRN 1007C,55 Fruit St, Boston, MA 02114 USA.
[Pol, Stanislas] Cochin Univ Hosp, Dept Hepatogastroenterol, 27 Rue Faubourg St Jacques, F-75679 Paris 14, France.
RP Jourdain, G (reprint author), Inst Rech Dev IRD France, PHPT, UMI 174, 187-10 Changklan Rd, Chiang Mai 50100, Thailand.; Jourdain, G (reprint author), Chiang Mai Univ, Fac Associated Med Sci, 110 Intawaroroj Rd, Chiang Mai 50200, Thailand.
EM gonzague.jourdain@ird.fr
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD) [U01HD071889]
FX The study activities are supported by a grant from the Eunice Kennedy
Shriver National Institute of Child Health & Human Development (NICHD)
(U01HD071889) under a cooperative agreement between NICHD, the Centers
for Disease Control and Prevention, United States of America, and
Institut de recherche pour le developpement, France.
NR 12
TC 1
Z9 1
U1 8
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2334
J9 BMC INFECT DIS
JI BMC Infect. Dis.
PD AUG 9
PY 2016
VL 16
AR 393
DI 10.1186/s12879-016-1734-5
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA DT2YM
UT WOS:000381347700010
PM 27506549
ER
PT J
AU Joyce, BT
Gao, T
Zheng, YA
Liu, L
Zhang, W
Dai, Q
Shrubsole, MJ
Hibler, EA
Cristofanilli, M
Zhang, H
Yang, HS
Vokonas, P
Cantone, L
Schwartz, J
Baccarelli, A
Hou, LF
AF Joyce, Brian T.
Gao, Tao
Zheng, Yinan
Liu, Lei
Zhang, Wei
Dai, Qi
Shrubsole, Martha J.
Hibler, Elizabeth A.
Cristofanilli, Massimo
Zhang, Hu
Yang, Hushan
Vokonas, Pantel
Cantone, Laura
Schwartz, Joel
Baccarelli, Andrea
Hou, Lifang
TI Prospective changes in global DNA methylation and cancer incidence and
mortality
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE Global DNA methylation; cancer incidence; cancer mortality
ID BLOOD LEUKOCYTE DNA; HEPATOCELLULAR-CARCINOMA; BLADDER-CANCER;
GASTRIC-CANCER; BREAST-CANCER; REPETITIVE ELEMENTS; LINE-1 METHYLATION;
COLORECTAL ADENOMA; PERIPHERAL-BLOOD; CELL DNA
AB Background: Methylation of repetitive elements Alu and LINE-1 in humans is considered a surrogate for global DNA methylation. Previous studies of blood-measured Alu/LINE-1 and cancer risk are inconsistent.
Methods: We studied 1259 prospective methylation measurements from blood drawn 1-4 times from 583 participants from 1999 to 2012. We used Cox regression to evaluate time-dependent methylation as a biomarker for cancer risk and mortality, and linear regression to compare mean differences in methylation over time by cancer status and analyse associations between rate of methylation change and cancer.
Results: Time-dependent LINE-1 methylation was associated with prostate cancer incidence (HR: 1.38, 95% CI: 1.01-1.88) and all-cancer mortality (HR: 1.41, 95% CI: 1.03-1.92). The first measurement of Alu methylation (HR: 1.39, 95% CI: 1.08-1.79) was associated with all-cancer mortality. Participants who ultimately developed cancer had lower mean LINE-1 methylation than cancer-free participants 10+ years pre-diagnosis (P<0.01). Rate of Alu methylation change was associated with all-cancer incidence (HR: 3.62, 95% CI: 1.09-12.10).
Conclusions: Our results add longitudinal data on blood Alu and LINE-1 methylation and cancer, and potentially contribute to their use as early-detection biomarkers. Future larger studies are needed and should account for the interval between blood sample collection and cancer diagnosis.
C1 [Joyce, Brian T.; Gao, Tao; Zheng, Yinan; Liu, Lei; Zhang, Wei; Hibler, Elizabeth A.; Zhang, Hu; Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
[Joyce, Brian T.] Univ Illinois, Sch Publ Hlth, Div Epidemiol Biostat, 1603 W Taylor St, Chicago, IL 60612 USA.
[Zheng, Yinan] Northwestern Univ, Inst Publ Hlth & Med, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
[Dai, Qi; Shrubsole, Martha J.] Vanderbilt Univ, Med Ctr, 2525 West End Ave,Suite 319, Nashville, TN 37203 USA.
[Cristofanilli, Massimo] Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, 676 N St Clair St,8th Floor, Chicago, IL 60611 USA.
[Yang, Hushan] Thomas Jefferson Univ, Div Populat Sci, Dept Med Oncol, Sidney Kimmel Canc Ctr, 834 Chestnut St,Suite 314, Philadelphia, PA 19107 USA.
[Vokonas, Pantel] VA Boston Healthcare Syst, VA Normat Aging Study, 150 South Huntington Ave, Boston, MA 02130 USA.
[Vokonas, Pantel] Boston Univ, Dept Med, Sch Med, Boston, MA 02118 USA.
[Cantone, Laura] Univ Milan, Dept Clin Sci & Community Hlth, Mol Epidemiol & Environm Epigenet Lab, San Barnaba 8, I-20122 Milan, Italy.
[Schwartz, Joel; Baccarelli, Andrea] Harvard Sch Publ Hlth, Dept Environm Hlth, 655 Huntington Ave, Boston, MA 02115 USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, 303 E Chicago Ave,Olson Pavil 8350, Chicago, IL 60611 USA.
RP Hou, LF (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.; Hou, LF (reprint author), Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, 303 E Chicago Ave,Olson Pavil 8350, Chicago, IL 60611 USA.
EM l-hou@northwestern.edu
RI Liu, Lei/B-4968-2009; Zheng, Yinan/E-5775-2017;
OI Liu, Lei/0000-0003-1844-338X; Cantone, Laura/0000-0003-3660-129X
FU Ziff Fund at the Harvard University Center for the Environment, NIEHS
grants [RO1-ES015172, 2RO1-ES015172, ES014663]; Cooperative Studies
Program/Epidemiology Research and Information Center of the U.S.
Department of Veterans Affairs; USEPA grant [RD-832416, RD-83479801];
Northwestern University Robert H. Lurie Comprehensive Cancer Center
Rosenberg Research Fund; National Institute of Environmental Health
Sciences [NIEHS R01-ES021733, NIEHS R01-ES015172, NIEHS P30-ES00002]
FX This work was supported by the Ziff Fund at the Harvard University
Center for the Environment, NIEHS grants RO1-ES015172, 2RO1-ES015172,
and ES014663. The Normative Aging Study is supported by the Cooperative
Studies Program/Epidemiology Research and Information Center of the U.S.
Department of Veterans Affairs and is a component of the Massachusetts
Veterans Epidemiology Research and Information Center, Boston, MA, USA.
In addition, this publication was made possible by USEPA grant RD-832416
and RD-83479801. LH received additional support from the Northwestern
University Robert H. Lurie Comprehensive Cancer Center Rosenberg
Research Fund. AB and JS received additional support from the National
Institute of Environmental Health Sciences (NIEHS R01-ES021733, NIEHS
R01-ES015172, and NIEHS P30-ES00002).
NR 48
TC 0
Z9 0
U1 3
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 AUG 9
PY 2016
VL 115
IS 4
BP 465
EP 472
DI 10.1038/bjc.2016.205
PG 8
WC Oncology
SC Oncology
GA DT2HZ
UT WOS:000381302700009
PM 27351216
ER
PT J
AU Killian, NJ
Watkins, PV
Davidson, LS
Barbour, DL
AF Killian, Nathan J.
Watkins, Paul V.
Davidson, Lisa S.
Barbour, Dennis L.
TI The Effects of Auditory Contrast Tuning upon Speech Intelligibility
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Article
DE auditory cortex; noise reduction; human; cochlear implant; primate
ID HEARING-IMPAIRED LISTENERS; COCHLEAR IMPLANT LISTENERS; MINIMUM SPECTRAL
CONTRAST; FREQUENCY-SELECTIVITY; VOWEL IDENTIFICATION; ACOUSTIC HEARING;
NOISE; ENHANCEMENT; RECOGNITION; RESOLUTION
AB We have previously identified neurons tuned to spectral contrast of wideband sounds in auditory cortex of awake marmoset monkeys. Because additive noise alters the spectral contrast of speech, contrast-tuned neurons, if present in human auditory cortex, may aid in extracting speech from noise. Given that this cortical function may be underdeveloped in individuals with sensorineural hearing loss, incorporating biologically-inspired algorithms into external signal processing devices could provide speech enhancement benefits to cochlear implantees. In this study we first constructed a computational signal processing algorithm to mimic auditory cortex contrast tuning. We then manipulated the shape of contrast channels and evaluated the intelligibility of reconstructed noisy speech using a metric to predict cochlear implant user perception. Candidate speech enhancement strategies were then tested in cochlear implantees with a hearing-in-noise test. Accentuation of intermediate contrast values or all contrast values improved computed intelligibility. Cochlear implant subjects showed significant improvement in noisy speech intelligibility with a contrast shaping procedure.
C1 [Killian, Nathan J.; Watkins, Paul V.; Barbour, Dennis L.] Washington Univ, Dept Biomed Engn, Lab Sensory Neurosci & Neuroengn, St Louis, MO 63130 USA.
[Davidson, Lisa S.] Washington Univ, Sch Med, Cent Inst Deaf, St Louis, MO USA.
[Killian, Nathan J.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA.
[Watkins, Paul V.] Global Solut Network Inc, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
RP Barbour, DL (reprint author), Washington Univ, Dept Biomed Engn, Lab Sensory Neurosci & Neuroengn, St Louis, MO 63130 USA.
EM dbarbour@wustl.edu
FU Wallace H. Coulter Foundation; National Institutes of health
[R01-DC009215]; Center for Integration of Medicine and Innovative
Technology
FX Supported by The Wallace H. Coulter Foundation and National Institutes
of health grant R01-DC009215 and The Center for Integration of Medicine
and Innovative Technology.
NR 39
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U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD AUG 9
PY 2016
VL 7
AR 1145
DI 10.3389/fpsyg.2076.07745
PG 16
WC Psychology, Multidisciplinary
SC Psychology
GA DS7WB
UT WOS:000380992500002
PM 27555826
ER
PT J
AU Bibbins-Domingo, K
Grossman, DC
Curry, SJ
Davidson, KW
Epling, JW
Garcia, FAR
Gillman, MW
Kemper, AR
Krist, AH
Kurth, AE
Landefeld, CS
LeFevre, M
Mangione, CM
Phillips, WR
Phipps, MG
Pignone, MP
Siu, AL
AF Bibbins-Domingo, Kirsten
Grossman, David C.
Curry, Susan J.
Davidson, Karina W.
Epling, John W., Jr.
Garcia, Francisco A. R.
Gillman, Matthew W.
Kemper, Alex R.
Krist, Alex H.
Kurth, Ann E.
Landefeld, C. Seth
LeFevre, Michael
Mangione, Carol M.
Phillips, William R.
Phipps, Maureen G.
Pignone, Michael P.
Siu, Albert L.
CA US Preventive Serv Task Force
TI Screening for Lipid Disorders in Children and Adolescents US Preventive
Services Task Force Recommendation Statement
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Review
ID FAMILIAL HYPERCHOLESTEROLEMIA; BLOOD; DYSLIPIDEMIA; PREVALENCE;
CHILDHOOD; THERAPY; DISEASE; TRENDS; RISK
AB IMPORTANCE Elevations in levels of total, low-density lipoprotein, and non-high-density lipoprotein cholesterol; lower levels of high-density lipoprotein cholesterol; and, to a lesser extent, elevated triglyceride levels are associated with risk of cardiovascular disease in adults.
OBJECTIVE To update the 2007 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in children, adolescents, and young adults.
EVIDENCE REVIEW The USPSTF reviewed the evidence on screening for lipid disorders in children and adolescents 20 years or younger-1 review focused on screening for heterozygous familial hypercholesterolemia, and 1 review focused on screening for multifactorial dyslipidemia.
FINDINGS Evidence on the quantitative difference in diagnostic yield between universal and selective screening approaches, the effectiveness and harms of long-term treatment and the harms of screening, and the association between changes in intermediate outcomes and improvements in adult cardiovascular health outcomes are limited. Therefore, the USPSTF concludes that the balance of benefits and harms cannot be determined.
CONCLUSIONS AND RECOMMENDATION The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders in children and adolescents 20 years or younger. (I statement)
C1 [Bibbins-Domingo, Kirsten] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Grossman, David C.] Grp Hlth Res Inst, Seattle, WA USA.
[Curry, Susan J.] Univ Iowa, Iowa City, IA USA.
[Davidson, Karina W.] Columbia Univ, New York, NY USA.
[Epling, John W., Jr.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA.
[Garcia, Francisco A. R.] Pima Cty Dept Hlth, Tucson, AZ USA.
[Gillman, Matthew W.] Harvard Med Sch, Boston, MA USA.
[Gillman, Matthew W.] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Kemper, Alex R.] Duke Univ, Durham, NC USA.
[Krist, Alex H.] Fairfax Family Practice Residency, Fairfax, VA USA.
[Krist, Alex H.] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Kurth, Ann E.] Yale Univ, New Haven, CT USA.
[Landefeld, C. Seth] Univ Alabama Birmingham, Birmingham, AL USA.
[LeFevre, Michael] Univ Missouri, Columbia, MO 65211 USA.
[Mangione, Carol M.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Phillips, William R.] Univ Washington, Seattle, WA 98195 USA.
[Phipps, Maureen G.] Brown Univ, Providence, RI 02912 USA.
[Pignone, Michael P.] Univ Texas Austin, Austin, TX 78712 USA.
[Siu, Albert L.] Mt Sinai Sch Med, New York, NY USA.
[Siu, Albert L.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
RP Bibbins-Domingo, K (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.
OI Epling, John W/0000-0001-9445-8669
FU Agency for Healthcare Research and Quality (AHRQ)
FX The USPSTF is an independent, voluntary body. The US Congress mandates
that the Agency for Healthcare Research and Quality (AHRQ) support the
operations of the USPSTF.
NR 32
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U1 3
U2 3
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 AUG 9
PY 2016
VL 316
IS 6
BP 625
EP 633
DI 10.1001/jama.2016.9852
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS7TK
UT WOS:000380985600015
ER
PT J
AU Liang, SH
Chen, JM
Normandin, MD
Chang, JS
Chang, GC
Taylor, CK
Trapa, P
Plummer, MS
Para, KS
Conn, EL
Lopresti-Morrow, L
Lanyon, LF
Cook, JM
Richter, KEG
Nolan, CE
Schachter, JB
Janat, F
Che, Y
Shanmugasundaram, V
Lefker, BA
Enerson, BE
Livni, E
Wang, L
Guehl, NJ
Patnaik, D
Wagner, FF
Perlis, R
Holson, EB
Haggarty, SJ
El Fakhri, G
Kurumbail, RG
Vasdev, N
AF Liang, Steven H.
Chen, Jinshan Michael
Normandin, Marc D.
Chang, Jeanne S.
Chang, George C.
Taylor, Christine K.
Trapa, Patrick
Plummer, Mark S.
Para, Kimberly S.
Conn, Edward L.
Lopresti-Morrow, Lori
Lanyon, Lorraine F.
Cook, James M.
Richter, Karl E. G.
Nolan, Charlie E.
Schachter, Joel B.
Janat, Fouad
Che, Ye
Shanmugasundaram, Veerabahu
Lefker, Bruce A.
Enerson, Bradley E.
Livni, Elijahu
Wang, Lu
Guehl, Nicolas J.
Patnaik, Debasis
Wagner, Florence F.
Perlis, Roy
Holson, Edward B.
Haggarty, Stephen J.
El Fakhri, Georges
Kurumbail, Ravi G.
Vasdev, Neil
TI Discovery of a Highly Selective Glycogen Synthase Kinase-3 Inhibitor
(PF-04802367) That Modulates Tau Phosphorylation in the Brain:
Translation for PET Neuroimaging
SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
LA English
DT Article
DE Alzheimer's disease; glycogen synthase kinase-3; phosphorylation;
positron emission tomography; tau proteins
ID ALZHEIMERS-DISEASE; TRANSGENIC MICE; GSK-3-BETA; RADIOSYNTHESIS;
RADIOTRACER; VIVO
AB Glycogen synthase kinase-3 (GSK-3) regulates multiple cellular processes in diabetes, oncology, and neurology. N-(3-(1H-1,2,4-triazol-1-yl)propyl)-5-(3-chloro-4-methoxyphenyl)oxazole-4-carboxamide (PF-04802367 or PF367) has been identified as a highly potent inhibitor, which is among the most selective antagonists of GSK-3 to date. Its efficacy was demonstrated in modulation of tau phosphorylation in vitro and in vivo. Whereas the kinetics of PF-367 binding in brain tissues are too fast for an effective therapeutic agent, the pharmacokinetic profile of PF-367 is ideal for discovery of radiopharmaceuticals for GSK-3 in the central nervous system. A C-11-isotopologue of PF-367 was synthesized and preliminary PET imaging studies in non-human primates confirmed that we have overcome the two major obstacles for imaging GSK-3, namely, reasonable brain permeability and displaceable binding.
C1 [Liang, Steven H.; Normandin, Marc D.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas J.; El Fakhri, Georges; Vasdev, Neil] Massachusetts Gen Hosp, Gordon Ctr Med Imaging & Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Liang, Steven H.; Normandin, Marc D.; Livni, Elijahu; Wang, Lu; Guehl, Nicolas J.; El Fakhri, Georges; Vasdev, Neil] Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA.
[Chen, Jinshan Michael; Chang, Jeanne S.; Chang, George C.; Taylor, Christine K.; Plummer, Mark S.; Para, Kimberly S.; Conn, Edward L.; Lopresti-Morrow, Lori; Lanyon, Lorraine F.; Cook, James M.; Richter, Karl E. G.; Nolan, Charlie E.; Schachter, Joel B.; Janat, Fouad; Che, Ye; Shanmugasundaram, Veerabahu; Enerson, Bradley E.; Kurumbail, Ravi G.] Pfizer Worldwide Res & Dev, Groton Labs, Eastern Point Rd, Groton, CT 06340 USA.
[Trapa, Patrick; Lefker, Bruce A.] Pfizer Worldwide Res & Dev, 610 Main St, Cambridge, MA 02139 USA.
[Wagner, Florence F.; Perlis, Roy; Holson, Edward B.] Broad Inst, Stanley Ctr Psychiat Res, 415 Main St, Cambridge, MA 02142 USA.
[Patnaik, Debasis; Perlis, Roy; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 185 Cambridge St, Boston, MA 02114 USA.
[Patnaik, Debasis; Perlis, Roy; Haggarty, Stephen J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, 185 Cambridge St, Boston, MA 02114 USA.
RP Vasdev, N (reprint author), Massachusetts Gen Hosp, Gordon Ctr Med Imaging & Nucl Med & Mol Imaging, Boston, MA 02114 USA.; Vasdev, N (reprint author), Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA.; Kurumbail, RG (reprint author), Pfizer Worldwide Res & Dev, Groton Labs, Eastern Point Rd, Groton, CT 06340 USA.
EM ravi.g.kurumbail@pfizer.com; vasdev.neil@mgh.harvard.edu
OI Patnaik, Debasis/0000-0002-9829-3352
FU Hauptman-Woodward Medical Research Institute; IMCA-CAT at Advanced
Photon Source, U.S. Department of Energy [DE-AC02-06CH11357]; NIH [NIDA
1K01DA038000]; Tau Consortium
FX We thank Rebecca Lewis, Justin Pine, Patricia Cosgrove, Jeffrey Asbill,
Dr. Dustin Wooten, Dr. T. Lee Collier, and Dr. Lee Josephson for
technical support and helpful discussions. We thank Seungil Han, Mark
Ammirati, Mathew Calabrese, Jayvardhan Pandit, and Mathew Griffor for
crystallographic studies, supported by Hauptman-Woodward Medical
Research Institute and IMCA-CAT at Advanced Photon Source, U.S.
Department of Energy (DE-AC02-06CH11357). S.H.L. is a recipient of an
NIH career development award (NIDA 1K01DA038000). S.J.H. was supported
in part by the Tau Consortium.
NR 32
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Z9 2
U1 6
U2 6
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1433-7851
EI 1521-3773
J9 ANGEW CHEM INT EDIT
JI Angew. Chem.-Int. Edit.
PD AUG 8
PY 2016
VL 55
IS 33
BP 9600
EP 9604
DI 10.1002/anie.201603797
PG 5
WC Chemistry, Multidisciplinary
SC Chemistry
GA DW0ZQ
UT WOS:000383372700023
PM 27355874
ER
PT J
AU Yetisen, AK
Montelongo, Y
Butt, H
AF Yetisen, Ali K.
Montelongo, Yunuen
Butt, Haider
TI Rewritable three-dimensional holographic data storage via optical forces
SO APPLIED PHYSICS LETTERS
LA English
DT Article
ID PHOTONIC CRYSTAL SENSORS; LASER-ABLATION; NANOSTRUCTURES; NANOSENSOR
AB The development of nanostructures that can be reversibly arranged and assembled into 3D patterns may enable optical tunability. However, current dynamic recording materials such as photorefractive polymers cannot be used to store information permanently while also retaining configurability. Here, we describe the synthesis and optimization of a silver nanoparticle doped poly(2-hydroxyethyl methacrylate-co-methacrylic acid) recording medium for reversibly recording 3D holograms. We theoretically and experimentally demonstrate organizing nanoparticles into 3D assemblies in the recording medium using optical forces produced by the gradients of standing waves. The nanoparticles in the recording medium are organized by multiple nanosecond laser pulses to produce reconfigurable slanted multilayer structures. We demonstrate the capability of producing rewritable optical elements such as multilayer Bragg diffraction gratings, 1D photonic crystals, and 3D multiplexed optical gratings. We also show that 3D virtual holograms can be reversibly recorded. This recording strategy may have applications in reconfigurable optical elements, data storage devices, and dynamic holographic displays. Published by AIP Publishing.
C1 [Yetisen, Ali K.] Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA.
[Yetisen, Ali K.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA.
[Yetisen, Ali K.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Montelongo, Yunuen] Imperial Coll London, Dept Chem, South Kensington Campus, London SW7 2AZ, England.
[Butt, Haider] Univ Birmingham, Sch Engn Sci, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England.
RP Yetisen, AK (reprint author), Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA.; Yetisen, AK (reprint author), MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
EM ayetisen@mgh.harvard.edu
OI Butt, Haider/0000-0003-2434-9525
FU Leverhulme Trust
FX The authors thank the Leverhulme Trust for research funding.
NR 23
TC 1
Z9 1
U1 24
U2 24
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0003-6951
EI 1077-3118
J9 APPL PHYS LETT
JI Appl. Phys. Lett.
PD AUG 8
PY 2016
VL 109
IS 6
AR 061106
DI 10.1063/1.4960710
PG 5
WC Physics, Applied
SC Physics
GA DV8JP
UT WOS:000383183600006
ER
PT J
AU Berger, AH
Brooks, AN
Wu, XY
Shrestha, Y
Chouinard, C
Piccioni, F
Bagul, M
Kamburov, A
Imielinski, M
Hogstrom, L
Zhu, C
Yang, XP
Pantel, S
Sakai, R
Watson, J
Kaplan, N
Campbell, JD
Singh, S
Root, DE
Narayan, R
Natoli, T
Lahr, DL
Tirosh, I
Tamayo, P
Getz, G
Wong, B
Doench, J
Subramanian, A
Golub, TR
Meyerson, M
Boehm, JS
AF Berger, Alice H.
Brooks, Angela N.
Wu, Xiaoyun
Shrestha, Yashaswi
Chouinard, Candace
Piccioni, Federica
Bagul, Mukta
Kamburov, Atanas
Imielinski, Marcin
Hogstrom, Larson
Zhu, Cong
Yang, Xiaoping
Pantel, Sasha
Sakai, Ryo
Watson, Jacqueline
Kaplan, Nathan
Campbell, Joshua D.
Singh, Shantanu
Root, David E.
Narayan, Rajiv
Natoli, Ted
Lahr, David L.
Tirosh, Itay
Tamayo, Pablo
Getz, Gad
Wong, Bang
Doench, John
Subramanian, Aravind
Golub, Todd R.
Meyerson, Matthew
Boehm, Jesse S.
TI High-throughput Phenotyping of Lung Cancer Somatic Mutations
SO CANCER CELL
LA English
DT Article
ID RNA INTERFERENCE SCREEN; TUMOR SAMPLES; LIVER-CANCER; HUMAN-CELLS;
GENOME; GENES; IDENTIFICATION; ADENOCARCINOMA; INHIBITION; GEFITINIB
AB Recent genome sequencing efforts have identified millions of somatic mutations in cancer. However, the functional impact of most variants is poorly understood. Here we characterize 194 somatic mutations identified in primary lung adenocarcinomas. We present an expression-based variant-impact phenotyping (eVIP) method that uses gene expression changes to distinguish impactful from neutral somatic mutations. eVIP identified 69% of mutations analyzed as impactful and 31% as functionally neutral. A subset of the impactful mutations induces xenograft tumor formation in mice and/or confers resistance to cellular EGFR inhibition. Among these impactful variants are rare somatic, clinically actionable variants including EGFR S645C, ARAF S214C and S214F, ERBB2 S418T, and multiple BRAF variants, demonstrating that rare mutations can be functionally important in cancer.
C1 [Berger, Alice H.; Brooks, Angela N.; Imielinski, Marcin; Watson, Jacqueline; Kaplan, Nathan; Campbell, Joshua D.; Golub, Todd R.; Meyerson, Matthew] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Berger, Alice H.; Brooks, Angela N.; Wu, Xiaoyun; Shrestha, Yashaswi; Chouinard, Candace; Kamburov, Atanas; Imielinski, Marcin; Hogstrom, Larson; Watson, Jacqueline; Campbell, Joshua D.; Narayan, Rajiv; Natoli, Ted; Lahr, David L.; Tamayo, Pablo; Getz, Gad; Wong, Bang; Subramanian, Aravind; Golub, Todd R.; Meyerson, Matthew; Boehm, Jesse S.] Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.
[Berger, Alice H.; Brooks, Angela N.; Kamburov, Atanas; Imielinski, Marcin; Campbell, Joshua D.; Getz, Gad; Meyerson, Matthew] Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA.
[Piccioni, Federica; Bagul, Mukta; Zhu, Cong; Yang, Xiaoping; Pantel, Sasha; Root, David E.; Doench, John] Broad Inst MIT & Harvard, Genet Perturbat Platform, Cambridge, MA 02142 USA.
[Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kamburov, Atanas; Getz, Gad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Sakai, Ryo] Katholieke Univ Leuven, Dept Elect Engn ESAT STADIUS, B-3000 Leuven, Belgium.
[Singh, Shantanu] Broad Inst MIT & Harvard, Imaging Platform, Cambridge, MA 02142 USA.
[Tirosh, Itay] Broad Inst MIT & Harvard, Cell Circuits & Epigen Program, Cambridge, MA 02142 USA.
[Golub, Todd R.] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA.
[Brooks, Angela N.] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA.
RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Meyerson, M; Boehm, JS (reprint author), Broad Inst MIT & Harvard, Canc Program, Cambridge, MA 02142 USA.; Meyerson, M (reprint author), Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA.
EM matthew_meyerson@dfci.harvard.edu; boehm@broadinstitute.org
OI Doench, John/0000-0002-3707-9889
FU Carlos Slim Foundation in Mexico; National Cancer Institute
[1R35CA197568]; American Cancer Society [122398-PF-12-080-01-TBG];
National Cancer Institute Pathway to Independence award [K99CA197762]
FX We thank members of the Meyerson and Golub labs for critical advice and
discussion. We thank Iris Fung for graphic design of the graphical
abstract. We thank Heidi Greulich and Tanaz Sharifnia for reagents and
advice. We are grateful for the feedback and advice from Anne Carpenter,
Eejung Kim, Nina Ilic, Lihua Zou, William Kim, Cory Johannessen, Steven
Corsello, and William Hahn. The work was conducted as part of the Slim
Initiative for Genomic Medicine, a project funded by the Carlos Slim
Foundation in Mexico, with additional support of National Cancer
Institute grant 1R35CA197568 and an American Cancer Society Research
Professorship to M.M., an American Cancer Society Postdoctoral Research
Fellowship (122398-PF-12-080-01-TBG) and a National Cancer Institute
Pathway to Independence award (K99CA197762) to A.H.B. A.N.B was a Merck
Fellow of the Damon Runyon Cancer Research Foundation (DRG-2138-12).
T.R.G. and M.M. are founders and equity holders of Foundation Medicine,
a for-profit company that provides next-generation sequencing diagnostic
services.
NR 47
TC 5
Z9 5
U1 4
U2 6
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 AUG 8
PY 2016
VL 30
IS 2
BP 214
EP 228
DI 10.1016/j.ccell.2016.06.022
PG 15
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DT2AC
UT WOS:000381282200007
PM 27478040
ER
PT J
AU Miranda, F
Mannion, D
Liu, SJ
Zheng, YY
Mangala, LS
Redondo, C
Herrero-Gonzalez, S
Xu, RY
Taylor, C
Chedom, DF
Karaminejadranjbar, M
Albukhari, A
Jiang, DH
Pradeep, S
Rodriguez-Aguayo, C
Lopez-Berestein, G
Salah, E
Azeez, KRA
Elkins, JM
Campo, L
Myers, KA
Klotz, D
Bivona, S
Dhar, S
Bast, RC
Saya, H
Choi, HG
Gray, NS
Fischer, R
Kessler, BM
Yau, C
Sood, AK
Motohara, T
Knapp, S
Ahmed, AA
AF Miranda, Fabrizio
Mannion, David
Liu, Shujuan
Zheng, Yiyan
Mangala, Lingegowda S.
Redondo, Clara
Herrero-Gonzalez, Sandra
Xu, Ruoyan
Taylor, Charlotte
Chedom, Donatien Fotso
Karaminejadranjbar, Mohammad
Albukhari, Ashwag
Jiang, Dahai
Pradeep, Sunila
Rodriguez-Aguayo, Cristian
Lopez-Berestein, Gabriel
Salah, Eidarus
Azeez, Kamal R. Abdul
Elkins, Jonathan M.
Campo, Leticia
Myers, Kevin A.
Klotz, Daniel
Bivona, Serena
Dhar, Sunanda
Bast, Robert C., Jr.
Saya, Hideyuki
Choi, Hwan Geun
Gray, Nathanael S.
Fischer, Roman
Kessler, Benedikt M.
Yau, Christopher
Sood, Anil K.
Motohara, Takeshi
Knapp, Stefan
Ahmed, Ahmed Ashour
TI Salt-Inducible Kinase 2 Couples Ovarian Cancer Cell Metabolism with
Survival at the Adipocyte-Rich Metastatic Niche
SO CANCER CELL
LA English
DT Article
ID ACTIVATED PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; TUMOR
MICROENVIRONMENT; SIGNALING CASCADE; PHOSPHORYLATION; SIK2; P85;
EXPRESSION; GLUCONEOGENESIS; IDENTIFICATION
AB The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is over-expressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo. Importantly, adipocytes induce calcium-dependent activation and autophosphorylation of SIK2. Activated SIK2 plays a dual role in augmenting AMPK-induced phosphorylation of acetyl-CoA carboxylase and in activating the PI3K/AKT pathway through p85 alpha-S154 phosphorylation. These findings identify SIK2 at the apex of the adipocyte-induced signaling cascades in cancer cells and make a compelling case for targeting SIK2 for therapy in ovarian cancer.
C1 [Miranda, Fabrizio; Mannion, David; Liu, Shujuan; Zheng, Yiyan; Redondo, Clara; Herrero-Gonzalez, Sandra; Xu, Ruoyan; Taylor, Charlotte; Chedom, Donatien Fotso; Karaminejadranjbar, Mohammad; Albukhari, Ashwag; Klotz, Daniel; Bivona, Serena; Ahmed, Ahmed Ashour] Univ Oxford, Weatherall Inst Mol Med, Ovarian Canc Cell Lab, Oxford OX3 9DS, England.
[Miranda, Fabrizio; Mannion, David; Liu, Shujuan; Zheng, Yiyan; Redondo, Clara; Herrero-Gonzalez, Sandra; Xu, Ruoyan; Taylor, Charlotte; Chedom, Donatien Fotso; Karaminejadranjbar, Mohammad; Albukhari, Ashwag; Klotz, Daniel; Bivona, Serena; Ahmed, Ahmed Ashour] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Oxford OX3 9DU, England.
[Mangala, Lingegowda S.; Jiang, Dahai; Pradeep, Sunila; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Gynecol Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Mangala, Lingegowda S.; Jiang, Dahai; Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Ctr RNAi & Noncoding RNA, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Redondo, Clara; Salah, Eidarus; Azeez, Kamal R. Abdul; Elkins, Jonathan M.; Knapp, Stefan] Univ Oxford, Nuffield Dept Med, Struct Genom Consortium, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England.
[Albukhari, Ashwag] King Abdulaziz Univ, Dept Biochem, Fac Sci, Jeddah 21551, Saudi Arabia.
[Rodriguez-Aguayo, Cristian; Lopez-Berestein, Gabriel; Bast, Robert C., Jr.] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA.
[Campo, Leticia; Myers, Kevin A.] Univ Oxford, Dept Oncol, Old Rd Campus Res Bldg,Roosevelt Dr, Oxford OX3 7DQ, England.
[Dhar, Sunanda] Oxford Univ Hosp, Dept Histopathol, Oxford OX3 9DU, England.
[Saya, Hideyuki] Keio Univ, Inst Adv Med Res, Sch Med, Div Gene Regulat, Tokyo 1608582, Japan.
[Choi, Hwan Geun; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Choi, Hwan Geun; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Fischer, Roman; Kessler, Benedikt M.; Knapp, Stefan] Univ Oxford, Target Discovery Inst, Nuffield Dept Med, Oxford OX3 7FZ, England.
[Yau, Christopher] NIHR Biomed Res Ctr, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England.
[Yau, Christopher] Univ Oxford, Dept Stat, 1 South Pk Rd, Oxford OX1 3TG, England.
[Motohara, Takeshi] Kumamoto Univ, Fac Life Sci, Dept Obstet & Gynecol, Kumamoto 8608556, Japan.
[Knapp, Stefan] Goethe Univ Frankfurt, Inst Pharmaceut Chem, Riedberg Campus, D-60438 Frankfurt, Germany.
[Knapp, Stefan] Buchmann Inst Life Sci, D-60438 Frankfurt, Germany.
RP Ahmed, AA (reprint author), Univ Oxford, Weatherall Inst Mol Med, Ovarian Canc Cell Lab, Oxford OX3 9DS, England.; Ahmed, AA (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Womens Ctr, Oxford OX3 9DU, England.
EM ahmed.ahmed@obs-gyn.ox.ac.uk
RI Fachbereich14, Dekanat/C-8553-2015; Bast, Robert/E-6585-2011;
OI Bast, Robert/0000-0003-4621-8462; Fischer, Roman/0000-0002-9715-5951;
Knapp, Stefan/0000-0001-5995-6494; Kessler,
Benedikt/0000-0002-8160-2446; Yau, Christopher/0000-0001-7615-8523
FU Medical Research Council; Ovarian Cancer Action; Oxford Biomedical
Research Center; National Institute for Health Research; Cancer Research
UK; Experimental Cancer Medicine Center; Helen Clarke Fund; Target
Ovarian Cancer; NIH [UH3TR000943, P50 CA083639]; RGK Foundation; MRC New
Investigator Research Grant [MR/L001411/1]; Wellcome Trust
[090532/Z/09/Z, 092809/Z/10/Z]; SGC [1097737]; AbbVie; Bayer Pharma AG;
Boehringer Ingelheim; Canada Foundation for Innovation; Genome Canada;
GlaxoSmithKline; Janssen; Lilly Canada; Novartis Research Foundation;
Ontario Ministry of Economic Development and Innovation; Pfizer; Takeda
FX We thank the Gynecological Oncology Multidisciplinary Team at Oxford for
help in recruiting patients, the Oxford Center for Histopathology
Research for their technical work, and Fulvio Miranda, Karl Morten, and
Matteo Morotti for helpful discussions. This work was funded by the
Medical Research Council, Ovarian Cancer Action, Oxford Biomedical
Research Center, the National Institute for Health Research, Cancer
Research UK, Experimental Cancer Medicine Center, Helen Clarke Fund,
Target Ovarian Cancer, NIH (UH3TR000943, P50 CA083639), and RGK
Foundation. C.Y. acknowledges the support of an MRC New Investigator
Research Grant (Ref. No. MR/L001411/1) and the Wellcome Trust Core Award
Grant Number 090532/Z/09/Z. S.K. and C.R. are supported by the SGC, a
registered charity (number 1097737) that receives funds from AbbVie,
Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for
Innovation, Genome Canada, GlaxoSmithKline, Janssen, Lilly Canada, the
Novartis Research Foundation, the Ontario Ministry of Economic
Development and Innovation, Pfizer, Takeda, and the Wellcome Trust
[092809/Z/10/Z].
NR 44
TC 2
Z9 2
U1 7
U2 10
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 AUG 8
PY 2016
VL 30
IS 2
BP 273
EP 289
DI 10.1016/j.ccell.2016.06.020
PG 17
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DT2AC
UT WOS:000381282200011
PM 27478041
ER
PT J
AU Inoue, S
Li, WDY
Tseng, A
Beerman, I
Elia, AJ
Bendall, SC
Lemonnier, F
Kron, KJ
Cescon, DW
Hao, ZY
Lind, EF
Takayama, N
Planello, AC
Shen, SY
Shih, AH
Larsen, DM
Li, QX
Snow, BE
Wakeham, A
Haight, J
Gorrini, C
Bassi, C
Thu, KL
Murakami, K
Elford, AR
Ueda, T
Straley, K
Yen, KE
Melino, G
Cimmino, L
Aifantis, I
Levine, RL
De Carvalho, DD
Lupien, M
Rossi, DJ
Nolan, GP
Cairns, RA
Mak, TW
AF Inoue, Satoshi
Li, Wanda Y.
Tseng, Alan
Beerman, Isabel
Elia, Andrew J.
Bendall, Sean C.
Lemonnier, Francois
Kron, Ken J.
Cescon, David W.
Hao, Zhenyue
Lind, Evan F.
Takayama, Naoya
Planello, Aline C.
Shen, Shu Yi
Shih, Alan H.
Larsen, Dana M.
Li, Qinxi
Snow, Bryan E.
Wakeham, Andrew
Haight, Jillian
Gorrini, Chiara
Bassi, Christian
Thu, Kelsie L.
Murakami, Kiichi
Elford, Alisha R.
Ueda, Takeshi
Straley, Kimberly
Yen, Katharine E.
Melino, Gerry
Cimmino, Luisa
Aifantis, Iannis
Levine, Ross L.
De Carvalho, Daniel D.
Lupien, Mathieu
Rossi, Derrick J.
Nolan, Garry P.
Cairns, Rob A.
Mak, Tak W.
TI Mutant IDH1 Downregulates ATM and Alters DNA Repair and Sensitivity to
DNA Damage Independent of TET2
SO CANCER CELL
LA English
DT Article
ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; SELF-RENEWAL;
ATAXIA-TELANGIECTASIA; EPIGENETIC REGULATORS; OXIDATIVE STRESS;
MUTATIONS; MICE; DIFFERENTIATION; CANCER
AB Mutations in the isocitrate dehydrogenase-1 gene (IDH1) are common drivers of acute myeloid leukemia (AML) but their mechanism is not fully understood. It is thought that IDH1 mutants act by inhibiting TET2 to alter DNA methylation, but there are significant unexplained clinical differences between IDH1- and TET2-mutant diseases. We have discovered that mice expressing endogenous mutant IDH1 have reduced numbers of hematopoietic stem cells (HSCs), in contrast to Tet2 knockout (TET2-KO) mice. Mutant IDH1 downregulates the DNA damage (DD) sensor ATM by altering histone methylation, leading to impaired DNA repair, increased sensitivity to DD, and reduced HSC self-renewal, independent of TET2. ATM expression is also decreased in human IDH1-mutated AML. These findings may have implications for treatment of IDH-mutant leukemia.
C1 [Inoue, Satoshi; Li, Wanda Y.; Tseng, Alan; Elia, Andrew J.; Lemonnier, Francois; Cescon, David W.; Hao, Zhenyue; Lind, Evan F.; Li, Qinxi; Snow, Bryan E.; Wakeham, Andrew; Haight, Jillian; Gorrini, Chiara; Bassi, Christian; Thu, Kelsie L.; Murakami, Kiichi; Elford, Alisha R.; Ueda, Takeshi; Cairns, Rob A.; Mak, Tak W.] Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada.
[Inoue, Satoshi; Li, Wanda Y.; Tseng, Alan; Elia, Andrew J.; Lemonnier, Francois; Kron, Ken J.; Cescon, David W.; Hao, Zhenyue; Lind, Evan F.; Takayama, Naoya; Planello, Aline C.; Shen, Shu Yi; Li, Qinxi; Snow, Bryan E.; Wakeham, Andrew; Haight, Jillian; Gorrini, Chiara; Bassi, Christian; Thu, Kelsie L.; Murakami, Kiichi; Elford, Alisha R.; De Carvalho, Daniel D.; Lupien, Mathieu; Cairns, Rob A.; Mak, Tak W.] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada.
[Inoue, Satoshi; Li, Wanda Y.; Tseng, Alan; Elia, Andrew J.; Lemonnier, Francois; Kron, Ken J.; Cescon, David W.; Hao, Zhenyue; Lind, Evan F.; Takayama, Naoya; Planello, Aline C.; Shen, Shu Yi; Li, Qinxi; Snow, Bryan E.; Wakeham, Andrew; Haight, Jillian; Gorrini, Chiara; Bassi, Christian; Thu, Kelsie L.; Murakami, Kiichi; Elford, Alisha R.; De Carvalho, Daniel D.; Lupien, Mathieu; Cairns, Rob A.; Mak, Tak W.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.
[Tseng, Alan; Kron, Ken J.; Planello, Aline C.; Shen, Shu Yi; De Carvalho, Daniel D.; Lupien, Mathieu; Mak, Tak W.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
[Beerman, Isabel; Rossi, Derrick J.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02133 USA.
[Beerman, Isabel] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Bendall, Sean C.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Planello, Aline C.] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Morphol, BR-13414903 Piracicaba, SP, Brazil.
[Shih, Alan H.; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Human Oncol & Pathogenesis Program, New York, NY 10065 USA.
[Larsen, Dana M.] Mbed Pathol, Toronto, ON M5J 2H2, Canada.
[Ueda, Takeshi] Hiroshima Univ, Res Inst Radiat Biol & Med, Dept Dis Model, Hiroshima 7348553, Japan.
[Straley, Kimberly; Yen, Katharine E.] Agios Pharmaceut, Cambridge, MA 02139 USA.
[Melino, Gerry] MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England.
[Melino, Gerry] Univ Roma Tor Vergata, Dept Expt Med & Surg, I-00133 Rome, Italy.
[Cimmino, Luisa; Aifantis, Iannis] NYU, Sch Med, Dept Pathol, Howard Hughes Med Inst, New York, NY 10016 USA.
[Nolan, Garry P.] Stanford Univ, Sch Med, Dept Microbiol & Immunol, Baxter Lab Stem Cell Biol, Stanford, CA 94305 USA.
RP Mak, TW (reprint author), Univ Hlth Network, Campbell Family Inst Breast Canc Res, Toronto, ON M5G 2C1, Canada.; Mak, TW (reprint author), Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada.; Mak, TW (reprint author), Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 1L7, Canada.; Mak, TW (reprint author), Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
EM tmak@uhnres.utoronto.ca
FU Canadian Institutes of Health Research; Leukemia and Lymphoma Society
FX We are grateful to Drs. John E. Dick (Princess Margaret Cancer Centre),
Atsushi Hirao (University of Kanazawa), and all members of the Mak
laboratory for their advice. We also appreciate the assistance of Ms.
Irene Ng and the staff members of the flow cytometer facility,
genotyping facility, and animal resource centre of the Princess Margaret
Cancer Centre. Finally, we are grateful to Dr. Mary Saunders for
scientific editing of the manuscript. This work was supported by grants
to Drs. T.W.M. and R.A.C. from the Canadian Institutes of Health
Research and the Leukemia and Lymphoma Society. K.E.Y. is an employee of
and has an ownership interest in Agios Pharmaceuticals.
NR 49
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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 AUG 8
PY 2016
VL 30
IS 2
BP 337
EP 348
DI 10.1016/j.ccell.2016.05.018
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DT2AC
UT WOS:000381282200015
PM 27424808
ER
PT J
AU Sandulache, VC
Hobbs, BP
Mohamed, ASR
Frank, SJ
Song, J
Ding, Y
Ger, R
Court, LE
Kalpathy-Cramer, J
Hazle, JD
Wang, JH
Awan, MJ
Rosenthal, DI
Garden, AS
Gunn, GB
Colen, RR
Elshafeey, N
Elbanan, M
Hutcheson, KA
Lewin, JS
Chambers, MS
Hofstede, TM
Weber, RS
Lai, SY
Fuller, CD
AF Sandulache, Vlad C.
Hobbs, Brian P.
Mohamed, Abdallah S. R.
Frank, Steven J.
Song, Juhee
Ding, Yao
Ger, Rachel
Court, Laurence E.
Kalpathy-Cramer, Jayashree
Hazle, John D.
Wang, Jihong
Awan, Musaddiq J.
Rosenthal, David I.
Garden, Adam S.
Gunn, G. Brandon
Colen, Rivka R.
Elshafeey, Nabil
Elbanan, Mohamed
Hutcheson, Katherine A.
Lewin, Jan S.
Chambers, Mark S.
Hofstede, Theresa M.
Weber, Randal S.
Lai, Stephen Y.
Fuller, Clifton D.
CA Joint Head Neck Radiotherapy-MRI D
TI Dynamic contrast-enhanced MRI detects acute radiotherapy-induced
alterations in mandibular microvasculature: prospective assessment of
imaging biomarkers of normal tissue injury
SO SCIENTIFIC REPORTS
LA English
DT Article
ID OROPHARYNGEAL CANCER; RADIATION-THERAPY; NECK-CANCER;
OSTEORADIONECROSIS; PERFUSION; HEAD; MANAGEMENT; CARCINOMA; DIAGNOSIS;
OUTCOMES
AB Normal tissue toxicity is an important consideration in the continued development of more effective external beam radiotherapy (EBRT) regimens for head and neck tumors. The ability to detect EBRT-induced changes in mandibular bone vascularity represents a crucial step in decreasing potential toxicity. To date, no imaging modality has been shown to detect changes in bone vascularity in real time during treatment. Based on our institutional experience with multi-parametric MRI, we hypothesized that DCE-MRI can provide in-treatment information regarding EBRT-induced changes in mandibular vascularity. Thirty-two patients undergoing EBRT treatment for head and neck cancer were prospectively imaged prior to, mid-course, and following treatment. DCE-MRI scans were co-registered to dosimetric maps to correlate EBRT dose and change in mandibular bone vascularity as measured by K-trans and V-e. DCE-MRI was able to detect dose-dependent changes in both K-trans and V-e in a subset of patients. One patient who developed ORN during the study period demonstrated decreases in K-trans and V-e following treatment completion. We demonstrate, in a prospective imaging trial, that DCE-MRI can detect dose-dependent alterations in mandibular bone vascularity during chemoradiotherapy, providing biomarkers that are physiological correlates of acute of acute mandibular vascular injury and recovery temporal kinetics.
C1 [Sandulache, Vlad C.; Hutcheson, Katherine A.; Lewin, Jan S.; Chambers, Mark S.; Hofstede, Theresa M.; Weber, Randal S.; Lai, Stephen Y.] UT MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX USA.
[Hobbs, Brian P.; Song, Juhee] UT MD Anderson Canc Ctr, Dept Biostat, Houston, TX USA.
[Mohamed, Abdallah S. R.; Frank, Steven J.; Rosenthal, David I.; Garden, Adam S.; Gunn, G. Brandon; Fuller, Clifton D.] UT MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA.
[Ding, Yao; Hazle, John D.; Wang, Jihong] UT MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX USA.
[Court, Laurence E.] UT MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX USA.
[Kalpathy-Cramer, Jayashree] MIT, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Div Hlth Sci & Technol, Charlestown, MA USA.
[Awan, Musaddiq J.] Case Western Reserve Univ, Dept Radiat Oncol, Cleveland, OH 44106 USA.
[Colen, Rivka R.; Elshafeey, Nabil; Elbanan, Mohamed] UT MD Anderson Canc Ctr, Dept Diagnost Radiol, Houston, TX USA.
[Lai, Stephen Y.] UT MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX USA.
[Mohamed, Abdallah S. R.] Univ Alexandria, Fac Med, Dept Clin Oncol & Nucl Med, Alexandria, Egypt.
RP Lai, SY (reprint author), UT MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX USA.; Fuller, CD (reprint author), UT MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX USA.; Lai, SY (reprint author), UT MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX USA.
EM sylai@mdanderson.org; CDFuller@mdanderson.org
OI Fuller, Clifton/0000-0002-5264-3994; Mohamed,
Abdallah/0000-0003-2064-7613
FU SWOG Hope Foundation; National Institutes of Health Paul Calabresi
Clinical Oncology Award Program [K12 CA088084]; Clinician Scientist Loan
Repayment Program [L30 CA136381-02]; Elekta AB/MD Anderson Consortium;
GE Medical Systems/MD Anderson Center for Advanced Biomedical Imaging
In-Kind Award; MD Anderson Center for Radiation Oncology Research; MD
Anderson Institutional Research Grant Program Award; National Cancer
Institute [R21 CA178450, R03 CA188162]; MD Anderson Institutional
Research Grant Program; NIH/NCI Cancer Center Support Grant [P30
CA016672]; National Institute for Dental and Craniofacial Research [R56
DE025248, R01 DE025248]
FX The authors would like to thank Petra van Houdt and Uulke van de Heide,
Department of Radiation Oncology, The Netherlands Cancer Institute,
Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands for
assistance and conceptual development of image post-processing workflow;
direct quality assurance, calculation, and image-post-processing of
pharmacokinetic parameters. Dr. Fuller received/receives grant support
from: the SWOG Hope Foundation Dr. Charles A. Coltman, Jr. Fellowship in
Clinical Trials; the National Institutes of Health Paul Calabresi
Clinical Oncology Award Program (K12 CA088084) and Clinician Scientist
Loan Repayment Program (L30 CA136381-02); Elekta AB/MD Anderson
Consortium; GE Medical Systems/MD Anderson Center for Advanced
Biomedical Imaging In-Kind Award; the MD Anderson Center for Radiation
Oncology Research, and an MD Anderson Institutional Research Grant
Program Award. Dr. Lai receives grant support from Institutional
Start-up Funds and the National Cancer Institute (R21 CA178450). Dr.
Hutcheson receives grant support from the MD Anderson Institutional
Research Grant Program and the National Cancer Institute (R03 CA188162).
Dr. Hobbs was partially supported by NIH/NCI Cancer Center Support Grant
(P30 CA016672). National Institute for Dental and Craniofacial Research
(R56 DE025248 and R01 DE025248) provided support for the cooperative
group to perform the included work. The listed funders/supporters played
no role in the study design, collection, analysis, interpretation of
data, manuscript writing, or decision to submit the report for
publication.
NR 34
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD AUG 8
PY 2016
VL 6
AR 29864
DI 10.1038/srep29864
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DT0YZ
UT WOS:000381210200001
ER
PT J
AU Toghyani, M
Gillam, JE
McNamara, AL
Kuncic, Z
AF Toghyani, M.
Gillam, J. E.
McNamara, A. L.
Kuncic, Z.
TI Polarisation-based coincidence event discrimination: an in silico study
towards a feasible scheme for Compton-PET
SO PHYSICS IN MEDICINE AND BIOLOGY
LA English
DT Article
DE Monte Carlo simulations; positron emission tomography; polarisation;
Compton imaging
ID ANGULAR-CORRELATION; PROTON-BEAMS; GAMMA-RAYS; ANNIHILATION; CAMERA;
SCATTERING; SIMULATION; DESIGN
AB Current positron emission tomography (PET) systems use temporally localised coincidence events discriminated by energy and time-of-flight information. The two annihilation photons are in an entangled polarisation state and, in principle, additional information from the polarisation correlation of photon pairs could be used to improve the accuracy of coincidence classification. In a previous study, we demonstrated that in principle, the polarisation correlation information could be transferred to an angular correlation in the distribution of scattered photon pairs in a planar Compton camera system. In the present study, we model a source-phantom-detector system using Geant4 and we develop a coincidence classification scheme that exploits the angular correlation of scattered annihilation quanta to improve the accuracy of coincidence detection. We find a 22% image quality improvement in terms of the peak signal-to-noise ratio when scattered coincidence events are discriminated solely by their angular correlation, thus demonstrating the feasibility of this novel classification scheme. By integrating scatter events (both single-single and single-only) with unscattered coincidence events discriminated using conventional methods, our results suggest that Compton-PET may be a promising candidate for optimal emission tomographic imaging.
C1 [Toghyani, M.; Kuncic, Z.] Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia.
[Gillam, J. E.] Univ Sydney, Fac Hlth Sci, Brain & Mind Ctr, Camperdown, NSW 2050, Australia.
[McNamara, A. L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Kuncic, Z (reprint author), Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia.
EM zdenka.kuncic@sydney.edu.au
RI McNamara, Aimee/C-9432-2009
OI McNamara, Aimee/0000-0001-8792-0464
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Z9 0
U1 2
U2 2
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 AUG 7
PY 2016
VL 61
IS 15
BP 5803
EP 5817
DI 10.1088/0031-9155/61/15/5803
PG 15
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA DX2NP
UT WOS:000384207500020
PM 27405797
ER
PT J
AU Ferencik, M
Hoffmann, U
Bamberg, F
Januzzi, JL
AF Ferencik, Maros
Hoffmann, Udo
Bamberg, Fabian
Januzzi, James L.
TI Highly sensitive troponin and coronary computed tomography angiography
in the evaluation of suspected acute coronary syndrome in the emergency
department
SO EUROPEAN HEART JOURNAL
LA English
DT Review
DE Acute coronary syndrome; Acute chest pain; Highly sensitive troponin;
Coronary computed tomography angiography
ID ACUTE CHEST-PAIN; FRACTIONAL FLOW RESERVE; LEFT-VENTRICULAR FUNCTION;
ACUTE MYOCARDIAL-INFARCTION; ACCELERATED DIAGNOSTIC PROTOCOL; 3RD
UNIVERSAL DEFINITION; ROMICAT-II TRIAL; DUAL-SOURCE CT; CARDIAC
TROPONIN; INTRAVASCULAR ULTRASOUND
AB The evaluation of patients presenting to the emergency department with suspected acute coronary syndrome (ACS) remains a clinical challenge. The traditional assessment includes clinical risk assessment based on cardiovascular risk factors with serial electrocardiograms and cardiac troponin measurements, often followed by advanced cardiac testing as inpatient or outpatient (i. e. stress testing, imaging). Despite this costly and lengthy work-up, there is a non-negligible rate of missed ACS with an increased risk of death. There is a clinical need for diagnostic strategies that will lead to rapid and reliable triage of patients with suspected ACS. We provide an overview of the evidence for the role of highly sensitive troponin (hsTn) in the rapid and efficient evaluation of suspected ACS. Results of recent research studies have led to the introduction of hsTn with rapid rule-in and rule-out protocols into the guidelines. Highly sensitive troponin increases the sensitivity for the detection of myocardial infarction and decreases time to diagnosis; however, it may decrease the specificity, especially when used as a dichotomous variable, rather than continuous variable as recommended by guidelines; this may increase clinician uncertainty. We summarize the evidence for the use of coronary computed tomography angiography (CTA) as the rapid diagnostic tool in this population when used with conventional troponin assays. Coronary CTA significantly decreases time to diagnosis and discharge in patients with suspected ACS, while being safe. However, it may lead to increase in invasive procedures and includes radiation exposure. Finally, we outline the opportunities for the combined use of hsTn and coronary CTA that may result in increased efficiency, decreased need for imaging, lower cost, and decreased radiation dose.
C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 SW Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA.
[Ferencik, Maros; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Ferencik, Maros; Hoffmann, Udo; Januzzi, James L.] Harvard Med Sch, Boston, MA 02115 USA.
[Ferencik, Maros; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Hoffmann, Udo; Januzzi, James L.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Bamberg, Fabian] Univ Tubingen, Dept Radiol, Tubingen, Germany.
RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 SW Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA.; Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Ferencik, M (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Ferencik, M (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
EM ferencik@ohsu.edu
FU American Heart Association [13FTF16450001]; NIH [U01HL092040,
U01HL092022]; Siemens Medical Solutions; Heart Flow Inc.; Bayer
Healthcare (Berlin, Germany); Siemens Healthcare (Forchheim, Germany);
Siemens; Thermo Fisher; Singulex
FX M.F.: research grant/significant: American Heart Association Fellow to
Faculty Award 13FTF16450001. U.H.: research grant/significant: NIH
U01HL092040, U01HL092022, Siemens Medical Solutions, and Heart Flow
Inc.; consultant/advisory board/significant: Heart Flow. F.B.:
unrestricted research grant: Bayer Healthcare (Berlin, Germany) and
Siemens Healthcare (Forchheim, Germany); speakers bureau: Bayer
Healthcare (Berlin, Germany) and Siemens Healthcare (Forchheim,
Germany). J.L.J.: research grant/significant: Siemens, Thermo Fisher,
and Singulex; consultant/advisory board/significant: Critical
Diagnostics, Sphingotec, and Roche.
NR 92
TC 3
Z9 3
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 7
PY 2016
VL 37
IS 30
BP 2397
EP +
DI 10.1093/eurheartj/ehw005
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW4FW
UT WOS:000383599100008
PM 26843275
ER
PT J
AU Chan, PYL
Tang, SM
Au, SCL
Rong, SS
Lau, HHW
Ko, STC
Ng, DSC
Chen, LJ
Yam, JCS
AF Chan, Priscilla Y. L.
Tang, Shu-Min
Au, Sunny C. L.
Rong, Shi-Song
Lau, Henry H. W.
Ko, Simon T. C.
Ng, Danny S. C.
Chen, Li Jia
Yam, Jason C. S.
TI Association of Gestational Hypertensive Disorders with Retinopathy of
prematurity: A Systematic Review and Meta-analysis
SO SCIENTIFIC REPORTS
LA English
DT Review
ID LOW-BIRTH-WEIGHT; RISK-FACTORS; INTERNATIONAL CLASSIFICATION;
PREECLAMPTIC MOTHERS; ANGIOGENIC FACTORS; NEONATAL OUTCOMES; INFANTS;
EXPERIENCE; NORTH
AB The role of gestational hypertensive disorders, which includes both pre-eclampsia and gestational hypertension, in the development of retinopathy of prematurity (ROP) has been controversial. Therefore, this systematic review and meta-analysis is to evaluate the association between gestational hypertensive disoders and ROP. Eligible studies published up to June 5, 2016 were identified from MEDLINE and EMBASE that evaluated the association between the two conditions. Totally 1142 published records were retrieved for screening, 925 of them eligible for detailed evaluation. Finally 19 studies involving 45281 infants with 5388 cases of ROP met our criteria for meta-analysis. Gestational hypertensive disorders were not associated with ROP (unadjusted OR: 0.89; P = 0.38; adjusted OR: 1.35; P = 0.18). Subgroup analyses also revealed no significant association between ROP with pre-eclampsia (unadjusted OR: 0.85; P = 0.29; adjusted OR: 1.29; P = 0.28) or with gestational hypertension (unadjusted OR: 1.10; P = 0.39; adjusted OR: 1.25; P = 0.60) separately. Sensitivity analysis indicated our results were robust. We concluded no significant association between gestational hypertensive disorders and ROP. More large scale well-conducted prospective cohorts on the topic are needed.
C1 [Chan, Priscilla Y. L.; Tang, Shu-Min; Au, Sunny C. L.; Rong, Shi-Song; Lau, Henry H. W.; Ng, Danny S. C.; Chen, Li Jia; Yam, Jason C. S.] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
[Ko, Simon T. C.] Tung Wah Eastern Hosp, Dept Ophthalmol, Hong Kong, Hong Kong, Peoples R China.
[Rong, Shi-Song] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Yam, JCS (reprint author), Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China.
EM yamcheuksing@cuhk.edu.hk
RI Yam, Jason/I-5682-2014; Chen, Li Jia/I-5078-2014
OI Yam, Jason/0000-0002-2156-1486; Chen, Li Jia/0000-0003-3500-5840
NR 40
TC 0
Z9 0
U1 1
U2 4
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 AUG 5
PY 2016
VL 6
AR 30732
DI 10.1038/srep30732
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS6HE
UT WOS:000380882100001
PM 27491726
ER
PT J
AU Friesen, M
Hudak, CS
Warren, CR
Xia, F
Cowan, CA
AF Friesen, Max
Hudak, Carolyn S.
Warren, Curtis R.
Xia, Fang
Cowan, Chad A.
TI Adipocyte insulin receptor activity maintains adipose tissue mass and
lifespan
SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
LA English
DT Article
DE Insulin receptor; Adipocyte-specific knockout mouse; Glucose metabolism;
Insulin resistance; Metabolic disease; Type 2 diabetes
ID RESISTANCE; GLUCOSE; MICE
AB Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion.
Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase.
Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis.
These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. (C) 2016 Published by Elsevier Inc.
C1 [Friesen, Max; Hudak, Carolyn S.; Warren, Curtis R.; Xia, Fang; Cowan, Chad A.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Friesen, Max] Leiden Univ, Med Ctr, Dept Anat & Embryol, NL-2300 RC Leiden, Netherlands.
[Cowan, Chad A.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Cowan, Chad A.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Cowan, CA (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cowan Lab, Sherman Fairchild Bldg,Rm 101-23,7 Divin Ave, Cambridge, MA 02138 USA.
EM maxfriesen@gmail.com; chadacowan@gmail.com
FU NIH/NIDDDK [R01DK095384-01]; Harvard University; Harvard Stem Cell
Institute
FX This work was supported by NIH/NIDDDK R01DK095384-01, startup funds to
CAC from Harvard University and funding from the Harvard Stem Cell
Institute.
NR 17
TC 0
Z9 0
U1 11
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0006-291X
EI 1090-2104
J9 BIOCHEM BIOPH RES CO
JI Biochem. Biophys. Res. Commun.
PD AUG 5
PY 2016
VL 476
IS 4
BP 487
EP 492
DI 10.1016/j.bbrc.2016.05.151
PG 6
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DR4QE
UT WOS:000379886500048
PM 27246738
ER
PT J
AU Urso, K
Alvarez, D
Cremasco, V
Tsang, K
Grauel, A
Lafyatis, R
von Andrian, UH
Ermann, J
Aliprantis, AO
AF Urso, Katia
Alvarez, David
Cremasco, Viviana
Tsang, Kelly
Grauel, Angelo
Lafyatis, Robert
von Andrian, Ulrich H.
Ermann, Joerg
Aliprantis, Antonios O.
TI IL4RA on lymphatic endothelial cells promotes T cell egress during
sclerodermatous graft versus host disease
SO JCI INSIGHT
LA English
DT Article
ID SYSTEMIC-SCLEROSIS; LYMPHOCYTE EGRESS; SPHINGOSINE 1-PHOSPHATE;
SPHINGOSINE-1-PHOSPHATE; FIBROSIS; CANCER; BLOOD; MECHANISMS;
EXPRESSION; SKIN
AB Systemic sclerosis (SSc) is a potentially fatal autoimmune disorder with limited therapeutic options. Sclerodermatous graft versus host disease (sclGvHD), induced by transfer of B10. D2 splenocytes into BALB/c Rag2(-/-) mice, models an inflammatory subset of SSc characterized by a prominent IL13-induced gene expression signature in the skin. Host mice deficient in IL4RA, a subunit of the type II IL4/IL13 receptor, are protected from sclGvHD. While IL4RA has a well-established role in Th2 differentiation and alternative macrophage activation, we report here a previously unappreciated function for IL4RA in lymphatic endothelial cells (LECs): regulation of activated T cell egress. Seven days after splenocyte transfer, Il4ra(-/-) hosts had increased numbers of activated graft CD4(+) T cells in skin draining lymph nodes (dLNs) but fewer T cells in efferent lymph, blood, and skin. Sphingosine-1 phosphate (S1P), master regulator of lymphocyte egress from LNs, was lower in dLNs of Il4ra(-/-) hosts with a corresponding decrease of S1P kinase 1 (Sphk1) expression in LECs. Bypassing the efferent lymphatics via i. v. injection of CD4(+) T cells from dLNs of Il4ra(-/-) sclGvHD mice restored clinical GvHD in secondary Il4ra(-/-) recipients. These results identify a role for IL4RA and suggest that modulation of lymphocyte egress from LNs may be effective in SSc and GvHD.
C1 [Urso, Katia; Tsang, Kelly; Ermann, Joerg; Aliprantis, Antonios O.] Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA.
[Urso, Katia; Tsang, Kelly; Ermann, Joerg; Aliprantis, Antonios O.] Harvard Med Sch, Boston, MA USA.
[Alvarez, David; von Andrian, Ulrich H.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA USA.
[Cremasco, Viviana; Grauel, Angelo] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.
[Lafyatis, Robert] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[von Andrian, Ulrich H.] Ragon Inst Massachusetts Gen Hosp MGH MIT & Harva, Cambridge, MA USA.
RP Aliprantis, AO (reprint author), Merck Res Labs, 33 Ave Louis Pasteur, Boston, MA 02115 USA.
EM antonios.aliprantis@gmail.com
NR 46
TC 1
Z9 1
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 AUG 4
PY 2016
VL 1
IS 12
AR e88057
DI 10.1172/jci.insight.88057
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA EB1NH
UT WOS:000387118800007
ER
PT J
AU Fuchsberger, C
Flannick, J
Teslovich, TM
Mahajan, A
Agarwala, V
Gaulton, KJ
Ma, C
Fontanillas, P
Moutsianas, L
McCarthy, DJ
Rivas, MA
Perry, JRB
Sim, X
Blackwell, TW
Robertson, NR
Rayner, NW
Cingolani, P
Locke, AE
Tajes, JF
Highland, HM
Dupuis, J
Chines, PS
Lindgren, CM
Hartl, C
Jackson, AU
Chen, H
Huyghe, JR
van de Bunt, M
Pearson, RD
Kumar, A
Muller-Nurasyid, M
Grarup, N
Stringham, HM
Gamazon, ER
Lee, J
Chen, YH
Scott, RA
Below, JE
Chen, P
Huang, J
Go, MJ
Stitzel, ML
Pasko, D
Parker, SCJ
Varga, TV
Green, T
Beer, NL
Day-Williams, AG
Ferreira, T
Fingerlin, T
Horikoshi, M
Hu, C
Huh, I
Ikram, MK
Kim, BJ
Kim, Y
Kim, YJ
Kwon, MS
Lee, J
Lee, S
Lin, KH
Maxwell, TJ
Nagai, Y
Wang, X
Welch, RP
Yoon, J
Zhang, W
Barzilai, N
Voight, BF
Han, BG
Jenkinson, CP
Kuulasmaa, T
Kuusisto, J
Manning, A
Ng, MCY
Palmer, ND
Balkau, B
Stancakova, A
Abboud, HE
Boeing, H
Giedraitis, V
Prabhakaran, D
Gottesman, O
Scott, J
Carey, J
Kwan, P
Grant, G
Smith, JD
Neale, BM
Purcell, S
Butterworth, AS
Howson, JMM
Lee, HM
Lu, YC
Kwak, SH
Zhao, W
Danesh, J
Lam, VKL
Park, KS
Saleheen, D
So, WY
Tam, CHT
Afzal, U
Aguilar, D
Arya, R
Aung, T
Chan, E
Navarro, C
Cheng, CY
Palli, D
Correa, A
Curran, JE
Rybin, D
Farook, VS
Fowler, SP
Freedman, BI
Griswold, M
Hale, DE
Hicks, PJ
Khor, CC
Kumar, S
Lehne, B
Thuillier, D
Lim, WY
Liu, J
van der Schouw, YT
Loh, M
Musani, SK
Puppala, S
Scott, WR
Yengo, L
Tan, ST
Taylor, HA
Thameem, F
Wilson, G
Wong, TY
Njolstad, PR
Levy, JC
Mangino, M
Bonnycastle, LL
Schwarzmayr, T
Fadista, J
Surdulescu, GL
Herder, C
Groves, CJ
Wieland, T
Bork-Jensen, J
Brandslund, I
Christensen, C
Koistinen, HA
Doney, ASF
Kinnunen, L
Esko, T
Farmer, AJ
Hakaste, L
Hodgkiss, D
Kravic, J
Lyssenko, V
Hollensted, M
Jorgensen, ME
Jorgensen, T
Ladenvall, C
Justesen, JM
Karajamaki, A
Kriebel, J
Rathmann, W
Lannfelt, L
Lauritzen, T
Narisu, N
Linneberg, A
Melander, O
Milani, L
Neville, M
Orho-Melander, M
Qi, L
Qi, QB
Roden, M
Rolandsson, O
Swift, A
Rosengren, AH
Stirrups, K
Wood, AR
Mihailov, E
Blancher, C
Carneiro, MO
Maguire, J
Poplin, R
Shakir, K
Fennell, T
DePristo, M
de Angelis, MH
Deloukas, P
Gjesing, AP
Jun, G
Nilsson, P
Murphy, J
Onofrio, R
Thorand, B
Hansen, T
Meisinger, C
Hu, FB
Isomaa, B
Karpe, F
Liang, LM
Peters, A
Huth, C
O'Rahilly, SP
Palmer, CNA
Pedersen, O
Rauramaa, R
Tuomilehto, J
Salomaa, V
Watanabe, RM
Syvanen, AC
Bergman, RN
Bharadwaj, D
Bottinger, EP
Cho, YS
Chandak, GR
Chan, JCN
Chia, KS
Daly, MJ
Ebrahim, SB
Langenberg, C
Elliott, P
Jablonski, KA
Lehman, DM
Jia, WP
Ma, RCW
Pollin, TI
Sandhu, M
Tandon, N
Froguel, P
Barroso, I
Teo, YY
Zeggini, E
Loos, RJF
Small, KS
Ried, JS
DeFronzo, RA
Grallert, H
Glaser, B
Metspalu, A
Wareham, NJ
Walker, M
Banks, E
Gieger, C
Ingelsson, E
Im, HK
Illig, T
Franks, PW
Buck, G
Trakalo, J
Buck, D
Prokopenko, I
Magi, R
Lind, L
Farjoun, Y
Owen, KR
Gloyn, AL
Strauch, K
Tuomi, T
Kooner, JS
Lee, JY
Park, T
Donnelly, P
Morris, AD
Hattersley, AT
Bowden, DW
Collins, FS
Atzmon, G
Chambers, JC
Spector, TD
Laakso, M
Strom, TM
Bell, GI
Blangero, J
Duggirala, R
Tai, ES
McVean, G
Hanis, CL
Wilson, JG
Seielstad, M
Frayling, TM
Meigs, JB
Cox, NJ
Sladek, R
Lander, ES
Gabriel, S
Burtt, NP
Mohlke, KL
Meitinger, T
Groop, L
Abecasis, G
Florez, JC
Scott, LJ
Morris, AP
Kang, HM
Boehnke, M
Altshuler, D
McCarthy, MI
AF Fuchsberger, Christian
Flannick, Jason
Teslovich, Tanya M.
Mahajan, Anubha
Agarwala, Vineeta
Gaulton, Kyle J.
Ma, Clement
Fontanillas, Pierre
Moutsianas, Loukas
McCarthy, Davis J.
Rivas, Manuel A.
Perry, John R. B.
Sim, Xueling
Blackwell, Thomas W.
Robertson, Neil R.
Rayner, N. William
Cingolani, Pablo
Locke, Adam E.
Tajes, Juan Fernandez
Highland, Heather M.
Dupuis, Josee
Chines, Peter S.
Lindgren, Cecilia M.
Hartl, Christopher
Jackson, Anne U.
Chen, Han
Huyghe, Jeroen R.
van de Bunt, Martijn
Pearson, Richard D.
Kumar, Ashish
Mueller-Nurasyid, Martina
Grarup, Niels
Stringham, Heather M.
Gamazon, Eric R.
Lee, Jaehoon
Chen, Yuhui
Scott, Robert A.
Below, Jennifer E.
Chen, Peng
Huang, Jinyan
Go, Min Jin
Stitzel, Michael L.
Pasko, Dorota
Parker, Stephen C. J.
Varga, Tibor V.
Green, Todd
Beer, Nicola L.
Day-Williams, Aaron G.
Ferreira, Teresa
Fingerlin, Tasha
Horikoshi, Momoko
Hu, Cheng
Huh, Iksoo
Ikram, Mohammad Kamran
Kim, Bong-Jo
Kim, Yongkang
Kim, Young Jin
Kwon, Min-Seok
Lee, Juyoung
Lee, Selyeong
Lin, Keng-Han
Maxwell, Taylor J.
Nagai, Yoshihiko
Wang, Xu
Welch, Ryan P.
Yoon, Joon
Zhang, Weihua
Barzilai, Nir
Voight, Benjamin F.
Han, Bok-Ghee
Jenkinson, Christopher P.
Kuulasmaa, Teemu
Kuusisto, Johanna
Manning, Alisa
Ng, Maggie C. Y.
Palmer, Nicholette D.
Balkau, Beverley
Stancakova, Alena
Abboud, Hanna E.
Boeing, Heiner
Giedraitis, Vilmantas
Prabhakaran, Dorairaj
Gottesman, Omri
Scott, James
Carey, Jason
Kwan, Phoenix
Grant, George
Smith, Joshua D.
Neale, Benjamin M.
Purcell, Shaun
Butterworth, Adam S.
Howson, Joanna M. M.
Lee, Heung Man
Lu, Yingchang
Kwak, Soo-Heon
Zhao, Wei
Danesh, John
Lam, Vincent K. L.
Park, Kyong Soo
Saleheen, Danish
So, Wing Yee
Tam, Claudia H. T.
Afzal, Uzma
Aguilar, David
Arya, Rector
Aung, Tin
Chan, Edmund
Navarro, Carmen
Cheng, Ching-Yu
Palli, Domenico
Correa, Adolfo
Curran, Joanne E.
Rybin, Denis
Farook, Vidya S.
Fowler, Sharon P.
Freedman, Barry I.
Griswold, Michael
Hale, Daniel Esten
Hicks, Pamela J.
Khor, Chiea-Chuen
Kumar, Satish
Lehne, Benjamin
Thuillier, Dorothee
Lim, Wei Yen
Liu, Jianjun
van der Schouw, Yvonne T.
Loh, Marie
Musani, Solomon K.
Puppala, Sobha
Scott, William R.
Yengo, Loic
Tan, Sian-Tsung
Taylor, Herman A., Jr.
Thameem, Farook
Wilson, Gregory, Sr.
Wong, Tien Yin
Njolstad, Pal Rasmus
Levy, Jonathan C.
Mangino, Massimo
Bonnycastle, Lori L.
Schwarzmayr, Thomas
Fadista, Joao
Surdulescu, Gabriela L.
Herder, Christian
Groves, Christopher J.
Wieland, Thomas
Bork-Jensen, Jette
Brandslund, Ivan
Christensen, Cramer
Koistinen, Heikki A.
Doney, Alex S. F.
Kinnunen, Leena
Esko, Tonu
Farmer, Andrew J.
Hakaste, Liisa
Hodgkiss, Dylan
Kravic, Jasmina
Lyssenko, Valeriya
Hollensted, Mette
Jorgensen, Marit E.
Jorgensen, Torben
Ladenvall, Claes
Justesen, Johanne Marie
Karajamaki, Annemari
Kriebel, Jennifer
Rathmann, Wolfgang
Lannfelt, Lars
Lauritzen, Torsten
Narisu, Narisu
Linneberg, Allan
Melander, Olle
Milani, Lili
Neville, Matt
Orho-Melander, Marju
Qi, Lu
Qi, Qibin
Roden, Michael
Rolandsson, Olov
Swift, Amy
Rosengren, Anders H.
Stirrups, Kathleen
Wood, Andrew R.
Mihailov, Evelin
Blancher, Christine
Carneiro, Mauricio O.
Maguire, Jared
Poplin, Ryan
Shakir, Khalid
Fennell, Timothy
DePristo, Mark
de Angelis, Martin Hrabe
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Tuomilehto, Jaakko
Salomaa, Veikko
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Bharadwaj, Dwaipayan
Bottinger, Erwin P.
Cho, Yoon Shin
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Chan, Juliana C. N.
Chia, Kee Seng
Daly, Mark J.
Ebrahim, Shah B.
Langenberg, Claudia
Elliott, Paul
Jablonski, Kathleen A.
Lehman, Donna M.
Jia, Weiping
Ma, Ronald C. W.
Pollin, Toni I.
Sandhu, Manjinder
Tandon, Nikhil
Froguel, Philippe
Barroso, Ines
Teo, Yik Ying
Zeggini, Eleftheria
Loos, Ruth J. F.
Small, Kerrin S.
Ried, Janina S.
DeFronzo, Ralph A.
Grallert, Harald
Glaser, Benjamin
Metspalu, Andres
Wareham, Nicholas J.
Walker, Mark
Banks, Eric
Gieger, Christian
Ingelsson, Erik
Im, Hae Kyung
Illig, Thomas
Franks, Paul W.
Buck, Gemma
Trakalo, Joseph
Buck, David
Prokopenko, Inga
Magi, Reedik
Lind, Lars
Farjoun, Yossi
Owen, Katharine R.
Gloyn, Anna L.
Strauch, Konstantin
Tuomi, Tiinamaija
Kooner, Jaspal Singh
Lee, Jong-Young
Park, Taesung
Donnelly, Peter
Morris, Andrew D.
Hattersley, Andrew T.
Bowden, Donald W.
Collins, Francis S.
Atzmon, Gil
Chambers, John C.
Spector, Timothy D.
Laakso, Markku
Strom, Tim M.
Bell, Graeme I.
Blangero, John
Duggirala, Ravindranath
Tai, E. Shyong
McVean, Gilean
Hanis, Craig L.
Wilson, James G.
Seielstad, Mark
Frayling, Timothy M.
Meigs, James B.
Cox, Nancy J.
Sladek, Rob
Lander, Eric S.
Gabriel, Stacey
Burtt, Noel P.
Mohlke, Karen L.
Meitinger, Thomas
Groop, Leif
Abecasis, Goncalo
Florez, Jose C.
Scott, Laura J.
Morris, Andrew P.
Kang, Hyun Min
Boehnke, Michael
Altshuler, David
McCarthy, Mark I.
TI The genetic architecture of type 2 diabetes
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PROTEIN INTERACTION NETWORKS; SUSCEPTIBILITY
LOCI; LOW-FREQUENCY; SEQUENCING ASSOCIATION; COMPLEX TRAITS; RARE
VARIANTS; HUMAN-DISEASE; RISK; HERITABILITY
AB The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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[Jablonski, Kathleen A.] George Washington Univ, Biostat Ctr, Rockville, MD USA.
[Pollin, Toni I.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Pollin, Toni I.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA.
[Tandon, Nikhil] All India Inst Med Sci, Dept Endocrinol & Metab, New Delhi, India.
[Froguel, Philippe; Prokopenko, Inga] Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Teo, Yik Ying] Natl Univ Singapore, Inst Life Sci, Singapore, Singapore.
[Teo, Yik Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore.
[Glaser, Benjamin] Hadassah Hebrew Univ Med Ctr, Endocrinol & Metab Serv, Jerusalem, Israel.
[Walker, Mark] Newcastle Univ, Inst Cellular Med, Sch Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, Hannover, NH, Germany.
[Illig, Thomas] Hannover Med Sch, Inst Human Genet, Hannover, NH, Germany.
[Lind, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Farjoun, Yossi] Broad Inst, Data Sci & Data Engn, Cambridge, MA USA.
[Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, FIMM, Helsinki, Finland.
[Kooner, Jaspal Singh; Chambers, John C.] Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
[Morris, Andrew D.] Ninewells Hosp & Med Sch, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland.
[Morris, Andrew D.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Hattersley, Andrew T.] Univ Exeter, Sch Med, Exeter, Devon, England.
[Atzmon, Gil] Univ Haifa, Dept Nat Sci, Haifa, Israel.
[Strom, Tim M.; Meitinger, Thomas] Tech Univ Munich, Inst Human Genet, Munich, Germany.
[Bell, Graeme I.] Univ Chicago, Dept Med Genet, Chicago, IL 60637 USA.
[Bell, Graeme I.] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Tai, E. Shyong] Duke NUS Med Sch Singapore, Cardiovasc & Metab Disorders Program, Singapore, Singapore.
[McVean, Gilean] Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Seielstad, Mark] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Seielstad, Mark] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Seielstad, Mark] Blood Syst Res Inst, San Francisco, CA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Sladek, Rob] McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada.
[Lander, Eric S.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Florez, Jose C.; Altshuler, David] Harvard Med Sch, Dept Med, Boston, MA USA.
[Florez, Jose C.; Altshuler, David] Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
[Altshuler, David] MIT, Dept Biol, Cambridge, MA USA.
RP Boehnke, M (reprint author), Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.; McCarthy, MI (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Nuffield Dept Med, Oxford, England.; McCarthy, MI (reprint author), Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
EM boehnke@umich.edu; mark.mccarthy@drl.ox.ac.uk
RI Hrabe de Angelis, Martin/F-5531-2012; Jun, Goo/F-1941-2017; Kinnunen,
Leena/B-7059-2012; van der Schouw, Yvonne/F-8327-2014; Ma,
Ronald/C-2788-2009; Yengo, Loic/D-2692-2017; Palmer, Colin/C-7053-2008;
Chan, Juliana /B-7918-2016; Peters, Annette/A-6117-2011; Park, Kyong
Soo/C-2265-2008; Justesen, Johanne Marie/L-6023-2015; Deloukas,
Panos/B-2922-2013; Hu, Cheng/C-3346-2008; Grallert, Harald/B-3424-2013;
Grarup, Niels/K-2807-2015
OI Varga, Tibor/0000-0002-2383-699X; Tai, E Shyong/0000-0003-2929-8966;
Hattersley, Andrew/0000-0001-5620-473X; Linneberg,
Allan/0000-0002-0994-0184; Hrabe de Angelis, Martin/0000-0002-7898-2353;
Jun, Goo/0000-0003-0891-0204; Gieger, Christian/0000-0001-6986-9554;
Kinnunen, Leena/0000-0001-8739-4812; mangino,
massimo/0000-0002-2167-7470; Koistinen, Heikki/0000-0001-7870-070X;
Meisinger, Christa/0000-0002-9026-6544; Chen, Han/0000-0002-9510-4923;
Tuomi, Tiinamaija/0000-0002-8306-6202; Small,
Kerrin/0000-0003-4566-0005; Khor, Chiea Chuen/0000-0002-1128-4729; van
der Schouw, Yvonne/0000-0002-4605-435X; Ma, Ronald/0000-0002-1227-803X;
Yengo, Loic/0000-0002-4272-9305; Palmer, Colin/0000-0002-6415-6560;
Chan, Juliana /0000-0003-1325-1194; Park, Kyong Soo/0000-0003-3597-342X;
Justesen, Johanne Marie/0000-0002-0484-8522; Deloukas,
Panos/0000-0001-9251-070X; Grarup, Niels/0000-0001-5526-1070
FU British Heart Foundation [RG/14/5/30893, SP/04/002, SP/09/002]; CIHR;
Medical Research Council [G0601261, G0601966, G0700931, G0800270,
G0900747-‐91070, MC_UU_12012/5, MC_UU_12015/1, MR/K002414/1,
MR/L01341X/1]; NCI NIH HHS [K12CA139160]; NHGRI NIH HHS [U01 HG005773,
U01HG005773, U54 HG003067, U54HG003067]; NHLBI NIH HHS
[HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C, R01 HL102830, R01HL102830]; NIA
NIH HHS [1R01AG042188, P01 AG027734, P01AG027734, P30 AG038072,
P30AG038072, R01 AG042188, R01 AG046949, R01AG046949]; NIDDK NIH HHS
[R01DK066358, 1RC2DK088389, DK072193, DK085501, DK085524, DK085526,
DK085545, DK085584, DK088389, DK093757, DK098032, K24 DK080140,
K24DK080140, P30 DK020595, P30DK020595, P60 DK020595, P60DK20595, R00
DK092251, R00 DK099240, R00DK092251, R01 DK066358, R01 DK072193, R01
DK073541, R01 DK093757, R01 DK098032, R01 DK101478, R01 DK106236,
R01DK062370, R01DK073541, R01DK098032, RC2 DK088389, RC2-‐DK088389,
RC2DK088389, U01 DK062370, U01 DK078616, U01 DK085501, U01 DK085524, U01
DK085526, U01 DK085545, U01 DK085584, U01DK085501, U01DK085526]; NIGMS
NIH HHS [T32 GM007753, T32GM007753]; NIMH NIH HHS [R01 MH090937, R01
MH101820, R01MH090937, R01MH101820]; NIMHD NIH HHS [U54 MD007588]; PHS
HHS [HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C]; Wellcome Trust [064890, 083948,
084723, 085475, 086596, 090367, 090532, 092447, 095101, 095552, 098017,
098051, 098381, 100956]
NR 68
TC 34
Z9 34
U1 38
U2 39
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 AUG 4
PY 2016
VL 536
IS 7614
BP 41
EP +
DI 10.1038/nature18642
PG 29
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200026
PM 27398621
ER
PT J
AU Lee, ASY
Kranzusch, PJ
Doudna, JA
Cate, JHD
AF Lee, Amy S. Y.
Kranzusch, Philip J.
Doudna, Jennifer A.
Cate, Jamie H. D.
TI eIF3d is an mRNA cap-binding protein that is required for specialized
translation initiation
SO NATURE
LA English
DT Article
ID DEPENDENT TRANSLATION; C-JUN; MECHANISM; MODEL; MTOR; PHOSPHORYLATION;
ACTIVATION; COMPLEXES; LINKING; QUALITY
AB Eukaryotic mRNAs contain a 5' cap structure that is crucial for recruitment of the translation machinery and initiation of protein synthesis. mRNA recognition is thought to require direct interactions between eukaryotic initiation factor 4E (eIF4E) and the mRNA cap. However, translation of numerous capped mRNAs remains robust during cellular stress, early development, and cell cycle progression(1) despite inactivation of eIF4E. Here we describe a cap-dependent pathway of translation initiation in human cells that relies on a previously unknown cap-binding activity of eIF3d, a subunit of the 800-kilodalton eIF3 complex. A 1.4 angstrom crystal structure of the eIF3d cap-binding domain reveals unexpected homology to endonucleases involved in RNA turnover, and allows modelling of cap recognition by eIF3d. eIF3d makes specific contacts with the cap, as exemplified by cap analogue competition, and these interactions are essential for assembly of translation initiation complexes on eIF3-specialized mRNAs(2) such as the cell proliferation regulator c-Jun (also known as JUN). The c-Jun mRNA further encodes an inhibitory RNA element that blocks eIF4E recruitment, thus enforcing alternative cap recognition by eIF3d. Our results reveal a mechanism of cap-dependent translation that is independent of eIF4E, and illustrate how modular RNA elements work together to direct specialized forms of translation initiation.
C1 [Lee, Amy S. Y.; Kranzusch, Philip J.; Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.
[Lee, Amy S. Y.; Kranzusch, Philip J.; Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA.
[Kranzusch, Philip J.; Doudna, Jennifer A.] Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA.
[Doudna, Jennifer A.; Cate, Jamie H. D.] Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.
[Doudna, Jennifer A.; Cate, Jamie H. D.] Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
[Doudna, Jennifer A.] Univ Calif Berkeley, Innovat Genom Initiat, Berkeley, CA 94720 USA.
[Lee, Amy S. Y.] Brandeis Univ, Dept Biol, Waltham, MA 02454 USA.
[Kranzusch, Philip J.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.
[Kranzusch, Philip J.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
RP Cate, JHD (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 229 Stanley Hall, Berkeley, CA 94720 USA.; Cate, JHD (reprint author), Univ Calif Berkeley, Ctr RNA Syst Biol, Berkeley, CA 94720 USA.; Cate, JHD (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA.; Cate, JHD (reprint author), Lawrence Berkeley Natl Lab, Phys Biosci Div, Berkeley, CA 94720 USA.
EM jcate@lbl.gov
FU UC Office of the President, Multicampus Research Programs and
Initiatives grant [MR-15-328599]; Program for Breakthrough Biomedical
Research; Sandler Foundation; NIH [S10RR025622]; NIGMS Center for RNA
Systems Biology [P50-GM201706]
FX The authors thank J. Berger and K. Chat for discussions. X-ray data were
collected at Beamline 8.3.1 of the Lawrence Berkeley National Laboratory
Advanced Light Source (ALS), supported in part by the UC Office of the
President, Multicampus Research Programs and Initiatives grant
MR-15-328599 and the Program for Breakthrough Biomedical Research, which
is partially funded by the Sandler Foundation. The authors are grateful
to J. Holton, G. Meigs (ALS), and T. Doukov (SSRL) for help with S-SAD
data collection. This work used the Vincent J. Proteomics/Mass
Spectrometry Laboratory at UC Berkeley, supported in part by NIH S10
Instrumentation Grant S10RR025622. This work was funded by the NIGMS
Center for RNA Systems Biology (P50-GM201706). J.A.D. is an HHMI
Investigator. A.S.Y.L. is supported as an American Cancer Society
Postdoctoral Fellow (PF-14-108-01-RMC) and P.J.K. is supported as an
HHMI Fellow of the Life Sciences Research Foundation.
NR 34
TC 6
Z9 6
U1 6
U2 6
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 AUG 4
PY 2016
VL 536
IS 7614
BP 96
EP +
DI 10.1038/nature18954
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7YM
UT WOS:000380999200037
PM 27462815
ER
PT J
AU Shaw, MA
Kombrinck, KW
McElhinney, KE
Sweet, DR
Flick, MJ
Palumbo, JS
Cheng, M
Esmon, NL
Esmon, CT
Brill, A
Wagner, DD
Degen, JL
Mullins, ES
AF Shaw, Maureen A.
Kombrinck, Keith W.
McElhinney, Kathryn E.
Sweet, David R.
Flick, Matthew J.
Palumbo, Joseph S.
Cheng, Mei
Esmon, Naomi L.
Esmon, Charles T.
Brill, Alexander
Wagner, Denisa D.
Degen, Jay L.
Mullins, Eric S.
TI Limiting prothrombin activation to meizothrombin is compatible with
survival but significantly alters hemostasis in mice
SO BLOOD
LA English
DT Article
ID THROMBIN MUTANT W215A/E217A; FUNCTIONAL-CHARACTERIZATION; TISSUE FACTOR;
TUMOR-CELLS; MOUSE MODEL; FACTOR-XIII; FACTOR-V; INTERMEDIATE;
DEFICIENCY; ANTICOAGULANT
AB Thrombin-mediated proteolysis is central to hemostatic function but also plays a prominent role in multiple disease processes. The proteolytic conversion of fII to alpha-thrombin (fIIa) by the prothrombinase complex occurs through 2 parallel pathways: (1) the inactive intermediate, prethrombin; or (2) the proteolytically active intermediate, meizothrombin (fIIa(MZ)). FIIa(MZ) has distinct catalytic properties relative to fIIa, including diminished fibrinogen cleavage and increased protein C activation. Thus, fII activation may differentially influence hemostasis and disease depending on the pathway of activation. To determine the in vivo physiologic and pathologic consequences of restricting thrombin generation to fIIa(MZ), mutations were introduced into the endogenous fII gene, resulting in expression of prothrombin carrying 3 amino acid substitutions (R157A, R268A, and K281A) to limit activation events to yield only fIIa(MZ). Homozygous fII(MZ) mice are viable, express fII levels comparable with fII(WT) mice, and have reproductive success. Although in vitro studies revealed delayed generation of fIIa(MZ) enzyme activity, platelet aggregation by fII(MZ) is similar to fII(WT). Consistent with prior analyses of human fIIa(MZ), significant prolongation of clotting times was observed for fII(MZ) plasma. Adult fII(MZ) animals displayed significantly compromised hemostasis in tail bleeding assays, but did not demonstrate overt bleeding. More notably, fII(MZ) mice had 2 significant phenotypic advantages over fII(WT) animals: protection from occlusive thrombosis after arterial injury and markedly diminished metastatic potential in a setting of experimental tumor metastasis to the lung. Thus, these novel animals will provide a valuable tool to assess the role of both fIIa and fIIa(MZ) in vivo.
C1 [Shaw, Maureen A.; McElhinney, Kathryn E.; Sweet, David R.; Palumbo, Joseph S.; Mullins, Eric S.] Cincinnati Childrens Res Fdn, Div Hematol, Canc & Blood Dis Inst, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA.
[Kombrinck, Keith W.; Flick, Matthew J.; Degen, Jay L.] Cincinnati Childrens Res Fdn, Div Expt Hematol & Canc Biol, Cincinnati, OH USA.
[Cheng, Mei; Esmon, Naomi L.; Esmon, Charles T.] Oklahoma Med Res Fdn, Coagulat Biol Lab, 825 NE 13th St, Oklahoma City, OK 73104 USA.
[Brill, Alexander] Univ Birmingham, Coll Med & Dent Sci, Inst Cardiovasc Sci, Birmingham, W Midlands, England.
[Brill, Alexander; Wagner, Denisa D.] Harvard Med Sch, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA USA.
[Brill, Alexander; Wagner, Denisa D.] Harvard Med Sch, Div Hematol Oncol, Boston Childrens Hosp, Boston, MA USA.
RP Mullins, ES (reprint author), Cincinnati Childrens Res Fdn, Div Hematol, Canc & Blood Dis Inst, MLC 7015,3333 Burnet Ave, Cincinnati, OH 45229 USA.
EM eric.mullins@cchmc.org
FU National Institutes of Health, National Heart, Lung and Blood Institute
[K08HL105672, R01HL102101]
FX This study was supported by National Institutes of Health, National
Heart, Lung and Blood Institute grants K08HL105672 (E.S.M.) and
R01HL102101 (D.D.W.).
NR 47
TC 1
Z9 1
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 AUG 4
PY 2016
VL 128
IS 5
BP 721
EP 731
DI 10.1182/blood-2015-11-680280
PG 11
WC Hematology
SC Hematology
GA DW7PI
UT WOS:000383843000016
PM 27252233
ER
PT J
AU Henssen, AG
Jiang, E
Zhuang, JL
Pinello, L
Socci, ND
Koche, R
Gonen, M
Villasante, CM
Armstrong, SA
Bauer, DE
Weng, ZP
Kentsis, A
AF Henssen, Anton G.
Jiang, Eileen
Zhuang, Jiali
Pinello, Luca
Socci, Nicholas D.
Koche, Richard
Gonen, Mithat
Villasante, Camila M.
Armstrong, Scott A.
Bauer, Daniel E.
Weng, Zhiping
Kentsis, Alex
TI Forward genetic screen of human transposase genomic rearrangements
SO BMC GENOMICS
LA English
DT Article
ID HAMSTER OVARY CELLS; T-LYMPHOCYTES; HPRT GENE; DESIGN; ART; LOCUS;
TELOMERASE; MUTATIONS; DELETION
AB Background: Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates.
Results: To enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 (HPRT1) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis. Here, we report the HPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates.
Conclusions: The discovered PSS motifs and high-throughput forward chemical genomic screening approach should prove useful for the elucidation of endogenous genome remodeling activities of PGBD5 and other domesticated human DNA transposases and recombinases.
C1 [Henssen, Anton G.; Jiang, Eileen; Villasante, Camila M.; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Mol Pharmacol Program, 1275 York Ave, New York, NY 10021 USA.
[Zhuang, Jiali; Weng, Zhiping] Univ Massachusetts, Sch Med, Program Bioinformat & Integrat Biol, Dept Biochem & Mol Pharmacol, Worcester, MA USA.
[Pinello, Luca; Bauer, Daniel E.] Dana Farber Canc Inst, Boston, MA USA.
[Pinello, Luca; Bauer, Daniel E.] Boston Childrens Hosp, Boston, MA USA.
[Socci, Nicholas D.] Mem Sloan Kettering Canc Ctr, Bioinformat Core, New York, NY USA.
[Koche, Richard; Armstrong, Scott A.] Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY USA.
[Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA.
[Armstrong, Scott A.; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA.
[Kentsis, Alex] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
RP Kentsis, A (reprint author), Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Mol Pharmacol Program, 1275 York Ave, New York, NY 10021 USA.; Kentsis, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA.; Kentsis, A (reprint author), Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA.
EM kentsisresearchgroup@gmail.com
FU University of Essen Pediatric Oncology Research Program; NIH [K08
DK093705, K08 CA160660]; Burroughs Wellcome Fund; Josie Robertson
Investigator Program; Sarcoma Foundation of America; NHGRI Career
Development Award [K99 HG008399]
FX This work was supported by the University of Essen Pediatric Oncology
Research Program (A.H.), NIH K08 DK093705 (D.E.B.), NIH K08 CA160660,
Burroughs Wellcome Fund, Josie Robertson Investigator Program, and the
Sarcoma Foundation of America (A.K.). L.P. is supported by NHGRI Career
Development Award K99 HG008399. We thank the MSKCC Integrated Genomics
Core Facility and Bioinformatics Core Facility for assistance with DNA
sequencing and analysis (NIH P30 CA008748).
NR 28
TC 1
Z9 1
U1 2
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2164
J9 BMC GENOMICS
JI BMC Genomics
PD AUG 4
PY 2016
VL 17
AR 548
DI 10.1186/s12864-016-2877-x
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA DT1EW
UT WOS:000381225500002
PM 27491780
ER
PT J
AU Polfus, LM
Khajuria, RK
Schick, UM
Pankratz, N
Pazoki, R
Brody, JA
Chen, MH
Auer, PL
Floyd, JS
Huang, J
Lange, L
van Rooij, FJA
Gibbs, RA
Metcalf, G
Muzny, D
Veeraraghavan, N
Walter, K
Chen, L
Yanek, L
Becker, LC
Peloso, GM
Wakabayashi, A
Kals, M
Metspalu, A
Esko, T
Fox, K
Wallace, R
Franceschini, N
Matijevic, N
Rice, KM
Bartz, TM
Lyytikainen, LP
Kahonen, M
Lehtimaki, T
Raitakari, OT
Li-Gao, R
Mook-Kanamori, DO
Lettre, G
van Duijn, CM
Franco, OH
Rich, SS
Rivadeneira, F
Hofman, A
Uitterlinden, AG
Wilson, JG
Psaty, BM
Soranzo, N
Dehghan, A
Boerwinkle, E
Zhang, XL
Johnson, AD
O'Donnell, CJ
Johnsen, JM
Reiner, AP
Ganesh, SK
Sankaran, VG
AF Polfus, Linda M.
Khajuria, Rajiv K.
Schick, Ursula M.
Pankratz, Nathan
Pazoki, Raha
Brody, Jennifer A.
Chen, Ming-Huei
Auer, Paul L.
Floyd, James S.
Huang, Jie
Lange, Leslie
van Rooij, Frank J. A.
Gibbs, Richard A.
Metcalf, Ginger
Muzny, Donna
Veeraraghavan, Narayanan
Walter, Klaudia
Chen, Lu
Yanek, Lisa
Becker, Lewis C.
Peloso, Gina M.
Wakabayashi, Aoi
Kals, Mart
Metspalu, Andres
Esko, Tonu
Fox, Keolu
Wallace, Robert
Franceschini, Nora
Matijevic, Nena
Rice, Kenneth M.
Bartz, Traci M.
Lyytikainen, Leo-Pekka
Kahonen, Mika
Lehtimaki, Terho
Raitakari, Olli T.
Li-Gao, Ruifang
Mook-Kanamori, Dennis O.
Lettre, Guillaume
van Duijn, Cornelia M.
Franco, Oscar H.
Rich, Stephen S.
Rivadeneira, Fernando
Hofman, Albert
Uitterlinden, Andre G.
Wilson, James G.
Psaty, Bruce M.
Soranzo, Nicole
Dehghan, Abbas
Boerwinkle, Eric
Zhang, Xiaoling
Johnson, Andrew D.
O'Donnell, Christopher J.
Johnsen, Jill M.
Reiner, Alexander P.
Ganesh, Santhi K.
Sankaran, Vijay G.
TI Whole-Exome Sequencing Identifies Loci Associated with Blood Cell Traits
and Reveals a Role for Alternative GFI1B Splice Variants in Human
Hematopoiesis
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID DIAMOND-BLACKFAN ANEMIA; GRAY PLATELET SYNDROME; HEMATOLOGICAL TRAITS;
GENETIC-VARIATION; GFI-1B; DIFFERENTIATION; METAANALYSIS; CONSORTIUM;
MUTATIONS; DISORDER
AB Circulating blood cell counts and indices are important indicators of hematopoietic function and a number of clinical parameters, such as blood oxygen-carrying capacity, inflammation, and hemostasis. By performing whole-exome sequence association analyses of hematologic quantitative traits in 15,459 community-dwelling individuals, followed by in silico replication in up to 52,024 independent samples, we identified two previously undescribed coding variants associated with lower platelet count: a common missense variant in CPS1 (rs1047891, MAF=0.33, discovery + replication p=6.38 x 10(-10)) and a rare synonymous variant in GFI1B (rs150813342, MAF=0.009, discovery + replication p=1.79 x 10(-27)). By performing CRISPR/Cas9 genome editing in hematopoietic cell lines and follow-up targeted knockdown experiments in primary human hematopoietic stem and progenitor cells, we demonstrate an alternative splicing mechanism by which the GFI1B rs150813342 variant suppresses formation of a GFI1B isoform that preferentially promotes megakaryocyte differentiation and platelet production. These results demonstrate how unbiased studies of natural variation in blood cell traits can provide insight into the regulation of human hematopoiesis.
C1 [Polfus, Linda M.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Khajuria, Rajiv K.; Wakabayashi, Aoi; Sankaran, Vijay G.] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Khajuria, Rajiv K.; Wakabayashi, Aoi; Sankaran, Vijay G.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Khajuria, Rajiv K.; Wakabayashi, Aoi; Sankaran, Vijay G.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Khajuria, Rajiv K.] Charite, Berlin Brandenburg Sch Regenerat Therapies, D-13353 Berlin, Germany.
[Schick, Ursula M.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Pankratz, Nathan] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA.
[Pazoki, Raha; van Rooij, Frank J. A.; Franco, Oscar H.; Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.
[Brody, Jennifer A.; Floyd, James S.; Rice, Kenneth M.; Bartz, Traci M.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Brody, Jennifer A.; Floyd, James S.; Rice, Kenneth M.; Bartz, Traci M.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Chen, Ming-Huei] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Auer, Paul L.] Univ Wisconsin Milwaukee, Sch Publ Hlth, Milwaukee, WI 53205 USA.
[Huang, Jie; Walter, Klaudia; Chen, Lu; Soranzo, Nicole] Wellcome Trust Sanger Inst, Human Genet, Hinxton CB10 1HH, England.
[Lange, Leslie] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Gibbs, Richard A.; Metcalf, Ginger; Muzny, Donna; Veeraraghavan, Narayanan] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Chen, Lu; Soranzo, Nicole] Univ Cambridge, Dept Haematol, Cambridge CB2 0AH, England.
[Yanek, Lisa; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, GeneSTAR Res Program,Div Gen Internal Med, Baltimore, MD 21205 USA.
[Peloso, Gina M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Kals, Mart; Metspalu, Andres; Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Fox, Keolu] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Wallace, Robert] Univ Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA.
[Franceschini, Nora] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA.
[Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Dept Surg, Houston, TX 77030 USA.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Tampere 33520, Finland.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Tampere 33521, Finland.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20520, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland.
[Li-Gao, Ruifang; Mook-Kanamori, Dennis O.] Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RA Leiden, Netherlands.
[Mook-Kanamori, Dennis O.] King Faisal Specialist Hosp & Res Ctr, Dept Biostat, Epidemiol, Epidemiol Sect, Riyadh 11211, Saudi Arabia.
[Mook-Kanamori, Dennis O.] King Faisal Specialist Hosp & Res Ctr, Dept Comp Sci, Riyadh 11211, Saudi Arabia.
[Lettre, Guillaume] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.
[Lettre, Guillaume] Univ Montreal, Montreal, PQ H1T 1C8, Canada.
[van Duijn, Cornelia M.; Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Zhang, Xiaoling] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Zhang, Xiaoling] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA.
[Zhang, Xiaoling] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA 02118 USA.
[Zhang, Xiaoling] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Johnson, Andrew D.] NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Johnsen, Jill M.] Bloodworks Northwest, Seattle, WA 98102 USA.
[Reiner, Alexander P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Womens Hlth Initiat Clin Coordinating Ctr, Seattle, WA 98109 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Ganesh, Santhi K.] Univ Michigan, Dept Human Genet, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
RP Sankaran, VG (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.; Sankaran, VG (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
EM sankaran@broadinstitute.org
RI Floyd, James/G-7563-2015; Johnson, Andrew/G-6520-2013
FU NIH [HL122684, DK103794, HL120791]; Wellcome Trust [WT098051, WT091310];
EU [257082, HEALTH-F5-2011-282510]; NIH Research (NIHR) Blood and
Transplant Research Unit (BTRU) in Donor Health and Genomics at the
University of Cambridge; NHS Blood and Transplant (NHSBT)
FX The work described in this manuscript was supported in part by NIH
grants HL122684 to S.K.G. and DK103794 and HL120791 to V.G.S. N.S. is
supported by the Wellcome Trust (grant codes WT098051 and WT091310), the
EU 7th Framework Programme (EPIGENESYS grant code 257082 and BLUEPRINT
grant code HEALTH-F5-2011-282510) and the NIH Research (NIHR) Blood and
Transplant Research Unit (BTRU) in Donor Health and Genomics at the
University of Cambridge in partnership with NHS Blood and Transplant
(NHSBT).
NR 33
TC 5
Z9 5
U1 2
U2 3
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 AUG 4
PY 2016
VL 99
IS 2
BP 481
EP 488
DI 10.1016/j.ajhg.2016.06.016
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA DT6TO
UT WOS:000381617200020
PM 27486782
ER
PT J
AU Kimball, AB
Okun, MM
Williams, DA
Gottlieb, AB
Papp, KA
Zouboulis, CC
Armstrong, AW
Kerdel, F
Gold, MH
Forman, SB
Korman, NJ
Giamarellos-Bourboulis, EJ
Crowley, JJ
Lynde, C
Reguiai, Z
Prens, EP
Alwawi, E
Mostafa, NM
Pinsky, B
Sundaram, M
Gu, YH
Carlson, DM
Jemec, GBE
AF Kimball, Alexa B.
Okun, Martin M.
Williams, David A.
Gottlieb, Alice B.
Papp, Kim A.
Zouboulis, Christos C.
Armstrong, April W.
Kerdel, Francisco
Gold, Michael H.
Forman, Seth B.
Korman, Neil J.
Giamarellos-Bourboulis, Evangelos J.
Crowley, Jeffrey J.
Lynde, Charles
Reguiai, Ziad
Prens, Errol-Prospero
Alwawi, Eihab
Mostafa, Nael M.
Pinsky, Brett
Sundaram, Murali
Gu, Yihua
Carlson, Dawn M.
Jemec, Gregor B. E.
TI Two Phase 3 Trials of Adalimumab for Hidradenitis Suppurativa
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID MODERATE; PREVALENCE; PSORIASIS; THERAPY; INVERSA; DISEASE; ALPHA
AB BACKGROUND
Hidradenitis suppurativa is a painful, chronic inflammatory skin disease with few options for effective treatment. In a phase 2 trial, adalimumab, an antibody against tumor necrosis factor a, showed efficacy against hidradenitis suppurativa.
METHODS
PIONEER I and II were similarly designed, phase 3 multicenter trials of adalimumab for hidradenitis suppurativa, with two double-blind, placebo-controlled periods. In period 1, patients were randomly assigned in a 1: 1 ratio to 40 mg of adalimumab weekly or matching placebo for 12 weeks. In period 2, patients were reassigned to adalimumab at a weekly or every-other-week dose or to placebo for 24 weeks. The primary end point was a clinical response, defined as at least a 50% reduction from baseline in the abscess and inflammatory-nodule count, with no increase in abscess or draining-fistula counts, at week 12.
RESULTS
We enrolled 307 patients in PIONEER I and 326 in PIONEER II. Clinical response rates at week 12 were significantly higher for the groups receiving adalimumab weekly than for the placebo groups: 41.8% versus 26.0% in PIONEER I (P=0.003) and 58.9% versus 27.6% in PIONEER II (P<0.001). Patients receiving adalimumab had significantly greater improvement than the placebo groups in rank-ordered secondary outcomes (lesions, pain, and the modified Sartorius score for disease severity) at week 12 in PIONEER II only. Serious adverse events in period 1 (excluding worsening of underlying disease) occurred in 1.3% of patients receiving adalimumab and 1.3% of those receiving placebo in PIONEER I and in 1.8% and 3.7% of patients, respectively, in PIONEER II. In period 2, the rates of serious adverse events were 4.6% or less in all the groups in both studies, with no significant between-group differences.
CONCLUSIONS
Treatment with adalimumab (40 mg weekly), as compared with placebo, resulted in significantly higher clinical response rates in both trials at 12 weeks; rates of serious adverse events were similar in the study groups.
C1 [Kimball, Alexa B.] Harvard Med Sch, Boston, MA USA.
[Kimball, Alexa B.] Massachusetts Gen Hosp, Boston, MA USA.
[Gottlieb, Alice B.] Tufts Med Ctr, Boston, MA USA.
[Okun, Martin M.; Williams, David A.; Alwawi, Eihab; Mostafa, Nael M.; Pinsky, Brett; Sundaram, Murali; Gu, Yihua; Carlson, Dawn M.] AbbVie, N Chicago, IL USA.
[Papp, Kim A.] Prob Med Res, Waterloo, ON, Canada.
[Papp, Kim A.] K Papp Clin Res, Waterloo, ON, Canada.
[Lynde, Charles] Lynde Ctr Dermatol, Markham, ON, Canada.
[Lynde, Charles] Prob Med Res, Markham, ON, Canada.
[Zouboulis, Christos C.] Dessau Med Ctr, Dept Dermatol, Dessau, Germany.
[Zouboulis, Christos C.] Dessau Med Ctr, Dept Venereol, Dessau, Germany.
[Zouboulis, Christos C.] Dessau Med Ctr, Dept Allergol, Dessau, Germany.
[Zouboulis, Christos C.] Dessau Med Ctr, Dept Immunol, Dessau, Germany.
[Armstrong, April W.] Univ So Calif, Los Angeles, CA USA.
[Crowley, Jeffrey J.] Bakersfield Dermatol, Bakersfield, CA USA.
[Kerdel, Francisco] Florida Acad Dermatol Ctr, Miami, FL USA.
[Forman, Seth B.] Forward Clin Trials, Tampa, FL USA.
[Gold, Michael H.] Tennessee Clin Res Ctr, Nashville, TN USA.
[Korman, Neil J.] Univ Hosp Case Med Ctr, Cleveland, OH USA.
[Giamarellos-Bourboulis, Evangelos J.] Univ Athens, Sch Med, Dept Internal Med 4, Athens, Greece.
[Reguiai, Ziad] CHU Reims, Hop Robert Debre, Serv Dermatol, Reims, France.
[Prens, Errol-Prospero] Erasmus Univ, Med Ctr, Rotterdam, Netherlands.
[Jemec, Gregor B. E.] Univ Copenhagen, Roskilde Hosp, Dept Dermatol, Copenhagen, Denmark.
[Jemec, Gregor B. E.] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark.
RP Kimball, AB (reprint author), 375 Longwood Ave,3rd Fl, Boston, MA 02215 USA.
EM harvardskinstudies@gmail.com
OI Jemec, Gregor/0000-0002-0712-2540
FU AbbVie
FX Funded by AbbVie; ClinicalTrials.gov numbers, NCT01468207 and
NCT01468233 for PIONEER I and PIONEER II, respectively.
NR 25
TC 8
Z9 8
U1 4
U2 5
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 AUG 4
PY 2016
VL 375
IS 5
BP 422
EP 434
DI 10.1056/NEJMoa1504370
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS7AN
UT WOS:000380934900006
PM 27518661
ER
PT J
AU Pritchard, CC
Mateo, J
Walsh, MF
De Sarkar, N
Abida, W
Beltran, H
Garofalo, A
Gulati, R
Carreira, S
Eeles, R
Elemento, O
Rubin, MA
Robinson, D
Lonigro, R
Hussain, M
Chinnaiyan, A
Vinson, J
Filipenko, J
Garraway, L
Taplin, ME
AlDubayan, S
Han, GC
Beightol, M
Morrissey, C
Nghiem, B
Cheng, HH
Montgomery, B
Walsh, T
Casadei, S
Berger, M
Zhang, L
Zehir, A
Vijai, J
Scher, HI
Sawyers, C
Schultz, N
Kantoff, PW
Solit, D
Robson, M
Van Allen, EM
Offit, K
de Bono, J
Nelson, PS
AF Pritchard, C. C.
Mateo, J.
Walsh, M. F.
De Sarkar, N.
Abida, W.
Beltran, H.
Garofalo, A.
Gulati, R.
Carreira, S.
Eeles, R.
Elemento, O.
Rubin, M. A.
Robinson, D.
Lonigro, R.
Hussain, M.
Chinnaiyan, A.
Vinson, J.
Filipenko, J.
Garraway, L.
Taplin, M. -E.
AlDubayan, S.
Han, G. C.
Beightol, M.
Morrissey, C.
Nghiem, B.
Cheng, H. H.
Montgomery, B.
Walsh, T.
Casadei, S.
Berger, M.
Zhang, L.
Zehir, A.
Vijai, J.
Scher, H. I.
Sawyers, C.
Schultz, N.
Kantoff, P. W.
Solit, D.
Robson, M.
Van Allen, E. M.
Offit, K.
de Bono, J.
Nelson, P. S.
TI Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate
Cancer
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID OVARIAN-CANCER; BREAST-CANCER; RISK; DISEASE; BRCA1; AGGRESSIVENESS;
ASSOCIATION; GUIDELINES; VARIANTS; GENOMICS
AB BACKGROUND
Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established.
METHODS
We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis. We isolated germline DNA and used multiplex sequencing assays to assess mutations in 20 DNA-repair genes associated with autosomal dominant cancer-predisposition syndromes.
RESULTS
A total of 84 germline DNA-repair gene mutations that were presumed to be deleterious were identified in 82 men (11.8%); mutations were found in 16 genes, including BRCA2 (37 men [5.3%]), ATM (11 [1.6%]), CHEK2 (10 [1.9% of 534 men with data]), BRCA1 (6 [0.9%]), RAD51D (3 [0.4%]), and PALB2 (3 [0.4%]). Mutation frequencies did not differ according to whether a family history of prostate cancer was present or according to age at diagnosis. Overall, the frequency of germline mutations in DNA-repair genes among men with metastatic prostate cancer significantly exceeded the prevalence of 4.6% among 499 men with localized prostate cancer (P<0.001), including men with high-risk disease, and the prevalence of 2.7% in the Exome Aggregation Consortium, which includes 53,105 persons without a known cancer diagnosis (P<0.001).
CONCLUSIONS
In our multicenter study, the incidence of germline mutations in genes mediating DNA-repair processes among men with metastatic prostate cancer was 11.8%, which was significantly higher than the incidence among men with localized prostate cancer. The frequencies of germline mutations in DNA-repair genes among men with metastatic disease did not differ significantly according to age at diagnosis or family history of prostate cancer.
C1 [Pritchard, C. C.; Beightol, M.; Morrissey, C.; Nghiem, B.; Cheng, H. H.; Montgomery, B.; Walsh, T.; Casadei, S.; Nelson, P. S.] Univ Washington, Seattle, WA 98195 USA.
[De Sarkar, N.; Gulati, R.; Nelson, P. S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.
[Mateo, J.; Carreira, S.; Eeles, R.; de Bono, J.] Inst Canc Res, London, England.
[Mateo, J.; Carreira, S.; Eeles, R.; de Bono, J.] Royal Marsden Hosp, London, England.
[Walsh, M. F.; Abida, W.; Berger, M.; Zhang, L.; Zehir, A.; Vijai, J.; Scher, H. I.; Sawyers, C.; Schultz, N.; Kantoff, P. W.; Solit, D.; Robson, M.; Offit, K.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Beltran, H.; Elemento, O.; Rubin, M. A.] Weill Cornell Med Coll, New York, NY USA.
[Vinson, J.; Filipenko, J.] Prostate Canc Clin Trials Consortium, New York, NY USA.
[Robinson, D.; Lonigro, R.; Hussain, M.; Chinnaiyan, A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Chinnaiyan, A.; Sawyers, C.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Garofalo, A.; Garraway, L.; Taplin, M. -E.; AlDubayan, S.; Han, G. C.; Van Allen, E. M.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave,Mailstop D4-100, Seattle, WA 98109 USA.
EM pnelson@fhcrc.org
OI Rubin, Mark/0000-0002-8321-9950
FU Stand Up To Cancer
FX Funded by Stand Up To Cancer and others.
NR 40
TC 28
Z9 30
U1 12
U2 20
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 AUG 4
PY 2016
VL 375
IS 5
BP 443
EP 453
DI 10.1056/NEJMoa1603144
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS7AN
UT WOS:000380934900008
PM 27433846
ER
PT J
AU Sheridan, RL
AF Sheridan, Robert L.
TI Fire-Related Inhalation Injury
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Review
ID LOW-TIDAL-VOLUME; SMOKE-INHALATION; BURN PATIENTS; LUNG INJURY;
SEVERITY; BRONCHOSCOPY; PNEUMONIA
C1 [Sheridan, Robert L.] Shriners Hosp Children, Burn Serv, 51 Blossom St, Boston, MA 02114 USA.
[Sheridan, Robert L.] Massachusetts Gen Hosp, Div Burns, Boston, MA 02114 USA.
[Sheridan, Robert L.] Harvard Med Sch, Dept Surg, Boston, MA USA.
RP Sheridan, RL (reprint author), Shriners Hosp Children, Burn Serv, 51 Blossom St, Boston, MA 02114 USA.
EM rsheridan@mgh.harvard.edu
NR 29
TC 2
Z9 2
U1 4
U2 8
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 AUG 4
PY 2016
VL 375
IS 5
BP 464
EP 469
DI 10.1056/NEJMra1601128
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS7AN
UT WOS:000380934900010
PM 27518664
ER
PT J
AU Mou, HM
Vinarsky, V
Tata, PR
Brazauskas, K
Choi, SH
Crooke, AK
Zhang, B
Solomon, GM
Turner, B
Bihler, H
Harrington, J
Lapey, A
Channick, C
Keyes, C
Freund, A
Artandi, S
Mense, M
Rowe, S
Engelhardt, JF
Hsu, YC
Rajagopal, J
AF Mou, Hongmei
Vinarsky, Vladimir
Tata, Purushothama Rao
Brazauskas, Karissa
Choi, Soon H.
Crooke, Adrianne K.
Zhang, Bing
Solomon, George M.
Turner, Brett
Bihler, Hermann
Harrington, Jan
Lapey, Allen
Channick, Colleen
Keyes, Colleen
Freund, Adam
Artandi, Steven
Mense, Martin
Rowe, Steven
Engelhardt, John F.
Hsu, Ya-Chieh
Rajagopal, Jayaraj
TI Dual SMAD Signaling Inhibition Enables Long-Term Expansion of Diverse
Epithelial Basal Cells
SO CELL STEM CELL
LA English
DT Article
ID HUMAN EPIDERMAL-KERATINOCYTES; HUMAN AIRWAY EPITHELIUM; STEM-CELLS;
CYSTIC-FIBROSIS; TGF-BETA; GROWTH-FACTOR; SELF-RENEWAL; MAINTENANCE;
NICHE; DIFFERENTIATION
AB Functional modeling of many adult epithelia is limited by the difficulty in maintaining relevant stem cell populations in culture. Here, we show that dual inhibition of SMAD signaling pathways enables robust expansion of primary epithelial basal cell populations. We find that TGF beta/BMP/SMAD pathway signaling is strongly activated in luminal and suprabasal cells of several epithelia, but suppressed in p63+ basal cells. In airway epithelium, SMAD signaling promotes differentiation, and its inhibition leads to stem cell hyperplasia. Using dual SMAD signaling inhibition in a feeder-free culture system, we have been able to expand airway basal stemcells from multiple species. Expanded cells can produce functional airway epithelium physiologically responsive to clinically relevant drugs, such as CFTR modulators. This approach is effective for the clonal expansion of single human cells and for basal cell populations from epithelial tissues from all three germ layers and therefore may be broadly applicable for modeling of epithelia.
C1 [Mou, Hongmei; Vinarsky, Vladimir; Tata, Purushothama Rao; Brazauskas, Karissa; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.
[Mou, Hongmei; Vinarsky, Vladimir; Tata, Purushothama Rao; Rajagopal, Jayaraj] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Mou, Hongmei; Brazauskas, Karissa; Lapey, Allen; Rajagopal, Jayaraj] Massachusetts Gen Hosp Children, Div Pediat Pulm Med, Boston, MA 02114 USA.
[Vinarsky, Vladimir; Channick, Colleen; Keyes, Colleen; Rajagopal, Jayaraj] Massachusetts Gen Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
[Choi, Soon H.; Crooke, Adrianne K.; Engelhardt, John F.] Univ Iowa, Coll Med, Dept Anat & Cell Biol, Iowa City, IA 52242 USA.
[Zhang, Bing; Hsu, Ya-Chieh] Harvard Univ, Dept Stem Cell & Regenerat Biol, 7 Divin Ave, Cambridge, MA 02138 USA.
[Zhang, Bing; Hsu, Ya-Chieh] Harvard Stem Cell Inst, 7 Divin Ave, Cambridge, MA 02138 USA.
[Solomon, George M.; Rowe, Steven] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35233 USA.
[Turner, Brett; Rowe, Steven] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL 35233 USA.
[Rowe, Steven] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL 35294 USA.
[Solomon, George M.; Rowe, Steven] Univ Alabama Birmingham, Gregory Fleming James Cyst Fibrosis Res Ctr, Birmingham, AL 35233 USA.
[Bihler, Hermann; Harrington, Jan; Mense, Martin] Cyst Fibrosis Fdn Therapeut, CFFT Lab, Lexington, MA 01730 USA.
[Freund, Adam; Artandi, Steven] Stanford Univ, Dept Med, Stanford, CA 94305 USA.
[Freund, Adam; Artandi, Steven] Stanford Univ, Dept Biochem, Stanford, CA 94305 USA.
[Rajagopal, Jayaraj] Massachusetts Eye & Ear, Div Otol & Laryngol, Boston, MA 02114 USA.
RP Rajagopal, J (reprint author), Massachusetts Gen Hosp, Ctr Regenerat Med, 185 Cambridge St, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Rajagopal, J (reprint author), Massachusetts Gen Hosp Children, Div Pediat Pulm Med, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Massachusetts Gen Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Boston, MA 02114 USA.; Rajagopal, J (reprint author), Massachusetts Eye & Ear, Div Otol & Laryngol, Boston, MA 02114 USA.
EM jrajagopal@partners.org
FU NIH [R01HL116756, R01HL118185, DK047967, HL051670, K08HL124298,
T32HL087735, K99HL127181, R00 AR063127]; Cystic Fibrosis Foundation
[RAJAGO12G0, RAJAGO12I0]; Smith Family Awards; March of Dimes Basil
O'Connor Starter Scholar Awards
FX J.R. is a New York Stem Cell Foundation Robertson Investigator and a
Maroni Research Scholar at MGH. We thank Marina Mazur (the University of
Alabama at Birmingham) for assistance with cell culture and the entire
J.R. laboratory for constructive comments. This research was supported
by grants from the NIH (R01HL116756 and R01HL118185 to J.R.; DK047967
and HL051670 to J.F.E; K08HL124298 to V.V.; T32HL087735 to H.M.;
K99HL127181 to P.R.T.; R00 AR063127 to Y.-C.H.), the Cystic Fibrosis
Foundation (RAJAGO12G0 and RAJAGO12I0 to J.R.), and the Smith Family
Awards and March of Dimes Basil O'Connor Starter Scholar Awards (to
Y.-C.H.).
NR 38
TC 3
Z9 3
U1 3
U2 3
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 AUG 4
PY 2016
VL 19
IS 2
BP 217
EP 231
DI 10.1016/j.stem.2016.05.012
PG 15
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA DT6VG
UT WOS:000381622000015
PM 27320041
ER
PT J
AU Carreras-Torres, R
Haycock, PC
Relton, CL
Martin, RM
Smith, GD
Kraft, P
Gao, C
Tworoger, S
Le Marchand, L
Wilkens, LR
Park, SL
Haiman, C
Field, JK
Davies, M
Marcus, M
Liu, G
Caporaso, NE
Christiani, DC
Wei, YY
Chen, C
Doherty, JA
Severi, G
Goodman, GE
Hung, RJ
Amos, CI
McKay, J
Johansson, M
Brennan, P
AF Carreras-Torres, Robert
Haycock, Philip C.
Relton, Caroline L.
Martin, Richard M.
Smith, George Davey
Kraft, Peter
Gao, Chi
Tworoger, Shelley
Le Marchand, Loic
Wilkens, Lynne R.
Park, Sungshim L.
Haiman, Christopher
Field, John K.
Davies, Michael
Marcus, Michael
Liu, Geoffrey
Caporaso, Neil E.
Christiani, David C.
Wei, Yongyue
Chen, Chu
Doherty, Jennifer A.
Severi, Gianluca
Goodman, Gary E.
Hung, Rayjean J.
Amos, Christopher I.
McKay, James
Johansson, Mattias
Brennan, Paul
TI The causal relevance of body mass index in different histological types
of lung cancer: A Mendelian randomization study
SO SCIENTIFIC REPORTS
LA English
DT Article
ID RISK; METAANALYSIS; ASSOCIATION; POPULATION; VARIANTS; INSIGHTS; OBESITY
AB Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) in BMI (4.65 Kg/m(2)) raised the risk for lung cancer overall (OR = 1.13; P = 0.10). This was driven by associations with squamous cell (SQ) carcinoma (OR = 1.45; P = 1.2 x 10(-3)) and small cell (SC) carcinoma (OR = 1.81; P = 0.01). An inverse trend was seen for adenocarcinoma (AD) (OR = 0.82; P = 0.06). In stratified analyses, a 1 SD increase in BMI was inversely associated with overall lung cancer in never smokers (OR = 0.50; P = 0.02). These results indicate that higher BMI may increase the risk of certain types of lung cancer, in particular SQ and SC carcinoma.
C1 [Carreras-Torres, Robert; McKay, James; Johansson, Mattias; Brennan, Paul] IARC, Genet Sect, Lyon, France.
[Haycock, Philip C.; Relton, Caroline L.; Martin, Richard M.; Smith, George Davey] Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.
[Martin, Richard M.] Univ Hosp Bristol NHS Fdn Trust, Natl Inst Hlth Res, Biomed Res Unit Nutr Diet & Lifestyle, Bristol BS2 8AE, Avon, England.
[Martin, Richard M.] Univ Bristol, Bristol BS2 8AE, Avon, England.
[Kraft, Peter; Gao, Chi; Tworoger, Shelley; Christiani, David C.; Wei, Yongyue] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Tworoger, Shelley] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Tworoger, Shelley] Harvard Med Sch, Boston, MA USA.
[Le Marchand, Loic; Wilkens, Lynne R.] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA.
[Park, Sungshim L.; Haiman, Christopher] Univ Southern Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Field, John K.; Davies, Michael; Marcus, Michael] Univ Liverpool, Inst Translat Med, Dept Mol & Clin Canc Med, Roy Castle Lung Canc Res Programme,Canc Res Ctr, Liverpool, Merseyside, England.
[Liu, Geoffrey] Princess Margaret Canc Ctr, Ontario Canc Inst, Toronto, ON, Canada.
[Caporaso, Neil E.] NCI, Genet Epidemiol Branch, DCEG, NIH, Rockville, MD USA.
[Christiani, David C.; Wei, Yongyue] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Christiani, David C.; Wei, Yongyue] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
[Chen, Chu] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, 1124 Columbia St, Seattle, WA 98104 USA.
[Doherty, Jennifer A.] Dartmouth Coll, Geisel Sch Med, Dept Epidemiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
[Severi, Gianluca] Human Genet Fdn HuGeF, Turin, Italy.
[Goodman, Gary E.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Hung, Rayjean J.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Dept Biomed Data Sci, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
RP Brennan, P (reprint author), IARC, Genet Sect, Lyon, France.
EM gep@iarc.fr
RI Liu, Geoffrey/N-4421-2016; Hung, Rayjean/A-7439-2013; Davey Smith,
George/A-7407-2013
OI Davey Smith, George/0000-0002-1407-8314
FU Cancer Research UK [C18281/A19169, C52724/A20138]; National Institute
for Health Research (NIHR) Bristol Nutritional Biomedical Research Unit
at University Hospitals Bristol NHS Foundation Trust; University of
Bristol; MRC Integrative Epidemiology Unit at the University of Bristol
[MC_UU_12013/1, MC_UU_12013/2]; NCI [UM1 CA186107, P01 CA87969, R01
CA49449, UM1 CA167552]
FX RCT, PCH, CLR, RMM, GDS, MJ, and PB are investigators or researchers on
a Cancer Research UK (C18281/A19169) Programme Grant (the Integrative
Cancer Epidemiology Programme). RMM is supported by the National
Institute for Health Research (NIHR) Bristol Nutritional Biomedical
Research Unit based at University Hospitals Bristol NHS Foundation Trust
and the University of Bristol. CLR and GDS are supported by funding from
the MRC Integrative Epidemiology Unit at the University of Bristol
(MC_UU_12013/1, MC_UU_12013/2). PCH is supported by a Cancer Research UK
Population Research Postdoctoral Fellowship (C52724/A20138). The views
expressed are those of the authors and not necessarily those of the NHS,
the NIHR, or the Department of Health. NCI grants: UM1 CA186107, P01
CA87969, R01 CA49449, UM1 CA167552. We would like to thank the
participants and staff of the NHS and HPFS for their valuable
contributions as well as the following state cancer registries for their
help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME,
MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA,
WA, WY. The authors assume full responsibility for analyses and
interpretation of these data.
NR 24
TC 1
Z9 1
U1 4
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 AUG 4
PY 2016
VL 6
AR 31121
DI 10.1038/srep31121
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS7MB
UT WOS:000380966500001
PM 27487993
ER
PT J
AU DiGiovanni, CW
Lin, SS
Daniels, TR
Glazebrook, M
Evangelista, P
Donahue, R
Beasley, W
Baumhauer, JF
AF DiGiovanni, Christopher W.
Lin, Sheldon S.
Daniels, Timothy R.
Glazebrook, Mark
Evangelista, Peter
Donahue, Rafe
Beasley, William
Baumhauer, Judith F.
TI The Importance of Sufficient Graft Material in Achieving Foot or Ankle
Fusion
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID AUTOGENOUS BONE-GRAFT; RETROGRADE INTRAMEDULLARY NAIL;
TIBIOTALOCALCANEAL ARTHRODESIS; SUBTALAR ARTHRODESIS;
COMPUTED-TOMOGRAPHY; FLATFOOT DEFORMITY; HINDFOOT FUSIONS; PROXIMAL
TIBIA; RHPDGF-BB; FIXATION
AB Background: Nonunion, an important complication following foot and ankle arthrodesis, causes substantial morbidity and disability. In patients undergoing hindfoot and ankle arthrodesis, autogenous bone graft (autograft) or a suitable alternative is often used to promote osseous fusion across the joint. This study assessed the importance of adequate graft material in the fusion space to achieve joint fusion during ankle and hindfoot arthrodesis.
Methods: This study used data from a previously published clinical trial of grafting material (recombinant human platelet-derived growth factor-BB with beta-tricalcium phosphate [rhPDGF-BB/beta-TCP] or autograft) for healing in hindfoot and ankle arthrodesis to correlate the amount of graft fill at 9 weeks with ultimate healing. Patients who received supplemental graft material for ankle or hindfoot arthrodesis for end-stage ankle or hindfoot arthritis were stratified according to nonunion risk factors and surgical fusion site. Patients underwent arthrodesis using standard rigid internal fixation. Graft fill was defined as "adequate" if the material occupied >= 50% of the cross-sectional area of the fusion space on a computed tomography (CT) scan made at 9 weeks. Fusion was defined as osseous bridging of >= 50% of each articulation on a CT scan made at 24 weeks. Three hundred and seventy-nine patients with 573 joints (383 managed with rhPDGF-BB/b-TCP and 190 managed with autograft) that underwent arthrodesis had complete follow-up with 9-week and 24-week CT scans available.
Results: Overall, 472 (82%) of 573 joints had adequate graft fill; of those, 383 (81%) were successfully fused at 24 weeks compared with 21 (21%) of 101 joints without adequate graft fill (p < 0.0001). Absolute fusion rate differences (joints with adequate fill minus those without adequate fill) were consistent across joints (61% to 63%) and for graft materials. The overall odds ratio (OR) of successful fusion in joints with adequate graft fill compared with those without adequate graft fill was 16.4 (95% confidence interval, 9.6 to 27.9).
Conclusions: This study demonstrates an association between the amount of graft material and successful hindfoot and ankle arthrodesis. Graft material filling of >= 50% of the fusion space at 9 weeks, regardless of type or origin, was associated with significantly higher fusion rates at 24 weeks.
C1 [DiGiovanni, Christopher W.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
[Lin, Sheldon S.] Rutgers New Jersey Med Sch, North Jersey Orthopaed Inst, Newark, NJ USA.
[Daniels, Timothy R.] St Michaels Hosp, Div Orthopaed Surg, Toronto, ON, Canada.
[Daniels, Timothy R.] Univ Toronto, Dept Surg, Toronto, ON, Canada.
[Glazebrook, Mark] Dalhousie Univ, Halifax, NS, Canada.
[Glazebrook, Mark] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada.
[Evangelista, Peter] Brown Univ, Rhode Isl Hosp, Warren Alpert Sch Med, Dept Diagnost Imaging, Providence, RI 02903 USA.
[Donahue, Rafe; Beasley, William] Wright Med Technol Inc, Franklin, TN USA.
[Baumhauer, Judith F.] Univ Rochester, Sch Med, Dept Orthopaed, Rochester, NY USA.
RP DiGiovanni, CW (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA.
EM CWDiGiovanni@MGH.Harvard.edu
FU BioMimetic Therapeutics, Inc.
FX Two authors, the statistician (R.D.) and the certified clinical research
professional responsible for organizational management of the study
(W.B.), are employees of BioMimetic Therapeutics, Inc. (Wright Medical,
Inc.); both were blinded to treatment assignments in the parent clinical
trial until after the database had been locked and the analysis plan
finalized. The remaining authors received funding from BioMimetic
Therapeutics, Inc. to cover research costs and/or were working as
consultants for BioMimetic Therapeutics, Inc. The sponsor did not
control the drafting and writing of the manuscript. On the Disclosure of
Potential Conflicts of Interest forms, which are provided with the
online version of the article, one or more of the authors checked "yes"
to indicate that the author had a relevant financial relationship in the
biomedical arena outside the submitted work and "yes" to indicate that
the author had other relationships or activities that could be perceived
to influence, or have the potential to influence, what was written in
this work.
NR 31
TC 1
Z9 1
U1 0
U2 0
PU JOURNAL BONE JOINT SURGERY
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02492 USA
SN 0021-9355
EI 1535-1386
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD AUG 3
PY 2016
VL 98
IS 15
BP 1260
EP 1267
DI 10.2106/JBJS.15.00879
PG 8
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA EN4AP
UT WOS:000395949900008
PM 27489316
ER
PT J
AU Parkkinen, M
Madanat, R
Lindahl, J
Makinen, TJ
AF Parkkinen, Markus
Madanat, Rami
Lindahl, Jan
Makinen, Tatu J.
TI Risk Factors for Deep Infection Following Plate Fixation of Proximal
Tibial Fractures
SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME
LA English
DT Article
ID SURGICAL SITE INFECTION; COMPARTMENT SYNDROME; OPERATIVE TREATMENT;
INCISION FASCIOTOMY; EXTERNAL FIXATION; COMPLICATIONS; MANAGEMENT;
SURGERY
AB Background: The risk factors are unclear for deep surgical site infection after plate fixation of proximal tibial fractures. The objective of this study was to identify the patient and surgical procedure-related risk factors for infection using established criteria for deep surgical site infection.
Methods: A total of 655 proximal tibial fractures were treated with open reduction and plate fixation at our center between 2004 and 2013. We identified 34 patients with deep surgical site infection. A control group of 136 patients was randomly selected from the non-infected cohort. Potential risk factors for deep surgical site infection were identified by reviewing surgical, medical, and radiographic records. Independent risk factors for infection were identified from multivariable logistic regression analysis using a stepwise procedure.
Results: The prevalence of deep surgical site infection was 5.2%, the mean age of affected patients was 55 years (range, 16 to 84 years), and 35% of patients were female. Twenty-eight of 34 deep infections were diagnosed within 2 months (acute onset), and only 6 infections were diagnosed >6 months after the index surgical procedure. Nine of the 28 acuteonset infections were treated with antibiotic therapy and debridement. Seventeen patients (50%) required muscle flap coverage, and 5 patients (15%) eventually required above-the-knee amputation. In the multivariable logistic regression analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs), independent predictors of infection were patient age of >= 50 years (OR, 3.6 [95% CI, 1.3 to 10.1]); obesity, defined as a body mass index of >= 30 kg/m(2) (OR, 6.5 [95% CI, 2.2 to 18.9]); alcohol abuse (OR, 6.7 [95% CI, 2.4 to 19.2]); OTA/AO-type-C fracture (OR, 2.8 [95% CI, 1.1 to 7.5]); use of a temporary spanning external fixator (OR, 3.9 [95% CI, 1.4 to 11.1]); and a 4-compartment fasciotomy (OR, 4.5 [95% CI, 1.3 to 15.7]).
Conclusions: There is high morbidity associated with deep surgical site infection in plated proximal tibial fractures. Patients who are >= 50 years of age, obese patients, those with a history of alcohol abuse, or those with an OTA/AO-type-C fracture are at high risk for infection. Performing a fasciotomy also increases the risk of deep infection and should be implemented with meticulous technique when deemed necessary.
C1 [Parkkinen, Markus; Lindahl, Jan] Univ Helsinki, Dept Orthopaed & Traumatol, Helsinki, Finland.
[Parkkinen, Markus; Lindahl, Jan] Helsinki Univ Hosp, Helsinki, Finland.
[Madanat, Rami] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Madanat, Rami] Harvard Med Sch, Boston, MA USA.
[Makinen, Tatu J.] Mt Sinai Hosp, Div Orthopaed Surg, Toronto, ON, Canada.
[Makinen, Tatu J.] Univ Toronto, Toronto, ON, Canada.
RP Parkkinen, M (reprint author), Univ Helsinki, Dept Orthopaed & Traumatol, Helsinki, Finland.; Parkkinen, M (reprint author), Helsinki Univ Hosp, Helsinki, Finland.
EM markus.parkkinen@hus.fi
NR 30
TC 0
Z9 0
U1 1
U2 1
PU JOURNAL BONE JOINT SURGERY
PI NEEDHAM
PA 20 PICKERING ST, NEEDHAM, MA 02492 USA
SN 0021-9355
EI 1535-1386
J9 J BONE JOINT SURG AM
JI J. Bone Joint Surg.-Am. Vol.
PD AUG 3
PY 2016
VL 98
IS 15
BP 1292
EP 1297
DI 10.2106/JBJS.15.00894
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA EN4AP
UT WOS:000395949900012
PM 27489320
ER
PT J
AU Georgitsi, M
Willsey, AJ
Mathews, CA
State, M
Scharf, JM
Paschou, P
AF Georgitsi, Marianthi
Willsey, A. Jeremy
Mathews, Carol A.
State, Matthew
Scharf, Jeremiah M.
Paschou, Peristera
TI The Genetic Etiology of Tourette Syndrome: Large-Scale Collaborative
Efforts on the Precipice of Discovery
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE Gilles de la Tourette syndrome; genetics of complex disorders;
neurodevelopmental disorders; GWAS (genomewide association study);
gene-environment interactions; next generation sequencing; collaborative
studies
ID OBSESSIVE-COMPULSIVE DISORDER; AUTISM SPECTRUM DISORDER; COPY NUMBER
VARIANTS; FAMILY-BASED SAMPLE; NEUROPSYCHIATRIC DISORDERS; BASAL
GANGLIA; TRANSLOCATION BREAKPOINT; HISTIDINE-DECARBOXYLASE; DOPAMINERGIC
GENES; RECEPTOR LOCUS
AB Gilles de la Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder that is characterized by multiple motor and phonic tics. It has a complex etiology with multiple genes likely interacting with environmental factors to lead to the onset of symptoms. The genetic basis of the disorder remains elusive. However, multiple resources and large-scale projects are coming together, launching a new era in the field and bringing us on the verge of discovery. The large-scale efforts outlined in this report are complementary and represent a range of different approaches to the study of disorders with complex inheritance. The Tourette Syndrome Association International Consortium for Genetics (TSAICG) has focused on large families, parent-proband trios and cases for large case-control designs such as genomewide association studies (GWAS), copy number variation (CNV) scans, and exome/genome sequencing. TIC Genetics targets rare, large effect size mutations in simplex trios, and multigenerational families. The European Multicentre Tics in Children Study (EMTICS) seeks to elucidate gene environment interactions including the involvement of infection and immune mechanisms in TS etiology. Finally, TS-EUROTRAIN, a Marie Curie Initial Training Network, aims to act as a platform to unify large-scale projects in the field and to educate the next generation of experts. Importantly, these complementary large-scale efforts are joining forces to uncover the full range of genetic variation and environmental risk factors for TS, holding great promise for identifying definitive TS susceptibility genes and shedding light into the complex pathophysiology of this disorder.
C1 [Georgitsi, Marianthi; Paschou, Peristera] Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece.
[Georgitsi, Marianthi] Aristotle Univ Thessaloniki, Dept Med, Thessaloniki, Greece.
[Willsey, A. Jeremy; State, Matthew] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Mathews, Carol A.] Univ Florida, Dept Psychiat, Sch Med, Gainesville, FL 32611 USA.
[Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
RP Paschou, P (reprint author), Democritus Univ Thrace, Dept Mol Biol & Genet, Alexandroupolis, Greece.; State, M (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.; Scharf, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.; Scharf, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
EM matthew.state@ucsf.edu; jscharf@partners.org; ppaschou@mbg.duth.gr
FU European Union under the Seventh Framework People Programme
(TS-EUROTRAIN (FP7-PEOPLE-ITN)) [316978-EMTICS (FP7/2007-2013), 278367];
NIH [U01NS40024, U01NS40024-09S1, K23MH085057, R01MH096767, K02NS085048,
R01MH092290, R01 MH092291, R01MH092292, R01MH092293, R01MH092513,
R01MH092516, R01 MH092520, R01MH092289, U24MH068457]; Tourette
Association of America; New Jersey Center for Tourette Syndrome and
Associated Disorders (NJCTS)
FX EMTICS and TS-EUROTRAIN are funded by the European Union under the
Seventh Framework People Programme (TS-EUROTRAIN (FP7-PEOPLE-2012-ITN),
Grant Agr.No.316978-EMTICS (FP7/2007-2013), Grant Agr.No. 278367).
TSAICG is funded by NIH U01NS40024, U01NS40024-09S1, K23MH085057,
R01MH096767, K02NS085048, and research funding from the Tourette
Association of America. TIC Genetics is funded by NIH (R01MH092290; R01
MH092291; R01MH092292; R01MH092293; R01MH092513; R01MH092516; R01
MH092520; R01MH092289; U24MH068457) and the New Jersey Center for
Tourette Syndrome and Associated Disorders (NJCTS).
NR 79
TC 3
Z9 3
U1 9
U2 13
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD AUG 3
PY 2016
VL 10
AR 351
DI 10.3389/fnins.2016.00357
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA DS9EQ
UT WOS:000381086000001
PM 27536211
ER
PT J
AU Yong, KJ
Basseres, DS
Welner, RS
Zhang, WC
Yang, H
Yan, B
Alberich-Jorda, M
Zhang, JY
de Figueiredo-Pontes, LL
Battelli, C
Hetherington, CJ
Ye, M
Zhang, H
Maroni, G
O'Brien, K
Magli, MC
Borczuk, AC
Varticovski, L
Kocher, O
Zhang, P
Moon, YC
Sydorenko, N
Cao, LX
Davis, TW
Thakkar, BM
Soo, RA
Iwama, A
Lim, B
Halmos, B
Neuberg, D
Tenen, DG
Levantini, E
AF Yong, Kol Jia
Basseres, Daniela S.
Welner, Robert S.
Zhang, Wen Cai
Yang, Henry
Yan, Benedict
Alberich-Jorda, Meritxell
Zhang, Junyan
de Figueiredo-Pontes, Lorena Lobo
Battelli, Chiara
Hetherington, Christopher J.
Ye, Min
Zhang, Hong
Maroni, Giorgia
O'Brien, Karen
Magli, Maria Cristina
Borczuk, Alain C.
Varticovski, Lyuba
Kocher, Olivier
Zhang, Pu
Moon, Young-Choon
Sydorenko, Nadiya
Cao, Liangxian
Davis, Thomas W.
Thakkar, Bhavin M.
Soo, Ross A.
Iwama, Atsushi
Lim, Bing
Halmos, Balazs
Neuberg, Donna
Tenen, Daniel G.
Levantini, Elena
TI Targeted BMI1 inhibition impairs tumor growth in lung adenocarcinomas
with low CEBP alpha expression
SO SCIENCE TRANSLATIONAL MEDICINE
LA English
DT Article
ID CCAAT/ENHANCER-BINDING-PROTEIN; ACUTE MYELOID-LEUKEMIA;
FACTOR-C/EBP-ALPHA; POSTTRANSCRIPTIONAL CONTROL; ADJUVANT CHEMOTHERAPY;
CELL-PROLIFERATION; DOWN-REGULATION; DRUG DISCOVERY; GENE SIGNATURE;
SELF-RENEWAL
AB Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBP alpha (CCAAT/enhancer binding protein a) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBP alpha suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBP alpha expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBP alpha expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBP alpha deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBP alpha-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBP alpha is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBP alpha loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBP alpha and high BMI1.
C1 [Yong, Kol Jia; Yang, Henry; Thakkar, Bhavin M.; Soo, Ross A.; Tenen, Daniel G.] Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore.
[Basseres, Daniela S.] Univ Sao Paulo, Inst Chem, Biochem Dept, BR-05508 Sao Paulo, Brazil.
[Basseres, Daniela S.; Welner, Robert S.; Zhang, Wen Cai; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Battelli, Chiara; Hetherington, Christopher J.; Ye, Min; Zhang, Hong; O'Brien, Karen; Kocher, Olivier; Zhang, Pu; Lim, Bing; Levantini, Elena] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Basseres, Daniela S.; Welner, Robert S.; Zhang, Wen Cai; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Battelli, Chiara; Hetherington, Christopher J.; Ye, Min; Zhang, Hong; O'Brien, Karen; Kocher, Olivier; Zhang, Pu; Lim, Bing; Tenen, Daniel G.; Levantini, Elena] Harvard Med Sch, Boston, MA 02215 USA.
[Basseres, Daniela S.; Welner, Robert S.; Alberich-Jorda, Meritxell; Zhang, Junyan; de Figueiredo-Pontes, Lorena Lobo; Hetherington, Christopher J.; Ye, Min; Zhang, Hong; O'Brien, Karen; Zhang, Pu; Tenen, Daniel G.; Levantini, Elena] Harvard Stem Cell Inst, Boston, MA 02215 USA.
[Welner, Robert S.] Univ Alabama Birmingham, Div Hematol & Oncol, Dept Med, Birmingham, AL 35233 USA.
[Zhang, Wen Cai; Lim, Bing] Genome Inst Singapore, Stem Cell & Dev Biol, Singapore 138672, Singapore.
[Yan, Benedict] KK Womens & Childrens Hosp, Dept Pathol & Lab Med, Singapore 119074, Singapore.
[Alberich-Jorda, Meritxell] ASCR, Inst Mol Genet, Prague 14200, Czech Republic.
[de Figueiredo-Pontes, Lorena Lobo] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Internal Med, Hematol Div, BR-14020 Sao Paulo, Brazil.
[Maroni, Giorgia; Magli, Maria Cristina; Levantini, Elena] Natl Res Council CNR, Inst Biomed Technol, I-56124 Pisa, Italy.
[Borczuk, Alain C.] Weill Cornell Univ, Med Ctr, Dept Pathol, New York, NY 10065 USA.
[Varticovski, Lyuba] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20817 USA.
[Moon, Young-Choon; Sydorenko, Nadiya; Cao, Liangxian; Davis, Thomas W.] PTC Therapeut, 100 Corp Court, South Plainfield, NJ 07080 USA.
[Soo, Ross A.] Univ Western Australia, Dept Hematol Oncol, Crawley, WA 6009, Australia.
[Iwama, Atsushi] Chiba Univ, Grad Sch Med, Dept Cellular & Mol Med, Chiba 2608670, Japan.
[Halmos, Balazs] Montefiore Hosp, Div Hematol Oncol, Bronx, NY 10461 USA.
[Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Battelli, Chiara] New England Canc Specialists, Scarborough, ME 04074 USA.
[O'Brien, Karen] Novartis Inst BioMed Res Inc, Cambridge, MA 02176 USA.
[Lim, Bing] Merck Res Labs, Translat Med Res Ctr, Singapore 138665, Singapore.
RP Tenen, DG (reprint author), Natl Univ Singapore, Canc Sci Inst, Singapore 117599, Singapore.; Levantini, E (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.; Tenen, DG; Levantini, E (reprint author), Harvard Med Sch, Boston, MA 02215 USA.; Tenen, DG; Levantini, E (reprint author), Harvard Stem Cell Inst, Boston, MA 02215 USA.; Levantini, E (reprint author), Natl Res Council CNR, Inst Biomed Technol, I-56124 Pisa, Italy.
EM csidgt@nus.edu.sg; elevanti@bidmc.harvard.edu
RI Basseres, Daniela/C-6623-2013
OI Basseres, Daniela/0000-0001-7745-3567
FU NIH/NCI (National Cancer Institute) Project 2 grant [P50 CA90578]; NCIS
(National University Cancer Institute of Singapore) Yong Siew Yoon
Research grant; Singapore Ministry of Health's National Medical Research
Council under its Singapore Translational Research (STaR) Investigator
Award; National Research Foundation of Singapore; Singapore Ministry of
Education under its Research Centres of Excellence initiative Project 3
[PO1 CA66996, 1R35CA197697]; FAMRI (Flight Attendant Medical Research
Institute) YCSA (Young Clinical Scientist Award) [052409]; FAMRI CIA
(Clinical Innovator Awards) [103063]; FAMRI YCSA [072165]; Doctors
Cancer Foundation Award; IASLC (International Association for the Study
of Lung Cancer) Award; MIUR (Ministry of Education, University and
Research) Flagship InterOmics Project; MSMT Navrat grant [LK21307]; Jose
Carreras fellowship [FIJC-10]; NCI [T32/K12/R25]; Agency for Science,
Technology and Research (A*STAR), Singapore; National Medical Research
Council of Singapore [NMRC/CG/NCIS/2010]; Dana-Farber/Harvard Cancer
Center support grant [5P30 CA006516]
FX This work was funded by NIH/NCI (National Cancer Institute) P50 CA90578
Project 2 grant (to D.G.T. and B.H.); the NCIS (National University
Cancer Institute of Singapore) Yong Siew Yoon Research grant through
donations from the Yong Loo Lin Trust, the Singapore Ministry of
Health's National Medical Research Council under its Singapore
Translational Research (STaR) Investigator Award, and the National
Research Foundation of Singapore and the Singapore Ministry of Education
under its Research Centres of Excellence initiative and PO1 CA66996
Project 3 and 1R35CA197697 grants (to D.G.T.); FAMRI (Flight Attendant
Medical Research Institute) YCSA (Young Clinical Scientist Award) 052409
and FAMRI CIA (Clinical Innovator Awards) 103063 (to E.L.); FAMRI YCSA
072165 (to D.S.B.); Doctors Cancer Foundation Award (to E.L.); IASLC
(International Association for the Study of Lung Cancer) Award (to
E.L.); MIUR (Ministry of Education, University and Research) Flagship
InterOmics Project (to E.L. and M.C.M.); and MSMT Navrat grant LK21307
(to M.-A.J.). R.S.W. was supported by a Jose Carreras fellowship,
FIJC-10. C.B. was supported by an NCI T32/K12/R25 award. W.C.Z. and
B.L.'s work was supported by Agency for Science, Technology and Research
(A*STAR), Singapore. R.A.S. was supported by the National Medical
Research Council of Singapore (NMRC/CG/NCIS/2010). D.N. was supported by
Dana-Farber/Harvard Cancer Center support grant 5P30 CA006516.
NR 50
TC 1
Z9 1
U1 4
U2 4
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 AUG 3
PY 2016
VL 8
IS 350
AR 350ra104
DI 10.1126/scitranslmed.aad6066
PG 10
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA DS4VP
UT WOS:000380780000006
PM 27488898
ER
PT J
AU Goel, S
Zhao, JJ
AF Goel, Shom
Zhao, Jean J.
TI CDK4/6 inhibition: the late harvest cycle begins
SO ONCOTARGET
LA English
DT Editorial Material
DE CDK4/6; cyclin; cell cycle; cancer; abemaciclib
ID CANCER
C1 [Goel, Shom] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[Zhao, Jean J.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Zhao, Jean J.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
RP Goel, S (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
EM shom_goel@dfci.har-vard.edu; Jean_Zhao@dfci.harvard.edu
NR 7
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 AUG 2
PY 2016
VL 7
IS 31
BP 48854
EP 48856
DI 10.18632/oncotarget.9576
PG 3
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY8ZS
UT WOS:000385422000002
PM 27391058
ER
PT J
AU Jiang, XN
Niu, MM
Chen, DS
Chen, J
Cao, Y
Li, XR
Ying, HQ
Bergholz, J
Zhang, YJ
Xiao, ZX
AF Jiang, Xinni
Niu, MengMeng
Chen, Deshi
Chen, Jing
Cao, Yang
Li, Xiaorong
Ying, Haoqiang
Bergholz, Johann
Zhang, Yujun
Xiao, Zhi-Xiong
TI Inhibition of Cdc42 is essential for Mig-6 suppression of cell migration
induced by EGF
SO ONCOTARGET
LA English
DT Article
DE Mig-6; Cdc42; EGF; migration
ID GROUP-II PAKS; BREAST-CANCER; LUNG-CANCER; RHO GTPASES; ENDOGENOUS
INHIBITOR; NEGATIVE REGULATOR; KINASE DOMAIN; E-CADHERIN; IN-VIVO;
EXPRESSION
AB The adaptor protein Mig-6 is a negative regulator of EGF signaling. It is shown that Mig-6 inhibits cell migration via direct interaction with the ErbB receptors, thereby inhibiting cross-phosphorylation or targeting the receptors for degradation. Mig-6 has also been shown to bind to and inhibit the Rho GTPase Cdc42 to suppress cytoskeletal rearrangement. However, the molecular mechanism(s) by which Mig-6 inhibits cell migration via Cdc42 is still not entirely clear. Here, we show that Mig-6 binding to Cdc42 is necessary and sufficient to inhibit EGF-induced filopodia formation and migration. This binding, mediated by four specific residues (I11, R12, M26, R30) in the Mig-6 CRIB domain, is essential for Mig-6 function. In addition, ectopic expression of Cdc42 reverses Mig-6 inhibition of cell migration. Mig-6 CRIB domain, alone, is sufficient to inhibit cell migration. Conversely, Mig-6 binding to EGFR is dispensable for Mig-6-mediated inhibition of cell migration. Moreover, we found that decreased Mig-6 expression correlates with cancer progression in breast and prostate cancers. Together, our results demonstrate that Mig-6 inhibition of Cdc42 signaling is critical in Mig-6 function to suppress cell migration and that dysregulation of this pathway may play a critical role in cancer development.
C1 [Jiang, Xinni; Niu, MengMeng; Chen, Deshi; Chen, Jing; Cao, Yang; Li, Xiaorong; Bergholz, Johann; Zhang, Yujun; Xiao, Zhi-Xiong] Sichuan Univ, Coll Life Sci, Ctr Growth Metab & Aging, Key Lab Bioresource & Ecoenvironm,Minist Educ, Chengdu 610014, Peoples R China.
[Ying, Haoqiang] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Bergholz, Johann] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
RP Xiao, ZX (reprint author), Sichuan Univ, Coll Life Sci, Ctr Growth Metab & Aging, Key Lab Bioresource & Ecoenvironm,Minist Educ, Chengdu 610014, Peoples R China.
EM jimzx@scu.edu.cn
FU National Key Basic Research Program (973 Program) of China
[2012CB910700]; National Natural Science Foundation of China (NSFC)
[81330054, 31171362]; NSFC [31350110216]
FX This work was supported by the National Key Basic Research Program (973
Program) of China (2012CB910700), National Natural Science Foundation of
China (NSFC) grant (81330054 and 31171362) to Z-X. X., and NSFC grant
(31350110216) to J.B.
NR 49
TC 0
Z9 0
U1 2
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD AUG 2
PY 2016
VL 7
IS 31
BP 49180
EP 49193
DI 10.18632/oncotarget.10205
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DY8ZS
UT WOS:000385422000029
PM 27341132
ER
PT J
AU Brundin, L
Sellgren, CM
Lim, CK
Grit, J
Palsson, E
Landen, M
Samuelsson, M
Lundgren, K
Brundin, P
Fuchs, D
Postolache, TT
Traskman-Bendz, L
Guillemin, GJ
Erhardt, S
AF Brundin, L.
Sellgren, C. M.
Lim, C. K.
Grit, J.
Palsson, E.
Landen, M.
Samuelsson, M.
Lundgren, K.
Brundin, P.
Fuchs, D.
Postolache, T. T.
Traskman-Bendz, L.
Guillemin, G. J.
Erhardt, S.
TI An enzyme in the kynurenine pathway that governs vulnerability to
suicidal behavior by regulating excitotoxicity and neuroinflammation
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID MAJOR DEPRESSIVE DISORDER; EPSILON-SEMIALDEHYDE DECARBOXYLASE;
HIGH-PROTEIN DIET; QUINOLINIC ACID; PICOLINIC-ACID; CHROMIUM PICOLINATE;
ASSESSMENT SCALE; CONTROLLED-TRIAL; TRYPTOPHAN; RAT
AB Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-D-aspartate receptor agonist, are increased. The enzyme amino-beta-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Asberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.
C1 [Brundin, L.; Grit, J.; Brundin, P.] Van Andel Res Inst, Ctr Neurodegenerat Sci, 3rd Floor,333 Bostwick Ave NE, Grand Rapids, MI 49503 USA.
[Sellgren, C. M.; Samuelsson, M.; Erhardt, S.] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden.
[Sellgren, C. M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Sellgren, C. M.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA USA.
[Lim, C. K.; Guillemin, G. J.] Macquarie Univ, Fac Med & Hlth Sci, Sydney, NSW, Australia.
[Palsson, E.; Landen, M.] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Samuelsson, M.; Lundgren, K.] Linkoping Univ, Dept Clin & Expt Med, Linkoping, Sweden.
[Fuchs, D.] Med Univ Innsbruck, Div Biol Chem, Ctr Chem & Biomed, Innsbruck, Austria.
[Postolache, T. T.] Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA.
[Postolache, T. T.] Rocky Mt MIRECC, Denver, CO USA.
[Traskman-Bendz, L.] Lund Univ, Dept Clin Sci, Sect Psychiat, Lund, Sweden.
[Guillemin, G. J.] NHMRC Ctr Res Excellence Suicide Prevent CRESP, Randwick, NSW, Australia.
RP Grit, J (reprint author), Van Andel Res Inst, Ctr Neurodegenerat Sci, 3rd Floor,333 Bostwick Ave NE, Grand Rapids, MI 49503 USA.
EM jamie.grit@vai.org
FU Swedish Research Council (VR) [2009-4284, 2011-4787, 2002-5297,
2008-2922, 2009-7052, 2013-2838]; Province of Scania clinical state
grants; Swedish Research Council [K2014-62X-14647-12-51]; Swedish
Federal Government [ALF 20130032]; NIH [1R01MH104622-01]; American
Foundation for Suicide Prevention [DIG 1-162-12]; Michigan State
University; Van Andel Research Institute; Australian Research Council;
National Health and Medical Research Council, Australia; Rocky Mountain
MIRECC; Merit Review CSRD grant [1 I01 CX001310- 01A1]; Joint Institute
for Food Safety and Applied Nutrition/ UMD [FDU.001418]
FX We acknowledge Zachary Madaj at the VARI core of bioinformatics and
statistics for the conduct of the longitudinal data analysis in this
study. The design of this study, collection of patient samples and data
analysis was funded by the Swedish Research Council (VR), no. 2009-4284
and 2011-4787 (LB), 2002-5297 and 2008-2922 (LT-B), 2009-7052 and
2013-2838 (SE), as well as the Province of Scania clinical state grants
(LB and LT-B). The collection of population-based controls was funded by
the Swedish Research Council (K2014-62X-14647-12-51) and the Swedish
Federal Government under the LUA/ALF agreement (ALF 20130032).
Laboratory analyses of the samples and data interpretation were also
supported by NIH 1R01MH104622-01 and a Distinguished Investigator Award
from the American Foundation for Suicide Prevention (DIG 1-162-12; TTP
and LB), Michigan State University and Van Andel Research Institute
(LB); the Australian Research Council and the National Health and
Medical Research Council, Australia (GJG), as well as and in part by the
Rocky Mountain MIRECC (TTP), the Merit Review CSR&D grant 1 I01
CX001310- 01A1 (TTP and LB) and the Joint Institute for Food Safety and
Applied Nutrition/ UMD through the cooperative agreement FDU.001418
(TTP).
NR 54
TC 3
Z9 3
U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD AUG 2
PY 2016
VL 6
AR e865
DI 10.1038/tp.2016.133
PG 9
WC Psychiatry
SC Psychiatry
GA DW1RV
UT WOS:000383421200004
PM 27483383
ER
PT J
AU Mormino, EC
Sperling, RA
Holmes, AJ
Buckner, RL
De Jager, PL
Smoller, JW
Sabuncu, MR
AF Mormino, Elizabeth C.
Sperling, Reisa A.
Holmes, Avram J.
Buckner, Randy L.
De Jager, Philip L.
Smoller, Jordan W.
Sabuncu, Mert R.
CA Alzheimer's Dis Neuroimaging Initi
TI Polygenic risk of Alzheimer disease is associated with early- and
late-life processes
SO NEUROLOGY
LA English
DT Article
ID PROGRESS; PLANS
AB Objective: To examine associations between aggregate genetic risk and Alzheimer disease (AD) markers in stages preceding the clinical symptoms of dementia using data from 2 large observational cohort studies.
Methods: We computed polygenic risk scores (PGRS) using summary statistics from the International Genomics of Alzheimer's Project genome-wide association study of AD. Associations between PGRS and AD markers (cognitive decline, clinical progression, hippocampus volume, and beta-amyloid) were assessed within older participants with dementia. Associations between PGRS and hippocampus volume were additionally examined within healthy younger participants (age 18-35 years).
Results: Within participants without dementia, elevated PGRS was associated with worse memory (p = 0.002) and smaller hippocampus (p = 0.002) at baseline, as well as greater longitudinal cognitive decline (memory: p = 0.0005, executive function: p = 0.01) and clinical progression (p < 0.00001). HighPGRS was associated with AD-like levels of beta-amyloid burden as measured with florbetapir PET (p = 0.03) but did not reach statistical significance for CSF beta-amyloid (p = 0.11). Within the younger group, higher PGRS was associated with smaller hippocampus volume (p = 0.05). This pattern was evident when examining a PGRS that included many loci below the genome-wide association study (GWAS)-level significance threshold (16,123 single nucleotide polymorphisms), but not when PGRS was restricted to GWAS-level significant loci (18 single nucleotide polymorphisms).
Conclusions: Effects related to common genetic risk loci distributed throughout the genome are detectable among individuals without dementia. The influence of this genetic risk may begin in early life and make an individual more susceptible to cognitive impairment in late life. Future refinement of polygenic risk scores may help identify individuals at risk for AD dementia.
C1 [Mormino, Elizabeth C.; Sperling, Reisa A.] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
[Sperling, Reisa A.] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA USA.
[Sperling, Reisa A.] Harvard Med Sch, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA USA.
[De Jager, Philip L.] Harvard Med Sch, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci,Dept Neurol, Boston, MA USA.
[De Jager, Philip L.] Harvard Med Sch, Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Inst Neurosci,Dept Psychiat, Boston, MA USA.
[De Jager, Philip L.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA.
[Holmes, Avram J.] Yale Univ, Dept Psychol, New Haven, CT USA.
[Holmes, Avram J.] Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA USA.
[Holmes, Avram J.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
[Buckner, Randy L.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
[Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA.
[Buckner, Randy L.; Sabuncu, Mert R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[De Jager, Philip L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Smoller, Jordan W.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.
RP Mormino, EC (reprint author), Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA.
EM bmormino@nmr.mgh.harvard.edu
FU NIH [F32AG044054, P01AG036694, K01MH099232, R01AG036836, K24MH094614,
K25EB013649]; Alzheimer's Disease Neuroimaging Initiative (ADNI) (NIH)
[U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012];
National Institute on Aging; National Institute of Biomedical Imaging
and Bioengineering; AbbVie; Alzheimer's Association; Alzheimer's Drug
Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen;
Bristol-Myers Squibb Company; CereSpir, Inc.; Eisai Inc.; Elan
Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La
Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE
Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research &
Development, LLC; Johnson & Johnson Pharmaceutical Research &
Development LLC; Lumosity; Lundbeck; Merck Co., Inc.; Meso Scale
Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis
Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier;
Takeda Pharmaceutical Company; Transition Therapeutics; Canadian
Institutes of Health Research
FX This work was funded by NIH grants F32AG044054 (E.C.M.), P01AG036694
(R.A.S.), K01MH099232 (A.J.H.), R01AG036836 (P.L.D.), K24MH094614
(J.W.S.), and K25EB013649 (M.R.S.). Data collection and sharing for this
project was funded by the Alzheimer's Disease Neuroimaging Initiative
(ADNI) (NIH grant U01 AG024904) and DOD ADNI (Department of Defense
award number W81XWH-12-2-0012). ADNI is funded by the National Institute
on Aging, the National Institute of Biomedical Imaging and
Bioengineering, and through contributions from the following: AbbVie;
Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon
Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company;
CereSpir, Inc.; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and
Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company
Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer
Immunotherapy Research & Development, LLC; Johnson & Johnson
Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck &
Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack
Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal
Imaging; Servier; Takeda Pharmaceutical Company; and Transition
Therapeutics. The Canadian Institutes of Health Research is providing
funds to support ADNI clinical sites in Canada. Private sector
contributions are facilitated by the Foundation for the National
Institutes of Health (www.fnih.org). The grantee organization is the
Northern California Institute for Research and Education, and the study
is coordinated by the Alzheimer's Disease Cooperative Study at the
University of California, San Diego. ADNI data are disseminated by the
Laboratory for NeuroImaging at the University of Southern California.
The data from younger participants were collected as part of the Brain
Genomics Superstruct Project (http://neuroinformatics.harvard.edu/gsp/).
NR 23
TC 2
Z9 2
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 AUG 2
PY 2016
VL 87
IS 5
BP 481
EP 488
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6LO
UT WOS:000382326500012
PM 27385740
ER
PT J
AU Hirschtritt, ME
Darrow, SM
Illmann, C
Osiecki, L
Grados, M
Sandor, P
Dion, Y
King, RA
Pauls, DL
Budman, CL
Cath, DC
Greenberg, E
Lyon, GJ
Yu, DM
McGrath, LM
McMahon, WM
Lee, PC
Delucchi, KL
Scharf, JM
Mathews, CA
AF Hirschtritt, Matthew E.
Darrow, Sabrina M.
Illmann, Cornelia
Osiecki, Lisa
Grados, Marco
Sandor, Paul
Dion, Yves
King, Robert A.
Pauls, David L.
Budman, Cathy L.
Cath, Danielle C.
Greenberg, Erica
Lyon, Gholson J.
Yu, Dongmei
McGrath, Lauren M.
McMahon, William M.
Lee, Paul C.
Delucchi, Kevin L.
Scharf, Jeremiah M.
Mathews, Carol A.
CA TSAICG
TI Social disinhibition is a heritable subphenotype of tics in Tourette
syndrome
SO NEUROLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; SYMPTOM DIMENSIONS; COMPONENTS; NUMBER;
MODEL; PAIR
AB Objective: To identify heritable symptom-based subtypes of Tourette syndrome (TS).
Methods: Forty-nine motor and phonic tics were examined in 3,494 individuals (1,191 TS probands and 2,303 first-degree relatives). Item-level exploratory factor and latent class analyses (LCA) were used to identify tic-based subtypes. Heritabilities of the subtypes were estimated, and associations with clinical characteristics were examined.
Results: A 6-factor exploratory factor analysis model provided the best fit, which paralleled the somatotopic representation of the basal ganglia, distinguished simple from complex tics, and separated out socially disinhibited and compulsive tics. The 5-class LCA model best distinguished among the following groups: unaffected, simple tics, intermediate tics without social disinhibition, intermediate with social disinhibition, and high rates of all tic types. Across models, a phenotype characterized by high rates of social disinhibition emerged. This phenotype was associated with increased odds of comorbid psychiatric disorders, in particular, obsessive-compulsive disorder and attention-deficit/hyperactivity disorder, earlier age at TS onset, and increased tic severity. The heritability estimate for this phenotype based on the LCA was 0.53 (SE 0.08, p 1.7 X 10(-18)).
Conclusions: Expanding on previous modeling approaches, a series of TS-related phenotypes, including one characterized by high rates of social disinhibition, were identified. These phenotypes were highly heritable and may reflect underlying biological networks more accurately than traditional diagnoses, thus potentially aiding future genetic, imaging, and treatment studies.
C1 [Hirschtritt, Matthew E.; Darrow, Sabrina M.; Delucchi, Kevin L.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Illmann, Cornelia; Osiecki, Lisa; Pauls, David L.; Greenberg, Erica; Yu, Dongmei; Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Psychiat & Neurodevel Genet Unit, Ctr Human Genet Res,Dept Psychiat, Boston, MA USA.
[Grados, Marco] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Sandor, Paul] Univ Toronto, Dept Psychiat, Toronto, ON M5S 1A1, Canada.
Univ Hlth Network, Youthdale Treatment Ctr, Toronto, ON, Canada.
[Dion, Yves] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada.
[King, Robert A.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
[Budman, Cathy L.] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.
[Cath, Danielle C.] Univ Utrecht, Fac Social & Behav Sci, Utrecht, Netherlands.
Altrecht Acad Anxiety Ctr, Utrecht, Netherlands.
[Lyon, Gholson J.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA.
[McGrath, Lauren M.] Amer Univ, Sch Educ, Washington, DC 20016 USA.
[McMahon, William M.] Univ Utah, Dept Psychiat, Salt Lake City, UT USA.
[Lee, Paul C.] Tripler Army Med Ctr, Dept Behav Hlth, Honolulu, HI 96859 USA.
[Scharf, Jeremiah M.] Harvard Med Sch, Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA USA.
[Scharf, Jeremiah M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Mathews, Carol A.] Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA.
RP Mathews, CA (reprint author), Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA.
EM carolmathews@ufl.edu
FU NIH [R01MH096767, U01NS040024, K23MH085057, K02MH00508, R01NS016648];
Tourette Syndrome Association
FX This work was supported by the NIH, grants R01MH096767 ("Refining the
Tourette syndrome phenotype across diagnoses to aid gene discovery,"
principal investigator [PI]: Carol Mathews), U01NS040024 ("A genetic
linkage study of GTS," PI: David Pauls/Jeremiah Scharf), K23MH085057
("Translational phenomics and genomics of Gilles de la Tourette
syndrome," PI: Jeremiah Scharf), K02MH00508 ("Genetics of a behavioral
disorder: Tourette syndrome," PI: David Pauls), and R01NS016648 ("A
genetic study of GTS, OCD, and ADHD," PI: David Pauls), and from the
Tourette Syndrome Association. These 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 the
manuscript; and decision to submit the manuscript for publication. None
of the funding agencies for this project (NINDS, NIMH, the Tourette
Syndrome Association) had any influence or played any role in (1) the
design or conduct of the study; (2) management, analysis, or
interpretation of the data; (3) preparation, review, or approval of the
manuscript. The views expressed in this publication are those of the
authors and do not reflect the official policy or position of the
Department of the Army, Department of Defense, or the US Government.
NR 28
TC 4
Z9 4
U1 1
U2 1
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 AUG 2
PY 2016
VL 87
IS 5
BP 497
EP 504
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6LO
UT WOS:000382326500014
PM 27371487
ER
PT J
AU Jack, CR
Bennett, DA
Blennow, K
Carrillo, MC
Feldman, HH
Frisoni, GB
Hampel, H
Jagust, WJ
Johnson, KA
Knopman, DS
Petersen, RC
Scheltens, P
Sperling, RA
Dubois, B
AF Jack, Clifford R., Jr.
Bennett, David A.
Blennow, Kaj
Carrillo, Maria C.
Feldman, Howard H.
Frisoni, Giovanni B.
Hampel, Harald
Jagust, William J.
Johnson, Keith A.
Knopman, David S.
Petersen, Ronald C.
Scheltens, Philip
Sperling, Reisa A.
Dubois, Bruno
TI A/T/N: An unbiased descriptive classification scheme for Alzheimer
disease biomarkers
SO NEUROLOGY
LA English
DT Review
ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; PRIMARY
PROGRESSIVE APHASIA; CREUTZFELDT-JAKOB-DISEASE; TRAUMATIC BRAIN-INJURY;
PITTSBURGH COMPOUND-B; CSF TOTAL TAU; CEREBROSPINAL-FLUID; A-BETA;
ASSOCIATION WORKGROUPS
AB Biomarkers have become an essential component of Alzheimer disease (AD) research and because of the pervasiveness of AD pathology in the elderly, the same biomarkers are used in cognitive aging research. A number of current issues suggest that an unbiased descriptive classification scheme for these biomarkers would be useful. We propose the "A/T/N" system in which 7 major AD biomarkers are divided into 3 binary categories based on the nature of the pathophysiology that each measures. "A" refers to the value of a beta-amyloid biomarker (amyloid PET or CSF A beta(42)); "T," the value of a tau biomarker (CSF phospho tau, or tau PET); and "N," biomarkers of neurodegeneration or neuronal injury ([F-18]-fluorodeoxyglucose-PET, structural MRI, or CSF total tau). Each biomarker category is rated as positive or negative. An individual score might appear as A+/T+/N-, or A+/T+/N-, etc. The A/T/N system includes the new modality tau PET. It is agnostic to the temporal ordering of mechanisms underlying AD pathogenesis. It includes all individuals in any population regardless of the mix of biomarker findings and therefore is suited to population studies of cognitive aging. It does not specify disease labels and thus is not a diagnostic classification system. It is a descriptive system for categorizing multidomain biomarker findings at the individual person level in a format that is easy to understand and use. Given the present lack of consensus among AD specialists on terminology across the clinically normal to dementia spectrum, a biomarker classification scheme will have broadest acceptance if it is independent from any one clinically defined diagnostic scheme.
C1 [Jack, Clifford R., Jr.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Knopman, David S.; Petersen, Ronald C.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Blennow, Kaj] Univ Gothenburg, Molndal Hosp, Sahlgrenska Univ Hosp, Neurochem Lab,Dept Neurosci & Physiol, Molndal, Sweden.
[Carrillo, Maria C.] Alzheimers Assoc, Chicago, IL USA.
[Feldman, Howard H.] Univ British Columbia, Div Neurol, UBC Hosp Clin Alzheimers Dis & Related Disorders, Vancouver, BC, Canada.
[Frisoni, Giovanni B.] Univ Hosp, Memory Clin, Geneva, Switzerland.
Univ Geneva, Geneva, Switzerland.
[Frisoni, Giovanni B.] Natl Ctr Alzheimers Dis, IRCCS Fatebenefratelli, Brescia, Italy.
[Hampel, Harald] Univ Paris 06, Sorbonne Univ, Paris, France.
Hop La Pitie Salpetriere, Inst Memoire & Malad Alzheimer IM2A, Paris, France.
[Hampel, Harald] Hop La Pitie Salpetriere, Inst Cerveau & Moelleepiniere ICM, Dept Neurol, Paris, France.
[Jagust, William J.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA.
[Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA.
[Johnson, Keith A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA.
[Scheltens, Philip] Vrije Univ Amsterdam, Alzheimer Ctr, Amsterdam, Netherlands.
[Scheltens, Philip] Vrije Univ Amsterdam, Dept Neurol, Amsterdam, Netherlands.
[Sperling, Reisa A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA.
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Alzheimer Res & Treatment, Boston, MA 02115 USA.
[Dubois, Bruno] Inst Cerveau & Moelle Epiniere, Ctr Malad Cognit & Comportementales, Paris, France.
[Dubois, Bruno] Univ Paris 06, Hop Salpetriere, AP HP, Paris, France.
RP Jack, CR (reprint author), Mayo Clin, Dept Radiol, Rochester, MN USA.
EM jack.clifford@mayo.edu
OI Feldman, Howard/0000-0002-9258-4538
FU NIA NIH HHS [P01 AG036694, K24 AG035007]
NR 60
TC 9
Z9 9
U1 3
U2 4
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 AUG 2
PY 2016
VL 87
IS 5
BP 539
EP 547
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU6LO
UT WOS:000382326500021
PM 27371494
ER
PT J
AU Gillis, WQ
Kirmizitas, A
Iwasaki, Y
Ki, DH
Wyrick, JM
Thomsen, GH
AF Gillis, William Q.
Kirmizitas, Arif
Iwasaki, Yasuno
Ki, Dong-Hyuk
Wyrick, Jonathan M.
Thomsen, Gerald H.
TI Gtpbp2 is a positive regulator of Wnt signaling and maintains low levels
of the Wnt negative regulator Axin
SO CELL COMMUNICATION AND SIGNALING
LA English
DT Article
DE Axin; GTPase; Gtpbp2; Wnt signaling; Xenopus embryo
ID BETA-CATENIN; XENOPUS EMBRYOS; PROTEIN STABILITY; PATHWAY;
PHOSPHORYLATION; GASTRULATION; UBIQUITINATION; TRANSCRIPTION;
DEGRADATION; INHIBITION
AB Background: Canonical Wnt signals, transduced by stabilized beta-catenin, play similar roles across animals in maintaining stem cell pluripotency, regulating cell differentiation, and instructing normal embryonic development. Dysregulated Wnt/beta-catenin signaling causes diseases and birth defects, and a variety of regulatory processes control this pathway to ensure its proper function and integration with other signaling systems. We previously identified GTP-binding protein 2 (Gtpbp2) as a novel regulator of BMP signaling, however further exploration revealed that Gtpbp2 can also affect Wnt signaling, which is a novel finding reported here.
Results: Knockdown of Gtpbp2 in Xenopus embryos causes severe axial defects and reduces expression of Spemann-Mangold organizer genes. Gtpbp2 knockdown blocks responses to ectopic Wnt8 ligand, such as organizer gene induction in ectodermal tissue explants and induction of secondary axes in whole embryos. However, organizer gene induction by ectopic Nodal2 is unaffected by Gtpbp2 knockdown. Epistasis tests, conducted by activating Wnt signal transduction at sequential points in the canonical pathway, demonstrate that Gtpbp2 is required downstream of Dishevelled and Gsk3 beta but upstream of beta-catenin, which is similar to the previously reported effects of Axin1 overexpression in Xenopus embryos. Focusing on Axin in Xenopus embryos, we find that knockdown of Gtpbp2 elevates endogenous or exogenous Axin protein levels. Furthermore, Gtpbp2 fusion proteins co-localize with Dishevelled and co-immunoprecipitate with Axin and Gsk3b.
Conclusions: We conclude that Gtpbp2 is required for canonical Wnt/beta-catenin signaling in Xenopus embryos. Our data suggest a model in which Gtpbp2 suppresses the accumulation of Axin protein, a rate-limiting component of the beta-catenin destruction complex, such that Axin protein levels negatively correlate with Gtpbp2 levels. This model is supported by the similarity of our Gtpbp2-Wnt epistasis results and previously reported effects of Axin overexpression, the physical interactions of Gtpbp2 with Axin, and the correlation between elevated Axin protein levels and lost Wnt responsiveness upon Gtpbp2 knockdown. A wide variety of cancer-causing Wnt pathway mutations require low Axin levels, so development of Gtpbp2 inhibitors may provide a new therapeutic strategy to elevate Axin and suppress aberrant beta-catenin signaling in cancer and other Wnt-related diseases.
C1 [Gillis, William Q.; Kirmizitas, Arif; Iwasaki, Yasuno; Ki, Dong-Hyuk; Wyrick, Jonathan M.; Thomsen, Gerald H.] SUNY Stony Brook, Ctr Dev Genet, Dept Biochem & Cell Biol, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA.
[Gillis, William Q.] SUNY Coll Old Westbury, Dept Biol Sci, Old Westbury, NY 11568 USA.
[Kirmizitas, Arif] Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England.
[Ki, Dong-Hyuk] Harvard Med Sch, Childrens Hosp Boston, Dana Farber Canc Inst, Dept Pediat Oncol,Div Hematol Oncol, Boston, MA USA.
RP Thomsen, GH (reprint author), SUNY Stony Brook, Ctr Dev Genet, Dept Biochem & Cell Biol, Grad Program Mol & Cellular Biol, Stony Brook, NY 11794 USA.
EM gerald.h.thomsen@stonybrook.edu
OI KIRMIZITAS, ARIF/0000-0001-6503-5974
FU NIH [5R01GM080462]; Carol Baldwin Foundation Award (Stony Brook TRO);
NIDDK [5T32DK007521]; NIGMS [1K12GM102778]
FX This work was supported by NIH grant 5R01GM080462, and a Carol Baldwin
Foundation Award (Stony Brook TRO 2014) to GHT. Support for WQG was from
NIDDK 5T32DK007521 and NIGMS 1K12GM102778.
NR 49
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 1478-811X
J9 CELL COMMUN SIGNAL
JI Cell Commun. Signal.
PD AUG 2
PY 2016
VL 14
AR 15
DI 10.1186/s12964-016-0138-x
PG 12
WC Cell Biology
SC Cell Biology
GA DT3MU
UT WOS:000381386200001
PM 27484226
ER
PT J
AU Duan-Porter, W
Goldstein, KM
McDuffie, JR
Hughes, JM
Clowse, MEB
Klap, RS
Masilamani, V
LaPointe, NMA
Nagi, A
Gierisch, JM
Williams, JW
AF Duan-Porter, Wei
Goldstein, Karen M.
McDuffie, Jennifer R.
Hughes, Jaime M.
Clowse, Megan E. B.
Klap, Ruth S.
Masilamani, Varsha
LaPointe, Nancy M. Allen
Nagi, Avishek
Gierisch, Jennifer M.
Williams, John W., Jr.
TI Reporting of Sex Effects by Systematic Reviews on Interventions for
Depression, Diabetes, and Chronic Pain
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; LOW-BACK-PAIN; ACUTE MYOCARDIAL-INFARCTION;
CARDIOVASCULAR RISK-FACTORS; SELF-MANAGEMENT EDUCATION; INDIVIDUAL
PATIENT DATA; LOW-GLYCEMIC-INDEX; QUALITY-OF-LIFE; CLINICAL-TRIALS; KNEE
OSTEOARTHRITIS
AB Systematic reviews (SRs) have the potential to contribute uniquely to the evaluation of sex and gender differences (termed "sex effects"). This article describes the reporting of sex effects by SRs on interventions for depression, type 2 diabetes mellitus, and chronic pain conditions (chronic low back pain, knee osteoarthritis, and fibromyalgia). It includes SRs published since 1 October 2009 that evaluate medications, behavioral interventions, exercise, quality improvement, and some condition-specific treatments. The reporting of sex effects by primary randomized, controlled trials is also examined. Of 313 eligible SRs (86 for depression, 159 for type 2 diabetes mellitus, and 68 for chronic pain), few (n = 29) reported sex effects. Most SRs reporting sex effects used metaregression, whereas 9 SRs used subgroup analysis or individual-patient data meta-analysis. The proportion of SRs reporting the sex distribution of primary studies varied from a low of 31% (n = 8) for low back pain to a high of 68% (n = 23) for fibromyalgia. Primary randomized, controlled trials also infrequently reported sex effects, and most lacked an adequate sample size to examine them. Therefore, all SRs should report the proportion of women enrolled in primary studies and evaluate sex effects using appropriate methods whenever power is adequate.
C1 Durham Vet Affairs Med Ctr, Durham, NC USA.
[Clowse, Megan E. B.] Duke Univ, Sch Med, 200 Trent Dr,7 Baker House, Durham, NC 27710 USA.
[Hughes, Jaime M.] Univ N Carolina, Campus Box 7200, Chapel Hill, NC 27599 USA.
Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
Durham Vet Affairs Med Ctr, Hlth Adm Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 600, Durham, NC 27701 USA.
[Duan-Porter, Wei; McDuffie, Jennifer R.; Masilamani, Varsha; Nagi, Avishek] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 600, Durham, NC 27701 USA.
[Goldstein, Karen M.; Gierisch, Jennifer M.] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev, 508 Fulton St, Durham, NC 27705 USA.
[Klap, Ruth S.] Vet Affairs West Los Angeles Med Ctr, 11301 Wilshire Blvd,Bldg 206,Room 231, Los Angeles, CA 90073 USA.
[LaPointe, Nancy M. Allen] Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
[Williams, John W., Jr.] Durham Vet Affairs Med Ctr, Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 500, Durham, NC 27701 USA.
RP Duan-Porter, W (reprint author), Durham Vet Affairs Med Ctr, Hlth Adm Hlth Serv Res & Dev, 411 West Chapel Hill St,Suite 600, Durham, NC 27701 USA.
EM wei.duan-porter@duke.edu
FU Veterans Affairs Office of Academic Affiliations [TPM 21-022]; Veterans
Health Administration Health Services Research Development [13-263]
FX By the Veterans Affairs Office of Academic Affiliations (fellowship
support TPM 21-022; Dr. Duan-Porter) and the Veterans Health
Administration Health Services Research & Development (Career
Development Award 13-263; Dr. Goldstein).
NR 122
TC 0
Z9 0
U1 6
U2 8
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 AUG 2
PY 2016
VL 165
IS 3
BP 184
EP +
DI 10.7326/M15-2877
PG 21
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS2HA
UT WOS:000380583300007
PM 27111355
ER
PT J
AU Barkoudah, E
Weinrauch, LA
AF Barkoudah, Ebrahim
Weinrauch, Larry A.
TI Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Barkoudah, Ebrahim; Weinrauch, Larry A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Barkoudah, Ebrahim] Harvard Med Sch, Boston, MA USA.
[Weinrauch, Larry A.] EP Joslin Res Lab, Boston, MA USA.
RP Barkoudah, E (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
NR 5
TC 0
Z9 0
U1 2
U2 2
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 AUG 2
PY 2016
VL 165
IS 3
BP 225
EP 225
DI 10.7326/L16-0100
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS2HA
UT WOS:000380583300013
PM 27479224
ER
PT J
AU Cain, KD
Sehgal, BR
Covinsky, KE
Kaelber, DC
Sehgal, AR
AF Cain, Katrice D.
Sehgal, Bindu R.
Covinsky, Kenneth E.
Kaelber, David C.
Sehgal, Ashwini R.
TI The Clinical Impact of Medical Journals
SO ANNALS OF INTERNAL MEDICINE
LA English
DT Letter
C1 [Cain, Katrice D.; Sehgal, Ashwini R.] Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Reducing Hlth Dispar, Cleveland, OH 44106 USA.
[Sehgal, Bindu R.] Premier Phys Ctr, Westlake, OH USA.
[Covinsky, Kenneth E.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA.
[Kaelber, David C.] Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Clin Informat Res & Educ, Cleveland, OH USA.
RP Cain, KD (reprint author), Case Western Reserve Univ, Metrohlth Med Ctr, Ctr Reducing Hlth Dispar, Cleveland, OH 44106 USA.
NR 4
TC 1
Z9 1
U1 1
U2 2
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 AUG 2
PY 2016
VL 165
IS 3
BP 227
EP 228
DI 10.7326/M16-1096
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DS2HA
UT WOS:000380583300016
PM 27294687
ER
PT J
AU McMillan, BJ
Tibbe, C
Jeon, H
Drabek, AA
Klein, T
Blacklow, SC
AF McMillan, Brian J.
Tibbe, Christine
Jeon, Hyesung
Drabek, Andrew A.
Klein, Thomas
Blacklow, Stephen C.
TI Electrostatic Interactions between Elongated Monomers Drive
Filamentation of Drosophila Shrub, a Metazoan ESCRT-III Protein
SO Cell Reports
LA English
DT Article
ID STRUCTURAL BASIS; MEMBRANE DEFORMATION; COMPLEX; CYTOKINESIS; PATHWAY;
HELICES; SYSTEM
AB The endosomal sorting complex required for transport (ESCRT) is a conserved protein complex that facilitates budding and fission of membranes. It executes a key step in many cellular events, including cytokinesis and multi-vesicular body formation. The ESCRT-III protein Shrub in flies, or its homologs in yeast (Snf7) or humans (CHMP4B), is a critical polymerizing component of ESCRT-III needed to effect membrane fission. We report the structural basis for polymerization of Shrub and define a minimal region required for filament formation. The X-ray structure of the Shrub core shows that individual monomers in the lattice interact in a staggered arrangement using complementary electrostatic surfaces. Mutations that disrupt interface salt bridges interfere with Shrub polymerization and function. Despite substantial sequence divergence and differences in packing interactions, the arrangement of Shrub subunits in the polymer resembles that of Snf7 and other family homologs, suggesting that this intermolecular packing mechanism is shared among ESCRT-III proteins.
C1 [McMillan, Brian J.; Drabek, Andrew A.; Blacklow, Stephen C.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Tibbe, Christine; Klein, Thomas] Univ Dusseldorf, D-40225 Dusseldorf, Germany.
[Jeon, Hyesung; Blacklow, Stephen C.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
RP Blacklow, SC (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Blacklow, SC (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM stephen_blacklow@hms.harvard.edu
FU NIH [CA092433, CA119070]; Deutsche Forschungsgemeinschaft (DFG) [SFB
1208]
FX This work was supported in part by NIH awards CA092433 and CA119070,
project 3 (to S.C.B.), and by the Deutsche Forschungsgemeinschaft (DFG)
through SFB 1208, project B01 (to T.K.).
NR 26
TC 1
Z9 1
U1 0
U2 1
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 AUG 2
PY 2016
VL 16
IS 5
BP 1211
EP 1217
DI 10.1016/j.celrep.2016.06.093
PG 7
WC Cell Biology
SC Cell Biology
GA DS4KE
UT WOS:000380749200003
PM 27452459
ER
PT J
AU Stratton, MS
Lin, CY
Anand, P
Tatman, PD
Ferguson, BS
Wickers, ST
Ambardekar, AV
Sucharov, CC
Bradner, JE
Haldar, SM
McKinsey, TA
AF Stratton, Matthew S.
Lin, Charles Y.
Anand, Priti
Tatman, Philip D.
Ferguson, Bradley S.
Wickers, Sean T.
Ambardekar, Amrut V.
Sucharov, Carmen C.
Bradner, James E.
Haldar, Saptarsi M.
McKinsey, Timothy A.
TI Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers Is
Suppressed by a MicroRNA
SO Cell Reports
LA English
DT Article
ID BROMODOMAIN PROTEIN BRD4; PULMONARY ARTERIAL-HYPERTENSION;
RIGHT-VENTRICULAR HYPERTROPHY; HEART-FAILURE; CELL IDENTITY; P-TEFB;
TRANSCRIPTIONAL ELONGATION; DILATED CARDIOMYOPATHY;
SELECTIVE-INHIBITION; CARDIAC-HYPERTROPHY
AB BRD4 governs pathological cardiac gene expression by binding acetylated chromatin, resulting in enhanced RNA polymerase II (Pol II) phosphorylation and transcription elongation. Here, we describe a signal-dependent mechanism for the regulation of BRD4 in cardiomyocytes. BRD4 expression is suppressed by microRNA-9 (miR-9), which targets the 3' UTR of the Brd4 transcript. In response to stress stimuli, miR-9 is downregulated, leading to derepression of BRD4 and enrichment of BRD4 at long-range super-enhancers (SEs) associated with pathological cardiac genes. A miR-9 mimic represses stimulus-dependent targeting of BRD4 to SEs and blunts Pol II phosphorylation at proximal transcription start sites, without affecting BRD4 binding to SEs that control constitutively expressed cardiac genes. These findings suggest that dynamic enrichment of BRD4 at SEs genome-wide serves a crucial role in the control of stress-induced cardiac gene expression and define a miR-dependent signaling mechanism for the regulation of chromatin state and Pol II phosphorylation.
C1 [Stratton, Matthew S.; Tatman, Philip D.; Ferguson, Bradley S.; Wickers, Sean T.; Ambardekar, Amrut V.; Sucharov, Carmen C.; McKinsey, Timothy A.] Univ Colorado Denver, Div Cardiol, Dept Med, Aurora, CO 80045 USA.
[Lin, Charles Y.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Anand, Priti; Haldar, Saptarsi M.] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA.
[Tatman, Philip D.; McKinsey, Timothy A.] Univ Colorado Denver, Med Scientist Training Program, Aurora, CO 80045 USA.
[Bradner, James E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Haldar, Saptarsi M.] UCSF Sch Med, Div Cardiol, Dept Med, San Francisco, CA 94143 USA.
[Haldar, Saptarsi M.] UCSF Sch Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
RP McKinsey, TA (reprint author), Univ Colorado Denver, Div Cardiol, Dept Med, Aurora, CO 80045 USA.; McKinsey, TA (reprint author), Univ Colorado Denver, Med Scientist Training Program, Aurora, CO 80045 USA.
EM timothy.mckinsey@ucdenver.edu
FU NIH [R01HL127240, R01HL116848, R21AG043822, DK093821]; American Heart
Association [14510001]; T32 training grant; F32 fellowship from NIH
[5T32HL007822, F32HL126354]; US Department of Defense CDMRP [CA120184];
Scientist Development Grant (from American Heart Association); Boettcher
Foundation's Webb-Waring Biomedical Research Program; NIH/NCATS Colorado
CTSA grant [UL1 TR001082]
FX We thank miRagen Therapeutics for the control mimic, members of the K.
Song lab for assistance with microscopy, and C. Vinson (NCI) for
Ad-dnAP-1/AFos. This work was supported by NIH R01HL127240 (to J.E.B.,
S.M.H., and T.A.M.). T.A.M. was also supported by the NIH (R01HL116848
and R21AG043822) and the American Heart Association (Grant-in-Aid
14510001). S.M.H. was also supported by NIH DK093821. M.S.S. was funded
by a T32 training grant and an F32 fellowship from the NIH (5T32HL007822
and F32HL126354). C.Y.L. is supported by a US Department of Defense
CDMRP CA120184 postdoctoral fellowship. A.V.A. is supported by a
Scientist Development Grant (from the American Heart Association) and
the Boettcher Foundation's Webb-Waring Biomedical Research Program. The
REDCap database used in the maintenance of the human cardiac tissue bank
was supported by NIH/NCATS Colorado CTSA grant UL1 TR001082.
NR 46
TC 0
Z9 0
U1 7
U2 7
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 AUG 2
PY 2016
VL 16
IS 5
BP 1366
EP 1378
DI 10.1016/j.celrep.2016.06.074
PG 13
WC Cell Biology
SC Cell Biology
GA DS4KE
UT WOS:000380749200017
PM 27425608
ER
PT J
AU Heydari, B
Abdullah, S
Pottala, JV
Shah, R
Abbasi, S
Mandry, D
Francis, SA
Lumish, H
Ghoshhajra, BB
Hoffmann, U
Appelbaum, E
Feng, JZH
Blankstein, R
Steigner, M
McConnell, JP
Harris, W
Antman, EM
Jerosch-Herold, M
Kwong, RY
AF Heydari, Bobak
Abdullah, Shuaib
Pottala, James V.
Shah, Ravi
Abbasi, Siddique
Mandry, Damien
Francis, Sanjeev A.
Lumish, Heidi
Ghoshhajra, Brian B.
Hoffmann, Udo
Appelbaum, Evan
Feng, Jiazhuo H.
Blankstein, Ron
Steigner, Michael
McConnell, Joseph P.
Harris, William
Antman, Elliott M.
Jerosch-Herold, Michael
Kwong, Raymond Y.
TI Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After
Acute Myocardial Infarction The OMEGA-REMODEL Randomized Clinical Trial
SO CIRCULATION
LA English
DT Article
DE endomyocardial fibrosis; fatty acids, omega-3; infarction; magnetic
resonance imaging; ventricular remodeling
ID EXTRACELLULAR-MATRIX EXPANSION; AMERICAN-HEART-ASSOCIATION; HEALTH-CARE
PROFESSIONALS; ADIPONECTIN SECRETION; FATTY-ACIDS; DISEASE; DYSFUNCTION;
OMEGA-3-FATTY-ACIDS; QUANTIFICATION; CARVEDILOL
AB BACKGROUND: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown.
METHODS: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1: 1 to 6 months of high-dose omega-3 fatty acids (n= 180) or placebo (n= 178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size.
RESULTS: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (-5.8%, P= 0.017), and noninfarct myocardial fibrosis (-5.6%, P= 0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with highdose omega-3 fatty acid therapy.
CONCLUSIONS: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guidelinebased standard of care.
C1 [Heydari, Bobak; Abdullah, Shuaib; Shah, Ravi; Abbasi, Siddique; Mandry, Damien; Feng, Jiazhuo H.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Noninvas Cardiovasc Imaging Sect, 75 Francis St, Boston, MA 02115 USA.
[Heydari, Bobak; Abdullah, Shuaib; Shah, Ravi; Abbasi, Siddique; Mandry, Damien; Feng, Jiazhuo H.; Blankstein, Ron; Steigner, Michael; Jerosch-Herold, Michael; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
[Heydari, Bobak; Abdullah, Shuaib; Shah, Ravi; Abbasi, Siddique; Mandry, Damien; Feng, Jiazhuo H.; Antman, Elliott M.; Kwong, Raymond Y.] Brigham & Womens Hosp, Dept Med, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA.
[Pottala, James V.; Harris, William] Univ South Dakota, Sanford Sch Med, Dept Internal Med, Sioux Falls, SD USA.
[Shah, Ravi; Francis, Sanjeev A.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Lumish, Heidi; Ghoshhajra, Brian B.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Appelbaum, Evan] Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA.
[McConnell, Joseph P.] Hlth Diagnost Lab Inc, Richmond, VA USA.
[Harris, William] OmegaQuant Analyt LLC, Sioux Falls, SD USA.
RP Kwong, RY (reprint author), Brigham & Womens Hosp, Dept Med, Cardiovasc Div, Cardiac Magnet Resonance Imaging, 75 Francis St, Boston, MA 02115 USA.; Kwong, RY (reprint author), Harvard Med Sch, Med, 75 Francis St, Boston, MA 02115 USA.
EM rykwong@partners.org
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health
FX The National Heart, Lung, and Blood Institute of the National Institutes
of Health funded this study.
NR 37
TC 7
Z9 7
U1 5
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 AUG 2
PY 2016
VL 134
IS 5
BP 378
EP +
DI 10.1161/CIRCULATIONAHA.115.019949
PG 17
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DS2NB
UT WOS:000380612600007
PM 27482002
ER
PT J
AU Kirtane, AJ
Doshi, D
Leon, MB
Lasala, JM
Ohman, EM
O'Neill, WW
Shroff, A
Cohen, MG
Palacios, IF
Beohar, N
Uriel, N
Kapur, NK
Karmpaliotis, D
Lombardi, W
Dangas, GD
Parikh, MA
Stone, GW
Moses, JW
AF Kirtane, Ajay J.
Doshi, Darshan
Leon, Martin B.
Lasala, John M.
Ohman, E. Magnus
O'Neill, William W.
Shroff, Adhir
Cohen, Mauricio G.
Palacios, Igor F.
Beohar, Nirat
Uriel, Nir
Kapur, Navin K.
Karmpaliotis, Dimitri
Lombardi, William
Dangas, George D.
Parikh, Manish A.
Stone, Gregg W.
Moses, Jeffrey W.
TI Treatment of Higher-Risk Patients With an Indication for
Revascularization Evolution Within the Field of Contemporary
Percutaneous Coronary Intervention
SO CIRCULATION
LA English
DT Article
DE angioplasty; coronary artery disease; coronary occlusion; heart failure;
percutaneous coronary intervention
ID QUALITY-OF-LIFE; ELEVATION MYOCARDIAL-INFARCTION; ASSOCIATION
TASK-FORCE; ARTERY-BYPASS SURGERY; CARDIOVASCULAR DATA REGISTRY;
AMERICAN-HEART-ASSOCIATION; APPROPRIATE USE CRITERIA; CHRONIC TOTAL
OCCLUSIONS; THORACIC-SURGEONS; UNITED-STATES
AB Patients with severe coronary artery disease with a clinical indication for revascularization but who are at high procedural risk because of patient comorbidities, complexity of coronary anatomy, and/or poor hemodynamics represent an understudied and potentially underserved patient population. Through advances in percutaneous interventional techniques and technologies and improvements in patient selection, current percutaneous coronary intervention may allow appropriate patients to benefit safely from revascularization procedures that might not have been offered in the past. The burgeoning interest in these procedures in some respects reflects an evolutionary step within the field of percutaneous coronary intervention. However, because of the clinical complexity of many of these patients and procedures, it is critical to develop dedicated specialists within interventional cardiology who are trained with the cognitive and technical skills to select these patients appropriately and to perform these procedures safely. Preprocedural issues such as multidisciplinary risk and treatment assessments are highly relevant to the successful treatment of these patients, and knowledge gaps and future directions to improve outcomes in this emerging area are discussed. Ultimately, an evolution of contemporary interventional cardiology is necessary to treat the increasingly higher-risk patients with whom we are confronted.
C1 [Kirtane, Ajay J.; Doshi, Darshan; Leon, Martin B.; Karmpaliotis, Dimitri; Parikh, Manish A.; Stone, Gregg W.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Herbert & Sandi Feinberg Intervent Cardiol & Hear, New York, NY USA.
[Kirtane, Ajay J.; Doshi, Darshan; Leon, Martin B.; Karmpaliotis, Dimitri; Parikh, Manish A.; Stone, Gregg W.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA.
[Lasala, John M.] Washington Univ, St Louis, MO USA.
[Ohman, E. Magnus] Duke Univ, Med Ctr, Program Adv Coronary Dis, Durham, NC USA.
[O'Neill, William W.] Henry Ford Hosp, Detroit, MI USA.
[Shroff, Adhir] Univ Illinois, Chicago, IL USA.
[Cohen, Mauricio G.] Univ Miami, Miller Sch Med, Miami, FL 33136 USA.
[Palacios, Igor F.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Beohar, Nirat] Mt Sinai Med Ctr, Miami, FL USA.
[Uriel, Nir] Univ Chicago, Chicago, IL 60637 USA.
[Kapur, Navin K.] Tufts Med Ctr, Boston, MA USA.
[Lombardi, William] Univ Washington, Med Ctr, Seattle, WA 98195 USA.
[Dangas, George D.] Mt Sinai Med Ctr, New York, NY 10029 USA.
RP Kirtane, AJ (reprint author), 161 Ft Washington Ave,6th Floor, New York, NY 10032 USA.
EM akirtane@columbia.edu
FU Boston Scientific; Medtronic; Abbott Vascular; Abiomed; St. Jude
Medical; Eli Lilly; Abiomed Inc.; Daiichi Sankyo; Gilead Sciences;
Daiichi-Sankyo/Eli Lilly and Co; AstraZeneca; Boehringer Ingelheim;
Bristol-Myers Squibb; Janssen Pharmaceuticals; Liposcience; Medicines
Company; Merck/Schering Plow; Pozen; Roche; Sanofi-Aventis; WebMD;
Thoratec; Heartware; Cardiac Assist; Maquet; Bristol-Myers
Squibb/Sanofi; Eli Lilly and Co/Daiichi-Sankyo; Covidien; Regado
Biosciences; Maya Medical; Merck Co
FX Dr Kirtane reports institutional research grants to Columbia University
from Boston Scientific, Medtronic, Abbott Vascular, Abiomed, St. Jude
Medical, and Eli Lilly. Dr Doshi reports an educational grant from
Abiomed Inc. Dr Karmpaliotis reports serving on the speakers' bureau for
Abbott Vascular, Boston Scientific, Medtronic, and Asahi. Dr Leon
reports serving on the advisory board for Boston Scientific and
Medtronic. Dr. Lasala reports speaker fees from Abiomed, St. Jude
Medical, Eli Lilly, Boston Scientific, and Daiichi Sankyo; serving on
the advisory board for Abiomed and Boston Scientific; and being a
stockholder in Abiomed. Dr Ohman has received grant support from Gilead
Sciences and Daiichi-Sankyo/Eli Lilly and Co, as well as consultant fees
from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead
Sciences, Janssen Pharmaceuticals, Liposcience, The Medicines Company,
Merck/Schering Plow, Pozen, Roche, Sanofi-Aventis, and WebMD. Dr Shroff
has been a consultant for Medtronic, Abiomed, Terumo Medical, and The
Medicines Company. Dr Cohen has been on the speakers' bureau for
Medtronic; has been a consultant for AstraZeneca, Abiomed, Daiichi
Sankyo, and Terumo Medical; and has received research support from
Boston Scientific and Abbott Vascular. Dr Uriel has been a consultant
for Thoratec, Heartware, Abiomed, and Medtronic and has received grant
support from Thoratec and Heartware. Dr Kapur reports serving on the
speakers' bureau for Abiomed, Maquet, and Heartware; being a consultant
for Abiomed, Cardiac Assist, Maquet, and Thoratec; and receiving
research support from Abiomed, Cardiac Assist, and Maquet. Dr Dangas
reports institutional research grant support from The Medicines Company,
Bristol-Myers Squibb/Sanofi, and Eli Lilly and Co/Daiichi-Sankyo, as
well as consulting fees from Abbott Vascular, AstraZeneca, Boston
Scientific, Covidien, Janssen Pharmaceuticals, Regado Biosciences, Maya
Medical, Merck & Co, and The Medicines Company. Dr Lombardi has served
as a consultant to Abbott Vascular, Boston Scientific, and Abiomed; has
been on the advisory board for Abbott Vascular and Boston Scientific; is
an employee (spouse) of Spectranetics; and holds equity in Bridgepoint
Medical Systems. Dr Parikh reports serving on the speakers' bureau for
Abbott Vascular, Medtronic, CSI, and Boston Scientific and on the
advisory board for Abbott Vascular, Medtronic, and Philips. Dr Moses
reports consultant fees from Boston Scientific and Abiomed. The
remaining authors report no conflicts.
NR 47
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 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD AUG 2
PY 2016
VL 134
IS 5
BP 422
EP +
DI 10.1161/CIRCULATIONAHA.116.022061
PG 17
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DS2NB
UT WOS:000380612600010
PM 27482004
ER
PT J
AU Kousoulis, AA
Ioakeim-Ioannidou, M
Economopoulos, KP
AF Kousoulis, Antonis A.
Ioakeim-Ioannidou, Myrsini
Economopoulos, Konstantinos P.
TI Access to health for refugees in Greece: lessons in inequalities
SO International Journal for Equity in Health
LA English
DT Article
DE Access; Conflict; Greece; Inequality; Migrants; Refugee; Syria
ID INTERVENTIONS
AB Eastern Greek islands have been direct passageways of (mainly Syrian) refugees to the European continent over the past year. However, basic medical care has been insufficient. Despite calls for reform, the Greek healthcare system has for many years been costly and dysfunctional, lacking universal equity of access. Thus, mainly volunteers look after the refugee camps in the Greek islands under adverse conditions. Communicable diseases, trauma related injuries and mental health problems are the most common issues facing the refugees. The rapid changes in the epidemiology of multiple conditions that are seen in countries with high immigration rates, like Greece, demand pragmatic solutions. Best available knowledge should be used in delivering health interventions. So far, Greece is failed by international aid, and cross-border policies have not effectively tackled underlying reasons for ill-health in this context, like poverty, conflict and equity of access.
C1 [Kousoulis, Antonis A.; Ioakeim-Ioannidou, Myrsini; Economopoulos, Konstantinos P.] Soc Jr Doctors, Athens, Greece.
[Kousoulis, Antonis A.] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, 10 Norwood Ave, London HA0 1LY, England.
[Ioakeim-Ioannidou, Myrsini] Univ Athens, Sch Med, Athens, Greece.
[Economopoulos, Konstantinos P.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
RP Kousoulis, AA (reprint author), Soc Jr Doctors, Athens, Greece.; Kousoulis, AA (reprint author), London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, 10 Norwood Ave, London HA0 1LY, England.
EM antonis.kousoulis@lshtm.ac.uk
FU Society of Junior Doctors
FX The Society of Junior Doctors funded expenses for deployment of members
to Lesbos. None other source for the study.
NR 7
TC 1
Z9 1
U1 19
U2 30
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-9276
J9 INT J EQUITY HEALTH
JI Int. J. Equity Health
PD AUG 2
PY 2016
VL 15
AR 122
DI 10.1186/s12939-016-0409-6
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DS3DM
UT WOS:000380663200001
PM 27485633
ER
PT J
AU Lee, VS
Halabi, CM
Hoffman, EP
Carmichael, N
Leshchiner, I
Lian, CG
Bierhals, AJ
Vuzman, D
Mecham, RP
Frank, NY
Stitziel, NO
AF Lee, Vivian S.
Halabi, Carmen M.
Hoffman, Erin P.
Carmichael, Nikkola
Leshchiner, Ignaty
Lian, Christine G.
Bierhals, Andrew J.
Vuzman, Dana
Mecham, Robert P.
Frank, Natasha Y.
Stitziel, Nathan O.
CA Brigham Genomic Med
TI Loss of function mutation in LOX causes thoracic aortic aneurysm and
dissection in humans
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE whole-genome sequencing; CRISPR/Cas9; aortic dissection; genetics; lysyl
oxidase
ID LYSYL-OXIDASE; MARFAN-SYNDROME; CROSS-LINKING; MOUSE; MICE; EXPRESSION;
ELASTIN; BETA; HAPLOINSUFFICIENCY; ELASTOGENESIS
AB Thoracic aortic aneurysms and dissections (TAAD) represent a substantial cause of morbidity and mortality worldwide. Many individuals presenting with an inherited form of TAAD do not have causal mutations in the set of genes known to underlie disease. Using whole-genome sequencing in two first cousins with TAAD, we identified a missense mutation in the lysyl oxidase (LOX) gene (c.893T > G encoding p.Met298Arg) that cosegregated with disease in the family. Using clustered regularly interspaced short palindromic repeats (CRISPR)/clustered regularly interspaced short palindromic repeats-associated protein-9 nuclease (Cas9) genome engineering tools, we introduced the human mutation into the homologous position in the mouse genome, creating mice that were heterozygous and homozygous for the human allele. Mutant mice that were heterozygous for the human allele displayed disorganized ultrastructural properties of the aortic wall characterized by fragmented elastic lamellae, whereas mice homozygous for the human allele died shortly after parturition from ascending aortic aneurysm and spontaneous hemorrhage. These data suggest that a missense mutation in LOX is associated with aortic disease in humans, likely through insufficient cross-linking of elastin and collagen in the aortic wall. Mutation carriers may be predisposed to vascular diseases because of weakened vessel walls under stress conditions. LOX sequencing for clinical TAAD may identify additional mutation carriers in the future. Additional studies using our mouse model of LOX-associated TAAD have the potential to clarify the mechanism of disease and identify novel therapeutics specific to this genetic cause.
C1 [Lee, Vivian S.; Halabi, Carmen M.; Mecham, Robert P.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA.
[Halabi, Carmen M.] Washington Univ, Sch Med, Dept Pediat, Div Nephrol, St Louis, MO 63110 USA.
[Hoffman, Erin P.; Carmichael, Nikkola; Leshchiner, Ignaty; Vuzman, Dana; Frank, Natasha Y.] Brigham & Womens Hosp, Div Genet, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Carmichael, Nikkola; Leshchiner, Ignaty; Lian, Christine G.; Vuzman, Dana; Frank, Natasha Y.] Harvard Med Sch, Boston, MA 02115 USA.
[Lian, Christine G.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Bierhals, Andrew J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63110 USA.
[Frank, Natasha Y.] VA Boston Healthcare Syst, Boston, MA 02132 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Med, Div Cardiovasc, St Louis, MO 63110 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63110 USA.
[Hoffman, Erin P.] Littleton Adventist Hosp, Dept Oncol, Littleton, CO 80122 USA.
RP Frank, NY (reprint author), Brigham & Womens Hosp, Div Genet, Dept Med, 75 Francis St, Boston, MA 02115 USA.; Frank, NY (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Frank, NY (reprint author), VA Boston Healthcare Syst, Boston, MA 02132 USA.; Stitziel, NO (reprint author), Washington Univ, Sch Med, Dept Med, Div Cardiovasc, St Louis, MO 63110 USA.; Stitziel, NO (reprint author), Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.; Stitziel, NO (reprint author), Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO 63110 USA.
EM nfrank@partners.org; nstitziel@wustl.edu
FU Hope Center Transgenic Vectors Core and Mouse Genetics Core at the
Washington University School of Medicine; National Heart, Lung, and
Blood Institute [R01HL105314, R01HL53325, K08HL114642, R01HL131961,
T32HL125241]; National Institute of Biomedical Imaging and
Bioengineering Training Grant [T32EB18266]; Foundation for Barnes-Jewish
Hospital
FX We thank the family presented here for participating in this study. We
also thank Russell Knutsen and Marilyn Levy for the mouse physiology and
EM studies, respectively; and Phillip Trackman (Boston University) for
assistance with the LOX activity assay. This work was supported, in
part, by the Hope Center Transgenic Vectors Core and Mouse Genetics Core
at the Washington University School of Medicine. Funds supporting this
work were provided by National Heart, Lung, and Blood Institute Grants
R01HL105314 (to R.P.M.), R01HL53325 (to R.P.M.), K08HL114642 (to
N.O.S.), and R01HL131961 (to N.O.S.). V.S.L. was supported by National
Institute of Biomedical Imaging and Bioengineering Training Grant
T32EB18266 and National Heart, Lung, and Blood Institute Training Grant
T32HL125241. C.M.H. is a Scholar of the Child Health Research Center at
Washington University School of Medicine (K12-HD076224). R.P.M. and
N.O.S. are also supported, in part, by The Foundation for Barnes-Jewish
Hospital.
NR 47
TC 2
Z9 2
U1 3
U2 5
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 AUG 2
PY 2016
VL 113
IS 31
BP 8759
EP 8764
DI 10.1073/pnas.1601442113
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DS2HH
UT WOS:000380586600061
PM 27432961
ER
PT J
AU Kahle, KT
Flores, B
Bharucha-Goebel, D
Zhang, JW
Donkervoort, S
Hegde, M
Hussain, G
Duran, D
Liang, B
Sun, DD
Bonnemann, CG
Delpire, E
AF Kahle, Kristopher T.
Flores, Bianca
Bharucha-Goebel, Diana
Zhang, Jinwei
Donkervoort, Sandra
Hegde, Madhuri
Hussain, Gulnaz
Duran, Daniel
Liang, Bo
Sun, Dandan
Bonnemann, Carsten G.
Delpire, Eric
TI Peripheral motor neuropathy is associated with defective kinase
regulation of the KCC3 cotransporter
SO Science Signaling
LA English
DT Article
ID CATION-CHLORIDE COTRANSPORTERS; CONDITIONAL MOUSE MODEL; CELL-VOLUME
HOMEOSTASIS; K+-CL-COTRANSPORTER; CORPUS-CALLOSUM; MISSENSE MUTATIONS;
ANDERMANN-SYNDROME; HEREDITARY MOTOR; DISEASE; MICE
AB Using exome sequencing, we identified a de novo mutation (c.2971A>G; T991A) in SLC12A6, the gene encoding the K+-Cl(-)cotransporter KCC3, in a patient with an early-onset, progressive, and severe peripheral neuropathy primarily affecting motor neurons. Normally, the WNK kinase-dependent phosphorylation of T-991 tonically inhibits KCC3; however, cell swelling triggers Thr(991) dephosphorylation to activate the transporter and restore cell volume. KCC3 (T991A) mutation in patient cells abolished Thr(991) phosphorylation, resulted in constitutive KCC3 activity, and compromised cell volume homeostasis. KCC3(T991A/T991A) mutant mice exhibited constitutive KCC3 activity and recapitulated aspects of the clinical, electrophysiological, and histopathological findings of the patient. These results suggest that the function of the peripheral nervous system depends on finely tuned, kinase-regulated KCC3 activity and implicate abnormal cell volume homeostasis as a previously unreported mechanism of axonal degeneration.
C1 [Kahle, Kristopher T.; Zhang, Jinwei; Duran, Daniel] Yale Sch Med, Ctr Mendelian Genom, Dept Neurosurg, New Haven, CT 06510 USA.
[Kahle, Kristopher T.; Zhang, Jinwei; Duran, Daniel] Yale Sch Med, Ctr Mendelian Genom, Dept Pediat & Cellular & Mol Physiol, New Haven, CT 06510 USA.
[Flores, Bianca; Delpire, Eric] Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA.
[Bharucha-Goebel, Diana; Donkervoort, Sandra; Bonnemann, Carsten G.] NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, Bethesda, MD 20814 USA.
[Bharucha-Goebel, Diana] Childrens Natl Hlth Syst, Dept Neurol, Washington, DC 20010 USA.
[Zhang, Jinwei] Univ Dundee, Coll Life Sci, Prot Phosphorylat & Ubiquitylat Unit, MRC, Dundee DD15EH, Scotland.
[Hegde, Madhuri] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA.
[Hussain, Gulnaz; Sun, Dandan] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA.
[Hussain, Gulnaz; Sun, Dandan] Vet Affairs Pittsburgh Hlth Care Syst, Geriatr Res, Educ & Clin Ctr, Pittsburgh, PA 15240 USA.
[Liang, Bo] Harvard Med Sch, Dept MicroBiol, Boston, MA 02114 USA.
[Liang, Bo] Harvard Med Sch, Dept Immunobiol, Boston, MA 02114 USA.
RP Delpire, E (reprint author), Vanderbilt Univ, Sch Med, Dept Anesthesiol, Nashville, TN 37232 USA.; Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, Bethesda, MD 20814 USA.
EM carsten.bonnemann@nih.gov; eric.delpire@vanderbilt.edu
OI Duran, Daniel/0000-0001-6888-252X; Zhang, Jinwei/0000-0001-8683-509X
FU NIH [GM74771, 2T32MH064913-11A1, T32-AR056993]; Harvard-Massachusetts
Institute of Technology Neuroscience Grant; Manton Center for Orphan
Disease Research at Harvard Medical School; March of Dimes Basil
O'Connor Award; NINDS
FX This work was supported by NIH research grant GM74771 (E.D.). K.T.K. was
supported by a Harvard-Massachusetts Institute of Technology
Neuroscience Grant, the Manton Center for Orphan Disease Research at
Harvard Medical School, and the March of Dimes Basil O'Connor Award.
C.G.B. is supported by intramural funds of the NINDS. B.F. and D.B.G.
received support from NIH grants 2T32MH064913-11A1 and T32-AR056993,
respectively.
NR 51
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U1 1
U2 1
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 1945-0877
EI 1937-9145
J9 SCI SIGNAL
JI Sci. Signal.
PD AUG 2
PY 2016
VL 9
IS 439
AR ra77
DI 10.1126/scisignal.aae0546
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DS4VJ
UT WOS:000380779400001
PM 27485015
ER
PT J
AU Paganetti, H
Yu, CX
Orton, CG
AF Paganetti, Harald
Yu, Cedric X.
Orton, Colin G.
TI Photon radiotherapy has reached its limit in terms of catching up
dosimetrically with proton therapy
SO MEDICAL PHYSICS
LA English
DT Editorial Material
ID BODY RADIATION-THERAPY; DELIVERY
C1 [Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Paganetti, Harald] Harvard Med Sch, Boston, MA 02114 USA.
[Yu, Cedric X.] Univ Maryland, Sch Med, Dept Radiat Oncol, Baltimore, MD 21201 USA.
RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Paganetti, H (reprint author), Harvard Med Sch, Boston, MA 02114 USA.
EM hpaganetti@mgh.harvard.edu; yu002@umaryland.edu
NR 12
TC 0
Z9 0
U1 1
U2 1
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD AUG
PY 2016
VL 43
IS 8
BP 4470
EP 4472
DI 10.1118/1.4954790
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EN2UW
UT WOS:000395866800002
PM 27487862
ER
PT J
AU Andreasen, D
Van Leemput, K
Edmund, JM
AF Andreasen, Daniel
Van Leemput, Koen
Edmund, Jens M.
TI A patch-based pseudo-CT approach for MRI-only radiotherapy in the pelvis
SO MEDICAL PHYSICS
LA English
DT Article
DE radiotherapy; MRI-only; pseudo-CT; patch; pelvis
ID ULTRASHORT ECHO TIME; MAGNETIC-RESONANCE; ATTENUATION CORRECTION;
COMPUTED-TOMOGRAPHY; RADIATION-THERAPY; ELECTRON-DENSITY; BRAIN;
SEQUENCES; PROSTATE; PET/MRI
AB Purpose: In radiotherapy based only on magnetic resonance imaging (MRI), knowledge about tissue electron densities must be derived from the MRI. This can be achieved by converting the MRI scan to the so-called pseudo-computed tomography (pCT). An obstacle is that the voxel intensities in conventional MRI scans are not uniquely related to electron density. The authors previously demonstrated that a patch-based method could produce accurate pCTs of the brain using conventional Ti-weighted MRI scans. The method was driven mainly by local patch similarities and relied on simple affine registrations between an atlas database of the co-registered MRI/CT scan pairs and the MRI scan to be converted. In this study, the authors investigate the applicability of the patch-based approach in the pelvis. This region is challenging for a method based on local similarities due to the greater inter-patient variation. The authors benchmark the method against a baseline pCT strategy where all voxels inside the body contour are assigned a water-equivalent bulk density. Furthermore, the authors implement a parallelized approximate patch search strategy to speed up the pCT generation time to a more clinically relevant level.
Methods: The data consisted of CT and T-1-weighted MRI scans of 10 prostate patients. pCTs were generated using an approximate patch search algorithm in a leave-one-out fashion and compared with the CT using frequently described metrics such as the voxel-wise mean absolute error (MAE(VOX)) and the deviation in water-equivalent path lengths. Furthermore, the dosimetric accuracy was tested for a volumetric modulated arc therapy plan using dose volume histogram (DVH) point deviations and gamma-index analysis.
Results: The patch-based approach had an average MAE,x of 54 HU; median deviations of less than 0.4% in relevant DVH points and a gamma-index pass rate of 0.97 using a 1%/1 mm criterion. The patch-based approach showed a significantly better performance than the baseline water pCT in almost all metrics. The approximate patch search strategy was 70x faster than a brute-force search, with an average prediction time of 20.8 min.
Conclusions: The authors showed that a patch-based method based on affine registrations and T-1-weighted MRI could generate accurate pCTs of the pelvis. The main source of differences between pCT and CT was positional changes of air pockets and body outline. (C) 2016 American Association of Physicists in Medicine.
C1 [Andreasen, Daniel; Van Leemput, Koen] Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark.
[Andreasen, Daniel; Edmund, Jens M.] Univ Copenhagen, Gentofte & Herlev Hosp, Dept Oncol, Radiotherapy Res Unit, DK-2730 Herlev, Denmark.
[Van Leemput, Koen] Harvard Med Sch, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.
RP Andreasen, D (reprint author), Tech Univ Denmark, Dept Appl Math & Comp Sci, DK-2800 Lyngby, Denmark.; Andreasen, D (reprint author), Univ Copenhagen, Gentofte & Herlev Hosp, Dept Oncol, Radiotherapy Res Unit, DK-2730 Herlev, Denmark.
EM dana@dtu.dk
FU Varian Medical Systems, Inc.
FX This work was supported by a research grant from Varian Medical Systems,
Inc.
NR 44
TC 2
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U1 0
U2 0
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD AUG
PY 2016
VL 43
IS 8
BP 4742
EP 4752
DI 10.1118/1.4958676
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EN2UW
UT WOS:000395866800032
PM 27487892
ER
PT J
AU Andreyev, A
Celler, A
Ozsahin, I
Sitek, A
AF Andreyev, A.
Celler, A.
Ozsahin, I.
Sitek, A.
TI Resolution recovery for Compton camera using origin ensemble algorithm
SO MEDICAL PHYSICS
LA English
DT Article
DE Compton camera; resolution recovery; origin ensemble; image
reconstruction
ID IMAGE-RECONSTRUCTION; GAMMA-CAMERA; SPATIAL-RESOLUTION; EMISSION;
TOMOGRAPHY; SCATTERING; PET
AB Purpose: Compton cameras (CCs) use electronic collimation to reconstruct the images of activity distribution. Although this approach can greatly improve imaging efficiency, due to complex geometry of the CC principle, image reconstruction with the standard iterative algorithms, such as ordered subset expectation maximization (OSEM), can be very time-consuming, even more so if resolution recovery (RR) is implemented. We have previously shown that the origin ensemble (OE) algorithm can be used for the reconstruction of the CC data. Here we propose a method of extending our OE algorithm to include RR.
Methods: To validate the proposed algorithm we used Monte Carlo simulations of a CC composed of multiple layers of pixelated CZT detectors and designed for imaging small animals. A series of CC acquisitions of small hot spheres and the Derenzo phantom placed in air were simulated. Images obtained from (a) the exact data, (b) blurred data but reconstructed without resolution recovery, and (c) blurred and reconstructed with resolution recovery were compared. Furthermore, the reconstructed contrast-to-background ratios were investigated using the phantom with nine spheres placed in a hot background.
Results: Our simulations demonstrate that the proposed method allows for the recovery of the resolution loss that is due to imperfect accuracy of event detection. Additionally, tests of camera sensitivity corresponding to different detector configurations demonstrate that the proposed CC design has sensitivity comparable to PET. When the same number of events were considered, the computation time per iteration increased only by a factor of 2 when OE reconstruction with the resolution recovery correction was performed relative to the original OE algorithm. We estimate that the addition of resolution recovery to the OSEM would increase reconstruction times by 2-3 orders of magnitude per iteration.
Conclusions: The results of our tests demonstrate the improvement of image resolution provided by the OE reconstructions with resolution recovery. The quality of images and their contrast are similar to those obtained from the OE reconstructions from scans simulated with perfect energy and spatial resolutions. (C) 2016 American Association of Physicists in Medicine.
C1 [Andreyev, A.] Philips Healthcare, Highland Hts, OH 44143 USA.
[Andreyev, A.; Celler, A.] Univ British Columbia, Med Imaging Res Grp, Vancouver, BC V5Z 1M9, Canada.
[Andreyev, A.; Celler, A.] Vancouver Coastal Hlth Res Inst, Vancouver, BC V5Z 1M9, Canada.
[Ozsahin, I.; Sitek, A.] Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02114 USA.
[Ozsahin, I.; Sitek, A.] Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA.
[Sitek, A.] Brigham & Womens Hosp, Boston, MA 02114 USA.
[Sitek, A.] Harvard Med Sch, Boston, MA 02114 USA.
[Sitek, A.] Philips Res, Cambridge, MA 02141 USA.
RP Sitek, A (reprint author), Massachusetts Gen Hosp, Gordon Ctr Med Imaging, Boston, MA 02114 USA.; Sitek, A (reprint author), Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA.; Sitek, A (reprint author), Philips Res, Cambridge, MA 02141 USA.
EM sarkadiu@gmail.com
FU NIH [R21HL-106474, R21EB016315]; Canadian Institute of Health Research
(CIHR) Institute of Genetics [NHG-91363]; TUBITAK [2219]
FX This work was supported in part by NIH Nos. R21HL-106474 and
R21EB016315, by the Canadian Institute of Health Research (CIHR)
Institute of Genetics (Catalyst Grant No. NHG-91363), and by TUBITAK
2219 award.
NR 19
TC 0
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U1 0
U2 0
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD AUG
PY 2016
VL 43
IS 8
BP 4866
EP 4876
DI 10.1118/1.4959551
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EN2UW
UT WOS:000395866800044
PM 27487904
ER
PT J
AU Toltz, A
Hoesl, M
Schuemann, J
Seuntjens, J
Lu, HM
Paganetti, H
AF Toltz, Allison
Hoesl, Michaela
Schuemann, Jan
Seuntjens, Jan
Lu, Hsiao-Ming
Paganetti, Harald
TI Time-resolved diode dosimetry for in vivo proton therapy range
verification: calibration through numerical modeling
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Meeting of the
Canadian-Organization-of-Medical-Physicists
CY JUL 20-23, 2016
CL St Johns, CANADA
SP Canadian Org Med Physicists
C1 McGill Univ, Montreal, PQ H3A 2T5, Canada.
Harvard Univ, Cambridge, MA 02138 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD AUG
PY 2016
VL 43
IS 8
MA 16
BP 4939
EP 4939
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EN2UW
UT WOS:000395866800089
ER
PT J
AU Collins-Fekete, CA
Beaulieu, L
Seco, J
AF Collins-Fekete, Charles-Antoine
Beaulieu, Luc
Seco, Joao
TI On the use of proton radiography to reduce beam range uncertainties and
improve patient positioning accuracy in proton therapy
SO MEDICAL PHYSICS
LA English
DT Meeting Abstract
CT 62nd Annual Scientific Meeting of the
Canadian-Organization-of-Medical-Physicists
CY JUL 20-23, 2016
CL St Johns, CANADA
SP Canadian Org Med Physicists
C1 Univ Laval, CHU Quebec, Quebec City, PQ, Canada.
Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD AUG
PY 2016
VL 43
IS 8
MA 01
BP 4955
EP 4955
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA EN2UW
UT WOS:000395866800143
ER
PT J
AU Pyxaras, SA
Hunziker, L
Chieffo, A
Meliga, E
Latib, A
Park, SJ
Onuma, Y
Capranzano, P
Valgimigli, M
Narbute, I
Makkar, RR
Palacios, IF
Kim, YH
Buszman, PP
Chakravarty, T
Sheiban, I
Mehran, R
Margey, R
Agnihotri, A
Marra, S
Capodanno, D
Leon, MB
Moses, JW
Fajadet, J
Lefevre, T
Morice, MC
Erglis, A
Tamburino, C
Alfieri, O
Serruys, PW
Colombo, A
Naber, CK
AF Pyxaras, Stylianos A.
Hunziker, Lukas
Chieffo, Alaide
Meliga, Emanuele
Latib, Azeem
Park, Seung-Jung
Onuma, Yoshinobu
Capranzano, Piera
Valgimigli, Marco
Narbute, Inga
Makkar, Raj R.
Palacios, Igor F.
Kim, Young-Hak
Buszman, Piotr P.
Chakravarty, Tarun
Sheiban, Imad
Mehran, Roxana
Margey, Ronan
Agnihotri, Arvind
Marra, Sebastiano
Capodanno, Davide
Leon, Martin B.
Moses, Jeffrey W.
Fajadet, Jean
Lefevre, Thierry
Morice, Marie-Claude
Erglis, Andrejs
Tamburino, Corrado
Alfieri, Ottavio
Serruys, Patrick W.
Colombo, Antonio
Naber, Christoph K.
TI Long-term clinical outcomes after percutaneous coronary intervention
versus coronary artery bypass grafting for acute coronary syndrome from
the DELTA registry: a multicentre registry evaluating percutaneous
coronary intervention versus coronary artery bypass grafting for left
main treatment
SO EUROINTERVENTION
LA English
DT Article
DE acute coronary syndrome; coronary artery bypass grafting (CABG);
outcome; percutaneous coronary intervention (PCI); unprotected left main
ID DRUG-ELUTING STENTS; BARE-METAL STENTS; FOLLOW-UP; REVASCULARIZATION
REGISTRY; SYNTAX SCORE; DISEASE; TRIAL; SURGERY; LESIONS; ANGIOPLASTY
AB Aims: Our aim was to compare, in a large unprotected left main coronary artery (ULMCA) all-comer registry, the long-term clinical outcome after percutaneous coronary intervention (PCI) with first-generation drug-eluting stents (DES) versus coronary artery bypass grafting (CABG) in patients with acute coronary syndrome (ACS).
Methods and results: Of a total of 2,775 patients enrolled in the Drug Eluting Stents for Left Main Coronary Artery Disease (DELTA) multicentre registry, 379 (13.7%) patients with ACS treated with PCI (n= 272) or CABG (n= 107) were analysed. Baseline demographics were considerably different in the two groups before propensity matching. No significant differences emerged for the composite endpoint of all-cause death, myocardial infarction (MI), and cerebrovascular accident (HR 1.11, 95% CI: 0.63-1.94; p= 0.727), all-cause death (HR 1.26, 95% CI: 0.68-2.32; p= 0.462), the composite endpoint of all-cause death and MI (HR 1.02, 95% CI: 0.56-1.84; p= 0.956), and major adverse cardiac and cerebrovascular events (HR 0.82, 95% CI: 0.50-1.36; p= 0.821). However, a higher incidence of target vessel revascularisation (HR 4.67, 95% CI: 1.33-16.47; p= 0.008) was observed in the PCI compared with the CABG group, which was confirmed in the propensity score-matched analysis.
Conclusions: In the DELTA all-comer, multinational registry, PCI for ACS in ULMCA is associated with comparable clinical outcomes to those observed with CABG at long-term follow-up, despite the use of first-generation DES.
C1 [Pyxaras, Stylianos A.; Hunziker, Lukas; Naber, Christoph K.] Elisabeth Krankenhaus Essen, Contilia Heart & Vasc Ctr, Klara Kopp Weg 1, D-45138 Essen, Germany.
[Chieffo, Alaide; Latib, Azeem; Alfieri, Ottavio; Colombo, Antonio] Ist Sci San Raffaele, Dept Cardiothorac & Vasc Dis, Milan, Italy.
[Meliga, Emanuele] AO Ordine Mauriziano Umberto I, Intervent Cardiol Unit, Turin, Italy.
[Park, Seung-Jung; Kim, Young-Hak] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Cardiol,Ctr Med Res & Informat, Seoul, South Korea.
[Onuma, Yoshinobu; Valgimigli, Marco; Serruys, Patrick W.] Erasmus MC, Thoraxctr, Rotterdam, Netherlands.
[Capranzano, Piera; Capodanno, Davide; Tamburino, Corrado] Univ Catania, Ferrarotto Hosp, Cardiovasc Dept, Catania, Italy.
[Narbute, Inga; Erglis, Andrejs] Pauls Stradins Clin Univ Hosp, Latvian Ctr Cardiol, Riga, Latvia.
[Narbute, Inga; Erglis, Andrejs] Univ Latvia, Inst Cardiol, Riga, Latvia.
[Makkar, Raj R.; Chakravarty, Tarun] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
[Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA 02114 USA.
[Palacios, Igor F.; Margey, Ronan; Agnihotri, Arvind] Harvard Med Sch, Boston, MA USA.
[Buszman, Piotr P.] Amer Heart Poland Inc, Katowice, Poland.
[Sheiban, Imad; Marra, Sebastiano] Univ Turin, S Giovanni Battista Molinette Hosp, Div Cardiol, Intervent Cardiol, Turin, Italy.
[Mehran, Roxana] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Leon, Martin B.; Moses, Jeffrey W.] Columbia Univ, Med Ctr, New York, NY USA.
[Leon, Martin B.; Moses, Jeffrey W.] Cardiovasc Res Fdn, New York, NY USA.
[Fajadet, Jean] Clin Pasteur, Toulouse, France.
[Lefevre, Thierry; Morice, Marie-Claude] ICPS, Gen Sante, Massy, France.
RP Pyxaras, SA (reprint author), Elisabeth Krankenhaus Essen, Contilia Heart & Vasc Ctr, Klara Kopp Weg 1, D-45138 Essen, Germany.
EM steliospyxaras@gmail.com
FU Lilly; Medtronic; Bristol-Myers Squibb/Sanofi, The Medicines Company;
Lilly/Daiichi Sankyo; Abbott Vascular; Biotronik; Sadra Medical;
Stentys; Icon
FX D. Capodanno has received speaker's honoraria from Eli Lilly and
AstraZeneca. R. Makkar is a consultant to Medtronic and Abiomed, has
received speaker's fees from Lilly and Medtronic, and has received
equity from Entourage Medical Technologies. R. Mehran is a consultant to
Abbott Vascular, The Medicines Company, Janssen, and Regado, and has
received research grant support from Bristol-Myers Squibb/Sanofi, The
Medicines Company, and Lilly/Daiichi Sankyo. C. Naber is a speaker for
Abbott Vascular, Cordis, Biotronik, Biosensors, Cirdus, Medtronic,
Stentys, Daiichi Sankyo, and The Medicines Company, has received
research support from Abbott Vascular, Biotronik, Sadra Medical,
Stentys, and Icon, and is on the advisory board of Biotronik and Abbott
Vascular. J. Moses is a consultant to Cordis and Boston Scientific. The
other authors have no conflicts of interest to declare. The Guest Editor
has no conflicts of interest to declare.
NR 21
TC 3
Z9 3
U1 0
U2 0
PU EUROPA EDITION
PI TOULOUSE CEDEX 6
PA 19 ALLEES JEAN JAURES B P 61508, TOULOUSE CEDEX 6, 31015, FRANCE
SN 1774-024X
EI 1969-6213
J9 EUROINTERVENTION
JI EuroIntervention
PD AUG
PY 2016
VL 12
IS 5
BP E623
EP E631
DI 10.4244/EIJV12I5A102
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EK6MX
UT WOS:000394039800014
PM 27497362
ER
PT J
AU Young, JS
Chen, J
Miller, ML
Vu, V
Tian, C
Moon, JJ
Alegre, ML
Sciammas, R
Chong, AS
AF Young, J. S.
Chen, J.
Miller, M. L.
Vu, V.
Tian, C.
Moon, J. J.
Alegre, M. -L.
Sciammas, R.
Chong, A. S.
TI Delayed Cytotoxic T Lymphocyte-Associated Protein 4-Immunoglobulin
Treatment Reverses Ongoing Alloantibody Responses and Rescues Allografts
From Acute Rejection
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
DE basic (laboratory) research; science; immunosuppression; immune
modulation; organ transplantation in general; immunobiology;
alloantibody; animal models: murine; B cell biology; immunosuppressant;
fusion proteins and monoclonal antibodies: belatacept; immunosuppressive
regimens; rescue
ID ANTIBODY-MEDIATED REJECTION; DONOR-SPECIFIC ANTIBODIES; FOLLICULAR
HELPER-CELLS; INDOLEAMINE 2,3-DIOXYGENASE; KIDNEY-TRANSPLANTATION;
DENDRITIC CELLS; GRAFT-SURVIVAL; COSTIMULATORY BLOCKADE;
RENAL-TRANSPLANTATION; HEART-TRANSPLANTATION
AB Antibody-mediated rejection has emerged as the leading cause of late graft loss in kidney transplant recipients, and inhibition of donor-specific antibody production should lead to improved transplant outcomes. The fusion protein cytotoxic T lymphocyte-associated protein 4-immunoglobulin (CTLA4-Ig) blocks T cell activation and consequently inhibits T-dependent B cell antibody production, and the current paradigm is that CTLA4-Ig is effective with naive T cells and less so with activated or memory T cells. In this study, we used a mouse model of allosensitization to investigate the efficacy of continuous CTLA4-Ig treatment, initiated 7 or 14 days after sensitization, for inhibiting ongoing allospecific B cell responses. Delayed treatment with CTLA4-Ig collapsed the allospecific germinal center B cell response and inhibited alloantibody production. Using adoptively transferred T cell receptor transgenic T cells and a novel approach to track endogenous graft-specific T cells, we demonstrate that delayed CTLA4-Ig minimally inhibited graft-specific CD4(+) and T follicular helper responses. Remarkably, delaying CTLA4-Ig until day 6 after transplantation in a fully mismatched heart transplant model inhibited alloantibody production and prevented acute rejection, whereas transferred hyperimmune sera reversed the effects of delayed CTLA4-Ig. Collectively, our studies revealed the unexpected efficacy of CTLA4-Ig for inhibiting ongoing B cell responses even when the graft-specific T cell response was robustly established.
Young et al report on the unexpected efficacy of CTLA4-Ig at halting ongoing B cell responses even when treatment is initiated after the graft-specific T cell response is robustly established.
C1 [Young, J. S.; Chen, J.; Vu, V.; Tian, C.; Sciammas, R.; Chong, A. S.] Univ Chicago, Dept Surg, Sect Transplantat, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Miller, M. L.; Alegre, M. -L.] Univ Chicago, Dept Med, Rheumatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Moon, J. J.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
[Moon, J. J.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA.
[Moon, J. J.] Harvard Med Sch, Boston, MA USA.
[Sciammas, R.] Houston Methodist Hosp, Res Inst, Ctr Immunobiol & Transplant Res, Dept Surg, Houston, TX USA.
RP Chong, AS (reprint author), Univ Chicago, Dept Surg, Sect Transplantat, 5841 S Maryland Ave, Chicago, IL 60637 USA.
EM achong@uchicago.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health (NIH) [1R01AI110513, P01AI097113]; American Heart
Association (AHA) [15POST25700452]; Respiratory Biology Training Grant
[T32 HL07605]; Cardiovascular Pathophysiology and Biochemistry Training
Grant [T32 HL07237]; HHMI Med-into-Grad Program training grant
[56006772]; AHA [13PRE14550022, 15PRE22180007]; NIH Tetramer Core
Facility [HHSN272201300006C]
FX We are grateful to Dr. Wink Baldwin, Cleveland Clinic, for his generous
assistance in developing the C4d immunohistochemistry and to Ms. Rachel
C Young for her artistic contributions. This work was supported in part
by grants (1R01AI110513, P01AI097113) from the National Institute of
Allergy and Infectious Diseases, National Institutes of Health (NIH).
J.Y. received an American Heart Association (AHA) postdoctoral
fellowship award and was funded by a Respiratory Biology Training Grant
(T32 HL07605). J.S.Y. received an AHA postdoctoral fellowship award
(15POST25700452) and was funded by a Respiratory Biology Training Grant
(T32 HL07605). M.L.M. was funded by the Cardiovascular Pathophysiology
and Biochemistry Training Grant (T32 HL07237), an HHMI Med-into-Grad
Program training grant (56006772) and two AHA predoctoral fellowships
(13PRE14550022 and 15PRE22180007). MHC class I tetramers were provided
by the NIH Tetramer Core Facility (contract HHSN272201300006C).
NR 59
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD AUG
PY 2016
VL 16
IS 8
BP 2312
EP 2323
DI 10.1111/ajt.13761
PG 12
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DR6QR
UT WOS:000380026900012
ER
PT J
AU Sacher, AG
Paweletz, C
Dahlberg, SE
Alden, RS
O'Connell, A
Feeney, N
Mach, SL
Janne, PA
Oxnard, GR
AF Sacher, Adrian G.
Paweletz, Cloud
Dahlberg, Suzanne E.
Alden, Ryan S.
O'Connell, Allison
Feeney, Nora
Mach, Stacy L.
Jaenne, Pasi A.
Oxnard, Geoffrey R.
TI Prospective Validation of Rapid Plasma Genotyping for the Detection of
EGFR and KRAS Mutations in Advanced Lung Cancer
SO JAMA ONCOLOGY
LA English
DT Article
ID SMALL-CELL-LUNG; FACTOR RECEPTOR MUTATION; CIRCULATING TUMOR DNA;
DROPLET DIGITAL PCR; ACQUIRED-RESISTANCE; GEFITINIB; THERAPY;
CHEMOTHERAPY; SURVIVAL; AZD9291
AB IMPORTANCE Plasma genotyping of cell-free DNA has the potential to allow for rapid noninvasive genotyping while avoiding the inherent shortcomings of tissue genotyping and repeat biopsies.
OBJECTIVE To prospectively validate plasma droplet digital PCR (ddPCR) for the rapid detection of common epidermal growth factor receptor (EGFR) and KRAS mutations, as well as the EGFR T790M acquired resistance mutation.
DESIGN, SETTING, AND PARTICIPANTS Patients with advanced nonsquamous non-small-cell lung cancer (NSCLC) who either (1) had a new diagnosis and were planned for initial therapy or (2) had developed acquired resistance to an EGFR kinase inhibitor and were planned for rebiopsy underwent initial blood sampling and immediate plasma ddPCR for EGFR exon 19 del, L858R, T790M, and/or KRAS G12X between July 3, 2014, and June 30, 2015, at a National Cancer Institute-designated comprehensive cancer center. All patients underwent biopsy for tissue genotyping, which was used as the reference standard for comparison; rebiopsy was required for patients with acquired resistance to EGFR kinase inhibitors. Test turnaround time (TAT) was measured in business days from blood sampling until test reporting.
MAIN OUTCOMES AND MEASURES Plasma ddPCR assay sensitivity, specificity, and TAT.
RESULTS Of 180 patients with advanced NSCLC (62% female; median [range] age, 62 [37-93] years), 120 cases were newly diagnosed; 60 had acquired resistance. Tumor genotype included 80 EGFR exon 19/L858R mutants, 35 EGFR T790M, and 25 KRAS G12X mutants. Median (range) TAT for plasma ddPCR was 3 (1-7) days. Tissue genotyping median (range) TAT was 12 (1-54) days for patients with newly diagnosed NSCLC and 27 (1-146) days for patients with acquired resistance. Plasma ddPCR exhibited a positive predictive value of 100% (95% CI, 91%-100%) for EGFR 19 del, 100% (95% CI, 85%-100%) for L858R, and 100% (95% CI, 79%-100%) for KRAS, but lower for T790M at 79% (95% CI, 62%-91%). The sensitivity of plasma ddPCR was 82%(95% CI, 69%-91%) for EGFR 19 del, 74%(95% CI, 55%-88%) for L858R, and 77%(95% CI, 60%-90%) for T790M, but lower for KRAS at 64%(95% CI, 43%-82%). Sensitivity for EGFR or KRAS was higher in patients with multiple metastatic sites and those with hepatic or bone metastases, specifically.
CONCLUSIONS AND RELEVANCE Plasma ddPCR detected EGFR and KRAS mutations rapidly with the high specificity needed to select therapy and avoid repeat biopsies. This assay may also detect EGFR T790M missed by tissue genotyping due to tumor heterogeneity in resistant disease.
C1 [Sacher, Adrian G.; Alden, Ryan S.; Mach, Stacy L.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Sacher, Adrian G.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Sacher, Adrian G.; Jaenne, Pasi A.; Oxnard, Geoffrey R.] Harvard Med Sch, Boston, MA USA.
[Paweletz, Cloud; O'Connell, Allison; Feeney, Nora; Jaenne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02115 USA.
[Dahlberg, Suzanne E.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Dahlberg, Suzanne E.] Harvard TH Chan Sch Publ Hlth, Boston, MA USA.
RP Sacher, AG; Oxnard, GR (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM ags2185@cumc.columbia.edu; geoffrey_oxnard@dfci.harvard.edu
FU US Department of Defense; National Cancer Institute of the National
Institutes of Health [R01CA135257, R01CA114465, P50CA090578]; Phi Beta
Psi Sorority; Stading-Younger Cancer Foundation; International
Association for the Study of Lung Cancer; Canadian Institutes of Health
Research; Canadian Association of Medical Oncologists; Kaplan Research
Fund
FX This research was supported in part by the US Department of Defense, the
National Cancer Institute of the National Institutes of Health (grants
R01CA135257, R01CA114465, and P50CA090578), the Phi Beta Psi Sorority,
the Stading-Younger Cancer Foundation, the International Association for
the Study of Lung Cancer, the Canadian Institutes of Health Research,
the Canadian Association of Medical Oncologists, and the Kaplan Research
Fund.
NR 28
TC 27
Z9 29
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 AUG
PY 2016
VL 2
IS 8
BP 1014
EP 1022
DI 10.1001/jamaoncol.2016.0173
PG 9
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700010
PM 27055085
ER
PT J
AU Singh, JA
Yu, SH
AF Singh, Jasvinder A.
Yu, Shaohua
TI Time Trends, Predictors, and Outcome of Emergency Department Use for
Gout: A Nationwide US Study
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE GOUT; EMERGENCY ROOM; CHARGES; HOSPITALIZATION; INPATIENT USE;
HEALTHCARE USE
ID HEALTH-CARE UTILIZATION; HOSPITAL ADMISSIONS; GENERAL-POPULATION;
TREATMENT PATTERNS; UNITED-STATES; ARTHRITIS; HYPERURICEMIA;
COMORBIDITIES; COSTS
AB Objective. To assess gout-related emergency department (ED) use/charges and discharge disposition.
Methods. We used the US National ED Sample (NEDS) data to examine the time trends in total ED visits and charges and ED-related hospitalizations with gout as the primary diagnosis. We assessed multivariable-adjusted predictors of ED charges and hospitalization for gout-related visits using the 2012 NEDS data.
Results. There were 180,789, 201,044, and 205,152 ED visits in 2009, 2010, and 2012 with gout as the primary diagnosis, with total ED charges of $195 million, $239 million, and $287 million, respectively; these accounted for 0.14%-0.16% of all ED visits. Mean/median 2012 ED charges/visit were $1398/$956. Of all gout-related ED visits, 7.7% were admitted to the hospital in 2012. Mean/median length of hospital stay was 3.9/2.6 days and mean/median inpatient charge/admission with gout as the primary diagnosis was $22,066/$15,912 in 2012. In multivariable-adjusted analyses, these factors were associated with higher ED charges: older age, female sex, highest income quartile, being uninsured, metropolitan residence, Western United States hospital location, heart disease, renal failure, heart failure, hypertension (HTN), diabetes, osteoarthritis (OA), and chronic obstructive pulmonary disease (COPD). These factors were associated with higher odds of hospitalization: older age, Northeast location, metropolitan teaching hospital, higher income quartile, heart disease, renal failure, heart failure, hyperlipidemia, HTN, diabetes, COPD, and OA, whereas self-pay insurance status was associated with lower odds of hospitalization, following an ED visit for gout.
Conclusion. Absolute ED use and charges for gout increased over time, but relative use remained stable. Modifiable comorbidity factors associated with higher gout-related use should be targeted to reduce morbidity and healthcare use.
C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA.
[Singh, Jasvinder A.; Yu, Shaohua] UAB, Sch Med, Dept Med, Birmingham, AL USA.
[Singh, Jasvinder A.; Yu, Shaohua] UAB, Sch Publ Hlth, Div Epidemiol, Birmingham, AL USA.
[Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA.
RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA.
EM Jasvinder.md@gmail.com
FU UAB Division of Rheumatology; US National Institute of Arthritis and
Musculoskeletal and Skin Diseases [P50 AR060772]
FX Supported by research funds from the UAB Division of Rheumatology and
the resources and use of facilities at the Birmingham VA Medical Center.
JAS is also supported by a grant from the US National Institute of
Arthritis and Musculoskeletal and Skin Diseases (P50 AR060772).
NR 20
TC 1
Z9 1
U1 1
U2 1
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
EI 1499-2752
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2016
VL 43
IS 8
BP 1581
EP 1588
DI 10.3899/jrheum.151419
PG 8
WC Rheumatology
SC Rheumatology
GA DS6HG
UT WOS:000380882300021
ER
PT J
AU Hou, LP
Bergen, SE
Akula, N
Song, J
Hultman, CM
Landen, M
Adli, M
Alda, M
Ardau, R
Arias, B
Aubry, JM
Backlund, L
Badner, JA
Barrett, TB
Bauer, M
Baune, BT
Bellivier, F
Benabarre, A
Bengesser, S
Berrettini, WH
Bhattacharjee, AK
Biernacka, JM
Birner, A
Bloss, CS
Brichant-Petitjean, C
Bui, ET
Byerley, W
Cervantes, P
Chillotti, C
Cichon, S
Colom, F
Coryell, W
Craig, DW
Cruceanu, C
Czerski, PM
Davis, T
Dayer, A
Degenhardt, F
Del Zompo, M
DePaulo, JR
Edenberg, HJ
Etain, B
Falkai, P
Foroud, T
Forstner, AJ
Frisen, L
Frye, MA
Fullerton, JM
Gard, S
Garnham, JS
Gershon, ES
Goes, FS
Greenwood, TA
Grigoroiu-Serbanescu, M
Hauser, J
Heilbronner, U
Heilmann-Heimbach, S
Herms, S
Hipolito, M
Hitturlingappa, S
Hoffmann, P
Hofmann, A
Jamain, S
Jimenez, E
Kahn, JP
Kassem, L
Kelsoe, JR
Kittel-Schneider, S
Kliwicki, S
Koller, DL
Konig, B
Lackner, N
Laje, G
Lang, M
Lavebratt, C
Lawson, WB
Leboyer, M
Leckband, SG
Liu, CY
Maaser, A
Mahon, PB
Maier, W
Maj, M
Manchia, M
Martinsson, L
McCarthy, MJ
McElroy, SL
McInnis, MG
McKinney, R
Mitchell, PB
Mitjans, M
Mondimore, FM
Monteleone, P
Muhleisen, TW
Nievergelt, CM
Nothen, MM
Novak, T
Nurnberger, JI
Nwulia, EA
Osby, U
Pfennig, A
Potash, JB
Propping, P
Reif, A
Reininghaus, E
Rice, J
Rietschel, M
Rouleau, GA
Rybakowski, JK
Schalling, M
Scheftner, WA
Schofield, PR
Schork, NJ
Schulze, TG
Schumacher, J
Schweizer, BW
Severino, G
Shekhtman, T
Shilling, PD
Simhandl, C
Slaney, CM
Smith, EN
Squassina, A
Stamm, T
Stopkova, P
Streit, F
Strohmaier, J
Szelinger, S
Tighe, SK
Tortorella, A
Turecki, G
Vieta, E
Volkert, J
Witt, SH
Wright, A
Zandi, PP
Zhang, P
Zollner, S
McMahon, FJ
AF Hou, Liping
Bergen, Sarah E.
Akula, Nirmala
Song, Jie
Hultman, Christina M.
Landen, Mikael
Adli, Mazda
Alda, Martin
Ardau, Raffaella
Arias, Barbara
Aubry, Jean-Michel
Backlund, Lena
Badner, Judith A.
Barrett, Thomas B.
Bauer, Michael
Baune, Bernhard T.
Bellivier, Frank
Benabarre, Antonio
Bengesser, Susanne
Berrettini, Wade H.
Bhattacharjee, Abesh Kumar
Biernacka, Joanna M.
Birner, Armin
Bloss, Cinnamon S.
Brichant-Petitjean, Clara
Bui, Elise T.
Byerley, William
Cervantes, Pablo
Chillotti, Caterina
Cichon, Sven
Colom, Francesc
Coryell, William
Craig, David W.
Cruceanu, Cristiana
Czerski, Piotr M.
Davis, Tony
Dayer, Alexandre
Degenhardt, Franziska
Del Zompo, Maria
DePaulo, J. Raymond
Edenberg, Howard J.
Etain, Bruno
Falkai, Peter
Foroud, Tatiana
Forstner, Andreas J.
Frisen, Louise
Frye, Mark A.
Fullerton, Janice M.
Gard, Sebastien
Garnham, Julie S.
Gershon, Elliot S.
Goes, Fernando S.
Greenwood, Tiffany A.
Grigoroiu-Serbanescu, Maria
Hauser, Joanna
Heilbronner, Urs
Heilmann-Heimbach, Stefanie
Herms, Stefan
Hipolito, Maria
Hitturlingappa, Shashi
Hoffmann, Per
Hofmann, Andrea
Jamain, Stephane
Jimenez, Esther
Kahn, Jean-Pierre
Kassem, Layla
Kelsoe, John R.
Kittel-Schneider, Sarah
Kliwicki, Sebastian
Koller, Daniel L.
Koenig, Barbara
Lackner, Nina
Laje, Gonzalo
Lang, Maren
Lavebratt, Catharina
Lawson, William B.
Leboyer, Marion
Leckband, Susan G.
Liu, Chunyu
Maaser, Anna
Mahon, Pamela B.
Maier, Wolfgang
Maj, Mario
Manchia, Mirko
Martinsson, Lina
McCarthy, Michael J.
McElroy, Susan L.
McInnis, Melvin G.
McKinney, Rebecca
Mitchell, Philip B.
Mitjans, Marina
Mondimore, Francis M.
Monteleone, Palmiero
Muehleisen, Thomas W.
Nievergelt, Caroline M.
Noethen, Markus M.
Novak, Tomas
Nurnberger, John I., Jr.
Nwulia, Evaristus A.
Osby, Urban
Pfennig, Andrea
Potash, James B.
Propping, Peter
Reif, Andreas
Reininghaus, Eva
Rice, John
Rietschel, Marcella
Rouleau, Guy A.
Rybakowski, Janusz K.
Schalling, Martin
Scheftner, William A.
Schofield, Peter R.
Schork, Nicholas J.
Schulze, Thomas G.
Schumacher, Johannes
Schweizer, Barbara W.
Severino, Giovanni
Shekhtman, Tatyana
Shilling, Paul D.
Simhandl, Christian
Slaney, Claire M.
Smith, Erin N.
Squassina, Alessio
Stamm, Thomas
Stopkova, Pavla
Streit, Fabian
Strohmaier, Jana
Szelinger, Szabolcs
Tighe, Sarah K.
Tortorella, Alfonso
Turecki, Gustavo
Vieta, Eduard
Volkert, Julia
Witt, Stephanie H.
Wright, Adam
Zandi, Peter P.
Zhang, Peng
Zollner, Sebastian
McMahon, Francis J.
TI Genome-wide association study of 40,000 individuals identifies two novel
loci associated with bipolar disorder
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID TO-CASE RATIO; X-CHROMOSOME; GENETIC ASSOCIATION; STATISTICAL POWER;
SPECTRUM DISORDER; LITHIUM TREATMENT; COMPLEX TRAITS; RISK LOCI;
SCHIZOPHRENIA; POPULATION
AB Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behaviour. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used similar to 2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, P = 5.87 x 10(-9); odds ratio (OR) = 1.12) and markers within ERBB2 (rs2517959, P = 4.53 x 10(-9); OR = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
C1 [Hou, Liping; Akula, Nirmala; Bui, Elise T.; Kassem, Layla; Laje, Gonzalo; Schulze, Thomas G.; McMahon, Francis J.] NIMH, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Bergen, Sarah E.; Song, Jie; Hultman, Christina M.; Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Bergen, Sarah E.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Landen, Mikael] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden.
[Adli, Mazda; Stamm, Thomas] Charite, Campus Charite Mitte, Dept Psychiat & Psychotherapy, Berlin, Germany.
[Alda, Martin; Garnham, Julie S.; Slaney, Claire M.] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
[Ardau, Raffaella; Chillotti, Caterina] Hosp Univ Agcy Cagliari, Clin Pharmacol Unit, Cagliari, Italy.
[Arias, Barbara; Mitjans, Marina] Univ Barcelona, CIBERSAM, Dept Biol Anim, Unitat Antropol Dp Biol Anim,Fac Biol, Barcelona, Spain.
[Arias, Barbara; Mitjans, Marina] Univ Barcelona, CIBERSAM, Inst Biomed IBUB, Barcelona, Spain.
[Aubry, Jean-Michel; Dayer, Alexandre] Univ Hosp Geneva, Mood Disorders Unit, Dept Mental Hlth & Psychiat, Geneva, Switzerland.
[Backlund, Lena; Lavebratt, Catharina; Schalling, Martin] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Backlund, Lena; Lavebratt, Catharina; Osby, Urban; Schalling, Martin] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.
[Badner, Judith A.; Gershon, Elliot S.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Barrett, Thomas B.] Portland VA Med Ctr, Portland, OR USA.
[Bauer, Michael; Pfennig, Andrea] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, Dresden, Germany.
[Baune, Bernhard T.; Davis, Tony; Hitturlingappa, Shashi] Univ Adelaide, Discipline Psychiat, Adelaide, SA, Australia.
[Bellivier, Frank; Brichant-Petitjean, Clara] Univ Paris Diderot, INSERM UMR S 1144, Pole Psychiat, Grp Hosp Lariboisiere F Widal,AP HP, Paris, France.
[Benabarre, Antonio; Colom, Francesc; Jimenez, Esther; Vieta, Eduard] Univ Barcelona, IDIBAPS, CIBERSAM, Bipolar Disorder Program,Inst Neurosci,Hosp Clin, Barcelona, Spain.
[Bengesser, Susanne; Birner, Armin; Lackner, Nina; Reininghaus, Eva] Med Univ Graz, Special Outpatient Ctr Bipolar Affect Disorder, Graz, Austria.
[Berrettini, Wade H.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA.
[Bhattacharjee, Abesh Kumar; Greenwood, Tiffany A.; Kelsoe, John R.; McKinney, Rebecca; Nievergelt, Caroline M.; Shekhtman, Tatyana; Shilling, Paul D.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Biernacka, Joanna M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Biernacka, Joanna M.; Frye, Mark A.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA.
[Bloss, Cinnamon S.; Schork, Nicholas J.; Smith, Erin N.] Scripps Translat Sci Inst, La Jolla, CA USA.
[Byerley, William] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Cervantes, Pablo] McGill Univ, Ctr Hlth, Disorders Program, Montreal, PQ, Canada.
[Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Maaser, Anna; Muehleisen, Thomas W.; Noethen, Markus M.; Propping, Peter; Schumacher, Johannes] Univ Bonn, Inst Human Genet, Bonn, Germany.
[Cichon, Sven; Degenhardt, Franziska; Forstner, Andreas J.; Heilmann-Heimbach, Stefanie; Herms, Stefan; Hoffmann, Per; Hofmann, Andrea; Maaser, Anna; Muehleisen, Thomas W.; Noethen, Markus M.; Schumacher, Johannes] Univ Bonn, Life Brain Ctr, Dept Genom, Bonn, Germany.
[Cichon, Sven; Hoffmann, Per; Muehleisen, Thomas W.] Res Ctr Julich, Inst Neurosci & Med INM 1, Julich, Germany.
[Cichon, Sven; Herms, Stefan; Hoffmann, Per] Univ Basel, Div Med Genet, Basel, Switzerland.
[Cichon, Sven; Herms, Stefan; Hoffmann, Per] Univ Basel, Dept Biomed, Basel, Switzerland.
[Coryell, William] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[Craig, David W.; Szelinger, Szabolcs] Translat Genom Res Inst, Phoenix, AZ USA.
[Cruceanu, Cristiana; Turecki, Gustavo] McGill Univ, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada.
[Czerski, Piotr M.; Hauser, Joanna] Poznan Univ Med Sci, Psychiat Genet Unit, Poznan, Poland.
[Del Zompo, Maria; Manchia, Mirko; Severino, Giovanni; Squassina, Alessio] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy.
[DePaulo, J. Raymond; Goes, Fernando S.; Mahon, Pamela B.; Mondimore, Francis M.; Schulze, Thomas G.; Schweizer, Barbara W.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Edenberg, Howard J.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA.
[Etain, Bruno; Jamain, Stephane; Leboyer, Marion] Univ Paris Est Creteil, INSERM U955, Psychiat Translat, Pole Psychiat & Addictol,Hop Univ Henri Mondor, Creteil, France.
[Falkai, Peter] Ludwig Maximilians Univ Munchen, Dept Psychiat & Psychotherapy, Munich, Germany.
[Foroud, Tatiana; Koller, Daniel L.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA.
[Frisen, Louise; Martinsson, Lina] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Frisen, Louise] Child & Adolescent Psychiat Res Ctr, Stockholm, Sweden.
[Fullerton, Janice M.] Neurosci Res Australia, Psychiat Genet, Sydney, NSW, Australia.
[Fullerton, Janice M.; Schofield, Peter R.] Univ New South Wales, Sch Med Sci, Sydney, NSW 2052, Australia.
[Gard, Sebastien] Hop Charles Perrens, Psychiat Serv, Bordeaux, France.
[Grigoroiu-Serbanescu, Maria] Alexandru Obregia Clin Psychiat Hosp, Biometr Psychiat Genet Res Unit, Bucharest, Romania.
[Heilbronner, Urs; Schulze, Thomas G.] Ludwig Maximilians Univ Munchen, Inst Psychiat Phen & Genom, Munich, Germany.
[Heilbronner, Urs; Schulze, Thomas G.] Georg August Univ Gottingen, Univ Med Ctr, Dept Psychiat & Psychotherapy, Gottingen, Germany.
[Hipolito, Maria; Lawson, William B.; Nwulia, Evaristus A.] Howard Univ Hosp, Dept Psychiat & Behav Sci, Washington, DC USA.
[Kahn, Jean-Pierre] Univ Lorraine, Ctr Psychotherap Nancy, Serv Psychiat & Psychol Clin, Nancy, France.
[Kittel-Schneider, Sarah; Reif, Andreas; Volkert, Julia] Univ Hosp Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany.
[Kliwicki, Sebastian; Rybakowski, Janusz K.] Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland.
[Koenig, Barbara] Landesklinikum Neunkirchen, Dept Psychiat & Psychotherapeuth Med, Neunkirchen, Austria.
[Lang, Maren; Rietschel, Marcella; Schulze, Thomas G.; Streit, Fabian; Strohmaier, Jana; Witt, Stephanie H.] Heidelberg Univ, Dept Genet Epidemiol Psychiat, Cent Inst Mental Hlth, Med Fac Mannheim, Mannheim, Germany.
[Leckband, Susan G.] VA San Diego Healthcare Syst, Dept Pharm, San Diego, CA USA.
[Liu, Chunyu] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Maier, Wolfgang] Univ Bonn, Dept Psychiat, Bonn, Germany.
[Maj, Mario; Monteleone, Palmiero; Tortorella, Alfonso] Univ Naples SUN, Dept Psychiat, Naples, Italy.
[Manchia, Mirko] Dalhousie Univ, Dept Pharmacol, Halifax, NS, Canada.
[McCarthy, Michael J.] VA San Diego Healthcare Syst, Dept Psychiat, San Diego, CA USA.
[McElroy, Susan L.] Univ Cincinnati, Coll Med, Lindner Ctr HOPE, Mason, OH USA.
[McInnis, Melvin G.; Zhang, Peng; Zollner, Sebastian] Univ Michigan, Dept Psychiat, Ann Arbor, MI USA.
[Mitchell, Philip B.; Wright, Adam] Univ New South Wales, Sch Psychiat, Sydney, NSW, Australia.
[Mitchell, Philip B.; Wright, Adam] Black Dog Inst, Sydney, NSW, Australia.
[Monteleone, Palmiero] Univ Salerno, Dept Med & Surg, Neurosci Sect, Salerno, Italy.
[Novak, Tomas; Stopkova, Pavla] Natl Inst Mental Hlth, Klecany, Czech Republic.
[Nurnberger, John I., Jr.] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA.
[Nurnberger, John I., Jr.] Karolinska Inst, Dept Neurobiol Care Sci & Soc, Stockholm, Sweden.
[Potash, James B.; Tighe, Sarah K.] Univ Iowa, Sch Med, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA.
[Rice, John] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Rouleau, Guy A.] McGill Univ, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada.
[Scheftner, William A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Schofield, Peter R.] Neurosci Res Australia, Mental Illness, Sydney, NSW, Australia.
[Simhandl, Christian] Bipolar Ctr Wiener Neustadt, Wiener Neustadt, Austria.
[Zandi, Peter P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
RP McMahon, FJ (reprint author), NIMH, Human Genet Branch, Intramural Res Program, 35 Convent Dr,Rm 1A201, Bethesda, MD 20892 USA.
EM mcmahonf@mail.nih.gov
OI Mitjans, Marina/0000-0001-5543-7320; Novak, Tomas/0000-0001-9156-9654;
Squassina, Alessio/0000-0001-7415-7607; Maaser,
Anna/0000-0002-9440-0712; Dayer, Alexandre/0000-0002-4490-9780
FU National Institute of Mental Health (NIMH) [ZIA-MH00284311]; NARSAD
Young Investigator Award
FX This work was supported by the National Institute of Mental Health
(NIMH) Intramural Research Program (ZIA-MH00284311; NCT00001174) and a
NARSAD Young Investigator Award to L.H.
NR 62
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U1 4
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD AUG 1
PY 2016
VL 25
IS 15
BP 3383
EP 3394
DI 10.1093/hmg/ddw181
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA EJ2YK
UT WOS:000393077300018
PM 27329760
ER
PT J
AU Newman, AB
Sanders, JL
Kizer, JR
Boudreau, RM
Odden, MC
Al Hazzouri, AZ
Arnold, AM
AF Newman, Anne B.
Sanders, Jason L.
Kizer, Jorge R.
Boudreau, Robert M.
Odden, Michelle C.
Al Hazzouri, Adina Zeki
Arnold, Alice M.
TI Trajectories of function and biomarkers with age: the CHS All Stars
Study
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Ageing; disability; gait speed; grip strength; cognitive function;
biomarkers
ID CHRONIC KIDNEY-DISEASE; DISABLED OLDER WOMEN; DNA METHYLATION AGE;
CARDIOVASCULAR HEALTH; CYSTATIN-C; DEHYDROEPIANDROSTERONE-SULFATE;
PREDICT MORTALITY; BODY-COMPOSITION; GAIT SPEED; ALL-CAUSE
AB Background: Multimorbidity is a major driver of physical and cognitive impairment, but rates of decline are also related to ageing. We sought to determine trajectories of decline in a large cohort by disease status, and examined their correspondence with biomarkers of ageing processes including growth hormone, sex steroid, inflammation, visceral adiposity and kidney function pathways.
Methods: We have followed the 5888 participants in the Cardiovascular Health Study (CHS) for healthy ageing and longevity since 1989-90. Gait speed, grip strength, modified mini-mental status examination (3MSE) and the digit symbol substitution test (DSST) were assessed annually to 1998-99 and again in 2005-06. Insulin-like growth hormone (IGF-1), dehydroepiandrosterone sulphate (DHEAS), interleukin-6 (IL-6), adiponectin and cystatin-C were assessed 3-5 times from stored samples. Health status was updated annually and dichotomized as healthy vs not healthy. Trajectories for each function measure and biomarker were estimated using generalized estimating equations as a function of age and health status using standardized values.
Results: Trajectories of functional decline showed strong age acceleration late in life in healthy older men and women as well as in chronically ill older adults. Adiponectin, IL-6 and cystatin-C tracked with functional decline in all domains; cystatin-C was consistently associated with functional declines independent of other biomarkers. DHEAS was independently associated with grip strength and IL-6 with grip strength and gait speed trajectories.
Conclusion: Functional decline in late life appears to mark a fundamental ageing process in that it occurred and was accelerated in late life regardless of health status. Cystatin C was most consistently associated with these functional declines.
C1 [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA.
[Sanders, Jason L.] Massachusetts Gen Hosp, Harvard Affiliated Emergency Med Residency, Boston, MA 02114 USA.
[Sanders, Jason L.] Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Boudreau, Robert M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Odden, Michelle C.] Oregon State Univ, Dept Epidemiol, Corvallis, OR 97331 USA.
[Al Hazzouri, Adina Zeki] Univ Miami, Dept Epidemiol, Miami, FL USA.
[Arnold, Alice M.] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA.
RP Newman, AB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, A527 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15261 USA.
EM newmana@edc.pitt.edu
FU National Institute on Ageing (NIA) [AG023629, HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086]; National Heart, Lung, and Blood
Institute (NHLBI) [HL080295]; University of Pittsburgh Claude D. Pepper
Older Americans Independence Center [P30-AG-024827]
FX This research was supported by AG023629 from the National Institute on
Ageing (NIA) and contracts HHSN268201200036C, HHSN268200800007C,
N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083
and N01HC85086, and grant HL080295, from the National Heart, Lung, and
Blood Institute (NHLBI), with additional contribution from the National
Institute of Neurological Disorders and Stroke (NINDS). Additional
support was provided by the University of Pittsburgh Claude D. Pepper
Older Americans Independence Center: P30-AG-024827.
NR 57
TC 1
Z9 1
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD AUG
PY 2016
VL 45
IS 4
BP 1135
EP 1145
DI 10.1093/ije/dyw092
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA EJ4JD
UT WOS:000393182000028
PM 27272182
ER
PT J
AU Hsieh, DT
Whiteway, SL
Rohena, LO
Thiele, EA
AF Hsieh, David T.
Whiteway, Susan L.
Rohena, Luis O.
Thiele, Elizabeth A.
TI Tuberous sclerosis complex Five new things
SO NEUROLOGY-CLINICAL PRACTICE
LA English
DT Review
ID GIANT-CELL ASTROCYTOMA; NEUROPSYCHIATRIC DISORDERS TAND; INFANTILE
SPASMS; EPILEPSY SURGERY; CORTICAL TUBERS; EVEROLIMUS; CHILDREN;
VIGABATRIN; DIFFUSION; ABNORMALITIES
AB Purpose of review: Tuberous sclerosis complex (TSC) is a variably expressed neurocutaneous genetic disorder characterized by hamartomatous growths inmultiple organ systems. Neurologic involvement often confers the most severe symptoms, and can include epilepsy, increased intracranial pressure from hydrocephalus, intellectual deficits, and autism. The purpose of this review is to provide a neurologically focused update in the diagnosis and treatment of these complications in patients with TSC. Recent findings: We highlight 5 new areas of understanding in TSC: the neurobiology of TSC and its translation into clinical practice, vigabatrin in the treatment of infantile spasms, the role of tubers and epilepsy surgery, the treatment of subependymal giant cell astrocytomas, and TSC-related neuropsychiatric disorders. Summary: These recent advances in diagnosis and treatment give our patients with TSC and their families hope for the future for improved care and possible preventive cures, to the end goal of improving quality of life.
C1 [Hsieh, David T.] San Antonio Mil Med Ctr, Dept Pediat, Div Child Neurol, Jbsa Ft Sam Houston, TX USA.
[Whiteway, Susan L.] San Antonio Mil Med Ctr, Dept Pediat, Div Hematol Oncol, Jbsa Ft Sam Houston, TX USA.
[Rohena, Luis O.] San Antonio Mil Med Ctr, Dept Pediat, Div Med Genet, Jbsa Ft Sam Houston, TX USA.
[Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Pediat Epilepsy Program, Boston, MA 02114 USA.
RP Hsieh, DT (reprint author), San Antonio Mil Med Ctr, Dept Pediat, Div Child Neurol, Jbsa Ft Sam Houston, TX USA.
EM david.t.hsieh.mil@mail.mil
NR 46
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 2163-0402
EI 2163-0933
J9 NEUROL-CLIN PRACT
JI Neurol.-Clin. Pract.
PD AUG
PY 2016
VL 6
IS 4
BP 339
EP 347
DI 10.1212/CPJ.0000000000000260
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA EJ3GW
UT WOS:000393101600012
ER
PT J
AU Soni, NJ
Franco-Sadud, R
Schnobrich, D
Dancel, R
Tierney, DM
Salame, G
Restrepo, MI
McHardy, P
AF Soni, Nilam J.
Franco-Sadud, Ricardo
Schnobrich, Daniel
Dancel, Ria
Tierney, David M.
Salame, Gerard
Restrepo, Marcos I.
McHardy, Paul
TI Ultrasound guidance for lumbar puncture
SO NEUROLOGY-CLINICAL PRACTICE
LA English
DT Review
ID GUIDED SPINAL-ANESTHESIA; EPIDURAL-ANESTHESIA; EMERGENCY-DEPARTMENT;
LANDMARKS; SPACE; ULTRASONOGRAPHY; LEVEL; IDENTIFICATION; VISUALIZATION;
METAANALYSIS
AB Purpose of review: To review the literature and describe techniques to use ultrasound to guide performance of lumbar puncture (LP). Recent findings: Ultrasound evaluation of the lumbar spine has been shown in randomized trials to improve LP success rates while reducing the number of attempts and the number of traumatic taps. Summary: Ultrasound mapping of the lumbar spine reveals anatomical information that is not obtainable by physical examination, including depth of the ligamentum flavum, width of the interspinous spaces, and spinal bone abnormalities, including scoliosis. Using static ultrasound, the lumbar spine anatomy is visualized in transverse and longitudinal planes and the needle insertion site is marked. Using real-time ultrasound guidance, the needle tip is tracked in a paramedian plane as it traverses toward the ligamentum flavum. Future research should focus on efficient methods to train providers, cost-effectiveness of ultrasound-guided LP, and the role of new needle-tracking technologies to facilitate the procedure.
C1 [Soni, Nilam J.] South Texas Vet Hlth Care Syst, Sect Hosp Med, San Antonio, TX USA.
[Soni, Nilam J.; Restrepo, Marcos I.] South Texas Vet Hlth Care Syst, Sect Pulm & Crit Care Med, San Antonio, TX USA.
Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Franco-Sadud, Ricardo] Med Coll Wisconsin, Div Gen Internal Med, Sect Hosp Med, Milwaukee, WI 53226 USA.
[Schnobrich, Daniel] Univ Minnesota, Div Gen Internal Med, Minneapolis, MN USA.
[Dancel, Ria] Univ N Carolina, Div Gen Med & Epidemiol, Chapel Hill, NC USA.
[Tierney, David M.] Abbott NW Hosp, Dept Med Educ, Minneapolis, MN USA.
[Salame, Gerard] Univ Colorado, Denver Hlth Hosp, Div Hosp Med, Boulder, CO 80309 USA.
[McHardy, Paul] Sunnybrook Hlth Sci Ctr, Dept Anesthesia, Toronto, ON, Canada.
RP Soni, NJ (reprint author), South Texas Vet Hlth Care Syst, Sect Hosp Med, San Antonio, TX USA.; Soni, NJ (reprint author), South Texas Vet Hlth Care Syst, Sect Pulm & Crit Care Med, San Antonio, TX USA.
EM sonin@uthscsa.edu
FU National Heart, Lung, and Blood Institute [K23HL096054]
FX Partially supported by award K23HL096054 (MIR) from the National Heart,
Lung, and Blood Institute.
NR 42
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 2163-0402
EI 2163-0933
J9 NEUROL-CLIN PRACT
JI Neurol.-Clin. Pract.
PD AUG
PY 2016
VL 6
IS 4
BP 358
EP 368
DI 10.1212/CPJ.0000000000000265
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA EJ3GW
UT WOS:000393101600014
ER
PT J
AU Zapata, JA
Widera, E
AF Zapata, Josue A.
Widera, Eric
TI Partial Codes-A Symptom of a Larger Problem
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Zapata, Josue A.] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA.
[Zapata, Josue A.] San Francisco VA Med Ctr, Div Hosp Med, San Francisco, CA USA.
[Widera, Eric] San Francisco VA Med Ctr, Palliat Care & Hosp Serv, San Francisco, CA USA.
[Widera, Eric] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA.
RP Zapata, JA (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Dept Internal Med, 4150 Clement St,Bldg 203,1A-81, San Francisco, CA 94121 USA.
EM josue.zapata@ucsf.edu
NR 8
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD AUG
PY 2016
VL 176
IS 8
BP 1058
EP 1059
DI 10.1001/jamainternmed.2016.2540
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT0AN
UT WOS:000381145000005
PM 27295527
ER
PT J
AU Leventhal, JS
Ross, MJ
AF Leventhal, Jeremy S.
Ross, Michael J.
TI LAPping up dead cells to prevent lupus nephritis: a novel role for
noncanonical autophagy in autoimmunity
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID DEFICIENCY; CLEARANCE
AB The mechanisms underlying the development of systemic lupus erythematosus and lupus nephritis remain poorly understood. A recent study demonstrates that deficiencies in the immune system's ability to degrade scavenged dead cells via noncanonical autophagy is sufficient to break immune tolerance and produce features commonly seen in lupus, including circulating autoantibodies, inflammatory cytokines, and nephritis. This work provides a possible mechanism for the association of polymorphisms in autophagy genes with the risk of lupus.
C1 [Leventhal, Jeremy S.; Ross, Michael J.] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
[Leventhal, Jeremy S.; Ross, Michael J.] James J Peters Bronx Vet Affairs Med Ctr, Div Renal, Bronx, NY USA.
RP Leventhal, JS (reprint author), Icahn Sch Med Mt Sinai, Div Nephrol, 1 Gustave L Levy Pl,Box 1243, New York, NY 10029 USA.
EM Jeremy.leventhal@mssm.edu
FU NIDDK NIH HHS [K08 DK090217]
NR 9
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 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD AUG
PY 2016
VL 90
IS 2
BP 238
EP 239
DI 10.1016/j.kint.2016.06.001
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA EI6BZ
UT WOS:000392581300001
PM 27418084
ER
PT J
AU Mino-Kenudson, M
AF Mino-Kenudson, Mari
TI Cons: Can liquid biopsy replace tissue biopsy?-the US experience
SO TRANSLATIONAL LUNG CANCER RESEARCH
LA English
DT Editorial Material
ID LUNG-CANCER PATIENTS; NUCLEIC-ACIDS; PLASMA DNA; ADENOCARCINOMA;
CLASSIFICATION; BIOMARKERS; SOCIETY; NSCLC; CELLS
C1 [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 20
TC 2
Z9 2
U1 2
U2 2
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 2218-6751
EI 2226-4477
J9 TRANSL LUNG CANCER R
JI Transl. Lung Cancer Res.
PD AUG
PY 2016
VL 5
IS 4
BP 424
EP 427
DI 10.21037/tlcr.2016.08.01
PG 4
WC Oncology
SC Oncology
GA EI5QK
UT WOS:000392549200010
PM 27655060
ER
PT J
AU Mino-Kenudson, M
AF Mino-Kenudson, Mari
TI Rebuttal from Dr. Mino-Kenudson
SO TRANSLATIONAL LUNG CANCER RESEARCH
LA English
DT Editorial Material
ID CIRCULATING TUMOR DNA; LUNG-CANCER PATIENTS; ADENOCARCINOMA; PLASMA;
QUANTIFICATION; BIOMARKERS; EXPERIENCE; MUTATIONS; BIOPSIES; TISSUE
C1 [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 17
TC 1
Z9 1
U1 1
U2 1
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 2218-6751
EI 2226-4477
J9 TRANSL LUNG CANCER R
JI Transl. Lung Cancer Res.
PD AUG
PY 2016
VL 5
IS 4
BP 430
EP 432
DI 10.21037/tlcr.2016.08.02
PG 3
WC Oncology
SC Oncology
GA EI5QK
UT WOS:000392549200012
PM 27657667
ER
PT J
AU Navar, AM
Peterson, ED
Li, S
Goldberg, AC
Virani, SS
Roger, VL
Robinson, JG
Wilson, PWF
Elassal, J
Lee, LV
Wang, TY
AF Navar, A. M.
Peterson, E. D.
Li, S.
Goldberg, A. C.
Virani, S. S.
Roger, V. L.
Robinson, J. G.
Wilson, P. W. F.
Elassal, J.
Lee, L. V.
Wang, T. Y.
TI Are clinicians following statin intensity recommendations? Insights in
135 U.S community practices in the PALM registry
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Navar, A. M.; Peterson, E. D.; Li, S.; Wang, T. Y.] Duke Clin Res Inst, Durham, NC USA.
[Goldberg, A. C.] Washington Univ, Sch Med, St Louis, MO USA.
[Virani, S. S.] VA Med Ctr, Houston, TX USA.
[Roger, V. L.] Mayo Clin, Rochester, MN USA.
[Robinson, J. G.] Univ Iowa, Iowa City, IA USA.
[Wilson, P. W. F.] Emory Univ, Atlanta, GA 30322 USA.
[Elassal, J.] Regeneron Pharmaceut Inc, 777 Old Saw Mill River Rd, Tarrytown, NY 10591 USA.
[Lee, L. V.] Sanofi Pharmaceut, Bridgewater, MA 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 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 273
BP 32
EP 32
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869500098
ER
PT J
AU Verjans, JW
Ughi, GJ
Osborn, EA
Gerboud, EM
Takx, RA
Tawakol, A
Tearney, GJ
Jaffer, FA
AF Verjans, J. W.
Ughi, G. J.
Osborn, E. A.
Gerboud, E. M.
Takx, R. A.
Tawakol, A.
Tearney, G. J.
Jaffer, F. A.
TI Multimodality intravascular molecular imaging of inflammation and
endothelial permeability independently predicts plaque progression over
time
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Verjans, J. W.] Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands.
[Ughi, G. J.; Tearney, G. J.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.
[Osborn, E. A.; Tawakol, A.; Jaffer, F. A.] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA USA.
[Gerboud, E. M.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
[Takx, R. A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P519
BP 51
EP 52
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869500157
ER
PT J
AU Stefanescu, A
Armstrong, A
Kennedy, KF
Nykanen, D
Aboulhosn, J
Bhatt, AB
AF Stefanescu, A.
Armstrong, A.
Kennedy, K. F.
Nykanen, D.
Aboulhosn, J.
Bhatt, A. B.
TI Risk factors for adverse events after catheter-based procedures in
adolescents and adults with congenital heart disease - a report from the
IMPACT registry
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Stefanescu, A.; Bhatt, A. B.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA.
[Armstrong, A.] Nationwide Childrens Hosp, Cardiol, St Louis, MO USA.
[Kennedy, K. F.] St Lukes Hosp, Kansas City, MO USA.
[Nykanen, D.] Arnold Palmer Hosp Children Cardiol & Cardiac Cat, Orlando, FL USA.
[Aboulhosn, J.] Univ Calif Los Angeles, Los Angeles, CA 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 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 1116
BP 201
EP 202
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501030
ER
PT J
AU Wolsk, E
Claggett, B
Kober, L
Diaz, R
Dickstein, K
Gerstein, HC
Lawson, FC
Bentley-Lewis, R
Maggioni, AP
McMurray, JJV
Probstfield, JL
Riddle, MC
Solomon, SD
Tardif, JC
Pfeffer, MA
AF Wolsk, E.
Claggett, B.
Kober, L.
Diaz, R.
Dickstein, K.
Gerstein, H. C.
Lawson, F. C.
Bentley-Lewis, R.
Maggioni, A. P.
McMurray, J. J. V.
Probstfield, J. L.
Riddle, M. C.
Solomon, S. D.
Tardif, J. -C.
Pfeffer, M. A.
TI Changes in BNP prior to major cardiovascular events in patients with
type 2 diabetes and a recent coronary event
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Wolsk, E.; Claggett, B.; Solomon, S. D.; Pfeffer, M. A.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Kober, L.] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
[Diaz, R.] Estudios Cardiol Latinoamer ECLA, Rosario, Santa Fe, Argentina.
[Dickstein, K.] Univ Bergen, Bergen, Norway.
[Gerstein, H. C.] McMaster Univ, Hamilton, ON, Canada.
[Lawson, F. C.] Sanofi US, Bridgewater, MA USA.
[Bentley-Lewis, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Maggioni, A. P.] Assoc Nazl Med Cardiol Osped Res Ctr, Florence, Italy.
[McMurray, J. J. V.] Cardiovasc Res Ctr Glasgow, Glasgow, Lanark, Scotland.
[Probstfield, J. L.] Univ Washington, Seattle, WA 98195 USA.
[Riddle, M. C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Tardif, J. -C.] Montreal Heart Inst, Montreal, PQ, Canada.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P1173
BP 220
EP 220
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501086
ER
PT J
AU Jiannan, J
Xing, L
Hou, J
Jia, H
Hu, S
Tian, J
Lin, L
Li, L
Zhu, Y
Zheng, G
Ren, X
Yu, H
Zhang, S
Yu, B
Jang, IK
AF Jiannan, J.
Xing, L.
Hou, J.
Jia, H.
Hu, S.
Tian, J.
Lin, L.
Li, L.
Zhu, Y.
Zheng, G.
Ren, X.
Yu, H.
Zhang, S.
Yu, B.
Jang, I. K.
TI Comparison of three chronic kidney disease epidemiology collaboration
(CKD-EPI) equations for prediction of coronary plaque vulnerability: an
optical coherence tomography study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Jiannan, J.; Xing, L.; Hou, J.; Jia, H.; Hu, S.; Tian, J.; Lin, L.; Li, L.; Zhu, Y.; Zheng, G.; Ren, X.; Yu, H.; Zhang, S.; Yu, B.] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China.
[Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 1309
BP 231
EP 231
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501120
ER
PT J
AU Yin, O
Miller, R
Ruff, CT
Morrow, D
Antman, EM
Mercuri, M
Braunwald, E
Giugliano, RP
Truitt, K
AF Yin, O.
Miller, R.
Ruff, C. T.
Morrow, D.
Antman, E. M.
Mercuri, M.
Braunwald, E.
Giugliano, R. P.
Truitt, K.
TI Linking intrinsic factor X activity, a biologically relevant
pharmacodynamic marker, to edoxaban plasma concentration and clinical
outcomes in the ENGAGE AF-TIMI 48 trial
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Yin, O.; Miller, R.; Mercuri, M.; Truitt, K.] Daiichi Sankyo Pharma Dev, Edison, NJ USA.
[Ruff, C. T.; Morrow, D.; Antman, E. M.; Braunwald, E.; Giugliano, R. P.] Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 1354
BP 234
EP 235
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501130
ER
PT J
AU Zhu, YC
Zheng, GH
Hu, SN
Jia, HB
Dai, JN
Li, LL
Wang, C
Afolabi, A
Mustafina, I
Hou, JB
Zhang, SS
Yu, B
Jang, IK
AF Zhu, Y. C.
Zheng, G. H.
Hu, S. N.
Jia, H. B.
Dai, J. N.
Li, L. L.
Wang, C.
Afolabi, A.
Mustafina, I.
Hou, J. B.
Zhang, S. S.
Yu, B.
Jang, I. K.
TI Relation between lipid lowering therapy and plaque progression based on
10-year framingham risk score: an optical coherence tomography study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Zhu, Y. C.; Zheng, G. H.; Hu, S. N.; Jia, H. B.; Dai, J. N.; Li, L. L.; Wang, C.; Afolabi, A.; Mustafina, I.; Hou, J. B.; Yu, B.] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China.
[Zhang, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P1382
BP 243
EP 243
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501155
ER
PT J
AU Tanimoto, T
Parsenghian, MH
Petrov, AD
Nakahara, T
Kawai, H
Nishimura, R
Weisbart, RH
Chan, G
Richieri, RA
Reynolds, GT
Sengupta, PP
Haider, N
Blankenberg, FG
Strauss, HW
Narula, J
AF Tanimoto, T.
Parsenghian, M. H.
Petrov, A. D.
Nakahara, T.
Kawai, H.
Nishimura, R.
Weisbart, R. H.
Chan, G.
Richieri, R. A.
Reynolds, G. T.
Sengupta, P. P.
Haider, N.
Blankenberg, F. G.
Strauss, H. W.
Narula, J.
TI Cardioprotective effects of Fv-HSP70 injection on ischemic/reperfusion
injury
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Tanimoto, T.; Petrov, A. D.; Nakahara, T.; Kawai, H.; Sengupta, P. P.; Haider, N.; Strauss, H. W.; Narula, J.] Mt Sinai Sch Med, Cardiol, New York, NY USA.
[Parsenghian, M. H.; Richieri, R. A.; Reynolds, G. T.] Rubicon Biotechnol, Lake Forest, IL USA.
[Nishimura, R.; Weisbart, R. H.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Chan, G.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Blankenberg, F. G.] Lucile Salter Packard Childrens Hosp, Stanford, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P1801
BP 370
EP 370
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501567
ER
PT J
AU Fanola, CL
Giugliano, RP
Trevisan, M
Nordio, F
Ruff, CT
Antman, EM
Braunwald, E
AF Fanola, C. L.
Giugliano, R. P.
Trevisan, M.
Nordio, F.
Ruff, C. T.
Antman, E. M.
Braunwald, E.
CA TIMI Study Grp
TI A novel risk prediction score in atrial fibrillation for a net clinical
outcome from the ENGAGE AF-TIMI 48 randomized clinical trial
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Fanola, C. L.; Giugliano, R. P.; Trevisan, M.; Nordio, F.; Ruff, C. T.; Antman, E. M.; Braunwald, E.; TIMI Study Grp] Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 1876
BP 393
EP 394
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869501643
ER
PT J
AU Hilgendorf, I
Lindau, A
Haerdtner, C
Hergeth, S
Dufner, B
Hoppe, N
Stachon, P
Willecke, F
Wolf, D
Robbins, CS
Swirski, FK
Libby, P
Bode, C
Zirlik, A
AF Hilgendorf, I.
Lindau, A.
Haerdtner, C.
Hergeth, S.
Dufner, B.
Hoppe, N.
Stachon, P.
Willecke, F.
Wolf, D.
Robbins, C. S.
Swirski, F. K.
Libby, P.
Bode, C.
Zirlik, A.
TI SYK inhibitor fostamtinib protects from early but not established
atherosclerosis when local macrophage proliferation dominates lesion
turnover
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Hilgendorf, I.; Lindau, A.; Haerdtner, C.; Hergeth, S.; Dufner, B.; Hoppe, N.; Stachon, P.; Willecke, F.; Wolf, D.; Bode, C.; Zirlik, A.] Univ Freiburg, Heart Ctr Freiburg, Freiburg, Germany.
[Robbins, C. S.] Toronto Gen Hosp, Toronto, ON, Canada.
[Swirski, F. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Libby, P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P2408
BP 453
EP 454
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869502179
ER
PT J
AU Piccini, J
Goodman, S
Levitan, B
Yuan, Z
Hankey, GJ
Singer, DE
Becker, R
Breithardt, G
Berkowitz, S
Halperin, J
Nessel, C
Hacke, W
Mahaffey, KW
Fox, KAA
Patel, MR
AF Piccini, J.
Goodman, S.
Levitan, B.
Yuan, Z.
Hankey, G. J.
Singer, D. E.
Becker, R.
Breithardt, G.
Berkowitz, S.
Halperin, J.
Nessel, C.
Hacke, W.
Mahaffey, K. W.
Fox, K. A. A.
Patel, M. R.
CA ROCKET AF
TI Net clinical benefit of rivaroxaban compared with warfarin in patients
with atrial fibrillation
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Piccini, J.; Patel, M. R.] Duke Clin Res Inst, Durham, England.
[Goodman, S.] Univ Toronto, Toronto, ON, Canada.
[Levitan, B.; Yuan, Z.; Nessel, C.] Johnson & Johnson Pharmaceut, Raritan, NJ USA.
[Hankey, G. J.] Univ Western Australia, Perth, WA, Australia.
[Singer, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Becker, R.] Univ Cincinnati, Cincinnati, OH USA.
[Breithardt, G.] Univ Med Ctr, Munster, Germany.
[Berkowitz, S.] Bayer HealthCare Pharmaceut, Whippany, NJ USA.
[Halperin, J.] Mt Sinai Sch Med, New York, NY USA.
[Hacke, W.] Heidelberg Univ, Heidelberg, Germany.
[Mahaffey, K. W.] Stanford Univ, Palo Alto, CA 94304 USA.
[Fox, K. A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
NR 0
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P2566
BP 500
EP 500
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869502333
ER
PT J
AU Orgel, R
Wojdyla, D
Huberman, D
Becker, RC
Berkowitz, SD
Breithardt, G
Hacke, W
Halperin, JL
Hankey, GJ
Mahaffey, KW
Nessel, CC
Singer, DE
Fox, KAA
Jones, WS
Patel, MR
AF Orgel, R.
Wojdyla, D.
Huberman, D.
Becker, R. C.
Berkowitz, S. D.
Breithardt, G.
Hacke, W.
Halperin, J. L.
Hankey, G. J.
Mahaffey, K. W.
Nessel, C. C.
Singer, D. E.
Fox, K. A. A.
Jones, W. S.
Patel, M. R.
TI Systemic embolization in patients with atrial fibrillation: results from
ROCKET AF
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Orgel, R.; Wojdyla, D.; Jones, W. S.; Patel, M. R.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Huberman, D.] North Carolina State Univ, Dept Stat, Raleigh, NC USA.
[Becker, R. C.] Univ Cincinnati, Cincinnati, OH USA.
[Berkowitz, S. D.] Bayer HealthCare, Whippany, NJ USA.
[Breithardt, G.] Univ Hosp Munster, Munster, Germany.
[Hacke, W.] Heidelberg Univ, Heidelberg, Germany.
[Halperin, J. L.] Mt Sinai Sch Med, New York, NY USA.
[Hankey, G. J.] Univ Western Australia, Sch Med & Pharmacol, Crawley, Australia.
[Mahaffey, K. W.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Nessel, C. C.] Janssen Pharmaceut Res & Dev, Raritan, NJ USA.
[Singer, D. E.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Fox, K. A. A.] Univ Edinburgh, Royal Infirm Edinburgh, Edinburgh, Midlothian, Scotland.
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P2602
BP 511
EP 511
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869502369
ER
PT J
AU Papafaklis, MI
Vergallo, R
Andreou, I
Yonetsu, T
Bourantas, CV
Sakellarios, A
Fotiadis, DI
Feldman, CL
Michalis, LK
Jang, IK
Stone, PH
AF Papafaklis, M. I.
Vergallo, R.
Andreou, I.
Yonetsu, T.
Bourantas, C. V.
Sakellarios, A.
Fotiadis, D. I.
Feldman, C. L.
Michalis, L. K.
Jang, I. K.
Stone, P. H.
TI Prediction of culprit lesions in patients with acute coronary syndrome
by assessing the hemodynamic forces acting on plaques: a
three-dimensional frequency-domain optical coherence tomography study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Papafaklis, M. I.; Andreou, I.; Feldman, C. L.; Stone, P. H.] Harvard Med Sch, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA.
[Vergallo, R.; Yonetsu, T.; Jang, I. K.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Bourantas, C. V.] UCL, Dept Cardiovasc Sci, London, England.
[Sakellarios, A.; Fotiadis, D. I.] Univ Ioannina, Dept Mat Sci, Ioannina, Greece.
[Michalis, L. K.] Univ Ioannina, Sch Med, Dept Cardiol 2, Ioannina, Greece.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 2988
BP 600
EP 600
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869503002
ER
PT J
AU Hu, S
Jia, H
Xing, L
Hou, J
Hang, L
Zhang, S
Yu, B
Jang, IK
AF Hu, S.
Jia, H.
Xing, L.
Hou, J.
Hang, L.
Zhang, S.
Yu, B.
Jang, I. K.
TI Vascular healing is delayed after drug-eluting stent implantation in
patients with acute coronary syndromes caused by plaque erosion compared
to plaque rupture: an optical coherence tomography study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Hu, S.; Jia, H.; Hou, J.; Zhang, S.; Yu, B.] Harbin Med Univ, Dept Cardiol, Affiliated Hosp 2, Harbin, Peoples R China.
[Xing, L.; Jang, I. K.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Hang, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 3079
BP 606
EP 607
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869503022
ER
PT J
AU Afolabi, A
Hu, S
Jia, H
Li, L
Dai, J
Feng, L
Zhu, Y
Zheng, G
Wang, C
Dai, Z
Mustafina, I
Hou, J
Zhang, S
Yu, B
Jang, I
AF Afolabi, A.
Hu, S.
Jia, H.
Li, L.
Dai, J.
Feng, L.
Zhu, Y.
Zheng, G.
Wang, C.
Dai, Z.
Mustafina, I.
Hou, J.
Zhang, S.
Yu, B.
Jang, I.
TI Does spotty calcification attenuate the plaque progression in
non-culprit plaque underlying lipid-lowering therapy: an midterm optical
coherence tomography study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Afolabi, A.; Hu, S.; Jia, H.; Li, L.; Dai, J.; Feng, L.; Zhu, Y.; Zheng, G.; Wang, C.; Dai, Z.; Mustafina, I.; Hou, J.; Yu, B.] Harbin Med Univ, Affiliated Hosp 2, Harbin, Peoples R China.
[Afolabi, A.; Hu, S.; Jia, H.; Li, L.; Dai, J.; Feng, L.; Zhu, Y.; Zheng, G.; Wang, C.; Dai, Z.; Mustafina, I.; Hou, J.; Yu, B.] Key Lab Myocardial Ischemia, Dept Cardiol, Harbin, Peoples R China.
[Zhang, S.] Harbin Med Univ, Affiliated Hosp 2, Dept Cardiol, Harbin, Peoples R China.
[Jang, I.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P3464
BP 680
EP 681
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869503262
ER
PT J
AU Piccini, J
Washam, JB
Simon, DN
Thomas, LE
Hylek, EM
Fonarow, GC
Mahaffey, KW
Gersh, BJ
Kowey, PR
Ansell, JE
Go, AS
Reiffel, JA
Singer, DE
Pokorney, SD
Peterson, ED
AF Piccini, J.
Washam, J. B.
Simon, D. N.
Thomas, L. E.
Hylek, E. M.
Fonarow, G. C.
Mahaffey, K. W.
Gersh, B. J.
Kowey, P. R.
Ansell, J. E.
Go, A. S.
Reiffel, J. A.
Singer, D. E.
Pokorney, S. D.
Peterson, E. D.
CA ORBIT AF Investigators
TI Pharmacotherapy for atrial fibrillation in patients with chronic kidney
disease: insights from the outcomes registry for better informed
treatment of atrial fibrillation (ORBIT AF)
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Piccini, J.; Washam, J. B.; Simon, D. N.; Thomas, L. E.; Pokorney, S. D.; Peterson, E. D.] Duke Clin Res Inst, Durham, NC USA.
[Hylek, E. M.] Boston Univ, Boston, MA 02215 USA.
[Fonarow, G. C.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Mahaffey, K. W.] Stanford Univ, Palo Alto, CA 94304 USA.
[Gersh, B. J.] Mayo Clin, Rochester, MN USA.
[Kowey, P. R.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Ansell, J. E.] Lenox Hill Hosp, New York, NY 10021 USA.
[Go, A. S.] Kaiser Permanente No Calif, Oakland, CA USA.
[Reiffel, J. A.] Columbia Univ, New York, NY USA.
[Singer, D. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P3479
BP 685
EP 685
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869503277
ER
PT J
AU Halbach, M
Abraham, WT
Butter, C
Ducharme, A
Klug, D
Little, WC
Lovett, E
Schafer, JE
Senni, E
Swarup, V
Wachter, R
Weaver, FA
Zile, MR
Muller-Ehmsen, J
AF Halbach, M.
Abraham, W. T.
Butter, C.
Ducharme, A.
Klug, D.
Little, W. C.
Lovett, E.
Schafer, J. E.
Senni, E.
Swarup, V.
Wachter, R.
Weaver, F. A.
Zile, M. R.
Muller-Ehmsen, J.
TI Baroreflex activation therapy for the treatment of heart failure with
reduced ejection fraction in patients with and without coronary artery
disease
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Halbach, M.] Cologne Univ Hosp, Ctr Heart, Dept Internal Med 3, Cologne, Germany.
[Abraham, W. T.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Butter, C.] Immanuel Heart Ctr Bernau, Med Sch Brandenburg, Dept Cardiol, Bernau, Germany.
[Ducharme, A.] Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.
[Klug, D.] Lille Univ Hosp, Dept Cardiol A, Lille, France.
[Little, W. C.] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA.
[Lovett, E.] CVRx Inc, Minneapolis, MN USA.
[Schafer, J. E.] NAMSA Inc, Dept Stat, Minneapolis, MN USA.
[Senni, E.] Osped Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy.
[Swarup, V.] Arizona Heart Hosp, Dept Electrophysiol, Phoenix, AZ USA.
[Wachter, R.] Univ Med Gottingen, Gottingen, Germany.
[Wachter, R.] German Cardiovasc Res Ctr, Clin Cardiol & Pneumol, Gottingen, Germany.
[Weaver, F. A.] Univ Southern Calif, Div Vasc Surg & Endovasc Therapy, Keck Sch Med, Los Angeles, CA USA.
[Zile, M. R.] Med Univ South Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA.
[Muller-Ehmsen, J.] Asklepios Clin Altona, Dept Med, Hamburg, Germany.
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 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P3612
BP 724
EP 725
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869503409
ER
PT J
AU Wang, ZJ
Zhang, LL
Elmariah, S
Zhou, YJ
AF Wang, Z. J.
Zhang, L. L.
Elmariah, S.
Zhou, Y. J.
TI Prevalence and prognosis in patients with known or suspected myocardial
ischemia but no obstructive coronary artery disease
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Wang, Z. J.; Zhang, L. L.; Zhou, Y. J.] Capital Med Univ, Anzhen Hosp, Beijing, Peoples R China.
[Elmariah, S.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 4067
BP 799
EP 799
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869504043
ER
PT J
AU Christophersen, IE
Magnani, JW
Yin, X
Barnard, J
Chung, M
Lubitz, SA
Benjamin, EJ
Ellinor, PT
AF Christophersen, I. E.
Magnani, J. W.
Yin, X.
Barnard, J.
Chung, M.
Lubitz, S. A.
Benjamin, E. J.
Ellinor, P. T.
CA CHARGE Investigators
TI Meta-analyses in > 44,000 individuals identify fifteen genetic loci
associated with the electrocardiographic P-wave
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Christophersen, I. E.; Lubitz, S. A.; Ellinor, P. T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Magnani, J. W.; Benjamin, E. J.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
[Yin, X.] NHLBI, Framingham, MA USA.
[Yin, X.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Barnard, J.; Chung, M.] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Barnard, J.; Chung, M.] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.
[Barnard, J.; Chung, M.] Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P4313
BP 841
EP 841
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869504173
ER
PT J
AU Soeda, T
Uemura, S
Vergallo, R
Minami, Y
Ong, DS
Gao, L
Lee, H
Saito, Y
Jang, IK
AF Soeda, T.
Uemura, S.
Vergallo, R.
Minami, Y.
Ong, D. S.
Gao, L.
Lee, H.
Saito, Y.
Jang, I. K.
TI Incidence and clinical impact of OCT findings after metallic stent
implantation
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Soeda, T.; Saito, Y.] Nara Med Univ, Cardiol, Nara, Japan.
[Uemura, S.] Kawasaki Med Univ, Cardiovasc Med, Kurashiki, Okayama, Japan.
[Vergallo, R.] Univ Cattolica Sacro Cuore, Cardiovasc Sci, Rome, Italy.
[Minami, Y.; Ong, D. S.; Gao, L.; Jang, I. K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA.
[Lee, H.] Massachusetts Gen Hosp, Biostat Ctr, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P4406
BP 867
EP 867
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869504261
ER
PT J
AU Jia, HB
Hu, S
Rocco, V
Liu, H
Xu, M
Soeda, T
Minami, Y
Hou, J
Zhang, S
Yu, B
Jang, IK
AF Jia, H. B.
Hu, S.
Rocco, V.
Liu, H.
Xu, M.
Soeda, T.
Minami, Y.
Hou, J.
Zhang, S.
Yu, B.
Jang, I. K.
TI Progression of atherosclerotic plaques adjacent to the edges of
drug-eluting stent: a 3-time optical coherence tomography and
intravascular ultrasound study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Jia, H. B.; Hu, S.; Liu, H.; Xu, M.; Hou, J.; Zhang, S.; Yu, B.] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol, Harbin, Peoples R China.
[Rocco, V.; Soeda, T.; Minami, Y.; Jang, I. K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P4433
BP 874
EP 875
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869504288
ER
PT J
AU Beri, N
Daniels, L
Jaffe, AS
Mueller, C
Peacock, F
Hollander, J
Defilippi, C
Anand, I
Wu, A
Apple, F
Limkakeng, A
Schreiber, D
Nagurney, JT
Clopton, P
Maisel, A
AF Beri, N.
Daniels, L.
Jaffe, A. S.
Mueller, C.
Peacock, F.
Hollander, J.
Defilippi, C.
Anand, I.
Wu, A.
Apple, F.
Limkakeng, A.
Schreiber, D.
Nagurney, J. T.
Clopton, P.
Maisel, A.
TI Copeptin to rule out myocardial infarction in blacks versus Caucasians
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Beri, N.] Univ Calif San Diego, Internal Med, San Diego, CA 92103 USA.
[Daniels, L.; Maisel, A.] Univ Calif San Diego, Internal Med, Cardiol, San Diego, CA 92103 USA.
[Jaffe, A. S.] Mayo Clin, Cardiol, Internal Med, Rochester, MN USA.
[Mueller, C.] Univ Hosp Basel, Cardiol, Internal Med, Basel, Switzerland.
[Peacock, F.] Baylor Coll Med, Emergency Med, Houston, TX USA.
[Hollander, J.] Thomas Jefferson Univ Hosp, Emergency Med, Philadelphia, PA USA.
[Defilippi, C.] Univ Maryland, Cardiol, Internal Med, Baltimore, MD 21201 USA.
[Anand, I.] Univ Minnesota, Internal Med, Cardiol, Minneapolis, MN USA.
[Wu, A.] Univ Calif San Francisco, Lab Med, San Francisco, CA 94143 USA.
[Apple, F.] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA.
[Limkakeng, A.] Duke Univ, Med Ctr, Emergency Med, Durham, NC 27706 USA.
[Schreiber, D.] Stanford Univ, Emergency Med, Palo Alto, CA 94304 USA.
[Nagurney, J. T.] Massachusetts Gen Hosp, Emergency Med, Boston, MA 02114 USA.
[Clopton, P.] Vet Affairs San Diego Hlth Care Syst, Res, San Diego, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P4796
BP 981
EP 981
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869504650
ER
PT J
AU Sager, H
Dutta, P
Dahlman, J
Hulsmans, M
Courties, G
Sun, Y
Heidt, T
Borodovsky, A
Fitzgerald, K
Libby, P
Langer, R
Weissleder, R
Swirski, F
Anderson, D
Nahrendorf, M
AF Sager, H.
Dutta, P.
Dahlman, J.
Hulsmans, M.
Courties, G.
Sun, Y.
Heidt, T.
Borodovsky, A.
Fitzgerald, K.
Libby, P.
Langer, R.
Weissleder, R.
Swirski, F.
Anderson, D.
Nahrendorf, M.
TI Nanoparticle-enabled RNAi in endothelial cells attenuates inflammation
in atherosclerosis and acute myocardial infarction
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Sager, H.] German Heart Ctr Munich, Dept Cardiol, Munich, Germany.
[Dutta, P.] Univ Pittsburgh, Pittsburgh, PA USA.
[Dahlman, J.; Langer, R.; Anderson, D.] MIT, Cambridge, MA 02139 USA.
[Hulsmans, M.; Courties, G.; Sun, Y.; Weissleder, R.; Swirski, F.; Nahrendorf, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Heidt, T.] Univ Freiburg, Freiburg, Germany.
[Borodovsky, A.; Fitzgerald, K.] Alnylam Pharmaceut, Cambridge, MA USA.
[Libby, P.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
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 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 4864
BP 989
EP 989
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869505011
ER
PT J
AU Arsiwala, T
Van Tits, LJ
Miranda, MX
Nussbaum, K
Weber, J
Blyszczuk, P
Stivala, S
Beer, JH
Greter, M
Becher, B
Hottiger, MO
Mostoslavsky, R
Eriksson, U
Luescher, TF
Matter, CM
AF Arsiwala, T.
Van Tits, L. J.
Miranda, M. X.
Nussbaum, K.
Weber, J.
Blyszczuk, P.
Stivala, S.
Beer, J. H.
Greter, M.
Becher, B.
Hottiger, M. O.
Mostoslavsky, R.
Eriksson, U.
Luescher, T. F.
Matter, C. M.
TI Bone marrow-specific Sirt6 deletion enhances atherosclerosis and foam
cell formation via an increase in macrophage scavenger receptor 1
expression
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Arsiwala, T.; Van Tits, L. J.; Miranda, M. X.; Weber, J.; Blyszczuk, P.; Stivala, S.; Eriksson, U.] Univ Zurich, Ctr Mol Cardiol, Zurich, Switzerland.
[Nussbaum, K.; Greter, M.; Becher, B.] Univ Zurich, Inst Expt Immunol, Zurich, Switzerland.
[Beer, J. H.] Cantonal Hosp Baden, Internal Med, Baden, Switzerland.
[Hottiger, M. O.] Univ Zurich, Dept Mol Mechanisms Dis, Zurich, Switzerland.
[Mostoslavsky, R.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Luescher, T. F.; Matter, C. M.] Univ Zurich Hosp, Div Cardiol, Zurich, Switzerland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 4866
BP 990
EP 990
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869505013
ER
PT J
AU Bittner, D
Mayrhofer, T
Puchner, S
Lu, M
Maurovich-Horvat, P
Ghemigian, K
Kitslaar, P
Broersen, A
Bamberg, F
Truong, Q
Schlett, C
Hoffmann, U
Ferencik, M
AF Bittner, D.
Mayrhofer, T.
Puchner, S.
Lu, M.
Maurovich-Horvat, P.
Ghemigian, K.
Kitslaar, P.
Broersen, A.
Bamberg, F.
Truong, Q.
Schlett, C.
Hoffmann, U.
Ferencik, M.
TI Coronary CTA specific definitions of high-risk plaque features optimized
for the detection of ACS: results from the ROMICAT II trial
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Bittner, D.; Mayrhofer, T.; Lu, M.; Ghemigian, K.; Hoffmann, U.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Puchner, S.] Med Univ Vienna, Vienna, Austria.
[Maurovich-Horvat, P.] Semmelweis Univ, Budapest, Hungary.
[Kitslaar, P.; Broersen, A.] Leiden Univ, Med Ctr, Leiden, Netherlands.
[Bamberg, F.] Univ Tubingen, Tubingen, Germany.
[Truong, Q.] Weill Cornell Med Coll, New York, NY USA.
[Schlett, C.] Univ Heidelberg Hosp, Heidelberg, Germany.
[Ferencik, M.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
NR 0
TC 0
Z9 0
U1 4
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 5137
BP 1024
EP 1025
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869505117
ER
PT J
AU Jia, HB
Hu, S
Liu, H
Xu, M
Rocco, V
Soeda, T
Zhang, S
Hou, J
Yu, B
Jang, IK
AF Jia, H. B.
Hu, S.
Liu, H.
Xu, M.
Rocco, V.
Soeda, T.
Zhang, S.
Hou, J.
Yu, B.
Jang, I. K.
TI Degree of luminal narrowing and culprit plaque morphology in patients
with acute coronary syndrome: an optical coherence tomography study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Jia, H. B.; Hu, S.; Liu, H.; Xu, M.; Zhang, S.; Hou, J.; Yu, B.] Harbin Med Univ, Affiliated Hosp 2, Key Lab Myocardial Ischemia, Dept Cardiol, Harbin, Peoples R China.
[Rocco, V.] Univ Cattolica Sacro Cuore, Cardiol, Rome, Italy.
[Soeda, T.] Nara Med Univ, Nara, Japan.
[Jang, I. K.] Massachusetts Gen Hosp, Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P5288
BP 1068
EP 1068
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869505259
ER
PT J
AU Grapsa, J
Tan, TC
Howard, LSGE
Dawson, D
Gibbs, JSR
Picard, MH
Nihoyannopoulos, P
AF Grapsa, J.
Tan, T. C.
Howard, L. S. G. E.
Dawson, D.
Gibbs, J. S. R.
Picard, M. H.
Nihoyannopoulos, P.
TI Regression of RV mass and interventricular septal curvature duration
predict mortality in patients with pre-capillary pulmonary hypertension:
a follow up study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Grapsa, J.; Howard, L. S. G. E.; Dawson, D.; Gibbs, J. S. R.; Nihoyannopoulos, P.] Hammersmith Hosp, London, England.
[Tan, T. C.; Picard, M. H.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 5752
BP 1187
EP 1187
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869505649
ER
PT J
AU Navar, AM
Wang, TY
Zakroysky, P
Li, S
Goldberg, AC
Virani, SS
Roger, VL
Robinson, JG
Wilson, PWF
Lee, LV
Elassal, J
Peterson, ED
AF Navar, A. M.
Wang, T. Y.
Zakroysky, P.
Li, S.
Goldberg, A. C.
Virani, S. S.
Roger, V. L.
Robinson, J. G.
Wilson, P. W. F.
Lee, L. V.
Elassal, J.
Peterson, E. D.
TI Patient receptiveness to statin therapy is higher when presented with
lifetime risk rather than 10-year risk of cardiovascular disease:
insights from the PALM registry
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Navar, A. M.; Wang, T. Y.; Zakroysky, P.; Li, S.; Peterson, E. D.] Duke Clin Res Inst, Durham, NC USA.
[Goldberg, A. C.] Washington Univ, Sch Med, St Louis, MO USA.
[Virani, S. S.] VA Med Ctr, Houston, TX USA.
[Roger, V. L.] Mayo Clin, Rochester, MN USA.
[Robinson, J. G.] Univ Iowa, Iowa City, IA USA.
[Wilson, P. W. F.] Emory Univ, Atlanta, GA 30322 USA.
[Lee, L. V.] Sanofi Pharmaceut, Bridgewater, NJ USA.
[Elassal, J.] Regeneron Pharmaceut, Tarrytown, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P5927
BP 1216
EP 1216
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869506080
ER
PT J
AU Beghetti, M
Channick, R
Chin, K
Di Scala, L
Gaine, S
Ghofrani, HA
Hoeper, M
Lang, I
McLaughlin, V
Preiss, R
Rubin, L
Simonneau, G
Sitbon, O
Tapson, V
Galie, N
AF Beghetti, M.
Channick, R.
Chin, K.
Di Scala, L.
Gaine, S.
Ghofrani, H. A.
Hoeper, M.
Lang, I.
McLaughlin, V.
Preiss, R.
Rubin, L.
Simonneau, G.
Sitbon, O.
Tapson, V.
Galie, N.
TI Selexipag for pulmonary arterial hypertension associated with congenital
heart disease (PAH-CHD) after defect correction: insights from the
randomized controlled GRIPHON study
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Beghetti, M.] Hop Enfants, Geneva, Switzerland.
[Channick, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Chin, K.] Univ Texas Southwestern Med Sch, Dallas, TX USA.
[Di Scala, L.; Preiss, R.] Actel Pharmaceut Ltd, Allschwil, Switzerland.
[Gaine, S.] Mater Misericordiae Univ Hosp, Natl Pulm Hypertens Unit, Dublin, Ireland.
[Ghofrani, H. A.] Univ Giessen & Marburg Lung Ctr UGMLC, Giessen, Germany.
[Hoeper, M.] Hannover Med Sch, Hannover, Germany.
[Hoeper, M.] German Ctr Lung Res, Dept Resp Med, Hannover, Germany.
[Lang, I.] Med Univ Vienna, Div Cardiol, Dept Internal Med 2, Allgemeines Krankenhaus, Vienna, Austria.
[McLaughlin, V.] Univ Michigan Hlth Syst, Div Cardiovasc Med, Ann Arbor, MI USA.
[Rubin, L.] Univ Calif San Diego, Div Pulm & Crit Care Med, San Diego, CA 92103 USA.
[Simonneau, G.; Sitbon, O.] Univ Paris Sud, Hop Univ Bicetre, Le Kremlin Bicetre, France.
[Tapson, V.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Galie, N.] Univ Bologna, Ist Malattie Apparato Cardiovasc, Bologna, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 6092
BP 1243
EP 1243
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869506160
ER
PT J
AU Pawar, SP
Kim, EJK
Gupte, GG
Afable, MA
Strymish, JS
Simon, SRS
Orlander, JDO
Vimalananda, VV
AF Pawar, S. P.
Kim, E. J. K.
Gupte, G. G.
Afable, M. A.
Strymish, J. S.
Simon, S. R. S.
Orlander, J. D. O.
Vimalananda, V. V.
TI Variations in cardiology electronic consultation use in a large
integrated healthcare system in the United States
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Pawar, S. P.] Boston Univ, Sch Med, Dept Internal Med, Boston, MA 02118 USA.
[Kim, E. J. K.; Vimalananda, V. V.] Bedford Vet Affairs Med Ctr, Ctr Healthcare Org & Implementat Res, Bedford, MA USA.
[Gupte, G. G.] Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, Boston, MA USA.
[Afable, M. A.; Simon, S. R. S.] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA.
[Strymish, J. S.; Orlander, J. D. O.] VA Boston Healthcare Syst, West Roxbury, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA P6168
BP 1264
EP 1264
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869506226
ER
PT J
AU Celeng, C
Maurovich-Horvat, P
Ghoshhajra, BB
Merkely, B
Leiner, T
Takx, RAP
AF Celeng, C.
Maurovich-Horvat, P.
Ghoshhajra, B. B.
Merkely, B.
Leiner, T.
Takx, R. A. P.
TI Prognostic value of obstructive coronary artery disease on CTA in
diabetic patients: a meta-analysis
SO EUROPEAN HEART JOURNAL
LA English
DT Meeting Abstract
CT Congress of the European-Society-of-Cardiology (ESC)
CY AUG 27-31, 2016
CL Rome, ITALY
SP European Soc Cardiol
C1 [Celeng, C.; Maurovich-Horvat, P.; Merkely, B.] Semmelweis Univ, MTA SE Cardiovasc Imaging Res Grp, Heart & Vasc Ctr, Budapest, Hungary.
[Ghoshhajra, B. B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Prog, Boston, MA USA.
[Leiner, T.; Takx, R. A. P.] Univ Med Ctr Utrecht, Radiol, Utrecht, Netherlands.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
EI 1522-9645
J9 EUR HEART J
JI Eur. Heart J.
PD AUG 1
PY 2016
VL 37
SU 1
MA 6604
BP 1397
EP 1397
PG 1
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW7YL
UT WOS:000383869506651
ER
PT J
AU Bateman, BT
Huybrechts, KF
Cohen, J
Mogun, H
Desai, RJ
Patorno, E
Hernandez-Diaz, S
AF Bateman, Brian T.
Huybrechts, Krista F.
Cohen, Jacqueline
Mogun, Helen
Desai, Rishi J.
Patorno, Elisabetta
Hernandez-Diaz, Sonia
TI Pregnancy Outcomes in Women with Chronic Hypertension Initiated on
Labetalol versus Methyldopa
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Bateman, Brian T.; Huybrechts, Krista F.; Mogun, Helen; Desai, Rishi J.; Patorno, Elisabetta] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Bateman, Brian T.; Huybrechts, Krista F.; Mogun, Helen; Desai, Rishi J.; Patorno, Elisabetta] Harvard Med Sch, Boston, MA USA.
[Cohen, Jacqueline; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 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 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 21
BP 15
EP 16
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483501021
ER
PT J
AU Esposito, DB
Yin, R
Russo, LJ
del Carmen, MG
Goldstein, SR
Patsner, B
Lanes, SF
AF Esposito, Daina B.
Yin, Ruihua
Russo, Leo J.
del Carmen, Marcela G.
Goldstein, Steven R.
Patsner, Bruce
Lanes, Stephan F.
TI Development and Validation of an Algorithm to Identify Endometrial
Adenocarcinoma in US Administrative Claims Data
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Esposito, Daina B.; Yin, Ruihua; Lanes, Stephan F.] HealthCore Inc, Safety & Epidemiol, Andover, MA USA.
[Russo, Leo J.] Pfizer Inc, Collegeville, PA USA.
[del Carmen, Marcela G.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Goldstein, Steven R.] NYU, Sch Med, New York, NY USA.
[Patsner, Bruce] Inova Hlth Syst, Fairfax, VA 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 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 267
BP 159
EP 160
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483501265
ER
PT J
AU Rough, K
Huybrechts, KF
Hernandez-Diaz, S
Desai, RJ
Patorno, E
Bateman, BT
AF Rough, Kathryn
Huybrechts, Krista F.
Hernandez-Diaz, Sonia
Desai, Rishi J.
Patorno, Elisabetta
Bateman, Bateman T.
TI Detection of Aberrant Opioid Use in Prescription Claims Data: Comparison
and Validation of Five Algorithms
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Rough, Kathryn; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Bateman T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Bateman T.] Harvard Med Sch, Boston, MA USA.
[Bateman, Bateman T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 369
BP 216
EP 216
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502005
ER
PT J
AU Park, Y
Hernandez-Diaz, S
Bateman, BT
Cohen, J
Patorno, E
Mogun, H
Huybrechts, KF
AF Park, Yoonyoung
Hernandez-Diaz, Sonia
Bateman, Brian T.
Cohen, Jacqueline
Patorno, Elisabetta
Mogun, Helen
Huybrechts, Krista F.
TI Continuation of Atypical Antipsychotic Medications During Pregnancy and
the Risk of Gestational Diabetes
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Park, Yoonyoung; Bateman, Brian T.; Patorno, Elisabetta; Mogun, Helen; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Park, Yoonyoung; Bateman, Brian T.; Patorno, Elisabetta; Mogun, Helen; Huybrechts, Krista F.] Harvard Med Sch, Boston, MA USA.
[Park, Yoonyoung; Hernandez-Diaz, Sonia; Cohen, Jacqueline] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 404
BP 235
EP 236
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502037
ER
PT J
AU Huybrechts, KF
Bateman, BT
Hernandez-Diaz, S
Desai, RJ
Rough, K
Mogun, H
Patorno, E
AF Huybrechts, Krista F.
Bateman, Brian T.
Hernandez-Diaz, Sonia
Desai, Rishi J.
Rough, Kathryn
Mogun, Helen
Patorno, Elisabetta
TI Psychotropic Medications and the Risk of Neonatal Withdrawal
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Huybrechts, Krista F.; Bateman, Brian T.; Desai, Rishi J.; Rough, Kathryn; Mogun, Helen; Patorno, Elisabetta] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Huybrechts, Krista F.; Bateman, Brian T.; Desai, Rishi J.; Rough, Kathryn; Mogun, Helen; Patorno, Elisabetta] Harvard Med Sch, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Hernandez-Diaz, Sonia; Rough, Kathryn] Harvard TH Chan Sch Publ Hlth, Boston, MA 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 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 444
BP 260
EP 260
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502077
ER
PT J
AU Park, Y
Bateman, BT
Kim, D
Hernandez-Diaz, S
Patorno, E
Glynn, RJ
Mogun, H
Huybrechts, KF
AF Park, Yoonyoung
Bateman, Brian T.
Kim, Dae
Hernandez-Diaz, Sonia
Patorno, Elisabetta
Glynn, Robert J.
Mogun, Helen
Huybrechts, Krista F.
TI Comparative Safety of Antipsychotic Medications in Hospitalized
Myocardial Infarction Patients
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Park, Yoonyoung; Bateman, Brian T.; Kim, Dae; Patorno, Elisabetta; Glynn, Robert J.; Mogun, Helen; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Park, Yoonyoung; Bateman, Brian T.; Kim, Dae; Patorno, Elisabetta; Glynn, Robert J.; Mogun, Helen; Huybrechts, Krista F.] Harvard Med Sch, Boston, MA USA.
[Park, Yoonyoung; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
[Kim, Dae] Beth Israel Deaconess Med Ctr, Dept Med, Div Gerontol, Boston, MA 02215 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 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 447
BP 262
EP 262
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502080
ER
PT J
AU Cohen, JM
Patorno, E
Huybrechts, KF
Park, Y
Bateman, BT
Hernandez-Diaz, S
AF Cohen, Jacqueline M.
Patorno, Elisabetta
Huybrechts, Krista F.
Park, Yoonyoung
Bateman, Brian T.
Hernandez-Diaz, Sonia
TI Mood Stabilizer Use and Risk of Ischemic Placental Disease
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Cohen, Jacqueline M.; Park, Yoonyoung; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Patorno, Elisabetta; Huybrechts, Krista F.; Park, Yoonyoung; Bateman, Brian T.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Patorno, Elisabetta; Huybrechts, Krista F.; Park, Yoonyoung; Bateman, Brian T.] Harvard Med Sch, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 507
BP 297
EP 297
PG 1
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502140
ER
PT J
AU Bateman, BT
Huybrechts, KF
Booth, J
Briggs, H
Flood, P
Bauer, M
Landau, R
AF Bateman, Brian T.
Huybrechts, Krista F.
Booth, Jessica
Briggs, Holly
Flood, Pamela
Bauer, Melissa
Landau, Ruth
TI Opioid Use Following Discharge After Cesarean Delivery
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Bateman, Brian T.; Huybrechts, Krista F.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Bateman, Brian T.; Huybrechts, Krista F.; Briggs, Holly] Harvard Med Sch, Boston, MA USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA 02114 USA.
[Booth, Jessica] Wake Forest Univ, Dept Anesthesiol, Winston Salem, NC 27109 USA.
[Briggs, Holly] Brigham & Womens Hosp, Dept Anesthesiol, 75 Francis St, Boston, MA 02115 USA.
[Flood, Pamela] Stanford Univ, Dept Anesthesiol, Palo Alto, CA 94304 USA.
[Bauer, Melissa] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA.
[Landau, Ruth] Columbia Univ, Dept Anesthesiol, New York, NY 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 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 567
BP 330
EP 331
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502199
ER
PT J
AU Rough, K
Hernandez-Diaz, S
Huybrechts, KF
Desai, RJ
Patorno, E
Bateman, BT
AF Rough, Kathryn
Hernandez-Diaz, Sonia
Huybrechts, Krista F.
Desai, Rishi J.
Patorno, Elisabetta
Bateman, Brian T.
TI Increase in Aberrant Prescription Opioid Use by Pregnant Women in a
Nationwide Cohort of Medicaid Beneficiaries
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Meeting Abstract
C1 [Rough, Kathryn; Hernandez-Diaz, Sonia] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Rough, Kathryn; Huybrechts, Krista F.; Desai, Rishi J.; Patorno, Elisabetta; Bateman, Brian T.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Bateman, Brian T.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
SU S3
MA 569
BP 331
EP 332
PG 2
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DY9VP
UT WOS:000385483502201
ER
PT J
AU Bachert, C
Hellings, P
Mullol, J
Hamilos, D
Naclerio, R
Joish, VN
Mannent, L
Evans, R
Abbe, A
Amand, C
Taniou, C
Zhang, D
Fan, C
Pirozzi, G
Graham, N
Mastey, V
Mahajan, S
Staudinger, H
Eckert, L
Khan, A
AF Bachert, C.
Hellings, P.
Mullol, J.
Hamilos, D.
Naclerio, R.
Joish, V. N.
Mannent, L.
Evans, R.
Abbe, A.
Amand, C.
Taniou, C.
Zhang, D.
Fan, C.
Pirozzi, G.
Graham, N.
Mastey, V
Mahajan, S.
Staudinger, H.
Eckert, L.
Khan, A.
TI Dupilumab improves health-related quality of life and absenteeism in
nasal polyposis patients: results from a phase 2a trial
SO ALLERGY
LA English
DT Meeting Abstract
CT Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology
CY JUN 11-15, 2016
CL Vienna, AUSTRIA
SP European Acad Allergy & Clin Immunol
C1 [Bachert, C.] Ghent Univ Hosp, Ghent, Belgium.
[Hellings, P.] Univ Hosp Leuven, Dept Otorhinolaryngol Head & Neck Surg, Leuven, Belgium.
[Mullol, J.] Hosp Clin IDIBAPS, Clin & Expt Resp Immunoallergy, Barcelona, Spain.
[Hamilos, D.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
[Naclerio, R.] Univ Chicago, Chicago, IL 60637 USA.
[Joish, V. N.; Evans, R.; Graham, N.; Mastey, V] Regeneron Pharmaceut Inc, Tarrytown, NY USA.
[Mannent, L.; Abbe, A.; Amand, C.; Eckert, L.; Khan, A.] Sanofi R&D, Chilly Mazarin, France.
[Taniou, C.] Experis IT, Chilly Mazarin, France.
[Zhang, D.; Fan, C.; Pirozzi, G.; Mahajan, S.; Staudinger, H.] Sanofi R&D, Bridgewater, MA 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 0105-4538
EI 1398-9995
J9 ALLERGY
JI Allergy
PD AUG
PY 2016
VL 71
SU 102
SI SI
MA 19
BP 12
EP 12
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DW5JI
UT WOS:000383679800020
ER
PT J
AU Hourihane, J
Allen, K
Shreffler, W
Dunngalvin, G
Baumert, J
Zurzolo, G
Gurrin, L
Dunngalvin, A
Nordlee, J
Taylor, S
AF Hourihane, J.
Allen, K.
Shreffler, W.
Dunngalvin, G.
Baumert, J.
Zurzolo, G.
Gurrin, L.
Dunngalvin, A.
Nordlee, J.
Taylor, S.
TI Peanut allergen threshold study: validation of eliciting doses using a
novel, single-dose challenge protocol
SO ALLERGY
LA English
DT Meeting Abstract
CT Meeting of the European-Academy-of-Allergy-and-Clinical-Immunology
CY JUN 11-15, 2016
CL Vienna, AUSTRIA
SP European Acad Allergy & Clin Immunol
C1 [Hourihane, J.] Univ Coll Cork, Cork, Ireland.
[Allen, K.; Zurzolo, G.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Shreffler, W.] Harvard Med Sch, Massachusetts Gen Hosp, Food Allergy Ctr, Boston, MA USA.
[Shreffler, W.] Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Dunngalvin, G.; Dunngalvin, A.] Univ Coll, Appl Psychol, Cork, Ireland.
[Baumert, J.; Nordlee, J.; Taylor, S.] Univ Nebraska, Food Allergy Res & Resource Program, Lincoln, NE USA.
[Gurrin, L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic, Australia.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-4538
EI 1398-9995
J9 ALLERGY
JI Allergy
PD AUG
PY 2016
VL 71
SU 102
SI SI
MA 1364
BP 104
EP 104
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA DW5JI
UT WOS:000383679800208
ER
PT J
AU Burke, TF
Ahn, R
Nelson, BD
Hines, R
Kamara, J
Oguttu, M
Dulo, L
Achieng, E
Achieng, B
Natarajan, A
Maua, J
Kargbo, SAS
Altawil, Z
Tester, K
de Redon, E
Niang, M
Abdalla, K
Eckardt, MJ
AF Burke, T. F.
Ahn, R.
Nelson, B. D.
Hines, R.
Kamara, J.
Oguttu, M.
Dulo, L.
Achieng, E.
Achieng, B.
Natarajan, A.
Maua, J.
Kargbo, S. A. S.
Altawil, Z.
Tester, K.
de Redon, E.
Niang, M.
Abdalla, K.
Eckardt, M. J.
TI A postpartum haemorrhage package with condom uterine balloon tamponade:
a prospective multi-centre case series in Kenya, Sierra Leone, Senegal,
and Nepal
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Maternal mortality; postpartum haemorrhage; uterine balloon tamponade
ID MATERNAL DEATH; BAKRI BALLOON; MANAGEMENT
AB Objective To evaluate the effectiveness and safety of an ultra-low-cost uterine balloon tamponade package (ESM-UBT (TM)) for facility-based management of uncontrolled postpartum haemorrhage (PPH) in Kenya, Sierra Leone, Senegal, and Nepal.
Design Prospective multi-centre case series.
Setting Facilities in resource-scarce areas of Kenya, Sierra Leone, Nepal, and Senegal.
Population Women with uncontrolled postpartum haemorrhage in 307 facilities across the four countries.
Methods A standardised ESM-UBT package was implemented in 307 facilities over 29 months (1 September 2012 to 1 February 2015). Data were collected via a multi-pronged approach including data card completion, chart reviews, and provider interviews. Beginning in August 2014, women who had previously undergone UBT placement were sought and queried regarding potential complications associated with UBT use.
Main outcome measures All-cause survival, survival from PPH, and post-UBT use complications (surgery, hospitalisation, antibiotics for pelvic infection) associated with UBT use.
Results 201 UBTs were placed for uncontrolled vaginal haemorrhage refractory to all other interventions. In all, 38% (71/188) of women were either unconscious or confused at the time of UBT insertion. All-cause survival was 95% (190/201). However, 98% (160/163) of women survived uncontrolled PPH if delivery occurred at an ESM-UBT online facility. One (1/151) potential UBT-associated complication (postpartum endometritis) was identified and two improvised UBTs were placed in women with a ruptured uterus.
Conclusions These pilot data suggest that the ESM-UBT package is a clinically promising and safe method to arrest uncontrolled postpartum haemorrhage and save women's lives. The UBT was successfully placed by all levels of facility-based providers. Future studies are needed to further evaluate the effectiveness of ESM-UBT in low-resource settings.
C1 [Burke, T. F.; Ahn, R.; Nelson, B. D.; Hines, R.; Kamara, J.; Natarajan, A.; Altawil, Z.; Tester, K.; de Redon, E.; Eckardt, M. J.] Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA.
[Burke, T. F.; Ahn, R.; Nelson, B. D.; Natarajan, A.] Harvard Med Sch, Boston, MA USA.
[Oguttu, M.; Dulo, L.; Achieng, E.; Achieng, B.] Kisumu Med & Educ Trust, Kisumu, Kenya.
[Maua, J.] Minist Hlth, Div Reprod & Maternal Hlth, Nairobi, Kenya.
[Kargbo, S. A. S.] Minist Hlth & Sanitat, Div Reprod Hlth, Freetown, Sierra Leone.
[Niang, M.] Ctr Format & Rech Sante Reprod, Dakar, Senegal.
[Abdalla, K.] UNICEF, Nairobi, Kenya.
[Eckardt, M. J.] Boston Med Ctr, Dept Obstet & Gynecol, Boston, MA USA.
RP Burke, TF (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Global Hlth & Human Rights, Zero Emerson Pl,Suite 104, Boston, MA 02114 USA.
EM tfburke@partners.org
OI Nelson, Brett/0000-0002-5049-1798
FU Izumi Foundation; Ujenzi Charitable Trust; Humanitarian Innovation Fund;
United States Agency for International Development (USAID); Government
of Norway; Bill & Melinda Gates Foundation; Grand Challenges Canada; UK
Government
FX The Every Second Matters for Mothers and Babies Uterine Balloon
Tamponade research program (ESM-UBT TM) is made possible through the
generous support of the Izumi Foundation, the Ujenzi Charitable Trust,
the Humanitarian Innovation Fund and the Saving Lives at Birth partners:
the United States Agency for International Development (USAID), the
Government of Norway, the Bill & Melinda Gates Foundation, Grand
Challenges Canada, and the UK Government. This manuscript was prepared
by MGH and does not necessarily reflect the views of the funding
partners.
NR 14
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
EI 1471-0528
J9 BJOG-INT J OBSTET GY
JI BJOG
PD AUG
PY 2016
VL 123
IS 9
BP 1532
EP 1540
DI 10.1111/1471-0528.13550
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DW3SS
UT WOS:000383563700026
PM 26223284
ER
PT J
AU Otto, MW
Pollack, MH
Dowd, SM
Hofmann, SG
Pearlson, G
Szuhany, KL
Gueorguieva, R
Krystal, JH
Simon, NM
Tolin, DF
AF Otto, Michael W.
Pollack, Mark H.
Dowd, Sheila M.
Hofmann, Stefan G.
Pearlson, Godfrey
Szuhany, Kristin L.
Gueorguieva, Ralitza
Krystal, John H.
Simon, Naomi M.
Tolin, David F.
TI RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL
THERAPY FOR PANIC DISORDER
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE anxiety; panic attacks/agoraphobia; CBT; clinical trials;
pharmacotherapy
ID OBSESSIVE-COMPULSIVE DISORDER; SOCIAL ANXIETY DISORDER; EXPOSURE
SESSIONS; FEAR EXTINCTION; PSYCHOTHERAPY; ANTIDEPRESSANT; AGORAPHOBIA;
SCALE; PHARMACOTHERAPY; COMBINATION
AB Background: Initial studies have provided a mixed perspective of the efficacy of d-cycloserine (DCS) for augmenting the efficacy of exposure-based cognitive behavioral therapy (CBT) for panic disorder. In this multicenter trial, we examine the magnitude of DCS augmentation effects for an ultra-brief program of CBT. Methods: We conducted a double-blind, controlled trial at three treatment sites, randomizing 180 adults with a primary diagnosis of panic disorder to five sessions of treatment, with study pill (50 mg DCS or matching placebo) administered 1 hr prior to the final three sessions. Two booster sessions were subsequently provided, and outcome was assessed at posttreatment and 1-month, 2-month, and 6-month follow-up assessments. The primary outcome was the degree of reduction in the Panic Disorder Severity Scale. Additional analyses examined the role of severity and current antidepressant or benzodiazepine use as moderators of DCS augmentation effects. Results: DCS augmentation resulted in significant benefit only early in the trial, with no beneficial effects of DCS augmentation evident at follow-up evaluations. We did not find that baseline severity or antidepressant or benzodiazepine use moderated DCS efficacy, but benzodiazepine use was associated with lower efficacy of CBT regardless of augmentation condition. Conclusions: Consistent with other recent multicenter trials, the benefit of DCS was less than indicated by pilot study and reflected an acceleration of treatment response evident at treatment endpoint, but no advantage in response over follow-up evaluation. Our results did not support severity or concomitant medication moderators observed in previous trials of DCS augmentation. (C) 2016 Wiley Periodicals, Inc.
C1 [Otto, Michael W.; Hofmann, Stefan G.; Szuhany, Kristin L.] Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,5th Floor, Boston, MA 02215 USA.
[Pollack, Mark H.; Dowd, Sheila M.] Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA.
[Pearlson, Godfrey; Tolin, David F.] Inst Living, Hartford, CT USA.
[Pearlson, Godfrey; Tolin, David F.] Yale Univ, Sch Med, Hartford, CT USA.
[Gueorguieva, Ralitza] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
[Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Krystal, John H.] Yale New Haven Med Ctr, 20 York St, New Haven, CT 06504 USA.
[Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA.
[Simon, Naomi M.] Harvard Med Sch, Boston, MA USA.
RP Otto, MW (reprint author), Boston Univ, Dept Psychol & Brain Sci, 648 Beacon St,5th Floor, Boston, MA 02215 USA.
EM mwotto@bu.edu
RI Hofmann, Stefan/B-8769-2014;
OI Hofmann, Stefan/0000-0002-3548-9681; Gueorguieva,
Ralitza/0000-0003-0944-5973
FU NIH; Pfizer; Janssen; Edgemont Pharmaceuticals; Clintara; Otsuka
Pharmaceutical; NIH/NCCIH [R01AT007257]; NIH/NIMH [R01MH099021,
R34MH099311, R34MH086668, R21MH102646, R21MH101567, K23MH100259];
Department of the Army; American Foundation for Suicide Prevention;
Department of Defense; Highland Street Foundation; Palo Alto Health
Sciences, Inc.
FX Dr. Otto reports serving, in the last 3 years, as a paid consultant for
MicroTransponder Inc., Concert Pharmaceuticals, and ProPhase, providing
expert consensus opinion for Otsuka Pharmaceuticals, receiving royalty
support for use of the SIGH-A from ProPhase, receiving book royalties
from Oxford University Press, Routledge, and Springer, and receiving
research support for other projects from NIH.; Dr. Dowd reports
receiving research funding from Pfizer, Janssen and Edgemont
Pharmaceuticals and serves as a paid consultant with Clintara and Otsuka
Pharmaceutical.; Dr. Hofmann receives support from NIH/NCCIH
(R01AT007257), NIH/NIMH (R01MH099021, R34MH099311, R34MH086668,
R21MH102646, R21MH101567, K23MH100259), and the Department of the Army
for work unrelated to the studies reported in this article. He receives
compensation for his work as an advisor from the Palo Alto Health
Sciences and Otsuka America Pharmaceutical, Inc., and for his work as a
Subject Matter Expert from John Wiley & Sons, Inc. and SilverCloud
Health, Inc. He also receives royalties and payments for his editorial
work from various publishers.; Dr. Simon reports research grants from
the American Foundation for Suicide Prevention, Department of Defense,
Highland Street Foundation, and NIH; speaking/CME/consulting from the
MGH Psychiatry Academy and Pfizer Pharmaceuticals, and spousal equity
from G Zero and Gatekeeper.; Dr. Tolin reports receiving research
funding from Palo Alto Health Sciences, Inc.
NR 39
TC 1
Z9 1
U1 13
U2 13
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 AUG
PY 2016
VL 33
IS 8
BP 737
EP 745
DI 10.1002/da.22531
PG 9
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DW5TH
UT WOS:000383709300008
PM 27315514
ER
PT J
AU Harris, JR
AF Harris, Jay R.
TI Treatment of Regional Lymph Nodes in Breast Cancer-Not Recommended for
All Patients With 1 to 3 Positive Auxiliary Nodes
SO JAMA ONCOLOGY
LA English
DT Editorial Material
ID SENTINEL NODE; RADIOTHERAPY; IRRADIATION; SURGERY; TRIAL; WOMEN
C1 [Harris, Jay R.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,YC 1473, Boston, MA 02215 USA.
RP Harris, JR (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave,YC 1473, Boston, MA 02215 USA.
EM jharris@lroc.harvard.edu
NR 5
TC 1
Z9 1
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 AUG
PY 2016
VL 2
IS 8
BP 991
EP 992
DI 10.1001/jamaoncol.2016.0222
PG 2
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700002
PM 27253737
ER
PT J
AU Bukowski, A
Chavarri-Guerra, Y
Goss, PE
AF Bukowski, Alexandra
Chavarri-Guerra, Yanin
Goss, Paul E.
TI The Potential Role of Patient Navigation in Low- and Middle-Income
Countries for Patients With Cancer
SO JAMA ONCOLOGY
LA English
DT Editorial Material
ID DIAGNOSTIC RESOLUTION; IMPACT
C1 [Bukowski, Alexandra; Chavarri-Guerra, Yanin; Goss, Paul E.] Global Canc Inst, Boston, MA USA.
[Bukowski, Alexandra; Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Program, 55 Fruit St,Lawrence House,Room 302, Boston, MA 02114 USA.
[Goss, Paul E.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Hematol & Oncol, Mexico City, DF, Mexico.
RP Goss, PE (reprint author), Massachusetts Gen Hosp, Ctr Canc, Avon Int Breast Canc Program, 55 Fruit St,Lawrence House,Room 302, Boston, MA 02114 USA.
EM pgoss@partners.org
NR 7
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 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD AUG
PY 2016
VL 2
IS 8
BP 994
EP 995
DI 10.1001/jamaoncol.2016.0766
PG 2
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700004
PM 27228333
ER
PT J
AU Nikiforov, YE
Seethala, RR
Tallini, G
Baloch, ZW
Basolo, F
Thompson, LDR
Barletta, JA
Wenig, BM
Al Ghuzlan, A
Kakudo, K
Giordano, TJ
Alves, VA
Khanafshar, E
Asa, SL
El-Naggar, AK
Gooding, WE
Hodak, SP
Lloyd, RV
Maytal, G
Mete, O
Nikiforova, MN
Nose, V
Papotti, M
Poller, DN
Sadow, PM
Tischler, AS
Tuttle, M
Wall, KB
LiVolsi, VA
Randolph, GW
Ghossein, RA
AF Nikiforov, Yuri E.
Seethala, Raja R.
Tallini, Giovanni
Baloch, Zubair W.
Basolo, Fulvio
Thompson, Lester D. R.
Barletta, Justine A.
Wenig, Bruce M.
Al Ghuzlan, Abir
Kakudo, Kennichi
Giordano, Thomas J.
Alves, Venancio A.
Khanafshar, Elham
Asa, Sylvia L.
El-Naggar, Adel K.
Gooding, William E.
Hodak, Steven P.
Lloyd, Ricardo V.
Maytal, Guy
Mete, Ozgur
Nikiforova, Marina N.
Nose, Vania
Papotti, Mauro
Poller, David N.
Sadow, Peter M.
Tischler, Arthur S.
Tuttle, Michael
Wall, Kathryn B.
LiVolsi, Virginia A.
Randolph, Gregory W.
Ghossein, Ronald A.
TI Nomenclature Revision for Encapsulated Follicular Variant of Papillary
Thyroid Carcinoma A Paradigm Shift to Reduce Overtreatment of Indolent
Tumors
SO JAMA ONCOLOGY
LA English
DT Article
ID UNITED-STATES; OBSERVER VARIATION; NUCLEAR FEATURES; BRAF V600E; CANCER;
DIAGNOSIS; OVERDIAGNOSIS; IMPACT; NEOPLASMS; PATTERNS
AB IMPORTANCE Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.
OBJECTIVE To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
DESIGN, SETTING, AND PARTICIPANTS International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
MAIN OUTCOMES AND MEASURES Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.
RESULTS Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6%(95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3%(95% CI, 92.1%-96.0%) for NIFTP.
CONCLUSIONS AND RELEVANCE Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
C1 [Nikiforov, Yuri E.; Seethala, Raja R.; Nikiforova, Marina N.] Univ Pittsburgh, Dept Pathol, 3477 Euler Way,Room 8031, Pittsburgh, PA 15213 USA.
[Tallini, Giovanni] Univ Bologna, Sch Med, Dept Med DIMES, Anat Pathol, Bologna, Italy.
[Baloch, Zubair W.; LiVolsi, Virginia A.] Hosp Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA USA.
[Basolo, Fulvio] Univ Pisa, Dept Surg Med & Mol Pathol, Pisa, Italy.
[Thompson, Lester D. R.] Southern Calif Permanente Med Grp, Woodland Hills, CA USA.
[Barletta, Justine A.] Brigham & Womens Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA.
[Wenig, Bruce M.] Mt Sinai Hlth Syst, Dept Pathol, New York, NY USA.
[Al Ghuzlan, Abir] Dept Med Biol & Pathol, Gustave Roussy Canc Campus Grand Paris, Villejuif, France.
[Kakudo, Kennichi] Kindai Univ, Fac Med, Dept Pathol & Lab Med, Ikoma City, Japan.
[Giordano, Thomas J.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA.
[Giordano, Thomas J.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Alves, Venancio A.] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo, Brazil.
[Alves, Venancio A.] Hosp Alemao Oswaldo Cruz, Dept Pathol, Sao Paulo, Brazil.
[Khanafshar, Elham] Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA.
[Asa, Sylvia L.; Mete, Ozgur] Univ Hlth Network, Dept Pathol, Toronto, ON, Canada.
[El-Naggar, Adel K.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Gooding, William E.] Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA USA.
[Hodak, Steven P.] NYU, Sch Med, Div Endocrinol & Metab, New York, NY USA.
[Lloyd, Ricardo V.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Maytal, Guy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Nose, Vania; Sadow, Peter M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Nose, Vania; Sadow, Peter M.] Harvard Med Sch, Dept Pathol, Boston, MA USA.
[Papotti, Mauro] Univ Turin, Dept Oncol, Turin, Italy.
[Poller, David N.] Queen Alexandra Hosp, Dept Pathol, Portsmouth, Hants, England.
[Tischler, Arthur S.] Tufts Univ, Sch Med, Tufts Med Ctr, Dept Pathol & Lab Med, Boston, MA 02111 USA.
[Tuttle, Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol, New York, NY 10021 USA.
[Wall, Kathryn B.] Thyroid Canc Survivors Assoc Inc, Raleigh, NC USA.
[Randolph, Gregory W.] Massachusetts Eye & Ear Infirm, Gen & Thyroid & Parathyroid Endocrine Surg Div, Boston, MA 02114 USA.
[Ghossein, Ronald A.] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA.
RP Nikiforov, YE (reprint author), Univ Pittsburgh, Dept Pathol, 3477 Euler Way,Room 8031, Pittsburgh, PA 15213 USA.
EM nikiforovye@upmc.edu
OI BASOLO, FULVIO/0000-0003-1657-5020
FU National Cancer Institute [P30CA047904]; UPCI; University of Pittsburgh
Medical Center (UPMC); CBLPath, Inc (Rye Brook, NY)
FX This project used the University of Pittsburgh Cancer Institute (UPCI)
Biostatistics Facility that is supported in part by award P30CA047904
from the National Cancer Institute. Molecular analysis was supported in
part by funds from the UPCI and University of Pittsburgh Medical Center
(UPMC). The Endocrine Pathology Society conference for reevaluation of
the encapsulated follicular variant of papillary thyroid carcinoma held
on March 20-21 in Boston, Massachusetts, was supported by an education
grant from CBLPath, Inc (Rye Brook, NY).
NR 35
TC 35
Z9 35
U1 556
U2 556
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 AUG
PY 2016
VL 2
IS 8
BP 1023
EP 1029
DI 10.1001/jamaoncol.2016.0386
PG 7
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700011
PM 27078145
ER
PT J
AU Chen, G
McQuade, JL
Panka, DJ
Hudgens, CW
Amin-Mansour, A
Mu, XJ
Bahl, S
Jane-Valbuena, J
Wani, KM
Reuben, A
Creasy, CA
Jiang, H
Cooper, ZA
Roszik, J
Bassett, RL
Joon, AY
Simpson, LM
Mouton, RD
Glitza, IC
Patel, SP
Hwu, WJ
Amaria, RN
Diab, A
Hwu, P
Lazar, AJ
Wargo, JA
Garraway, LA
Tetzlaff, MT
Sullivan, RJ
Kim, KB
Davies, MA
AF Chen, Guo
McQuade, Jennifer L.
Panka, David J.
Hudgens, Courtney W.
Amin-Mansour, Ali
Mu, Xinmeng Jasmine
Bahl, Samira
Jane-Valbuena, Judit
Wani, Khalida M.
Reuben, Alexandre
Creasy, Caitlyn A.
Jiang, Hong
Cooper, Zachary A.
Roszik, Jason
Bassett, Roland L., Jr.
Joon, Aron Y.
Simpson, Lauren M.
Mouton, Rosalind D.
Glitza, Isabella C.
Patel, Sapna P.
Hwu, Wen-Jen
Amaria, Rodabe N.
Diab, Adi
Hwu, Patrick
Lazar, Alexander J.
Wargo, Jennifer A.
Garraway, Levi A.
Tetzlaff, Michael T.
Sullivan, Ryan J.
Kim, Kevin B.
Davies, Michael A.
TI Clinical, Molecular, and Immune Analysis of Dabrafenib-Trametinib
Combination Treatment for BRAF Inhibitor-Refractory Metastatic Melanoma
A Phase 2 Clinical Trial
SO JAMA ONCOLOGY
LA English
DT Article
ID ACQUIRED-RESISTANCE; MEK INHIBITION; RAF INHIBITION; SOLID TUMORS;
MUTATIONS; PATHWAY; BRAF(V600E); VEMURAFENIB; THERAPY; CANCER
AB IMPORTANCE Combined treatment with dabrafenib and trametinib (CombiDT) achieves clinical responses in only about 15% of patients with BRAF inhibitor (BRAFi)-refractory metastatic melanoma in contrast to the higher response rate observed in BRAFi-naive patients. Identifying correlates of response and mechanisms of resistance in this population will facilitate clinical management and rational therapeutic development.
OBJECTIVE To determine correlates of benefit from CombiDT therapy in patients with BRAFi-refractory metastatic melanoma.
DESIGN, SETTING, AND PARTICIPANTS Single-center, single-arm, open-label phase 2 trial of CombiDT treatment in patients with BRAF V600 metastatic melanoma resistant to BRAFi monotherapy conducted between September 2012 and October 2014 at the University of Texas MD Anderson Cancer Center. Key eligibility criteria for participants included BRAF V600 metastatic melanoma, prior BRAFi monotherapy, measurable disease (RECIST 1.1), and tumor accessible for biopsy.
INTERVENTIONS Patients were treated with dabrafenib (150mg, twice daily) and trametinib (2mg/d) continuously until disease progression or intolerance. All participants underwent a mandatory baseline biopsy, and optional biopsy specimens were obtained on treatment and at disease progression. Whole-exome sequencing, reverse transcription polymerase chain reaction analysis for BRAF splicing, RNA sequencing, and immunohistochemical analysis were performed on tumor samples, and blood was analyzed for levels of circulating BRAF V600.
MAIN OUTCOMES AND MEASURES The primary end point was overall response rate (ORR). Progression-free survival (PFS) and overall survival (OS) were secondary clinical end points.
RESULTS A total of 28 patients were screened, and 23 enrolled. Among evaluable patients, the confirmed ORR was 10%; disease control rate (DCR) was 45%, and median PFS was 13 weeks. Clinical benefit was associated with duration of prior BRAFi therapy greater than 6 months (DCR, 73% vs 11% for <= 6 months; P=.02) and decrease in circulating BRAF V600 at day 8 of cycle 1 (DCR, 75% vs 18% for no decrease; P=.02) but not with pretreatment mitogen-activated protein kinase (MAPK) pathway mutations or activation. Biopsy specimens obtained during treatment demonstrated that CombiDT therapy failed to achieve significant MAPK pathway inhibition or immune infiltration in most patients.
CONCLUSIONS AND RELEVANCE The baseline presence of MAPK pathway alterations was not associated with benefit from CombiDT in patients with BRAFi-refractory metastatic melanoma. Failure to inhibit the MAPK pathway provides a likely explanation for the limited clinical benefit of CombiDT in this setting. Circulating BRAF V600 is a promising early biomarker of clinical response.
C1 [Chen, Guo; Creasy, Caitlyn A.; Roszik, Jason; Simpson, Lauren M.; Mouton, Rosalind D.; Glitza, Isabella C.; Patel, Sapna P.; Hwu, Wen-Jen; Amaria, Rodabe N.; Diab, Adi; Hwu, Patrick; Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Melanoma Med Oncol, Houston, TX 77030 USA.
[McQuade, Jennifer L.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA.
[Panka, David J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Hudgens, Courtney W.; Wani, Khalida M.; Lazar, Alexander J.; Tetzlaff, Michael T.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Hudgens, Courtney W.; Wani, Khalida M.; Lazar, Alexander J.; Tetzlaff, Michael T.] Univ Texas MD Anderson Canc Ctr, Dept Translat & Mol Pathol, Houston, TX 77030 USA.
[Amin-Mansour, Ali; Mu, Xinmeng Jasmine; Bahl, Samira; Jane-Valbuena, Judit; Garraway, Levi A.] Broad Inst, Cambridge, MA USA.
[Reuben, Alexandre; Jiang, Hong; Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA.
[Reuben, Alexandre; Jiang, Hong; Cooper, Zachary A.; Wargo, Jennifer A.] Univ Texas MD Anderson Canc Ctr, Dept Genom Med, Houston, TX 77030 USA.
[Bassett, Roland L., Jr.; Joon, Aron Y.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Sullivan, Ryan J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Kim, Kevin B.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Davies, Michael A.] Univ Texas MD Anderson Canc Ctr, Dept Syst Biol, Houston, TX 77030 USA.
RP Davies, MA (reprint author), Univ Texas MD Anderson Canc Ctr, 1515 Holcombe,Unit 0430, Houston, TX 77030 USA.
EM mdavies@mdanderson.org
FU Cancer Prevention and Research Institute of Texas [RP120505,
1R01CA187076-01, 5R01CA154710-03, P50 CA093459, P30 CA016672]; Dr Miriam
and Sheldon G. Adelson Medical Research Foundation; University of Texas
MD Anderson Cancer Center Melanoma Moon Shots Program; ASCO Young
Investigator Award; T32 Institutional Training Grant [T32 CA009666]; NIH
[1K08CA160692-01A1]; Melanoma Research Alliance Team Science Award;
Kennedy Memorial Foundation [0727030]
FX This work was supported by the Cancer Prevention and Research Institute
of Texas (RP120505, 1R01CA187076-01, 5R01CA154710-03, P50 CA093459, and
P30 CA016672), the Dr Miriam and Sheldon G. Adelson Medical Research
Foundation, and the University of Texas MD Anderson Cancer Center
Melanoma Moon Shots Program. Dr McQuade is supported by an ASCO Young
Investigator Award and a T32 Institutional Training Grant (T32
CA009666). Dr Wargo acknowledges NIH grants 1K08CA160692-01A1, the
Melanoma Research Alliance Team Science Award, and the Kennedy Memorial
Foundation grant # 0727030.
NR 33
TC 1
Z9 1
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 AUG
PY 2016
VL 2
IS 8
BP 1056
EP 1064
DI 10.1001/jamaoncol.2016.0509
PG 9
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700017
PM 27124486
ER
PT J
AU Liu, D
Plimack, ER
Hoffman-Censits, J
Garraway, LA
Bellmunt, J
Van Allen, E
Rosenberg, JE
AF Liu, David
Plimack, Elizabeth R.
Hoffman-Censits, Jean
Garraway, Levi A.
Bellmunt, Joaquim
Van Allen, Eliezer
Rosenberg, Jonathan E.
TI Clinical Validation of Chemotherapy Response Biomarker ERCC2 in
Muscle-Invasive Urothelial Bladder Carcinoma
SO JAMA ONCOLOGY
LA English
DT Letter
ID CISPLATIN SENSITIVITY; REPAIR
C1 [Liu, David; Garraway, Levi A.; Bellmunt, Joaquim; Van Allen, Eliezer] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Garraway, Levi A.; Van Allen, Eliezer] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Hoffman-Censits, Jean] Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA.
[Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
RP Rosenberg, JE (reprint author), Mem Sloan Kettering Canc Ctr, Sidney Kimmel Ctr Prostate & Urol Canc, 353 E 68th St, New York, NY 10065 USA.
EM rosenbj1@mskcc.org
NR 5
TC 2
Z9 2
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 AUG
PY 2016
VL 2
IS 8
BP 1094
EP 1096
DI 10.1001/jamaoncol.2016.1056
PG 4
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700025
PM 27310333
ER
PT J
AU Sacher, AG
Alden, RS
Oxnard, GR
AF Sacher, Adrian G.
Alden, Ryan S.
Oxnard, Geoffrey R.
TI Early Intervention in Lung Cancers With Rapid Plasma Genotyping for EGFR
and KRAS Mutations Reply
SO JAMA ONCOLOGY
LA English
DT Letter
C1 [Sacher, Adrian G.; Alden, Ryan S.; Oxnard, Geoffrey R.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
[Sacher, Adrian G.; Oxnard, Geoffrey R.] Brigham & Womens Hosp, Harvard Med Sch, 75 Francis St, Boston, MA 02115 USA.
[Sacher, Adrian G.] Columbia Univ, New York Presbyterian Hosp, New York, NY USA.
RP Oxnard, GR (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave, Boston, MA 02115 USA.
EM geoffrey_oxnard@dfci.harvard.edu
NR 3
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 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD AUG
PY 2016
VL 2
IS 8
BP 1096
EP 1097
DI 10.1001/jamaoncol.2016.1963
PG 3
WC Oncology
SC Oncology
GA DW5RN
UT WOS:000383704700027
PM 27388452
ER
PT J
AU Goldstone, RN
McCormack, MC
Khan, SI
Salinas, HM
Meppelink, A
Randolph, MA
Watkins, MT
Redmond, RW
Austen, WG
AF Goldstone, Robert N.
McCormack, Michael C.
Khan, Saiqa I.
Salinas, Harry M.
Meppelink, Amanda
Randolph, Mark A.
Watkins, Michael T.
Redmond, Robert W.
Austen, William G., Jr.
TI Photochemical Tissue Passivation Reduces Vein Graft Intimal Hyperplasia
in a Swine Model of Arteriovenous Bypass Grafting
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE cardiovascular disease; collagen; hyperplasia; intima-media thickness;
vein graft
ID SMOOTH-MUSCLE-CELLS; SAPHENOUS-VEIN; GROWTH-FACTOR; PIG MODEL; DISEASE;
REVASCULARIZATION; PATHOPHYSIOLOGY; ASSOCIATION; MECHANISMS; STRATEGIES
AB Background-Bypass grafting remains the standard of care for coronary artery disease and severe lower extremity ischemia. Efficacy is limited by poor long-term venous graft patency secondary to intimal hyperplasia (IH) caused by venous injury upon exposure to arterial pressure. We investigate whether photochemical tissue passivation (PTP) treatment of vein grafts modulates smooth muscle cell (SMC) proliferation and migration, and inhibits development of IH.
Methods and Results-PTP was performed at increasing fluences up to 120 J/cm(2) on porcine veins. Tensiometry performed to assess vessel elasticity/stiffness showed increased stiffness with increasing fluence until plateauing at 90 J/cm(2) (median, interquartile range [IQR]). At 90 J/cm(2), PTP-treated vessels had a 10-fold greater Young's modulus than untreated controls (954 [IQR, 2217] vs 99 kPa [IQR, 63]; P= 0.03). Each pig received a PTP-treated and untreated carotid artery venous interposition graft. At 4-weeks, intimal/medial areas were assessed. PTP reduced the degree of IH by 66% and medial hypertrophy by 49%. Intimal area was 3.91 (IQR, 1.2) and 1.3 mm(2) (IQR, 0.97; P <= 0.001) in untreated and PTP-treated grafts, respectively. Medial area was 9.2 (IQR, 3.2) and 4.7 mm(2) (IQR, 2.0; P <= 0.001) in untreated and PTP-treated grafts, respectively. Immunohistochemistry was performed to assess alpha-smooth muscle actin (SMA) and proliferating cell nuclear antigen (PCNA). Objectively, there were less SMA-positive cells within the intima/media of PTP-treated vessels than controls. There was an increase in PCNA-positive cells within control vein grafts (18% [IQR, 5.3]) versus PTP-treated vein grafts (5% [IQR, 0.9]; P= 0.02).
Conclusions-By strengthening vein grafts, PTP decreases SMC proliferation and migration, thereby reducing IH.
C1 [Goldstone, Robert N.; McCormack, Michael C.; Khan, Saiqa I.; Salinas, Harry M.; Meppelink, Amanda; Randolph, Mark A.; Austen, William G., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA USA.
[Watkins, Michael T.] Harvard Med Sch, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA USA.
[Redmond, Robert W.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA.
[Redmond, Robert W.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA.
RP Austen, WG (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg & Burn Surg, 15 Parkman St,WAC 435, Boston, MA 02114 USA.
EM wausten@partners.org
FU American College of Surgeons Resident Research Scholarship; Partners
HealthCare Innovation Development Grant
FX This project was funded by the American College of Surgeons Resident
Research Scholarship and a Partners HealthCare Innovation Development
Grant.
NR 29
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 AUG
PY 2016
VL 5
IS 8
AR e003856
DI 10.1161/JAHA.116.003856
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6DE
UT WOS:000386714900037
ER
PT J
AU Karacsonyi, J
Alaswad, K
Jaffer, FA
Yeh, RW
Patel, M
Bahadorani, J
Karatasakis, A
Danek, BA
Doing, A
Grantham, JA
Karmpaliotis, D
Moses, JW
Kirtane, A
Parikh, M
Ali, Z
Lombardi, WL
Kandzari, DE
Lembo, N
Garcia, S
Wyman, MR
Alame, A
Nguyen-Trong, PKJ
Resendes, E
Kalsaria, P
Rangan, BV
Ungi, I
Thompson, CA
Banerjee, S
Brilakis, ES
AF Karacsonyi, Judit
Alaswad, Khaldoon
Jaffer, Farouc A.
Yeh, Robert W.
Patel, Mitul
Bahadorani, John
Karatasakis, Aris
Danek, Barbara A.
Doing, Anthony
Grantham, J. Aaron
Karmpaliotis, Dimitri
Moses, Jeffrey W.
Kirtane, Ajay
Parikh, Manish
Ali, Ziad
Lombardi, William L.
Kandzari, David E.
Lembo, Nicholas
Garcia, Santiago
Wyman, Michael R.
Alame, Aya
Nguyen-Trong, Phuong-Khanh J.
Resendes, Erica
Kalsaria, Pratik
Rangan, Bavana V.
Ungi, Imre
Thompson, Craig A.
Banerjee, Subhash
Brilakis, Emmanouil S.
TI Use of Intravascular Imaging During Chronic Total Occlusion Percutaneous
Coronary Intervention: Insights From a Contemporary Multicenter Registry
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE chronic total occlusion; intravascular ultrasound; optical coherence
tomography; percutaneous coronary intervention
ID OPTICAL COHERENCE TOMOGRAPHY; REVERSE CONTROLLED ANTEGRADE; ELUTING
STENT IMPLANTATION; IN-HOSPITAL OUTCOMES; HYBRID APPROACH; RETROGRADE
TRACKING; ULTRASOUND GUIDANCE; PROCEDURAL OUTCOMES; CTO REGISTRY;
RECANALIZATION
AB Background-Intravascular imaging can facilitate chronic total occlusion (CTO) percutaneous coronary intervention.
Methods and Results-We examined the frequency of use and outcomes of intravascular imaging among 619 CTO percutaneous coronary interventions performed between 2012 and 2015 at 7 US centers. Mean age was 65.4 +/- 10 years and 85% of the patients were men. Intravascular imaging was used in 38%: intravascular ultrasound in 36%, optical coherence tomography in 3%, and both in 1.45%. Intravascular imaging was used for stent sizing (26.3%), stent optimization (38.0%), and CTO crossing (35.7%, antegrade in 27.9%, and retrograde in 7.8%). Intravascular imaging to facilitate crossing was used more frequently in lesions with proximal cap ambiguity (49% versus 26%, P<0.0001) and with retrograde as compared with antegrade-only cases (67% versus 31%, P<0.0001). Despite higher complexity (Japanese CTO score: 2.86 +/- 1.19 versus 2.43 +/- 1.19, P=0.001), cases in which imaging was used for crossing had similar technical and procedural success (92.8% versus 89.6%, P=0.302 and 90.1% versus 88.3%, P=0.588, respectively) and similar incidence of major cardiac adverse events (2.7% versus 3.2%, P=0.772). Use of intravascular imaging was associated with longer procedure (192 minutes [interquartile range 130, 255] versus 131 minutes [90, 192], P<0.0001) and fluoroscopy (71 minutes [44, 93] versus 39 minutes [25, 69], P<0.0001) time.
Conclusions-Intravascular imaging is frequently performed during CTO percutaneous coronary intervention both for crossing and for stent selection/optimization. Despite its use in more complex lesion subsets, intravascular imaging was associated with similar rates of technical and procedural success for CTO percutaneous coronary intervention.
C1 [Karacsonyi, Judit; Karatasakis, Aris; Danek, Barbara A.; Alame, Aya; Nguyen-Trong, Phuong-Khanh J.; Resendes, Erica; Kalsaria, Pratik; Rangan, Bavana V.; Banerjee, Subhash; Brilakis, Emmanouil S.] VA North Texas Healthcare Syst, Dallas, TX USA.
[Karacsonyi, Judit; Karatasakis, Aris; Danek, Barbara A.; Alame, Aya; Nguyen-Trong, Phuong-Khanh J.; Resendes, Erica; Rangan, Bavana V.; Banerjee, Subhash; Brilakis, Emmanouil S.] UT Southwestern Med Ctr, Dallas, TX USA.
[Karacsonyi, Judit; Ungi, Imre] Univ Szeged, Dept Internal Med 2, Div Invas Cardiol, Szeged, Hungary.
[Karacsonyi, Judit; Ungi, Imre] Univ Szeged, Ctr Cardiol, Szeged, Hungary.
[Alaswad, Khaldoon] Henry Ford Hosp, Detroit, MI 48202 USA.
[Jaffer, Farouc A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Jaffer, Farouc A.] Harvard Med Sch, Boston, MA USA.
[Yeh, Robert W.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 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.
[Doing, Anthony] Med Ctr Rockies, Loveland, CO USA.
[Grantham, J. Aaron] Mid Amer Heart Inst, Kansas City, MO USA.
[Karmpaliotis, Dimitri; Moses, Jeffrey W.; Kirtane, Ajay; Parikh, Manish; Ali, Ziad] Columbia Univ, New York, NY USA.
[Lombardi, William L.] Univ Washington, Seattle, WA 98195 USA.
[Kandzari, David E.; Lembo, Nicholas] Piedmont Heart Inst, Atlanta, GA USA.
[Garcia, Santiago] Minneapolis VA Healthcare Syst, Minneapolis, MN USA.
[Garcia, Santiago] Univ Minnesota, Minneapolis, MN USA.
[Wyman, Michael R.] Torrance Mem Med Ctr, Torrance, CA 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
OI Parikh, Manish/0000-0002-8612-5407
FU Clinical and Translational Science Awards National Institutes of Health
Grant [UL1-RR024982]
FX This was work was supported by Clinical and Translational Science Awards
National Institutes of Health Grant UL1-RR024982.
NR 38
TC 0
Z9 0
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 AUG
PY 2016
VL 5
IS 8
AR e003890
DI 10.1161/JAHA.116.003890
PG 13
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA EA6DE
UT WOS:000386714900039
ER
PT J
AU Madenci, AL
Stetson, A
Weldon, CB
Lehmann, LE
AF Madenci, Arin L.
Stetson, Alyssa
Weldon, Christopher B.
Lehmann, Leslie E.
TI Safety of peritoneal and pleural drain placement in pediatric stem cell
transplant recipients with severe veno-occlusive disease
SO PEDIATRIC TRANSPLANTATION
LA English
DT Article
DE hematopoietic stem cell transplantation; pediatric; veno-occlusive
disease; sinusoidal obstruction syndrome; peritoneal drain; pleural
drain
ID BONE-MARROW-TRANSPLANTATION; INTENSIVE-CARE UNIT; OPERATING-ROOM;
RISK-FACTORS; CHILDREN; LIVER; COMPLICATIONS; DEFIBROTIDE; MORTALITY;
SURVIVAL
AB Hepatic VOD (veno-occlusive disease) is a serious complication of HSCT (hematopoietic stem cell transplantation) and has historically been associated with high mortality. This obstruction to hepatic flow often results in fluid collections in the peritoneal and pleural cavities. Catheter placement to drain ascites or pleural fluid may reduce intra-abdominal hypertension and/or improve respiratory parameters. The safety of these interventions among critically ill, immunocompromised children is unknown. Among 32 HSCT recipients (2000-2012) with severe VOD, we assessed the primary outcome of procedural complication from peritoneal drain placement. Twenty-four (75%) patients underwent peritoneal drain placement. No patient sustained visceral perforation or hemorrhage with drain placement. Overall mortality was 47% (n = 15). The procedure was not associated with increased overall mortality (p > 0.99). Eight (25%) peritoneal drains required replacement for malfunction. Of 24 patients with peritoneal drains, one (4%) patient had a positive culture from ascitic fluid. Eight (25%) patients underwent pleural drain placement. No pleural drain-related procedural complication or infection occurred. Four (50%) of the eight patients with pleural drains had de-escalation in oxygen requirement at drain removal, compared to time of placement. In this study, peritoneal and pleural drains were safe interventions for children with severe VOD.
C1 [Madenci, Arin L.; Weldon, Christopher B.] Boston Childrens Hosp, Dept Surg, Boston, MA USA.
[Madenci, Arin L.; Weldon, Christopher B.; Lehmann, Leslie E.] Harvard Med Sch, Boston, MA USA.
[Madenci, Arin L.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
[Stetson, Alyssa; Weldon, Christopher B.; Lehmann, Leslie E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA.
[Lehmann, Leslie E.] Boston Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA USA.
RP Lehmann, LE (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM leslie_lehmann@dfci.harvard.edu
OI Madenci, Arin/0000-0003-1258-7278
NR 24
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1397-3142
EI 1399-3046
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD AUG
PY 2016
VL 20
IS 5
BP 687
EP 691
DI 10.1111/petr.12730
PG 5
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA DW4CS
UT WOS:000383590300014
PM 27373552
ER
PT J
AU Castillo, JJ
Palomba, ML
Advani, R
Treon, SP
AF Castillo, Jorge J.
Palomba, M. Lia
Advani, Ranjana
Treon, Steven P.
TI Ibrutinib in Waldenstrom macroglobulinemia: latest evidence and clinical
experience
SO THERAPEUTIC ADVANCES IN HEMATOLOGY
LA English
DT Review
DE Bruton's tyrosine kinase; ibrutinib; lymphoplasmacytic lymphoma;
Waldenstrom macroglobulinemia
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; BRUTON TYROSINE KINASE; MANTLE-CELL
LYMPHOMA; END RESULTS DATABASE; ATRIAL-FIBRILLATION; INNATE IMMUNITY;
PRIMARY THERAPY; WHIM-SYNDROME; RITUXIMAB; DEXAMETHASONE
AB Ibrutinib is an oral Bruton's tyrosine kinase (BTK) inhibitor, which has recently gained approval by the United States (US) Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of patients with symptomatic Waldenstrom macroglobulinemia (WM). Herein, we review the role of BTK in the pathophysiology of WM, and present the results of the preclinical and clinical studies that led to the initial investigation and later approval of ibrutinib in WM. We also discuss aspects associated with ibrutinib therapy in WM patients, especially focusing on genomic profiling and the impact on response to ibrutinib, and the management of adverse events.
C1 [Castillo, Jorge J.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave, Boston, MA 02115 USA.
[Palomba, M. Lia] Mem Sloan Kettering Canc Ctr, Div Hematol, 1275 York Ave, New York, NY 10021 USA.
[Advani, Ranjana] Stanford Univ, Med Ctr, Div Oncol, Stanford, CA USA.
[Treon, Steven P.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA.
RP Castillo, JJ (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, 450 Brookline Ave, Boston, MA 02115 USA.
EM Jorgej_castillo@dfci.harvard.edu
NR 49
TC 0
Z9 0
U1 1
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 2040-6207
EI 2040-6215
J9 THER ADV HEMATOL
JI Ther. Adv. Hematol.
PD AUG
PY 2016
VL 7
IS 4
BP 179
EP 186
DI 10.1177/2040620716654102
PG 8
WC Hematology
SC Hematology
GA DW5AF
UT WOS:000383653400001
PM 27493708
ER
PT J
AU Arora, M
Gowda, S
Tuscano, J
AF Arora, Mili
Gowda, Sonia
Tuscano, Joseph
TI A comprehensive review of lenalidomide in B-cell non-Hodgkin lymphoma
SO THERAPEUTIC ADVANCES IN HEMATOLOGY
LA English
DT Review
DE lenalidomide; non-Hodgkin lymphoma; rituximab
ID SINGLE-AGENT LENALIDOMIDE; PHASE-II; PLUS RITUXIMAB; PROGNOSTIC-FACTORS;
OPEN-LABEL; TRIAL; MULTICENTER; INDOLENT; THERAPY; DEXAMETHASONE
AB Lenalidomide, an immunomodulatory drug that the US Food and Drug Administration (FDA) approved for the treatment of multiple myeloma, 5q-myelodysplasia and mantle-cell lymphoma (MCL), has encouraging efficacy in other B-cell malignancies. Its unique mechanism of action is in part due to altering the tumor microenvironment and potentiating the activity of T and natural-killer (NK) cells. Impressive clinical activity and excellent tolerability allows broad applicability. Lenalidomide has been used in a wide range of B-cell malignancies for years, but in 2013, the FDA marked its approval as a single agent only in relapsed/refractory mantle-cell lymphoma. Perhaps most impressive is the efficacy of lenalidomide when combined with monoclonal antibodies. Impressive efficacy and toxicity profiles with the combination of lenalidomide and rituximab in B-cell lymphomas in both the upfront and relapsed/refractory setting may allow a shift in our current treatment paradigm in both indolent and aggressive non-Hodgkin lymphoma (NHL). This review will summarize the current data in the relapsed/refractory and front-line setting of NHL with single-agent lenalidomide as well as its use in combination with other agents.
C1 [Tuscano, Joseph] UC Davis Med Ctr, Northern Carolina Healthcare Syst, Div Hematol & Oncol, Dept Internal Med,Dept Vet Affairs, 4501 X St, Sacramento, CA 95817 USA.
[Arora, Mili; Gowda, Sonia] Dept Internal Med, Div Hematol & Oncol, Sacramento, CA USA.
[Arora, Mili] US Dept Vet Affairs, Northern Carolina Healthcare Syst, Sacramento, CA USA.
RP Tuscano, J (reprint author), UC Davis Med Ctr, Northern Carolina Healthcare Syst, Div Hematol & Oncol, Dept Internal Med,Dept Vet Affairs, 4501 X St, Sacramento, CA 95817 USA.
EM joseph.tuscano@ucdmc.ucdavis.edu
NR 51
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 2040-6207
EI 2040-6215
J9 THER ADV HEMATOL
JI Ther. Adv. Hematol.
PD AUG
PY 2016
VL 7
IS 4
BP 209
EP 221
DI 10.1177/2040620716652861
PG 13
WC Hematology
SC Hematology
GA DW5AF
UT WOS:000383653400004
PM 27493711
ER
PT J
AU Ohye, B
Kelly, H
Chen, Y
Zakarian, RJ
Simon, NM
Bui, E
AF Ohye, Bonnie
Kelly, Hope
Chen, Yang
Zakarian, Rebecca J.
Simon, Naomi M.
Bui, Eric
TI Staying Strong With Schools: A Civilian School-Based Intervention to
Promote Resilience for Military-Connected Children
SO MILITARY MEDICINE
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; FACING WARTIME DEPLOYMENTS;
FAMILY-CENTERED PREVENTION; COMMUNITIES; SUPPORT; IMPACT
AB Since September 11, 2001, over 2 million U.S. service members have been deployed to Iraq or Afghanistan, resulting in hundreds of thousands of military-connected children (MCC) having experienced a parental deployment. Although parental deployments have significantly burdened these children, few evidence-based interventions designed to support their resilience to these stressors are available. To address this gap, we developed a civilian school-based intervention to promote resilience in MCC living in the community. Our intervention, Staying Strong With Schools (SSWS), aims to deliver: a training to all school professionals early in the school year to educate them about challenges for children and families experiencing parental deployment and signs of deployment-related distress; and a year-long training for the school guidance counselor who coordinates communication and provides psychosocial support to MCC within the school community. We piloted SSWS in two civilian elementary schools and found promising feasibility and acceptability.
C1 [Ohye, Bonnie; Kelly, Hope; Chen, Yang; Zakarian, Rebecca J.; Simon, Naomi M.; Bui, Eric] Red Sox Fdn, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA.
[Ohye, Bonnie; Kelly, Hope; Chen, Yang; Zakarian, Rebecca J.; Simon, Naomi M.; Bui, Eric] Massachusetts Gen Hosp, Home Base Program, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA.
[Ohye, Bonnie; Simon, Naomi M.; Bui, Eric] Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA.
RP Ohye, B (reprint author), Red Sox Fdn, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA.; Ohye, B (reprint author), Massachusetts Gen Hosp, Home Base Program, One Bowdoin Sq,Suite 650, Boston, MA 02114 USA.; Ohye, B (reprint author), Harvard Med Sch, 25 Shattuck St, Boston, MA 02115 USA.
NR 28
TC 0
Z9 0
U1 0
U2 0
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 AUG
PY 2016
VL 181
IS 8
BP 872
EP 877
DI 10.7205/MILMED-D-15-00234
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW5MI
UT WOS:000383688900033
PM 27483526
ER
PT J
AU Pasquina, PF
Isaacson, BM
Johnson, E
Rhoades, DS
Lindholm, MP
Grindle, GG
Cooper, RA
AF Pasquina, Paul F.
Isaacson, Brad M.
Johnson, Elizabeth
Rhoades, Daniel S.
Lindholm, Mark P.
Grindle, Garrett G.
Cooper, Rory A.
TI A Patient-Controlled Analgesia Adaptor to Mitigate Postsurgical Pain for
Combat Casualties With Multiple Limb Amputation: A Case Series
SO MILITARY MEDICINE
LA English
DT Article
ID REHABILITATION
AB The use of explosive armaments during Operation Iraqi Freedom, Operation Enduring Freedom, and Operation New Dawn has resulted in a significant number of injured U.S. service members. These weapons often generate substantial extremity trauma requiring multiple surgical procedures to preserve life, limb, and restore function. For those individuals who require multiple surgeries, the use of patient-controlled analgesia (PCA) devices can be an effective way to achieve adequate pain management and promote successful rehabilitation and recovery during inpatient treatment. A subpopulation of patients are unable to independently control a PCA device because of severe multiple limb dysfunction and/or loss. In response to the needs of these patients, our team designed and developed a custom adaptor to assist service members who would otherwise not be able to use a PCA. Patient feedback of the device indicated a positive response, improved independence, and overall satisfaction during inpatient hospitalization.
C1 [Pasquina, Paul F.; Isaacson, Brad M.; Johnson, Elizabeth; Rhoades, Daniel S.; Lindholm, Mark P.] Uniformed Serv Univ Hlth Sci, Ctr Rehabil Sci Res, Dept Phys Med & Rehabil, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
[Pasquina, Paul F.; Isaacson, Brad M.; Rhoades, Daniel S.; Lindholm, Mark P.] Walter Reed Natl Mil Med Ctr, Dept Rehabil, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
[Isaacson, Brad M.; Johnson, Elizabeth] Henry M Jackson Fdn Adv Mil Med, 6720A Rockledge Dr,100, Bethesda, MD 20817 USA.
[Grindle, Garrett G.; Cooper, Rory A.] Univ Pittsburgh, US Dept Vet Affairs, Human Engn Res Labs, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA.
[Grindle, Garrett G.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, 6425 Penn Ave,Suite 400, Pittsburgh, PA 15206 USA.
RP Pasquina, PF (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Rehabil Sci Res, Dept Phys Med & Rehabil, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.; Pasquina, PF (reprint author), Walter Reed Natl Mil Med Ctr, Dept Rehabil, 8901 Wisconsin Ave, Bethesda, MD 20889 USA.
FU Department of Defense [HU0001-11-1-0004, HU0001-15-2-0003]; Henry M.
Jackson Foundation for the Advancement of Military Medicine
FX This article is based on a work supported by the Department of Defense
to the Center for Rehabilitation Science Research, Department of
Physical Medicine and Rehabilitation, Uniformed Services University of
Health Sciences (HU0001-11-1-0004, HU0001-15-2-0003) and The Henry M.
Jackson Foundation for the Advancement of Military Medicine.
NR 13
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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 AUG
PY 2016
VL 181
IS 8
BP E948
EP E951
DI 10.7205/MILMED-D-15-00315
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW5MI
UT WOS:000383688900002
PM 27483540
ER
PT J
AU Moy, ML
Martinez, CH
Kadri, R
Roman, P
Holleman, RG
Kim, HM
Nguyen, HQ
Cohen, MD
Goodrich, DE
Giardino, ND
Richardson, CR
AF Moy, Marilyn L.
Martinez, Carlos H.
Kadri, Reema
Roman, Pia
Holleman, Robert G.
Kim, Hyungjin Myra
Nguyen, Huong Q.
Cohen, Miriam D.
Goodrich, David E.
Giardino, Nicholas D.
Richardson, Caroline R.
TI Long-Term Effects of an Internet-Mediated Pedometer-Based Walking
Program for Chronic Obstructive Pulmonary Disease: Randomized Controlled
Trial
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE bronchitis, chronic; emphysema; pulmonary disease, chronic obstructive;
quality of life; exercise; motor activity; Internet
ID DAILY STEP COUNT; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; PROSPECTIVE
COHORT; CLINICAL-PRACTICE; HEALTH-STATUS; US COHORT; COPD;
REHABILITATION; COMORBIDITIES
AB Background: Regular physical activity (PA) is recommended for persons with chronic obstructive pulmonary disease (COPD). Interventions that promote PA and sustain long-term adherence to PA are needed.
Objective: We examined the effects of an Internet-mediated, pedometer-based walking intervention, called Taking Healthy Steps, at 12 months.
Methods: Veterans with COPD (N=239) were randomized in a 2:1 ratio to the intervention or wait-list control. During the first 4 months, participants in the intervention group were instructed to wear the pedometer every day, upload daily step counts at least once a week, and were provided access to a website with four key components: individualized goal setting, iterative feedback, educational and motivational content, and an online community forum. The subsequent 8-month maintenance phase was the same except that participants no longer received new educational content. Participants randomized to the wait-list control group were instructed to wear the pedometer, but they did not receive step-count goals or instructions to increase PA. The primary outcome was health-related quality of life (HRQL) assessed by the St George's Respiratory Questionnaire Total Score (SGRQ-TS); the secondary outcome was daily step count. Linear mixed-effect models assessed the effect of intervention over time. One participant was excluded from the analysis because he was an outlier. Within the intervention group, we assessed pedometer adherence and website engagement by examining percent of days with valid step-count data, number of log-ins to the website each month, use of the online community forum, and responses to a structured survey.
Results: Participants were 93.7% male (223/238) with a mean age of 67 (SD 9) years. At 12 months, there were no significant between-group differences in SGRQ-TS or daily step count. Between-group difference in daily step count was maximal and statistically significant at month 4 (P<.001), but approached zero in months 8-12. Within the intervention group, mean 76.7% (SD 29.5) of 366 days had valid step-count data, which decreased over the months of study (P<.001). Mean number of log-ins at least once during the study by 83.8% (129/154) of participants. Responses to questions assessing participants' goal commitment and intervention engagement were not significantly different at 12 months compared to 4 months.
Conclusions: An Internet-mediated, pedometer-based PA intervention, although efficacious at 4 months, does not maintain improvements in HRQL and daily step counts at 12 months. Waning pedometer adherence and website engagement by the intervention group were observed. Future efforts should focus on improving features of PA interventions to promote long-term behavior change and sustain engagement in PA.
C1 [Moy, Marilyn L.] VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Boston, MA USA.
[Moy, Marilyn L.] Harvard Med Sch, Boston, MA USA.
[Martinez, Carlos H.] Univ Michigan Hlth Syst, Pulm & Crit Care Div, Ann Arbor, MI USA.
[Kadri, Reema; Richardson, Caroline R.] Univ Michigan, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA.
[Kadri, Reema; Roman, Pia; Holleman, Robert G.; Kim, Hyungjin Myra; Goodrich, David E.; Richardson, Caroline R.] VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA.
[Kim, Hyungjin Myra] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Nguyen, Huong Q.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA 91101 USA.
[Cohen, Miriam D.] VA New York Harbor, Pulm Med Sect, Brooklyn, NY USA.
[Giardino, Nicholas D.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
RP Richardson, CR (reprint author), Univ Michigan, Dept Family Med, 1018 Fuller St, Ann Arbor, MI 48104 USA.
EM caroli@umich.edu
OI Nguyen, Huong/0000-0002-3650-3705
FU Department of Veterans Affairs, Health Services Research and Development
Service [IIR 09-366]; Department of Veterans Affairs, Rehabilitation
Research and Development Service [F6847W]; NIH National Heart, Lung and
Blood Institute [T32 HL007749-20]
FX We thank the Veterans for their participation in this research study.
The study was funded by Department of Veterans Affairs, Health Services
Research and Development Service (Grant IIR 09-366, Richardson);
Department of Veterans Affairs, Rehabilitation Research and Development
Service (Career Development Award, F6847W, Moy); and NIH National Heart,
Lung and Blood Institute (Grant T32 HL007749-20, Martinez). None of the
funding bodies had any role in the design, collection, analysis or
interpretation of the data, in writing the manuscript, or in the
decision to submit the manuscript for publication.
NR 45
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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 AUG
PY 2016
VL 18
IS 8
AR e215
DI 10.2196/jmir.5622
PG 14
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA EC9WT
UT WOS:000388495700003
PM 27502583
ER
PT J
AU Pfammatter, A
Spring, B
Saligram, N
Dave, R
Gowda, A
Blais, L
Arora, M
Ranjani, H
Ganda, O
Hedeker, D
Reddy, S
Ramalingam, S
AF Pfammatter, Angela
Spring, Bonnie
Saligram, Nalini
Dave, Raj
Gowda, Arun
Blais, Linelle
Arora, Monika
Ranjani, Harish
Ganda, Om
Hedeker, Donald
Reddy, Sethu
Ramalingam, Sandhya
TI mHealth Intervention to Improve Diabetes Risk Behaviors in India: A
Prospective, Parallel Group Cohort Study
SO JOURNAL OF MEDICAL INTERNET RESEARCH
LA English
DT Article
DE mHealth; diabetes; health promotion
ID PREVENTION PROGRAM; HEALTH; PROJECTIONS; PREVALENCE
AB Background: In low/middle income countries like India, diabetes is prevalent and health care access limited. Most adults have a mobile phone, creating potential for mHealth interventions to improve public health. To examine the feasibility and initial evidence of effectiveness of mDiabetes, a text messaging program to improve diabetes risk behaviors, a global nonprofit organization (Arogya World) implemented mDiabetes among one million Indian adults.
Objective: A prospective, parallel cohort design was applied to examine whether mDiabetes improved fruit, vegetable, and fat intakes and exercise.
Methods: Intervention participants were randomly selected from the one million Nokia subscribers who elected to opt in to mDiabetes. Control group participants were randomly selected from non-Nokia mobile phone subscribers. mDiabetes participants received 56 text messages in their choice of 12 languages over 6 months; control participants received no contact. Messages were designed to motivate improvement in diabetes risk behaviors and increase awareness about the causes and complications of diabetes. Participant health behaviors (exercise and fruit, vegetable, and fat intake) were assessed between 2012 and 2013 via telephone surveys by blinded assessors at baseline and 6 months later. Data were cleaned and analyzed in 2014 and 2015.
Results: 982 participants in the intervention group and 943 in the control group consented to take the phone survey at baselne. At the end of the 6-month period, 611 (62.22%) in the intervention and 632 (67.02%) in the control group completed the follow-up telephone survey. Participants receiving texts demonstrated greater improvement in a health behavior composite score over 6 months, compared with those who received no messages F(1, 1238) = 30.181, P<.001, 95% CI, 0.251-0.531. Fewer intervention participants demonstrated health behavior decline compared with controls. Improved fruit, vegetable, and fat consumption (P<.01) but not exercise were observed in those receiving messages, as compared with controls.
Conclusions: A text messaging intervention was feasible and showed initial evidence of effectiveness in improving diabetes-related health behaviors, demonstrating the potential to facilitate population-level behavior change in a low/middle income country.
C1 [Pfammatter, Angela; Spring, Bonnie] Northwestern Univ, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
[Saligram, Nalini; Ramalingam, Sandhya] Arogya World, Naperville, IL USA.
[Dave, Raj] Hlth ARC, Pennington, NJ USA.
[Gowda, Arun] Focus Sci Res Ctr, Bengaluru, India.
[Blais, Linelle] Emory Univ, Emory Ctr Training & Tech Assistance, Atlanta, GA 30322 USA.
[Blais, Linelle] Emory Univ, Emory Ctr Behav Sci & Hlth Educ, Atlanta, GA 30322 USA.
[Arora, Monika] Publ Hlth Fdn India, New Delhi, Haryana, India.
[Ranjani, Harish] Madras Diabet Res Fdn, Madras, Tamil Nadu, India.
[Ganda, Om; Reddy, Sethu] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Hedeker, Donald] Univ Chicago, Chicago, IL 60637 USA.
RP Pfammatter, A (reprint author), Northwestern Univ, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
EM angela.pfammatter@northwestern.edu
RI Emchi, Karma/Q-1952-2016
FU Aetna International; Lifescan Inc. (a Johnson & Johnson company); MSD
India; Amgen; Sanofi; Amarin Pharma
FX The authors acknowledge study partners Nokia and Emory University and
Mallory Stasko and H. Gene McFadden for their expertise, hard work, and
support. This study was directed by Arogya World, which received funding
from Aetna International, Lifescan Inc. (a Johnson & Johnson company),
and MSD India. The funding sources had no involvement in the conduct of
the study, writing of the manuscript, or decision to submit for
publication. The research protocol was approved by the Centre for
Chronic Disease Control of India, New Delhi and registered in the
Australian New Zealand Clinical Trials Registry #ACTRN12615000423516.
Linelle Blais received compensation to write the text messages used in
the current study. Om Ganda has a grant with Amarin Pharma for an
ongoing multi-center RCT, receives consulting fees from Amgen and
Sanofi, and receives speaker honoraria from Merck and Janssen. S. Sethu
Reddy was vice-president of medical affairs at Merck, Sharp, and Dohme
until December of 2013 and receives speaker honoraria from Merck, Sharp,
and Dohme. No financial disclosures were reported by other authors.
NR 24
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U2 4
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 AUG
PY 2016
VL 18
IS 8
AR e207
DI 10.2196/jmir.5712
PG 9
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA EC9WT
UT WOS:000388495700012
PM 27496271
ER
PT J
AU Gullbrand, SE
Ashinsky, BG
Martin, JT
Pickup, S
Smith, LJ
Mauck, RL
Smith, HE
AF Gullbrand, Sarah E.
Ashinsky, Beth G.
Martin, John T.
Pickup, Stephen
Smith, Lachlan J.
Mauck, Robert L.
Smith, Harvey E.
TI Correlations Between Quantitative T2 and T1 rho MRI, Mechanical
Properties and Biochemical Composition in a Rabbit Lumbar Intervertebral
Disc Degeneration Model
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE T2; T1 rho; magnetic resonance imaging; intervertebral disc
degeneration; biomechanics
ID RELAXATION-TIMES; NUCLEUS PULPOSUS; PROTEOGLYCAN CONTENT; CARTILAGE;
CHYMOPAPAIN; T-2
AB Improved diagnostic measures for intervertebral disc degeneration are necessary to facilitate early detection and treatment. The aim of this study was to correlate changes in mechanical and biochemical properties with the quantitative MRI parameters T2 and T1 rho in rabbit lumbar discs using an ex vivo chymopapain digestion model. Rabbit lumbar spinal motion segments from animals less than 6 months of age were injected with 100 mu l of saline (control) or chymopapain at 3, 15, or 100U/ml (n = 5 per group). T2 and T1 rho MRI series were obtained at 4.7T. Specimens were mechanically tested in tension-compression and creep. Normalized nucleus pulposus (NP) water and GAG contents were quantified. Stepwise multiple linear regression was performed to determine which parameters contributed significantly to changes in NP T2 and T1 rho. When all groups were included, multiple regression yielded a model with GAG, compressive modulus, and the creep time constants as variables significantly impacting T2 (multiple r(2) = 0.64, p = 0.006). GAG and neutral zone (NZ) modulus were identified as variables contributing to T1 rho (multiple r(2) = 0.28, p = 0.08). When specimens with advanced degeneration were excluded from the multiple regression analysis, T2 was significantly predicted by compressive modulus, tau(1), and water content (multiple r(2) = 0.71, p = 0.009), while no variables were significant predictors in the model for T1 rho. These results indicate that quantitative MRI can detect changes in the mechanical and biochemical properties of the degenerated disc. T2 may be more sensitive to early stage degenerative changes than T1 rho, while both quantitative MRI parameters are sensitive to advanced degeneration. (C) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
C1 [Gullbrand, Sarah E.; Ashinsky, Beth G.; Martin, John T.; Smith, Lachlan J.; Mauck, Robert L.; Smith, Harvey E.] Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA.
[Gullbrand, Sarah E.; Martin, John T.; Smith, Lachlan J.; Mauck, Robert L.; Smith, Harvey E.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA.
[Pickup, Stephen] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Smith, Lachlan J.] Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA.
RP Smith, HE (reprint author), Univ Penn, McKay Orthopaed Res Lab, Dept Orthopaed Surg, Philadelphia, PA 19104 USA.; Smith, HE (reprint author), Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA 19104 USA.
EM harvey.smith@uphs.upenn.edu
FU Department of Veterans' Affairs [IK2 RX00147]; Penn Center for
Musculoskeletal Disorders [P30 AR050950]
FX Grant sponsor: Department of Veterans' Affairs; Grant number: IK2
RX00147; Grant sponsor: Penn Center for Musculoskeletal Disorders; Grant
number: P30 AR050950.
NR 33
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U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD AUG
PY 2016
VL 34
IS 8
SI SI
BP 1382
EP 1388
DI 10.1002/jor.23269
PG 7
WC Orthopedics
SC Orthopedics
GA DW5VU
UT WOS:000383716300010
PM 27105019
ER
PT J
AU Muriuki, MG
Havey, RM
Voronov, LI
Carandang, G
Zindrick, MR
Lorenz, MA
Lomasney, L
Patwardhan, AG
AF Muriuki, Muturi G.
Havey, Robert M.
Voronov, Leonard I.
Carandang, Gerard
Zindrick, Michael R.
Lorenz, Mark A.
Lomasney, Laurie
Patwardhan, Avinash G.
TI Effects of Motion Segment Level, Pfirrmann Intervertebral Disc
Degeneration Grade and Gender on Lumbar Spine Kinematics
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE range of motion; high and low flexibility zone; rotational stiffness;
hysteresis; MRI
ID ANULUS FIBROSUS; FLEXIBILITY; STIFFNESS; MECHANICS; BEHAVIOR
AB MRI allows non-invasive assessment of intervertebral disc degeneration with the added clinical benefit of using nonionizing radiation. What has remained unclear is the relationship between assessed disc degeneration and lumbar spine kinematics. Kinematic outcomes of 54 multi-segment (L1-Sacrum) lumbar spine specimens were calculated to discover if such an underlying relationship exists with degeneration assessed using the Pfirrmann grading system. Further analyses were also conducted to determine if kinematic outcomes were affected by motion segment level, gender or applied compressive preload. Range of motion, hysteresis, high flexibility zone size and rotational stiffness in flexion-extension, lateral bending and axial rotation were the kinematic outcomes. Caudal intervertebral discs in our study sample were more degenerative than cranial discs. L5-S1 discs had the largest flexion-extension range of motion (p < 0.005) and L1-L2 discs the lowest flexion high flexibility zone size (p < 0.013). No other strict cranial-caudal differences in kinematic outcomes were found. Low flexibility zone rotational stiffness increased with disc degeneration grade in extension, lateral bending and axial rotation (p < 0.001). Trends towards higher hysteresis and lower range of motion with increased degeneration were observed in flexion-extension and lateral bending. Applied compressive preload increased flexion-extension hysteresis and augmented the effect of degeneration on hysteresis (p < 0.0005). Female specimens had about one degree larger range of motion in all rotational modes, and higher flexion extension hysteresis (p = 0.016). These results suggest that gender differences exist in lumbar spine kinematics. Additionally high disc loads, applied compressive preload or applied moment, are needed to kinematically distinguish discs with different levels of degeneration. (C) 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.
C1 [Muriuki, Muturi G.; Havey, Robert M.; Voronov, Leonard I.; Carandang, Gerard; Zindrick, Michael R.; Lorenz, Mark A.; Patwardhan, Avinash G.] US Dept Vet Affairs, Musculoskeletal Biomech Lab, Edward Hines Jr VA Hosp, Hines, IL 60141 USA.
[Havey, Robert M.; Voronov, Leonard I.; Zindrick, Michael R.; Lorenz, Mark A.; Patwardhan, Avinash G.] Loyola Univ Chicago, Dept Orthopaed Surg & Rehabil, Maywood, IL USA.
[Lomasney, Laurie] Loyola Univ Chicago, Dept Radiol, Maywood, IL USA.
[Zindrick, Michael R.; Lorenz, Mark A.] Hinsdale Orthopaed Associates, Hinsdale, IL USA.
RP Muriuki, MG (reprint author), US Dept Vet Affairs, Musculoskeletal Biomech Lab, Edward Hines Jr VA Hosp, Hines, IL 60141 USA.
EM muturi_muriuki@yahoo.com
OI Muriuki, Muturi/0000-0002-0620-9169
FU US Department of Veterans Affairs
FX This work was supported in part by the US Department of Veterans
Affairs.
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U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD AUG
PY 2016
VL 34
IS 8
SI SI
BP 1389
EP 1398
DI 10.1002/jor.23232
PG 10
WC Orthopedics
SC Orthopedics
GA DW5VU
UT WOS:000383716300011
PM 26990567
ER
PT J
AU Hanske, J
Meyer, CP
Sammon, JD
Choueiri, TK
Menon, M
Lipsitz, SR
Noldus, J
Nguyen, PL
Sun, M
Trinh, QD
AF Hanske, Julian
Meyer, Christian P.
Sammon, Jesse D.
Choueiri, Toni K.
Menon, Mani
Lipsitz, Stuart R.
Noldus, Joachim
Nguyen, Paul L.
Sun, Maxine
Quoc-Dien Trinh
TI The influence of marital status on the use of breast, cervical, and
colorectal cancer screening
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Preventive services; Screening; Cancer; USPSTF; Marital status; BRFSS
ID PREVENTIVE SERVICES; PARTICIPATION; SURVIVAL; RISK
AB Purpose. To examine the impact of marital status on the use of screening for breast, cervical, and colorectal cancer.
Methods. Werelied on 2012 Behavioral Risk Factor Surveillance System Survey age-appropriate screening cohorts. Appropriate screening for breast, cervical, and colorectal cancerwas determined according to United States Preventive Services Task Force recommendations in effect at the time of the 2012 survey. Complex samples logistic regression models were performed to examine the effect of marital status on cancer screening.
Results. Overall, 81.6, 83.9, and 68.9% of married participants underwent breast, cervical, and colorectal cancer, respectively, relative to 74.2, 75.1, and 60.9% for divorced/widowed/separated, individuals, and 74.7, 78.7, and 53.4% for never married individuals. Marital status (married vs. never married) was an independent predictor of screening for all cancers examined: breast cancer, odds ratio (OR): 1.42 (95% confidence interval [CI]: 1.251.61); cervical cancer, OR: 1.29 (95% CI: 1.16-1.43); colorectal cancer, OR: 1.63 (95% CI: 1.51-1.77). Gender-specific subgroup analyses for colorectal cancer suggests that marital status may exert a greater effect in men, relative to women (married men: OR 1.75, 95% CI: 1.56-1.96; married women: OR: 1.52, 95% CI: 1.35-1.70).
Conclusion. Being married is associated with increased utilization of breast, cervical, and colorectal cancer screening. The influence of marital status was greater in men relative to women eligible for colorectal cancer screening. Our results emphasize the importance of social determinants of health-seeking behaviors. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Hanske, Julian; Meyer, Christian P.; Lipsitz, Stuart R.; Sun, Maxine; Quoc-Dien Trinh] Harvard Med Sch, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA USA.
[Hanske, Julian; Meyer, Christian P.; Lipsitz, Stuart R.; Sun, Maxine; Quoc-Dien Trinh] Harvard Med Sch, Brigham & Womens Hosp, Div Urol Surg, Boston, MA USA.
[Hanske, Julian; Noldus, Joachim] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany.
[Meyer, Christian P.] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany.
[Sammon, Jesse D.; Menon, Mani] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA.
[Choueiri, Toni K.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Nguyen, Paul L.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA.
RP Trinh, QD (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Div Urol Surg, 45 Francis St,ASB 2-3, Boston, MA 02115 USA.
EM qtrinh@bwh.harvard.edu
FU Heinrich Hertz-Stiftung; Vattikuti Urology Institute; Walter Morris-Hale
Distinguished Chair in Urologic Oncology at Brigham and Women's Hospital
FX Julian Hanske is supported by a grant from the Heinrich Hertz-Stiftung.
Quoc-Dien Trinh is supported by an unrestricted educational grant from
the Vattikuti Urology Institute and the Professor Walter Morris-Hale
Distinguished Chair in Urologic Oncology at Brigham and Women's
Hospital.
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PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD AUG
PY 2016
VL 89
BP 140
EP 145
DI 10.1016/j.ypmed.2016.05.017
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA EC7KJ
UT WOS:000388316700020
PM 27215758
ER
PT J
AU Muralidhar, V
Nguyen, PL
Tucker-Seeley, RD
AF Muralidhar, Vinayak
Nguyen, Paul L.
Tucker-Seeley, Reginald D.
TI Recent relocation and decreased survival following a cancer diagnosis
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Relocation; Psychosocial stress; Cancer-specific mortality; Healthcare
disparities; Metastatic cancer
ID PSYCHOLOGICAL DISTRESS; OLDER-ADULTS; RESIDENTIAL-MOBILITY;
SOCIOECONOMIC-STATUS; FINANCIAL HARDSHIP; SOCIAL NETWORKS; RISK-FACTORS;
HEALTH; ASSOCIATION; MORTALITY
AB Objective. To determine the impact of recent relocation prior to a cancer diagnosis on cancer-specific outcomes.
Methods. We identified 272,718 patients with two different entries in the Surveillance, Epidemiology, and End Results database within 3 years of each other. Those who had relocated to a different county between entries were identified and we determined the risk of stage IV disease or cancer-specific mortality among relocators and non-relocators after adjusting for other patient-specific demographic and clinical factors.
Results. A total of 4639( 1.7%) patients relocated to a new county within 3 years prior to a second cancer diagnosis and 268,079( 98.3%) patients did not. Patients who had relocated to a new area were more likely to be diagnosed with stage IV cancer( 25.2% vs. 20.8%; adjusted odds ratio = 1.27; 95% confidence interval [CI], 1.18-1.37; P < 0.001), and had an increased risk of 10-year cancer-specific mortality( 20.9% vs. 17.9%; adjusted hazard ratio 1.26; 95% CI, 1.17-1.36; P < 0.001).
Conclusion. These results suggest that recent relocation to a new county prior to a cancer diagnosis is associated with an increased risk of late-stage presentation and worse cancer-specific mortality. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Muralidhar, Vinayak] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Nguyen, Paul L.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA.
[Nguyen, Paul L.] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Tucker-Seeley, Reginald D.] Harvard TH Chan Sch Publ Hlth, Dana Farber Canc Inst, Ctr Community Based Res, Dept Social & Behav Sci, Boston, MA USA.
RP Tucker-Seeley, RD (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, LW743,450 Brookline Ave, Boston, MA 02115 USA.
EM vmuralidhar@partners.org; pnguyen@LROC.harvard.edu;
retucker@hsph.harvard.edu
FU IDEA2 Program - Peter C. Farrell Fund; Prostate Cancer Foundation;
Fitz's Cancer Warriors; David and Cynthia Chapin; Hugh Simons in Honor
of Frank and Anne Simons; Scott Forbes and Gina Ventre Fund; National
Cancer Institute [CA169041]
FX This work was supported by grants from the IDEA2 Program supported by
the Peter C. Farrell (1967) Fund, The Prostate Cancer Foundation, Fitz's
Cancer Warriors, David and Cynthia Chapin, Hugh Simons in Honor of Frank
and Anne Simons, The Scott Forbes and Gina Ventre Fund, and an anonymous
grant. Dr. Tucker-Seeley is funded by a K01 career development award
(Grant # CA169041) from the National Cancer Institute. The funding
sources had no role in the study.
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PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD AUG
PY 2016
VL 89
BP 245
EP 250
DI 10.1016/j.ypmed.2016.06.007
PG 6
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA EC7KJ
UT WOS:000388316700034
PM 27287662
ER
PT J
AU Winkelman, JW
Mackie, SE
Mei, LA
Platt, S
Schoerning, L
AF Winkelman, John W.
Mackie, Susan E.
Mei, Leslie A.
Platt, Samuel
Schoerning, Laura
TI A method to switch from oral dopamine agonists to rotigotine in patients
with restless legs syndrome and mild augmentation
SO SLEEP MEDICINE
LA English
DT Article
DE Restless legs syndrome; Rotigotine; Augmentation; Pramipexole;
Ropinirole
ID EKBOM DISEASE; DIAGNOSTIC-CRITERIA; TRANSDERMAL PATCH;
PARKINSON-DISEASE; OVERNIGHT SWITCH; DOUBLE-BLIND; OPEN-LABEL; DAYTIME;
EPIDEMIOLOGY; MANAGEMENT
AB Background: We examined the short- and long-term efficacy and tolerability of a cross-titration algorithm from oral dopamine agonists to the rotigotine transdermal patch in patients dissatisfied with their restless legs syndrome (RLS) treatment, predominantly with mild augmentation.
Methods: Patients with RLS (n = 20) were recruited at a single site. The cross-titration consisted of decreasing oral dopaminergic agents (ropinirole by 1 mg or pramipexole by 0.25 mg) and increasing rotigotine by 1 mg every two days. Efficacy and adverse events (AEs) were assessed at one, three, six and 12 months after the switch.
Results: Patients had moderate severe RLS symptoms at the baseline (mean international restless legs syndrome (IRLS) score 19.4 +/- 5.5); 85% had augmentation and 45% reported afternoon RLS symptoms. The baseline mean pramipexole equivalent dose was 0.6 +/- 0.3 mg. At Week 5, 85% (17/20) had successfully switched from their oral dopamine agonist to rotigotine (mean dose 2.5 +/- 0.6 mg; change in IRLS score: 6.7 +/- 8.4, p = 0.002); 14 patients were CGI-I responders (much or very much improved). Three patients withdrew due to lack of efficacy. Twelve months after cross-titration, 10 patients continued on rotigotine, of whom four required either higher doses of rotigotine or supplemental RLS medication compared with their optimal Week 5 dose; five patients withdrew due to AEs and two due to lack of efficacy.
Conclusion: A cross-titration to rotigotine was efficacious after five weeks in 70% of patients dissatisfied with RLS treatment, most of whom had mild augmentation. At one year following the medication switch, 50% had discontinued rotigotine due to lack of continued efficacy or side effects. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Winkelman, John W.; Mackie, Susan E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA.
[Winkelman, John W.; Mackie, Susan E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, 1 Bowdoin Sq, Boston, MA 02114 USA.
Harvard Med Sch, Brigham & Womens Hosp, Dept Med, 25 Shattuck St, Boston, MA 02115 USA.
[Mei, Leslie A.; Platt, Samuel] Massachusetts Gen Hosp, 1 Bowdoin Sq, Boston, MA 02114 USA.
[Schoerning, Laura] Marian Univ, 3200 Cold Spring Rd, Indianapolis, IN USA.
RP Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq, Boston, MA 02114 USA.; Winkelman, JW (reprint author), Massachusetts Gen Hosp, Dept Neurol, 1 Bowdoin Sq, Boston, MA 02114 USA.
EM JWWINKELMAN@partners.org
FU UCB Biosciences, Inc.
FX This work was funded as an investigator-initiated trial by UCB
Biosciences, Inc. Statistical and data management assistance was
provided by Samuel Platt BA.
NR 23
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD AUG
PY 2016
VL 23
BP 18
EP 23
DI 10.1016/j.sleep.2016.05.004
PG 6
WC Clinical Neurology
SC Neurosciences & Neurology
GA ED0ON
UT WOS:000388541900003
PM 27810181
ER
PT J
AU Ellimoottil, C
Skolarus, T
Gettman, M
Boxer, R
Kutikov, A
Lee, BR
Shelton, J
Morgan, T
AF Ellimoottil, Chandy
Skolarus, Ted
Gettman, Matthew
Boxer, Richard
Kutikov, Alexander
Lee, Benjamin R.
Shelton, Jeremy
Morgan, Todd
TI Telemedicine in Urology: State of the Art
SO UROLOGY
LA English
DT Review
ID RANDOMIZED CONTROLLED-TRIAL; REMOTE VIDEO VISITS; RADICAL PROSTATECTOMY;
FOLLOW-UP; CARE; SURGERY; TELEHEALTH; SATISFACTION; SYSTEM;
REIMBURSEMENT
AB Whereas telemedicine is recognized as one of the fastest-growing components of the healthcare system, the status of telemedicine use in urology is largely unknown. In this narrative review, we detail studies that investigate the use of televisits and teleconsultations for urologic conditions. Moreover, we discuss current regulatory and reimbursement policies. Finally, we discuss the significant barriers to widespread dissemination and implementation of telemedicine and reasons why the field of urology may be positioned to become a leader in the provision of telemedicine services. Published by Elsevier Inc.
C1 Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA.
[Ellimoottil, Chandy] Univ Michigan, Inst Healthcare Policy & Innovat, 2800 Plymouth Rd,NCRC Bldg 14,G100-13, Ann Arbor, MI 48109 USA.
VA Ann Arbor Healthcare Syst, Ctr Clin Management Res, Ann Arbor, MI USA.
Mayo Clin, Coll Med, Dept Urol, Rochester, MN USA.
Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA.
Temple Univ Hlth Syst, Fox Chase Canc Ctr, Div Urol Oncol, Philadelphia, PA USA.
Univ Arizona, Dept Urol, Tucson, AZ USA.
Vet Affairs Greater Los Angeles, Los Angeles, CA USA.
RP Ellimoottil, C (reprint author), Univ Michigan, Inst Healthcare Policy & Innovat, 2800 Plymouth Rd,NCRC Bldg 14,G100-13, Ann Arbor, MI 48109 USA.
EM cellimoo@med.umich.edu
FU Agency for Healthcare Research and Quality [1F32HS024193-01]
FX This research was supported by the Agency for Healthcare Research and
Quality (1F32HS024193-01 to Dr. Ellimoottil).
NR 51
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U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD AUG
PY 2016
VL 94
BP 10
EP 15
DI 10.1016/j.urology.2016.02.061
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA DW5OU
UT WOS:000383696400010
PM 27109596
ER
PT J
AU Bennett, CL
Prasad, SM
Kennedy, WA
AF Bennett, Charles L.
Prasad, Sandip M.
Kennedy, William A., II
TI Telemedicine in Urology: State of the Art
SO UROLOGY
LA English
DT Editorial Material
C1 [Bennett, Charles L.] Univ South Carolina, Coll Pharm, Hollins Natl Canc Inst, Designated Canc Ctr, Charleston, SC 29424 USA.
[Prasad, Sandip M.] Med Univ South Carolina, Dept Urol, Charleston, SC USA.
[Prasad, Sandip M.] Ralph H Johnson VAMC, Dept Surg, Urol Sect, Charleston, SC USA.
[Kennedy, William A., II] Stanford Univ, Med Ctr, Dept Urol, Palo Alto, CA 94304 USA.
RP Bennett, CL (reprint author), Univ South Carolina, Coll Pharm, Hollins Natl Canc Inst, Designated Canc Ctr, Charleston, SC 29424 USA.
NR 2
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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 0090-4295
EI 1527-9995
J9 UROLOGY
JI Urology
PD AUG
PY 2016
VL 94
BP 15
EP 16
DI 10.1016/j.urology.2016.02.062
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA DW5OU
UT WOS:000383696400011
PM 27207146
ER
PT J
AU Midkiff, KD
Andrews, EB
Gilsenan, AW
Deapen, DM
Harris, DH
Schymura, MJ
Hornicek, FJ
AF Midkiff, Kirk D.
Andrews, Elizabeth B.
Gilsenan, Alicia W.
Deapen, Dennis M.
Harris, David H.
Schymura, Maria J.
Hornicek, Francis J.
TI The experience of accommodating privacy restrictions during
implementation of a large-scale surveillance study of an osteoporosis
medication
SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
LA English
DT Article
DE epidemiology; oncology; postmarketing product surveillance; privacy;
public health; survey; retrospective studies; pharmacoepidemiology
ID HEALTH RESEARCH; IMPACT; RULE; BIAS
AB Purpose To explore whether privacy restrictions developed to protect patients have complicated research within a 15-year surveillance study conducted with US cancer registries.
Methods Data from enrolling 27 cancer registries over a 10-year period were examined to describe the amount of time needed to obtain study approval. We also analyzed the proportion of patients that completed a research interview out of the total reported by the registries and examined factors thought to influence this measure.
Results The average length of the research review process from submission to approval of the research was 7 months (range, <1 to 24 months), and it took 6 months or more to obtain approval of the research at 41% of the cancer registries. Most registries (78%) required additional permission steps to gain access to patients for research. After adjustment for covariates, the interview response proportion was 110% greater (ratio of response proportion = 2.1; 95% confidence interval: 1.3, 3.3) when the least restrictive versus the most restrictive permission steps were required. An interview was more often completed for patients (or proxies) if patients were alive, within a year of being diagnosed, or identified earlier in the study.
Conclusions Lengthy research review processes increased the time between diagnosis and provision of patient information to the researcher. Requiring physician permission for access to patients was associated with lower subject participation. A single national point of entry for use of cancer registry data in health research is worthy of consideration to make the research approval process efficient. (C) 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.
C1 [Midkiff, Kirk D.; Andrews, Elizabeth B.; Gilsenan, Alicia W.; Harris, David H.] RTI Int, RTI Hlth Solut, Dept Pharmacoepidemiol & Risk Management, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
[Deapen, Dennis M.] Univ Southern Calif, Keck Sch Med, Los Angeles Canc Surveillance Program, Los Angeles, CA USA.
[Schymura, Maria J.] New York State Dept Hlth, New York State Canc Registry, Albany, NY USA.
[Hornicek, Francis J.] Massachusetts Gen Hosp, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA 02114 USA.
RP Midkiff, KD (reprint author), RTI Int, RTI Hlth Solut, Dept Pharmacoepidemiol & Risk Management, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA.
EM kmidkiff@rti.org
FU Eli Lilly Company
FX The surveillance study, which served as the basis for the analysis in
this paper, is being conducted by RTI International with support from
Eli Lilly & Company. Drs. Deapen, Schymura, and Hornicek did not receive
funding to support this work. The analyses presented in this paper were
initiated by the investigators and not the sponsoring agency. The
authors would like to thank Dr. Kenneth Rothman for his guidance on
analytical methods and careful and considerate review of the paper. The
authors would like to thank Mr. Dave McSorley for his careful review of
the programming code and for his assistance in preparation of additional
adjusted estimates. The authors also thank Ms. Ginger Powell, Ms. Diana
Goss, and Ms. Amy Ladner for their ongoing contributions to this study,
especially with regard to data management. Finally, this analysis would
not have been possible without the participation and support of the
cancer registries that have agreed to identify cases for the ongoing
postmarketing study. Data used in this report were provided by the
following individual cancer registries and departments of health:
Alabama Department of Public Health; Alabama Statewide Cancer Registry;
Arizona Department of Health Services; Arizona Cancer Registry;
California Department of Public Health; California Cancer Registry;
Colorado Department of Public Health and Environment; Colorado Central
Cancer Registry; Florida Department of Health; Florida Cancer Data
System; Dana Farber/Harvard Cancer Center; Brigham and Women's Hospital;
Massachusetts General Hospital; University of Hawaii Cancer Center,
Hawaii Tumor Registry; the Sidney Kimmel Comprehensive Cancer Center at
Johns Hopkins; Indiana State Department of Health; Indiana State Cancer
Registry; University of Iowa; State Health Registry of Iowa; University
of Kentucky, Markey Cancer Control Program; Kentucky Cancer Registry,
University of Southern California Cancer Surveillance Program; Louisiana
State University Health Sciences Center; Louisiana Tumor Registry;
Michigan Department of Community Health; Michigan Cancer Surveillance
Program; Minnesota Department of Health; Minnesota Cancer Surveillance
System; University of Missouri; Missouri Cancer Registry; North Carolina
Department of Health and Human Services, Division of Public Health;
North Carolina Central Cancer Registry; The Rutgers Cancer Institute of
New Jersey, Rutgers University; New Jersey State Cancer Registry; New
York State Department of Health; New York State Cancer Registry; Ohio
Department of Health; Ohio Cancer Incidence Surveillance System; Bureau
of Health Statistics & Research, Pennsylvania Department of Health;
Pennsylvania Cancer Registry; South Carolina Department of Health and
Environmental Control; South Carolina Central Cancer Registry; Tennessee
Department of Health; Tennessee Cancer Registry; Texas Department of
State Health Services; Texas Cancer Registry; University of Texas M.D.
Anderson Cancer Center; University of Utah; Utah Cancer Registry; State
of Washington Department of Social and Health Services; Washington State
Cancer Registry; the Surveillance, Epidemiology, and End Results (SEER)
Program of the National Cancer Institute (NCI); and the National Program
of Cancer Registries (NPCR) of the Centers for Disease Control and
Prevention (CDC). Use of these data does not imply that these
registries, their departments of health, the CDC, or NCI either agrees
or disagrees with any representations, analyses, interpretations, or
conclusions.
NR 19
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-8569
EI 1099-1557
J9 PHARMACOEPIDEM DR S
JI Pharmacoepidemiol. Drug Saf.
PD AUG
PY 2016
VL 25
IS 8
BP 960
EP 968
DI 10.1002/pds.4008
PG 9
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA DW4VW
UT WOS:000383642100012
PM 27091234
ER
PT J
AU Cuaron, JJ
MacDonald, SM
Cahlon, O
AF Cuaron, John J.
MacDonald, Shannon M.
Cahlon, Oren
TI Novel applications of proton therapy in breast carcinoma
SO CHINESE CLINICAL ONCOLOGY
LA English
DT Review
DE Protons; breast cancer; indications; technique
ID RELATIVE BIOLOGICAL EFFECTIVENESS; MODULATED RADIATION-THERAPY;
EXTERNAL-BEAM RADIOTHERAPY; PROSPECTIVE CLINICAL-TRIAL; EFFECTIVENESS
RBE VALUES; LINEAR-ENERGY-TRANSFER; PHASE-II TRIAL; EARLY-STAGE;
RANDOMIZED-TRIAL; CANCER PATIENTS
AB This review will focus on the indications, clinical experience, and technical considerations of proton beam radiation therapy in the treatment of patients with breast cancer. For patients with early stage disease, proton therapy delivers less dose to non-target breast tissue for patients receiving partial breast irradiation ( PBI) therapy, which may result in improved cosmesis but requires further investigation. For patients with locally advanced breast cancer requiring treatment to the regional lymph nodes, proton therapy allows for an improved dosimetric profile compared with conventional photon and electron techniques. Early clinical results demonstrate acceptable toxicity. The possible reduction in cardiopulmonary events as a result of reduced dose to organs at risk will be tested in a randomized control trial of protons vs. photons.
C1 [Cuaron, John J.; Cahlon, Oren] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
[MacDonald, Shannon M.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA.
RP Cuaron, JJ (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA.
EM cuaronj@mskcc.org
NR 88
TC 0
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U1 2
U2 2
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 2304-3865
EI 2304-3873
J9 CHIN CLIN ONCOL
JI Chin. Clin. Oncol.
PD AUG
PY 2016
VL 5
IS 4
AR UNSP 52
DI 10.21037/cco.2016.06.04
PG 15
WC Oncology
SC Oncology
GA EB7QR
UT WOS:000387585100006
PM 27558253
ER
PT J
AU Kass, JI
Mehta, V
AF Kass, Jason I.
Mehta, Vikas
TI Positron emission tomography-CT surveillance versus neck dissection in
advanced head and neck cancer: time for a paradigm shift in management
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
ID SQUAMOUS-CELL CARCINOMA; PET/CT
C1 [Kass, Jason I.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Div Otolaryngol Head & Neck Surg, Boston, MA 02218 USA.
[Mehta, Vikas] LSU Hlth Sci Ctr Shreveport, Dept Otolaryngol Head & Neck Surg, 1501 Kings Hwy Room 9-203, Shreveport, LA 71130 USA.
RP Mehta, V (reprint author), LSU Hlth Sci Ctr Shreveport, Dept Otolaryngol Head & Neck Surg, 1501 Kings Hwy Room 9-203, Shreveport, LA 71130 USA.
EM dr.vikasmehta@gmail.com
NR 8
TC 0
Z9 0
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 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD AUG
PY 2016
VL 5
SU 2
BP S203
EP S204
DI 10.21037/tcr.2016.08.03
PG 2
WC Oncology
SC Oncology
GA EB4KI
UT WOS:000387340000013
ER
PT J
AU Li, GZ
Raut, CP
AF Li, George Z.
Raut, Chandrajit P.
TI Pazopanib: a new therapeutic option for advanced gastrointestinal
stromal tumors
SO TRANSLATIONAL CANCER RESEARCH
LA English
DT Editorial Material
C1 [Li, George Z.; Raut, Chandrajit P.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
[Raut, Chandrajit P.] Dana Farber Canc Inst, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA.
RP Raut, CP (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
EM craut@bwh.harvard.edu
NR 0
TC 0
Z9 0
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 2218-676X
EI 2219-6803
J9 TRANSL CANCER RES
JI Transl. Cancer Res.
PD AUG
PY 2016
VL 5
SU 2
BP S240
EP S242
DI 10.21037/tcr.2016.08.14
PG 3
WC Oncology
SC Oncology
GA EB4KI
UT WOS:000387340000022
ER
PT J
AU Goel, S
Krop, IE
AF Goel, S.
Krop, I. E.
TI PIK3CA mutations in HER2-positive breast cancer: an ongoing conundrum
SO ANNALS OF ONCOLOGY
LA English
DT Editorial Material
C1 [Goel, S.; Krop, I. E.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Krop, IE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
EM ian_krop@dfci.harvard.edu
NR 0
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Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD AUG
PY 2016
VL 27
IS 8
BP 1368
EP 1372
DI 10.1093/annonc/mdw246
PG 5
WC Oncology
SC Oncology
GA DV8JH
UT WOS:000383182800003
PM 27358378
ER
PT J
AU Scelo, G
Hofmann, JN
Banks, RE
Bigot, P
Bhatt, RS
Cancel-Tassin, G
Chew, SK
Creighton, CJ
Cussenot, O
Davis, IJ
Escudier, B
Frayling, TM
Haggstrom, C
Hildebrandt, MAT
Holcatova, I
Johansson, M
Linehan, WM
McDermott, DF
Nathanson, KL
Ogawa, S
Perlman, EJ
Purdue, MP
Stattin, P
Swanton, C
Vasudev, NS
Wu, X
Znaor, A
Brennan, P
Chanock, SJ
AF Scelo, G.
Hofmann, J. N.
Banks, R. E.
Bigot, P.
Bhatt, R. S.
Cancel-Tassin, G.
Chew, S. K.
Creighton, C. J.
Cussenot, O.
Davis, I. J.
Escudier, B.
Frayling, T. M.
Haggstrom, C.
Hildebrandt, M. A. T.
Holcatova, I.
Johansson, M.
Linehan, W. M.
McDermott, D. F.
Nathanson, K. L.
Ogawa, S.
Perlman, E. J.
Purdue, M. P.
Stattin, P.
Swanton, C.
Vasudev, N. S.
Wu, X.
Znaor, A.
Brennan, P.
Chanock, S. J.
TI International cancer seminars: a focus on kidney cancer
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE kidney cancer; genomics; epidemiology; clinical research
ID RENAL-CELL CARCINOMA; GENOME-WIDE ASSOCIATION; GENETIC-BASIS;
HETEROGENEITY; LANDSCAPE; DISEASE; TUMOR; RISK
AB Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.Recent years have seen important advances in our understanding of the etiology, biology and genetics of kidney cancer. To summarize important achievements and identify prominent research questions that remain, a workshop was organized by IARC and the US NCI. A series of 'difficult questions' were formulated, which should be given future priority in the areas of population, genomic and clinical research.
C1 [Scelo, G.; Johansson, M.; Znaor, A.; Brennan, P.] Int Agcy Res Canc, Sect Genet, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
[Hofmann, J. N.; Purdue, M. P.; Chanock, S. J.] NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA.
[Banks, R. E.; Vasudev, N. S.] St James Univ Hosp, Leeds Inst Canc Studies & Pathol, Canc Res UK Ctr, Clin & Biomed Prote Grp, Leeds, W Yorkshire, England.
[Bigot, P.] CHU Angers, Dept Urol, Angers, France.
[Bhatt, R. S.; McDermott, D. F.] Dana Farber Harvard Canc Ctr, Kidney Canc Program, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA USA.
[Cancel-Tassin, G.; Cussenot, O.] CeRePP, Grp Rech GRC UPMC 5, Paris, France.
[Chew, S. K.] UCL, UCL Canc Inst, Translat Canc Therapeut Lab, London, England.
[Creighton, C. J.] Baylor Coll Med, Duncan Canc Center Biostat, Houston, TX 77030 USA.
[Davis, I. J.] UNC, Sch Med, Dept Genet, Chapel Hill, NC USA.
[Escudier, B.] Inst Gustave Roussy, Dept Med Oncol, Villejuif, France.
[Frayling, T. M.] Univ Exeter, Sch Med, Exeter, Devon, England.
[Haggstrom, C.; Stattin, P.] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
[Haggstrom, C.] Umea Univ, Dept Biobank Res, Umea, Sweden.
[Hildebrandt, M. A. T.] Univ Texas MD Anderson Canc Ctr, Canc Prevent & Populat Sci, Div OVP, Dept Epidemiol, Houston, TX 77030 USA.
[Holcatova, I.] Charles Univ Prague, Fac Med 2, Inst Publ Hlth & Prevent Med, Prague, Czech Republic.
[Linehan, W. M.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Nathanson, K. L.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Ogawa, S.] Univ Tokyo, Grad Sch Med, Tokyo, Japan.
[Perlman, E. J.] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA.
[Swanton, C.] UCL, Hosp & Canc Inst, London, England.
[Wu, X.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
RP Brennan, P (reprint author), Int Agcy Res Canc, Sect Genet, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM brennanp@iarc.fr
OI Cancel-Tassin, Geraldine/0000-0002-9583-6382
FU International Agency for Research on Cancer (IARC); Division of Cancer
Epidemiology and Genetics (DCEG) of the US National Cancer Institute
FX Organization of production of this seminar was funded jointly by the
International Agency for Research on Cancer (IARC) and the Division of
Cancer Epidemiology and Genetics (DCEG) of the US National Cancer
Institute (no grant number applicable).
NR 31
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U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD AUG
PY 2016
VL 27
IS 8
BP 1382
EP 1385
DI 10.1093/annonc/mdw186
PG 4
WC Oncology
SC Oncology
GA DV8JH
UT WOS:000383182800008
PM 27130845
ER
PT J
AU Clement, PM
Gauler, T
Machiels, JP
Haddad, RI
Fayette, J
Licitra, LF
Tahara, M
Cohen, EEW
Cupissol, D
Grau, JJ
Guigay, J
Caponigro, F
de Castro, G
de Souza Viana, L
Keilholz, U
del Campo, JM
Cong, XJ
Ehrnrooth, E
Vermorken, JB
AF Clement, P. M.
Gauler, T.
Machiels, J. P.
Haddad, R. I.
Fayette, J.
Licitra, L. F.
Tahara, M.
Cohen, E. E. W.
Cupissol, D.
Grau, J. J.
Guigay, J.
Caponigro, F.
de Castro, G., Jr.
de Souza Viana, L.
Keilholz, U.
del Campo, J. M.
Cong, X. J.
Ehrnrooth, E.
Vermorken, J. B.
CA LUX-H&N 1 Investigators
TI Afatinib versus methotrexate in older patients with second-line
recurrent and/or metastatic head and neck squamous cell carcinoma:
subgroup analysis of the LUX-Head & Neck 1 trial(aEuro)
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE afatinib; methotrexate; HNSCC; second-line; phase III; older
ID CHEMOTHERAPY PLUS CETUXIMAB; PLATINUM-BASED THERAPY; OPEN-LABEL; CANCER
AB In the LUX-Head & Neck 1 study, older age (a parts per thousand yen65 years) did not adversely affect the benefit in patient-reported outcomes and antitumor activity observed with afatinib over methotrexate, which was consistent with findings from the overall population. Safety in older patients was also consistent with the overall population, favoring afatinib in terms of fewer dose reductions and discontinuations.In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged a parts per thousand yen65 and < 65 years.
Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed.
Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged a parts per thousand yen65 years (older) and 73% (239 afatinib; 116 methotrexate) < 65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups.
Advancing age (a parts per thousand yen65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.
NCT01345682 (ClinicalTrials.gov).
C1 [Clement, P. M.] Katholieke Univ Leuven, Dept Oncol, Herestr 49, B-3000 Leuven, Belgium.
[Clement, P. M.] UZ Leuven, Dept Gen Med Oncol, Leuven, Belgium.
[Gauler, T.] Univ Hosp Essen, West German Canc Ctr, Dept Med Canc Res, Essen, Germany.
[Machiels, J. P.] Catholic Univ Louvain, Clin Univ St Luc, Med Oncol Serv, Inst Roi Albert 2, Brussels, Belgium.
[Machiels, J. P.] Catholic Univ Louvain, Inst Rech Clin & Expt Pole MIRO, Brussels, Belgium.
[Haddad, R. I.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Fayette, J.] Univ Lyon, Ctr Leon Berard, Dept Med Oncol, Lyon, France.
[Licitra, L. F.] Fdn IRCCS Ist Nazl Tumori, Dept Med Oncol, Milan, Italy.
[Tahara, M.] Natl Canc Ctr Hosp East, Head & Neck Med Oncol, Kashiwa, Chiba, Japan.
[Cohen, E. E. W.] Univ Calif San Diego, Dept Med, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Cupissol, D.] Inst Canc Montpellier Val dAurelle, Med Oncol Serv, Montpellier, France.
[Grau, J. J.] Hosp Clin Barcelona, Dept Med Oncol, Barcelona, Spain.
[Grau, J. J.] Univ Barcelona, Barcelona, Spain.
[Guigay, J.] Gustave Roussy, Dept Med Oncol, Villejuif, France.
[Guigay, J.] Ctr Antoine Lacassagne, Nice, France.
[Caponigro, F.] Natl Tumor Inst Naples, Head & Neck Med Oncol, Head & Neck, Dept Melanoma,Soft Tissues,Muscolo Scheletal, Naples, Italy.
[de Castro, G., Jr.] Inst Canc Estado Sao Paulo, Oncol Clin, Sao Paulo, Brazil.
[de Souza Viana, L.] Hosp Canc Barretos, Dept Med Oncol, Sao Paulo, Brazil.
[Keilholz, U.] Charite Comprehens Canc Ctr, Berlin, Germany.
[del Campo, J. M.] Hosp Univ Vall DHebron, Dept Med Oncol, Barcelona, Spain.
[Cong, X. J.] Boehringer Ingelheim Pharmaceut Inc, Biometr & Data Management, Ridgefield, CT USA.
[Ehrnrooth, E.] Boehringer Ingelheim Danmark AS, Div Oncol, Copenhagen, Denmark.
[Vermorken, J. B.] Univ Antwerp Hosp, Dept Med Oncol, Edegem, Belgium.
RP Clement, PM (reprint author), Katholieke Univ Leuven, Dept Oncol, Herestr 49, B-3000 Leuven, Belgium.
EM paul.clement@uzleuven.be
RI Licitra, Lisa/C-6271-2017
OI Licitra, Lisa/0000-0003-0623-4118
FU Boehringer Ingelheim
FX This work was supported by Boehringer Ingelheim. There is no applicable
grant number for this work.
NR 15
TC 2
Z9 2
U1 3
U2 3
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 AUG
PY 2016
VL 27
IS 8
BP 1585
EP 1593
DI 10.1093/annonc/mdw151
PG 9
WC Oncology
SC Oncology
GA DV8JH
UT WOS:000383182800029
PM 27084954
ER
PT J
AU Nipp, RD
El-Jawahri, A
Fishbein, JN
Gallagher, ER
Stagl, JM
Park, ER
Jackson, VA
Pirl, WF
Greer, JA
Temel, JS
AF Nipp, R. D.
El-Jawahri, A.
Fishbein, J. N.
Gallagher, E. R.
Stagl, J. M.
Park, E. R.
Jackson, V. A.
Pirl, W. F.
Greer, J. A.
Temel, J. S.
TI Factors associated with depression and anxiety symptoms in family
caregivers of patients with incurable cancer(aEuro)
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE palliative care; mood; advanced cancer; caregivers; depression; anxiety
ID QUALITY-OF-LIFE; ILL CANCER-PATIENTS; BURDEN; PREPAREDNESS; PREVALENCE;
PROGNOSIS; DISTRESS; HEALTH; NEEDS
AB In this study, we found that patients with incurable cancer and their family caregivers experience high rates of depression and anxiety symptoms, with FC anxiety levels exceeding those of the patients. We identified patient and FC factors associated with FCs' psychological distress, including patients' coping strategies and prognostic understanding.Family caregivers (FCs) are critically important for patients with cancer, yet they may experience psychological distress related to caregiving demands. We sought to describe rates of depression and anxiety in FCs of patients with incurable cancer and identify factors associated with these symptoms to determine those at greatest risk for psychological distress.
We performed a cross-sectional analysis of baseline data from a randomized trial of early palliative care. We assessed depression and anxiety using the Hospital Anxiety and Depression Scale in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer and their FCs. We also assessed patients' quality of life (Functional Assessment of Cancer Therapy-General), coping strategies (Brief COPE), and their report of the primary goal of their cancer treatment. We used linear regression with purposeful selection of covariates to identify factors associated with FC depression and anxiety symptoms.
We enrolled 78.6% (n = 275) of potentially eligible FCs. The majority were female (69.1%) and married to the patient (66.2%). While the proportion of FCs and patients reporting depression did not differ (16.4% versus 21.5%, P = 0.13), FCs were more likely to report anxiety compared with patients (42.2% versus 28.4%, P < 0.001). Patients' use of acceptance coping was associated with lower FC depression (B = -0.42, P < 0.001), while emotional support coping was associated with higher FC depression (B = 0.69, P = 0.001) and lower FC anxiety (B = -0.70, P < 0.001). Patient report that their primary goal of their treatment was to 'cure my cancer' was associated with higher FC depression (B = 0.72, P = 0.03).
Patients with incurable cancer and their FCs report high levels of depression and anxiety symptoms. We demonstrated that patients' coping strategies and prognostic understanding were associated with FC depression and anxiety symptoms, underscoring the importance of targeting these risk factors when seeking to address the psychological distress experienced by FCs.
C1 [Nipp, R. D.; El-Jawahri, A.; Gallagher, E. R.; Temel, J. S.] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA.
[Fishbein, J. N.; Stagl, J. M.; Park, E. R.; Pirl, W. F.; Greer, J. A.] Massachusetts Gen Hosp, Dept Psychiat, Div Palliat Care, Boston, MA 02114 USA.
[Jackson, V. A.] Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Boston, MA 02114 USA.
[Nipp, R. D.] Harvard Med Sch, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
RP Nipp, RD (reprint author), Harvard Med Sch, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.; Nipp, RD (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol & Oncol, Dept Med, 55 Fruit St,Yawkey 7B, Boston, MA 02114 USA.
EM rnipp@mgh.harvard.edu
FU National Institute of Nursing Research [NR012735]; National Cancer
Institute [CA181253]
FX This work was supported by the National Institute of Nursing Research
R01 (NR012735 to JST); and the National Cancer Institute K24 (CA181253
to JST).
NR 26
TC 1
Z9 1
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 AUG
PY 2016
VL 27
IS 8
BP 1607
EP 1612
DI 10.1093/annonc/mdw205
PG 6
WC Oncology
SC Oncology
GA DV8JH
UT WOS:000383182800032
PM 27177859
ER
PT J
AU Hashim, D
Sartori, S
Brennan, P
Curado, MP
Wunsch, V
Divaris, K
Olshan, AF
Zevallos, JP
Winn, DM
Franceschi, S
Castellsague, X
Lissowska, J
Rudnai, P
Matsuo, K
Morgenstern, H
Chen, C
Vaughan, TL
Hofmann, JN
D'Souza, G
Haddad, RI
Wu, H
Lee, YC
Hashibe, M
La Vecchia, C
Boffetta, P
AF Hashim, D.
Sartori, S.
Brennan, P.
Curado, M. P.
Wunsch-Filho, V.
Divaris, K.
Olshan, A. F.
Zevallos, J. P.
Winn, D. M.
Franceschi, S.
Castellsague, X.
Lissowska, J.
Rudnai, P.
Matsuo, K.
Morgenstern, H.
Chen, C.
Vaughan, T. L.
Hofmann, J. N.
D'Souza, G.
Haddad, R. I.
Wu, H.
Lee, Y. -C.
Hashibe, M.
La Vecchia, C.
Boffetta, P.
TI The role of oral hygiene in head and neck cancer: results from
International Head and Neck Cancer Epidemiology (INHANCE) consortium
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE head and neck neoplasms; oral neoplasms; pharyngeal neoplasms; oral
hygiene; pooled analyses
ID SQUAMOUS-CELL CARCINOMA; ILL-FITTING DENTURES; RISK-FACTORS;
PERIODONTAL-DISEASE; DIABETES-MELLITUS; POOLED ANALYSIS; TOOTH LOSS;
HEALTH; COHORT; ALCOHOL
AB This pooled analysis describes the largest and most comprehensive assessment of the association between oral hygiene indicators and HNCs to date, including oral cavity, laryngeal, hypopharyngeal, and oropharyngeal cancers. We found good oral hygiene is associated with lower risk of HNC. Improvements in oral hygiene by increasing oral hygiene literacy, particularly for annual dentist visits and daily tooth brushing, may be protective against HNC.Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs.
In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), < 5 missing teeth, tooth brushing at least daily, and visiting a dentist a parts per thousand yenonce a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption.
Inverse associations with any HNC, in the hypothesized direction, were observed for < 5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for a parts per thousand currency sign 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer.
Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.
C1 [Sartori, S.; Wu, H.; Boffetta, P.] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Brennan, P.; Franceschi, S.] Int Agcy Res Canc, Lyon, France.
[Curado, M. P.] CIPE ACCAMARGO, Epidemiol, Sao Paulo, Brazil.
[Wunsch-Filho, V.] Univ Sao Paulo, Sch Publ Hlth, Sao Paulo, Brazil.
[Divaris, K.] Univ N Carolina, Sch Publ Hlth, Dept Pediat Dent, Chapel Hill, NC USA.
[Olshan, A. F.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Zevallos, J. P.] Univ N Carolina, Dept Otolaryngol Head & Neck Surg, Chapel Hill, NC USA.
[Winn, D. M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Castellsague, X.] Catalan Inst Oncol ICO IDIBELL, Lhospitalet De Llobregat, Spain.
[Castellsague, X.] CIBERESP, Madrid, Spain.
[Lissowska, J.] M Sklasodowska Curie Mem Canc Ctr & Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Rudnai, P.] Natl Publ Hlth Ctr, Budapest, Hungary.
[Matsuo, K.] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
[Morgenstern, H.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, H.] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA.
[Chen, C.; Vaughan, T. L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Hofmann, J. N.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[D'Souza, G.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Haddad, R. I.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[Lee, Y. -C.; Hashibe, M.] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA.
[Lee, Y. -C.; Hashibe, M.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[La Vecchia, C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Boffetta, P.] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
RP Hashim, D (reprint author), Icahn Sch Med Mt Sinai, Dept Prevent Med, 1 Gustave L Levy Pl, New York, NY 10029 USA.
EM dana.hashim@mssm.edu
RI Castellsague Pique, Xavier/N-5795-2014; Kowalski, Luiz/D-1701-2012;
Curado, Maria Paula/M-6200-2013; Divaris, Kimon/E-4706-2011;
OI Castellsague Pique, Xavier/0000-0002-0802-3595; Kowalski,
Luiz/0000-0001-5865-9308; Curado, Maria Paula/0000-0001-8172-2483;
Divaris, Kimon/0000-0003-1290-7251; La Vecchia,
Carlo/0000-0003-1441-897X
FU NIH [NCI R03CA113157, R01CA061188, P50CA090388, R01DA011386,
R03CA077954, T32CA009142, U01CA096134, R21ES011667, R01CA048996,
R01DE012609, R01CA030022, DE016631, R01CA051845]; NIDCR [R03DE016611];
Latin America: Fondo para la Investigacion Cientifica y Tecnologica
(FONCYT) Argentina; IMIM (Barcelona); Fundaco de Amparo a Pesquisa no
Estado de Sao Paulo (FAPESP) [01/01768-2]; European Commission
[IC18-CT97-0222]; National Institute of Environmental Health Sciences
[P30ES010126]; NCI, NIH, United States; Fondo de Investigaciones
Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662,
BAE 01/5013]; International Union Against Cancer (UICC);
Yamagiwa-Yoshida Memorial International Cancer Study Grant; European
Commission INCO-COPERNICUS Program [IC15-CT98-0332]; Alper Research
Program for Environmental Genomics of the UCLA Jonsson Comprehensive
Cancer Center; Ministry of Education, Science, Sports, Culture and
Technology of Japan [17015052]; Ministry of Health, Labour and Welfare
of Japan [H20-002]
FX The INHANCE Consortium was supported by NIH grants NCI R03CA113157 and
NIDCR R03DE016611. Studies participating in the pooled analysis were
supported by: Latin America: Fondo para la Investigacion Cientifica y
Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a
Pesquisa no Estado de Sao Paulo (FAPESP) (No. 01/01768-2), and European
Commission (IC18-CT97-0222). North Carolina (1994-1997): NIH
(R01CA061188), and in part by a grant from the National Institute of
Environmental Health Sciences (P30ES010126). US multicenter: The
Intramural Program of the NCI, NIH, United States (No grant number
applicable). International Multicenter study: Fondo de Investigaciones
Sanitarias (FIS) of the Spanish Government (FIS 97/0024, FIS 97/0662,
BAE 01/5013), International Union Against Cancer (UICC), and
Yamagiwa-Yoshida Memorial International Cancer Study Grant. Central
Europe study: World Cancer Research Fund and the European Commission
INCO-COPERNICUS Program (Contract No. IC15-CT98-0332). Los Angeles
study: NIH (P50CA090388, R01DA011386, R03CA077954, T32CA009142,
U01CA096134, R21ES011667) and the Alper Research Program for
Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center.
Japan study: Scientific Research grant from the Ministry of Education,
Science, Sports, Culture and Technology of Japan (17015052) and a grant
for the ThirdTerm Comprehensive 10-Year Strategy for Cancer Control from
the Ministry of Health, Labour and Welfare of Japan (H20-002). Seattle
study (1985-1995): NIH (R01CA048996, R01DE012609). Seattle-LEO study:
NIH (R01CA030022). Puerto Rico study: jointly funded by National
Institutes of Health NCI and NIDCR intramural programs (No grant number
applicable). Baltimore: NIH (DE016631). Memorial Sloan Kettering Cancer
Center, New York, USA: NIH (R01CA051845). HOTSPOT: Johns Hopkins Richard
Gelb Cancer Prevention Award (no grant number applicable).
NR 38
TC 1
Z9 1
U1 4
U2 6
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 AUG
PY 2016
VL 27
IS 8
BP 1619
EP 1625
DI 10.1093/annonc/mdw224
PG 7
WC Oncology
SC Oncology
GA DV8JH
UT WOS:000383182800034
PM 27234641
ER
PT J
AU Kasugai, Y
Yoshida, N
Ohshima, K
Matsuo, K
Seto, M
Tsuzuki, S
AF Kasugai, Yumiko
Yoshida, Noriaki
Ohshima, Koichi
Matsuo, Keitaro
Seto, Masao
Tsuzuki, Shinobu
TI New mouse model of acute adult T-cell leukemia generated by
transplantation of AKT, BCLxL, and HBZ-transduced T cells
SO CANCER SCIENCE
LA English
DT Article
DE AKT; ATL; BCLxL; HBZ; mouse model
ID GENE; LEUKEMIA/LYMPHOMA; PROLIFERATION; LYMPHOMA; FEATURES; MICE
AB Adult T-cell leukemia/lymphoma (ATL) develops in human T-cell leukemia virus type 1 (HTLV-1) carriers. Although the HTLV-1-encoded HBZ gene is critically involved, HBZ alone is insufficient and additional, cooperative "hits" are required for the development of ATL. Candidate cooperative hits are being defined, but methods to rapidly explore their roles in ATL development in collaboration with HBZ are lacking. Here, we present a new mouse model of acute type ATL that can be generated rapidly by transplanting in vitro-induced T cells that have been retrovirally transduced with HBZ and two cooperative genes, BCLxL and AKT, into mice. Co-transduction of HBZ and BCLxL/AKT allowed these T cells to grow in vitro in the absence of cytokines (Flt3-ligand and interleukin-7), which did not occur with any two-gene combination. Although transplanted T cells were a mixture of cells transduced with different combinations of the genes, tumors that developed in mice were composed of HBZ/BCLxL/AKT triply transduced T cells, showing the synergistic effect of the three genes. The genetic/epigenetic landscape of ATL has only recently been elucidated, and the roles of additional "hits" in ATL pathogenesis remain to be explored. Our model provides a versatile tool to examine the roles of these hits, in collaboration with HBZ, in the development of acute ATL.
C1 [Kasugai, Yumiko; Matsuo, Keitaro; Tsuzuki, Shinobu] Aichi Canc Ctr, Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
[Yoshida, Noriaki; Ohshima, Koichi; Seto, Masao] Kurume Univ, Sch Med, Dept Pathol, Kurume, Fukuoka, Japan.
[Yoshida, Noriaki] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
RP Tsuzuki, S (reprint author), Aichi Canc Ctr, Res Inst, Div Mol Med, Chikusa Ku, 1-1 Kanokoden, Nagoya, Aichi 4648681, Japan.
EM stsuzuki@aichi-cc.jp
OI Yoshida, Noriaki/0000-0001-7001-0106; Matsuo,
Keitaro/0000-0003-1761-6314
FU Ministry of Health, Labor, and Welfare of Japan
[H26-Kakushingann-Ippan-010]; Japan Agency for Medical Research and
Development [15ck0106015h0102]
FX Ministry of Health, Labor, and Welfare of Japan
(H26-Kakushingann-Ippan-010); Japan Agency for Medical Research and
Development (15ck0106015h0102).
NR 19
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1347-9032
EI 1349-7006
J9 CANCER SCI
JI Cancer Sci.
PD AUG
PY 2016
VL 107
IS 8
BP 1072
EP 1078
DI 10.1111/cas.12974
PG 7
WC Oncology
SC Oncology
GA EB0BU
UT WOS:000387009200002
PM 27223899
ER
PT J
AU Habib, SL
Abboud, HE
AF Habib, Samy L.
Abboud, Hanna E.
TI Tuberin regulates reactive oxygen species in renal proximal cells,
kidney from rodents, and kidney from patients with tuberous sclerosis
complex
SO CANCER SCIENCE
LA English
DT Article
DE Kidney; renal cells; reactive oxygen species; tumor suppressor gene;
tumorigenesis
ID OXIDATIVE DNA-DAMAGE; NADPH-OXIDASE; DIABETIC-NEPHROPATHY;
ENDOTHELIAL-CELLS; PROSTATE-CANCER; EXPRESSION; DISEASE; SUPEROXIDE;
NOX4; ACTIVATION
AB Reactive oxygen species (ROS) are an important endogenous source of DNA damage and oxidative stress in all cell types. Deficiency in tuberin resulted in increased oxidative DNA damage in renal cells. In this study, the role of tuberin in the regulating of ROS and NADPH oxidases was investigated. Formation of ROS and activity of NADPH oxidases were significantly higher in mouse embryonic fibroblasts and in primary culture of rat renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells. In addition, expression of NADPH oxidase (Nox)1, Nox2, and Nox4 (Nox isoforms) was higher in mouse embryonic fibroblasts and renal proximal tubular epithelial tuberin-deficient cells compared to wild-type cells. Furthermore, activity levels of NADPH oxidases and protein expression of all Nox isoforms were higher in the renal cortex of rat deficient in tuberin. However, treatment of tuberin-deficient cells with rapamycin showed significant decrease in protein expression of all Nox. Significant increase in protein kinase C beta II expression was detected in tuberin-deficient cells, whereas inhibition of protein kinase C beta II by bisindolylmaleimide I resulted in decreased protein expression of all Nox isoforms. In addition, treatment of mice deficient in tuberin with rapamycin resulted in significant decrease in all Nox protein expression. Moreover, protein and mRNA expression of all Nox were highly expressed in tumor kidney tissue of patients with tuberous sclerosis complex compared to control kidney tissue of normal subjects. These data provide the first evidence that tuberin plays a novel role in regulating ROS generation, NADPH oxidase activity, and Nox expression that may potentially be involved in development of kidney tumor in patients with tuberous sclerosis complex.
C1 [Habib, Samy L.; Abboud, Hanna E.] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Dept, San Antonio, TX USA.
[Habib, Samy L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Abboud, Hanna E.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA.
RP Habib, SL (reprint author), Univ Texas Hlth Sci Ctr San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM habib@uthscsa.edu
FU American Heart Association; South Texas Veterans Healthcare System
FX American Heart Association; South Texas Veterans Healthcare System.
NR 46
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1347-9032
EI 1349-7006
J9 CANCER SCI
JI Cancer Sci.
PD AUG
PY 2016
VL 107
IS 8
BP 1092
EP 1100
DI 10.1111/cas.12984
PG 9
WC Oncology
SC Oncology
GA EB0BU
UT WOS:000387009200004
PM 27278252
ER
PT J
AU Raciborska, A
Bilska, K
Weclawek-Tompol, J
Ussowicz, M
Pogorzala, M
Janowska, J
Rychlowska-Pruszynska, M
Rodriguez-Galindo, C
Helwich, E
AF Raciborska, Anna
Bilska, Katarzyna
Weclawek-Tompol, Jadwiga
Ussowicz, Marek
Pogorzala, Monika
Janowska, Joanna
Rychlowska-Pruszynska, Magdalena
Rodriguez-Galindo, Carlos
Helwich, Ewa
TI Solid Cancers in the Premature and the Newborn: Report of Three National
Referral Centers
SO PEDIATRICS AND NEONATOLOGY
LA English
DT Article
DE neonate; perinatal cancer; premature; survival; treatment
ID SACROCOCCYGEAL TERATOMA; MESOBLASTIC NEPHROMA; RENAL TUMORS;
NEUROBLASTOMA; HEMANGIOPERICYTOMA; INFANTS
AB Background: Advances in multidisciplinary care for pediatric cancer have resulted in significant improvement in cure rates over the last decades; however, these advances have not been uniform across all age groups. Cancer is an important cause of perinatal mortality, yet the full spectrum of malignant neoplasms in newborns is not well defined.
Methods: The authors have reviewed the clinical features and outcomes of 37 newborns with congenital malignant tumors treated at three referral centers in North, Central, and South Poland between 1980 and 2014. Event-free survival (EFS) and overall survival (OS) rates were estimated by Kaplan-Meier methods and compared using long-rank test and Cox models.
Results: Twenty-two patients were diagnosed prenatally. The most common diagnoses were neuroblastoma (48.7%), followed by malignant germ-cell tumor (16.2%), and Wilms' tumor (8.1%). Neuroblastoma was the most common malignancy among full-term infants, and malignant sacrococcygeal teratoma was the most common malignancy in premature infants. Thirty patients (81%) are alive with a median follow-up of 4.8 years from diagnosis. Patients with Wilms' tumor and malignant germ-cell tumors had the best outcomes (5-year OS 100% for both), whereas the worst prognosis was observed for sarcoma patients (5-year OS 72.92%). Premature infants had better outcome than full-term infants (5-year OS 92.8% vs. 72.58%, respectively).
Conclusion: Although rare, neonatal cancers can present with an aggressive clinical behavior, but they have a generally good outcome. Early diagnosis and management by expert multidisciplinary teams that integrate perinatal medicine experts with pediatric and surgical oncologists are critical. Centralized care with clear referral pathways that facilitate early initiation of specialized treatment should be prioritized. Copyright (C) 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.
C1 [Raciborska, Anna; Bilska, Katarzyna; Rychlowska-Pruszynska, Magdalena] Inst Mother & Child Hlth, Dept Surg Oncol Children & Youth, Ul Kasprzaka 17a, PL-01211 Warsaw, Poland.
[Weclawek-Tompol, Jadwiga; Ussowicz, Marek] Wroclaw Med Univ, Dept & Clin Pediat Oncol Hematol & Bone Marrow Tr, Wroclaw, Poland.
[Pogorzala, Monika] Nicolaus Copernicus Univ, Dept Pediat Hematol & Oncol, Coll Med, Bydgoszcz, Poland.
[Janowska, Joanna; Helwich, Ewa] Inst Mother & Child Hlth, Neonatal Intens Care Unit, Warsaw, Poland.
[Rodriguez-Galindo, Carlos] Harvard Med Sch, Dana Farber Canc Inst, Pediat Oncol, Boston, MA USA.
[Rodriguez-Galindo, Carlos] Harvard Med Sch, Childrens Hosp, Boston, MA USA.
RP Raciborska, A (reprint author), Inst Mother & Child Hlth, Dept Surg Oncol Children & Youth, Ul Kasprzaka 17a, PL-01211 Warsaw, Poland.
EM anna.raciborska@hoga.pl
NR 22
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER TAIWAN
PI TAIPEI
PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2,
TAIPEI, 10449, TAIWAN
SN 1875-9572
J9 PEDIATR NEONATOL
JI Pediatr. Neonatol.
PD AUG
PY 2016
VL 57
IS 4
BP 295
EP 301
DI 10.1016/j.pedneo.2015.08.007
PG 7
WC Pediatrics
SC Pediatrics
GA EA9UP
UT WOS:000386990500007
PM 26934827
ER
PT J
AU Liang, JS
Lee, SP
Pulli, B
Chen, JW
Kao, SC
Tsang, YM
Hsieh, KLC
AF Liang, Jao-Shwann
Lee, Shiou-Ping
Pulli, Benjamin
Chen, John W.
Kao, Sheng-Chuan
Tsang, Yuk-Ming
Hsieh, Kevin Li-Chun
TI Microstructural Changes in Absence Seizure Children: A Diffusion Tensor
Magnetic Resonance Imaging Study
SO PEDIATRICS AND NEONATOLOGY
LA English
DT Article
DE absence seizures; diffusion tensor imaging; magnetic resonance imaging;
mean diffusivity; tractography
ID SPIKE-WAVE SEIZURES; GENERALIZED PENICILLIN EPILEPSY; CORPUS-CALLOSUM;
FIBER TRACTOGRAPHY; WAG/RIJ RATS; OPTIC-NERVE; MRI; DISCHARGES; BRAIN;
ABNORMALITIES
AB Background: Absence seizures are a subtype of epileptic seizures clinically characterized by transient alterations in states of consciousness and by electroencephalography indicating diffuse spike-wave discharges (SWD). Conventional brain magnetic resonance imaging (MRI) is not routinely used to establish the diagnosis, but rather to rule out other diseases. The present study investigated tissue integrity in children with SWD epilepsy using diffusion tensor imaging (DTI).
Methods: Magnetic resonance imaging (MRI)-DTI was conducted in 18 patients with absence seizures and 10 control participants. Brain areas were evaluated using diffusion maps, and fractional anisotropy (FA), mean diffusivity (MD), parallel diffusivity (lambda parallel to), and perpendicular diffusivity (lambda perpendicular to) values were extracted and analyzed. Tractography at the regions of abnormal diffusion indices was then reconstructed in each group, and tract symmetry was evaluated by an index of asymmetry (AI). Statistical analyses were performed using nonparametric Mann-Whitney U tests, with p values < 0.05 indicating statistical significance.
Results: Compared to the control group, patients with SWD epilepsy had lower FA values and higher MD values at the genu of the corpus callosum. There was also a stronger negative correlation between MD and FA values at the genu of the corpus callosum in patients than in control participants. The AI for the fiber tracts through the genu of the corpus callosum in the SWD group was significantly higher than that of the control group, indicating that tract distribution was more asymmetric in patients with epilepsy. There were no significant differences between groups in diffusion indices for other brain areas.
Conclusion: We observed microstructural changes in the genu of the corpus callosum, as well as reduced FA values, increased lambda perpendicular to values, increased MD values, and asymmetric distribution of fiber tracts, indicating that DTI is more sensitive than conventional MRI to detect brain abnormalities in children with absence seizures. Copyright (C) 2015, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC.
C1 [Liang, Jao-Shwann] Far Eastern Mem Hosp, Dept Pediat, New Taipei, Taiwan.
[Lee, Shiou-Ping] Far Eastern Mem Hosp, Div Med Imaging, Dept Radiol, New Taipei, Taiwan.
[Pulli, Benjamin; Chen, John W.; Kao, Sheng-Chuan; Tsang, Yuk-Ming] Harvard Med Sch, Ctr Syst Biol, Massachusetts Gen Hosp, Boston, MA USA.
[Pulli, Benjamin; Chen, John W.; Kao, Sheng-Chuan; Tsang, Yuk-Ming] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA.
[Hsieh, Kevin Li-Chun] Taipei Med Univ Hosp, Dept Med Imaging, 252,Wu Hsing St, Taipei 110, Taiwan.
[Hsieh, Kevin Li-Chun] Taipei Med Univ, Coll Med, Translat Imaging Res Ctr, Taipei, Taiwan.
RP Hsieh, KLC (reprint author), Taipei Med Univ Hosp, Dept Med Imaging, 252,Wu Hsing St, Taipei 110, Taiwan.
EM Kevinh9396@gmail.com
NR 40
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER TAIWAN
PI TAIPEI
PA RM N-412, 4F, CHIA HSIN BUILDING 11, NO 96, ZHONG SHAN N ROAD SEC 2,
TAIPEI, 10449, TAIWAN
SN 1875-9572
J9 PEDIATR NEONATOL
JI Pediatr. Neonatol.
PD AUG
PY 2016
VL 57
IS 4
BP 318
EP 325
DI 10.1016/j.pedneo.2015.10.003
PG 8
WC Pediatrics
SC Pediatrics
GA EA9UP
UT WOS:000386990500010
PM 26750405
ER
PT J
AU Funk, LM
Jolles, SA
Voils, CI
AF Funk, Luke M.
Jolles, Sally A.
Voils, Corrine I.
TI Obesity as a disease: has the AMA resolution had an impact on how
physicians view obesity?
SO SURGERY FOR OBESITY AND RELATED DISEASES
LA English
DT Editorial Material
DE Health services; Obesity; Public health
ID BARIATRIC SURGERY; WEIGHT BIAS; CARE
AB Background: In 2013, the American Medical Association (AMA) passed a resolution characterizing obesity as a disease. It is unclear whether primary care physicians (PCPs) agree with this characterization and how their agreement or lack thereof affects their treatment of patients with obesity.
Objectives: We sought to understand PCP opinions about the AMA obesity resolution and how it has affected management of patients with obesity.
Setting: Small, medium, and large communities in Wisconsin
Methods: Focus groups were conducted with PCPs in Wisconsin. PCPs were asked whether they considered obesity a disease and what they factored into this consideration, including the AMA decision. A directed approach to content analysis was used to analyze the data. A taxonomy of consensus codes was developed, coding summaries were generated, and representative quotes were identified.
Results: Three focus groups comprising a total of 16 PCP participants were conducted. Not all PCPs were aware of the AMA resolution. PCPs held divergent opinions on whether obesity represented a disease, primarily focusing their considerations on obesity as a risk factor versus a disease. They also discussed how considering obesity as a disease affects the patient doctor relationship, insurance coverage, physician reimbursement, and research.
Conclusion: The AMA resolution did not appear to have made a significant impact on PCP opinions or management practices in our focus groups in Wisconsin. Follow-up surveys that quantify the prevalance of these opinions and practices at the state and national levels would be highly informative. (Surg Obes Relat Dis 2016;12:1431-1435.) Published by Elsevier Inc. on behalf of American Society for Metabolic and Bariatric Surgery.
C1 [Funk, Luke M.; Jolles, Sally A.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
[Funk, Luke M.; Jolles, Sally A.] Univ Wisconsin, Dept Surg, Wisconsin Surg Outcomes Res Program WiSOR, Sch Med & Publ Hlth, Madison, WI USA.
[Voils, Corrine I.] Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Voils, Corrine I.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
RP Funk, LM (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, 600 Highland Ave,H4-728 Clin Sci Ctr, Madison, WI 53792 USA.
EM funk@surgery.wisc.edu
NR 14
TC 1
Z9 1
U1 3
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1550-7289
EI 1878-7533
J9 SURG OBES RELAT DIS
JI Surg. Obes. Relat. Dis.
PD AUG
PY 2016
VL 12
IS 7
BP 1431
EP 1435
DI 10.1016/j.soard.2016.05.009
PG 5
WC Surgery
SC Surgery
GA EA9TJ
UT WOS:000386987300031
PM 27444860
ER
PT J
AU Decker, BK
Harris, PL
Muder, RR
Hong, JH
Singh, N
Sonel, AF
Clancy, CJ
AF Decker, Brooke K.
Harris, Patricia L.
Muder, Robert R.
Hong, Jae H.
Singh, Nina
Sonel, Ali F.
Clancy, Cornelius J.
TI Improving the Diagnosis of Legionella Pneumonia within a Healthcare
System through a Systematic Consultation and Testing Program
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Rationale: Legionella testing is not recommended for all patients with pneumonia, but rather for particular patient subgroups. As a result, the overall incidence of Legionella pneumonia may be underestimated.
Objectives: To determine the incidence of Legionella pneumonia in a veteran population in an endemic area after introduction of a systematic infectious diseases consultation and testing program.
Methods: In response to a 2011-2012 outbreak, the VA Pittsburgh Healthcare System mandated infectious diseases consultations and testing for Legionella by urine antigen and sputum culture in all patients with pneumonia.
Measurements and Main Results: Between January 2013 and December 2015, 1,579 cases of pneumonia were identified. The incidence of pneumonia was 788/100,000 veterans per year, including 352/100,000 veterans per year and 436/100,000 veterans per year with community-associated pneumonia (CAP) and health care-associated pneumonia, respectively. Ninety-eight percent of patients with suspected pneumonia were tested for Legionella by at least one method. Legionella accounted for 1% of pneumonia cases (n = 16), including 1.7% (12/706) and 0.6% (4/873) of CAP and health care-associated pneumonia, respectively. The yearly incidences of Legionella pneumonia and Legionella CAP were 7.99 and 5.99/100,000 veterans, respectively. The sensitivities of urine antigen and sputum culture were 81% and 60%, respectively; the specificity of urine antigen was >99.97%. Urine antigen testing and Legionella cultures increased by 65% and 330%, respectively, after introduction of our program.
Conclusions: Systematic testing of veterans in an endemic area revealed a higher incidence of Legionella pneumonia and CAP than previously reported. Widespread urine antigen testing was not limited by false positivity.
C1 [Decker, Brooke K.; Hong, Jae H.; Singh, Nina; Clancy, Cornelius J.] Infect Dis Sect, Pittsburgh, PA USA.
[Harris, Patricia L.; Sonel, Ali F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Decker, Brooke K.; Muder, Robert R.; Hong, Jae H.; Singh, Nina; Clancy, Cornelius J.] Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA.
RP Decker, BK (reprint author), VA Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C ID Sect,111E-U, Pittsburgh, PA 15240 USA.
EM brooke.decker@va.gov
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 AUG
PY 2016
VL 13
IS 8
BP 1289
EP 1293
DI 10.1513/AnnalsATS.201510-715BC
PG 5
WC Respiratory System
SC Respiratory System
GA DZ8JV
UT WOS:000386117600019
PM 27243279
ER
PT J
AU Berning, JN
Poor, AD
Buckley, SM
Patel, KR
Lederer, DJ
Goldstein, NE
Brodie, D
Baldwin, MR
AF Berning, Joel N.
Poor, Armeen D.
Buckley, Sarah M.
Patel, Komal R.
Lederer, David J.
Goldstein, Nathan E.
Brodie, Daniel
Baldwin, Matthew R.
TI A Novel Picture Guide to Improve Spiritual Care and Reduce Anxiety in
Mechanically Ventilated Adults in the Intensive Care Unit
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Rationale: Hospital chaplains provide spiritual care that helps patients facing serious illness cope with their symptoms and prognosis, yet because mechanically ventilated patients cannot speak, spiritual care of these patients has been limited.
Objectives: To determine the feasibility and measure the effects of chaplain-led picture-guided spiritual care for mechanically ventilated adults in the intensive care unit (ICU).
Methods: We conducted a quasi-experimental study at a tertiary care hospital between March 2014 and July 2015. Fifty mechanically ventilated adults in medical or surgical ICUs without delirium or dementia received spiritual care by a hospital chaplain using an illustrated communication card to assess their spiritual affiliations, emotions, and needs and were followed until hospital discharge. Feasibility was assessed as the proportion of participants able to identify spiritual affiliations, emotions, and needs using the card. Among the first 25 participants, we performed semistructured interviews with 8 ICU survivors to identify how spiritual care helped them. For the subsequent 25 participants, we measured anxiety (on 100-mm visual analog scales [VAS]) immediately before and after the first chaplain visit, and we performed semistructured interviews with 18 ICU survivors with added measurements of pain and stress (on +/- 100-mm VAS).
Measurements and Main Results: The mean (SD) age was 59 (+/- 16) years, median mechanical ventilation days was 19.5 (interquartile range, 7-29 d), and 15 (30%) died in-hospital. Using the card, 50 (100%) identified a spiritual affiliation, 47 (94%) identified one or more emotions, 45 (90%) rated their spiritual pain, and 36 (72%) selected a chaplain intervention. Anxiety after the first visit decreased 31% (mean score change, -20; 95% confidence interval, -33 to -7). Among 28 ICU survivors, 26 (93%) remembered the intervention and underwent semistructured interviews, of whom 81% felt more capable of dealing with their hospitalization and 0% felt worse. The 18 ICU survivors who underwent additional VAS testing during semistructured follow-up interviews reported a 49-point reduction in stress (95% confidence interval, -72 to -24) and no significant change in physical pain that they attributed to picture-guided spiritual care.
Conclusions: Chaplain-led picture-guided spiritual care is feasible among mechanically ventilated adults and shows potential for reducing anxiety during and stress after an ICU admission.
C1 [Berning, Joel N.] NewYork Presbyterian Hosp, Pastoral Care & Educ Dept, New York, NY USA.
[Poor, Armeen D.; Buckley, Sarah M.; Patel, Komal R.; Lederer, David J.; Brodie, Daniel; Baldwin, Matthew R.] Columbia Univ, Coll Phys & Surg, Div Pulm Allergy & Crit Care, New York, NY USA.
[Lederer, David J.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Goldstein, Nathan E.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA.
[Goldstein, Nathan E.] James J Peters VA Med Ctr, Geriatr Res Educ & Clin Ctr, New York, NY USA.
RP Baldwin, MR (reprint author), Div Pulm Allergy & Crit Care, 622 West 168th St,PH-8E Room 101, New York, NY 10032 USA.
EM mrb45@cumc.columbia.edu
FU National Institutes of Health [UL1 TR000040, KL2 TR000081, K23AG045560]
FX Supported by National Institutes of Health grants UL1 TR000040, KL2
TR000081, and K23AG045560. The views expressed in this article do not
communicate an official position of National Institutes of Health.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 AUG
PY 2016
VL 13
IS 8
BP 1333
EP 1342
DI 10.1513/AnnalsATS.201512-831OC
PG 10
WC Respiratory System
SC Respiratory System
GA DZ8JV
UT WOS:000386117600025
PM 27097049
ER
PT J
AU Kamdar, BB
Knauert, MP
Jones, SF
Parsons, EC
Parthasarathy, S
Pisani, MA
AF Kamdar, Biren B.
Knauert, Melissa P.
Jones, Shirley F.
Parsons, Elizabeth C.
Parthasarathy, Sairam
Pisani, Margaret A.
CA Sleep ICU SLEEPii Task Force
TI Perceptions and Practices Regarding Sleep in the Intensive Care Unit A
Survey of 1,223 Critical Care Providers
SO ANNALS OF THE AMERICAN THORACIC SOCIETY
LA English
DT Article
AB Rationale: Poor sleep affects a majority of critically ill patients and is believed to be associated with adverse intensive care unit (ICU) outcomes such as delirium. While recent guidelines recommend sleep promotion efforts to improve delirium and other ICU outcomes, little is known about critical care providers' beliefs regarding sleep in the ICU.
Objectives: To evaluate providers' perceptions and practices regarding sleep in the ICU.
Methods: From April to July 2014, the Sleep in the ICU Survey was disseminated to ICU providers via institutional e-mail lists and four international critical care society distribution lists.
Measurements and Main Results: A total of 1,223 surveys were completed by providers from 24 countries. Respondents were primarily nurses (59%) or physicians (39%). Most respondents indicated that ICU patients experienced " poor" or " very poor" sleep 75%) and that poor sleep could affect the ICU recovery process (88%). Respondents also felt that poor sleep was associated with negative ICU outcomes such as the development of delirium (97%), longer length of stay (88%), poor participation in physical therapy (87%), and delayed liberation from mechanical ventilation (83%). The minority (32%) of providers had sleep-promoting protocols; these providers tended to believe their patients slept longer and experienced better sleep quality.
Conclusions: Though most clinicians believe that sleep in the ICU is poor and adversely affects patient outcomes, a minority of the ICUs represented by our respondents have sleep promotion protocols. These findings highlight discordant provider perceptions and practices surrounding sleep in the ICU, as well as a possible lack of available evidence-based guidelines for promoting sleep in the ICU.
C1 [Kamdar, Biren B.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 10833 Le Conte Ave,Room 37-131 CHS, Los Angeles, CA 90095 USA.
[Knauert, Melissa P.; Pisani, Margaret A.] Yale Univ, Sch Med, Sect Pulm Crit Care & Sleep Med, New Haven, CT USA.
[Jones, Shirley F.] Texas A&M Hlth Sci Ctr Coll Med, Baylor Scott & White Healthcare, Div Pulm Crit Care & Sleep Med, Temple, TX USA.
[Parsons, Elizabeth C.] Univ Washington, Div Pulm & Crit Care Med, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
[Parthasarathy, Sairam] Univ Arizona, Div Pulm & Crit Care Med, Tucson, AZ USA.
RP Kamdar, BB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, 10833 Le Conte Ave,Room 37-131 CHS, Los Angeles, CA 90095 USA.
EM bkamdar@mednet.ucla.edu
OI Kamdar, Biren/0000-0002-9245-6229
FU UCLA Clinical and Translational Science Institute (CTSI) National
Institutes of Health (NIH)/National Center for Advancing Translational
Sciences (NCATS) [UCLA UL1TR000124]; Yale Claude D. Pepper Older
Americans Independence Center [P30AG021342]; NIH/NCATS [KL2 TR000140]
FX B.B.K. is currently supported by a Career Development Award from the
UCLA Clinical and Translational Science Institute (CTSI) National
Institutes of Health (NIH)/National Center for Advancing Translational
Sciences (NCATS) (UCLA UL1TR000124). M.P.K. is currently supported by a
Career Development Award from the Yale Claude D. Pepper Older Americans
Independence Center (P30AG021342) and by a CTSA grant from the NIH/NCATS
(KL2 TR000140). The views expressed here are those of the authors and do
not reflect the position or policy of the Department of Veterans
Affairs.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 AUG
PY 2016
VL 13
IS 8
BP 1370
EP 1377
DI 10.1513/AnnalsATS.201601-087OC
PG 8
WC Respiratory System
SC Respiratory System
GA DZ8JV
UT WOS:000386117600029
PM 27104770
ER
PT J
AU Cardet, JC
Ash, S
Kusa, T
Camargo, CA
Israel, E
AF Cardet, Juan Carlos
Ash, Samuel
Kusa, Tope
Camargo, Carlos A., Jr.
Israel, Elliot
TI Insulin resistance modifies the association between obesity and current
asthma in adults
SO EUROPEAN RESPIRATORY JOURNAL
LA English
DT Article
ID BODY-MASS INDEX; METABOLIC SYNDROME; UNITED-STATES; SELECTIVE INSULIN;
PREVALENCE; COHORT; AIRWAY; LUNG; IDENTIFICATION; INFLAMMATION
AB Insulin resistance potentiates the association between obesity and childhood asthma, but this relationship appears inconsistent in relatively small studies of adults. We investigated effect modification in adults using the National Health and Nutrition Examination Survey 2003-2012, a large, nationally representative database.
Insulin resistance and a history of physician-diagnosed current asthma were obtained from 12 421 adults, ages 18-85 years. We used logistic regression to determine associations between obesity and current asthma, adjusting for age, sex, race/ethnicity, poverty income ratio and smoking status. An interaction term evaluated effect modification by insulin resistance of the obesity-asthma association.
As expected, obesity was positively associated with current asthma. Insulin resistance modified this association, with obesity measured as body mass index, waist circumference or waist-to-height ratio. The relationship between obesity and current asthma was stronger with increasing insulin resistance tertiles (OR 2.05, 95% CI 2.76-3.00; p-value for interaction 0.03). This association was robust to adjustments for other components of the metabolic syndrome (hypertriglyceridaemia, hypertension, hyperglycaemia and systemic inflammation). None of these components were themselves effect modifiers of the obesity-asthma association.
In this large, nationally representative sample, insulin resistance modified the association between obesity and current asthma in adults. Targeting insulin resistance may represent a novel therapeutic strategy for obese patients with asthma.
C1 [Cardet, Juan Carlos; Israel, Elliot] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St, Boston, MA 02115 USA.
[Cardet, Juan Carlos; Ash, Samuel; Israel, Elliot] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA.
[Kusa, Tope] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Israel, E (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM eisrael@partners.org
FU National Institute of Allergy and Infectious Diseases, a National
Institutes of Health Diversity Supplement [3U19AI095219-04S1];
[U19AI095219-01]
FX This work was supported by grants from the National Institute of Allergy
and Infectious Diseases, a National Institutes of Health Diversity
Supplement (3U19AI095219-04S1), and funds from centre grant
U19AI095219-01 to J.C. Cardet. Funding information for this article has
been deposited with FundRef.
NR 37
TC 3
Z9 3
U1 1
U2 1
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 AUG
PY 2016
VL 48
IS 2
BP 403
EP 410
DI 10.1183/13993003.00246-2016
PG 8
WC Respiratory System
SC Respiratory System
GA DZ6FQ
UT WOS:000385957400018
PM 27103388
ER
PT J
AU Tabung, FK
Smith-Warner, SA
Chavarro, JE
Wu, K
Fuchs, CS
Hu, FB
Chan, AT
Willett, WC
Giovannucci, EL
AF Tabung, Fred K.
Smith-Warner, Stephanie A.
Chavarro, Jorge E.
Wu, Kana
Fuchs, Charles S.
Hu, Frank B.
Chan, Andrew T.
Willett, Walter C.
Giovannucci, Edward L.
TI Development and Validation of an Empirical Dietary Inflammatory Index
SO JOURNAL OF NUTRITION
LA English
DT Article
DE hypothesis-driven; dietary patterns; dietary inflammatory potential;
inflammatory markers; inflammation
ID FOOD-FREQUENCY QUESTIONNAIRE; C-REACTIVE PROTEIN;
CORONARY-HEART-DISEASE; TOTAL-ENERGY INTAKE; COLORECTAL-CANCER;
NUTRITIONAL EPIDEMIOLOGY; POSTMENOPAUSAL WOMEN; ENDOTHELIAL DYSFUNCTION;
SYSTEMIC INFLAMMATION; PLASMA-CONCENTRATIONS
AB Background: Knowledge on specific biological pathways mediating disease occurrence (e.g., inflammation) may be utilized to construct hypotheses-driven dietary patterns that take advantage of current evidence on disease-related hypotheses and the statistical methods of a posteriori patterns.
Objective: We developed and validated an empirical dietary inflammatory index (EDII) based on food groups.
Methods: We entered 39 pre-defined food groups in reduced rank regression models followed by stepwise linear regression analyses in the Nurses' Health Study (NHS, n = 5230) to identify a dietary pattern most predictive of 3 plasma inflammatory markers: interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor a receptor 2 (TNF alpha R2). We evaluated the construct validity of the EDII in 2 independent samples from NHS-II (n = 1002) and Health Professionals Follow-up Study (HPFS, n = 2632) using multivariable-adjusted linear regression models to examine how well the EDII predicted concentrations of IL-6, CRP, TNFaR2, adiponectin, and an overall inflammatory marker score combining all biomarkers.
Results: The EDII is the weighted sum of 18 food groups; 9 are anti-inflammatory and 9 proinflammatory. In NHS-II and HPFS, the EDII significantly predicted concentrations of all biomarkers. For example, the relative concentrations comparing extreme EDII quintiles in NHS-II were: adiponectin, 0.88 (95% CI, 0.80, 0.96), P-trend = 0.003; and CRP, 1.52 (95% CI, 1.18, 1.97), P-trend = 0.002. Corresponding associations in HPFS were: 0.87 (95% CI, 0.82, 0.92), P-trend < 0.0001; and 1.23 (95% CI, 1.09, 1.40), P-trend = 0.002.
Conclusion: The EDII represents, to our knowledge, a novel, hypothesis-driven, empirically derived dietary pattern that assesses diet quality based on its inflammatory potential. Its strong construct validity in independent samples of women and men indicates its usefulness in assessing the inflammatory potential of whole diets. Additionally, the EDII may be calculated in a standardized and reproducible manner across different populations thus circumventing a major limitation of dietary patterns derived from the same study in which they are applied.
C1 [Tabung, Fred K.; Smith-Warner, Stephanie A.; Chavarro, Jorge E.; Wu, Kana; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Tabung, Fred K.; Smith-Warner, Stephanie A.; Chavarro, Jorge E.; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chavarro, Jorge E.; Fuchs, Charles S.; Hu, Frank B.; Chan, Andrew T.; Willett, Walter C.; Giovannucci, Edward L.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Chavarro, Jorge E.; Fuchs, Charles S.; Hu, Frank B.; Willett, Walter C.; Giovannucci, Edward L.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA.
RP Tabung, FK (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.; Tabung, FK (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
EM ftabung@hsph.harvard.edu
FU NIH [P30DK046200, U54 CA155426, UM1 CA 167552, UM1 CA 186107, UM1 CA
176726]
FX JEC and FBH were supported by NIH grants P30DK046200 and U54 CA155426.
The Health Professionals Follow- Up Study, Nurses' Health Study, and
Nurses Health Study II cohorts are supported by NIH grants UM1 CA
167552, UM1 CA 186107, and UM1 CA 176726, respectively.
NR 64
TC 3
Z9 3
U1 11
U2 11
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD AUG
PY 2016
VL 146
IS 8
BP 1560
EP 1570
DI 10.3945/jn.115.228718
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DZ8OT
UT WOS:000386130900013
PM 27358416
ER
PT J
AU Goulet, JL
Kerns, RD
Bair, M
Becker, WC
Brennan, P
Burgess, DJ
Carroll, CM
Dobscha, S
Driscoll, MA
Fenton, BT
Fraenkel, L
Haskell, SG
Heapy, AA
Higgins, DM
Hoff, RA
Hwang, U
Justice, AC
Piette, JD
Sinnott, P
Wandner, L
Womack, JA
Brandt, CA
AF Goulet, Joseph L.
Kerns, Robert D.
Bair, Matthew
Becker, William C.
Brennan, Penny
Burgess, Diana J.
Carroll, Constance M.
Dobscha, Steven
Driscoll, Mary A.
Fenton, Brenda T.
Fraenkel, Liana
Haskell, Sally G.
Heapy, Alicia A.
Higgins, Diana M.
Hoff, Rani A.
Hwang, Ula
Justice, Amy C.
Piette, John D.
Sinnott, Patsi
Wandner, Laura
Womack, Julie A.
Brandt, Cynthia A.
TI The musculoskeletal diagnosis cohort: examining pain and pain care among
veterans
SO PAIN
LA English
DT Article
DE Pain; Musculoskeletal disorders; Mental health comorbidity; Cohort
studies; Veterans; Epidemiology
ID LOW-BACK-PAIN; IRAQI FREEDOM; SYSTEM; COMORBIDITY; DEPRESSION;
FREEDOM/OPERATION; TRANSFORMATION; PREVALENCE; DISORDERS; TRENDS
AB Musculoskeletal disorders (MSDs) are highly prevalent, painful, and costly disorders. The MSD Cohort was created to characterize variation in pain, comorbidities, treatment, and outcomes among patients with MSD receiving Veterans Health Administration care across demographic groups, geographic regions, and facilities. We searched electronic health records to identify patients treated in Veterans Health Administration who had ICD-9-CM codes for diagnoses including, but not limited to, joint, back, and neck disorders, and osteoarthritis. Cohort inclusion criteria were 2 or more outpatient visits occurring within 18 months of one another or one inpatient visit with an MSD diagnosis between 2000 and 2011. The first diagnosis is the index date. Pain intensity numeric rating scale (NRS) scores, comorbid medical and mental health diagnoses, pain-related treatments, and other characteristics were collected retrospectively and prospectively. The cohort included 5,237,763 patients; their mean age was 59, 6% were women, 15% identified as black, and 18% reported severe pain (NRS >= 7) on the index date. Nontraumatic joint disorder (27%), back disorder (25%), and osteoarthritis (21%) were the most common MSD diagnoses. Patients entering the cohort in recent years had more concurrent MSD diagnoses and higher NRS scores. The MSD Cohort is a rich resource for collaborative pain-relevant health service research.
C1 [Goulet, Joseph L.; Kerns, Robert D.; Becker, William C.; Carroll, Constance M.; Driscoll, Mary A.; Fenton, Brenda T.; Fraenkel, Liana; Haskell, Sally G.; Heapy, Alicia A.; Hoff, Rani A.; Justice, Amy C.; Wandner, Laura; Womack, Julie A.; Brandt, Cynthia A.] VA Connecticut Healthcare Syst, Pain Res Informat Multimorbid & Educ Ctr PRIME, 950 Campbell Ave,35a, West Haven, CT 06516 USA.
[Bair, Matthew] Richard L Roudebush VAMC, VA Ctr Hlth Informat & Commun, Indianapolis, IN USA.
[Brennan, Penny] VA Palo Alto Hlth Care Syst, HSR&D Ctr Innovat Implementat, Palo Alto, CA USA.
[Burgess, Diana J.] Minneapolis Vet Affairs Healthcare Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA.
[Dobscha, Steven] VA Portland Hlth care Syst, Ctr Improve Veteran Involvement Care CIVIC, Portland, OR USA.
[Higgins, Diana M.] VA Boston Healthcare Syst, Anesthesiol Crit Care & Pain Med Service, Res Serv, Boston, MA USA.
[Hwang, Ula] James J Peters VAMC, Geriatr Res Educ & Clin Ctr, Bronx, NY USA.
[Piette, John D.] VA Ann Arbor Healthcare Syst, VA Ctr Clin Management Res, Ann Arbor, MI USA.
[Sinnott, Patsi] VA Palo Alto Hlth Care Syst, Hlth Econ Resource Ctr, Menlo Pk, CA USA.
RP Goulet, JL (reprint author), VA Connecticut Healthcare Syst, 950 Campbell Ave,35a, West Haven, CT 06516 USA.
EM joseph.goulet@va.gov
OI Goulet, Joseph/0000-0002-0842-804X
FU Veterans Health Administration Health Services Research Development
[CREATE 12-012, CIN 13-407]
FX This work was supported by the Veterans Health Administration Health
Services Research & Development grants CREATE 12-012 (Kerns, Goulet, and
Brandt Primary Investigators) and CIN 13-407 (Kerns Primary
Investigator).
NR 39
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 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD AUG
PY 2016
VL 157
IS 8
BP 1696
EP 1703
DI 10.1097/j.pain.0000000000000567
PG 8
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA DZ7AB
UT WOS:000386014000018
PM 27023420
ER
PT J
AU Beavers, WN
Skaar, EP
AF Beavers, William N.
Skaar, Eric P.
TI Neutrophil-generated oxidative stress and protein damage in
Staphylococcus aureus
SO PATHOGENS AND DISEASE
LA English
DT Review
DE Staphylococcus aureus; oxidative stress; neutrophils; protein oxidation;
antioxidant defenses; host-pathogen interface
ID NITRIC-OXIDE SYNTHASE; SMALL-COLONY VARIANTS; HYDROPEROXIDE REDUCTASE
AHPC; REPRESSES BIOFILM FORMATION; PEROXIDE-CHLORIDE SYSTEM;
HYPOCHLOROUS ACID; HYDROGEN-PEROXIDE; SUPEROXIDE-DISMUTASE; TYROSINE
NITRATION; BACILLUS-SUBTILIS
AB Staphylococcus aureus is a ubiquitous, versatile and dangerous pathogen. It colonizes over 30% of the human population, and is one of the leading causes of death by an infectious agent. During S. aureus colonization and invasion, leukocytes are recruited to the site of infection. To combat S. aureus, leukocytes generate an arsenal of reactive species including superoxide, hydrogen peroxide, nitric oxide and hypohalous acids that modify and inactivate cellular macromolecules, resulting in growth defects or death. When S. aureus colonization cannot be cleared by the immune system, antibiotic treatment is necessary and can be effective. Yet, this organism quickly gains resistance to each new antibiotic it encounters. Therefore, it is in the interest of human health to acquire a deeper understanding of how S. aureus evades killing by the immune system. Advances in this field will have implications for the design of future S. aureus treatments that complement and assist the host immune response. In that regard, this review focuses on how S. aureus avoids host-generated oxidative stress, and discusses the mechanisms used by S. aureus to survive oxidative damage including antioxidants, direct repair of damaged proteins, sensing oxidant stress and transcriptional changes. This review will elucidate areas for studies to identify and validate future antimicrobial targets.
C1 [Beavers, William N.; Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, US Dept Vet Affairs,Vanderbilt Inst Chem Biol,Med, 1161 21st Ave South, Nashville, TN 37232 USA.
[Skaar, Eric P.] Vanderbilt Univ, Sch Med, Tennessee Valley Healthcare Syst, US Dept Vet Affairs,Vanderbilt Inst Chem Biol, 1161 21st Ave S, Nashville, TN 37232 USA.
RP Skaar, EP (reprint author), Vanderbilt Univ, Dept Microbiol & Immunol, 1161 21st Ave South, Nashville, TN 37232 USA.
EM eric.skaar@vanderbilt.edu
FU National Institutes of Health [T32 AI007474 21, R01 AI069233, R01
AI73843]
FX The writing of this manuscript was supported by the National Institutes
of Health through fellowships to WNB (T32 AI007474 21) and research
grants to EPS (R01 AI069233 and R01 AI73843).
NR 153
TC 1
Z9 1
U1 5
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2049-632X
J9 PATHOG DIS
JI Pathog. Dis.
PD AUG
PY 2016
VL 74
IS 6
AR ftw060
DI 10.1093/femspd/ftw060
PG 15
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DY3UG
UT WOS:000385019700008
ER
PT J
AU Falvey, JR
Burke, RE
Malone, D
Ridgeway, KJ
McManus, BM
Stevens-Lapsley, JE
AF Falvey, Jason R.
Burke, Robert E.
Malone, Daniel
Ridgeway, Kyle J.
McManus, Beth M.
Stevens-Lapsley, Jennifer E.
TI Role of Physical Therapists in Reducing Hospital Readmissions:
Optimizing Outcomes for Older Adults During Care Transitions From
Hospital to Community
SO PHYSICAL THERAPY
LA English
DT Editorial Material
ID RANDOMIZED CONTROLLED-TRIAL; LOW-INCOME SENIORS; LENGTH-OF-STAY;
FUNCTIONAL STATUS; HEART-FAILURE; DISCHARGE SUMMARIES; 30-DAY
READMISSION; GAIT SPEED; HOME; RISK
AB Hospital readmissions in older adult populations are an emerging quality indicator for acute care hospitals. Recent evidence has linked functional decline during and after hospitalization with an elevated risk of hospital readmission. However, models of care that have been developed to reduce hospital readmission rates do not adequately address functional deficits. Physical therapists, as experts in optimizing physical function, have a strong opportunity to contribute meaningfully to care transition models and demonstrate the value of physical therapy interventions in reducing readmissions. Thus, the purposes of this perspective article are: (1) to describe the need for physical therapist input during care transitions for older adults and (2) to outline strategies for expanding physical therapy participation in care transitions for older adults, with an overall goal of reducing avoidable 30-day hospital readmissions.
C1 [Falvey, Jason R.; Malone, Daniel; Ridgeway, Kyle J.; Stevens-Lapsley, Jennifer E.] Univ Colorado Anschutz Med Campus, Dept Phys Med & Rehabil, Phys Therapy Program, Mail Stop C244,13121 East 17th Ave,Room 3116, Aurora, CO 80045 USA.
[Falvey, Jason R.] Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
[Burke, Robert E.] Univ Colorado Anschutz Med Campus, Res & Hosp Med Sect, Denver VA Med Ctr, Aurora, CO USA.
[Burke, Robert E.] Univ Colorado Anschutz Med Campus, Dept Med, Aurora, CO USA.
[Ridgeway, Kyle J.] Univ Colorado Hosp, Aurora, CO USA.
[McManus, Beth M.] Univ Colorado Anschutz Med Campus, Sch Publ Hlth, Dept Hlth Syst Management & Policy, Aurora, CO USA.
[Stevens-Lapsley, Jennifer E.] Vet Affairs Geriatr Res Educ & Clin Ctr, Denver, CO USA.
RP Falvey, JR (reprint author), Univ Colorado Anschutz Med Campus, Dept Phys Med & Rehabil, Phys Therapy Program, Mail Stop C244,13121 East 17th Ave,Room 3116, Aurora, CO 80045 USA.; Falvey, JR (reprint author), Denver Vet Affairs Med Ctr, Denver, CO 80220 USA.
EM Jason.Falvey@ucdenver.edu
FU NICHD NIH HHS [K12 HD055931]
NR 66
TC 1
Z9 1
U1 1
U2 1
PU AMER PHYSICAL THERAPY ASSOC
PI ALEXANDRIA
PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA
SN 0031-9023
EI 1538-6724
J9 PHYS THER
JI Phys. Ther.
PD AUG
PY 2016
VL 96
IS 8
BP 1124
EP 1133
DI 10.2522/ptj.20150526
PG 10
WC Orthopedics; Rehabilitation
SC Orthopedics; Rehabilitation
GA DZ9AQ
UT WOS:000386165800002
PM 26939601
ER
PT J
AU Ferrario, CM
Ahmad, S
Varagic, J
Cheng, CP
Groban, L
Wang, H
Collawn, JF
Dell'Italia, LJ
AF Ferrario, Carlos M.
Ahmad, Sarfaraz
Varagic, Jasmina
Cheng, Che Ping
Groban, Leanne
Wang, Hao
Collawn, James F.
Dell'Italia, Louis J.
TI Intracrine angiotensin II functions originate from noncanonical pathways
in the human heart
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Review
DE angiotensin-(1-12); angiotensin converting enzyme inhibitors; heart
chymase; hypertension; heart failure
ID MAST-CELL CHYMASE; MOLECULAR-WEIGHT ANGIOTENSINOGEN; CONVERTING
ENZYME-INHIBITION; AMINO-ACID-SEQUENCE; BLOOD-PRESSURE; CARDIOVASCULAR
EVENTS; INTRACELLULAR RENIN; RECEPTOR BLOCKERS; FORMING PATHWAYS;
CARDIAC RENIN
AB Although it is well-known that excess renin angiotensin system (RAS) activity contributes to the pathophysiology of cardiac and vascular disease, tissue-based expression of RAS genes has given rise to the possibility that intracellularly produced angiotensin II (Ang II) may be a critical contributor to disease processes. An extended form of angiotensin I (Ang I), the dodecapeptide angiotensin-(1-12) [Ang-(1-12)], that generates Ang II directly from chymase, particularly in the human heart, reinforces the possibility that an alternative noncanonical renin independent pathway for Ang II formation may be important in explaining the mechanisms by which the hormone contributes to adverse cardiac and vascular remodeling. This review summarizes the work that has been done in evaluating the functional significance of Ang-(1-12) and how this substrate generated from angiotensinogen by a yet to be identified enzyme enhances knowledge about Ang II pathological actions.
C1 [Ferrario, Carlos M.; Ahmad, Sarfaraz; Varagic, Jasmina] Wake Forest Univ, Hlth Sci Ctr, Dept Surg, Winston Salem, NC 27109 USA.
[Ferrario, Carlos M.; Ahmad, Sarfaraz; Varagic, Jasmina] Wake Forest Univ, Hlth Sci Ctr, Dept Internal Med Nephrol, Winston Salem, NC 27109 USA.
[Ferrario, Carlos M.; Ahmad, Sarfaraz; Varagic, Jasmina] Wake Forest Univ, Hlth Sci Ctr, Dept Physiol Pharmacol, Winston Salem, NC 27109 USA.
[Varagic, Jasmina; Groban, Leanne] Wake Forest Univ, Hypertens & Vasc Res Ctr, Winston Salem, NC 27109 USA.
[Cheng, Che Ping] Wake Forest Univ, Hlth Sci Ctr, Dept Internal Med, Sect Cardiovasc Med, Winston Salem, NC 27109 USA.
[Groban, Leanne; Wang, Hao] Wake Forest Univ, Hlth Sci Ctr, Dept Anesthesiol, Winston Salem, NC 27109 USA.
[Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Cell Biol, Birmingham, AL 35294 USA.
[Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA.
[Collawn, James F.; Dell'Italia, Louis J.] Univ Alabama Birmingham, Dept Physiol, Birmingham, AL 35294 USA.
[Dell'Italia, Louis J.] Univ Alabama Birmingham, Div Cardiovasc Dis, Birmingham, AL 35294 USA.
[Dell'Italia, Louis J.] Birmingham Vet Affairs Med Ctr, Dept Vet Affairs, Birmingham, AL USA.
RP Ferrario, CM (reprint author), Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27157 USA.
EM cferrari@wakehealth.edu
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [2P01 HL-051952]
FX The studies described here were funded, in part, by Program Project
Grant 2P01 HL-051952 from the National Heart, Lung, and Blood Institute
of the National Institutes of Health.
NR 160
TC 2
Z9 3
U1 0
U2 0
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 AUG
PY 2016
VL 311
IS 2
BP H404
EP H414
DI 10.1152/ajpheart.00219.2016
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA DY3DK
UT WOS:000384970800010
PM 27233763
ER
PT J
AU Adler, JT
Markmann, JF
Yeh, H
AF Adler, Joel T.
Markmann, James F.
Yeh, Heidi
TI Renal allograft thrombosis after living donor transplantation: risk
factors and obstacles to retransplantation
SO CLINICAL TRANSPLANTATION
LA English
DT Article
DE policy; renal transplantation; retransplantation; sensitization;
thrombosis
ID KIDNEY-TRANSPLANTATION; VASCULAR COMPLICATIONS; SINGLE-CENTER;
RECIPIENTS; SURVIVAL
AB Introduction: Early allograft thrombosis is a devastating complication that often leads to graft loss after living donor kidney transplantation. In addition to the psychological effects on donor and recipient, it could make future kidney matches challenging due to sensitization.
Patients and Methods: The Scientific Registry of Transplant Recipients (SRTR) was queried for adult patients undergoing living donor renal transplantation from 2001 to 2010. Sensitization was defined as a panel reactive antibody of >= 50%. Early allograft thrombosis included events within 30 d of transplantation.
Results: In multivariable logistic regression, recipient female gender (odds ratio [OR] 2.24, p < 0.001) and right kidneys (OR 1.46, p < 0.001) were associated with increased risk of thrombosis, while increasing recipient age per 10 yr (OR 0.62, p < 0.001) and recipient Asian race/ethnicity (OR 0.34, p = 0.02) were protective. In a time-varying Cox model examining factors affecting the likelihood of retransplantation, the chance of retransplantation was 37% lower (p = 0.01) once patients became sensitized. The median time to sensitization after transplantation was 288 d.
Conclusions: Even with relatively brief exposure to foreign antigen, sensitization occurs and delays retransplantation for recipients of living donor kidneys with early allograft thrombosis.
C1 [Adler, Joel T.; Markmann, James F.; Yeh, Heidi] Massachusetts Gen Hosp, Div Transplant Surg, Dept Surg, Boston, MA 02114 USA.
[Adler, Joel T.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA.
RP Yeh, H (reprint author), Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 516, Boston, MA 02114 USA.
EM hyeh@partners.org
OI Adler, Joel/0000-0001-8190-3444
FU Arthur Tracy Cabot fellowship from the Center for Surgery and Public
Health at Brigham and Women's Hospital
FX JTA is funded by the Arthur Tracy Cabot fellowship from the Center for
Surgery and Public Health at Brigham and Women's Hospital.
NR 19
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0902-0063
EI 1399-0012
J9 CLIN TRANSPLANT
JI Clin. Transplant.
PD AUG
PY 2016
VL 30
IS 8
BP 864
EP 871
DI 10.1111/ctr.12750
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DZ3OI
UT WOS:000385757400001
PM 27101358
ER
PT J
AU Myer, L
Phillips, TK
Zerbe, A
Ronan, A
Hsiao, NY
Mellins, CA
Remien, RH
Le Roux, SM
Brittain, K
Ciaranello, A
Petro, G
McIntyre, JA
Abrams, EJ
AF Myer, Landon
Phillips, Tamsin K.
Zerbe, Allison
Ronan, Agnes
Hsiao, Nei-Yuan
Mellins, Claude A.
Remien, Robert H.
Le Roux, Stanzi M.
Brittain, Kirsty
Ciaranello, Andrea
Petro, Greg
McIntyre, James A.
Abrams, Elaine J.
TI Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health
(MCH): Rationale and Design of the MCH-ART Study
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; antiretroviral therapy; PMTCT; integration; adherence; retention
ID SUB-SAHARAN AFRICA; HIV TRANSMISSION; SOUTH-AFRICA; PREVENTION; WOMEN;
PREGNANCY; ADHERENCE; IMPLEMENTATION; SERVICES; REGIMENS
AB Background: Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women.
Methods: We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants.
Results: MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention.
Discussion: Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH.
C1 [Myer, Landon; Phillips, Tamsin K.; Le Roux, Stanzi M.; Brittain, Kirsty; McIntyre, James A.] Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, Anzio Rd, ZA-7925 Cape Town, South Africa.
[Myer, Landon; Phillips, Tamsin K.; Ronan, Agnes; Brittain, Kirsty] Univ Cape Town, Sch Publ Hlth & Family Med, Ctr Infect Dis Epidemiol & Res, Cape Town, South Africa.
[Zerbe, Allison; Abrams, Elaine J.] Columbia Univ, Mailman Sch Publ Hlth, ICAP, New York, NY USA.
[Hsiao, Nei-Yuan] Univ Cape Town, Groote Schuur Hosp, Natl Hlth Lab Serv, Cape Town, South Africa.
[Hsiao, Nei-Yuan] Univ Cape Town, Div Med Virol, Cape Town, South Africa.
[Mellins, Claude A.; Remien, Robert H.] New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA.
[Mellins, Claude A.; Remien, Robert H.] Columbia Univ, New York, NY USA.
[Ciaranello, Andrea] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Petro, Greg] Univ Cape Town, New Somerset Hosp, Dept Obstet & Gynaecol, Cape Town, South Africa.
[McIntyre, James A.] Anova Hlth Inst, Johannesburg, South Africa.
[Abrams, Elaine J.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
RP Myer, L (reprint author), Univ Cape Town, Sch Publ Hlth & Family Med, Div Epidemiol & Biostat, Anzio Rd, ZA-7925 Cape Town, South Africa.
EM landon.myer@uct.ac.za
FU President's Emergency Plan for AIDS Relief through National Institute of
Child Health and Human Development [1R01HD074558]; Elizabeth Glaser
Pediatric AIDS Foundation; South African Medical Research Council;
Fogarty Foundation (NIH Fogarty International Center) [5R25TW009340];
Office of AIDS Research
FX Supported by the President's Emergency Plan for AIDS Relief through the
National Institute of Child Health and Human Development, Grant
1R01HD074558. Additional funding comes from the Elizabeth Glaser
Pediatric AIDS Foundation, the South African Medical Research Council,
the Fogarty Foundation (NIH Fogarty International Center Grant
#5R25TW009340), and the Office of AIDS Research.
NR 26
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 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD AUG 1
PY 2016
VL 72
SU 2
BP S189
EP S196
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA DY6YG
UT WOS:000385275100014
PM 27355508
ER
PT J
AU Takx, RAP
Ishai, A
Truong, QA
MacNabb, MH
Scherrer-Crosbie, M
Tawakol, A
AF Takx, Richard A. P.
Ishai, Amorina
Truong, Quynh A.
MacNabb, Meghan H.
Scherrer-Crosbie, Marielle
Tawakol, Ahmed
TI Supraclavicular Brown Adipose Tissue F-18-FDG Uptake and Cardiovascular
Disease
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE brown adipose tissue; positron-emission tomography; arterial FDG uptake;
cardiovascular disease
ID INSULIN-RESISTANCE; ADULT HUMANS; INFLAMMATION; RISK;
FLUORODEOXYGLUCOSE; EVENTS; FAT; ATHEROSCLEROSIS; TOMOGRAPHY; PET/CT
AB Preclinical data suggest a negative correlation between brown adipose tissue (BAT) and the degree of coronary atherosclerosis. We sought to evaluate the relationship between F-18-FDG uptake in supraclavicular BAT in relation to arterial inflammation and subsequent cardiovascular disease (CVD) events in humans. Methods: Individuals who underwent F-18-FDG PET/CT for clinical indications but who did not have either cancer or known atherosclerotic disease at the time of imaging were included. A radiologist masked to clinical data measured F-18-FDG uptake within BAT (in the supraclavicular region) as well as in subcutaneous adipose tissues. Tissue density was evaluated using CT (Hounsfield units). Arterial inflammation was assessed by measuring arterial F-18-FDG uptake and calculating target-to-background ratio. CVD events were independently adjudicated by masked cardiologists. Thereafter, the relationship between BAT activity and CVD events was evaluated. Results: A total of 443 patients (age, 55 y [44-66 y]; 44% men; body mass index [BMI], 26 [range, 23-31]) were included, and 30 patients experienced a cardiovascular event during a median follow-up of 4 y. BAT activity negatively correlated with arterial inflammation (r = -0.178, P < 0.01), a relationship that persisted after correcting for age and BMI (r = -0.147, P < 0.01). When either high sensitivity or high accuracy thresholds (from receiver-operating curve analyses) were used to define elevated BAT, high BAT was associated with a reduced risk of CVD events (P = 0.048), even after correcting for age (P = 0.037). Conclusion: Our results suggest that increased supraclavicular BAT activity is inversely associated with arterial inflammation, independently of age and BMI. Additionally, increased BAT may be associated with fewer cardiovascular events.
C1 [Takx, Richard A. P.; Ishai, Amorina; MacNabb, Meghan H.; Tawakol, Ahmed] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Takx, Richard A. P.; Ishai, Amorina; MacNabb, Meghan H.; Scherrer-Crosbie, Marielle; Tawakol, Ahmed] Harvard Med Sch, Boston, MA USA.
[Takx, Richard A. P.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[Truong, Quynh A.] Weill Cornell Coll Med, Dept Radiol, New York, NY USA.
[Scherrer-Crosbie, Marielle] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Tawakol, A (reprint author), Massachusetts Gen Hosp, 165 Cambridge St,Ste 400, Boston, MA 02114 USA.
EM atawakol@partners.org
NR 29
TC 2
Z9 2
U1 1
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD AUG 1
PY 2016
VL 57
IS 8
BP 1221
EP 1225
DI 10.2967/jnumed.115.166025
PG 5
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY6UJ
UT WOS:000385263600017
PM 26795284
ER
PT J
AU Sonis, ST
Mendes, RA
AF Sonis, Stephen T.
Mendes, Rui Amaral
TI Could the PI3K canonical pathway be a common link between chronic
inflammatory conditions and oral carcinogenesis?
SO JOURNAL OF ORAL PATHOLOGY & MEDICINE
LA English
DT Review
DE candidiasis; graft-vs.-host disease; inflammation; lichen planus; oral
carcinogenesis; PI3K signaling pathways
ID SQUAMOUS-CELL CARCINOMA; VERSUS-HOST-DISEASE; CANDIDA-ALBICANS; CANCER;
HEAD; TRANSPLANTATION; INTERLEUKIN-6; ACTIVATION; SURVIVAL; TARGETS
AB The association between chronic inflammatory disorders and oral carcinogenesis has been both a source of interest and contention. Based upon its central importance in oral carcinogenesis, the finding that the PI3k/Akt/mTOR pathway is activated in oral lichen planus, chronic graftversus-host disease, and chronic oral candidiasis suggests that it may provide a link between benign and malignant oral conditions. Here, we discuss a possible mechanistic rationale that addresses the activation of this important signaling pathway and its downstream events, while correlating it with the carcinogenic potential of chronic oral disorders.
C1 [Sonis, Stephen T.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Sonis, Stephen T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Sonis, Stephen T.] Biomodels LLC, Boston, MA USA.
[Mendes, Rui Amaral] Case Western Reserve Univ, Sch Dent Med, Dept Oral & Maxillofacial Med & Diagnost Sci, Oral & Maxillofacial Med, Cleveland, OH 44106 USA.
RP Sonis, ST (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM ssonis@partners.org
OI Amaral Mendes, Rui/0000-0001-7628-8598
NR 42
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0904-2512
EI 1600-0714
J9 J ORAL PATHOL MED
JI J. Oral Pathol. Med.
PD AUG
PY 2016
VL 45
IS 7
BP 469
EP 474
DI 10.1111/jop.12436
PG 6
WC Dentistry, Oral Surgery & Medicine; Pathology
SC Dentistry, Oral Surgery & Medicine; Pathology
GA DZ2ZL
UT WOS:000385711900001
PM 26991523
ER
PT J
AU Karp, JF
DiNapoli, EA
Wetherell, J
Bolon, C
Rodriguez, E
Shega, J
Weiner, DK
AF Karp, Jordan F.
DiNapoli, Elizabeth A.
Wetherell, Julie
Bolon, Chloe
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 IX: Anxiety
SO PAIN MEDICINE
LA English
DT Article
DE Anxiety; Low Back Pain; Chronic Pain; Avoidance Behavior; Cognitive
Behavior Therapy; Fear
ID COGNITIVE-BEHAVIORAL THERAPY; PRIMARY-CARE PATIENTS; CHRONIC
MUSCULOSKELETAL PAIN; LATE-LIFE ANXIETY; PSYCHIATRIC-DISORDERS;
MENTAL-DISORDERS; CONTROLLED-TRIAL; METAANALYSIS; PREVALENCE; DEPRESSION
AB Objective. As a part of a series of articles designed to deconstruct chronic low back pain (CLBP) in older adults, this article focuses on anxiety-a significant contributor of reduced health-related quality of life, increased use of medical services, and heightened disability in older adults with CLBP.
Methods. A modified Delphi technique was used to develop an algorithm for the screening and clinical care of older adults with CLBP and anxiety. A 4-member content expert panel and a nine-member primary care panel were involved in this iterative development process. Evidence underlying the recommendations is not strictly based on VA populations; therefore, the algorithm can be applied in both VHA and civilian settings. The illustrative clinical case was taken from one of the contributor's clinical practice.
Results. We present a treatment algorithm and supporting tables to be used by providers treating older adults who have anxiety and CLBP. A case of an older adult with anxiety and CLBP is provided to illustrate the approach to management.
Conclusions. To promote early engagement in evidence-based treatments, providers should routinely evaluate anxiety in older adults with CLBP using a screening and treatment algorithm.
C1 [Karp, Jordan F.; Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Karp, Jordan F.; DiNapoli, Elizabeth A.; Bolon, Chloe; Weiner, Debra K.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA.
[Karp, Jordan F.; Weiner, Debra K.] Univ Pittsburgh, Clin & Translat Sci Inst, Pittsburgh, PA USA.
[DiNapoli, Elizabeth A.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA.
[Wetherell, Julie] VA San Diego Healthcare Syst, San Diego, CA USA.
[Wetherell, Julie] Univ Calif San Diego, San Diego, CA 92103 USA.
[Rodriguez, Eric; Weiner, Debra K.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA.
[Shega, Joseph] VITAS Healthcare, Miami, FL USA.
RP Weiner, DK (reprint author), 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 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.
NR 57
TC 1
Z9 1
U1 9
U2 9
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 AUG
PY 2016
VL 17
IS 8
BP 1423
EP 1435
DI 10.1093/pm/pnw135
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA DZ1WQ
UT WOS:000385632800006
PM 27346887
ER
PT J
AU Park, EM
Deal, AM
Check, DK
Hanson, LC
Reeder-Hayes, KE
Mayer, DK
Yopp, JM
Song, MK
Muriel, AC
Rosenstein, DL
AF Park, Eliza M.
Deal, Allison M.
Check, Devon K.
Hanson, Laura C.
Reeder-Hayes, Katherine E.
Mayer, Deborah K.
Yopp, Justin M.
Song, Mi-Kyung
Muriel, Anna C.
Rosenstein, Donald L.
TI Parenting concerns, quality of life, and psychological distress in
patients with advanced cancer
SO PSYCHO-ONCOLOGY
LA English
DT Article
ID SOCIAL SUPPORT SURVEY; BREAST-CANCER; INCURABLE CANCER; CHILDREN;
EXPERIENCES; DEPRESSION; PROGRAM; QUESTIONNAIRE; INTERVENTION;
PREVALENCE
AB Objective: Parents with life-limiting illness anticipate the loss of their parental role and the long-term consequences of their illness on their children. The purpose of this study was to examine relationships between parenting concerns, quality of life (QOL), and symptoms of depression and anxiety in parents with advanced cancer who have dependent children.
Methods: Sixty-three parents diagnosed with a Stage IV solid malignancy completed the Hospital Anxiety Depression Scale (HADS), Parenting Concerns Questionnaire (PCQ), and Functional Assessment of Cancer Therapy General (FACT-C). The Medical Outcomes Study Social Support Survey (social support) and Eastern Cooperative Oncology Group (ECOG) performance status were assessed as potential covariates. We performed descriptive statistics and multivariable linear regression models for depression, anxiety, and QOL measures.
Results: Mean PCQ score was 2.3 (SD 0.9), reflecting mild to moderate parenting concerns. Average depression and anxiety scores were 6.0 (SD 4.2) and 8.2 (SD 3.9), respectively. PCQ scores were associated with depressive symptoms (r = 0.46, p < 0.001), anxiety symptoms (r =0.52, p < 0.0001), and QOL scores (r= 0.60, p <0.001). The relationship of PCQ scores to anxiety symptoms (B=1.5 p = 0.016) and QOL (B= 5.7, p =0.02) remained significant after controlling for ECOG status, social support, and treatment status.
Conclusions: Parenting concerns are associated with anxiety and depressive symptoms and worse QOL in parents diagnosed with advanced cancer. Further studies that evaluate how parental status affects coping and psychological distress in advanced cancer are needed. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Park, Eliza M.; Yopp, Justin M.; Rosenstein, Donald L.] Univ N Carolina, Dept Psychiat, 170 Manning Dr,Campus Box 7305, Chapel Hill, NC 27599 USA.
[Deal, Allison M.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA.
[Check, Devon K.] Univ N Carolina, Dept Hlth Policy & Management, Chapel Hill, NC USA.
[Hanson, Laura C.] Univ N Carolina, Dept Med, Div Geriatr Med, Chapel Hill, NC USA.
[Hanson, Laura C.] Univ N Carolina, Dept Med, Palliat Care Program, Chapel Hill, NC USA.
[Reeder-Hayes, Katherine E.; Rosenstein, Donald L.] Univ N Carolina, Dept Med, Div Hematol & Oncol, Chapel Hill, NC USA.
[Mayer, Deborah K.; Song, Mi-Kyung] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA.
[Muriel, Anna C.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
RP Park, EM (reprint author), Univ N Carolina, Dept Psychiat, 170 Manning Dr,Campus Box 7305, Chapel Hill, NC 27599 USA.
EM leeza_park@med.unc.edu
FU North Carolina University Cancer Research Fund; National Center for
Advancing Translational Sciences (NCATS), National Institutes of Health
[1UL1TR001111]
FX The project described was supported by the North Carolina University
Cancer Research Fund and the National Center for Advancing Translational
Sciences (NCATS), National Institutes of Health, through Grant Award
Number 1UL1TR001111. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
NIH.
NR 26
TC 2
Z9 2
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD AUG
PY 2016
VL 25
IS 8
BP 942
EP 948
DI 10.1002/pon.3935
PG 7
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA DZ3CO
UT WOS:000385721800009
PM 26282575
ER
PT J
AU Ackman, JB
Gaissert, HA
Lanuti, M
Digumarthy, SR
Shepard, JAO
Halpern, EF
Wright, CD
AF Ackman, Jeanne B.
Gaissert, Henning A.
Lanuti, Michael
Digumarthy, Subba R.
Shepard, Jo-Anne O.
Halpern, Elkan F.
Wright, Cameron D.
TI Impact of Nonvascular Thoracic MR Imaging on the Clinical Decision
Making of Thoracic Surgeons: A 2-year Prospective Study
SO RADIOLOGY
LA English
DT Article
ID SOLITARY PULMONARY NODULES; SIGNAL INTENSITY; CYSTIC-FIBROSIS; POTENTIAL
ROLE; CT; DIAGNOSIS; DISEASE; MASSES; DIFFERENTIATION; MEDIASTINUM
AB Purpose: To determine the impact of nonvascular thoracic magnetic resonance (MR) imaging on the clinical decision making and diagnostic certainty of thoracic surgeons.
Materials and Methods: Seven thoracic surgeons at Massachusetts General Hospital, an academic quaternary referral hospital, participated in this 2-year, prospective, institution review board-approved, HIPAA-compliant pre-and post-MR imaging survey study after completing a one-time demographic survey. Between July 16, 2013, and July 13, 2015, each time a thoracic surgeon ordered a nonvascular thoracic MR imaging study via radiology order entry, he or she was sent a link to the pre-test survey that ascertained the clinical rationale for MR imaging, the clinical management plan if MR imaging was not an option, and pre-test diagnostic certainty. Upon completion of the MR imaging report, the surgeon was sent a link to the post-test survey assessing if/how MR imaging changed clinical management, the surgeon's comfort with the clinical management plan, and post-test diagnostic certainty. Data were analyzed with Student t, Wilcoxon, and McNemar tests.
Results: A total of 99 pre-and post-test surveys were completed. Most MR imaging studies (64 of 99 [65%]) were requested because of indeterminate computed tomographic findings. The use of MR imaging significantly reduced the number of planned surgical interventions (P < .001), modified the surgical approach in 54% (14 of 26) of surgical cases, and increased surgeon comfort with the patient management plan in 95% (94 of 99) of cases. Increased diagnostic certainty as a result of MR imaging was highly significant (P < .0001). In 21% (21 of 99) of cases, definitive MR imaging results warranted no further follow-up or clinical care.
Conclusion: In appropriate cases, assessment with nonvascular thoracic MR imaging substantially affects the clinical decision making and diagnostic certainty of thoracic surgeons.
C1 [Ackman, Jeanne B.; Digumarthy, Subba R.; Shepard, Jo-Anne O.] Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Dept Radiol, 55 Fruit St,Founders House 202, Boston, MA 02114 USA.
[Gaissert, Henning A.; Lanuti, Michael; Wright, Cameron D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Founders House 202, Boston, MA 02114 USA.
[Halpern, Elkan F.] Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, 55 Fruit St,Founders House 202, Boston, MA 02114 USA.
RP Ackman, JB (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Imaging & Intervent, Dept Radiol, 55 Fruit St,Founders House 202, Boston, MA 02114 USA.
EM jackman@mgh.harvard.edu
FU Cambridge Healthtech
FX J.B.A. disclosed no relevant relationships. H.A.G. disclosed no relevant
relationships. M.L. disclosed no relevant relationships. S.R.D.
disclosed no relevant relationships. J.A.O.S. Activities related to the
present article: disclosed no relevant relationships. Activities not
related to the present article: provided expert testimony for CRICO.
Other relationships: disclosed no relevant relationships. E.F.H.
Activities related to the present article: disclosed no relevant
relationships. Activities not related to the present article: consultant
for Hologic, Gamma Medica, and Real Imaging; payment for lectures from
Cambridge Healthtech; and travel/accommodation/meeting expenses from
RSNA. Other relationships: disclosed no relevant relationships. C.D.W.
disclosed no relevant relationships.
NR 36
TC 2
Z9 2
U1 1
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD AUG
PY 2016
VL 280
IS 2
BP 464
EP 474
DI 10.1148/radiol.2016152004
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY6UW
UT WOS:000385265200014
PM 26909650
ER
PT J
AU Ahmadi, E
Katnani, HA
Besheli, LD
Gu, Q
Atefi, R
Villeneuve, MY
Eskandar, E
Lev, MH
Golby, AJ
Gupta, R
Bonmassar, G
AF Ahmadi, Emad
Katnani, Husam A.
Besheli, Laleh Daftari
Gu, Qiang
Atefi, Reza
Villeneuve, Martin Y.
Eskandar, Emad
Lev, Michael H.
Golby, Alexandra J.
Gupta, Rajiv
Bonmassar, Giorgio
TI An Electrocorticography Grid with Conductive Nanoparticles in a Polymer
Thick Film on an Organic Substrate Improves CT and MR Imaging
SO RADIOLOGY
LA English
DT Article
ID EPILEPSY; ARRAYS; STATE
AB Purpose: To develop an electrocorticography (ECoG) grid by using deposition of conductive nanoparticles in a polymer thick film on an organic substrate (PTFOS) that induces minimal, if any, artifacts on computed tomographic (CT) and magnetic resonance (MR) images and is safe in terms of tissue reactivity and MR heating.
Materials and Methods: All procedures were approved by the Animal Care and Use Committee and complied with the Public Health Services Guide for the Care and Use of Animals. Electrical functioning of PTFOS for cortical recording and stimulation was tested in two mice. PTFOS disks were implanted in two mice; after 30 days, the tissues surrounding the implants were harvested, and tissue injury was studied by using immunostaining. Five neurosurgeons rated mechanical properties of PTFOS compared with conventional grids by using a three-level Likert scale. Temperature increases during 30 minutes of 3-T MR imaging were measured in a head phantom with no grid, a conventional grid, and a PTFOS grid. Two neuroradiologists rated artifacts on CT and MR images of a cadaveric head specimen with no grid, a conventional grid, and a PTFOS grid by using a four-level Likert scale, and the mean ratings were compared between grids.
Results: Oscillatory local field potentials were captured with cortical recordings. Cortical stimulations in motor cortex elicited muscle contractions. PTFOS implants caused no adverse tissue reaction. Mechanical properties were rated superior to conventional grids (x(2) test, P<.05). The temperature increase during MR imaging for the three cases of no grid, PTFOS grid, and conventional grid was 3.84 degrees C, 4.05 degrees C, and 10.13 degrees C, respectively. PTFOS induced no appreciable artifacts on CT and MR images, and PTFOS image quality was rated significantly higher than that with conventional grids (two-tailed t test, P<.05).
Conclusion: PTFOS grids may be an attractive alternative to conventional ECoG grids with regard to mechanical properties, 3-T MR heating profile, and CT and MR imaging artifacts. (C) RSNA, 2016
C1 [Ahmadi, Emad; Atefi, Reza; Villeneuve, Martin Y.; Bonmassar, Giorgio] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 75 Third Ave,Room 1-402, Charlestown, MA 02129 USA.
[Ahmadi, Emad; Besheli, Laleh Daftari; Lev, Michael H.; Gupta, Rajiv] Harvard Med Sch, Massachusetts Gen Hosp, Adv X Ray Imaging Sci Ctr, Dept Radiol, Boston, MA USA.
[Katnani, Husam A.; Eskandar, Emad] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA.
[Gu, Qiang] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA.
[Golby, Alexandra J.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA.
RP Bonmassar, G (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 75 Third Ave,Room 1-402, Charlestown, MA 02129 USA.
EM giorgio@nmr.mgh.harvard.edu
FU National Institutes of Health [5R43NS071988-02, U01-NS075026,
1R21EB016449-01A1]; National Center for Research Resources
[P41-RR14075]; National Center for Image Guided Therapy [P41EB015898];
MIND Institute
FX Supported by the National Center for Research Resources (grant
P41-RR14075), National Center for Image Guided Therapy (grant
P41EB015898), and the MIND Institute.; This research was supported by
the National Institutes of Health (grants 5R43NS071988-02, U01-NS075026,
and 1R21EB016449-01A1)
NR 20
TC 0
Z9 0
U1 2
U2 2
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD AUG
PY 2016
VL 280
IS 2
BP 595
EP 601
DI 10.1148/radiol.2016142529
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY6UW
UT WOS:000385265200028
PM 26844363
ER
PT J
AU Karras, E
Lu, NJ
Zuo, GX
Tu, XM
Stephens, B
Draper, J
Thompson, C
Bossarte, RM
AF Karras, Elizabeth
Lu, Naiji
Zuo, Guoxin
Tu, Xin M.
Stephens, Brady
Draper, John
Thompson, Caitlin
Bossarte, Robert M.
TI Measuring Associations of the Department of Veterans Affairs' Suicide
Prevention Campaign on the Use of Crisis Support Services
SO SUICIDE AND LIFE-THREATENING BEHAVIOR
LA English
DT Article
ID MASS-MEDIA CAMPAIGNS; HEALTH BEHAVIOR; CALLS
AB Campaigns have become popular in public health approaches to suicide prevention; however, limited empirical investigation of their impact on behavior has been conducted. To address this gap, utilization patterns of crisis support services associated with the Department of Veterans Affairs' Veterans Crisis Line (VCL) suicide prevention campaign were examined. Daily call data for the National Suicide Prevention Lifeline, VCL, and 1-800-SUICIDE were modeled using a novel semi-varying coefficient method. Analyses reveal significant increases in call volume to both targeted and broad resources during the campaign. Findings underscore the need for further research to refine measurement of the effects of these suicide prevention efforts.
C1 [Karras, Elizabeth; Tu, Xin M.; Stephens, Brady] US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA.
[Karras, Elizabeth; Tu, Xin M.] Univ Rochester, Dept Psychiat, Rochester, NY USA.
[Lu, Naiji; Tu, Xin M.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA.
[Zuo, Guoxin] Cent China Normal Univ, Sch Math & Stat, Wuhan, Peoples R China.
[Draper, John] Link2Hlth Solut Inc, Natl Suicide Prevent Lifeline, New York, NY USA.
[Thompson, Caitlin] US Dept Vet Affairs, Mental Hlth Serv, Suicide Prevent & Community Engagement Program, Washington, DC USA.
[Bossarte, Robert M.] US Dept Vet Affairs, Program Epidemiol, Postdeployment Hlth Off Publ Hlth, Washington, DC USA.
[Bossarte, Robert M.] Harvard Univ, Dept Epidemiol, Cambridge, MA 02138 USA.
RP Karras, E (reprint author), US Dept Vet Affairs, VISN Ctr Excellence Suicide Prevent 2, 400 Ft Hill Ave, Canandaigua, NY 14424 USA.
EM Elizabeth.Karras@va.gov
NR 22
TC 1
Z9 1
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0363-0234
EI 1943-278X
J9 SUICIDE LIFE-THREAT
JI Suicide Life-Threat. Behav.
PD AUG
PY 2016
VL 46
IS 4
BP 447
EP 456
DI 10.1111/sltb.12231
PG 10
WC Psychiatry; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA DZ2XM
UT WOS:000385706100005
PM 26880716
ER
PT J
AU Virani, SS
AF Virani, Salim S.
TI The 2013 ACC/AHA Cholesterol Management Guideline: Clearing the
Confusion from Noncontroversial Components
SO TEXAS HEART INSTITUTE JOURNAL
LA English
DT Editorial Material
DE Cholesterol LDL/blood; coronary artery disease/prevention & control;
guideline implementation; hypercholesterolemia/drug therapy; provider
behavior; risk assessment; societies, medical; statins
C1 [Virani, Salim S.] Hlth Serv Res & Dev Ctr Innovat, Michael E DeBakey Vet Affairs Med Ctr, Hlth Policy Qual & Informat Program, Houston, TX 77030 USA.
[Virani, Salim S.] Baylor Coll Med, Dept Med, Sect Cardiovasc Res, Houston, TX 77030 USA.
[Virani, Salim S.] Methodist DeBakey Heart & Vasc Ctr, Ctr Cardiovasc Dis Prevent, 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
NR 6
TC 0
Z9 0
U1 0
U2 0
PU TEXAS HEART INST
PI HOUSTON
PA PO BOX 20345, HOUSTON, TX 77225-0345 USA
SN 1526-6702
J9 TEX HEART I J
JI Tex. Heart Inst. J.
PD AUG
PY 2016
VL 43
IS 4
BP 313
EP 314
DI 10.14503/THIJ-16-5798
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DZ5RH
UT WOS:000385918700010
PM 27547139
ER
PT J
AU Kasinath, BS
AF Kasinath, Balakuntalam S.
TI The podocyte and the proteoglycan
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Editorial Material
ID GLOMERULAR-BASEMENT-MEMBRANE; HEPARAN-SULFATE; PROTEINURIA
C1 [Kasinath, Balakuntalam S.] Univ Texas San Antonio, Hlth Sci Ctr, South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Kasinath, BS (reprint author), Univ Texas San Antonio, Hlth Sci Ctr, Dept Med, MC7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM kasinath@uthscsa.edu
NR 9
TC 0
Z9 0
U1 0
U2 0
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD AUG 1
PY 2016
VL 311
IS 2
BP F310
EP F311
DI 10.1152/ajprenal.00295.2016
PG 2
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA DY3FP
UT WOS:000384976500008
PM 27226109
ER
PT J
AU Uchendu, US
Omalu, BI
Cifu, DX
Egede, LE
AF Uchendu, Uchenna S.
Omalu, Bennet I.
Cifu, David X.
Egede, Leonard E.
TI Repeated Concussions: Time to Spur Action Among Vulnerable Veterans
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID TRAUMATIC BRAIN-INJURY; ENCEPHALOPATHY
C1 [Uchendu, Uchenna S.] US Dept Vet Affairs, Washington, DC USA.
[Omalu, Bennet I.] Univ Calif Davis, Dept Pathol, Davis, CA 95616 USA.
[Cifu, David X.] Virginia Commonwealth Univ, Sch Med, Richmond, VA 23284 USA.
[Cifu, David X.] US Dept Vet Affairs, Richmond, VA USA.
[Egede, Leonard E.] Med Univ South Carolina, Charleston, SC USA.
[Egede, Leonard E.] US Dept Vet Affairs, Charleston, SC USA.
RP Uchendu, US (reprint author), US Dept Vet Affairs, Off Hlth Equ, 810 Vermont Ave NW, Washington, DC 20420 USA.
EM Uchenna.Uchendu2@va.gov
NR 7
TC 0
Z9 0
U1 2
U2 2
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD AUG
PY 2016
VL 106
IS 8
BP 1366
EP 1368
DI 10.2105/AJPH.2016.303293
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DY3HK
UT WOS:000384981200024
PM 27310350
ER
PT J
AU Diaz-Gil, D
Haerter, F
Falcinelli, S
Ganapati, S
Hettiarachchi, GK
Simons, JCP
Zhang, B
Grabitz, SD
Duarte, IM
Cotten, JF
Eikermann-Haerter, K
Deng, H
Chamberlin, NL
Isaacs, L
Briken, V
Eikermann, M
AF Diaz-Gil, Daniel
Haerter, Friederike
Falcinelli, Shane
Ganapati, Shweta
Hettiarachchi, Gaya K.
Simons, Jeroen C. P.
Zhang, Ben
Grabitz, Stephanie D.
Duarte, Ingrid Moreno
Cotten, Joseph F.
Eikermann-Haerter, Katharina
Deng, Hao
Chamberlin, Nancy L.
Isaacs, Lyle
Briken, Volker
Eikermann, Matthias
TI A Novel Strategy to Reverse General Anesthesia by Scavenging with the
Acyclic Cucurbit[n]uril-type Molecular Container Calabadion 2
SO ANESTHESIOLOGY
LA English
DT Article
ID NEUROMUSCULAR-BLOCKING-AGENTS; BURST SUPPRESSION; BRAIN-INJURY;
KETAMINE; ETOMIDATE; RATS; EMERGENCE; PROPOFOL; MODEL; SLEEP
AB Background: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery.
Methods: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity.
Results: Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium-based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-a-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16: 1 (95% CI, 10 to 26: 1) for the reversal of ketamine and 3: 1 (95% CI, 2 to 5: 1) for the reversal of etomidate.
Conclusions: Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.
C1 [Diaz-Gil, Daniel; Haerter, Friederike; Simons, Jeroen C. P.; Grabitz, Stephanie D.; Duarte, Ingrid Moreno; Cotten, Joseph F.; Eikermann, Matthias] Harvard Med Sch, Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Eikermann-Haerter, Katharina] Harvard Med Sch, Massachusetts Gen Hosp, Radiol, Boston, MA USA.
[Deng, Hao] Harvard Med Sch, Massachusetts Gen Hosp, Biostat, Boston, MA USA.
[Falcinelli, Shane; Hettiarachchi, Gaya K.; Briken, Volker] Univ Maryland, Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Zhang, Ben; Grabitz, Stephanie D.; Isaacs, Lyle] Univ Maryland, Chem & Biochem, College Pk, MD 20742 USA.
[Chamberlin, Nancy L.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Neurol, Boston, MA USA.
[Eikermann, Matthias] Univ Duisburg Essen, Univ Hosp Essen, Anesthesia & Crit Care Med, Essen, Germany.
RP Eikermann, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM meikermann@partners.org
RI Isaacs, Lyle/B-4472-2009;
OI Isaacs, Lyle/0000-0002-4079-332X; Briken, Volker/0000-0001-5830-6107
FU Department of Anesthesia, Critical Care and Pain Medicine at
Massachusetts General Hospital, Boston, Massachusetts; State of Maryland
Technology Development Corporation (TEDCO), Columbia, Maryland; National
Institutes of Health, Bethesda, Maryland [R01 HL117871, R01 CA168365];
Howard Hughes Medical Institute (Chevy Chase, Maryland)
FX Supported by the Department of Anesthesia, Critical Care and Pain
Medicine at Massachusetts General Hospital, Boston, Massachusetts; the
State of Maryland Technology Development Corporation (TEDCO), Columbia,
Maryland; the National Institutes of Health, Bethesda, Maryland (R01
HL117871 and R01 CA168365); and a grant to the University of Maryland
from the Howard Hughes Medical Institute (Chevy Chase, Maryland)
Undergraduate Science Education Program.
NR 46
TC 1
Z9 1
U1 3
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 AUG
PY 2016
VL 125
IS 2
BP 333
EP 345
DI 10.1097/ALN.0000000000001199
PG 13
WC Anesthesiology
SC Anesthesiology
GA DY3VC
UT WOS:000385022200013
PM 27341276
ER
PT J
AU Nanji, KC
Bates, DW
AF Nanji, Karen C.
Bates, David W.
TI Counting Errors: Medication or Medical? Reply
SO ANESTHESIOLOGY
LA English
DT Letter
ID ADVERSE DRUG EVENTS; HEALTH-CARE PERSONNEL; INTENSIVE-CARE;
HOSPITALIZED-PATIENTS; ADMINISTRATION ERROR; AMBULATORY-CARE;
ANESTHESIA; FACILITIES; DIVERSION; FREQUENCY
C1 [Nanji, Karen C.; Bates, David W.] Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
RP Nanji, KC (reprint author), Massachusetts Gen Hosp, Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
EM knanji@partners.org
FU NIGMS NIH HHS [T32 GM007592]
NR 44
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 AUG
PY 2016
VL 125
IS 2
BP 432
EP 437
DI 10.1097/ALN.0000000000001188
PG 7
WC Anesthesiology
SC Anesthesiology
GA DY3VC
UT WOS:000385022200041
PM 27433765
ER
PT J
AU Ladha, KS
Bateman, BT
AF Ladha, Karim S.
Bateman, Brian T.
TI Epidurals and Chronic Postsurgical Pain: Is It Lack of Evidence or Poor
Design? Reply
SO ANESTHESIOLOGY
LA English
DT Letter
C1 [Ladha, Karim S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Toronto Gen Hosp, Toronto, ON, Canada.
Univ Toronto, Toronto, ON, Canada.
RP Ladha, KS (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
EM karim.ladha@post.harvard.edu
FU NICHD NIH HHS [K08 HD075831]
NR 2
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 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD AUG
PY 2016
VL 125
IS 2
BP 440
EP 441
DI 10.1097/ALN.0000000000001192
PG 3
WC Anesthesiology
SC Anesthesiology
GA DY3VC
UT WOS:000385022200045
PM 27433769
ER
PT J
AU Kopterides, P
Mayr, FB
Yende, S
AF Kopterides, Petros
Mayr, Florian B.
Yende, Sachin
TI Understanding the sepsis mortality belt: time to buckle down!
SO ANNALS OF TRANSLATIONAL MEDICINE
LA English
DT Editorial Material
ID UNITED-STATES
C1 [Kopterides, Petros; Mayr, Florian B.; Yende, Sachin] Univ Pittsburgh, Dept Crit Care Med, CRISMA Ctr, Pittsburgh, PA USA.
[Mayr, Florian B.; Yende, Sachin] Vet Affairs Pittsburgh Healthcare Syst, Univ Dr Campus,Room 2A128, Pittsburgh, PA 15240 USA.
RP Mayr, FB (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr Campus,Room 2A128, Pittsburgh, PA 15240 USA.
EM florian.mayr@va.gov
NR 10
TC 0
Z9 0
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 2305-5839
EI 2305-5847
J9 ANN TRANSL MED
JI ANN. TRANSL. MED.
PD AUG
PY 2016
VL 4
IS 16
AR 319
DI 10.21037/atm.2016.08.01
PG 2
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DY0NM
UT WOS:000384793500021
PM 27668239
ER
PT J
AU Mc Causland, FR
Asafu-Adjei, J
Betensky, RA
Palevsky, PM
Waikar, SS
AF Mc Causland, Finnian R.
Asafu-Adjei, Josephine
Betensky, Rebecca A.
Palevsky, Paul M.
Waikar, Sushrut S.
TI Comparison of Urine Output among Patients Treated with More Intensive
Versus Less Intensive RRT: Results from the Acute Renal Failure Trial
Network Study
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID ACUTE KIDNEY INJURY; CRITICALLY-ILL PATIENTS; CONTINUOUS VENOVENOUS
HEMOFILTRATION; REPLACEMENT THERAPY; HEMODIALYSIS; RECOVERY; SURVIVAL;
MULTICENTER; PROGNOSIS; OUTCOMES
AB Background and objectives Intensive RRT may have adverse effects that account for the absence of benefit observed in randomized trials of more intensive versus less intensive RRT. We wished to determine the association of more intensive RRT with changes in urine output as a marker of worsening residual renal function in critically ill patients with severe AKI.
Design, setting, participants, & measurements The Acute Renal Failure Trial Network Study (n=1124) was a multicenter trial that randomized critically ill patients requiring initiation of RRT to more intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 ml/kg per hour) versus less intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 ml/kg per hour) RRT. Mixed linear regression models were fit to estimate the association of RRT intensity with change in daily urine output in survivors through day 7 (n=871); Cox regression models were fit to determine the association of RRT intensity with time to >= 50% decline in urine output in all patients through day 28.
Results Mean age of participants was 60 +/- 15 years old, 72% were men, and 30% were diabetic. In unadjusted models, among patients who survived >= 7 days, mean urine output was, on average, 31.7 ml/d higher (95% confidence interval, 8.2 to 55.2 ml/d) for the less intensive group compared with the more intensive group (P=0.01). More intensive RRT was associated with 29% greater unadjusted risk of decline in urine output of >= 50% (hazard ratio, 1.29; 95% confidence interval, 1.10 to 1.51).
Conclusions More intensive versus less intensive RRT is associated with a greater reduction in urine output during the first 7 days of therapy and a greater risk of developing a decline in urine output of >= 50% in critically ill patients with severe AKI.
C1 [Mc Causland, Finnian R.; Waikar, Sushrut S.] Brigham & Womens Hosp, Dept Med, Div Renal, Boston, MA 02115 USA.
[Mc Causland, Finnian R.; Waikar, Sushrut S.] Harvard Med Sch, Boston, MA USA.
[Asafu-Adjei, Josephine] Univ North Carolina Chapel Hill, Sch Nursing, Dept Biostat, Chapel Hill, NC USA.
[Betensky, Rebecca A.] Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Palevsky, Paul M.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA.
[Palevsky, Paul M.] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA.
RP Mc Causland, FR (reprint author), Brigham & Womens Hosp, MRB 4, Boston, MA 02446 USA.
EM fmccausland@partners.org
FU American Heart Association; NIDDK [DK102511, DK093574, DK075941,
U01DK085660, R01DK103784]; Cooperative Studies Program of the Department
of Veterans Affairs (VA) Office of Research and Development; NIDDK
FX F.R.M. was supported by an American Heart Association award from 2014 to
2015 and is currently supported by NIDDK grant DK102511. S.S.W. is
supported by NIDDK grants DK093574, DK075941, U01DK085660, and
R01DK103784. The ATN Study was performed by the ATN Study investigators
and supported by the Cooperative Studies Program of the Department of
Veterans Affairs (VA) Office of Research and Development and the NIDDK.
NR 36
TC 2
Z9 2
U1 1
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD AUG
PY 2016
VL 11
IS 8
BP 1335
EP 1342
DI 10.2215/CJN.10991015
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA DY1BP
UT WOS:000384830200006
PM 27449661
ER
PT J
AU Afkarian, M
Katz, R
Bansal, N
Correa, A
Kestenbaum, B
Himmelfarb, J
de Boer, IH
Young, B
AF Afkarian, Maryam
Katz, Ronit
Bansal, Nisha
Correa, Adolfo
Kestenbaum, Bryan
Himmelfarb, Jonathan
de Boer, Ian H.
Young, Bessie
TI Diabetes, Kidney Disease, and Cardiovascular Outcomes in the Jackson
Heart Study
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; ALL-CAUSE MORTALITY; UNITED-STATES;
COLLABORATIVE METAANALYSIS; ATHEROSCLEROSIS RISK; GENERAL-POPULATION;
ETHNIC DISPARITIES; ALBUMINURIA; COMPLICATIONS; EPIDEMIOLOGY
AB Background and objectives Blacks have high rates of cardiovascular disease and mortality. Diabetes and CKD, risk factors for cardiovascular mortality in the general population, are common among blacks. We sought to assess their contribution to cardiovascular disease and mortality in blacks.
Design, setting, participants, & measurements This observational cohort study was of 3211 participants in the Jackson Heart Study (enrolled 2000-2004). Rates of incident stroke, incident coronary heart disease, and cardiovascular mortality were quantified in participants with diabetes, CKD (eGFR < 60 ml/min per 1.73 m(2), urine albumin-to-creatinine ratio >= 30 mg/g, or both), or both through 2012, with a median follow-up of 6.99 years.
Results Four hundred fifty-six (14.2%) participants had only diabetes, 257 (8.0%) had only CKD, 201 (6.3%) had both, and 2297 (71.5%) had neither. Diabetes without CKD was associated with excess risks of incident stroke, incident coronary heart disease, and cardiovascular mortality after adjustment for demographic and clinical covariates, including prevalent cardiovascular disease (excess incidence rates, 2.6; 95% confidence interval, 0.5 to 4.7; 2.6; 95% confidence interval, 0.3 to 4.8; and 2.4; 95% confidence interval, 0.4 to 4.3 per 1000 person-years, respectively). CKD without diabetes was associated with comparable nonsignificant excess risks for incident stroke and coronary heart disease (2.5; 95% confidence interval, -0.1 to 5.2 and 2.4; 95% confidence interval, -0.8 to 5.5 per 1000 person-years, respectively) but a larger excess risk for cardiovascular mortality (7.3; 95% confidence interval, 3.0 to 11.5 per 1000 person-years). Diabetes and CKD together were associated with greater excess risks for incident stroke (13.8; 95% confidence interval, 5.3 to 22.3 per 1000 person-years), coronary heart disease (12.8; 95% confidence interval, 4.9 to 20.8 per 1000 person-years), and cardiovascular mortality (14.8; 95% confidence interval, 7.2 to 22.3 per 1000 person-years). The excess risks associated with the combination of diabetes and CKD were larger than those associated with established risk factors, including prevalent cardiovascular disease.
Conclusions The combination of diabetes and kidney disease is associated with substantial excess risks of cardiovascular events and mortality among blacks.
C1 [Afkarian, Maryam; Katz, Ronit; Bansal, Nisha; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA.
[Afkarian, Maryam; Katz, Ronit; Bansal, Nisha; Kestenbaum, Bryan; Himmelfarb, Jonathan] Univ Washington, Div Nephrol, Seattle, WA 98195 USA.
[Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Med, Jackson Heart Study, Jackson, MS 39216 USA.
[de Boer, Ian H.; Young, Bessie] Univ Washington, Kidney Res Inst, Div Nephrol, Vet Affairs Puget Sound, Seattle, WA 98195 USA.
RP Afkarian, M (reprint author), Box 359606,325 9th Ave, Seattle, WA 98104 USA.
EM afkarian@u.washington.edu
FU National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK)
[K23DK089017, R01DK104706]; Satellite Healthcare; National Institutes of
Health NIDDK [1R01DK102134-01]; NIDDK [R01DK087726, R01DK088762];
Veterans Affairs Puget Sound Health Care System (Seattle, WA); National
Heart, Lung, and Blood Institute [HHSN268201300046C, HHSN268201300047C,
HHSN268201300048C, HHSN268201300049C, HHSN268201300050C]; National
Institute on Minority Health and Health Disparities
FX M.A. was supported by grants K23DK089017 and R01DK104706 from the
National Institute of Diabetes, Digestive, and Kidney Disease (NIDDK)
and a Norman S. Coplon Extramural Grant from Satellite Healthcare. R.K.,
I.H.d.B., and B.Y. were supported by National Institutes of Health NIDDK
grant 1R01DK102134-01. I.H.d.B. was supported by grants R01DK087726 and
R01DK088762 from the NIDDK. I.H.d.B. and B.Y. are also supported, in
part, by funding from the Veterans Affairs Puget Sound Health Care
System (Seattle, WA). The Jackson Heart Study is supported by contracts
HHSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, and HHSN268201300050C from the National Heart, Lung,
and Blood Institute and the National Institute on Minority Health and
Health Disparities.
NR 40
TC 3
Z9 3
U1 1
U2 1
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
EI 1555-905X
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD AUG
PY 2016
VL 11
IS 8
BP 1384
EP 1391
DI 10.2215/CJN.13111215
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA DY1BP
UT WOS:000384830200012
PM 27340284
ER
PT J
AU Mair, CA
Quinones, AR
Pasha, MA
AF Mair, Christine A.
Quinones, Ana R.
Pasha, Maha A.
TI Care Preferences Among Middle-Aged and Older Adults With Chronic Disease
in Europe: Individual Health Care Needs and National Health Care
Infrastructure
SO GERONTOLOGIST
LA English
DT Article
DE Caregiving-informal; Caregiving-formal; Health care policy
ID LONG-TERM-CARE; PUBLIC-ATTITUDES; FAMILY CAREGIVERS; WELFARE-STATE;
NURSING-HOME; PERCEPTIONS; DEMENTIA; CONTEXTS; POLICIES; MODERATE
AB Purpose of the Study: The purpose of this study is to expand knowledge of care options for aging populations cross-nationally by examining key individual-level and nation-level predictors of European middle-aged and older adults' preferences for care.
Design and Methods: Drawing on data from the Survey of Health, Ageing and Retirement in Europe and the Organisation for Economic Co-operation and Development, we analyze old age care preferences of a sample of 6,469 adults aged 50 and older with chronic disease in 14 nations. Using multilevel modeling, we analyze associations between individual-level health care needs and nation-level health care infrastructure and preference for family-based (vs. state-based) personal care.
Results: We find that middle-aged and older adults with chronic disease whose health limits their ability to perform paid work, who did not receive personal care from informal sources, and who live in nations with generous long-term care funding are less likely to prefer family-based care and more likely to prefer state-based care.
Implications: We discuss these findings in light of financial risks in later life and the future role of specialized health support programs, such as long-term care.
C1 [Mair, Christine A.] Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
[Quinones, Ana R.; Pasha, Maha A.] Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland VA Med Ctr, Portland, OR 97201 USA.
RP Mair, CA (reprint author), Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, 1000 Hilltop Circle, Baltimore, MD 21250 USA.
EM christine_mair@umbc.edu
FU NHLBI NIH HHS [R25 HL105430]
NR 38
TC 1
Z9 1
U1 3
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0016-9013
EI 1758-5341
J9 GERONTOLOGIST
JI Gerontologist
PD AUG
PY 2016
VL 56
IS 4
BP 687
EP 701
DI 10.1093/geront/gnu119
PG 15
WC Gerontology
SC Geriatrics & Gerontology
GA DY0AU
UT WOS:000384760000012
PM 26035873
ER
PT J
AU Thompson, B
Molina, Y
Viswanath, K
Warnecke, R
Prelip, ML
AF Thompson, Beti
Molina, Yamile
Viswanath, Kasisomayajula
Warnecke, Richard
Prelip, Michael L.
TI Strategies To Empower Communities To Reduce Health Disparities
SO HEALTH AFFAIRS
LA English
DT Article
ID OF-THE-LITERATURE; PARTICIPATORY RESEARCH; PROMOTION
AB Community-based participatory research is a promising approach to reducing health disparities. It empowers individuals and communities to become the major players in solving their own health problems. We discuss the use of community-based participatory research and other strategies to enhance empowerment. We also discuss projects from the Centers for Population Health and Health Disparities that have empowered communities to achieve positive health outcomes aimed at reducing disparities. We offer recommendations to policy makers for involving residents in efforts to achieve health equity.
C1 [Thompson, Beti; Molina, Yamile] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
[Viswanath, Kasisomayajula] Dana Farber Canc Inst, Dept Med Oncol, Popular Sci, Boston, MA 02115 USA.
[Viswanath, Kasisomayajula] Harvard TH Chan Sch Publ Hlth, Human Dev & Hlth, Boston, MA USA.
[Warnecke, Richard] Univ Illinois, Ctr Hlth Policy, Chicago, IL USA.
[Prelip, Michael L.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Community Hlth Sci, Los Angeles, CA USA.
RP Thompson, B (reprint author), Fred Hutchinson Canc Res Ctr, Canc Prevent Program, 1124 Columbia St, Seattle, WA 98104 USA.
EM bthompso@fhcrc.org
FU NCI NIH HHS [U54 CA203000, P50 CA148143, U54 CA202995, R25 CA092408, U54
CA202997]
NR 30
TC 2
Z9 2
U1 1
U2 1
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD AUG
PY 2016
VL 35
IS 8
BP 1424
EP 1428
DI 10.1377/hlthaff.2015.1364
PG 5
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DY0QO
UT WOS:000384801500013
PM 27503967
ER
PT J
AU Kato, S
Lippman, SM
Flaherty, KT
Kurzrock, R
AF Kato, Shumei
Lippman, Scott M.
Flaherty, Keith T.
Kurzrock, Razelle
TI The Conundrum of Genetic "Drivers" in Benign Conditions
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Review
ID CELL LUNG-CANCER; TUMOR-SUPPRESSOR GENE; CONGENITAL MELANOCYTIC NEVI;
GROWTH-FACTOR RECEPTOR-3; INFLAMMATORY MYOFIBROBLASTIC TUMORS;
ONCOGENE-INDUCED SENESCENCE; INTEGRATED GENOMIC ANALYSIS; TYROSINE
KINASE INHIBITOR; DOSE-ESCALATION TRIAL; CARCINOMA IN-SITU
AB Advances in deep genomic sequencing have identified a spectrum of cancer-specific passenger and driver aberrations. Clones with driver anomalies are believed to be positively selected during carcinogenesis. Accumulating evidence, however, shows that genomic alterations, such as those in BRAF, RAS, EGFR, HER2, FGFR3, PIK3CA, TP53, CDKN2A, and NF1/2, all of which are considered hallmark drivers of specific cancers, can also be identified in benign and premalignant conditions, occasionally at frequencies higher than in their malignant counterparts. Targeting these genomic drivers can produce dramatic responses in advanced cancer, but the effects on their benign counterparts are less clear. This benign-malignant phenomenon is well illustrated in studies of BRAF V600E mutations, which are paradoxically more frequent in benign nevi (similar to 80%) than in dysplastic nevi (similar to 60%) or melanoma (similar to 40%-45%). Similarly, human epidermal growth factor receptor 2 is more commonly overexpressed in ductal carcinoma in situ (similar to 27%-56%) when compared with invasive breast cancer (similar to 11%-20%). FGFR3 mutations in bladder cancer also decrease with tumor grade (low-grade tumors, similar to 61%; high-grade, similar to 11%). "Driver" mutations also occur in nonmalignant settings: TP53 mutations in synovial tissue from rheumatoid arthritis and FGFR3 mutations in seborrheic keratosis. The latter observations suggest that the oncogenicity of these alterations may be tissue context-dependent. The conversion of benign conditions to premalignant disease may involve other genetic events and/or epigenetic reprogramming. Putative driver mutations can also be germline and associated with increased cancer risk (eg, germline RAS or TP53 alterations), but germline FGFR3 or NF2 abnormalities do not predispose to malignancy. We discuss the enigma of genetic "drivers" in benign and premalignant conditions and the implications for prevention strategies and theories of tumorigenesis.
C1 [Kato, Shumei] Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, 1400 Holcombe Blvd, Houston, TX 77030 USA.
[Lippman, Scott M.; Kurzrock, Razelle] Univ Calif San Diego, Moores Canc Ctr, Ctr Personalized Canc Therapy, La Jolla, CA USA.
[Lippman, Scott M.; Kurzrock, Razelle] Univ Calif San Diego, Moores Canc Ctr, Div Hematol & Oncol, La Jolla, CA USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Ctr Canc, Henri & Belinda Termeer Ctr Targeted Therapies, Boston, MA USA.
RP Kato, S (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Invest Canc Therapeut, 1400 Holcombe Blvd, Houston, TX 77030 USA.; Lippman, SM (reprint author), Univ Calif San Diego, Moores Canc Ctr, 3855 Hlth Sci Dr 0658, La Jolla, CA 92093 USA.
EM shumei.kato@gmail.com; slippman@ucsd.edu
FU Joan and Irwin Jacobs philanthropic fund; National Cancer Institute [P30
CA016672-36]
FX Funded in part by the Joan and Irwin Jacobs philanthropic fund (Razelle
Kurzrock) and National Cancer Institute grant P30 CA016672-36 (Scott M.
Lippman and Razelle Kurzrock).
NR 192
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD AUG
PY 2016
VL 108
IS 8
AR djw036
DI 10.1093/jnci/djw036
PG 13
WC Oncology
SC Oncology
GA DY3UD
UT WOS:000385019300011
ER
PT J
AU Post, RM
Kupka, R
Keck, PE
McElroy, SL
Altshuler, LL
Frye, MA
Rowe, M
Grunze, H
Suppes, T
Leverich, GS
Nolen, WA
AF Post, Robert M.
Kupka, Ralph
Keck, Paul E., Jr.
McElroy, Susan L.
Altshuler, Lori L.
Frye, Mark A.
Rowe, Michael
Grunze, Heinz
Suppes, Trisha
Leverich, Gabriele S.
Nolen, Willem A.
TI Further Evidence of a Cohort Effect in Bipolar Disorder: More Early
Onsets and Family History of Psychiatric Illness in More Recent Epochs
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
DE Bipolar Disorder
ID AGE-OF-ONSET; MENTAL-HEALTH-SURVEY; MOOD-DISORDERS; LIFETIME PREVALENCE;
UNITED-STATES; BIRTH-COHORT; AT-ONSET; PARENTS; RISK; METAANALYSIS
AB Objective: Given that a cohort effect is rarely mentioned as one of the possible contributors to the increased incidence of childhood-onset bipolar disorder in the United States, we reexamined evidence for the phenomenon within our outpatient Bipolar Collaborative Network.
Methods: 968 outpatients (mean age, 41 years) with DSM bipolar disorder from 1995 to 2002 from 4 sites in the United States and 3 in the Netherlands and Germany (abbreviated as Europe) gave informed consent and provided detailed demographic, illness, and family history information on a patient questionnaire. Family history of bipolar disorder, depression, suicide attempt, alcohol abuse, substance abuse, and "other" illness was collected for each parent and the 4 grandparents. Age at onset and family history of illness burden were then assessed as a function of the age of the patient at network entry.
Results: Data for patients aged 35 years or older (n = 613) were included in the first analysis. Compared to older patients, those who were younger when they entered the network had an earlier age at onset of their bipolar disorder (r = 0.33, P < .001). Similarly, the youngest patients at entry (representing the most recent cohorts) had parents and grandparents with more psychiatric illness than patients born in earlier cohorts (n = 968).
Conclusions: These preliminary data, taken with the substantial literature, suggest a cohort effect for earlier age at onset of bipolar disorder and greater burden of psychiatric disorders in 2 generations of direct progenitors of our patients. The resulting likely increase in severity of bipolar illness in future generations based on this earlier age at onset and increased familial loading, particularly in the United States, deserves focused clinical and public health attention and attempts at amelioration.
C1 [Post, Robert M.; Rowe, Michael; Leverich, Gabriele S.] Bipolar Collaborat Network, Bethesda, MD USA.
[Post, Robert M.] George Washington Univ, Dept Psychiat & Behav Sci, Washington, DC USA.
[Kupka, Ralph] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.
[Keck, Paul E., Jr.] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, Cincinnati, OH 45221 USA.
[Keck, Paul E., Jr.; McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA.
[McElroy, Susan L.] Univ Cincinnati, Biol Psychiat Program, Coll Med, Cincinnati, OH 45221 USA.
[Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Altshuler, Lori L.] VA Greater Los Angeles Healthcare Syst, Dept Psychiat, West Los Angeles Healthcare Ctr, Los Angeles, CA USA.
[Frye, Mark A.] Mayo Clin, Dept Psychiat & Psychol, Rochester, MN USA.
[Grunze, Heinz] Newcastle Univ, Inst Neurosci & Campus Aging & Vital, Wolfson Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England.
[Suppes, Trisha] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA.
[Suppes, Trisha] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Nolen, Willem A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
RP Post, RM (reprint author), 5415 W Cedar Ln,Ste 201-B, Bethesda, MD 20814 USA.
EM robert.post@speakeasy.net
OI Grunze, Heinz/0000-0003-4712-8979
FU Stanley Medical Research Institute
FX Support was provided by the Stanley Medical Research Institute from
1995-2002.
NR 47
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U1 5
U2 5
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 AUG
PY 2016
VL 77
IS 8
BP 1043
EP 1049
DI 10.4088/JCP.15m10121
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DY0OO
UT WOS:000384796300017
PM 27379705
ER
PT J
AU Yeung, A
Martinson, MA
Baer, L
Chen, J
Clain, A
Williams, A
Chang, TE
Trinh, NHT
Alpert, JE
Fava, M
AF Yeung, Albert
Martinson, Max A.
Baer, Lee
Chen, Justin
Clain, Alisabet
Williams, Aya
Chang, Trina E.
Trinh, Nhi-Ha T.
Alpert, Jonathan E.
Fava, Maurizio
TI The Effectiveness of Telepsychiatry-Based Culturally Sensitive
Collaborative Treatment for Depressed Chinese American Immigrants: A
Randomized Controlled Trial
SO JOURNAL OF CLINICAL PSYCHIATRY
LA English
DT Article
DE Cross-Cultural Psychiatry; Depression
ID OF-LIFE ENJOYMENT; PRIMARY-CARE; ASIAN-AMERICANS; RATING-SCALE;
SATISFACTION QUESTIONNAIRE; HEALTH; OUTCOMES; EPIDEMIOLOGY; RELIABILITY;
DISPARITIES
AB Objective: This study evaluates the effectiveness of a telepsychiatry-based culturally sensitive collaborative treatment (T-CSCT) intervention to improve treatment outcomes for depressed Chinese American immigrants.
Methods: Participants were Chinese Americans recruited from primary care settings from February 1, 2009, to July 31, 2012, with DSM-IV major depressive disorder (MDD) identified by the Mini-International Neuropsychiatric Interview. Eligible patients were randomized to receive either T-CSCT or treatment as usual (TAU) for 6 months. T-CSCT involves (1) cultural consultation via videoconference and (2) care management. The primary outcome measure was the 17-item Hamilton Depression Rating Scale (HDRS17); positive response was defined as a >= 50% decrease in HDRS17 score, and remission was defined as HDRS17 score <= 7. Secondary outcome measures were the Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Outcomes were compared using multivariate logistic regression and mixedmodel for repeated measures methods.
Results: Among participants (N = 190), 63% were female, and the mean (SD) age was 50 (14.5) years. They were randomized to T-CSCT (n = 97; 51%) or TAU (n = 93; 49%). Using multivariate logistic regression analyses, the odds of achieving response and remission were significantly greater for the T-CSCT group compared to the control group (odds ratio [OR] = 3.9 [95% CI, 1.9 to 7.8] and 4.4 [95% CI, 1.9 to 9.9], respectively). Multivariate general linear model analyses showed that patients in the T-CSCT group had significantly greater improvement over time in HDRS17 (F-4,F-95 = 4.59, P = .002), CGI-S (F4,95 = 4.22, P = .003), and CGI-I (F-4,F-95 = 2.95, P = .02) scores.
Conclusions: T-CSCT is effective in improving treatment outcomes of Chinese immigrants with MDD.
C1 [Yeung, Albert; Martinson, Max A.; Baer, Lee; Chen, Justin; Clain, Alisabet; Williams, Aya; Chang, Trina E.; Trinh, Nhi-Ha T.; Alpert, Jonathan E.; Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq, Boston, MA 02114 USA.
[Yeung, Albert] South Cove Community Hlth Ctr, Boston, MA USA.
RP Yeung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 1 Bowdoin Sq, Boston, MA 02114 USA.
EM ayeung@partners.org
FU National Institutes of Health (NIH) [R01 MH079831]; National Institutes
of Health (Bethesda, Maryland) [R01 MH079831]
FX The study was supported by the National Institutes of Health (NIH;
Bethesda, Maryland) grant R01 MH079831 and is registered on
ClinicalTrials.gov (NCT00854542).
NR 41
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U1 1
U2 1
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 AUG
PY 2016
VL 77
IS 8
BP E996
EP E1002
DI 10.4088/JCP.15m09952
PG 7
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DY0OO
UT WOS:000384796300006
PM 27561153
ER
PT J
AU Williams, WW
Delmonico, FL
AF Williams, Winfred W.
Delmonico, Francis L.
TI The End of Racial Disparities in Kidney Transplantation? Not So Fast!
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Editorial Material
ID DECEASED DONOR KIDNEYS; DISEASE; VARIANTS; ACCESS; APOL1
C1 [Williams, Winfred W.] Harvard Med Sch, Massachusetts Gen Hosp, Transplant Ctr, Div Nephrol, Boston, MA USA.
[Delmonico, Francis L.] Harvard Med Sch, Massachusetts Gen Hosp, Transplant Ctr, Dept Surg, Boston, MA USA.
RP Williams, WW (reprint author), Massachusetts Gen Hosp, Transplant Ctr, 165 Cambridge St,Suite 302, Boston, MA 02114 USA.; Williams, WW (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA.
EM wwwilliams@mgh.harvard.edu
NR 13
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U1 0
U2 0
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD AUG
PY 2016
VL 27
IS 8
BP 2224
EP 2226
DI 10.1681/ASN.2016010005
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA DY3PM
UT WOS:000385006100004
PM 26952001
ER
PT J
AU Lu, Y
Wei, J
Stec, DE
Roman, RJ
Ge, Y
Cheng, L
Liu, EY
Zhang, J
Hansen, PBL
Fan, F
Juncos, LA
Wang, L
Pollock, J
Huang, PL
Fu, YL
Wang, SH
Liu, RS
AF Lu, Yan
Wei, Jin
Stec, David E.
Roman, Richard J.
Ge, Ying
Cheng, Liang
Liu, Eddie Y.
Zhang, Jie
Hansen, Pernille B. Laerkegaard
Fan, Fan
Juncos, Luis A.
Wang, Lei
Pollock, Jennifer
Huang, Paul L.
Fu, Yiling
Wang, Shaohui
Liu, Ruisheng
TI Macula Densa Nitric Oxide Synthase 1 beta Protects against
Salt-Sensitive Hypertension
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID II-INDUCED HYPERTENSION; TUBULOGLOMERULAR FEEDBACK; BLOOD-PRESSURE;
RAT-KIDNEY; COLLECTING DUCT; DIETARY SALT; ANGIOTENSIN; ISOFORMS; CELLS;
HEART
AB Nitric oxide (NO) is an important negative modulator of tubuloglomerular feedback responsiveness. We recently found that macula densa expresses alpha-, beta-, and gamma-splice variants of neuronal nitric oxide synthase 1 (NOS1), and NOS1 beta expression in the macula densa increases on a high-salt diet. This study tested whether upregulation of NOS1 beta expression in the macula densa affects sodium excretion and salt-sensitive hypertension by decreasing tubuloglomerular feedback responsiveness. Expression levels of NOS1 beta mRNA and protein were 30- and five-fold higher, respectively, than those of NOS1 alpha in the renal cortex of C57BL/6 mice. Furthermore, macula densa NO production was similar in the isolated perfused juxtaglomerular apparatus of wild-type (WT) and nitric oxide synthase 1 alpha-knockout (NOS1 alpha KO) mice. Compared with control mice, mice with macula densa-specific knockout of all nitric oxide synthase 1 isoforms (MD-NOS1KO) had a significantly enhanced tubuloglomerular feedback response and after acute volume expansion, significantly reduced GFR, urine flow, and sodium excretion. Mean arterial pressure increased significantly in MD-NOS1KO mice (P < 0.01) but not NOS1flox/flox mice fed a high-salt diet. After infusion of angiotensin II, mean arterial pressure increased by 61.6 mmHg in MD-NOS1KO mice versus 32.0 mmHg in WT mice (P < 0.01) fed a high-salt diet. These results indicate that NOS1 beta is a primary NOS1 isoform expressed in the macula densa and regulates the tubuloglomerular feedback response, the natriuretic response to acute volume expansion, and the development of salt-sensitive hypertension. These findings show a novel mechanism for salt sensitivity of BP and the significance of tubuloglomerular feedback response in long-term control of sodium excretion and BP.
C1 [Lu, Yan; Wei, Jin; Zhang, Jie; Wang, Lei; Wang, Shaohui; Liu, Ruisheng] Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, 12901 Bruce B Downs Blvd,MDC 8, Tampa, FL 33612 USA.
[Lu, Yan; Stec, David E.; Cheng, Liang; Liu, Eddie Y.; Juncos, Luis A.; Fu, Yiling; Liu, Ruisheng] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Roman, Richard J.; Ge, Ying; Fan, Fan] Univ Mississippi, Med Ctr, Dept Pharmacol, Jackson, MS 39216 USA.
[Hansen, Pernille B. Laerkegaard] Univ Southern Denmark, Dept Cardiovasc & Renal Res, Odense, Denmark.
[Pollock, Jennifer] Univ Alabama Birmingham, Dept Med, Div Nephrol, Birmingham, AL 35294 USA.
[Huang, Paul L.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
RP Liu, RS (reprint author), Univ S Florida, Coll Med, Dept Mol Pharmacol & Physiol, 12901 Bruce B Downs Blvd,MDC 8, Tampa, FL 33612 USA.
EM ruisheng@health.usf.edu
FU National Institutes of Health [DK104184, DK099276, DK098582,
P01HL051971]
FX This work was supported by National Institutes of Health Grants DK104184
(to R.J.R.), DK099276 (to R.L.), DK098582 (to R.L.), and P01HL051971 (to
core facility).
NR 53
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U1 3
U2 4
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD AUG
PY 2016
VL 27
IS 8
BP 2346
EP 2356
DI 10.1681/ASN.2015050515
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA DY3PM
UT WOS:000385006100016
PM 26647426
ER
PT J
AU Naimark, DMJ
Grams, ME
Matsushita, K
Black, C
Drion, I
Fox, CS
Inker, LA
Ishani, A
Jee, SH
Kitamura, A
Lea, JP
Nally, J
Peralta, CA
Rothenbacher, D
Ryu, S
Tonelli, M
Yatsuya, H
Coresh, J
Gansevoort, RT
Warnock, DG
Woodward, M
de Jong, PE
AF Naimark, David M. J.
Grams, Morgan E.
Matsushita, Kunihiro
Black, Corri
Drion, Iefke
Fox, Caroline S.
Inker, Lesley A.
Ishani, Areef
Jee, Sun Ha
Kitamura, Akihiko
Lea, Janice P.
Nally, Joseph
Peralta, Carmen Alicia
Rothenbacher, Dietrich
Ryu, Seungho
Tonelli, Marcello
Yatsuya, Hiroshi
Coresh, Josef
Gansevoort, Ron T.
Warnock, David G.
Woodward, Mark
de Jong, Paul E.
CA CKD Prognosis Consortium
TI Past Decline Versus Current eGFR and Subsequent Mortality Risk
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE;
COLLABORATIVE METAANALYSIS; POPULATION COHORTS; HIGHER ALBUMINURIA;
ALL-CAUSE; CARDIOVASCULAR-DISEASE; DEATH; EQUATION
AB A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope, <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.
C1 [Naimark, David M. J.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Nephrol, Toronto, ON, Canada.
[Naimark, David M. J.] Univ Toronto, Fac Med, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada.
[Grams, Morgan E.; Matsushita, Kunihiro; Coresh, Josef; Woodward, Mark] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Grams, Morgan E.] Johns Hopkins Univ, Dept Med, Div Nephrol, Baltimore, MD USA.
[Black, Corri] Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland.
[Drion, Iefke] Isala Clin, Ctr Diabet, Zwolle, Netherlands.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Ctr Populat Studies, Framingham, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA.
[Fox, Caroline S.] Harvard Med Sch, Boston, MA USA.
[Inker, Lesley A.] Tufts Med Ctr, Div Nephrol, Boston, MA USA.
[Ishani, Areef] Minneapolis Vet Affairs Hlth Care Syst, Nephrol Sect, Minneapolis, MN USA.
[Jee, Sun Ha] Yonsei Univ, Inst Hlth Promot, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul, South Korea.
[Kitamura, Akihiko] Osaka Ctr Canc & Cardiovasc Dis Prevent, Osaka, Japan.
[Lea, Janice P.] Emory Univ, Sch Med, Div Renal, Atlanta, GA 30322 USA.
[Nally, Joseph] Glickman Urol & Kidney Inst, Dept Hypertens & Nephrol, Cleveland, OH USA.
[Peralta, Carmen Alicia] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Peralta, Carmen Alicia] San Francisco VA Med Ctr, San Francisco, CA USA.
[Rothenbacher, Dietrich] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Rothenbacher, Dietrich] Univ Ulm, Inst Epidemiol & Med Biometry, Ulm, Germany.
[Ryu, Seungho] Sunkgyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Seoul, South Korea.
[Tonelli, Marcello] Univ Calgary, Dept Med, Calgary, AB, Canada.
[Yatsuya, Hiroshi] Fujita Hlth Univ, Dept Publ Hlth, Toyoake, Aichi, Japan.
[Gansevoort, Ron T.; de Jong, Paul E.] Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands.
[Warnock, David G.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Woodward, Mark] Univ Oxford, Nuffield Dept Populat Hlth, George Inst Global Hlth, Oxford, England.
[Woodward, Mark] Univ Sydney, George Inst Global Hlth, Sydney, NSW, Australia.
RP Coresh, J (reprint author), Chron Kidney Dis Prognosis Consortium, Data Coordinating Ctr, 2024 East Monument St, Baltimore, MD 21287 USA.
EM ckdpc@jhmi.edu
RI Tonelli, Marcello/B-3028-2009; Brenner, Hermann/B-4627-2017
OI Brenner, Hermann/0000-0002-6129-1572
FU US National Kidney Foundation; National Institute of Diabetes and
Digestive and Kidney Diseases [R01DK100446-01]; National Institutes of
Health
FX The Chronic Kidney Disease Prognosis Consortium (CKD-PC) Data
Coordinating Center is funded, in part, by a program grant from the US
National Kidney Foundation (funding sources include AbbVie and Amgen,
Inc.) and National Institute of Diabetes and Digestive and Kidney
Diseases Grant R01DK100446-01. A variety of sources have supported
enrollment and data collection, including laboratory measurements, as
well as follow-up in the collaborating cohorts of the CKD-PC. These
funding sources include government agencies, such as the National
Institutes of Health, and medical research councils as well as
foundations and industry sponsors, and they are listed in Supplemental
Appendix 3. Individual cohort and collaborator support is listed in
Supplemental Appendix 3.
NR 29
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U1 2
U2 2
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD AUG
PY 2016
VL 27
IS 8
BP 2456
EP 2466
DI 10.1681/ASN.2015060688
PG 11
WC Urology & Nephrology
SC Urology & Nephrology
GA DY3PM
UT WOS:000385006100025
PM 26657865
ER
PT J
AU Schirda, CV
Zhao, TJ
Andronesi, OC
Lee, Y
Pan, JW
Mountz, JM
Hetherington, HP
Boada, FE
AF Schirda, Claudiu V.
Zhao, Tiejun
Andronesi, Ovidiu C.
Lee, Yoojin
Pan, Jullie W.
Mountz, James M.
Hetherington, Hoby P.
Boada, Fernando E.
TI In Vivo Brain Rosette Spectroscopic Imaging (RSI) with LASER Excitation,
Constant Gradient Strength Readout, and Automated LCModel Quantification
for all Voxels
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE fast spectroscopic imaging; normalized SNR efficiency; Rosette
trajectories; RSI; sensitivity; LASER; brain
ID K-SPACE TRAJECTORIES; PHASED-ARRAY COILS; REAL-TIME MOTION;
CHEMICAL-SHIFT; MR SPECTROSCOPY; SINGLE-SHOT; ACQUISITION; NMR;
REDUCTION; ARTIFACTS
AB Purpose: To optimize the Rosette trajectories for high-sensitivity in vivo brain spectroscopic imaging and reduced gradient demands.
Methods: Using LASER localization, a rosette based sampling scheme for in vivo brain spectroscopic imaging data on a 3 Tesla (T) system is described. The two-dimensional (2D) and 3D rosette spectroscopic imaging (RSI) data were acquired using 20 x 20 in-plane resolution (8 x 8 mm(2)), and 1 (2D) -18 mm (1.1 cc) or 12 (3D) -8 mm partitions (0.5 cc voxels). The performance of the RSI acquisition was compared with a conventional spectroscopic imaging (SI) sequence using LASER localization and 2D or 3D elliptical phase encoding (ePE). Quantification of the entire RSI data set was performed using an LCModel based pipeline.
Results: The RSI acquisitions took 32 s for the 2D scan, and as short as 5 min for the 3D 20 x 20 x 12 scan, using a maximum gradient strength G(max) = 5.8 mT/m and slew-rate S-max = 45 mT/m/ms. The Bland-Altman agreement between RSI and ePE CSI, characterized by the 95% confidence interval for their difference (RSI-ePE), is within 13% of the mean (RSI+ePE)/2. Compared with the 3D ePE at the same nominal resolution, the effective RSI voxel size was three times smaller while the measured signal-to-noise ratio sensitivity, after normalization for differences in effective size, was 43% greater. Conclusio
n: 3D LASER-RSI is a fast, high-sensitivity spectroscopic imaging sequence, which can acquire medium-to-high resolution SI data in clinically acceptable scan times (5-10 min), with reduced stress on the gradient system. (C) 2015 Wiley Periodicals, Inc.
C1 [Schirda, Claudiu V.; Lee, Yoojin; Pan, Jullie W.; Mountz, James M.; Hetherington, Hoby P.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA.
[Zhao, Tiejun] Siemens Med Solutions USA Inc, Siemens Healthcare, Pittsburgh, PA USA.
[Andronesi, Ovidiu C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Pan, Jullie W.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA.
[Boada, Fernando E.] NYU, Dept Radiol, 560 1St Ave, New York, NY 10016 USA.
RP Schirda, CV (reprint author), Univ Pittsburgh, Sch Med, MRRC, UPMC, 200 Lothrop St,PUH B824, Pittsburgh, PA 15213 USA.
EM claudiu.schirda@gmail.com
OI Schirda, Claudiu/0000-0002-5036-0640
FU National Institutes of Health [1R01EB011639, 1R01NS081772, 1R01NS090417,
R01-EB009871, U01 CA140230]; University of Pittsburgh Cancer Institute
In Vivo Imaging Facility [P30CA047904]
FX Grant sponsor: National Institutes of Health; Grant numbers:
1R01EB011639, 1R01NS081772, 1R01NS090417, R01-EB009871, U01 CA140230;
Grant sponsor: University of Pittsburgh Cancer Institute In Vivo Imaging
Facility; Grant number: P30CA047904.
NR 45
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 AUG
PY 2016
VL 76
IS 2
BP 380
EP 390
DI 10.1002/mrm.25896
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3MR
UT WOS:000384997900002
PM 26308482
ER
PT J
AU Guerin, B
Stockmann, JP
Baboli, M
Torrado-Carvajal, A
Stenger, AV
Wald, LL
AF Guerin, Bastien
Stockmann, Jason P.
Baboli, Mehran
Torrado-Carvajal, Angel
Stenger, Andrew V.
Wald, Lawrence L.
TI Robust Time-Shifted Spoke Pulse Design in the Presence of Large B0
Variations with Simultaneous Reduction of Through-Plane Dephasing,
B1+Effects, and the Specific Absorption Rate Using Parallel Transmission
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE spokes; parallel transmission; B0 artefact; B1+homogeneity; specific
absorption rate
ID Z-SHIM METHOD; REDUCING SUSCEPTIBILITY ARTIFACTS; TAILORED RF PULSES;
FUNCTIONAL MRI; HUMAN BRAIN; GRADIENT COMPENSATION;
IMAGE-RECONSTRUCTION; FIELD INHOMOGENEITY; SIGNAL LOSSES; GLOBAL SAR
AB Purpose: To design parallel transmission spokes pulses with time-shifted profiles for joint mitigation of intensity variations due to B1+ effects, signal loss due to through-plane dephasing, and the specific absorption rate (SAR) at 7T.
Methods: We derived a slice-averaged small tip angle (SA-STA) approximation of the magnetization signal at echo time that depends on the B1+ transmit profiles, the through-slice B0 gradient and the amplitude and time-shifts of the spoke waveforms. We minimize a magnitude least-squares objective based on this signal equation using a fast interior-point approach with analytical expressions of the Jacobian and Hessian.
Results: Our algorithm runs in less than three minutes for the design of two-spoke pulses subject to hundreds of local SAR constraints. On a B0/B1+ head phantom, joint optimization of the channel-dependent time-shifts and spoke amplitudes allowed signal recovery in high-B0 regions at no increase of SAR. Although the method creates uniform magnetization profiles (ie, uniform intensity), the flip angle varies across the image, which makes it ill-suited to T1-weighted applications.
Conclusions: The SA-STA approach presented in this study is best suited to T2*-weighted applications with long echo times that require signal recovery around high B0 regions. (C) 2015 Wiley Periodicals, Inc.
C1 [Guerin, Bastien; Stockmann, Jason P.; Wald, Lawrence L.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA USA.
[Stockmann, Jason P.] Harvard Univ, Dept Phys, Cambridge, MA 02138 USA.
[Baboli, Mehran; Stenger, Andrew V.] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA.
[Torrado-Carvajal, Angel] Univ Rey Juan Carlos, Med Image Anal & Biometry Lab, Mostoles, Spain.
[Torrado-Carvajal, Angel] Madrid MIT M Vis Consortium, Madrid, Spain.
[Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA.
RP Guerin, B (reprint author), 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA.
EM guerin@nmr.mgh.harvard.edu
FU National Institutes of Health [R01-EB006847-08, P41-EB015896-17]
FX Grant sponsor: National Institutes of Health; Grant numbers:
R01-EB006847-08 and P41-EB015896-17.
NR 39
TC 1
Z9 1
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 AUG
PY 2016
VL 76
IS 2
BP 540
EP 554
DI 10.1002/mrm.25902
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DY3MR
UT WOS:000384997900017
PM 26444717
ER
PT J
AU Hauschild, A
Chapman, PB
Robert, C
Larkin, J
Haanen, JB
Ribas, A
Hogg, D
Hamid, O
Ascierto, PA
Testori, A
Lorigan, P
Dummer, R
Sosman, JA
Flaherty, KT
Wongchenko, MJ
Yan, Y
Chang, I
Coleman, S
Caro, I
Mcarthur, GA
AF Hauschild, A.
Chapman, P. B.
Robert, C.
Larkin, J.
Haanen, J. B.
Ribas, A.
Hogg, D.
Hamid, O.
Ascierto, P. A.
Testori, A.
Lorigan, P.
Dummer, R.
Sosman, J. A.
Flaherty, K. T.
Wongchenko, M. J.
Yan, Y.
Chang, I.
Coleman, S.
Caro, I.
Mcarthur, G. A.
TI Impact of key prognostic factors on long-term overall survival in
BRAF(V600)-mutated metastatic melanoma patients treated with vemurafenib
in the BRIM-3 study
SO MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Hauschild, A.] Univ Hosp Schleswig Holstein, Kiel, Germany.
[Chapman, P. B.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Robert, C.] Inst Gustave Roussy, Paris, France.
[Larkin, J.] Royal Marsden NHS Fdn Trust, London, England.
[Haanen, J. B.] Netherlands Canc Inst, Amsterdam, Netherlands.
[Ribas, A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Hogg, D.] Princess Margaret Hosp, Toronto, ON, Canada.
[Hogg, D.] Univ Hlth Network, Toronto, ON, Canada.
[Hamid, O.] Angeles Clin & Res Inst, Los Angeles, CA USA.
[Ascierto, P. A.] Ist Nazl Tumori Fdn G Pascale, Naples, Italy.
[Testori, A.] Ist Europeo Oncol, Milan, Italy.
[Lorigan, P.] Univ Manchester, Manchester, Lancs, England.
[Dummer, R.] Univ Zurich, Zurich, Switzerland.
[Sosman, J. A.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA.
[Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wongchenko, M. J.; Yan, Y.; Chang, I.; Coleman, S.; Caro, I.] Genentech Inc, San Francisco, CA 94080 USA.
[Mcarthur, G. A.] Peter MacCallum Canc Ctr, East Melbourne, Australia.
[Mcarthur, G. A.] Univ Melbourne, Parkville, Vic, Australia.
NR 0
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 0960-8931
EI 1473-5636
J9 MELANOMA RES
JI Melanoma Res.
PD AUG
PY 2016
VL 26
SU 1
MA P057
BP E39
EP E40
PG 2
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA DW3RR
UT WOS:000383560800075
ER
PT J
AU Hauschild, A
Larkin, J
Ribas, A
Dreno, B
Flaherty, KT
Ascierto, PA
Lewis, KD
Mckenna, E
Zhu, Q
Mun, Y
Mcarthur, GA
AF Hauschild, A.
Larkin, J.
Ribas, A.
Dreno, B.
Flaherty, K. T.
Ascierto, P. A.
Lewis, K. D.
Mckenna, E.
Zhu, Q.
Mun, Y.
Mcarthur, G. A.
TI Identification of prognostic subgroups for overall survival in patients
(pts) with BRAF(V600)-mutated metastatic melanoma treated with
vemurafenib +/- cobimetinib: a pooled exploratory analysis of the
BRIM-2, BRIM-3, BRIM-7, and coBRIM studies
SO MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Hauschild, A.] Univ Hosp Schleswig Holstein, Kiel, Germany.
[Larkin, J.] Royal Marsden NHS Fdn Trust, London, England.
[Ribas, A.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA.
[Dreno, B.] Nantes Univ, Nantes, France.
[Flaherty, K. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ascierto, P. A.] Fdn G Pascale, Ist Nazl Tumori, Naples, Italy.
[Lewis, K. D.] Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA.
[Mckenna, E.; Zhu, Q.; Mun, Y.] Genentech Inc, San Francisco, CA 94080 USA.
[Mcarthur, G. A.] Peter MacCallum Canc Ctr, East Melbourne, Australia.
[Mcarthur, G. A.] Univ Melbourne, Parkville, Vic, Australia.
NR 0
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 0960-8931
EI 1473-5636
J9 MELANOMA RES
JI Melanoma Res.
PD AUG
PY 2016
VL 26
SU 1
MA SY8-5
BP E1
EP E2
PG 2
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA DW3RR
UT WOS:000383560800003
ER
PT J
AU Schadendorf, D
Larkin, J
Chiarion-Sileni, V
Gonzalez, R
Rutkowski, P
Grob, JJ
Cowey, CL
Lao, C
Taylor, F
Sabater, J
Walker, D
Bhore, R
Wolchok, J
Hodi, FS
AF Schadendorf, D.
Larkin, J.
Chiarion-Sileni, V.
Gonzalez, R.
Rutkowski, P.
Grob, J. -J.
Cowey, C. L.
Lao, C.
Taylor, F.
Sabater, J.
Walker, D.
Bhore, R.
Wolchok, J.
Hodi, F. S.
TI Efficacy and quality of life outcomes in patients with advanced melanoma
(MEL) who discontinued treatment with nivolumab (NIVO) plus ipilimumab
(IPI) due to toxicity in a phase 3 trial (CheckMate 067)
SO MELANOMA RESEARCH
LA English
DT Meeting Abstract
C1 [Schadendorf, D.] Univ Hosp Essen, Dept Dermatol, Essen, Germany.
[Larkin, J.] Royal Marsden Hosp, London, England.
[Chiarion-Sileni, V.] Ist Oncol Veneto, Veneto, Italy.
[Gonzalez, R.] Univ Colorado, Denver, CO USA.
[Rutkowski, P.] Maria Sklodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Rutkowski, P.] Inst Oncol, Warsaw, Poland.
[Grob, J. -J.] Hosp Timone, Marseille, France.
[Cowey, C. L.] Texas Oncol Baylor Canc Ctr, Dallas, TX USA.
[Lao, C.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Taylor, F.] Adelphi Values LTD, Boston, MA USA.
[Sabater, J.; Walker, D.; Bhore, R.] Bristol Myers Squibb, Princeton, NJ USA.
[Wolchok, J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
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 0960-8931
EI 1473-5636
J9 MELANOMA RES
JI Melanoma Res.
PD AUG
PY 2016
VL 26
SU 1
MA SY12-4
BP E4
EP E4
PG 1
WC Oncology; Dermatology; Medicine, Research & Experimental
SC Oncology; Dermatology; Research & Experimental Medicine
GA DW3RR
UT WOS:000383560800006
ER
PT J
AU Molinie, B
Wang, JK
Lim, KS
Hillebrand, R
Lu, ZX
Van Wittenberghe, N
Howard, BD
Daneshvar, K
Mullen, AC
Dedon, P
Xing, Y
Giallourakis, CC
AF Molinie, Benoit
Wang, Jinkai
Lim, Kok Seong
Hillebrand, Roman
Lu, Zhi-xiang
Van Wittenberghe, Nicholas
Howard, Benjamin D.
Daneshvar, Kaveh
Mullen, Alan C.
Dedon, Peter
Xing, Yi
Giallourakis, Cosmas C.
TI m(6)A-LAIC-seq reveals the census and complexity of the m(6)A
epitranscriptome
SO NATURE METHODS
LA English
DT Article
ID MESSENGER-RNA METHYLATION; EMBRYONIC STEM-CELLS;
SINGLE-NUCLEOTIDE-RESOLUTION; NUCLEIC-ACID MODIFICATIONS; LONG NONCODING
RNA; ALTERNATIVE POLYADENYLATION; GENE-EXPRESSION; N-6-METHYLADENOSINE;
SEQ; N6-METHYLADENOSINE
AB N-6-Methyladenosine (m(6)A) is a widespread, reversible chemical modification of RNA molecules, implicated in many aspects of RNA metabolism. Little quantitative information exists as to either how many transcript copies of particular genes are m(6)A modified ('m(6)A levels') or the relationship of m(6)A modification(s) to alternative RNA isoforms. To deconvolute the m(6)A epitranscriptome, we developed m(6)A-level and isoform-characterization sequencing (m(6)A-LAIC-seq). We found that cells exhibit a broad range of nonstoichiometric m(6)A levels with cell-type specificity. At the level of isoform characterization, we discovered widespread differences in the use of tandem alternative polyadenylation (APA) sites by methylated and nonmethylated transcript isoforms of individual genes. Strikingly, there is a strong bias for methylated transcripts to be coupled with proximal APA sites, resulting in shortened 3' untranslated regions, while nonmethylated transcript isoforms tend to use distal APA sites. m(6)A-LAIC-seq yields a new perspective on transcriptome complexity and links APA usage to m(6)A modifications.
C1 [Molinie, Benoit; Van Wittenberghe, Nicholas; Howard, Benjamin D.; Daneshvar, Kaveh; Mullen, Alan C.; Giallourakis, Cosmas C.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA.
[Wang, Jinkai; Lu, Zhi-xiang; Xing, Yi] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Lim, Kok Seong; Hillebrand, Roman; Dedon, Peter] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Giallourakis, Cosmas C.] Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
[Giallourakis, Cosmas C.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA.
RP Giallourakis, CC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA.; Xing, Y (reprint author), Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.; Giallourakis, CC (reprint author), Harvard Stem Cell Inst, Cambridge, MA 02138 USA.; Giallourakis, CC (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA.
EM yxing@ucla.edu; cgiallourakis@mgh.harvard.edu
RI Lu, Zhixiang/G-4521-2014;
OI Lu, Zhixiang/0000-0001-9230-2169; Daneshvar, Kaveh/0000-0002-7863-0489
FU MGH startup; ECOR grants; National Institutes of Health (NIH)
[R01GM088342]; Eli & Edythe Broad Center of Regenerative Medicine and
Stem Cell Research at UCLA; Rose Hills Foundation Research Award; Alfred
Sloan Research Fellowship; National Research Foundation of Singapore
through the Singapore-MIT Alliance for Research and Technology; National
Institute of Environmental Health Science [ES002109, ES024615]; National
Science Foundation [CHE-1308839]; NIH [DK090122]
FX This study was supported by an MGH startup and ECOR grants to C.C.G.
This study was also supported by National Institutes of Health (NIH)
grant R01GM088342 and an Eli & Edythe Broad Center of Regenerative
Medicine and Stem Cell Research at UCLA and Rose Hills Foundation
Research Award to Y.X. Y.X. is supported by an Alfred Sloan Research
Fellowship. P.D. was supported by the National Research Foundation of
Singapore through the Singapore-MIT Alliance for Research and
Technology, National Institute of Environmental Health Science grants
ES002109 and ES024615, and National Science Foundation grant
CHE-1308839. A.C.M. was supported by NIH grant DK090122. We thank D.
Mirsky for copy editing the manuscript. We thank J. Wan for technical
support on data analyses. We thank H. Chang, P. Batista, and K. Jeffrey
for reading the manuscript and providing helpful comments.
NR 55
TC 8
Z9 8
U1 9
U2 10
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 AUG
PY 2016
VL 13
IS 8
BP 692
EP +
DI 10.1038/nmeth.3898
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA DY6AT
UT WOS:000385188700026
PM 27376769
ER
PT J
AU Zurnic, I
Hutter, S
Rzeha, U
Stanke, N
Reh, J
Mullers, E
Hamann, MV
Kern, T
Gerresheim, GK
Lindel, F
Serrao, E
Lesbats, P
Engelman, AN
Cherepanov, P
Lindemann, D
AF Zurnic, Irena
Huetter, Sylvia
Rzeha, Ute
Stanke, Nicole
Reh, Juliane
Muellers, Erik
Hamann, Martin V.
Kern, Tobias
Gerresheim, Gesche K.
Lindel, Fabian
Serrao, Erik
Lesbats, Paul
Engelman, Alan N.
Cherepanov, Peter
Lindemann, Dirk
TI Interactions of Prototype Foamy Virus Capsids with Host Cell Polo-Like
Kinases Are Important for Efficient Viral DNA Integration
SO PLOS PATHOGENS
LA English
DT Article
ID CORE PROTEIN; HIV-1 INFECTION; RETROVIRAL INTEGRATION; REVERSE
TRANSCRIPTION; NUCLEAR-LOCALIZATION; BOX DOMAIN; IN-VIVO; GAG; PLK1;
PHOSPHORYLATION
AB Unlike for other retroviruses, only a few host cell factors that aid the replication of foamy viruses (FVs) via interaction with viral structural components are known. Using a yeast-two-hybrid (Y2H) screen with prototype FV (PFV) Gag protein as bait we identified human polo-like kinase 2 (hPLK2), a member of cell cycle regulatory kinases, as a new interactor of PFV capsids. Further Y2H studies confirmed interaction of PFV Gag with several PLKs of both human and rat origin. A consensus Ser-Thr/Ser-Pro (S-T/S-P) motif in Gag, which is conserved among primate FVs and phosphorylated in PFV virions, was essential for recognition by PLKs. In the case of rat PLK2, functional kinase and polo-box domains were required for interaction with PFV Gag. Fluorescently-tagged PFV Gag, through its chromatin tethering function, selectively relocalized ectopically expressed eGFP-tagged PLK proteins to mitotic chromosomes in a Gag STP motif-dependent manner, confirming a specific and dominant nature of the Gag-PLK interaction in mammalian cells. The functional relevance of the Gag-PLK interaction was examined in the context of replication-competent FVs and single-round PFV vectors. Although STP motif mutated viruses displayed wild type (wt) particle release, RNA packaging and intra-particle reverse transcription, their replication capacity was decreased 3-fold in single-cycle infections, and up to 20-fold in spreading infections over an extended time period. Strikingly similar defects were observed when cells infected with single-round wt Gag PFV vectors were treated with a pan PLK inhibitor. Analysis of entry kinetics of the mutant viruses indicated a post-fusion defect resulting in delayed and reduced integration, which was accompanied with an enhanced preference to integrate into heterochromatin. We conclude that interaction between PFV Gag and cellular PLK proteins is important for early replication steps of PFV within host cells.
C1 [Zurnic, Irena; Huetter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Muellers, Erik; Hamann, Martin V.; Kern, Tobias; Gerresheim, Gesche K.; Lindel, Fabian; Lindemann, Dirk] Tech Univ Dresden, Inst Virol, Med Fac Carl Gustav Carus, Dresden, Germany.
[Zurnic, Irena; Huetter, Sylvia; Rzeha, Ute; Stanke, Nicole; Reh, Juliane; Muellers, Erik; Hamann, Martin V.; Kern, Tobias; Gerresheim, Gesche K.; Lindel, Fabian; Lindemann, Dirk] Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden, Dresden, Germany.
[Serrao, Erik; Engelman, Alan N.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.
[Lesbats, Paul; Cherepanov, Peter] Francis Crick Inst, Clare Hall Labs, S Mimms, Herts, England.
[Rzeha, Ute] Univ Potsdam, Messeserv, Potsdam, Germany.
[Rzeha, Ute] Univ Potsdam, Technol Transfer, NutriAct Innovat Off, Potsdam, Germany.
[Muellers, Erik] AstraZeneca R&D Gothenburg, Discovery Sci, Molndal, Sweden.
[Kern, Tobias] Tech Univ Dresden, Inst Microbiol, Dresden, Germany.
[Gerresheim, Gesche K.] Univ Giessen, Inst Biochem, Fac Med, Giessen, Germany.
RP Lindemann, D (reprint author), Tech Univ Dresden, Inst Virol, Med Fac Carl Gustav Carus, Dresden, Germany.; Lindemann, D (reprint author), Tech Univ Dresden, CRTD DFG Ctr Regenerat Therapies Dresden, Dresden, Germany.
EM dirk.lindemann@tu-dresden.de
RI Cherepanov, Peter/F-6859-2010;
OI Cherepanov, Peter/0000-0002-0634-538X; Mullers, Erik/0000-0002-2176-3248
FU DIGS-BB fellowship; Deutsche Forschungsgemeinschaft [Li621/3-3,
Li621/4-1, Li621/4-2, Li621/6-1]; US National Institutes of Health [R01
AI052014, P30 AI060354]
FX IZ, EM and MVH were partially supported by a DIGS-BB fellowship
(https://tu-dresden.de/exzellenz/graduiertenschule/digsbb). This work
was partially supported by grants from the Deutsche
Forschungsgemeinschaft (http://www.dfg.de/en/index.jsp) (Li621/3-3,
Li621/4-1, Li621/4-2, Li621/6-1) to DL and from the US National
Institutes of Health (R01 AI052014 to ANE; P30 AI060354 to Harvard
University Center for AIDS Research). The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 83
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Z9 1
U1 1
U2 1
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 AUG
PY 2016
VL 12
IS 8
AR e1005860
DI 10.1371/journal.ppat.1005860
PG 36
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DW1AV
UT WOS:000383376000062
PM 27579920
ER
PT J
AU Stern, TA
AF Stern, Theodore A.
TI Catastrophic Complications Related to Psychopharmacologic Practice
SO PSYCHIATRIC ANNALS
LA English
DT Editorial Material
C1 [Stern, Theodore A.] Harvard Med Sch, Psychiat Field Psychosomat Med Consultat, Boston, MA USA.
[Stern, Theodore A.] Massachusetts Gen Hosp, Avery D Weisman Psychiat Consultat Serv, Boston, MA 02114 USA.
[Stern, Theodore A.] Massachusetts Gen Hosp, Off Clin Careers, Boston, MA 02114 USA.
RP Stern, TA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Warren Bldg,Room 605, Boston, MA 02114 USA.
EM TStern@Partners.org
NR 1
TC 0
Z9 0
U1 0
U2 0
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 AUG
PY 2016
VL 46
IS 8
BP 436
EP 437
DI 10.3928/00485713-20160721-03
PG 2
WC Psychiatry
SC Psychiatry
GA DY3VI
UT WOS:000385023000003
ER
PT J
AU Carlo, AD
Alpert, JE
AF Carlo, Andrew D.
Alpert, Jonathan E.
TI Catastrophic Drug-Drug Interactions in Psychopharmacology
SO PSYCHIATRIC ANNALS
LA English
DT Article
DE m
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; MONOAMINE-OXIDASE INHIBITORS;
TORSADE-DE-POINTES; TRICYCLIC ANTIDEPRESSANTS; PSYCHOTROPIC-DRUGS;
SEROTONIN TOXICITY; QTC PROLONGATION; CLOMIPRAMINE; INTERVAL; CRITERIA
AB Drug interactions may reflect pharmacokinetic processes, pharmacodynamic processes, or both. Some interactions are classified as idiosyncratic, as their mechanisms are not yet understood. Drug inter-actions involving psychotropic medications are ubiquitous; they typically result in changes in drug levels and/or drug effects. Fortunately, most drug interactions in psychiatry do not result in serious harm. Some drug interactions, however, are potentially catastrophic. The focus of this review is on the principal mechanisms of drug interactions and on potentially serious and life-threatening adverse consequences (eg, serotonin syndrome, hypertensive crises, arrhythmias, anticholinergic toxicity, seizures, dermatologic emergencies, bleeding, respiratory depression) of drug interactions in psychiatry. Patients with refractory psychiatric disorders, as well as medical comorbidity, often require treatment with complex drug regimens. The risk of catastrophic drug interactions involving psychotropic medications may be minimized by knowledge of the mechanisms of drug interactions and by familiarity with the rare, yet potentially life-threatening drug interactions that involve psychotropic medications.
C1 [Carlo, Andrew D.] Massachusetts Gen Hosp, McLean Hosp, Adult Psychiat Residency Program, Boston, MA 02114 USA.
[Carlo, Andrew D.] Harvard Med School, Psychiat, Boston, MA USA.
[Alpert, Jonathan E.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA.
[Alpert, Jonathan E.] Massachusetts Gen Hosp, Depress Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA.
RP Carlo, AD (reprint author), Massachusetts Gen Hosp, WACC 812, 15 Parkman St, Boston, MA 02114 USA.
EM acarlo@partners.org
FU Luye Pharmaceuticals
FX Jonathan E. Alpert discloses consultant fees from Luye Pharmaceuticals
and a royalty from Belvoir Publications Inc. The remaining author has no
relevant financial relationships to disclose.
NR 30
TC 0
Z9 0
U1 3
U2 3
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 AUG
PY 2016
VL 46
IS 8
BP 439
EP 447
DI 10.3928/00485713-20160623-01
PG 9
WC Psychiatry
SC Psychiatry
GA DY3VI
UT WOS:000385023000004
ER
PT J
AU Carlo, AD
Alpert, JE
AF Carlo, Andrew D.
Alpert, Jonathan E.
TI Clinically Relevant Complications of Drug-Food Interactions in
Psychopharmacology
SO PSYCHIATRIC ANNALS
LA English
DT Article
ID LEVOTHYROXINE; METABOLISM; ABSORPTION; LURASIDONE; THERAPY; DIET
AB Although often overlooked, the interaction of psychotropic medications with food or dietary health supplements can be clinically relevant, and in some cases it may be catastrophic. In this review, we highlight clinically significant drug-food interactions in psychiatry, including those related to hypertensive crises with mono amine oxidase inhibitors, absorption of medications (such as levothyroxine, ziprasidone, and lurasidone), coadministration with food, the excretion of lithium and other medications in the setting of dietary changes, and the impact of grapefruit juice, St. John's wort, cruciferous vegetables, charbroiled meats, dietary supplements, and alcohol on drug metabolism, Routine inquiry about dietary habits and use of dietary supplements as well as enhanced anticipation and monitoring for potential drug-food interactions is an integral component of optimal psychopharmacologic practice.
C1 [Carlo, Andrew D.] Massachusetts Gen Hosp, McLean Hosp, Adult Psychiat Residency Program, Boston, MA 02114 USA.
[Carlo, Andrew D.] Harvard Med Sch, Psychiat, Boston, MA USA.
[Alpert, Jonathan E.] Massachusetts Gen Hosp, Psychiat, Boston, MA 02114 USA.
[Alpert, Jonathan E.] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA.
RP Carlo, AD (reprint author), Massachusetts Gen Hosp, WACC 812, 15 Parkman St, Boston, MA 02114 USA.
EM acorlo@portners.org
FU Luye Pharmaceuticals
FX Jonathan E. Alpert discloses consultant fees from Luye Pharmaceuticals
and a royalty from Belvoir Publications Inc. The remaining author has no
relevant financial relationships to disclose.
NR 25
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 AUG
PY 2016
VL 46
IS 8
BP 448
EP 455
DI 10.3928/00485713-20160613-01
PG 8
WC Psychiatry
SC Psychiatry
GA DY3VI
UT WOS:000385023000005
ER
PT J
AU Stevens, JR
Rodgers, JJ
Stern, TA
AF Stevens, Jonathan R.
Rodgers, Joshua J.
Stern, Theodore A.
TI Idiosyncratic Adverse Reactions to Psychotropic Medications
SO PSYCHIATRIC ANNALS
LA English
DT Article
ID NEUROLEPTIC MALIGNANT SYNDROME; ATTENTION-DEFICIT/HYPERACTIVITY
DISORDER; RANDOMIZED CONTROLLED-TRIAL; TOXIC EPIDERMAL NECROLYSIS;
STEVENS-JOHNSON SYNDROME; INDUCED LIVER-INJURY; ANTIEPILEPTIC DRUGS;
LITHIUM; CHILDREN; PRIAPISM
AB Idiosyncratic adverse events related to psychotropic medications are prevalent and problematic, and they are the most frequent cause of postmarketing (or black-box) warnings and withdrawals of drugs from the market. This review examines the clinical nature of idiosyncratic adverse events, predictors of their onset, and the role of clinician awareness in avoiding irreversible and serious injury from medications prescribed for psychiatric conditions. Idiosyncratic reactions can be minimized or avoided by knowledge of risk factors, cautious use (or avoidance) of specific agents in subpopulations at risk, informed dose titration, and careful monitoring of clinical response.
C1 [Stevens, Jonathan R.] Menninger Clin, Outpatient Serv, Houston, TX USA.
[Stevens, Jonathan R.; Rodgers, Joshua J.] Baylor Coll Med, Psychiat & Behav Sci, Houston, TX 77030 USA.
[Rodgers, Joshua J.] Menninger Clin, 12301 Main St, Houston, TX 77035 USA.
[Stern, Theodore A.] Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA.
RP Stevens, JR (reprint author), Menninger Clin, 12301 Main St, Houston, TX 77035 USA.
EM jonstevens@menninger.edu
FU Academy of Psychosomatic Medicine
FX Theodore A. Stern receives a salary for his work as Editor-in-Chief of
the journal Psychosomatics (Academy of Psychosomatic Medicine), has
received royalties from Elsevier for his role as Editor of Massachusetts
General Hospital Comprehensive Clinical Psychiatry, and for his role as
Editor of Massachusetts General Hospital Psychiatry Update and Board
Preparation. The remaining authors have no relevant financial
relationships to disclose.
NR 65
TC 0
Z9 0
U1 0
U2 0
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 AUG
PY 2016
VL 46
IS 8
BP 456
EP 465
DI 10.3928/00485713-20160622-01
PG 10
WC Psychiatry
SC Psychiatry
GA DY3VI
UT WOS:000385023000006
ER
PT J
AU Jenkins, J
Glass, S
AF Jenkins, James
Glass, Sean
TI Catastrophic Complications Related to Psychopharmacologic Drug
Withdrawal
SO PSYCHIATRIC ANNALS
LA English
DT Article
ID ANTIDEPRESSANT DISCONTINUATION SYNDROME; SUPERSENSITIVITY PSYCHOSIS;
ATYPICAL ANTIPSYCHOTICS; DIAGNOSTIC-CRITERIA; SYMPTOMS; BENZODIAZEPINES;
RECOMMENDATIONS; DETOXIFICATION; MANAGEMENT; DISORDER
AB Numerous physical and psychiatric effects can be attributed to the cessation of psychotropic medications, similar to those agents with abuse potential. In addition, drug withdrawal can exacerbate underlying psychiatric conditions and alter disease course and long-term outcomes. This article discusses specific withdrawal syndromes associated with several classes of psychotropic medications to increase prescriber awareness when tapering and discontinuing psychotropic medications, thereby facilitating discussions with patients about the risks of withdrawal.
C1 [Jenkins, James] Massachusetts Gen Hosp, McLean Hosp, Adult Psychiat Residency Program, Boston, MA 02114 USA.
[Jenkins, James; Glass, Sean] Harvard Med Sch, Psychiat, Boston, MA USA.
[Glass, Sean] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Jenkins, J (reprint author), Mailstop 109,115 Mill St, Belmont, MA 02478 USA.
EM jajenkins@partners.org
NR 32
TC 0
Z9 0
U1 1
U2 1
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 AUG
PY 2016
VL 46
IS 8
BP 466
EP 472
DI 10.3928/00485713-20160621-01
PG 7
WC Psychiatry
SC Psychiatry
GA DY3VI
UT WOS:000385023000007
ER
PT J
AU Pasqualucci, L
Zhang, BC
AF Pasqualucci, Laura
Zhang, Baochun
TI Genetic drivers of NF-kappa B deregulation in diffuse large B-cell
lymphoma
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE DLBCL; Germinal center; NF-kappa B; Genetic lesions
ID GERMINAL-CENTER; ACTIVATION; SURVIVAL; IMMUNOGLOBULIN; LYMPHOCYTES;
EXPRESSION; DYNAMICS; CENTERS; PROLIFERATION; INACTIVATION
AB Diffuse large B cell lymphoma (DLBCL) is the most common form of B cell non-Hodgkin lymphoma worldwide and comprises a heterogeneous group of malignancies that originate from the malignant transformation of germinal center (GC) B cells. Over the past decade, significant improvement has been achieved in our understanding of the molecular pathogenesis underlying this disease, thanks in part to the implementation of powerful genomic technologies allowing genome-wide structural and functional analyses. These studies revealed the presence of multiple oncogenic alterations dysregulating signal transduction pathways that are normally required for the normal biology of the cells from which these tumors are derived. Among the pathways identified as recurrent targets of genetic lesions in DLBCL, NF-kappa B has emerged as a central player in the development and maintenance of this disease, particularly in the less curable, activated B cell (ABC)-like subtype. These lesions reveal vulnerabilities of the lymphoma cells that can be exploited for the design of more rationale therapeutic approaches. The purpose of this review is to summarize recent progresses in understanding the role of NF-kappa B deregulation in the pathogenesis of DLBCL, with emphasis on the genetic basis underlying its aberrant activation, in relationship to the normal biology of B lymphocytes, and the modelling of these lesions in the mouse. (C) 2016 Published by Elsevier Ltd.
C1 [Pasqualucci, Laura] Columbia Univ, Inst Canc Genet, Dept Pathol & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Zhang, Baochun] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
RP Pasqualucci, L (reprint author), Columbia Univ, Inst Canc Genet, Dept Pathol & Cell Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
EM lp171@columbia.edu
FU American Society of Hematology Scholar Award; [R01CA172492-02]
FX Supported in part by Grant R01CA172492-02 (to L.P.) and an American
Society of Hematology Scholar Award (to B. Z.).
NR 54
TC 1
Z9 1
U1 1
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD AUG
PY 2016
VL 39
BP 26
EP 31
DI 10.1016/j.semcancer.2016.08.001
PG 6
WC Oncology
SC Oncology
GA DY1NY
UT WOS:000384862900004
PM 27546290
ER
PT J
AU Matthews, GM
Simoes, RD
Dhimolea, E
Sheffer, M
Gandolfi, S
Dashevsky, O
Sorrell, JD
Mitsiades, CS
AF Matthews, Geoffrey M.
Simoes, Ricardo de Matos
Dhimolea, Eugen
Sheffer, Michal
Gandolfi, Sara
Dashevsky, Olga
Sorrell, Jeffrey D.
Mitsiades, Constantine S.
TI NF-kappa B dysregulation in multiple myeloma
SO SEMINARS IN CANCER BIOLOGY
LA English
DT Review
DE Myeloma; NF-kappaB; Microenvironment; Stromal cells; Proteasome
inhibitors
ID PROTEASOME INHIBITOR BORTEZOMIB; PANOBINOSTAT PLUS BORTEZOMIB; CHRONIC
LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; MARROW STROMAL CELLS;
SUPPRESSOR-CELLS; BREAST-CANCER; PHASE-II; HEMATOLOGIC MALIGNANCIES;
COMBINATION THERAPY
AB The nuclear factor-kappa B (NF-kappa B) transcription factor family plays critical roles in the pathophysiology of hematologic neoplasias, including multiple myeloma. The current review examines the roles that this transcription factor system plays in multiple myeloma cells and the nonmalignant accessory cells of the local microenvironment; as well as the evidence indicating that a large proportion of myeloma patients harbor genomic lesions which perturb diverse genes regulating the activity of NF-kappa B. This article also discusses the therapeutic targeting of the NF-kappa B pathway using proteasome inhibitors, a pharmacological class that has become a cornerstone in the therapeutic management of myeloma; and reviews some of the future challenges and opportunities for NF-kappa B-related research in myeloma. (C) 2016 Published by Elsevier Ltd.
C1 [Matthews, Geoffrey M.; Simoes, Ricardo de Matos; Dhimolea, Eugen; Sheffer, Michal; Gandolfi, Sara; Dashevsky, Olga; Sorrell, Jeffrey D.; Mitsiades, Constantine S.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
RP Mitsiades, CS (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Dept Med, 450 Brookline Ave,Harvard Inst Med Bldg, Boston, MA 02215 USA.
EM Constantine_Mitsiades@dfci.harvard.edu
FU National Institutes of Health [R01 CA127435, R01 CA179483, R01
CA196664]; Shawna Ashlee Corman Investigatorship in Multiple Myeloma
Research; de Gunzburg Myeloma Research Fund; Cobb Family Myeloma
Research Fund; Chambers Family Advanced Myeloma Research Fund; Leukemia
and Lymphoma Society; Multiple Myeloma Research Foundation; RJ Corman
Multiple Myeloma Research Fund; Claudia Adams Barr Program in Cancer
Research; American Australian Association; International Myeloma
Foundation; Human Frontier Science Program
FX The research studies of CSM have been supported by Grants R01 CA127435,
R01 CA179483 and R01 CA196664 from the National Institutes of Health,
the Shawna Ashlee Corman Investigatorship in Multiple Myeloma Research,
the de Gunzburg Myeloma Research Fund, the Cobb Family Myeloma Research
Fund, the Chambers Family Advanced Myeloma Research Fund, the Leukemia
and Lymphoma Society Translational Research Program and Quest for Cure
Program, the Multiple Myeloma Research Foundation and the RJ Corman
Multiple Myeloma Research Fund. CSM and ED are also supported by the
Claudia Adams Barr Program in Cancer Research. GMM has been supported by
the American Australian Association and the International Myeloma
Foundation. MS is supported by the Human Frontier Science Program.
NR 144
TC 1
Z9 1
U1 4
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1044-579X
J9 SEMIN CANCER BIOL
JI Semin. Cancer Biol.
PD AUG
PY 2016
VL 39
BP 68
EP 76
DI 10.1016/j.semcancer.2016.08.005
PG 9
WC Oncology
SC Oncology
GA DY1NY
UT WOS:000384862900009
PM 27544796
ER
PT J
AU Yeboah, A
Cohen, RI
Rabolli, C
Yarmush, ML
Berthiaume, F
AF Yeboah, Agnes
Cohen, Rick I.
Rabolli, Charles
Yarmush, Martin L.
Berthiaume, Francois
TI Elastin-Like Polypeptides: A Strategic Fusion Partner for Biologics
SO BIOTECHNOLOGY AND BIOENGINEERING
LA English
DT Review
DE elastin-like peptides (ELP); ELPylation; biologics; biopharmaceutical;
purification
ID AFFINITY PRECIPITATION; RECOMBINANT PROTEINS; ELP-Z; ESCHERICHIA-COLI;
MONOCLONAL-ANTIBODY; TRANSGENIC PLANTS; PURIFICATION; EXPRESSION;
PEPTIDES; TOBACCO
AB Elastin-like peptides (ELPs) are derivatives of tropoelastin with a unique property that allows them to stay soluble below a certain critical temperature but reversibly form aggregates above that temperature. Since they are derived from tropoelastin, ELPs are biocompatible, non-toxic, and non-immunogenic. The unique properties of ELPs have made them a desirable class of fusion tags used in several biomedical applications including targeted drug delivery and enhancing the half-life of protein drugs. The most significant property of an ELP is that when fused to other proteins, the phase transition property of the ELP is maintained, and the target protein can be purified using the thermally driven property of the ELP. The ELP tag purification process is simple and inexpensive, and involves cycling the protein above and below the transition temperature of the ELP fusion followed by centrifugation to obtain the desired protein, without any need for chromatography. Consequently, using ELPs as a purification tag should be potentially interesting to biopharmaceutical companies who spend a significant percentage of their manufacturing costs on expensive protein purification techniques such as chromatography and filtration. However, ELP tags have not yet been used for commercial protein purification due to some challenges of translating this technique, which has been demonstrated mostly in academic laboratories, to a biotechnology manufacturing environment. The article first reviews the state-of-the-art in protein "ELPylation," and discusses some applications which have benefitted from using ELP as a fusion tag. Then, the article discusses the main advantages of using ELP as a purification tag, and evaluates the remaining hurdles for its implementation in industrial protein production. (C) 2016 Wiley Periodicals, Inc.
C1 [Yeboah, Agnes] Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ USA.
[Cohen, Rick I.; Rabolli, Charles; Yarmush, Martin L.; Berthiaume, Francois] Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA.
[Yarmush, Martin L.] Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA.
[Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA USA.
RP Berthiaume, F (reprint author), Rutgers State Univ, Dept Biomed Engn, 599 Taylor Rd, Piscataway, NJ 08854 USA.
EM fberthia@rci.rutgers.edu
FU Shriners Hospitals for Children; New Jersey Commission for Spinal Cord
Research
FX Contract grant sponsor: Shriners Hospitals for Children; Contract grant
sponsor: New Jersey Commission for Spinal Cord Research
NR 68
TC 0
Z9 1
U1 13
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-3592
EI 1097-0290
J9 BIOTECHNOL BIOENG
JI Biotechnol. Bioeng.
PD AUG
PY 2016
VL 113
IS 8
BP 1617
EP 1627
DI 10.1002/bit.25998
PG 11
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DX9XU
UT WOS:000384751100001
PM 27111242
ER
PT J
AU Xicola, RM
Bontu, S
Doyle, BJ
Rawson, J
Garre, P
Lee, E
de la Hoya, M
Bessa, X
Clofent, J
Bujanda, L
Balaguer, F
Castellvi-Bel, S
Alenda, C
Jover, R
Ruiz-Ponte, C
Syngal, S
Andreu, M
Carracedo, A
Castells, A
Newcomb, PA
Lindor, N
Potter, JD
Baron, JA
Ellis, NA
Caldes, T
LLor, X
AF Xicola, Rosa M.
Bontu, Sneha
Doyle, Brian J.
Rawson, Jamie
Garre, Pilar
Lee, Esther
de la Hoya, Miguel
Bessa, Xavier
Clofent, Joan
Bujanda, Luis
Balaguer, Francesc
Castellvi-Bel, Sergi
Alenda, Cristina
Jover, Rodrigo
Ruiz-Ponte, Clara
Syngal, Sapna
Andreu, Montserrat
Carracedo, Angel
Castells, Antoni
Newcomb, Polly A.
Lindor, Noralane
Potter, John D.
Baron, John A.
Ellis, Nathan A.
Caldes, Trinidad
LLor, Xavier
TI Association of a let-7 miRNA binding region of TGFBR1 with hereditary
mismatch repair proficient colorectal cancer (MSS HNPCC)
SO CARCINOGENESIS
LA English
DT Article
ID WIDE LINKAGE SCAN; COLON-CANCER; SUSCEPTIBILITY; RISK; VARIANTS;
CRITERIA; TGFBR1-ASTERISK-6A; PREDISPOSITION; POLYMORPHISMS; PROGRESSION
AB We describe an association between TGFBR1 polymorphism rs868 and mismatch repair proficient hereditary colorectal cancers. This polymorphism results in more binding of TGFBR1 to let-7b-5p miRNA, which would result in lower expression of TGFBR1 and thus higher colorectal cancer risk.The purpose of this study was to identify novel colorectal cancer (CRC)-causing alleles in unexplained familial CRC cases. In order to do so, coding regions in five candidate genes (MGMT, AXIN2, CTNNB1, TGFBR1 and TGFBR2) were sequenced in 11 unrelated microsatellite-stable hereditary non-polyposis CRC (MSS HNPCC) cases. Selected genetic variants were genotyped in a discovery set of 27 MSS HNPCC cases and 85 controls. One genetic variant, rs67687202, in TGFBR1 emerged as significant (P = 0.002), and it was genotyped in a replication set of 87 additional MSS HNPCC-like cases and 338 controls where it was also significantly associated with MSS HNPCC cases (P = 0.041). In the combined genotype data, rs67687202 was associated with a moderate increase in CRC risk (OR = 1.68; 95% CI = 1.13-2.50; P = 0.010). We tested a highly correlated SNP rs868 in 723 non-familial CRC cases compared with 629 controls, and it was not significantly associated with CRC risk (P = 0.370). rs868 is contained in a let-7 miRNA binding site in the 3'UTR of TGFBR1, which might provide a functional basis for the association in MSS HNPCC. In luciferase assays, the risk-associated allele for rs868 was associated with half the luciferase expression in the presence of miRNA let-7b-5p compared with protective allele, suggesting more binding of let-7b-5p and less TGFBR1 expression. Thus, rs868 potentially is a CRC risk-causing allele. Our results support the concept that rs868 is associated with lower TGFBR1 expression thereby increasing CRC risk.
C1 [Xicola, Rosa M.; Bontu, Sneha; LLor, Xavier] Yale Univ, Dept Med, New Haven, CT 06520 USA.
[Xicola, Rosa M.; Bontu, Sneha; LLor, Xavier] Yale Univ, Ctr Canc, New Haven, CT 06520 USA.
[Doyle, Brian J.; Rawson, Jamie; Lee, Esther] Univ Illinois, Dept Med, Chicago, IL USA.
[Doyle, Brian J.; Rawson, Jamie; Lee, Esther] Univ Illinois, Ctr Canc, Chicago, IL USA.
[Garre, Pilar; de la Hoya, Miguel; Caldes, Trinidad] Hosp Clin San Carlos, IdISSC, Lab Oncol Mol, Madrid, Spain.
[Bessa, Xavier; Andreu, Montserrat] Hosp del Mar, Dept Gastroenterol, Barcelona, Catalonia, Spain.
[Clofent, Joan] Hosp Sagunto, Dept Gastroenterol, Valencia, Spain.
[Bujanda, Luis] Univ Pais Vasco UPV EHU, Hosp Donostia, Inst Biodonostia, Dept Gastroenterol,CIBERehd, San Sebastian, Spain.
[Balaguer, Francesc; Castellvi-Bel, Sergi; Castells, Antoni] Univ Barcelona, Hosp Clin, Dept Gastroenterol, IDIBAPS,CIBERehd, Barcelona, Spain.
[Alenda, Cristina; Jover, Rodrigo] Hosp Gen Univ Alicante, Dept Gastroenterol, Alicante, Spain.
[Alenda, Cristina; Jover, Rodrigo] Hosp Gen Univ Alicante, Dept Pathol, Alicante, Spain.
[Ruiz-Ponte, Clara; Carracedo, Angel] FPGMX, SERGAS, Ctr Invest Biomed Red Enfermedades Raras CIBERer, Grp Med Xen,IDIS, Santiago De Compostela, Galiza, Spain.
[Syngal, Sapna] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Newcomb, Polly A.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Lindor, Noralane] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA.
[Potter, John D.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, 1124 Columbia St, Seattle, WA 98104 USA.
[Potter, John D.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Potter, John D.] Ctr Publ Hlth Res, Wellington, New Zealand.
[Baron, John A.] Dartmouth Coll, Dept Biostat & Epidemiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA.
[Ellis, Nathan A.] Univ Arizona, Dept Cellular & Mol Med, Tucson, AZ USA.
RP LLor, X (reprint author), Yale Univ, Dept Med, New Haven, CT 06520 USA.; LLor, X (reprint author), Yale Univ, Ctr Canc, New Haven, CT 06520 USA.; Caldes, T (reprint author), Hosp Clin San Carlos, IdISSC, Lab Oncol Mol, Madrid, Spain.
EM trinidad.caldes@salud.madrid.org; xavier.llor@yale.edu
OI Bessa Caserras, Xavier/0000-0003-4680-1228
FU Sirazi Foundation; University of Illinois at Chicago, Office of the Vice
Chancellor for Research; Department of Medicine and Cancer Center of the
University of Illinois; ISCIII (Spain) [PI13/02588, RD12/0036/006];
European Regional Development FEDER funds; National Cancer Institute
[UM1 CA167551]
FX This work was supported in part by Sirazi Foundation; Area of Excellence
Award from the University of Illinois at Chicago, Office of the Vice
Chancellor for Research; the Department of Medicine and Cancer Center of
the University of Illinois (X.L.). T.C., P.G. and M.d.H. were supported
by PI13/02588 and RD12/0036/006 from ISCIII (Spain) and the European
Regional Development FEDER funds. The Colon Cancer Family Registry
(CCFR) was supported by grant UM1 CA167551 from the National Cancer
Institute. The following CCFR centers provided samples and data for this
study: Australasian Colorectal Cancer Family Registry (U01/U24
CA097735), USC Consortium Colorectal Cancer Family Registry (U01/U24
CA074799), Mayo Clinic Cooperative Family Registry for Colon Cancer
Studies (U01/U24 CA074800), Ontario Registry for Studies of Familial
Colorectal Cancer (U01/U24 CA074783), Seattle Colorectal Cancer Family
Registry (U01/U24 CA074794) and University of Hawaii Colorectal Cancer
Family Registry (U01/U24 CA074806).
NR 50
TC 0
Z9 0
U1 5
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD AUG
PY 2016
VL 37
IS 8
BP 751
EP 758
DI 10.1093/carcin/bgw064
PG 8
WC Oncology
SC Oncology
GA DV8OF
UT WOS:000383195600002
PM 27234654
ER
PT J
AU Lanham, HJ
Palmer, RF
Leykum, LK
McDaniel, RR
Nutting, PA
Stange, KC
Crabtree, BF
Miller, WL
Jaen, CR
AF Lanham, Holly Jordan
Palmer, Raymond F.
Leykum, Luci K.
McDaniel, Reuben R., Jr.
Nutting, Paul A.
Stange, Kurt C.
Crabtree, Benjamin F.
Miller, William L.
Jaen, Carlos Roberto
TI Trust and Reflection in Primary Care Practice Redesign
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Practice redesign; relationships; reflection; sensemaking; learning
ID CENTERED MEDICAL HOME; NATIONAL DEMONSTRATION PROJECT; COMPLEXITY
SCIENCE; HEALTH-CARE; TRANSFORMATION; LESSONS; TEAMS; ORGANIZATIONS;
SENSEMAKING; SAFETY
AB Objective. To test a conceptual model of relationships, reflection, sensemaking, and learning in primary care practices transitioning to patient-centered medical homes (PCMH).
Data Sources/Study Setting. Primary data were collected as part of the American Academy of Family Physicians' National Demonstration Project of the PCMH.
Study Design. We conducted a cross-sectional survey of clinicians and staff from 36 family medicine practices across the United States. Surveys measured seven characteristics of practice relationships (trust, diversity, mindfulness, heedful interrelation, respectful interaction, social/task relatedness, and rich and lean communication) and three organizational attributes (reflection, sensemaking, and learning) of practices.
Data Collection/Extraction Methods. We surveyed 396 clinicians and practice staff. We performed a multigroup path analysis of the data. Parameter estimates were calculated using a Bayesian estimation method. Principal Findings. Trust and reflection were important in explaining the characteristics of practice relationships and their associations with sensemaking and learning. The strongest associations between relationships, sensemaking, and learning were found under conditions of high trust and reflection. The weakest associations were found under conditions of low trust and reflection.
Conclusions. Trust and reflection appear to play a key role in moderating relationships, sensemaking, and learning in practices undergoing practice redesign.
C1 [Lanham, Holly Jordan; Leykum, Luci K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hosp Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
[Lanham, Holly Jordan; Palmer, Raymond F.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
[Lanham, Holly Jordan; Leykum, Luci K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Lanham, Holly Jordan; Leykum, Luci K.; McDaniel, Reuben R., Jr.] Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, San Antonio, TX USA.
[Nutting, Paul A.] Ctr Res Strategies, Denver, CO USA.
[Stange, Kurt C.] Case Western Reserve Univ, Dept Family Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Stange, Kurt C.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Stange, Kurt C.] Case Western Reserve Univ, Dept Sociol, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Crabtree, Benjamin F.] Rutgers Robert Wood Johnson Med Sch, Dept Family Med & Community Hlth, New Brunswick, NJ USA.
[Miller, William L.] Lehigh Valley Hlth Network, Dept Family Med, Allentown, PA USA.
[Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, Res Adv Community Hlth Ctr, San Antonio, TX 78229 USA.
[Jaen, Carlos Roberto] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, Res Adv Community Hlth Ctr, San Antonio, TX 78229 USA.
RP Lanham, HJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med Hosp Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.; Lanham, HJ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA.; Lanham, HJ (reprint author), South Texas Vet Hlth Care Syst, San Antonio, TX USA.; Lanham, HJ (reprint author), Univ Texas Austin, Dept Informat Risk & Operat Management, McCombs Sch Business, San Antonio, TX USA.
EM lanham@uthscsa.edu
FU American Academy of Family Physicians; Commonwealth Fund, a national,
private foundation based in New York City; Department of Veterans
Affairs; Veterans Health Administration; Health Services Research and
Development Service [CDA 07-022]; South Texas Veterans Health Care
System; Charles and Elizabeth Prothro Chair in Health Care Management,
the University of Texas at Austin; Harry and Elsa Jiler American Cancer
Society; National Cancer Institute [K05 CA140237]
FX The authors express their appreciation for the cooperation and
dedication of the physicians and staff of the family practices that
participated in the NDP. We also thank the anonymous reviewers for their
comments and insights. The American Academy of Family Physicians
provided funding support for this evaluation, including a Research
Center grant. The evaluation was also partially supported by the
Commonwealth Fund, a national, private foundation based in New York City
that supports independent research on health care issues and makes
grants to improve health care practice and policy. LKL was supported by
the Department of Veterans Affairs, Veterans Health Administration, and
Health Services Research and Development Service (CDA 07-022) and her
investigator salary support is provided through this funding and through
the South Texas Veterans Health Care System. RMD receives support from
the Charles and Elizabeth Prothro Chair in Health Care Management, the
University of Texas at Austin. KCS was supported in part by the Harry
and Elsa Jiler American Cancer Society Clinical Research Professorship.
BFC was supported in part by a National Cancer Institute K05 Senior
Investigator Award (K05 CA140237).
NR 72
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U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
EI 1475-6773
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2016
VL 51
IS 4
BP 1489
EP 1514
DI 10.1111/1475-6773.12415
PG 26
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DX9VO
UT WOS:000384745300010
PM 26611650
ER
PT J
AU Keating, NL
Kouri, EM
He, YL
Freedman, RA
Volya, R
Zaslavsky, AM
AF Keating, Nancy L.
Kouri, Elena M.
He, Yulei
Freedman, Rachel A.
Volya, Rita
Zaslavsky, Alan M.
TI Location Isn't Everything: Proximity, Hospital Characteristics, Choice
of Hospital, and Disparities for Breast Cancer Surgery Patients
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Breast cancer; surgery; health care disparities; hospital racial
composition; distance
ID ACUTE MYOCARDIAL-INFARCTION; SEER-MEDICARE DATA; QUALITY-OF-CARE;
HEALTH-CARE; BLACK PATIENTS; RACIAL DISPARITIES; UNDERGO-SURGERY;
UNITED-STATES; SATISFACTION; CONCORDANCE
AB Objective. Assess the relative importance of proximity and other hospital characteristics in the choice of hospital for breast cancer surgery by race/ethnicity.
Data. SEER-Medicare data.
Study Design. Observational study of women aged >65 years receiving surgery for stage I/II/III breast cancer diagnosed in 1992-2007 in Detroit (N = 10,746 white/black), Atlanta (N = 4,018 white/black), Los Angeles (N = 9,433 white/black/Asian/Hispanic), and San Francisco (N = 4,856 white/black/Asian). We calculated the distance from each patient's census tract of residence to each area hospital. We estimated discrete choice models for the probability of receiving surgery at each hospital based on distance and assessed whether deviations from these predictions entailed interactions of hospital characteristics with the patient's race/ethnicity. We identified high-quality hospitals by rates of adjuvant radiation therapy and by survey measures of patient experiences, and we assessed how observed surgery rates at high-quality hospitals deviated from those predicted based on distance alone.
Principal Findings. Proximity was significantly associated with hospital choice in all areas. Minority more often than white breast cancer patients had surgery at hospitals with more minority patients, those treating more Medicaid patients, and in some areas, lower quality hospitals.
Conclusions. Residential location alone does not explain concentration of racial/ethnic-minority breast cancer surgery patients in certain hospitals that are sometimes of lower quality.
C1 [Keating, Nancy L.; Kouri, Elena M.; Volya, Rita; Zaslavsky, Alan M.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
[He, Yulei] Ctr Dis Control & Prevent, Off Res & Methodol, Natl Ctr Hlth Stat, Hyattsville, MD USA.
[Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Keating, NL (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.; Keating, NL (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
FU California Department of Public Health as part of the statewide cancer
reporting program; National Cancer Institute's Surveillance,
Epidemiology and End Results Program [N01-PC-35136, N01-PC-35139,
N02-PC-15105]; Centers for Disease Control and Prevention's National
Program of Cancer Registries [U55/CCR921930-02]; Susan G. Komen for the
Cure
FX This study used the linked SEER-Medicare database. The interpretation
and reporting of these data are the sole responsibility of the authors.
The authors acknowledge the efforts of the Applied Research Program,
NCI; the Office of Research, Development and Information, CMS;
Information Management Services (IMS), Inc.; and the Surveillance,
Epidemiology, and End Results (SEER) Program tumor registries in the
creation of the SEER-Medicare database. The collection of the California
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 under contract N01-PC-35136 awarded to the Northern
California Cancer Center, contract N01-PC-35139 awarded to the
University of Southern California, and contract N02-PC-15105 awarded to
the Public Health Institute; and the Centers for Disease Control and
Prevention's National Program of Cancer Registries, under agreement
#U55/CCR921930-02 awarded to the Public Health Institute. The ideas and
opinions expressed herein are those of the author(s) and endorsement by
the State of California, Department of Public Health the National Cancer
Institute, and the Centers for Disease Control and Prevention or their
Contractors and Subcontractors is not intended nor should be inferred.
This paper was developed while Yulei He was at Harvard Medical School.
The findings and conclusions in this paper are those of the authors and
do not necessarily represent the official position of the National
Center for Health Statistics, Centers for Disease Control and
Prevention. The study was supported by Susan G. Komen for the Cure.
NR 28
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U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
EI 1475-6773
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2016
VL 51
IS 4
BP 1561
EP 1583
DI 10.1111/1475-6773.12443
PG 23
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DX9VO
UT WOS:000384745300014
PM 26800094
ER
PT J
AU Keating, NL
Landrum, MB
Huskamp, HA
Kouri, EM
Prigerson, HG
Schrag, D
Maciejewski, PK
Hornbrook, MC
Haggstrom, DA
AF Keating, Nancy L.
Landrum, Mary Beth
Huskamp, Haiden A.
Kouri, Elena M.
Prigerson, Holly G.
Schrag, Deborah
Maciejewski, Paul K.
Hornbrook, Mark C.
Haggstrom, David A.
TI Dartmouth Atlas Area-Level Estimates of End-of-Life Expenditures: How
Well Do They Reflect Expenditures for Prospectively Identified Advanced
Lung Cancer Patients?
SO HEALTH SERVICES RESEARCH
LA English
DT Article
DE Variation; health care expenditures; lung cancer
ID UNITED-STATES; REGIONAL-VARIATIONS; CARE; MEDICARE; OUTCOMES; HOSPITALS;
SERVICES; COSTS
AB Objective. Assess validity of the retrospective Dartmouth hospital referral region (HRR) end-of-life spending measures by comparing with health care expenditures from diagnosis to death for prospectively identified advanced lung cancer patients.
Data/Setting/Design. We calculated health care spending from diagnosis (2003-2005) to death or through 2011 for 885 patients aged >= 65 years with advanced lung cancer using Medicare claims. We assessed the association between Dartmouth HRR-level spending in the last 2 years of life and patient-level spending using linear regression with random HRR effects, adjusting for patient characteristics.
Findings. For each $1 increase in the Dartmouth metric, spending for our cohort increased by $0.74 (p < .001). The Dartmouth spending variable explained 93.4 percent of the HRR-level variance in observed spending.
Conclusions. HRR-level spending estimates for deceased patient cohorts reflect area-level care intensity for prospectively identified advanced lung cancer patients.
C1 [Keating, Nancy L.; Landrum, Mary Beth; Huskamp, Haiden A.; Kouri, Elena M.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
[Prigerson, Holly G.] New York Presbyterian Hosp, Ctr Res End Of Life Care, Weill Cornell Med Coll, New York, NY USA.
[Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Maciejewski, Paul K.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA.
[Hornbrook, Mark C.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA.
[Haggstrom, David A.] Indiana Univ Sch Med, VA HSR & D Ctr Hlth Informat & Commun, Indianapolis, IN 46202 USA.
RP Keating, NL (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA.; Keating, NL (reprint author), Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
EM keating@hcp.med.harvard.edu
FU National Cancer Institute [1R01CA164021, K24CA181510, 5U01CA093344-08];
National Cancer Institute (NCI) [U01 CA093344]; NCI [U01 CA093332];
Harvard Medical School/ Northern California Cancer Center [U01
CA093324]; RAND/UCLA [U01 CA093348]; University of Alabama at Birmingham
[U01 CA093329]; University of Iowa [U01 CA093339]; University of North
Carolina [U01 CA093326]; Department of Veteran's Affairs grant [CRS
02-164]
FX This work was funded by 1R01CA164021 from the National Cancer Institute.
Dr. Keating is also supported by K24CA181510 from the National Cancer
Institute. This original Cancer Care Outcomes Research and Surveillance
(CanCORS) Consortium study was supported by grants from the National
Cancer Institute (NCI) to the Statistical Coordinating Center (U01
CA093344) and the NCI-supported Primary Data Collection and Research
Centers (Dana Farber Cancer Institute/Cancer Research Network U01
CA093332, Harvard Medical School/ Northern California Cancer Center U01
CA093324, RAND/UCLA U01 CA093348, University of Alabama at Birmingham
U01 CA093329, University of Iowa U01 CA093339, University of North
Carolina U01 CA093326) and by a Department of Veteran's Affairs grant to
the Durham VA Medical Center CRS 02-164. The CanCORS II data collection
was funded by 5U01CA093344-08 from the National Cancer Institute to the
Cancer Care Outcomes Research and Surveillance (CanCORS) Consortium
Statistical Coordinating Center. The authors thank Rita Volya, MS, for
expert programming assistance.
NR 20
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U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0017-9124
EI 1475-6773
J9 HEALTH SERV RES
JI Health Serv. Res.
PD AUG
PY 2016
VL 51
IS 4
BP 1584
EP 1594
DI 10.1111/1475-6773.12440
PG 11
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DX9VO
UT WOS:000384745300015
PM 26799913
ER
PT J
AU Dekel, S
Stanger, V
Georgakopoulos, ER
Stuebe, CM
Dishy, GA
AF Dekel, Sharon
Stanger, Varda
Georgakopoulos, Emily R.
Stuebe, Caren M.
Dishy, Gabriella A.
TI Peripartum Depression, Traditional Culture, and Israeli Society
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE peripartum depression; traditional culture; posttraumatic stress
symptoms; ultra-Orthodox; Israel
ID POSTTRAUMATIC-STRESS-DISORDER; POSTPARTUM DEPRESSION; RISK-FACTORS;
POSTNATAL DEPRESSION; MENTAL-ILLNESS; SYMPTOMS; WOMEN; PREVALENCE;
COHORT; ASSOCIATION
AB Although it is known that culture affects psychopathology, the nature of the relationship between culture and peripartum depression (PPD) is not fully understood. Here we report on 2 cases of Israeli women who are affiliated with traditional cultural groups that emphasize reproduction but developed PPD after childbirth. The first woman is an ultra-Orthodox Israeli Jew and the second is an Israeli Arab. The 2 cases illustrate the effect of cultural beliefs and rituals on the conceptualization, treatment, and trajectory of PPD. The cases suggest a complex relationship between traditional cultures and PPD, including the possibility that cultural factors may have both adaptive and maladaptive consequences. Future qualitative and quantitative studies are needed to further clarify this relationship.
C1 [Dekel, Sharon; Georgakopoulos, Emily R.; Stuebe, Caren M.; Dishy, Gabriella A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Dekel, Sharon] Harvard Med Sch, Boston, MA USA.
[Stanger, Varda] Sheba Med Ctr, Ramat Gan, Israel.
[Stanger, Varda] Bar Ilan Univ, IL-52100 Ramat Gan, Israel.
[Georgakopoulos, Emily R.; Stuebe, Caren M.] Boston Univ, Boston, MA 02215 USA.
RP Dekel, S (reprint author), Massachusetts Gen Hosp East, PTSD Res Lab, 120 Second Ave, Charlestown, MA 02129 USA.
EM sdekel@mgh.harvard.edu
FU Claflin Distinguished Scholar Award; Brain and Behavior (NARSAD) grant
FX This work was supported by the Claflin Distinguished Scholar Award and
the Brain and Behavior (NARSAD) grant awarded to Dr. Dekel.
NR 35
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U1 6
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9762
EI 1097-4679
J9 J CLIN PSYCHOL
JI J. Clin. Psychol.
PD AUG
PY 2016
VL 72
IS 8
SI SI
BP 784
EP 794
DI 10.1002/jclp.22360
PG 11
WC Psychology, Clinical
SC Psychology
GA DW4NO
UT WOS:000383620200004
PM 27487164
ER
PT J
AU Karimnejad, K
Czerny, MS
Lookabaugh, S
Lee, DJ
Mikulec, AA
AF Karimnejad, K.
Czerny, M. S.
Lookabaugh, S.
Lee, D. J.
Mikulec, A. A.
TI Gender and laterality in semicircular canal dehiscence syndrome
SO JOURNAL OF LARYNGOLOGY AND OTOLOGY
LA English
DT Article
DE Semicircular Canals; Vertigo; Hearing Loss; Conductive; Temporal Lobe;
Parietal Lobe; Health Status
ID VIBRATION-INDUCED NYSTAGMUS; CONDUCTIVE HEARING-LOSS; TULLIO PHENOMENON;
CLINICAL-EXPERIENCE; COMPUTED-TOMOGRAPHY; HUMAN BRAIN; CASE SERIES;
SUPERIOR; SYMPTOMS; MANAGEMENT
AB Objective: To determine if there is gender or laterality predilection in patients with semicircular canal dehiscence syndrome.
Methods: A multi-institutional chart review was performed to identify patients diagnosed with semicircular canal dehiscence between 2000 and 2015. A systematic literature search was conducted using PubMed to further identify patients with semicircular canal dehiscence. Age, gender and laterality data were collected. Statistical analysis was performed to evaluate for gender or laterality preponderance.
Results: A total of 682 patients with semicircular canal dehiscence were identified by literature and chart review. Mean age of diagnosis was 49.75 years (standard deviation = 15.33). Semicircular canal dehiscence was associated with a statistically significant female predominance (chi-square = 7.185, p = 0.007); the female-to-male ratio was 1.2 to 1. Left-sided semicircular canal dehiscence was most common, followed by right-sided then bilateral (chi-square = 23.457, p < 0.001).
Conclusion: Semicircular canal dehiscence syndrome is most commonly left-sided and exhibits a female predominance. This may be secondary to morphological cerebral hemisphere asymmetries in both sexes and a predilection of women to seek more medical care than men.
C1 [Karimnejad, K.; Mikulec, A. A.] St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave,6FDT, St Louis, MO 63110 USA.
[Czerny, M. S.] Ear Nose & Throat Inst Southern Illinois, Swansea, W Glam, Wales.
[Lookabaugh, S.] Univ Rochester, Med Ctr, Dept Otolaryngol, New York, NY USA.
[Lee, D. J.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA.
RP Mikulec, AA (reprint author), St Louis Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, 3635 Vista Ave,6FDT, St Louis, MO 63110 USA.
EM mikuleca@slu.edu
NR 49
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U1 1
U2 1
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 0022-2151
EI 1748-5460
J9 J LARYNGOL OTOL
JI J. Laryngol. Otol.
PD AUG
PY 2016
VL 130
IS 8
BP 712
EP 716
DI 10.1017/S0022215116008185
PG 5
WC Otorhinolaryngology
SC Otorhinolaryngology
GA DX9KQ
UT WOS:000384714600004
PM 27345153
ER
PT J
AU Altawalbeh, SM
Thorpe, CT
Zgibor, JC
Kane-Gill, S
Kang, YH
Thorpe, JM
AF Altawalbeh, Shoroq M.
Thorpe, Carolyn T.
Zgibor, Janice C.
Kane-Gill, Sandra
Kang, Yihuang
Thorpe, Joshua M.
TI Antileukotriene Agents Versus Long-Acting Beta-Agonists in Older Adults
with Persistent Asthma: A Comparison of Add-On Therapies
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE asthma; older adults; cardiovascular; Medicare
ID INHALED CORTICOSTEROIDS; UNITED-STATES; CONTROLLER MEDICATIONS;
CARDIOVASCULAR-DISEASE; RESOURCE UTILIZATION; ELDERLY-PATIENTS;
MONTELUKAST; SAFETY; EXACERBATIONS; SURVEILLANCE
AB ObjectivesTo compare the effectiveness and cardiovascular safety of long-acting beta-agonists (LABAs) with those of leukotriene receptor antagonists (LTRAs) as add-on treatments in older adults with asthma already taking inhaled corticosteroids (ICSs).
DesignRetrospective cohort study.
SettingMedicare fee-for-service (FFS) claims (2009-10) for a 10% random sample of beneficiaries continuously enrolled in Parts A, B, and D in 2009.
ParticipantsMedicare beneficiaries aged 66 and older continuously enrolled in FFS Medicare with Part D coverage with a diagnosis of asthma before 2009 treated exclusively with ICSs plus LABAs or ICSs plus LTRAs (N = 14,702).
MeasurementsThe augmented inverse propensity-weighted estimator was used to compare the effect of LABA add-on therapy with that of LTRA add-on therapy on asthma exacerbations requiring inpatient, emergency, or outpatient care and on cardiovascular (CV) events, adjusting for demographic characteristics, comorbidities, and county-level healthcare-access variables.
ResultsThe primary analysis showed that LTRA add-on treatment was associated with greater odds of asthma-related hospitalizations or emergency department visits (odds ratio (OR) = 1.4, P < .001), as well as outpatient exacerbations requiring oral corticosteroids or antibiotics (OR = 1.41, P < .001) than LABA treatment. LTRA add-on therapy was also less effective in controlling acute symptoms, as indicated by greater use of short-acting beta agonists (rate ratio = 1.58, P < .001). LTRA add-on treatment was associated with lower odds of experiencing a CV event than LABA treatment (OR = 0.86, P = .006).
ConclusionThis study provides new evidence specific to older adults to help healthcare providers weigh the risks and benefits of these add-on treatments. Further subgroup analysis is needed to personalize asthma treatments in this high-risk population.
C1 [Altawalbeh, Shoroq M.] Univ Pittsburgh, Dept Pharmaceut Sci, Ctr Clin Pharmaceut Sci, Pittsburgh, PA USA.
[Thorpe, Carolyn T.; Kane-Gill, Sandra; Thorpe, Joshua M.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA.
[Thorpe, Carolyn T.; Thorpe, Joshua M.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Zgibor, Janice C.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
Natl Sun Yat Sen Univ, Dept Informat Management, Kaohsiung, Taiwan.
RP Altawalbeh, SM (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 3501 Terrace St,916 Salk, Pittsburgh, PA 15261 USA.
EM sha55@pitt.edu
FU University of Pittsburgh School of Pharmacy; Pittsburgh Claude D. Pepper
Older Americans Independence Center [NIA P30 AGAG024827]
FX The University of Pittsburgh School of Pharmacy and the Pittsburgh
Claude D. Pepper Older Americans Independence Center (NIA P30
AGAG024827) provided support for this study.
NR 50
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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 AUG
PY 2016
VL 64
IS 8
BP 1592
EP 1600
DI 10.1111/jgs.14235
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DW3KW
UT WOS:000383541500009
PM 27351988
ER
PT J
AU Linos, E
Chren, MM
Cenzer, IS
Covinsky, KE
AF Linos, Eleni
Chren, Mary-Margaret
Cenzer, Irena Stijacic
Covinsky, Kenneth E.
TI Skin Cancer in US Elderly Adults: Does Life Expectancy Play a Role in
Treatment Decisions?
SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
LA English
DT Article
DE skin cancer; basal cell carcinoma; squamous cell carcinoma; end of life
ID BASAL-CELL CARCINOMA; OLDER-ADULTS; VALIDATION; INDEX; CARE; END
AB ObjectivesTo examine whether life expectancy influences treatment pattern of nonmelanoma skin cancer, or keratinocyte carcinoma (KC), the most common malignancy and the fifth most costly cancer to Medicare.
DesignNationally representative cross-sectional study.
SettingNationally representative Health and Retirement Study linked to Medicare claims.
ParticipantsTreatments (N = 9,653) from individuals aged 65 and older treated for basal or squamous cell carcinoma between 1992 and 2012 (N = 2,702) were included.
MeasurementsLimited life expectancy defined according to aged 85 and older, medical comorbidities, Charlson Comorbidity Index score of 3 or greater, difficulty in at least one activity of daily living (ADL), and a Lee index of 13 or greater. Treatment type (Mohs micrographic surgery (MMS) (most intensive, highest cost), excision, or electrodesiccation and curettage (ED&C) (least intensive, lowest cost)), according to procedure code.
ResultsMost KCs (61%) were treated surgically. Rates of MMS (19%), excision (42%), and ED&C (39%) were no different in participants with limited life expectancy and those with normal life expectancy. For example, 19% of participants with difficulty or dependence in ADLs, 20% of those with a Charlson comorbidity score greater than 3, and 15% of those in their last year of life underwent MMS; participants who died within 1 year of diagnosis were treated in the same way as those who lived longer.
ConclusionA one-size-fits-all approach in which advanced age, health status, functional status, and prognosis are not associated with intensiveness of treatment appears to guide treatment for KC, a generally nonfatal condition. Although intensive treatment of skin cancer when it causes symptoms may be indicated regardless of life expectancy, persons with limited life expectancy should be given choices to ensure that the treatment matches their goals and preferences.
C1 [Linos, Eleni; Chren, Mary-Margaret] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Cenzer, Irena Stijacic; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA.
[Cenzer, Irena Stijacic; Covinsky, Kenneth E.] San Francisco VA Med Ctr, San Francisco, CA USA.
RP Linos, E (reprint author), Dept Dermatol, 2340 Sutter St,Room N421 Mail Code Box 0808, San Francisco, CA 94143 USA.
EM linose@derm.ucsf.edu
FU National Institutes of Health through the National Center for Research
Resources [KL2RR024130]; National Institute of Arthritis and
Musculoskeletal and Skin Diseases [K24 AR052667, R01 AR 054983];
National Institute of Nursing Research [R01 NR013347]; Claude D. Pepper
Older Americans Independence Center at the National Institute on Aging,
National Institutes of Health [P30 AG044281]
FX This work was supported by the National Institutes of Health through the
National Center for Research Resources (Grant KL2RR024130 to EL), the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(Grants K24 AR052667 and R01 AR 054983 to MMC), the National Institute
of Nursing Research (Grant R01 NR013347 to KC), and the Claude D. Pepper
Older Americans Independence Center at the National Institute on Aging,
National Institutes of Health (Grant P30 AG044281 to KC).
NR 23
TC 0
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U1 4
U2 4
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 AUG
PY 2016
VL 64
IS 8
BP 1610
EP 1615
DI 10.1111/jgs.14202
PG 6
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DW3KW
UT WOS:000383541500011
PM 27303932
ER
PT J
AU Wallin, JJ
Bendell, JC
Funke, R
Sznol, M
Korski, K
Jones, S
Hernandez, G
Mier, J
He, X
Hodi, FS
Denker, M
Leveque, V
Canamero, M
Babitski, G
Koeppen, H
Ziai, J
Sharma, N
Gaire, F
Chen, DS
Waterkamp, D
Hegde, PS
McDermott, DF
AF Wallin, Jeffrey J.
Bendell, Johanna C.
Funke, Roel
Sznol, Mario
Korski, Konstanty
Jones, Suzanne
Hernandez, Genevive
Mier, James
He, Xian
Hodi, F. Stephen
Denker, Mitchell
Leveque, Vincent
Canamero, Marta
Babitski, Galina
Koeppen, Hartmut
Ziai, James
Sharma, Neeraj
Gaire, Fabien
Chen, Daniel S.
Waterkamp, Daniel
Hegde, Priti S.
McDermott, David F.
TI Atezolizumab in combination with bevacizumab enhances antigen-specific
T-cell migration in metastatic renal cell carcinoma
SO NATURE COMMUNICATIONS
LA English
DT Article
ID TUMOR; CANCER; GROWTH; PHASE; ANTIBODY; IDENTIFICATION; VACCINE; TRIAL;
MICE
AB Anti-tumour immune activation by checkpoint inhibitors leads to durable responses in a variety of cancers, but combination approaches are required to extend this benefit beyond a subset of patients. In preclinical models tumour-derived VEGF limits immune cell activity while anti-VEGF augments intra-tumoral T-cell infiltration, potentially through vascular normalization and endothelial cell activation. This study investigates how VEGF blockade with bevacizumab could potentiate PD-L1 checkpoint inhibition with atezolizumab in mRCC. Tissue collections are before treatment, after bevacizumab and after the addition of atezolizumab. We discover that intra-tumoral CD8(+) T cells increase following combination treatment. A related increase is found in intra-tumoral MHC-I, Th1 and T-effector markers, and chemokines, most notably CX3CL1 (fractalkine). We also discover that the fractalkine receptor increases on peripheral CD8(+) T cells with treatment. Furthermore, trafficking lymphocyte increases are observed in tumors following bevacizumab and combination treatment. These data suggest that the anti-VEGF and anti-PD-L1 combination improves antigen-specific T-cell migration.
C1 [Wallin, Jeffrey J.; Funke, Roel; Hernandez, Genevive; He, Xian; Denker, Mitchell; Leveque, Vincent; Koeppen, Hartmut; Ziai, James; Sharma, Neeraj; Chen, Daniel S.; Waterkamp, Daniel; Hegde, Priti S.] Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
[Bendell, Johanna C.; Jones, Suzanne] Sarah Cannon Res Inst, GI Oncol Res, Drug Dev Unit, 250 25th Ave North,Suite 100, Nashville, TN 37203 USA.
[Sznol, Mario] Yale Canc Ctr, Dept Internal Med, New Haven, CT 06511 USA.
[Sznol, Mario] Yale Canc Ctr, Melanoma Unit, New Haven, CT 06511 USA.
[Korski, Konstanty; Canamero, Marta; Babitski, Galina; Gaire, Fabien] Roche Diagnost GmbH, Nonnenwald 2, D-82377 Penzberg, Germany.
[Mier, James; McDermott, David F.] Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA.
[Hodi, F. Stephen] Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave, Boston, MA 02215 USA.
RP Wallin, JJ (reprint author), Genentech Inc, 1 DNA Way, San Francisco, CA 94080 USA.
EM jwallin@gene.com
FU Genentech, Inc., a member of the Roche Group
FX This study was sponsored by Genentech, Inc., a member of the Roche
Group, which provided the study drug. Some of the authors of this
manuscript are employees of Genentech/Roche. The remaining authors
declare no competing financial interests.
NR 28
TC 6
Z9 6
U1 7
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD AUG
PY 2016
VL 7
AR 12624
DI 10.1038/ncomms12624
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DX9AU
UT WOS:000384686000001
PM 27571927
ER
PT J
AU Chau, NG
Hammerman, PS
AF Chau, Nicole G.
Hammerman, Peter S.
TI Heads Up! Predictive Gene Signatures in Head and Neck Cancer May Be
Coming Soon
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CHEMOTHERAPY PLUS CETUXIMAB; SQUAMOUS-CELL CARCINOMA; LUNG-CANCER;
EXPRESSION; SUBTYPES; EXTREME
AB Cetuximab-platinum chemotherapy is used for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC); however, a minority of patients benefit. Gene expression profiling (GEP) of HNSCCs with prolonged responses to cetuximab-chemotherapy demonstrate basal subtype traits including signatures of EGFR signaling and hypoxic differentiation. GEP of short-response patients show RAS activation. (C) 2016 AACR.
C1 [Chau, Nicole G.; Hammerman, Peter S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Chau, Nicole G.; Hammerman, Peter S.] Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA.
RP Hammerman, PS (reprint author), Harvard Med Sch, 450 Brookline Ave, Boston, MA 02215 USA.; Hammerman, PS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM peter_hammerman@dfci.harvard.edu
NR 12
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 AUG 1
PY 2016
VL 22
IS 15
BP 3710
EP 3712
DI 10.1158/1078-0432.CCR-16-0582
PG 3
WC Oncology
SC Oncology
GA DU5QE
UT WOS:000382265600002
PM 27129579
ER
PT J
AU Padron, E
Dezern, A
Andrade-Campos, M
Vaddi, K
Scherle, P
Zhang, Q
Ma, Y
Balasis, ME
Tinsley, S
Ramadan, H
Zimmerman, C
Steensma, DP
Roboz, GJ
Lancet, JE
List, AF
Sekeres, MA
Komrokji, RS
AF Padron, Eric
Dezern, Amy
Andrade-Campos, Marcio
Vaddi, Kris
Scherle, Peggy
Zhang, Qing
Ma, Yan
Balasis, Maria E.
Tinsley, Sara
Ramadan, Hanadi
Zimmerman, Cassandra
Steensma, David P.
Roboz, Gail J.
Lancet, Jeffrey E.
List, Alan F.
Sekeres, Mikkael A.
Komrokji, Rami S.
CA Myelodysplastic Syndrome Clinical
TI A Multi-Institution Phase I Trial of Ruxolitinib in Patients with
Chronic Myelomonocytic Leukemia (CMML)
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MYELODYSPLASTIC/MYELOPROLIFERATIVE NEOPLASMS MDS/MPN; QUALITY-OF-LIFE;
MYELODYSPLASTIC SYNDROMES; RESPONSE CRITERIA; MYELOID-LEUKEMIA;
GENE-MUTATIONS; MYELOFIBROSIS; AZACITIDINE; INHIBITOR; PROPOSAL
AB Purpose: To conduct a phase I clinical trial exploring the safety and efficacy of ruxolitinib, a JAK1/2 inhibitor, for chronic myelomonocytic leukemia (CMML).
Experimental Design: Patients with CMML-1 were included without regard to previous therapy. Key exclusion criteria included an absolute neutrophil count (ANC) < 0.25 x 10(3) cells/dL and a platelet count < 35 x 10(3) cells/dL. Four cohorts were enrolled using a "rolling six" study design, with doses ranging from 5 to 20 mg twice daily of ruxolitinib in 5-mg dose escalations.
Results: Between March 2013 and January 2015, 20 patients were enrolled and treated with ruxolitinib. Seventy percent of patients had the proliferative subtype and 47% had higher risk disease by the Global MD Anderson Scoring System. Eight patients (42%) received a prior hypomethylating agent. No dose-limiting toxicities for ruxolitinib were identified. One subject had grade (G) 3 thrombocytopenia with no other drug-associated G3 or G4 adverse events. The mean duration of therapy was 122 days (range, 28-409 days). Four had hematologic improvement and one patient had a partial response per 2006 International Working Group (IWG) criteria. Five of 9 patients with splenomegaly had a reduction in spleen size. Ten of 11 patients with reported disease-related symptoms had clinically meaningful or complete resolution. When combining IWG and spleen responses, a total response rate of 35% (n = 7) was identified. Correlative analysis demonstrated a reduction in inflammatory cytokines and GM-CSF-dependent STAT5 phosphorylation.
Conclusions: The recommended phase II dose of ruxolitinib is 20 mg twice daily. We demonstrate that ruxolitinib has promising activity in CMML with particular benefit in those with disease-related B symptoms that warrants further study. (C) 2016 AACR.
C1 [Padron, Eric; Zhang, Qing; Ma, Yan; Balasis, Maria E.; Tinsley, Sara; Ramadan, Hanadi; Lancet, Jeffrey E.; List, Alan F.; Komrokji, Rami S.] H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol, Tampa, FL USA.
[Dezern, Amy] Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD USA.
[Andrade-Campos, Marcio] CIBERER, IIS A, CIBER Enfermedades Raras, Translat Res Unit, Zaragoza, Spain.
[Vaddi, Kris; Scherle, Peggy] Incyte Corp, Wilmington, DE USA.
[Zimmerman, Cassandra; Sekeres, Mikkael A.] Cleveland Clin, Taussig Canc Inst, Leukemia Program, Cleveland, OH 44106 USA.
[Steensma, David P.] Dana Farber Canc Inst, Dept Med Oncol, Adult Leukemia Program, Boston, MA 02115 USA.
[Roboz, Gail J.] Cornell Univ, Weill Med Coll, Leukemia Program, New York, NY 10021 USA.
RP Padron, E (reprint author), H Lee Moffitt Canc Ctr & Res Inst, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM eric.padron@moffitt.org
FU Evans Foundation; American Society of Hematology Junior Faculty Scholar
Award; Incyte Corporation
FX This study was supported (in part) by research funding from the Evans
Foundation (E. Padron and R.S. Komrokji), the American Society of
Hematology Junior Faculty Scholar Award (E. Padron), and Incyte
Corporation (E. Padron).
NR 35
TC 7
Z9 8
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 AUG 1
PY 2016
VL 22
IS 15
BP 3746
EP 3754
DI 10.1158/1078-0432.CCR-15-2781
PG 9
WC Oncology
SC Oncology
GA DU5QE
UT WOS:000382265600007
PM 26858309
ER
PT J
AU Telli, ML
Timms, KM
Reid, J
Hennessy, B
Mills, GB
Jensen, KC
Szallasi, Z
Barry, WT
Winer, EP
Tung, N
Isakoff, SJ
Ryan, PD
Greene-Colozzi, A
Gutin, A
Sangale, Z
Iliev, D
Neff, C
Abkevich, V
Jones, JT
Lanchbury, JS
Hartman, AR
Garber, JE
Ford, JM
Silver, DP
Richardson, AL
AF Telli, Melinda L.
Timms, Kirsten M.
Reid, Julia
Hennessy, Bryan
Mills, Gordon B.
Jensen, Kristin C.
Szallasi, Zoltan
Barry, William T.
Winer, Eric P.
Tung, NadineM.
Isakoff, Steven J.
Ryan, Paula D.
Greene-Colozzi, April
Gutin, Alexander
Sangale, Zaina
Iliev, Diana
Neff, Chris
Abkevich, Victor
Jones, Joshua T.
Lanchbury, Jerry S.
Hartman, Anne-Renee
Garber, Judy E.
Ford, James M.
Silver, Daniel P.
Richardson, Andrea L.
TI Homologous Recombination Deficiency (HRD) Score Predicts Response to
Platinum-Containing Neoadjuvant Chemotherapy in Patients with
Triple-Negative Breast Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID POLY(ADP-RIBOSE) POLYMERASE; OVARIAN-CANCER; DNA-DAMAGE; REPAIR;
CARBOPLATIN; BRCA1; HETEROZYGOSITY; GEMCITABINE; SENSITIVITY; INHIBITION
AB Purpose: BRCA1/2-mutated and some sporadic triple-negative breast cancers (TNBC) have DNA repair defects and are sensitive to DNA-damaging therapeutics. Recently, three independent DNA-based measures of genomic instability were developed on the basis of loss of heterozygosity (LOH), telomeric allelic imbalance (TAI), and large-scale state transitions (LST).
Experimental Design: We assessed a combined homologous recombination deficiency (HRD) score, an unweighted sum of LOH, TAI, and LST scores, in three neoadjuvant TNBC trials of platinum-containing therapy. We then tested the association of HR deficiency, defined as HRD score >= 42 or BRCA1/2 mutation, with response to platinum-based therapy.
Results: In a trial of neoadjuvant platinum, gemcitabine, and iniparib, HR deficiency predicted residual cancer burden score of 0 or I (RCB 0/I) and pathologic complete response (pCR; OR = 4.96, P = 0.0036; OR = 6.52, P = 0.0058). HR deficiency remained a significant predictor of RCB 0/I when adjusted for clinical variables (OR = 5.86, P = 0.012). In two other trials of neoadjuvant cisplatin therapy, HR deficiency predicted RCB 0/I and pCR (OR = 10.18, P = 0.0011; OR = 17.00, P = 0.0066). In a multivariable model of RCB 0/I, HR deficiency retained significance when clinical variables were included (OR = 12.08, P = 0.0017). When restricted to BRCA1/2 nonmutated tumors, response was higher in patients with high HRD scores: RCB 0/I P = 0.062, pCR P = 0.063 in the neoadjuvant platinum, gemcitabine, and iniparib trial; RCB0/I P = 0.0039, pCRP = 0.018 in the neoadjuvant cisplatin trials.
Conclusions: HR deficiency identifies TNBC tumors, including BRCA1/2 nonmutated tumors more likely to respond to platinum-containing therapy. (C) 2016 AACR.
C1 [Telli, Melinda L.; Jensen, Kristin C.; Ford, James M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Timms, Kirsten M.; Reid, Julia; Gutin, Alexander; Sangale, Zaina; Iliev, Diana; Neff, Chris; Abkevich, Victor; Jones, Joshua T.; Lanchbury, Jerry S.; Hartman, Anne-Renee] Myriad Genet Inc, Salt Lake City, UT USA.
[Hennessy, Bryan; Mills, Gordon B.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Szallasi, Zoltan] Tech Univ Denmark, Lyngby, Denmark.
[Szallasi, Zoltan] Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
[Szallasi, Zoltan; Barry, William T.; Winer, Eric P.; Tung, NadineM.; Isakoff, Steven J.; Garber, Judy E.; Silver, Daniel P.; Richardson, Andrea L.] Harvard Med Sch, Boston, MA USA.
[Barry, William T.; Winer, Eric P.; Greene-Colozzi, April; Garber, Judy E.; Silver, Daniel P.; Richardson, Andrea L.] Dana Farber Canc Inst, 450 Brookline Ave,SM 868B, Boston, MA 02215 USA.
[Tung, NadineM.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Isakoff, Steven J.; Ryan, Paula D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Richardson, Andrea L.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Richardson, Andrea L.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Silver, DP (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,SM 868B, Boston, MA 02215 USA.
EM Daniel_Silver@DFCI.Harvard.Edu
FU Adelson Medical Research Foundation; AstraZeneca; Critical Outcome
Technologies; Komen Research Foundation; Nanostrong; Ambry Genetics;
Myriad Genetics; Natera
FX G.B. Mills has ownership interest (including patents) in Catena
Pharmaceuticals, PTV Ventures, Spindletop Ventures, and Myriad Genetics,
reports receiving speakers bureau honoraria from AstraZeneca, Eli Lilly,
ISIS Pharmaceuticals, Nuevolution, and Symphogen, is a
consultant/advisory board member for Adventist Health, AstraZeneca,
Blend, Catena Pharmaceuticals, Critical Outcome Technologies, HaIaI Bio
Korea, ImmunoMET, Millennium Pharmaceuticals, Nuevolution, Precision
Medicine, Provista Diagnostics, Signalchem Lifesciences, and Symphogen,
and reports receiving commercial research grants from Adelson Medical
Research Foundation, AstraZeneca, Critical Outcome Technologies, Komen
Research Foundation, and Nanostrong. S.J. Isakoff is a
consultant/advisory board member for Myriad Genetics. K.M. Timms, A.
Gutin, and V. Abkevich have ownership interest (including patents) in
Myriad Genetics Inc. J.E. Garber reports receiving commercial research
grants from Ambry Genetics and Myriad Genetics. J.M. Ford reports
receiving commercial research grants from Myriad Genetics and Natera.
D.P. Silver and A.L. Richardson are listed as co-inventors on a patent
on telomeric allelic imbalance, which is owned by the Dana-Farber Cancer
Institute and licensed to Myriad Genetics. No potential conflicts of
interest were disclosed by the other authors.
NR 31
TC 12
Z9 12
U1 8
U2 8
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 AUG 1
PY 2016
VL 22
IS 15
BP 3764
EP 3773
DI 10.1158/1078-0432.CCR-15-2477
PG 10
WC Oncology
SC Oncology
GA DU5QE
UT WOS:000382265600009
PM 26957554
ER
PT J
AU Mima, K
Nishihara, R
Yang, JH
Dou, RX
Masugi, Y
Shi, Y
da Silva, A
Cao, Y
Song, MY
Nowak, J
Gu, MC
Li, WW
Morikawa, T
Zhang, XH
Wu, KN
Baba, H
Giovannucci, EL
Meyerhardt, JA
Chan, AT
Fuchs, CS
Qian, ZR
Ogino, S
AF Mima, Kosuke
Nishihara, Reiko
Yang, Juhong
Dou, Ruoxu
Masugi, Yohei
Shi, Yan
da Silva, Annacarolina
Cao, Yin
Song, Mingyang
Nowak, Jonathan
Gu, Mancang
Li, Wanwan
Morikawa, Teppei
Zhang, Xuehong
Wu, Kana
Baba, Hideo
Giovannucci, Edward L.
Meyerhardt, Jeffrey A.
Chan, Andrew T.
Fuchs, Charles S.
Qian, Zhi Rong
Ogino, Shuji
TI MicroRNA MIR21 (miR-21) and PTGS2 Expression in Colorectal Cancer and
Patient Survival
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ISLAND METHYLATOR PHENOTYPE; MOLECULAR PATHOLOGICAL EPIDEMIOLOGY; BRAF
MUTATION STATUS; III COLON-CANCER; MICROSATELLITE INSTABILITY; ASPIRIN
USE; LINKING INFLAMMATION; PIK3CA MUTATION; STAGE; ASSOCIATION
AB Purpose: Prostaglandin-endoperoxide synthase 2 (PTGS2, cyclooxygenase-2; a target of aspirin) produces inflammatory mediator prostaglandin E-2 (PGE(2)), and contributes to colorectal neoplasia development. PTGS2-driven inflammatory responses can induce tumor expression of microRNA MIR21 (miR-21) that can increase local PGE(2) level by downregulating PGE(2)-metabolizing enzymes. We hypothesized that the prognostic association of tumor MIR21 expression level in colorectal carcinoma might depend on inflammatory tumor microenvironment and be stronger in tumors expressing high-level PTGS2.
Experimental Design: Utilizing 765 rectal and colon cancer specimens in the Nurses' Health Study and the Health Professionals Follow-up Study, we measured MIR21 expression by quantitative reverse transcription PCR, and PTGS2 expression by immunohistochemistry. Cox proportional hazards regression model was used to assess statistical interaction between MIR21 and PTGS2 in colorectal cancer-specific survival analysis, con-trolling for potential confounders including microsatellite instability, CpG island methylator phenotype, LINE-1 methylation level, and KRAS, BRAF, and PIK3CA mutations.
Results: Tumor MIR21 expression level was associated with higher colorectal cancer-specific mortality (Ptrend = 0.029), and there was a statistically significant interaction between MIR21 and PTGS2 (Pinteraction = 0.0004). The association between MIR21 expression and colorectal cancer-specific mortality was statistically significant in PTGS2-high cancers (multivariable hazard ratio of the highest vs. lowest quartile of MIR21, 2.28; 95% confidence interval, 1.42-3.67; P-trend = 0.0004) but not in PTGS2-absent/low cancers (P-trend = 0.22).
Conclusions: MIR21 expression level in colorectal carcinoma is associated with worse clinical outcome, and this association is stronger in carcinomas expressing high-level PTGS2, suggesting complex roles of immunity and inflammation in tumor progression. (C) 2016 AACR.
C1 [Mima, Kosuke; Nishihara, Reiko; Yang, Juhong; Dou, Ruoxu; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Gu, Mancang; Li, Wanwan; Meyerhardt, Jeffrey A.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Mima, Kosuke; Nishihara, Reiko; Yang, Juhong; Dou, Ruoxu; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Nowak, Jonathan; Gu, Mancang; Li, Wanwan; Zhang, Xuehong; Giovannucci, Edward L.; Meyerhardt, Jeffrey A.; Chan, Andrew T.; Fuchs, Charles S.; Qian, Zhi Rong; Ogino, Shuji] Harvard Med Sch, Boston, MA USA.
[Nishihara, Reiko; Cao, Yin; Song, Mingyang; Wu, Kana; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Nishihara, Reiko; Cao, Yin; Song, Mingyang; Giovannucci, Edward L.; Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Nishihara, Reiko] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Nowak, Jonathan; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,Room M422, Boston, MA 02115 USA.
[Morikawa, Teppei] Univ Tokyo, Grad Sch Med, Dept Pathol, Tokyo, Japan.
[Zhang, Xuehong; Giovannucci, Edward L.; Chan, Andrew T.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Baba, Hideo] Kumamoto Univ, Grad Sch Med Sci, Dept Surg Gastroenterol, Kumamoto, Japan.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 450 Brookline Ave,Room M422, Boston, MA 02115 USA.
EM shuji_ogino@dfci.harvard.edu
OI Masugi, Yohei/0000-0002-6952-4043
FU U.S. NIH [P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, P50
CA127003, R01 CA137178, R01 CA151993, R35 CA197735, K07 CA190673];
Project P Fund; Friends of the Dana-Father Cancer Institute; Bennett
Family Fund; Entertainment Industry Foundation through National
Colorectal Cancer Research Alliance; Program for Advancing Strategic
International Networks to Accelerate the Circulation of Talented
Researchers from Japan Society for the Promotion of Science; Nurses'
Health Study; Health Professionals Follow-up Study
FX This work was supported by U.S. NIH grants (P01 CA87969 to M.J.
Stampfer*; UM1 CA186107 to M.J. Stampfer*; P01 CA55075 to W.C. Willett*;
UM1 CA167552 to W.C. Willett*; P50 CA127003 to C.S. Fuchs; R01 CA137178
to A.T. Chan.; R01 CA151993 to S. Ogino; R35 CA197735 to S. Ogino; and
K07 CA190673 to R. Nishihara); and by grants from the Project P Fund,
The Friends of the Dana-Father Cancer Institute, Bennett Family Fund,
and the Entertainment Industry Foundation through National Colorectal
Cancer Research Alliance. K. Mima is supported by a grant from Program
for Advancing Strategic International Networks to Accelerate the
Circulation of Talented Researchers from Japan Society for the Promotion
of Science.; These grants support tissue collection in the Nurses'
Health Study and the Health Professionals Follow-up Study. Because the
authors used colorectal carcinoma tissue specimens from the Nurses'
Health Study and the Health Professionals Follow-up Study, the
information for these grants is included even though M.J. Stampfer and
W.C. Willet are not listed authors.
NR 52
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Z9 2
U1 6
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD AUG 1
PY 2016
VL 22
IS 15
BP 3841
EP 3848
DI 10.1158/1078-0432.CCR-15-2173
PG 8
WC Oncology
SC Oncology
GA DU5QE
UT WOS:000382265600017
PM 26957558
ER
PT J
AU Hanaford, AR
Archer, TC
Price, A
Kahlert, UD
Maciac-Zyk, J
Nikkhah, G
Kim, JW
Ehrenberger, T
Clemons, PA
Dancik, V
Seashore-Ludlow, B
Viswanathan, V
Stewart, ML
Rees, MG
Shamji, A
Schreiber, S
Fraenkel, E
Pomeroy, SL
Mesirov, JP
Tamayo, P
Eberhart, CG
Raabe, EH
AF Hanaford, Allison R.
Archer, Tenley C.
Price, Antoinette
Kahlert, Ulf D.
Maciac-Zyk, Jarek
Nikkhah, Guido
Kim, Jong Wook
Ehrenberger, Tobias
Clemons, Paul A.
Dancik, Vlado
Seashore-Ludlow, Brinton
Viswanathan, Vasanthi
Stewart, Michelle L.
Rees, Matthew G.
Shamji, Alykhan
Schreiber, Stuart
Fraenkel, Ernest
Pomeroy, Scott L.
Mesirov, Jill P.
Tamayo, Pablo
Eberhart, Charles G.
Raabe, Eric H.
TI DiSCoVERing Innovative Therapies for Rare Tumors: Combining Genetically
Accurate Disease Models with In Silico Analysis to Identify Novel
Therapeutic Targets
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID SET ENRICHMENT ANALYSIS; NEURAL STEM-CELLS; C-MYC; ANAPLASTIC
MEDULLOBLASTOMA; DRUG-SENSITIVITY; BREAST-CANCER; MOUSE MODELS; KINASE
4/6; PD 0332991; INHIBITION
AB Purpose: We used human stem and progenitor cells to develop a genetically accurate novel model of MYC-driven Group 3 medulloblastoma. We also developed a new informatics method, Disease-model Signature versus Compound-Variety Enriched Response ("DiSCoVER"), to identify novel therapeutics that target this specific disease subtype.
Experimental Design: Human neural stem and progenitor cells derived from the cerebellar anlage were transduced with oncogenic elements associated with aggressive medulloblastoma. An in silico analysis method for screening drug sensitivity databases (DiSCoVER) was used in multiple drug sensitivity datasets. We validated the top hits from this analysis in vitro and in vivo.
Results: Human neural stem and progenitor cells transformed with c-MYC, dominant-negative p53, constitutively active AKT and hTERT formed tumors in mice that recapitulated Group 3 medulloblastoma in terms of pathology and expression profile. DiSCoVER analysis predicted that aggressive MYC-driven Group 3 medulloblastoma would be sensitive to cyclin-dependent kinase (CDK) inhibitors. The CDK 4/6 inhibitor palbociclib decreased proliferation, increased apoptosis, and significantly extended the survival of mice with orthotopic medulloblastoma xenografts.
Conclusions: We present a new method to generate genetically accurate models of rare tumors, and a companion computational methodology to find therapeutic interventions that target them. We validated our human neural stem cell model of MYC-driven Group 3 medulloblastoma and showed that CDK 4/6 inhibitors are active against this subgroup. Our results suggest that palbociclib is a potential effective treatment for poor prognosis MYC-driven Group 3 medulloblastoma tumors in carefully selected patients. (C) 2016 AACR.
C1 [Hanaford, Allison R.; Price, Antoinette; Eberhart, Charles G.; Raabe, Eric H.] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.
[Archer, Tenley C.; Kim, Jong Wook; Ehrenberger, Tobias; Clemons, Paul A.; Schreiber, Stuart; Fraenkel, Ernest; Pomeroy, Scott L.; Mesirov, Jill P.; Tamayo, Pablo] Eli & Edythe L Broad Inst MIT & Harvard, Cambridge, MA USA.
[Archer, Tenley C.; Pomeroy, Scott L.] Harvard Med Sch, Boston Childrens Hosp, Dept Neurol, Cambridge, MA USA.
[Kahlert, Ulf D.; Maciac-Zyk, Jarek] Heinrich Heine Univ Hosp, Dept Neurosurg, Dusseldorf, Germany.
[Nikkhah, Guido] Univ Hosp, Dept Neurosurg, Stuttgart, Germany.
[Kim, Jong Wook] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ehrenberger, Tobias; Fraenkel, Ernest] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Clemons, Paul A.; Dancik, Vlado; Seashore-Ludlow, Brinton; Viswanathan, Vasanthi; Stewart, Michelle L.; Rees, Matthew G.; Shamji, Alykhan; Schreiber, Stuart] Broad Inst, Ctr Sci Therapeut, Cambridge, MA USA.
[Schreiber, Stuart] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Schreiber, Stuart] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Mesirov, Jill P.; Tamayo, Pablo] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Mesirov, Jill P.; Tamayo, Pablo] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Raabe, Eric H.] Johns Hopkins Sch Med, Div Pediat Oncol, Baltimore, MD USA.
RP Eberhart, CG (reprint author), Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA.; Raabe, EH (reprint author), Johns Hopkins Univ Hosp, Bloomberg 11379,1800 Orleans St, Baltimore, MD 21287 USA.
EM ceberha@jhmi.edu; eraabe2@jhmi.edu
OI Fraenkel, Ernest/0000-0001-9249-8181; Seashore-Ludlow,
Brinton/0000-0001-8658-5967
FU NCI [P30 CA006973, R01NS055089]; NIH [R01 CA154480, R01 109467,
R01GM074024]
FX St. Baldrick's Foundation, Hyundai Hope on Wheels, and Giant Food
Pediatric Cancer Research Fund, The Spencer Grace Foundation, The Deming
Family, and The Children's Brain Tumor Foundation (to E.H. Raabe); NCI
Core Grant to the Johns Hopkins SKCCC P30 CA006973, and R01NS055089 (to
C.G. Eberhart), NIH R01 CA154480 (to J.P. Mesirov and P. Tamayo), NIH
R01 109467 (to J.P. Mesirov and S.L. Pomeroy), NIH R01GM074024 (to J.P.
Mesirov and P. Tamayo). Comprehensive Cancer Center Freiburg (to U.D.
Kahlert, J. Maciaczyk, and G. Nikkhah). NCI's Cancer Target Discovery
and Development (CTD2) Network U01CA176152 (to S.L. Schreiber).
NR 60
TC 2
Z9 2
U1 3
U2 3
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 AUG 1
PY 2016
VL 22
IS 15
BP 3903
EP 3914
DI 10.1158/1078-0432.CCR-15-3011
PG 12
WC Oncology
SC Oncology
GA DU5QE
UT WOS:000382265600023
PM 27012813
ER
PT J
AU Du, YT
Ter-Minassian, M
Brais, L
Brooks, N
Waldron, A
Chan, JA
Lin, XH
Kraft, P
Christiani, DC
Kulke, MH
AF Du, Yeting
Ter-Minassian, Monica
Brais, Lauren
Brooks, Nichole
Waldron, Amanda
Chan, Jennifer A.
Lin, Xihong
Kraft, Peter
Christiani, David C.
Kulke, Matthew H.
TI Genetic associations with neuroendocrine tumor risk: results from a
genome-wide association study
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE neuroendocrine tumours; genetic risk
ID CARCINOID-TUMORS; MUTATIONS; PARAGANGLIOMA; PHEOCHROMOCYTOMA; CANCER;
MEN1
AB The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted.
C1 [Du, Yeting; Ter-Minassian, Monica; Lin, Xihong; Kraft, Peter; Christiani, David C.] Harvard Sch Publ Hlth, Boston, MA USA.
[Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A.; Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Kulke, MH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM matthew_kulke@dfci.harvard.edu
FU Dana-Farber/Harvard SPORE Grant in Gastrointestinal Center
[P50CA127003]; Goldhirsh-Yellin Foundation Fund for Neuroendocrine Tumor
Research; Gitta and Saul Kurlat Fund for Neuroendocrine Tumor Research;
Jane Dybowski Fund for Neuroendocrine Cancer; McIntyre Family Fund for
Neuroendocrine Tumor Research; Lipson Family Fund; Murphy Family Fund
for Carcinoid Tumor Research; Caring for Carcinoid Foundation;
[R01CA151532]
FX This work was supported by Grant #R01CA151532 (to M H K),
Dana-Farber/Harvard SPORE Grant in Gastrointestinal Center (Grant
#P50CA127003) and Goldhirsh-Yellin Foundation Fund for Neuroendocrine
Tumor Research. The authors gratefully acknowledge additional support
from the Gitta and Saul Kurlat Fund for Neuroendocrine Tumor Research,
Jane Dybowski Fund for Neuroendocrine Cancer, McIntyre Family Fund for
Neuroendocrine Tumor Research, Lipson Family Fund, the Murphy Family
Fund for Carcinoid Tumor Research, and the Caring for Carcinoid
Foundation.
NR 34
TC 0
Z9 0
U1 0
U2 0
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD AUG
PY 2016
VL 23
IS 8
BP 587
EP 594
DI 10.1530/ERC-16-0171
PG 8
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA DX2HM
UT WOS:000384188900004
PM 27492634
ER
PT J
AU Watson, LR
Binek, A
Wang, Z
Mackay, C
Moon, J
Kedzierska, K
Good-Jacobson, K
Belz, G
Groom, J
AF Watson, L-R
Binek, A.
Wang, Z.
Mackay, C.
Moon, J.
Kedzierska, K.
Good-Jacobson, K.
Belz, G.
Groom, J.
TI Migration and transcriptional regulation of TFH cell differentiation
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Watson, L-R; Binek, A.; Groom, J.] Walter & Eliza Hall Inst Med Res, Dept Immunol & Mol Immunol, Parkville, Vic, Australia.
[Wang, Z.; Kedzierska, K.] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia.
[Mackay, C.] Pfizer Inc, Inflammat & Immunol, Cambridge, MA USA.
[Moon, J.] Massachusetts Gen Hosp, Charlestown, MA USA.
[Moon, J.] Harvard Med Sch, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA.
[Good-Jacobson, K.] Monash Univ, Dept Microbiol, Clayton, Vic, Australia.
[Belz, G.] Walter & Eliza Hall Inst Med Res, Dept Mol Immunol, Parkville, Vic, Australia.
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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 1231
BP 57
EP 57
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610400114
ER
PT J
AU Weber, GF
Chousterman, BG
He, S
Fenn, AM
Nairz, M
Anzai, A
Brenner, T
Uhle, F
Iwamoto, Y
Robbins, CS
Noiret, L
Maier, SL
Znnchen, T
Rahbari, NN
Schlch, S
Klotasche-Von Ameln, A
Chavakis, T
Weitz, J
Hofer, S
Weigand, MA
Nahrendorf, M
Weissleder, R
Swirski, FK
AF Weber, G. F.
Chousterman, B. G.
He, S.
Fenn, A. M.
Nairz, M.
Anzai, A.
Brenner, T.
Uhle, F.
Iwamoto, Y.
Robbins, C. S.
Noiret, L.
Maier, S. L.
Znnchen, T.
Rahbari, N. N.
Schlch, S.
Klotasche-Von Ameln, A.
Chavakis, T.
Weitz, J.
Hofer, S.
Weigand, M. A.
Nahrendorf, M.
Weissleder, R.
Swirski, F. K.
TI Interleukin-3 amplifies acute inflammation and is a potential
therapeutic target in sepsis
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Weber, G. F.] Univ Klinikum Erlangen, FAU Erlangen Nurnberg, Dept Surg, Erlangen, Germany.
[Weber, G. F.; Chousterman, B. G.; He, S.; Fenn, A. M.; Nairz, M.; Anzai, A.; Iwamoto, Y.; Robbins, C. S.; Noiret, L.; Nahrendorf, M.; Weissleder, R.; Swirski, F. K.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA.
[Brenner, T.; Uhle, F.; Hofer, S.; Weigand, M. A.] Heidelberg Univ, Univ Klinikum Heidelberg, Dept Anaesthesiol, Heidelberg, Germany.
[Maier, S. L.; Znnchen, T.; Rahbari, N. N.; Schlch, S.; Weitz, J.] Tech Univ Dresden, Dept Surg, Univ Klinikum Dresden, Dresden, Germany.
[Klotasche-Von Ameln, A.; Chavakis, T.] Tech Univ Dresden, Univ Klinikum Dresden, Dept Clin Pathochem, Dresden, Germany.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 116
BP 83
EP 83
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610400167
ER
PT J
AU Lin, C
Chang, HW
Tsai, PS
Reinecker, HC
Chiang, HS
AF Lin, C.
Chang, H. W.
Tsai, P. S.
Reinecker, H. C.
Chiang, H. S.
TI Lfc attenuates tumorigenesis during colitis-associated cancer
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Lin, C.; Chiang, H. S.] Natl Taiwan Univ, Life Sci, Taipei, Taiwan.
[Chang, H. W.; Tsai, P. S.] Natl Taiwan Univ, Sch Vet Med, Taipei, Taiwan.
[Reinecker, H. C.] Harvard Med Sch, Gastrointestinal Unit, Massachusetts Gen Hosp, Boston, MA USA.
[Reinecker, H. C.] Harvard Med Sch, Ctr Study Inflammatory Bowel Dis, Massachusetts Gen Hosp, Boston, MA 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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 280
BP 371
EP 371
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610400746
ER
PT J
AU Abdalla, T
Roda, MA
Li, JD
Blalock, JE
Gaggar, A
Xu, X
AF Abdalla, T.
Roda, Abdul M.
Li, J. -D
Blalock, J. E.
Gaggar, A.
Xu, X.
TI Prolyl endopeptidase (PE) activity in the immune system of smoking mice
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Abdalla, T.; Li, J. -D; Blalock, J. E.; Gaggar, A.; Xu, X.] Univ Alabama Birmingham, Med, Birmingham, AL USA.
[Roda, Abdul M.] Univ Utrecht, Pharmaceut Sci, Utrecht, Netherlands.
[Blalock, J. E.; Gaggar, A.; Xu, X.] UAB Program Protease & Matrix Biol, Birmingham, AL USA.
[Gaggar, A.] Birmingham VA Med Ctr, Birmingham, 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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 353
BP 407
EP 407
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610401009
ER
PT J
AU Nirschl, C
Liu, Y
Kim, TG
Rezai, M
Dannenfelser, R
Zhu, Q
Chau, D
Fuentes, JD
Gulati, N
Song-Zhao, G
Krueger, J
Sarin, K
Troyanskaya, O
Suarez-Farinas, M
Anandasabapathy, N
AF Nirschl, C.
Liu, Y.
Kim, T. -G
Rezai, M.
Dannenfelser, R.
Zhu, Q.
Chau, D.
Fuentes, Ducolan J.
Gulati, N.
Song-Zhao, G.
Krueger, J.
Sarin, K.
Troyanskaya, O.
Suarez-Farinas, M.
Anandasabapathy, N.
TI Homeostatic monophagocyte signatures regulate anti-tumor immunity
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Nirschl, C.; Liu, Y.; Kim, T. -G; Chau, D.; Song-Zhao, G.] Harvard Med Sch, Brigham & Womens Hosp, Dermatol, Boston, MA USA.
[Rezai, M.; Sarin, K.] Stanford Univ, Dermatol, Stanford, CA 94305 USA.
[Dannenfelser, R.; Zhu, Q.; Troyanskaya, O.] Princeton Univ, Simmons Fdn, Princeton, NJ 08544 USA.
[Fuentes, Ducolan J.; Gulati, N.; Krueger, J.] Rockefeller Univ, Lab Invest Dermatol, 1230 York Ave, New York, NY 10021 USA.
[Suarez-Farinas, M.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Anandasabapathy, N.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Ctr, Dermatol,Harvard Stem Cell Inst, Boston, MA 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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 4708
BP 510
EP 510
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610401219
ER
PT J
AU Knoblich, K
Siew, SML
Parekkadan, B
Turley, S
Fletcher, A
AF Knoblich, K.
Siew, S. M. -L
Parekkadan, B.
Turley, S.
Fletcher, A.
TI Human fibroblastic reticular cells of secondary lymphoid organs regulate
T cell activation and proliferation through four overlapping mechanisms
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Knoblich, K.; Siew, S. M. -L; Fletcher, A.] Univ Birmingham, Inst Immunol & Immunotherapy, Birmingham, W Midlands, England.
[Parekkadan, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Parekkadan, B.] Harvard Med Sch, Ctr Engn Med & Surg Serv, Boston, MA USA.
[Turley, S.] Genentech Inc, Dept Canc Immunol, San Francisco, CA 94080 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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 724
BP 706
EP 707
PG 2
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610401613
ER
PT J
AU Kamphorst, AO
Wieland, A
Yang, S
Nasti, T
Zhang, R
Barber, DL
Konieczny, BT
Koenig, L
Yu, K
Sica, G
Owonikoko, TK
Sharpe, AH
Freeman, GJ
Blazar, BR
Turka, LA
Pillai, R
Ramalingam, SS
Araki, K
Ahmed, R
AF Kamphorst, A. O.
Wieland, A.
Yang, S.
Nasti, T.
Zhang, R.
Barber, D. L.
Konieczny, B. T.
Koenig, L.
Yu, K.
Sica, G.
Owonikoko, T. K.
Sharpe, A. H.
Freeman, G. J.
Blazar, B. R.
Turka, L. A.
Pillai, R.
Ramalingam, S. S.
Araki, K.
Ahmed, R.
TI Rescue of exhausted CD8 T cells by PD-1 targeted therapies is
CD28-dependent
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Kamphorst, A. O.; Wieland, A.; Yang, S.; Nasti, T.; Konieczny, B. T.; Araki, K.; Ahmed, R.] Emory Univ, Sch Med, Microbiol & Immunol, Emory Vaccine Ctr, Atlanta, GA USA.
[Yang, S.] Cent S Univ, Xiangya Sch Med, Changsha, Hunan, Peoples R China.
[Zhang, R.; Turka, L. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zhang, R.; Turka, L. A.] Harvard Med Sch, Dept Surg, Boston, MA USA.
[Barber, D. L.] NIAID, Parasit Dis Lab, Bethesda, MD USA.
[Koenig, L.; Yu, K.; Owonikoko, T. K.; Pillai, R.; Ramalingam, S. S.] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Winship Canc Inst, Atlanta, GA USA.
[Sica, G.] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA.
[Sharpe, A. H.] Harvard Med Sch, Boston, MA USA.
[Freeman, G. J.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Blazar, B. R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA.
NR 0
TC 0
Z9 0
U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 963
BP 793
EP 793
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610401788
ER
PT J
AU Guillerey, C
de Andrade, LF
Miles, K
Vuckovic, S
Chesi, M
Bergsagel, LP
Geoffrey, RH
Martinet, L
Smyth, MJ
AF Guillerey, C.
de Andrade, L. F.
Miles, K.
Vuckovic, S.
Chesi, M.
Bergsagel, L. P.
Geoffrey, R. H.
Martinet, L.
Smyth, M. J.
TI Therapeutic potential anti-CD137 mAbs in multiple myeloma
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Guillerey, C.; de Andrade, L. F.; Miles, K.; Martinet, L.; Smyth, M. J.] QIMR Berghofer, Immunol Canc & Infect Lab, Herston, Qld, Australia.
[Guillerey, C.; Smyth, M. J.] Univ Queensland, Sch Med, Herston, Qld, Australia.
[de Andrade, L. F.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA.
[Vuckovic, S.] QIMR Berghofer, Bone Marrow Transplantat Lab, Herston, Qld, Australia.
[Bergsagel, L. P.] Mayo Clin, Ctr Comprehens Canc, Scottsdale, AZ USA.
[Martinet, L.] INSERM, UMR 1037, Canc Res Ctr Toulouse, Toulouse, France.
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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 764
BP 1005
EP 1006
PG 2
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610402418
ER
PT J
AU Vajjhala, P
Lu, A
Brown, D
Sagulenko, V
Schroder, K
Stow, J
Wu, H
Stacey, K
AF Vajjhala, P.
Lu, A.
Brown, D.
Sagulenko, V
Schroder, K.
Stow, J.
Wu, H.
Stacey, K.
TI Molecular arrangement and activation of procaspases-1 and-8 at
inflammasomes
SO EUROPEAN JOURNAL OF IMMUNOLOGY
LA English
DT Meeting Abstract
CT International Congress of Immunology (ICI)
CY AUG 21-26, 2016
CL Melbourne, AUSTRALIA
C1 [Vajjhala, P.; Sagulenko, V; Stacey, K.] Univ Queensland, Sch Chem & Mol Biosci, Brisbane, Qld, Australia.
[Lu, A.; Wu, H.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA.
[Lu, A.; Wu, H.] Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA.
[Brown, D.; Schroder, K.; Stow, J.; Stacey, K.] Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
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 0014-2980
EI 1521-4141
J9 EUR J IMMUNOL
JI Eur. J. Immunol.
PD AUG
PY 2016
VL 46
SU 1
SI SI
MA 3551
BP 1031
EP 1031
PG 1
WC Immunology
SC Immunology
GA DW4KA
UT WOS:000383610402470
ER
PT J
AU Stirling, L
MacLean, J
AF Stirling, Leia
MacLean, Julie
TI Roadmap for the Development of at-Home Telemonitoring Systems to Augment
Occupational Therapy
SO IEEE TRANSACTIONS ON HUMAN-MACHINE SYSTEMS
LA English
DT Article
DE Cognitive task analysis (CTA); decision making; human-computer
interaction; motion primitives; situation awareness (SA)
ID UPPER EXTREMITY FUNCTION; HUMAN MOTION CAPTURE; PHYSICAL REHABILITATION;
MOVEMENT SMOOTHNESS; MULTIPLE-SCLEROSIS; VIRTUAL-REALITY;
CEREBRAL-PALSY; LIMB FUNCTION; BRAIN-INJURY; TELEREHABILITATION
AB While the literature supports the potential to provide occupational therapy through telemedicine, there are several design challenges embedded in creating an at-home telemonitoring system that can visualize the complex biomechanical data required for clinical decision making. The challenge highlighted here is the development of measures that align with current decision making methods, which will support the integration and translation of the technology. A modified cognitive task analysis methodology is presented that is composed of three segments: characterizing the subject matter, defining relevant information, and formalizing requirements. This method was implemented through observations of eight therapists over 21 patient sessions. There were nine unique modes of interaction observed between the clinician and patient. Embedded within these interactions were 14 different features monitored. Relevant performance measures were defined from these interactions to provide perception and comprehension situation awareness (SA) to the clinician about the patients task performance. Using specific activities observed during therapy sessions, sample metrics and a visualization are presented that followed from the SA requirements. Finally, the technological challenges associated with making these measurements were identified.
C1 [Stirling, Leia] MIT, Dept Aeronaut & Astronaut, Inst Med Engn & Sci, Cambridge, MA 02139 USA.
[MacLean, Julie] Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA.
RP Stirling, L (reprint author), MIT, Dept Aeronaut & Astronaut, Inst Med Engn & Sci, Cambridge, MA 02139 USA.; MacLean, J (reprint author), Massachusetts Gen Hosp, Dept Occupat Therapy, Boston, MA 02114 USA.
EM leia@mit.edu; jlmaclean@partners.org
FU National Science Foundation [1453141]
FX This work was supported by the National Science Foundation under Award
1453141.
NR 82
TC 0
Z9 0
U1 11
U2 11
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2168-2291
EI 2168-2305
J9 IEEE T HUM-MACH SYST
JI IEEE T. Hum.-Mach. Syst.
PD AUG
PY 2016
VL 46
IS 4
BP 569
EP 580
DI 10.1109/THMS.2015.2506729
PG 12
WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics
SC Computer Science
GA DX3NL
UT WOS:000384279700008
ER
PT J
AU Rannikmae, K
Woodfield, R
Anderson, CS
Charidimou, A
Chiewvit, P
Greenberg, SM
Jeng, JS
Meretoja, A
Palm, F
Putaala, J
Rinkel, GJE
Rosand, J
Rost, NS
Strbian, D
Tatlisumak, T
Tsai, CF
Wermer, MJH
Werring, D
Yeh, SJ
Salman, RA
Sudlow, CLM
AF Rannikmae, Kristiina
Woodfield, Rebecca
Anderson, Craig S.
Charidimou, Andreas
Chiewvit, Pipat
Greenberg, Steven M.
Jeng, Jiann-Shing
Meretoja, Atte
Palm, Frederic
Putaala, Jukka
Rinkel, Gabriel J. E.
Rosand, Jonathan
Rost, Natalia S.
Strbian, Daniel
Tatlisumak, Turgut
Tsai, Chung-Fen
Wermer, Marieke J. H.
Werring, David
Yeh, Shin-Joe
Salman, Rustam Al-Shahi
Sudlow, Cathie L. M.
TI Reliability of intracerebral hemorrhage classification systems: A
systematic review
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Review
DE Cerebral hemorrhage; cerebrovascular disorders; reproducibility of
results; reliability; systematic review; classification system
ID INTEROBSERVER AGREEMENT; SMASH-U; STROKE; POPULATION; PREDICTION;
MORTALITY; HYPERTENSION; ASSOCIATION; MICROBLEEDS; GUIDELINES
AB Background Accurately distinguishing non-traumatic intracerebral hemorrhage (ICH) subtypes is important since they may have different risk factors, causal pathways, management, and prognosis. We systematically assessed the inter- and intra-rater reliability of ICH classification systems.
Methods We sought all available reliability assessments of anatomical and mechanistic ICH classification systems from electronic databases and personal contacts until October 2014. We assessed included studies' characteristics, reporting quality and potential for bias; summarized reliability with kappa value forest plots; and performed meta-analyses of the proportion of cases classified into each subtype.
Summary of review We included 8 of 2152 studies identified. Inter- and intra-rater reliabilities were substantial to perfect for anatomical and mechanistic systems (inter-rater kappa values: anatomical 0.78-0.97 [six studies, 518 cases], mechanistic 0.89-0.93 [three studies, 510 cases]; intra-rater kappas: anatomical 0.80-1 [three studies, 137 cases], mechanistic 0.92-0.93 [two studies, 368 cases]). Reporting quality varied but no study fulfilled all criteria and none was free from potential bias. All reliability studies were performed with experienced raters in specialist centers. Proportions of ICH subtypes were largely consistent with previous reports suggesting that included studies are appropriately representative.
Conclusions Reliability of existing classification systems appears excellent but is unknown outside specialist centers with experienced raters. Future reliability comparisons should be facilitated by studies following recently published reporting guidelines.
C1 [Rannikmae, Kristiina; Woodfield, Rebecca; Salman, Rustam Al-Shahi; Sudlow, Cathie L. M.] Univ Edinburgh, Ctr Clin Brain Sci, Chancellors Bldg,49 Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland.
[Anderson, Craig S.] Royal Prince Alfred Hosp, George Inst Global Hlth, Camperdown, NSW, Australia.
[Anderson, Craig S.] Univ Sydney, Sydney, NSW 2006, Australia.
[Charidimou, Andreas; Werring, David] UCL Inst Neurol, Stroke Res Grp, Dept Brain Repair & Rehabil, London, England.
[Charidimou, Andreas; Werring, David] Natl Hosp Neurol & Neurosurg, London, England.
[Chiewvit, Pipat] Mahidol Univ, Dept Radiol, Fac Med, Siriraj Hosp, Salaya, Thailand.
[Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Jeng, Jiann-Shing; Yeh, Shin-Joe] Natl Taiwan Univ Hosp, Stroke Ctr, Taipei, Taiwan.
[Jeng, Jiann-Shing; Yeh, Shin-Joe] Natl Taiwan Univ Hosp, Dept Neurol, Taipei, Taiwan.
[Meretoja, Atte; Putaala, Jukka; Strbian, Daniel; Tatlisumak, Turgut] Univ Helsinki, Dept Neurol, Cent Hosp, FIN-00014 Helsinki, Finland.
[Meretoja, Atte] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Melbourne, Vic 3010, Australia.
[Meretoja, Atte] Univ Melbourne, Dept Florey, Royal Melbourne Hosp, Melbourne, Vic 3010, Australia.
[Palm, Frederic] Stadt Klinikum Ludwigshafen, Dept Neurol, Ludwigshafen, Germany.
[Rinkel, Gabriel J. E.] Univ Med Ctr Utrecht, Dept Neurol & Neurosurg, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
[Rosand, Jonathan; Rost, Natalia S.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Tatlisumak, Turgut] Gothenburg Univ, Inst Neurosci & Physiol, Sahlgrenska Acad, S-41124 Gothenburg, Sweden.
[Tatlisumak, Turgut] Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden.
[Tsai, Chung-Fen] Fu Jen Catholic Univ, Dept Neurol, Cardinal Tien Hosp, Sch Med, New Taipei, Taiwan.
[Wermer, Marieke J. H.] Leiden Univ, Dept Neurol, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Sudlow, Cathie L. M.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland.
[Sudlow, Cathie L. M.] UK Biobank, Stockport, Lancs, England.
RP Sudlow, CLM (reprint author), Univ Edinburgh, Ctr Clin Brain Sci, Chancellors Bldg,49 Little France Crescent, Edinburgh EH16 4SB, Midlothian, Scotland.
EM cathie.sudlow@ed.ac.uk
OI Al-Shahi Salman, Rustam/0000-0002-2108-9222
FU Edinburgh Stroke Research and Amenities Endowments Fund; UK Biobank;
Scottish Funding Council; Chest Heart and Stroke Scotland; Medical
Research Council; Greek State Scholarship Foundation; Stroke
Association; British Heart Foundation; Higher Education Funding Council
for England; National Health and Medical Research Council of Australia
FX We thank M Moragas (Consultant Neurologist, NHS Lothian) for help with
translating a Spanish article.The author(s) disclosed receipt of the
following financial support for the research, authorship, and/or
publication of this article: K Rannikmae: Edinburgh Stroke Research and
Amenities Endowments Fund, UK Biobank; C Sudlow: Scottish Funding
Council, UK Biobank; R Woodfield: UK Biobank, Chest Heart and Stroke
Scotland; R Al-Shahi Salman: Medical Research Council; A Charidimou:
Greek State Scholarship Foundation, Stroke Association, British Heart
Foundation; D Werring: Higher Education Funding Council for England,
Stroke Association, British Heart Foundation; CS Anderson: National
Health and Medical Research Council of Australia. Details of funding for
P Chiewvit, S Greenberg, J-S Jeng, A Meretoja, F Palm, J Putaala, G
Rinkel, J Rosand, NS Rost, D Strbian, T Tatlisumak, MJH Wermer, and S-J
Yeh : found in Meretoja et al.,7 Chiewvit et al.,8
Rost et al.,16 Yeh et al.,22 Wermer et
al.,24 Palm et al.25
NR 31
TC 2
Z9 2
U1 3
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD AUG
PY 2016
VL 11
IS 6
BP 626
EP 636
DI 10.1177/1747493016641962
PG 11
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DS7VJ
UT WOS:000380990700008
PM 27091144
ER
PT J
AU Jordan, JT
AF Jordan, Justin T.
TI Neurologic Immune-Related Adverse Events in Oncology Care
SO JAMA NEUROLOGY
LA English
DT Editorial Material
ID IPILIMUMAB; MELANOMA; ANTIBODY; THERAPY; CANCER; TRIAL
C1 [Jordan, Justin T.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Jordan, Justin T.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
RP Jordan, JT (reprint author), Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey Bldg,Ste 9E, Boston, MA 02114 USA.
EM jtjordan@mgh.harvard.edu
NR 10
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 907
EP 908
DI 10.1001/jamaneurol.2016.1564
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900002
PM 27271299
ER
PT J
AU Akoudad, S
Wolters, FJ
Viswanathan, A
de Bruijn, RF
van der Lugt, A
Hofman, A
Koudstaal, PJ
Ikram, MA
Vernooij, MW
AF Akoudad, Saloua
Wolters, Frank J.
Viswanathan, Anand
de Bruijn, Renee F.
van der Lugt, Aad
Hofman, Albert
Koudstaal, Peter J.
Ikram, M. Arfan
Vernooij, Meike W.
TI Association of Cerebral Microbleeds With Cognitive Decline and Dementia
SO JAMA NEUROLOGY
LA English
DT Article
ID ALZHEIMERS-DISEASE; ROTTERDAM-SCAN; LOBAR MICROBLEEDS; BRAIN
MICROBLEEDS; ISCHEMIC-STROKE; RISK-FACTORS; IMPAIRMENT; MRI; PREVALENCE;
DYSFUNCTION
AB IMPORTANCE Cerebral microbleeds are hypothesized downstream markers of brain damage caused by vascular and amyloid pathologic mechanisms. To date, whether their presence is associated with cognitive deterioration in the general population remains unclear.
OBJECTIVE To determine whether microbleeds, and more specifically microbleed count and location, are associated with an increased risk for cognitive impairment and dementia in the general population.
DESIGN, SETTING, AND PARTICIPANTS The Rotterdam Study, a prospective population-based study set in the general community, assessed the presence, number, and location of microbleeds at baseline (August 2005 to December 2011) on magnetic resonance imaging studies of the brain in 4841 participants 45 years or older. Participants underwent neuropsychological testing at 2 points a mean (SD) of 5.9 (0.6) years apart and were followed up for incident dementia throughout the study period until January 1, 2013. The association of microbleeds with cognitive decline and dementia was studied using multiple linear regression, linear mixed-effects modeling, and Cox proportional hazards.
EXPOSURES Cerebral microbleed presence, location, and number.
MAIN OUTCOMES AND MEASURES Cognitive decline measured by a decrease in neuropsychological test battery scores (Mini-Mental State Examination, Letter Digit Substitution Task, Word Fluency Test, Stroop test, 15-word Verbal Learning Test, and Purdue Pegboard Test) and compound scores (eg, G factor, executive function, information processing speed, memory, motor speed) and dementia.
RESULTS In total, 3257 participants (1758 women [54.7%]; mean [SD] age, 59.6 [7.8] years) underwent baseline and follow-up cognitive testing. Microbleed prevalence was 15.3% (median [interquartile range] count, 1 [1-88]). The presence of more than 4 microbleeds was associated with cognitive decline. Lobar (with or without cerebellar) microbleeds were associated with a decline in executive functions (mean difference in z score, -0.31; 95% CI, -0.51 to -0.11; P = .003), information processing (mean difference in z score, -0.44; 95% CI, -0.65 to -0.22; P < .001), and memory function (mean difference in z score, -0.34; 95% CI, -0.64 to -0.03; P = .03), whereas microbleeds in other brain regions were associated with a decline in information processing and motor speed (mean difference in z score, -0.61; 95% CI, -1.05 to -0.17; P = .007). After a mean (SD) follow-up of 4.8 (1.4) years, 72 participants developed dementia, of whom 53 had Alzheimer dementia. The presence of microbleeds was associated with an increased risk for dementia after adjustment for age, sex, and educational level (hazard ratio, 2.02; 95% CI, 1.25-3.24), including Alzheimer dementia (hazard ratio, 2.10; 95% CI, 1.21-3.64).
CONCLUSIONS AND RELEVANCE In the general population, a high microbleed count was associated with an increased risk for cognitive deterioration and dementia. Microbleeds thus mark the presence of diffuse vascular and neurodegenerative brain damage.
C1 [Akoudad, Saloua; Wolters, Frank J.; de Bruijn, Renee F.; Hofman, Albert; Ikram, M. Arfan; Vernooij, Meike W.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Na28-18,Postbus 2040, NL-3000 CA Rotterdam, Netherlands.
[Akoudad, Saloua; van der Lugt, Aad; Ikram, M. Arfan; Vernooij, Meike W.] Univ Med Ctr Rotterdam, Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Akoudad, Saloua; Wolters, Frank J.; de Bruijn, Renee F.; Koudstaal, Peter J.; Ikram, M. Arfan] Univ Med Ctr Rotterdam, Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
RP Ikram, MA (reprint author), Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Na28-18,Postbus 2040, NL-3000 CA Rotterdam, Netherlands.
EM m.a.ikram@erasmusmc.nl
FU Erasmus Medical Center and Erasmus University; Netherlands Organization
for Health Research and Development; Research Institute for Diseases in
the Elderly; Ministry of Education, Culture and Science; Ministry for
Health, Welfare and Sports; European Commission; Municipality of
Rotterdam
FX This study is supported by Erasmus Medical Center and Erasmus
University, the Netherlands Organization for Health Research and
Development, the Research Institute for Diseases in the Elderly, the
Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the European Commission, and the Municipality of
Rotterdam.
NR 49
TC 5
Z9 5
U1 6
U2 6
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 934
EP 943
DI 10.1001/jamaneurol.2016.1017
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900014
PM 27271785
ER
PT J
AU Boulouis, G
Morotti, A
Brouwers, B
Charidimou, A
Jessel, MJ
Auriel, E
Pontes-Neto, O
Ayres, A
Vashkevich, A
Schwab, KM
Rosand, J
Viswanathan, A
Gurol, ME
Greenberg, SM
Goldstein, JN
AF Boulouis, Gregoire
Morotti, Andrea
Brouwers, Bart
Charidimou, Andreas
Jessel, Michael J.
Auriel, Eitan
Pontes-Neto, Octavio
Ayres, Alison
Vashkevich, Anastasia
Schwab, Kristin M.
Rosand, Jonathan
Viswanathan, Anand
Gurol, Mahmut E.
Greenberg, Steven M.
Goldstein, Joshua N.
TI Association Between Hypodensities Detected by Computed Tomography and
Hematoma Expansion in Patients With Intracerebral Hemorrhage
SO JAMA NEUROLOGY
LA English
DT Article
ID ANGIOGRAPHY SPOT SIGN; BLOOD-PRESSURE REDUCTION; HYPERTENSIVE
CEREBRAL-HEMORRHAGE; HEALTH-CARE PROFESSIONALS; ACTIVATED FACTOR-VII;
CONTRAST EXTRAVASATION; STROKE ASSOCIATION; SWIRL SIGN; PREDICTION;
MORTALITY
AB IMPORTANCE Hematoma expansion is a potentially modifiable predictor of poor outcome following an acute intracerebral hemorrhage (ICH). The ability to identify patients with ICH who are likeliest to experience hematoma expansion and therefore likeliest to benefit from expansion-targeted treatments remains an unmet need. Hypodensities within an ICH detected by noncontrast computed tomography (NCCT) have been suggested as a predictor of hematoma expansion.
OBJECTIVE To determine whether hypodense regions, irrespective of their specific patterns, are associated with hematoma expansion in patients with ICH.
DESIGN, SETTING, AND PARTICIPANTS We analyzed a large cohort of 784 patients with ICH (the development cohort; 55.6% female), examined NCCT findings for any hypodensity, and replicated our findings on a different cohort of patients (the replication cohort; 52.7% female). Baseline and follow-up NCCT data from consecutive patients with ICH presenting to a tertiary care hospital between 1994 and 2015 were retrospectively analyzed. Data analyses were performed between December 2015 and January 2016.
MAIN OUTCOMES AND MEASURES Hypodensities were analyzed by 2 independent blinded raters. The association between hypodensities and hematoma expansion (>6 cm(3) or 33% of baseline volume) was determined by multivariable logistic regression after controlling for other variables associated with hematoma expansion in univariate analyses with P <= .10.
RESULTS A total of 1029 patients were included in the analysis. In the development and replication cohorts, 222 of 784 patients (28.3%) and 99 of 245 patients (40.4%; 321 of 1029 patients [31.2%]), respectively, had NCCT scans that demonstrated hypodensities at baseline (kappa = 0.87 for interrater reliability). In univariate analyses, hypodensities were associated with hematoma expansion (86 of 163 patients with hematoma expansion had hypodensities [52.8%], whereas 136 of 621 patients without hematoma expansion had hypodensities [21.9%]; P < .001). The association between hypodensities and hematoma expansion remained significant (odds ratio, 3.42 [95% CI, 2.21-5.31]; P < .001) in a multivariable model; other independent predictors of hematoma expansion were a CT angiography spot sign, a shorter time to CT, warfarin use, and older age. The independent predictive value of hypodensities was again demonstrated in the replication cohort (odds ratio, 4.37 [95% CI, 2.05-9.62]; P < .001).
CONCLUSION AND RELEVANCE Hypodensities within an acute ICH detected on an NCCT scan may predict hematoma expansion, independent of other clinical and imaging predictors. This novel marker may help clarify the mechanism of hematoma expansion and serve as a useful addition to clinical algorithms for determining the risk of and treatment stratification for hematoma expansion.
C1 [Boulouis, Gregoire; Morotti, Andrea; Brouwers, Bart; Charidimou, Andreas; Jessel, Michael J.; Auriel, Eitan; Pontes-Neto, Octavio; Ayres, Alison; Vashkevich, Anastasia; Schwab, Kristin M.; Rosand, Jonathan; Viswanathan, Anand; Gurol, Mahmut E.; Greenberg, Steven M.; Goldstein, Joshua N.] Harvard Med Sch, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
[Brouwers, Bart] Univ Utrecht, Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurosurg, Utrecht, Netherlands.
[Rosand, Jonathan; Goldstein, Joshua N.] Harvard Med Sch, Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA USA.
[Goldstein, Joshua N.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
RP Boulouis, G (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Dept Neurol,Stroke Res Ctr, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
EM gregoireboulouis@gmail.com
OI Boulouis, Gregoire/0000-0001-8422-9205
FU National Institutes of Health [R01-AG026484, R01-NS073344]; J. William
Fulbright Scholarship; Monahan Foundation Biomedical Research Grant
FX This work was supported by National Institutes of Health grants
R01-AG026484 (Dr Greenberg) and R01-NS073344 (Dr Goldstein). Dr Boulouis
was supported by a J. William Fulbright Scholarship and a Monahan
Foundation Biomedical Research Grant.
NR 49
TC 1
Z9 1
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 961
EP 968
DI 10.1001/jamaneurol.2016.1218
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900017
PM 27323314
ER
PT J
AU Biffi, A
Bailey, D
Anderson, CD
Ayres, AM
Gurol, EM
Greenberg, SM
Rosand, J
Viswanathan, A
AF Biffi, Alessandro
Bailey, Destiny
Anderson, Christopher D.
Ayres, Alison M.
Gurol, Edip M.
Greenberg, Steven M.
Rosand, Jonathan
Viswanathan, Anand
TI Risk Factors Associated With Early vs Delayed Dementia After
Intracerebral Hemorrhage
SO JAMA NEUROLOGY
LA English
DT Article
ID CEREBRAL AMYLOID ANGIOPATHY; MILD COGNITIVE IMPAIRMENT; WHITE-MATTER
LESIONS; TELEPHONE INTERVIEW; ALZHEIMERS-DISEASE; APOE GENOTYPE; STATUS
TICS; MICROBLEEDS; MRI; METAANALYSIS
AB IMPORTANCE Patients who have experienced intracerebral hemorrhage (ICH) appear to develop cognitive impairment at high rates, both early after ICH and over the long term.
OBJECTIVE To identify and compare risk factors for early and delayed dementia after ICH.
DESIGN, SETTING, AND PARTICIPANTS A longitudinal study enrolled patients who had experienced ICH from January 1, 2006, to December 31, 2013. A total of 738 participants 18 years or older, without pre-ICH dementia, who presented to a tertiary care academic institution with primary ICH were included in the analyses of early post-ICH dementia (EPID). After accounting for incident dementia and mortality at 6 months, 435 participants were included in the analyses of delayed post-ICH dementia (DPID).
EXPOSURES Intracerebral hemorrhage.
MAIN OUTCOMES AND MEASURES Cognitive performancewas captured using the modified Telephone Interview for Cognitive Status test. Outcomes included EPID, diagnosed within 6 months after ICH, and DPID, diagnosed beyond 6 months after ICH.
RESULTS Among 738 patients who had experienced ICH (mean [SD] age, 74.3 [12.1] years; 384 men [52.0%]), 140 (19.0%) developed dementia within 6 months. A total of 435 patients without dementia at 6 months were followed up longitudinally (median follow-up, 47.4 months; interquartile range, 43.4-52.1 months), with an estimated yearly incidence of dementia of 5.8% (95% CI, 5.1%-7.0%). Larger hematoma size (hazard ratio [HR], 1.47 per 10-mL increase; 95% CI, 1.09-1.97; P < .001 for heterogeneity) and lobar location of ICH (HR, 2.04; 95% CI, 1.06-3.91; P = .02 for heterogeneity) were associated with EPID but not with DPID. Educational level (HR, 0.60; 95% CI, 0.40-0.89; P < .001 for heterogeneity), incident mood symptoms (HR, 1.29; 95% CI, 1.02-1.63; P = .01 for heterogeneity), and white matter disease as defined via computed tomography (HR, 1.70; 95% CI, 1.07-2.71; P = .04 for heterogeneity) were associated with DPID but not EPID.
CONCLUSIONS AND RELEVANCE Incident dementia early after ICH is strongly associated with hematoma size and location. Delayed incident dementia is frequent among patients who have experienced ICH and is not prominently associated with acute characteristics of ICH. These findings suggest the existence of heterogeneous biological mechanisms accounting for early vs delayed cognitive decline among patients who have experienced ICH.
C1 [Biffi, Alessandro; Bailey, Destiny; Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,Mailbox CPZN 6818, Boston, MA 02114 USA.
[Biffi, Alessandro; Bailey, Destiny; Anderson, Christopher D.; Ayres, Alison M.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand] Massachusetts Gen Hosp, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA.
[Biffi, Alessandro; Anderson, Christopher D.; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Div Stroke, Boston, MA 02114 USA.
[Biffi, Alessandro] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care & Emergency Neurol, Boston, MA 02114 USA.
[Anderson, Christopher D.; Gurol, Edip M.; Greenberg, Steven M.; Rosand, Jonathan; Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Div Behav Neurol, Boston, MA 02114 USA.
[Anderson, Christopher D.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Psychiat, Div Neuropsychiat, Boston, MA 02114 USA.
RP Biffi, A (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,Mailbox CPZN 6818, Boston, MA 02114 USA.
EM abiffi@partners.org
OI Anderson, Christopher/0000-0002-0053-2002
FU National Institutes of Health [R25NS065743, R01NS063925, R01NS059727,
K23NS086873, P50NS051343, R01AG26484]
FX The authors' work on this study was supported by grants R25NS065743,
R01NS063925, R01NS059727, K23NS086873, P50NS051343, and R01AG26484 from
the National Institutes of Health.
NR 31
TC 0
Z9 0
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 969
EP 976
DI 10.1001/jamaneurol.2016.0955
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900018
PM 27295605
ER
PT J
AU Charidimou, A
Martinez-Ramirez, S
Reijmer, YD
Oliveira, J
Lauer, A
Roongpiboonsopit, D
Frosch, M
Vashkevich, A
Ayres, A
Rosand, J
Gurol, ME
Greenberg, SM
Viswanathan, A
AF Charidimou, Andreas
Martinez-Ramirez, Sergi
Reijmer, Yael D.
Oliveira-Filho, Jamary
Lauer, Arne
Roongpiboonsopit, Duangnapa
Frosch, Matthew
Vashkevich, Anastasia
Ayres, Alison
Rosand, Jonathan
Gurol, Mahmut Edip
Greenberg, Steven M.
Viswanathan, Anand
TI Total Magnetic Resonance Imaging Burden of Small Vessel Disease in
Cerebral Amyloid Angiopathy An Imaging- Pathologic Study of Concept
Validation
SO JAMA NEUROLOGY
LA English
DT Article
ID CORTICAL SUPERFICIAL SIDEROSIS; RECURRENT INTRACEREBRAL HEMORRHAGE;
ENLARGED PERIVASCULAR SPACES; LACUNAR STROKE; MRI; MICROBLEEDS; MARKER;
COHORT; PREVALENCE; DIAGNOSIS
AB IMPORTANCE Cerebral amyloid angiopathy (CAA) is characteristically associated with magnetic resonance imaging (MRI) biomarkers of small vessel brain injury, including strictly lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. Although these neuroimaging markers reflect distinct pathophysiologic aspects in CAA, no studies to date have combined these structural imaging features to gauge total brain small vessel disease burden in CAA.
OBJECTIVES To investigate whether a composite score can be developed to capture the total brain MRI burden of small vessel disease in CAA and to explore whether this score contributes independent and complementary information about CAA severity, defined as intracerebral hemorrhage during life or bleeding-related neuropathologic changes.
DESIGN, SETTING, AND PARTICIPANTS This retrospective, cross-sectional study examined a single-center neuropathologic CAA cohort of eligible patients from the Massachusetts General Hospital from January 1, 1997, through December 31, 2012. Data analysis was performed from January 2, 2015, to January 9, 2016. Patients with pathologic evidence of CAA (ie, any presence of CAA from routinely collected brain biopsy specimen, biopsy specimen at hematoma evacuation, or autopsy) and available brain MRI sequences of adequate quality, including T2-weighted, T2*-weighted gradient-recalled echo, and/or susceptibility-weighted imaging and fluid-attenuated inversion recovery sequences, were considered for the study.
MAIN OUTCOMES AND MEASURES Brain MRIswere rated for lobar cerebral microbleeds, cortical superficial siderosis, centrum semiovale perivascular spaces, and white matter hyperintensities. All 4 MRI lesions were incorporated into a prespecified ordinal total small vessel disease score, ranging from 0 to 6 points. Associations with severity of CAA-associated vasculopathic changes (fibrinoid necrosis and concentric splitting of the wall), clinical presentation, number of intracerebral hemorrhages, and other imaging markers not included in the score were explored using logistic and ordinal regression.
RESULTS In total, 105 patients with pathologically defined CAA were included: 52 with autopsies, 22 with brain biopsy specimens, and 31 with pathologic samples from hematoma evacuations. The mean (range) age of the patients was 73 (71-74) years, and 55 (52.4%) were women. In multivariable ordinal regression analysis, severity of CAA-associated vasculopathic changes (odds ratio, 2.40; 95% CI, 1.06-5.45; P =.04) and CAA presentation with symptomatic intracerebral hemorrhage (odds ratio, 2.23; 95% CI, 1.07-4.64; P =.03) were independently associated with the total MRI small vessel disease score. The score was associated with small, acute, diffusion-weighted imaging lesions and posterior white matter hyperintensities in adjusted analyses.
CONCLUSIONS AND RELEVANCE This study provides evidence of concept validity of a total MRI small vessel disease score in CAA. After further validation, this approach can be potentially used in prospective clinical studies.
C1 [Charidimou, Andreas; Martinez-Ramirez, Sergi; Reijmer, Yael D.; Oliveira-Filho, Jamary; Lauer, Arne; Roongpiboonsopit, Duangnapa; Vashkevich, Anastasia; Ayres, Alison; Rosand, Jonathan; Gurol, Mahmut Edip; Greenberg, Steven M.; Viswanathan, Anand] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program,Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
[Frosch, Matthew] Harvard Med Sch, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA USA.
[Rosand, Jonathan] Harvard Med Sch, Massachusetts Gen Hosp, Div Neurocrit Care & Emergency Neurol, Boston, MA USA.
[Rosand, Jonathan] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA USA.
RP Charidimou, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Stroke Res, Hemorrhag Stroke Res Program,Dept Neurol, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
EM andreas.charidimou.09@ucl.ac.uk
FU National Institutes of Health [5RO1AG047975, 5P5OAG005134, 5K23AGO28726,
RO1AG26484]
FX This study was supported by grants 5RO1AG047975, 5P5OAG005134,
5K23AGO28726 (Dr Viswanathan), and RO1AG26484 (Dr Greenberg) from the
National Institutes of Health.
NR 47
TC 3
Z9 3
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 994
EP 1001
DI 10.1001/jamaneurol.2016.0832
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900022
PM 27366898
ER
PT J
AU Walcott, BP
Stapleton, CJ
Choudhri, O
Patel, AB
AF Walcott, Brian P.
Stapleton, Christopher J.
Choudhri, Omar
Patel, Aman B.
TI Flow Diversion for the Treatment of Intracranial Aneurysms
SO JAMA NEUROLOGY
LA English
DT Review
ID PIPELINE EMBOLIZATION DEVICE; ANTERIOR CHOROIDAL ARTERY; ENDOVASCULAR
TREATMENT; CEREBRAL ANEURYSMS; FOLLOW-UP; SACCULAR ANEURYSMS;
SURGICAL-TREATMENT; DIVERTOR STENT; EXPERIENCE; MULTICENTER
AB IMPORTANCE Brain aneurysms have traditionally been treated with surgical clipping or endovascular coiling techniques. With these modalities, many large or complex aneurysms remain difficult to treat. A new option, flow diversion, is now available to treat aneurysms.
OBJECTIVE To summarize the clinical progression of flow diversion technology, from an experimental treatment to a commonly used method to treat large or complex aneurysms.
EVIDENCE REVIEW References for this topical review were identified by searches of PubMed and GoogleScholar between January 2000 and January 2016. The search terms aneurysm, flow diverter, stent, pipeline, FRED, SURPASS, SILK, flow diversion, and endovascular were used. Ongoing clinical trials were identified using the same search terms in the clinicaltrial. gov registry. Attention was focused on current indications, rates of complications, and areas of ongoing study in randomized clinical trials.
FINDINGS Flow diversion is a treatment approved by the US Food and Drug Administration for brain aneurysms that redirects blood flow away from the aneurysm, thereby promoting growth of a new endothelial lining across the aneurysm opening. Cure rates with this technology are high and complication rates are low.
CONCLUSIONS AND RELEVANCE Flow diversion is a disruptive technology that has changed the way many brain aneurysms are treated. It is currently a preferred treatment option for large or giant wide-necked proximal internal carotid artery aneurysms. Ongoing randomized studies will help to more rigorously determine the efficacy of flow diversion.
C1 [Walcott, Brian P.; Choudhri, Omar] Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA.
[Stapleton, Christopher J.; Patel, Aman B.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA.
[Stapleton, Christopher J.; Patel, Aman B.] Harvard Med Sch, Boston, MA USA.
RP Walcott, BP (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,Room M779, San Francisco, CA 94143 USA.
EM brian.walcott@ucsf.edu
FU Penumbra; Covidien
FX Dr Patel reported serving as a paid consultant for Penumbra and
Covidien. No other disclosures were reported.
NR 52
TC 1
Z9 1
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 1002
EP 1008
DI 10.1001/jamaneurol.2016.0609
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900023
PM 27294446
ER
PT J
AU Nguyen, L
Hur, C
AF Nguyen, Long
Hur, Chin
TI Proton Pump Inhibitors and Dementia Incidence
SO JAMA NEUROLOGY
LA English
DT Letter
ID RISK
C1 [Nguyen, Long; Hur, Chin] Massachusetts Gen Hosp, Gastroenterol, Boston, MA 02114 USA.
RP Hur, C (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM chur@mgh.harvard.edu
OI Hur, Chin/0000-0002-2819-7576
NR 5
TC 0
Z9 0
U1 3
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 1027
EP 1028
DI 10.1001/jamaneurol.2016.1962
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900034
PM 27322752
ER
PT J
AU Arsava, EM
Ay, H
AF Arsava, Ethem Murat
Ay, Hakan
TI Instrument for Predicting Early Stroke Recurrence: Ambiguity and Biases
Reply
SO JAMA NEUROLOGY
LA English
DT Letter
ID ISCHEMIC-STROKE; RISK
C1 [Arsava, Ethem Murat] Hacettepe Univ, Dept Neurol, Fac Med, Ankara, Turkey.
[Ay, Hakan] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA USA.
[Ay, Hakan] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA USA.
RP Ay, H (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA.
EM hay@mgh.harvard.edu
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD AUG
PY 2016
VL 73
IS 8
BP 1031
EP 1032
DI 10.1001/jamaneurol.2016.1727
PG 3
WC Clinical Neurology
SC Neurosciences & Neurology
GA DX2MS
UT WOS:000384204900039
PM 27368069
ER
PT J
AU Heist, RS
Sequist, LV
Borger, D
Gainor, JF
Arellano, RS
Le, LP
Dias-Santagata, D
Clark, JW
Engelman, JA
Shaw, AT
Lafrate, AJ
AF Heist, Rebecca S.
Sequist, Lecia V.
Borger, Darrell
Gainor, Justin F.
Arellano, Ronald S.
Le, Long P.
Dias-Santagata, Dora
Clark, Jeffrey W.
Engelman, Jeffrey A.
Shaw, Alice T.
Lafrate, A. John
TI Acquired Resistance to Crizotinib in NSCLC with MET Exon 14 Skipping
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE NSCLC; MET exon 14 skipping; Acquired resistance; Targeted therapy
ID CELL LUNG-CANCER; MUTATIONS; INHIBITORS; REVEALS
AB Introduction: MET proto-oncogene, receptor tyrosine kinase gene (MET) exon 14 skipping is a targetable alteration in lung cancer. Treatment with MET proto-oncogene, receptor tyrosine kinase inhibitor can cause dramatic responses in patients whose cancers have MET exon 14 skipping. Little is known, however, about acquired resistance in patients with MET exon 14 skipping.
Methods: Biopsy specimens obtained at baseline and at the time of progression for a patient being treated with crizotinib were compared using targeted next-generation sequencing to assess for mechanisms of resistance.
Results: An acquired mutation in the MET kinase domain, D1228N, was found at time of progression on crizotinib in a patient with MET exon 14 skipping.
Conclusions: One potential mechanism of acquired resistance to crizotinib in patients with MET exon 14 skipping is through second-site mutations in the MET gene. Understanding mechanisms of resistance will be important in optimizing therapy in these patients. (C) 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.
C1 [Heist, Rebecca S.; Sequist, Lecia V.; Borger, Darrell; Gainor, Justin F.; Clark, Jeffrey W.; Engelman, Jeffrey A.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA.
[Borger, Darrell; Le, Long P.; Dias-Santagata, Dora; Lafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Arellano, Ronald S.] Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA.
RP Heist, RS (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St, Boston, MA 02114 USA.
EM rheist@partners.org
FU Be a Piece of the Solution; LungStrong; Targeting a Cure for Lung
Cancer; [5R01CA164273]
FX Crizotinib was provided as part of a clinical trial by Pfizer. This
study was supported by funding from 5R01CA164273 (to Drs. Shaw and
Engelman) and funding from the following foundations: Be a Piece of the
Solution; LungStrong; and Targeting a Cure for Lung Cancer.
NR 15
TC 10
Z9 11
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD AUG
PY 2016
VL 11
IS 8
BP 1242
EP 1245
DI 10.1016/j.jtho.2016.06.013
PG 4
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA DS8XW
UT WOS:000381067300007
PM 27343442
ER
PT J
AU Della-Torre, E
Lanzillotta, M
Campochiaro, C
Bozzalla, E
Bozzolo, E
Bandiera, A
Bazzigaluppi, E
Canevari, C
Modorati, G
Stone, JH
Manfredi, A
Doglioni, C
AF Della-Torre, Emanuel
Lanzillotta, Marco
Campochiaro, Corrado
Bozzalla, Emanuele
Bozzolo, Enrica
Bandiera, Alessandro
Bazzigaluppi, Elena
Canevari, Carla
Modorati, Giulio
Stone, John H.
Manfredi, Angelo
Doglioni, Claudio
TI Antineutrophil cytoplasmic antibody positivity in IgG4-related disease:
A case report and review of the literature
SO MEDICINE
LA English
DT Review
DE antineutrophil cytoplasmic antibodies; case report; granulomatosis with
polyangiitis; IgG4; IgG4-related disease; rituximab; vasculitis
ID WEGENERS-GRANULOMATOSIS; HYPERTROPHIC PACHYMENINGITIS; RETROPERITONEAL
FIBROSIS; AUTOANTIBODIES ANCA; SYSTEMIC VASCULITIS; IGG SUBCLASSES;
POLYANGIITIS
AB Background:IgG4-related disease (IgG4-RD) is a fibroinflammatory condition characterized by serum IgG4 elevation and tissue infiltration of IgG4-positive plasma cells. Substantial overlap between IgG4-RD and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) exists in terms of organ involvement and histopathological features. A positive ANCA assay is regarded as a highly specific finding in favor of an AAV, and generally influences away from a diagnosis of IgG4-RD. Recent reports, however, have raised the possibility that some patients with IgG4-RD are ANCA positive, thus suggesting reconsideration of the role of ANCA in the diagnostic workup. In the present work, we describe the first case of concomitant biopsy-proven IgG4-RD and granulomatosis with polyangiitis (GPA), demonstrating antiproteinase 3 (PR3) ANCA of the IgG4 subclass in the patient's serum. We also review the literature in order to provide clinicians with tools for interpreting ANCA positivity in IgG4-RD patients.Case summary:A 51-year-old woman was referred for left exopthalmos due to lacrimal gland enlargement and increased serum IgG4 concentration. IgG4-RD was suspected and further imaging studies disclosed multiple pulmonary masses in the right lung. Histological analysis of the left lacrimal gland was diagnostic for IgG4-RD, but lung biopsy showed typical features of GPA. ANCA assay was positive for anti-PR3 antibodies. Further immunofluorescence studies demonstrated anti-PR3 antibodies of IgG1 and IgG4 subclass. Treatment with rituximab induced swift remission of both IgG4-RD and GPA manifestations. We identified 9 other reports of patients with IgG4-RD and positive ANCA in the English literature, 5 cases with biopsy-proven IgG4-RD and 4 cases in whom IgG4-RD was diagnosed presumptively. Four patients had also histological evidence of concomitant AAV.Conclusion:The present work demonstrates that ANCA positivity in patients with biopsy-proven IgG4-RD should prompt the exclusion of a concomitant vasculitic process; a positive ANCA does not exclude the diagnosis of IgG4-RD; confirmation through immunoenzymatic assays of the ANCA specificity, clinical-pathological correlation, and histopathological evaluation remain crucial steps for the differential diagnosis between AAV and IgG4-RD.
C1 [Della-Torre, Emanuel; Lanzillotta, Marco; Campochiaro, Corrado; Bozzalla, Emanuele; Manfredi, Angelo; Doglioni, Claudio] Univ Vita Salute San Raffaele, IRCCS San Raffaele Sci Inst, Milan, Italy.
[Della-Torre, Emanuel; Manfredi, Angelo] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, Milan, Italy.
[Della-Torre, Emanuel; Campochiaro, Corrado; Bozzolo, Enrica; Manfredi, Angelo] IRCCS San Raffaele Sci Inst, Unit Med & Clin Immunol, Via Olgettina 60, I-20132 Milan, Italy.
[Bandiera, Alessandro] IRCCS San Raffaele Sci Inst, Dept Thorac Surg, Milan, Italy.
[Bazzigaluppi, Elena] IRCCS San Raffaele Sci Inst, Lab Diagnost Res, Milan, Italy.
[Canevari, Carla] IRCCS San Raffaele Sci Inst, Div Nucl Med, Milan, Italy.
[Modorati, Giulio] IRCCS San Raffaele Sci Inst, Dept Ophthalmol, Milan, Italy.
[Stone, John H.] Harvard Med Sch, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA USA.
[Doglioni, Claudio] IRCCS San Raffaele Sci Inst, Pathol Unit, Milan, Italy.
RP Della-Torre, E (reprint author), IRCCS San Raffaele Sci Inst, Unit Med & Clin Immunol, Via Olgettina 60, I-20132 Milan, Italy.
EM dellatorre.emanuel@hsr.it
FU "Fondazione Italiana per la Ricerca sull' Artrite" (FIRA Onlus)
FX This work was supported in part by a grant from the "Fondazione Italiana
per la Ricerca sull' Artrite" (FIRA Onlus 2014).
NR 36
TC 0
Z9 0
U1 8
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0025-7974
EI 1536-5964
J9 MEDICINE
JI Medicine (Baltimore)
PD AUG
PY 2016
VL 95
IS 34
AR e4633
DI 10.1097/MD.0000000000004633
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DX0DV
UT WOS:000384032900039
PM 27559962
ER
PT J
AU Dams, J
Balzer-Geldsetzer, M
Siebert, U
Deuschl, G
Schuepbach, WMM
Krack, P
Timmermann, L
Schnitzler, A
Reese, JP
Dodel, R
AF Dams, Judith
Balzer-Geldsetzer, Monika
Siebert, Uwe
Deuschl, Guenther
Schuepbach, W. M. Michael
Krack, Paul
Timmermann, Lars
Schnitzler, Alfons
Reese, Jens-Peter
Dodel, Richard
CA EARLYSTIM-Investigators
TI Cost-effectiveness of neurostimulation in Parkinson's disease with early
motor complications
SO MOVEMENT DISORDERS
LA English
DT Article
DE early Parkinson's disease; dyskinesia; deep brain stimulation; Markov
model; cost-utility analysis
ID DEEP-BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; FOLLOW-UP; METAANALYSIS;
PREDICTORS; OUTCOMES; GERMANY; TRIAL; LIFE
AB BackgroundRecent research efforts have focused on the effects of deep brain stimulation of the subthalamic nucleus (STN DBS) for selected patients with mild-to-moderate PD experiencing motor complications.
ObjectivesWe assessed the cost utility of subthalamic DBS compared with the best medical treatment for German patients below the age of 61 with early motor complications of PD.
MethodsWe applied a previously published Markov model that integrated health utilities based on EuroQoL and direct costs over patients' lifetime adjusted to the German health care payer perspective (year of costing: 2013). Effectiveness was evaluated using the Parkinson's Disease Questionnaire 39 summary index. We performed sensitivity analyses to assess uncertainty.
ResultsIn the base-case analysis, the incremental cost-utility ratio for STN DBS compared to best medical treatment was 22,700 Euros per quality-adjusted life year gained. The time to, and costs for, battery exchange had a major effect on the incremental cost-utility ratios, but never exceeded a threshold of 50,000 Euros per quality-adjusted life year.
ConclusionsOur decision analysis supports the fact that STN DBS at earlier stages of the disease is cost-effective in patients below the age of 61 when compared with the best medical treatment in the German health care system. This finding was supported by detailed sensitivity analyses reporting robust results. Whereas the EARLYSTIM study has shown STN DBS to be superior to medical therapy with respect to quality of life for patients with early motor complications, this further analysis has shown its cost-effectiveness. (c) 2016 International Parkinson and Movement Disorder Society
C1 [Dams, Judith; Balzer-Geldsetzer, Monika; Dodel, Richard] Univ Marburg, Dept Neurol, Baldingerstr, D-35043 Marburg, Germany.
[Siebert, Uwe] UMIT Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Hlth Serv Res & HealthTechnol Asse, Halle, Germany.
[Siebert, Uwe] Harvard Med Sch, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA USA.
[Siebert, Uwe] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Siebert, Uwe] Harvard Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Deuschl, Guenther] Univ Kiel, Dept Neurol, Kiel, Germany.
[Schuepbach, W. M. Michael] Univ Paris 06, Inst Cerveau & Moelle Epiniere, Ctr Invest Clin 9503, AP HP,Dept Neurol, Paris, France.
[Schuepbach, W. M. Michael] CHU Pitie Salpetriere, INSERM, Paris, France.
[Schuepbach, W. M. Michael] Univ Hosp Bern, Dept Neurol, Movement Disorders Ctr, Bern, Switzerland.
[Schuepbach, W. M. Michael] Univ Bern, Bern, Switzerland.
[Krack, Paul] Grenoble Alpes Univ, Univ Hosp INSERM U836, Dept Neurol, St Martin Dheres, France.
[Timmermann, Lars] Univ Hosp Cologne, Dept Neurol, Cologne, Germany.
[Schnitzler, Alfons] Univ Dusseldorf, Inst Clin Neurosci & Med Psychol, Dusseldorf, Germany.
[Reese, Jens-Peter] Univ Marburg, Dept Med Sociol & Social Med, Marburg, Germany.
[Dodel, Richard] Univ Duisburg Essen, Dept Geriatr, Essen, Germany.
RP Dodel, R (reprint author), Univ Marburg, Dept Neurol, Baldingerstr, D-35043 Marburg, Germany.
EM dodel@med.uni-marburg.de
OI Volkmann, Jens/0000-0002-9570-593X
FU Teva; Medtronic; Boston Scientific; Orkyn; Novartis; UGH; LVL; St Jude
FX G.D. has board membership for Teva Pharmaceuticals and Novartis received
lecture fees from Teva M.S. has received research support from Medtronic
and Boston Scientific, lecture fees from Medtronic, and travel
reimbursements from Zambon, Merz Pharma, Boston Scientific, and
Medtronic and has been serving as a consultant for Medtronic and Aleva.
P.K. has received research support from Orkyn, Novartis, UGH, Medtronic,
LVL, Boston Scientific, and St Jude and honoraria for lecturing or
consultation from the International Parkinson and Movement Disorder
Society, Lundbeck, Boehringer Ingelheim, Novartis, UGH, Medtronic,
Orkyn, Abbott, Orion, TEVA, and Boston Scientific. L.I. has served as a
consultant for Medtronic, Boston Scientific, and St. Jude and received
speakers' honoraria in symposia sponsored by Medtronic, Boston
Scientific, and St. Jude. The institution of L.T. received unrestricted
research grants by Medtronic and Boston Scientific. A.S. has served as a
consultant for Medtronic Inc, Boston Scientific, and St. Jude Medical
and received lecture fees from Boston Scientific, St. Jude Medical, and
Medtronic Inc.
NR 35
TC 1
Z9 1
U1 5
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD AUG
PY 2016
VL 31
IS 8
BP 1183
EP 1191
DI 10.1002/mds.26740
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA DU9ST
UT WOS:000382558800019
PM 27506638
ER
PT J
AU DeLisi, LE
AF DeLisi, Lynn E.
TI Signing off as Editor-in-Chief
SO SCHIZOPHRENIA RESEARCH
LA English
DT Editorial Material
ID SCHIZOPHRENIA; PATHOLOGY
C1 [DeLisi, Lynn E.] Harvard Med Sch, VA Boston Healthcare Syst, Psychiat, 940 Belmont Ave, Brockton, MA 02301 USA.
RP DeLisi, LE (reprint author), Harvard Med Sch, VA Boston Healthcare Syst, Psychiat, 940 Belmont Ave, Brockton, MA 02301 USA.
EM Lynn_DeLisi@hms.harvard.edu
NR 6
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
EI 1573-2509
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD AUG
PY 2016
VL 175
IS 1-3
BP 2
EP 3
DI 10.1016/j.schres.2016.06.026
PG 2
WC Psychiatry
SC Psychiatry
GA DS5GA
UT WOS:000380808200002
PM 27444218
ER
PT J
AU Raja, AS
Mower, WR
Nishijima, DK
Hendey, GW
Baumann, BM
Medak, AJ
Rodriguez, RM
AF Raja, Ali S.
Mower, William R.
Nishijima, Daniel K.
Hendey, Gregory W.
Baumann, Brigitte M.
Medak, Anthony J.
Rodriguez, Robert M.
TI Prevalence and Diagnostic Performance of Isolated and Combined NEXUS
Chest CT Decision Criteria
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID MULTISYSTEM TRAUMA PATIENTS; BLUNT TRAUMA; COMPUTED-TOMOGRAPHY; OBVIOUS
SIGNS; INJURY; RADIOGRAPHY; INSTRUMENT
AB Objectives: The use of chest computed tomography (CT) to evaluate emergency department patients with adult blunt trauma is rising. The NEXUS Chest CT decision instruments are highly sensitive identifiers of adult blunt trauma patients with thoracic injuries. However, many patients without injury exhibit one of more of the criteria so cannot be classified "low risk." We sought to determine screening performance of both individual and combined NEXUS Chest CT criteria as predictors of thoracic injury to inform chest CT imaging decisions in "non-low-risk" patients.
Methods: This was a secondary analysis of data on patients in the derivation and validation cohorts of the prospective, observational NEXUS Chest CT study, performed September 2011 to May 2014 in 11 Level I trauma centers. Institutional review board approval was obtained at all study sites. Adult blunt trauma patients receiving chest CT were included. The primary outcome was injury and major clinical injury prevalence and screening performance in patients with combinations of one, two, or three of seven individual NEXUS Chest CT criteria.
Results: Across the 11 study sites, rates of chest CT performance ranged from 15.5% to 77.2% (median = 43.6%). We found injuries in 1,493/5,169 patients (28.9%) who had chest CT; 269 patients (5.2%) had major clinical injury (e.g., pneumothorax requiring chest tube). With sensitivity of 73.7 (95% confidence interval [CI] = 68.1 to 78.6) and specificity of 83.9 (95% CI = 83.6 to 84.2) for major clinical injury, abnormal chest-x-ray (CXR) was the single most important screening criterion. When patients had only abnormal CXR, injury and major clinical injury prevalences were 60.7% (95% CI = 52.2% to 68.6%) and 12.9% (95% CI = 8.3% to 19.4%), respectively. Injury and major clinical injury prevalences when any other single criterion alone (other than abnormal CXR) was present were 16.8% (95% CI = 15.2% to 18.6%) and 1.1% (95% CI = 0.1% to 1.8%), respectively. Injury and major clinical injury prevalences among patients when two and three criteria (not abnormal CXR) were present were 25.5% (95% CI = 23.1% to 28.0%) and 3.2% (95% CI = 2.3% to 4.4%) and 34.9% (95% CI = 31.0% to 39.0%) and 2.7% (95% CI = 1.6% to 4.5%), respectively.
Conclusions: We recommend that clinicians check for the six clinical NEXUS Chest CT criteria and review the CXR (if obtained). If patients have one clinical criterion (other than abnormal CXR), they will have a very low risk of clinically major injury. We recommend that clinicians discuss the potential risks and benefit of chest CT in these cases. The risks of injury and major clinical injury rise incrementally with more criteria, rendering the risk/benefit ratio toward performing CT in most cases. If the patient has an abnormal CXR, the risks of major clinical injury and minor injury are considerably higher than with the other criteria-chest CT may be indicated in cases requiring greater anatomic detail and injury characterization. (C) 2016 by the Society for Academic Emergency Medicine
C1 [Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Raja, Ali S.] Harvard Med Sch, Boston, MA 02115 USA.
[Mower, William R.] Univ Calif Los Angeles, Dept Emergency Med, Los Angeles, CA USA.
[Nishijima, Daniel K.] Univ Calif Davis, Dept Emergency Med, Davis, CA 95616 USA.
[Hendey, Gregory W.] San Francisco Fresno Med Educ Program, Dept Emergency Med, San Francisco, CA USA.
[Baumann, Brigitte M.] Rowan Univ, Cooper Med Sch, Dept Emergency Med, Camden, NJ USA.
[Medak, Anthony J.] Univ Calif San Diego, Sch Med, Dept Emergency Med, San Diego, CA 92103 USA.
[Rodriguez, Robert M.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA.
RP Raja, AS (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.; Raja, AS (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM ASRaja@partners.org
FU University of California Center for Health Quality and Innovation (CHQI)
FX Funded by University of California Center for Health Quality and
Innovation (CHQI).
NR 22
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
EI 1553-2712
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD AUG
PY 2016
VL 23
IS 8
BP 863
EP 869
DI 10.1111/acem.13010
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA DW1BQ
UT WOS:000383378200003
PM 27163732
ER
PT J
AU Collins, SP
Levy, PD
Martindale, JL
Dunlap, ME
Storrow, AB
Pang, PS
Albert, NM
Felker, GM
Fermann, GJ
Fonarow, GC
Givertz, MM
Hollander, JE
Lanfear, DE
Lenihan, DJ
Lindenfeld, JM
Peacock, WF
Sawyer, DB
Teerlink, JR
Butler, J
AF Collins, Sean P.
Levy, Phillip D.
Martindale, Jennifer L.
Dunlap, Mark E.
Storrow, Alan B.
Pang, Peter S.
Albert, Nancy M.
Felker, G. Michael
Fermann, Gregory J.
Fonarow, Gregg C.
Givertz, Michael M.
Hollander, Judd E.
Lanfear, David E.
Lenihan, Daniel J.
Lindenfeld, JoAnn M.
Peacock, W. Frank
Sawyer, Douglas B.
Teerlink, John R.
Butler, Javed
TI Clinical and Research Considerations for Patients With Hypertensive
Acute Heart Failure: A Consensus Statement from the Society for Academic
Emergency Medicine and the Heart Failure Society of America Acute Heart
Failure Working Group
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID CARDIOGENIC PULMONARY-EDEMA; WORSENING RENAL-FUNCTION; SCANDINAVIAN
ENALAPRIL SURVIVAL; HAND-CARRIED ULTRASOUND; BLOOD-PRESSURE;
ISOSORBIDE-DINITRATE; NONINVASIVE VENTILATION; FLUID ACCUMULATION;
TRANSDERMAL NITROGLYCERIN; INTRAVENOUS ENALAPRILAT
AB Management approaches for patients in the emergency department (ED) who present with acute heart failure (AHF) have largely focused on intravenous diuretics. Yet, the primary pathophysiologic derangement underlying AHF in many patients is not solely volume overload. Patients with hypertensive AHF (H-AHF) represent a clinical phenotype with distinct pathophysiologic mechanisms that result in elevated ventricular filling pressures. To optimize treatment response and minimize adverse events in this subgroup, we propose that clinical management be tailored to a conceptual model of disease that is based on these mechanisms. This consensus statement reviews the relevant pathophysiology, clinical characteristics, approach to therapy, and considerations for clinical trials in ED patients with H-AHF. (C) 2016 by the Society for Academic Emergency Medicine
C1 [Collins, Sean P.; Storrow, Alan B.] Vanderbilt Univ, Dept Emergency Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Levy, Phillip D.] Wayne State Univ, Dept Emergency Med, Detroit, MI USA.
[Martindale, Jennifer L.] SUNY Downstate, Dept Emergency Med, Brooklyn, NY USA.
[Dunlap, Mark E.] Case Western Univ, Dept Med, Cleveland, OH USA.
[Pang, Peter S.] Indiana Univ, Dept Emergency Med, Indianapolis, IN 46204 USA.
[Albert, Nancy M.] Cleveland Clin, Dept Med, Cleveland, OH 44106 USA.
[Felker, G. Michael] Duke Univ, Dept Med, Durham, NC USA.
[Fermann, Gregory J.] Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA.
[Fonarow, Gregg C.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Givertz, Michael M.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Hollander, Judd E.] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA.
[Lanfear, David E.] Henry Ford Hlth Syst, Dept Med, Detroit, MI USA.
[Lenihan, Daniel J.; Lindenfeld, JoAnn M.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA.
[Sawyer, Douglas B.] Maine Med Ctr, Dept Med, Portland, ME 04102 USA.
[Teerlink, John R.] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA.
[Butler, Javed] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA.
RP Collins, SP (reprint author), Vanderbilt Univ, Dept Emergency Med, 221 Kirkland Hall, Nashville, TN 37235 USA.
EM sean.collins@vanderbilt.edu
NR 91
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
EI 1553-2712
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD AUG
PY 2016
VL 23
IS 8
BP 922
EP 931
DI 10.1111/acem.13025
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA DW1BQ
UT WOS:000383378200011
PM 27286136
ER
PT J
AU Neogi, T
Choi, HK
AF Neogi, Tuhina
Choi, Hyon K.
TI Pursuit of a Dual-Benefit Antigout Drug: A First Look at Arhalofenate
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Editorial Material
ID NUTRITION EXAMINATION SURVEY; OF-RHEUMATOLOGY GUIDELINES;
NATIONAL-HEALTH; GOUT; MANAGEMENT; HYPERURICEMIA; PREVALENCE; AGENT
C1 [Neogi, Tuhina] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Choi, Hyon K.] Boston Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02118 USA.
[Choi, Hyon K.] Harvard Med Sch, Boston, MA USA.
RP Neogi, T (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 650 Albany St,X Bldg,Suite 200, Boston, MA 02118 USA.
EM tneogi@bu.edu
FU NIAMS NIH HHS [P60 AR047785]
NR 16
TC 0
Z9 0
U1 0
U2 0
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 AUG
PY 2016
VL 68
IS 8
BP 1793
EP 1796
DI 10.1002/art.39687
PG 4
WC Rheumatology
SC Rheumatology
GA DW2UX
UT WOS:000383498400001
PM 26990165
ER
PT J
AU Baker, JF
Sauer, BC
Cannon, GW
Teng, CC
Michaud, K
Ibrahim, S
Jorgenson, E
Davis, L
Caplan, L
Cannella, A
Mikuls, TR
AF Baker, Joshua F.
Sauer, Brian C.
Cannon, Grant W.
Teng, Chia-Chen
Michaud, Kaleb
Ibrahim, Said
Jorgenson, Erik
Davis, Lisa
Caplan, Liron
Cannella, Amy
Mikuls, Ted R.
TI Changes in Body Mass Related to the Initiation of Disease-Modifying
Therapies in Rheumatoid Arthritis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID WEIGHT CHANGE; RISK-FACTORS; US VETERANS; INDEX; LEFLUNOMIDE;
METHOTREXATE; MORTALITY; ACCURACY; COMORBIDITY; INHIBITORS
AB Objective. Unintentional weight loss is important and can be predictive of long-term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database.
Methods. Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C-reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m(2). Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques.
Results. In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (beta = 20.41 kg/m(2), 95% confidence interval [95% CI] -0.46, -0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (beta = 0.072 kg/m(2), 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses.
Conclusion. Leflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA.
C1 [Baker, Joshua F.; Jorgenson, Erik] Philadelphia VA Med Ctr, Philadelphia, PA USA.
[Baker, Joshua F.; Ibrahim, Said; Jorgenson, Erik] Univ Penn, Philadelphia, PA 19104 USA.
[Sauer, Brian C.; Cannon, Grant W.; Teng, Chia-Chen] Salt Lake City VA Med Ctr, Salt Lake City, UT USA.
[Sauer, Brian C.; Cannon, Grant W.; Teng, Chia-Chen] Univ Utah, Salt Lake City, UT USA.
[Michaud, Kaleb; Cannella, Amy; Mikuls, Ted R.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA.
[Ibrahim, Said] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
[Davis, Lisa; Caplan, Liron] Denver VA Med Ctr, Denver, CO USA.
[Cannella, Amy; Mikuls, Ted R.] VA Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA.
RP Baker, JF (reprint author), Hosp Univ Penn, Div Rheumatol, Dept Med, 5 White Bldg,3600 Spruce St, Philadelphia, PA 19104 USA.
EM bakerjo@uphs.upenn.edu
FU Veterans Affairs Clinical Science Research and Development Career
Development Award [IK2-CX000955]; K24 Mid-Career Development Award from
National Institutes of Musculoskeletal and Skin Disorders
[1K24-AR-055259-01]; Veterans Affairs Merit Award
FX Supported by a Veterans Affairs Clinical Science Research and
Development Career Development Award (IK2-CX000955 to Dr. Baker), a K24
Mid-Career Development Award from the National Institutes of
Musculoskeletal and Skin Disorders (1K24-AR-055259-01 to Dr. Ibrahim),
and a Veterans Affairs Merit Award (to Dr. Mikuls).
NR 35
TC 1
Z9 1
U1 2
U2 2
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 AUG
PY 2016
VL 68
IS 8
BP 1818
EP 1827
DI 10.1002/art.39647
PG 10
WC Rheumatology
SC Rheumatology
GA DW2UX
UT WOS:000383498400006
PM 26882094
ER
PT J
AU Wolf, BJ
Spainhour, JC
Arthur, JM
Janech, MG
Petri, M
Oates, JC
AF Wolf, Bethany J.
Spainhour, John C.
Arthur, John M.
Janech, Michael G.
Petri, Michelle
Oates, Jim C.
TI Development of Biomarker Models to Predict Outcomes in Lupus Nephritis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID MONOCYTE CHEMOATTRACTANT; ERYTHEMATOSUS; CLASSIFICATION; URINE; CELLS;
INFLAMMATION; CHEMOKINES; PROTEIN-1; EFFICACY; SAFETY
AB Objective. The American College of Rheumatology guidelines for the treatment of lupus nephritis recommend change in induction therapy when response to therapy has not occurred within 6 months. Response is not defined, and renal fibrosis can occur while waiting for this end point. Therefore, a decision support tool to better define response is needed to guide clinicians when starting patients on therapy. This study was undertaken to identify biomarker models with sufficient predictive power to develop such a tool.
Methods. Urine samples from 140 patients with biopsy-proven lupus nephritis who had not yet started induction therapy were analyzed for a panel of urinary biomarkers. Univariate receiver operating characteristic (ROC) curves were generated for each individual biomarker and compared to the ROC area under the curve values from machine learning models developed using random forest algorithms. Biomarker models of outcome developed with novel markers in addition to clinical markers were compared to those developed with traditional clinical markers alone.
Results. Models developed with the combined traditional and novel biomarker panels demonstrated clinically meaningful predictive power. Markers most predictive of response were chemokines, cytokines, and markers of cellular damage.
Conclusion. This is the first study to demonstrate the power of low-abundance biomarker panels and machine learning algorithms for predicting lupus nephritis outcomes. This is a critical first step in research to develop clinically meaningful decision support tools.
C1 [Wolf, Bethany J.; Spainhour, John C.; Arthur, John M.; Janech, Michael G.; Oates, Jim C.] Med Univ South Carolina, Charleston, SC USA.
[Spainhour, John C.] Georgia Inst Technol, Atlanta, GA 30332 USA.
[Spainhour, John C.] Emory Univ, Atlanta, GA 30322 USA.
[Arthur, John M.; Janech, Michael G.; Oates, Jim C.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Petri, Michelle] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
RP Oates, JC (reprint author), Dept Med, Div Rheumatol & Immunol, Clin Sci Bldg,96 Jonathan Lucas St,Suite 816, Charleston, SC 29425 USA.
EM oatesjc@musc.edu
FU VA Merit Award [1I01CX000218-01]; NIH/National Institute of Arthritis
and Musculoskeletal and Skin Diseases [R21-AR-051719]; Medical
University of South Carolina General and Clinical Research Center
[M01-RR-001070]; South Carolina Clinical and Translational Research
Institute; academic home at the Medical University of South Carolina
(through NIH/National Center for Research Resources) [UL1-RR-029882];
Multidisciplinary Clinical Research Center at the Medical University of
South Carolina [P60-A-R062755]; VA Research Enhancement Award Program
award; NephCure Kidney International Young Investigator Career
Development Award; Hopkins Lupus Cohort [AR-43727]; NIH/National Center
for Research Resources [UL1-RR-025005]
FX Supported in part by a VA Merit Award (1I01CX000218-01), NIH/National
Institute of Arthritis and Musculoskeletal and Skin Diseases grant
R21-AR-051719, the Medical University of South Carolina General and
Clinical Research Center (through NIH grant M01-RR-001070), the South
Carolina Clinical and Translational Research Institute, with an academic
home at the Medical University of South Carolina (through NIH/National
Center for Research Resources grant number UL1-RR-029882), and the
Multidisciplinary Clinical Research Center at the Medical University of
South Carolina (through NIH grant P60-A-R062755). Support also came from
a VA Research Enhancement Award Program award. Subject material (urine
samples for biomarker analysis and clinical data) were provided by
Genentech (from the Lupus Nephritis Assessment of Rituximab [LUNAR]
study; ClinicalTrials.gov identifier: NCT00282347) and Bristol-Myers
Squibb (from the Abatacept in Lupus Nephritis study; ClinicalTrials.gov
identifier: NCT00430677) and their investigators. Dr. Janech's work was
supported by a NephCure Kidney International Young Investigator Career
Development Award. Dr. Petri's work was supported by the Hopkins Lupus
Cohort (through NIH grant AR-43727) and NIH/National Center for Research
Resources grant UL1-RR-025005.
NR 38
TC 2
Z9 2
U1 4
U2 4
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 AUG
PY 2016
VL 68
IS 8
BP 1955
EP 1963
DI 10.1002/art.39623
PG 9
WC Rheumatology
SC Rheumatology
GA DW2UX
UT WOS:000383498400020
PM 26867033
ER
PT J
AU Saag, KG
Whelton, A
Becker, MA
MacDonald, P
Hunt, B
Gunawardhana, L
AF Saag, Kenneth G.
Whelton, Andrew
Becker, Michael A.
MacDonald, Patricia
Hunt, Barbara
Gunawardhana, Lhanoo
TI Impact of Febuxostat on Renal Function in Gout Patients With
Moderate-to-Severe Renal Impairment
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; URIC-ACID; HYPERURICEMIA; URATE; ALLOPURINOL;
GUIDELINES; EFFICACY; SAFETY; CLASSIFICATION; COMORBIDITIES
AB Objective. Renal impairment is a risk factor for gout and a barrier to optimal gout management. We undertook this exploratory study to obtain data that have been heretofore limited regarding the safety and efficacy of febuxostat in patients with moderate-to-severe renal impairment (estimated glomerular filtration rate [GFR] 15-50 ml/minute/1.73m(2)).
Methods. Ninety-six gout patients with moderate-to-severe renal impairment were enrolled in a 12-month multicenter, randomized, double-blind, placebo-controlled study. Patients were randomly assigned at a 1: 1: 1 ratio to receive 30 mg febuxostat twice daily, 40/80 mg febuxostat once daily, or placebo. The primary efficacy end point was the change in serum creatinine (Cr) level from baseline to month 12. Secondary end points included the change in estimated GFR from baseline to month 12 and the proportion of patients with a serum uric acid (UA) level of <6.0 mg/dl at month 12.
Results. At month 12, there were no significant differences in the change in serum Cr level from baseline, or in the change in estimated GFR from baseline, in either febuxostat group compared to the placebo group. The proportion of patients with a serum UA level of <6.0 mg/dl at month 12 was significantly greater in both febuxostat groups compared to the placebo group (both P < 0.001). At least 1 treatment-emergent adverse event (TEAE) occurred in 78.1% of patients receiving 30 mg febuxostat twice daily, 87.5% of patients receiving 40/80 mg febuxostat once daily, and 78.1% of patients receiving placebo. TEAEs most frequently involved the categories of renal failure and impairment and renal function analyses.
Conclusion. Febuxostat proved to be efficacious in serum UA reduction and was well tolerated in gout patients with moderate-to-severe renal impairment. Patients randomly assigned to receive febuxostat demonstrated significantly lower serum UA levels and no significant deterioration in renal function.
C1 [Saag, Kenneth G.] Birmingham VA Med Ctr, Birmingham, AL USA.
[Saag, Kenneth G.] Univ Alabama Birmingham, Birmingham, AL USA.
[Whelton, Andrew] Johns Hopkins Univ, Baltimore, MD USA.
[Becker, Michael A.] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA.
[MacDonald, Patricia; Hunt, Barbara; Gunawardhana, Lhanoo] Takeda Pharmaceut, Deerfield, IL USA.
RP Saag, KG (reprint author), Univ Alabama Birmingham, Div Clin Immunol, Dept Med, 1720 2nd Ave South, Birmingham, AL 35294 USA.; Saag, KG (reprint author), Univ Alabama Birmingham, Div Rheumatol, Dept Med, 1720 2nd Ave South, Birmingham, AL 35294 USA.
EM Ksaag@uab.edu
FU Takeda Pharmaceuticals
FX Under the direction of the authors, Meryl Gersh of AlphaBioCom provided
writing, editing, and formatting assistance; this work was funded by
Takeda Pharmaceuticals.
NR 24
TC 4
Z9 5
U1 2
U2 2
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 AUG
PY 2016
VL 68
IS 8
BP 2035
EP 2043
DI 10.1002/art.39654
PG 9
WC Rheumatology
SC Rheumatology
GA DW2UX
UT WOS:000383498400028
PM 26894653
ER
PT J
AU Castillo, JJ
Kanan, S
Meid, K
Manning, R
Hunter, ZR
Treon, SP
AF Castillo, Jorge J.
Kanan, Sandra
Meid, Kirsten
Manning, Robert
Hunter, Zachary R.
Treon, Steven P.
TI Rituximab intolerance in patients with Waldenstrom macroglobulinaemia
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE Waldenstrom macroglobulinaemia; Lymphoplasmacytic lymphoma; rituximab;
infusion
ID FOLLICULAR LYMPHOMA; 1ST-LINE TREATMENT; PLUS RITUXIMAB; OPEN-LABEL;
TRIAL; PHASE-3; FLUDARABINE; THERAPY
C1 [Castillo, Jorge J.; Kanan, Sandra; Meid, Kirsten; Manning, Robert; Hunter, Zachary R.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA.
[Castillo, Jorge J.; Treon, Steven P.] Harvard Med Sch, Boston, MA 02115 USA.
RP Castillo, JJ (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA.; Castillo, JJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA.
EM jorgej_castillo@dfci.harvard.edu
OI Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691
NR 10
TC 4
Z9 4
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 AUG
PY 2016
VL 174
IS 4
BP 645
EP 648
DI 10.1111/bjh.13794
PG 5
WC Hematology
SC Hematology
GA DW6PX
UT WOS:000383774500020
PM 26523929
ER
PT J
AU Finn, JP
Nguyen, KL
Han, F
Zhou, Z
Salusky, I
Ayad, I
Hu, P
AF Finn, J. P.
Nguyen, K. -L.
Han, F.
Zhou, Z.
Salusky, I.
Ayad, I.
Hu, P.
TI Cardiovascular MRI with ferumoxytol
SO CLINICAL RADIOLOGY
LA English
DT Review
ID SUPERPARAMAGNETIC IRON-OXIDE; MAGNETIC-RESONANCE ANGIOGRAPHY; ACUTE
KIDNEY INJURY; AORTIC-VALVE IMPLANTATION; NEPHROGENIC SYSTEMIC FIBROSIS;
ACUTE MYOCARDIAL-INFARCTION; CONGENITAL HEART-DISEASE; BLOOD-POOL AGENT;
CONTRAST AGENT; SPATIAL-RESOLUTION
AB The practice of contrast-enhanced magnetic resonance angiography (CEMRA) has changed significantly in the span of a decade. Concerns regarding gadolinium (Gd)-associated nephrogenic systemic fibrosis in those with severely impaired renal function spurred developments in low-dose CEMRA and non-contrast MRA as well as efforts to seek alternative MR contrast agents. Originally developed for MR imaging use, ferumoxytol (an ultra-small superparamagnetic iron oxide nanoparticle), is currently approved by the US Food and Drug Administration for the treatment of iron deficiency anaemia in adults with renal disease. Since its clinical availability in 2009, there has been rising interest in the scientific and clinical use of ferumoxytol as an MR contrast agent. The unique physicochemical and pharmacokinetic properties of ferumoxytol, including its long intravascular half-life and high r(1) relaxivity, support a spectrum of MRI applications beyond the scope of Gd-based contrast agents. Moreover, whereas Gd is not found in biological systems, iron is essential for normal metabolism, and nutritional iron deficiency poses major public health challenges worldwide. Once the carbohydrate shell of ferumoxytol is degraded, the elemental iron at its core is incorporated into the reticuloendothelial system. These considerations position ferumoxytol as a potential game changer in the field of CEMRA and MRI. In this paper, we aim to summarise our experience with the cardiovascular applications of ferumoxytol and provide a brief synopsis of ongoing investigations on ferumoxytol-enhanced MR applications. (C) 2016 Published by Elsevier Ltd on behalf of The Royal College of Radiologists.
C1 [Finn, J. P.; Nguyen, K. -L.; Han, F.; Zhou, Z.; Salusky, I.; Ayad, I.; Hu, P.] Univ Calif Los Angeles, David Geffen Sch Med, Diagnost Cardiovasc Imaging Lab, Los Angeles, CA 90095 USA.
[Finn, J. P.; Han, F.; Zhou, Z.; Hu, P.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA.
[Nguyen, K. -L.] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Los Angeles, CA 90095 USA.
[Nguyen, K. -L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
[Salusky, I.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA.
[Salusky, I.] Univ Calif Los Angeles, David Geffen Sch Med, Div Pediat Nephrol, Los Angeles, CA 90095 USA.
RP Finn, JP (reprint author), Univ Calif Los Angeles, Dept Radiol Sci, Peter V Ueberroth Bldg Suite 3371, Los Angeles, CA 90095 USA.
EM pfinn@mednet.ucla.edu
OI Nguyen, Kim-Lien/0000-0002-8854-2976
FU National Heart, Lung, and Blood Institute [R01HL127153]
FX This work is supported by grant R01HL127153 from the National Heart,
Lung, and Blood Institute.
NR 65
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Z9 2
U1 2
U2 3
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0009-9260
EI 1365-229X
J9 CLIN RADIOL
JI Clin. Radiol.
PD AUG
PY 2016
VL 71
IS 8
SI SI
BP 796
EP 806
DI 10.1016/j.crad.2016.03.020
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DW0ST
UT WOS:000383353400009
PM 27221526
ER
PT J
AU Tiffany, E
Wilder, CM
Miller, SC
Winhusen, T
AF Tiffany, Elizabeth
Wilder, Christine M.
Miller, Shannon C.
Winhusen, Theresa
TI Knowledge of and interest in opioid overdose education and naloxone
distribution among US veterans on chronic opioids for addiction or pain
SO DRUGS-EDUCATION PREVENTION AND POLICY
LA English
DT Article
DE Education; harm reduction; methadone; naloxone; opiate; opiates; opiate
use; risk
ID TAKE-HOME NALOXONE; NONFATAL HEROIN OVERDOSE; INJECTION-DRUG USERS;
FRANCISCO BAY AREA; UNITED-STATES; INTRAMUSCULAR NALOXONE;
SCREENING-TEST; PREVENTION; INTRANASAL; MANAGEMENT
AB Aims: The Veterans Health Administration (VHA) is implementing opioid overdose (OOD) education and naloxone distribution to reduce rising rates of OOD deaths. This study assessed knowledge and interest in OOD prevention with naloxone at a VHA hospital where naloxone kits were not yet available. Methods: Veterans receiving opioids for 3 months, including 52 from the Opioid Substitution Clinic (OSC) and 38 from the Pain Management Clinic (PMC), were interviewed about their attitudes and experience with OOD and naloxone. Findings: 52% of OSC and 21% of PMC veterans reported having ever experienced an OOD. Less than half had heard of naloxone and none owned a naloxone kit. After a brief explanation, 73% of OSC and 55% of PMC veterans reported wanting a kit. Veterans who reported wanting a kit were more likely to have witnessed (p<0.001) and/or experienced (p<0.001) an OOD and were more likely to have used intravenous drugs in their lifetimes (p<0.05). Conclusions: Participants were not well informed about naloxone but many OSC veterans had a history of OOD and were interested in having a naloxone kit. There was also a subgroup of veterans prescribed opioids for chronic pain who had a history of OOD and were interested in naloxone.
C1 [Tiffany, Elizabeth; Wilder, Christine M.; Miller, Shannon C.; Winhusen, Theresa] Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, 260 Stetson St 3200, Cincinnati, OH 45219 USA.
[Wilder, Christine M.; Miller, Shannon C.] US Dept Vet Affairs, Med Ctr, Cincinnati, OH USA.
RP Tiffany, E (reprint author), Univ Cincinnati, Dept Psychiat & Behav Neurosci, Coll Med, 260 Stetson St 3200, Cincinnati, OH 45219 USA.
EM kraftem@ucmail.uc.edu
FU Department of Veterans Affairs; Research in Addiction Medicine Scholars
(RAMS) Program, National Institute on Drug Abuse [R25DA033211]
FX This report is based upon work supported by the Department of Veterans
Affairs and the Research in Addiction Medicine Scholars (RAMS) Program,
National Institute on Drug Abuse Award Number R25DA033211.
NR 42
TC 1
Z9 1
U1 4
U2 4
PU TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND
SN 0968-7637
EI 1465-3370
J9 DRUG-EDUC PREV POLIC
JI Drug-Educ. Prev. Policy
PD AUG
PY 2016
VL 23
IS 4
BP 322
EP 327
DI 10.3109/09687637.2015.1106442
PG 6
WC Substance Abuse
SC Substance Abuse
GA DW8CU
UT WOS:000383881700007
ER
PT J
AU Kataoka, A
Scherrer-Crosbie, M
Senior, R
Garceau, P
Valbuena, S
Celutkiene, J
Hastings, JL
Cheema, AN
Lara, A
Srbinovska-Kostovska, E
Hessian, R
Poggio, D
Goldweit, R
Saric, M
Dajani, KA
Kohn, JA
Shaw, LJ
Reynolds, HR
Picard, MH
AF Kataoka, Akihisa
Scherrer-Crosbie, Marielle
Senior, Roxy
Garceau, Patrick
Valbuena, Silvia
Celutkiene, Jelena
Hastings, Jeffrey L.
Cheema, Asim N.
Lara, Alfonso
Srbinovska-Kostovska, Elizabeta
Hessian, Renee
Poggio, Daniele
Goldweit, Richard
Saric, Muhamed
Dajani, Khaled A.
Kohn, Jeffrey A.
Shaw, Leslee J.
Reynolds, Harmony R.
Picard, Michael H.
TI Transient Ischemic Dilatation during Stress Echocardiography: An
Additional Marker of Significant Myocardial Ischemia
SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED
TECHNIQUES
LA English
DT Article
DE stress echocardiography; myocardial ischemia; coronary artery disease
ID CORONARY-ARTERY-DISEASE; VENTRICULAR CAVITY DILATION; CARDIAC
RESYNCHRONIZATION; PROGNOSTIC IMPORTANCE; TL-201 SCINTIGRAPHY; HEART;
VOLUME; TRIAL
AB AimLeft ventricular (LV) transient ischemic dilatation (TID) is not clear how it relates to inducible myocardial ischemia during stress echocardiography (SE).
Methods and ResultsEighty-eight SEs were examined from the site certification phase of the ISCHEMIA Trial. LV end-diastolic volume (EDV) and end-systolic volume (ESV) were measured at rest and peak stages and the percent change calculated. Moderate or greater ischemia was defined as 3 segments with stress-induced severe hypokinesis or akinesis. Optimum cut points in stress-induced percent EDV and ESV change that identified moderate or greater myocardial ischemia were analyzed. Analysis from percentage distribution identified a > 13% LV volume increase in EDV or a > 9% LV volume increase in ESV as the optimum cutoff points for moderate or greater ischemia. Using these definitions for TID, there were 27 (31%) with TIDESV and 12 (14%) with TIDEDV. By logistic regression analysis and receiver operating characteristic curves, the percent change in ESV had a stronger association with moderate or greater myocardial ischemia than that of EDV change. Compared to those without TIDESV, cases with TIDESV had larger extent of inducible wall-motion abnormalities, lower peak stress LVEF, and higher likelihood of moderate or grater ischemia. For moderate or greater myocardial ischemia detection, TIDESV had a sensitivity of 46%, specificity of 83%, positive predictive value of 70%, and negative predictive value of 64%.
ConclusionTransient ischemic dilatation by SE is a marker of extensive myocardial ischemia and can be used as an additional marker of higher risk.
C1 [Kataoka, Akihisa; Scherrer-Crosbie, Marielle; Picard, Michael H.] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.
[Kataoka, Akihisa; Scherrer-Crosbie, Marielle; Picard, Michael H.] Harvard Med Sch, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.
[Senior, Roxy] Natl Heart & Lung Inst, Div Cardiol, Dept Cardiovasc Med, London, England.
[Senior, Roxy] Imperial Coll, London, England.
[Garceau, Patrick] Montreal Heart Inst, Dept Med, Montreal, PQ, Canada.
[Valbuena, Silvia] La Paz Univ Hosp, Dept Cardiol, Madrid, Spain.
[Celutkiene, Jelena] Vilnius Univ Hosp, Santariskiu Clin, Ctr Cardiol & Angiol, Vilnius, Lithuania.
[Hastings, Jeffrey L.] VN Texas Hlth Care Syst, Div Cardiol, Dallas, TX USA.
[Cheema, Asim N.] St Michaels Hosp, Div Cardiol, Toronto, ON, Canada.
[Lara, Alfonso] La Raza Natl Med Ctr, Specialty Hosp, Dept Med, Mexico City, DF, Mexico.
[Srbinovska-Kostovska, Elizabeta] Univ Clin Cardiol, Dept Internal Med, Skopje, Macedonia.
[Hessian, Renee] Univ Ottawa, Inst Heart, Div Cardiol, Dept Med, Ottawa, ON, Canada.
[Poggio, Daniele] Monza Polyclin, Div Cardiol, Dept Med, Monza, Italy.
[Goldweit, Richard] Englewood Hosp & Med Ctr, Div Cardiol, Dept Med, Englewood, NJ USA.
[Saric, Muhamed] NYU, Dept Med, Div Cardiol, Med Ctr, 550 1St Ave, New York, NY 10016 USA.
[Dajani, Khaled A.] Loyola Univ, Med Ctr, Dept Med, Div Cardiol, Maywood, IL 60153 USA.
[Kohn, Jeffrey A.] New York Med Associates, Dept Med, New York, NY USA.
[Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA.
[Reynolds, Harmony R.] NYU, Dept Med, Div Cardiol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA.
RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.; Picard, MH (reprint author), Harvard Med Sch, 55 Fruit St,Yawkey 5E, Boston, MA 02114 USA.
EM mhpicard@mgh.harvard.edu
OI Picard, Michael/0000-0002-9264-3243; Saric, Muhamed/0000-0001-7682-3749
FU Japanese Society of Echocardiography Overseas Research Fellowship;
Uehara Memorial Foundation Research Fellowship; National Heart, Lung,
and Blood Institute [5U01HL105561-02, 1U01HL10556-01]
FX We thank Dr. Zeng Xin, Dr. Yong Hyun Park, Ms. Dana Oliver for their
assistance in this project. This work was supported by grants from the
Japanese Society of Echocardiography Overseas Research Fellowship and
Uehara Memorial Foundation Research Fellowship (Dr. Kataoka), and the
National Heart, Lung, and Blood Institute (5U01HL105561-02,
1U01HL10556-01).
NR 22
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0742-2822
EI 1540-8175
J9 ECHOCARDIOGR-J CARD
JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech.
PD AUG
PY 2016
VL 33
IS 8
BP 1202
EP 1208
DI 10.1111/echo.13222
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW0TF
UT WOS:000383354900010
PM 27040889
ER
PT J
AU Malhotra, R
Bakken, K
D'Elia, E
Lewis, GD
AF Malhotra, Rajeev
Bakken, Kristian
D'Elia, Emilia
Lewis, Gregory D.
TI Cardiopulmonary Exercise Testing in Heart Failure
SO JACC-HEART FAILURE
LA English
DT Article
DE cardiopulmonary exercise testing; exercise physiology; heart failure;
oxygen uptake; ventilatory efficiency
ID PRESERVED EJECTION FRACTION; PEAK OXYGEN-CONSUMPTION; GAS-EXCHANGE;
OSCILLATORY VENTILATION; CARDIAC RESYNCHRONIZATION; PROGNOSTIC
IMPORTANCE; SUBMAXIMAL EXERCISE; AMBULATORY PATIENTS; CONTROLLED-TRIAL;
EFFICIENCY
AB Exercise intolerance, indicated by dyspnea and fatigue during exertion, is a cardinal manifestation of heart failure (HF). Cardiopulmonary exercise testing (CPET) precisely defines maximum exercise capacity through measurement of peak oxygen uptake (VO2). Peak VO2 values have a critical role in informing patient selection for advanced HF interventions such as heart transplantation and ventricular assist devices. Oxygen uptake and ventilatory patterns obtained during the submaximal portion of CPET are also valuable to recognize because of their ease of ascertainment during low-level exercise, relevance to ability to perform activities of daily living, independence from volitional effort, and strong relationship to prognosis in HF. The ability of peak VO2 and other CPET variables to be measured reproducibly and to accurately reflect HF severity is increasingly recognized and endorsed by scientific statements. Integration of CPET with invasive hemodynamic monitoring and cardiac imaging during exercise provides comprehensive characterization of multisystem reserve capacity that can inform prognosis and the need for cardiac interventions. Here, we review both practical aspects of conducting CPETs in patients with HF for clinical and research purposes as well as interpretation of gas exchange patterns across the spectrum of preclinical HF to advanced HF. (C) 2016 by the American College of Cardiology Foundation.
C1 [Malhotra, Rajeev; Lewis, Gregory D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA USA.
[Bakken, Kristian; Lewis, Gregory D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA USA.
[D'Elia, Emilia] Hosp Papa Giovanni XXIII, Cardiovasc Dept, Bergamo, Italy.
[D'Elia, Emilia] Univ Pavia, Pavia, Italy.
RP Lewis, GD (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,55 Fruit St, Boston, MA 02114 USA.
EM glewis@partners.org
OI Malhotra, Rajeev/0000-0003-0120-4630
FU NHLBI NIH HHS [K08 HL111210]
NR 66
TC 4
Z9 4
U1 9
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD AUG
PY 2016
VL 4
IS 8
BP 607
EP 616
DI 10.1016/j.jchf.2016.03.022
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DW1ME
UT WOS:000383406500001
PM 27289406
ER
PT J
AU Schlosser, RJ
Mulligan, JK
Hyer, JM
Karnezis, TT
Gudis, DA
Soler, ZM
AF Schlosser, Rodney J.
Mulligan, Jennifer K.
Hyer, J. Madison
Karnezis, Tom T.
Gudis, David A.
Soler, Zachary M.
TI Mucous Cytokine Levels in Chronic Rhinosinusitis-Associated Olfactory
Loss
SO JAMA OTOLARYNGOLOGY-HEAD & NECK SURGERY
LA English
DT Article
ID ENDOSCOPIC SINUS SURGERY; NECROSIS-FACTOR-ALPHA; NASAL POLYPS;
IDENTIFICATION; INTERLEUKIN-6; MODEL
AB IMPORTANCE Olfactory loss is a frequent symptom of patients with chronic rhinosinusitis (CRS), but our understanding of how inflammatory cytokines affect olfaction is limited.
OBJECTIVES To examine whether inflammatory cytokines are present in the olfactory cleft and whether they correlate with objective olfaction.
DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, patients with CRS underwent quantitative olfactory testing using the Sniffin Sticks test to calculate a composite threshold discrimination identification (TDI) score from October 21, 2013, to November 12, 2015. Nasal mucus was collected using a sponge placed in the olfactory cleft for 5 minutes, and Cytometric Bead Array was used to measure secreted immunomodulatory products. Correlations between TDI score and secreted mediators were then calculated. Data analysis was performed from October 15, 2015, to December 17, 2015.
MAIN OUTCOMES AND MEASURES Composite TDI scores and mean secreted mediator levels in mucus from the olfactory cleft.
RESULTS Thirty-four patients were enrolled (mean [SD] age, 57.3 [15.7] years; female, 21 [61.8%]; white, 26 [76.5]). The TDI scores were lower in patients with CRS with nasal polyps (CRSwNP) than in patients with CRS without nasal polyps (CRSsNP) (difference, 8.7; 95% CI, 2.5-15.0; P = .007). Interleukin (IL) 5 levels were inversely correlated with TDI scores in patients with CRSwNP and those with CRSsNP (mean [SE] beta estimate, -46.56 [15.11]; P = .005), whereas IL-6, IL-7, and vascular endothelial growth factor A were positively correlated with TDI scores only in the CRSwNP cohort. Subscale olfactory TDI scores followed similar correlations to composite TDI scores.
CONCLUSIONS AND RELEVANCE In this study, inflammatory cytokines were found in mucus collected from the olfactory cleft. Levels of IL-5, in addition to other cytokines, were associated with objective olfactory function. Further inquiry is needed to establish the source of mucous cytokines and establish whether they play a causal role in olfactory loss.
C1 [Schlosser, Rodney J.; Mulligan, Jennifer K.; Karnezis, Tom T.; Gudis, David A.; Soler, Zachary M.] Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Mail Stop Code 550, Charleston, SC 29425 USA.
[Schlosser, Rodney J.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Mulligan, Jennifer K.] Med Univ South Carolina, Dept Pediat, Charleston, SC 29425 USA.
[Hyer, J. Madison] Med Univ South Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
RP Soler, ZM (reprint author), Med Univ South Carolina, Dept Otolaryngol Head & Neck Surg, 135 Rutledge Ave,Mail Stop Code 550, Charleston, SC 29425 USA.
EM solerz@musc.edu
FU National Institute on Deafness and Other Communication Disorders [R03
DC013651-01]; OptiNose; IntersectENT
FX All authors have completed and submitted the ICMJE Form for Disclosure
of Potential Conflicts of Interest. Dr Schlosser reported receiving
grant support from OptiNose and IntersectENT and working as a consultant
for Olympus and Meda. Dr Soler reported receiving support from grant R03
DC013651-01 from the National Institute on Deafness and Other
Communication Disorders and working as a consultant for Olympus. No
other disclosures were reported.
NR 23
TC 2
Z9 2
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6181
EI 2168-619X
J9 JAMA OTOLARYNGOL
JI JAMA Otolaryngol-Head Neck Surg.
PD AUG
PY 2016
VL 142
IS 8
BP 731
EP 737
DI 10.1001/jamaoto.2016.0927
PG 7
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DW6PS
UT WOS:000383774000003
PM 27228459
ER
PT J
AU Storch, EA
Wilhelm, S
Sprich, S
Henin, A
Micco, J
Small, BJ
McGuire, J
Mutch, J
Lewin, AB
Murphy, TK
Geller, DA
AF Storch, Eric A.
Wilhelm, Sabine
Sprich, Susan
Henin, Aude
Micco, Jamie
Small, Brent J.
McGuire, Joseph
Mutch, Jane
Lewin, Adam B.
Murphy, Tanya K.
Geller, Daniel A.
TI Efficacy of Augmentation of Cognitive Behavior Therapy With
Weight-Adjusted D-Cycloserine vs Placebo in Pediatric
Obsessive-Compulsive Disorder A Randomized Clinical Trial
SO JAMA PSYCHIATRY
LA English
DT Article
ID SOCIAL ANXIETY DISORDER; POSTTRAUMATIC-STRESS-DISORDER; EXPOSURE
THERAPY; FEAR EXTINCTION; TREATMENT RESPONSE; OCD TREATMENT; CHILDREN;
SCALE; ENHANCEMENT; RELIABILITY
AB IMPORTANCE Cognitive behavior therapy (CBT) among youth with obsessive-compulsive disorder (OCD) is effective, but many patients remain symptomatic after intervention. D-cycloserine, a partial agonist at the N-methyl-D-aspartate receptor in the amygdala, has been associated with enhanced CBT outcome for OCD among adults but requires evaluation among youth.
OBJECTIVES To examine the relative efficacy of weight-adjusted D-cycloserine (25 or 50mg) vs placebo augmentation of CBT for youth with OCD and to assess if concomitant antidepressant medication moderated effects.
DESIGN, SETTING, AND PARTICIPANTS In a placebo-controlled randomized clinical trial, 142 youths (age range, 7-17 years) enrolled between June 1, 2011, and January 30, 2015, at 2 academic health science centers (University of South Florida and Massachusetts General Hospital) with a primary diagnosis of OCD were randomized in a double-blind fashion to D-cycloserine plus CBT or placebo plus CBT. Intent-to-treat analysis was performed.
INTERVENTIONS Patients were randomly assigned in a 1: 1 ratio to either 10 sessions of D-cycloserine plus CBT or placebo plus CBT. D-cycloserine (25 or 50mg) or placebo was taken 1 hour before sessions 4 through 10.
MAIN OUTCOMES AND MEASURES Children's Yale-Brown Obsessive Compulsive Scale at randomization, biweekly, midtreatment, and posttreatment. Secondary outcomes included the Clinical Global Impressions-Severity or Clinical Global Impressions-Improvement, remission status, Children's Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Children's Obsessive-Compulsive Impact Scale-Parent Version.
RESULTS The study cohort comprised 142 participants. Their mean (SD) age was 12.7 (2.9) years, and 53.5%(76 of 142) were female. A mixed-effects model using all available data indicated significant declines in the Children's Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions-Severity. No significant interaction between treatment group and changes in the Children's Yale-Brown Obsessive Compulsive Scale and Clinical Global Impressions-Severity indicated that the D-cycloserine plus CBT group and the placebo plus CBT group declined at similar rates per assessment point on the Children's Yale-Brown Obsessive Compulsive Scale total score (estimate, -2.31, 95% CI, -2.79 to -1.83 and estimate, -2.03, 95% CI, -2.47 to -1.58, respectively) and Clinical Global Impressions-Severity (estimate, -0.29, 95% CI, -0.35 to -0.22 and estimate, -0.23, 95% CI, -0.29 to -0.17, respectively). No group differences in secondary outcomes were present. Antidepressant medication use at baseline did not moderate changes for either group.
CONCLUSIONS AND RELEVANCE D-cycloserine augmentation of CBT did not confer additional benefit relative to placebo among youth with OCD. Other augmentation approaches should be examined to enhance outcome.
C1 [Storch, Eric A.; Mutch, Jane; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, Tampa, FL USA.
[Storch, Eric A.] Univ S Florida, Dept Hlth Policy & Management, Tampa, FL USA.
[Storch, Eric A.; Lewin, Adam B.; Murphy, Tanya K.] Univ S Florida, Dept Psychiat & Behav Neurosci, Tampa, FL USA.
[Storch, Eric A.] Rogers Behav Hlth Tampa Bay, Tampa, FL USA.
[Storch, Eric A.; Murphy, Tanya K.] Johns Hopkins All Childrens Hosp, St Petersburg, FL USA.
[Wilhelm, Sabine; Sprich, Susan; Henin, Aude; Micco, Jamie; Geller, Daniel A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Wilhelm, Sabine; Sprich, Susan; Henin, Aude; Micco, Jamie; Geller, Daniel A.] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
[Small, Brent J.] Univ S Florida, Sch Aging Studies, Tampa, FL USA.
[McGuire, Joseph] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
RP Storch, EA (reprint author), Univ S Florida, Dept Pediat, 880 Sixth St S,POB 7523, St Petersburg, FL 33701 USA.
EM estorch@health.usf.edu
FU National Institute of Mental Health [1R01MH093381, 5R01MH093402]
FX This work was supported by grants 1R01MH093381 (Dr Storch) and
5R01MH093402 (Dr Geller) from the National Institute of Mental Health.
NR 47
TC 4
Z9 4
U1 7
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD AUG
PY 2016
VL 73
IS 8
BP 779
EP 788
DI 10.1001/jamapsychiatry.2016.1128
PG 10
WC Psychiatry
SC Psychiatry
GA DW9OX
UT WOS:000383991700007
PM 27367832
ER
PT J
AU VanderWeele, TJ
Li, SS
Tsai, AC
Kawachi, I
AF VanderWeele, Tyler J.
Li, Shanshan
Tsai, Alexander C.
Kawachi, Ichiro
TI Association Between Religious Service Attendance and Lower Suicide Rates
Among US Women
SO JAMA PSYCHIATRY
LA English
DT Article
ID NATIONALLY REPRESENTATIVE SAMPLE; SOCIAL INTEGRATION;
SENSITIVITY-ANALYSIS; AFRICAN-AMERICANS; UNITED-STATES; BEHAVIOR;
DEPRESSION; MORTALITY; IDEATION; COHORT
AB IMPORTANCE Previous studies have linked suicide risk with religious participation, but the majority have used ecologic, cross-sectional, or case-control data.
OBJECTIVE To examine the longitudinal association between religious service attendance and suicide and the joint associations of suicide with service attendance and religious affiliation.
DESIGN, SETTING, AND PARTICIPANTS We evaluated associations between religious service attendance and suicide from 1996 through June 2010 in a large, long-term prospective cohort, the Nurses' Health Study, in an analysis that included 89 708 women. Religious service attendance was self-reported in 1992 and 1996. Data analysis was conducted from 1996 through 2010.
MAIN OUTCOMES AND MEASURES Cox proportional hazards regression models were used to examine the association between religious service attendance and suicide, adjusting for demographic covariates, lifestyle factors, medical history, depressive symptoms, and social integration measures. We performed sensitivity analyses to examine the influence of unmeasured confounding.
RESULTS Among 89 708 women aged 30 to 55 years who participated in the Nurses' Health Study, attendance at religious services once per week or more was associated with an approximately 5-fold lower rate of suicide compared with never attending religious services (hazard ratio, 0.16; 95% CI, 0.06-0.46). Service attendance once or more per week vs less frequent attendance was associated with a hazard ratio of 0.05 (95% CI, 0.006-0.48) for Catholics but only 0.34 (95% CI, 0.10-1.10) for Protestants (P = .05 for heterogeneity). Results were robust in sensitivity analysis and to exclusions of persons who were previously depressed or had a history of cancer or cardiovascular disease. There was evidence that social integration, depressive symptoms, and alcohol consumption partially mediated the association among those occasionally attending services, but not for those attending frequently.
CONCLUSIONS AND RELEVANCE In this cohort of US women, frequent religious service attendance was associated with a significantly lower rate of suicide.
C1 [VanderWeele, Tyler J.; Li, Shanshan] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA.
[VanderWeele, Tyler J.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[VanderWeele, Tyler J.] Harvard Univ, Inst Quantitat Social Sci, Program Integrat Knowledge & Human Flourishing, Cambridge, MA 02138 USA.
[Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA.
[Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda.
[Kawachi, Ichiro] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
RP VanderWeele, TJ (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge Bldg, Boston, MA 02115 USA.
EM tvanderw@hsph.harvard.edu
FU National Institutes of Health [UM1 CA186107]; Templeton Foundation
FX The Nurses' Health Study was funded by grant UM1 CA186107 from the
National Institutes of Health. The analysis and paper was supported by a
research grant from the Templeton Foundation.
NR 36
TC 7
Z9 7
U1 10
U2 10
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD AUG
PY 2016
VL 73
IS 8
BP 845
EP 851
DI 10.1001/jamapsychiatry.2016.1243
PG 7
WC Psychiatry
SC Psychiatry
GA DW9OX
UT WOS:000383991700014
PM 27367927
ER
PT J
AU Lilley, EJ
Cauley, CE
Cooper, Z
AF Lilley, Elizabeth J.
Cauley, Christy E.
Cooper, Zara
TI Using a Palliative Care Framework for Seriously Ill Surgical Patients
The Example of Malignant Bowel Obstruction
SO JAMA SURGERY
LA English
DT Editorial Material
ID CARCINOMATOSIS
C1 [Lilley, Elizabeth J.] Rutgers Robert Wood Johnson Med Sch, Dept Surg, Brunswick, NJ USA.
[Lilley, Elizabeth J.; Cooper, Zara] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, One Brigham Circle,1620 Tremont St,Ste 4-020, Boston, MA 02120 USA.
[Cauley, Christy E.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Cauley, Christy E.] Ariadne Labs, Boston, MA USA.
[Cooper, Zara] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
RP Lilley, EJ (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, One Brigham Circle,1620 Tremont St,Ste 4-020, Boston, MA 02120 USA.
EM elilley@bwh.harvard.edu
OI Lilley, Elizabeth/0000-0002-3617-9829
FU NCI NIH HHS [R25 CA092203]
NR 7
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD AUG
PY 2016
VL 151
IS 8
BP 695
EP 696
DI 10.1001/jamasurg.2016.0057
PG 2
WC Surgery
SC Surgery
GA DW6QD
UT WOS:000383775100005
PM 27096440
ER
PT J
AU Rosengart, TK
Kent, KC
Bland, KI
Britt, LD
Eberlein, TJ
Gewertz, BL
Hunter, JG
Lillemoe, KD
Pellegrini, CA
Schulick, RD
Stain, SC
Weigel, RJ
AF Rosengart, Todd K.
Kent, K. Craig
Bland, Kirby I.
Britt, L. D.
Eberlein, Timothy J.
Gewertz, Bruce Labe
Hunter, John G.
Lillemoe, Keith D.
Pellegrini, Carlos A.
Schulick, Richard D.
Stain, Steven Charles
Weigel, Ronald J.
TI Key Tenets of Effective Surgery Leadership Perspectives From the Society
of Surgical Chairs Mentorship Sessions
SO JAMA SURGERY
LA English
DT Review
AB This Special Communication summarizes the key points raised at the Society of Surgical Chairs mentorship panel sessions held at the 2014 and 2015 annual meetings of the society. Highlights of these expert panel discussions include senior chairs' insights into successfully dealing with increasingly complex academic medical organizations and horizontal department management expectations in the context of the arrival of the Millennial Generation into the work force. Three key tenets of effective surgery leadership that arose from these sessions deal with the importance of (1) collaboration and cooperativity, (2) humanized relationships and mentorship, and (3) operational efficiency. Overall, the panel consensus for the future of surgery leadership was optimistic while recognizing that the demands of chairmanship are considerable.
C1 [Rosengart, Todd K.] Baylor Coll Med, Houston, TX 77030 USA.
[Kent, K. Craig] Univ Wisconsin, Sch Med, Madison, WI USA.
[Bland, Kirby I.] Univ Alabama Birmingham, Birmingham, AL USA.
[Britt, L. D.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA.
[Eberlein, Timothy J.] Washington Univ, Sch Med, St Louis, MO USA.
[Gewertz, Bruce Labe] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA.
[Hunter, John G.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Lillemoe, Keith D.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Pellegrini, Carlos A.] Univ Washington, Seattle, WA 98195 USA.
[Schulick, Richard D.] Univ Colorado, Anschutz Med Campus, Aurora, CO USA.
[Stain, Steven Charles] Albany Med Coll, Albany, NY 12208 USA.
[Weigel, Ronald J.] Univ Iowa, Coll Med, Iowa City, IA USA.
RP Rosengart, TK (reprint author), Baylor Coll Med, Michael E DeBakey Dept Surg, 1 Baylor Plz, Houston, TX 77030 USA.
EM todd.rosengart@bcm.edu
NR 7
TC 0
Z9 0
U1 2
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD AUG
PY 2016
VL 151
IS 8
BP 768
EP 770
DI 10.1001/jamasurg.2016.0405
PG 3
WC Surgery
SC Surgery
GA DW6QD
UT WOS:000383775100020
PM 27096328
ER
PT J
AU Minami, CA
Dahlke, AR
Barnard, C
Kinnier, CV
Rajaram, RR
Noskin, GA
Bilimoria, KY
AF Minami, Christina A.
Dahlke, Allison R.
Barnard, Cynthia
Kinnier, Christine V.
Rajaram, Ravi R.
Noskin, Gary A.
Bilimoria, Karl Y.
TI Association Between Hospital Characteristics and Performance on the New
Hospital-Acquired Condition Reduction Program's Surgical Site Infection
Measures
SO JAMA SURGERY
LA English
DT Letter
C1 [Minami, Christina A.; Dahlke, Allison R.; Rajaram, Ravi R.; Bilimoria, Karl Y.] Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, 633 N St Clair,20th Floor, Chicago, IL 60611 USA.
[Minami, Christina A.; Dahlke, Allison R.; Rajaram, Ravi R.; Bilimoria, Karl Y.] Northwestern Univ, Ctr Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA.
[Barnard, Cynthia] Northwestern Mem HealthCare, Div Qual, Chicago, IL USA.
[Kinnier, Christine V.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Noskin, Gary A.] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Dept Med, Chicago, IL 60611 USA.
RP Bilimoria, KY (reprint author), Northwestern Univ, Surg Outcomes & Qual Improvement Ctr, Dept Surg, Feinberg Sch Med, 633 N St Clair,20th Floor, Chicago, IL 60611 USA.
EM k-bilimoria@northwestern.edu
NR 5
TC 1
Z9 1
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6254
EI 2168-6262
J9 JAMA SURG
JI JAMA Surg.
PD AUG
PY 2016
VL 151
IS 8
BP 777
EP 779
DI 10.1001/jamasurg.2016.0408
PG 3
WC Surgery
SC Surgery
GA DW6QD
UT WOS:000383775100024
PM 27050254
ER
PT J
AU Robinaugh, DJ
Millner, AJ
McNally, RJ
AF Robinaugh, Donald J.
Millner, Alexander J.
McNally, Richard J.
TI Identifying Highly Influential Nodes in the Complicated Grief Network
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Article
DE network analysis; centrality; complicated grief; expected influence;
persistent complex bereavement disorder
ID BEREAVEMENT; CENTRALITY; DISORDER; TRIAL; MODEL
AB The network approach to psychopathology conceptualizes mental disorders as networks of mutually reinforcing nodes (i.e., symptoms). Researchers adopting this approach have suggested that network topology can be used to identify influential nodes, with nodes central to the network having the greatest influence on the development and maintenance of the disorder. However, because commonly used centrality indices do not distinguish between positive and negative edges, they may not adequately assess the nature and strength of a node's influence within the network. To address this limitation, we developed 2 indices of a node's expected influence (EI) that account for the presence of negative edges. To evaluate centrality and EI indices, we simulated single-node interventions on randomly generated networks. In networks with exclusively positive edges, centrality and EI were both strongly associated with observed node influence. In networks with negative edges, EI was more strongly associated with observed influence than was centrality. We then used data from a longitudinal study of bereavement to examine the association between (a) a node's centrality and EI in the complicated grief (CG) network and (b) the strength of association between change in that node and change in the remainder of the CG network from 6- to 18-months postloss. Centrality and EI were both correlated with the strength of the association between node change and network change. Together, these findings suggest high-EI nodes, such as emotional pain and feelings of emptiness, may be especially important to the etiology and treatment of CG.
C1 [Robinaugh, Donald J.] Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Room 644, Boston, MA 02114 USA.
[Robinaugh, Donald J.] Harvard Med Sch, Boston, MA USA.
[Millner, Alexander J.; McNally, Richard J.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
RP Robinaugh, DJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 1 Bowdoin Sq,Room 644, Boston, MA 02114 USA.
EM drobinaugh@partners.org
FU Nancy Pritzker Research Network; National Institute of Aging
[AG15948-01, AG610757-01, AG05561-01]
FX The Changing Lives of Older Couples study was supported by grants from
the Nancy Pritzker Research Network and the National Institute of Aging
(Grants AG15948-01; AG610757-01; AG05561-01). We thank Sacha Epskamp,
Eiko Fried, Susanne Hoeppner, Robin Mankel, and two anonymous reviewers
for their helpful feedback on earlier drafts of this article.
NR 28
TC 1
Z9 1
U1 1
U2 2
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0021-843X
EI 1939-1846
J9 J ABNORM PSYCHOL
JI J. Abnorm. Psychol.
PD AUG
PY 2016
VL 125
IS 6
BP 747
EP 757
DI 10.1037/abn0000181
PG 11
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA DV6PN
UT WOS:000383059200001
PM 27505622
ER
PT J
AU Aaron, SE
Gregory, CM
Simpson, AN
AF Aaron, Stacey E.
Gregory, Chris M.
Simpson, Annie N.
TI Lower Odds of Poststroke Symptoms of Depression When Physical Activity
Guidelines Met: National Health and Nutrition Examination Survey
2011-2012
SO JOURNAL OF PHYSICAL ACTIVITY & HEALTH
LA English
DT Article
DE Patient Health Questionnaire-9; Global Physical Activity Questionnaire;
MET-minute/week
ID QUALITY-OF-LIFE; ANTIDEPRESSANT THERAPY; FUNCTIONAL RECOVERY; STROKE
PATIENTS; POST STROKE; ADULTS; EXERCISE; METAANALYSIS; ASSOCIATION;
DISORDERS
AB Background: One-third of individuals with stroke report symptoms of depression, which has a negative impact on recovery. Physical activity (PA) is a potentially effective therapy. Our objective was to examine the associations of subjectively assessed PA levels and symptoms of depression in a nationally representative stroke sample. Methods: We conducted a cross-sectional study of 175 adults in the National Health and Nutrition Examination Survey 2011-2012 cycle. Moderate, vigorous, and combination equivalent PA metabolic equivalent (MET)-minutes per week averages were derived from the Global Physical Activity Questionnaire, and the 2008 Physical Activity Guidelines/American College of Sports Medicine recommendations of >= 500 MET -minutes per week of moderate, vigorous, or combination equivalent PA were used as cut points. Depression symptoms were measured using the Patient Health Questionnaire-9. Results: Meeting moderate PA guidelines resulted in 74% lower odds of having depression symptoms (P < .0001) and 89% lower odds of major symptoms of depression (P = .0003). Meeting vigorous guidelines showed a 91% lower odds of having mild symptoms of depression (P = .04). Participating in some moderate, vigorous, or combination equivalent PA revealed the odds of depression symptoms 13 times greater compared with meeting guidelines (P = .005); odds of mild symptoms of depression were 9 times greater (P = .01); and odds of major symptoms of depression were 15 times greater (P = .006). Conclusions: There is a lower risk of developing mild symptoms of depression when vigorous guidelines for PA are met and developing major symptoms of depression when moderate guidelines met. Participating in some PA is not enough to reduce the risk of depression symptoms.
C1 [Aaron, Stacey E.; Gregory, Chris M.] Med Univ South Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Gregory, Chris M.] Med Univ South Carolina, Div Phys Therapy, Charleston, SC USA.
[Gregory, Chris M.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Simpson, Annie N.] Med Univ South Carolina, Dept Healthcare Leadership & Management, Charleston, SC USA.
RP Aaron, SE (reprint author), Med Univ South Carolina, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
EM aarons@musc.edu
FU NIGMS NIH HHS [P20 GM109040]
NR 41
TC 0
Z9 0
U1 1
U2 1
PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1543-3080
EI 1543-5474
J9 J PHYS ACT HEALTH
JI J. Phys. Act. Health
PD AUG
PY 2016
VL 13
IS 8
BP 903
EP 909
DI 10.1123/jpah.2015-0446
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DW1OV
UT WOS:000383413400014
PM 27145542
ER
PT J
AU Caragacianu, DL
Mayer, EL
Chun, YS
Caterson, S
Bellon, JR
Wong, JS
Troyan, S
Rhei, E
Dominici, LS
Economy, KE
Tung, NM
Schapira, L
Partridge, A
Calvillo, KZ
AF Caragacianu, Diana L.
Mayer, Erica L.
Chun, Yoon S.
Caterson, Stephanie
Bellon, Jennifer R.
Wong, Julia S.
Troyan, Susan
Rhei, Esther
Dominici, Laura S.
Economy, Katherine E.
Tung, Nadine M.
Schapira, Lidia
Partridge, Ann
Calvillo, Katherina Zabicki
TI Immediate Breast Reconstruction Following Mastectomy in Pregnant Women
With Breast Cancer
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE pregnancy; malignancy; reconstructive surgery; fetal outcomes;
multidisciplinary care
ID SKIN-SPARING MASTECTOMY; RADIATION-THERAPY; SURGICAL OUTCOMES;
POSTMASTECTOMY RECONSTRUCTION; IRRADIATED BREAST; RISK; RADIOTHERAPY;
RECURRENCE; ANESTHESIA; IMPACT
AB Background: Surgical management of breast cancer in pregnancy (BCP) requires balancing benefits of therapy with potential risks to the developing fetus. Minimal data describe outcomes after mastectomy with immediate breast reconstruction (IR) in pregnant patients.
Methods: Retrospective review was performed of patients who underwent IR after mastectomy within a BCP cohort. Parameters included intraand post-operative complications, short-term maternal/fetal outcomes, surgery duration, and delayed reconstruction in non-IR cohort.
Results: Of 82 patients with BCP, 29 (35%) had mastectomy during pregnancy: 10 (34%) had IR, 19(66%) did not. All IR utilized tissue expander (TE) placement. Mean gestational age (GA) at IR was 16.2 weeks. Mean surgery duration was 198 min with IR versus 157 min without IR. Those with IR delivered at, or close to, term infants of normal birthweight. No fetal or major obstetrical complications were seen. Post-mastectomy radiation (PMRT) was provided after pregnancy in 2 (20%) patients in the IR cohort and 12 (63%) in the non-IR cohort. All patients in the IR cohort successfully transitioned to permanent implant.
Conclusions: This report represents one of the largest series describing IR during BCP. IR after mastectomy increased surgery duration, but was not associated with adverse obstetrical or fetal outcomes. IR with TE may preserve reconstructive options when PMRT is indicated. (C) 2016 Wiley Periodicals, Inc.
C1 [Caragacianu, Diana L.; Mayer, Erica L.; Bellon, Jennifer R.; Wong, Julia S.; Troyan, Susan; Rhei, Esther; Dominici, Laura S.; Partridge, Ann; Calvillo, Katherina Zabicki] Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave,Yawkey 14,Suite 1440, Boston, MA 02115 USA.
[Chun, Yoon S.; Caterson, Stephanie; Economy, Katherine E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Tung, Nadine M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Schapira, Lidia] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Calvillo, KZ (reprint author), Dana Farber Brigham & Womens Canc Ctr, 450 Brookline Ave,Yawkey 14,Suite 1440, Boston, MA 02115 USA.
EM kzcalvillo@partners.org
NR 43
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
EI 1096-9098
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD AUG 1
PY 2016
VL 114
IS 2
BP 140
EP 143
DI 10.1002/jso.24308
PG 4
WC Oncology; Surgery
SC Oncology; Surgery
GA DW6RQ
UT WOS:000383779000002
PM 27392534
ER
PT J
AU Langerhuizen, DWG
Janssen, SJ
van der Vliet, QMJ
Raskin, KA
Ferrone, ML
Hornicek, FJ
Schwab, JH
Lozano-Calderon, SA
AF Langerhuizen, David W. G.
Janssen, Stein J.
van der Vliet, Quirine M. J.
Raskin, Kevin A.
Ferrone, Marco L.
Hornicek, Francis J.
Schwab, Joseph H.
Lozano-Calderon, Santiago A.
TI Metastasectomy, Intralesional Resection, or Stabilization Only in the
Treatment of Bone Metastases From Renal Cell Carcinoma
SO JOURNAL OF SURGICAL ONCOLOGY
LA English
DT Article
DE bone metastasis; renal cell carcinoma; metastasectomy; intralesional
curettage; resection
ID SKELETAL METASTASES; OSSEOUS METASTASES; PATIENT SURVIVAL; SURGERY;
KIDNEY
AB Background: The mainstay of treatment for bone metastases from renal cell carcinoma is surgery. We assessed if there was a difference in local recurrence, reoperation, and survival between patients who underwent metastasectomy, intralesional curettage, or stabilization only for renal cell carcinoma metastasis to the appendicular skeleton, and if there was a difference in these outcomes based on margin status.
Methods: This retrospective study included 183 patients; 48% underwent metastasectomy (n = 88, margins: 64 negative; 20 positive; 4 unclear), 30% intralesional curettage (n = 54), and 22% stabilization only (n = 41).
Results: The recurrence rate differed and was highest after stabilization only (39%), followed by intralesional curettage (22%), and metastasectomy (12%) (P = 0.003). However, we found no difference in reoperation rate (P = 0.847). Survival was better in patients who underwent metastasectomy (P = 0.020). The recurrence rate was lower in patients who had a negative margin (5%) as compared to those with a positive margin (26%) (P< 0.001). However, we found no difference in reoperation rate (P = 0.97). Negative margins showed better survival (P< 0.001).
Conclusions: Our findings emphasize the importance of obtaining negative margins in patients with a good life expectancy, as lower recurrence rate can be attained at a not significant additional risk for reoperation, with a potential impact on survival. (C) 2016 Wiley Periodicals, Inc.
C1 [Langerhuizen, David W. G.; Janssen, Stein J.; van der Vliet, Quirine M. J.; Raskin, Kevin A.; Hornicek, Francis J.; Schwab, Joseph H.; Lozano-Calderon, Santiago A.] Harvard Med Sch, Massachusetts Gen Hosp, Orthopaed Oncol Serv, Dept Orthopaed Surg, Boston, MA USA.
[Ferrone, Marco L.] Harvard Med Sch, Brigham & Womens Hosp, Orthopaed Oncol Serv, Dept Orthopaed Surg, Boston, MA USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Janssen, SJ (reprint author), Massachusetts Gen Hosp, Orthopaed Surg, Room 3-946,Yawkey Bldg,55 Fruit St, Boston, MA 02114 USA.
EM steinjanssen@gmail.com
NR 23
TC 1
Z9 1
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-4790
EI 1096-9098
J9 J SURG ONCOL
JI J. Surg. Oncol.
PD AUG 1
PY 2016
VL 114
IS 2
BP 237
EP 245
DI 10.1002/jso.24284
PG 9
WC Oncology; Surgery
SC Oncology; Surgery
GA DW6RQ
UT WOS:000383779000018
PM 27156495
ER
PT J
AU Shera, CA
Abdala, C
AF Shera, Christopher A.
Abdala, Carolina
TI Frequency shifts in distortion-product otoacoustic emissions evoked by
swept tones
SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA
LA English
DT Article
ID BASILAR-MEMBRANE RESPONSES; SWEEPING PRIMARIES; FINE-STRUCTURE;
INNER-EAR; DPOAE; NEWBORNS; DELAYS; ADULTS; DISPERSION; BREAKING
AB When distortion-product otoacoustic emissions (DPOAEs) are evoked using stimuli whose instantaneous frequencies change rapidly and continuously with time (swept tones), the oscillatory interference pattern known as distortion-product fine structure shifts slightly along the frequency axis in the same direction as the sweep. By analogy with the temporal mechanisms thought to underlie the differing efficacies of up-and down-swept stimuli as perceptual maskers (e.g., Schroeder-phase complexes), fine-structure shifts have been ascribed to the phase distortion associated with dispersive wave propagation in the cochlea. This paper tests an alternative hypothesis and finds that the observed shifts arise predominantly as a methodological side effect of the analysis procedures commonly used to extract delayed emissions from the measured time waveform. Approximate expressions for the frequency shifts of DPOAE distortion and reflection components are derived, validated with computer simulations, and applied to account for DPOAE fine-structure shifts measured in human subjects. Component magnitudes are shown to shift twice as much as component phases. Procedures for compensating swept-tone measurements to obtain estimates of the total DPOAE and its components measured at other sweep rates or in the sinusoidal steady state are presented. (C) 2016 Acoustical Society of America.
C1 [Shera, Christopher A.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA.
[Shera, Christopher A.; Abdala, Carolina] Univ Southern Calif, Keck Sch Med, Caruso Dept Otolaryngol, 1540 Alcazar St, Los Angeles, CA 90033 USA.
RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA.; Shera, CA (reprint author), Univ Southern Calif, Keck Sch Med, Caruso Dept Otolaryngol, 1540 Alcazar St, Los Angeles, CA 90033 USA.
EM christopher.shera@gmail.com
FU NIH/NIDCD [R01 DC003687, R01 DC003552]
FX The authors thank Karolina Charaziak and John Guinan for helpful
comments on the manuscript and Ping Luo and Amanda Ortmann for help with
subject testing and data analysis. Supported by NIH/NIDCD Grant Nos. R01
DC003687 (CAS) and R01 DC003552 (CA).
NR 33
TC 0
Z9 0
U1 0
U2 0
PU ACOUSTICAL SOC AMER AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0001-4966
EI 1520-8524
J9 J ACOUST SOC AM
JI J. Acoust. Soc. Am.
PD AUG
PY 2016
VL 140
IS 2
BP 936
EP 944
DI 10.1121/1.4960592
PG 9
WC Acoustics; Audiology & Speech-Language Pathology
SC Acoustics; Audiology & Speech-Language Pathology
GA DW8OT
UT WOS:000383916100030
PM 27586726
ER
PT J
AU Galovski, TE
Peterson, ZD
Beagley, MC
Strasshofer, DR
Held, P
Fletcher, TD
AF Galovski, Tara E.
Peterson, Zoe D.
Beagley, Marin C.
Strasshofer, David R.
Held, Philip
Fletcher, Thomas D.
TI Exposure to Violence During Ferguson Protests: Mental Health Effects for
Law Enforcement and Community Members
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; POLICE OFFICERS; PTSD SYMPTOMS; TRAUMA;
SYMPTOMATOLOGY; DEPRESSION; SEVERITY; ANGER
AB There is little information available on the mental health effects of exposure to shared community violence such as the August 2014 violence that occurred in Ferguson, Missouri. This study sought to examine the relationship between proximity to community violence and mental health in both community members and police officers. We recruited 565 adults (community, n = 304, and police, n = 261) exposed to the violence in Ferguson to complete measures of proximity to violence, posttraumatic stress, depression, and anger. Using structural equation modeling, we assessed aspects of proximity to violenceconnectedness, direct exposure, fear from exposure, media exposure, reactions to media, and life interruptionas correlates of posttraumatic stress disorder (PTSD) symptoms, depression, and anger. The final model yielded (n = 432), (2)(d = 12) = 7.4, p = .830; comparative fit index = 1.0, root mean square error of approximation = 0 [0, .04]. All aspects of proximity except direct exposure were associated with mental health outcomes. There was no moderation as a function of community versus police. Race moderated the relationship between life interruptions and negative outcomes; interruption was related to distress for White, but not Black community members. Based on group comparisons, community members reported more symptoms of PTSD and depression than law enforcement ((2)(p) = .06 and .02, respectively). Black community members reported more PTSD and depression than White community members ((2)(p) = .05 and .02, respectively). Overall, distress was high, and mental health interventions are likely indicated for some individuals exposed to the Ferguson events.
Resumen EFECTOS DE LA EXPOSICIN A LA VIOLENCIA EN FERGUSON Hay muy poca informacion disponible sobre los efectos en la salud mental de la exposicion a violencia comunitaria compartida tales como la violencia en Agosto del 2014 ocurrida en Ferguson, Missouri. Este estudio busco examinar la relacion entre la proximidad a la violencia comunitaria y la salud mental en los miembros de la comunidad y oficiales de policia. Reclutamos 565 adultos (comunidad [n = 304] y policia [n = 261]) expuestos a la violencia en Ferguson para completar medidas de proximidad a la violencia, estres postraumatico, depresion y rabia. Usando la ecuacion de modelamiento estructural, evaluamos los aspectos de proximidad a la violencia - conectividad, exposicion directa, miedo por exposicion, exposicion a los medios, reacciones a los medios e interrupcion de la vida - como correlatos de trastorno por estres postraumatico (TEPT), depresion y rabia. En el modelo final (n = 432),X (2) (d = 12); p = .830, CFI = 1.0, RMSEA = 0 [0,.04], todos los aspectos de la proximidad excepto la exposicion directa se asociaron con los resultados en la salud mental. No hubo moderacion en funcion de la membresia en la comunidad versus la muestra de la policia. La raza modero la relacion entre las interrupciones de vida y los resultados negativos, la interrupcion estuvo relacionada a la angustia para miembros de la comunidad Blancos pero no para los Negros. Basado en comparaciones por grupo, los miembros de la comunidad reportaron mas sintomas de TEPT y depresion que la policia (p(2) = .06 y .02, respectivamente), y los miembros de la comunidad Negra reportaron mas TEPT y depresion que los miembros de la comunidad Blanca (p2 = .05 y .02, respectivamente). En general, la angustia fue alta y las intervenciones de salud mental fueron probablemente indicadas para algunos individuos expuestos a los eventos de Ferguson.
C1 [Galovski, Tara E.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Peterson, Zoe D.; Beagley, Marin C.; Strasshofer, David R.] Univ Missouri, Ctr Trauma Recovery, Dept Psychol Sci, St Louis, MO 63121 USA.
[Held, Philip] Rush Univ, Med Ctr, Dept, Chicago, IL 60612 USA.
RP Galovski, TE (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, 150 South Huntington Ave 116B-3, Boston, MA 02130 USA.
EM Tara.Galovski@va.gov
OI Peterson, Zoe/0000-0003-2975-1062
FU University of Missouri-St. Louis (UMSL), College of Arts and Sciences
(CAS) internal research grant mechanism; College of Nursing, University
of Missouri-St. Louis
FX Participants' payments were funded by the University of Missouri-St.
Louis (UMSL), College of Arts and Sciences (CAS) internal research grant
mechanism. Participant recruitment was funded, in part, by the College
of Nursing, University of Missouri-St. Louis.
NR 33
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U1 15
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2016
VL 29
IS 4
BP 283
EP 292
DI 10.1002/jts.22105
PG 10
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW2MW
UT WOS:000383477500001
PM 27254474
ER
PT J
AU Shipherd, JC
Salters-Pedneault, K
Matza, A
AF Shipherd, Jillian C.
Salters-Pedneault, Kristalyn
Matza, Alexis
TI Intrusive Cognitive Content and Postdeployment Distress
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; MEMORIES; TRAUMA; SAMPLE; IRAQ;
HYPOTHESIS; VALIDATION; DEPLOYMENT; VETERANS; THOUGHTS
AB Although intrusive cognitions (ICs) are common posttrauma, little is known about trauma-related IC content, or associations between IC content and posttraumatic adjustment. A mixed-method cross-sectional approach was used in a secondary analysis of IC content and postdeployment distress. Participants were 1,521 U.S. Army soldiers 3-12 months postdeployment reporting their most distressing postdeployment ICs (mean number of ICs reported was 1.20). ICs were transcribed and content was categorized by 13 emergent themes. The most commonly reported ICs were of injury or death (48.2%) and combat (43.5%), and soldiers with probable posttraumatic stress disorder (PTSD; n = 187) were more likely to report the presence of these ICs, (2)s(1) = 35.27, ps < .001, s < .16 than those without probable PTSD (n = 1,331). Other domains also emerged frequently, including ICs about friends (31.0%), family (15.8%), and leadership concerns (13.8%). IC content was a small, but significant correlate of distress after adjusting for combat exposure (R-2 .02, ps .001). The presence of ICs of injury or death, combat, military sexual trauma, health, leadership, and family (s > .06, ps < .02) were unique correlates of distress. Results suggested that ICs about a wide range of topics should be addressed in postdeployment interventions.
Resumen Cognicion Intrusiva Post Despliegue Aunque las cogniciones intrusivas (CI) son comunes post trauma, se sabe poco acerca de su contenido relacionado al trauma, o de las asociaciones entre su contenido y la adaptacion post-traumatica. Se uso una aproximacion transversal de metodo mixto en un analisis secundario de contenido de CI y sufrimiento post despliegue. Los participantes fueron 1.521 soldados del ejercito de USA, que reportaron sus mas angustiantes CI post despliegue, 3 a 12 meses posterior a este (el numero promedio de CI reportadas fue 1.20). Las CI fueron transcritas y su contenido fue categorizado en 13 temas emergentes. Las CI mas comunmente reportadas fueron de dano o muerte (48,2%) y combate (43,5%), y los soldados con probable TEPT (n = 187) reportaban con mayor probabilidad la presencia de estas CI, (2)s (1) = 35.27, ps < .001, s < .16 que aquellos sin probable TEPT (n = 1331). Otros dominios, que tambien emergieron frecuentemente, incluyen CI acerca de amigos (31,0%), familia (15,8%) y preocupaciones de liderazgo (13,8%). El contenido de las CI se correlaciono de forma pequena pero significativa con el sufrimiento luego de ajustar por exposicion a combate (R 2 > .02, ps < .001). La presencia de CIs de lesion o muerte, combate, trauma sexual militar salud, liderazgo y familia (s > .06, ps < .02) fueron correlatos unicos de sufrimiento. Los resultados sugieren que se deberia abordar las CI acerca de un amplio rango de temas en las intervenciones post despliegue.
C1 [Shipherd, Jillian C.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02118 USA.
[Shipherd, Jillian C.; Matza, Alexis] Vet Hlth Adm, Off Patient Care Serv, Lesbian Gay Bisexual & Transgender Program 10P4Y, Washington, DC USA.
[Salters-Pedneault, Kristalyn] Eastern Connecticut State Univ, Dept Psychol, Willimantic, CT 06226 USA.
[Matza, Alexis] Boston VA Res Inst, Boston, MA USA.
RP Shipherd, JC (reprint author), VA Boston Healthcare Syst, Womens Hlth Sci Div 116B 3, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA.
EM Jillian.Shipherd@va.gov
FU U.S. Army Medical Research and Materiel Command [W81XWH-09-1-0535]
FX This research was supported by the U.S. Army Medical Research and
Materiel Command (award# W81XWH-09-1-0535). This trial is registered in
the Defense Technical Information Database (DTIC), Accession #579178.
NR 37
TC 0
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U1 12
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2016
VL 29
IS 4
BP 301
EP 308
DI 10.1002/jts.22113
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW2MW
UT WOS:000383477500003
PM 27405098
ER
PT J
AU Jackson, CE
Green, JD
Bovin, MJ
Vasterling, JJ
Holowka, DW
Ranganathan, G
Rosen, RC
Keane, TM
Marx, BP
AF Jackson, Colleen E.
Green, Jonathan D.
Bovin, Michelle J.
Vasterling, Jennifer J.
Holowka, Darren W.
Ranganathan, Gayatri
Rosen, Raymond C.
Keane, Terence M.
Marx, Brian P.
TI Mild Traumatic Brain Injury, PTSD, and Psychosocial Functioning Among
Male and Female US OEF/OIF Veterans
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; ENDURING FREEDOM; NATIONAL-GUARD; IRAQ;
HEALTH; AFGHANISTAN; SOLDIERS; METAANALYSIS; ASSOCIATION; IMPAIRMENT
AB This study examined the unique and combined relationship between mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) with psychosocial functioning in a cohort of 1,312 U.S. male and female veterans of Operations Enduring Freedom (OEF) and Iraqi Freedom (OIF) enrolled in the Veterans After-Discharge Longitudinal Registry (Project VALOR). We assessed mTBI with structured screening questions reflective of current TBI classification standards and PTSD via the SCID-IV PTSD module; all other variables were assessed by self-report questionnaires. We identified significant diagnostic group differences in psychosocial functioning for both sexes. Individuals with PTSD, with or without a history of mTBI, reported significantly worse psychosocial functioning than individuals with mTBI alone or neither mTBI nor PTSD (males, (2)(p) = .11, p < .001; females, (2)(p) = .14, p < .001), even after adjusting for demographics and severity of chronic pain. The results suggested that veterans experiencing PTSD, regardless of whether they had a history of mTBI, were at increased risk for long-term psychosocial impairment. Further research examining possible benefits from improved access to resources and treatment to address these needs would be valuable.
Resumen Este estudio examino la relacion unica y combinada entre la lesion cerebral traumatica leve (LCTL) y trastorno por estres postraumatico (TEPT) con el funcionamiento psicosocial en una cohorte de 1.312 hombres y mujeres veteranos de las operaciones Enduring Freedom (OEF) y Libertad Iraqui (OIF) inscritos en el Registro Longitudinal de Veteranos despues de descargos (Proyecto VALOR). Se evaluo LCTL con preguntas de screening estructuradas que reflejan los criterios de clasificacion de LCT actual y trastorno por estres postraumatico a traves del modulo de TEPT SCID-IV; todas las demas variables se evaluaron mediante cuestionarios de auto-reporte. Se identificaron diferencias significativas entre los grupos de diagnostico en el funcionamiento psicosocial para ambos sexos, de tal manera que las personas con trastorno de estres postraumatico, con o sin historial de LCTL, reportaron significativamente peor funcionamiento psicosocial en comparacion con los individuos con LCTL solo o los que no tenian LCTL ni trastorno por estres postraumatico (hombres, 2 p = 0,11, p <0,001; mujeres, 2 p = 0,14, p <0,001), incluso despues de ajustar las variables demograficas y la severidad del dolor cronico. Los resultados sugieren que los veteranos que experimentan trastorno por estres postraumatico, independientemente de si tenian un historial de LCTL, estaban en mayor riesgo de deterioro psicosocial a largo plazo. Futuras investigaciones que examinen los posibles beneficios de un acceso mejorado a los recursos y el tratamiento para dirigir estas necesidades serian valiosas.
C1 [Jackson, Colleen E.] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA USA.
[Jackson, Colleen E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders TRACTS, Boston, MA USA.
[Jackson, Colleen E.; Green, Jonathan D.; Bovin, Michelle J.; Vasterling, Jennifer J.; Holowka, Darren W.; Keane, Terence M.; Marx, Brian P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Green, Jonathan D.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA.
[Bovin, Michelle J.; Vasterling, Jennifer J.; Holowka, Darren W.; Keane, Terence M.; Marx, Brian P.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA USA.
[Ranganathan, Gayatri; Rosen, Raymond C.] New England Res Inst, 9 Galen St, Watertown, MA 02172 USA.
RP Marx, BP (reprint author), VA Boston Healthcare Syst 116B 4, Natl Ctr PTSD, Behav Sci Div, 150 South Huntington Ave, Boston, MA 02130 USA.
EM brian.marx@va.gov
NR 39
TC 0
Z9 0
U1 10
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2016
VL 29
IS 4
BP 309
EP 316
DI 10.1002/jts.22110
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW2MW
UT WOS:000383477500004
PM 27405050
ER
PT J
AU DiMauro, J
Renshaw, KD
Smith, BN
Vogt, D
AF DiMauro, Jennifer
Renshaw, Keith D.
Smith, Brian N.
Vogt, Dawne
TI Perceived Support From Multiple Sources: Associations With PTSD Symptoms
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; SOCIAL SUPPORT; GENDER-DIFFERENCES;
MULTIDIMENSIONAL SCALE; OEF/OIF VETERANS; MENTAL-HEALTH; RISK-FACTORS;
DEPLOYMENT; COMBAT; METAANALYSIS
AB Perceived social support is negatively associated with severity of posttraumatic stress disorder (PTSD), but the literature lacks data about specific sources of support. Using 2 service member (SM) samples (n = 207 and 465), this study examined perceived support from family/friends and the broader public. SMs perceived high support from both sources. In multivariate regressions, perceived support from the broader public was not significantly associated with severity of PTSD symptoms, but it demonstrated a nearly identical effect size ( = -.21) as support from family/friends ( = -.23) in a sample of active duty and National Guard/Reserve SMs. We found that, SMs perceived high levels of support from the broader public, with modest evidence that such perceptions may relate to severity of PTSD.
Resumen Apoyo Percibido desde Multiples Fuentes en TEPT El apoyo social percibido esta negativamente asociado con la severidad del trastorno por estres postraumatico (TEPT) pero la literatura carece de datos acerca de las fuentes de apoyo. Utilizando 2 muestras de miembros de servicio (MS) (n = 207; 465), este estudio examino el apoyo percibido desde la familia/amigos y del publico en general. Los MSs percibieron alto apoyo de ambas fuentes. En una regresion multivariada, el apoyo percibido desde el publico en general no estuvo significativamente asociado con la severidad de los sintomas de TEPT, pero demostro un casi identico tamano del efecto ( = -.21) como el apoyo desde la familia/amigos ( = -.23) en una muestra de servicio activo y Guardia Nacional/ Reserva MSs. En conclusion, MSs percibieron altos niveles de apoyo desde el publico en general, con una modesta evidencia que tales percepciones pueden estar relacionadas con la severidad de TEPT.
C1 [DiMauro, Jennifer; Renshaw, Keith D.] George Mason Univ, Dept Psychol, 4400 Univ Dr,MSN 3F5, Fairfax, VA 22030 USA.
[Smith, Brian N.; Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA.
[Smith, Brian N.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
RP DiMauro, J (reprint author), George Mason Univ, Dept Psychol, 4400 Univ Dr,MSN 3F5, Fairfax, VA 22030 USA.
EM jdimauro@gmu.edu
FU Department of Veterans Affairs, Health Services Research and Development
Service [DHI 05-130-3, DHI 09-086]
FX This project was supported by two Department of Veterans Affairs, Health
Services Research and Development Service grants: "Further Development
and Validation of the DRRI" (DHI 05-130-3), Dawne Vogt, Principal
Investigator; and "Validation of Modified DRRI Scales in a National
Sample of OEF/OIF Veterans" (DHI 09-086), Dawne Vogt, Principal
Investigator.
NR 35
TC 0
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U1 10
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2016
VL 29
IS 4
BP 332
EP 339
DI 10.1002/jts.22114
PG 8
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW2MW
UT WOS:000383477500007
PM 27459310
ER
PT J
AU Sawyer, AT
Liverant, GI
Jun, JJ
Lee, DJ
Cohen, AL
Dutra, SJ
Pizzagalli, DA
Sloan, DM
AF Sawyer, Alice T.
Liverant, Gabrielle I.
Jun, Janie J.
Lee, Daniel J.
Cohen, Andrew L.
Dutra, Sunny J.
Pizzagalli, Diego A.
Sloan, Denise M.
TI Punishment Learning in US Veterans With Posttraumatic Stress Disorder
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID DEPRESSION; SCALE
AB Learning processes have been implicated in the development and course of posttraumatic stress disorder (PTSD); however, little is currently known about punishment-based learning in PTSD. The current study investigated impairments in punishment-based learning in U.S. veterans. We expected that veterans with PTSD would demonstrate greater punishment-based learning compared to a non-PTSD control group. We compared a PTSD group with and without co-occurring depression (n = 27) to a control group (with and without trauma exposure) without PTSD or depression (n = 29). Participants completed a computerized probabilistic punishment-based learning task. Compared to the non-PTSD control group, veterans with PTSD showed significantly greater punishment-based learning. Specifically, there was a significant Block x Group interaction, F(1, 54) = 4.12, p = .047, (2) = .07. Veterans with PTSD demonstrated greater change in response bias for responding toward a less frequently punished stimulus across blocks. The observed hypersensitivity to punishment in individuals with PTSD may contribute to avoidant responses that are not specific to trauma cues.
Resumen Aprendizaje por castigo y TEPT El procesamiento del aprendizaje ha estado implicado en el desarrollo y curso del trastorno por estres postraumatico (TEPT); sin embargo, poco se sabe actualmente acerca del aprendizaje basado en el castigo en el TEPT. El presente estudio investigo los deterioros potenciales en el aprendizaje basado en el castigo entre participantes veteranos. Nosotros esperabamos que los veteranos con TEPT pudieran demostrar mayor aprendizaje basado en el castigo comparados con el grupo control sin TEPT. Comparamos un grupo con TEPT con y sin depresion comorbida (n = 27) a un grupo control (con y sin exposicion a trauma) sin TEPT o depresion (n = 29). Los veteranos completaron una tarea de aprendizaje basado en el castigo probabilistico computarizado. En relacion con el grupo control sin TEPT, los veteranos con TEPT demostraron significativamente mayor aprendizaje basado en el castigo. En concreto, habia un Bloque significativo x interaccion del grupo, F(1,54) = 4.12, p = .047, ?(2) = .07, tales que los veteranos con TEPT demostraron mayores cambios en el sesgo de respuesta para responder a un estimulo que es castigado con menos frecuencia a traves de bloques. En consecuencia, la hipersensibilidad al castigo en los individuos con TEPT puede contribuir a las respuestas de evitacion que no son especificos a las senales de trauma. Se discuten las implicaciones clinicas junto con la consideracion de la comorbilidad con depresion.
C1 [Sawyer, Alice T.; Jun, Janie J.; Lee, Daniel J.; Sloan, Denise M.] VA Boston Healthcare Syst, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA.
[Liverant, Gabrielle I.] Suffolk Univ, Dept Psychol, Boston, MA 02114 USA.
[Jun, Janie J.; Lee, Daniel J.; Sloan, Denise M.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Lee, Daniel J.] Auburn Univ, Dept Psychol, Auburn, AL 36849 USA.
[Cohen, Andrew L.; Pizzagalli, Diego A.] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA.
[Cohen, Andrew L.; Pizzagalli, Diego A.] Harvard Med Sch, Belmont, MA USA.
[Dutra, Sunny J.] Yale Univ, Dept Psychol, New Haven, CT USA.
[Sloan, Denise M.] VA Natl Ctr PTSD, Behav Sci Div, Boston, MA USA.
RP Sloan, DM (reprint author), VA Boston Healthcare Syst, 150 S Huntington Ave 116B-4, Boston, MA 02130 USA.
EM denise.sloan@va.gov
FU VA National Center for PTSD, Behavioral Science Division; NIMH [R01
MH068376, R01 MH101521]
FX This work was supported by VA National Center for PTSD, Behavioral
Science Division. Diego A. Pizzagalli was partially supported by NIMH
grants R01 MH068376 and R01 MH101521. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH and the Department of Veteran Affairs.
NR 23
TC 0
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U1 4
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2016
VL 29
IS 4
BP 374
EP 378
DI 10.1002/jts.22109
PG 5
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW2MW
UT WOS:000383477500012
PM 27459209
ER
PT J
AU Sautter, FJ
Glynn, SM
Becker-Cretu, JJ
Senturk, D
Armelie, AP
Wielt, DB
AF Sautter, Frederic J.
Glynn, Shirley M.
Becker-Cretu, Julia J.
Senturk, Damla
Armelie, Aaron P.
Wielt, Dustin B.
TI Structured Approach Therapy for Combat-Related PTSD in Returning US
Veterans: Complementary Mediation by Changes in Emotion Functioning
SO JOURNAL OF TRAUMATIC STRESS
LA English
DT Article
ID POSTTRAUMATIC-STRESS-DISORDER; IRAQ; AFGHANISTAN; SYMPTOMS; TRIAL;
SCALE; FEAR; WAR
AB To address the impact of combat-related posttraumatic stress disorder (PTSD) on U.S. Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) veterans, the investigators developed a 12-session manualized PTSD treatment for couples called structured approach therapy (SAT). A randomized controlled trial had shown that 29 OEF/OIF veterans with combat-related PTSD who had participated in SAT showed significantly greater reductions in PTSD compared to 28 veterans receiving a 12-session PTSD family education intervention (Sautter, Glynn, Cretu, Senturk, & Vaught, 2015). We conducted supplemental follow-up and mediation analyses, which tested the hypothesis that changes in emotion functioning play a significant role in the decreases in PTSD symptoms primarily observed in veterans who had received SAT. Veterans assigned to the SAT condition showed significantly greater decreases than those assigned to PTSD family education in emotion regulation problems (p < .001, Cohen's f(2) = .18) and fear of intense emotions (p <.001, Cohen's f2 =.152). Decreases in both emotion regulation problems (mediated effect: ab =.36), and fear of intense emotions (mediated effect: ab =.24) were found to be complementary mediators of reductions in PTSD symptoms greater with SAT. These findings suggest that SAT may aid veterans in improving their ability to regulate trauma-related emotions.
C1 [Sautter, Frederic J.] Southeast Louisiana Vet Hlth Care Syst, New Orleans, LA USA.
[Sautter, Frederic J.; Becker-Cretu, Julia J.; Armelie, Aaron P.] Tulane Univ, Sch Med, Dept Psychiat, 1430 Tulane Ave, New Orleans, LA 70112 USA.
[Glynn, Shirley M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Glynn, Shirley M.] Univ Calif Los Angeles, Welcome Back Vet Family Resilience Ctr, Los Angeles, CA USA.
[Senturk, Damla] Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA.
[Senturk, Damla] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA USA.
[Wielt, Dustin B.] Raymond G Murphy VA Med Ctr, Albuquerque, NM USA.
RP Sautter, FJ (reprint author), Tulane Univ, Sch Med, Dept Psychiat & Behav Sci, 1440 Canal St TB 53, New Orleans, LA 70112 USA.
EM fredericsautter@msn.com
FU VA Research Rehabilitation and Development (RRD) Program [B6756R]; South
Central Mental Illness Research Education and Clinical Center (MIRECC)
FX This work was supported in part by a Merit Review grant (No. B6756R)
from the VA Research Rehabilitation and Development (RR&D) Program and a
Supplemental Funding Award from the South Central Mental Illness
Research Education and Clinical Center (MIRECC) to Frederic J. Sautter.
The authors thank Dr. Michelle Sherman for her consultation in
developing both treatment manuals, and Dr. Amanda Vaught, Marin
Casselli, and Allison Abel for their contributions.
NR 15
TC 0
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U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-9867
EI 1573-6598
J9 J TRAUMA STRESS
JI J. Trauma Stress
PD AUG
PY 2016
VL 29
IS 4
BP 384
EP 387
DI 10.1002/jts.22120
PG 4
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DW2MW
UT WOS:000383477500014
PM 27472747
ER
PT J
AU Campo, M
Al-Halabi, H
Khandekar, M
Shaw, AT
Sequist, LV
Willers, H
AF Campo, Meghan
Al-Halabi, Hani
Khandekar, Melin
Shaw, Alice T.
Sequist, Lecia V.
Willers, Henning
TI Integration of Stereotactic Body Radiation Therapy With Tyrosine Kinase
Inhibitors in Stage IV Oncogene-Driven Lung Cancer
SO ONCOLOGIST
LA English
DT Article
ID GROWTH-FACTOR-RECEPTOR; PHASE I/II TRIAL; DOSE-ESCALATION TRIAL;
ACQUIRED-RESISTANCE; BRAIN METASTASES; OLIGOMETASTATIC LESIONS; EGFR
MUTATIONS; II-TRIAL; EXTRACRANIAL OLIGOMETASTASES; OLIGOPROGRESSIVE
DISEASE
AB Genotype-based selection of patients for targeted therapies has had a substantial impact on the treatment of non-small cell lung cancers (NSCLCs). Tyrosine kinase inhibitors (TKIs) directed at cancers driven by oncogenes, such as epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangements, often achieve dramatic responses and result in prolonged survival compared with chemotherapy. However, TKI resistance invariably develops. Disease progression can be limited to only one or a few sites and might not be symptomatic, raising the important question of whether this type of oligoprogression warrants a change in systemic therapy or consideration of local treatment. Recent clinical observations suggest a growing role for stereotactic body radiation therapy (SBRT) in the treatment of oligoprogressive and perhaps even oligopersistent disease (primary and/or metastases) in oncogene-driven NSCLC. SBRTmight allow patients to continue with existing TKI treatments longer and delay the need to switch to other systemic options. We review the current data with regard to the use of SBRT for metastatic NSCLC and particularly oncogene-driven disease. Although there is great promise in the marriage of targeted therapies with SBRT, prospective data are urgently needed. In the meantime, such strategies are being used in carefully selected patients, with risk-adapted SBRT dose-fractionation regimens used to optimize the therapeutic index.
C1 [Campo, Meghan] Dana Farber Partners CancerCare, Hematol Oncol Fellowship Program, Boston, MA USA.
[Al-Halabi, Hani; Khandekar, Melin; Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Shaw, Alice T.; Sequist, Lecia V.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Shaw, Alice T.; Sequist, Lecia V.] Harvard Med Sch, Boston, MA USA.
RP Willers, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA.
EM hwillers@mgh.harvard.edu
NR 107
TC 1
Z9 1
U1 3
U2 3
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD AUG
PY 2016
VL 21
IS 8
BP 964
EP 973
DI 10.1634/theoncologist.2015-0508
PG 10
WC Oncology
SC Oncology
GA DW1HC
UT WOS:000383392900009
PM 27354669
ER
PT J
AU Fathi, AT
Chi, AS
AF Fathi, Amir T.
Chi, Andrew S.
TI Urine 2-Hydroxyglutarate in Glioma Reply
SO ONCOLOGIST
LA English
DT Letter
C1 [Fathi, Amir T.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02115 USA.
[Chi, Andrew S.] NYU, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY USA.
RP Fathi, AT (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Boston, MA 02115 USA.
NR 2
TC 0
Z9 0
U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD AUG
PY 2016
VL 21
IS 8
DI 10.1634/theoncologist.2016-0138
PG 1
WC Oncology
SC Oncology
GA DW1HC
UT WOS:000383392900018
ER
PT J
AU Baeten, JM
Heffron, R
Kidoguchi, L
Mugo, NR
Katabira, E
Bukusi, EA
Asiimwe, S
Haberer, JE
Morton, J
Ngure, K
Bulya, N
Odoyo, J
Tindimwebwa, E
Hendrix, C
Marzinke, MA
Ware, NC
Wyatt, MA
Morrison, S
Haugen, H
Mujugira, A
Donnell, D
Celum, C
AF Baeten, Jared M.
Heffron, Renee
Kidoguchi, Lara
Mugo, Nelly R.
Katabira, Elly
Bukusi, Elizabeth A.
Asiimwe, Stephen
Haberer, Jessica E.
Morton, Jennifer
Ngure, Kenneth
Bulya, Nulu
Odoyo, Josephine
Tindimwebwa, Edna
Hendrix, Craig
Marzinke, Mark A.
Ware, Norma C.
Wyatt, Monique A.
Morrison, Susan
Haugen, Harald
Mujugira, Andrew
Donnell, Deborah
Celum, Connie
CA Partners Demonstration Project Tea
TI Integrated Delivery of Antiretroviral Treatment and Pre-exposure
Prophylaxis to HIV-1-Serodiscordant Couples: A Prospective
Implementation Study in Kenya and Uganda
SO PLOS MEDICINE
LA English
DT Article
ID AFRICAN WOMEN; HIV-INFECTION; COST-EFFECTIVENESS; PREVENTION; THERAPY;
MEN
AB Background
Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.
Methods and Findings
Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (>= 85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7-6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0-0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.
Conclusions
Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of < 0.5% per year compared to an expected incidence of > 5% per year.
C1 [Baeten, Jared M.; Heffron, Renee; Kidoguchi, Lara; Mugo, Nelly R.; Bukusi, Elizabeth A.; Morton, Jennifer; Morrison, Susan; Haugen, Harald; Mujugira, Andrew; Donnell, Deborah; Celum, Connie] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Baeten, Jared M.; Celum, Connie] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Baeten, Jared M.; Heffron, Renee; Celum, Connie] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Mugo, Nelly R.] Kenya Govt Med Res Ctr, Clin Res Ctr, Nairobi, Kenya.
[Katabira, Elly; Bulya, Nulu] Makerere Univ, Infect Dis Inst, Kampala, Uganda.
[Bukusi, Elizabeth A.; Odoyo, Josephine] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya.
[Asiimwe, Stephen; Tindimwebwa, Edna] Kabwohe Clin Res Ctr, Kabwohe, Uganda.
[Haberer, Jessica E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ngure, Kenneth] Jomo Kenyatta Univ Agr & Technol, Coll Hlth Sci, Nairobi, Kenya.
[Marzinke, Mark A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Ware, Norma C.; Wyatt, Monique A.] Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA USA.
[Wyatt, Monique A.] Harvard Global, Cambridge, MA USA.
[Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
RP Baeten, JM (reprint author), Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.; Baeten, JM (reprint author), Univ Washington, Dept Med, Seattle, WA 98195 USA.; Baeten, JM (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
EM jbaeten@uw.edu
RI Hendrix, Craig/G-4182-2014
OI Hendrix, Craig/0000-0002-5696-8665
FU National Institute of Mental Health of the US National Institutes of
Health [R01 MH095507]; Bill & Melinda Gates Foundation [OPP1056051]; US
Agency for International Development [AID-OAA-A-12-00023]
FX The Partners Demonstration Project was funded by the National Institute
of Mental Health of the US National Institutes of Health (grant R01
MH095507), the Bill & Melinda Gates Foundation (grant OPP1056051), and
through the US Agency for International Development (cooperative
agreement AID-OAA-A-12-00023). Gilead Sciences donated the PrEP
medication but had no role in data collection or analysis. The results
and interpretation presented here do not necessarily reflect the views
of the study funders. The study funders had no role in study design,
data collection, data analysis, data interpretation, or writing of the
report.
NR 22
TC 5
Z9 5
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD AUG
PY 2016
VL 13
IS 8
AR e1002099
DI 10.1371/journal.pmed.1002099
PG 17
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW0UD
UT WOS:000383357400017
PM 27552090
ER
PT J
AU Ly, J
Sathananthan, V
Griffiths, T
Kanjee, Z
Kenny, A
Gordon, N
Basu, G
Battistoli, D
Dorr, L
Lorenzen, B
Thomson, DR
Waters, A
Moore, UG
Roberts, R
Smith, WL
Siedner, MJ
Kraemer, JD
AF Ly, John
Sathananthan, Vidiya
Griffiths, Thomas
Kanjee, Zahir
Kenny, Avi
Gordon, Nicholas
Basu, Gaurab
Battistoli, Dale
Dorr, Lorenzo
Lorenzen, Breeanna
Thomson, Dana R.
Waters, Ami
Moore, Uriah G.
Roberts, Ruth
Smith, Wilmot L.
Siedner, Mark J.
Kraemer, John D.
TI Facility-Based Delivery during the Ebola Virus Disease Epidemic in Rural
Liberia: Analysis from a Cross-Sectional, Population-Based Household
Survey
SO PLOS MEDICINE
LA English
DT Article
ID SUB-SAHARAN AFRICA; NOVEMBER 2014; WEST-AFRICA; HEALTH; MORTALITY;
OUTBREAK; DISTRICT; LESSONS; NEWBORN; SYSTEM
AB Background
The Ebola virus disease (EVD) epidemic has threatened access to basic health services through facility closures, resource diversion, and decreased demand due to community fear and distrust. While modeling studies have attempted to estimate the impact of these disruptions, no studies have yet utilized population-based survey data.
Methods and Findings
We conducted a two-stage, cluster-sample household survey in Rivercess County, Liberia, in March-April 2015, which included a maternal and reproductive health module. We constructed a retrospective cohort of births beginning 4 y before the first day of survey administration (beginning March 24, 2011). We then fit logistic regression models to estimate associations between our primary outcome, facility-based delivery (FBD), and time period, defined as the pre-EVD period (March 24, 2011-June 14, 2014) or EVD period (June 15, 2014-April 13, 2015). We fit both univariable and multivariable models, adjusted for known predictors of facility delivery, accounting for clustering using linearized standard errors. To strengthen causal inference, we also conducted stratified analyses to assess changes in FBD by whether respondents believed that health facility attendance was an EVD risk factor. A total of 1,298 women from 941 households completed the survey. Median age at the time of survey was 29 y, and over 80% had a primary education or less. There were 686 births reported in the pre-EVD period and 212 in the EVD period. The unadjusted odds ratio of facility-based delivery in the EVD period was 0.66 (95% confidence interval [CI] 0.48-0.90, p-value = 0.010). Adjustment for potential confounders did not change the observed association, either in the principal model (adjusted odds ratio [AOR] = 0.70, 95% CI 0.50-0.98, p = 0.037) or a fully adjusted model (AOR = 0.69, 95% CI 0.50-0.97, p = 0.033). The association was robust in sensitivity analyses. The reduction in FBD during the EVD period was observed among those reporting a belief that health facilities are or may be a source of Ebola transmission (AOR = 0.59, 95% CI 0.36-0.97, p = 0.038), but not those without such a belief (AOR = 0.90, 95% CI 0.59-1.37, p = 0.612). Limitations include the possibility of FBD secular trends coincident with the EVD period, recall errors, and social desirability bias.
Conclusions
We detected a 30% decreased odds of FBD after the start of EVD in a rural Liberian county with relatively few cases. Because health facilities never closed in Rivercess County, this estimate may under-approximate the effect seen in the most heavily affected areas. These are the first population-based survey data to show collateral disruptions to facility-based delivery caused by the West African EVD epidemic, and they reinforce the need to consider the full spectrum of implications caused by public health emergencies.
C1 [Ly, John; Waters, Ami] Last Mile Hlth, Med Team, Zwedru, Liberia.
[Sathananthan, Vidiya; Griffiths, Thomas; Kenny, Avi; Gordon, Nicholas; Basu, Gaurab] Last Mile Hlth, Monitoring & Evaluat Team, Zwedru, Liberia.
[Kanjee, Zahir] Brigham & Womens Hosp, Div Global Hlth Equ, 75 Francis St, Boston, MA 02115 USA.
[Basu, Gaurab] Cambridge Hlth Alliance, Cambridge, MA USA.
[Basu, Gaurab; Siedner, Mark J.] Harvard Med Sch, Boston, MA 02115 USA.
[Battistoli, Dale; Dorr, Lorenzo; Lorenzen, Breeanna] Last Mile Hlth, Implementat Team, Cestos City, Liberia.
[Thomson, Dana R.] Harvard Med Sch, Dept Global Hlth & Social Med, Boston, MA USA.
[Moore, Uriah G.; Roberts, Ruth; Smith, Wilmot L.] Liberian Minist Hlth & Social Welf, Rivercess Cty Hlth Team, Cestos City, Liberia.
[Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
[Kraemer, John D.] Georgetown Univ, Dept Hlth Syst Adm, Washington, DC 20057 USA.
[Kraemer, John D.] Georgetown Univ, African Studies Program, Washington, DC 20057 USA.
[Kanjee, Zahir] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Waters, Ami] Univ Calif San Francisco, Sch Med, San Francisco, CA USA.
RP Siedner, MJ (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Siedner, MJ (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.; Kraemer, JD (reprint author), Georgetown Univ, Dept Hlth Syst Adm, Washington, DC 20057 USA.; Kraemer, JD (reprint author), Georgetown Univ, African Studies Program, Washington, DC 20057 USA.
EM msiedner@mgh.harvard.edu; jdk32@georgetown.edu
OI Kenny, Avi/0000-0002-9465-7307
FU Direct Relief; National Institutes of Health [K23 MH099916]; UBS Optimus
Foundation
FX Direct Relief and UBS Optimus Foundation provided programmatic
evaluation funds to Last Mile Health for the survey on which this
analysis was conducted (no grant identification numbers). The funders
had no role in the study design, data collection and analysis, decision
to publish, or preparation of the manuscript. MJS receives research
support from the National Institutes of Health (K23 MH099916).
NR 84
TC 3
Z9 3
U1 3
U2 3
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD AUG
PY 2016
VL 13
IS 8
AR e1002096
DI 10.1371/journal.pmed.1002096
PG 17
WC Medicine, General & Internal
SC General & Internal Medicine
GA DW0UD
UT WOS:000383357400016
PM 27482706
ER
PT J
AU Popp, I
Grosu, AL
Niedermann, G
Duda, DG
AF Popp, Ilinca
Grosu, Anca Ligia
Niedermann, Gabriele
Duda, Dan G.
TI Immune modulation by hypofractionated stereotactic radiation therapy:
Therapeutic implications
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Review
DE SBRT; SRS; Checkpoint blockade; Abscopal effect
ID CELL LUNG-CANCER; COLONY-STIMULATING FACTOR; MONOCLONAL-ANTIBODY
THERAPY; RESISTANT PROSTATE-CANCER; PHASE I/II TRIAL; CD8(+) T-CELLS;
BREAST-CANCER; TUMOR-CELLS; HEPATOCELLULAR-CARCINOMA; ANTITUMOR IMMUNITY
AB Stereotactic body radiation therapy (SBRT) has become an attractive treatment modality and a safe, non-invasive alternative to surgery to control primary or secondary malignant tumors. While emphasis has been on the local tumor control as a treatment objective for SBRT, the rare but intriguing observations of abscopal (or out-of-field) effects have pointed to the exciting possibility of activating anti-tumor immunity by using high-dose radiation. This review summarizes the available evidence supporting immune modulation by SBRT alone, as well as its potential combination with immunotherapy. Promising preclinical research has revealed an array of immune changes following SBRT, which could affect the balance between anti-tumor immunity and tumor-promoting immunosuppression. However, shifting this balance in the clinical setting to obtain survival benefits has rarely been achieved so far, emphasizing the need for a better understanding of the interactions between high-dose radiotherapy and immunity or immunotherapy. Nevertheless, the combination of SBRT with immunotherapy, particularly with immune checkpoint blockers, has the clear potential to substantially increase the rate of abscopal effects. This warrants further research in this area, both in mechanistic preclinical studies and in clinical trials incorporating correlative studies. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Popp, Ilinca; Grosu, Anca Ligia; Niedermann, Gabriele] Univ Med Ctr Freiburg, Dept Radiat Oncol, Freiburg, Germany.
[Popp, Ilinca; Grosu, Anca Ligia; Niedermann, Gabriele] German Canc Consortium DKTK, Partner Site Freiburg, Freiburg, Germany.
[Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Labs, Boston, MA USA.
[Duda, Dan G.] Harvard Med Sch, Boston, MA USA.
RP Duda, DG (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA.
EM gduda@partners.org
NR 118
TC 3
Z9 3
U1 6
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD AUG
PY 2016
VL 120
IS 2
BP 185
EP 194
DI 10.1016/j.radonc.2016.07.013
PG 10
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DW0EQ
UT WOS:000383314100001
PM 27495145
ER
PT J
AU Huynh, E
Coroller, TP
Narayan, V
Agrawal, V
Hou, Y
Romano, J
Franco, I
Mak, RH
Aerts, HJWL
AF Huynh, Elizabeth
Coroller, Thibaud P.
Narayan, Vivek
Agrawal, Vishesh
Hou, Ying
Romano, John
Franco, Idalid
Mak, Raymond H.
Aerts, Hugo J. W. L.
TI CT-based radiomic analysis of stereotactic body radiation therapy
patients with lung cancer
SO RADIOTHERAPY AND ONCOLOGY
LA English
DT Article
DE Radiomics; Imaging; Stereotactic body radiation therapy; Lung cancer
ID FALSE DISCOVERY RATE; PROSPECTIVE PHASE-II; EARLY-STAGE; ADJUVANT
CHEMOTHERAPY; SURVIVAL MODELS; RADIOTHERAPY; OUTCOMES; SCANS;
VARIABILITY; PERFORMANCE
AB Background: Radiomics uses a large number of quantitative imaging features that describe the tumor phenotype to develop imaging biomarkers for clinical outcomes. Radiomic analysis of pre-treatment computed-tomography (CT) scans was investigated to identify imaging predictors of clinical outcomes in early stage non-small cell lung cancer (NSCLC) patients treated with stereotactic body radiation therapy (SBRT).
Materials and methods: CT images of 113 stage I-II NSCLC patients treated with SBRT were analyzed. Twelve radiomic features were selected based on stability and variance. The association of features with clinical outcomes and their prognostic value (using the concordance index (CI)) was evaluated. Radiomic features were compared with conventional imaging metrics (tumor volume and diameter) and clinical parameters.
Results: Overall survival was associated with two conventional features (volume and diameter) and two radiomic features (LoG 3D run low gray level short run emphasis and stats median). One radiomic feature (Wavelet LLH stats range) was significantly prognostic for distant metastasis (CI = 0.67, q-value < 0.1), while none of the conventional and clinical parameters were. Three conventional and four radiomic features were prognostic for overall survival.
Conclusion: This exploratory analysis demonstrates that radiomic features have potential to be prognostic for some outcomes that conventional imaging metrics cannot predict in SBRT patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Huynh, Elizabeth; Coroller, Thibaud P.; Narayan, Vivek; Agrawal, Vishesh; Hou, Ying; Romano, John; Franco, Idalid; Mak, Raymond H.; Aerts, Hugo J. W. L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Aerts, Hugo J. W. L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Huynh, E (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA.
EM ehuynh@lroc.harvard.edu
RI Aerts, Hugo/P-6350-2015;
OI Aerts, Hugo/0000-0002-2122-2003; Coroller, Thibaud/0000-0001-7662-8724
FU National Institute of Health [NIH-USA U24CA194354, NIH-USA U01CA190234];
Kaye Scholar Award; Brigham and Women's Hospital Department of Radiation
Oncology Clinical Translational Grant
FX Authors acknowledge financial support from the National Institute of
Health (NIH-USA U24CA194354, and NIH-USA U01CA190234). This project was
partially funded by the Kaye Scholar Award and the Brigham and Women's
Hospital Department of Radiation Oncology Clinical Translational Grant.
The study sponsors had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 49
TC 3
Z9 3
U1 9
U2 9
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-8140
J9 RADIOTHER ONCOL
JI Radiother. Oncol.
PD AUG
PY 2016
VL 120
IS 2
BP 258
EP 266
DI 10.1016/j.radonc.2016.05.024
PG 9
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA DW0EQ
UT WOS:000383314100013
PM 27296412
ER
PT J
AU Linnoila, J
Pittock, SJ
AF Linnoila, Jenny
Pittock, Sean J.
TI Autoantibody-Associated Central Nervous System Neurologic Disorders
SO SEMINARS IN NEUROLOGY
LA English
DT Article
DE paraneoplastic; autoimmune; encephalitis; antibodies; immunotherapy
ID METHYL-D-ASPARTATE; NMDA RECEPTOR ENCEPHALITIS; PARANEOPLASTIC
CEREBELLAR DEGENERATION; HERPES-SIMPLEX ENCEPHALITIS;
ANTIBODY-ASSOCIATED ENCEPHALOPATHY; CALCIUM-CHANNEL ANTIBODIES; SLEEP
BEHAVIOR DISORDER; BRAIN-STEM ENCEPHALITIS; RAPID-EYE-MOVEMENT; CELL
LUNG-CANCER
AB Autoimmune neurology is a rapidly evolving new subspecialty driven by the discovery of novel neural- (neuronal- or glial-) specific autoantibodies and their target antigens. The neurologic manifestations affecting the central nervous system include encephalitis, dementia, epilepsy, and movement and sleep disorders. Laboratory testing is now available for most of these neural-specific autoantibodies, which serve as diagnostic markers, in some instances directing the physician toward specific cancer types (e.g., N-methyl-D-aspartic acid receptor antibodies for teratoma, collapsin response mediator protein 5 for small-cell lung cancer) and assisting in therapeutic decision making. Antibodies targeting intracellular proteins serve as markers of cytotoxic effector T-cell mediated injury, which is generally poorly responsive to immunotherapy. By contrast, antibodies targeting extracellular plasma membrane proteins may act as pathogenic effectors and often infer good responses to immunotherapy. Diagnosing these conditions and implementing treatment as early into the clinical course as possible ensures the best possible clinical outcomes. An adequate immunotherapy trial to assess maximum reversibility of symptoms, as assessed through objective functional measures, is crucial and can help to determine whether maintenance therapy is needed.
C1 [Linnoila, Jenny] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Pittock, Sean J.] Mayo Clin, Coll Med, Dept Lab Med Pathol, Rochester, MN USA.
[Pittock, Sean J.] Mayo Clin, Dept Neurol, Coll Med, Rochester, MN USA.
RP Linnoila, J (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
EM Linnoila.Jenny@mgh.harvard.edu
NR 104
TC 0
Z9 0
U1 4
U2 4
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0271-8235
EI 1098-9021
J9 SEMIN NEUROL
JI Semin. Neurol.
PD AUG
PY 2016
VL 36
IS 4
BP 382
EP 396
DI 10.1055/s-0036-1585453
PG 15
WC Clinical Neurology
SC Neurosciences & Neurology
GA DW8RJ
UT WOS:000383922900013
PM 27643908
ER
PT J
AU De Clercq, DJH
Tavernier, J
Lievens, S
Van Calenbergh, S
AF De Clercq, Dries J. H.
Tavernier, Jan
Lievens, Sam
Van Calenbergh, Serge
TI Chemical Dimerizers in Three-Hybrid Systems for Small Molecule-Target
Protein Profiling
SO ACS CHEMICAL BIOLOGY
LA English
DT Review
ID FRAGMENT COMPLEMENTATION ASSAYS; REGULATED GENE-EXPRESSION; DIMERIZATION
IN-VIVO; COVALENT TMP-TAG; DRUG DISCOVERY; DIHYDROFOLATE-REDUCTASE;
SYNTHETIC LIGANDS; DEXAMETHASONE-METHOTREXATE; SACCHAROMYCES-CEREVISIAE;
TRANSCRIPTIONAL CONTROL
AB The identification of the molecular targets and mechanisms underpinning the beneficial or detrimental effects of small-molecule leads and drugs constitutes a crucial aspect of current drug discovery. Over the last two decades, three-hybrid (3H) systems have progressively taken an important position in the armamentarium of small molecule-target protein profiling technologies. Yet, a prerequisite for successful 3H analysis is the availability of appropriate chemical inducers of dimerization. Herein, we present a comprehensive and critical overview of the chemical dimerizers specifically applied in both yeast and mammalian three-hybrid systems for small molecule-target protein profiling within the broader scope of target deconvolution and drug discovery. Furthermore, examples and alternative suggestions for typical components of chemical dimerizers for 3H systems are discussed. As illustrated, more tools have become available that increase the sensitivity and efficiency of 3H-based screening platforms. Hence, it is anticipated that the great potential of 3H systems will further materialize in important contributions to drug discovery.
C1 [De Clercq, Dries J. H.; Van Calenbergh, Serge] Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, B-9000 Ghent, Belgium.
[Tavernier, Jan; Lievens, Sam] VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.
[Tavernier, Jan; Lievens, Sam] Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium.
[De Clercq, Dries J. H.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.
[De Clercq, Dries J. H.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Lievens, Sam] Orionis Biosci, B-9052 Ghent, Belgium.
RP Van Calenbergh, S (reprint author), Univ Ghent, Fac Pharmaceut Sci, Med Chem Lab, B-9000 Ghent, Belgium.; Lievens, S (reprint author), VIB, Dept Med Prot Res, B-9000 Ghent, Belgium.; Lievens, S (reprint author), Univ Ghent, Dept Biochem, Fac Med & Hlth Sci, B-9000 Ghent, Belgium.; Lievens, S (reprint author), Orionis Biosci, B-9052 Ghent, Belgium.
EM slievens@orionisbio.com; serge.vancalenbergh@ugent.be
FU IUAP [P6/36]; ERC Advanced grant (CYRE) [340941]; Fund for Scientific
Research-Flanders (FWO-V); Ghent University (BOF)
FX J.T. was supported by a grant from IUAP P6/36, and is a recipient of an
ERC Advanced grant (CYRE,340941). S.V.C. and J.T. received support from
the Fund for Scientific Research-Flanders (FWO-V). D.D.C. obtained a
Ph.D. grant from the special Research Fund of Ghent University (BOF).
NR 131
TC 0
Z9 0
U1 13
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD AUG
PY 2016
VL 11
IS 8
BP 2075
EP 2090
DI 10.1021/acschembio.5b00811
PG 16
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DT9UL
UT WOS:000381847700001
PM 27267544
ER
PT J
AU Sundberg, TB
Liang, YK
Wu, HX
Choi, HG
Kim, ND
Sim, T
Johannessen, L
Petrone, A
Khor, B
Graham, DB
Latorre, IJ
Phillips, AJ
Schreiber, SL
Perez, J
Shamji, AF
Gray, NS
Xavier, RJ
AF Sundberg, Thomas B.
Liang, Yanke
Wu, Huixian
Choi, Hwan Geun
Kim, Nam Doo
Sim, Taebo
Johannessen, Liv
Petrone, Adam
Khor, Bernard
Graham, Daniel B.
Latorre, Isabel J.
Phillips, Andrew J.
Schreiber, Stuart L.
Perez, Jose
Shamji, Alykhan F.
Gray, Nathanael S.
Xavier, Ramnik J.
TI Development of Chemical Probes for Investigation of Salt-Inducible
Kinase Function in Vivo
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID SIK2; MICE; PHOSPHORYLATION; INFLAMMATION; MACROPHAGES; HOMEOSTASIS;
ADIPOCYTES; CANCER; HDAC4; CELLS
AB Salt-inducible kinases (SIKs) are promising therapeutic targets for modulating cytokine responses during innate immune activation. The study of SIK inhibition in animal models of disease has been limited by the lack of selective small-molecule probes suitable for modulating SIK function in vivo. We used the pan-SIK inhibitor HG-9-91-01 as a starting point to develop improved analogs, yielding a novel probe 5 (YKL-05-099) that displays increased selectivity for SIKs versus other kinases and enhanced pharmacokinetic properties. Well-tolerated doses of YKL-05-099 achieve free serum concentrations above its IC50 for SIK2 inhibition for >16 h and reduce phosphorylation of a known SIK substrate in vivo. While in vivo active doses of YKL-05-099 recapitulate the effects of SIK inhibition on inflammatory cytokine responses, they did not induce metabolic abnormalities observed in Sik2 knockout mice. These results identify YKL-05-099 as a useful probe to investigate SIK function in vivo and further support the development of SIK inhibitors for treatment of inflammatory disorders.
C1 [Sundberg, Thomas B.; Petrone, Adam; Phillips, Andrew J.; Perez, Jose] Broad Inst, Ctr Dev Therapeut, Cambridge, MA 02142 USA.
[Liang, Yanke; Choi, Hwan Geun; Johannessen, Liv; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Liang, Yanke; Choi, Hwan Geun; Johannessen, Liv; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
[Wu, Huixian; Schreiber, Stuart L.; Shamji, Alykhan F.] Broad Inst, Ctr Sci Therapeut, Cambridge, MA 02142 USA.
[Kim, Nam Doo] Daegu Gyeongbuk Med Innovat Fdn, Daegu 41061, South Korea.
[Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 136791, South Korea.
[Khor, Bernard; Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.
[Graham, Daniel B.; Latorre, Isabel J.; Xavier, Ramnik J.] Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Graham, Daniel B.] Harvard Med Sch, Dept Med, Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Schreiber, Stuart L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.
[Schreiber, Stuart L.] Howard Hughes Med Inst, Cambridge, MA 02142 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
RP Gray, NS (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.; Xavier, RJ (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA.
EM Nathanael_Gray@DFCI.HARVARD.EDU; xavier@molbio.mgh.harvard.edu
FU National Institutes of Health [K08DK104021, U01DK062432, P30DK043351,
R01AI095499]; Michael J. Fox Foundation for Parkinson's Research;
Claudia Adams Barr Program for Innovative Cancer Research; Crohn's AMP;
Colitis Foundation of America [500229]; Leona M. and Harry B. Helmsley
Charitable Trust [500203]
FX Research reported in this publication was supported by funding from the
National Institutes of Health Grants K08DK104021 (B.K.), U01DK062432 and
P30DK043351 (R.J.X.), and R01AI095499 (N.S.G.); Michael J. Fox
Foundation for Parkinson's Research (N.S.G); Claudia Adams Barr Program
for Innovative Cancer Research (N.S.G); Crohn's & Colitis Foundation of
America Grant 500229 (to R.J.X.); and The Leona M. and Harry B. Helmsley
Charitable Trust Grant 500203 (to S.L.S. and R.J.X.). S.L.S. is an
Investigator of the Howard Hughes Medical Institute.
NR 21
TC 1
Z9 1
U1 6
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD AUG
PY 2016
VL 11
IS 8
BP 2105
EP 2111
DI 10.1021/acschembio.6b00217
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DT9UL
UT WOS:000381847700004
PM 27224444
ER
PT J
AU Surdel, MC
Dutter, BF
Sulikowski, GA
Skaar, EP
AF Surdel, Matthew C.
Dutter, Brendan F.
Sulikowski, Gary A.
Skaar, Eric P.
TI Bacterial Nitric Oxide Synthase Is Required for the Staphylococcus
aureus Response to Heme Stress
SO ACS INFECTIOUS DISEASES
LA English
DT Article
DE Staphylococcus aureus; heme stress response; nitric oxide synthase;
small-molecule optimization
ID US HOSPITALS; INFECTIONS; TOXICITY; BIOSYNTHESIS; VIRULENCE; IRON;
ACTIVATION; MOLECULE; SYSTEM; GENE
AB Staphylococcus aureus is a pathogen that causes significant morbidity and mortality worldwide. Within the vertebrate host, S. aureus requires heme as a nutrient iron source and as a cofactor for multiple cellular processes. Although required for pathogenesis, excess heme is toxic. S. aureus employs a two-component system, the heme sensor system (HssRS), to sense and protect against heme toxicity. Upon activation, HssRS induces the expression of the heme-regulated transporter (HrtAB), an efflux pump that alleviates heme toxicity. The ability to sense and respond to heme is critical for the pathogenesis of numerous Gram-positive organisms, yet the mechanism of heme sensing remains unknown. Compound '3981 was identified in a high-throughput screen as an activator of staphylococcal HssRS that triggers HssRS independently of heme accumulation. '3981 is toxic to S. aureus; however, derivatives of '3981 were synthesized that lack toxicity while retaining HssRS activation, enabling the interrogation of the heme stress response without confounding toxic effects of the parent molecule. Using '3981 derivatives as probes of the heme stress response, numerous genes required for '3981-induced activation of HssRS were uncovered. Specifically, multiple genes involved in the production of nitric oxide were identified, including the gene encoding bacterial nitric oxide synthase (bNOS). bNOS protects S. aureus from oxidative stress imposed by heme. Taken together, this work identifies bNOS as crucial for the S. aureus heme stress response, providing evidence that nitric oxide synthesis and heme sensing are intertwined.
C1 [Surdel, Matthew C.; Skaar, Eric P.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.
[Dutter, Brendan F.; Sulikowski, Gary A.] Vanderbilt Univ, Dept Chem, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA.
[Skaar, Eric P.] US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.
RP Skaar, EP (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 USA.; Skaar, EP (reprint author), US Dept Vet Affairs, Tennessee Valley Healthcare Syst, Nashville, TN 37212 USA.
EM eric.skaar@vanderbilt.edu
FU National Institute of General Medical Studies for the Vanderbilt
Medical-Scientist Training Program [T32 GM07347, R01AI069233,
R01AI073843, T32GM065086]
FX We thank members of the E.P.S laboratory for their critical reading of
the manuscript. The reagents were provided by the Network on
Antimicrobial Resistance in Staphylococcus aureus for distribution by
BEI Resources, Nebraska Transposon Mutant Library Screening Array,
NR-48501. This work was supported by Public Health Service award T32
GM07347 from the National Institute of General Medical Studies for the
Vanderbilt Medical-Scientist Training Program (M.C.S.), R01AI069233
(M.C.S. and E.P.S), R01AI073843 (M.C.S. and E.P.S.), and T32GM065086
(B.F.D.).
NR 37
TC 0
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U1 1
U2 1
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 2373-8227
J9 ACS INFECT DIS
JI ACS Infect. Dis.
PD AUG
PY 2016
VL 2
IS 8
BP 572
EP 578
DI 10.1021/acsinfecdis.6b00081
PG 7
WC Chemistry, Medicinal; Infectious Diseases
SC Pharmacology & Pharmacy; Infectious Diseases
GA DT6HI
UT WOS:000381584900006
PM 27626297
ER
PT J
AU Abuelezam, NN
McCormick, AW
Fussell, T
Afriyie, AN
Wood, R
DeGruttola, V
Freedberg, KA
Lipsitch, M
Seage, GR
AF Abuelezam, Nadia N.
McCormick, Alethea W.
Fussell, Thomas
Afriyie, Abena N.
Wood, Robin
DeGruttola, Victor
Freedberg, Kenneth A.
Lipsitch, Marc
Seage, George R., III
TI Can the Heterosexual HIV Epidemic be Eliminated in South Africa Using
Combination Prevention? A Modeling Analysis
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE acquired immunodeficiency syndrome; agent-based models; HIV; human
immunodeficiency virus; mathematical modeling; South Africa
ID RANDOMIZED CONTROLLED-TRIAL; SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY;
COST-EFFECTIVENESS; MALE CIRCUMCISION; CAUSAL INFERENCE; PREEXPOSURE
PROPHYLAXIS; CLINICAL IMPACT; COTE-DIVOIRE; INFECTION
AB Little is known about how combining efficacious interventions for human immunodeficiency virus (HIV) prevention could lead to HIV elimination. We used an agent-based simulation model, the HIV calibrated dynamic model, to assess the potential for HIV elimination in South Africa. We examined several scenarios (from continuation of the current status quo to perfect achievement of targets) with differing combinations of male condom use, adult male circumcision, HIV testing, and early antiretroviral therapy (ART). We varied numerous parameters, including the proportion of adult males circumcised, the frequency of condom use during sex acts, acceptance of HIV testing, linkage to health care, criteria for ART initiation, ART viral suppression rates, and loss to follow-up. Maintaining current levels of combination prevention would lead to increasing HIV incidence and prevalence in South Africa, while the perfect combination scenario was projected to eliminate HIV on a 50-year time scale from 2013 to 2063. Perfecting testing and treatment, without changing condom use or circumcision rates, resulted in an 89% reduction in HIV incidence but not elimination. Universal adult male circumcision alone resulted in a 21% incidence reduction within 20 years. Substantial decreases in HIV incidence are possible from sufficient uptake of both primary prevention and ART, but with continuation of the status quo, HIV elimination in South Africa is unlikely within a 50-year time scale.
C1 [Abuelezam, Nadia N.; McCormick, Alethea W.; Fussell, Thomas; Afriyie, Abena N.; Lipsitch, Marc; Seage, George R., III] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
[Wood, Robin] Univ Cape Town, Inst Infect Dis & Mol Med, Desmond Tutu HIV Ctr, Cape Town, South Africa.
[DeGruttola, Victor] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Freedberg, Kenneth A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Freedberg, Kenneth A.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA.
[Freedberg, Kenneth A.] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA.
[Freedberg, Kenneth A.] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA.
[Lipsitch, Marc] Harvard TH Chan Sch Publ Hlth, Ctr Communicable Dis Dynam, Boston, MA USA.
[Lipsitch, Marc] Harvard TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA USA.
RP Abuelezam, NN (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA.
EM nna465@mail.harvard.edu
FU National Institutes of Health from the National Institute of Allergy and
Infectious Diseases [R01-AI-058736, T32-AI-007535, T32-AI-007433];
National Institute of Mental Health [R01-MH-087328]; National Institute
of General Medical Sciences [R01-GM-11652]
FX This study was funded by the National Institutes of Health (grants
R01-AI-058736, T32-AI-007535, and T32-AI-007433 from the National
Institute of Allergy and Infectious Diseases; grant R01-MH-087328 from
the National Institute of Mental Health; and grant R01-GM-11652 from the
National Institute of General Medical Sciences).
NR 61
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U1 4
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD AUG 1
PY 2016
VL 184
IS 3
BP 239
EP 248
DI 10.1093/aje/kwv344
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DV8HG
UT WOS:000383177500010
PM 27416841
ER
PT J
AU Dinkler, JM
Sugar, CA
Escarce, JJ
Ong, MK
Mangione, CM
AF Dinkler, John M.
Sugar, Catherine A.
Escarce, Jose J.
Ong, Michael K.
Mangione, Carol M.
TI Does Age Matter? Association Between Usual Source of Care and
Hypertension Control in the US Population: Data From NHANES 2007-2012
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE age; blood pressure; hypertension; usual source of care
ID BLOOD-PRESSURE; UNITED-STATES; ENDOTHELIAL DYSFUNCTION; NATIONAL-HEALTH;
ADULTS; PREVENTION; IMPUTATION; PHYSICIAN; PATTERNS; SERVICES
AB The positive role of having a usual source of care (USOC) on the receipt of preventative services is known. However, associations between USOC and hypertension control and the differential association across age groups is unknown in the US population.
We used data from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2012. Multivariable logistic regression was used to evaluate the association between having a USOC and hypertension control. The differential effect of USOC on hypertension control by age was assessed using predicted marginal effects across age groups in the multivariable logistic model.
In adjusted analyses, those with a USOC had higher odds of hypertension control (odds ratio = 3.89, 95% confidence interval (CI): 2.15-6.98). The marginal effect of having a USOC is associated with a 30 percentage point higher probability of controlled blood pressure compared to those without a USOC (marginal probability = 0.30, 95% CI: 0.19-0.41). The marginal effect of USOC on hypertension control varied by age groups, with a statistically significantly lower marginal effect of USOC on hypertension seen among those older than 74 years of age (marginal probability = 0.27, 95% CI: 0.18-0.36) and younger than 35 years of age (marginal probability = 0.23, 95% CI: 0.14-0.33).
Having a USOC is significantly associated with improved hypertension control in the US population. The variation in the association across age groups has important implications in targeting age-specific antihypertensive strategies to reduce the burden of hypertension in the US population.
C1 [Dinkler, John M.] Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA.
[Dinkler, John M.; Escarce, Jose J.; Mangione, Carol M.] UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA.
[Sugar, Catherine A.] UCLA Fielding Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA.
[Escarce, Jose J.; Ong, Michael K.; Mangione, Carol M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Ong, Michael K.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA.
RP Dinkler, JM (reprint author), Univ Calif Los Angeles, Dept Med, Div Cardiol, Los Angeles, CA 90024 USA.; Dinkler, JM (reprint author), UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA.
EM jdinkler@mednet.ucla.edu
FU National Institutes of Health [T32HL007895-16]
FX Dr Dinkler receives grant funding from the National Institutes of Health
(T32HL007895-16).
NR 37
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U1 4
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD AUG
PY 2016
VL 29
IS 8
BP 934
EP 940
DI 10.1093/ajh/hpw010
PG 7
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DV8HQ
UT WOS:000383178500006
PM 26884134
ER
PT J
AU Ho, AK
Bartels, CM
Thorpe, CT
Pandhi, N
Smith, MA
Johnson, HM
AF Ho, Aaron K.
Bartels, Christie M.
Thorpe, Carolyn T.
Pandhi, Nancy
Smith, Maureen A.
Johnson, Heather M.
TI Achieving Weight Loss and Hypertension Control Among Obese Adults: A US
Multidisciplinary Group Practice Observational Study
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; hypertension; obesity; primary care; weight management
ID BODY-MASS INDEX; HIGH BLOOD-PRESSURE; SCIENTIFIC STATEMENT;
ADMINISTRATIVE DATA; MORTALITY RISK; YOUNG-ADULTS; COMMITTEE; EDUCATION;
OVERWEIGHT; MANAGEMENT
AB Among adults with hypertension, obesity independently contributes to cardiovascular disease. Weight loss and hypertension control are critical to reduce cardiovascular events. The purpose of this study was to evaluate rates and predictors of achieving weight loss among adults who achieved hypertension control within 1 year of developing incident hypertension.
Retrospective electronic health record analysis was performed of a parts per thousand yen18 year olds with a body mass index a parts per thousand yen30.0kg/m(2), who received regular primary care from 2008 to 2011 and achieved hypertension control. Exclusions were less than 60 days follow-up, prior hypertension diagnosis, prior antihypertensive prescription, or pregnancy. The primary outcome was clinically significant weight loss (a parts per thousand yen5kg); the secondary outcome was modest (2.0-4.9kg) weight loss. Multinomial logistic regression identified predictors of achieving weight loss (a parts per thousand yen5 or 2.0-4.9kg) compared to no significant weight loss (< 2kg).
Of the 2,906 obese patients who achieved hypertension control, 72% (n = 2,089) did not achieve at least 2.0kg weight loss. Overall, 12% (n = 351) achieved a parts per thousand yen5kg weight loss. Young adults (18-39 year olds; odds ratio (OR): 2.47, 95% confidence interval (CI): 1.63-3.47), middle-aged adults (40-59 year olds; OR: 2.32, 95% CI: 1.59-3.37), and patients prescribed antihypertensive medication (OR: 1.37, 95% CI: 1.07-1.76) were more likely to achieve clinically significant weight loss and hypertension control. Age remained a significant predictor for 2.0-4.9kg weight loss.
Despite achieving hypertension control, the majority of obese patients did not achieve clinically significant weight loss. Effective weight loss interventions with dedicated hypertension treatment are needed to decrease cardiovascular events in this high-risk population.
C1 [Ho, Aaron K.; Bartels, Christie M.; Johnson, Heather M.] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Bartels, Christie M.; Pandhi, Nancy; Smith, Maureen A.; Johnson, Heather M.] Univ Wisconsin, Hlth Innovat Program, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Thorpe, Carolyn T.] Vet Affairs Pittsburgh Healthcare Syst, Hlth Serv Res & Dev, Pittsburgh, PA USA.
[Thorpe, Carolyn T.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA.
[Pandhi, Nancy; Smith, Maureen A.] Univ Wisconsin, Dept Family Med, Sch Med & Publ Hlth, Madison, WI USA.
[Smith, Maureen A.] Univ Wisconsin, Dept Populat Hlth Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Smith, Maureen A.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Madison, WI USA.
RP Johnson, HM (reprint author), Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA.; Johnson, HM (reprint author), Univ Wisconsin, Hlth Innovat Program, Sch Med & Publ Hlth, Madison, WI 53706 USA.
EM hm2@medicine.wisc.edu
FU Clinical and Translational Science Award program, previously through the
National Center for Research Resources (NCRR) [UL1RR025011]; National
Center for Advancing Translational Sciences of the National Institutes
of Health (NIH) [U54TR000021]; National Heart, Lung, and Blood Institute
of the NIH [K23HL112907]; University of Wisconsin (UW) Centennial
Scholars Program of the University of Wisconsin School of Medicine and
Public Health; National Institute of Arthritis and Musculoskeletal and
Skin Diseases of the NIH [K23AR062381]; National Institute on Aging of
the NIH [K08AG029527]
FX The authors gratefully acknowledge Katie Ronk, BS and Patrick Ferguson,
MPH for data preparation and Jamie LaMantia, BS and Colleen Brown, BA
for manuscript preparation. This original research was supported by the
Clinical and Translational Science Award program, previously through the
National Center for Research Resources (NCRR - UL1RR025011) and now by
the National Center for Advancing Translational Sciences of the National
Institutes of Health (NIH) under award number U54TR000021. H.M.J. is
supported by the National Heart, Lung, and Blood Institute of the NIH
(K23HL112907) and also by the University of Wisconsin (UW) Centennial
Scholars Program of the University of Wisconsin School of Medicine and
Public Health. C.M.B. is supported by the National Institute of
Arthritis and Musculoskeletal and Skin Diseases of the NIH
(K23AR062381). N.P. is supported by the National Institute on Aging of
the NIH (K08AG029527). The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
NIH. Additional funding for this project was provided by the UW Health
Innovation Program and the UW School of Medicine and Public Health from
The Wisconsin Partnership Program. Some preliminary findings reported in
this manuscript were presented in poster form at the American Heart
Association 2014 Annual Scientific Sessions in Chicago, IL on 15-19
November 2014.
NR 39
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U1 3
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD AUG
PY 2016
VL 29
IS 8
BP 984
EP 991
DI 10.1093/ajh/hpw020
PG 8
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DV8HQ
UT WOS:000383178500012
PM 26917445
ER
PT J
AU Ramey, LN
McInnis, KC
Palmer, WE
AF Ramey, Lindsay N.
McInnis, Kelly C.
Palmer, William E.
TI Femoral Neck Stress Fracture: Can MRI Grade Help Predict
Return-to-Running Time?
SO AMERICAN JOURNAL OF SPORTS MEDICINE
LA English
DT Article
DE femoral neck stress fracture; magnetic resonance imaging;
rehabilitation; hip; stress fractures
ID RISK-FACTORS; INJURIES; BONE; MANAGEMENT; TRACK; PLAY; CLASSIFICATION;
AGE; HIP
AB Background: Limited research is available regarding return-to-running (RTR) time after femoral neck stress fractures. While studies have shown the prognostic value of image-based grading scales for stress fractures at other sites, few have included femoral neck stress fractures.
Purpose: To determine if the grade of femoral neck stress fractures based on magnetic resonance imaging (MRI) characteristics correlates with RTR time.
Study Design: Cohort study; Level of evidence, 3.
Methods: This study included 24 patients (mean age, 32.9 years; range, 18-51 years) who were diagnosed with 27 femoral neck stress fractures by MRI from 2009 to 2015 at a single sports medicine clinic. All fractures were compression sided and were treated nonoperatively. Charts were reviewed for patient demographics and RTR time. Images were graded from 1 to 4 using the Arendt stress fracture severity scale. Statistical analysis was performed using survival analysis and Cox proportional hazard model to compare the RTR time between grades. Cox regression was repeated, adjusted for age, bone mineral density (BMD), and body mass index (BMI).
Results: The mean (standard error of the mean) RTR time in weeks for patients with fractures graded 1 to 4 was 7.4 +/- 2.7 (range, 4-11), 13.8 +/- 3.8 (range, 6-21), 14.7 +/- 3.5 (range, 8.5-24), and 17.5 +/- 3.4 (range, 10-32), respectively. Survival analysis indicated that there was a statistically significant effect of fracture grade on RTR time (P = .0065). The Cox model indicated a statistically significant difference in RTR time between grades 1 and 2 (P = .036), 1 and 3 (P = .014), and 1 and 4 (P = .002). The unadjusted hazard ratio was significant (P = .037). There were no statistically significant differences between the remaining grades (P = .82 for grades 2 and 3, P = .37 for grades 2 and 4, and P = .31 for grades 3 and 4). Age (P = .71) and BMD (P = .81) did not have an effect on RTR time. The hazard ratio remained significant (P = .05) after adjusting for age and BMD. BMI tended to have an effect on RTR time (P = .09). After adding BMI to the adjustment, the hazard ratio decreased in significance (P = .13), although sample size also decreased.
Conclusion: Grade 2 to 4 femoral neck stress fractures require longer RTR time than do grade 1 injuries. Patients with lower BMI tend to require a longer RTR time.
C1 [Ramey, Lindsay N.; McInnis, Kelly C.; Palmer, William E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ramey, Lindsay N.; McInnis, Kelly C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Charlestown, MA USA.
[Ramey, Lindsay N.; McInnis, Kelly C.; Palmer, William E.] Harvard Med Sch, Cambridge, MA USA.
[McInnis, Kelly C.] Massachusetts Gen Hosp, Div Orthoped, Boston, MA 02114 USA.
[Palmer, William E.] Massachusetts Gen Hosp, Div Radiol, Boston, MA 02114 USA.
RP Ramey, LN (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 300 First Ave, Boston, MA 02129 USA.
EM lnr8t@virginia.edu
NR 30
TC 1
Z9 1
U1 1
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0363-5465
EI 1552-3365
J9 AM J SPORT MED
JI Am. J. Sports Med.
PD AUG
PY 2016
VL 44
IS 8
BP 2122
EP 2129
DI 10.1177/0363546516648319
PG 8
WC Orthopedics; Sport Sciences
SC Orthopedics; Sport Sciences
GA DU4UM
UT WOS:000382208100029
PM 27261475
ER
PT J
AU Amri, R
Klos, CL
Bordeianou, L
Berger, DL
AF Amri, Ramzi
Klos, Coen L.
Bordeianou, Liliana
Berger, David L.
TI The prognostic value of lymph node ratio in colon cancer is independent
of resection length
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Colon cancer; Lymph node ratio; Resection length; Outcomes; Survival;
Disease-free survival
ID COMPLETE MESOCOLIC EXCISION; COLORECTAL-CANCER; SURVIVAL; SURGERY;
LIGATION; ADENOCARCINOMA; NUMBER
AB BACKGROUND: Lymph node ratio (LNR), the ratio of tumor-positive lymph nodes (+LN) to the total number of resected lymph nodes (rLN), predicts recurrence and survival in colon cancer. Variations in colonic resection length (RL) may influence rLN, +LN, or both, thereby potentially impacting LNR and its prognostic value in colon cancer.
METHODS: All colon cancer patients treated surgically at our center from 2004 to 2011 were included in an institutional review board-approved data repository (n = 1,039).
RESULTS: Larger RL was associated with increased rLN (rho = .22; P < .001) but not with +LN (P = .21). In node-positive patients (n = 411), RL-adjusted LNR had weaker correlations with death (rho = .338 vs .373, both P < .001) or metastatic disease (rho = .303 vs .345; both P < .001) and a smaller area under the curve (death: .695 vs .715, metastasis: .675 vs .699). Findings were similar in segmental, extended segmental, and total colectomy subgroups.
CONCLUSIONS: Provided that resections are performed following standard oncologic principles, our analysis shows that RL does not significantly impact the prognostic value of LNR in colon cancer. Correcting LNR for RL seems redundant and may even act as noise distorting LNR values. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Amri, Ramzi; Bordeianou, Liliana; Berger, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA.
[Klos, Coen L.] Washington Univ, Sch Med, Dept Surg, Sect Colon & Rectal Surg, St Louis, MO 63110 USA.
RP Berger, DL (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA.
EM dberger@mgh.harvard.edu
OI Amri, Ramzi/0000-0001-7416-6650
FU Harvard Catalyst\The Harvard Clinical and Translational Science Center
(National Center for Research Resources, National Institutes of Health)
[8UL1TR000170-05]; Harvard Catalyst\The Harvard Clinical and
Translational Science Center (National Center for Advancing
Translational Sciences, National Institutes of Health)
[8UL1TR000170-05]; Harvard Catalyst\The Harvard Clinical and
Translational Science Center (Harvard University and its affiliated
academic health care centers); Dutch Cancer Society; Dutch Digestive
Society; Amsterdam University Funds; Fulbright Foundation
FX This work was conducted with support from Harvard Catalyst vertical bar
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
8UL1TR000170-05 and financial contributions from Harvard University and
its affiliated academic health care centers). This work was also
supported by the Dutch Cancer Society, the Dutch Digestive Society, the
Amsterdam University Funds, and the Fulbright Foundation. R.A. has
received funding from the Fulbright Foundation, the Dutch Cancer
Society, the Dutch Digestive Society, and Harvard Catalyst vertical bar
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
8UL1TR000170-05 and financial contributions from Harvard University and
its affiliated academic health care centers).
NR 23
TC 2
Z9 2
U1 2
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
EI 1879-1883
J9 AM J SURG
JI Am. J. Surg.
PD AUG
PY 2016
VL 212
IS 2
BP 251
EP 257
DI 10.1016/j.amjsurg.2015.10.037
PG 7
WC Surgery
SC Surgery
GA DU5EF
UT WOS:000382234300010
PM 27156798
ER
PT J
AU Jones, CE
Hollis, RH
Wahl, TS
Oriel, BS
Itani, KMF
Morris, MS
Hawn, MT
AF Jones, Caroline E.
Hollis, Robert H.
Wahl, Tyler S.
Oriel, Brad S.
Itani, Kamal M. F.
Morris, Melanie S.
Hawn, Mary T.
TI Transitional care interventions and hospital readmissions in surgical
populations: a systematic review
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Review
DE Transitional care; Hospital readmission; Health services research;
Population health; Patient-centered care; Patient discharge
ID MEDICARE BENEFICIARIES; POSTOPERATIVE READMISSION; 30-DAY READMISSION;
COLORECTAL-CANCER; RANDOMIZED-TRIAL; SURGERY PATIENTS; GENERAL-SURGERY;
FOLLOW-UP; QUALITY; PROGRAM
AB BACKGROUND: Despite hospital readmission being a targeted quality metric, few studies have focused on the surgical patient population. We performed a systematic review of transitional care interventions and their effect on hospital readmissions after surgery.
DATA SOURCES: PubMed was searched for studies evaluating transitional care interventions in surgical populations within the years 1995 to 2015. Of 3,527 abstracts identified, 3 randomized controlled trials and 7 observational cohort studies met inclusion criteria.
CONCLUSIONS: Discharge planning programs reduced readmissions by 11.5% (P = .001), 12.5% (P = .04), and 23% (P = .26). Patient education interventions reduced readmissions by 14% (P = .28) and 23.5%(P < .05). Primary care follow- up reduced readmissions by 8.3% for patients after high-risk surgeries (P < .001). Home visits reduced readmissions by 7.69% (P = .023) and 4% (P = .161), respectively. Therefore, improving discharge planning, patient education, and follow- up communication may reduce readmissions. Published by Elsevier Inc.
C1 [Jones, Caroline E.; Hollis, Robert H.; Wahl, Tyler S.; Morris, Melanie S.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Jones, Caroline E.; Hollis, Robert H.; Wahl, Tyler S.; Morris, Melanie S.] Birmingham Vet Adm Hosp, Birmingham, AL USA.
[Oriel, Brad S.; Itani, Kamal M. F.] VA Boston Hlth Care Syst, Boston, MA USA.
[Oriel, Brad S.; Itani, Kamal M. F.] Tufts Univ, Sch Med, Dept Surg, Boston, MA 02111 USA.
[Hawn, Mary T.] Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA.
[Hawn, Mary T.] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
RP Hawn, MT (reprint author), Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA.; Hawn, MT (reprint author), VA Palo Alto Hlth Care Syst, Palo Alto, CA 94304 USA.
EM mhawn@stanford.edu
FU National Institutes of Health [T32 CA091078-13]; Agency for Healthcare
Research and Quality grant [T32 4T32HS013852-13]
FX The opinions expressed are those of the authors and do not necessarily
reflect those of the Department of Veterans Affairs of the United States
Government. R. H. is supported by grant T32 CA091078-13 from the
National Institutes of Health. T. W. is supported by the Agency for
Healthcare Research and Quality grant T32 4T32HS013852-13.
NR 42
TC 0
Z9 0
U1 7
U2 7
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9610
EI 1879-1883
J9 AM J SURG
JI Am. J. Surg.
PD AUG
PY 2016
VL 212
IS 2
BP 327
EP 335
DI 10.1016/j.amjsurg.2016.04.004
PG 9
WC Surgery
SC Surgery
GA DU5EF
UT WOS:000382234300020
PM 27353404
ER
PT J
AU Di Giacomo, G
Golijanin, P
Sanchez, G
Provencher, MT
AF Di Giacomo, Giovanni
Golijanin, Petar
Sanchez, George
Provencher, Matthew T.
TI Radiographic Analysis of the Hill-Sachs Lesion in Anteroinferior
Shoulder Instability After First-Time Dislocations
SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY
LA English
DT Article
ID RECURRENT ANTERIOR DISLOCATION; HUMERAL HEAD; DEFECTS; FAILURE; REPAIRS;
TRACK
AB Purpose: To identify the relation between the Hill-Sachs (H-S) angle and arm position at the time of the initial dislocation, and to see if this correlates with the glenoid track. Methods: A total of 102 patients (89 male patients, 87.2%), with a mean age of 32 years (range, 17 to 38 years), were divided into 2 groups, abduction (ABD) and adduction (ADD), dependent on the position of the arm at the time of the instability event. All patients were evaluated with bilateral computed tomography scans (3-dimensional) to define the H-S position on the glenoid track and to measure the H-S angle. One-way analysis of variance was used to compare the H-S angle between the 2 groups. Results: Dislocation occurred in ABD in 45 patients (44.1%) and in ADD in 57 (55.9%). The H-S angle was 32.4 degrees +/- 4.7 degrees in the ABD group versus 16.1 degrees +/- 2.9 degrees in the ADD group. All patients' injuries were "on-track" glenoid injuries in both groups. Conclusions: This study identified a difference in the H-S angle relative to arm position at the time of initial dislocation. Patients whose injury occurred in the ABD position showed a higher H-S angle, leading to an increased risk of engagement, because the long axis of the H-S lesion is parallel to the glenoid in a position of function. Thus arm position at the time of the initial instability event may be a risk factor for engagement and higher risk of recurrence.
C1 [Di Giacomo, Giovanni] Concordia Hosp Special Surg, Dept Orthopaed Surg, Rome, Italy.
[Golijanin, Petar] Geisel Sch Med Dartmouth, Hanover, NH USA.
[Sanchez, George; Provencher, Matthew T.] Massachusetts Gen Hosp, Sports Med Serv, Boston, MA 02114 USA.
RP Provencher, MT (reprint author), MGH Sports Med Ctr, Sports Med Serv, 175 Cambridge St,Fourth Floor, Boston, MA 02114 USA.
EM MattProvencher@gmail.com
FU Arthrex; American Orthopaedic Society for Sports Medicine/Arthroscopy
Association of North America
FX The authors report the following potential conflict of interest or
source of funding: G.D.G. receives support from Arthrex. M.T.P. receives
support from American Orthopaedic Society for Sports
Medicine/Arthroscopy Association of North America. No money.
Arthrex/Joint Restoration Foundation. Peer Reviewed Orthopaedic Research
Program. Shoulder instability database. Arthrex. Suture washer and pec
button. Elsevier. Arthroscopy journal, shoulder instability textbook,
and rehabilitation textbook.
NR 21
TC 2
Z9 2
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0749-8063
EI 1526-3231
J9 ARTHROSCOPY
JI Arthroscopy
PD AUG
PY 2016
VL 32
IS 8
BP 1509
EP 1514
DI 10.1016/j.arthro.2016.01.022
PG 6
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA DV8ZT
UT WOS:000383229800009
PM 27039213
ER
PT J
AU Hansen, KJ
Favreau, JT
Guyette, JP
Tao, ZW
Coffin, ST
Cunha-Gavidia, A
D'Amore, B
Perreault, LR
Fitzpatrick, JP
DeMartino, A
Gaudette, GR
AF Hansen, Katrina J.
Favreau, John T.
Guyette, Jacques P.
Tao, Ze-Wei
Coffin, Spencer T.
Cunha-Gavidia, Anny
D'Amore, Brian
Perreault, Luke R.
Fitzpatrick, John P.
DeMartino, Angelica
Gaudette, Glenn R.
TI Functional Effects of Delivering Human Mesenchymal Stem Cell-Seeded
Biological Sutures to an Infarcted Heart
SO BIORESEARCH OPEN ACCESS
LA English
DT Article
DE biomaterials; cardiology; stem cells; tissue engineering
ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR FUNCTION; MARROW
MONONUCLEAR-CELLS; PHASE CORRELATION; RANDOMIZED-TRIAL; CLINICAL-TRIAL;
INTRACORONARY; FAILURE; TRANSPLANTATION; SURVIVAL
AB Stem cell therapy has the potential to improve cardiac function after myocardial infarction (MI); however, existing methods to deliver cells to the myocardium, including intramyocardial injection, suffer from low engraftment rates. In this study, we used a rat model of acute MI to assess the effects of human mesenchymal stem cell (hMSC)-seeded fibrin biological sutures on cardiac function at 1 week after implant. Biological sutures were seeded with quantum dot (Qdot)-loaded hMSCs for 24 h before implantation. At 1 week postinfarct, the heart was imaged to assess mechanical function in the infarct region. Regional parameters assessed were regional stroke work (RSW) and systolic area of contraction (SAC) and global parameters derived from the pressure waveform. MI (n = 6) significantly decreased RSW (0.026+/-0.011) and SAC (0.022+/-0.015) when compared with sham operation (RSW: 0.141+/-0.009; SAC: 0.166+/-0.005, n = 6) (p < 0.05). The delivery of unseeded biological sutures to the infarcted hearts did not change regional mechanical function compared with the infarcted hearts (RSW: 0.032+/-0.004, SAC: 0.037+/-0.008, n = 6). The delivery of hMSC-seeded sutures exerted a trend toward increase of regional mechanical function compared with the infarcted heart (RSW: 0.057+/-0.011; SAC: 0.051+/-0.014, n = 6). Global function showed no significant differences between any group (p > 0.05); however, there was a trend toward improved function with the addition of either unseeded or seeded biological suture. Histology demonstrated that Qdot-loaded hMSCs remained present in the infarcted myocardium after 1 week. Analysis of serial sections of Masson's trichrome staining revealed that the greatest infarct size was in the infarct group (7.0%+/-2.2%), where unseeded (3.8%+/-0.6%) and hMSC-seeded (3.7%+/-0.8%) suture groups maintained similar infarct sizes. Furthermore, the remaining suture area was significantly decreased in the unseeded group compared with that in the hMSC-seeded group (p < 0.05). This study demonstrated that hMSC-seeded biological sutures are a method to deliver cells to the infarcted myocardium and have treatment potential.
C1 [Hansen, Katrina J.; Favreau, John T.; Guyette, Jacques P.; Tao, Ze-Wei; Coffin, Spencer T.; Cunha-Gavidia, Anny; D'Amore, Brian; Perreault, Luke R.; Fitzpatrick, John P.; DeMartino, Angelica; Gaudette, Glenn R.] Worcester Polytech Inst, Dept Biomed Engn, 60 Prescott St, Worcester, MA 01605 USA.
[Guyette, Jacques P.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Tao, Ze-Wei] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA.
RP Gaudette, GR (reprint author), Worcester Polytech Inst, Dept Biomed Engn, 60 Prescott St, Worcester, MA 01605 USA.
EM gaudette@wpi.edu
FU NHLBI NIH HHS [R01 HL115282]
NR 39
TC 0
Z9 0
U1 4
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2164-7844
EI 2164-7860
J9 BIORESEARCH OPEN ACC
JI BioResearch Open Access
PD AUG
PY 2016
VL 5
IS 1
BP 249
EP 260
DI 10.1089/biores.2016.0026
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DV9SR
UT WOS:000383282500001
PM 27610271
ER
PT J
AU Warner, ET
Ballman, KV
Strand, C
Boughey, JC
Buzdar, AU
Carey, LA
Sikov, WM
Partridge, AH
AF Warner, Erica T.
Ballman, Karla V.
Strand, Carrie
Boughey, Judy C.
Buzdar, Aman U.
Carey, Lisa A.
Sikov, William M.
Partridge, Ann H.
TI Impact of race, ethnicity, and BMI on achievement of pathologic complete
response following neoadjuvant chemotherapy for breast cancer: a pooled
analysis of four prospective Alliance clinical trials (A151426)
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Breast cancer; Race; Ethnicity; Body mass index; Pathologic complete
response
ID BODY-MASS INDEX; ADJUVANT CHEMOTHERAPY; CONSERVING SURGERY;
RACIAL-DIFFERENCES; TUMOR BIOLOGY; WHITE WOMEN; STAGE-II; SURVIVAL;
OUTCOMES; SUBTYPES
AB Previous studies demonstrated poor response to neoadjuvant systemic therapy (NST) for breast cancer among black women and women who are overweight or obese, but this may be due to chemotherapy underdosing. We assessed associations of race, ethnicity, and body mass index (BMI) with pathologic complete response (pCR) in clinical trial populations. 1797 women enrolled in four NST trials (CALGB 40601, 40603; ACOSOG Z1041, Z1071) were included. Tumor subtypes were defined by estrogen receptor (ER) and HER2 status. Logistic regression generated odds ratios (OR) and 95 % confidence intervals (CI) for the associations of race, ethnicity, and BMI with in-breast pCR adjusting for subtype, study arm, lymph node status, tumor size, and tumor grade. 253 (14.1 %) were black, 199 (11.1 %) Hispanic, 520 (28.9 %) overweight, and 743 (41.4 %) obese. Compared to whites, Blacks and Hispanics were more likely to be obese and Blacks were more likely to have triple-negative cancer. pCR rates differed significantly by tumor subtype. In multivariate analyses, neither race (black vs white: OR 1.18, 95 % CI 0.85-1.62) nor ethnicity (Hispanic vs non-Hispanic; OR 1.30, 95 % CI 0.67-2.53) were significant predictors of pCR overall or by subtype. Overweight and obese women had lower pCR rates in ER+/HER2+, but higher pCR rates in ER-/HER2+ cancers. There was no difference in pCR according to race or ethnicity. Overall, there was no major difference in pCR rates by BMI. These findings suggest that pCR with optimally dosed NST is a function of tumor, rather than patient, biology.
C1 [Warner, Erica T.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
[Ballman, Karla V.] Weill Cornell Med Coll, 402 East 67th St, New York, NY 10065 USA.
[Strand, Carrie] Alliance Stat & Data Ctr, 1216 Second St SW, Rochester, MN 55902 USA.
[Boughey, Judy C.] Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA.
[Buzdar, Aman U.] Univ Texas MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Carey, Lisa A.] Univ North Carolina Chapel Hill, Lineberger Comprehens Canc Ctr, 101 Manning Dr, Chapel Hill, NC 27514 USA.
[Sikov, William M.] Brown Univ, Women & Infants Hosp Rhode Isl, 101 Dudley St, Providence, RI 02905 USA.
[Sikov, William M.] Brown Univ, Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA.
[Partridge, Ann H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Partridge, Ann H.] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
RP Warner, ET (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM ewarner@mgh.harvard.edu
FU National Cancer Institute of the National Institutes of Health
[UG1CA189823, U10CA180790, U10CA180838, U10CA180858, U10CA180867]; NCI
[K01CA188075]
FX The authors would like to acknowledge Dr. Olwen Hahn for her
contributions to the included studies. Research reported in this
publication was supported by the National Cancer Institute of the
National Institutes of Health under the Award Number UG1CA189823 (to the
Alliance for Clinical Trials in Oncology NCORP Grant), U10CA180790,
U10CA180838, U10CA180858, and U10CA180867. Dr. Warner was supported by
NCI Grant K01CA188075. The content is solely the responsibility of the
authors and does not necessarily represent the official views of the
National Institutes of Health. The study sponsors had no role in study
design, collection, analysis, and interpretation of data, writing the
report, or the decision to submit the report for publication. Dr. Warner
had full access to all the data in the study and takes responsibility
for the integrity of the data and the accuracy of the data analysis.
NR 51
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD AUG
PY 2016
VL 159
IS 1
BP 109
EP 118
DI 10.1007/s10549-016-3918-5
PG 10
WC Oncology
SC Oncology
GA DV3UA
UT WOS:000382847800010
PM 27449492
ER
PT J
AU Vaz-Luis, I
Lin, NU
Keating, NL
Barry, WT
Lii, J
Burstein, HJ
Winer, EP
Freedman, RA
AF Vaz-Luis, Ines
Lin, Nancy U.
Keating, Nancy L.
Barry, William T.
Lii, Joyce
Burstein, Harold J.
Winer, Eric P.
Freedman, Rachel A.
TI Treatment of early-stage human epidermal growth factor 2-positive
cancers among medicare enrollees: age and race strongly associated with
non-use of trastuzumab
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Trastuzumab; Breast cancer; HER2-positive; SEER-medicare
ID HER2-POSITIVE BREAST-CANCER; ADJUVANT CHEMOTHERAPY; RACIAL-DIFFERENCES;
COMORBIDITY INDEX; OLDER PATIENTS; HEART-FAILURE; UNITED-STATES;
FOLLOW-UP; THERAPY; WOMEN
AB Adjuvant trastuzumab for human epidermal growth factor receptor-2 (HER2)-positive breast cancer is highly efficacious regardless of age. Recent data suggested that many older patients with HER2-positive disease do not receive adjuvant trastuzumab. Nevertheless, some of this 'under-treatment' may be clinically appropriate. We used Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify patients aged aeyen 66 with stage aeyen Ib-III, HER2-positive breast cancer diagnosed during 2010-2011 (HER2 status available) who did not have a history of congestive heart failure. We described all systemic treatments received and sociodemographic and clinical characteristics associated with treatment patterns. Among 770 women 44.4 % did not receive trastuzumab, including 21.8 % who received endocrine therapy only, 6.3 % who received chemotherapy (+/- endocrine therapy) and 16.2 % who did not receive any systemic therapy. In addition to age and grade, race was strongly associated with non-use of trastuzumab (64.4 % of Non-Hispanic blacks vs. 43.6 % of whites did not receive trastuzumab, adjusted ORNon-Hispanic black vs. white = 3.14, 95 %CI = 1.38-7.17), and many patients with stage III disease did not receive trastuzumab. Further, 16.2 % of patients did not receive any systemic treatment and this occurred more frequently for black patients. Over 40 % of older patients with indication to receive adjuvant trastuzumab did not receive it and nearly 20 % of these patients did not receive any other treatment. Although treatment omission may be appropriate in some cases, we observed concerning differences in trastuzumab receipt, particularly for black women. Strategies to optimize care for older patients and to eliminate treatment disparities are urgently needed.
C1 [Vaz-Luis, Ines; Lin, Nancy U.; Burstein, Harold J.; Winer, Eric P.; Freedman, Rachel A.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
[Barry, William T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.
[Lii, Joyce] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM inesv_luis@dfci.harvard.edu; rafreedman@partners.org
FU Fundacao para a Ciencia e Tecnologia [HMSP-ICS/0004/2011]; Dana-Farber
Cancer Institute Friends Grant
FX The study was supported by Fundacao para a Ciencia e Tecnologia
(HMSP-ICS/0004/2011, Career Development Award) (to I Vaz-Luis) and
Dana-Farber Cancer Institute Friends Grant (to R Freedman and I Vaz
Luis).
NR 37
TC 1
Z9 1
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD AUG
PY 2016
VL 159
IS 1
BP 151
EP 162
DI 10.1007/s10549-016-3927-4
PG 12
WC Oncology
SC Oncology
GA DV3UA
UT WOS:000382847800014
PM 27484879
ER
PT J
AU D'Souza, N
Hashimoto, D
Gurusamy, K
Aggarwal, R
AF D'Souza, N.
Hashimoto, D.
Gurusamy, K.
Aggarwal, R.
TI Are Patients Safe During Trainee Performed Surgery? A Meta-Analysis of
Trainee versus Consultant Outcomes in Surgery
SO BRITISH JOURNAL OF SURGERY
LA English
DT Meeting Abstract
CT International Surgical Congress of the
Association-of-Surgeons-of-Great-Britain-and-Ireland
CY 2016
CL Belfast, IRELAND
SP Assoc Surg Great Britain & Ireland
C1 [D'Souza, N.] Wessex Deanery, Wessex, England.
[Hashimoto, D.] Massachussets Gen Hosp, Boston, MA USA.
[Gurusamy, K.] UCL Med Sch, London, England.
[Aggarwal, R.] McGill Univ, Montreal, PQ, Canada.
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 0007-1323
EI 1365-2168
J9 BRIT J SURG
JI Br. J. Surg.
PD AUG
PY 2016
VL 103
SU 6
SI SI
MA 0057
BP 47
EP 47
PG 1
WC Surgery
SC Surgery
GA DV9VF
UT WOS:000383289600134
ER
PT J
AU Incio, J
Liu, H
Suboj, P
Chin, SM
Chen, IX
Pinter, M
Ng, MR
Nia, HT
Grahovac, J
Kao, S
Babykutty, S
Huang, YH
Jung, K
Rahbari, NN
Han, XX
Chauhan, VP
Martin, JD
Kahn, J
Huang, PG
Desphande, V
Michaelson, J
Michelakos, TP
Ferrone, CR
Soares, R
Boucher, Y
Fukumura, D
Jain, RK
AF Incio, Joao
Liu, Hao
Suboj, Priya
Chin, Shan M.
Chen, Ivy X.
Pinter, Matthias
Ng, Mei R.
Nia, Hadi T.
Grahovac, Jelena
Kao, Shannon
Babykutty, Suboj
Huang, Yuhui
Jung, Keehoon
Rahbari, Nuh N.
Han, Xiaoxing
Chauhan, Vikash P.
Martin, John D.
Kahn, Julia
Huang, Peigen
Desphande, Vikram
Michaelson, James
Michelakos, Theodoros P.
Ferrone, Cristina R.
Soares, Raquel
Boucher, Yves
Fukumura, Dai
Jain, Rakesh K.
TI Obesity-Induced Inflammation and Desmoplasia Promote Pancreatic Cancer
Progression and Resistance to Chemotherapy
SO CANCER DISCOVERY
LA English
DT Article
ID HIGH-FAT DIET; SUBTYPE AT1 RECEPTORS; TUMOR BLOOD-VESSELS; BODY-MASS
INDEX; DUCTAL ADENOCARCINOMA; ANGIOTENSIN-II; ADIPOSE-TISSUE; STELLATE
CELLS; SELECTIVE INHIBITOR; SIGNALING PATHWAYS
AB It remains unclear how obesity worsens treatment outcomes in patients with pancreatic ductal adenocarcinoma (PDAC). In normal pancreas, obesity promotes inflammation and fibrosis. We found in mouse models of PDAC that obesity also promotes desmoplasia associated with accelerated tumor growth and impaired delivery/efficacy of chemotherapeutics through reduced perfusion. Genetic and pharmacologic inhibition of angiotensin-II type-1 receptor reverses obesity-augmented desmoplasia and tumor growth and improves response to chemotherapy. Augmented activation of pancreatic stellate cells (PSC) in obesity is induced by tumor-associated neutrophils (TAN) recruited by adipocyte-secreted IL1 beta. PSCs further secrete IL1 beta, and inactivation of PSCs reduces IL1 beta expression and TAN recruitment. Furthermore, depletion of TANs, IL1 beta inhibition, or inactivation of PSCs prevents obesity-accelerated tumor growth. In patients with pancreatic cancer, we confirmed that obesity is associated with increased desmoplasia and reduced response to chemotherapy. We conclude that cross-talk between adipocytes, TANs, and PSCs exacerbates desmoplasia and promotes tumor progression in obesity.
SIGNIFICANCE : Considering the current obesity pandemic, unraveling the mechanisms underlying obesity- induced cancer progression is an urgent need. We found that the aggravation of desmoplasia is a key mechanism of obesity- promoted PDAC progression. Importantly, we discovered that clinically available antifi brotic/infl ammatory agents can improve the treatment response of PDAC in obese hosts. Cancer Discov; 6(8); 852-69. (C) 2016 AACR.
C1 [Incio, Joao; Liu, Hao; Suboj, Priya; Chin, Shan M.; Chen, Ivy X.; Pinter, Matthias; Ng, Mei R.; Nia, Hadi T.; Grahovac, Jelena; Kao, Shannon; Babykutty, Suboj; Huang, Yuhui; Jung, Keehoon; Rahbari, Nuh N.; Han, Xiaoxing; Chauhan, Vikash P.; Martin, John D.; Kahn, Julia; Huang, Peigen; Boucher, Yves; Fukumura, Dai; Jain, Rakesh K.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs, Boston, MA USA.
[Incio, Joao] Hosp Sao Joao, Dept Internal Med, Oporto, Portugal.
[Incio, Joao; Soares, Raquel] Univ Porto, Inst Innovat & Res Heath I3S, Metab Nutr & Endocrinol Grp, Dept Biochem,Fac Med, Oporto, Portugal.
[Liu, Hao] Harvard Med Sch, Biol & Biomed Sci, Boston, MA USA.
[Suboj, Priya] St Xaviers Coll, Dept Bot & Biotechnol, Trivandrum, Kerala, India.
[Chen, Ivy X.] Harvard Univ, Harvard Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Babykutty, Suboj] Mar Ivanios Coll Nalanchira, Dept Zool, Trivandrum, Kerala, India.
[Desphande, Vikram; Michaelson, James; Ferrone, Cristina R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA.
[Michaelson, James] Massachusetts Gen Hosp, Lab Quantitat Med, Boston, MA 02114 USA.
[Michaelson, James] Massachusetts Gen Hosp, Div Surg Oncol, Gillette Ctr Womens Canc, Boston, MA 02114 USA.
[Michaelson, James] Harvard Med Sch, Boston, MA 02114 USA.
[Michelakos, Theodoros P.; Ferrone, Cristina R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA USA.
[Michelakos, Theodoros P.; Ferrone, Cristina R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA USA.
RP Fukumura, D; Jain, RK (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs, Boston, MA USA.
EM dai@steele.mgh.harvard.edu; jain@steele.mgh.harvard.edu
OI Martin, John/0000-0002-9828-8203; Grahovac, Jelena/0000-0003-1430-8682
FU NIH [CA80124, CA85140, CA96915, CA115767, CA126642]; Lustgarten
Foundation; Foundation for Science and Technology (Portugal, POPH/FSE
funding program); Austrian Science Fund (FWF) [J3747-B28]
FX This study was supported in part by the NIH (CA80124, CA85140, CA96915,
CA115767, and CA126642 to R.K. Jain and D. Fukumura), the Lustgarten
Foundation (research grant to R.K. Jain), the Foundation for Science and
Technology (Portugal, POPH/FSE funding program, fellowship and research
grant to J. Incio), and the Austrian Science Fund (FWF), project number
J3747-B28 (to M. Pinter).
NR 73
TC 10
Z9 10
U1 3
U2 3
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 AUG
PY 2016
VL 6
IS 8
BP 852
EP 869
DI 10.1158/2159-8290.CD-15-1177
PG 18
WC Oncology
SC Oncology
GA DW0TO
UT WOS:000383355900023
PM 27246539
ER
PT J
AU Aguirre, AJ
Meyers, RM
Weir, BA
Vazquez, F
Zhang, CZ
Ben-David, U
Cook, A
Ha, G
Harrington, WF
Doshi, MB
Kost-Alimova, M
Gill, S
Xu, H
Ali, LD
Jiang, GZ
Pantel, S
Lee, Y
Goodale, A
Cherniack, AD
Oh, C
Kryukov, G
Cowley, GS
Garraway, LA
Stegmaier, K
Roberts, CW
Golub, TR
Meyerson, M
Root, DE
Tsherniak, A
Hahn, WC
AF Aguirre, Andrew J.
Meyers, Robin M.
Weir, Barbara A.
Vazquez, Francisca
Zhang, Cheng-Zhong
Ben-David, Uri
Cook, April
Ha, Gavin
Harrington, William F.
Doshi, Mihir B.
Kost-Alimova, Maria
Gill, Stanley
Xu, Han
Ali, Levi D.
Jiang, Guozhi
Pantel, Sasha
Lee, Yenarae
Goodale, Amy
Cherniack, Andrew D.
Oh, Coyin
Kryukov, Gregory
Cowley, Glenn S.
Garraway, Levi A.
Stegmaier, Kimberly
Roberts, Charles W.
Golub, Todd R.
Meyerson, Matthew
Root, David E.
Tsherniak, Aviad
Hahn, William C.
TI Genomic Copy Number Dictates a Gene-Independent Cell Response to
CRISPR/Cas9 Targeting
SO CANCER DISCOVERY
LA English
DT Article
ID ONE-STEP GENERATION; CANCER; CRISPR-CAS9; ACTIVATION; TRANSCRIPTION;
SCREENS; SYSTEM; MICE; QUANTIFICATION; REARRANGEMENTS
AB The CRISPR/Cas9 system enables genome editing and somatic cell genetic screens in mammalian cells. We performed genome-scale loss-of-function screens in 33 cancer cell lines to identify genes essential for proliferation/survival and found a strong correlation between increased gene copy number and decreased cell viability after genome editing. Within regions of copy-number gain, CRISPR/Cas9 targeting of both expressed and unexpressed genes, as well as intergenic loci, led to significantly decreased cell proliferation through induction of a G(2) cell-cycle arrest. By examining single-guide RNAs that map to multiple genomic sites, we found that this cell response to CRISPR/Cas9 editing correlated strongly with the number of target loci. These observations indicate that genome targeting by CRISPR/Cas9 elicits a gene-independent antiproliferative cell response. This effect has important practical implications for the interpretation of CRISPR/Cas9 screening data and confounds the use of this technology for the identification of essential genes in amplified regions.
SIGNIFICANCE: We found that the number of CRISPR/Cas9-induced DNA breaks dictates a geneindependent antiproliferative response in cells. These observations have practical implications for using CRISPR/Cas9 to interrogate cancer gene function and illustrate that cancer cells are highly sensitive to site-specific DNA damage, which may provide a path to novel therapeutic strategies. Cancer Discov; 6( 8); 914-29. (C) 2016 AACR.
C1 [Aguirre, Andrew J.; Weir, Barbara A.; Vazquez, Francisca; Zhang, Cheng-Zhong; Cook, April; Ha, Gavin; Doshi, Mihir B.; Gill, Stanley; Kryukov, Gregory; Garraway, Levi A.; Stegmaier, Kimberly; Golub, Todd R.; Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Aguirre, Andrew J.; Meyers, Robin M.; Weir, Barbara A.; Vazquez, Francisca; Zhang, Cheng-Zhong; Ben-David, Uri; Cook, April; Ha, Gavin; Harrington, William F.; Doshi, Mihir B.; Kost-Alimova, Maria; Gill, Stanley; Xu, Han; Ali, Levi D.; Jiang, Guozhi; Pantel, Sasha; Lee, Yenarae; Goodale, Amy; Cherniack, Andrew D.; Oh, Coyin; Kryukov, Gregory; Cowley, Glenn S.; Garraway, Levi A.; Stegmaier, Kimberly; Roberts, Charles W.; Golub, Todd R.; Meyerson, Matthew; Root, David E.; Tsherniak, Aviad; Hahn, William C.] Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA.
[Aguirre, Andrew J.; Garraway, Levi A.; Hahn, William C.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Aguirre, Andrew J.; Garraway, Levi A.; Stegmaier, Kimberly; Golub, Todd R.; Meyerson, Matthew; Hahn, William C.] Harvard Med Sch, Boston, MA USA.
[Garraway, Levi A.; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Stegmaier, Kimberly] Boston Childrens Hosp, Boston, MA USA.
[Roberts, Charles W.] St Jude Childrens Res Hosp, Memphis, TN USA.
[Meyerson, Matthew] Harvard Med Sch, Dept Pathol, Boston, MA USA.
[Meyerson, Matthew; Hahn, William C.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA.
[Hahn, William C.] Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave,Dana 1538, Boston, MA 02215 USA.
RP Tsherniak, A (reprint author), Broad Inst Harvard & MIT, 415 Main St, Cambridge, MA 02142 USA.; Hahn, WC (reprint author), Dana Farber Canc Inst, Med Oncol, 450 Brookline Ave,Dana 1538, Boston, MA 02215 USA.
EM aviad@broadinstitute.org; william_hahn@dfci.harvard.edu
OI Oh, Coyin/0000-0002-5732-3471
FU Pancreatic Cancer Action Network Samuel Stroum Fellowship; Hope Funds
for Cancer Postdoctoral Fellowship; American Society of Clinical
Oncology Young Investigator Award; Dana-Farber Cancer Institute Hale
Center for Pancreatic Cancer; Perry S. Levy Endowed Fellowship; Harvard
Catalyst and Harvard Clinical and Translational Science Center [UL1
TR001102]; Slim Initiative for Genomic Medicine; Carlos Slim Foundation
in Mexico; [R01 CA130988]; [U01 CA199253]; [U01 CA176058]; [P01
CA154303]; [P50 CA12700323]
FX This project was supported by R01 CA130988 (W.C. Hahn), U01 CA199253
(W.C. Hahn), U01 CA176058 (W.C. Hahn), P01 CA154303 (W.C. Hahn), and P50
CA12700323 (W.C. Hahn and A.J. Aguirre). A.J. Aguirre was supported by
the Pancreatic Cancer Action Network Samuel Stroum Fellowship, Hope
Funds for Cancer Postdoctoral Fellowship, American Society of Clinical
Oncology Young Investigator Award, Dana-Farber Cancer Institute Hale
Center for Pancreatic Cancer, Perry S. Levy Endowed Fellowship, and the
Harvard Catalyst and Harvard Clinical and Translational Science Center
(UL1 TR001102). This work was conducted as part of the Slim Initiative
for Genomic Medicine, a project funded by the Carlos Slim Foundation in
Mexico.
NR 48
TC 15
Z9 16
U1 3
U2 3
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 AUG
PY 2016
VL 6
IS 8
BP 914
EP 929
DI 10.1158/2159-8290.CD-16-0154
PG 16
WC Oncology
SC Oncology
GA DW0TO
UT WOS:000383355900027
PM 27260156
ER
PT J
AU Pernar, CH
Markt, SC
McKay, RR
Mucci, LA
AF Pernar, Claire H.
Markt, Sarah C.
McKay, Rana R.
Mucci, Lorelei A.
TI CHALLENGE Trial 1 Year Feasibility Results-Letter
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Letter
ID PHYSICAL-ACTIVITY; CANCER-DIAGNOSIS; SURVIVAL
C1 [Pernar, Claire H.; Markt, Sarah C.; Mucci, Lorelei A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[McKay, Rana R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Pernar, CH (reprint author), Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave,Kresge 911, Boston, MA 02115 USA.
EM cpernar@mail.harvard.edu
FU NCI NIH HHS [T32 CA009001]; NIEHS NIH HHS [T32 ES007069]
NR 5
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 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD AUG
PY 2016
VL 25
IS 8
BP 1277
EP 1277
DI 10.1158/1055-9965.EPI-16-0393
PG 1
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DV6JV
UT WOS:000383042300012
PM 27418272
ER
PT J
AU Sridharan, V
Gjini, E
Liao, XY
Chau, NG
Haddad, RI
Severgnini, M
Hammerman, P
El-Naggar, A
Freeman, GJ
Hodi, FS
Rodig, SJ
Dranoff, G
Schoenfeld, JD
AF Sridharan, Vishwajith
Gjini, Evisa
Liao, Xiaoyun
Chau, Nicole G.
Haddad, Robert I.
Severgnini, Mariano
Hammerman, Peter
El-Naggar, Adel
Freeman, Gordon J.
Hodi, F. Stephen
Rodig, Scott J.
Dranoff, Glenn
Schoenfeld, Jonathan D.
TI Immune Profiling of Adenoid Cystic Carcinoma: PD-L2 Expression and
Associations with Tumor-Infiltrating Lymphocytes
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID CELL LUNG-CANCER; METASTATIC MELANOMA; MUTATIONAL LANDSCAPE; ANTI-PD-L1
ANTIBODY; BREAST-CANCER; NECK-CANCER; BLOCKADE; IMMUNOTHERAPY;
IPILIMUMAB; HEAD
AB Adenoid cystic carcinoma (ACC) is among the most lethal salivary gland tumors, with no treatments for metastatic disease that prolong survival. We examined tissue from 28 primary and metastatic ACC deposits obtained from 21 patients for infiltrating immune cells and PD-L1/PD-L2 expression and determined mRNA profiles of over 1,400 oncogenic and immune-related genes. We also assessed the effect of chemoradiation on immune mediators in a patient who had serial biopsies available. Most tumors expressed PD-L2 but had few infiltrating immune cells. Lack of immune-cell infiltrate was associated with expression of genes in the beta-catenin/Wnt and PI3K pathways. Additionally, certain transcripts linked to growth and invasion were differentially expressed among primary and metastatic deposits. Chemoradiation appeared to increase CD8(+) effector T cells, decrease regulatory T cells, and promote a systemic humoral response. These data suggest a potential role for PD-L2 inhibition and immune modulation as treatment for patients with ACC. (C) 2016 AACR.
C1 [Sridharan, Vishwajith; 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.
[Gjini, Evisa; Liao, Xiaoyun] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Severgnini, Mariano; Hodi, F. Stephen] Brigham & Womens Hosp, Dana Farber Canc Ctr, Ctr Immunooncol, 75 Francis St, Boston, MA 02115 USA.
[Chau, Nicole G.; Haddad, Robert I.; Hammerman, Peter; Freeman, Gordon J.; Hodi, F. Stephen] Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Med Oncol, 75 Francis St, Boston, MA 02115 USA.
[El-Naggar, Adel] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Dana Farber Canc Ctr, 75 Francis St, Boston, MA 02115 USA.
[Dranoff, Glenn] Novartis Inst Biomed Res, Cambridge, MA USA.
RP Schoenfeld, JD (reprint author), Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave,DA L2-57, Boston, MA 02114 USA.
EM jdschoenfeld@partners.org
FU NCI NIH HHS [P30 CA016672]
NR 56
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 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD AUG
PY 2016
VL 4
IS 8
BP 679
EP 687
DI 10.1158/2326-6066.CIR-16-0031
PG 9
WC Oncology; Immunology
SC Oncology; Immunology
GA DV6NE
UT WOS:000383052800006
PM 27312343
ER
PT J
AU Song, MY
Konijeti, GG
Yuan, C
Ananthakrishnan, AN
Ogino, S
Fuchs, CS
Giovannucci, EL
Ng, K
Chan, AT
AF Song, Mingyang
Konijeti, Gauree Gupta
Yuan, Chen
Ananthakrishnan, Ashwin N.
Ogino, Shuji
Fuchs, Charles S.
Giovannucci, Edward L.
Ng, Kimmie
Chan, Andrew T.
TI Plasma 25-Hydroxyvitamin D, Vitamin D Binding Protein, and Risk of
Colorectal Cancer in the Nurses' Health Study
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID GROUP-SPECIFIC COMPONENT; MACROPHAGE ACTIVATING FACTOR; C5A DES ARG;
GC-GLOBULIN; INFLAMMATORY MARKERS; CONTROLLED-TRIAL; SCREENING TRIAL;
SERUM; CALCIUM; MORTALITY
AB Total circulating 25-hydroxyvitamin D [25(OH) D)] has been associated with lower risk of colorectal cancer. The physiologic mechanism, however, may be more directly related to the free or bioavailable fraction of 25(OH) D, which is influenced by levels of vitaminD binding protein (VDBP). We assessed the association of prediagnosis total, free, and bioavailable 25(OH) D and VDBP with colorectal cancer risk among predominantly white women in the Nurses' Health Study (NHS) who provided a blood specimen in 1989-1990. We documented 378 cases of colorectal cancer through 2011 and matched them to 689 controls according to age and time of blood draw. We genotyped two common polymorphisms in the gene coding VDBP and calculated free and bioavailable 25(OH) D levels based on total 25(OH) D, VDBP, albumin, and their estimated genotype-specific binding affinities. Total 25(OH) D was associated with lower colorectal cancer risk (P for trend = 0.01). Compared with women in the lowest quintile of total 25 (OH) D, those in the highest quintile had a multivariable-adjusted odds ratio (OR) for colorectal cancer of 0.54 [95% confidence interval (CI), 0.33-0.87]. Comparing extreme quintiles, we did not find any significant association with risk of colorectal cancer for VDBP (OR, 0.98; 95% CI, 0.65-1.47), free 25(OH) D (OR, 0.71; 95% CI, 0.46-1.10), or bioavailable 25(OH) D (OR, 0.92; 95% CI, 0.60-1.42). In conclusion, prediagnosis levels of total, but not free or bioavailable 25(OH) D, were associated with lower colorectal cancer risk. Although our findings support an inverse association of vitamin D with colorectal cancer, this association does not appear to be due to the unbound or bioavailable fraction of circulating vitamin D. (C) 2016 AACR.
C1 [Song, Mingyang; Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA.
[Song, Mingyang; Ananthakrishnan, Ashwin N.; Ogino, Shuji; Fuchs, Charles S.; Giovannucci, Edward L.; Ng, Kimmie; Chan, Andrew T.] Harvard Med Sch, Boston, MA USA.
[Song, Mingyang; Ananthakrishnan, Ashwin N.; Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Song, Mingyang; Yuan, Chen; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
[Konijeti, Gauree Gupta] Scripps Clin, Div Gastroenterol, La Jolla, CA 92037 USA.
[Konijeti, Gauree Gupta] Scripps Translat Sci Inst, La Jolla, CA USA.
[Ogino, Shuji; Fuchs, Charles S.; Ng, Kimmie] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, Div MPE Mol Pathol Epidemiol, 75 Francis St, Boston, MA 02115 USA.
[Ogino, Shuji; Giovannucci, Edward L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Fuchs, Charles S.; Giovannucci, Edward L.; Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Chan, Andrew T.] Broad Inst Massachusetts Inst Technol & Harvard, Cambridge, MA USA.
RP Chan, AT (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St,GRJ 825C, Boston, MA 02114 USA.
EM achan@mgh.harvard.edu
FU NIH [UM1 CA186107, P01 CA87969, R01 CA49449, R01 CA137178, R01 CA151993,
R35 CA197735, K07 CA148894, K24 DK098311, P50 CA127003]; NIH/NCATS [KL2
TR001112]; American Society of Clinical Oncology/Conquer Cancer
Foundation
FX This work was supported by the NIH (UM1 CA186107 to M.J. Stampfer, P01
CA87969 to M.J. Stampfer, R01 CA49449 to S.E. Hankinson, R01 CA137178 to
A.T. Chan, R01 CA151993 to S. Ogino, R35 CA197735 to S. Ogino, K07
CA148894 to K. Ng, K24 DK098311 to A.T. Chan, and P50 CA127003 to C.S.
Fuchs and NIH/NCATS Grant Number KL2 TR001112 to G.G. Konijeti) and the
American Society of Clinical Oncology/Conquer Cancer Foundation (to C.S.
Fuchs).
NR 52
TC 2
Z9 2
U1 3
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD AUG
PY 2016
VL 9
IS 8
BP 664
EP 672
DI 10.1158/1940-6207.CAPR-16-0053
PG 9
WC Oncology
SC Oncology
GA DV7AZ
UT WOS:000383089500006
PM 27246684
ER
PT J
AU Peloso, GM
Lange, LA
Varga, TV
Nickerson, DA
Smith, JD
Griswold, ME
Musani, S
Polfus, LM
Mei, H
Gabriel, S
Quarells, RC
Altshuler, D
Boerwinkle, E
Daly, MJ
Neale, B
Correa, A
Reiner, AP
Wilson, JG
Kathiresan, S
AF Peloso, Gina M.
Lange, Leslie A.
Varga, Tibor V.
Nickerson, Deborah A.
Smith, Joshua D.
Griswold, Michael E.
Musani, Solomon
Polfus, Linda M.
Mei, Hao
Gabriel, Stacey
Quarells, Rakale Collins
Altshuler, David
Boerwinkle, Eric
Daly, Mark J.
Neale, Benjamin
Correa, Adolfo
Reiner, Alex P.
Wilson, James G.
Kathiresan, Sekar
TI Association of Exome Sequences With Cardiovascular Traits Among Blacks
in the Jackson Heart Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE alleles; exome; lipids; missense; mutation
ID OF-FUNCTION MUTATIONS; GENOME-WIDE ASSOCIATION; BLOOD-LIPIDS; PCSK9;
VARIANTS; DISEASE; CHOLESTEROL; POPULATION; APOC3; RISK
AB Background-The correlation of null alleles with human phenotypes can provide insight into gene function in humans. In individuals of African ancestry, we set out to identify null and damaging missense variants, and test these variants for association with a range of cardiovascular phenotypes.
Methods and Results-We performed whole-exome sequencing in 3223 black individuals from the Jackson Heart Study and found a total of 729 666 variant sites with minor allele frequency <5%, including 17 263 null variants and 49 929 missense variants predicted to be damaging by in silico algorithms. We tested null and damaging missense variants within each gene for association with 36 cardiovascular traits. We found 3 associations that met our prespecified level of significance (alpha=1.1x10(-7)). Null and damaging missense variants in PCSK9 were associated with 36 mg/dL lower low-density lipoprotein cholesterol (P=3x10-21). Three individuals in their 50s with complete PCSK9 deficiency (each compound heterozygote for PCSK9 p. Y142X and p. C679X) were identified, with one having a coronary artery calcification score in the 83rd percentile despite a low-density lipoprotein cholesterol of 32 mg/dL. A damaging missense variant in HBQ1 (p. G52A) was associated with a 2 pg/cell lower mean corpuscular hemoglobin (P=9x10(-13)) and rare damaging missense variants in VPS13A with higher red blood cell distribution width (P=9.9x10(-8)).
Conclusions-A limited number of null/damaging alleles with a large effect on cardiovascular traits were detectable in approximate to 3000 black individuals.
C1 [Peloso, Gina M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-248, Boston, MA 02114 USA.
[Daly, Mark J.; Neale, Benjamin] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Peloso, Gina M.; Gabriel, Stacey; Altshuler, David; Daly, Mark J.; Neale, Benjamin; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Varga, Tibor V.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Nickerson, Deborah A.; Smith, Joshua D.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Griswold, Michael E.; Mei, Hao] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
[Musani, Solomon] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Correa, Adolfo] Univ Mississippi, Med Ctr, Dept Pediat & Med, Jackson, MS 39216 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Polfus, Linda M.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA.
[Quarells, Rakale Collins] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Altshuler, David; Kathiresan, Sekar] Harvard Med Sch, Dept Med, Boston, MA USA.
[Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 5-248, Boston, MA 02114 USA.; Peloso, GM (reprint author), Boston Univ, Dept Biostat, 801 Massachusetts Ave,3rd Floor, Boston, MA 02118 USA.
EM gpeloso@bu.edu; skathiresan@partners.org
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health [K01HL125751]; Research Scholar award from the Massachusetts
General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan
Family Foundation [R01HL107816]; Fondation Leducq; National Heart, Lung,
and Blood Institute [HHSN268201300046C, HHSN268201300047C,
HHSN268201300048C, HHSN2682013 00049C, HHSN268201300050C]; National
Institute on Minority Health and Health Disparities; National Institute
on Minority Health and Health Disparities [1RC4MD005964]
FX G.M.P. is supported by the National Heart, Lung, and Blood Institute of
the National Institutes of Health under Award Number K01HL125751. S.K.
is 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. The
Jackson Heart Study is supported by contracts HHSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN2682013 00049C, and
HHSN268201300050C from the National Heart, Lung, and Blood Institute and
the National Institute on Minority Health and Health Disparities. The
MH-GRID Network (Investigators: Rakale C. Quarells, Gary H. Gibbons,
Donna K. Arnett, Robert L. Davis, Suzanne M. Leal, Deborah A. Nickerson,
James Perkins, Charles N. Rotimi, Joel H. Saltz, Herman A. Taylor, and
James G. Wilson) was supported, in part, by a grant from the National
Institute on Minority Health and Health Disparities (grant #
1RC4MD005964).
NR 36
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 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD AUG
PY 2016
VL 9
IS 4
BP 368
EP 374
DI 10.1161/CIRCGENETICS.116.001410
PG 7
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA DU5EC
UT WOS:000382234000008
PM 27422940
ER
PT J
AU Baggish, AL
AF Baggish, Aaron L.
TI Exercise-Induced Cardiac Remodeling Competitive Athletes Are Just the
Tip of the Iceberg
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE Editorials; athlete; blood pressure; cross-sectional studies; exercise;
habit
ID MAGNETIC-RESONANCE; ENDURANCE; HEART; MASS
C1 [Baggish, Aaron L.] Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA.
RP Baggish, AL (reprint author), Massachusetts Gen Hosp, Cardiovasc Performance Program, Yawkey Suite 5B,55 Fruit St, Boston, MA 02114 USA.
EM abaggish@partners.org
NR 19
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 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD AUG
PY 2016
VL 9
IS 8
AR e005321
DI 10.1161/CIRCIMAGING.116.005321
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DU5FF
UT WOS:000382236900016
ER
PT J
AU Ferencik, M
AF Ferencik, Maros
TI Insights Into Coronary Plaque Microstructure Differences Between Women
and Men
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE Editorials; acute coronary syndrome; atherosclerosis; coronary artery
disease; optical coherence tomography; women's health; smoking
ID OPTICAL COHERENCE TOMOGRAPHY; ROMICAT-II TRIAL; ACUTE CHEST-PAIN;
SEX-DIFFERENCES; RISK; ATHEROSCLEROSIS; ANGIOGRAPHY; OUTCOMES; EVENTS;
BURDEN
C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA.
[Ferencik, Maros] Harvard Med Sch, Dept Radiol, Boston, MA USA.
[Ferencik, Maros] Harvard Med Sch, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA USA.
RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA.
EM ferencik@ohsu.edu
NR 20
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD AUG
PY 2016
VL 9
IS 8
AR e005343
DI 10.1161/CIRCIMAGING.116.005343
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DU5FF
UT WOS:000382236900021
ER
PT J
AU ter Maaten, JM
Damman, K
Hanberg, JS
Givertz, MM
Metra, M
O'Connor, CM
Teerlink, JR
Ponikowski, P
Cotter, G
Davison, B
Cleland, JG
Bloomfield, DM
Hillege, HL
van Veldhuisen, DJ
Voors, AA
Testani, JM
AF ter Maaten, Jozine M.
Damman, Kevin
Hanberg, Jennifer S.
Givertz, Michael M.
Metra, Marco
O'Connor, Christopher M.
Teerlink, John R.
Ponikowski, Piotr
Cotter, Gad
Davison, Beth
Cleland, John G.
Bloomfield, Daniel M.
Hillege, Hans L.
van Veldhuisen, Dirk J.
Voors, Adriaan A.
Testani, Jeffrey M.
TI Hypochloremia, Diuretic Resistance, and Outcome in Patients With Acute
Heart Failure
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE blood urea nitrogen; chlorides; creatinine; diuretics; electrolytes
ID SENSING MECHANISM; EUROPEAN-SOCIETY; TASK-FORCE; CHLORIDE; ASSOCIATION;
ROLOFYLLINE; GUIDELINES; MANAGEMENT; ANTAGONIST; CARDIOLOGY
AB Background-Chloride plays a role in renal salt sensing, neurohormonal activation, and regulation of diuretic targets, and hypochloremia predicts mortality in acute heart failure (AHF). AHF therapies, such as diuretics, alter chloride homeostasis. We studied the association between (changes in) chloride levels and diuretic responsiveness, decongestion, and mortality in patients with AHF.
Methods and Results-Patients hospitalized for AHF in the PROTECT trial (n=2033) with serum chloride levels within 24 hours of admission and 14 days later were studied (n=1960). Hypochloremia was defined as serum chloride <96 mEq/L. Mean baseline chloride was 100.8+/-5.0 mEq/L. Low baseline chloride was associated with high bicarbonate, poor diuretic response, less hemoconcentration, and worsening heart failure (all P<0.01). Newly developed hypochloremia at day 14 was common and associated with a decline in renal function and an increase in blood urea nitrogen (P<0.01). In multivariable analyses, chloride measured at day 14, but not baseline chloride, was strongly and independently associated with mortality through 180 days (hazard ratio per unit decrease: 1.07 [1.03-1.10]; P<0.001). In comparison, sodium was not significantly associated with mortality after multivariable adjustment at any time point. Hypochloremia at baseline that resolved was not associated with mortality (P=0.55), but new or persistent hypochloremia at day 14 was associated with increased mortality (hazard ratio: 3.11 [2.17-4.46]; P<0.001).
Conclusions-Low serum chloride at AHF hospital admission was strongly associated with impaired decongestion. New or persistent hypochloremia 14 days later was independently associated with reduced survival, whereas hypochloremia that resolved by day 14 was not.
C1 [ter Maaten, Jozine M.; Damman, Kevin; Hillege, Hans L.; van Veldhuisen, Dirk J.; Voors, Adriaan A.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands.
[ter Maaten, Jozine M.; Hanberg, Jennifer S.; Testani, Jeffrey M.] Yale Univ, Sch Med, Program Appl Translat Res, New Haven, CT USA.
[Givertz, Michael M.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Metra, Marco] Univ Brescia, I-25121 Brescia, Italy.
[O'Connor, Christopher M.] Inova Heart & Vasc Inst, Falls Church, VA USA.
[Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland.
[Cotter, Gad; Davison, Beth] Momentum Res, Durham, NC USA.
[Cleland, John G.] Univ Hull, Kingston Upon Hull, Yorks, England.
[Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA.
[Testani, Jeffrey M.] Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA.
RP Voors, AA (reprint author), Univ Med Ctr Groningen, Hanzepl 1, NL-9713 GZ Groningen, Netherlands.
EM a.a.voors@umcg.nl
RI Ponikowski, Piotr/O-6454-2015
OI Ponikowski, Piotr/0000-0002-3391-7064
FU NovoCardia, a subsidiary of Merck
FX The PROTECT trial was supported by NovoCardia, a subsidiary of Merck.
NR 20
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Z9 2
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD AUG
PY 2016
VL 9
IS 8
AR UNSP e003109
DI 10.1161/CIRCHEARTFAILURE.116.003109
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DU5EQ
UT WOS:000382235400009
ER
PT J
AU Kanwal, F
Kramer, JR
El-Serag, HB
Frayne, S
Clark, J
Cao, YM
Taylor, T
Smith, D
White, D
Asch, SM
AF Kanwal, Fasiha
Kramer, Jennifer R.
El-Serag, Hashem B.
Frayne, Susan
Clark, Jack
Cao, Yumei
Taylor, Thomas
Smith, Donna
White, Donna
Asch, Steven M.
TI Race and Gender Differences in the Use of Direct Acting Antiviral Agents
for Hepatitis C Virus
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE Veterans; healthcare disparities; access; quality; hepatitis
ID GENOTYPE 1 INFECTION; RACIAL-DIFFERENCES; VETERANS-AFFAIRS; HCV;
ABT-450/R-OMBITASVIR; LEDIPASVIR; SOFOSBUVIR; DASABUVIR; RIBAVIRIN;
CIRRHOSIS
AB Background. Direct acting antiviral agents (DAA) are highly effective yet expensive. Disparities by race and/or gender often exist in the use of costly medical advances as they become available.
Methods. We examined a cohort of hepatitis C virus (HCV) patients who received care at the Veterans Administration facilities nationwide. We evaluated the effect of race and gender on DAA receipt after adjusting for socioeconomic status, liver disease severity, comorbidity, and propensity for healthcare use. To determine if disparities had changed over time, we conducted a similar analysis of HCV patients who were seen in the previous standard of care treatment era.
Results. Of the 145 596 patients seen in the current DAA era, 17 791 (10.2%) received treatment during the first 16 months of DAA approval. Black patients had 21% lower odds of receiving DAA than whites (odds ratio [OR] = 0.79; 95% confidence interval [CI],.75,.84). Overall, women were as likely to receive treatment as men (OR = 0.99; 95% CI,.90-1.09). However, the odds of receiving DAAs were 29% lower for younger women compared with younger men (OR = 0.71, 95% CI, .54-.93). Similar to the DAA cohort, black patients had significantly lower odds of receiving treatment than whites (OR = 0.74, 95% CI, .69-.79) in the previous treatment era. The racial difference between the 2 eras did not reach statistical significance.
Conclusions. There were unexplained differences among HCV population subgroups in the receipt of new DAA treatment. Targeted interventions are needed for black patients and younger women.
C1 [Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.; Cao, Yumei; Smith, Donna; White, Donna] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Ctr Innovat Qual Effectiveness & Safety IQuESt, Houston, TX 77030 USA.
[Kanwal, Fasiha; El-Serag, Hashem B.] Baylor Coll Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA.
[Kanwal, Fasiha; Kramer, Jennifer R.; El-Serag, Hashem B.; White, Donna] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA.
[Kanwal, Fasiha; El-Serag, Hashem B.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Frayne, Susan; Taylor, Thomas; Asch, Steven M.] VA Palo Alto Healthcare Syst, Fostering High Value Care, Ctr Innovat Implementat Ci2i, Stanford, CA USA.
[Clark, Jack] Edith Nourse Rogers Mem Vet Hosp, Ctr Healthcare Org & Implementat, Boston, MA USA.
[Clark, Jack] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02215 USA.
RP Kanwal, F (reprint author), Michael E DeBakey VA, Ctr Innovat Qual Effectiveness & Safety IQuESt, 2002 Holcombe Blvd,Ste 152, Houston, TX 77030 USA.; Kanwal, F (reprint author), Baylor Coll Med, 2002 Holcombe Blvd,Ste 152, Houston, TX 77030 USA.
EM kanwal@bcm.edu
FU Department of Veterans Affairs, Veterans Health Administration, Office
of Research and Development Service [VA IIR 13-059]
FX The research was supported in part by the Department of Veterans
Affairs, Veterans Health Administration, Office of Research and
Development Service (VA IIR 13-059). F.K. is a physician research
scientist at the Center for Innovations in Quality, Effectiveness, and
Safety (#CIN 13-413), Michael E. DeBakey Veterans Affairs Medical
Center, Houston, Texas.
NR 31
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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 AUG 1
PY 2016
VL 63
IS 3
BP 291
EP 299
DI 10.1093/cid/ciw249
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DV8QP
UT WOS:000383201900001
PM 27131869
ER
PT J
AU Turbett, SE
Mansour, MK
AF Turbett, Sarah E.
Mansour, Michael K.
TI Fecal ESBL Screening: Are We Ready for This Information?
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE ESBL; infection control; fecal colonization; Enterobacteriaceae;
screening
ID RESISTANT STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; INTENSIVE-CARE;
INFECTION; COLONIZATION; RISK; ENTEROBACTERIACEAE; CARRIAGE;
DECOLONIZATION
C1 [Turbett, Sarah E.; Mansour, Michael K.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[Turbett, Sarah E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Mansour, MK (reprint author), Massachusetts Gen Hosp, Jackson Bldg 1328A,55 Fruit St, Boston, MA 02114 USA.
EM mkmansour@mgh.harvard.edu
FU NIAID NIH HHS [K08 AI110655]
NR 20
TC 0
Z9 0
U1 2
U2 2
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 AUG 1
PY 2016
VL 63
IS 3
BP 319
EP 321
DI 10.1093/cid/ciw288
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA DV8QP
UT WOS:000383201900004
PM 27143673
ER
PT J
AU Tasdemir-Yilmaz, OE
Segal, RA
AF Tasdemir-Yilmaz, Ozge E.
Segal, Rosalind A.
TI There and back again: coordinated transcription, translation and
transport in axonal survival and regeneration
SO CURRENT OPINION IN NEUROBIOLOGY
LA English
DT Article
ID MESSENGER-RNA LOCALIZATION; BETA-ACTIN SYNTHESIS; BINDING-PROTEIN 1;
NERVOUS-SYSTEM; NEURONAL SURVIVAL; PERIPHERAL-NERVE; GROWTH; INJURY;
COMPLEX; SIGNAL
AB Neurons are highly polarized cells with axonal and dendritic projections that extend over long distances. Target-derived neurotrophins provide local axonal cues that function in developing neurons, while physical or chemical injuries to long axons initiate local environmental cues in mature neurons. In both instances initial responses at the location of stimulation or injury must be coordinated with changes in the transcriptional program and subsequent changes in axonal protein content. To achieve this coordination, intracellular signals move 'there and back again' between axons and the nucleus. Here, we review new findings on neuronal responses to growth factors and injury and highlight the coordination of transcription, translation and transport required to mediate communication between axons and cell bodies.
C1 [Tasdemir-Yilmaz, Ozge E.; Segal, Rosalind A.] Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA.
[Tasdemir-Yilmaz, Ozge E.; Segal, Rosalind A.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
RP Segal, RA (reprint author), Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA.; Segal, RA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA.
EM Rosalind_segal@dfci.harvard.edu
FU National Institutes of Health [RO1 NS050674, T32 AG000222]
FX We would like to apologize to authors whose studies were not included in
this review due to space constraints. We would like to thank Katherina
Cosker, Sarah Pease, Xuesong Zhao, Maria Pazyra-Murphy and Emily
Chadwick for helpful comments and editing. Our research is supported by
the National Institutes of Health grant RO1 NS050674 (RAS) and T32
AG000222 (OETY).
NR 47
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U1 3
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-4388
EI 1873-6882
J9 CURR OPIN NEUROBIOL
JI Curr. Opin. Neurobiol.
PD AUG
PY 2016
VL 39
BP 62
EP 68
DI 10.1016/j.conb.2016.04.006
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA DU6VI
UT WOS:000382352300010
PM 27131422
ER
PT J
AU O'Neill, AC
Shinagare, AB
Kurra, V
Tirumani, SH
Jagannathan, JP
Baheti, AD
Hornick, JL
George, S
Ramaiya, NH
AF O'Neill, A. C.
Shinagare, A. B.
Kurra, V.
Tirumani, S. H.
Jagannathan, J. P.
Baheti, A. D.
Hornick, J. L.
George, S.
Ramaiya, N. H.
TI Assessment of metastatic risk of gastric GIST based on treatment-naive
CT features
SO EJSO
LA English
DT Article
DE Gastrointestinal stromal tumor; Stomach; CT; Risk stratification;
Metastasis
ID GASTROINTESTINAL STROMAL TUMORS; TERM-FOLLOW-UP; COMPUTED-TOMOGRAPHY;
CONSENSUS APPROACH; DIAGNOSIS; PATHOLOGY; PROGNOSIS; SURVIVAL; STOMACH
AB Objective: To study whether the CT features of treatment-naive gastric GIST may be used to assess metastatic risk.
Methods: In this MB approved retrospective study, with informed consent waived, contrast enhanced CT images of 143 patients with pathologically confirmed treatment-naive gastric GIST (74 men, 69 women; mean age 61 years, SD +/- 14) were reviewed in consensus by two oncoradiologists blinded to clinicopathologic features and clinical outcome and morphologic features were recorded. The metastatic spread was recorded using available imaging studies and electronic medical records (median follow up 40 months, interquartile range, IQR, 21-61). The association of maximum size in any plane (<= 10 cm or >10 cm), outline (smooth or irregular/lobulated), cystic areas (<= 50% or >50%), exophytic component (<= 50% or >50%), and enhancing solid component (present or absent) with metastatic disease were analyzed using univariate (Fisher's exact test) and multivariate (logistic regression) analysis.
Results: Metastatic disease developed in 42 (29%) patients (28 at presentation, 14 during follow-up); 23 (16%) patients died. On multivariate analysis, tumor size >10 cm (p = 0.0001, OR 9.9), irregular/lobulated outline (p = 0.001, OR 5.6) and presence of a enhancing solid component (p < 0.0001, OR 9.1) were independent predictors of metastatic disease. On subgroup analysis, an irregular/lobulated outline and an enhancing solid component were more frequently associated with metastases in tumors <= 5 cm and >5-<= 10 cm (p < 0.05).
Conclusion: CT morphologic features can be used to assess the metastatic risk of treatment-naive gastric GIST. Risk assessment based on pretreatment CT is especially useful for patients receiving neoadjuvant tyrosine kinase inhibitors and those with tumors <5 cm in size. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [O'Neill, A. C.; Shinagare, A. B.; Kurra, V.; Tirumani, S. H.; Jagannathan, J. P.; Baheti, A. D.; Ramaiya, N. H.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
[Hornick, J. L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[George, S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.
EM ashinagare@partners.org
FU Bayer; Novartis; Pfizer; ARIAD; RSNA Research Scholar Grant [RSCH1422]
FX Suzanne George has consulting and research funding from Bayer, Novartis,
Pfizer and ARIAD.; This research project was not funded; however, Atul
Shinagare is now supported by RSNA Research Scholar Grant, #RSCH1422.
The grant support began after this research project was completed, but
before submission of the manuscript to EJSO.
NR 23
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Z9 2
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0748-7983
EI 1532-2157
J9 EJSO-EUR J SURG ONC
JI EJSO
PD AUG
PY 2016
VL 42
IS 8
BP 1222
EP 1228
DI 10.1016/j.ejso.2016.03.032
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA DV5XW
UT WOS:000383005000018
PM 27178777
ER
PT J
AU DeVore, AD
Hellkamp, AS
Becker, RC
Berkowitz, SD
Breithardt, G
Hacke, W
Halperin, JL
Hankey, GJ
Mahaffey, KW
Nessel, CC
Singer, DE
Fox, KAA
Patel, MR
Piccini, JP
AF DeVore, Adam D.
Hellkamp, Anne S.
Becker, Richard C.
Berkowitz, Scott D.
Breithardt, Guenter
Hacke, Werner
Halperin, Jonathan L.
Hankey, Graeme J.
Mahaffey, Kenneth W.
Nessel, Christopher C.
Singer, Daniel E.
Fox, Keith A. A.
Patel, Manesh R.
Piccini, Jonathan P.
CA ROCKET AF Steering Comm
TI Hospitalizations in patients with atrial fibrillation: an analysis from
ROCKET AF
SO EUROPACE
LA English
DT Article
DE Hospitalization; Atrial fibrillation; Outcomes; Stroke; Rivaroxaban
ID HEART-FAILURE; UNITED-STATES; TRIAL; RATES; PREVALENCE; MANAGEMENT;
STANDARD; OUTCOMES; SAFETY; TRENDS
AB The high costs associated with treatment for atrial fibrillation (AF) are primarily due to hospital care, but there are limited data to understand the reasons for and predictors of hospitalization in patients with AF.
The ROCKET AF trial compared rivaroxaban with warfarin for stroke prophylaxis in AF. We described the frequency of and reasons for hospitalization during study follow-up and utilized Cox proportional hazards models to assess for baseline characteristics associated with all-cause hospitalization. Of 14 171 patients, 14% were hospitalized at least once. Of 2614 total hospitalizations, 41% were cardiovascular including 4% for AF; of the remaining, 12% were for bleeding. Compared with patients not hospitalized, hospitalized patients were older (74 vs. 72 years), and more frequently had diabetes (46 vs. 39%), prior MI (23 vs. 16%), and paroxysmal AF (19 vs. 17%), but less frequently had prior transient ischaemic attack/stroke (49 vs. 56%). After multivariable adjustment, lung disease [hazard ratio (HR) 1.46, 95% confidence interval (CI) 1.29-1.66], diabetes [1.22, (1.11-1.34)], prior MI [1.27, (1.13-1.42)], and renal dysfunction [HR 1.07 per 5 unit GFR < 65 mL/min, (1.04-1.10)] were associated with increased hospitalization risk. Treatment assignment was not associated with differential rates of hospitalization.
Nearly 1 in 7 of the moderate-to-high-risk patients with AF enrolled in this trial was hospitalized within 2 years, and both AF and bleeding were rare causes of hospitalization. Further research is needed to determine whether care pathways directed at comorbid conditions among AF patients could reduce the need for and costs associated with hospitalization.
C1 [DeVore, Adam D.; Hellkamp, Anne S.; Patel, Manesh R.; Piccini, Jonathan P.] Duke Clin Res Inst, Durham, NC 27705 USA.
[DeVore, Adam D.; Patel, Manesh R.; Piccini, Jonathan P.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Becker, Richard C.] Univ Cincinnati, Cincinnati, OH USA.
[Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA.
[Breithardt, Guenter] Hosp Univ Munster, Munster, Germany.
[Hacke, Werner] Heidelberg Univ, Heidelberg, Germany.
[Halperin, Jonathan L.] Mt Sinai Sch Med, New York, NY USA.
[Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia.
[Mahaffey, Kenneth W.] Stanford Univ, Stanford, CA 94305 USA.
[Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA.
[Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
RP DeVore, AD (reprint author), Duke Clin Res Inst, Durham, NC 27705 USA.; DeVore, AD (reprint author), Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
EM adam.devore@duke.edu
RI Hankey, Graeme /H-4968-2014;
OI Hankey, Graeme /0000-0002-6044-7328; DeVore, Adam/0000-0002-4679-2221
FU Janssen Research & Development LLC, Raritan, NJ; Bayer HealthCare AG,
Leverkusen, Germany; Janssen Research and Development
FX This work was supported by the Janssen Research & Development LLC,
Raritan, NJ and Bayer HealthCare AG, Leverkusen, Germany. Funding to pay
the Open Access publication charges for this article was provided by
Janssen Research and Development.
NR 18
TC 1
Z9 1
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1099-5129
EI 1532-2092
J9 EUROPACE
JI Europace
PD AUG
PY 2016
VL 18
IS 8
BP 1135
EP 1142
DI 10.1093/europace/euv404
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DV8TD
UT WOS:000383208700005
PM 27174904
ER
PT J
AU Wakili, R
Siebermair, J
Fichtner, S
Sinner, MF
Klocker, E
Olesch, L
Hilberath, JN
Sarai, S
Clauss, S
Sattler, S
Kaab, S
Estner, HL
AF Wakili, Reza
Siebermair, Johannes
Fichtner, Stephanie
Sinner, Moritz F.
Klocker, Eva
Olesch, Lucia
Hilberath, Jan N.
Sarai, Samira
Clauss, Sebastian
Sattler, Stefan
Kaeaeb, Stefan
Estner, Heidi L.
TI One-year clinical outcome after ablation with a novel multipolar
irrigated ablation catheter for treatment of atrial fibrillation:
potential implications for clinical use
SO EUROPACE
LA English
DT Article
DE Arrhythmia; Atrial fibrillation; Ablation; Pulmonary vein isolation;
nMARQ catheter
ID PULMONARY VEIN ISOLATION; CIRCULAR MAPPING CATHETER; RADIOFREQUENCY
ABLATION; NMARQ ABLATION; MANAGEMENT; EFFICACY
AB Pulmonary vein isolation (PVI) is an established therapy for atrial fibrillation (AF). However, PVI remains a time-consuming procedure. A novel multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ (TM)) is aiming to improve PVI. We investigated the influence on procedural parameters and assessed clinical outcomes after PVI using this novel catheter.
Fifty-eight consecutive patients with paroxysmal AF were equally allocated (n = 29/group) to PVI treatment with (i) the novel multipolar ablation catheter (nMARQ (TM)) and (ii) a standard single-tip ablation catheter (SAC). Study endpoints included procedure time, fluoroscopy time, radiation dose, RF time, number of energy applications, and clinical outcome defined as freedom from AF after a single procedure. Successful PVI was confirmed by a separate circular, multipolar mapping catheter in all patients treated with the nMARQ (TM). Pulmonary vein isolation was achieved in 100% in the SAC group. In the nMARQ (TM) group, PVI was suggested in all patients. However, confirmatory mapping revealed persistent pulmonary vein (PV) conduction in 19 out of 29 nMARQ (TM) patients. These patients underwent further ablation, which still failed to achieve PVI in 5 of the 29 nMARQ (TM) patients, mainly due to significant temperature rise in the oesophagus and device-related limitations reaching the right inferior PV. Mean fluoroscopy time (31 +/- 12 vs. 23 +/- 10 min, P < 0.05) and (132 +/- 37 vs. 109 +/- 30 min, P < 0.05) were longer in nMARQ (TM) vs. SAC patients. Radiofrequency time was shorter in nMARQ (TM) vs. SAC group (21 +/- 9 vs. 35 +/- 12 min, P < 0.001). Radiation dose and the number of energy applications did not differ between both groups. Clinical outcome analysis revealed no significant differences (nMARQ (TM): 72 vs. SAC: 72%) after a mean follow-up of 373 +/- 278 days.
The use of the nMARQ (TM) catheter is associated with important device-related limitations to achieve successful PVI. However, clinical outcomes were equivalent in nMARQ (TM)- and SAC-treated patients.
C1 [Wakili, Reza; Siebermair, Johannes; Fichtner, Stephanie; Sinner, Moritz F.; Klocker, Eva; Olesch, Lucia; Sarai, Samira; Clauss, Sebastian; Sattler, Stefan; Kaeaeb, Stefan; Estner, Heidi L.] Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany.
[Wakili, Reza; Kaeaeb, Stefan] Partner Site Munich Heart Alliance, German Cardiovasc Res Ctr DZHK, Munich, Germany.
[Hilberath, Jan N.] Univ Tubingen, Dept Anesthesiol & Crit Care Med, Tubingen, Germany.
[Clauss, Sebastian] Harvard Med Sch, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA.
RP Wakili, R (reprint author), Univ Munich, Univ Hosp Munich, Dept Med 1, Munich, Germany.; Wakili, R (reprint author), Partner Site Munich Heart Alliance, German Cardiovasc Res Ctr DZHK, Munich, Germany.
EM reza.wakili@med.uni-muenchen.de
FU German Center for Cardiovascular Research (DZHK)
FX The study was funded by the German Center for Cardiovascular Research
(DZHK).
NR 14
TC 2
Z9 2
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1099-5129
EI 1532-2092
J9 EUROPACE
JI Europace
PD AUG
PY 2016
VL 18
IS 8
BP 1170
EP 1178
DI 10.1093/europace/euv349
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DV8TD
UT WOS:000383208700010
PM 26759125
ER
PT J
AU Hofmarcher, MM
Festl, E
Bishop-Tarver, L
AF Hofmarcher, Maria M.
Festl, Eva
Bishop-Tarver, Leslie
TI Health sector employment growth calls for improvements in labor
productivity
SO HEALTH POLICY
LA English
DT Article
DE Health workforce; Productivity; Delivery models
ID UNITED-KINGDOM; CARE; EXPENDITURE; INSURANCE; EDUCATION; SERVICES;
LESSONS; DISEASE; REFORM; STATES
AB While rising costs of healthcare have put increased fiscal pressure on public finance, job growth in the health sector has had a stabilizing force on overall employment levels not least in times of economic crises.
In 2014 EU-15 countries employed 21 million people in the health and social care sector. Between 2000 and 2014 the share of employed persons in this sector rose from 9.5% to 12.5% of the total labor force in EU-15 countries. Over time labor input growth has shifted towards residential care activities and social work while labor in human health activities including hospitals and ambulatory care still comprises the major share. About half of the human health labor force works in hospital. Variation of health and social care employment is large even in countries with generally comparable institutional structures. While standard measures of productivity in health and social care are not yet comparable across countries, we argue that labor productivity of a growing health work force needs more attention. The long-term stability of the health system will require care delivery models that better utilize a growing health work force in concert with smart investments in digital infrastructure to support this transition. In light of this, more research is needed to explain variations in health and social care labor endowments, to identify effective policy measures of labor productivity enhancement including enhanced efforts to develop comparable productivity indicators in these areas. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Hofmarcher, Maria M.] HealthSystemIntelligence, Josefstadterstr 14, A-1080 Vienna, Austria.
[Hofmarcher, Maria M.] Med Univ Vienna, Dept Hlth Econ, Kinderspitalgasse 15-1, A-1090 Vienna, Austria.
[Festl, Eva] Kenyongasse 18, A-1070 Vienna, Austria.
[Bishop-Tarver, Leslie] Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St, Boston, MA 02114 USA.
RP Hofmarcher, MM (reprint author), HealthSystemIntelligence, Josefstadterstr 14, A-1080 Vienna, Austria.; Hofmarcher, MM (reprint author), Med Univ Vienna, Dept Hlth Econ, Kinderspitalgasse 15-1, A-1090 Vienna, Austria.
EM maria.hofmarcher@healthsystemintelligence.eu; evafestl@hotmail.com;
lbishop@post.harvard.edu
NR 81
TC 0
Z9 0
U1 8
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0168-8510
EI 1872-6054
J9 HEALTH POLICY
JI Health Policy
PD AUG
PY 2016
VL 120
IS 8
BP 894
EP 902
DI 10.1016/j.healthpol.2016.06.001
PG 9
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DW0DC
UT WOS:000383310100006
PM 27370916
ER
PT J
AU Salahuddin, S
Wenger, JB
Zhang, DS
Thadhani, R
Karumanchi, SA
Rana, S
AF Salahuddin, Saira
Wenger, Julia B.
Zhang, Dongsheng
Thadhani, Ravi
Karumanchi, S. Ananth
Rana, Sarosh
TI KRYPTOR-automated angiogenic factor assays and risk of
preeclampsia-related adverse outcomes
SO HYPERTENSION IN PREGNANCY
LA English
DT Article
DE Adverse maternal and perinatal outcomes; angiogenic factors;
hypertension; KRYPTOR assay; proteinuria; suspected preeclampsia; triage
ID PLACENTAL GROWTH-FACTOR; SUSPECTED PREECLAMPSIA; ANTIANGIOGENIC FACTORS;
WOMEN; HYPERTENSION; BIOMARKERS; DIAGNOSIS; PREGNANCY; DISEASE
AB Objective: To evaluate KRYPTOR assays for circulating soluble fms-like tyrosine kinase-1 (sFlt1) and placental growth factor (PlGF) in risk assessment of adverse outcomes in women with suspected preeclampsia. Methods: We studied 412 women carrying a singleton pregnancy from a previous study cohort who were evaluated for suspected preeclampsia. Another 434 nonpreeclamptic patients with plasma samples drawn throughout pregnancy were used to derive normative data. Plasma sFlt1 and PlGF levels were measured on the automated KRYPTOR platform and evaluated for prediction of adverse maternal and perinatal outcomes within 2 weeks. Normative values were used to create a ratio of markers and these values were reported as multiples of median (MoM) for women with and without adverse outcomes. The KRYPTOR assay results were also compared with previously reported measurements obtained using the automated Elecsys platform. Results: Among participants presenting at <34 weeks (N = 110), patients with subsequent adverse outcome had higher sFlt1, lower PlGF, and higher sFlt1/PlGF ratio compared with women without adverse outcomes: the median (25th, 75th centile) sFlt1 (pg/ml), 9030 (3197, 12,140) versus 1976 (1248, 2937); PlGF (pg/ml), 36 (16, 111) versus 318 (108, 629); and ratio, 285.6 (32.2, 758.5) versus 6.1 (2.3, 20.3) (all p < 0.0001). Higher sFlt1/PlGF ratio correlated negatively with timing of delivery (r = -0.60, p < 0.001) and the risk of adverse outcomes was markedly elevated among women in highest tertile compared with lower tertile (odds ratio, 14.77; 95% confidence interval (CI), 4.28-51.00). The addition of sFlt1/PlGF ratio (85) to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (AUC 0.89 (95% CI): 0.82, 0.95) for hypertension, proteinuria, and sFlt1/PlGF (AUC = 0.75 (0.65, 0.85)) for hypertension alone (p = 0.002). Compared with normative controls, women who were evaluated for preeclampsia without adverse outcomes had higher MoM for sFlt1/PlGF ratio; these values were further elevated in women with adverse outcomes. sFlt1/PlGF ratios measured on the KRYPTOR platform were highly correlated with measurements obtained using Elecys platform (r = 0.97, p < 0.001). Conclusions: In women with suspected preeclampsia presenting prior to 34 weeks of gestation, KRYPTOR assays for circulating sFlt1 and PlGF when used in conjunction with standard clinical evaluation performs well in the prediction of adverse maternal and perinatal outcomes occurring within 2 weeks of presentation.
C1 [Salahuddin, Saira; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA.
[Salahuddin, Saira; Wenger, Julia B.; Zhang, Dongsheng; Thadhani, Ravi; Karumanchi, S. Ananth; Rana, Sarosh] Harvard Med Sch, Boston, MA USA.
[Wenger, Julia B.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA.
[Zhang, Dongsheng; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol, Boston, MA 02215 USA.
[Zhang, Dongsheng; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA.
[Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chicago, IL 60637 USA.
RP Karumanchi, SA (reprint author), Beth Israel Deaconess Med Ctr, 99 Brookline Ave,RN 363, Boston, MA 02215 USA.
EM sananth@bidmc.harvard.edu
FU NIH [K24]; Howard Hughes Medical Institute; ThermoFisher Scientific
FX Ravi Thadhani received funding from K24 award from NIH and S. Ananth
Karumanchi was supported by Howard Hughes Medical Institute and has
received grant support from ThermoFisher Scientific.
NR 27
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Z9 0
U1 0
U2 0
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1064-1955
EI 1525-6065
J9 HYPERTENS PREGNANCY
JI Hypertens. Pregnancy
PD AUG
PY 2016
VL 35
IS 3
BP 330
EP 345
DI 10.3109/10641955.2016.1148162
PG 16
WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease
SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology
GA DV5KN
UT WOS:000382966100007
PM 27028795
ER
PT J
AU James-Todd, T
Cohen, A
Wenger, J
Brown, F
AF James-Todd, Tamarra
Cohen, Allison
Wenger, Julia
Brown, Florence
TI Time-specific placental growth factor (PlGF) across pregnancy and infant
birth weight in women with preexisting diabetes
SO HYPERTENSION IN PREGNANCY
LA English
DT Article
DE Angiogenic factors; macrosomia; placenta; pregnancy
ID CIRCULATING ANGIOGENIC FACTORS; GLUCOSE-LEVELS; FETAL-GROWTH; TYPE-1;
SERUM; MACROSOMIA; PREECLAMPSIA; MELLITUS; OUTCOMES; RISK
AB Objective: Determine the independent association between time-specific placental growth factor (PIGF)a marker of placental vasculatureand infant birth weight in offspring of mothers with preexisting type 1 and 2 diabetes. Methods: A total of 150 women were recruited from Joslin Diabetes Center's/Beth Israel Deaconess Medical Center's Diabetes in Pregnancy Program. PlGF was measured up to four times during pregnancy. Infant birth weight and covariate data were collected from medical records. Hemoglobin A1c was assessed from drawn blood samples. We used generalized linear and log-binomial models to calculate the change in continuous birth weight, as well as macrosomia for every unit change in time-specific ln-transformed PlGF, respectively. Models were adjusted for potential confounders. Results: Approximately 75% of women had type 1 diabetes. Third trimester PlGF levels were significantly associated with infant birth weight (r = 0.24, p = 0.02 at 27-34 weeks; r = 0.26, p < 0.009 for 36-40 weeks). After full adjustment, there was a 6.1% and 6.6% increase in birth weight for gestational age percentile for each unit increase in ln-transformed PlGF level at 27-34 weeks and 35-40 weeks, respectively (95% CI for 27-34 weeks gestation: 1.1, 11.0, and 95% CI for 35-40 weeks gestation: 0.7%, 12.5%). We found a statistically significant increased risk of macrosomia among women with higher ln-transformed PlGF levels (RR: 1.72; 95% CI: 1.09, 2.70). Associations were not mediated by hemoglobin A1c. Conclusions: Third trimester PlGF levels were associated with higher birth weight in women with preexisting diabetes. These findings may provide insight to the pathophysiology of fetal overgrowth in women with diabetes.
C1 [James-Todd, Tamarra] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Dept Epidemiol, Boston, MA USA.
[Cohen, Allison; Brown, Florence] Joslin Diabet Ctr, Adult Diabet Sect, One Joslin Pl, Boston, MA 02215 USA.
[Cohen, Allison; Wenger, Julia; Brown, Florence] Harvard Med Sch, One Joslin Pl, Boston, MA 02215 USA.
[Wenger, Julia] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA.
RP Brown, F (reprint author), Joslin Diabet Ctr, Adult Diabet Sect, One Joslin Pl, Boston, MA 02215 USA.; Brown, F (reprint author), Harvard Med Sch, One Joslin Pl, Boston, MA 02215 USA.
EM Florence.Brown@joslin.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [K12HD051959]; Department of Medicine Seed funds from the
Clinical Investigator Training Program: Beth Israel Deaconess Medical
Center - Harvard/MIT 290 Health Sciences and Technology
FX This study was funded by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (K12HD051959) and the Department
of Medicine Seed funds from the Clinical Investigator Training Program:
Beth Israel Deaconess Medical Center - Harvard/MIT 290 Health Sciences
and Technology.
NR 26
TC 0
Z9 0
U1 1
U2 1
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1064-1955
EI 1525-6065
J9 HYPERTENS PREGNANCY
JI Hypertens. Pregnancy
PD AUG
PY 2016
VL 35
IS 3
BP 436
EP 446
DI 10.3109/10641955.2016.1172085
PG 11
WC Obstetrics & Gynecology; Physiology; Peripheral Vascular Disease
SC Obstetrics & Gynecology; Physiology; Cardiovascular System & Cardiology
GA DV5KN
UT WOS:000382966100017
PM 27336414
ER
PT J
AU Hope, WW
Walsh, TJ
Goodwin, J
Peloquin, CA
Howard, A
Kurtzberg, J
Mendizabal, A
Confer, DL
Bulitta, J
Baden, LR
Neely, MN
Wingard, JR
AF Hope, William W.
Walsh, Thomas J.
Goodwin, Joanne
Peloquin, Charles A.
Howard, Alan
Kurtzberg, Joanne
Mendizabal, Alan
Confer, Dennis L.
Bulitta, Jurgen
Baden, Lindsey R.
Neely, Michael N.
Wingard, John R.
CA Blood Marrow Transplant Clinical
TI Voriconazole pharmacokinetics following HSCT: results from the BMT CTN
0101 trial
SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; FUNGAL-INFECTIONS; AMPHOTERICIN-B;
ASPERGILLOSIS; PROPHYLAXIS; FLUCONAZOLE; POSACONAZOLE; PHARMACODYNAMICS;
ITRACONAZOLE; GUIDELINES
AB Voriconazole is a first-line agent for the prevention and treatment of a number of invasive fungal diseases. Relatively little is known about the relationship between drug exposure and the prevention of invasive fungal infections.
A pharmacokinetic-pharmacodynamic substudy was performed as part of the BMT CTN 0101 trial, which was a randomized clinical trial comparing voriconazole with fluconazole for the prevention of invasive fungal infections in HSCT recipients. A previously described population pharmacokinetic model was used to calculate the maximum a posteriori Bayesian estimates for 187 patients. Drug exposure in each patient was quantified in terms of the average AUC and average trough concentrations. The relationship between drug exposure and the probability of breakthrough infection was investigated using logistic regression. AUC and trough concentrations in patients with and without breakthrough infection were compared.
Pharmacokinetic data from each patient were readily described using the maximum a posteriori Bayesian estimates. There were only five patients that had a breakthrough infection while receiving voriconazole in the first 100 days post-HSCT. For these patients, there was no statistically significant relationship between the average AUC or average trough concentration and the probability of breakthrough infection [OR (95% CI) 1.026 (0.956-1.102) and 1.108 (0.475-2.581), respectively]. P value for these estimates was 0.474 and 0.813, respectively.
Given the very small number of proven/probable infections, it was difficult to identify any differences in drug exposure in HSCT recipients with and without breakthrough fungal infections.
C1 [Hope, William W.; Goodwin, Joanne] Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England.
[Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med, Dept Med, New York, NY 10021 USA.
[Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med, Dept Pediat, New York, NY 10021 USA.
[Walsh, Thomas J.] Cornell Univ, Transplantat Oncol Infect Dis Program, Weill Cornell Med, Dept Microbiol & Immunol, New York, NY 10021 USA.
[Peloquin, Charles A.; Wingard, John R.] Univ Florida, Gainesville, FL USA.
[Howard, Alan] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Kurtzberg, Joanne] Duke Univ, Durham, NC USA.
[Mendizabal, Alan] Emmes Corp, Rockville, MD USA.
[Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA.
[Bulitta, Jurgen] Univ Florida, Coll Pharm, Dept Pharmaceut, Ctr Pharmacometr & Syst Pharmacol, Orlando, FL USA.
[Baden, Lindsey R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Neely, Michael N.] Univ Southern Calif, Los Angeles, CA USA.
RP Hope, WW (reprint author), Univ Liverpool, Dept Mol & Clin Pharmacol, Liverpool, Merseyside, England.
EM william.hope@liverpool.ac.uk
OI Hope, William/0000-0001-6187-878X
FU University of Liverpool; National Institutes of Health Research (NIHR)
in the UK; National Institutes of Health [R01 HD070886, R01 GM068968]
FX This study was supported by internal funding from the University of
Liverpool. W. W. H. is supported by a Clinician Scientist Award from the
National Institutes of Health Research (NIHR) in the UK. T. J. W. is a
Scholar of the Henry Schueler Foundation, an Investigator of Pediatric
Infectious Diseases of the Sharp Family Foundation and a Scholar of the
Save our Sick Kids Foundation. M. N. N. is supported by National
Institutes of Health R01 HD070886 and R01 GM068968.
NR 25
TC 1
Z9 1
U1 2
U2 2
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 AUG
PY 2016
VL 71
IS 8
BP 2234
EP 2240
DI 10.1093/jac/dkw127
PG 7
WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy
GA DV9GU
UT WOS:000383249500027
PM 27121401
ER
PT J
AU Josephs, K
Hu, W
Hillis, A
Dickerson, B
Graff-Radford, N
Davis, C
Akinyemi, R
Ogunniyi, A
Taner, N
Graff-Radford, J
Ali, A
Tang-Wai, D
Wicklund, M
Pasquier, F
Lebert, F
Snowden, J
Fox, N
Grossman, M
Onyike, C
AF Josephs, K.
Hu, W.
Hillis, A.
Dickerson, B.
Graff-Radford, N.
Davis, C.
Akinyemi, R.
Ogunniyi, A.
Taner, N.
Graff-Radford, J.
Ali, A.
Tang-Wai, D.
Wicklund, M.
Pasquier, F.
Lebert, F.
Snowden, J.
Fox, N.
Grossman, M.
Onyike, C.
TI Frontotemporal dementia in patients of African descent
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Josephs, K.; Graff-Radford, J.] Mayo Clin, Neurol, Rochester, MN USA.
[Hu, W.] Emory Univ, Sch Med, Neurol, Atlanta, GA USA.
[Hillis, A.; Davis, C.] Johns Hopkins Med, Neurol, Baltimore, MD USA.
[Dickerson, B.] Massachusets Gen Hosp, Neurol, Boston, MA USA.
[Graff-Radford, N.; Taner, N.] Mayo Clin, Neurol, Jacksonville, FL 32224 USA.
[Akinyemi, R.; Ogunniyi, A.] Univ Ibadan, Neurol, Ibadan, Nigeria.
[Ali, A.] Univ Hosp West Indies, Neurol, Mona, Jamaica.
[Tang-Wai, D.] Univ Toronto, Neurol, Toronto, ON, Canada.
[Wicklund, M.] Univ Florida, Neurol, Gainesville, FL USA.
[Pasquier, F.; Lebert, F.] Ctr Hosp Reg & Univ Lille, Neurol, Lille, France.
[Snowden, J.] Univ Manchester, Neurol, Manchester, Lancs, England.
[Fox, N.] UCL, Inst Neurol, London, England.
[Grossman, M.] Univ Penn, Neurol, Philadelphia, PA 19104 USA.
[Onyike, C.] Johns Hopkins Med, Neuropsychiat, Baltimore, MD 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA DB6
BP 229
EP 229
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400028
ER
PT J
AU Dick, KM
Boeve, BF
Borroni, B
Boxer, A
Brice, A
Butler, CR
Couratier, P
Dickerson, BC
Ducharme, S
Finger, E
Galimberti, D
Gerhard, A
Ghoshal, N
Graff, C
Grossman, M
Hodges, JR
Huey, ED
Laforce, R
Le Ber, I
Levin, J
Mackenzie, R
Masellis, M
Martinaud, O
Mendonca, A
Moreno, F
Nicholas, M
Onyike, CU
Otto, M
Roberson, ED
Rogalski, E
Rosen, HJ
Rowe, JB
Sanchez-Valle, R
Santana, I
Sorbi, S
van Swieten, J
Synofzik, M
Tagliavini, F
Vandenberghe, R
Roher, JD
AF Dick, K. M.
Boeve, B. F.
Borroni, B.
Boxer, A.
Brice, A.
Butler, C. R.
Couratier, P.
Dickerson, B. C.
Ducharme, S.
Finger, E.
Galimberti, D.
Gerhard, A.
Ghoshal, N.
Graff, C.
Grossman, M.
Hodges, J. R.
Huey, E. D.
Laforce, R., Jr.
Le Ber, I.
Levin, J.
Mackenzie, R.
Masellis, M.
Martinaud, O.
Mendonca, A.
Moreno, F.
Nicholas, M.
Onyike, C. U.
Otto, M.
Roberson, E. D.
Rogalski, E.
Rosen, H. J.
Rowe, J. B.
Sanchez-Valle, R.
Santana, I.
Sorbi, S.
van Swieten, J.
Synofzik, M.
Tagliavini, F.
Vandenberghe, R.
Roher, J. D.
TI Symptom onset in genetic frontotemporal dementia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Dick, K. M.; Nicholas, M.; Roher, J. D.] UCL, Inst Neurol, Dementia Res Ctr, London, England.
[Boeve, B. F.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Boeve, B. F.] Mayo Clin, Ctr Sleep Med, Rochester, MN USA.
[Borroni, B.] Univ Brescia, Dept Med & Expt Sci, Neurol Unit, Brescia, Italy.
[Boxer, A.; Rosen, H. J.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
[Brice, A.] Univ Paris 06, Ctr Rech, Inst Cerveau & Moelle Epiniere, Paris, France.
[Butler, C. R.] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
[Couratier, P.] CHU Dupuytren, Serv Neurol, Limoges, France.
[Dickerson, B. C.] Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, Charlestown, MA USA.
[Dickerson, B. C.] Harvard Med Sch, Charlestown, MA USA.
[Ducharme, S.] McGill Univ, McConnell Brain Imaging Ctr, Montreal Neurol Inst, 3801 Univ St, Montreal, PQ, Canada.
[Finger, E.] Univ Western Ontario, Dept Clin Neurol Sci, London, ON, Canada.
[Galimberti, D.] Univ Milan, Dept Physiopathol & Transplantat, Ist Ricovero & Cura Carattere Sci Osped Policlin, Neurol Unit,Fdn Ca Granda, Milan, Italy.
[Gerhard, A.] Univ Manchester, Wolfson Mol Imaging Ctr, Manchester, Lancs, England.
[Ghoshal, N.] Washington Univ, Sch Med, St Louis, MO USA.
[Graff, C.] Karolinska Inst, Div Neurogeriatr, Ctr Alzheimer Res, Dept Neurobiol Care Sci & Soc, Huddinge, Sweden.
[Graff, C.] Karolinska Univ Hosp, Dept Geriatr Med, Genet Unit, Stockholm, Sweden.
[Grossman, M.] Univ Penn, Penn Frontotemporal Degenerat Ctr, Dept Neurol, Philadelphia, PA 19104 USA.
[Hodges, J. R.] Neurosci Res Australia, Sydney, NSW, Australia.
[Hodges, J. R.] Australian Res Council Ctr Excellence Cognit & It, Sydney, NSW, Australia.
[Hodges, J. R.] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia.
[Huey, E. D.] Columbia Univ, Dept Psychiat, New York, NY USA.
[Huey, E. D.] Columbia Univ, Dept Neurol, New York, NY USA.
[Laforce, R., Jr.] Univ Laval, Clin Interdisciplinaire Memoire, Dept Sci Neurol, Hop Enfant Jesus, Quebec City, PQ G1K 7P4, Canada.
[Laforce, R., Jr.] Univ Laval, Fac Med, Quebec City, PQ G1K 7P4, Canada.
[Le Ber, I.] Univ Paris 06, Sorbonne Univ, Inst Cerveau & Moelle Epiniere ICM, CNRS,INSERM,U1127,UMR 7225,UMR S 1127,Hop Pitie S, Paris, France.
[Le Ber, I.] Hop La Pitie Salpetriere, AP HP, Ctr Reference Demences Rares, Paris, France.
[Levin, J.] Univ Munich, Neurol Dept, Marchioninistr, Munich, Germany.
[Mackenzie, R.] Univ British Columbia, Dept Pathol & Lab Med, Div Neuropathol, Vancouver, BC V5Z 1M9, Canada.
[Masellis, M.] Univ Toronto, Sunnybrook Res Inst, Div Neurol, LC Campbell Cognit Neurol Res Unit,Dept Med,Sunny, Toronto, ON, Canada.
[Martinaud, O.] Rouen Univ Hosp, Dept Neurol, Rouen, France.
[Mendonca, A.] Inst Mol Med, Lab Neurosci, Lisbon, Portugal.
[Moreno, F.] Univ Basque Country, Inst Biodonostia, Neurosci Area, San Sebastian, Spain.
[Moreno, F.] Univ Basque Country, Dept Neurosci, San Sebastian, Spain.
[Nicholas, M.] London Sch Hyg & Trop Med, Dept Med Stat, London, England.
[Onyike, C. U.] Johns Hopkins Univ, Baltimore, MD USA.
[Otto, M.] Univ Ulm, Dept Neurol, Ulm, Germany.
[Roberson, E. D.] Center Neurodegenerat & Expt Therapeut, Dept Neurol, Birmingham, AL USA.
[Roberson, E. D.] Center Neurodegenerat & Expt Therapeut, Dept Neurobiol, Birmingham, AL USA.
[Rogalski, E.] Northwestern Univ, Cognit Neurol, Evanston, IL 60208 USA.
[Rogalski, E.] Northwestern Univ, Alzheimers Dis Ctr, Evanston, IL 60208 USA.
[Rowe, J. B.] Univ Cambridge, Dept Clin Neurosci, Cambridge, England.
[Sanchez-Valle, R.] Hosp Clin Barcelona, Alzheimers Dis & Other Cognit Disorders Unit, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Barcelona, Spain.
[Santana, I.] Univ Coimbra, Ctr Neurosci & Cell Biol, Coimbra, Portugal.
[Sorbi, S.] Univ Florence, Dept Neurosci Psychol Drug Res & Child Hlth, Florence, Italy.
[van Swieten, J.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Synofzik, M.] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany.
[Synofzik, M.] German Res Ctr Neurodegenerat Dis DZNE, Tubingen, Germany.
[Tagliavini, F.] Fdn Ist Ricovero & Cura Carattere Sci, Ist Neurol Carlo Besta, Milan, Italy.
[Vandenberghe, R.] Univ Leuven, Dept Neurol, Lab Cognit Neurol, Leuven, Belgium.
[Vandenberghe, R.] Univ Hosp Leuven Gasthuisberg, Leuven, Belgium.
RI Levin, Johannes/E-4052-2010
OI Levin, Johannes/0000-0001-5092-4306
NR 0
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA DB8
BP 232
EP 233
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400033
ER
PT J
AU Taylor, L
McMillan, P
Liachko, N
Saxton, A
Strovas, T
Kraemer, B
AF Taylor, L.
McMillan, P.
Liachko, N.
Saxton, A.
Strovas, T.
Kraemer, B.
TI TTBK1/2 hyper-activation drives pTau and pTDP accumulation
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Taylor, L.; Kraemer, B.] Univ Washington, Med Gerontol & Geriatr Med, Seattle, WA 98195 USA.
[McMillan, P.; Liachko, N.; Saxton, A.; Strovas, T.; Kraemer, B.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA.
[Saxton, A.; Kraemer, B.] Seattle Inst Biomed & Clin Res, Seattle, WA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA DB11
BP 236
EP 236
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400041
ER
PT J
AU Fong, SS
Navarrete, CD
Perfecto, SE
Carr, AR
Jimenez, EE
Mendez, MF
AF Fong, S. S.
Navarrete, C. D.
Perfecto, S. E.
Carr, A. R.
Jimenez, E. E.
Mendez, M. F.
TI Emotion and moral dilemmas in behavioral variant frontotemporal dementia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Fong, S. S.; Perfecto, S. E.; Jimenez, E. E.; Mendez, M. F.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Fong, S. S.; Carr, A. R.; Jimenez, E. E.; Mendez, M. F.] VA Greater Los Angeles Healthcare Ctr, Neurol, Los Angeles, CA USA.
[Navarrete, C. D.] Michigan State Univ, Psychol, E Lansing, MI 48824 USA.
[Mendez, M. F.] Univ Calif Los Angeles, Psychiat & Biobehav Sci, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P55
BP 264
EP 265
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400111
ER
PT J
AU Paholpak, P
Li-Jung, L
Carr, DR
Jimenez, E
Barrows, RJ
Sabodash, V
Mendez, MF
AF Paholpak, P.
Li-Jung, L.
Carr, D. R.
Jimenez, E.
Barrows, R. J.
Sabodash, V.
Mendez, M. F.
TI Prolonged visual facial gaze in frontotemporal dementia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Paholpak, P.] Khon Kaen Univ, Psychiat, Khon Kaen, Thailand.
[Paholpak, P.; Carr, D. R.; Jimenez, E.; Barrows, R. J.; Sabodash, V.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA.
[Paholpak, P.; Jimenez, E.; Barrows, R. J.; Sabodash, V.; Mendez, M. F.] Greater Los Angeles VA Healthcare Syst, Neurol, Los Angeles, CA USA.
[Li-Jung, L.] Univ Calif Los Angeles, Med, Los Angeles, CA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P53
BP 264
EP 264
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400109
ER
PT J
AU Paholpak, P
Carr, DR
Barsuglia, JP
Barrows, RJ
Jimenez, E
Lee, GJ
Mendez, MF
AF Paholpak, P.
Carr, D. R.
Barsuglia, J. P.
Barrows, R. J.
Jimenez, E.
Lee, G. J.
Mendez, M. F.
TI Person-based vs. generalized impulsivity disinhibition in frontotemporal
dementia and Alzheimer's disease
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Paholpak, P.] Khon Kaen Univ, Psychiat, Khon Kaen, Thailand.
[Paholpak, P.; Carr, D. R.; Barrows, R. J.; Jimenez, E.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA.
[Paholpak, P.; Carr, D. R.; Barsuglia, J. P.; Barrows, R. J.; Jimenez, E.; Mendez, M. F.] Greater Los Angeles VA Healthcare Syst, Neurol, Los Angeles, CA USA.
[Lee, G. J.] Loma Linda Univ, Psychol, Loma Linda, CA 92350 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P54
BP 264
EP 264
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400110
ER
PT J
AU Boeve, B
Rosen, H
Boxer, A
Coppola, G
Dheel, C
Dickerson, B
Faber, K
Fields, J
Foroud, T
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Hsiung, R
Huey, E
Irwin, D
Kantarci, K
Karydas, A
Knopman, D
Kornak, J
Kramer, J
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Rankin, K
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Vetor, A
Weintraub, S
Wszolek, Z
AF Boeve, B.
Rosen, H.
Boxer, A.
Coppola, G.
Dheel, C.
Dickerson, B.
Faber, K.
Fields, J.
Foroud, T.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Hsiung, R.
Huey, E.
Irwin, D.
Kantarci, K.
Karydas, A.
Knopman, D.
Kornak, J.
Kramer, J.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Rankin, K.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Vetor, A.
Weintraub, S.
Wszolek, Z.
TI Similar findings on clinical and neuropsychological measures in
asymptomatic mutation versus non-mutation carriers: preliminary data
from LEFFTDS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA.
[Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA.
[Coppola, G.] UCLA, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA USA.
[Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN USA.
[Ghoshal, N.; Graff-Radford, N.] Washington Univ, St Louis, MO USA.
[Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA.
[Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA USA.
[Hsiao, J.; Phelps, C.] NIA, Bethesda, MD USA.
[Hsiung, R.; Mackenzie, I.] Univers British Columbia, Vancouver, BC, Canada.
[Kukull, W.] Univ Washington, Seattle, WA USA.
[Sutherland, M.] NINDS, Bethesda, MD USA.
[Toga, A.] USC, LONI, Los Angeles, CA USA.
[Weintraub, S.] Northwestern Univ, Chicago, IL 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P118
BP 287
EP 287
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400173
ER
PT J
AU Rosen, H
Boeve, B
Boxer, A
Coppola, G
Dheel, C
Dickerson, B
Faber, K
Fields, J
Faroud, T
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Hsiung, GYR
Huey, ED
Irwin, D
Kantarci, K
Karydas, A
Knopman, D
Kornak, J
Kramer, J
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Rankin, K
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Vetor, A
Weintraub, S
Wszolek, Z
AF Rosen, H.
Boeve, B.
Boxer, A.
Coppola, G.
Dheel, C.
Dickerson, B.
Faber, K.
Fields, J.
Faroud, T.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Hsiung, G. -Y. R.
Huey, E. D.
Irwin, D.
Kantarci, K.
Karydas, A.
Knopman, D.
Kornak, J.
Kramer, J.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Rankin, K.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Vetor, A.
Weintraub, S.
Wszolek, Z.
TI Differences on neuropsychiatric measures in asymptomatic (CDR=0) versus
mildly symptomatic (CDR=0.5) mutation carriers: preliminary data from
LEFFTDS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Rosen, H.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA.
[Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA.
[Coppola, G.; Toga, A.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Faber, K.; Faroud, T.] Indiana Univ, Indianapolis, IN 46204 USA.
[Ghoshal, N.; Vetor, A.] Washington Univ, St Louis, MO USA.
[Goldman, J.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA.
[Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA.
[Hsiung, G. -Y. R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Weintraub, S.] Norhtwestern Univ, Chicago, IL 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P119
BP 287
EP 287
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400174
ER
PT J
AU Kramer, J
Weintraub, S
Boeve, B
Rosen, H
Boxer, A
Coppola, G
Dheel, C
Dickerson, B
Faber, K
Fields, J
Faroud, T
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Hsiung, R
Huey, E
Irwin, D
Kantarci, K
Karydas, A
Knopman, D
Kornak, J
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Rankin, K
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Vetor, A
Wszolek, Z
AF Kramer, J.
Weintraub, S.
Boeve, B.
Rosen, H.
Boxer, A.
Coppola, G.
Dheel, C.
Dickerson, B.
Faber, K.
Fields, J.
Faroud, T.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Hsiung, R.
Huey, E.
Irwin, D.
Kantarci, K.
Karydas, A.
Knopman, D.
Kornak, J.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Rankin, K.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Vetor, A.
Wszolek, Z.
TI Differences on neuropsychological measures in asymptomatic (CDR=0)
versus mildly symptomatic (CDR=0.5) mutation carriers: preliminary data
from LEFFTDS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Kramer, J.; Rosen, H.; Boxer, A.; Heuer, H.; Kantarci, K.; Kornak, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA.
[Weintraub, S.] Northwestern, Chicago, IL USA.
[Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA.
[Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Faber, K.; Faroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Ghoshal, N.] Washington Univ, St Louis, MO USA.
[Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA.
[Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA.
[Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Toga, A.] USC, LONI, Los Angeles, CA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P127
BP 290
EP 291
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400182
ER
PT J
AU Fong, S
Mendez, MF
AF Fong, S.
Mendez, M. F.
TI Variables affecting emotional reactivity to socioemotional stimuli in
frontotemporal dementia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Fong, S.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA.
[Fong, S.; Mendez, M. F.] VA Greater Los Angeles Healthcare Ctr, Neurol, Los Angeles, CA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P148
BP 298
EP 298
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400202
ER
PT J
AU Rankin, K
Kramer, J
Rosen, H
Boeve, B
Boxer, A
Coppola, G
Dickerson, B
Dheel, C
Fields, J
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Hsiung, R
Huey, E
Irwin, D
Kantarci, K
Karydas, A
Kornak, J
Knopman, D
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Vetor, A
Weintraub, S
Wszolek, Z
AF Rankin, K.
Kramer, J.
Rosen, H.
Boeve, B.
Boxer, A.
Coppola, G.
Dickerson, B.
Dheel, C.
Fields, J.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Hsiung, R.
Huey, E.
Irwin, D.
Kantarci, K.
Karydas, A.
Kornak, J.
Knopman, D.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Vetor, A.
Weintraub, S.
Wszolek, Z.
TI Differences on novel measures of social comportment in asymptomatic
(CDR=0) versus mildly symptomatic (CDR=0.5) mutation carriers:
preliminary data from LEFFTDS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Rankin, K.; Kramer, J.; Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Miller, B.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA.
[Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA.
[Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ghoshal, N.] Washington Univ, St Louis, MO USA.
[Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA.
[Grossman, M.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA.
[Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Toga, A.] USC LONI, Los Angeles, CA USA.
[Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P150
BP 299
EP 299
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400204
ER
PT J
AU Fong, SS
Carr, AR
Daianu, M
Deutsch, MB
Jimenez, EE
Juarez, KO
Mather, MM
Paholpak, P
Perfecto, SE
Thompson, PM
Mendez, MF
AF Fong, S. S.
Carr, A. R.
Daianu, M.
Deutsch, M. B.
Jimenez, E. E.
Juarez, K. O.
Mather, M. M.
Paholpak, P.
Perfecto, S. E.
Thompson, P. M.
Mendez, M. F.
TI The attribution of animacy and agency in frontotemporal dementia vs.
Alzheimer's disease
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Fong, S. S.; Deutsch, M. B.; Jimenez, E. E.; Juarez, K. O.; Mather, M. M.; Paholpak, P.; Perfecto, S. E.; Mendez, M. F.] Univ Calif Los Angeles, Neurol, Los Angeles, CA USA.
[Fong, S. S.; Carr, A. R.; Deutsch, M. B.; Jimenez, E. E.; Juarez, K. O.; Mather, M. M.; Paholpak, P.; Mendez, M. F.] VA Greater Los Angeles Healthcare Ctr, Neurol, Los Angeles, CA USA.
[Daianu, M.; Thompson, P. M.] Univ Southern Calif, Imaging Genet Ctr, Mark & Mary Stevens Neuroimaging & Informat Inst, Los Angeles, CA USA.
[Deutsch, M. B.] Icahn Sch Med Mt Sinai, Neurol, New York, NY 10029 USA.
[Paholpak, P.] Khon Kaen Univ, Psychiat, Khon Kaen, Thailand.
[Thompson, P. M.] Univ Southern Calif, Psychiat, Los Angeles, CA USA.
[Thompson, P. M.] Univ Southern Calif, Radiol, Los Angeles, CA USA.
[Thompson, P. M.] Univ Southern Calif, Engn, Los Angeles, CA USA.
[Thompson, P. M.] Univ Southern Calif, Pediat, Los Angeles, CA USA.
[Thompson, P. M.] Univ Southern Calif, Ophthalmol, Los Angeles, CA USA.
[Thompson, P. M.] Univ Southern Calif, Neurol, Los Angeles, CA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P153
BP 300
EP 300
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400207
ER
PT J
AU Boeve, B
Rosen, H
Boxer, A
Coppola, G
Dheel, C
Dickerson, B
Faber, K
Fields, J
Foroud, T
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Hsiung, R
Huey, E
Irwin, D
Kantarci, K
Karydas, A
Knopman, D
Kornak, J
Kramer, J
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Rankin, K
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Vetor, A
Weintraub, S
Wszolek, Z
AF Boeve, B.
Rosen, H.
Boxer, A.
Coppola, G.
Dheel, C.
Dickerson, B.
Faber, K.
Fields, J.
Foroud, T.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Hsiung, R.
Huey, E.
Irwin, D.
Kantarci, K.
Karydas, A.
Knopman, D.
Kornak, J.
Kramer, J.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Rankin, K.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Vetor, A.
Weintraub, S.
Wszolek, Z.
TI Characteristics and Progress on the Initial 147 Subjects in the
Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects
(LEFFTDS) Protocol
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Boeve, B.; Dheel, C.; Fields, J.; Gavrilova, R.; Kantarci, K.; Knopman, D.] Mayo Clin, Rochester, MN USA.
[Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] UCSF, San Francisco, CA USA.
[Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA.
[Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA.
[Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Hsiao, J.; Phelps, C.] NIA, Bethesda, MD 20892 USA.
[Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Sutherland, M.] NINDS, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
[Toga, A.] LONI, USC, Los Angeles, CA USA.
[Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P172
BP 309
EP 309
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400226
ER
PT J
AU Knopman, D
Boeve, B
Rosen, H
Boxer, A
Coppola, G
Dheel, C
Dickerson, B
Faber, K
Fields, J
Foroud, T
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Huey, E
Hsiung, R
Irwin, D
Kantarci, K
Karydas, A
Kornak, J
Kramer, J
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Rankin, K
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Weintraub, S
Wszolek, Z
Vetor, A
AF Knopman, D.
Boeve, B.
Rosen, H.
Boxer, A.
Coppola, G.
Dheel, C.
Dickerson, B.
Faber, K.
Fields, J.
Foroud, T.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Huey, E.
Hsiung, R.
Irwin, D.
Kantarci, K.
Karydas, A.
Kornak, J.
Kramer, J.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Rankin, K.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Weintraub, S.
Wszolek, Z.
Vetor, A.
TI Absence of differences on key measures in mildly (CDR=0.5) versus
overtly (CDR >= 1) symptomatic mutation carriers: preliminary data from
LEFFTDS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Knopman, D.; Boeve, B.; Dheel, C.] Mayo Clin, Neurol, Rochester, MN USA.
[Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA.
[Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Fields, J.; Gavrilova, R.; Kantarci, K.] Mayo Clin, Rochester, MN USA.
[Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA.
[Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA.
[Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Hsiao, J.; Phelps, C.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Toga, A.] LONI, USC, Los Angeles, CA USA.
[Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P189
BP 316
EP 316
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400243
ER
PT J
AU Knopman, D
Boeve, B
Rosen, H
Boxer, A
Coppola, G
Dheel, C
Dickerson, B
Faber, K
Fields, J
Foroud, T
Gavrilova, R
Ghoshal, N
Goldman, J
Graff-Radford, N
Grossman, M
Heuer, H
Hsiao, J
Hsiung, R
Huey, E
Irwin, D
Kantarci, K
Karydas, A
Kramer, J
Kukull, W
Mackenzie, I
Miller, B
Phelps, C
Rademakers, R
Rankin, K
Shaw, L
Sutherland, M
Toga, A
Trojanowski, J
Vetor, A
Weintraub, S
Wszolek, Z
AF Knopman, D.
Boeve, B.
Rosen, H.
Boxer, A.
Coppola, G.
Dheel, C.
Dickerson, B.
Faber, K.
Fields, J.
Foroud, T.
Gavrilova, R.
Ghoshal, N.
Goldman, J.
Graff-Radford, N.
Grossman, M.
Heuer, H.
Hsiao, J.
Hsiung, R.
Huey, E.
Irwin, D.
Kantarci, K.
Karydas, A.
Kramer, J.
Kukull, W.
Mackenzie, I.
Miller, B.
Phelps, C.
Rademakers, R.
Rankin, K.
Shaw, L.
Sutherland, M.
Toga, A.
Trojanowski, J.
Vetor, A.
Weintraub, S.
Wszolek, Z.
TI Differences on clinical measures in asymptomatic (CDR=0) versus mildly
symptomatic (CDR=0.5) mutation carriers: preliminary data from LEFFTDS
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Knopman, D.; Boeve, B.; Dheel, C.; Gavrilova, R.] Mayo Clin, Neurol, Rochester, MN USA.
[Rosen, H.; Boxer, A.; Heuer, H.; Karydas, A.; Kramer, J.; Miller, B.; Rankin, K.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 USA.
[Coppola, G.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Faber, K.; Foroud, T.; Vetor, A.] Indiana Univ, Indianapolis, IN 46204 USA.
[Fields, J.] Mayo Clin, Psychiat, Rochester, MN USA.
[Ghoshal, N.] Washington Univ, St Louis, MO 63130 USA.
[Goldman, J.; Huey, E.] Columbia Univ, New York, NY USA.
[Graff-Radford, N.; Rademakers, R.; Wszolek, Z.] Mayo Clin, Jacksonville, FL USA.
[Grossman, M.; Irwin, D.; Shaw, L.; Trojanowski, J.] Univ Penn, Philadelphia, PA 19104 USA.
[Hsiao, J.; Phelps, C.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada.
[Kantarci, K.] Mayo Clin, Radiol, Rochester, MN USA.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Toga, A.] LONI, USC, Los Angeles, CA USA.
[Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P191
BP 317
EP 317
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400245
ER
PT J
AU Gendron, T
van Blitterswijk, M
Bieniek, K
Daughrity, L
Jiang, J
Rush, B
Pedraza, O
Lucas, J
Murray, M
Desaro, P
Robertson, A
Overstreet, K
Thomas, C
Crook, J
Castanedes-Casey, M
Rousseau, L
Josephs, K
Parisi, J
Knopman, D
Petersen, R
Boeve, B
Graff-Radford, N
Rademakers, R
Lagier-Tourenne, C
Edbauer, D
Cleveland, D
Dickson, D
Petrucelli, L
Boylan, K
AF Gendron, T.
van Blitterswijk, M.
Bieniek, K.
Daughrity, L.
Jiang, J.
Rush, B.
Pedraza, O.
Lucas, J.
Murray, M.
Desaro, P.
Robertson, A.
Overstreet, K.
Thomas, C.
Crook, J.
Castanedes-Casey, M.
Rousseau, L.
Josephs, K.
Parisi, J.
Knopman, D.
Petersen, R.
Boeve, B.
Graff-Radford, N.
Rademakers, R.
Lagier-Tourenne, C.
Edbauer, D.
Cleveland, D.
Dickson, D.
Petrucelli, L.
Boylan, K.
TI Cerebellar c9RAN proteins associate with clinical and neuropathological
characteristics of C9ORF72 repeat expansion carriers
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Gendron, T.; van Blitterswijk, M.; Bieniek, K.; Daughrity, L.; Murray, M.; Castanedes-Casey, M.; Rousseau, L.; Rademakers, R.; Dickson, D.; Petrucelli, L.] Mayo Clin, Neurosci, Jacksonville, FL 32224 USA.
[Jiang, J.; Cleveland, D.] Univ Calif San Diego, Ludwig Inst, La Jolla, CA USA.
[Rush, B.; Pedraza, O.; Lucas, J.; Desaro, P.; Robertson, A.; Overstreet, K.; Graff-Radford, N.; Boylan, K.] Mayo Clin, Neurol, Jacksonville, FL 32224 USA.
[Thomas, C.; Crook, J.] Mayo Clin, Sect Biostat, Jacksonville, FL 32224 USA.
[Josephs, K.; Parisi, J.; Knopman, D.; Petersen, R.; Boeve, B.] Mayo Clin, Neurol, Rochester, MN USA.
[Lagier-Tourenne, C.] Massachusetts Gen Hosp, Inst Neurodegenerat Dis, Charlestown, MA USA.
[Edbauer, D.] Univ Munich, Inst Metab Biochem, Munich, Germany.
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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P251
BP 339
EP 340
PG 2
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400303
ER
PT J
AU Collins, J
Montal, V
Gorno-Tempini, ML
Dickerson, B
AF Collins, J.
Montal, V.
Gorno-Tempini, M. L.
Dickerson, B.
TI Focal temporal pole atrophy and network degeneration in semantic variant
primary progressive aphasia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Collins, J.; Dickerson, B.] Massachusetts Gen Hosp, Neurol, Charlestown, MA USA.
[Collins, J.; Dickerson, B.] Harvard Med Sch, Charlestown, MA USA.
[Montal, V.] Univ Autonoma Barcelona, Neurol, Barcelona, Spain.
[Gorno-Tempini, M. L.] Univ Calif San Francisco, Neurol, San Francisco, CA 94143 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P264
BP 345
EP 345
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400316
ER
PT J
AU Veronelli, L
Makaretz, SJ
Quimby, M
Corbo, M
Dickerson, BC
AF Veronelli, L.
Makaretz, S. J.
Quimby, M.
Corbo, M.
Dickerson, B. C.
TI Predictors of conversion to dementia in primary progressive aphasia
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Veronelli, L.; Corbo, M.] Casa Cura Policlin, Dept Neurorehabil Sci, Milan, Italy.
[Veronelli, L.; Makaretz, S. J.; Quimby, M.; Dickerson, B. C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Veronelli, L.; Makaretz, S. J.; Quimby, M.; Dickerson, B. C.] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P300
BP 357
EP 357
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400352
ER
PT J
AU Dutt, S
Binney, R
Heuer, H
Luong, P
Attygalle, S
Bhatt, P
Marx, G
Elofson, J
Tartaglia, MC
Litvan, I
McGinnis, S
Dickerson, B
Kornak, J
Waltzman, D
Voltarelli, L
Schuff, N
Rabinovici, G
Kramer, J
Jack, C
Miller, B
Boxer, A
AF Dutt, S.
Binney, R.
Heuer, H.
Luong, P.
Attygalle, S.
Bhatt, P.
Marx, G.
Elofson, J.
Tartaglia, M. C.
Litvan, I.
McGinnis, S.
Dickerson, B.
Kornak, J.
Waltzman, D.
Voltarelli, L.
Schuff, N.
Rabinovici, G.
Kramer, J.
Jack, C.
Miller, B.
Boxer, A.
TI Rapid progression of brain atrophy in progressive supranuclear palsy and
corticobasal degeneration
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Dutt, S.; Binney, R.; Heuer, H.; Luong, P.; Attygalle, S.; Bhatt, P.; Marx, G.; Elofson, J.; Waltzman, D.; Voltarelli, L.; Rabinovici, G.; Kramer, J.; Miller, B.; Boxer, A.] UCSF, Neurol, San Francisco, CA USA.
[Binney, R.] Temple Univ, Commun Sci & Disorders, Philadelphia, PA 19122 USA.
[Tartaglia, M. C.] Univ Toronto, Toronto, ON, Canada.
[Litvan, I.] Univ Calif San Diego, Neurosci, San Diego, CA USA.
[McGinnis, S.; Dickerson, B.] Massachusetts Gen Hosp, Gerontol, Charlestown, MA USA.
[Kornak, J.] UCSF, Epidemiol & Biostat, San Francisco, CA USA.
[Waltzman, D.] Stanford Univ, Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Schuff, N.] UCSF, Radiol, San Francisco, CA USA.
[Jack, C.] Mayo Clin, Radiol, Rochester, MN 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P313
BP 363
EP 363
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400365
ER
PT J
AU Luong, D
Voltarelli, L
Heuer, H
Kornak, J
Domoto-Reilly, K
Dickerson, B
Litvan, I
Tartaglia, MC
Miller, B
Boxer, A
AF Luong, D.
Voltarelli, L.
Heuer, H.
Kornak, J.
Domoto-Reilly, K.
Dickerson, B.
Litvan, I.
Tartaglia, M. C.
Miller, B.
Boxer, A.
TI Measuring clinical and cognitive decline in CBD and PSP for multicenter
clinical trials - the 4-repeat tauopathy neuroimaging initiative (4RTNI)
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Luong, D.; Voltarelli, L.; Heuer, H.; Kornak, J.; Miller, B.; Boxer, A.] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA USA.
[Domoto-Reilly, K.; Dickerson, B.] Massachusetts Gen Hosp, Frontotemporal Disorders Unit, Boston, MA 02114 USA.
[Litvan, I.] Univ Calif San Diego, Dept Neurosci, Movement Disorder Ctr, San Diego, CA 92103 USA.
[Tartaglia, M. C.] Univ Toronto, Tanz Ctr Res Neurodegenerat Dis, Toronto, ON, Canada.
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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P335
BP 371
EP 371
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400386
ER
PT J
AU Boxer, A
Rosen, H
Boeve, B
Heuer, H
Laxineta, S
Grossman, M
Coppola, G
Dickerson, B
Bordelon, Y
Conwit, R
Dheel, C
Faber, K
Feldman, H
Ferguson, J
Fields, J
Fong, J
Foroud, T
Galpern, W
Ghoshal, N
Graff-Radford, N
Hsiung, R
Huey, E
Irwin, D
Kantarci, K
Kaufer, D
Karydas, A
Klein, A
Knopman, D
Kornak, J
Kramer, J
Kukull, W
Litvan, I
Mackenzie, I
Mendez, M
Miller, B
Miller, M
Onyike, C
Pantelyat, A
Rademakers, R
Roberson, E
Sutherland, M
Tartaglia, MC
Tatton, N
Toga, A
Vetor, A
Weintraub, S
Wszolek, Z
AF Boxer, A.
Rosen, H.
Boeve, B.
Heuer, H.
Laxineta, S.
Grossman, M.
Coppola, G.
Dickerson, B.
Bordelon, Y.
Conwit, R.
Dheel, C.
Faber, K.
Feldman, H.
Ferguson, J.
Fields, J.
Fong, J.
Foroud, T.
Galpern, W.
Ghoshal, N.
Graff-Radford, N.
Hsiung, R.
Huey, E.
Irwin, D.
Kantarci, K.
Kaufer, D.
Karydas, A.
Klein, A.
Knopman, D.
Kornak, J.
Kramer, J.
Kukull, W.
Litvan, I.
Mackenzie, I.
Mendez, M.
Miller, B.
Miller, M.
Onyike, C.
Pantelyat, A.
Rademakers, R.
Roberson, E.
Sutherland, M.
Tartaglia, M. C.
Tatton, N.
Toga, A.
Vetor, A.
Weintraub, S.
Wszolek, Z.
TI Characteristics and progress on the Initial 256 participants in the
advancing research and treatment in frontotemporal lobar degeneration
(ARTFL) North American Rare disease clinical research consortium
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Boxer, A.; Rosen, H.; Heuer, H.; Laxineta, S.; Fong, J.; Karydas, A.; Kornak, J.; Kramer, J.; Miller, B.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Boeve, B.; Dheel, C.; Fields, J.; Kantarci, K.; Knopman, D.; Miller, M.] Mayo Clin, Rochester, MN USA.
[Grossman, M.; Irwin, D.] Univ Penn, Philadelphia, PA 19104 USA.
[Coppola, G.; Bordelon, Y.; Mendez, M.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Dickerson, B.] Massachusetts Gen Hosp, Cambridge, MA USA.
[Conwit, R.; Ferguson, J.; Sutherland, M.] NIH, Bldg 10, Bethesda, MD 20892 USA.
[Faber, K.; Foroud, T.; Vetor, A.] NCRAD, Indianapolis, IN USA.
[Feldman, H.; Hsiung, R.; Mackenzie, I.] Univ British Columbia, Vancouver, BC, Canada.
[Galpern, W.] Janssen Pharmaceut, Washington, DC USA.
[Ghoshal, N.] Washington Univ, St Louis, MO USA.
[Graff-Radford, N.; Rademakers, R.; Roberson, E.; Wszolek, Z.] Mayo Clin, Jacksonville, FL 32224 USA.
[Huey, E.] Columbia Univ, New York, NY USA.
[Kaufer, D.] Univ N Carolina, Chapel Hill, NC USA.
[Klein, A.] CurePSP, New York, NY USA.
[Kukull, W.] Univ Washington, Seattle, WA 98195 USA.
[Litvan, I.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Mendez, M.; Onyike, C.; Pantelyat, A.] Johns Hopkins Univ, Baltimore, MD USA.
[Roberson, E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Tartaglia, M. C.] Univ Toronto, Toronto, ON, Canada.
[Tatton, N.] AFTD, Radnor, PA USA.
[Toga, A.] Univ Southern Calif, Los Angeles, CA USA.
[Weintraub, S.] Northwestern Univ, Chicago, IL 60611 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P352
BP 379
EP 379
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400403
ER
PT J
AU Rosen, H
Knopman, D
Dickerson, B
Boeve, B
Urbano, M
Caplan, A
Laxineta, S
Miller, B
AF Rosen, H.
Knopman, D.
Dickerson, B.
Boeve, B.
Urbano, M.
Caplan, A.
Laxineta, S.
Miller, B.
TI Results from the frontotemporal lobar degeneration neuroimaging
initiative (FTLDNI)
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Rosen, H.; Urbano, M.; Caplan, A.; Laxineta, S.; Miller, B.] Univ Calif San Francisco, Neurol, San Francisco, CA USA.
[Knopman, D.; Boeve, B.] Mayo Clin, Rochester, MN USA.
[Dickerson, B.] Massachusetts Gen Hosp, Boston, MA 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 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P393
BP 396
EP 396
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400444
ER
PT J
AU Castrillon, G
Velilla, L
Giraldo, M
Zapata, A
Bustamante, C
Lopera, F
Quiroz, Y
AF Castrillon, G.
Velilla, L.
Giraldo, M.
Zapata, A.
Bustamante, C.
Lopera, F.
Quiroz, Y.
TI Functional connectivity differences between behavioral-variant
frontotemporal dementia and early-onset Alzheimer's disease
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Meeting Abstract
CT 10th International Conference on Frontotemporal Dementias
CY AUG 31-SEP 02, 2016
CL Munich, GERMANY
C1 [Castrillon, G.; Bustamante, C.] Inst Alta Tecnol Med, Medellin, Colombia.
[Castrillon, G.] TUM NIC, Techn Univ Munich, Munich, Colombia.
[Velilla, L.; Giraldo, M.; Zapata, A.; Lopera, F.; Quiroz, Y.] Grp Neuroci Antioquia, Medellin, Colombia.
[Quiroz, Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD AUG
PY 2016
VL 138
SU 1
SI SI
MA P424
BP 407
EP 407
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA DU9WI
UT WOS:000382568400475
ER
PT J
AU Chandra, RV
Chan, NC
Leslie-Mazwi, TM
Mehta, BP
Hirsch, JA
AF Chandra, Ronil V.
Chan, Noel C.
Leslie-Mazwi, Thabele M.
Mehta, Brijesh P.
Hirsch, Joshua A.
TI Platelet function testing: does a randomized controlled trial settle the
debate?
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Editorial Material
DE Aneurysm; Platelets
ID NEUROINTERVENTIONAL PROCEDURES; THERAPY; PRASUGREL; STANDARD
C1 [Chandra, Ronil V.] Monash Hlth, Monash Imaging, Intervent Neuroradiol Unit, 246 Clayton Rd, Melbourne, Vic 3168, Australia.
[Chandra, Ronil V.; Chan, Noel C.] Monash Univ, Dept Med, Melbourne, Vic, Australia.
[Chan, Noel C.] Monash Hlth, Dept Haematol, Melbourne, Vic, Australia.
[Leslie-Mazwi, Thabele M.; Hirsch, Joshua A.] Harvard Med Sch, Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA USA.
[Mehta, Brijesh P.] Mem Neurosci Inst, Hollywood, FL USA.
RP Chandra, RV (reprint author), Monash Hlth, Monash Imaging, Intervent Neuroradiol Unit, 246 Clayton Rd, Melbourne, Vic 3168, Australia.
EM ronil.chandra@monashhealth.org
NR 11
TC 0
Z9 0
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
EI 1759-8486
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD AUG
PY 2016
VL 8
IS 8
BP 768
EP 769
DI 10.1136/neurintsurg-2015-011954
PG 2
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA DU3YO
UT WOS:000382148800007
PM 26206806
ER
PT J
AU Hirsch, JA
Leslie-Mazwi, TM
Patel, AB
Rabinov, JD
Gonzalez, RG
Barr, RM
Nicola, GN
Klucznik, RP
Prestigiacomo, CJ
Manchikanti, L
AF Hirsch, Joshua A.
Leslie-Mazwi, Thabele M.
Patel, Aman B.
Rabinov, James D.
Gonzalez, Ramon G.
Barr, Robert M.
Nicola, Gregory N.
Klucznik, Richard P.
Prestigiacomo, Charles J.
Manchikanti, Laxmaiah
TI MACRA: background, opportunities and challenges for the
neurointerventional specialist
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Review
DE Political; Economics
ID SUSTAINABLE GROWTH-RATE; INTERVENTIONAL PAIN MANAGEMENT; RELATIVE-VALUE;
STICK POLICY; RATE FORMULA; CARE; REPEAL; CARROT; PRIMER
AB The legislative branch of government took many by surprise when it announced the Medicare Access and CHIP Reauthorization Act of 2015. Once the Act was passed, President Obama quickly signed this bipartisan, bicameral effort into law. A foundational element of this legislation was the permanent repeal of the sustainable growth rate formula. Physicians and their patients were appropriately enthusiastic about this development. The Medicare Access and CHIP Reauthorization Act of 2015 included additional elements of considerable interest to neurointerventional specialists.
C1 [Hirsch, Joshua A.; Leslie-Mazwi, Thabele M.; Patel, Aman B.; Rabinov, James D.] Harvard Med Sch, Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA.
[Gonzalez, Ramon G.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA USA.
[Barr, Robert M.] Mecklenburg Radiol Associates PA, Charlotte, NC USA.
[Nicola, Gregory N.] Hackensack Univ, Med Ctr, Hackensack, NJ USA.
[Klucznik, Richard P.] Cornell Univ, Weill Med Coll, Houston Methodist Neurol Inst, Houston, TX USA.
[Prestigiacomo, Charles J.] Rutgers New Jersey Med Sch, Dept Neurol Surg, Newark, NJ USA.
[Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA.
[Manchikanti, Laxmaiah] Univ Louisville, Dept Anesthesiol & Perioperat Med, Louisville, KY 40292 USA.
RP Hirsch, JA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, NeuroEndovasc Program, Boston, MA 02114 USA.
EM Hirsch@snisonline.org
NR 26
TC 9
Z9 9
U1 1
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
EI 1759-8486
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD AUG
PY 2016
VL 8
IS 8
BP 868
EP 874
DI 10.1136/neurintsurg-2015-011952
PG 7
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA DU3YO
UT WOS:000382148800027
PM 26220409
ER
PT J
AU Jinno, S
Hasegawa, K
Neogi, T
Goto, T
Dubreuil, M
AF Jinno, Sadao
Hasegawa, Kohei
Neogi, Tuhina
Goto, Tadahiro
Dubreuil, Maureen
TI Trends in Emergency Department Visits and Charges for Gout in the United
States between 2006 and 2012
SO JOURNAL OF RHEUMATOLOGY
LA English
DT Article
DE GOUT; EPIDEMIOLOGY; OUTCOME ASSESSMENT
ID HEALTH; CARE; FREQUENCY
AB Objective. To examine temporal trends in the rate of gout emergency department (ED) visits and charges in the United States between 2006 and 2012.
Methods. A serial cross-sectional analysis of the Nationwide Emergency Department Sample.
Results. The rate of ED visits for gout in adults overall increased from 75.0 to 85.4 per 100,000 persons over the study period (14% increase, p < 0.001), and increased 29% for those aged 45-54 years. Nationwide ED charges increased from $156 million to $281 million (80% increase, p < 0.001).
Conclusion. Between 2006 and 2012, the rate of gout ED visits increased among US adults, most notably in those aged 45-54 years.
C1 [Jinno, Sadao; Neogi, Tuhina; Dubreuil, Maureen] Boston Univ, Sch Med, Dept Med, Rheumatol Sect, Boston, MA 02118 USA.
[Hasegawa, Kohei] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Neogi, Tuhina] Boston Univ, Sch Med, Dept Med, Sect Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA.
[Goto, Tadahiro; Dubreuil, Maureen] VA Boston Healthcare Syst, Boston, MA USA.
RP Jinno, S (reprint author), Boston Univ, Sch Med, Dept Med, Rheumatol Sect, Boston, MA 02118 USA.
EM Sadao.jinno@bmc.org
FU NIAMS NIH HHS [P60 AR047785]
NR 15
TC 3
Z9 3
U1 0
U2 0
PU J RHEUMATOL PUBL CO
PI TORONTO
PA 365 BLOOR ST E, STE 901, TORONTO, ONTARIO M4W 3L4, CANADA
SN 0315-162X
EI 1499-2752
J9 J RHEUMATOL
JI J. Rheumatol.
PD AUG
PY 2016
VL 43
IS 8
BP 1589
EP 1592
DI 10.3899/jrheum.151432
PG 4
WC Rheumatology
SC Rheumatology
GA DS6HG
UT WOS:000380882300022
PM 27252429
ER
PT J
AU Spence, RT
Zargaran, E
Hameed, SM
Navsaria, P
Nicol, A
AF Spence, Richard Trafford
Zargaran, Eiman
Hameed, S. Morad
Navsaria, Pradeep
Nicol, Andrew
TI Mobile health technology transforms injury severity scoring in South
Africa
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Injury severity scoring; mHealth technology; Quality improvement
ID KAMPALA TRAUMA SCORE; QUALITY IMPROVEMENT PROGRAM; IN-HOSPITAL
MORTALITY; LOW-RESOURCE SETTINGS; DATA-BANK ITDB; TRISS METHOD; CARE;
SURVEILLANCE; SCALE; EXPERIENCE
AB Background: The burden of data collection associated with injury severity scoring has limited its application in areas of the world with the highest incidence of trauma.
Material and Methods: Since January 2014, electronic records (electronic Trauma Health Records [eTHRs]) replaced all handwritten records at the Groote Schuur Hospital Trauma Unit in South Africa. Data fields required for Glasgow Coma Scale, Revised Trauma Score, Kampala Trauma Score, Injury Severity Score (ISS), and Trauma Score-Injury Severity Score calculations are now prospectively collected. Fifteen months after implementation of eTHR, the injury severity scores were compared as predictors of mortality on three accounts: (1) ability to discriminate (area under receiver operating curve, ROC); (2) ability to calibrate (observed versus expected ratio, O/E); and (3) feasibility of data collection (rate of missing data).
Results: A total of 7460 admissions were recorded by eTHR from April 1, 2014 to July 7, 2015, including 770 severely injured patients (ISS > 15) and 950 operations. The mean age was 33.3 y (range 13-94), 77.6% were male, and the mechanism of injury was penetrating in 39.3% of cases. The cohort experienced a mortality rate of 2.5%. Patient reserve predictors required by the scores were 98.7% complete, physiological injury predictors were 95.1% complete, and anatomic injury predictors were 86.9% complete. The discrimination and calibration of Trauma Score-Injury Severity Score was superior for all admissions (ROC 0.9591 and O/E 1.01) and operatively managed patients (ROC 0.8427 and O/E 0.79). In the severely injured cohort, the discriminatory ability of Revised Trauma Score was superior (ROC 0.8315), but no score provided adequate calibration.
Conclusions: Emerging mobile health technology enables reliable and sustainable injury severity scoring in a high-volume trauma center in South Africa. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Spence, Richard Trafford] Massachusetts Gen Hosp, Codman Ctr, Dept Surg, Boston, MA 02114 USA.
[Spence, Richard Trafford; Hameed, S. Morad; Navsaria, Pradeep; Nicol, Andrew] Univ Cape Town, Groote Schuur Hosp, Ctr Trauma, Dept Gen Surg, Cape Town, South Africa.
[Zargaran, Eiman] Univ British Columbia, Dept Surg, Vancouver, BC, Canada.
[Spence, Richard Trafford] Groote Schuur Hosp, Dept Gen Surg, Main Rd, ZA-7935 Cape Town, South Africa.
RP Spence, RT (reprint author), Codman Ctr Clin Effectiveness Surg, Charles River Plaza,Suite 403,165 Cambridge St, Boston, MA 02114 USA.
EM Spnric004@myuct.ac.za
NR 36
TC 1
Z9 1
U1 2
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD AUG
PY 2016
VL 204
IS 2
BP 384
EP 392
DI 10.1016/j.jss.2016.05.021
PG 9
WC Surgery
SC Surgery
GA DU5CP
UT WOS:000382230100015
PM 27565074
ER
PT J
AU Varley, PR
Feske, U
Gao, S
Stone, RA
Zhang, SJ
Monte, R
Arnold, RM
Hall, DE
AF Varley, Patrick R.
Feske, Ulrike
Gao, Shasha
Stone, Roslyn A.
Zhang, Sijian
Monte, Robert
Arnold, Robert M.
Hall, Daniel E.
TI Time required to review research protocols at 10 Veterans Affairs
Institutional Review Boards
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Quality improvement; Ethics committee; Efficiency
ID CLINICAL-RESEARCH; QUALITY; MULTICENTER; OVERSIGHT; EVENTS; REFORM;
COSTS
AB Background: Despite perceptions that institutional review boards ( IRBs) delay research, little is known about how long it takes to secure IRB approval. We retrospectively quantified IRB review times at 10 large Veterans Affairs (VA) IRBs.
Methods: We collected IRB records pertaining to a stratified random sample of research protocols drawn from 10 of the 26 largest VA IRBs. Two independent analysts abstracted dates from the IRB records, from which we calculated overall and incremental review times. We used multivariable linear regression to assess variation in total and incremental review times by IRB and review level (i.e., exempt, expedited, or full board) and to identify potential targets for efforts to improve the efficiency and uniformity of the IRB review process.
Results: In a sample of 277 protocols, the mean review time was 112 d (95% confidence interval [CI]: 105-120). Compared with full-board reviews at IRB 1, average review times at IRBs 3, 8, 9, and 10 were 27 (95% CI: 6-48), 37 (95% CI: 11-63), 45 (95% CI: 20-69), and 24 (95% CI: 2-45) d shorter, and at IRB 6, times were 56 (95% CI: 28-84) d longer. Across all IRBs, expedited reviews were 44 (95% CI: 30-58) d shorter on average than were full-board reviews, with no significant difference between exempt and full-board reviews. However, after subtracting the time required for Research and Development Committee review, exempt reviews were 21 (95% CI: 1-41) d shorter on average than were full-board reviews.
Conclusions: IRB review times differ significantly by IRB and review level. Few VA IRBs approach a consensus panel goal of 60 d for IRB review. The unexpectedly longer review times for exempt protocols in the VA can be attributed to time required for Research and Development Committee review. Prospective, routine collection of key time points in the IRB review process could inform IRB-specific initiatives for reducing VA IRB review times. Published by Elsevier Inc.
C1 [Varley, Patrick R.; Hall, Daniel E.] Univ Pittsburgh, Dept Surg, Pittsburgh, PA USA.
[Feske, Ulrike; Gao, Shasha; Stone, Roslyn A.; Zhang, Sijian; Hall, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr,151C, Pittsburgh, PA 15240 USA.
[Monte, Robert] VA Pittsburgh Healthcare Syst, Vet Engn Resource Ctr, Pittsburgh, PA USA.
[Arnold, Robert M.] Univ Pittsburgh, Dept Gen Internal Med, Pittsburgh, PA USA.
RP Hall, DE (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Bldg 30,Univ Dr,151C, Pittsburgh, PA 15240 USA.
EM hallde@upmc.edu
FU U.S. Department of Veterans Affairs, Veterans Health Administration,
Office of Research and Development, Health Services Research and
Development [CDA 08-281, SDR 11-399-1]
FX This research was supported by supported by the U.S. Department of
Veterans Affairs, Veterans Health Administration, Office of Research and
Development, Health Services Research and Development (CDA 08-281 and
SDR 11-399-1). We are grateful to Laura Lupovitz for her careful coding
of IRB review times, the staff of the VA Pittsburgh Veterans Engineering
Resource Center for their assistance with process flow mapping, and for
the participation and support of the IRB staff at each of the
participating institutions. Weare also grateful to Michael Fine, Bruce
Ling, Charles Lidz, Galen Switzer, Susan Zickmund, Barbara Hanusa and
Aram Dobalian who were involved in other parts of this research and
served throughout as advisors to our team.
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PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD AUG
PY 2016
VL 204
IS 2
BP 481
EP 489
DI 10.1016/j.jss.2016.06.004
PG 9
WC Surgery
SC Surgery
GA DU5CP
UT WOS:000382230100027
PM 27565086
ER
PT J
AU Fearing, CM
Melton, DW
Lei, XF
Hancock, H
Wang, HZ
Sarwar, ZU
Porter, L
McHale, M
McManus, LM
Shireman, PK
AF Fearing, Caitlin M.
Melton, David W.
Lei, Xiufen
Hancock, Heather
Wang, Hanzhou
Sarwar, Zaheer U.
Porter, Laurel
McHale, Matthew
McManus, Linda M.
Shireman, Paula K.
TI Increased Adipocyte Area in Injured Muscle With Aging and Impaired
Remodeling in Female Mice
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Sarcopenia; Muscle regeneration; Monocyte; macrophage
ID CONTRACTION-INDUCED INJURY; MOUSE SKELETAL-MUSCLE; AGE-RELATED-CHANGES;
SATELLITE CELLS; MALE RATS; FIBRO/ADIPOGENIC PROGENITORS; MACROPHAGE
PHENOTYPE; STEM-CELLS; OLD RATS; REGENERATION
AB We demonstrated that young male and female mice similarly regenerated injured skeletal muscle; however, female mice transiently increased adipocyte area within regenerated muscle in a sex hormone-dependent manner. We extended these observations to investigate the effect of aging and sex on sarcopenia and muscle regeneration. Cardiotoxin injury to the tibialis anterior muscle of young, middle, and old-aged C57Bl/6J male and female mice was used to measure regenerated myofiber cross-sectional area (CSA), adipocyte area, residual necrosis, and inflammatory cell recruitment. Baseline (uninjured) myofiber CSA was decreased in old mice of both sexes compared to young and middle-aged mice. Regenerated CSA was similar in male mice in all age groups until baseline CSA was attained but decreased in middle and old age female mice compared to young females. Furthermore, adipocyte area within regenerated muscle was transiently increased in young females compared to young males and these sex-dependent increases persisted in middle and old age female mice and were associated with increased Pparg. Young female mice had more pro-inflammatory monocytes/macrophages in regenerating muscle than young male mice and increased Sca-1(+)CD45(-)cells. In conclusion, sex and age influence pro-inflammatory cell recruitment, muscle regeneration, and adipocyte area following skeletal muscle injury.
C1 [Fearing, Caitlin M.; Melton, David W.; Lei, Xiufen; Hancock, Heather; Wang, Hanzhou; Sarwar, Zaheer U.; Porter, Laurel; McHale, Matthew; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, San Antonio, TX 78229 USA.
[Melton, David W.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Melton, David W.; McManus, Linda M.; Shireman, Paula K.] Univ Texas Hlth Sci Ctr San Antonio, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA.
[McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
[McManus, Linda M.] Univ Texas Hlth Sci Ctr San Antonio, Dept Periodont, San Antonio, TX 78229 USA.
[Shireman, Paula K.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Surg, Div Vasc & Endovasc Surg, 7703 Floyd Curl Dr MSC 7741, San Antonio, TX 78229 USA.
EM shireman@uthscsa.edu
FU National Institutes of Health [HL074236, HL110743, CA054174]; Nathan
Shock Centers of Excellence in Basic Biology of Aging [AG013319];
Veterans Administration Merit Review [1I01BX001186]; University of Texas
Health Science Center, San Antonio; CTSA grant [UL1 TR001120]
FX These studies were supported, in part, by grants from the National
Institutes of Health (HL074236, HL110743), Nathan Shock Centers of
Excellence in Basic Biology of Aging (AG013319), and the Veterans
Administration Merit Review (1I01BX001186). Data were generated in the
Flow Cytometry Facility, which was supported by the University of Texas
Health Science Center, San Antonio and a grant from the National
Institutes of Health (CA054174) to the Cancer Therapy & Research Center
and UL1 TR001120 (CTSA grant).
NR 71
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PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD AUG
PY 2016
VL 71
IS 8
BP 992
EP 1004
DI 10.1093/gerona/glv104
PG 13
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DV9BX
UT WOS:000383235400002
PM 26273023
ER
PT J
AU Yaffe, K
Peltz, CB
Ewing, SK
McCulloch, CE
Cummings, SR
Cauley, JA
Hillier, TA
Ensrud, KE
AF Yaffe, Kristine
Peltz, Carrie B.
Ewing, Susan K.
McCulloch, Charles E.
Cummings, Steve R.
Cauley, Jane A.
Hillier, Teresa A.
Ensrud, Kristine E.
TI Long-term Cognitive Trajectories and Mortality in Older Women
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Cognitive trajectories; Global cognition; Executive function; All-cause
mortality; Cardiovascular mortality; Oldest old
ID ALZHEIMERS-DISEASE; EXECUTIVE FUNCTION; COMMUNITY SAMPLE; RISK-FACTORS;
ASSOCIATION; DECLINE; SURVIVAL; DEMENTIA; HEALTH; LIFE
AB Few studies have examined whether change in cognition is linked to mortality. This study examined the relationship between cognitive trajectories in older age and risk of death.
We studied community-dwelling, nondemented women aged 65+ (mean age = 71) enrolled in a prospective study of aging and followed up to 25 years. A modified Mini-Mental State Examination (mMMSE) and Trail Making Task Part B (TMTB) were administered at multiple visits during follow-up. We examined the association between cognitive trajectories (analyzed by quintiles) from baseline to age 80 (n = 7,477 for mMMSE and n = 6,503 for TMTB) and all-cause mortality after age 80 using Cox regression models, both unadjusted and adjusted for education, physical activity, alcohol, depression score, current smoking and history of hypertension and diabetes. Cause of death was determined from death certificates, classified as cardiovascular, cancer and other.
Women with greater rate of decline were older, less educated, less physically active, had higher depression score and were more likely to have a history of hypertension and diabetes (all p < .01). Participants with the greatest decline (quintile 1) had an increased risk of death (mMMSE hazard ratio [HR] = 1.28; TMTB HR = 1.43] and those with the least decline (quintile 5) had a decreased risk of death (mMMSE HR = 0.73; TMTB HR = 0.61) compared with intermediate decliners (quintiles 2-4). Cognitive trajectories were associated with cardiovascular mortality and other causes of death, but not cancer deaths.
Our study suggests that greater decline in general cognition or executive function is associated with higher rates of mortality in oldest-old women.
C1 [Yaffe, Kristine; Ewing, Susan K.; McCulloch, Charles E.; Cummings, Steve R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine; Ewing, Susan K.; McCulloch, Charles E.; Cummings, Steve R.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine; Ewing, Susan K.; McCulloch, Charles E.; Cummings, Steve R.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yaffe, Kristine; Peltz, Carrie B.] San Francisco VA Med Ctr, Dept Mental Hlth, San Francisco, CA USA.
[Peltz, Carrie B.] NCIRE Vet Hlth Res Inst, San Francisco, CA USA.
[Cauley, Jane A.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Hillier, Teresa A.] Kaiser Permanente Ctr Hlth Res Northwest Hawaii, Portland, OR USA.
[Ensrud, Kristine E.] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA.
[Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Dept Med, Minneapolis, MN USA.
RP Peltz, CB (reprint author), 4150 Clement St 116H, San Francisco, CA 94121 USA.
EM carrie.peltz2@va.gov
OI Cauley, Jane A/0000-0003-0752-4408
FU National Institutes of Health; National Institute on Aging [R01
AG005407, R01 AR35582, R01 AR35583, R01 AR35584, R01 AG005394, R01
AG027574, R01 AG027576]
FX The Study of Osteoporotic Fractures is supported by National Institutes
of Health funding. The National Institute on Aging provides support
under the following grant numbers: R01 AG005407, R01 AR35582, R01
AR35583, R01 AR35584, R01 AG005394, R01 AG027574, and R01 AG027576.
NR 40
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U1 4
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD AUG
PY 2016
VL 71
IS 8
BP 1074
EP 1080
DI 10.1093/gerona/glw003
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DV9BX
UT WOS:000383235400012
PM 26843186
ER
PT J
AU Mischoulon, D
Zajecka, J
Freeman, MP
Fava, M
AF Mischoulon, David
Zajecka, John
Freeman, Marlene P.
Fava, Maurizio
TI Does folic acid interfere with lamotrigine?
SO LANCET PSYCHIATRY
LA English
DT Letter
ID DEPRESSION; METAANALYSIS; PLACEBO; TRIALS
C1 [Mischoulon, David; Freeman, Marlene P.; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Zajecka, John] Rush Univ, Med Ctr, Womans Board Depress Treatment Res Ctr, Chicago, IL 60612 USA.
RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM dmischoulon@partners.org
FU AstraZeneca; Avanir Pharmaceuticals; Cerecor; Eli Lilly and Company;
EnVivo Pharmaceuticals; Euthymics Bioscience; Forest Pharmaceuticals;
FORUM Pharmaceuticals; Janssen RD; Johnson & Johnson Pharmaceutical
Research Development; Lundbeck; Methylation Sciences; National Center
for Complementary and Alternative Medicine (NCCAM); National
Coordinating Center for Integrative Medicine (NiiCM); National Institute
of Drug Abuse (NIDA); National Institute of Mental Health (NIMH);
Neuralstem; Novartis AG; PamLab; Pfizer; PharmoRx Therapeutics;
Photothera; Reckitt Benckiser; Roche Pharmaceuticals; RCT Logic; Stanley
Medical Research Institute (SMRI), Takeda; Tal Medical
FX DM reports non-financial support from PamLab; research support from
PharmoRx, Fisher Wallace; and received eicosapentaenoic acid (EPA) for
study from Nordic Naturals, outside the submitted work. JZ reports
grants from Actavis, Alkermes, Allergan, AstraZeneca, Axsome,
Cyberonics, EIMindA, Cheryl T Herman Foundation, Hoffman-La Roche,
Janssen, Neuralstem, Otsuka, National Institutes of Health, Abbvie,
Avanir, Eli Lilly, and Pamlab/Nestle; and grants and personal fees from
Forest, Naurex, Shire, and Takeda; personal fees from Abbvie, Avanir,
and Eli Lilly, outside the submitted work. MPF reports grants and is on
the advisory board of Takeda, grants from JayMac Pharmaceuticals, is on
the advisory board of JDS therapeutics, Sunovion, and Sage; does medical
editing for DSM nutritionals and the GOED newsletter; and is on the
independent data safety monitoring committee of Johnson & Johnson
Janssen, outside the submitted work. MF reports receiving research
medications from Pamlab; grants for research support from AstraZeneca,
Avanir Pharmaceuticals, Cerecor, Eli Lilly and Company, EnVivo
Pharmaceuticals, Euthymics Bioscience, Forest Pharmaceuticals, FORUM
Pharmaceuticals, Janssen R&D, Johnson & Johnson Pharmaceutical Research
& Development, Lundbeck, Methylation Sciences, National Center for
Complementary and Alternative Medicine (NCCAM), National Coordinating
Center for Integrative Medicine (NiiCM), National Institute of Drug
Abuse (NIDA), National Institute of Mental Health (NIMH), Neuralstem,
Novartis AG, PamLab, Pfizer, PharmoRx Therapeutics, Photothera, Reckitt
Benckiser, Roche Pharmaceuticals, RCT Logic (formerly Clinical Trials
Solutions), Stanley Medical Research Institute (SMRI), Takeda, Tal
Medical; advisory board or consultant work from Acadia, Alkermes,
AstraZeneca, Auspex, Avanir Pharmaceuticals, AXSOME Therapeutics,
Biogen, Bristol-Myers Squibb, Cerecor, Dinippon Sumitomo Pharma Co, Eli
Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals, FORUM
Pharmaceuticals, GenOmind, GlaxoSmithKline, Intracellular, Janssen
Pharmaceutica, Johnson & Johnson Pharmaceutical Research & Development,
LLC, Lundbeck, Merck & Co, MSI Methylation Sciences, Naurex, Nestle
Health Sciences, Neuralstem, Novartis AG, Nutrition 21, Osmotica, Otsuka
Pharmaceuticals, Pamlab, Pfizer, PharmoRx Therapeutics, PPD, Puretech
Ventures, PsychoGenics, RCT Logic (formerly Clinical Trials Solutions),
Ridge Diagnostics, Roche, Sanofi-Aventis US, Servier Laboratories,
Sunovion Pharmaceuticals, Taisho Pharmaceutical, Takeda Pharmaceutical,
Tal Medical, VistaGenl; and personal fees from speaking and publishing
from American Society of Clinical Psychopharmacology, Belvoir Media
Group, CME Institute/Physicians Postgraduate Press, MGH Psychiatry
Academy; and equity holdings from Compellis and PsyBrain outside the
submitted work. DM wrote the first draft of the letter and discussed
relevant clinical trials of folate augmentation. JZ and MF provided
discussion about mechanisms of action, and relevant references. MPF
provided discussion about the impact of folic acid in pregnancy and
neural tube defects, and relevant references. All authors have approved
this submitted version.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2215-0374
J9 LANCET PSYCHIAT
JI Lancet Psychiatry
PD AUG
PY 2016
VL 3
IS 8
BP 704
EP 705
PG 2
WC Psychiatry
SC Psychiatry
GA DU5TU
UT WOS:000382276500009
PM 27475760
ER
PT J
AU Netea, MG
Joosten, LAB
Li, Y
Kumar, V
Oosting, M
Smeekens, S
Jaeger, M
ter Horst, R
Schirmer, M
Vlamakis, H
Notebaart, R
Pavelka, N
Aguirre-Gamboa, RR
Swertz, MA
Tunjungputri, RN
van de Heijden, W
Franzosa, EA
Ng, A
Graham, D
Lassen, K
Schraa, K
Netea-Maier, R
Smit, J
de Mast, Q
van de Veerdonk, F
Kullberg, BJ
Tack, C
van de Munckhof, I
Rutten, J
van der Graaf, J
Franke, L
Hofker, M
Jonkers, I
Platteel, M
Maatman, A
Fu, JY
Zhernakova, A
van der Meer, JWM
Dinarello, CA
van der Ven, A
Huttenhouwer, C
Koenen, H
Joosten, I
Xavier, RJ
Wijmenga, C
AF Netea, Mihai G.
Joosten, Leo A. B.
Li, Yang
Kumar, Vinod
Oosting, Marije
Smeekens, Sanne
Jaeger, Martin
ter Horst, Rob
Schirmer, Melanie
Vlamakis, Hera
Notebaart, Richard
Pavelka, Norman
Aguirre-Gamboa, Raul Raul
Swertz, Morris A.
Tunjungputri, Rahajeng N.
van de Heijden, Wouter
Franzosa, Eric A.
Ng, Aylwin
Graham, Daniel
Lassen, Kara
Schraa, Kiki
Netea-Maier, Romana
Smit, Jan
de Mast, Quirijn
van de Veerdonk, Frank
Kullberg, Bart Jan
Tack, Cees
van de Munckhof, Inge
Rutten, Joost
van der Graaf, Jacqueline
Franke, Lude
Hofker, Marten
Jonkers, Iris
Platteel, Mathieu
Maatman, Astrid
Fu, Jingyuan
Zhernakova, Alexandra
van der Meer, Jos W. M.
Dinarello, Charles A.
van der Ven, Andre
Huttenhouwer, Curtis
Koenen, Hans
Joosten, Irma
Xavier, Ramnik J.
Wijmenga, Cisca
TI Understanding human immune function using the resources from the Human
Functional Genomics Project
SO NATURE MEDICINE
LA English
DT Letter
C1 [Netea, Mihai G.; Joosten, Leo A. B.; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; ter Horst, Rob; Notebaart, Richard; Pavelka, Norman; Tunjungputri, Rahajeng N.; van de Heijden, Wouter; Schraa, Kiki; Netea-Maier, Romana; Smit, Jan; de Mast, Quirijn; van de Veerdonk, Frank; Kullberg, Bart Jan; Tack, Cees; van de Munckhof, Inge; Rutten, Joost; van der Graaf, Jacqueline; van der Meer, Jos W. M.; Dinarello, Charles A.; van der Ven, Andre] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.
[Netea, Mihai G.; Joosten, Leo A. B.; Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; ter Horst, Rob; Notebaart, Richard; Pavelka, Norman; Tunjungputri, Rahajeng N.; van de Heijden, Wouter; Schraa, Kiki; Netea-Maier, Romana; Smit, Jan; de Mast, Quirijn; van de Veerdonk, Frank; Kullberg, Bart Jan; Tack, Cees; van de Munckhof, Inge; Rutten, Joost; van der Graaf, Jacqueline; van der Meer, Jos W. M.; Dinarello, Charles A.; van der Ven, Andre] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands.
[Li, Yang; Kumar, Vinod; Aguirre-Gamboa, Raul Raul; Swertz, Morris A.; Franke, Lude; Hofker, Marten; Jonkers, Iris; Platteel, Mathieu; Maatman, Astrid; Fu, Jingyuan; Zhernakova, Alexandra; Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Schirmer, Melanie; Vlamakis, Hera; Franzosa, Eric A.; Ng, Aylwin; Graham, Daniel; Lassen, Kara; Huttenhouwer, Curtis; Xavier, Ramnik J.] Harvard Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA.
[Schirmer, Melanie; Vlamakis, Hera; Franzosa, Eric A.; Ng, Aylwin; Graham, Daniel; Lassen, Kara; Huttenhouwer, Curtis; Xavier, Ramnik J.] Harvard Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA.
[Schirmer, Melanie; Vlamakis, Hera; Franzosa, Eric A.; Ng, Aylwin; Graham, Daniel; Lassen, Kara; Huttenhouwer, Curtis; Xavier, Ramnik J.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA.
[Pavelka, Norman] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore.
[Dinarello, Charles A.] Univ Colorado, Dept Infect Dis, Denver, CO 80202 USA.
[Koenen, Hans; Joosten, Irma] Radboud Univ Nijmegen, Med Ctr, Dept Lab Med, Lab Med Immunol, Nijmegen, Netherlands.
RP Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.; Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands.
EM mihai.netea@radboudumc.nl
RI Smeekens, Sanne/G-8307-2011; Oosting, Marije/H-7437-2015; Franke,
Lude/P-7036-2016; Wijmenga, Cisca/D-2173-2009;
OI Smeekens, Sanne/0000-0002-7835-914X; Franke, Lude/0000-0002-5159-8802;
Pavelka, Norman/0000-0003-4542-9970
NR 10
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U1 3
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2016
VL 22
IS 8
BP 831
EP 833
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DS7YV
UT WOS:000381000200005
PM 27490433
ER
PT J
AU Deeks, SG
Lewin, SR
Ross, AL
Ananworanich, J
Benkirane, M
Cannon, P
Chomont, N
Douek, D
Lifson, JD
Lo, YR
Kuritzkes, D
Margolis, D
Mellors, J
Persaud, D
Tucker, JD
Barre-Sinoussi, F
Alter, G
Auerbach, J
Autran, B
Barouch, DH
Behrens, G
Cavazzana, M
Chen, ZW
Cohen, EA
Corbelli, GM
Eholie, S
Eyal, N
Fidler, S
Garcia, L
Grossman, C
Henderson, G
Henrich, TJ
Jefferys, R
Kiem, HP
McCune, J
Moodley, K
Newman, PA
Nijhuis, M
Nsubuga, MS
Ott, M
Palmer, S
Richman, D
Saez-Cirion, A
Sharp, M
Siliciano, J
Silvestri, G
Singh, J
Spire, B
Taylor, J
Tolstrup, M
Valente, S
van Lunzen, J
Walensky, R
Wilson, I
Zack, J
AF Deeks, Steven G.
Lewin, Sharon R.
Ross, Anna Laura
Ananworanich, Jintanat
Benkirane, Monsef
Cannon, Paula
Chomont, Nicolas
Douek, Daniel
Lifson, Jeffrey D.
Lo, Ying-Ru
Kuritzkes, Daniel
Margolis, David
Mellors, John
Persaud, Deborah
Tucker, Joseph D.
Barre-Sinoussi, Francoise
Alter, Galit
Auerbach, Judith
Autran, Brigitte
Barouch, Dan H.
Behrens, Georg
Cavazzana, Marina
Chen, Zhiwei
Cohen, Eric A.
Corbelli, Giulio Maria
Eholie, Serge
Eyal, Nir
Fidler, Sarah
Garcia, Laurindo
Grossman, Cynthia
Henderson, Gail
Henrich, Timothy J.
Jefferys, Richard
Kiem, Hans-Peter
McCune, Joseph
Moodley, Keymanthri
Newman, Peter A.
Nijhuis, Monique
Nsubuga, Moses Supercharger
Ott, Melanie
Palmer, Sarah
Richman, Douglas
Saez-Cirion, Asier
Sharp, Matthew
Siliciano, Janet
Silvestri, Guido
Singh, Jerome
Spire, Bruno
Taylor, Jeffrey
Tolstrup, Martin
Valente, Susana
van Lunzen, Jan
Walensky, Rochelle
Wilson, Ira
Zack, Jerome
CA Int AIDS Soc Cure Working Grp
TI International AIDS Society global scientific strategy: towards an HIV
cure 2016
SO NATURE MEDICINE
LA English
DT Article
ID CD4(+) T-CELLS; SUPPRESSIVE ANTIRETROVIRAL THERAPY; BROADLY NEUTRALIZING
ANTIBODIES; HISTONE DEACETYLASE INHIBITOR; HIGHLY PATHOGENIC SIV; LATENT
HIV-1; VIRAL RESERVOIR; IN-VIVO; TREATMENT INTERRUPTION; RALTEGRAVIR
INTENSIFICATION
AB Antiretroviral therapy is not curative. Given the challenges in providing lifelong therapy to a global population of more than 35 million people living with HIV, there is intense interest in developing a cure for HIV infection. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. This Perspective summarizes the group's strategy.
C1 [Deeks, Steven G.; Auerbach, Judith; Henrich, Timothy J.; McCune, Joseph] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Lewin, Sharon R.] Univ Melbourne, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia.
[Lewin, Sharon R.] Royal Melbourne Hosp, Melbourne, Vic, Australia.
[Lewin, Sharon R.] Alfred Hosp, Dept Infect Dis, Melbourne, Vic, Australia.
[Lewin, Sharon R.] Monash Univ, Melbourne, Vic, Australia.
[Ross, Anna Laura] ANRS, Int & Sci Relat Off, Paris, France.
[Ananworanich, Jintanat] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD 20910 USA.
[Ananworanich, Jintanat] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA.
[Benkirane, Monsef] Univ Montpellier, CNRS UPR 1142, Inst Human Genet, Mol Virol Lab, Montpellier, France.
[Cannon, Paula] Univ Southern Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Chomont, Nicolas] Univ Montreal, Fac Med, CRCHUM, Montreal, PQ, Canada.
[Chomont, Nicolas] Univ Montreal, Fac Med, Dept Microbiol Infectiol & Immunol, Montreal, PQ, Canada.
[Douek, Daniel] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Lifson, Jeffrey D.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab, Frederick, MD 21702 USA.
[Lo, Ying-Ru] World Hlth Org Reg Off Western Pacific, Manila, Philippines.
[Kuritzkes, Daniel; Henrich, Timothy J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Margolis, David; Henderson, Gail] Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA.
[Mellors, John] Univ Pittsburgh, Dept Med, Div Infect Dis, 930 Scaife Hall, Pittsburgh, PA 15260 USA.
[Persaud, Deborah] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
[Persaud, Deborah] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Tucker, Joseph D.] Univ North Carolina Project China, Guangzhou, Guangdong, Peoples R China.
[Barre-Sinoussi, Francoise] Inst Pasteur, Paris, France.
[Alter, Galit; Barouch, Dan H.] MIT & Harvard, Ragon Inst MGH, Boston, MA USA.
[Autran, Brigitte] Univ Paris 06, Sorbonne Univ, CIMI, Paris, France.
[Autran, Brigitte] CIMI Paris, INSERM, U1135, Paris, France.
[Autran, Brigitte] Hop La Pitie Salpetriere, AP HP, Dept Immunol, Paris, France.
[Barouch, Dan H.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Behrens, Georg] Hannover Med Sch, Clin Immunol & Rhematol, Hannover, Germany.
[Cavazzana, Marina] Hop Necker Enfants Malad, Ctr Invest Clin Biotherapie, Paris, France.
[Chen, Zhiwei] Univ Hong Kong, AIDS Inst, Pok Fu Lam, Hong Kong, Peoples R China.
[Cohen, Eric A.] Univ Montreal, Inst Rech Clin Montreal, Montreal, PQ, Canada.
[Corbelli, Giulio Maria] European AIDS Treatment Grp, Rome, Italy.
[Eholie, Serge] Ctr Hosp Univ Treichville, Programme PAC CI, Abidjan, Cote Ivoire.
[Eyal, Nir] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA.
[Fidler, Sarah] Imperial Coll London, Dept Med, London, England.
[Garcia, Laurindo] B Change Grp, Manila, Philippines.
[Grossman, Cynthia] NIMH, NIH, Bethesda, MD 20892 USA.
[Jefferys, Richard] Treatment Act Grp, New York, NY 10016 USA.
[Kiem, Hans-Peter] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Moodley, Keymanthri] Univ Stellenbosch, Dept Med, Ctr Med Eth & Law, Western Cape, South Africa.
[Newman, Peter A.] Univ Toronto, Factor Inwentash Fac Social Work, Toronto, ON, Canada.
[Nijhuis, Monique] Univ Med Ctr Utrecht, Dept Med Microbiol, Virol, Utrecht, Netherlands.
[Nsubuga, Moses Supercharger] Joint Clin Res Ctr, Kampala, Uganda.
[Ott, Melanie] Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA.
[Palmer, Sarah] Univ Sydney, Westmead Millennium Inst Med Res, Sydney, NSW, Australia.
[Richman, Douglas] Virginia San Diego Healthcare Syst, San Diego, CA 92161 USA.
[Richman, Douglas] Univ Calif San Diego, San Diego, CA 92103 USA.
[Saez-Cirion, Asier] Inst Pasteur, Paris, France.
[Sharp, Matthew] Independent HIV Educ & Advocacy Consultant, San Francisco, CA USA.
[Siliciano, Janet] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Silvestri, Guido] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA.
[Singh, Jerome] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa.
[Spire, Bruno] INSERM, UMR S912, Marseille, France.
[Taylor, Jeffrey] CARE Collaboratory Community Advisory Board, Palm Springs, CA USA.
[Tolstrup, Martin] Aarhus Univ, Inst Clin Med, Aarhus, Denmark.
[Valente, Susana] Scripps Res Inst, Dept Immunol & Microbial Sci, Jupiter, FL 33458 USA.
[van Lunzen, Jan] ViiV Healthcare, London, England.
[Walensky, Rochelle] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Wilson, Ira] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA.
[Zack, Jerome] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Deeks, SG (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
EM steven.deeks@ucsf.edu
RI Behrens, Georg/Q-4486-2016; Spire, Bruno/F-5546-2013;
OI Spire, Bruno/0000-0002-3546-8020; Deeks, Steven/0000-0001-6371-747X;
Saez-Cirion, Asier/0000-0003-2406-7536; Lewin, Sharon
Ruth/0000-0002-0330-8241
FU federal funds from the NCI/NIH [HHSN261200800001E]
FX J.L. is supported in part by federal funds from the NCI/NIH under
contract no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the DHHS, nor does mention
of trade names, commercial products or organizations imply endorsement
by the U.S. government. The views expressed are those of the authors and
should not be construed to represent the positions of the U.S. Army, the
Department of Defense or the US National Institutes of Health. Y.-R.L.
is a World Health Organization (WHO) staff member. The opinions herein
are those of the authors and should not be construed as official or
representing the views of the WHO. The authors acknowledge T. Rasmussen,
T. Mota and M. Crane for assistance with preparation of figures.
NR 125
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PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2016
VL 22
IS 8
BP 839
EP 850
DI 10.1038/nm.4108
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DS7YV
UT WOS:000381000200009
PM 27400264
ER
PT J
AU Wang, WZ
Wang, LW
Lu, JJ
Siedlak, SL
Fujioka, H
Liang, JJ
Jiang, SR
Ma, XP
Jiang, Z
da Rocha, EL
Sheng, M
Choi, H
Lerou, PH
Li, H
Wang, XL
AF Wang, Wenzhang
Wang, Luwen
Lu, Junjie
Siedlak, Sandra L.
Fujioka, Hisashi
Liang, Jingjing
Jiang, Sirui
Ma, Xiaopin
Jiang, Zhen
da Rocha, Edroaldo Lummertz
Sheng, Max
Choi, Heewon
Lerou, Paul H.
Li, Hu
Wang, Xinglong
TI The inhibition of TDP-43 mitochondrial localization blocks its neuronal
toxicity
SO NATURE MEDICINE
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION;
ALZHEIMERS-DISEASE; SPLICING REGULATION; PROTEIN-PROTEIN; TRANSGENIC
MICE; MOTOR-NEURONS; RNA TARGETS; MUTATIONS; DEMENTIA
AB Genetic mutations in TAR DNA-binding protein 43 (TARDBP, also known as TDP-43) cause amyotrophic lateral sclerosis (ALS), and an increase in the presence of TDP-43 (encoded by TARDBP) in the cytoplasm is a prominent histopathological feature of degenerating neurons in various neurodegenerative diseases. However, the molecular mechanisms by which TDP-43 contributes to ALS pathophysiology remain elusive. Here we have found that TDP-43 accumulates in the mitochondria of neurons in subjects with ALS or frontotemporal dementia (FTD). Disease-associated mutations increase TDP-43 mitochondrial localization. In mitochondria, wild-type (WT) and mutant TDP-43 preferentially bind mitochondria-transcribed messenger RNAs (mRNAs) encoding respiratory complex I subunits ND3 and ND6, impair their expression and specifically cause complex I disassembly. The suppression of TDP-43 mitochondrial localization abolishes WT and mutant TDP-43-induced mitochondrial dysfunction and neuronal loss, and improves phenotypes of transgenic mutant TDP-43 mice. Thus, our studies link TDP-43 toxicity directly to mitochondrial bioenergetics and propose the targeting of TDP-43 mitochondrial localization as a promising therapeutic approach for neurodegeneration.
C1 [Wang, Wenzhang; Wang, Luwen; Siedlak, Sandra L.; Jiang, Sirui; Ma, Xiaopin; Jiang, Zhen; Sheng, Max; Choi, Heewon; Wang, Xinglong] Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
[Lu, Junjie] Brigham & Womens Hosp, Dept Pediat Newborn Med, 75 Francis St, Boston, MA 02115 USA.
[Fujioka, Hisashi] Case Western Reserve Univ, Electron Microscopy Core Facil, Cleveland, OH 44106 USA.
[Liang, Jingjing] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[da Rocha, Edroaldo Lummertz; Li, Hu] Mayo Clin, Dept Mol Pharmacol & Expt Therapeut, Rochester, MN USA.
[Lerou, Paul H.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
RP Wang, XL (reprint author), Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA.
EM xinglong.wang@case.edu
OI Wang, Wenzhang/0000-0003-4426-019X
FU US National Institutes of Health [R03AG044680, 1R01NS089604]; US
Alzheimer's Association [2014-NIRG-301299]; University Hospitals of
Cleveland, USA (SPITZ Innovation Pilot Grant); Eunice Kennedy Shriver
National Institute of Child Health and Human Development Brain and
Tissue Bank for Developmental Disorders at the University of Maryland,
Baltimore, Maryland, USA [HHSN275200900011C, N01-HD-9-0011]
FX This study is supported by grants from the US National Institutes of
Health (R03AG044680 and 1R01NS089604 to X.W.), the US Alzheimer's
Association (2014-NIRG-301299 to X.W.) and the University Hospitals of
Cleveland, USA (2012 SPITZ Innovation Pilot Grant to X.W.). Human spinal
cord frozen tissues were obtained from the Eunice Kennedy Shriver
National Institute of Child Health and Human Development Brain and
Tissue Bank for Developmental Disorders at the University of Maryland,
Baltimore, Maryland, USA, contract HHSN275200900011C, ref. no.
N01-HD-9-0011. We also thank G. Perry and X. Zhu for providing
paraffin-embedded human spinal cord tissues.
NR 61
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PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2016
VL 22
IS 8
BP 869
EP +
DI 10.1038/nm.4130
PG 14
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DS7YV
UT WOS:000381000200012
PM 27348499
ER
PT J
AU Theurl, I
Hilgendorf, I
Nairz, M
Tymoszuk, P
Haschka, D
Asshoff, M
He, S
Gerhardt, LMS
Holderried, TAW
Seifert, M
Sopper, S
Fenn, AM
Anzai, A
Rattik, S
McAlpine, C
Theurl, M
Wieghofer, P
Iwamoto, Y
Weber, GF
Harder, NK
Chousterman, BG
Arvedson, TL
McKee, M
Wang, FD
Lutz, OMD
Rezoagli, E
Babitt, JL
Berra, L
Prinz, M
Nahrendorf, M
Weiss, G
Weissleder, R
Lin, HY
Swirski, FK
AF Theurl, Igor
Hilgendorf, Ingo
Nairz, Manfred
Tymoszuk, Piotr
Haschka, David
Asshoff, Malte
He, Shun
Gerhardt, Louisa M. S.
Holderried, Tobias A. W.
Seifert, Markus
Sopper, Sieghart
Fenn, Ashley M.
Anzai, Atsushi
Rattik, Sara
McAlpine, Cameron
Theurl, Milan
Wieghofer, Peter
Iwamoto, Yoshiko
Weber, Georg F.
Harder, Nina K.
Chousterman, Benjamin G.
Arvedson, Tara L.
McKee, Mary
Wang, Fudi
Lutz, Oliver M. D.
Rezoagli, Emanuele
Babitt, Jodie L.
Berra, Lorenzo
Prinz, Marco
Nahrendorf, Matthias
Weiss, Guenter
Weissleder, Ralph
Lin, Herbert Y.
Swirski, Filip K.
TI On-demand erythrocyte disposal and iron recycling requires transient
macrophages in the liver
SO NATURE MEDICINE
LA English
DT Article
ID RED-BLOOD-CELLS; TISSUE MACROPHAGES; MICROARRAY DATA; CHRONIC DISEASE;
MOUSE MODEL; SPI-C; HOMEOSTASIS; HEPCIDIN; ANEMIA; MICE
AB Iron is an essential component of the erythrocyte protein hemoglobin and is crucial to oxygen transport in vertebrates. In the steady state, erythrocyte production is in equilibrium with erythrocyte removal(1). In various pathophysiological conditions, however, erythrocyte life span is compromised severely, which threatens the organism with anemia and iron toxicity(2,3). Here we identify an on-demand mechanism that clears erythrocytes and recycles iron. We show that monocytes that express high levels of lymphocyte antigen 6 complex, locus C1 (LY6C1, also known as Ly-6C) ingest stressed and senescent erythrocytes, accumulate in the liver via coordinated chemotactic cues, and differentiate into ferroportin 1 (FPN1, encoded by SLC40A1)-expressing macrophages that can deliver iron to hepatocytes. Monocyte-derived FPN(1+)Tim-4(neg) macrophages are transient, reside alongside embryonically derived T cell immunoglobulin and mucin domain containing 4 (Timd4, also known as Tim-4)(high) Kupffer cells (KCs), and depend on the growth factor Csf1 and the transcription factor Nrf2 (encoded by Nfe2/2). The spleen, likewise, recruits iron-loaded Ly-6C(high) monocytes, but these do not differentiate into iron-recycling macrophages, owing to the suppressive action of Csf2. The accumulation of a transient macrophage population in the liver also occurs in mouse models of hemolytic anemia, anemia of inflammation, and sickle cell disease. Inhibition of monocyte recruitment to the liver during stressed erythrocyte delivery leads to kidney and liver damage. These observations identify the liver as the primary organ that supports rapid erythrocyte removal and iron recycling, and uncover a mechanism by which the body adapts to fluctuations in erythrocyte integrity.
C1 [Theurl, Igor; Hilgendorf, Ingo; Nairz, Manfred; He, Shun; Gerhardt, Louisa M. S.; Fenn, Ashley M.; Anzai, Atsushi; Rattik, Sara; McAlpine, Cameron; Iwamoto, Yoshiko; Weber, Georg F.; Harder, Nina K.; Chousterman, Benjamin G.; McKee, Mary; Babitt, Jodie L.; Nahrendorf, Matthias; Weissleder, Ralph; Lin, Herbert Y.; Swirski, Filip K.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Theurl, Igor; Hilgendorf, Ingo; Nairz, Manfred; He, Shun; Gerhardt, Louisa M. S.; Fenn, Ashley M.; Anzai, Atsushi; Rattik, Sara; McAlpine, Cameron; Iwamoto, Yoshiko; Weber, Georg F.; Harder, Nina K.; Chousterman, Benjamin G.; McKee, Mary; Rezoagli, Emanuele; Babitt, Jodie L.; Berra, Lorenzo; Nahrendorf, Matthias; Weissleder, Ralph; Lin, Herbert Y.; Swirski, Filip K.] Harvard Med Sch, Boston, MA 02115 USA.
[Theurl, Igor; Hilgendorf, Ingo; Nairz, Manfred; He, Shun; Gerhardt, Louisa M. S.; Fenn, Ashley M.; Anzai, Atsushi; Rattik, Sara; McAlpine, Cameron; Iwamoto, Yoshiko; Weber, Georg F.; Harder, Nina K.; Chousterman, Benjamin G.; Nahrendorf, Matthias; Weissleder, Ralph; Swirski, Filip K.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Theurl, Igor; Tymoszuk, Piotr; Haschka, David; Asshoff, Malte; Seifert, Markus; Weiss, Guenter] Med Univ Innsbruck, Dept Internal Med 6, Infect Dis, Immunol,Rheumatol,Pneumol, Innsbruck, Austria.
[Hilgendorf, Ingo] Univ Freiburg, Heart Ctr Freiburg, Freiburg, Germany.
[Holderried, Tobias A. W.] Univ Hosp Bonn, Dept Internal Med Oncol Hematol & Rheumatol 3, Bonn, Germany.
[Sopper, Sieghart] Med Univ Innsbruck, Dept Internal Med 5, Innsbruck, Austria.
[Theurl, Milan] Med Univ Innsbruck, Dept Ophthalmol & Optometry, Innsbruck, Austria.
[Wieghofer, Peter; Prinz, Marco] Univ Freiburg, Med Ctr, Inst Neuropathol, Freiburg, Germany.
[Wieghofer, Peter] Univ Freiburg, Fac Biol, Freiburg, Germany.
[Arvedson, Tara L.] Amgen Inc, Dept Oncol, Thousand Oaks, CA 91320 USA.
[McKee, Mary; Babitt, Jodie L.; Lin, Herbert Y.] Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA.
[Wang, Fudi] Zhejiang Univ, Inst Nutr & Food Safety, Nutr Discovery Innovat Ctr, Dept Nutr,Sch Publ Hlth,Sch Med, Hangzhou, Zhejiang, Peoples R China.
[Lutz, Oliver M. D.] Austrian Drug Screening Inst, Innsbruck, Austria.
[Rezoagli, Emanuele; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anaesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Prinz, Marco] Univ Freiburg, BIOSS Ctr Biol Signalling Studies, Freiburg, Germany.
[Weissleder, Ralph] Harvard Med Sch, Dept Syst Biol, Boston, MA USA.
RP Lin, HY; Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.; Lin, HY; Swirski, FK (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Swirski, FK (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Lin, HY (reprint author), Massachusetts Gen Hosp, Div Nephrol, Program Membrane Biol, Boston, MA 02114 USA.
EM Lin.Herbert@mgh.harvard.edu; fswirski@mgh.harvard.edu
FU US National Institutes of Health (NIH) [1R01HL095612, R01HL128264,
R56AI104695]; Massachusetts General Hospital's Howard M. Goodman
Fellowship [R01DK071837]; Max Kade Foundation; Austrian Science Fund
(FWF) [P28302-B30, P24749-B13, HI 1573/1-1, HI 1573/2-1]; German
Research Foundation; FWF Erwin Schroedinger Fellowship [J3486-B13];
Boehringer Ingelheim Fonds; National Natural Science Foundation of China
[31530034, 31225013]
FX This work was supported in part by US National Institutes of Health
(NIH) grants 1R01HL095612, R01HL128264, R56AI104695 and the
Massachusetts General Hospital's Howard M. Goodman Fellowship (to
F.K.S.) and R01DK071837 (to H.Y.L.). I.T. was supported by the Max Kade
Foundation and grants by the Austrian Science Fund (FWF) (P28302-B30 and
P24749-B13)). I.H. (HI 1573/1-1, HI 1573/2-1) and G.F.W. were supported
by the German Research Foundation. M. Nairz was supported by an FWF
Erwin Schroedinger Fellowship (J3486-B13). L.M.S.G. and N.K.H. were
supported by the Boehringer Ingelheim Fonds. F.W. was supported by the
National Natural Science Foundation of China (31530034 and 31225013). We
thank D. Capen for help in electron microscopy; N. Bonheur and M. Waring
for help with cell sorting; A. Lindau for technical assistance; C.
Haerdtner, J. Kornemann, and J. Zou for help with flow cytometry; D.
Brown for interpretation of electron microscopy images; C. Robbins for
the mouse drawing; and K. Joyes for editing the manuscript.
NR 40
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U1 4
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2016
VL 22
IS 8
BP 945
EP +
DI 10.1038/nm.4146
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DS7YV
UT WOS:000381000200021
PM 27428900
ER
PT J
AU Li, Y
Oosting, M
Deelen, P
Ricano-Ponce, I
Smeekens, S
Jaeger, M
Matzaraki, V
Swertz, MA
Xavier, RJ
Franke, L
Wijmenga, C
Joosten, LAB
Kumar, V
Netea, MG
AF Li, Yang
Oosting, Marije
Deelen, Patrick
Ricano-Ponce, Isis
Smeekens, Sanne
Jaeger, Martin
Matzaraki, Vasiliki
Swertz, Morris A.
Xavier, Ramnik J.
Franke, Lude
Wijmenga, Cisca
Joosten, Leo A. B.
Kumar, Vinod
Netea, Mihai G.
TI Inter-individual variability and genetic influences on cytokine
responses to bacteria and fungi
SO NATURE MEDICINE
LA English
DT Article
ID CHRONIC MUCOCUTANEOUS CANDIDIASIS; HUMAN IMMUNE-SYSTEM; DISEASE
SUSCEPTIBILITY; INFECTIOUS-DISEASE; PROTEIN ABUNDANCE; STAT1 MUTATIONS;
LIVER-DISEASE; LOW-FREQUENCY; WHOLE-BLOOD; VARIANTS
AB Little is known about the inter-individual variation of cytokine responses to different pathogens in healthy individuals. To systematically describe cytokine responses elicited by distinct pathogens and to determine the effect of genetic variation on cytokine production, we profiled cytokines produced by peripheral blood mononuclear cells from 197 individuals of European origin from the 200 Functional Genomics (200FG) cohort in the Human Functional Genomics Project (http://www.humanfunctionalgenomics.org), obtained over three different years. We compared bacteria- and fungi-induced cytokine profiles and found that most cytokine responses were organized around a physiological response to specific pathogens, rather than around a particular immune pathway or cytokine. We then correlated genome-wide single-nucleotide polymorphism (SNP) genotypes with cytokine abundance and identified six cytokine quantitative trait loci (QTLs). Among them, a cytokine QTL at the NAA35-GOLM1 locus markedly modulated interleukin (IL)-6 production in response to multiple pathogens and was associated with susceptibility to candidemia. Furthermore, the cytokine QTLs that we identified were enriched among SNPs previously associated with infectious diseases and heart diseases. These data reveal and begin to explain the variability in cytokine production by human immune cells in response to pathogens.
C1 [Li, Yang; Deelen, Patrick; Ricano-Ponce, Isis; Matzaraki, Vasiliki; Swertz, Morris A.; Franke, Lude; Wijmenga, Cisca; Kumar, Vinod] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Joosten, Leo A. B.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.
[Oosting, Marije; Smeekens, Sanne; Jaeger, Martin; Joosten, Leo A. B.; Netea, Mihai G.] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands.
[Deelen, Patrick; Swertz, Morris A.] Univ Groningen, Univ Med Ctr Groningen, Genom Coordinat Ctr, Groningen, Netherlands.
[Xavier, Ramnik J.] Harvard Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA.
[Xavier, Ramnik J.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA USA.
[Xavier, Ramnik J.] Harvard Med Sch, Boston, MA USA.
[Xavier, Ramnik J.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA.
RP Kumar, V (reprint author), Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.; Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands.; Netea, MG (reprint author), Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands.
EM v.kumar@umcg.nl; mihai.netea@radboudumc.nl
RI Smeekens, Sanne/G-8307-2011; Oosting, Marije/H-7437-2015; Franke,
Lude/P-7036-2016; Wijmenga, Cisca/D-2173-2009;
OI Smeekens, Sanne/0000-0002-7835-914X; Franke, Lude/0000-0002-5159-8802;
Deelen, Patrick/0000-0002-5654-3966
FU ERC Consolidator Grant [3310372]; ERC Advanced Grant (FP)/ERC
[2012-322698]; Dutch Digestive Diseases Foundation [MLDS WO11-30];
European Union's Seventh Framework Programme (EU FP7) TANDEM project
[HEALTH-F3-2012-305279]; Netherlands Organization for Scientific
Research (NWO) VENI grant [863.13.011]; Netherlands Organization for
Scientific Research [184021007]
FX The authors thank all volunteers from the 200 Functional Genomics cohort
of the Human Functional Genomics Project for participation in the study.
The authors would like to thank K. McIntyre for editing the final text.
This study was partially supported by a ERC Consolidator Grant (3310372)
to M.G.N. and by the ERC Advanced Grant (FP/2007-2013/ERC grant
2012-322698 to C.W.), the Dutch Digestive Diseases Foundation (MLDS
WO11-30 to C.W. and V.K.), the European Union's Seventh Framework
Programme (EU FP7) TANDEM project (HEALTH-F3-2012-305279 to C.W. and
V.K.), and a Netherlands Organization for Scientific Research (NWO) VENI
grant (863.13.011 to Y.L.). This study made use of data generated by the
'Genome of the Netherlands' project, which is funded by the Netherlands
Organization for Scientific Research (grant no. 184021007). The data
were made available as a Rainbow Project of BBMRI-NL.
NR 54
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U1 6
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD AUG
PY 2016
VL 22
IS 8
BP 952
EP +
DI 10.1038/nm.4139
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DS7YV
UT WOS:000381000200022
PM 27376574
ER
PT J
AU Schiff, D
Schrag, D
AF Schiff, David
Schrag, Deborah
TI Living in a material world: tumor-treating fields at the top of the
charts
SO NEURO-ONCOLOGY
LA English
DT Editorial Material
ID ALTERNATING ELECTRIC-FIELDS; COST-EFFECTIVENESS; GLIOBLASTOMA
C1 [Schiff, David] Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22903 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Schiff, D (reprint author), Univ Virginia, Neurooncol Ctr, Box 800432, Charlottesville, VA 22903 USA.
EM davidschiff@virginia.edu
NR 10
TC 0
Z9 0
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD AUG
PY 2016
VL 18
IS 8
BP 1033
EP 1034
DI 10.1093/neuonc/now138
PG 2
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA DV9TT
UT WOS:000383285800001
PM 27382117
ER
PT J
AU Arvold, ND
Lee, EQ
Mehta, MP
Margolin, K
Alexander, BM
Lin, NU
Anders, CK
Soffietti, R
Camidge, DR
Vogelbaum, MA
Dunn, IF
Wen, PY
AF Arvold, Nils D.
Lee, Eudocia Q.
Mehta, Minesh P.
Margolin, Kim
Alexander, Brian M.
Lin, Nancy U.
Anders, Carey K.
Soffietti, Riccardo
Camidge, D. Ross
Vogelbaum, Michael A.
Dunn, Ian F.
Wen, Patrick Y.
TI Updates in the management of brain metastases
SO NEURO-ONCOLOGY
LA English
DT Review
DE brain metastases; chemotherapy; stereotactic radiosurgery; surgery;
whole brain radiation
ID CELL LUNG-CANCER; POSTOPERATIVE RESECTION CAVITY;
THERAPY-ONCOLOGY-GROUP; HER2-POSITIVE BREAST-CANCER; NERVOUS-SYSTEM
PROGRESSION; QUALITY-OF-LIFE; PHASE-II TRIAL; LAPATINIB PLUS
CAPECITABINE; CLINICAL-PRACTICE GUIDELINE; TYROSINE KINASE INHIBITORS
AB The clinical management/understanding of brain metastases (BM) has changed substantially in the last 5 years, with key advances and clinical trials highlighted in this review. Several of these changes stem from improvements in systemic therapy, which have led to better systemic control and longer overall patient survival, associated with increased time at risk for developing BM. Development of systemic therapies capable of preventing BM and controlling both intracranial and extracranial disease once BM are diagnosed is paramount. The increase in use of stereotactic radiosurgery alone for many patients with multiple BM is an outgrowth of the desire to employ treatments focused on local control while minimizing cognitive effects associated with whole brain radiotherapy. Complications from BM and their treatment must be considered in comprehensive patient management, especially with greater awareness that the majority of patients do not die from their BM. Being aware of significant heterogeneity in prognosis and therapeutic options for patients with BM is crucial for appropriate management, with greater attention to developing individual patient treatment plans based on predicted outcomes; in this context, recent prognostic models of survival have been extensively revised to incorporate molecular markers unique to different primary cancers.
C1 [Arvold, Nils D.] St Lukes Radiat Oncol Associates, St Lukes Canc Ctr, Whiteside Inst Clin Res, Duluth, MN USA.
[Arvold, Nils D.] Univ Minnesota, Duluth, MN 55812 USA.
[Lee, Eudocia Q.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA.
[Lee, Eudocia Q.; Alexander, Brian M.; Lin, Nancy U.; Dunn, Ian F.; Wen, Patrick Y.] Harvard Med Sch, Boston, MA USA.
[Mehta, Minesh P.] Univ Maryland, Med Ctr, Dept Radiat Oncol, Baltimore, MD 21201 USA.
[Margolin, Kim] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA USA.
[Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA.
[Lin, Nancy U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Anders, Carey K.] Univ N Carolina, Dept Med, Div Hematol Oncol, Chapel Hill, NC USA.
[Soffietti, Riccardo] Univ Turin, Dept Neurol Neurooncol, Turin, Italy.
[Camidge, D. Ross] Univ Colorado, Div Med Oncol, Denver, CO 80202 USA.
[Vogelbaum, Michael A.] Cleveland Clin, Dept Neurosurg, Cleveland, OH 44106 USA.
[Dunn, Ian F.] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA.
RP Arvold, ND (reprint author), St Lukes Radiat Oncol Associates, St Lukes Canc Ctr, Lakeview Bldg,1001 East Super St,Suite L101, Duluth, MN 55802 USA.
EM nils.arvold@slhduluth.com
OI mehta, minesh/0000-0002-4812-5713
FU Novocure; Cellectar; Genentech; GlaxoSmithKline; Array Biopharma;
Oncothyreon; Kadmon; Novartis; Puma
FX There was no specific funding source for the information presented in
this review article. M.P.M.: research funding from Novocure and
Cellectar. N.U.L.: research funding from Genentech, GlaxoSmithKline,
Array Biopharma, Oncothyreon, Kadmon, Novartis, and Puma.
NR 149
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U1 7
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD AUG
PY 2016
VL 18
IS 8
BP 1043
EP 1065
DI 10.1093/neuonc/now127
PG 23
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA DV9TT
UT WOS:000383285800004
PM 27382120
ER
PT J
AU Shah, K
AF Shah, Khalid
TI Stem cell-based therapies for tumors in the brain: are we there yet?
SO NEURO-ONCOLOGY
LA English
DT Review
DE brain tumors; glioblastoma (GBM); receptors; stem cells; therapeutics
ID MESENCHYMAL STROMAL CELLS; NEURAL PROGENITOR CELLS; APOPTOSIS-INDUCING
LIGAND; SUICIDE GENE-THERAPY; MALIGNANT GLIOMA; INTRACRANIAL GLIOMA;
IN-VITRO; ONCOLYTIC VIROTHERAPY; INTRACEREBRAL GLIOMA; INTRANASAL
DELIVERY
AB Advances in understanding adult stem cell biology have facilitated the development of novel cell-based therapies for cancer. Recent developments in conventional therapies (eg, tumor resection techniques, chemotherapy strategies, and radiation therapy) for treating both metastatic and primary tumors in the brain, particularly glioblastoma have not resulted in a marked increase in patient survival. Preclinical studies have shown that multiple stem cell types exhibit inherent tropism and migrate to the sites of malignancy. Recent studies have validated the feasibility potential of using engineered stem cells as therapeutic agents to target and eliminate malignant tumor cells in the brain. This review will discuss the recent progress in the therapeutic potential of stem cells for tumors in the brain and also provide perspectives for future preclinical studies and clinical translation.
C1 [Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Stem Cell Therapeut & Imaging Program, Boston, MA USA.
[Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Mol Neurotherapy & Imaging Lab, Boston, MA USA.
[Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Shah, Khalid] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Shah, Khalid] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Shah, K (reprint author), 5403,Bldg 149,13th St, Charlestown, MA 01810 USA.
EM kshah@mgh.harvard.edu
FU [R01CA138922]; [R01CA173077]
FX This work was supported by R01CA138922 and R01CA173077.
NR 145
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U1 9
U2 9
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD AUG
PY 2016
VL 18
IS 8
BP 1066
EP 1078
DI 10.1093/neuonc/now096
PG 13
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA DV9TT
UT WOS:000383285800005
PM 27282399
ER
PT J
AU Lee, A
Lavoie, B
Pan, J
Kim, J
Zenali, M
Wilcox, R
Callas, P
Velez, M
Moses, P
Kuo, B
Mawe, G
AF Lee, A.
Lavoie, B.
Pan, J.
Kim, J.
Zenali, M.
Wilcox, R.
Callas, P.
Velez, M.
Moses, P.
Kuo, B.
Mawe, G.
TI Gender differences in serotonergic signaling are present in the duodenum
in functional dyspepsia
SO NEUROGASTROENTEROLOGY AND MOTILITY
LA English
DT Meeting Abstract
C1 [Lee, A.; Lavoie, B.; Pan, J.; Kim, J.; Zenali, M.; Wilcox, R.; Callas, P.; Velez, M.; Moses, P.; Mawe, G.] Univ Vermont, Burlington, VT USA.
[Lee, A.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kuo, B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1350-1925
EI 1365-2982
J9 NEUROGASTROENT MOTIL
JI Neurogastroenterol. Motil.
PD AUG
PY 2016
VL 28
SU 1
SI SI
MA 25
BP 12
EP 13
PG 2
WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences
SC Gastroenterology & Hepatology; Neurosciences & Neurology
GA DV9VS
UT WOS:000383290900026
ER
PT J
AU Palombo, DJ
Keane, MM
Verfaellie, M
AF Palombo, D. J.
Keane, M. M.
Verfaellie, M.
TI Using future thinking to reduce temporal discounting: Under what
circumstances are the medial temporal lobes critical?
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Hippocampus; Amnesia; Temporal discounting; Delay discounting; Semantic
future thinking
ID MENTAL TIME-TRAVEL; DECISION-MAKING; INTERTEMPORAL CHOICE; EPISODIC
PROSPECTION; MEMORY; HIPPOCAMPUS; AMNESIA; EVENTS; PERSPECTIVE;
KNOWLEDGE
AB The capacity to envision the future plays an important role in many aspects of cognition, including our ability to make optimal, adaptive choices. Past work has shown that the medial temporal lobe (MTL) is necessary for decisions that draw on episodic future thinking. By contrast, little is known about the role of the MTL in decisions that draw on semantic future thinking. Accordingly, the present study investigated whether the MTL contributes to one form of decision making, namely intertemporal choice, when such decisions depend on semantic consideration of the future. In an intertemporal choice task, participants must select either a smaller amount of money that is available in the present or a larger amount of money that would be available at a future date. Amnesic individuals with MTL damage and healthy control participants performed such a task in which, prior to making a choice, they engaged in a semantic generation exercise, wherein they generated items that they would purchase with the future reward. In experiment 1, we found that, relative to a baseline condition involving standard intertemporal choice, healthy individuals were more inclined to select a larger, later reward over a smaller, present reward after engaging in semantic future thinking. By contrast, amnesic participants were paradoxically less inclined to wait for a future reward following semantic future thinking. This finding suggests that amnesics may have had difficulty "tagging" the generated item(s) as belonging to the future. Critically, experiment 2 showed that when the generated items were presented alongside the intertemporal choices, both controls and amnesic participants shifted to more patient choices. These findings suggest that the MTL is not needed for making optimal decisions that draw on semantic future thinking as long as scaffolding is provided to support accurate time tagging. Together, these findings stand to better clarify the role of the MTL in decision making. Published by Elsevier Ltd.
C1 [Palombo, D. J.; Keane, M. M.; Verfaellie, M.] VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA.
[Palombo, D. J.; Keane, M. M.; Verfaellie, M.] Boston Univ, Sch Med, Dept Psychiat, 72 East Concord St, Boston, MA 02118 USA.
[Keane, M. M.] Wellesley Coll, Dept Psychol, 106 Cent St, Wellesley, MA 02481 USA.
RP Palombo, DJ (reprint author), VA Boston Healthcare Syst, 150 South Huntington Ave, Boston, MA 02130 USA.
EM palombo@bu.edu
FU National Institutes of Mental Health [MH093431]; Clinical Science
Research and Development Service of the Department of Veterans Affairs
[IO1 CX000925]; Faculty Award from Wellesley College; Canadian
Institutes of Health Research Postdoctoral Fellowship Award
FX D. J. P., M. M. K. and M. V. designed the research. D. J. P. conducted
the research and analyses and wrote the manuscript with input from M. M.
K. and M. V. This research was supported by the National Institutes of
Mental Health (Grant number: MH093431) and the Clinical Science Research
and Development Service of the Department of Veterans Affairs (Grant
number: IO1 CX000925). The research was also supported by a Faculty
Award from Wellesley College to M. M. K. and a Canadian Institutes of
Health Research Postdoctoral Fellowship Award to D. J. P. The authors
thank Rose Hopkins and Keely Burke for research assistance. The authors
additionally thank the two anonymous reviewers for their insightful
comments on the manuscript. The authors declare no conflicts of
interest. The contents of this manuscript do not represent the views of
the U.S. Department of Veterans Affairs or the United States Government.
NR 31
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U1 7
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD AUG
PY 2016
VL 89
BP 437
EP 444
DI 10.1016/j.neuropsychologia.2016.07.002
PG 8
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA DV5XD
UT WOS:000383003100041
PM 27384755
ER
PT J
AU Klug, TE
Rusan, M
Fuursted, K
Ovesen, T
AF Klug, Tejs Ehlers
Rusan, Maria
Fuursted, Kurt
Ovesen, Therese
TI Peritonsillar Abscess: Complication of Acute Tonsillitis or Weber's
Glands Infection?
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Review
DE pathogenesis; peritonsillar abscess; acute tonsillitis
ID A STREPTOCOCCAL PHARYNGITIS; SORE THROAT; OUTPATIENT MANAGEMENT; QUINSY
TONSILLECTOMY; NEEDLE ASPIRATION; GENERAL-PRACTICE;
FUSOBACTERIUM-NECROPHORUM; ANTIBIOTIC-TREATMENT; PENICILLIN THERAPY;
CLINICAL HISTORY
AB Objective To review the literature concerning the 2 primary hypotheses put forth to explain the pathogenesis of peritonsillar abscess: the acute tonsillitis hypothesis (peritonsillar abscess is a complication of acute tonsillitis) and the Weber gland hypothesis (peritonsillar abscess is an infection of Weber's glands).
Data Sources PubMed, EMBASE.
Review Methods Data supporting or negating one hypothesis or the other were elicited from the literature.
Conclusions Several findings support the acute tonsillitis hypothesis. First, the 2 main pathogens in peritonsillar abscess have been recovered from pus aspirates and bilateral tonsillar tissues with high concordance rates, suggesting that both tonsils are infected in patients with peritonsillar abscess. Second, studies report signs of acute tonsillitis in the days prior to and at the time of peritonsillar abscess. Third, antibiotic treatment reduces the risk of abscess development in patients with acute tonsillitis. However, some findings suggest involvement of the Weber's glands in peritonsillar abscess pathogenesis. First, high amylase levels have been found in peritonsillar pus. Second, the majority of peritonsillar abscesses are located at the superior tonsillar pole in proximity of the Weber's glands. We propose a unified hypothesis whereby bacteria initially infect the tonsillar mucosa and spread via the salivary duct system to the peritonsillar space, where an abscess is formed.
Implications for Practice Our findings support the rationale for antibiotic treatment of patients with severe acute tonsillitis to reduce the risk of abscess development. Improved understanding of peritonsillar abscess pathogenesis is important for the development of efficient prevention strategies.
C1 [Klug, Tejs Ehlers; Rusan, Maria; Ovesen, Therese] Aarhus Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, Aarhus, Denmark.
[Rusan, Maria] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Fuursted, Kurt] Statens Serum Inst, Dept Microbiol & Infect Control, Copenhagen, Denmark.
RP Klug, TE (reprint author), Aarhus Univ Hosp, Dept Otorhinolaryngol Head & Neck Surg, NBG, Bldg 10,Noerrebrogade 44, DK-8000 Aarhus C, Denmark.
EM tejsehlersklug@hotmail.com
NR 92
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U1 0
U2 0
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
EI 1097-6817
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD AUG
PY 2016
VL 155
IS 2
BP 199
EP 207
DI 10.1177/0194599816639551
PG 9
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DU4OZ
UT WOS:000382193700002
PM 27026737
ER
PT J
AU Doyle, EJ
Gratton, MA
Varvares, MA
AF Doyle, Edward J., III
Gratton, Michael Anne
Varvares, Mark A.
TI Impact of Sensory and Motor Defects on Oral Function in an Animal Model
SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY
LA English
DT Article; Proceedings Paper
CT AAO-HNSF Annual Meeting and OTO EXPO
CY SEP 27-30, 2015
CL Dallas, TX
SP AAO, HNSF
DE glossectomy; rat; oral function; surgery; consumption
ID HYPOGLOSSAL NERVE; RECONSTRUCTION; FOOD; FLAPS
AB Objective To evaluate the combined functional impact on swallowing of tongue sensory and motor loss using a rat model.
Study Design Rats underwent selective neurectomies with transection of the motor (hypoglossal) nerve or motor and sensory (lingual) nerves. Postoperative functional parameters were followed for 2 weeks.
Setting Translational research.
Subjects and Methods Thirty-six adolescent male Wistar rats were divided into 4 groups: anesthetic (n = 6), sham surgery (n = 8), hypoglossal transection (n = 10), and hypoglossal and lingual transection (n = 12). Each morning on postoperative days 1 to 14, the water and food intake were quantified and the animal weighed. Two-way analyses of variance (SigmaPlot; SYSTAT, San Jose, California) were performed with factors of group and postoperative day (POD) to analyze whether a significant difference existed between water intake, pellet consumption, and weight change.
Results The hypoglossal and lingual group consumed significantly less water during PODs 1 to 2 and significantly less food during PODs 1 to 3 than any other group. This established a significant difference in body weight between the hypoglossal and lingual group and all other groups for the duration of the study. Measured parameters in the hypoglossal group better approximated those of the control anesthetic and sham groups.
Conclusions The addition of a sensory loss to a motor deficit involving the oral tongue results in a measurably significant difference in weight gain, a marker of function, compared with rats with only a motor deficit. Additional studies are needed to determine if there would be similar findings in a model of sensate vs asensate oral tongue reconstruction.
C1 [Doyle, Edward J., III; Gratton, Michael Anne] St Louis Univ, Dept Otolaryngol, St Louis, MO 63103 USA.
[Varvares, Mark A.] Harvard Med Sch, Dept Otol, Boston, MA USA.
[Varvares, Mark A.] Harvard Med Sch, Dept Laryngol, Boston, MA USA.
[Varvares, Mark A.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
RP Varvares, MA (reprint author), Massachusetts Eye & Ear, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA.
EM Mark_varvares@meei.harvard.edu
NR 14
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U1 2
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0194-5998
EI 1097-6817
J9 OTOLARYNG HEAD NECK
JI Otolaryngol. Head Neck Surg.
PD AUG
PY 2016
VL 155
IS 2
BP 246
EP 251
DI 10.1177/0194599816635629
PG 6
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DU4OZ
UT WOS:000382193700006
PM 26980910
ER
PT J
AU Mouilso, ER
Tuerk, PW
Schnurr, PP
Rauch, SAM
AF Mouilso, Emily R.
Tuerk, Peter W.
Schnurr, Paula P.
Rauch, Sheila A. M.
TI Addressing the Gender Gap: Prolonged Exposure for PTSD in Veterans
SO PSYCHOLOGICAL SERVICES
LA English
DT Article
DE effectiveness; female veterans; posttraumatic stress disorder; prolonged
exposure therapy
ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; TRAUMATIC
BRAIN-INJURY; HEALTH-STATUS; SEXUAL TRAUMA; WOMEN; MILITARY; OUTCOMES;
FEMALE; CARE
AB As the proportion of women serving in the United States military continues to increase, more female veterans are being treated for posttraumatic stress disorder (PTSD) in Department of Veterans Affairs (VA) health care settings. Prolonged Exposure (PE) therapy is an evidence-based treatment for PTSD and is often used in VA settings. However, only a few studies have investigated the effectiveness of PE specifically for female veterans with appropriate power. Results of these studies have varied, with similar effects between female and male veterans on par with civilian effects, and more recently, better outcomes for female veterans receiving PE compared with male veterans. The current study contextualizes the evidence from those studies and considers new data regarding clinical outcomes pre- and posttreatment for a large (N = 325) sample of male and female veterans treated with PE in a PTSD specialty clinic. Results indicate a large statistically significant decrease in PTSD as measured by PTSD Checklist (PCL) scores for both male and female veterans treated with PE (d = 1.33). No difference in effectiveness and no difference in treatment completion rates were found between male and female veterans. Our findings support the effectiveness of PE for the treatment of PTSD in female as well as male veterans. Results are compared and contrasted to previous findings in the literature taking into account heterogeneity in methodological and ecological factors among the studies. Emphasis is placed on context of care issues to further the empirical conversation regarding meeting the mental health needs of female veterans.
C1 [Mouilso, Emily R.; Tuerk, Peter W.] Ralph H Johnson VA Med Ctr, Charleston, SC USA.
[Mouilso, Emily R.; Tuerk, Peter W.] Med Univ South Carolina, Charleston, SC USA.
[Schnurr, Paula P.] Natl Ctr PTSD, White River Jct, VT USA.
[Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA.
[Rauch, Sheila A. M.] Dept Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Rauch, Sheila A. M.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Mouilso, Emily R.] Charlie Norwood VA Med Ctr, Augusta, GA 30901 USA.
RP Mouilso, ER (reprint author), Charlie Norwood VA Med Ctr, Augusta, GA 30901 USA.
EM emilymouilso@gmail.com
FU Department of Veteran Affairs, Veterans Health Administration, Office of
Research and Development, Clinical Sciences Research and Development
FX Dr. Peter W. Tuerk's contribution to this article was partially
supported by a Career Development Award (CDA-2) from the Department of
Veteran Affairs, Veterans Health Administration, Office of Research and
Development, Clinical Sciences Research and Development (PI: Peter W.
Tuerk).
NR 54
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U1 2
U2 2
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1541-1559
EI 1939-148X
J9 PSYCHOL SERV
JI Psychol. Serv.
PD AUG
PY 2016
VL 13
IS 3
BP 308
EP 316
DI 10.1037/ser0000040
PG 9
WC Psychology, Clinical
SC Psychology
GA DV7HC
UT WOS:000383106000012
PM 26121077
ER
PT J
AU Marques, L
Dixon, L
Valentine, SE
Borba, CPC
Simon, NM
Stirman, SW
AF Marques, Luana
Dixon, Louise
Valentine, Sarah E.
Borba, Christina P. C.
Simon, Naomi M.
Stirman, Shannon Wiltsey
TI Providers' Perspectives of Factors Influencing Implementation of
Evidence-Based Treatments in a Community Mental Health Setting: A
Qualitative Investigation of the Training-Practice Gap
SO PSYCHOLOGICAL SERVICES
LA English
DT Article
DE implementation; communities; attitudes; evidence-based treatments
ID POSTTRAUMATIC-STRESS-DISORDER; COGNITIVE PROCESSING THERAPY; RANDOMIZED
CONTROLLED-TRIAL; EVIDENCE-BASED PSYCHOTHERAPIES; CLINICIAN
PERSPECTIVES; BEHAVIORAL TREATMENT; EXPOSURE THERAPY; ASSAULT VICTIMS;
PTSD SYMPTOMS; ATTITUDES
AB This study aims to elucidate relations between provider perceptions of aspects of the consolidated framework for implementation research (Damschroder et al., 2009) and provider attitudes toward the implementation of evidence-based treatments (EBTs) in an ethnically diverse community health setting. Guided by directed content analysis, we analyzed 28 semistructured interviews that were conducted with providers during the pre-implementation phase of a larger implementation study for cognitive processing therapy for posttraumatic stress disorder (Resick et al., 2008). Our findings extend the existing literature by also presenting provider-identified client-level factors that contribute to providers' positive and negative attitudes toward EBTs. Provider-identified client-level factors include the following: client motivation to engage in treatment, client openness to EBTs, support networks of family and friends, client use of community and government resources, the connection and relationship with their therapist, client treatment adherence, client immediate needs or crises, low literacy or illiteracy, low levels of education, client cognitive limitations, and misconceptions about therapy. These results highlight the relations between provider perceptions of their clients, provider engagement in EBT training, and subsequent adoption of EBTs. We present suggestions for future implementation research in this area.
C1 [Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
[Marques, Luana; Valentine, Sarah E.; Borba, Christina P. C.; Simon, Naomi M.] Harvard Med Sch, Dept Psychiat, Boston, MA USA.
[Dixon, Louise] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA.
[Valentine, Sarah E.; Borba, Christina P. C.; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Stirman, Shannon Wiltsey] US Dept Vet Affairs, Palo Alto, CA USA.
[Stirman, Shannon Wiltsey] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Stirman, Shannon Wiltsey] Natl Ctr PTSD, Disseminat & Training Div, Palo Alto, CA USA.
RP Marques, L (reprint author), Massachusetts Gen Hosp, Community Psychiat PRIDE, 70 Everett Ave,Suite 516, Chelsea, MA 02150 USA.
EM lmarques@mgh.harvard.edu
OI Wiltsey Stirman, Shannon/0000-0001-9917-5078
FU National Institutes of Health Grant [K23 MH096029-01A1]
FX This study was funded by the National Institutes of Health Grant K23
MH096029-01A1 awarded to Luana Marques. The authors express sincere
gratitude to the providers who collaborated in this study and the
project's research assistants.
NR 63
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U1 7
U2 7
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1541-1559
EI 1939-148X
J9 PSYCHOL SERV
JI Psychol. Serv.
PD AUG
PY 2016
VL 13
IS 3
BP 322
EP 331
DI 10.1037/ser0000087
PG 10
WC Psychology, Clinical
SC Psychology
GA DV7HC
UT WOS:000383106000014
PM 27281696
ER
PT J
AU Henderson, AW
Turner, AP
Williams, RM
Norvell, DC
Hakimi, KN
Czerniecki, JM
AF Henderson, Alison W.
Turner, Aaron P.
Williams, Rhonda M.
Norvell, Daniel C.
Hakimi, Kevin N.
Czerniecki, Joseph M.
TI Sexual Activity After Dysvascular Lower Extremity Amputation
SO REHABILITATION PSYCHOLOGY
LA English
DT Article
DE amputation; sexual activity; dysvascular disease; satisfaction with life
ID QUALITY-OF-LIFE; LOWER-LIMB AMPUTATION; PAIN GRADE QUESTIONNAIRE;
ERECTILE DYSFUNCTION; MAJOR DEPRESSION; SINGLE-ITEM; SELF-REPORT;
NATIONAL-SURVEY; ADULT AMPUTEES; PHANTOM PAIN
AB Objective: This study examined the prevalence and correlates of sexual activity among individuals experiencing their first dysvascular lower extremity amputation. Design: A prospective cohort was recruited from 4 Veterans Affairs Medical Centers. Of 198 potential participants who met inclusion criteria, 113 (57%) agreed to participate within 7 days of amputation (baseline) and 6 weeks, 4 months, and 12 months post-amputation; 105 completed the sexual activity items at baseline. Measures included self-reported frequency of sexual activity; desire for more or less sexual activity; importance of sexual activity to satisfaction with life; Patient Health Questionnaire-9; Locomotor Capability Index-5; pain intensity/frequency; quality of life. Results: Depending on the time period post-amputation, 11%-24% reported engaging in any sexual activity, although a majority indicated that sexual activity is very important to their satisfaction with life. Frequency of sexual activity increased between 6 weeks and 4 and 12 months post-amputation. In univariate analyses, older age was associated with decreased sexual activity at all time points; at 4 and 12 months, greater mobility was associated with increased sexual activity. In multivariable models, mobility was associated with sexual activity at 4 and 12 months; age and race remained associated with sexual activity at 4 and 12 months, respectively. At all time points, frequency and importance of sexual activity were significantly associated with one another. Conclusions: Although a minority of individuals engaged in any sexual activity during the study period, it remained an important factor in overall satisfaction with life. Younger age and improved mobility were associated with increased sexual activity. Rehabilitation specialists are encouraged to address sexuality and, if relevant, incorporate it into rehabilitation goals.
Impact and Implications
Although individuals with lower extremity amputation (LEA) endorse continued interest in sexual activity, this important aspect of life is often underemphasized by care providers and researchers alike. This study is the first to examine sexual activity among those with recent LEA longitudinally, evaluating the frequency as well as correlates of sexual activity at four time points in the year following amputation. Consistent with their healthy peers of comparable age, individuals with recent LEA secondary to dysvascular disease continue to identify sexual activity as important to their overall satisfaction with life, although only a minority (depending on the time period post-amputation, between 11 and 24%) report engaging in any sexual activity in the year following amputation. In practice, many rehabilitation care providers often fail to address sexuality and sexual activity explicitly among those with recent dysvascular LEA. Rehabilitation psychologists, physicians and other care providers can play a key role in ensuring sexuality is addressed, possibly framing it within the broader context of activities of daily living (ADLs), particularly as increased mobility is associated with increased frequency of sexual activity.
C1 [Henderson, Alison W.] Vet Affairs VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA 98108 USA.
[Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA.
[Turner, Aaron P.; Williams, Rhonda M.; Hakimi, Kevin N.; Czerniecki, Joseph M.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Norvell, Daniel C.] Spectrum Res Inc, Tacoma, WA USA.
RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, RCS-117,1660 South Columbian Way, Seattle, WA 98108 USA.
EM Aaron.Turner@va.gov
FU U.S. Department of Veterans Affairs, Office of Research and Development,
Rehabilitation Research and Development Service [A41241, B4927W]
FX This work was supported by Merit Review Award A41241 and Career
Development Award B4927W from the U.S. Department of Veterans Affairs,
Office of Research and Development, Rehabilitation Research and
Development Service. The contents do not represent the views of the U.S.
Department of Veterans Affairs or the U.S. government.
NR 66
TC 0
Z9 0
U1 7
U2 7
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0090-5550
EI 1939-1544
J9 REHABIL PSYCHOL
JI Rehabil. Psychol.
PD AUG
PY 2016
VL 61
IS 3
BP 260
EP 268
DI 10.1037/rep0000087
PG 9
WC Psychology, Clinical; Rehabilitation
SC Psychology; Rehabilitation
GA DV9HR
UT WOS:000383251900005
PM 27253221
ER
PT J
AU Dhakal, LP
Sen, A
Stanko, CM
Rawal, B
Heckman, MG
Hoyne, JB
Dimberg, EL
Freeman, ML
Ng, LK
Rabinstein, AA
Freeman, WD
AF Dhakal, Laxmi P.
Sen, Ayan
Stanko, Carlene M.
Rawal, Bhupendra
Heckman, Michael G.
Hoyne, Jonathan B.
Dimberg, Elliot L.
Freeman, Michelle L.
Ng, Lauren K.
Rabinstein, Alejandro A.
Freeman, William D.
TI Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients
Treated with Therapeutic Hypothermia
SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT
LA English
DT Article
ID INTERNATIONAL LIAISON COMMITTEE; EMERGENCY CARDIOVASCULAR CARE;
AMERICAN-HEART-ASSOCIATION; COMATOSE SURVIVORS;
CARDIOPULMONARY-RESUSCITATION; ISCHEMIC COMA; PROGNOSTICATION;
PREDICTION; GUIDELINES; STATEMENT
AB Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p=0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved.
C1 [Dhakal, Laxmi P.; Freeman, Michelle L.; Ng, Lauren K.; Freeman, William D.] Mayo Clin, Dept Crit Care, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
[Dhakal, Laxmi P.; Dimberg, Elliot L.; Ng, Lauren K.; Freeman, William D.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Sen, Ayan] Mayo Clin, Dept Pulm & Crit Care Med, Phoenix, AZ USA.
[Stanko, Carlene M.] Mayo Clin, CRISP, Jacksonville, FL 32224 USA.
[Rawal, Bhupendra; Heckman, Michael G.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Jacksonville, FL 32224 USA.
[Hoyne, Jonathan B.] Mayo Clin, Dept Lab Med & Pathol, Jacksonville, FL 32224 USA.
[Ng, Lauren K.; Freeman, William D.] Mayo Clin, Dept Neurosurg, Jacksonville, FL 32224 USA.
[Rabinstein, Alejandro A.] Mayo Clin, Dept Crit Care, Rochester, MN USA.
[Rabinstein, Alejandro A.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Dhakal, Laxmi P.] Wesley Med Ctr, Neurocrit Care Unit, Wichita, KS USA.
[Rawal, Bhupendra] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
RP Freeman, WD (reprint author), Mayo Clin, Dept Crit Care, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM freeman.william1@mayo.edu
NR 21
TC 1
Z9 1
U1 1
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-7658
EI 2153-7933
J9 THER HYPOTHERMIA TEM
JI Ther. Hypothermia Temp. Manag.
PD AUG
PY 2016
VL 6
IS 3
BP 116
EP 121
DI 10.1089/ther.2015.0035
PG 6
WC Critical Care Medicine
SC General & Internal Medicine
GA DV9RC
UT WOS:000383277700003
PM 27135180
ER
PT J
AU Bader, MK
Guanci, MM
Figueroa, SA
Brophy, GM
Laux, C
AF Bader, Mary Kay
Guanci, Mary McKenna
Figueroa, Stephen A.
Brophy, Gretchen M.
Laux, Chris
TI Clinical Q & A: Translating Therapeutic Temperature Management from
Theory to Practice
SO THERAPEUTIC HYPOTHERMIA AND TEMPERATURE MANAGEMENT
LA English
DT Article
ID HOSPITAL CARDIAC-ARREST; HYPOTHERMIA; THROMBOSIS; RESUSCITATION;
SEIZURES
C1 [Bader, Mary Kay] Mission Hosp, Mission Viejo, CA 92691 USA.
[Guanci, Mary McKenna] Massachusetts Gen Hosp, Neurosci Intens Care, Boston, MA 02114 USA.
[Figueroa, Stephen A.] Univ Texas Southwestern Med Ctr Dallas, Div Neurocrit Care, Dallas, TX 75390 USA.
[Brophy, Gretchen M.] Virginia Commonwealth Univ, Med Coll Virginia Campus, Richmond, VA USA.
[Laux, Chris] Harborview Med Ctr, Seattle, WA USA.
RP Bader, MK (reprint author), Mission Hosp, Mission Viejo, CA 92691 USA.
NR 22
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 2153-7658
EI 2153-7933
J9 THER HYPOTHERMIA TEM
JI Ther. Hypothermia Temp. Manag.
PD AUG
PY 2016
VL 6
IS 3
BP 146
EP 149
DI 10.1089/ther.2016.29016.mkb
PG 4
WC Critical Care Medicine
SC General & Internal Medicine
GA DV9RC
UT WOS:000383277700008
PM 27504625
ER
PT J
AU Lanuti, M
AF Lanuti, Michael
TI Managing Controversial Issues in Thoracic Surgery Preface
SO THORACIC SURGERY CLINICS
LA English
DT Editorial Material
C1 [Lanuti, Michael] Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, Thorac Oncol,Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
RP Lanuti, M (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, Thorac Oncol,Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM mlanuti@mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 3
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1547-4127
J9 THORAC SURG CLIN
JI Thorac. Surg. Clin.
PD AUG
PY 2016
VL 26
IS 3
BP IX
EP IX
DI 10.1016/j.thorsurg.2016.05.001
PG 1
WC Respiratory System; Surgery
SC Respiratory System; Surgery
GA DT2ST
UT WOS:000381331400001
PM 27427531
ER
PT J
AU Lanuti, M
AF Lanuti, Michael
TI Surgical Management of Oligometastatic Non-Small Cell Lung Cancer
SO THORACIC SURGERY CLINICS
LA English
DT Article
DE Oligometastases; Metastases; Non-small lung cancer; Surgery;
Metastectomy
ID PHASE-II-TRIAL; SYNCHRONOUS BRAIN METASTASES; ISOLATED ADRENAL
METASTASIS; TNM STAGE GROUPINGS; LAPAROSCOPIC ADRENALECTOMY;
PROGNOSTIC-FACTORS; CEREBRAL METASTASIS; CARCINOMA; RESECTION; SURVIVAL
AB Patients harboring stage IV non-small cell lung cancer represent a heterogeneous population with limited life expectancy. Targeted chemotherapy and immunotherapy have improved median survival for a minority of patients. A subset of patients with solitary foci of metastatic disease appears to have improved survival compared to others with stage IV NSCLC. The role of aggressive local control with curative intent for all disease sites in synchronous oligometastatic disease lacks randomized data; however, published retrospective series from single institutions suggest improved survival in highly selected patients (11-30%, 5-year survival) with low morbidity and mortality <2%.
C1 [Lanuti, Michael] Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
RP Lanuti, M (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM MLanuti@mgh.harvard.edu
NR 47
TC 0
Z9 0
U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1547-4127
J9 THORAC SURG CLIN
JI Thorac. Surg. Clin.
PD AUG
PY 2016
VL 26
IS 3
BP 287
EP +
DI 10.1016/j.thorsurg.2016.04.002
PG 9
WC Respiratory System; Surgery
SC Respiratory System; Surgery
GA DT2ST
UT WOS:000381331400006
PM 27427523
ER
PT J
AU Sihag, S
Muniappan, A
AF Sihag, Smita
Muniappan, Ashok
TI Lymph Node Dissection and Pulmonary Metastasectomy
SO THORACIC SURGERY CLINICS
LA English
DT Article
DE Lymph node; Lung; Metastasectomy
ID RENAL-CELL CARCINOMA; LUNG METASTASECTOMY; COLORECTAL ADENOCARCINOMA;
SURGICAL RESECTION; PROGNOSTIC-FACTOR; BREAST-CANCER; SURVIVAL;
INVOLVEMENT; EXPERIENCE; LYMPHADENECTOMY
AB Unexpected lymph node involvement is observed in approximately 20% of all patients undergoing pulmonary metastasectomy. Lymph node metastasis is often associated with decreased survival in patients with pulmonary metastases. The incidence of lymph node involvement is related to a variety of patient and tumor variables. This article reviews the indications and role for lymph node assessment at pulmonary metastasectomy.
C1 [Sihag, Smita; Muniappan, Ashok] Harvard Med Sch, Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
RP Muniappan, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM amuniappan@partners.org
NR 36
TC 0
Z9 0
U1 3
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1547-4127
J9 THORAC SURG CLIN
JI Thorac. Surg. Clin.
PD AUG
PY 2016
VL 26
IS 3
BP 315
EP +
DI 10.1016/j.thorsurg.2016.04.004
PG 10
WC Respiratory System; Surgery
SC Respiratory System; Surgery
GA DT2ST
UT WOS:000381331400009
PM 27427526
ER
PT J
AU Edwards, KS
Parish, SJ
Rosen, RC
Garvert, DW
Spangler, SL
Ruzek, JI
AF Edwards, Katharine S.
Parish, Sharon J.
Rosen, Raymond C.
Garvert, Donn W.
Spangler, Shana L.
Ruzek, Josef I.
TI A Standardized Patient Methodology to Assess Cognitive-Behavioral
Therapy (CBT) Skills Performance: Development and Testing in a
Randomized Controlled Trial of Web-Based Training
SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY
LA English
DT Article
DE dissemination; training; assessment; standardized patient; objective
standardized clinical examination (OSCE)
ID STRUCTURED CLINICAL EXAMINATION; SUBSTANCE-ABUSE; PROFESSIONAL
PSYCHOLOGY; COMPETENCE BENCHMARKS; TREATMENT PROVIDERS; INTERVENTION;
PSYCHIATRY; IMPLEMENTATION; DISSEMINATION; SCALE
AB Competency-based training is increasingly important in mental health as practitioners are trained in the use of evidence-based treatments for posttraumatic stress disorder (PTSD) and other disorders. Clinical skills according to this model are assessed in various ways, including the use of standardized patient (SP) interviews. This study investigated the reliability and feasibility of using a telephone-based SP interview to evaluate cognitive-behavioral therapy (CBT) skills within a large, randomized trial of online training. This paper describes the development of a standardized SP methodology for the larger study, including case illustration, SP training, development of trainee skills assessment metrics, and rater training. A post hoc substudy evaluated SP performance across time. For the larger study, 2 out of 3 skills assessment metrics showed satisfactory performance and demonstrated consistently good interitem and interrater reliability. The substudy found that SPs were adherent and faithful to their intended character, with little evidence of performance drift. Based on these findings, telephone SP methodologies are a promising technology for large-scale clinical skills assessment in psychology.
C1 [Edwards, Katharine S.] Stanford Univ, Stanford, CA 94305 USA.
[Parish, Sharon J.] Weill Cornell Med Sch, New York, NY USA.
[Parish, Sharon J.] NewYork Presbyterian Hosp, Med Serv, Westchester Div, New York, NY USA.
[Rosen, Raymond C.] New England Res Inst Inc, Watertown, MA USA.
[Garvert, Donn W.; Ruzek, Josef I.] VA Palo Alto Hlth Care Syst, Natl Ctr PTSD, Menlo Pk, CA USA.
[Spangler, Shana L.] VA Greater Los Angeles Healthcare Syst, PTSD, North Hills, CA USA.
RP Edwards, KS (reprint author), Stanford Univ, Dept Cardiovasc Med, 300 Pasteur Dr,Room H2103, Stanford, CA 94305 USA.
EM ksedwards@stanford.edu
NR 49
TC 0
Z9 0
U1 6
U2 6
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1931-3918
EI 1931-3926
J9 TRAIN EDUC PROF PSYC
JI Train. Educ. Prof. Psychol.
PD AUG
PY 2016
VL 10
IS 3
BP 149
EP 156
DI 10.1037/tep0000119
PG 8
WC Psychology, Educational
SC Psychology
GA DV7HQ
UT WOS:000383107400004
ER
PT J
AU Kauth, MR
Shipherd, JC
Barrera, TL
Ortigo, K
Jones, KR
AF Kauth, Michael R.
Shipherd, Jillian C.
Barrera, Terri L.
Ortigo, Kile
Jones, Kenneth R.
TI Trainees' Perceptions of the Veterans Health Administration
Interprofessional Psychology Fellowships in Lesbian, Gay, Bisexual, and
Transgender Health
SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY
LA English
DT Article
DE LGBT; veterans; training; psychology; VHA
ID CARE; COMPETENCE; PROGRAMS; STUDENTS; BIAS
AB To improve the capacity to provide quality health care to lesbian, gay, bisexual and transgender (LGBT) veterans and promote LGBT cultural competence among clinical staff, the United States Veterans Health Administration (VHA) competitively awarded 9 1-year interprofessional postdoctoral psychology fellowships in LGBT health. The interprofessional training model, which involves working with and learning from other disciplines, mirrors the VHA's approach to integrate LGBT services across clinical programs. Fellows' experiences and satisfaction with their training were examined for the first 2 years of the fellowships. Despite variability in clinical and staff educational activities across sites, all fellows reported strong satisfaction with their training experience. The fellows described considerable exposure to other disciplines, working most often with primary care physicians, nurses, and social workers in addition to psychologists. Fellows most enjoyed creating new clinical services and programs for LGBT veterans that would remain after their fellowship year. Consistent with VHA's goal for training programs, the majority of fellows planned to remain in the federal health-care system, having accepted staff positions at a VHA facility or other federal agency. The VHA psychology fellowships in LGBT health appear to be feasible and successful and may serve as a model for fellowships in LGBT health in other agencies or for other disciplines such as primary care, social work, nursing, or endocrinology.
C1 [Kauth, Michael R.; Shipherd, Jillian C.; Jones, Kenneth R.] Vet Hlth Adm, Washington, DC USA.
[Kauth, Michael R.; Barrera, Terri L.] Vet Affairs South Cent Mental Illness Res Educ &, Houston, TX USA.
[Kauth, Michael R.; Barrera, Terri L.] Vet Affairs Hlth Serv Res & Dev Ctr Innovat Qual, Houston, TX USA.
[Kauth, Michael R.] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA.
[Shipherd, Jillian C.] Vet Affairs Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA USA.
[Shipherd, Jillian C.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Barrera, Terri L.] Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA.
[Ortigo, Kile] Vet Affairs Palo Alto Healthcare Syst, Natl Ctr PTSD, Palo Alto, CA USA.
[Ortigo, Kile] Vet Res Inst, Palo Alto, CA USA.
RP Kauth, MR (reprint author), Michael E DeBakey VA Med Ctr, Vet Affairs152, 2002 Holcombe Blvd, Houston, TX 77030 USA.
EM Michael.Kauth@va.gov
FU United States Veterans Affairs South Central Mental Illness Research,
Education and Clinical Center; Houston Veterans Affairs Health Services
Research and Development Center for Innovations in Quality,
Effectiveness and Safety [CIN13-413]
FX THIS WORK WAS SUPPORTED in part by the United States Veterans Affairs
South Central Mental Illness Research, Education and Clinical Center and
the Houston Veterans Affairs Health Services Research and Development
Center for Innovations in Quality, Effectiveness and Safety (CIN13-413).
NR 19
TC 0
Z9 0
U1 4
U2 4
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1931-3918
EI 1931-3926
J9 TRAIN EDUC PROF PSYC
JI Train. Educ. Prof. Psychol.
PD AUG
PY 2016
VL 10
IS 3
BP 165
EP 170
DI 10.1037/tep0000123
PG 6
WC Psychology, Educational
SC Psychology
GA DV7HQ
UT WOS:000383107400006
ER
PT J
AU Liu, QQ
Tomaszewicz, K
Hutchinson, L
Hornick, JL
Woda, B
Yu, HB
AF Liu, Qingqing
Tomaszewicz, Keith
Hutchinson, Lloyd
Hornick, Jason L.
Woda, Bruce
Yu, Hongbo
TI Somatic mutations in histiocytic sarcoma identified by next generation
sequencing
SO VIRCHOWS ARCHIV
LA English
DT Article
DE Histiocytic sarcoma; Next generation sequencing; Somatic mutations; BRAF
proto-oncogene
ID BRAF MUTATIONS; SIGNALING PATHWAY; LUNG-CANCER; CELL; POLYMORPHISMS;
CHEMOTHERAPY; NEOPLASMS; CARCINOMA; MELANOMA; LEUKEMIA
AB Histiocytic sarcoma is a rare malignant neoplasm of presumed hematopoietic origin showing morphologic and immunophenotypic evidence of histiocytic differentiation. Somatic mutation importance in the pathogenesis or disease progression of histiocytic sarcoma was largely unknown. To identify somatic mutations in histiocytic sarcoma, we studied 5 histiocytic sarcomas [3 female and 2 male patients; mean age 54.8 (20-72), anatomic sites include lymph node, uterus, and pleura] and matched normal tissues from each patient as germ line controls. Somatic mutations in 50 "Hotspot" oncogenes and tumor suppressor genes were examined using next generation sequencing. Three (out of five) histiocytic sarcoma cases carried somatic mutations in BRAF. Among them, G464V [variant frequency (VF) of 43.6 %] and G466R (VF of 29.6 %) located at the P loop potentially interfere with the hydrophobic interaction between P and activating loops and ultimately activation of BRAF. Also detected was BRAF somatic mutation N581S (VF of 7.4 %), which was located at the catalytic loop of BRAF kinase domain: its role in modifying kinase activity was unclear. A similar mutational analysis was also performed on nine acute monocytic/monoblastic leukemia cases, which did not identify any BRAF somatic mutations. Our study detected several BRAF mutations in histiocytic sarcomas, which may be important in understanding the tumorigenesis of this rare neoplasm and providing mechanisms for potential therapeutical opportunities.
C1 [Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Woda, Bruce; Yu, Hongbo] UMass Mem Med Ctr, Worcester, MA 01605 USA.
[Liu, Qingqing; Tomaszewicz, Keith; Hutchinson, Lloyd; Woda, Bruce; Yu, Hongbo] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.
[Liu, Qingqing] Univ Texas MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd, Houston, TX 77030 USA.
[Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Yu, Hongbo] VA Boston Healthcare Syst, Pathol & Lab Med Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
RP Yu, HB (reprint author), UMass Mem Med Ctr, Worcester, MA 01605 USA.; Yu, HB (reprint author), Univ Massachusetts, Sch Med, Worcester, MA 01655 USA.; Yu, HB (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, 1400 VFW Pkwy, West Roxbury, MA 02132 USA.
EM Hongbo.Yu@va.gov
NR 34
TC 1
Z9 1
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0945-6317
EI 1432-2307
J9 VIRCHOWS ARCH
JI Virchows Arch.
PD AUG
PY 2016
VL 469
IS 2
BP 233
EP 241
DI 10.1007/s00428-016-1965-2
PG 9
WC Pathology
SC Pathology
GA DU4DL
UT WOS:000382162100012
PM 27259537
ER
PT J
AU Weber, ML
Liang, MC
Flaherty, KT
Heier, JS
AF Weber, Marissa L.
Liang, Michelle C.
Flaherty, Keith T.
Heier, Jeffrey S.
TI Subretinal Fluid Associated With MEK Inhibitor Use in the Treatment of
Systemic Cancer
SO JAMA OPHTHALMOLOGY
LA English
DT Article
ID MELANOMA; RETINOPATHY; TOXICITIES; MUTATIONS; PATHWAY; BRAF
AB IMPORTANCE The use of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitors has become more common in the treatment of systemic cancer. These agents have been associated with a central serous-like retinopathy in some patients. Recognition of such retinal findings and the relatively benign nature of these events is important to avoid unnecessary intervention, including the cessation of a potentially life-prolonging medication.
OBJECTIVES To evaluate the presence and characteristics of subretinal fluid (SRF) associated with the use of MEK inhibitors in the treatment of systemic cancer and to correlate the presence of SRF with visual acuity and symptoms over time.
DESIGN, SETTING, AND PARTICIPANTS Post hoc analysis was conducted of prospectively collected data from 51 patients with locally advanced or metastatic cancer undergoing treatment with the MEK inhibitor binimetinib in 1 of 4 clinical trials. All clinical trial participants underwent complete ophthalmic examination by retina specialists at a private practice in Boston, Massachusetts, and were monitored between February 29, 2012, and January 8, 2014. The examination included Snellen-measured visual acuity, dilated fundus examination, and spectral-domain optical coherence tomography at baseline, biweekly for 2 months, then monthly for the remainder of their trial participation. Post hoc design and data analysis were performed between December 1, 2013, and June 20, 2014.
MAIN OUTCOMES AND MEASURES Visual symptoms, visual acuity, fundus appearance, and the presence and characteristics of SRF noted on optical coherence tomography. The characteristics of angiograms performed at the discretion of the treating physician were reviewed.
RESULTS Of the 51 participants, 18 (35%) were men; the mean (SD) age was 60 (13) years (range, 32-87 years). Forty-six (90%) study participants developed SRF during the study period, with 9 (20%) experiencing symptoms at any point. The mean (SD) central retinal thickness of 39 study participants who developed SRF at the first visit increased from 280 (26) mu m at baseline to 316 (43) mu m at the first visit after starting binimetinib treatment (paired t test, P < .001). On examination, SRF appeared as elevated, yellow-orange pockets in the fovea and/or along the arcades. Corresponding optical coherence tomographic imaging revealed SRF beneath the interdigitation zone. The fovea was affected in 37 of 46 (80%) individuals; the location of SRF accumulation varied. Visual symptoms were mild and mainly transient, occurring in 9 participants with SRF (20%; 95% CI, 10%-33%). Only 2 participants (4%) were found to have SRF at the last study visit after discontinuation of treatment with binimetinib. Both had Snellen-measured visual acuity of 20/25 or better.
CONCLUSIONS AND RELEVANCE The presence of SRF was common in study participants undergoing treatment with the MEK inhibitor binimetinib. Visual symptoms were mild and mainly transient. The presence of SRF did not lead to permanent ocular sequelae. Cessation of life-extending treatment with MEK inhibitors is not indicated when SRF is present.
C1 [Weber, Marissa L.; Liang, Michelle C.; Heier, Jeffrey S.] Ophthalm Consultants Boston, 50 Staniford St,Ste 600, Boston, MA 02114 USA.
[Weber, Marissa L.] Walter Reed Natl Mil Med Ctr, Ophthalmol Serv, Bethesda, MD USA.
[Liang, Michelle C.] Tufts Med Ctr, New England Eye Ctr, Boston, MA USA.
[Flaherty, Keith T.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
RP Heier, JS (reprint author), Ophthalm Consultants Boston, 50 Staniford St,Ste 600, Boston, MA 02114 USA.
EM jsheier@eyeboston.com
FU Aerpio; Alcon/LPath; Allergan; Avalanche; Bayer; EyeGate; Foresight
Biotherapeutics; Forsight Vision4; Genentech; Icon Therapeutics; Janssen
RD; Kala Pharmaceuticals; Kanghong; Kato Pharmaceuticals; Novartis
Pharmaceuticals; Ohr Pharmaceuticals; QLT; Regeneron; RetroSense;
Santen; Shire; Stealth Biotherapeutics; Thrombogenics; Vision Medicines;
Xcovery; Acucela; Astellas; Corcept; Ophthotech; Sanofi/Genzyme
FX Dr Heier is a paid consultant for Aerpio, Alcon/LPath, Allergan,
Avalanche, Bayer, EyeGate, Foresight Biotherapeutics, Forsight Vision4,
Genentech, Icon Therapeutics, Janssen R&D, Kala Pharmaceuticals,
Kanghong, Kato Pharmaceuticals, Novartis Pharmaceuticals, Ohr
Pharmaceuticals, QLT, Regeneron, RetroSense, Santen, Shire, Stealth
Biotherapeutics, Thrombogenics, Vision Medicines, and Xcovery. He
receives research grants from Acucela, Alcon/LPath, Allergan, Astellas,
Corcept, Genentech, Kala Pharmaceuticals, Kato Pharmaceuticals, Novartis
Pharmaceuticals, Ohr Pharmaceuticals, Ophthotech, QLT, Regeneron,
Sanofi/Genzyme, Stealth Biotherapeutics, and Thrombogenics. He owns
stock in and is on the Board of Directors for Ocular Therapeutix. Dr
Flaherty has received an honorarium as a consultant for Novartis. No
other disclosures were reported.
NR 16
TC 1
Z9 1
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6165
EI 2168-6173
J9 JAMA OPHTHALMOL
JI JAMA Ophthalmol.
PD AUG
PY 2016
VL 134
IS 8
BP 855
EP 862
DI 10.1001/jamaophthalmol.2016.0090
PG 8
WC Ophthalmology
SC Ophthalmology
GA DT1AD
UT WOS:000381213200005
PM 27309887
ER
PT J
AU Christophersen, IE
Yin, XY
Larson, MG
Lubitz, SA
Magnani, JW
McManus, DD
Ellinor, PT
Benjamin, EJ
AF Christophersen, Ingrid E.
Yin, Xiaoyan
Larson, Martin G.
Lubitz, Steven A.
Magnani, Jared W.
McManus, David D.
Ellinor, Patrick T.
Benjamin, Emelia J.
TI A comparison of the CHARGE-AF and the CHA(2)DS(2)-VASc risk scores for
prediction of atrial fibrillation in the Framingham Heart Study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID PROPORTIONAL HAZARDS MODEL; AFRICAN-AMERICANS; SURVIVAL ANALYSIS;
COMPETING RISKS; ISCHEMIC-STROKE; CHADS(2); COHORT; VALIDATION;
OUTCOMES; SUBDISTRIBUTION
AB Background Atrial fibrillation (AF) affects more than 33 million individuals worldwide and increases risks of stroke, heart failure, and death. The CHARGE-AF risk score was developed to predict incident AF in three American cohorts and it was validated in two European cohorts. The CHA(2)DS(2)-VASc risk score was derived to predict risk of stroke, peripheral embolism, and pulmonary embolism in individuals with AF, but it has been increasingly used for AF risk prediction. We compared CHARGE-AF risk score versus CHA(2)DS(2)-VASc risk score for incident AF risk in a community-based cohort.
Methods and Results We studied Framingham Heart Study participants aged 46 to 94 years without prevalent AF and with complete covariates. We predicted AF risk using Fine-Gray proportional sub-distribution hazards regression. We used the Wald chi(2) statistic for model fit, C-statistic for discrimination, and Hosmer-Lemeshow (HL) chi(2) statistic for calibration. We included 9722 observations (mean age 63.9 +/- 10.6 years, 56% women) from 4548 unique individuals: 752 (16.5%) developed incident AF and 793 (17.4%) died. The mean CHARGE-AF score was 12.0 +/- 1.2 and the sub-distribution hazard ratio (sHR) for AF per unit increment was 2.15 (95% CI, 99-131%; P <.0001). The mean CHA(2)DS(2)-VASc score was 2.0 +/- 1.5 and the sHR for AF per unit increment was 1.43 (95% CI, 37%-51%; P<.0001). The CHARGE-AF model had better fit than CHA(2)DS(2)-VASc (Wald chi(2) = 403 vs 209, both with 1 df), improved discrimination (C-statistic = 0.75, 95% CI, 0.73-0.76 vs C-statistic = 0.71, 95% CI, 0.69-0.73), and better calibration (HL chi(2) = 5.6, P =.69 vs HL chi(2) = 28.5, P <.0001).
Conclusion The CHARGE-AF risk score performed better than the CHA(2)DS(2)-VASc risk score at predicting AF in a community-based cohort.
C1 [Christophersen, Ingrid E.; Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Christophersen, Ingrid E.; Lubitz, Steven A.; Ellinor, Patrick T.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Christophersen, Ingrid E.] Vestre Viken Hosp Trust, Brum Hosp, Dept Med Res, Drammen, Norway.
[Yin, Xiaoyan; Larson, Martin G.; Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham, MA USA.
[Yin, Xiaoyan; Larson, Martin G.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Framingham Heart Study, Boston, MA 02215 USA.
[Yin, Xiaoyan; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA.
[Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA.
[McManus, David D.] Univ Massachusetts, Sch Med, Dept Med, Cardiovasc Med Div, Worcester, MA USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
RP Benjamin, EJ (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.; Benjamin, EJ (reprint author), Boston Univ, Sch Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM emelia@bu.edu
FU Bayer HealthCare
FX Dr Ellinor is a principal investigator on a grant from Bayer HealthCare
to the Broad Institute.
NR 52
TC 1
Z9 1
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2016
VL 178
BP 45
EP 54
DI 10.1016/j.ahj.2016.05.004
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DT6JK
UT WOS:000381590300006
PM 27502851
ER
PT J
AU Vemulapalli, S
Hellkamp, AS
Jones, WS
Piccini, JP
Mahaffey, KW
Becker, RC
Hankey, GJ
Berkowitz, SD
Nessel, CC
Breithardt, G
Singer, DE
Fox, KAA
Patel, MR
AF Vemulapalli, Sreekanth
Hellkamp, Anne S.
Jones, W. Schuyler
Piccini, Jonathan P.
Mahaffey, Kenneth W.
Becker, Richard C.
Hankey, Graeme J.
Berkowitz, Scott D.
Nessel, Christopher C.
Breithardt, Guenter
Singer, Daniel E.
Fox, Keith A. A.
Patel, Manesh R.
TI Blood pressure control and stroke or bleeding risk in anticoagulated
patients with atrial fibrillation: Results from the ROCKET AF Trial
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID ASPIRIN THERAPY; ISCHEMIC-STROKE; UNITED-STATES; HYPERTENSION;
PREVENTION; WARFARIN; RIVAROXABAN; PREDICTORS; EVENTS; ONSET
AB Background We conducted a retrospective analysis examining the association between systolic blood pressure (SBP) or hypertension bracket and stroke risk in patients with atrial fibrillation (AF).
Methods The study included 14,256 anticoagulated patients in the ROCKET AF trial. Cox proportional hazards models were used to compare the risk of adverse outcomes by European Society of Cardiology hypertension bracket and screening SBP.
Results In total, 90.5% of patients had hypertension (55.8% controlled, 34.6% uncontrolled). The adjusted risk of stroke or systemic embolism (SE) increased significantly for every 10-mm Hg increase in screening SBP (hazard ratio [HR] 1.07, 95% CI 1.02-1.13). There was a trend toward an increased adjusted risk of stroke or SE in patients with controlled (HR 1.22, 95% CI 0.89-1.66) and uncontrolled hypertension (HR 1.42, 95% CI 1.03-1.95) (P =.06). In contrast, the adjusted risk of major bleeding was similar between hypertensive brackets and did not vary significantly by screening SBP. The benefit of rivaroxaban versus warfarin in preventing stroke or SE was consistent among patients regardless of SBP (P interaction = .69).
Conclusions In a trial of anticoagulated patients with AF, increasing screening SBP was independently associated with stroke and SE, and one-third of patients had uncontrolled hypertension. The relative effectiveness and safety of rivaroxaban versus warfarin were consistent across all levels of screening SBP. A single SBP may be an important factor in reducing the overall risk of stroke and SE in anticoagulated patients with AF.
C1 [Vemulapalli, Sreekanth; Hellkamp, Anne S.; Jones, W. Schuyler; Piccini, Jonathan P.; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Mahaffey, Kenneth W.] Stanford Univ, Stanford, CA 94305 USA.
[Becker, Richard C.] Univ Cincinnati, Cincinnati, OH USA.
[Hankey, Graeme J.] Univ Western Australia, Perth, WA, Australia.
[Berkowitz, Scott D.] Bayer HealthCare Pharmaceut, Whippany, NJ USA.
[Nessel, Christopher C.] Janssen Res & Dev, Raritan, NJ USA.
[Breithardt, Guenter] Univ Hosp Munster, Dept Cardiovasc Med, Munster, Germany.
[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, Midlothian, Scotland.
[Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland.
RP Vemulapalli, S (reprint author), Duke Univ, Med Ctr, Box 3026, Durham, NC 27710 USA.
EM sreekanth.vemulapalli@duke.edu
RI Hankey, Graeme /H-4968-2014
OI Hankey, Graeme /0000-0002-6044-7328
FU Janssen Research Development; Bayer HealthCare
FX This work and the ROCKET AF trial were supported by Janssen Research &
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 25
TC 0
Z9 0
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2016
VL 178
BP 74
EP 84
DI 10.1016/j.ahj.2016.05.001
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DT6JK
UT WOS:000381590300009
PM 27502854
ER
PT J
AU Decker, C
Garavalia, L
Garavalia, B
Gialde, E
Yeh, RW
Spertus, J
Chhatriwalla, AK
AF Decker, Carole
Garavalia, Linda
Garavalia, Brian
Gialde, Elizabeth
Yeh, Robert W.
Spertus, John
Chhatriwalla, Adnan K.
TI Understanding physician-level barriers to the use of individualized risk
estimates in percutaneous coronary intervention
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID BLEEDING AVOIDANCE STRATEGIES; ELEVATION MYOCARDIAL-INFARCTION; DUAL
ANTIPLATELET THERAPY; COLLEGE-OF-CARDIOLOGY; DECISION-MAKING;
HEALTH-CARE; PREMATURE DISCONTINUATION; QUALITATIVE RESEARCH;
ATRIAL-FIBRILLATION; HEART-ASSOCIATION
AB Background The foundation of precision medicine is the ability to tailor therapy based upon the expected risks and benefits of treatment for each individual patient. In a prior study, we implemented a software platform, ePRISM, to execute validated risk-stratification models for patients undergoing percutaneous coronary intervention and found substantial variability in the use of the personalized estimates to tailor care. A better understanding of physicians' perspectives about the use of individualized risk-estimates is needed to overcome barriers to their adoption.
Methods In a qualitative research study, we conducted interviews, in-person or by telephone, with 27 physicians at 8 centers that used ePRISM until thematic saturation occurred. Data were coded using descriptive content analyses.
Results Three major themes emerged among physicians who did not use ePRISM to support decision making: (1) "Experience versus Evidence," physicians' preference to rely upon personal experience and subjective assessments rather than objective risk estimates; (2) "Omission of Therapy," the perception that the use of risk models leads to unacceptable omission of potentially beneficial therapy; and (3) "Unnecessary Information," the opinion that information derived from risk models is not needed because physicians' decision making is already sound and they already know the information.
Conclusions Barriers to the use of risk models in clinical practice include physicians' perceptions that their experience is sufficient, that models may lead to omission of therapy in patients that may benefit from therapy, and that they already provide good care. Anticipating and overcoming these barriers may improve the adoption of precision medicine.
C1 [Decker, Carole; Garavalia, Brian; Gialde, Elizabeth; Spertus, John; Chhatriwalla, Adnan K.] St Lukes Mid Amer Heart Inst, 4300 Wornall Rd,Suite 2000, Kansas City, MO 64111 USA.
[Decker, Carole; Garavalia, Linda; Spertus, John; Chhatriwalla, Adnan K.] Univ Missouri, Kansas City, MO 64110 USA.
[Yeh, Robert W.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Chhatriwalla, AK (reprint author), St Lukes Mid Amer Heart Inst, 4300 Wornall Rd,Suite 2000, Kansas City, MO 64111 USA.
EM achhatriwalla@saint-lukes.org
OI Garavalia, Linda/0000-0002-8156-4435
FU Health Outcomes Sciences
FX The following author disclosures are provided for the previous 3 years
and the immediate future: Drs Decker, L. Garavalia, B. Garavalia, Yeh,
and Chhatriwalla: none; Dr Spertus: equity interest in Health Outcomes
Sciences, which distributes and supports ePRISM; Ms Gialde: consulting
honoraria from Health Outcomes Sciences.
NR 48
TC 1
Z9 1
U1 1
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD AUG
PY 2016
VL 178
BP 190
EP 197
DI 10.1016/j.ahj.2016.03.027
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DT6JK
UT WOS:000381590300024
PM 27502869
ER
PT J
AU Manian, FA
Kelly, E
AF Manian, Farrin A.
Kelly, Erik
TI Lower Extremity Acute Bacterial Skin and Soft Tissue Infection Following
Total Knee Arthroplasty
SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES
LA English
DT Article
DE Cellulitis; Knee; Arthroplasty; Infection
ID CELLULITIS; REPLACEMENT
AB Background: Although total knee arthroplasty (TKA) is one of the most common orthopedic procedures, its association with subsequent acute bacterial skin and soft tissue infections (ABSSTIs) in the ipsilateral limb has not been studied.
Methods: This was a retrospective study of patients with prior unilateral TKA who were diagnosed with ABSSTI 4 weeks or more postoperatively in the absence of surgical site infection. The odds of ABSSTI in the TKA limb was compared to that of the contralateral "control" limb in the same patient in the presence or absence of local predisposing factors for ABSSTI in the lower extremities (e.g., chronic venous insufficiency).
results: Of 94 patients studied, 58 (62%) were women; mean age was 74.5 years. The mean body mass index was 33.1 kg/m(2). One or more local predisposing factors were present in 53 (56.4%) patients. The mean interval between TKA and ABSSTI was 65.1 months (range: 1-239 months), with cellulitis alone diagnosed in 88 (94%) patients. ABSSTI involved the TKA limb of 68 (72.3%) patients and was significantly more likely to be diagnosed in the same limb in the absence of local predisposing factors (36 of 41 patients, odds ratio = 7.2, 95% CI: 2.8-23.5); the odds of TKA limb involvement was also higher in the presence of such factors but did not quite reach statistical significance (odds ratio = 1.5, 95% CI: 0.8-2.8).
Conclusions: TKA appears to predispose to ABSSTIs in the ipsilateral lower extremity often years after the procedure, particularly in the absence of other local factors.
C1 [Manian, Farrin A.; Kelly, Erik] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
RP Manian, FA (reprint author), Massachusetts Gen Hosp, Dept Med, 50 Stanlford,503 B, Boston, MA 02114 USA.
EM Fmanian@MGH.Harvard.edu
NR 16
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 0002-9629
EI 1538-2990
J9 AM J MED SCI
JI Am. J. Med. Sci.
PD AUG
PY 2016
VL 352
IS 2
BP 154
EP 158
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA DV1GG
UT WOS:000382668000006
PM 27524213
ER
PT J
AU Grant, JE
Leppink, EW
Tsai, J
Chamberlain, SR
Redden, SA
Curley, EE
Odlaug, BL
Keuthen, NJ
AF Grant, Jon E.
Leppink, Eric W.
Tsai, Jerry
Chamberlain, Samuel R.
Redden, Sarah A.
Curley, Erin E.
Odlaug, Brian L.
Keuthen, Nancy J.
TI Does comorbidity matter in body-focused repetitive behavior disorders?
SO ANNALS OF CLINICAL PSYCHIATRY
LA English
DT Article
ID SKIN-PICKING DISORDER; HAIR-PULLING DISORDER; OBSESSIVE-COMPULSIVE
DISORDER; STEREOTYPIC MOVEMENT-DISORDER; DYSMORPHIC DISORDER; CORTICAL
THICKNESS; TRICHOTILLOMANIA; EXCORIATION; PREVALENCE
AB BACKGROUND: Trichotillomania (TTM) and skin-picking disorder (SPD) have been characterized as body-focused repetitive behavior disorders (BFRBs). Because BFRBs frequently co-occur, we sought to discover the similarities and differences for individuals having both TTM and SPD as opposed to 1 of these disorders.
METHODS: Participants with primary TTM (N = 421) were evaluated regarding the comorbidity of SPD, and participants with primary SPD (N = 124) were evaluated regarding the comorbidity of TTM. The effects of comorbidity overlap on demographic and clinical measures were evaluated.
RESULTS: Of the 421 participants with primary TTM, 61 (14.5%) had co-occurring SPD. Of 124 participants with primary SPD, 21 (16.9%) had comorbid TTM. Participants with primary TTM and comorbid SPD had significantly more severe tricho tillomania symptoms and were more likely to have major depressive disorder than those with TTM alone. Participants with primary SPD and comorbid TTM reported significantly more severe skin-picking symptoms than those who had only SPD.
CONCLUSIONS: Individuals with co-occurring TTM and SPD may have more problematic symptoms with the primary repetitive behavior. Hair pullers with comorbid SPD were more likely to have comorbid depression. Evaluating patients for multiple BFRBs may be important to assess the severity of symptoms and may have treatment implications.
C1 [Grant, Jon E.; Leppink, Eric W.; Tsai, Jerry; Redden, Sarah A.] Univ Chicago, Pritzker Sch Med, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave,MC-3077, Chicago, IL 60637 USA.
[Chamberlain, Samuel R.] Univ Cambridge, Cambridge & Peterborough NHS Fdn Trust CPFT, Dept Psychiat, Cambridge, England.
[Curley, Erin E.; Keuthen, Nancy J.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Odlaug, Brian L.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Odlaug, Brian L.] H Lundbeck & Co AS, Valby, Denmark.
RP Grant, JE (reprint author), Univ Chicago, Pritzker Sch Med, Dept Psychiat & Behav Neurosci, 5841 S Maryland Ave,MC-3077, Chicago, IL 60637 USA.
EM jongrant@uchicago.edu
FU Trichotillomania Learning Center; BFRB Precision Medicine Initiative
FX This study was funded by the Trichotillomania Learning Center and its
BFRB Precision Medicine Initiative.
NR 29
TC 0
Z9 0
U1 6
U2 6
PU QUADRANT HEALTHCOM INC
PI PARSIPPANY
PA 7 CENTURY DRIVE, STE 302, PARSIPPANY, NJ 07054-4603 USA
SN 1040-1237
EI 1547-3325
J9 ANN CLIN PSYCHIATRY
JI Ann. Clin. Psychiatry
PD AUG
PY 2016
VL 28
IS 3
BP 175
EP 181
PG 7
WC Psychiatry
SC Psychiatry
GA DV1VL
UT WOS:000382710100004
PM 27490833
ER
PT J
AU Moschovis, PP
Hibberd, PL
AF Moschovis, Peter P.
Hibberd, Patricia L.
TI Pulse oximetry: an important first step in improving health outcomes,
but is of little use if there is no oxygen
SO ARCHIVES OF DISEASE IN CHILDHOOD
LA English
DT Editorial Material
ID CHILDHOOD PNEUMONIA
C1 [Moschovis, Peter P.] Massachusetts Gen Hosp, Div Global Hlth, 125 Nashua St,8th Floor, Boston, MA 02114 USA.
[Moschovis, Peter P.] Massachusetts Gen Hosp, Div Pulm Crit Care Med, 125 Nashua St,8th Floor, Boston, MA 02114 USA.
[Hibberd, Patricia L.] Massachusetts Gen Hosp Children, Div Global Hlth, Boston, MA USA.
RP Moschovis, PP (reprint author), Massachusetts Gen Hosp, Div Global Hlth, 125 Nashua St,8th Floor, Boston, MA 02114 USA.; Moschovis, PP (reprint author), Massachusetts Gen Hosp, Div Pulm Crit Care Med, 125 Nashua St,8th Floor, Boston, MA 02114 USA.
EM pmoschovis@mgh.harvard.edu
FU NCCIH NIH HHS [K24 AT003683]; NHLBI NIH HHS [F32 HL124951]
NR 6
TC 0
Z9 0
U1 0
U2 0
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0003-9888
EI 1468-2044
J9 ARCH DIS CHILD
JI Arch. Dis. Child.
PD AUG
PY 2016
VL 101
IS 8
BP 685
EP 685
DI 10.1136/archdischild-2015-310055
PG 1
WC Pediatrics
SC Pediatrics
GA DU9ZX
UT WOS:000382578000001
PM 27073158
ER
PT J
AU Dorans, KS
Wilker, EH
Li, WY
Rice, MB
Ljungman, PL
Schwartz, J
Coull, BA
Kloog, I
Koutrakis, P
D'Agostino, RB
Massaro, JM
Hoffmann, U
O'Donnell, CJ
Mittleman, MA
AF Dorans, Kirsten S.
Wilker, Elissa H.
Li, Wenyuan
Rice, Mary B.
Ljungman, Petter L.
Schwartz, Joel
Coull, Brent A.
Kloog, Itai
Koutrakis, Petros
D'Agostino, Ralph B., Sr.
Massaro, Joseph M.
Hoffmann, Udo
O'Donnell, Christopher J.
Mittleman, Murray A.
TI Residential Proximity to Major Roads, Exposure to Fine Particulate
Matter, and Coronary Artery Calcium: The Framingham Heart Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE air pollution; atherosclerosis; coronary artery calcium; epidemiology;
multidetector computed tomography
ID LONG-TERM EXPOSURE; INTIMA-MEDIA THICKNESS; ACUTE MYOCARDIAL-INFARCTION;
AIR-POLLUTION; CARDIOVASCULAR-DISEASE; SCIENTIFIC STATEMENT;
ATHEROSCLEROSIS; ASSOCIATION; METAANALYSIS; MORTALITY
AB Objective Long-term exposure to traffic and particulate matter air pollution is associated with a higher risk of cardiovascular disease, potentially via atherosclerosis promotion. Prior research on associations of traffic and particulate matter with coronary artery calcium Agatston score (CAC), an atherosclerosis correlate, has yielded inconsistent findings. Given this background, we assessed whether residential proximity to major roadway or fine particulate matter were associated with CAC in a Northeastern US study.
Approach and Results We measured CAC 2 times from 2002 to 2005 and 2008 to 2011 among Framingham Offspring or Third-Generation Cohort participants. We assessed associations of residential distance to major roadway and residential fine particulate matter (2003 average; spatiotemporal model) with detectable CAC, using generalized estimating equation regression. We used linear mixed effects models to assess associations with log(e)(CAC). We also assessed associations with CAC progression. Models were adjusted for demographic variables, socioeconomic position markers, and time. Among 3399 participants, 51% had CAC measured twice. CAC was detectable in 47% of observations. At first scan, mean age was 52.2 years (standard deviation 11.7); 51% male. There were no consistent associations with detectable CAC, continuous CAC, or CAC progression. We observed heterogeneous associations of distance to major roadway with odds of detectable CAC by hypertensive status; interpretation of these findings is questionable.
Conclusions Our findings add to prior work and support evidence against strong associations of traffic or fine particulate matter with the presence, extent, or progression of CAC in a region with relatively low levels of and little variation in fine particulate matter.
C1 [Dorans, Kirsten S.; Wilker, Elissa H.; Li, Wenyuan; Schwartz, Joel; Mittleman, Murray A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Wilker, Elissa H.; Schwartz, Joel; Koutrakis, Petros] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA.
[Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dorans, Kirsten S.; Wilker, Elissa H.; Li, Wenyuan; Rice, Mary B.; Ljungman, Petter L.; Mittleman, Murray A.] Harvard Med Sch, Cardiovasc Epidemiol Res Unit, Dept Cardiol, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Rice, Mary B.] Harvard Med Sch, Div Pulm Crit Care & Sleep Med, Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Hoffmann, Udo] Harvard Med Sch, Cardiac MR PET CT Program, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA.
[O'Donnell, Christopher J.] Harvard Med Sch, Cardiovasc Med, Brigham & Womens Hosp, Boston, MA USA.
[Ljungman, Petter L.] Karolinska Inst, Inst Environm Med, Environm Epidemiol Unit, Stockholm, Sweden.
[Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, Beer Sheva, Israel.
[D'Agostino, Ralph B., Sr.; Massaro, Joseph M.; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA.
[D'Agostino, Ralph B., Sr.; Massaro, Joseph M.; O'Donnell, Christopher J.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[O'Donnell, Christopher J.] Boston Vet Adm Hlth Syst, Cardiol Sect, Dept Med, Boston, MA USA.
RP Mittleman, MA (reprint author), Harvard TH Chan Sch Publ Hlth, 677 Huntington Ave,Suite 505, Boston, MA 02215 USA.
EM mmittlem@hsph.harvard.edu
OI Dorans, Kirsten/0000-0002-3182-5633
FU National Institutes of Health (NIH) [NHLBI T32 HL007575, NIEHS R00
ES022243, K23ES026204]; US Environmental Protection Agency [RD-83479801,
RD-83587201]; NHLBI's Framingham Heart Study [HHSN268201500001I]
FX This work was supported by the National Institutes of Health (NIH; NHLBI
T32 HL007575; NIEHS R00 ES022243, K23ES026204). This publication was
made possible by US Environmental Protection Agency grants RD-83479801
and RD-83587201. Its contents are solely the responsibility of the
grantee and do not necessarily represent the official views of the US
Environmental Protection Agency. Further, US Environmental Protection
Agency does not endorse the purchase of any commercial products or
services mentioned in the publication. From the Framingham Heart Study
of the NHLBI of the NIH and Boston University School of Medicine; this
work was supported by the NHLBI's Framingham Heart Study (Contract No.
HHSN268201500001I). The views expressed in this manuscript are those of
the authors and do not necessarily represent the views of the NHLBI, the
NIH, or the US Department of Health and Human Services.
NR 34
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Z9 3
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD AUG
PY 2016
VL 36
IS 8
BP 1679
EP 1685
DI 10.1161/ATVBAHA.116.307141
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DT4TM
UT WOS:000381474000025
PM 27312220
ER
PT J
AU Januzzi, JL
Lyass, A
Liu, YY
Gaggin, H
Trebnick, A
Maisel, AS
D'Agostino, RB
Wang, TJ
Massaro, J
Vasan, RS
AF Januzzi, James L., Jr.
Lyass, Asya
Liu, Yuyin
Gaggin, Hanna
Trebnick, April
Maisel, Alan S.
D'Agostino, Ralph B., Sr.
Wang, Thomas J.
Massaro, Joseph
Vasan, Ramachandran S.
TI Circulating Proneurotensin Concentrations and Cardiovascular Disease
Events in the Community: The Framingham Heart Study
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE diabetes mellitus; myocardial infarction; nucleotides; risk factors;
stroke
ID NEUROTENSIN; BIOMARKERS; PEPTIDE; SORT1
AB Objective Neurotensin is a peptide whose receptor (sortilin receptor 1) is linked to cardiovascular disease (CVD) development. We hypothesized concentrations of proneurotensin (stable profragment of neurotensin) would predict incident cardiovascular events in community-based subjects.
Approach and Results Blood samples from 3439 participants in the Framingham Heart Study (FHS) Offspring cohort (mean age 59.2 years, 47.1% male) were tested for proneurotensin. Primary outcome of interest was incident hard CVD (myocardial infarction, stroke, and cardiovascular death); interaction between proneurotensin concentration with sex, low-density lipoprotein concentrations, and sortilin receptor 1 single-nucleotide polymorphisms was sought. At baseline, those in the highest log-proneurotensin quartile were younger and heavier (P<0.001); across proneurotensin quartiles, more prevalent hard CVD (from 3% to 7%; P<0.001) and diabetes mellitus (from 6% to 14%; P<0.001) were present. In age- and sex-adjusted models, log-proneurotensin concentrations predicted incident hard CVD (hazard ratio [HR], 1.24 per SD change in log-proneurotensin; 95% confidence intervals [CIs], 1.11-1.39; P<0.001), a finding that remained on adjustment for standard CVD risk factors (HR, 1.13; 95% CI, 1.01-1.27; P=0.03). Elevated log-proneurotensin concentrations were associated with shorter time to first event (P=0.02). We found no effect modification by sex, low-density lipoprotein concentration, or sortilin receptor 1 single-nucleotide polymorphisms. Concentrations of proneurotensin were modestly associated with left ventricular mass and coronary artery calcium in these subjects.
Conclusions Higher concentrations of proneurotensin are associated with a greater risk of incident cardiovascular events in the community. This association did not vary according to sex, baseline low-density lipoprotein, or sortilin receptor 1 genotype.
C1 [Januzzi, James L., Jr.; Lyass, Asya; Gaggin, Hanna; D'Agostino, Ralph B., Sr.; Wang, Thomas J.; Massaro, Joseph; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Januzzi, James L., Jr.; Gaggin, Hanna] Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA.
[Januzzi, James L., Jr.; Gaggin, Hanna; Trebnick, April] Harvard Clin Res Inst, Dept Cardiometab Trials, Boston, MA USA.
[Lyass, Asya; Liu, Yuyin; D'Agostino, Ralph B., Sr.; Massaro, Joseph] Harvard Clin Res Inst, Dept Biostat, Boston, MA USA.
[Lyass, Asya; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Liu, Yuyin; Massaro, Joseph] Boston Univ, Med Ctr, Dept Biostat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Med Ctr, Dept Preventat Med, Boston, MA 02215 USA.
[Maisel, Alan S.] Vet Affairs Med Ctr, Heart Failure Sect, San Diego, CA 92161 USA.
[Wang, Thomas J.] Vanderbilt Univ Sch Med, Div Cardiol, Nashville, TN USA.
RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, Div Cardiol, Yawkey 5B,55 Fruit St, Boston, MA 02114 USA.
EM jjanuzzi@mgh.harvard.edu
FU Hutter Family Professorship in the Field of Cardiology; DeSanctis
Endowed Clinical Scholar in Medicine Fund; Clark Fund for Cardiac
Research Innovation; National Heart Lung and Blood Institute
[N01-HC-25195, HHSN268201500001I]
FX Dr Januzzi is supported, in part, by the Hutter Family Professorship in
the Field of Cardiology, as well as the DeSanctis Endowed Clinical
Scholar in Medicine Fund. Dr Gaggin is supported. in part, by the Clark
Fund for Cardiac Research Innovation. Dr Vasan is supported, in part, by
National Heart Lung and Blood Institute contracts N01-HC-25195 and
HHSN268201500001I.
NR 14
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 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD AUG
PY 2016
VL 36
IS 8
BP 1692
EP 1697
DI 10.1161/ATVBAHA.116.307847
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DT4TM
UT WOS:000381474000027
PM 27312221
ER
PT J
AU Perez, DL
Torous, J
Stern, AP
Padmanabhan, JL
Keshavan, MS
AF Perez, David L.
Torous, John
Stern, Adam P.
Padmanabhan, Jaya L.
Keshavan, Matcheri S.
TI Response to "Tandon et al. Psychiatry is a clinical neuroscience, but
how do we move the field''
SO ASIAN JOURNAL OF PSYCHIATRY
LA English
DT Editorial Material
ID NETWORK; FUTURE
C1 [Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
[Perez, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA.
[Torous, John] Harvard Longwood Psychiat Residency Training Prog, Boston, MA USA.
[Torous, John] Harvard Med Sch, Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA.
[Torous, John; Stern, Adam P.; Padmanabhan, Jaya L.; Keshavan, Matcheri S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA USA.
[Stern, Adam P.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA USA.
[Padmanabhan, Jaya L.] McLean Hosp, Dept Behav Neurol & Neuropsychiat, Belmont, MA USA.
RP Perez, DL (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA.; Perez, DL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St, Charlestown, MA 02129 USA.
EM dlperez@partners.org
OI Padmanabhan, Jaya/0000-0003-3958-5424
NR 10
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1876-2018
EI 1876-2026
J9 ASIAN J PSYCHIATR
JI Asian J. Psychiatr.
PD AUG
PY 2016
VL 22
BP 15
EP 16
DI 10.1016/j.ajp.2016.03.005
PG 2
WC Psychiatry
SC Psychiatry
GA DU1WQ
UT WOS:000382001400004
PM 27520888
ER
PT J
AU Chandra, RM
Arora, L
Mehta, UM
Asnaani, A
Radhakrishnan, R
AF Chandra, Rohit M.
Arora, Lily
Mehta, Urvakhsh M.
Asnaani, Anu
Radhakrishnan, Rajiv
TI Asian Indians in America: The influence of values and culture on mental
health
SO ASIAN JOURNAL OF PSYCHIATRY
LA English
DT Review
DE Asian Indians; Culture; Values; Mental health; Cross-cultural
ID UNITED-STATES; ALCOHOL-USE; 1ST-EPISODE PSYCHOSIS; PREVALENCE RATES; USE
DISORDERS; SCHIZOPHRENIA; SUICIDE; WOMEN; DEPRESSION; SYMPTOMS
AB Asian Indians represent a significant portion of the largest growing race of Asians in the past decade in the United States. This selective review examines major cultural themes related to first-and second-generation Asian Indians living in the United States as they impact psychological and psychiatric dysfunction in this population. Specifically, we review the impact of Asian Indian culture on mental health, discuss the impact of acculturation and ethnic identity development on the mental health of Indian-Americans, and focus on typical mental health problems of Asian Indian adolescents, women and elderly in America. Finally, we provide a brief overview of empirically-supported treatment approaches and cultural considerations for additional treatments relevant to this population. This review is intended to provide an important foundation for more systematic empirically-driven investigation into better understanding how Asian Indian cultural themes impact mental health for Indian-Americans, and how to develop effective treatments for these issues in this cultural group. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Chandra, Rohit M.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Arora, Lily] Rutgers State Univ, New Jersey Med Sch, Newark, NJ USA.
[Mehta, Urvakhsh M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Mehta, Urvakhsh M.] Natl Inst Mental Hlth & Neurosci NIMHANS, Bangalore, Karnataka, India.
[Asnaani, Anu] Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, 3535 Market St,Suite 600 North, Philadelphia, PA 19104 USA.
[Radhakrishnan, Rajiv] Yale Univ, Sch Med, New Haven, CT USA.
RP Asnaani, A (reprint author), Univ Penn, Dept Psychiat, Ctr Treatment & Study Anxiety, 3535 Market St,Suite 600 North, Philadelphia, PA 19104 USA.
EM aasnaani@mail.med.upenn.edu
NR 81
TC 0
Z9 0
U1 13
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1876-2018
EI 1876-2026
J9 ASIAN J PSYCHIATR
JI Asian J. Psychiatr.
PD AUG
PY 2016
VL 22
BP 202
EP 209
DI 10.1016/j.ajp.2015.09.011
PG 8
WC Psychiatry
SC Psychiatry
GA DU1WQ
UT WOS:000382001400045
PM 26442987
ER
PT J
AU Anderson, L
Razavi, M
Skates, S
Anderson, NG
Pearson, TW
AF Anderson, Leigh
Razavi, Morteza
Skates, Steven
Anderson, Norman G.
Pearson, Terry W.
TI Squeezing more value from the analytes we have: personal baselines for
multiple analytes in serial DBS
SO BIOANALYSIS
LA English
DT Editorial Material
DE DBS; MS; panels; personalized
C1 [Anderson, Leigh; Razavi, Morteza; Pearson, Terry W.] SISCAPA Assay Technol, Washington, DC USA.
[Anderson, Leigh; Razavi, Morteza; Pearson, Terry W.] SISCAPA Assay Technol, Victoria, BC, Canada.
[Skates, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Skates, Steven] Harvard Med Sch, Boston, MA USA.
[Anderson, Norman G.] Viral Def Fdn, Rockville, MD USA.
RP Anderson, L (reprint author), SISCAPA Assay Technol, Washington, DC USA.; Anderson, L (reprint author), SISCAPA Assay Technol, Victoria, BC, Canada.
EM leighanderson@siscapa.com
NR 12
TC 1
Z9 1
U1 0
U2 0
PU FUTURE SCI LTD
PI LONDON
PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND
SN 1757-6180
EI 1757-6199
J9 BIOANALYSIS
JI Bioanalysis
PD AUG
PY 2016
VL 8
IS 15
BP 1539
EP 1542
DI 10.4155/bio-2016-0088
PG 4
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA DS8LR
UT WOS:000381035400002
PM 27277878
ER
PT J
AU Thomas, EG
Toufaily, MH
Westgate, MN
Hunt, AT
Lin, AE
Holmes, LB
AF Thomas, Emma G.
Toufaily, M. Hassan
Westgate, Marie-Noel
Hunt, Anne-Therese
Lin, Angela E.
Holmes, Lewis B.
TI Impact of elective termination on the occurrence of severe birth defects
identified in a hospital-based active malformations surveillance program
(1999 to 2002)
SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY
LA English
DT Article
DE malformations surveillance; elective termination; severity of
malformations; occurrence of malformations
ID PRENATAL-DIAGNOSIS; NEWBORN-INFANTS; CLASSIFICATION; PREVALENCE; TRENDS
AB BackgroundThe number of affected infants and the types of malformations identified by a malformation surveillance programs can be impacted if elective terminations for malformations are not included.
MethodsThe occurrence of malformations in all newborn infants was determined in a daily review of the findings in the pediatricians' examinations and those of all consultants. In addition, the findings in autopsies of all elective terminations were reviewed to identify all fetuses with structural abnormalities. A severity scale was used to subdivide the malformations. To establish the impact of elective termination, the malformed infants identified in the Active Malformations Surveillance Program at Brigham and Women's Hospital in Boston were analyzed for the 2 years before and after the hospital decreased significantly the number of elective terminations temporarily (1999-2000 vs. 2001-2002). The effect on the number of malformations identified at birth, as well as malformations of greater severity, was determined.
ResultsThe number of terminated fetuses with malformations decreased dramatically after termination services were interrupted (p<0.0001). There were no differences in the prevalence rates of all malformations in the 2 years before and after the change in access to elective terminations. However, there were significant decreases in the number of infants identified with lethal/life-limiting and severe/handicapping malformations.
ConclusionIn the surveillance for malformations among newborn infants, the inclusion of malformed fetuses from elective terminations had a significant effect on the number of infants with the more severe malformations identified. Birth Defects Research (Part A) 106:659-666, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Thomas, Emma G.; Toufaily, M. Hassan; Westgate, Marie-Noel; Lin, Angela E.; Holmes, Lewis B.] Harvard Med Sch, Brigham & Womens Hosp, Dept Pediat Newborn Med, Act Malformat Surveillance Program, Boston, MA USA.
[Thomas, Emma G.; Toufaily, M. Hassan; Westgate, Marie-Noel; Lin, Angela E.; Holmes, Lewis B.] Harvard Med Sch, MassGen Hosp Children, Med Genet Unit, Boston, MA USA.
[Hunt, Anne-Therese] Hunt Consulting Associates, Thetford Ctr, VT USA.
RP Toufaily, MH (reprint author), MassGen Hosp Children, Med Genet Unit, 175 Cambridge St,5th Floor, Boston, MA 02114 USA.
EM htoufaily@mgh.harvard.edu
NR 15
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-0752
EI 1542-0760
J9 BIRTH DEFECTS RES A
JI Birth Defects Res. Part A-Clin. Mol. Teratol.
PD AUG
PY 2016
VL 106
IS 8
BP 659
EP 666
DI 10.1002/bdra.23510
PG 8
WC Developmental Biology; Toxicology
SC Developmental Biology; Toxicology
GA DV3RC
UT WOS:000382839700003
PM 27116560
ER
PT J
AU Ramachandran, J
Santo, L
Siu, KT
Panaroni, C
Raje, N
AF Ramachandran, J.
Santo, L.
Siu, K. T.
Panaroni, C.
Raje, N.
TI Pim2 is important for regulating DNA damage response in multiple myeloma
cells
SO BLOOD CANCER JOURNAL
LA English
DT Article
ID SERINE/THREONINE KINASE PIM-2; DOXORUBICIN; INHIBITION; RADIATION;
SURVIVAL; THERAPY; CANCERS; GROWTH; TUMOR
AB Pan proviral integrations of Moloney virus (PIM) inhibition in multiple myeloma (MM) results in reduced cell viability in tested human-derived MM cell lines and reduces tumor burden in xenograft mouse models, making PIMs important therapeutic targets for the disease. PIM kinase inhibitors are currently being tested clinically in MM. We sought to elucidate the role of the various PIMs in MM. Our data demonstrate that Pim2 has a significant role in MM cell cytotoxicity. Our data provide evidence for a novel role for Pim2 in the regulation of the DNA damage response (DDR). Knockdown of Pim2 upregulates several downstream DDR markers, mimicking the effects of doxorubicin (Dox) treatment of MM cells, and suggesting a role for the kinase as a negative regulator of this pathway. Dox-induced DNA damage results in a decrease in Pim2 levels, placing the kinase directly downstream of the site of Dox-DNA binding. Overexpression of Pim2 confers a slight survival advantage against Dox through antiapoptotic activity, further underscoring its relevance in the DDR pathway. These data provide insights into a novel mechanism of PIM kinase activity and provide the framework for designing therapeutic approaches in MM.
C1 [Ramachandran, J.; Santo, L.; Siu, K. T.; Panaroni, C.; Raje, N.] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, POB 216,55 Fruit St, Boston, MA 02114 USA.
RP Raje, N (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, POB 216,55 Fruit St, Boston, MA 02114 USA.
EM nraje@mgh.harvard.edu
FU internal Multiple Myeloma Research Fund at MGH
FX This work was supported by an internal Multiple Myeloma Research Fund at
MGH.
NR 20
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 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD AUG
PY 2016
VL 6
AR e462
DI 10.1038/bcj.2016.73
PG 7
WC Oncology
SC Oncology
GA DU3MG
UT WOS:000382114300008
PM 27564460
ER
PT J
AU Wise, R
Anzueto, A
Dahl, R
Dusser, D
Calverley, P
AF Wise, Robert
Anzueto, Antonio
Dahl, Ronald
Dusser, Daniel
Calverley, Peter
TI Tiotropium safety in 'real-world' populations
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Letter
ID OBSTRUCTIVE PULMONARY-DISEASE; TIOSPIR TRIAL; RESPIMAT; COPD
C1 [Wise, Robert] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Anzueto, Antonio] Univ Texas San Antonio, San Antonio, TX USA.
[Anzueto, Antonio] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Dahl, Ronald] Odense Univ Hosp, Odense C, Denmark.
[Dusser, Daniel] Univ Paris 05, Sorbonne Paris Cite, Hop Cochin, AP HP,Serv Pneumol, Paris, France.
[Calverley, Peter] Univ Liverpool, Inst Ageing & Chron Dis, Liverpool, Merseyside, England.
RP Wise, R (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
EM rwise@jhmi.edu
NR 10
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
EI 1365-2125
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD AUG
PY 2016
VL 82
IS 2
BP 562
EP 563
DI 10.1111/bcp.12972
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DU9AV
UT WOS:000382509500025
PM 27197835
ER
PT J
AU Ardeljan, D
Taylor, MS
Burns, KH
Boeke, JD
Espey, MG
Woodhouse, EC
Howcroft, TK
AF Ardeljan, Daniel
Taylor, Martin S.
Burns, Kathleen H.
Boeke, Jef D.
Espey, Michael Graham
Woodhouse, Elisa C.
Howcroft, Thomas Kevin
TI Meeting Report: The Role of the Mobilome in Cancer
SO CANCER RESEARCH
LA English
DT Editorial Material
ID SOMATIC L1 RETROTRANSPOSITION; TRANSPOSABLE ELEMENTS; HUMAN BRAIN;
EXPRESSION; MUTAGENESIS; DROSOPHILA; MOSAICISM; EVOLUTION; CARCINOMA;
GENOMES
AB Approximately half of the human genome consists of repetitive sequence attributed to the activities of mobile DNAs, including DNA transposons, RNA transposons, and endogenous retroviruses. Of these, only long interspersed elements (LINE-1 or L1) and sequences copied by LINE-1 remain mobile in our species today. Although cells restrict L1 activity by both transcriptional and posttranscriptional mechanisms, L1 derepression occurs in developmental and pathologic contexts, including many types of cancers. However, we have limited knowledge of the extent and consequences of L1 expression in premalignancies and cancer. Participants in this NIH strategic workshop considered key questions to enhance our understanding of mechanisms and roles the mobilome may play in cancer biology. (C) 2016 AACR.
C1 [Ardeljan, Daniel; Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Ardeljan, Daniel] Johns Hopkins Univ, Sch Med, Med Scientist Training Program, Baltimore, MD USA.
[Taylor, Martin S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Burns, Kathleen H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Boeke, Jef D.] NYU, Langone Med Ctr, Inst Syst Genet, New York, NY USA.
[Espey, Michael Graham; Woodhouse, Elisa C.; Howcroft, Thomas Kevin] NCI, Div Canc Biol, NIH, Rockville, MD USA.
RP Woodhouse, EC (reprint author), NCI, Tumor Biol & Metastasis Branch, 9609 Med Ctr Dr,Room 6W416, Bethesda, MD 20892 USA.
EM woodhousee@mail.nih.gov
OI Taylor, Martin/0000-0001-5824-142X
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [R01 CA163705]; NIGMS NIH
HHS [T32 GM007309, P50 GM107632]
NR 29
TC 0
Z9 0
U1 2
U2 2
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 AUG 1
PY 2016
VL 76
IS 15
BP 4316
EP 4319
DI 10.1158/0008-5472.CAN-15-3421
PG 4
WC Oncology
SC Oncology
GA DU6AO
UT WOS:000382295300004
PM 27527733
ER
PT J
AU Jiang, X
Bugno, J
Hu, C
Yang, Y
Herold, T
Qi, J
Chen, P
Gurbuxani, S
Arnovitz, S
Strong, J
Ferchen, K
Ulrich, B
Weng, HY
Wang, YG
Huang, H
Li, SL
Neilly, MB
Larson, RA
Le Beau, MM
Bohlander, SK
Jin, J
Li, ZJ
Bradner, JE
Hong, S
Chen, JJ
AF Jiang, Xi
Bugno, Jason
Hu, Chao
Yang, Yang
Herold, Tobias
Qi, Jun
Chen, Ping
Gurbuxani, Sandeep
Arnovitz, Stephen
Strong, Jennifer
Ferchen, Kyle
Ulrich, Bryan
Weng, Hengyou
Wang, Yungui
Huang, Hao
Li, Shenglai
Neilly, Mary Beth
Larson, Richard A.
Le Beau, Michelle M.
Bohlander, Stefan K.
Jin, Jie
Li, Zejuan
Bradner, James E.
Hong, Seungpyo
Chen, Jianjun
TI Eradication of Acute Myeloid Leukemia with FLT3 Ligand-Targeted miR-150
Nanoparticles
SO CANCER RESEARCH
LA English
DT Article
ID SUPPORTED LIPID-BILAYERS; POLY(AMIDOAMINE) DENDRIMERS; THERAPEUTIC
TARGET; NORMAL CYTOGENETICS; MLL TRANSLOCATIONS; PAMAM DENDRIMERS; SIRNA
DELIVERY; HOLE FORMATION; CANCER CELLS; GROUP-B
AB Acute myeloid leukemia (AML) is a common and fatal form of hematopoietic malignancy. Overexpression and/or mutations of FLT3 have been shown to occur in the majority of cases of AML. Our analysis of a large-scale AML patient cohort (N = 562) indicates that FLT3 is particularly highly expressed in some subtypes of AML, such as AML with t(11q23)/MLL-rearrangements or FLT3-ITD. Such AML subtypes are known to be associated with unfavorable prognosis. To treat FLT3-overexpressing AML, we developed a novel targeted nanoparticle system: FLT3 ligand (FLT3L)-conjugated G7 poly(amidoamine) (PAMAM) nanosized dendriplex encapsulating miR-150, a pivotal tumor suppressor and negative regulator of FLT3. We show that the FLT3L-guided miR-150 nanoparticles selectively and efficiently target FLT3-overexpressing AML cells and significantly inhibit viability/growth and promote apoptosis of the AML cells. Our proof-of-concept animal model studies demonstrate that the FLT3L-guided miR-150 nanoparticles tend to concentrate in bone marrow, and significantly inhibit progression of FLT3-overexpressing AML in vivo, while exhibiting no obvious side effects on normal hematopoiesis. Collectively, we have developed a novel targeted therapeutic strategy, using FLT3L-guided miR-150-based nanoparticles, to treat FLT3-overexpressing AML with high efficacy and minimal side effects. (C) 2016 AACR.
C1 [Jiang, Xi; Hu, Chao; Strong, Jennifer; Ferchen, Kyle; Weng, Hengyou; Wang, Yungui; Chen, Jianjun] Univ Cincinnati, Dept Canc Biol, Cincinnati, OH USA.
[Jiang, Xi; Hu, Chao; Chen, Ping; Arnovitz, Stephen; Ulrich, Bryan; Weng, Hengyou; Wang, Yungui; Huang, Hao; Li, Shenglai; Neilly, Mary Beth; Larson, Richard A.; Le Beau, Michelle M.; Li, Zejuan; Chen, Jianjun] Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Bugno, Jason; Yang, Yang; Hong, Seungpyo] Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL USA.
[Hu, Chao; Wang, Yungui; Jin, Jie] Zhejiang Univ, Affiliated Hosp 1, Dept Hematol, Hangzhou, Zhejiang, Peoples R China.
[Hu, Chao; Wang, Yungui; Jin, Jie] Zhejiang Univ, Key Lab Hematopoiet Malignancy, Hangzhou, Zhejiang, Peoples R China.
[Herold, Tobias] Univ Munich, Univ Hosp Grosshadern, Dept Internal Med 3, Munich, Germany.
[Qi, Jun; Bradner, James E.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA.
[Gurbuxani, Sandeep] Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Bohlander, Stefan K.] Univ Auckland, Dept Mol Med & Pathol, Auckland, New Zealand.
[Hong, Seungpyo] Yonsei Univ, Underwood Int Coll, Div Integrated Sci & Engn, Inchon, South Korea.
RP Jiang, X (reprint author), Univ Cincinnati, Dept Canc Biol, Cincinnati, OH USA.; Jiang, X (reprint author), Univ Chicago, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave, Chicago, IL 60637 USA.; Hong, S (reprint author), Univ Illinois, Coll Pharm, Dept Biopharmaceut Sci, Chicago, IL USA.; Hong, S (reprint author), Yonsei Univ, Underwood Int Coll, Div Integrated Sci & Engn, Inchon, South Korea.; Chen, JJ (reprint author), Univ Cincinnati, 3125 Eden Ave,Room 3316, Cincinnati, OH 45219 USA.
EM jiangx4@uc.edu; sphong@uic.edu; chen3jj@uc.edu
OI Larson, Richard/0000-0001-9168-3203
FU NCI NIH HHS [R01 CA182528, R01 CA127277, R01 CA178454]
NR 46
TC 0
Z9 0
U1 7
U2 7
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 AUG 1
PY 2016
VL 76
IS 15
BP 4470
EP 4480
DI 10.1158/0008-5472.CAN-15-2949
PG 11
WC Oncology
SC Oncology
GA DU6AO
UT WOS:000382295300017
PM 27280396
ER
PT J
AU Oddo, D
Sennott, EM
Barault, L
Valtorta, E
Arena, S
Cassingena, A
Filiciotto, G
Marzolla, G
Elez, E
van Geel, RMJM
Bartolini, A
Crisafulli, G
Boscaro, V
Godfrey, JT
Buscarino, M
Cancelliere, C
Linnebacher, M
Corti, G
Truini, M
Siravegna, G
Grasselli, J
Gallicchio, M
Bernards, R
Schellens, JHM
Tabernero, J
Engelman, JA
Sartore-Bianchi, A
Bardelli, A
Siena, S
Corcoran, RB
Di Nicolantonio, F
AF Oddo, Daniele
Sennott, Erin M.
Barault, Ludovic
Valtorta, Emanuele
Arena, Sabrina
Cassingena, Andrea
Filiciotto, Genny
Marzolla, Giulia
Elez, Elena
van Geel, Robin M. J. M.
Bartolini, Alice
Crisafulli, Giovanni
Boscaro, Valentina
Godfrey, Jason T.
Buscarino, Michela
Cancelliere, Carlotta
Linnebacher, Michael
Corti, Giorgio
Truini, Mauro
Siravegna, Giulia
Grasselli, Julieta
Gallicchio, Margherita
Bernards, Rene
Schellens, Jan H. M.
Tabernero, Josep
Engelman, Jeffrey A.
Sartore-Bianchi, Andrea
Bardelli, Alberto
Siena, Salvatore
Corcoran, Ryan B.
Di Nicolantonio, Federica
TI Molecular Landscape of Acquired Resistance to Targeted Therapy
Combinations in BRAF-Mutant Colorectal Cancer
SO CANCER RESEARCH
LA English
DT Article
ID MUTATIONS CONFER RESISTANCE; RAF INHIBITOR RESISTANCE; MEK INHIBITORS;
BRAF(V600E) INHIBITION; METASTATIC MELANOMA; COLON-CANCER; EGFR;
AMPLIFICATION; VEMURAFENIB; CETUXIMAB
AB Although recent clinical trials of BRAF inhibitor combinations have demonstrated improved efficacy in BRAF-mutant colorectal cancer, emergence of acquired resistance limits clinical benefit. Here, we undertook a comprehensive effort to define mechanisms underlying drug resistance with the goal of guiding development of therapeutic strategies to overcome this limitation. We generated a broad panel of BRAF-mutant resistant cell line models across seven different clinically relevant drug combinations. Combinatorial drug treatments were able to abrogate ERK1/2 phosphorylation in parental-sensitive cells, but not in their resistant counterparts, indicating that resistant cells escaped drug treatments through one or more mechanisms leading to biochemical reactivation of the MAPK signaling pathway. Genotyping of resistant cells identified gene amplification of EGFR, KRAS, and mutant BRAF, as well as acquired mutations in KRAS, EGFR, and MAP2K1. These mechanisms were clinically relevant, as we identified emergence of a KRAS G12C mutation and increase of mutant BRAF V600E allele frequency in the circulating tumor DNA of a patient at relapse from combined treatment with BRAF and MEK inhibitors. To identify therapeutic combinations capable of overcoming drug resistance, we performed a systematic assessment of candidate therapies across the panel of resistant cell lines. Independent of the molecular alteration acquired upon drug pressure, most resistant cells retained sensitivity to vertical MAPK pathway suppression when combinations of ERK, BRAF, and EGFR inhibitors were applied. These therapeutic combinations represent promising strategies for future clinical trials in BRAF-mutant colorectal cancer. (C) 2016 AACR.
C1 [Oddo, Daniele; Barault, Ludovic; Arena, Sabrina; Filiciotto, Genny; Marzolla, Giulia; Siravegna, Giulia; Bardelli, Alberto; Di Nicolantonio, Federica] Univ Torino, Dept Oncol, Str Prov 142,Km 3-95, I-10060 Turin, Italy.
[Oddo, Daniele; Barault, Ludovic; Arena, Sabrina; Filiciotto, Genny; Marzolla, Giulia; Bartolini, Alice; Crisafulli, Giovanni; Buscarino, Michela; Cancelliere, Carlotta; Corti, Giorgio; Siravegna, Giulia; Bardelli, Alberto; Di Nicolantonio, Federica] IRCCS, Candiolo Canc Inst FPO, Turin, Italy.
[Sennott, Erin M.; Godfrey, Jason T.; Engelman, Jeffrey A.; Corcoran, Ryan B.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Valtorta, Emanuele; Cassingena, Andrea; Truini, Mauro; Sartore-Bianchi, Andrea; Siena, Salvatore] Grande Osped Metropolitano Niguarda, Niguarda Canc Ctr, Milan, Italy.
[Elez, Elena; Grasselli, Julieta; Tabernero, Josep] Vall dHebron Univ Hosp, Barcelona, Spain.
[Elez, Elena; Grasselli, Julieta; Tabernero, Josep] Univ Autonoma Barcelona, Inst Oncol VHIO, Barcelona, Spain.
[van Geel, Robin M. J. M.; Bernards, Rene; Schellens, Jan H. M.] Netherlands Canc Inst, Amsterdam, Netherlands.
[Boscaro, Valentina; Gallicchio, Margherita] Univ Turin, Dept Drug Sci & Technol, Turin, Italy.
[Linnebacher, Michael] Univ Rostock, Div Mol Oncol & Immunotherapy, Dept Gen Surg, Rostock, Germany.
[Siravegna, Giulia] FIRC Inst Mol Oncol IFOM, Milan, Italy.
[Engelman, Jeffrey A.; Corcoran, Ryan B.] Harvard Med Sch, Dept Med, Boston, MA USA.
[Siena, Salvatore] Univ Milan, Dept Oncol, Milan, Italy.
RP Di Nicolantonio, F (reprint author), Univ Torino, Dept Oncol, Str Prov 142,Km 3-95, I-10060 Turin, Italy.
EM federica.dinicolantonio@unito.it
RI Di Nicolantonio, Federica/A-2503-2011;
OI Di Nicolantonio, Federica/0000-0001-9618-2010; Bernards,
Rene/0000-0001-8677-3423; ARENA, Sabrina/0000-0002-1318-2494
FU NCI NIH HHS [K08 CA166510, P50 CA127003]
NR 49
TC 6
Z9 6
U1 11
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 AUG 1
PY 2016
VL 76
IS 15
BP 4504
EP 4515
DI 10.1158/0008-5472.CAN-16-0396
PG 12
WC Oncology
SC Oncology
GA DU6AO
UT WOS:000382295300020
PM 27312529
ER
PT J
AU Feldman, AZ
Brown, FM
AF Feldman, Anna Z.
Brown, Florence M.
TI Management of Type 1 Diabetes in Pregnancy
SO CURRENT DIABETES REPORTS
LA English
DT Review
DE Type 1 diabetes; Pregnancy; Preconception; Postpartum
ID RANDOMIZED-CONTROLLED-TRIAL; SUBCUTANEOUS INSULIN INFUSION; AMERICAN
THYROID ASSOCIATION; FETAL LUNG MATURATION; METABOLIC-CONTROL;
CONGENITAL-MALFORMATIONS; SEVERE HYPOGLYCEMIA; PRECONCEPTION CARE;
PERINATAL OUTCOMES; GLUCOSE-TOLERANCE
AB Women with type 1 diabetes (T1DM) have unique needs during the preconception, pregnancy, and postpartum periods. Preconception counseling is essential for women with T1DM to minimize pregnancy risks. The goals of preconception care should be tight glycemic control with a hemoglobin A1c (A1C) < 7 % and as close to 6 % as possible, without significant hypoglycemia. This will lower risks of congenital malformations, preeclampsia, and perinatal mortality. The safety of medications should be assessed prior to conception. Optimal control of retinopathy, hypertension, and nephropathy should be achieved. During pregnancy, the goal A1C is near-normal at < 6 %, without excessive hypoglycemia. There is no clear evidence that continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) is superior in achieving the desired tight glycemic control of T1DM during pregnancy. Data regarding continuous glucose monitoring (CGM) in pregnant women with T1DM is conflicting regarding improved glycemic control. However, a recent CGM study does provide some distinct patterns of glucose levels associated with large for gestational age infants. Frequent eye exams during pregnancy are essential due to risk of progression of retinopathy during pregnancy. Chronic hypertension treatment goals are systolic blood pressure 110129 mmHg and diastolic blood pressure 65-79 mmHg. Labor and delivery target plasma glucose levels are 80110 mg/dl, and an insulin drip is recommended to achieve these targets during active labor. Postpartum, insulin doses must be reduced and glucoses closely monitored in women with T1DM because of the enhanced insulin sensitivity after delivery. Breastfeeding is recommended and should be highly encouraged due to maternal benefits including increased insulin sensitivity and weight loss and infant and childhood benefits including reduced prevalence of overweight. In this article, we discuss the care of pregnant patients with T1DM.
C1 [Feldman, Anna Z.; Brown, Florence M.] Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA.
RP Brown, FM (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02115 USA.
EM florence.brown@joslin.harvard.edu
NR 141
TC 0
Z9 0
U1 4
U2 5
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
EI 1539-0829
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD AUG
PY 2016
VL 16
IS 8
AR 76
DI 10.1007/s11892-016-0765-z
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU1UR
UT WOS:000381995900010
PM 27337958
ER
PT J
AU Gonzalez-Franquesa, A
Burkart, AM
Isganaitis, E
Patti, ME
AF Gonzalez-Franquesa, Alba
Burkart, Alison M.
Isganaitis, Elvira
Patti, Mary-Elizabeth
TI What Have Metabolomics Approaches Taught Us About Type 2 Diabetes?
SO CURRENT DIABETES REPORTS
LA English
DT Review
DE Metabolomics; Type 2 diabetes; Insulin resistance; Insulin secretion
ID STIMULATED INSULIN-SECRETION; AMINO-ACID-CONCENTRATIONS; BETA-CELL
DYSFUNCTION; FOR-GESTATIONAL-AGE; Y GASTRIC BYPASS; CHILDHOOD OBESITY;
GUT MICROBIOME; BRANCHED-CHAIN; FATTY-ACID; SKELETAL-MUSCLE
AB Type 2 diabetes (T2D) is increasing worldwide, making identification of biomarkers for detection, staging, and effective prevention strategies an especially critical scientific and medical goal. Fortunately, advances in metabolomics techniques, together with improvements in bioinformatics and mathematical modeling approaches, have provided the scientific community with new tools to describe the T2D metabolome. The metabolomics signatures associated with T2D and obesity include increased levels of lactate, glycolytic intermediates, branched-chain and aromatic amino acids, and longchain fatty acids. Conversely, tricarboxylic acid cycle intermediates, betaine, and other metabolites decrease. Future studies will be required to fully integrate these and other findings into our understanding of diabetes pathophysiology and to identify biomarkers of disease risk, stage, and responsiveness to specific treatments.
C1 [Gonzalez-Franquesa, Alba; Burkart, Alison M.; Isganaitis, Elvira; Patti, Mary-Elizabeth] Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
RP Patti, ME (reprint author), Div Res, 1 Joslin Pl, Boston, MA 02215 USA.
EM mary.elizabeth.patti@joslin.harvard.edu
OI Gonzalez-Franquesa, Alba/0000-0001-9081-753X
FU American Diabetes Association; NIH [T32 DK 007260]; Harold Whitworth
Pierce Charitable Trust Postdoctoral Fellowship; Boston Nutrition and
Obesity Research Center; NIH; Bristol-Myers Squibb; Janssen; Nuclea;
Medimmune; Joslin DRC grant [P30 DK036836]; [K99R00 HD064793]
FX AG-F gratefully acknowledges support from the American Diabetes
Association (mentored research fellowship to MEP). AMB acknowledges
research support from the NIH (T32 DK 007260) and the Harold Whitworth
Pierce Charitable Trust Postdoctoral Fellowship. EI acknowledges grant
support from K99R00 HD064793 and Boston Nutrition and Obesity Research
Center. MEP acknowledges research support from the NIH, American
Diabetes Association, Bristol-Myers Squibb, Janssen, Nuclea, Medimmune,
and Joslin DRC grant P30 DK036836.
NR 135
TC 1
Z9 1
U1 25
U2 27
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
EI 1539-0829
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD AUG
PY 2016
VL 16
IS 8
AR 74
DI 10.1007/s11892-016-0763-1
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU1UR
UT WOS:000381995900008
PM 27319324
ER
PT J
AU Kahraman, S
Okawa, ER
Kulkarni, RN
AF Kahraman, Sevim
Okawa, Erin R.
Kulkarni, Rohit N.
TI Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail
for Type 2 Diabetes?
SO CURRENT DIABETES REPORTS
LA English
DT Review
DE Diabetes; Human pluripotent stem cells; Induced pluripotent stem cells;
Differentiation; Pancreatic beta cells
ID INSULIN-SECRETING CELLS; 10-YEAR FOLLOW-UP; IN-VITRO; PROGENITOR CELLS;
GLUCOSE CONTROL; GENETIC ARCHITECTURE; TOLERANCE INDUCTION;
SUSCEPTIBILITY LOCI; ANTIDIABETIC DRUGS; WIDE ASSOCIATION
AB Diabetes is a progressive disease affecting millions of people worldwide. There are several medications and treatment options to improve the life quality of people with diabetes. One of the strategies for the treatment of diabetes could be the use of human pluripotent stem cells or induced pluripotent stem cells. The recent advances in differentiation of stem cells into insulin-secreting beta-like cells in vitro make the transplantation of the stem cell-derived beta-like cells an attractive approach for treatment of type 1 and type 2 diabetes. While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases.
C1 [Kahraman, Sevim; Okawa, Erin R.; Kulkarni, Rohit N.] Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA.
[Kahraman, Sevim; Okawa, Erin R.; Kulkarni, Rohit N.] Harvard Med Sch, Boston, MA 02215 USA.
[Okawa, Erin R.] Boston Childrens Hosp, Div Endocrinol, Dept Med, Boston, MA 02215 USA.
[Kulkarni, Rohit N.] Harvard Stem Cell Inst, Boston, MA 02215 USA.
RP Kulkarni, RN (reprint author), Joslin Diabet Ctr, Sect Islet Cell Biol & Regenerat Med, Boston, MA 02215 USA.; Kulkarni, RN (reprint author), Harvard Med Sch, Boston, MA 02215 USA.; Kulkarni, RN (reprint author), Harvard Stem Cell Inst, Boston, MA 02215 USA.
EM Rohit.Kulkarni@joslin.harvard.edu
NR 67
TC 0
Z9 0
U1 6
U2 7
PU CURRENT MEDICINE GROUP
PI PHILADELPHIA
PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA
SN 1534-4827
EI 1539-0829
J9 CURR DIABETES REP
JI Curr. Diabetes Rep.
PD AUG
PY 2016
VL 16
IS 8
AR 70
DI 10.1007/s11892-016-0764-0
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DU1UR
UT WOS:000381995900004
PM 27313072
ER
PT J
AU Schumacher, TN
Hacohen, N
AF Schumacher, Ton N.
Hacohen, Nir
TI Editorial overview: Cancer immunology: genomics & biomarkers: Cancer
immunity through the prism of genomics and proteomics
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Editorial Material
C1 [Schumacher, Ton N.] Netherlands Canc Inst, Div Immunol, Amsterdam, Netherlands.
[Hacohen, Nir] Broad Inst Harvard & MIT, 149 13th St, Charlestown, MA 02129 USA.
[Hacohen, Nir] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA.
RP Schumacher, TN (reprint author), Netherlands Canc Inst, Div Immunol, Amsterdam, Netherlands.
EM t.schumacher@nki.nl; nhacohen@mgh.harvard.edu
NR 0
TC 0
Z9 0
U1 4
U2 4
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2016
VL 41
BP IX
EP X
DI 10.1016/j.coi.2016.07.006
PG 2
WC Immunology
SC Immunology
GA DU7TI
UT WOS:000382417100002
PM 27506117
ER
PT J
AU Miao, D
Van Allen, EM
AF Miao, Diana
Van Allen, Eliezer M.
TI Genomic determinants of cancer immunotherapy
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID CELL LUNG-CANCER; CTLA-4 BLOCKADE; METASTATIC MELANOMA; UNTREATED
MELANOMA; PATIENT SURVIVAL; PD-1 BLOCKADE; SIPULEUCEL-T; PHASE-II;
IPILIMUMAB; NIVOLUMAB
AB Cancer immunotherapies including therapeutic vaccines, adoptive cell transfer, oncolytic viruses, and immune checkpoint blockade yield durable responses in many cancer types, but understanding of predictors of response is incomplete. Genomic characterization of human cancers has already contributed to the success of targeted therapies; in cancer immunotherapy, identification of tumor-specific antigens through whole-exome sequencing may be key to designing individualized, highly immunogenic therapeutic vaccines. Additionally, pre-treatment tumor mutational and gene expression signatures can predict which patients are most likely to benefit from cancer immunotherapy. Continued work in harnessing genomic, transcriptomic, and immunological data from clinical cohorts of immunotherapy-treated patients will bring the promises of precision medicine to immuno-oncology.
C1 [Miao, Diana; Van Allen, Eliezer M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Miao, Diana; Van Allen, Eliezer M.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
[Van Allen, Eliezer M.] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA.
RP Van Allen, EM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.; Van Allen, EM (reprint author), Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.; Van Allen, EM (reprint author), Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02215 USA.
EM eliezerm_vanallen@dfci.harvard.edu
NR 46
TC 3
Z9 3
U1 6
U2 6
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2016
VL 41
BP 32
EP 38
DI 10.1016/j.coi.2016.05.010
PG 7
WC Immunology
SC Immunology
GA DU7TI
UT WOS:000382417100007
PM 27254251
ER
PT J
AU Wucherpfennig, KW
Cartwright, ANR
AF Wucherpfennig, Kai W.
Cartwright, Adam N. R.
TI Genetic screens to study the immune system in cancer
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID WIDE CRISPR SCREEN; FUNCTIONAL GENOMICS; TUMOR SUPPRESSORS; SHRNA
LIBRARIES; HUMAN-CELLS; MOUSE; DIFFERENTIATION; REGULATORS; DISCOVERY;
LYMPHOMA
AB RNA interference and CRISPR/Cas9 technologies now enable systematic discovery of genes that regulate key pathways in the complex interaction between immune cells and tumor cells. Discovery screens are feasible in an in vivo setting, allowing identification of genes that limit the effectiveness of anti-tumor immunity. In vivo discovery screens can be informed by single cell RNA-seq experiments that define the differentially expressed genes between functionally distinct immune cell subpopulations, both in humans and relevant animal models. Novel targets for cancer immunotherapy are being defined by the in depth functional annotation of immunosuppressive pathways in the tumor microenvironment.
C1 [Wucherpfennig, Kai W.; Cartwright, Adam N. R.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.
[Wucherpfennig, Kai W.; Cartwright, Adam N. R.] Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA.
[Wucherpfennig, Kai W.] Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA.; Wucherpfennig, KW (reprint author), Harvard Med Sch, Dept Neurol, Boston, MA 02115 USA.; Wucherpfennig, KW (reprint author), Harvard Med Sch, Dept Microbiol & Immunobiol, Boston, MA 02115 USA.
EM kai_wucherpfennig@dfci.harvard.edu
FU Melanoma Research Alliance; Bridge Project of MIT/Koch Institute;
Dana-Farber/Harvard Cancer Center; NIH [1R01CA173750]
FX This work was supported by grants from the Melanoma Research Alliance,
the Bridge Project of MIT/Koch Institute and Dana-Farber/Harvard Cancer
Center, and the NIH (1R01CA173750).
NR 28
TC 0
Z9 0
U1 10
U2 10
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2016
VL 41
BP 55
EP 61
DI 10.1016/j.coi.2016.05:007
PG 7
WC Immunology
SC Immunology
GA DU7TI
UT WOS:000382417100010
PM 27309352
ER
PT J
AU Schumacher, TN
Hacohen, N
AF Schumacher, Ton N.
Hacohen, Nir
TI Neoantigens encoded in the cancer genome
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID T-CELLS; METASTATIC MELANOMA; CHECKPOINT BLOCKADE; CTLA-4 BLOCKADE; PD-1
BLOCKADE; NEO-ANTIGENS; TUMOR; IMMUNOTHERAPY; LYMPHOCYTES; THERAPY
AB Somatic mutations in the genome represent one of the major drivers of malignancy. However, non-synonymous mutations are also a source of mutated peptides that are presented by HLA molecules to induce protective CD4 and CD8 T cell responses. Consistent with this notion, the mutation burden of a tumor is correlated with local immunity as well as outcome of therapy and patient survival. Furthermore, neoantigen-specific T cells appear sufficient to control tumors prophylactically and therapeutically. While the role of neoantigens as a determinant of the foreignness of human cancers is now well established, major questions, including the relative importance of clonal vs subclonal neoantigens, and CD4 vs CD8 T cells, remain unanswered. We expect continued animal studies to address some of the open issues and ongoing clinical trials to establish the utility of therapeutic strategies to enhance neoantigen-specific T cell responses in human cancer.
C1 [Schumacher, Ton N.] Netherlands Canc Inst, Div Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.
[Hacohen, Nir] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
[Hacohen, Nir] Massachusetts Gen Hosp, Ctr Canc Immunol, Boston, MA 02114 USA.
[Hacohen, Nir] Broad Inst Harvard & MIT, Cambridge, MA USA.
RP Schumacher, TN (reprint author), Netherlands Canc Inst, Div Immunol, Plesmanlaan 121, NL-1066 CX Amsterdam, Netherlands.; Hacohen, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.; Hacohen, N (reprint author), Massachusetts Gen Hosp, Ctr Canc Immunol, Boston, MA 02114 USA.; Hacohen, N (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.
EM t.schumacher@nki.nl; nhacohen@mgh.harvard.edu
FU Dutch Cancer Society Queen Wilhelmina Award [NKI 2013-6122]; Blavatnik
Family Foundation; Dutch Cancer Society [NKI 2012-5463]
FX This work was supported by the Dutch Cancer Society Queen Wilhelmina
Award NKI 2013-6122 and Dutch Cancer Society grant NKI 2012-5463 (to
TNS), and the Blavatnik Family Foundation (to NH). We would like to
thank E. Fritsch (Neon Therapeutics) for valuable discussions. TNS and
NH are founders and stockholders of Neon Therapeutics. TNS is employee
and stockholder of Kite Pharma.
NR 44
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U1 14
U2 20
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD AUG
PY 2016
VL 41
BP 98
EP 103
DI 10.1016/j.coi.2016.07.005
PG 6
WC Immunology
SC Immunology
GA DU7TI
UT WOS:000382417100016
PM 27518850
ER
PT J
AU Cahn, A
Raz, I
Mosenzon, O
Leibowitz, G
Yanuv, I
Rozenberg, A
Iqbal, N
Hirshberg, B
Sjostrand, M
Stahre, C
Im, K
Kanevsky, E
Scirica, BM
Bhatt, DL
Braunwald, E
AF Cahn, Avivit
Raz, Itamar
Mosenzon, Ofri
Leibowitz, Gil
Yanuv, Ilan
Rozenberg, Aliza
Iqbal, Nayyar
Hirshberg, Boaz
Sjostrand, Mikaela
Stahre, Christina
Im, KyungAh
Kanevsky, Estella
Scirica, Benjamin M.
Bhatt, Deepak L.
Braunwald, Eugene
TI Predisposing Factors for Any and Major Hypoglycemia With Saxagliptin
Versus Placebo and Overall: Analysis From the SAVOR-TIMI 53 Trial
SO DIABETES CARE
LA English
DT Article
ID BASE-LINE CHARACTERISTICS; BLOOD-GLUCOSE CONTROL; DIABETES-MELLITUS;
VASCULAR OUTCOMES; TYPE-2; RISK; METAANALYSIS; INSULIN; COMPLICATIONS;
HYPERGLYCEMIA
AB OBJECTIVETo analyze the impact of adding saxagliptin versus placebo on the risk for hypoglycemia and to identify predictors of any and major hypoglycemia in patients with type 2 diabetes included in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) study.RESEARCH DESIGN AND METHODSPatients with type 2 diabetes (n = 16,492) were randomized to saxagliptin or placebo and followed for a median of 2.1 years. Associations between any hypoglycemia (symptomatic or glucose measurement <54 mg/dL) or major hypoglycemia (requiring extended assistance) and patient characteristics overall and by treatment allocation were studied.RESULTSAt least one hypoglycemic event was reported in 16.6% of patients, and 1.9% reported at least one major event. Patients allocated to saxagliptin versus placebo experienced higher rates of any (hazard ratio [HR] 1.16 [95% CI 1.08, 1.25]; P < 0.001) or major (HR 1.26 [1.01, 1.58]; P = 0.038) hypoglycemia. Hypoglycemia rates (any or major) were increased with saxagliptin in patients taking sulfonylureas (SURs) but not in those taking insulin. Rates were increased with saxagliptin in those with baseline HbA(1c) 7.0% and not in those with baseline HbA(1c) >7.0%. Multivariate analysis of the overall population revealed that independent predictors of any hypoglycemia were as follows: allocation to saxagliptin, long duration of diabetes, increased updated HbA(1c), macroalbuminuria, moderate renal failure, SUR use, and insulin use. Predictors of major hypoglycemia were allocation to saxagliptin, advanced age, black race, reduced BMI, long duration of diabetes, declining renal function, microalbuminuria, and use of short-acting insulin. Among SURs, glibenclamide was associated with increased risk of major but not any hypoglycemia.CONCLUSIONSThe identification of patients at risk for hypoglycemia can guide physicians to better tailor antidiabetic therapy.
C1 [Cahn, Avivit; Raz, Itamar; Mosenzon, Ofri; Leibowitz, Gil; Yanuv, Ilan; Rozenberg, Aliza] Hadassah Hebrew Univ Hosp, Diabet Unit, Jerusalem, Israel.
[Cahn, Avivit; Leibowitz, Gil] Hadassah Hebrew Univ Hosp, Endocrinol & Metab Unit, Jerusalem, Israel.
[Iqbal, Nayyar] AstraZeneca Res & Dev, Gaithersburg, MD USA.
[Hirshberg, Boaz] MedImmune, Gaithersburg, MD USA.
[Sjostrand, Mikaela; Stahre, Christina] AstraZeneca, Gothenburg, Sweden.
[Im, KyungAh; Kanevsky, Estella; Scirica, Benjamin M.; Bhatt, Deepak L.; Braunwald, Eugene] Harvard Med Sch, Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA USA.
RP Raz, I (reprint author), Hadassah Hebrew Univ Hosp, Diabet Unit, Jerusalem, Israel.
EM ntv502@netvision.net.il
FU AstraZeneca; Bristol-Myers Squibb; Boehringer Ingelheim; Elli Lilly and
Company; Merck Sharp Dohme; Novartis; Novo Nordisk; Sanofi; Hadassah
Hebrew University Hospital-Novo Nordisk; TIMI Study; Daiichi Sankyo;
GlaxoSmithKline; Gilead; Eisai; Biogen Idec; Boehringer; Ingelheim;
Boston Clinical Research Institute; Covance; Dr. Reddy's Laboratory;
Elsevier Practice Update Cardiology; Forest Laboratory; GE Healthcare;
Lexicon; St. Jude Medical; University of Calgary; TIMI Study Group;
Brigham; Women's Hospital
FX The SAVOR-TIMI 53 trial was funded by AstraZeneca and Bristol-Myers
Squibb. A.C. reports receipt of consulting fees and payment for lectures
from AstraZeneca, Boehringer Ingelheim, Elli Lilly and Company, Merck
Sharp & Dohme, Novartis, Novo Nordisk, and Sanofi. I.R. has served on
the advisory board for AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and
Company, Medscape LLC, Merck Sharp & Dohme, Novo Nordisk, Sanofi,
Orgenesis, SmartZyme Innovation Ltd., and LabStyle Innovations Corp.;
has been a consultant for AstraZeneca/Bristol-Meyers Squibb, Insuline
Medical, Gili Medical, KAMADA, and FutuRx; has served on the speaker's
bureau for AstraZeneca/Bristol-Meyers Squibb, Eli Lilly and Company,
Johnson & Johnson, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi,
and Teva; and is a stock-/shareholder of Insuline Medical, LabStyle
Innovations Corp., SmartZyme Innovation Ltd., Orgenesis, and GlucoMe.
O.M. has served on the advisory board for Novo Nordisk, Eli Lilly and
Company, Sanofi, Merck Sharp & Dohme, Boehringer Ingelheim, Janssen,
Novartis, and AstraZeneca; had grants paid to their institution as a
study physician by AstraZeneca and Bristol-Myers Squibb; has received
research grant support through Hadassah Hebrew University Hospital-Novo
Nordisk; and has served on the speaker's bureau for AstraZeneca,
Bristol-Myers Squibb, Novo Nordisk, Eli Lilly and Company, Sanofi,
Novartis, Merck Sharp & Dohme, and Boehringer Ingelheim. G.L. has
received speaker's honoraria from Novartis, Novo Nordisk, Eli Lilly and
Company, and Sanofi and has attended advisory board meetings for Sanofi
and AstraZeneca. N.I., M.S., and C.S. are employees of AstraZeneca. B.H.
is an employee of MedImmune, a subsidiary of AstraZeneca. B.M.S. has
received research grants via the TIMI Study and Brigham and Women's
Hospital from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo,
GlaxoSmithKline, Gilead, Eisai, and Merck Sharp & Dohme and consulting
fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Boston
Clinical Research Institute, Bristol-Myers Squibb, Covance, Dr. Reddy's
Laboratory, Eisai, Elsevier Practice Update Cardiology, Forest
Laboratory, GE Healthcare, Gilead, GlaxoSmithKline, Lexicon, Merck Sharp
& Dohme, St. Jude Medical, and the University of Calgary. D.L.B. has
served on the advisory board for Cardax, Elsevier Practice Update
Cardiology, Medscape Cardiology, and Regado Biosciences; has served on
the board of directors for Boston VA Research Institute and Society of
Cardiovascular Patient Care; has been the chair of the American Heart
Association Quality Oversight Committee; has served on the data
monitoring committee for the Duke Clinical Research Institute, the
Harvard Clinical Research Institute, the Mayo Clinic, and the Population
Health Research Institute; has received honoraria from the American
College of Cardiology (Senior Associate Editor, Clinical Trials and
News, ACC.; org), Belvoir Publications (Editor in Chief, Harvard Heart
Letter), the Duke Clinical Research Institute (clinical trial steering
committees), the Harvard Clinical Research Institute (clinical trial
steering committee), HMP Communications (editor in chief, Journal of
Invasive Cardiology), the Journal of the American College of Cardiology
(guest editor and associate editor), the Population Health Research
Institute (clinical trial steering committee), Slack Publications (chief
medical editor, Cardiology Today's Intervention), the Society of
Cardiovascular Patient Care (secretary/treasurer), WebMD (continuing
medical education steering committees), Clinical Cardiology (deputy
editor), NCDR-ACTION Registry Steering Committee (vice chair), and VA
CART Research and Publications Committee (chair); has received research
funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon,
Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The
Medicines Company; has received royalties from Elsevier (editor,
Cardiovascular Intervention: A Companion to Braunwald's Heart Disease);
has served as site co-investigator for Biotronik, Boston Scientific, and
St. Jude Medical; is a trustee of the American College of Cardiology;
and has performed unfunded research for FlowCo, PLx Pharma, and Takeda.
E.B. has received research grants via the TIMI Study Group and Brigham
and Women's Hospital from Merck Sharp & Dohme, Daiichi Sankyo,
GlaxoSmithKline, Bristol-Myers Squibb, Duke University, AstraZeneca,
Johnson & Johnson, Sanofi, and Novartis; has received consulting fees
from The Medicines Company, Sanofi, and Theravance Biopharma; and has
received payment for lectures from Menarini Group, Bayer, and Medscape.
No other potential conflicts of interest relevant to this article were
reported.
NR 35
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U1 2
U2 2
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 AUG
PY 2016
VL 39
IS 8
BP 1329
EP 1337
DI 10.2337/dc15-2763
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT4CN
UT WOS:000381427800025
PM 27222508
ER
PT J
AU Lachin, JM
Bebu, I
Nathan, DM
Zinman, B
Brillon, D
Backlund, JYC
Cleary, P
Orchard, TJ
AF Lachin, John M.
Bebu, Ionut
Nathan, David M.
Zinman, Bernard
Brillon, David
Backlund, Jye-Yu C.
Cleary, Patricia
Orchard, Trevor J.
CA Diabet Control Complications Trial
TI Mortality in Type 1 Diabetes in the DCCT/EDIC Versus the General
Population
SO DIABETES CARE
LA English
DT Article
ID ALL-CAUSE MORTALITY; LONG-TERM MORTALITY; FOLLOW-UP; PITTSBURGH
EPIDEMIOLOGY; COMPLICATIONS TRIAL; INTENSIVE TREATMENT; NATIONWIDE
COHORTS; MELLITUS; INTERVENTIONS; ASSOCIATION
AB OBJECTIVEHistorically, mortality in type 1 diabetes has exceeded that in the general population. We compared mortality in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study cohort to that of the current general U.S. population.RESEARCH DESIGN AND METHODSThe DCCT (1983-1993) compared intensive versus conventional therapy, with HbA(1c) levels of approximate to 7 vs. 9%, respectively, over an average of 6.5 years of treatment. EDIC is the observational follow-up study of the DCCT (1994 to the present). Vital status was ascertained for 97.5% of the original DCCT cohort (n = 1,441) after a mean of 27 years follow-up. Expected mortality during DCCT/EDIC was estimated using the current age-, sex-, and race-specific risks in the general U.S. population, and the observed versus expected mortality compared using standardized mortality ratios (SMRs) and Poisson regression models.RESULTSMortality in the DCCT intensive therapy group was nonsignificantly lower than that in the general U.S. population (SMR = 0.88 [95% CI 0.67, 1.16]), whereas mortality in the DCCT conventional therapy group was significantly greater than that in the general population (SMR = 1.31 [95% CI 1.05, 1.65]). The SMR increased with increasing mean HbA(1c), and above an HbA(1c) of 9%, the rate of increase in SMR among females was greater than that among males.CONCLUSIONSOverall mortality in the combined DCCT/EDIC cohort was similar to that of the general population but was higher in the DCCT conventional therapy group. Mortality increased significantly with increasing mean HbA(1c), more so among females than males, especially for HbA(1c) >9%.
C1 [Lachin, John M.; Bebu, Ionut; Backlund, Jye-Yu C.; Cleary, Patricia] George Washington Univ, Biostat Ctr, Rockville, MD 20052 USA.
[Nathan, David M.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
[Zinman, Bernard] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada.
[Brillon, David] Weill Cornell Med Coll, New York, NY USA.
[Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA USA.
RP Lachin, JM (reprint author), George Washington Univ, Biostat Ctr, Rockville, MD 20052 USA.
EM jml@bsc.gwu.edu
OI Lachin, John/0000-0001-9838-2841
FU Division of Diabetes Endocrinology and Metabolic Diseases of the
National Institute of Diabetes and Digestive and Kidney Diseases [U01
DK094176, U01 DK094157]; National Eye Institute; National Institute of
Neurological Disorders and Stroke; General Clinical Research Centers
Program; Clinical and Translational Science Center Program, Bethesda, MD
FX The DCCT/EDIC has been supported by cooperative agreement grants
(1982-1993 and 2012-2017) and contracts (1982-2012) with the Division of
Diabetes Endocrinology and Metabolic Diseases of the National Institute
of Diabetes and Digestive and Kidney Diseases (current grant numbers U01
DK094176 and U01 DK094157) and by the National Eye Institute, the
National Institute of Neurological Disorders and Stroke, the General
Clinical Research Centers Program (1993-2007), and the Clinical and
Translational Science Center Program (2006 to present), Bethesda, MD.
NR 31
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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 AUG
PY 2016
VL 39
IS 8
BP 1378
EP 1383
DI 10.2337/dc15-2399
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DT4CN
UT WOS:000381427800031
ER
PT J
AU Mifflin, J
AF Mifflin, Jeffrey
TI When I Was a Photographer
SO EARLY POPULAR VISUAL CULTURE
LA English
DT Book Review
C1 [Mifflin, Jeffrey] Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA.
RP Mifflin, J (reprint author), Massachusetts Gen Hosp, Arch & Special Collect, Boston, MA 02114 USA.
EM JMIFFLIN@mgh.harvard.edu
NR 1
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 1746-0654
EI 1746-0662
J9 EARLY POPUL VIS CULT
JI Early Popul. Vis. Cult.
PD AUG
PY 2016
VL 14
IS 3
BP 289
EP 291
DI 10.1080/17460654.2016.1189382
PG 3
WC Humanities, Multidisciplinary
SC Arts & Humanities - Other Topics
GA DU8WK
UT WOS:000382496200007
ER
PT J
AU Yang, L
Kirby, JE
Sunwoo, H
Lee, JT
AF Yang, Lin
Kirby, James E.
Sunwoo, Hongjae
Lee, Jeannie T.
TI Female mice lacking Xist RNA show partial dosage compensation and
survive to term
SO GENES & DEVELOPMENT
LA English
DT Article
DE genome balance; inverse effect; X inactivation; Xist; dosage
compensation; knockout mouse; transcriptomics
ID X-CHROMOSOME INACTIVATION; EARLY MOUSE EMBRYOS; GENE-EXPRESSION;
PREFERENTIAL INACTIVATION; DROSOPHILA-MELANOGASTER; CARDIOMYOCYTE
NUMBER; UP-REGULATION; LINKED GENES; MAMMALS; MAINTENANCE
AB X-chromosome inactivation (XCI) compensates for differences in X-chromosome number between male and female mammals. XCI is orchestrated by Xist RNA, whose expression in early development leads to transcriptional silencing of one X chromosome in the female. Knockout studies have established a requirement for Xist with inviability of female embryos that inherit an Xist deletion from the father. Here, we report that female mice lacking Xist RNA can, surprisingly, develop and survive to term. Xist-null females are born at lower frequency and are smaller at birth, but organogenesis is mostly normal. Transcriptomic analysis indicates significant overexpression of hundreds of X-linked genes across multiple tissues. Therefore, Xist-null mice can develop to term in spite of a deficiency of dosage compensation. However, the degree of X-autosomal dosage imbalance was less than anticipated (1.14-fold to 1.36-fold). Thus, partial dosage compensation can be achieved without Xist, supporting the idea of inherent genome balance. Nevertheless, to date, none of the mutant mice has survived beyond weaning stage. Sudden death is associated with failure of postnatal organ maturation. Our data suggest Xist-independent mechanisms of dosage compensation and demonstrate that small deviations from X-autosomal balance can have profound effects on overall fitness.
C1 [Yang, Lin; Sunwoo, Hongjae; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Yang, Lin; Sunwoo, Hongjae; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Yang, Lin; Sunwoo, Hongjae; Lee, Jeannie T.] Harvard Med Sch, Dept Genet, Boston, MA 02114 USA.
[Kirby, James E.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02114 USA.
RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.; Lee, JT (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Lee, JT (reprint author), Harvard Med Sch, Dept Genet, Boston, MA 02114 USA.
EM lee@molbio.mgh.harvard.edu
FU Agency for Science, Technology, and Research of Singapore; National
Institutes of Health [DA-R01-36895]; Rett Syndrome Research Trust
FX We thank R. Jaenisch for Xistfl/fl mice; R. Mostoslaysky, K.
Hochedlinger, W. Bender, B. Payer, and the Lee laboratory for valuable
advice and feedback; D. Lessing, T. Dial, and B. del Rosario for
critical reading of the manuscript, and W. Press for mouse colony
maintenance. This work was supported by grant funding from the Agency
for Science, Technology, and Research of Singapore (to L.Y.), the
National Institutes of Health (DA-R01-36895 to J.T.L.), and the Rett
Syndrome Research Trust (to J.T.L.). J.T.L. is also an Investigator of
the Howard Hughes Medical Institute.
NR 62
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U1 0
U2 0
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD AUG 1
PY 2016
VL 30
IS 15
BP 1747
EP 1760
DI 10.1101/gad.281162.116
PG 14
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA DU7RR
UT WOS:000382412800006
PM 27542829
ER
PT J
AU Grussendorf, KA
Trezza, CJ
Salem, AT
Al-Hashimi, H
Mattingly, BC
Kampmeyer, DE
Khan, LA
Hall, DH
Gobel, V
Ackley, BD
Buechner, M
AF Grussendorf, Kelly A.
Trezza, Christopher J.
Salem, Alexander T.
Al-Hashimi, Hikmat
Mattingly, Brendan C.
Kampmeyer, Drew E.
Khan, Liakot A.
Hall, David H.
Goebel, Verena
Ackley, Brian D.
Buechner, Matthew
TI Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains
Apical Tubule Structure in Caenorhabditis elegans
SO GENETICS
LA English
DT Article
DE tubulogenesis; trafficking; endosomes; IRG; immunity-related GTPase
ID RICH INTESTINAL PROTEIN; NUCLEOTIDE EXCHANGE FACTOR; EXCRETORY CELL;
C-ELEGANS; PORPHOBILINOGEN DEAMINASE; FACIOGENITAL DYSPLASIA; RESISTANCE
GTPASES; TOXOPLASMA-GONDII; INDUCIBLE GTPASES; IMMUNE-RESPONSE
AB Determination of luminal diameter is critical to the function of small single-celled tubes. A series of EXC proteins, including EXC-1, prevent swelling of the tubular excretory canals in Caenorhabditis elegans. In this study, cloning of exc-1 reveals it to encode a homolog of mammalian IRG proteins, which play roles in immune response and autophagy and are associated with Crohn's disease. Mutants in exc-1 accumulate early endosomes, lack recycling endosomes, and exhibit abnormal apical cytoskeletal structure in regions of enlarged tubules. EXC-1 interacts genetically with two other EXC proteins that also affect endosomal trafficking. In yeast two-hybrid assays, wild-type and putative constitutively active EXC-1 binds to the LIM-domain protein EXC-9, whose homolog, cysteine-rich intestinal protein, is enriched in mammalian intestine. These results suggest a model for IRG function in forming and maintaining apical tubule structure via regulation of endosomal recycling.
C1 [Grussendorf, Kelly A.; Trezza, Christopher J.; Salem, Alexander T.; Al-Hashimi, Hikmat; Mattingly, Brendan C.; Ackley, Brian D.; Buechner, Matthew] Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Dr,8035 Haworth Hall, Lawrence, KS 66045 USA.
[Grussendorf, Kelly A.; Kampmeyer, Drew E.] Minnesota State Univ, Dept Biol Sci, Mankato, MN 56001 USA.
[Khan, Liakot A.; Goebel, Verena] Harvard Med Sch, Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Dev Biol & Genet Core, Boston, MA 02114 USA.
[Hall, David H.] Albert Einstein Coll Med, Dept Neurosci, Ctr Caenorhabditis Elegans Anat, Bronx, NY 10461 USA.
[Grussendorf, Kelly A.] Univ Dubuque, Dept Nat & Appl Sci, Goldthorp Sci Ctr 309A, 1150 N Algona St, Dubuque, IA 52001 USA.
[Mattingly, Brendan C.] Univ Kansas, Regents Ctr, 12600 Quivira Rd, Overland Pk, KS 66213 USA.
RP Buechner, M (reprint author), Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Dr,8035 Haworth Hall, Lawrence, KS 66045 USA.
EM buechner@ku.edu
FU National Institute of General Medical Sciences [P41-GM-103311]; NIH
Office of Research Infrastructure Programs [P40-OD-010440]; National
Institutes of Health (NIH) [R03-NS-067323]; National Science Foundation;
University of Kansas Graduate Research Fund [2301744]; NIH Initiative
for Maximizing Student Development Program [R25-GM-62232]; NIH
[OD-010943]
FX We gratefully acknowledge helpful discussions with Stuart Macdonald,
Barth Grant, Erik Lundquist, Yoshiaki Azuma, Jamie Alan-Olson, Meera
Sundaram, Kathy Suprenant, Robert S. Cohen, and the elusive Edward M.
Hedgecock. We thank Shai Shaham for the gift of the worm strain
containing amphid sheath cell marker construct nsIs53. Plasmid L3691 was
a gift from A. Fire. We thank Nancy R. Hall for help with statistical
analyses. Molecular graphics and analyses were performed with the
University of California, San Francisco (UCSF)'s Chimera package,
developed by the UCSF Resource for Biocomputing, Visualization, and
Informatics (supported by National Institute of General Medical Sciences
grant P41-GM-103311). Some strains were provided by the Caenorhabditis
Genetics Center, which is funded by the NIH Office of Research
Infrastructure Programs (grant P40-OD-010440). Parts of this work were
supported by National Institutes of Health (NIH; grant R03-NS-067323).
M.B. was supported by the National Science Foundation. K.A.G. was
supported by the University of Kansas Graduate Research Fund award no.
2301744. C.T. was supported by the NIH Initiative for Maximizing Student
Development Program grant R25-GM-62232. D.H.H. was supported by NIH
grant OD-010943.
NR 75
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U1 3
U2 3
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
EI 1943-2631
J9 GENETICS
JI Genetics
PD AUG
PY 2016
VL 203
IS 4
BP 1789
EP +
DI 10.1534/genetics.116.192559
PG 23
WC Genetics & Heredity
SC Genetics & Heredity
GA DV0PZ
UT WOS:000382622700023
PM 27334269
ER
PT J
AU Rauh-Hain, JA
Birrer, M
del Carmen, MG
AF Rauh-Hain, J. Alejandro
Birrer, Michael
del Carmen, Marcela G.
TI Carcinosarcoma of the ovary, fallopian tube, and peritoneum: Prognostic
factors and treatment modalities
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Ovarian cancer; Ovarian carcinosarcoma; Chemotherapy
ID MIXED MESODERMAL TUMORS; PLATINUM-BASED CHEMOTHERAPY;
GYNECOLOGIC-ONCOLOGY-GROUP; RECURRENT EPITHELIAL OVARIAN; MULLERIAN
TUMORS; COMBINATION CHEMOTHERAPY; SURGICAL CYTOREDUCTION; UTERINE
CARCINOSARCOMA; PHASE-II; CANCER
AB Objective. Ovarian carcinosarcoma (OCS) is a rare malignancy accounting for only 1-4% of all ovarian cancers. The treatment of OCS is largely based on data from small case series and management of other histologic subtypes of epithelial ovarian cancer. We reviewed the literature pertinent to the pathology, pathogenesis, diagnosis, and management of women with OCS.
Methods. MEDLINE was searched in English for literature on OCS, focusing on the past 30 years. Given the rarity of this tumor, studies were not limited by design or number of reported patients.
Results. Molecular, epidemiologic, genetic, and histologic data indicate that most OCS are monoclonal. Patients with OCS generally present with advanced stage disease. Most of the available retrospective studies support the role of cytoreductive surgery in the management of OCS, with optimal debulking associated with improved survival. Platinum-based chemotherapy is the current accepted adjuvant treatment. Given the limited data regarding the management of recurrent OCS, patients are usually treated similarly to women diagnosed with other subtypes of epithelial ovarian cancer.
Conclusion. OCS represent a rare and aggressive histologic subtype of epithelial ovarian cancer. The goal of surgery is comprehensive staging in patients with early-stage disease and optimal cytoreduction patients with advanced-stage tumors. Platinum-based chemotherapy is the mainstay of adjuvant systemic treatment. Future studies are needed in order to elucidate the molecular basis for OCS and to evaluate the role of targeted therapy in its management. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Rauh-Hain, J. Alejandro; del Carmen, Marcela G.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA.
[Birrer, Michael] Harvard Med Sch, Massachusetts Gen Hosp, Div Med Oncol, Boston, MA USA.
RP Rauh-Hain, JA (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA.
EM jrauh-hain@partners.org
FU National Cancer Institute at the National Institutes of Health
[R25CA092203]; Deborah Kelly Center for Outcomes Research, Massachusetts
General Hospital
FX This work was supported by R25CA092203 from the National Cancer
Institute at the National Institutes of Health and The Deborah Kelly
Center for Outcomes Research, Massachusetts General Hospital.
NR 62
TC 0
Z9 0
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD AUG
PY 2016
VL 142
IS 2
BP 248
EP 254
DI 10.1016/j.ygyno.2016.06.003
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DS4EH
UT WOS:000380733700008
PM 27321238
ER
PT J
AU Esselen, KM
Terry, KL
Samuel, A
Elias, KM
Davis, M
Welch, WR
Muto, MG
Ng, SW
Berkowitz, RS
AF Esselen, Katharine M.
Terry, Kathryn L.
Samuel, Anicka
Elias, Kevin M.
Davis, Michelle
Welch, William R.
Muto, Michael G.
Ng, Shu-Wing
Berkowitz, Ross S.
TI Endosalpingiosis: More than just an incidental finding at the time of
gynecologic surgery?
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Endosalpingiosis; Fallopian tube; Endometriosis; Uterine cancer; Ovarian
cancer; Serous ovarian neoplasms
ID CHRONIC PELVIC PAIN; SEROUS TUMORS; OVARIAN-CANCER; TUBAL ORIGIN;
ENDOMETRIOSIS; LAPAROSCOPY; CARCINOMA; PRECURSOR
AB Objective. To describe the clinical characteristics of patients with endosalpingiosis (ES) and examine its association with endometriosis and gynecologic malignancies.
Methods. We queried the medical record for patients who underwent gynecologic surgery (Gynecologic Surgery Cohort (GSC), n = 58,161) from 1998 to 2013 at a single institution for the presence of "endosalpingiosis" (ES). Demographic and clinical characteristics were collected for patients with pathologically confirmed ES (n = 838). Within GSC, we compared the frequency of endometriosis and gynecologic malignancies with and without ES. We estimated the expected distribution of ovarian cancer subtypes using cases from the New England Case Control Study (NECC). We used chi-square tests to test for significant differences in frequency distributions and unconditional logistic regression to calculate multivariate odds ratios for the association between ES and ovarian cancer subtypes.
Results. We observed concurrent endometriosis (p < 0.0001), uterine cancer (p < 0.0001), and ovarian cancer (p < 0.0001) more frequently in women with ES. Women from the GSC with ES and ovarian cancer were more likely to have serous borderline (OR = 10.2, 95% CI = 5.1-20.7), clear cell (OR = 3.0, 95% CI = 1.1-8.0), and invasive mucinous tumors (OR = 5.0, 95% CI = 1.5-16.6) as compared to ovarian cancer cases from the NECC without ES, after accounting for age, race, menopausal status, parity, tubal ligation, and endometriosis.
Conclusion. Women with ES are more likely to also be diagnosed with endometriosis, uterine, and ovarian cancers. Further study is needed to understand these associations so we may appropriately counsel patients with ES diagnosed at time of gynecologic surgery. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Esselen, Katharine M.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA USA.
[Terry, Kathryn L.] Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet & Gynecol, Obstet & Gynecol Epidemiol Ctr, Boston, MA USA.
[Samuel, Anicka; Elias, Kevin M.; Davis, Michelle; Muto, Michael G.; Berkowitz, Ross S.] Harvard Med Sch, Dana Farber Canc Inst, Brigham & Womens Hosp, Div Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA USA.
[Welch, William R.] Harvard Med Sch, Brigham & Womens Hosp, Div Womens & Perinatal Pathol, Dept Pathol, Boston, MA USA.
[Ng, Shu-Wing] Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet & Gynecol, Lab Gynecol Oncol,Div Gynecol Oncol, Boston, MA USA.
RP Esselen, KM (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, 330 Brookline Ave, Boston, MA 02215 USA.
EM kesselen14@gmail.com
FU Expanding the Boundaries, Brigham and Women's Hospital, Internal
Research Funding
FX This project was funded by Expanding the Boundaries, Brigham and Women's
Hospital, Internal Research Funding.
NR 22
TC 2
Z9 2
U1 4
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD AUG
PY 2016
VL 142
IS 2
BP 255
EP 260
DI 10.1016/j.ygyno.2016.05.036
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DS4EH
UT WOS:000380733700009
PM 27261327
ER
PT J
AU Uppal, S
del Carmen, MG
Rice, LW
Reynolds, RK
Jolly, S
Bregar, A
Abdelsattar, ZM
Rauh-Hain, JA
AF Uppal, Shitanshu
del Carmen, Marcela G.
Rice, Laurel W.
Reynolds, R. Kevin
Jolly, Shruti
Bregar, Amy
Abdelsattar, Zaid M.
Rauh-Hain, J. Alejandro
TI Variation in care in concurrent chemotherapy administration during
radiation for locally advanced cervical cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Cervix cancer; Concurrent chemo radiation; Health disparities; Variation
in care
ID ADJUVANT CHEMOTHERAPY; IMPROVED SURVIVAL; NCCN GUIDELINES;
BREAST-CANCER; NIH ROADMAP; OUTCOMES; STAGE; ADHERENCE; IMPACT; VOLUME
AB Background. To evaluate the usage of concurrent chemo-radiotherapy (C-CRT) for the treatment of locally advanced cervical cancer.
Methods. Patients with locally invasive cervical carcinoma diagnosed between January 1, 2004 and December 31, 2012 from the National Cancer Database (NCDB) were included. Outcomes for patients undergoing radiation therapy only, 'RT alone' group were compared to those receiving chemotherapy concurrent with radiation C-CRT group'. Trends in utilization of C-CRT and factors associated with the deviation from standard of care were explored. Lastly, the effect of hospital volume on utilization of C-CRT was investigated.
Results. A total of 18,164 patients undergoing definitive radiation therapy were available for analysis. Utilization of C-CRT increased from 72.4% in 2004 to 84.3% in 2012 (p-trend < 0.001). After adjusting for patient, tumor, and treatment factors, a multivariable logistic regression model revealed increasing age, African-American race, Charlson-comorbidity index of >= 2, Medicaid insurance status, uninsured status, and Stage I disease were each independently associated with the lack of C-CRT. After adjusting for patient characteristics, low volume hospitals were noted to have overall significantly lower rates and greater variation in C-CRT administration. Patients in 'RT alone' group had an overall worse survival rate (adjusted-HR 1.47, 95%CI 1.4-1.56).
Conclusion. Rates of C-CRT administration varied significantly across hospitals in the United States. Hospitals with a high case volume had higher rates and more consistent patterns of C-CRT administration. Furthermore, we identified independent factors, all of which represent noteworthy health disparities, associated with lower rates of C-CRT administration. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Uppal, Shitanshu; Reynolds, R. Kevin] Univ Michigan, Div Gynecol Oncol, Ann Arbor, MI 48109 USA.
[del Carmen, Marcela G.; Bregar, Amy; Rauh-Hain, J. Alejandro] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol Vincent Obstet & Gynecol, Boston, MA USA.
[Rice, Laurel W.] Univ Wisconsin, Div Gynecol Oncol, Madison, WI USA.
[Jolly, Shruti] Univ Michigan, Div Radiat Oncol, Ann Arbor, MI 48109 USA.
[Uppal, Shitanshu; Abdelsattar, Zaid M.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA.
RP Uppal, S (reprint author), Univ Michigan, 1500 E Med Dr, Ann Arbor, MI 48109 USA.
EM uppal@med.umich.edu
NR 29
TC 1
Z9 1
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD AUG
PY 2016
VL 142
IS 2
BP 286
EP 292
DI 10.1016/j.ygyno.2016.05.026
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DS4EH
UT WOS:000380733700015
PM 27234144
ER
PT J
AU Lee, LJ
Howitt, B
Catalano, P
Tanaka, C
Murphy, R
Cimbak, N
DeMaria, R
Bu, P
Crum, C
Horowitz, N
Matulonis, U
Viswanathan, AN
AF Lee, Larissa J.
Howitt, Brooke
Catalano, Paul
Tanaka, Cynthia
Murphy, Rita
Cimbak, Nicole
DeMaria, Rebecca
Bu, Paula
Crum, Christopher
Horowitz, Neil
Matulonis, Ursula
Viswanathan, Akila N.
TI Prognostic importance of human papillomavirus (HPV) and p16 positivity
in squamous cell carcinoma of the vulva treated with radiotherapy
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Vulvar cancer; Human papillomavirus; Radiotherapy; p16
ID INTRAEPITHELIAL NEOPLASIA; LICHEN-SCLEROSUS; P16(INK4A) EXPRESSION;
OROPHARYNGEAL CANCER; IMPROVED SURVIVAL; CERVICAL-CANCER; HEAD; NECK;
DNA; PREVALENCE
AB Objective. HPV status is an important prognostic factor for patients with oropharyngeal, anal and cervical cancers treated with radiotherapy. This study evaluates the association between HPV and p16 status and outcome in a radiation-treated cohort with vulvar squamous cell carcinoma (SCC).
Methods. Patients with vulvar SCC who received radiotherapy with or without surgical resection between 1985 and 2011 were identified retrospectively. Immunostaining for p16 and multiplex PCR for HPV genotyping were performed using archival tumor tissue from 57 patients. Actuarial estimates of PFS, OS and in-field recurrence were calculated using the Kaplan-Meier method. Cox proportional hazards models were used for multivariable analysis. Median follow-up was 58 months among the 57 patients with an available tumor specimen.
Results. HPV prevalence was implied in 37% by (diffuse linear) p16 immunostaining and confirmed in 27% by HPV PCR with good agreement (K = 0.7). HPV-16 was identified in 80% of HPV-positive tumors. Women with p16-positive tumors had significantly higher 5-year PFS (65%,vs. 16%, p < 0.01) and OS (65% vs. 22%, p = 0.01) rates, as well as lower in-field relapse rates (19% vs. 75%, p < 0.01) compared to those with p16-negative disease. On multivariable analysis adjusted for age and stage, p16 positivity was significantly associated with better PFS (HR 0.4, 95% CI 0.2-0.9) and lower rates of in-field relapse (HR 0.2, 95% CI 0.06-0.6). Results were similar when analyzed by HPV DNA status.
Conclusion. In this study, the presence of HPV or its surrogate of p16 immunostaining was an independent prognostic factor for in-field relapse and survival in women with vulvar SCC treated with radiotherapy. This finding warrants validation in larger cohorts or the prospective setting. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lee, Larissa J.; Tanaka, Cynthia; Murphy, Rita; Cimbak, Nicole; DeMaria, Rebecca; Bu, Paula; Viswanathan, Akila N.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA.
[Howitt, Brooke; Crum, Christopher] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Horowitz, Neil] Brigham & Womens Hosp, Dept Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA.
[Catalano, Paul] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Matulonis, Ursula] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Lee, Larissa J.; Howitt, Brooke; Catalano, Paul; Crum, Christopher; Horowitz, Neil; Matulonis, Ursula; Viswanathan, Akila N.] Harvard Med Sch, Boston, MA USA.
RP Lee, LJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASBI-L2, Boston, MA 02115 USA.
EM llee@lroc.harvard.edu
FU Radiation Oncology Department at Brigham and Women's Hospital
FX We would like to thank Barbara Silver for critical reading of this
manuscript and the Radiation Oncology Department at Brigham and Women's
Hospital for funding this work.
NR 41
TC 2
Z9 2
U1 1
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD AUG
PY 2016
VL 142
IS 2
BP 293
EP 298
DI 10.1016/j.ygyno.2016.05.019
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DS4EH
UT WOS:000380733700016
PM 27210818
ER
PT J
AU Shah, R
Foldyna, B
Hoffmann, U
AF Shah, R.
Foldyna, B.
Hoffmann, U.
TI Outcomes of anatomical vs. functional testing for coronary artery
disease Lessons from the PROMISE trial
SO HERZ
LA English
DT Article
DE Coronary artery disease; Coronary angiography; Computed tomography;
Treatment outcome; Functional testing
ID FRACTIONAL FLOW RESERVE; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; ACUTE
CHEST-PAIN; CT ANGIOGRAPHY; DIAGNOSTIC PERFORMANCE; MYOCARDIAL-ISCHEMIA;
PROGNOSTIC VALUE; MEDICAL THERAPY; LEARNING-CURVE; CARDIAC EVENTS
AB The development of coronary artery disease (CAD) is a major, final common pathway in heart disease worldwide. With a rise in stress testing and increased scrutiny on cost-effectiveness and radiation exposure in medical imaging, a focus on the relative merits of anatomic versus functional characterization of CAD has emerged. In this context, coronary computed tomography angiography (CCTA) is a noninvasive alternative to functional testing as a first-line test for CAD detection but is complimentary in its nature. Here, we discuss the design, results, and implications of the PROMISE trial, a randomized comparative effectiveness study of 10,003 patients across 193 sites in the United States and Canada comparing the prognostic and diagnostic power of CCTA and standard stress testing. Specifically, we discuss the safety (e. g., contrast, radiation exposure) of CCTA versus functional testing in CAD, the need for improved selection for noninvasive testing, the frequency of downstream testing after anatomic or functional imaging, the use of imaging results in clinical management, and novel modalities of CAD risk determination using CCTA. PROMISE demonstrated that in a real-world, low-to-intermediate risk patient population referred to noninvasive testing for CAD, both CCTA and functional testing approaches have similar clinical, economic, and safety-based outcomes. We conclude with open questions in CAD imaging, specifically as they pertain to the utilization of CCTA.
C1 [Shah, R.; Foldyna, B.; Hoffmann, U.] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, 165 Cambridge St,Suite 400, Boston, MA 02114 USA.
EM uhoffmann@partners.org
NR 35
TC 0
Z9 0
U1 0
U2 0
PU URBAN & VOGEL
PI MUNICH
PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY
SN 0340-9937
EI 1615-6692
J9 HERZ
JI Herz
PD AUG
PY 2016
VL 41
IS 5
BP 384
EP 390
DI 10.1007/s00059-016-4451-3
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DT3SA
UT WOS:000381400000005
PM 27333988
ER
PT J
AU Tobyne, SM
Boratyn, D
Johnson, JA
Greve, DN
Mainero, C
Klawiter, EC
AF Tobyne, Sean M.
Boratyn, Daria
Johnson, Jessica A.
Greve, Douglas N.
Mainero, Caterina
Klawiter, Eric C.
TI A Surface-Based Technique for Mapping Homotopic Interhemispheric
Connectivity: Development, Characterization, and Clinical Application
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE functional connectivity; resting state; multiple sclerosis; corpus
callosum; human
ID INTRINSIC FUNCTIONAL CONNECTIVITY; CORPUS-CALLOSUM ATROPHY; HUMAN
CEREBRAL-CORTEX; GRAY-MATTER ATROPHY; MULTIPLE-SCLEROSIS; HUMAN BRAIN;
FIBER COMPOSITION; MAJOR DEPRESSION; MRI; FMRI
AB The functional organization of the human brain consists of a high degree of connectivity between interhemispheric homologous regions. The degree of homotopic organization is known to vary across the cortex and homotopic connectivity is high in regions that share cross-hemisphere structural connections or are activated by common input streams (e.g., the visual system). Damage to one or both regions, as well as damage to the connections between homotopic regions, could disrupt this functional organization. Here were introduce and test a computationally efficient technique, surface-based homotopic interhermispheric connectivity (sHIC), that leverages surface-based registration and processing techniques in an attempt to improve the spatial specificity and accuracy of cortical interhemispheric connectivity estimated with resting state functional connectivity. This technique is shown to be reliable both within and across subjects. sHIC is also characterized in a dataset of nearly 1000 subjects. We confirm previous results showing increased interhemispheric connectivity in primary sensory regions, and reveal a novel rostro-caudal functionally defined network level pattern of sHIC across the brain. In addition, we demonstrate a structural-functional relationship between sHIC and atrophy of the corpus callosum in multiple sclerosis (r = 0.2979, p = 0.0461). sHIC presents as a sensitive and reliable measure of cortical homotopy that may prove useful as a biomarker in neurologic disease. (C) 2016 Wiley Periodicals, Inc.
C1 [Tobyne, Sean M.; Boratyn, Daria; Klawiter, Eric C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Johnson, Jessica A.] Augustana Coll, Sioux Falls, SD USA.
[Greve, Douglas N.; Mainero, Caterina] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA.
RP Tobyne, SM (reprint author), 149 13th St,Room 2503, Charlestown, MA 02129 USA.
EM stobyne@nmr.mgh.har-vard.edu
FU National Institutes of Health [K23NS078044-04, R01NS078322-01-A1];
National Multiple Sclerosis Society [PP1853]
FX Contract grant sponsor: National Institutes of Health; Contract grant
numbers: K23NS078044-04 and R01NS078322-01-A1; Contract grant sponsor:
National Multiple Sclerosis Society; Contract grant number: PP1853
NR 77
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD AUG
PY 2016
VL 37
IS 8
BP 2849
EP 2868
DI 10.1002/hbm.23214
PG 20
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DU8UF
UT WOS:000382490000009
PM 27219660
ER
PT J
AU Govani, SM
Wiitala, WL
Stidham, RW
Saini, SD
Hou, JK
Feagins, LA
Sussman, JB
Higgins, PDR
Waljee, AK
AF Govani, Shail M.
Wiitala, Wyndy L.
Stidham, Ryan W.
Saini, Sameer D.
Hou, Jason K.
Feagins, Linda A.
Sussman, Jeremy B.
Higgins, Peter D. R.
Waljee, Akbar K.
TI Age Disparities in the Use of Steroid-sparing Therapy for Inflammatory
Bowel Disease
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE corticosteroids; elderly; escalation
ID ULCERATIVE-COLITIS; RISK; EPIDEMIOLOGY; MANAGEMENT
AB Background:Corticosteroids are effective rescue therapies for patients with inflammatory bowel disease (IBD), but have significant side effects, which may be amplified in the growing population of elderly patients with IBD. We aimed to compare the use of steroids and steroid-sparing therapies (immunomodulators and biologics) and rates of complications among elderly (65) and younger patients in a national cohort of veterans with IBD.Methods:We used national Veterans Health Administrative data to conduct a retrospective study of veterans with IBD between 2002 and 2010. Medications and the incidence of complications were obtained from the Veterans Health Administrative Decision Support Systems. Multivariate logistic regression accounting for facility-level clustering was used to identify predictors of use of steroid-sparing medications.Results:We identified 30,456 veterans with IBD. Of these, 94% were men and 40% were more than 65, and 32% were given steroids. Elderly veterans were less likely to receive steroids (23.8% versus 38.3%, P < 0.001) and were less likely to be prescribed steroid-sparing medications (25.5% versus 46.9%, respectively, P < 0.001). In multivariate analysis controlling for sex, age <65 (odds ratio, 2.19; 95% CI, 1.54-3.11) and gastroenterology care (odds ratio, 8.42; 95% CI, 6.18-11.47) were associated with initiation of steroid-sparing medications. After starting steroids, fracture rates increased in the elderly patients with IBD, whereas increases in venous thromboembolism and infections after starting steroids affected both age groups.Conclusions:Elderly veterans are less likely to receive steroids and steroid-sparing medications than younger veterans; elderly patients exposed to steroids were more likely to have fractures than the younger population.
C1 [Govani, Shail M.; Stidham, Ryan W.; Saini, Sameer D.; Sussman, Jeremy B.; Higgins, Peter D. R.; Waljee, Akbar K.] Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA.
[Govani, Shail M.; Saini, Sameer D.] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Wiitala, Wyndy L.; Sussman, Jeremy B.; Waljee, Akbar K.] VA Ctr Clin Management Res, Ann Arbor, MI USA.
[Saini, Sameer D.; Sussman, Jeremy B.; Waljee, Akbar K.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA.
[Hou, Jason K.] Houston VA HSR&D Ctr Excellence, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA.
[Hou, Jason K.] Baylor Coll Med, Dept Internal Med, Sect Gastroenterol & Hepatol, Houston, TX 77030 USA.
[Feagins, Linda A.] Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, VA North Texas Hlth Care Syst, Div Gastroenterol & Hepatol, Dallas, TX USA.
RP Govani, SM (reprint author), Dept Internal Med, 2215 Fuller Rd,Room 111D, Ann Arbor, MI 48105 USA.
EM shailg@umich.edu
FU VA HSR&D CDA-2 Career Development Award [1IK2HX000775]; VA HSR&D Center
for Innovations in Quality, Effectiveness and Safety at the Michael E.
DeBakey VA Medical Center, Houston, TX [CIN 13-413]; VA CDA [13-021]
FX A. K. Waljee's research is funded by a VA HSR&D CDA-2 Career Development
Award 1IK2HX000775. J. K. Hou's research is funded by the VA HSR&D
Center for Innovations in Quality, Effectiveness and Safety (#CIN
13-413), at the Michael E. DeBakey VA Medical Center, Houston, TX. J. B.
Sussman is supported by VA CDA 13-021. The sponsor had no role in the
design and conduct of the study; collection, management, analysis, and
interpretation of the data; preparation, review, or approval of the
manuscript; or decision to submit the manuscript for publication.
NR 21
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 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD AUG
PY 2016
VL 22
IS 8
BP 1923
EP 1928
DI 10.1097/MIB.0000000000000817
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DT4TX
UT WOS:000381475100019
PM 27416039
ER
PT J
AU DiNapoli, EA
Bramoweth, AD
Cinna, C
Kasckow, J
AF DiNapoli, Elizabeth A.
Bramoweth, Adam D.
Cinna, Christopher
Kasckow, John
TI Sedative hypnotic use among veterans with a newly reported mental health
disorder
SO INTERNATIONAL PSYCHOGERIATRICS
LA English
DT Article
DE sedatives and hypnotics; veterans; mental health; aged; inappropriate
prescriptions
ID INAPPROPRIATE MEDICATION USE; BENZODIAZEPINE USE; OLDER-ADULTS; ELDERLY
VETERANS; PRIMARY-CARE; INSOMNIA; METAANALYSIS; COMMUNITY; PEOPLE;
THERAPY
AB Background: This study compared sedative hypnotic use by type of mental health diagnosis and determined factors associated with use among older veterans (65+ years) with a newly reported mental health disorder.
Methods: This study used data from veterans who received primary care services at VA Pittsburgh Healthcare System (VAPHS) from January 1, 2007 to December 31, 2011 (n = 879).
Results: Sedative hypnotics were commonly used in older veterans within 12-months following a newly reported mental health disorder (19.9%), particularly amongst those with insomnia (41.7%). The number of newly reported mental health disorders was a significant factor associated with sedative hypnotic use, with the odds of use increasing by more than 200% in older adults with two newly reported disorders compared to those with one newly reported mental health disorder.
Conclusions: Continued efforts are needed to improve provider and patient awareness of the risks associated with sedative hypnotic use in older adults, as well as to increase access to and receipt of non-pharmacological mental health treatments for this vulnerable population.
C1 [DiNapoli, Elizabeth A.; Bramoweth, Adam D.; Cinna, Christopher; Kasckow, John] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA.
[DiNapoli, Elizabeth A.; Bramoweth, Adam D.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Cinna, Christopher] Duquesne Univ, Ctr Social & Publ Policy, Pittsburgh, PA 15219 USA.
[Kasckow, John] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Kasckow, John] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA.
RP Bramoweth, AD (reprint author), VA Pittsburgh Healthcare Syst, Res Off Bldg 151R,Univ Dr, Pittsburgh, PA 15240 USA.
EM Adam.Bramoweth@va.gov
NR 33
TC 0
Z9 0
U1 2
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1041-6102
EI 1741-203X
J9 INT PSYCHOGERIATR
JI Int. Psychogeriatr.
PD AUG
PY 2016
VL 28
IS 8
BP 1391
EP 1398
DI 10.1017/S1041610216000521
PG 8
WC Psychology, Clinical; Geriatrics & Gerontology; Gerontology; Psychiatry;
Psychology
SC Psychology; Geriatrics & Gerontology; Psychiatry
GA DU7IV
UT WOS:000382388300017
PM 27073116
ER
PT J
AU Wachterman, MW
Pilver, C
Smith, D
Ersek, M
Lipsitz, SR
Keating, NL
AF Wachterman, Melissa W.
Pilver, Corey
Smith, Dawn
Ersek, Mary
Lipsitz, Stuart R.
Keating, Nancy L.
TI Quality of End-of-Life Care Provided to Patients With Different Serious
Illnesses
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID NURSING-HOME RESIDENTS; PALLIATIVE CARE; VETERANS-AFFAIRS;
FAMILY-MEMBERS; INTENSIVE-CARE; HOSPITALIZED-PATIENTS;
POSTTRAUMATIC-STRESS; ADVANCED DEMENTIA; CANCER; DEATH
AB IMPORTANCE Efforts to improve end-of-life care have focused primarily on patients with cancer. High-quality end-of-life care is also critical for patients with other illnesses.
OBJECTIVE To compare patterns of end-of-life care and family-rated quality of care for patients dying with different serious illnesses.
DESIGN, SETTING, AND PARTICIPANTS A retrospective cross-sectional study was conducted in all 146 inpatient facilities within the Veteran Affairs health system among patients who died in inpatient facilities between October 1, 2009, and September 30, 2012, with clinical diagnoses categorized as end-stage renal disease (ESRD), cancer, cardiopulmonary failure (congestive heart failure or chronic obstructive pulmonary disease), dementia, frailty, or other conditions. Data analysis was conducted from April 1, 2014, to February 10, 2016.
MAIN OUTCOMES AND MEASURES Palliative care consultations, do-not- resuscitate orders, death in inpatient hospices, death in the intensive care unit, and family-reported quality of end-of-life care.
RESULTS Among 57 753 decedents, approximately half of the patients with ESRD, cardiopulmonary failure, or frailty received palliative care consultations (adjusted proportions, 50.4%, 46.7%, and 43.7%, respectively) vs 73.5% of patients with cancer and 61.4% of patients with dementia (P < .001). Approximately one-third of patients with ESRD, cardiopulmonary failure, or frailty (adjusted proportions, 32.3%, 34.1%, and 35.2%, respectively) died in the intensive care unit, more than double the rates among patients with cancer and those with dementia (13.4% and 8.9%, respectively) (P < .001). Rates of excellent quality of end-of-life care reported by 34 005 decedents' families were similar for patients with cancer and those with dementia (adjusted proportions, 59.2% and 59.3%; P = .61), but lower for patients with ESRD, cardiopulmonary failure, or frailty (54.8%, 54.8%, and 53.7%, respectively; all P <= .02 vs patients with cancer). This quality advantage was mediated by palliative care consultation, setting of death, and a code status of do-not- resuscitate; adjustment for these variables rendered the association between diagnosis and overall end-of-life care quality nonsignificant.
CONCLUSIONS AND RELEVANCE Family-reported quality of end-of-life care was significantly better for patients with cancer and those with dementia than for patients with ESRD, cardiopulmonary failure, or frailty, largely owing to higher rates of palliative care consultation and do-not- resuscitate orders and fewer deaths in the intensive care unit among patients with cancer and those with dementia. Increasing access to palliative care and goals of care discussions that address code status and preferred setting of death, particularly for patients with end-organ failure and frailty, may improve the overall quality of end-of-life care for Americans dying of these illnesses.
C1 [Wachterman, Melissa W.] VA Boston Healthcare Syst, Gen Internal Med Sect, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA.
[Wachterman, Melissa W.; Lipsitz, Stuart R.; Keating, Nancy L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
[Wachterman, Melissa W.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Pilver, Corey] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, Boston, MA USA.
[Smith, Dawn; Ersek, Mary] Dept Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA.
[Ersek, Mary] Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA.
[Keating, Nancy L.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA.
RP Wachterman, MW (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, 150 S Huntington Ave,Bldg 9, Boston, MA 02130 USA.
EM mwachterman@partners.org
FU National Palliative Care Research Center Junior Faculty Career
Development Award; National Institute on Aging [1K23AG049088-01A1];
Department of Veterans Affairs, Veterans Health Administration
FX Dr Wachterman received support from the National Palliative Care
Research Center Junior Faculty Career Development Award, from grant
1K23AG049088-01A1 from the National Institute on Aging, and from the
Department of Veterans Affairs, Veterans Health Administration.
NR 47
TC 13
Z9 13
U1 17
U2 17
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD AUG
PY 2016
VL 176
IS 8
BP 1095
EP 1102
DI 10.1001/jamainternmed.2016.1200
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT0AN
UT WOS:000381145000017
PM 27367547
ER
PT J
AU Fischer, SM
Bekelman, D
Bailey, FA
AF Fischer, Stacy M.
Bekelman, David
Bailey, F. Amos
TI Family Assessment of Quality of Care in the Last Month of Life
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID PALLIATIVE CARE; END
C1 [Fischer, Stacy M.; Bekelman, David; Bailey, F. Amos] Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med, Anschutz Med Campus,Mail Stop B180, Aurora, CO 80045 USA.
[Bekelman, David] Eastern Colorado Hlth Care Syst, Div Geriatr, Dept Internal Med, Dept Vet Affairs, Denver, CO USA.
[Bailey, F. Amos] Birmingham VA Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA.
RP Bailey, FA (reprint author), Univ Colorado, Div Gen Internal Med, Dept Med, Sch Med, Anschutz Med Campus,Mail Stop B180, Aurora, CO 80045 USA.
EM amos.bailey@ucdenver.edu
NR 5
TC 0
Z9 0
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD AUG
PY 2016
VL 176
IS 8
BP 1102
EP 1104
DI 10.1001/jamainternmed.2016.1208
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT0AN
UT WOS:000381145000018
PM 27367457
ER
PT J
AU Chen-Scarabelli, C
Scarabelli, TM
AF Chen-Scarabelli, Carol
Scarabelli, Tiziano M.
TI Syncope While Driving in Denmark
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
C1 [Chen-Scarabelli, Carol; Scarabelli, Tiziano M.] Birmingham VA Med Ctr, 700 S 19th St, Birmingham, AL 35233 USA.
[Scarabelli, Tiziano M.] Univ Alabama Birmingham, Med Ctr, Birmingham, AL USA.
RP Chen-Scarabelli, C (reprint author), Birmingham VA Med Ctr, 700 S 19th St, Birmingham, AL 35233 USA.
EM chenscarabelli@hotmail.com
NR 4
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD AUG
PY 2016
VL 176
IS 8
BP 1230
EP 1230
DI 10.1001/jamainternmed.2016.3723
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA DT0AN
UT WOS:000381145000051
PM 27479671
ER
PT J
AU LeBovidge, JS
Elverson, W
Timmons, KG
Hawryluk, EB
Rea, C
Lee, M
Schneider, LC
AF LeBovidge, Jennifer S.
Elverson, Wendy
Timmons, Karol G.
Hawryluk, Elena B.
Rea, Corinna
Lee, Margaret
Schneider, Lynda C.
TI Multidisciplinary interventions in the management of atopic dermatitis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Review
DE Atopic dermatitis; eczema; multidisciplinary; education; treatment;
quality of life; psychology; nutrition; nursing
ID THERAPEUTIC PATIENT EDUCATION; RANDOMIZED CONTROLLED-TRIAL; VITAMIN-D
DEFICIENCY; COWS MILK ALLERGY; QUALITY-OF-LIFE; YOUNG-CHILDREN; FOOD
ALLERGY; CLINICAL MANAGEMENT; INITIAL VALIDATION; TRAINING-PROGRAM
AB Atopic dermatitis (AD) is the most common pediatric skin disease. AD has a significant effect on patient and family quality of life caused by intense pruritus, sleep disruption, dietary and nutritional concerns, and psychological stress associated with the disease and its management. Multidisciplinary approaches to AD care have been developed in appreciation of the complex interplay among biological, psychological, behavioral, and dietary factors that affect disease control and the wide range of knowledge, skills, and support that patients and families require to effectively manage and cope with this condition. Common components of multidisciplinary treatment approaches include medical evaluation and management by an AD specialist, education and nursing care, psychological and behavioral support, and nutritional assessment and guidance. Models of care include both clinical programs and structured educational groups provided as adjuncts to standard clinical care. Available evidence suggests beneficial effects of multidisciplinary interventions in improving disease severity and quality of life, particularly for patients with moderate-to-severe disease. Additional research is needed to identify the best candidates for the various multidisciplinary approaches and evaluate the cost-effectiveness of these programs.
C1 [LeBovidge, Jennifer S.; Timmons, Karol G.; Schneider, Lynda C.] Boston Childrens Hosp, Div Immunol, Allergy Program, Boston, MA USA.
[Elverson, Wendy] Boston Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Ctr Nutr, Boston, MA USA.
[Hawryluk, Elena B.; Lee, Margaret] Boston Childrens Hosp, Div Immunol, Dermatol Program, Boston, MA USA.
[Rea, Corinna] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA USA.
[LeBovidge, Jennifer S.; Hawryluk, Elena B.; Rea, Corinna; Schneider, Lynda C.] Harvard Med Sch, Boston, MA USA.
[Hawryluk, Elena B.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA.
[Lee, Margaret] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02215 USA.
RP LeBovidge, JS (reprint author), Boston Childrens Hosp, Div Immunol, Fegan 6,300 Longwood Ave, Boston, MA 02115 USA.
EM jennifer.lebovidge@childrens.harvard.edu
FU APGNN
FX J. S. LeBovidge is a member of National Eczema Association Workgroup. W.
Elverson has received lecture fees from APGNN. L. C. Schneider is on the
National Eczema Association Scientific Advisory Board. The rest of the
authors declare that they have no relevant conflicts of interest.
NR 97
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Z9 2
U1 9
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD AUG
PY 2016
VL 138
IS 2
BP 325
EP 334
DI 10.1016/j.jaci.2016.04.003
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA DS5PY
UT WOS:000380835800001
PM 27497275
ER
PT J
AU Zgierska, AE
Burzinski, CA
Cox, J
Kloke, J
Singles, J
Mirgain, S
Stegner, A
Cook, DB
Backonja, M
AF Zgierska, Aleksandra E.
Burzinski, Cindy A.
Cox, Jennifer
Kloke, John
Singles, Janice
Mirgain, Shilagh
Stegner, Aaron
Cook, Dane B.
Backonja, Miroslav
TI Mindfulness Meditation-Based Intervention Is Feasible, Acceptable, and
Safe for Chronic Low Back Pain Requiring Long-Term Daily Opioid Therapy
SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
LA English
DT Article
ID CHRONIC NONCANCER PAIN; 3-YEAR FOLLOW-UP; PRIMARY-CARE; STRESS
REDUCTION; GUIDELINES; TRIALS; MODEL
AB Objective: Although mindfulness meditation (MM) is increasingly used for chronic pain treatment, limited evidence supports its clinical application for opioid-treated chronic low back pain (CLBP). The goal of this study was to determine feasibility, acceptability, and safety of an MM-based intervention in patients with CLBP requiring daily opioid therapy.
Design: 26-week pilot randomized controlled trial comparing MM-based intervention, combined with usual care, to usual care alone.
Setting: Outpatient.
Patients: Adults with CLBP treated with >= 30 mg of morphine-equivalent dose (MED) per day for 3 months or longer.
Interventions: Targeted MM-based intervention consisted of eight weekly 2-hour group sessions and home practice (30 minutes/d, 6 days/wk) during the study. "Usual care'' for opioid-treated CLBP was provided to participants by their regular clinicians.
Outcome measures: Feasibility and acceptability of the MM intervention were assessed by adherence to intervention protocol and treatment satisfaction among experimental participants. Safety was evaluated by inquiry about side effects/adverse events and opioid dose among all study participants.
Results: Thirty-five participants enrolled during the 10-week recruitment period. The mean age (+/- standard deviation) was 51.8 +/- 9.7 years; the patients were predominantly female, with substantial CLBP-related pain and disability, and treated with 148.3 +/- 129.2mg of MED per day. All participants completed baseline assessments; none missed both follow-up assessments or withdrew. Among experimental participants (n = 21), 19 attended 1 or more intervention sessions and 14 attended 4 or more. They reported, on average, 164.0 +/- 122.1 minutes of formal practice per week during the 26-week study and 103.5 +/- 111.5 minutes of brief, informal practice per week. Seventeen patients evaluated the intervention, indicating satisfaction; their qualitative responses described the course as useful for pain management (n = 10) and for improving pain coping skills (n = 8). No serious adverse events or safety concerns occurred among the study participants.
Conclusions: MM-based intervention is feasible, acceptable, and safe in opioid-treated CLBP.
C1 [Zgierska, Aleksandra E.; Burzinski, Cindy A.; Cox, Jennifer] Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, 1100 Delaplaine Court, Madison, WI 53715 USA.
[Kloke, John] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA.
[Singles, Janice; Mirgain, Shilagh] Univ Wisconsin, Sch Med & Publ Hlth, Dept Orthoped & Rehabil, Madison, WI USA.
[Stegner, Aaron; Cook, Dane B.] William S Middleton Mem Vet Adm Med Ctr, Res Serv, Madison, WI USA.
[Stegner, Aaron; Cook, Dane B.] Univ Wisconsin, Sch Educ, Dept Kinesiol, Madison, WI USA.
[Backonja, Miroslav] Univ Wisconsin, Dept Neurol, Sch Med & Publ Hlth, Madison, WI 53706 USA.
[Backonja, Miroslav] PRAHS Clin Res Co Lifetree, Salt Lake City, UT USA.
RP Zgierska, AE (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Family Med & Community Hlth, 1100 Delaplaine Court, Madison, WI 53715 USA.
EM Aleksandra.Zgierska@fammed.wisc.edu
FU National Institutes of Health (NIH) National Institute on Alcohol Abuse
and Alcoholism [K23AA017508]; University of Wisconsin-Madison; NIH
National Center for Advancing Translational Sciences [UL1TR000427]
FX The study is registered on ClinicalTrials.gov (NCT01775995). Dr.
Zgierska's work was supported by the K23AA017508 award from the National
Institutes of Health (NIH) National Institute on Alcohol Abuse and
Alcoholism and by funds from the University of Wisconsin-Madison. The
project was also supported by the Clinical and Translational Science
Award program through the NIH National Center for Advancing
Translational Sciences, grant UL1TR000427. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the NIH.
NR 51
TC 1
Z9 1
U1 9
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1075-5535
EI 1557-7708
J9 J ALTERN COMPLEM MED
JI J. Altern. Complement Med.
PD AUG
PY 2016
VL 22
IS 8
BP 610
EP 620
DI 10.1089/acm.2015.0314
PG 11
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA DU6AA
UT WOS:000382293700006
PM 27267151
ER
PT J
AU Mills, PJ
Wilson, KL
Pung, MA
Weiss, L
Patel, S
Doraiswamy, PM
Peterson, CT
Porter, V
Schadt, E
Chopra, D
Tanzi, RE
AF Mills, Paul J.
Wilson, Kathleen L.
Pung, Meredith A.
Weiss, Lizabeth
Patel, Sheila
Doraiswamy, P. Murali
Peterson, Christine Tara
Porter, Valencia
Schadt, Eric
Chopra, Deepak
Tanzi, Rudolph E.
TI The Self-Directed Biological Transformation Initiative and Well-Being
SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; HEALTH-CARE PRACTITIONERS; HEART-FAILURE
PATIENTS; POSITIVE PSYCHOLOGY; OLDER-ADULTS; CANCER-PATIENTS;
MENTAL-HEALTH; DOUBLE-BLIND; INTERVENTIONS; GRATITUDE
AB Objective: To examine the effects of a comprehensive residential mind-body program on well-being.
Design: The Self-Directed Biological Transformation Initiative was a quasi-randomized trial comparing the effects of participation in a 6-day Ayurvedic system of medicine-based comprehensive residential program with a 6-day residential vacation at the same retreat location.
Setting: Retreat setting.
Participants: 69 healthy women (n = 58) and men (n = 11) (mean age +/- standard deviation, 53.6 +/- 12 years).
Intervention: The Ayurvedic intervention addressed physical and emotional well-being through group meditation and yoga, massage, diet, adaptogenic herbs, lectures, and journaling.
Outcome measures: A battery of standardized questionnaires.
Results: Participants in the Ayurvedic program showed significant and sustained increases in ratings of spirituality (p < 0.01) and gratitude (p < 0.05) compared with the vacation group, which showed no change. The Ayurvedic participants also showed increased ratings for self-compassion (p < 0.01) as well as less anxiety at the 1-month follow-up (p < 0.05).
Conclusions: Findings suggest that a short-term intensive program providing holistic instruction and experience in mind-body healing practices can lead to significant and sustained increases in perceived well-being and that relaxation alone is not enough to improve certain aspects of well-being.
C1 [Mills, Paul J.; Wilson, Kathleen L.; Pung, Meredith A.; Patel, Sheila; Peterson, Christine Tara; Porter, Valencia; Chopra, Deepak] Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, La Jolla, CA 92093 USA.
[Mills, Paul J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Mills, Paul J.] Samueli Inst, Alexandria, VA USA.
[Weiss, Lizabeth; Patel, Sheila; Peterson, Christine Tara; Porter, Valencia; Chopra, Deepak] Chopra Ctr Wellbeing, Carlsbad, CA USA.
[Doraiswamy, P. Murali] Duke Univ, Duke Inst Brain Sci, Durham, NC USA.
[Schadt, Eric] Mt Sinai Hosp, Genet & Genom Sci, New York, NY 10029 USA.
[Tanzi, Rudolph E.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA.
RP Mills, PJ (reprint author), Univ Calif San Diego, Dept Family Med & Publ Hlth, 9500 Gilman Dr, La Jolla, CA 92093 USA.
EM pmills@ucsd.edu
FU Fred Foundation; MCJ Amelior Foundation; National Philanthropic Trust;
Walton Family Foundation; Chopra Foundation
FX Supported by the Fred Foundation, the MCJ Amelior Foundation, the
National Philanthropic Trust, the Walton Family Foundation, and the
Chopra Foundation.
NR 71
TC 1
Z9 1
U1 18
U2 18
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1075-5535
EI 1557-7708
J9 J ALTERN COMPLEM MED
JI J. Altern. Complement Med.
PD AUG
PY 2016
VL 22
IS 8
BP 627
EP 634
DI 10.1089/acm.2016.0002
PG 8
WC Integrative & Complementary Medicine
SC Integrative & Complementary Medicine
GA DU6AA
UT WOS:000382293700008
PM 27351443
ER
PT J
AU Kumari, M
Wang, X
Lantier, L
Lyubetskaya, A
Eguchi, J
Kang, S
Tenen, D
Roh, HC
Kong, XX
Kazak, L
Ahmad, R
Rosen, ED
AF Kumari, Manju
Wang, Xun
Lantier, Louise
Lyubetskaya, Anna
Eguchi, Jun
Kang, Sona
Tenen, Danielle
Roh, Hyun Cheol
Kong, Xingxing
Kazak, Lawrence
Ahmad, Rasheed
Rosen, Evan D.
TI IRF3 promotes adipose inflammation and insulin resistance and represses
browning
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID NF-KAPPA-B; ENDOPLASMIC-RETICULUM STRESS; GENE-EXPRESSION DATA;
IMMUNE-SYSTEM; IKK-EPSILON; ADAPTIVE THERMOGENESIS; TRANSCRIPTION
FACTORS; EPIGENOMIC ANALYSIS; MASTER REGULATORS; OBESE MICE
AB The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular and secreted factors promote the inflammatory milieu of obesity, but the transcriptional pathways that drive these processes are not well described. Although the canonical inflammatory transcription factor NF-kappa B is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family may also play a role in this process. Here, we determined that IRF3 expression is upregulated in the adipocytes of obese mice and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was associated with reductions in intra-adipose and systemic inflammation in the high fat-fed state, enhanced browning of subcutaneous fat, and increased adipose expression of GLUT4. Taken together, the data indicate that IRF3 is a major transcriptional regulator of adipose inflammation and is involved in maintaining systemic glucose and energy homeostasis.
C1 [Kumari, Manju; Wang, Xun; Lyubetskaya, Anna; Kang, Sona; Tenen, Danielle; Roh, Hyun Cheol; Kong, Xingxing; Rosen, Evan D.] Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA.
[Lantier, Louise] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Eguchi, Jun] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Nephrol Rheumatol Endocrinol & Metab, Okayama, Japan.
[Kazak, Lawrence] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA.
[Kazak, Lawrence] Harvard Med Sch, Dept Cell Biol, Boston, MA USA.
[Ahmad, Rasheed] Dasman Diabet Inst, Immunol & Innovat Cell Therapy Unit, Kuwait, Kuwait.
RP Rosen, ED (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, 330 Brookline Ave,E-CLS743, Boston, MA 02215 USA.
EM erosen@bidmc.harvard.edu
RI Lyubetskaya, Anna/A-6290-2017
FU NIH [R01 DK085171, DK102170]; Dasman Diabetes Institute; Kuwait
Foundation
FX This work was funded by NIH R01 DK085171 and DK102170 to E.D. Rosen, and
by funds from the Dasman Diabetes Institute and the Kuwait Foundation
for the Advancement of Sciences. We thank Ines Sousa Lima for assistance
in insulin signaling studies. Eleanna DeFilippis, Linus Tsai, and Su Xu
provided technical support and helpful discussions. Valerie Atizado and
Puthiyaveetil Shihab helped with IHC and qRT-PCR of human samples,
respectively. We also thank the Vanderbilt Mouse Metabolic Phenotyping
Center (DK059637) for performing the hyperinsulinemic-euglycemic clamps.
The Vanderbilt University Hormone Assay and Analytical Core performed
the hormone analysis (DK059637 and DK020593).
NR 61
TC 6
Z9 6
U1 4
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD AUG 1
PY 2016
VL 126
IS 8
BP 2839
EP 2854
DI 10.1172/JCI86080
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DU1BZ
UT WOS:000381943000010
PM 27400129
ER
PT J
AU Yu, J
Storer, BE
Kushekhar, K
Abu Zaid, M
Zhang, Q
Gafken, PR
Ogata, Y
Martin, PJ
Flowers, ME
Hansen, JA
Arora, M
Cutler, C
Jagasia, M
Pidala, J
Hamilton, BK
Chen, GL
Pusic, I
Lee, SJ
Paczesny, S
AF Yu, Jeffrey
Storer, Barry E.
Kushekhar, Kushi
Abu Zaid, Mohammad
Zhang, Qing
Gafken, Philip R.
Ogata, Yuko
Martin, Paul J.
Flowers, Mary E.
Hansen, John A.
Arora, Mukta
Cutler, Corey
Jagasia, Madan
Pidala, Joseph
Hamilton, Betty K.
Chen, George L.
Pusic, Iskra
Lee, Stephanie J.
Paczesny, Sophie
TI Biomarker Panel for Chronic Graft-Versus-Host Disease
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; BLOOD STEM-CELLS;
CLINICAL-TRIALS; CHRONIC GVHD; BONE-MARROW; T-CELLS; RISK-FACTORS;
TRANSPLANTATION; CRITERIA
AB Purpose
To identify diagnostic and prognostic markers of chronic graft-versus-host disease (cGVHD), the major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT).
Patients and Methods
Using a quantitative proteomics approach, we compared pooled plasma samples obtained at matched time points after HCT (median, 103 days) from 35 patients with cGVHD and 18 without cGVHD (data are available via ProteomeXchange with identifier PXD002762). Of 105 proteins showing at least a 1.25-fold difference in expression, 22 were selected on the basis of involvement in relevant pathways and enzyme-linked immunosorbent assay availability. Chemokine (C-X-C motif) ligand 9 (CXCL9) and suppression of tumorigenicity 2 (ST2) also were measured on the basis of previously determined associations with GVHD. Concentrations of the four lead biomarkers were measured at or after diagnosis in plasma from two independent verification cohorts (n = 391) to determine their association with cGVHD. Their prognostic ability when measured at approximately day + 100 after HCT was evaluated in plasma of a second verification cohort (n = 172).
Results
Of 24 proteins measured in the first verification cohort, nine proteins were associated with cGVHD, and only four (ST2, CXCL9, matrix metalloproteinase 3, and osteopontin) were necessary to compose a four-biomarker panel with an area under the receiver operating characteristic curve (AUC) of 0.89 and significant correlation with cGVHD diagnosis, cGVHD severity, and nonrelapse mortality. In a second verification cohort, this panel distinguished patients with cGVHD (AUC, 0.75), and finally, the panel measured at day + 100 could predict cGVHD occurring within the next 3 months with an AUC of 0.67 and 0.79 without and with known clinical risk factors, respectively.
Conclusion
We conclude that the biomarker panel measured at diagnosis or day + 100 after HCT may allow patient stratification according to risk of cGVHD. (C) 2016 by American Society of Clinical Oncology (C) 2016 by American Society of Clinical Oncology
C1 [Yu, Jeffrey; Kushekhar, Kushi; Abu Zaid, Mohammad; Paczesny, Sophie] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Storer, Barry E.; Zhang, Qing; Gafken, Philip R.; Ogata, Yuko; Martin, Paul J.; Flowers, Mary E.; Hansen, John A.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Storer, Barry E.] Univ Washington, Sch Med, Seattle, WA USA.
[Arora, Mukta] Univ Minnesota, Minneapolis, MN USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Jagasia, Madan] Vanderbilt Univ, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Pidala, Joseph] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Hamilton, Betty K.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Chen, George L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Pusic, Iskra] Washington Univ, Sch Med, St Louis, MO USA.
RP Paczesny, S (reprint author), Indiana Univ Sch Med, Dept Pediat, Wells Ctr Pediat Res, Melvin & Bren Simon Canc Ctr, 1044 W Walnut St,Room 425, Indianapolis, IN 46204 USA.; Paczesny, S (reprint author), Indiana Univ Sch Med, Dept Immunol, Wells Ctr Pediat Res, Melvin & Bren Simon Canc Ctr, 1044 W Walnut St,Room 425, Indianapolis, IN 46204 USA.
EM sophpacz@iu.edu
FU National Marrow Donor Program through the Amy Strelzer Manasevit Scholar
Grant [200513]; National Institutes of Health (NIH) [R01CA174667,
R01CA118953, U54CA163438]; National Center for Advancing Translational
Science (NCATS) Rare Diseases Clinical Research Network (RDCRN) [U54
CA163438]; Cancer Center Support Grant from the NIH [P30 CA015704];
Office of Rare Disease Research, NCATS
FX Supported by the National Marrow Donor Program through the Amy Strelzer
Manasevit Scholar Grant No. 200513 (S.P.) and National Institutes of
Health (NIH) Grants No. R01CA174667 (S.P.), R01CA118953 (S.J.L.), and
U54CA163438 (S.J.L.). The Chronic Graft-Versus-Host Disease Consortium
(Grant No. U54 CA163438) is part of the National Center for Advancing
Translational Science (NCATS) Rare Diseases Clinical Research Network
(RDCRN). RDCRN is an initiative of the Office of Rare Disease Research,
NCATS, funded through a collaboration between NCATS and the National
Cancer Institute. The Fred Hutchinson Cancer Research Center Proteomics
Facility is partially funded by Cancer Center Support Grant No. P30
CA015704 from the NIH.
NR 31
TC 7
Z9 7
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 AUG 1
PY 2016
VL 34
IS 22
BP 2583
EP U57
DI 10.1200/JCO.2015.65.9615
PG 10
WC Oncology
SC Oncology
GA DU8LQ
UT WOS:000382465300006
PM 27217465
ER
PT J
AU Dickler, MN
Barry, WT
Cirrincione, CT
Ellis, MJ
Moynahan, ME
Innocenti, F
Hurria, A
Rugo, HS
Lake, DE
Hahn, O
Schneider, BP
Tripathy, D
Carey, LA
Winer, EP
Hudis, CA
AF Dickler, Maura N.
Barry, William T.
Cirrincione, Constance T.
Ellis, Matthew J.
Moynahan, Mary Ellen
Innocenti, Federico
Hurria, Arti
Rugo, Hope S.
Lake, Diana E.
Hahn, Olwen
Schneider, Bryan P.
Tripathy, Debasish
Carey, Lisa A.
Winer, Eric P.
Hudis, Clifford A.
TI Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy
With or Without Bevacizumab for the Treatment of Postmenopausal Women
With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503
(Alliance)
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; FIRST-LINE THERAPY; ADJUVANT BEVACIZUMAB;
FACTOR EXPRESSION; PLUS BEVACIZUMAB; RANDOMIZED-TRIAL; DOUBLE-BLIND;
ESTROGEN; TAMOXIFEN; COMBINATION
AB Purpose
To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC).
Patients and Methods
Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, openlabel, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided alpha = .025, a target sample size of 352 patients was planned.
Results
From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v2%) and proteinuria (11% v 0%).
Conclusion
The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting. (C) 2016 by American Society of Clinical Oncology (C) 2016 by American Society of Clinical Oncology
C1 [Dickler, Maura N.; Moynahan, Mary Ellen; Lake, Diana E.; Hudis, Clifford A.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Barry, William T.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Winer, Eric P.] Dana Farber Partners Canc Care, Boston, MA USA.
[Cirrincione, Constance T.] Duke Univ, Durham, NC USA.
[Ellis, Matthew J.] Baylor Coll Med, Houston, TX 77030 USA.
[Tripathy, Debasish] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Innocenti, Federico; Carey, Lisa A.] Univ N Carolina, Chapel Hill, NC USA.
[Hurria, Arti] City Hope Natl Med Ctr, Duarte, CA USA.
[Rugo, Hope S.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hahn, Olwen] Alliance Clin Trials Oncol, Chicago, IL USA.
[Schneider, Bryan P.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
RP Dickler, MN (reprint author), Mem Sloan Kettering Canc Ctr, Weill Cornell Med Ctr, Breast Med Serv, 300 East 66th St, New York, NY 10065 USA.
EM dicklerm@mskcc.org
FU National Cancer Institute [U10CA031946, U10CA033601, U10CA180821,
U10CA180882]; Genentech; Novartis (letrozole); Memorial Sloan Kettering
Cancer Center [P30 CA008748]; Genentech (bevacizumab); [U10CA138561];
[U10CA180791]; [U10CA180795]; [U10CA180820]; [U10CA180838];
[U10CA180858]; [U10CA180867]; [U10CA180888]
FX Supported by National Cancer Institute Awards No. U10CA031946,
U10CA033601, U10CA180821, and U10CA180882 (to the Alliance for Clinical
Trials in Oncology); and in part by Grants No. U10CA138561, U10CA180791,
U10CA180795, U10CA180820, U10CA180838, U10CA180858, U10CA180867, and
U10CA180888; by Genentech (research funding and bevacizumab) and
Novartis (letrozole); and by Core Grant No. P30 CA008748 from Memorial
Sloan Kettering Cancer Center.
NR 51
TC 4
Z9 4
U1 8
U2 8
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 AUG 1
PY 2016
VL 34
IS 22
BP 2602
EP U86
DI 10.1200/JCO.2015.66.1595
PG 11
WC Oncology
SC Oncology
GA DU8LQ
UT WOS:000382465300008
PM 27138575
ER
PT J
AU McCarthy, AM
Bristol, M
Domchek, SM
Groeneveld, PW
Kim, Y
Motanya, UN
Shea, JA
Armstrong, K
AF McCarthy, Anne Marie
Bristol, Mirar
Domchek, Susan M.
Groeneveld, Peter W.
Kim, Younji
Motanya, U. Nkiru
Shea, Judy A.
Armstrong, Katrina
TI Health Care Segregation, Physician Recommendation, and Racial
Disparities in BRCA1/2 Testing Among Women With Breast Cancer
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; AFRICAN-AMERICAN WOMEN; TASK-FORCE
RECOMMENDATION; LOCALIZED PROSTATE-CANCER; US NURSING-HOMES; RESIDENTIAL
SEGREGATION; RISK-ASSESSMENT; PRECISION MEDICINE; FAMILY-HISTORY;
OVARIAN-CANCER
AB Purpose
Racial disparities in BRCA1/2 testing have been documented, but causes of these disparities are poorly understood. The study objective was to investigate whether the distribution of black and white patients across cancer providers contributes to disparities in BRCA1/2 testing.
Patients and Methods
We conducted a population-based study of women in Pennsylvania and Florida who were 18 to 64 years old and diagnosed with invasive breast cancer between 2007 and 2009, linking cancer registry data, the American Medical Association Physician Masterfile, and patient and physician surveys. The study included 3,016 women (69% white, 31% black), 808 medical oncologists, and 732 surgeons.
Results
Black women were less likely to undergo BRCA1/2 testing than white women (odds ratio [OR], 0.40; 95% CI, 0.34 to 0.48; P < .001). This difference was attenuated but not eliminated by adjustment for mutation risk, clinical factors, sociodemographic characteristics, and attitudes about testing (OR, 0.66; 95% CI, 0.53 to 0.81; P < .001). The care of black and white women was highly segregated across surgeons and oncologists (index of dissimilarity 64.1 and 61.9, respectively), but adjusting for clustering within physician or physician characteristics did not change the size of the testing disparity. Black women were less likely to report that they had received physician recommendation for BRCA1/2 testing even after adjusting for mutation risk (OR, 0.66; 95% CI, 0.54 to 0.82; P,.001). Adjusting for physician recommendation further attenuated the testing disparity (OR, 0.76; 95% CI, 0.57 to 1.02; P = .06).
Conclusion
Although black and white patients with breast cancer tend to see different surgeons and oncologists, this distribution does not contribute to disparities in BRCA1/2 testing. Instead, residual racial differences in testing after accounting for patient and physician characteristics are largely attributable to differences in physician recommendations. Efforts to address these disparities should focus on ensuring equity in testing recommendations. (C) 2016 by American Society of Clinical Oncology
C1 [McCarthy, Anne Marie; Bristol, Mirar; Kim, Younji; Armstrong, Katrina] Massachusetts Gen Hosp, 50 Staniford St,9-940F, Boston, MA 02114 USA.
[McCarthy, Anne Marie; Armstrong, Katrina] Harvard Med Sch, Boston, MA USA.
[Domchek, Susan M.; Groeneveld, Peter W.; Motanya, U. Nkiru; Shea, Judy A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP McCarthy, AM (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9-940F, Boston, MA 02114 USA.
EM amccarthy8@partners.org
FU National Cancer Institute, National Institutes of Health
[5-R01-CA133004-3]; Florida Department of Health (FDOH) [BE0910]; Bureau
of Health Statistics & Registries, Pennsylvania Department of Health
[IF-0317]
FX Supported by Grant No. 5-R01-CA133004-3 from the National Cancer
Institute, National Institutes of Health.; The Florida cancer incidence
data used in this report were collected by the Florida Cancer Data
System (FCDS) under contract with the Florida Department of Health
(FDOH) (Project N.: BE0910). The views expressed herein are solely those
of the author(s) and do not necessarily reflect those of the FCDS or
FDOH. The Bureau of Health Statistics & Registries, Pennsylvania
Department of Health, has also provided data for this study (Project N.:
IF-0317). The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations, or conclusions.
NR 66
TC 3
Z9 3
U1 7
U2 7
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 AUG 1
PY 2016
VL 34
IS 22
BP 2610
EP U96
DI 10.1200/JCO.2015.66.0019
PG 10
WC Oncology
SC Oncology
GA DU8LQ
UT WOS:000382465300009
PM 27161971
ER
PT J
AU Eneanya, ND
Winter, M
Cabral, H
Waite, K
Henault, L
Bickmore, T
Hanchate, A
Wolf, M
Paasche-Orlow, MK
AF Eneanya, Nwamaka D.
Winter, Michael
Cabral, Howard
Waite, Katherine
Henault, Lori
Bickmore, Timothy
Hanchate, Amresh
Wolf, Michael
Paasche-Orlow, Michael K.
TI Health Literacy and Education as Mediators of Racial Disparities in
Patient Activation Within an Elderly Patient Cohort
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article
DE Health literacy; education; patient activation; racial disparities
ID RANDOMIZED CONTROLLED-TRIAL; OLDER-ADULTS; SELF-MANAGEMENT;
SMOKING-CESSATION; MEASURE PAM; OUTCOMES; CARE; DEPRESSION; DISEASE;
VALIDATION
AB The Patient Activation Measure (PAM) assesses facets of patient engagement to identify proactive health behaviors and is an important predictor of health outcomes. Health literacy and education are also important for patient participation and successful navigation of the health care system. Because health literacy, education, and patient activation are associated with racial disparities, we sought to investigate whether health literacy and education would mediate racial differences in patient activation. Participants were 265 older adults who participated in a computer-based exercise interventional study. Health literacy was assessed using the Test of Functional Health Literacy in Adults (TOFHLA). Of 210 eligible participants, 72% self-identified as Black and 28% as White. In adjusted analyses, education and health literacy each significantly reduced racial differences in patient activation. These findings are especially important when considering emerging data on the significance of patient activation and new strategies to increase patient engagement.
C1 [Eneanya, Nwamaka D.] Harvard Med Sch, Dept Internal Med, Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA.
[Winter, Michael; Cabral, Howard] Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA.
[Waite, Katherine; Henault, Lori; Hanchate, Amresh; Paasche-Orlow, Michael K.] Boston Univ, Sch Med, Dept Internal Med, Sect Gen Internal Med,Boston Med Ctr, Boston, MA 02118 USA.
[Bickmore, Timothy; Wolf, Michael] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA.
RP Eneanya, ND (reprint author), Harvard Med Sch, Dept Internal Med, Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St,Suite 302, Boston, MA 02114 USA.
EM Aeneanya@partners.org
FU National Heart Lung and Blood Institute (NHLBI)
FX Funding: This work was supported through a National Heart Lung and Blood
Institute (NHLBI) Grant.
NR 53
TC 0
Z9 0
U1 5
U2 5
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
EI 1548-6869
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD AUG
PY 2016
VL 27
IS 3
BP 1427
EP 1440
PG 14
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA DT2RV
UT WOS:000381329000036
PM 27524777
ER
PT J
AU Zacharoulis, S
La Madrid, AM
Bandopadhayay, P
Chi, SN
Manley, P
Ullrich, NNJ
Marcus, K
Goumnerova, L
Scott, RM
Proctor, M
Young-Poussaint, T
De Girolami, U
Kieran, MW
AF Zacharoulis, Stergios
Morales La Madrid, Andres
Bandopadhayay, Pratiti
Chi, Susan N.
Manley, Peter
Ullrich, Nicole N. J.
Marcus, Karen
Goumnerova, Liliana
Scott, Robert M.
Proctor, Mark
Young-Poussaint, Tina
De Girolami, Umberto
Kieran, Mark W.
TI Central Versus Extraventricular Neurocytoma in Children: A
Clinicopathologic Comparison and Review of the Literature
SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
LA English
DT Article
DE central neurocytomas; extraventricular neurocytomas; MIB-1; children;
treatment
ID GAMMA-KNIFE RADIOSURGERY; MIB-1 LABELING INDEX; MR-IMAGING FINDINGS;
INTRAVENTRICULAR NEUROCYTOMA; INCOMPLETE RESECTION; CRANIOSPINAL
DISSEMINATION; TYPICAL NEUROCYTOMAS; CEREBRAL NEUROCYTOMA; AVAILABLE
TREATMENT; SPINAL-CORD
AB Background:Central neurocytomas (CN) are rare pediatric CNS tumors most often with a benign clinical course. Occasionally, these tumors occur outside the ventricles and are called extraventricular neurocytomas (EVN). We present a retrospective institutional analysis of children with neurocytoma with prolonged follow-up.Procedure:Twelve patients were diagnosed with neurocytoma at our institution between 1993 and 2004.Results:Six patients were male and the median age at diagnosis was 12 years (1.5 to 16 y). Seven patients had CN and 5 had EVN. Presenting symptoms included headaches (67%), vomiting (50%), nausea (33%), seizures (33%), and mental status changes (25%). Obstructive hydrocephalus was present at diagnosis in 42% of the cases. Younger age and seizures were more common in patients with EVN. Gross total resection (GTR) was achieved in 42% (5/12) of the patients. Patients with GTR received no adjuvant therapy upfront; 1 patient subsequently had recurrence with leptomeningeal disease. Patients with subtotal resection received additional treatment: 1 underwent reoperation (GTR), 2 patients received focal radiation, 2 patients received adjuvant chemotherapy, and 2 patients received craniospinal irradiation followed by chemotherapy. The 20-year overall survival for this cohort was 83% with event free survival of 56%. Overall survival for CNs was 100%, versus 40% for EVN. Event free survival for CNs was 57% and 53% for the EVNs. An MIB-1 fraction >2% was associated with worse prognosis.Conclusions:Neurocytomas are rare brain tumors in children usually cured with GTR. Adjuvant focal radiation therapy and/or chemotherapy may improve disease control in cases with subtotal resection, but case-by-case analysis should be done. EVNs might be associated with worse outcome due to a higher proliferative index.
C1 [Zacharoulis, Stergios] Royal Marsden NHS Fdn Trust, Children & Young Peoples Unit, Sutton, Surrey, England.
[Morales La Madrid, Andres; Bandopadhayay, Pratiti; Chi, Susan N.; Manley, Peter; Ullrich, Nicole N. J.; Marcus, Karen; Goumnerova, Liliana; Kieran, Mark W.] Dana Farber Canc Inst, Pediat Neurooncol, Boston, MA 02115 USA.
[Morales La Madrid, Andres; Bandopadhayay, Pratiti; Chi, Susan N.; Manley, Peter; Kieran, Mark W.] Boston Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA USA.
[Ullrich, Nicole N. J.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA.
[Marcus, Karen] Boston Childrens Hosp, Dept Radiat Oncol, Boston, MA USA.
[Goumnerova, Liliana; Scott, Robert M.; Proctor, Mark] Boston Childrens Hosp, Dept Neurosurg, Boston, MA USA.
[Young-Poussaint, Tina] Boston Childrens Hosp, Dept Radiol, Boston, MA USA.
[De Girolami, Umberto] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Morales La Madrid, Andres] Hosp St Joan de Deu, Dept Pediat Hematol & Oncol, Barcelona, Spain.
RP Kieran, MW (reprint author), Dana Farber Canc Inst, Pediat Med Neurooncol, 450 Brookline Ave,Rm D-3154, Boston, MA 02215 USA.
EM mark_kieran@dfci.harvard.edu
FU Stop&Shop Pediatric Brain Tumor Program; St Baldrick's Foundation
FX Supported in part by funding from the Stop&Shop Pediatric Brain Tumor
Program (M.W.K.) and by the St Baldrick's Foundation (A.M.L.M.).
NR 82
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 1077-4114
EI 1536-3678
J9 J PEDIAT HEMATOL ONC
JI J. Pediatr. Hematol. Oncol.
PD AUG
PY 2016
VL 38
IS 6
BP 479
EP 485
DI 10.1097/MPH.0000000000000627
PG 7
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA DU9SP
UT WOS:000382558300022
PM 27438020
ER
PT J
AU Ryu, WS
Schellingerhout, D
Jeong, SW
Nahrendorf, M
Kim, DE
AF Ryu, Wi-Sun
Schellingerhout, Dawid
Jeong, Sang-Wook
Nahrendorf, Matthias
Kim, Dong-Eog
TI Association between Serum Lipid Profiles and Early Neurological
Deterioration in Acute Ischemic Stroke
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Cerebral infarct; lipids and lipoproteins; apolipoproteins; early
neurological deterioration
ID APOLIPOPROTEIN-A-I; METABOLIC SYNDROME; RISK; INFARCTION;
ATHEROSCLEROSIS; HYPERGLYCEMIA; THROMBOLYSIS; MULTICENTER; PROGRESSION;
PREDICTORS
AB Background: Dyslipidemia is associated with chronic cardiovascular disease. However, the effect of dyslipidemia on acute ischemic stroke is unclear. We hypothesized that dyslipidemia could contribute to early neurological deterioration (END) after ischemic stroke. Methods: A total of 410 acute ischemic stroke patients who were admitted to our stroke center within 24 hours after ictus were consecutively included in this study. END was defined as any new neurological symptoms/signs or any neurological worsening occurring during the admission and/or within 3 weeks after the index stroke. Multivariable logistic regression was used to examine the independent association between lipid indices and END. Results: Mean age was 68.2 +/- 13.3 years, 241 (58.8%) were male, and 78 (19.0%) experienced END. Almost END occurred within 3 days after admission (n = 70, 89.7%), and the majority of END was stroke progression (n = 68, 87.1%). In univariate analysis, high-density lipoprotein (HDL)-cholesterol levels (per 1 mmol/L; odds ratio [OR] .37; 95% CI .17-.80; P = .012) and apolipoprotein B (apoB)/apoA-I ratio (per 1 increase; OR 3.71; 95% CI 1.48-9.29; P = .005) were associated with END. In the multivariable analysis, adjusted ORs of END for the highest quartile of HDL-cholesterol and apoB/apoA-I ratio were.42 (95% CI.19-. 94; P = .034) and 2.37 (95% CI 1.02-5.53; P = .045), respectively. The ratio of apoB/apoA-I was associated with END in large artery atherosclerosis stroke but not in other stroke subtypes. Conclusions: Independent association of low HDL-cholesterol and high apoB/apoA-I ratio with END warrants further research to investigate if correction of the lipid profile during the acute period of ischemic stroke could reduce the risk of END.
C1 [Ryu, Wi-Sun; Jeong, Sang-Wook; Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Stroke Ctr, Dept Neurol, Goyang, South Korea.
[Ryu, Wi-Sun; Jeong, Sang-Wook; Kim, Dong-Eog] Dongguk Univ, Ilsan Hosp, Korean Brain MRI Data Ctr, Goyang, South Korea.
[Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Radiol, Houston, TX USA.
[Schellingerhout, Dawid] Univ Texas MD Anderson Canc Ctr, Dept Expt Diagnost Imaging, Houston, TX USA.
[Nahrendorf, Matthias] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA.
[Nahrendorf, Matthias] Harvard Med Sch, Boston, MA USA.
RP Ryu, WS; Kim, DE (reprint author), Dongguk Univ, Ilsan Hosp, Dept Neurol, 814 Siksa Dong, Goyang Si, Gyeonggi Do, South Korea.
EM wisunryu@gmail.com; kdongeog@duih.org
FU Ministry of Health Welfare [HI12C1847, HI12C0066l]; National Research
Foundation - Korean government, Republic of Korea [NRF-2015K1A1A2028228]
FX This research was supported by grants of the Ministry of Health &
Welfare (HI12C1847 and HI12C0066l; Korea Health Technology R&D Project)
and the National Research Foundation (NRF-2015K1A1A2028228; Global
Research Program), funded by the Korean government, Republic of Korea.
NR 34
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
EI 1532-8511
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD AUG
PY 2016
VL 25
IS 8
BP 2024
EP 2030
DI 10.1016/j.jstrokecerebrovasdis.2016.05.009
PG 7
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DS7BO
UT WOS:000380937700038
PM 27256172
ER
PT J
AU Scott, JC
Woods, SP
Wrocklage, KM
Schweinsburg, BC
Southwick, SM
Krystal, JH
AF Scott, J. Cobb
Woods, Steven Paul
Wrocklage, Kristen M.
Schweinsburg, Brian C.
Southwick, Steven M.
Krystal, John H.
TI Prospective Memory in Posttraumatic Stress Disorder
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Posttraumatic stress disorder; Neuropsychology; Cognitive abilities;
Prospective memory; Memory; Anxiety
ID INTENTIONS SCREENING-TEST; NEUROPSYCHOLOGICAL PERFORMANCE;
NEUROCOGNITIVE DISORDERS; FUNCTIONAL OUTCOMES; COGNITIVE FUNCTION;
LOCUS-COERULEUS; HIV-INFECTION; YOUNG-ADULTS; OLDER-ADULTS; PTSD
AB Objectives: Neuropsychological studies of posttraumatic stress disorder (PTSD) have revealed deficits in attention/working memory, processing speed, executive functioning, and retrospective memory. However, little is known about prospective memory (PM) in PTSD, a clinically relevant aspect of episodic memory that supports the encoding and retrieval of intentions for future actions. Methods: Here we examined PM performance in 40 veterans with PTSD compared to 38 trauma comparison (TC) veterans who were exposed to combat but did not develop PTSD. All participants were administered the Memory for Intentions Test (MIST; Raskin, Buckheit, & Sherrod, 2010), a standardized and validated measure of PM, alongside a comprehensive neurocognitive battery, structured diagnostic interviews for psychiatric conditions, and behavioral questionnaires. Results: Veterans with PTSD performed moderately lower than TC on time-based PM, with errors primarily characterized as PM failure errors (i.e., omissions). However, groups did not differ in event-based PM, ongoing task performance, or post-test recognition of PM intentions for each trial. Lower time-based PM performance was specifically related to hyperarousal symptoms of PTSD. Time-based-performance was also associated with neuropsychological measures of retrospective memory and executive functions in the PTSD group. Nevertheless, PTSD was significantly associated with poorer PM above and beyond age and performance in retrospective memory and executive functions. Discussion: Results provide initial evidence of PM dysfunction in PTSD, especially in strategic monitoring during time-based PM tasks. Findings have potential implications for everyday functioning and health behaviors in persons with PTSD, and deserve replication and future study.
C1 [Scott, J. Cobb] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA USA.
[Scott, J. Cobb] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Woods, Steven Paul] Univ Houston, Dept Psychol, Houston, TX USA.
[Wrocklage, Kristen M.; Schweinsburg, Brian C.; Southwick, Steven M.; Krystal, John H.] Natl Ctr PTSD, Clin Neurosci Div, VA Connecticut Healthcare Syst, West Haven, CT USA.
[Wrocklage, Kristen M.; Schweinsburg, Brian C.; Southwick, Steven M.; Krystal, John H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA.
[Krystal, John H.] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT USA.
[Krystal, John H.] Yale New Haven Med Ctr, Psychiat Serv, 20 York St, New Haven, CT 06504 USA.
RP Scott, JC (reprint author), Philadelphia VA Med Ctr, MIRECC 116, 3900 Woodland Ave, Philadelphia, PA 19104 USA.
EM scott1@upenn.edu
FU Department of Veterans Affairs Career Development Award [IK2CX000772];
National Center for PTSD (NCPTSD); National Center for Advancing
Translational Science [1UH2TR000960-01]; Department of Veterans Affairs
(NCPTSD); National Institute on Alcohol Abuse and Alcoholism
[P50AA12870, M01RR00125]; Yale Center for Clinical Investigation [UL1
RR024139]; Neuroimaging Core for the VA/DOD Consortium; [R01MH073419];
[R01DA034497]
FX This study is dedicated to the memory of Henry Krystal, M.D., pioneer of
the impact of massive psychic trauma, who died on October 8, 2015. This
work was supported by a Department of Veterans Affairs Career
Development Award (IK2CX000772) to Dr. Scott, as well as the National
Center for PTSD (NCPTSD). Dr. Krystal's participation was supported by
the National Center for Advancing Translational Science
(1UH2TR000960-01), the Department of Veterans Affairs (NCPTSD), the
Neuroimaging Core for the VA/DOD Consortium to Alleviate PTSD, the
National Institute on Alcohol Abuse and Alcoholism (P50AA12870,
M01RR00125), and the Yale Center for Clinical Investigation (UL1
RR024139). Dr. Woods is supported by R01MH073419 and R01DA034497. The
views expressed in this article are those of the authors and do not
necessarily reflect the position or policy of the Department of Veterans
Affairs. The authors declare no conflicts of interest.
NR 77
TC 0
Z9 0
U1 15
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
EI 1469-7661
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD AUG
PY 2016
VL 22
IS 7
BP 724
EP 734
DI 10.1017/S1355617716000564
PG 11
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA DU8SQ
UT WOS:000382485100004
PM 27353125
ER
PT J
AU Lemos, R
Santana, I
Caetano, G
Bernardino, I
Morais, R
Farivar, R
Castelo-Branco, M
AF Lemos, Raquel
Santana, Isabel
Caetano, Gina
Bernardino, Ines
Morais, Ricardo
Farivar, Reza
Castelo-Branco, Miguel
TI Three-Dimensional Face Recognition in Mild Cognitive Impairment: A
Psychophysical and Structural MR Study
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Mild cognitive impairment; Cortical thickness; Vision; Fusiform; Dorsal
pathway; Ventral pathway; Structure-from-motion
ID HUMAN CEREBRAL-CORTEX; STRUCTURE-FROM-MOTION; EARLY ALZHEIMERS-DISEASE;
SURFACE-BASED ANALYSIS; MAGNOCELLULAR IMPAIRMENT; HUMAN BRAIN; DORSAL;
DEFICITS; FMRI; INTEGRATION
AB Objectives: Mild cognitive impairment (MCI) has been associated with a high risk of conversion to Alzheimer's dementia. In addition to memory complaints, impairments in the visuospatial domain have been reported in this condition. We have previously shown that deficits in perceiving structure-from-motion (SFM) objects are reflected in functional reorganization of brain activity within the visual ventral stream. Here we aimed to identify structural correlates of psychophysical complex face and object recognition performance in amnestic MCI patients (n=30 vs. n=25 controls). This study was, therefore, motivated by evidence from recent studies showing that a combination of visual information across dorsal and ventral visual streams may be needed for the perception of three-dimensional (3D) SFM objects. Methods: In our experimental paradigm, participants had to discriminate 3D SFM shapes (faces and objects) from 3D SFM meaningless (scrambled) shapes. Results: Morphometric analysis established neuroanatomical evidence for impairment in MCI as demonstrated by smaller hippocampal volumes. We found association between cortical thickness and face recognition performance, comprising the occipital lobe and visual ventral stream fusiform regions (overlapping the known location of face fusiform area) in the right hemisphere, in MCI. Conclusions: We conclude that impairment of 3D visual integration exists at the MCI stage involving also the visual ventral stream and contributing to face recognition deficits. The specificity of such observed structure-function correlation for faces suggests a special role of this processing pathway in health and disease.
C1 [Lemos, Raquel; Caetano, Gina; Bernardino, Ines; Castelo-Branco, Miguel] Univ Coimbra, Fac Med, Inst Biomed Imaging & Life Sci CNC IBILI, Visual Neurosci Lab,IBILI, Coimbra, Portugal.
[Lemos, Raquel] Univ Coimbra, Fac Psychol & Educ Sci, Coimbra, Portugal.
[Santana, Isabel] Ctr Hosp Univ Coimbra, Neurol Dept, Coimbra, Portugal.
[Morais, Ricardo] Ctr Hosp Univ Coimbra, Neuroradiol Dept, Coimbra, Portugal.
[Farivar, Reza] Harvard Med Sch, Charlestown, MA USA.
[Farivar, Reza] Massachusetts Gen Hosp, A Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Farivar, Reza] McGill Univ, McGill Vis Res, Montreal, PQ, Canada.
RP Castelo-Branco, M (reprint author), Univ Coimbra, IBILI Fac Med, Visual Neurosci Lab, P-3000354 Coimbra, Portugal.
EM mcbranco@ibili.uc.pt
RI Caetano, Gina/L-9340-2015;
OI Caetano, Gina/0000-0001-6878-6079; Castelo-Branco,
Miguel/0000-0003-4364-6373
FU Foundation for Science and Technology Portugal [SFRH/BD/74070/2010,
PIC/IC/83206/2007, PTDC/SAU-ENB/112306/2009, CENTRO-07-ST24-FEDER-00205,
FCT- UID/NEU/04539/2013]; COMPETE [POCI-01-0145-FEDER-007440]
FX Authors thank all the participants. Authors also thank Carlos Ferreira
and Joao Marques for help with MRI scanning, as well as Francisco
Caramelo and Joao Pereira for help with statistical analysis. None of
the authors have any conflict of interest related to this work. This
work was supported by grants from the Foundation for Science and
Technology Portugal: SFRH/BD/74070/2010 (to R.L.); PIC/IC/83206/2007 (to
I.S.); Programa Ciencia 2008 and PTDC/SAU-ENB/112306/2009 (to G.C.);
CENTRO-07-ST24-FEDER-00205, FCT- UID/NEU/04539/2013, and COMPETE,
POCI-01-0145-FEDER-007440 (to M.C.B.).
NR 66
TC 0
Z9 0
U1 2
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1355-6177
EI 1469-7661
J9 J INT NEUROPSYCH SOC
JI J. Int. Neuropsychol. Soc.
PD AUG
PY 2016
VL 22
IS 7
BP 744
EP 754
DI 10.1017/S135561771600059X
PG 11
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA DU8SQ
UT WOS:000382485100006
PM 27406061
ER
PT J
AU Sangji, NF
Bohnen, JD
Ramly, EP
Yeh, DD
King, DR
DeMoya, M
Butler, K
Fagenholz, PJ
Velmahos, GC
Chang, DC
Kaafarani, HMA
AF Sangji, Naveen F.
Bohnen, Jordan D.
Ramly, Elie P.
Yeh, Daniel D.
King, David R.
DeMoya, Marc
Butler, Kathryn
Fagenholz, Peter J.
Velmahos, George C.
Chang, David C.
Kaafarani, Haytham M. A.
TI Derivation and validation of a novel Emergency Surgery Acuity Score
(ESAS)
SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
LA English
DT Article
DE Emergency surgery; mortality score; quality benchmarking; perioperative
mortality; outcomes
ID GENERAL-SURGERY; DISEASE; MORTALITY; OUTCOMES; PREDICTORS; SEVERITY;
BURDEN; SYSTEM; SCALE; TOOL
AB BACKGROUND: There currently exists no preoperative risk stratification system for emergency surgery (ES). We sought to develop an Emergency Surgery Acuity Score (ESAS) that helps predict perioperative mortality in ES patients.
METHODS: Using the 2011 American College of Surgeons' National Surgical Quality Improvement Program (ACS-NSQIP) database (derivation cohort), we identified all surgical procedures that were classified as "emergent." A three-step methodology was then performed. First, multiple logistic regression models were created to identify independent predictors (e.g., patient demographics, comorbidities, and preoperative laboratory variables) of 30-day mortality in ES. Second, based on the relative impact of each identified predictor (i.e., odds ratio), using weighted averages, a novel score was derived. Third, using the 2012 ACS-NSQIP database (validation cohort), the score was validated by calculating its C statistic and evaluating its ability to predict 30-day mortality.
RESULTS: From 280,801 NSQIP cases, 18,439 ES cases were analyzed, of which 1,598 (8.7%) resulted in death at 30 days. The multiple logistic regression analyses identified 22 independent predictors of mortality. Based on the relative impact of these predictors, ESAS was derived with a total score range of 0 to 29. ESAS had a C statistic of 0.86; the probability of death at 30 days gradually increased from 0% to 36% then 100% at scores of 0, 11, and 22, respectively. In the validation phase, 19,552 patients were included, the mortality rate was 7.2%, and the ESAS C statistic stayed at 0.86.
CONCLUSION: We have therefore developed and validated a novel score, ESAS, that accurately predicts mortality in ES patients. Such a score could prove useful for (1) preoperative patient counseling, (2) identification of patients needing close postoperative monitoring, and (3) risk adjustment in any efforts at benchmarking the quality of ES. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.
C1 [Sangji, Naveen F.; Bohnen, Jordan D.; Ramly, Elie P.; Yeh, Daniel D.; King, David R.; DeMoya, Marc; Butler, Kathryn; Fagenholz, Peter J.; Velmahos, George C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
[Sangji, Naveen F.; Chang, David C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
[Sangji, Naveen F.; Chang, David C.; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA.
RP Kaafarani, HMA (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.; Kaafarani, HMA (reprint author), Harvard Med Sch, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM Haytham.kaafarani@mgh.harvard.edu
NR 28
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 2163-0755
EI 2163-0763
J9 J TRAUMA ACUTE CARE
JI J. Trauma Acute Care Surg.
PD AUG
PY 2016
VL 81
IS 2
BP 213
EP 220
DI 10.1097/TA.0000000000001059
PG 8
WC Critical Care Medicine; Surgery
SC General & Internal Medicine; Surgery
GA DS5CE
UT WOS:000380797300001
PM 27032007
ER
PT J
AU Gale, HI
Bobbitt, CA
Setty, BN
Sprinz, PG
Doros, G
Williams, DD
Morrison, TC
Kalajian, TA
Tu, P
Mundluru, SN
Castro-Aragon, I
AF Gale, Heather I.
Bobbitt, Christopher A.
Setty, Bindu N.
Sprinz, Philippa G.
Doros, Gheorghe
Williams, Don D.
Morrison, Trevor C.
Kalajian, Tyler A.
Tu, Powen
Mundluru, Shankar N.
Castro-Aragon, Ilse
TI Expected Sonographic Appearance of the Spleen in Children and Young
Adults With Sickle Cell Disease An Update
SO JOURNAL OF ULTRASOUND IN MEDICINE
LA English
DT Article
DE pediatrics; pediatric ultrasound; sickle cell disease; sonography;
spleen
ID ANEMIA; LIVER; TRANSFUSIONS; HYDROXYUREA; THALASSEMIA; RELAXATION;
ULTRASOUND; ASPLENIA; PATIENT; TISSUE
AB Objectives-To update the imaging literature regarding spleen appearances in young patients with sickle cell disease (SCD).
Methods-We conducted a retrospective study and included 112 patients age 0 to 21 years with SCD who had at least 1 abdominal sonogram at our institution between 1999 and 2011. Radiologic findings were compared between risk groups by chi(2) analysis. Findings were correlated with other imaging modalities when available.
Results-In our cohort, 35.7% of patients had autosplenectomy, and 8.0% had undergone surgical splenectomy. Only 5.0% of individuals age 0 to 5 years had auto splenectomy. In those who had not undergone surgical splenectomy or autosplenectomy, 76.2% had echogenic spleens, heterogeneous-appearing spleens, or both, and patients with the homozygous sickle cell anemia (HbSS) genotype were more likely to have an abnormal spleen echo texture. Patients treated with transfusions had echogenic spleens and had a higher frequency of splenic regeneration nodules. Most patients (80%) with splenomegaly did not require surgical splenectomy after 5.7 years of follow-up.
Conclusions-Twenty years ago, children with HbSS SCD were expected to have autosplenectomy by age 5 years. There have been changes in the radiologic appearance of the spleen in patients with SDC, likely due to improved supportive care and the use of acute and chronic transfusion therapy. We found that autosplenectomy is rare by age 5 years, and during childhood and adolescence, the spleen typically appears echogenic, heterogeneous, or both, depending on disease severity.
C1 [Gale, Heather I.] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
[Bobbitt, Christopher A.; Mundluru, Shankar N.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Setty, Bindu N.; Castro-Aragon, Ilse] Boston Univ, Boston Med Ctr, Boston, MA 02215 USA.
[Sprinz, Philippa G.] Hasbro Childrens Hosp, Providence, RI USA.
[Doros, Gheorghe] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Williams, Don D.] Univ Utah, Salt Lake City, UT USA.
[Morrison, Trevor C.] Beth Israel Deaconess Med Ctr, Brookline, MA USA.
[Kalajian, Tyler A.] Boston Univ, Sch Med, Dept Med Clin Sci, Grad Med Studies, Boston, MA 02118 USA.
[Tu, Powen] Stanford Univ, Stanford, CA 94305 USA.
RP Gale, HI (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
NR 30
TC 0
Z9 0
U1 2
U2 2
PU AMER INST ULTRASOUND MEDICINE
PI LAUREL
PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906
USA
SN 0278-4297
EI 1550-9613
J9 J ULTRAS MED
JI J. Ultrasound Med.
PD AUG 1
PY 2016
VL 35
IS 8
BP 1735
EP 1745
DI 10.7863/ultra.15.09023
PG 11
WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging
GA DU9HJ
UT WOS:000382527000014
PM 27353067
ER
PT J
AU Nathavitharana, RR
Peters, J
Lederer, P
von Delft, A
Farley, JE
Pai, M
Jaramillo, E
Raviglione, M
Nardell, E
AF Nathavitharana, Ruvandhi R.
Peters, Jurgens
Lederer, Philip
von Delft, Arne
Farley, Jason E.
Pai, Madhukar
Jaramillo, Ernesto
Raviglione, Mario
Nardell, Edward
TI Engaging health-care workers to reduce tuberculosis transmission
SO LANCET INFECTIOUS DISEASES
LA English
DT Editorial Material
ID DRUG-RESISTANT TUBERCULOSIS; INFECTION
C1 [Nathavitharana, Ruvandhi R.; Peters, Jurgens; Lederer, Philip; von Delft, Arne] TB Proof, Cape Town, South Africa.
[Nathavitharana, Ruvandhi R.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
[Peters, Jurgens] London Sch Hyg & Trop Med, Fac Infect & Trop Dis, London, England.
[Lederer, Philip] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[von Delft, Arne] Univ Cape Town, Fac Hlth Sci, Sch Publ Hlth & Family Med, Cape Town, South Africa.
[Farley, Jason E.] Johns Hopkins Univ, Sch Nursing & Med, Baltimore, MD USA.
[Pai, Madhukar] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada.
[Jaramillo, Ernesto; Raviglione, Mario] WHO, Global TB Programme, Geneva, Switzerland.
[Nardell, Edward] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA.
RP Nathavitharana, RR (reprint author), TB Proof, Cape Town, South Africa.; Nathavitharana, RR (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA.
EM rnathavi@bidmc.harvard.edu
FU NIAID NIH HHS [T32 AI007061]
NR 15
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD AUG
PY 2016
VL 16
IS 8
BP 883
EP 885
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA DU4XH
UT WOS:000382215700016
PM 27477968
ER
PT J
AU Anstead, GM
AF Anstead, Gregory M.
TI The centenary of the discovery of trench fever, an emerging infectious
disease of World War 1
SO LANCET INFECTIOUS DISEASES
LA English
DT Review
ID BARTONELLA-QUINTANA; RICKETTSIA QUINTANA; DISORDERED ACTION; RELAPSING
FEVER; WAR; EPIDEMIC; ETIOLOGY; HENSELAE; ORIGIN; FORCES
AB In 1915, a British medical officer on the Western Front reported on a soldier with relapsing fever, headache, dizziness, lumbago, and shin pain. Within months, additional cases were described, mostly in frontline troops, and the new disease was called trench fever. More than 1 million troops were infected with trench fever during World War 1, with each affected soldier unfit for duty for more than 60 days. Diagnosis was challenging, because there were no pathognomonic signs and symptoms and the causative organism could not be cultured. For 3 years, the transmission and cause of trench fever were hotly debated. In 1918, two commissions identified that the disease was louse-borne. The bacterium Rickettsia quintana was consistently found in the gut and faeces of lice that had fed on patients with trench fever and its causative role was accepted in the 1920s. The organism was cultured in the 1960s and reclassified as Bartonella quintana; it was also found to cause endocarditis, peliosis hepatis, and bacillary angiomatosis. Subsequently, B quintana infection has been identified in new populations in the Andes, in homeless people in urban areas, and in individuals with HIV. The story of trench fever shows how war can lead to the recrudescence of an infectious disease and how medicine approached an emerging infection a century ago.
C1 [Anstead, Gregory M.] South Texas Vet Hlth Care Syst, Med Serv, San Antonio, TX USA.
[Anstead, Gregory M.] Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA.
RP Anstead, GM (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Infect Dis, Dept Med, San Antonio, TX 78229 USA.
EM anstead@uthscsa.edu
NR 81
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1473-3099
EI 1474-4457
J9 LANCET INFECT DIS
JI Lancet Infect. Dis.
PD AUG
PY 2016
VL 16
IS 8
BP E164
EP E172
DI 10.1016/S1473-3099(16)30003-2
PG 9
WC Infectious Diseases
SC Infectious Diseases
GA DU4XH
UT WOS:000382215700003
PM 27375211
ER
PT J
AU Zimmaro, LA
Salmon, P
Naidu, H
Rowe, J
Phillips, K
Rebholz, WN
Giese-Davis, J
Cash, E
Dreeben, SJ
Bayley-Veloso, R
Jablonski, ME
Hicks, A
Siwik, C
Sephton, SE
AF Zimmaro, Lauren A.
Salmon, Paul
Naidu, Hemali
Rowe, Jonathan
Phillips, Kala
Rebholz, Whitney N.
Giese-Davis, Janine
Cash, Elizabeth
Dreeben, Samuel J.
Bayley-Veloso, Rene
Jablonski, Megan E.
Hicks, Allison
Siwik, Chelsea
Sephton, Sandra E.
TI Association of Dispositional Mindfulness with Stress, Cortisol, and
Well-Being Among University Undergraduate Students
SO MINDFULNESS
LA English
DT Article
DE Mindfulness; Stress; Cortisol; Well-being; Undergraduate
ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; COLLEGE-STUDENTS;
FUNCTIONAL CONNECTIVITY; ADRENOCORTICAL ACTIVITY; PSYCHOLOGICAL STRESS;
LONG-TERM; MEDITATION; REDUCTION; HEALTH
AB Mindfulness has been associated with better psychological and physical health; although, the mechanisms of these benefits are poorly understood. We explored the role of mindfulness in stress-health pathways among undergraduates at a large public university. Participants reported on demographic and academic variables and completed data collection at two time points during the academic semester, approximately one month apart. At each collection, measures of mindfulness, perceived stress, and psychological well-being were gathered. Students provided two days of home-based saliva collection for assessment of cortisol. Mean scores were computed for each of the measures, over the two assessments. Hierarchical multiple regressions adjusting for GPA, hours of paid employment per week, minority status, and living situation explored the impact of mindfulness in our stress-health model. Students with higher dispositional mindfulness reported significantly less perceived stress and had lower overall mean diurnal cortisol. Mindfulness was associated with greater psychological well-being. Exploratory analyses suggested that future research should explore the potential mediating or moderating relationships between mindfulness, perceived stress, and cortisol. Findings suggest that mindfulness may help attenuate both psychological and physiological stress responses to college stress.
C1 [Zimmaro, Lauren A.; Salmon, Paul; Naidu, Hemali; Rowe, Jonathan; Phillips, Kala; Rebholz, Whitney N.; Cash, Elizabeth; Bayley-Veloso, Rene; Jablonski, Megan E.; Hicks, Allison; Siwik, Chelsea; Sephton, Sandra E.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA.
[Giese-Davis, Janine] Univ Calgary, Dept Oncol, Div Psychosocial Oncol, Calgary, AB, Canada.
[Cash, Elizabeth] Univ Louisville, Sch Med, Dept Otolaryngol Head & Neck Surg & Communicat Di, Louisville, KY 40292 USA.
[Dreeben, Samuel J.] South Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA.
[Sephton, Sandra E.] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
RP Sephton, SE (reprint author), Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA.; Sephton, SE (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA.
EM psalmon@louisville.edu; sephton@louisville.edu
FU Office of the Vice President for Research at the University of
Louisville
FX This study was funded through an undergraduate research grant from the
Office of the Vice President for Research at the University of
Louisville, awarded to Paul Salmon, Ph.D.
NR 70
TC 0
Z9 0
U1 22
U2 27
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1868-8527
EI 1868-8535
J9 MINDFULNESS
JI Mindfulness
PD AUG
PY 2016
VL 7
IS 4
BP 874
EP 885
DI 10.1007/s12671-016-0526-8
PG 12
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DV3XX
UT WOS:000382860000009
ER
PT J
AU Felleman, BI
Stewart, DG
Simpson, TL
Heppner, PS
Kearney, DJ
AF Felleman, Benjamin I.
Stewart, David G.
Simpson, Tracy L.
Heppner, Pia S.
Kearney, David J.
TI Predictors of Depression and PTSD Treatment Response Among Veterans
Participating in Mindfulness-Based Stress Reduction
SO MINDFULNESS
LA English
DT Article
DE Mindfulness; PTSD; Depression; Treatment
ID COGNITIVE-BEHAVIORAL THERAPY; INTIMATE PARTNER VIOLENCE;
POSTTRAUMATIC-STRESS; PROCESSING THERAPY; ANXIETY DISORDERS; MAJOR
DEPRESSION; MODERATORS; PROGRAM; INTERVENTION; REPLICATION
AB Posttraumatic stress disorder (PTSD) and depression are prevalent and often co-occur among veterans. There is growing interest in the effects of mindfulness-based interventions among veterans. This study examined PTSD and depression outcomes, and baseline predictors of response, among veterans who participated in mindfulness-based stress reduction (MBSR). Participants included 116 veterans with PTSD before and after MBSR. Multilevel modeling assessed baseline predictors of change in PTSD and depressive symptoms. There were clinically significant reductions in PTSD and depression symptoms posttreatment and at 4 months follow-up. For PTSD, effect sizes were in the medium range posttreatment (d = -.63) and at follow-up (d = -.69), and for depression posttreatment (d = -.58) and at follow-up (d = -.70). Baseline PTSD was a significant predictor of slope (beta = .03, p = .04) on PTSD outcomes; higher baseline PTSD predicted greater rate of reduction in symptoms. For depression (beta = .04, p < .01,), those with severe or moderately severe depression exhibited the greatest rate of improvement. However, veterans with high symptom severity did remain symptomatic post-MBSR. These findings show preliminary support for MBSR in facilitating symptom reduction for veterans with severe PTSD and co-occurring depression.
C1 [Felleman, Benjamin I.; Stewart, David G.] Seattle Pacific Univ, Dept Psychol Family & Community, 3307 Third Ave W Ste 107, Seattle, WA 98119 USA.
[Felleman, Benjamin I.; Heppner, Pia S.] VA San Diego Hlth Care Syst, 3350 La Jolla Village Dr,116B, San Diego, CA 92161 USA.
[Simpson, Tracy L.] VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ CESAT, 1660 South Columbian Way, Seattle, WA USA.
[Simpson, Tracy L.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, 1959 NE Pacific St, Seattle, WA 98195 USA.
[Heppner, Pia S.] Univ Calif San Diego, Dept Psychiat, Gilman Dr,MC 0603, San Diego, CA USA.
[Kearney, David J.] VA Puget Sound Hlth Care Syst, 1660 South Columbian Way, Seattle, WA USA.
[Kearney, David J.] Univ Washington, Sch Med, Dept Med, 1959 NE Pacific St, Seattle, WA 98195 USA.
RP Felleman, BI (reprint author), Seattle Pacific Univ, Dept Psychol Family & Community, 3307 Third Ave W Ste 107, Seattle, WA 98119 USA.; Felleman, BI (reprint author), VA San Diego Hlth Care Syst, 3350 La Jolla Village Dr,116B, San Diego, CA 92161 USA.
EM benjamin.felleman@va.gov
NR 54
TC 0
Z9 0
U1 14
U2 14
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1868-8527
EI 1868-8535
J9 MINDFULNESS
JI Mindfulness
PD AUG
PY 2016
VL 7
IS 4
BP 886
EP 895
DI 10.1007/s12671-016-0527-7
PG 10
WC Psychology, Clinical; Psychiatry
SC Psychology; Psychiatry
GA DV3XX
UT WOS:000382860000010
ER
PT J
AU Scapin, G
Bertalot, T
Vicentini, N
Gatti, T
Tescari, S
De Filippis, V
Marega, C
Menna, E
Gasparella, M
Parnigotto, PP
Di Liddo, R
Filippini, F
AF Scapin, Giorgia
Bertalot, Thomas
Vicentini, Nicola
Gatti, Teresa
Tescari, Simone
De Filippis, Vincenzo
Marega, Carla
Menna, Enzo
Gasparella, Marco
Parnigotto, Pier Paolo
Di Liddo, Rosa
Filippini, Francesco
TI Neuronal commitment of human circulating multipotent cells by carbon
nanotube-polymer scaffolds and biomimetic peptides
SO NANOMEDICINE
LA English
DT Article
DE biomimetic peptides; carbon nanotubes; human circulating multipotent
cells; nanocomposite scaffold; neuronal differentiation; regenerative
medicine
ID MESENCHYMAL STEM-CELLS; RETINOIC ACID; STROMAL CELLS; PRIMARY CULTURES;
NERVOUS-SYSTEM; DIFFERENTIATION; TISSUE; BLOOD; EXPRESSION; MONOCYTES
AB Aim: We aimed to set up a self-standing, biomimetic scaffold system able to induce and support per se neuronal differentiation of autologous multipotent cells. Materials & methods: We isolated a population of human circulating multipotent cells (hCMCs), and used carbon nanotube/polymer nanocomposite scaffolds to mimic electrical/nanotopographical features of the neural environment, and biomimetic peptides reproducing axon guidance cues from neural proteins. Results: hCMCs showed high degree of stemness and multidifferentiative potential; stimuli from the scaffolds and biomimetic peptides could induce and boost hCMC differentiation toward neuronal lineage despite the absence of exogenously added, specific growth factors. Conclusion: This work suggests the scaffold-peptides system combined with autologous hCMCs as a functional biomimetic, self-standing prototype for neural regenerative medicine applications.
C1 [Scapin, Giorgia; Filippini, Francesco] Univ Padua, Dept Biol, I-35131 Padua, Italy.
[Bertalot, Thomas; Tescari, Simone; De Filippis, Vincenzo; Di Liddo, Rosa] Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy.
[Vicentini, Nicola; Gatti, Teresa; Marega, Carla; Menna, Enzo] Univ Padua, Dept Chem Sci, I-35131 Padua, Italy.
[Gasparella, Marco] Univ Padua, Dept Woman & Child Hlth, I-35128 Padua, Italy.
[Parnigotto, Pier Paolo] Caselle Selvazzano Dentro, Tissue Engn & Signaling ONLUS, I-35030 Padua, Italy.
[Scapin, Giorgia] Harvard Med Sch, Sect Islet Cell & Regenerat Biol, Joslin Diabet Ctr, Boston, MA 02215 USA.
[Scapin, Giorgia] Harvard Med Sch, Dept Med, Boston, MA 02215 USA.
RP Filippini, F (reprint author), Univ Padua, Dept Biol, I-35131 Padua, Italy.; Di Liddo, R (reprint author), Univ Padua, Dept Pharmaceut & Pharmacol Sci, I-35131 Padua, Italy.
EM rosa.diliddo@unipd.it; francesco.filippini@unipd.it
OI Gatti, Teresa/0000-0001-5343-8055
FU CaRiPaRo Foundation (Excellence Research Project); Italian Ministry of
Education, Universities and Research - MIUR [PRIN-20104XET32];
University of Padova, Italy [PRAT2015 CPDA151948]; [CPDR137224/13]
FX The authors acknowledge the financial support from CaRiPaRo Foundation
(Excellence Research Project 2011 to V De Filippis), the Italian
Ministry of Education, Universities and Research - MIUR (contract
PRIN-20104XET32 to E Menna) and the University of Padova, Italy (basic
"EX 60%" grants to R Di Liddo and F Filippini, Project PRAT2015
CPDA151948 to F Filippini). Research fellowship CPDR137224/13 to R Di
Liddo (supporting T Bertalot) and PhD fellowship to G Scapin are
gratefully acknowledged. The authors have no other relevant affiliations
or financial involvement with any organization or entity with a
financial interest in or financial conflict with the subject matter or
materials discussed in the manuscript apart from those disclosed.
NR 59
TC 1
Z9 1
U1 4
U2 4
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1743-5889
EI 1748-6963
J9 NANOMEDICINE-UK
JI Nanomedicine
PD AUG
PY 2016
VL 11
IS 15
BP 1929
EP 1946
DI 10.2217/nnm-2016-0150
PG 18
WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology
SC Biotechnology & Applied Microbiology; Science & Technology - Other
Topics
GA DS9NL
UT WOS:000381109900002
PM 27246559
ER
PT J
AU Ghaoui, R
Benavides, T
Lek, M
Waddell, LB
Kaur, S
North, KN
MacArthur, DG
Clarke, NF
Cooper, ST
AF Ghaoui, Roula
Benavides, Tatiana
Lek, Monkol
Waddell, Leigh B.
Kaur, Simranpreet
North, Kathryn N.
MacArthur, Daniel G.
Clarke, Nigel F.
Cooper, Sandra T.
TI TOR1AIP1 as a cause of cardiac failure and recessive limb-girdle
muscular dystrophy
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Genetics; Muscular dystrophy; Limb-girdle; Cardiac failure; Cardiac
transplant
ID LAMIN A/C GENE; MUTATIONS; INTERACTS; SKELETAL; MYOPATHY; PROTEIN
AB TorsinA-interacting protein 1 (TOR1AIP1) gene is a novel gene that has recently been described to cause limb-girdle muscular dystrophy (LGMD) with mild dilated cardiomyopathy. We report a family with mutations in TOR1AIP1 where the striking clinical feature is severe cardiac failure requiring cardiac transplant in two siblings, in addition to musculoskeletal weakness and muscular dystrophy. We demonstrate an absence of TOR1AIP1 protein expression in cardiac and skeletal muscles of affected siblings. We expand the phenotype of this gene to demonstrate the cardiac involvement and the importance of cardiac surveillance in patients with mutations in TOR1AIPI. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Ghaoui, Roula; Benavides, Tatiana; Waddell, Leigh B.; Kaur, Simranpreet; Clarke, Nigel F.; Cooper, Sandra T.] Childrens Hosp Westmead, Kids Res Inst, Inst Neurosci & Muscle Res, Sydney, NSW 2145, Australia.
[Ghaoui, Roula; Clarke, Nigel F.; Cooper, Sandra T.] Univ Sydney, Sydney Med Sch, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia.
[Lek, Monkol; MacArthur, Daniel G.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Lek, Monkol; MacArthur, Daniel G.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[North, Kathryn N.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Melbourne, Vic 3052, Australia.
RP Ghaoui, R; Cooper, ST (reprint author), Childrens Hosp Westmead, INMR, Westmead, NSW 2145, Australia.
EM roula.ghaoui@health.nsw.gov.au; Sandra.cooper@sydney.edu.au
RI North, Kathryn/K-6476-2012
OI North, Kathryn/0000-0003-0841-8009
FU National Health and Medical Research Council of Australia [1022707,
1031893, 1080587, 1035828, 1048816]; National Human Genome Research
Institute of the US National Institutes of Health (Medical Sequencing
Program) [U54 HG003067]; Novartis Foundation for Medical-Biological
Research
FX This work was funded by the National Health and Medical Research Council
of Australia grants 1022707 and 1031893 (both NFC and KNN), 1080587 to
DGM, KNN, NFC and STC, 1035828 (NFC) and 1048816 to STC. Exome
sequencing was supported by grants from the National Human Genome
Research Institute of the US National Institutes of Health (Medical
Sequencing Program grant U54 HG003067 to the Broad Institute principal
investigator, Lander). TBD was supported by the Novartis Foundation for
Medical-Biological Research.
NR 13
TC 2
Z9 2
U1 3
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
EI 1873-2364
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD AUG
PY 2016
VL 26
IS 8
BP 500
EP 503
DI 10.1016/j.nmd.2016.05.013
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DT5TK
UT WOS:000381545300004
PM 27342937
ER
PT J
AU Struck, AF
Carr, CM
Shah, V
Hesselink, JR
Haughton, VM
AF Struck, Aaron F.
Carr, Carrie M.
Shah, Vinil
Hesselink, John R.
Haughton, Victor M.
TI Cervical spinal canal narrowing in idiopathic syringomyelia
SO NEURORADIOLOGY
LA English
DT Article
DE Idiopathic syringomyelia; Cerebrospinal fluid; Cervical spinal canal;
CSF flow dynamics
ID CHIARI I MALFORMATION
AB The cervical spine in Chiari I patient with syringomyelia has significantly different anteroposterior diameters than it does in Chiari I patients without syringomyelia. We tested the hypothesis that patients with idiopathic syringomyelia (IS) also have abnormal cervical spinal canal diameters. The finding in both groups may relate to the pathogenesis of syringomyelia.
Local institutional review boards approved this retrospective study. Patients with IS were compared to age-matched controls with normal sagittal spine MR. All subjects had T1-weighted spin-echo (500/20) and T2-weighted fast spin-echo (2000/90) sagittal cervical spine images at 1.5 T. Readers blinded to demographic data and study hypothesis measured anteroposterior diameters at each cervical level. The spinal canal diameters were compared with a Mann-Whitney U test. The overall difference was assessed with a Friedman test. Seventeen subjects were read by two reviewers to assess inter-rater reliability.
Fifty IS patients with 50 age-matched controls were studied. IS subjects had one or more syrinxes varying from 1 to 19 spinal segments. Spinal canal diameters narrowed from C1 to C3 and then enlarged from C5 to C7 in both groups. Diameters from C2 to C4 were narrower in the IS group (p < 0.005) than in controls. The ratio of the C3 to the C7 diameters was also smaller (p = 0.004) in IS than controls. Collectively, the spinal canal diameters in the IS were significantly different from controls (Friedman test p < 0.0001).
Patients with IS have abnormally narrow upper and mid cervical spinal canal diameters and greater positive tapering between C3 and C7.
C1 [Struck, Aaron F.] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Wang 735, Boston, MA 02114 USA.
[Carr, Carrie M.] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Shah, Vinil] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
[Hesselink, John R.] Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA.
[Haughton, Victor M.] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
RP Struck, AF (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St Wang 735, Boston, MA 02114 USA.
EM astruck@mgh.harvard.edu
NR 14
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-3940
EI 1432-1920
J9 NEURORADIOLOGY
JI Neuroradiology
PD AUG
PY 2016
VL 58
IS 8
BP 771
EP 775
DI 10.1007/s00234-016-1701-2
PG 5
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DV2NN
UT WOS:000382757400004
PM 27194170
ER
PT J
AU Nathwani, N
Krishnan, AY
Richardson, PG
AF Nathwani, Nitya
Krishnan, Amrita Y.
Richardson, Paul G.
TI Routine Use of Autologous Stem Cell Transplantation in Multiple Myeloma
SO ONCOLOGY-NEW YORK
LA English
DT Editorial Material
ID LENALIDOMIDE; MULTICENTER; MAINTENANCE; THERAPY
C1 [Nathwani, Nitya; Krishnan, Amrita Y.] City Hope Canc Ctr, Judy & Bernard Briskin Ctr Myeloma, Duarte, CA 91010 USA.
[Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA.
RP Nathwani, N (reprint author), City Hope Canc Ctr, Judy & Bernard Briskin Ctr Myeloma, Duarte, CA 91010 USA.
NR 14
TC 0
Z9 0
U1 2
U2 2
PU UBM MEDICA
PI NORWALK
PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA
SN 0890-9091
J9 ONCOLOGY-NY
JI Oncology-NY
PD AUG
PY 2016
VL 30
IS 8
BP 747
EP 749
PG 3
WC Oncology
SC Oncology
GA DT4LN
UT WOS:000381452700010
ER
PT J
AU Scrivani, SJ
AF Scrivani, Steven J.
TI Oral and Maxillofacial Pain Preface
SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA
LA English
DT Editorial Material
C1 [Scrivani, Steven J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201 55 Fruit St, Boston, MA 02114 USA.
RP Scrivani, SJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201 55 Fruit St, Boston, MA 02114 USA.
EM sscrivani1@partners.org
NR 0
TC 0
Z9 0
U1 2
U2 2
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1042-3699
EI 1558-1365
J9 ORAL MAXIL SURG CLIN
JI Oral Maxillofac. Surg. Clin. N. Am.
PD AUG
PY 2016
VL 28
IS 3
BP XIII
EP XIII
DI 10.1016/j.coms.2016.06.013
PG 1
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DU1FN
UT WOS:000381953700001
PM 27475517
ER
PT J
AU Scrivani, SJ
Spierings, ELH
AF Scrivani, Steven J.
Spierings, Egilius L. H.
TI Classification and Differential Diagnosis of Oral and Maxillofacial Pain
SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Orofacial pain; Maxillofacial pain; Craniofacial pain; Classification;
Differential diagnosis; Diagnostic evaluation; Physical examination;
Diagnostic imaging
ID TEMPOROMANDIBULAR DISORDERS; NOCICEPTIVE NEURONS; DORSAL-HORN;
PROJECTIONS; COMPLEX; CORTEX; AREAS; RATS
AB Pain in the orofacial region is a common presenting symptom. The majority of symptoms are related to dental disease, and the cause can readily be established, the problem dealt with, and the pain eliminated. However, pain may persist and defy attempts at treatment. Intractable oral or facial pain can be diagnostically challenging. To make a definitive diagnosis and initiate proper treatment, a rigorous protocol for evaluation includes a thorough history and an appropriate comprehensive clinical examination and diagnostic testing, including chief complaint, history of present illness, medical history, physical examination, diagnostic studies, including imaging, and psychosocial evaluation.
C1 [Scrivani, Steven J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201,15 Parkman St,Suite 230, Boston, MA 02114 USA.
[Spierings, Egilius L. H.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
[Spierings, Egilius L. H.] Tufts Univ, Sch Dent Med, Boston, MA 02111 USA.
RP Scrivani, SJ (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Warren 1201,15 Parkman St,Suite 230, Boston, MA 02114 USA.
EM sscrivani1@partners.org
NR 15
TC 0
Z9 0
U1 3
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1042-3699
EI 1558-1365
J9 ORAL MAXIL SURG CLIN
JI Oral Maxillofac. Surg. Clin. N. Am.
PD AUG
PY 2016
VL 28
IS 3
BP 233
EP +
DI 10.1016/j.coms.2016.04.003
PG 15
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DU1FN
UT WOS:000381953700002
PM 27475504
ER
PT J
AU Kulich, RJ
Backstrom, J
Brownstein, J
Finkelman, M
Dhadwal, S
DiBennedetto, D
AF Kulich, Ronald J.
Backstrom, Jordan
Brownstein, Jennifer
Finkelman, Matthew
Dhadwal, Shuchi
DiBennedetto, David
TI A Model for Opioid Risk Stratification Assessing the Psychosocial
Components of Orofacial Pain
SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Opioid; Risk-management; Dentistry; Substance abuse; Interprofessional
ID NEONATAL ABSTINENCE SYNDROME; MISUSE MEASURE; SOAPP-R; CROSS-VALIDATION;
UNITED-STATES; SCREENER; ABUSE; REDUCTION; THERAPY; ANXIETY
AB This article describes a model of opiate risk stratification with a special focus on dentistry and oral surgery. A brief overview covers the scope of the US opioid abuse and misuse epidemic and the role of the dentist in mitigating the problems of diversion and misuse of controlled substances. The expanding role of dentistry is summarized. An assessment outlines gathering critical risk information, screening questionnaires, access to state prescription monitoring programs, and communication with cotreating providers. Special populations are discussed. Barriers and possible solutions for effective implementation of these strategies are summarized.
C1 [Kulich, Ronald J.; Brownstein, Jennifer; Dhadwal, Shuchi] Tufts Sch Dent Med, Craniofacial Pain & Headache Ctr, Dept Diagnost Sci, Boston, MA USA.
[Kulich, Ronald J.; Brownstein, Jennifer] Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Backstrom, Jordan] Boston Pain Care Ctr, Waltham, MA USA.
[Finkelman, Matthew] Tufts Univ, Sch Dent Med, Dept Biostat & Expt Design, 1 Kneeland St,7th Floor, Boston, MA 02129 USA.
[DiBennedetto, David] Boston Pain Care, Tufts Sch Dent Med, Dept Diagnost Sci, Boston, MA USA.
[Kulich, Ronald J.; Brownstein, Jennifer] 15 Parkman St, Boston, MA 02114 USA.
[Backstrom, Jordan; DiBennedetto, David] 85 First Ave, Waltham, MA 02451 USA.
[Dhadwal, Shuchi] 1 Kneeland St,,6th Floor,7th Floor, Boston, MA 02129 USA.
RP Kulich, RJ; Brownstein, J; Finkelman, M; Dhadwal, S (reprint author), 1 Kneeland St,,6th Floor,7th Floor, Boston, MA 02129 USA.
EM rkulich@mgh.harvard.edu
NR 53
TC 0
Z9 0
U1 3
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1042-3699
EI 1558-1365
J9 ORAL MAXIL SURG CLIN
JI Oral Maxillofac. Surg. Clin. N. Am.
PD AUG
PY 2016
VL 28
IS 3
BP 261
EP +
DI 10.1016/j.coms.2016.03.006
PG 14
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DU1FN
UT WOS:000381953700004
PM 27475506
ER
PT J
AU Bajwa, ZH
Smith, SS
Khawaja, SN
Scrivani, SJ
AF Bajwa, Zahid H.
Smith, Sarah S.
Khawaja, Shehryar N.
Scrivani, Steven J.
TI Cranial Neuralgias
SO ORAL AND MAXILLOFACIAL SURGERY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Cranial neuralgias; Trigeminal neuralgia; Compression
ID IDIOPATHIC TRIGEMINAL NEURALGIA; MICROVASCULAR DECOMPRESSION SURGERY;
GAMMA-KNIFE RADIOSURGERY; MULTIPLE-SCLEROSIS; HERPES-ZOSTER; NEUROPATHIC
PAIN; FACIAL-PAIN; POSTERIOR-FOSSA; INTERNATIONAL CLASSIFICATION;
GLOSSOPHARYNGEAL NEURALGIA
AB Advances in diagnostic modalities have improved the understanding of the pathophysiology of neuropathic pain involving head and face. Recent updates in nomenclature of cranial neuralgias and facial pain have rationalized accurate diagnosis. Clear diagnosis and localization of pain generators are paramount, leading to better use of medical and targeted surgical treatments.
C1 [Bajwa, Zahid H.] Tufts Univ, Sch Med, Boston Headache Inst, Boston Pain Care,Clin Res, Waltham, MA 02155 USA.
[Smith, Sarah S.] Boston Headache Inst, Boston Pain Care, Waltham, MA USA.
[Khawaja, Shehryar N.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Orofacial Pain Training Program, Boston, MA 02114 USA.
[Scrivani, Steven J.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Div Oral & Maxillofacial Pain, Orofacial Pain Residency Training Program, Boston, MA 02114 USA.
RP Bajwa, ZH (reprint author), Tufts Univ, Sch Med, Boston Headache Inst, Boston Pain Care,Clin Res, Waltham, MA 02155 USA.
EM zbajwa@bostonpaincare.com
NR 146
TC 1
Z9 1
U1 3
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1042-3699
EI 1558-1365
J9 ORAL MAXIL SURG CLIN
JI Oral Maxillofac. Surg. Clin. N. Am.
PD AUG
PY 2016
VL 28
IS 3
BP 351
EP +
DI 10.1016/j.coms.2016.04.001
PG 22
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DU1FN
UT WOS:000381953700009
PM 27475511
ER
PT J
AU Goldstein, RD
AF Goldstein, Richard D.
TI RE: Overall Postneonatal Mortality and Rates of SIDS Response
SO PEDIATRICS
LA English
DT Letter
ID DEATH
C1 [Goldstein, Richard D.] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
RP Goldstein, RD (reprint author), Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA.
EM richard_goldstein@dfci.harvard.edu
NR 3
TC 0
Z9 0
U1 3
U2 3
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2016
VL 138
IS 2
DI 10.1542/peds.2016-1592C
PG 1
WC Pediatrics
SC Pediatrics
GA DS7ZP
UT WOS:000381002500066
ER
PT J
AU Heyne, TF
AF Heyne, Thomas F.
TI Lanfranco's Dropsical Child: The First Depiction of Congenital Heart
Disease?
SO PEDIATRICS
LA English
DT Article
ID ART
C1 [Heyne, Thomas F.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
[Heyne, Thomas F.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA.
RP Heyne, TF (reprint author), Harvard Internal Med & Pediat Residency, 175 Cambridge St,5th Fl, Boston, MA 02114 USA.
EM theyne@partners.org
NR 17
TC 0
Z9 0
U1 0
U2 0
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2016
VL 138
IS 2
AR e20154594
DI 10.1542/peds.2015-4594
PG 4
WC Pediatrics
SC Pediatrics
GA DS7ZP
UT WOS:000381002500026
ER
PT J
AU Hoyme, HE
Kalberg, WO
Elliott, AJ
Blankenship, J
Buckley, D
Marais, AS
Manning, MA
Robinson, LK
Adam, MP
Abdul-Rahman, O
Jewett, T
Coles, CD
Chambers, C
Jones, KL
Adnams, CM
Shah, PE
Riley, EP
Charness, ME
Warren, KR
May, PA
AF Hoyme, H. Eugene
Kalberg, Wendy O.
Elliott, Amy J.
Blankenship, Jason
Buckley, David
Marais, Anna-Susan
Manning, Melanie A.
Robinson, Luther K.
Adam, Margaret P.
Abdul-Rahman, Omar
Jewett, Tamison
Coles, Claire D.
Chambers, Christina
Jones, Kenneth L.
Adnams, Colleen M.
Shah, Prachi E.
Riley, Edward P.
Charness, Michael E.
Warren, Kenneth R.
May, Philip A.
TI Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum
Disorders
SO PEDIATRICS
LA English
DT Article
ID MATERNAL RISK-FACTORS; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
PALPEBRAL FISSURE LENGTH; PREGNANCY RECOGNITION; HEAD CIRCUMFERENCE;
BIRTH-DEFECTS; NEUROBEHAVIORAL PROFILE; FULL SPECTRUM; BRAIN VOLUME;
SOUTH-AFRICA
AB The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors' combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism-funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol.
C1 [Hoyme, H. Eugene; Elliott, Amy J.; May, Philip A.] Sanford Res, Sioux Falls, SD USA.
[Hoyme, H. Eugene; Elliott, Amy J.; May, Philip A.] Univ South Dakota, Dept Pediat, Sanford Sch Med, Sioux Falls, SD USA.
[Hoyme, H. Eugene] Univ Arizona, Coll Med, Ctr Appl Genet & Genom, Tucson, AZ USA.
[Hoyme, H. Eugene] Univ Arizona, Coll Med, Dept Pediat, Tucson, AZ USA.
[Kalberg, Wendy O.; Blankenship, Jason; Buckley, David; May, Philip A.] Univ New Mexico, Ctr Alcoholism Substance Abuse & Addict, Albuquerque, NM 87131 USA.
[Marais, Anna-Susan] Univ Stellenbosch, Fac Med & Hlth Sci, Stellenbosch, South Africa.
[Manning, Melanie A.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Manning, Melanie A.] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA.
[Robinson, Luther K.] SUNY Buffalo, Sch Med & Biomed Sci, Dept Pediat, Buffalo, NY 14260 USA.
[Adam, Margaret P.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA.
[Abdul-Rahman, Omar] Univ Mississippi, Sch Med, Dept Pediat, Jackson, MS 39216 USA.
[Jewett, Tamison] Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27109 USA.
[Coles, Claire D.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
[Chambers, Christina; Jones, Kenneth L.] Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA.
[Adnams, Colleen M.] Univ Cape Town, Fac Hlth Sci, Dept Psychiat & Mental Hlth, Cape Town, South Africa.
[Shah, Prachi E.] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA.
[Riley, Edward P.] San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA.
[Charness, Michael E.] Harvard Med Sch, Dept Neurol, VA Boston Healthcare Syst, Boston, MA USA.
[Charness, Michael E.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Warren, Kenneth R.] NIAAA, Bethesda, MD USA.
[May, Philip A.] Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Inst Nutr Res, Chapel Hill, NC USA.
RP Hoyme, HE (reprint author), Sanford Hlth, Genet & Genom Med, POB 5039, Sioux Falls, SD 57117 USA.
EM gene.hoyme@sanfordhealth.org
FU National Institutes of Health (NIH): National Institute on Alcohol Abuse
and Alcoholism [R01 AA11685, R01/U01 AA01115134, U01
AA019879-01/NIH-NIAAA]; Oxnard Foundation, Newport Beach, CA; National
Institutes of Health (NIH)
FX This project was funded by the National Institutes of Health (NIH):
National Institute on Alcohol Abuse and Alcoholism grants R01 AA11685,
R01/U01 AA01115134, and U01 AA019879-01/NIH-NIAAA (Collaboration on
Fetal Alcohol Spectrum Disorders Prevalence); and by the Oxnard
Foundation, Newport Beach, CA. Funded by the National Institutes of
Health (NIH).
NR 112
TC 4
Z9 4
U1 19
U2 20
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2016
VL 138
IS 2
AR e20154256
DI 10.1542/peds.2015-4256
PG 18
WC Pediatrics
SC Pediatrics
GA DS7ZP
UT WOS:000381002500017
ER
PT J
AU Reisman, J
Arlington, L
Jensen, L
Louis, H
Suarez-Rebling, D
Nelson, BD
AF Reisman, Jonathan
Arlington, Lauren
Jensen, Lloyd
Louis, Henry
Suarez-Rebling, Daniela
Nelson, Brett D.
TI Newborn Resuscitation Training in Resource-Limited Settings: A
Systematic Literature Review
SO PEDIATRICS
LA English
DT Review
ID HELPING BABIES BREATHE; EMERGENCY CARDIOVASCULAR CARE; NEONATAL
RESUSCITATION; EDUCATIONAL INTERVENTION; RURAL ETHIOPIA;
CARDIOPULMONARY-RESUSCITATION; PEDIATRIC RESIDENTS; COGNITIVE KNOWLEDGE;
FRONTLINE PROVIDERS; BIRTH ATTENDANTS
AB CONTEXT: Birth asphyxia contributes substantially to neonatal mortality in low-and middle-income countries (LMICs). The effects of training birth attendants in neonatal resuscitation (NR) on mortality are limited by falloff of skills and knowledge over time and transference of learned skills into clinical practice.
OBJECTIVE: This review examined acquisition and retention of NR knowledge and skills by birth attendants in LMICs and the effectiveness of interventions to improve them.
DATA SOURCES: Medline, Cochrane, Embase, CINAHL, Bireme, and African Index Medicus databases were searched. We reviewed Web pages and reports from non-peer-reviewed (or "gray") literature sources addressing NR training in LMICs.
STUDY SELECTION: Articles on acquisition and retention of NR knowledge and skills, and interventions to improve them, were limited to LMICs.
RESULTS: The initial search identified 767 articles, of which 45 met all inclusion criteria. Of these, 31 articles analyzed acquisition of knowledge and skills, and 19 analyzed retention. Most studies found high acquisition rates, although birth attendants struggled to learn bag-mask ventilation. Although significant falloff of knowledge and skills occurred after training, refresher training seemed to improve retention. Results of the gray literature analysis suggest that formal, structured practice sessions improve retention.
LIMITATIONS: This review did not analyze training's direct impact on mortality.
CONCLUSIONS: Knowledge and skills falloff is a significant barrier to the success of NR training programs and possibly to reducing newborn mortality in LMICs. Refresher training and structured practice show significant promise. Additional research is needed to implement and assess retention improvement strategies in classroom and clinical settings.
C1 [Reisman, Jonathan] Childrens Hosp Philadelphia, Div Emergency Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
[Reisman, Jonathan; Arlington, Lauren; Louis, Henry; Suarez-Rebling, Daniela; Nelson, Brett D.] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA.
[Reisman, Jonathan; Nelson, Brett D.] Harvard Med Sch, Boston, MA USA.
[Jensen, Lloyd] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
RP Reisman, J (reprint author), Childrens Hosp Philadelphia, Div Emergency Med, 34th St & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM reisman.jonathan@gmail.com
OI Nelson, Brett/0000-0002-5049-1798
FU Children's Investment Fund
FX Funding for this study was provided by the Children's Investment Fund.
NR 80
TC 0
Z9 0
U1 7
U2 7
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD AUG
PY 2016
VL 138
IS 2
AR e20154490
DI 10.1542/peds.2015-4490
PG 16
WC Pediatrics
SC Pediatrics
GA DS7ZP
UT WOS:000381002500025
ER
PT J
AU Giannikou, K
Malinowska, IA
Pugh, TJ
Yan, R
Tseng, YY
Oh, C
Kim, J
Tyburczy, ME
Chekaluk, Y
Liu, Y
Alesi, N
Finlay, GA
Wu, CL
Signoretti, S
Meyerson, M
Getz, G
Boehm, JS
Henske, EP
Kwiatkowski, DJ
AF Giannikou, Krinio
Malinowska, Izabela A.
Pugh, Trevor J.
Yan, Rachel
Tseng, Yuen-Yi
Oh, Coyin
Kim, Jaegil
Tyburczy, Magdalena E.
Chekaluk, Yvonne
Liu, Yang
Alesi, Nicola
Finlay, Geraldine A.
Wu, Chin-Lee
Signoretti, Sabina
Meyerson, Matthew
Getz, Gad
Boehm, Jesse S.
Henske, Elizabeth P.
Kwiatkowski, David J.
TI Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the
Primary and Sufficient Driver Event for Renal Angiomyolipoma Development
SO PLOS GENETICS
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; SPORADIC PULMONARY LYMPHANGIOLEIOMYOMATOSIS;
ANALYSIS TOOLKIT; CANCER GENOMICS; TSC2; MUTATIONS; TUMOR; MTOR; GENE;
HETEROZYGOSITY
AB Renal angiomyolipoma is a kidney tumor in the perivascular epithelioid (PEComa) family that is common in patients with Tuberous Sclerosis Complex (TSC) and Lymphangioleiomyomatosis (LAM) but occurs rarely sporadically. Though histologically benign, renal angiomyolipoma can cause life-threatening hemorrhage and kidney failure. Both angiomyolipoma and LAM have mutations in TSC2 or TSC1. However, the frequency and contribution of other somatic events in tumor development is unknown. We performed whole exome sequencing in 32 resected tumor samples (n = 30 angiomyolipoma, n = 2 LAM) from 15 subjects, including three with TSC. Two germline and 22 somatic inactivating mutations in TSC2 were identified, and one germline TSC1 mutation. Twenty of 32 (62%) samples showed copy neutral LOH (CN-LOH) in TSC2 or TSC1 with at least 8 different LOH regions, and 30 of 32 (94%) had biallelic loss of either TSC2 or TSC1. Whole exome sequencing identified a median of 4 somatic non-synonymous coding region mutations (other than in TSC2/TSC1), a mutation rate lower than nearly all other cancer types. Three genes with mutations were known cancer associated genes (BAP1, ARHGAP35 and SPEN), but they were mutated in a single sample each, and were missense variants with uncertain functional effects. Analysis of sixteen angiomyolipomas from a TSC subject showed both second hit point mutations and CN-LOH in TSC2, many of which were distinct, indicating that they were of independent clonal origin. However, three tumors had two shared mutations in addition to private somatic mutations, suggesting a branching evolutionary pattern of tumor development following initiating loss of TSC2. Our results indicate that TSC2 and less commonly TSC1 alterations are the primary essential driver event in angiomyolipoma/LAM, whereas other somatic mutations are rare and likely do not contribute to tumor development.
C1 [Giannikou, Krinio; Malinowska, Izabela A.; Yan, Rachel; Tyburczy, Magdalena E.; Chekaluk, Yvonne; Liu, Yang; Alesi, Nicola; Signoretti, Sabina; Henske, Elizabeth P.; Kwiatkowski, David J.] Harvard Med Sch, Brigham & Womens Hosp, Div Pulm & Crit Care Med & Genet, Boston, MA 02115 USA.
[Pugh, Trevor J.; Tseng, Yuen-Yi; Oh, Coyin; Kim, Jaegil; Meyerson, Matthew; Getz, Gad; Boehm, Jesse S.; Henske, Elizabeth P.; Kwiatkowski, David J.] Broad Inst Harvard & MIT, Cambridge, MA 02139 USA.
[Finlay, Geraldine A.] Tufts Univ New England Med Ctr, Boston, MA USA.
[Wu, Chin-Lee] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Henske, EP; Kwiatkowski, DJ (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Pulm & Crit Care Med & Genet, Boston, MA 02115 USA.; Henske, EP; Kwiatkowski, DJ (reprint author), Broad Inst Harvard & MIT, Cambridge, MA 02139 USA.
EM EHENSKE@BWH.HARVARD.EDU; dk@rics.bwh.harvard.edu
OI Oh, Coyin/0000-0002-5732-3471
FU NIH NHLBI RCI [HL100655]; NIH NCI [1P01CA120964]; Broad Institute
Scientific Projects to Accelerate Research and Collaboration (SPARC)
program; Engles Fund for TSC and LAM Research
FX Funding sources for this work are: NIH NHLBI RCI HL100655; NIH NCI
1P01CA120964; the Broad Institute Scientific Projects to Accelerate
Research and Collaboration (SPARC) program; and the Engles Fund for TSC
and LAM Research. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 50
TC 3
Z9 3
U1 6
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2016
VL 12
IS 8
AR e1006242
DI 10.1371/journal.pgen.1006242
PG 18
WC Genetics & Heredity
SC Genetics & Heredity
GA DU7LA
UT WOS:000382394500038
ER
PT J
AU Heilbronner, S
Monk, IR
Brozyna, JR
Heinrichs, DE
Skaar, EP
Peschel, A
Foster, TJ
AF Heilbronner, Simon
Monk, Ian R.
Brozyna, Jeremy R.
Heinrichs, David E.
Skaar, Eric P.
Peschel, Andreas
Foster, Timothy J.
TI Competing for Iron: Duplication and Amplification of the isd Locus in
Staphylococcus lugdunensis HKU09-01 Provides a Competitive Advantage to
Overcome Nutritional Limitation
SO PLOS GENETICS
LA English
DT Article
ID GENE AMPLIFICATION; HAEMOPHILUS-INFLUENZAE; GENOME SEQUENCE; B LOCUS;
AUREUS; RESISTANCE; EVOLUTION; HEME; ACQUISITION; TRANSPOSON
AB Staphylococcus lugdunensis is a coagulase negative bacterial pathogen that is particularly associated with severe cases of infectious endocarditis. Unique amongst the coagulase-negative staphylococci, S. lugdunensis harbors an iron regulated surface determinant locus (isd). This locus facilitates the acquisition of heme as a source of nutrient iron during infection and allows iron limitation caused by "nutritional immunity" to be overcome. The isd locus is duplicated in S. lugdunensis HKU09-01 and we show here that the duplication is intrinsically unstable and undergoes accordion-like amplification and segregation leading to extensive isd copy number variation. Amplification of the locus increased the level of expression of Isd proteins and improved binding of hemoglobin to the cell surface of S. lugdunensis. Furthermore, Isd overexpression provided an advantage when strains were competing for a limited amount of hemoglobin as the sole source of iron. Gene duplications and amplifications (GDA) are events of fundamental importance for bacterial evolution and are frequently associated with antibiotic resistance in many species. As such, GDAs are regarded as evolutionary adaptions to novel selective pressures in hostile environments pointing towards a special importance of isd for S. lugdunensis. For the first time we show an example of a GDA that involves a virulence factor of a Gram-positive pathogen and link the GDA directly to a competitive advantage when the bacteria were struggling with selective pressures mimicking "nutritional immunity".
C1 [Heilbronner, Simon; Monk, Ian R.; Foster, Timothy J.] Trinity Coll Dublin, Dept Microbiol, Dublin, Ireland.
[Heilbronner, Simon; Peschel, Andreas] Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, Tubingen, Germany.
[Monk, Ian R.] Univ Melbourne, Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Parkville, Vic, Australia.
[Brozyna, Jeremy R.; Heinrichs, David E.] Univ Western Ontario, Dept Microbiol & Immunol, London, ON, Canada.
[Skaar, Eric P.] Vanderbilt Univ, Sch Med, Dept Pathol Microbiol & Immunol, Nashville, TN 37212 USA.
[Skaar, Eric P.] Tennessee Valley Healthcare Syst, US Dept Vet Affairs, Nashville, TN USA.
RP Heilbronner, S (reprint author), Trinity Coll Dublin, Dept Microbiol, Dublin, Ireland.; Heilbronner, S (reprint author), Univ Tubingen, Interfac Inst Microbiol & Infect Med, Infect Biol, Tubingen, Germany.
EM simon.heilbronner@uni-tuebingen.de
OI Monk, Ian/0000-0001-6982-8074
FU Irish Research Council for Science, Engineering and Technology
[RS2000192]; Science Foundation Ireland [08/IN.1/B1854]; German Academic
exchange (DAAD) [50722682]; European Research Council [GA 655978];
German Research Council [SFB766]; NIH [R01 AI069233, R01 AI073843];
Department of Veterans Affairs [INFB-024-13F]; Canadian Institutes of
Health Research [MOP-38002]; Deutsche Forschungsgemeinschaft; "Open
Access Publishing Fund" of the University of Tubingen
FX We acknowledge the support of the Irish Research Council for Science,
Engineering and Technology for an Embark scholarship (RS2000192) to SH
(http://www.research.ie/. We acknowledge the support of the Science
Foundation Ireland for a Programme Investigator grant (08/IN.1/B1854) to
TJF (http://www.sfi.ie/). We acknowledge the support of the German
Academic exchange (DAAD) for a stipend for the "retrieval of German
Scientist working abroad" (50722682) to SH (https://www.daad.de/en/). We
acknowledge the support of the European Research Council for their
support by providing a MSC-individual fellowship (GA 655978) to SH
(https://erc.europa.eu/). Work in the laboratory of AP was supported by
the SFB766 grant from the German Research Council
(http://www.dfg.de/en/). Work in the laboratory of EPS is supported by
NIH R01 AI069233 and R01 AI073843 (http://grants.nih.gov/grants/oer.htm)
and Department of Veterans Affairs Merit Award INFB-024-13F
(http://www.research.va.gov/default.cfm). Work in the laboratory of DEH
is supported by Canadian Institutes of Health Research grant MOP-38002
(http://www.cihr-irsc.gc.ca/e/193.html). We acknowledge support by
"Deutsche Forschungsgemeinschaft" and the "Open Access Publishing Fund"
of the University of Tubingen. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 48
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 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD AUG
PY 2016
VL 12
IS 8
AR e1006246
DI 10.1371/journal.pgen.1006246
PG 25
WC Genetics & Heredity
SC Genetics & Heredity
GA DU7LA
UT WOS:000382394500041
PM 27575058
ER
PT J
AU Li, A
Makar, RS
Hurwitz, S
Uhl, L
Kaufman, RM
Stowell, CP
Dzik, WS
Bendapudi, PK
AF Li, Ang
Makar, Robert S.
Hurwitz, Shelley
Uhl, Lynne
Kaufman, Richard M.
Stowell, Christopher P.
Dzik, Walter S.
Bendapudi, Pavan K.
TI Treatment with or without plasma exchange for patients with acquired
thrombotic microangiopathy not associated with severe ADAMTS13
deficiency: a propensity score-matched study
SO TRANSFUSION
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING
PROTEASE; THROMBOCYTOPENIC PURPURA; EXPERIENCE; SUBSTRATE; DIAGNOSIS;
OUTCOMES; ASSAY; VWF
AB BACKGROUNDTherapeutic plasma exchange (TPE) is a proven treatment for thrombotic thrombocytopenic purpura (TTP) characterized by severe ADAMTS13 deficiency, but the efficacy of TPE in suspected TTP with an ADAMTS13 activity level of more than 10% remains controversial.
STUDY DESIGN AND METHODSWe conducted a propensity score (PS)-matched study of 186 adult patients included in the Harvard Thrombotic Microangiopathy (TMA) Research Collaborative registry who presented with TMA suggestive of TTP but an ADAMTS13 activity level of more than 10%.
RESULTSBefore matching, patients treated with TPE (n=71) differed from untreated patients (n=115) by several clinical measures. PS matching was performed to address clinical disparities between the two groups and resulted in a well-balanced cohort of 59 TPE-treated patients paired with 59 untreated controls, all of whom had TMA. After matching, we observed no significant difference in the primary outcome of 90-day survival between the treated and untreated groups (hazard ratio, 0.88; 95% confidence interval [CI], 0.44-1.77; p=0.72). In-hospital mortality (odds ratio [OR], 0.77; 95% CI, 0.34-1.75; p=0.53) and the percentage of patients with platelet count recovery (OR, 1.58; 95% CI, 0.77-3.26; p=0.21) also did not differ significantly between the two matched groups.
CONCLUSIONOur data suggest that routine use of TPE in the diverse group of TMA patients without severe ADAMTS13 deficiency may not significantly improve outcomes.
C1 [Li, Ang] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Makar, Robert S.; Stowell, Christopher P.; Dzik, Walter S.; Bendapudi, Pavan K.] Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA.
[Dzik, Walter S.; Bendapudi, Pavan K.] Massachusetts Gen Hosp, Div Hematol, Yawkey 7,55 Fruit St, Boston, MA 02114 USA.
[Hurwitz, Shelley] Brigham & Womens Hosp, Ctr Clin Invest, 75 Francis St, Boston, MA 02115 USA.
[Kaufman, Richard M.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Uhl, Lynne] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
[Li, Ang; Makar, Robert S.; Hurwitz, Shelley; Uhl, Lynne; Kaufman, Richard M.; Stowell, Christopher P.; Dzik, Walter S.; Bendapudi, Pavan K.] Harvard Med Sch, Boston, MA USA.
RP Bendapudi, PK (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7,55 Fruit St, Boston, MA 02114 USA.
EM pkbendapudi@partners.org
FU Luick Family Fund of the Massachusetts General Hospital; American
Society of Hematology HONORS Program
FX This work was generously supported by the Luick Family Fund of the
Massachusetts General Hospital and the American Society of Hematology
HONORS Program (AL).
NR 31
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD AUG
PY 2016
VL 56
IS 8
BP 2069
EP 2077
DI 10.1111/trf.13654
PG 9
WC Hematology
SC Hematology
GA DU8ZP
UT WOS:000382506100022
PM 27232383
ER
PT J
AU Gutierrez-Martinez, P
Rossi, DJ
Beerman, I
AF Gutierrez-Martinez, Paula
Rossi, Derrick J.
Beerman, Isabel
TI DNA Damage and Aging Around the Clock
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Editorial Material
ID HEMATOPOIETIC STEM-CELLS; SELF-RENEWAL
AB The hematopoietic system undergoes many changes during aging, but the causes and molecular mechanisms behind these changes are not well understood. Wang et al. have recently implicated a circadian rhythm gene, Per2, as playing a role in the DNA damage response and in the expression of lymphoid genes in aged hematopoietic stem cells.
C1 [Gutierrez-Martinez, Paula; Rossi, Derrick J.; Beerman, Isabel] Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA.
[Gutierrez-Martinez, Paula; Rossi, Derrick J.; Beerman, Isabel] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA USA.
[Rossi, Derrick J.] Harvard Med Sch, Dept Pediat, Boston, MA USA.
[Rossi, Derrick J.] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Beerman, I (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Program Cellular & Mol Med, Boston, MA USA.; Beerman, I (reprint author), Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA USA.
EM Isabel.Beerman@childrens.harvard.edu
FU NHLBI NIH HHS [U01 HL099997, R01 HL107630, U19 HL129903, U01 HL107440];
NIA NIH HHS [K01 AG050813]; NIDDK NIH HHS [UC4 DK104218]
NR 10
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
EI 1471-499X
J9 TRENDS MOL MED
JI Trends Mol. Med
PD AUG
PY 2016
VL 22
IS 8
BP 635
EP 637
DI 10.1016/j.molmed.2016.06.006
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DT5NR
UT WOS:000381530400003
PM 27345866
ER
PT J
AU Westring, A
McDonald, JM
Carr, P
Grisso, JA
AF Westring, Alyssa
McDonald, Jennifer M.
Carr, Phyllis
Grisso, Jeane Ann
TI An Integrated Framework for Gender Equity in Academic Medicine
SO ACADEMIC MEDICINE
LA English
DT Editorial Material
ID FACULTY; CULTURE
AB In 2008, the National Institutes of Health funded 14 R01 grants to study causal factors that promote and support women's biomedical careers. The Research Partnership on Women in Biomedical Careers, a multi-institutional collaboration of the investigators, is one product of this initiative.
A comprehensive framework is needed to address change at many levels-department, institution, academic community, and beyond-and enable gender equity in the development of successful biomedical careers. The authors suggest four distinct but interrelated aspects of culture conducive to gender equity: equal access to resources and opportunities, minimizing unconscious gender bias, enhancing work-life balance, and leadership engagement. They review the collection of eight articles in this issue, which each address one or more of the four dimensions of culture. The articles suggest that improving mentormentee fit, coaching grant reviewers on unconscious bias, and providing equal compensation and adequate resources for career development will contribute positively to gender equity in academic medicine.
Academic medicine must adopt an integrated perspective on culture for women and acknowledge the multiple facets essential to gender equity. To effect change, culture must be addressed both within and beyond academic health centers (AHCs). Leaders within AHCs must examine their institutions' processes, resources, and assessment for fairness and transparency; mobilize personnel and financial resources to implement evidence-based initiatives; and assign accountability for providing transparent progress assessments. Beyond AHCs, organizations must examine their operations and implement change to ensure parity of funding, research, and leadership opportunities as well as transparency of assessment and accreditation.
C1 [Westring, Alyssa] Depaul Univ, Management, Driehaus Coll Business, Chicago, IL 60604 USA.
[Carr, Phyllis] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Carr, Phyllis] Harvard Med Sch, Boston, MA USA.
[Grisso, Jeane Ann] Univ Penn, Med, Publ Hlth, Philadelphia, PA 19104 USA.
RP Westring, A (reprint author), 1 E Jackson Blvd, Chicago, IL 60604 USA.
EM awestrin@depaul.edu
NR 20
TC 2
Z9 2
U1 7
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-2446
EI 1938-808X
J9 ACAD MED
JI Acad. Med.
PD AUG
PY 2016
VL 91
IS 8
BP 1041
EP 1044
DI 10.1097/ACM.0000000000001275
PG 4
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA DS5HT
UT WOS:000380813000010
PM 27276008
ER
PT J
AU Freund, KM
Raj, A
Kaplan, SE
Terrin, N
Breeze, JL
Urech, TH
Carr, PL
AF Freund, Karen M.
Raj, Anita
Kaplan, Samantha E.
Terrin, Norma
Breeze, Janis L.
Urech, Tracy H.
Carr, Phyllis L.
TI Inequities in Academic Compensation by Gender: A Follow-up to the
National Faculty Survey Cohort Study
SO ACADEMIC MEDICINE
LA English
DT Article
ID PART-TIME; PHYSICIAN-RESEARCHERS; SEX-DIFFERENCES; MEDICINE;
NEGOTIATION; EQUITY; SALARY; ADVANCEMENT; WOMEN; PRODUCTIVITY
AB Purpose
Cross-sectional studies have demonstrated gender differences in salaries within academic medicine. No research has assessed longitudinal compensation patterns. This study sought to assess longitudinal patterns by gender in compensation, and to understand factors associated with these differences in a longitudinal cohort.
Method
A 17-year longitudinal follow-up of the National Faculty Survey was conducted with a random sample of faculty from 24 U.S. medical schools. Participants employed full-time at initial and follow-up time periods completed the survey. Annual pretax compensation during academic year 2012-2013 was compared by gender. Covariates assessed included race/ethnicity; years since first academic appointment; retention in academic career; academic rank; departmental affiliation; percent effort distribution across clinical, teaching, administrative, and research duties; marital and parental status; and any leave or part-time status in the years between surveys.
Results
In unadjusted analyses, women earned a mean of $20,520 less than men (P = .03); women made 90 cents for every dollar earned by their male counterparts. This difference was reduced to $16,982 (P = .04) after adjusting for covariates. The mean difference of $15,159 was no longer significant (P = .06) when adjusting covariates and for those who had ever taken a leave or worked part-time.
Conclusions
The continued gender gap in compensation cannot be accounted for by metrics used to calculate salary. Institutional actions to address these disparities include both initial appointment and annual salary equity reviews, training of senior faculty and administrators to understand implicit bias, and training of women faculty in negotiating skills.
C1 [Freund, Karen M.] Tufts Univ, Sch Med, Med Ctr, Med, Boston, MA 02111 USA.
[Raj, Anita] Univ Calif San Diego, Sch Med, Med & Global Publ Hlth, La Jolla, CA 92093 USA.
[Raj, Anita] Univ Calif San Diego, Sch Med, Ctr Gender Equ & Hlth, La Jolla, CA 92093 USA.
[Kaplan, Samantha E.] Boston Univ, Sch Med, Divers, Boston, MA 02118 USA.
[Terrin, Norma; Breeze, Janis L.] Tufts Clin & Translat Sci Inst, Biostat Epidemiol & Res Design Ctr, Boston, MA USA.
[Terrin, Norma; Breeze, Janis L.] Tufts Med Ctr, Boston, MA 02111 USA.
[Urech, Tracy H.] VA Palo Alto Healthcare Syst, VA HSR&D Ctr Innovat Implementat, Palo Alto, CA USA.
[Carr, Phyllis L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Carr, Phyllis L.] Harvard Med Sch, Boston, MA USA.
RP Freund, KM (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, 800 Washington St,Box 63, Boston, MA 02111 USA.
EM kfreund@tuftsmedicalcenter.org
FU National Institute of General Medical Sciences [R01 GM088470]; Office of
Research in Women's Health, National Institutes of Health
FX The project described was supported by award number R01 GM088470 from
the National Institute of General Medical Sciences and Office of
Research in Women's Health, National Institutes of Health.
NR 26
TC 9
Z9 9
U1 6
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-2446
EI 1938-808X
J9 ACAD MED
JI Acad. Med.
PD AUG
PY 2016
VL 91
IS 8
BP 1068
EP 1073
DI 10.1097/ACM.0000000000001250
PG 6
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA DS5HT
UT WOS:000380813000018
PM 27276007
ER
PT J
AU Raj, A
Carr, PL
Kaplan, SE
Terrin, N
Breeze, JL
Freund, KM
AF Raj, Anita
Carr, Phyllis L.
Kaplan, Samantha E.
Terrin, Norma
Breeze, Janis L.
Freund, Karen M.
TI Longitudinal Analysis of Gender Differences in Academic Productivity
Among Medical Faculty Across 24 Medical Schools in the United States
SO ACADEMIC MEDICINE
LA English
DT Article
ID RESEARCH GRANT APPLICATIONS; SEX-DIFFERENCES; RESPONSIBILITIES;
HOSPITALISTS; SATISFACTION; RESEARCHERS; DISPARITIES; AUTHORSHIP;
RESIDENTS; WOMEN
AB Purpose
To examine gender differences in academic productivity, as indicated by publications and federal grant funding acquisition, among a longitudinal cohort of medical faculty from 24 U.S. medical schools, 1995 to 2012-2013.
Method
Data for this research were taken from the National Faculty Survey involving a survey with medical faculty recruited from medical schools in 1995, and followed up in 2012-2013. Data included surveys and publication and grant funding databases. Outcomes were number of publications, h-index, and principal investigator on a federal grant in the prior two years. Gender differences were assessed using negative binomial regression models for publication and h-index outcomes, and logistic regression for the grant funding outcome; analyses adjusted for race/ethnicity, rank, specialty area, and years since first academic appointment.
Results
Data were available for 1,244 of the 1,275 (98%) subjects eligible for the follow-up study. Men were significantly more likely than women to be married/partnered, have children, and hold the rank of professor (P < .0001). Adjusted regression models documented that women had a lower rate of publication (relative number = 0.71; 95% CI = 0.63, 0.81; P < .0001) and h-index (relative number = 0.81; 95% CI = 0.73, 0.90; P < .0001) relative to men, but there was no gender difference in grant funding.
Conclusions
Women faculty acquired federal funding at similar rates as male faculty, yet lagged behind in terms of publications and their impact. Medical academia must consider how to help address ongoing gender disparities in publication records.
C1 [Raj, Anita] Univ Calif San Diego, Sch Med, Med & Global Publ Hlth, San Diego, CA 92103 USA.
[Raj, Anita] Univ Calif San Diego, Sch Med, Ctr Gender Equ & Hlth, San Diego, CA 92103 USA.
[Carr, Phyllis L.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Carr, Phyllis L.] Harvard Med Sch, Boston, MA USA.
[Kaplan, Samantha E.] Boston Univ, Sch Med, Divers, Boston, MA 02118 USA.
[Terrin, Norma; Breeze, Janis L.] Tufts Clin & Translat Sci Inst, Biostat Epidemiol & Res Design Ctr, Boston, MA USA.
[Terrin, Norma; Breeze, Janis L.] Tufts Med Ctr, Boston, MA 02111 USA.
[Freund, Karen M.] Tufts Univ, Sch Med, Med, Tufts Med Ctr, Boston, MA 02111 USA.
RP Freund, KM (reprint author), Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, 800 Washington St,Box 63, Boston, MA 02111 USA.
EM kfreund@tuftsmedicalcenter.org
FU National Institute of General Medical Sciences [R01GM088470]; Office of
Research in Women's Health, National Institutes of Health
FX The project described was supported by award number R01GM088470 from the
National Institute of General Medical Sciences and Office of Research in
Women's Health, National Institutes of Health.
NR 26
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U1 4
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-2446
EI 1938-808X
J9 ACAD MED
JI Acad. Med.
PD AUG
PY 2016
VL 91
IS 8
BP 1074
EP 1079
DI 10.1097/ACM.0000000000001251
PG 6
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA DS5HT
UT WOS:000380813000019
PM 27276002
ER
PT J
AU West, RK
Ravona-Springer, R
Heymann, A
Schmeidler, J
Leroith, D
Koifman, K
D'Arcy, RCN
Song, XW
Guerrero-Berroa, E
Preiss, R
Hoffman, H
Sano, M
Silverman, JM
Schnaider-Beeri, M
AF West, Rebecca K.
Ravona-Springer, Ramit
Heymann, Anthony
Schmeidler, James
Leroith, Derek
Koifman, Keren
D'Arcy, Ryan C. N.
Song, Xiaowei
Guerrero-Berroa, Elizabeth
Preiss, Rachel
Hoffman, Hadas
Sano, Mary
Silverman, Jeremy M.
Schnaider-Beeri, Michal
TI Waist circumference is correlated with poorer cognition in elderly type
2 diabetes women
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Cognitive performance; Waist circumference; Type 2 diabetes mellitus;
Risk factors; Dementia
ID RISK-FACTORS; CARDIOVASCULAR RISK; DEMENTIA; IMPAIRMENT; OLDER;
ASSOCIATION; ADIPOSITY; OBESITY; DECLINE
AB Introduction: Waist circumference is associated with type 2 diabetes (T2D) and cognition, yet the relationship between waist circumference and cognition in individuals with T2D is not well understood.
Methods: We studied the relationship of waist circumference with five cognitive outcomes (executive functioning, language/semantic categorization, attention/working memory, episodic memory, and an overall cognition measure) in 845 cognitively normal elderly with type 2 diabetes (T2D).
esults: In women, waist circumference was correlated with significantly lower language and/or semantic categorization performance (P < .0001), executive functioning (P = .026), and overall cognition (P = .003) after controlling for age, education, BMI, and cardiovascular, diabetes related, APOE 64, and inflammatory potential confounders. Attention/working memory (P = .532) and episodic memory (P = .144) were not associated with waist circumference. These correlations were not found in men.
Discussion: These results suggest that central adiposity in elderly women with T2D may increase their risk for dementia. (C) 2016 Published by Elsevier Inc. on behalf of The Alzheimer's Association.
C1 [West, Rebecca K.; Schmeidler, James; Guerrero-Berroa, Elizabeth; Sano, Mary; Silverman, Jeremy M.; Schnaider-Beeri, Michal] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Ravona-Springer, Ramit; Koifman, Keren; Preiss, Rachel; Hoffman, Hadas; Schnaider-Beeri, Michal] Sheba Med Ctr, Joseph Sagol Neurosci Ctr, Ramat Gan, Israel.
[Heymann, Anthony] Maccabi Healthcare Serv, Tel Aviv, Israel.
[Heymann, Anthony] Tel Aviv Univ, Sackler Sch Med, Dept Family Med, Tel Aviv, Israel.
[Leroith, Derek] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
[D'Arcy, Ryan C. N.; Song, Xiaowei] Simon Fraser Univ, Metro Vancouver, BC, Canada.
[D'Arcy, Ryan C. N.; Song, Xiaowei] Fraser Hlth, Surrey Mem Hosp, Metro Vancouver, BC, Canada.
[Guerrero-Berroa, Elizabeth; Sano, Mary; Silverman, Jeremy M.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA.
RP West, RK (reprint author), Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
EM rebecca.west@mssm.edu
FU MA grants [R01 AG034087, P50 AG05138]; Helen Bader Foundation;
Alzheimer's Association [MNIRGD-14-321113]; Irma T. Hirschl Scholar
award
FX This study was supported by MA grants R01 AG034087 to Dr. Beeri and P50
AG05138 to Dr. Sano, the Helen Bader Foundation, and the Alzheimer's
Association grant MNIRGD-14-321113 to Dr. Guerrero-Berroa, and the Irma
T. Hirschl Scholar award to Dr. Beeri.
NR 20
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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 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD AUG
PY 2016
VL 12
IS 8
BP 925
EP 929
DI 10.1016/j.jalz.2016.03.017
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA DT1ND
UT WOS:000381248500009
PM 27149905
ER
PT J
AU McIlvennan, CK
Swetz, KM
AF McIlvennan, Colleen K.
Swetz, Keith M.
TI Lack of Agreement With What We Think Is Right Does Not Necessarily Equal
an Ethical Problem: Respecting Patients' Goals of Care
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
ID LIFE; END; PERSPECTIVES; DEVICE
C1 [McIlvennan, Colleen K.] Univ Colorado, Sch Med, Boulder, CO 80309 USA.
[Swetz, Keith M.] Univ Alabama, Sch Med, Tuscaloosa, AL 35487 USA.
[Swetz, Keith M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA.
RP Swetz, KM (reprint author), UAB Ctr Palliat & Support Care, 1720 2nd Ave South BDB 650, Birmingham, AL 35294 USA.
EM kswetz@uabmc.edu
NR 10
TC 1
Z9 1
U1 1
U2 1
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD AUG
PY 2016
VL 16
IS 8
BP 13
EP 15
DI 10.1080/15265161.2016.1187220
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA DS6OI
UT WOS:000380901100006
PM 27366837
ER
PT J
AU Blosnich, JR
Brenner, LA
Bossarte, RM
AF Blosnich, John R.
Brenner, Lisa A.
Bossarte, Robert M.
TI Population mental health among US military veterans: results of the
Veterans Health Module of the Behavioral Risk Factor Surveillance
System, 2011-2012
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Veterans health; Suicidal ideation; Attempted suicide; Mental health
services
ID SUICIDE MORTALITY; UNITED-STATES; IDEATION; SERVICE; HISTORY
AB Purpose: To examine mental health indicators, in aggregate and stratified by sex, among a population based sample of U.S. military veterans.
Methods: Data are from veteran who completed the Veterans Health Module (VHM) of the 2011 and 2012 Behavioral Risk Factor Surveillance System (n = 10,406). VHM items included lifetime diagnoses of mental illnesses, service in a combat zone, sources of mental health care, and past 12-month suicidal ideation and attempt. We used weighted, multiple logistic regression models, adjusted for sociodemographics, to examine differences in suicidal ideation and attempt among men and women.
Results: Overall, 5.0% of the sample reported recent suicidal ideation and 1.0% reported attempting suicide. Among men, unemployment was positively associated with suicidal ideation, and combat exposure was negatively associated with suicidal ideation. Being separated, divorced, or widowed was positively associated with suicidal ideation among women. After adjusting for sociodemographic and VHM variables, veterans who sought mental health treatment from both Veterans Affairs (VA) and non-VA facilities had more than fourfold increased odds of suicidal ideation than veteran who sought mental health treatment from only VA facilities (adjusted odds ratio = 4.02; 95% confidence interval 1.23-13.13).
Conclusions: Correlates of suicidal ideation differ between male and female veterans. Veterans who use both non-VA and VA facilities for mental health services may have greater risk of self-directed violence. Published by Elsevier Inc.
C1 [Blosnich, John R.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Brenner, Lisa A.] Rocky Mt Mental Illness Res Educ & Clin Ctr, Denver, CO USA.
[Brenner, Lisa A.] Univ Colorado, Anschutz Sch Med, Dept Psychiat, Aurora, CO USA.
[Brenner, Lisa A.] Univ Colorado, Anschutz Sch Med, Dept Neurol, Aurora, CO USA.
[Brenner, Lisa A.] Univ Colorado, Anschutz Sch Med, Dept Phys Med & Rehabil, Aurora, CO USA.
[Bossarte, Robert M.] US Dept Vet Affairs, Post Deployment Hlth Serv, Washington, DC USA.
[Bossarte, Robert M.] Univ Rochester, Dept Psychiat, Rochester, NY USA.
RP Blosnich, JR (reprint author), VA Pittsburgh Healthcare Syst, US Dept Vet Affairs, Ctr Hlth Equ Res & Promot, Univ Dr C 151C U,Bldg 30, Pittsburgh, PA 15240 USA.
EM john.blosnich@va.gov
FU VA Health Service Research Development [CDA 14-408]
FX This work was supported by a career development award to [name masked
for review] from VA Health Service Research & Development (CDA 14-408).
The opinions expressed in this work are those of the authors and do not
necessarily represent those of the funders, institutions, the Department
of Veterans Affairs, or the U.S. Government.
NR 24
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U1 6
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD AUG
PY 2016
VL 26
IS 8
BP 592
EP 596
DI 10.1016/j.annepidem.2016.06.009
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DU3HU
UT WOS:000382102200010
PM 27448820
ER
PT J
AU Chatelle, C
Bodien, YG
Carlowicz, C
Wannez, S
Charland-Verville, V
Gosseries, O
Laureys, S
Seel, RT
Giacino, JT
AF Chatelle, Camille
Bodien, Yelena G.
Carlowicz, Cecilia
Wannez, Sarah
Charland-Verville, Vanessa
Gosseries, Olivia
Laureys, Steven
Seel, Ron T.
Giacino, Joseph T.
TI Detection and Interpretation of Impossible and Improbable Coma Recovery
Scale-Revised Scores
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Brain injuries; Consciousness disorders; Outcome assessment (health
care); Rehabilitation
ID MINIMALLY CONSCIOUS STATE; VEGETATIVE STATE; LEVEL
AB Objective: To determine the frequency with which specific Coma Recovery Scale-Revised (CRS-R) subscale scores co-occur as a means of providing clinicians and researchers with an empirical method of assessing CRS-R data quality.
Design: We retrospectively analyzed CRS-R subscale scores in hospital inpatients diagnosed with disorders of consciousness (DOCs) to identify impossible and improbable subscore combinations as a means of detecting inaccurate and unusual scores. Impossible subscore combinations were based on violations of CRS-R scoring guidelines. To determine improbable subscore combinations, we relied on the Mahalanobis distance, which detects outliers within a distribution of scores. Subscore pairs that were not observed at all in the database (ie, frequency of occurrence = 0%) were also considered improbable.
Setting: Specialized DOC program and university hospital.
Participants: Patients diagnosed with DOCs (N=1190; coma: n=76, vegetative state: n=464, minimally conscious state: n=586, emerged from minimally conscious state: n=64; 794 men; mean age, 43 +/- 20y; traumatic etiology: n=747; time postinjury, 162 +/- 568d).
Interventions: Not applicable.
Main Outcome Measure: Impossible and improbable CRS-R subscore combinations.
Results: Of the 1190 CRS-R profiles analyzed, 4.7% were excluded because they met scoring criteria for impossible co-occurrence. Among the 1137 remaining profiles, 12.2% (41/336) of possible subscore combinations were classified as improbable.
Conclusions: Clinicians and researchers should take steps to ensure the accuracy of CRS-R scores. To minimize the risk of diagnostic error and erroneous research findings, we have identified 9 impossible and 36 improbable CRS-R subscore combinations. The presence of any one of these subscore combinations should trigger additional data quality review. (C) 2016 by the American Congress of Rehabilitation Medicine
C1 [Chatelle, Camille; Bodien, Yelena G.; Carlowicz, Cecilia; Giacino, Joseph T.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Chatelle, Camille; Bodien, Yelena G.; Carlowicz, Cecilia; Giacino, Joseph T.] Harvard Med Sch, Boston, MA USA.
[Chatelle, Camille] Massachusetts Gen Hosp, Lab NeuroImaging Coma & Consciousness, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
[Chatelle, Camille; Wannez, Sarah; Charland-Verville, Vanessa; Gosseries, Olivia; Laureys, Steven] Univ Hosp Liege, GIGA Res Ctr, Coma Sci Grp, Liege, Belgium.
[Gosseries, Olivia] Univ Wisconsin, Dept Psychol, 1202 W Johnson St, Madison, WI 53706 USA.
[Gosseries, Olivia] Univ Wisconsin, Dept Psychiat, Madison, WI 53706 USA.
[Seel, Ron T.] Shepherd Ctr, Crawford Res Inst, Atlanta, GA USA.
RP Chatelle, C (reprint author), Massachusetts Gen Hosp, Lab NeuroImaging Coma & Consciousness, 175 Cambridge St,Ste 300, Boston, MA 02114 USA.
EM cchatelle@partners.org
RI Laureys, Steven/A-3349-2011
FU National Institute on Disability, Independent Living, and Rehabilitation
Research, Department of Health and Human Services, Administration for
Community Living [90DP0039-01-00]; James S. McDonnell Foundation;
Harvard Catalyst \ The Harvard Clinical and Translational Science Center
(National Center for Research Resources); Harvard Catalyst \ The Harvard
Clinical and Translational Science Center (National Center for Advancing
Translational Sciences, National Institutes of Health) [UL1 TR001102];
Harvard University and its affiliated academic health care centers;
Belgian American Educational Foundation; Wallonie Bruxelles
International Concerted Research Action; Belgian Funds for Scientific
Research, European Commission; European Foundation for Biomedical
Research
FX Supported by the National Institute on Disability, Independent Living,
and Rehabilitation Research, Department of Health and Human Services,
Administration for Community Living (grant no. 90DP0039-01-00); The
James S. McDonnell Foundation; Harvard Catalyst vertical bar 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 no. UL1 TR001102); financial
contributions from Harvard University and its affiliated academic health
care centers; The Belgian American Educational Foundation; Wallonie
Bruxelles International Concerted Research Action; Belgian Funds for
Scientific Research, European Commission; and the European Foundation
for Biomedical Research.
NR 13
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U1 1
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD AUG
PY 2016
VL 97
IS 8
BP 1295
EP 1300
DI 10.1016/j.apmr.2016.02.009
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA DT1LM
UT WOS:000381244200011
PM 26944708
ER
PT J
AU Kesinger, MR
Juengst, SB
Bertisch, H
Niemeier, JP
Krellman, JW
Pugh, M
Kumar, RG
Sperry, JL
Arenth, PM
Fann, JR
Wagner, AK
AF Kesinger, Matthew R.
Juengst, Shannon B.
Bertisch, Hillary
Niemeier, Janet P.
Krellman, Jason W.
Pugh, MaryJo
Kumar, Raj G.
Sperry, Jason L.
Arenth, Patricia M.
Fann, Jesse R.
Wagner, Amy K.
TI Acute Trauma Factor Associations With Suicidality Across the First 5
Years After Traumatic Brain Injury
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Brain injuries; Injury Severity Score; Multiple trauma; Rehabilitation;
Suicidal ideation; Suicide; attempted
ID DEPLOYED MILITARY PERSONNEL; SUBSTANCE-ABUSE; RISK-FACTORS; CHRONIC
PAIN; FOLLOW-UP; DEPRESSION; IDEATION; REHABILITATION; POPULATION;
PREVALENCE
AB Objective: To determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI).
Design: Factors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TRIMS) databases.
Setting: Level I trauma centers, inpatient rehabilitation centers, and the community.
Participants: Participants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575).
Interventions: Not applicable.
Main Outcome Measures: SI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe.
Results: There were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio = 2.73; 95% confidence interval, 1.55-4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio =1.69; 95% confidence interval, 1.11-2.86; P=.015). Severity of ECI was not associated with SA.
Conclusions: Severe ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI. (C) 2016 by the American Congress of Rehabilitation Medicine
C1 [Kesinger, Matthew R.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Juengst, Shannon B.; Kumar, Raj G.; Arenth, Patricia M.; Wagner, Amy K.] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, 3471 Fifth Ave, Pittsburgh, PA 15213 USA.
[Bertisch, Hillary] NYU, Dept Rehabil Med, Sch Med, New York, NY USA.
[Niemeier, Janet P.] Carolinas Med Ctr, Dept Phys Med & Rehabil, Charlotte, NC 28203 USA.
[Niemeier, Janet P.] Univ N Carolina, Chapel Hill, NC USA.
[Krellman, Jason W.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY 10029 USA.
[Pugh, MaryJo] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
[Pugh, MaryJo] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Sperry, Jason L.] Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA USA.
[Fann, Jesse R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Wagner, Amy K.] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA.
[Wagner, Amy K.] Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA.
[Wagner, Amy K.] Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA.
RP Juengst, SB (reprint author), Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, 3471 Fifth Ave, Pittsburgh, PA 15213 USA.
EM sbj7@pitt.edu
FU National Institute on Disability, Independent Living, and Rehabilitation
Research (NIDILRR) [90DP0041]; NIDILRR [90DP0038, 90DP0047]; National
Institutes of Health [NIH K23GM093032]; National Institute of Mental
Health Medical Student Research Fellowship [TL1TR000005, R25 MH054318];
Rusk Advanced Rehabilitation Research Training Postdoctoral Fellowship
[NIDILRR 90AR5014-01-00]; Polytrauma Rehabilitation Center Traumatic
Brain Injury Model System; Department of Veterans Affairs (VA)
FX Support for the collection of the original data was by the National
Institute on Disability, Independent Living, and Rehabilitation Research
(NIDILRR) (grant no. 90DP0041); and the National Trauma Data Bank.
Support for the content of this article was by the NIDILRR (grant nos.
90DP0038 and 90DP0047); the National Institutes of Health (grant no. NIH
K23GM093032); the National Institute of Mental Health Medical Student
Research Fellowship (fellowship no. TL1TR000005) administered by the
University of Pittsburgh (grant no. R25 MH054318); a Rusk Advanced
Rehabilitation Research Training Postdoctoral Fellowship (grant no.
NIDILRR 90AR5014-01-00); and the Polytrauma Rehabilitation Center
Traumatic Brain Injury Model System.; The Polytrauma Rehabilitation
Center Traumatic Brain Injury Model System is a funded collaboration
between the Department of Veterans Affairs (VA) and the National
Institute on Disability, Independent Living, and Rehabilitation Research
(NIDILRR). The NIDILRR is a center within the Administration for
Community Living (ACL), Department of Health and Human Services (HHS).
The contents of this article do not necessarily represent the policy of
the VA, NIDILRR, ACL, NIH, or HHS, and endorsement of this content by
the Federal Government should not be assumed.
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD AUG
PY 2016
VL 97
IS 8
BP 1301
EP 1308
DI 10.1016/j.apmr.2016.02.017
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA DT1LM
UT WOS:000381244200012
PM 26987622
ER
PT J
AU Ward, RE
Beauchamp, MK
Latham, NK
Leveille, SG
Percac-Lima, S
Kurlinski, L
Ni, PS
Goldstein, R
Jette, AM
Bean, JF
AF Ward, Rachel E.
Beauchamp, Marla K.
Latham, Nancy K.
Leveille, Suzanne G.
Percac-Lima, Sanja
Kurlinski, Laura
Ni, Pengsheng
Goldstein, Richard
Jette, Alan M.
Bean, Jonathan F.
TI Neuromuscular Impairments Contributing to Persistently Poor and
Declining Lower-Extremity Mobility Among Older Adults: New Findings
Informing Geriatric Rehabilitation
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article; Proceedings Paper
CT Meeting of the Gerontological-Society-of-America
CY NOV 08, 2014
CL Washington, DC
SP Gerontol Soc Amer
DE Aged; Mobility limitation; Muscle strength; Range of motion; articular;
Rehabilitation
ID GONIOMETRIC MEASUREMENTS; RISK-ASSESSMENT; LIMITED ELDERS; PERFORMANCE;
DISABILITY; WOMEN; KYPHOSIS; BALANCE; RELIABILITY; ATTRIBUTES
AB Objective: To identify neuromuscular impairments most predictive of unfavorable mobility outcomes in late life. Design: Longitudinal cohort study.
Setting: Research clinic.
Participants: Community-dwelling primary care patients aged >= 65 years (N=391) with self-reported mobility modifications, randomly selected from a research registry.
Interventions: Not applicable.
Main Outcome Measures: Categories of decline in and persistently poor mobility across baseline, 1 and 2 years of follow-up in the Lower-Extremity Function scales of the Late-Life Function and Disability Instrument. The following categories of impairment were assessed as potential predictors of mobility change: strength (leg strength), speed of movement (leg velocity, reaction time, rapid leg coordination), range of motion (ROM) (knee flexion/knee extension/ankle ROM), asymmetry (asymmetry of leg strength and knee flexion/extension ROM measures), and trunk stability (trunk extensor endurance, kyphosis).
Results: The largest effect sizes were found for baseline weaker leg strength (odds ratio [95% confidence interval]: 3.45 [1.72-6.95]), trunk extensor endurance (2.98 [1.56-5.70]), and slower leg velocity (2.35 [1.21-4.58]) predicting a greater likelihood of persistently poor function over 2 years. Baseline weaker leg strength, trunk extensor endurance, and restricted knee flexion motion also predicted a greater likelihood of decline in function (1.72 [1.10-2.70], 1.83 [1.13-2.95], and 2.03 [1.24-3.35], respectively).
Conclusions: Older adults exhibiting poor mobility may be prime candidates for rehabilitation focused on improving these impairments. These findings lay the groundwork for developing interventions aimed at optimizing rehabilitative care and disability prevention, and highlight the importance of both well-recognized (leg strength) and novel impairments (leg velocity, trunk extensor muscle endurance). (C) 2016 by the American Congress of Rehabilitation Medicine
C1 [Ward, Rachel E.; Bean, Jonathan F.] Boston Vet Affairs Healthcare Syst, New England Geriatr Res Educ & Clin Ctr, Boston, MA USA.
[Ward, Rachel E.; Leveille, Suzanne G.; Percac-Lima, Sanja; Kurlinski, Laura; Goldstein, Richard; Bean, Jonathan F.] Harvard Med Sch, Boston, MA USA.
[Ward, Rachel E.; Kurlinski, Laura; Goldstein, Richard; Bean, Jonathan F.] Spaulding Rehabil Hosp, 1575 Cambridge St, Cambridge, MA 02138 USA.
[Beauchamp, Marla K.] McMaster Univ, Sch Rehabil Sci, Hamilton, ON, Canada.
[Latham, Nancy K.; Ni, Pengsheng; Jette, Alan M.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA USA.
[Leveille, Suzanne G.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
[Percac-Lima, Sanja] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Ward, RE (reprint author), Spaulding Rehabil Hosp, 1575 Cambridge St, Cambridge, MA 02138 USA.
EM reward@partners.org
RI Bean, Jonathan/F-5798-2017
OI Bean, Jonathan/0000-0001-8385-8210
FU NCRR NIH HHS [UL1 RR025758]; NIA NIH HHS [R01 AG032052]; NICHD NIH HHS
[K24 HD070966]
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U1 3
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PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD AUG
PY 2016
VL 97
IS 8
BP 1316
EP 1322
DI 10.1016/j.apmr.2016.03.003
PG 7
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA DT1LM
UT WOS:000381244200014
PM 27056644
ER
PT J
AU Goverman, J
Mathews, K
Nadler, D
Henderson, E
McMullen, K
Herndon, D
Meyer, W
Fauerbach, JA
Wiechman, S
Carrougher, G
Ryan, CM
Schneider, JC
AF Goverman, J.
Mathews, K.
Nadler, D.
Henderson, E.
McMullen, K.
Herndon, D.
Meyer, W., III
Fauerbach, J. A.
Wiechman, S.
Carrougher, G.
Ryan, C. M.
Schneider, J. C.
TI Satisfaction with life after burn: A Burn Model System National Database
Study
SO BURNS
LA English
DT Article
DE Burn; Satisfaction with life; Outcome
ID QUALITY-OF-LIFE; STRESS-DISORDER; INJURY; HEALTH; PREDICTORS;
DEPRESSION; SYMPTOMS; INTEGRATION; VALIDATION; EXPERIENCE
AB Objectives: While mortality rates after burn are low, physical and psychosocial impairments are common. Clinical research is focusing on reducing morbidity and optimizing quality of life. This study examines self-reported Satisfaction With Life Scale scores in a longitudinal, multicenter cohort of survivors of major burns. Risk factors associated with Satisfaction With Life Scale scores are identified.
Methods: Data from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) Burn Model System (BMS) database for burn survivors greater than 9 years of age, from 1994 to 2014, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures were the individual items and total Satisfaction With Life Scale (SWLS) scores at time of hospital discharge (pre-burn recall period) and 6, 12, and 24 months after burn. The SWLS is a validated 5-item instrument with items rated on a 1-7 Likert scale. The differences in scores over time were determined and scores for burn survivors were also compared to a non-burn, healthy population. Step-wise regression analysis was performed to determine predictors of SWLS scores at different time intervals.
Results: The SWLS was completed at time of discharge (1129 patients), 6 months after burn (1231 patients), 12 months after burn (1123 patients), and 24 months after burn (959 patients). There were no statistically significant differences between these groups in terms of medical or injury demographics. The majority of the population was Caucasian (62.9%) and male (72.6%), with a mean TBSA burned of 22.3%. Mean total SWLS scores for burn survivors were unchanged and significantly below that of a non-burn population at all examined time points after burn. Although the mean SWLS score was unchanged over time, a large number of subjects demonstrated improvement or decrement of at least one SWLS category. Gender, TBSA burned, LOS, and school status were associated with SWLS scores at 6 months; scores at 12 months were associated with LOS, school status, and amputation; scores at 24 months were associated with LOS, school status, and drug abuse.
Conclusions: In this large, longitudinal, multicenter cohort of burn survivors, satisfaction with life after burn was consistently lower than that of non-burn norms. Furthermore mean SWLS scores did not improve over the two-year follow-up period. This study demonstrates the need for continued efforts to improve patient-centered long term satisfaction with life after burn. (C) 2016 Elsevier Ltd and ISBI. All rights reserved.
C1 [Goverman, J.; Mathews, K.; Henderson, E.; Ryan, C. M.; Schneider, J. C.] Harvard Med Sch, Massachusetts Gen Hosp, Surg Serv, Sumner Redstone Burn Ctr, Boston, MA USA.
[Goverman, J.; Mathews, K.; Nadler, D.; Ryan, C. M.; Schneider, J. C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
[Goverman, J.; Ryan, C. M.; Schneider, J. C.] Shriners Hosp Children Boston, Boston, MA USA.
[McMullen, K.] Univ Washington, Seattle, WA USA.
[Herndon, D.; Meyer, W., III] Shriners Hosp Children Galveston, Galveston, TX USA.
[Herndon, D.; Meyer, W., III] Univ Texas Med Branch, Dept Surg, Galveston, TX 77555 USA.
[Meyer, W., III] Univ Texas Med Branch, Sch Med, Dept Psychiat & Behav Sci, Galveston, TX 77555 USA.
[Fauerbach, J. A.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Wiechman, S.] Univ Washington, Burn Ctr, Harborview Med Ctr, Dept Rehabil Med,Psychol, Seattle, WA 98195 USA.
[Carrougher, G.] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Wiechman, S.] Harborview Med Ctr, Seattle, WA USA.
RP Schneider, JC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA.
EM jcschneider@partners.org
FU National Institute on Disability, Independent Living, and Rehabilitation
Research (NIDILRR) [90DP0035]
FX The contents of this manuscript were developed under a grant from the
National Institute on Disability, Independent Living, and Rehabilitation
Research (NIDILRR grant number 90DP0035). NIDILRR is a Center within the
Administration for Community Living (ACL), Department of Health and
Human Services (HHS). The contents of this manuscript do not necessarily
represent the policy of NIDILRR, ACL, HHS, and you should not assume
endorsement by the Federal Government.
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0305-4179
EI 1879-1409
J9 BURNS
JI Burns
PD AUG
PY 2016
VL 42
IS 5
BP 1067
EP 1073
DI 10.1016/j.bunis.2016.01.018
PG 7
WC Critical Care Medicine; Dermatology; Surgery
SC General & Internal Medicine; Dermatology; Surgery
GA DU7SD
UT WOS:000382414000008
PM 27215148
ER
PT J
AU Ryan, CM
Cartwright, S
Schneider, JC
Tompkins, RG
Kazis, LE
AF Ryan, Colleen M.
Cartwright, Sara
Schneider, Jeffrey C.
Tompkins, Ronald G.
Kazis, Lewis E.
TI The burn outcome questionnaires: Patient and family reported outcome
metrics for children of all ages
SO BURNS
LA English
DT Letter
ID QUALITY-OF-LIFE; ASSOCIATION/SHRINERS-HOSPITALS; HEALTH OUTCOMES;
YOUNG-ADULTS; RECOVERY; INJURY; VALIDATION
C1 [Ryan, Colleen M.; Schneider, Jeffrey C.; Tompkins, Ronald G.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA.
[Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA USA.
[Ryan, Colleen M.; Cartwright, Sara; Schneider, Jeffrey C.] Harvard Med Sch, Spaulding Rehabil Hosp, Boston, MA USA.
[Kazis, Lewis E.] Boston Univ, Dept Hlth Policy & Management, Sch Publ Hlth, Ctr Assessment Pharmaceut Practices, Boston, MA USA.
RP Ryan, CM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA.
EM cryan@partners.org
OI Ryan, Colleen/0000-0002-6455-936X
NR 17
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0305-4179
EI 1879-1409
J9 BURNS
JI Burns
PD AUG
PY 2016
VL 42
IS 5
BP 1144
EP 1145
DI 10.1016/j.burns.2015.10.033
PG 2
WC Critical Care Medicine; Dermatology; Surgery
SC General & Internal Medicine; Dermatology; Surgery
GA DU7SD
UT WOS:000382414000023
PM 26803370
ER
PT J
AU Nishimura, K
Shindo, S
Movila, A
Kayal, R
Abdullah, A
Savitri, IJ
Ikeda, A
Yamaguchi, T
Howait, M
Al-Dharrab, A
Mira, A
Han, XZ
Kawai, T
AF Nishimura, Kazuaki
Shindo, Satoru
Movila, Alexandru
Kayal, Rayyan
Abdullah, Albassam
Savitri, Irma Josefina
Ikeda, Atsushi
Yamaguchi, Tsuguno
Howait, Mohammed
Al-Dharrab, Ayman
Mira, Abdulghani
Han, Xiaozhe
Kawai, Toshihisa
TI TRAP-positive osteoclast precursors mediate ROS/NO-dependent
bactericidal activity via TLR4
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Osteoclast; Bacteria; Phagocytosis; Toll-like receptor;
Tartrate-resistant acid phosphatase; Reactive oxygen species; Nitric
oxide; RANKL
ID TOLL-LIKE RECEPTORS; COLONY-STIMULATING FACTOR; IN-VITRO;
BONE-RESORPTION; INNATE IMMUNITY; INTERFERON-BETA; RANK LIGAND;
DIFFERENTIATION; INHIBITION; PERIODONTITIS
AB Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coil in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coll. and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coll.phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Nishimura, Kazuaki; Shindo, Satoru; Movila, Alexandru; Abdullah, Albassam; Ikeda, Atsushi; Yamaguchi, Tsuguno; Han, Xiaozhe; Kawai, Toshihisa] Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA.
[Nishimura, Kazuaki] Tohoku Univ Hosp, Maxillooral Disorders, Sendai, Miyagi, Japan.
[Shindo, Satoru] Univ Tokushima, Inst Hlth Biosci, Dept Conservat Dent, Grad Sch, Tokushima, Japan.
[Kayal, Rayyan; Abdullah, Albassam; Howait, Mohammed; Al-Dharrab, Ayman; Mira, Abdulghani] King Abdulaziz Univ, Fac Dent, Jeddah, Saudi Arabia.
[Savitri, Irma Josefina] Airlangga Univ, Dept Periodont, Jawa Timur, Indonesia.
[Yamaguchi, Tsuguno] LION Corp, Res & Dev Headquarters, 100 Tajima Odawara, Odawara, Kanagawa, Japan.
[Han, Xiaozhe; Kawai, Toshihisa] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA.
RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol & Infect Dis, 245 First St, Cambridge, MA 02142 USA.
EM knishimura@dent.tohoku.ac.jp; c301351004@tokushima-u.ac.jp;
amovila@forsyth.org; rkayal@kau.edu.sa; albassam.a@hotmail.com;
irmaudijanto@gmail.com; aikeda@forsyth.org; tsuguno@gmail.com;
mhowait@icloud.com; aaldharab@kau.edu.sa; amira@kau.edu.sa;
XHan@forsyth.org; tkawai@forsyth.org
RI Howait, Mohammed/K-4478-2016
OI Howait, Mohammed/0000-0002-6268-4941
FU NIH [RO1 DE-018499, RO1 DE-019917, R56 DE023807, R01DE025255]; National
Institute of Dental and Craniofacial Research (NIDCR) [T32 DE 7327-12];
King Abdulaziz University (KAU)
FX This work was partially supported by NIH grants RO1 DE-018499, RO1
DE-019917, R56 DE023807 and R01DE025255 and T32 DE 7327-12 from National
Institute of Dental and Craniofacial Research (NIDCR) and a research
fund from King Abdulaziz University (KAU).
NR 62
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U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD AUG
PY 2016
VL 97
BP 330
EP 341
DI 10.1016/j.freeradbiomed.2016.06.021
PG 12
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DU0VZ
UT WOS:000381924100030
PM 27343691
ER
PT J
AU Wu, N
Wang, Y
Yang, LB
Cho, KS
AF Wu, Nan
Wang, Yi
Yang, Lanbo
Cho, Kin-Sang
TI Signaling Networks of Retinal Ganglion Cell Formation and the Potential
Application of Stem Cell-Based Therapy in Retinal Degenerative Diseases
SO HUMAN GENE THERAPY
LA English
DT Article
ID NEURAL PROGENITOR CELLS; DEVELOPING MOUSE RETINA; ROD PHOTORECEPTOR
DEVELOPMENT; IN-VITRO DIFFERENTIATION; TRANSCRIPTION FACTOR NRL; DOMAIN
FACTOR BRN-3B; LEUCINE-ZIPPER NRL; CRX-DEFICIENT MICE; VERTEBRATE
RETINA; SONIC HEDGEHOG
AB Retinal degenerative diseases such as age-related macular degeneration, retinitis pigmentosa, and glaucoma result in permanent loss of retinal neurons and vision. Stem cell therapy could be a novel treatment strategy to restore visual function. In an ideal situation, a homogenous population of stem cell-derived retinal neurons with high purity is used for replacement therapy. Thus, it is crucial to elucidate the molecular mechanisms that regulate the development of retinal progenitor cells and subsequent generation of specific retinal neurons. Here, recent findings concerning the intrinsic and extrinsic factors that regulate retinal progenitor cell maintenance and differentiation are summarized, especially transcriptional factors and extrinsic signals. Understanding these mechanisms is indispensable because they have potential clinical applications, chiefly the generation of specific retinal cells such as retinal ganglion cells to treat glaucoma and other optic neuropathy diseases.
C1 [Wu, Nan; Wang, Yi] Third Mil Med Univ, Southwest Hosp, Southwest Eye Hosp, Dept Ophthalmol, Chongqing, Peoples R China.
[Yang, Lanbo; Cho, Kin-Sang] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA USA.
RP Cho, KS (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM kinsang_cho@meei.harvard.edu
FU National Natural Science Foundation of China [30901645]; Youth
Innovation Fund of the Third Military Medical University [2009XQN29]
FX The study was supported by grants from National Natural Science
Foundation of China (grant no. 30901645) and the Youth Innovation Fund
of the Third Military Medical University (grant no. 2009XQN29).
NR 150
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U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD AUG
PY 2016
VL 27
IS 8
BP 609
EP 620
DI 10.1089/hum.2016.083
PG 12
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA DU6AQ
UT WOS:000382295500005
PM 27466076
ER
EF