FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Jelly, CA
Jiang, YD
Hoeft, M
Liang, YF
AF Jelly, Christina Anne
Jiang, Yandong
Hoeft, Mark
Liang, Yafen
TI Transesophageal Echocardiography Assisting in the Diagnosis of
Intraabdominal Hemorrhage During Cardiac Arrest
SO A & A CASE REPORTS
LA English
DT Article
ID NONCARDIAC SURGERY
AB Transesophageal echocardiography (TEE) has been frequently used to identify potential etiologies of intraoperative cardiac arrest for noncardiac surgical patients. However, rescue TEE to assist in the diagnosis of intraabdominal hemorrhage has never been reported. We present a patient who developed cardiac arrest on emergence after an elective abdominal surgery. Intraoperative TEE revealed hypovolemia with hyperdynamic left and right ventricles. It also demonstrated a 3.3- by 13.2-cm circular perihepatic fluid collection on transgastric views raising concern for major intraabdominal hemorrhage as the cause for the cardiac arrest. This prompted surgical reexploration, which confirmed the diagnosis. We suggest that transgastric views to identify intraabdominal fluid collections should be considered during a rescue TEE if intraabdominal hemorrhage is suspected.
C1 [Jelly, Christina Anne; Hoeft, Mark] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Jiang, Yandong; Liang, Yafen] Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA.
RP Liang, YF (reprint author), Vanderbilt Univ, Med Ctr, Dept Anesthesiol, Nashville, TN 37232 USA.
EM yafen.liang@vanderbilt.edu
NR 5
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 2325-7237
J9 A A CASE REP
JI A A Case Rep.
PD APR 1
PY 2016
VL 6
IS 7
BP 201
EP 203
DI 10.1213/XAA.0000000000000284
PG 3
WC Anesthesiology
SC Anesthesiology
GA DI6FV
UT WOS:000373595500008
PM 26795911
ER
PT J
AU Tipps, ME
Raybuck, JD
Kozell, LB
Lattal, KM
Buck, KJ
AF Tipps, Megan E.
Raybuck, Jonathan D.
Kozell, Laura B.
Lattal, K. Matthew
Buck, Kari J.
TI G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3
Knock-Out Mice Show Enhanced Ethanol Reward
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE GIRK Channels; Reward; Conditioned Place Preference; Fear Conditioning;
Ethanol
ID CONDITIONED PLACE PREFERENCE; VENTRAL TEGMENTAL AREA; NULL MUTANT MICE;
GIRK CHANNELS; ALCOHOL ADDICTION; DOPAMINE SYSTEM; DRUG-ADDICTION; K+
CHANNELS; HYBRID MICE; NEURONS
AB BackgroundG protein-gated inwardly rectifying potassium (GIRK) channels contribute to the effects of a number of drugs of abuse, including ethanol. However, the roles of individual subunits in the rewarding effects of ethanol are poorly understood.
MethodsWe compare conditioned place preference (CPP) in GIRK3 subunit knock-out (GIRK3(-/-)), heterozygote (GIRK3(+/-)), and wild-type (WT) mice. In addition, the development of locomotor tolerance/sensitization and the effects of EtOH intoxication on associative learning (fear conditioning) are also assessed.
ResultsOur data show significant EtOH CPP in GIRK3(-/-) and GIRK3(+/-) mice, but not in the WT littermates. In addition, we demonstrate that these effects are not due to differences in EtOH metabolism, the development of EtOH tolerance/sensitivity, or associative learning abilities. While there were no consistent genotype differences in the fear conditioning assay, our data do show a selective sensitization of the impairing effects of EtOH intoxication on contextual learning, but no effect on cued learning.
ConclusionsThese findings suggest that GIRK3 plays a role in EtOH reward. Furthermore, the selectivity of this effect suggests that GIRK channels could be an effective therapeutic target for the prevention and/or treatment of alcoholism.
C1 [Tipps, Megan E.; Kozell, Laura B.; Buck, Kari J.] Portland VA Med Ctr, Portland Alcohol Res Ctr, Portland, OR USA.
[Tipps, Megan E.; Raybuck, Jonathan D.; Kozell, Laura B.; Lattal, K. Matthew; Buck, Kari J.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, 3181 SW Sam Jackson Pk Rd,Mail Code L470, Portland, OR 97239 USA.
RP Tipps, ME (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, 3181 SW Sam Jackson Pk Rd,Mail Code L470, Portland, OR 97239 USA.
EM metipps@gmail.com
OI Kozell, Laura/0000-0003-3059-2046
FU NIH [F32 AA022011, T32 AA07468, F32DA031537, T32 DA07262, R01 AA011114,
P60 AA10760, R24 AA020245, R01 DA005228, R01 DA025922]; VA; U.S.
Department of the Army/DOD-TATRC [W81XWH-12-2-0048]
FX This work was supported by NIH F32 AA022011 and T32 AA07468 (MET); NIH
F32DA031537 and T32 DA07262 (JDR); NIH R01 AA011114, P60 AA10760, R24
AA020245, R01 DA005228, and the VA (KJB); NIH R01 DA025922 and U.S.
Department of the Army/DOD-TATRC: W81XWH-12-2-0048 (KML).
NR 52
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD APR
PY 2016
VL 40
IS 4
BP 857
EP 864
DI 10.1111/acer.13012
PG 8
WC Substance Abuse
SC Substance Abuse
GA DI8GK
UT WOS:000373739300023
PM 27012303
ER
PT J
AU Berg, DD
Bonaca, MP
Braunwald, E
Corbalan, R
Goto, S
Kiss, RG
Murphy, SA
Scirica, BM
Spinar, J
Morrow, DA
AF Berg, David D.
Bonaca, Marc P.
Braunwald, Eugene
Corbalan, Ramon
Goto, Shinya
Kiss, Robert G.
Murphy, Sabina A.
Scirica, Benjamin M.
Spinar, Jindrich
Morrow, David A.
TI Outcomes in Stable Patients With Previous Atherothrombotic Events
Receiving Vorapaxar Who Experience a New Acute Coronary Event (from TRA2
degrees P-TIMI 50)
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID THROMBIN-RECEPTOR ANTAGONIST; SECONDARY PREVENTION
AB Vorapaxar is a first-in-class protease-activated receptor-1 antagonist indicated for secondary prevention in stable patients with previous myocardial infarction (MI) or peripheral artery disease and no cerebrovascular disease. Vorapaxar is not recommended for initiation in the acute phase of acute coronary syndromes (ACS) because of an unfavorable balance between bleeding and efficacy when started in that setting. The aim of this analysis was to investigate outcomes in patients who experienced a new ACS while receiving vorapaxar for long-term secondary prevention. Thrombin Receptor Antagonist in Secondary Prevention of Atherothrombotic ischemic Events-Thrbmbolysis In Myocardial Infarction 50 was a randomized, double-blind, placebo-controlled trial of vorapaxar (n = 26,449). We evaluated bleeding and ischemic events during the acute care of patients with a new ACS during the trial. During a median follow-up of 30 months, 799 patients (8.9%) randomized to vorapaxar and 913 (10.0%) to placebo had a new ACS event (p = 0.003); 87% and 86%, respectively, were on study therapy at the time of the event. In a landmark analysis through 7 days after ACS, the rates of Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe bleeding were 0.8% versus 0.8% (hazard ratio [HR] 0.99, 95% CI 0.33 to 2.94) and GUSTO moderate/severe bleeding were 2.5% versus 1.6% (HR 1.59, 95% CI 0.78 to 3.24) with vorapaxar versus placebo. The effect of vorapaxar on cardiovascular death, MI, or stroke (2.4% vs 4.4%; HR 0.54, 95% CI 0,31 to 0.93; p = 0.027) was consistent with the, overall trial result. In conclusion, in patients who experience a new ACS event while receiving vorapaxar for secondary prevention, continuing therapy was associated with favorable efficacy without excess severe bleeding during the period of acute ACS management. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Berg, David D.; Bonaca, Marc P.; Braunwald, Eugene; Murphy, Sabina A.; Scirica, Benjamin M.; Morrow, David A.] Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA.
[Corbalan, Ramon] Catholic Univ Chile, Dept Cardiol, Sch Med, Santiago, Chile.
[Goto, Shinya] Tokai Univ, Sch Med, Dept Med, Isehara, Kanagawa 25911, Japan.
[Kiss, Robert G.] Mil Hosp, Dept Cardiol, Budapest, Hungary.
[Spinar, Jindrich] Univ Hosp, Dept Cardiol, Brno, Czech Republic.
RP Morrow, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp,Dept Med,Med Sch, Boston, MA 02115 USA.
EM dmorrow@partners.org
FU Merck and Co.
FX TRA2 degrees P-TIMI 50 (http://www.clinicaltrials.gov, NCT00526474) was
supported by Merck and Co.
NR 5
TC 2
Z9 2
U1 4
U2 5
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD APR 1
PY 2016
VL 117
IS 7
BP 1055
EP 1058
DI 10.1016/j.amjcard.2015.12.052
PG 4
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DI5FH
UT WOS:000373523800004
PM 26876014
ER
PT J
AU Vaduganathan, M
Marti, CN
Mentz, RJ
Greene, SJ
Ambrosy, AP
Subacius, HP
Fonarow, GC
Chioncel, O
Bazari, H
Maggioni, AP
Zannad, F
Konstam, MA
Sato, N
Gheorghiade, M
Butler, J
AF Vaduganathan, Muthiah
Marti, Catherine N.
Mentz, Robert J.
Greene, Stephen J.
Ambrosy, Andrew P.
Subacius, Hans P.
Fonarow, Gregg C.
Chioncel, Ovidiu
Bazari, Hasan
Maggioni, Aldo P.
Zannad, Faiez
Konstam, Marvin A.
Sato, Naoki
Gheorghiade, Mihai
Butler, Javed
CA EVEREST Trial Investigators
TI Serum Osmolality and Postdischarge Outcomes After Hospitalization for
Heart Failure
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID LEFT-VENTRICULAR DYSFUNCTION; EVEREST; TOLVAPTAN; TRIAL; ACTIVATION
AB Serum osmolality may fluctuate with neurohormonal activation and in response to certain therapeutics in patients with heart failure (HF). The clinical relevance of osmolality in patients with HF has not been defined. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF <= 40%). Median follow-up was 9.9 months. The association between discharge osmolality and all-cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was nonlinear; and thus, patients were divided into low (<= 284), normal (285 to 300), and high (>= 300 mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290 to 304) mOsm/kg. Patients in the low osmolality group (n = 454,12.1%) were more likely to be younger, men, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p <0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p = 0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p = 0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (hazard ratio 1.61, 95% CI 1.19 to 2.17) and the composite endpoint (hazard ratio 1.37, 95% CI 1.06 to 1.75) in the low osmolality group. These associations were not seen in patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were nonsignificant (p >0.4). In conclusion, low discharge serum osmolality was independently predictive of worse postdischarge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized patients with HF. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Vaduganathan, Muthiah] Harvard Univ, Brigham & Womens Hosp, Heart & Vasc Ctr, Sch Med, Boston, MA 02115 USA.
[Bazari, Hasan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA.
[Marti, Catherine N.] Emory Univ, Sch Med, Div Cardiol, Atlanta, GA 30322 USA.
[Mentz, Robert J.; Greene, Stephen J.; Ambrosy, Andrew P.] Duke Univ, Med Ctr, Durham, NC USA.
[Subacius, Hans P.] Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Fonarow, Gregg C.] Ronald Reagan Univ Calif Los Angeles Med Ctr, Ahmanson Univ Calif Los Angeles Cardiomyopathy Ct, Los Angeles, CA USA.
[Chioncel, Ovidiu] Inst Cardiovasc Dis Prof C Iliescu, Cardiol, Bucharest, Romania.
[Maggioni, Aldo P.] Italian Assoc Hosp Cardiologists Res Ctr, Florence, Italy.
[Zannad, Faiez] Nancy Univ, Dept Cardiol, Nancy, France.
[Konstam, Marvin A.] Tufts Med Ctr, Boston, MA USA.
[Sato, Naoki] Musashi Kosugi Hosp, Nippon Med Sch, Tokyo, Japan.
[Gheorghiade, Mihai] Northwestern Univ, Ctr Cardiovasc Innovat, Feinberg Sch Med, Chicago, IL 60611 USA.
[Butler, Javed] SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA.
RP Butler, J (reprint author), SUNY Stony Brook, Div Cardiol, Stony Brook, NY 11794 USA.
EM javed.butler@stonybrookmedicine.edu
OI chioncel, ovidiu/0000-0002-3197-3628; Vaduganathan,
Muthiah/0000-0003-0885-1953; Maggioni, Aldo Pietro/0000-0003-2764-6779
FU Otsuka Inc. (Rockville, Maryland)
FX Otsuka Inc. (Rockville, Maryland) provided financial and material
support for the EVEREST trial. Database management was performed by the
sponsor.
NR 10
TC 3
Z9 3
U1 1
U2 2
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD APR 1
PY 2016
VL 117
IS 7
BP 1144
EP 1150
DI 10.1016/j.amjcard.2015.12.059
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DI5FH
UT WOS:000373523800018
PM 26851146
ER
PT J
AU Quraishi, SA
Camargo, CA
Manson, JE
AF Quraishi, Sadeq A.
Camargo, Carlos A., Jr.
Manson, JoAnn E.
TI Low vitamin D status in Europe: moving from evidence to sound public
health policies
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Editorial Material
ID D-BINDING PROTEIN; D DEFICIENCY
C1 [Quraishi, Sadeq A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
[Manson, JoAnn E.] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA.
RP Manson, JE (reprint author), Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA.
EM jmanson@rics.bwh.harvard.edu
FU NCI NIH HHS [R01 CA138962]; NIAMS NIH HHS [R01 AR059775]
NR 12
TC 0
Z9 0
U1 2
U2 6
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD APR
PY 2016
VL 103
IS 4
BP 957
EP 958
DI 10.3945/ajcn.116.132274
PG 2
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DI3VI
UT WOS:000373426400001
PM 26984486
ER
PT J
AU Rosendorff, C
AF Rosendorff, Clive
CA Writing Comm
TI Treatment of Hypertension in Patients with Coronary Artery Disease. A
Case-Based Summary of the 2015 AHA/ACC/ASH Scientific Statement
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE Acute Coronary Syndrome; Coronary Artery Disease; Heart Failure;
Hypertension; Myocardial Infarction; Stable Angina; Unstable Angina
ID COLLEGE-OF-CARDIOLOGY; LEFT-VENTRICULAR DYSFUNCTION;
CONVERTING-ENZYME-INHIBITOR; ACUTE MYOCARDIAL-INFARCTION;
AMERICAN-HEART-ASSOCIATION; PREVENTIVE-CARDIOVASCULAR-NURSES;
BLOOD-PRESSURE CONTROL; HIGH-RISK PATIENTS; RANDOMIZED-TRIAL; PRACTICE
GUIDELINES
AB The 2015 American Heart Association/American College of Cardiology/American Society of Hypertension Scientific Statement "Treatment of Hypertension in Patients with Coronary Artery Disease" is summarized in the context of a clinical case. The Statement deals with target blood pressures, and the optimal agents for the treatment of hypertension in patients with stable angina, in acute coronary syndromes, and in patients with ischemic heart failure. In all cases, the recommended blood pressure target is < 140/90 mm Hg, but < 130/80 mm Hg may be appropriate, especially in those with a history of a previous myocardial infarction or stroke, or at high risk for developing either. These numbers may need to be revised after the publication of the SPRINT data. Appropriate management should include beta-blockers, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and in the case of heart failure, aldosterone antagonists. Thiazide or thiazide-like (chlorthalidone) diuretics and calcium channel blockers can be used for the management of hypertension, but the evidence for improved outcomes compared with other agents in hypertension with coronary artery disease is meager. Loop diuretics should be reserved for patients with New York Heart Association Class III and IV heart failure or with a glomerular filtration rate of < 30 mL/min. Published by Elsevier Inc.
C1 Mt Sinai Heart, New York, NY USA.
Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
James J Peters VA Med Ctr, Bronx, NY 10468 USA.
RP Rosendorff, C (reprint author), James J Peters VA Med Ctr, Med 111, 130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM clive.rosendorff@va.gov
OI Allison, Matthew/0000-0003-0777-8272
NR 37
TC 2
Z9 2
U1 2
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD APR
PY 2016
VL 129
IS 4
BP 372
EP 378
DI 10.1016/j.amjmed.2015.10.045
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI4RH
UT WOS:000373486500021
PM 26655222
ER
PT J
AU Lin, BM
Curhan, SG
Wang, M
Eavey, R
Stankovic, KM
Curhan, GC
AF Lin, Brian M.
Curhan, Sharon G.
Wang, Molin
Eavey, Roland
Stankovic, Konstantina M.
Curhan, Gary C.
TI Hypertension, Diuretic Use, and Risk of Hearing Loss
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Furosemide; Hearing loss; Hypertension; Prospective study; Thiazide
diuretics
ID FOOD FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY;
STRIA-VASCULARIS; OLDER-ADULTS; NATIONAL-HEALTH; IMPAIRMENT; FUROSEMIDE;
WOMEN; PREVALENCE; REPRODUCIBILITY
AB BACKGROUND: Hearing loss is highly prevalent among adults in the United States. Hypertension also is common and often treated with diuretics. Hypertension may increase the risk of hearing loss by decreasing vascular supply to the stria vascularis. Use of thiazides has been anecdotally associated with hearing loss. In small studies, furosemide use has been associated with hearing loss that is usually reversible, but can be permanent. We investigated the relation among hypertension, diuretic use, and hearing loss in a prospective cohort of 54,721 women in the Nurses' Health Study I, 1994 to 2012.
METHODS: Eligible participants included 54,721 female nurses aged 48 to 73 years in 1994 who provided information on thiazide diuretic and furosemide use in 1994, answered the question on hearing loss over their lifetime in 2012, and did not report hearing loss with date of onset before date of onset of hypertension diagnosis or medication use. The outcome was self-reported hearing loss. Cox proportional hazards regression was used to adjust for potential confounders.
RESULTS: During 774,096 person-years of follow-up, 19,296 cases of hearing loss were reported (incidence rate, 25 cases per 1000 person-years). At baseline in 1994, the mean age was 57.9 years and mean body mass index was 26.3 kg/m2. Some 30.8% of participants had a history of hypertension. History of hypertension was independently associated with a modestly higher risk of hearing loss (multivariable adjusted relative risk, 1.04 [1.01-1.07]). Among women with a history of hypertension, neither thiazide diuretic (multivariable adjusted relative risk, 1.07 [0.99-1.16]) nor furosemide use (multivariable adjusted relative risk, 0.91 [0.75-1.09]) was significantly associated with risk of hearing loss when compared with women not taking antihypertensive medications. There was no significant effect modification by age.
CONCLUSIONS: History of hypertension was associated with a small increased risk of hearing loss. Thiazide diuretic use and furosemide use were not associated with risk of hearing loss among women with a history of hypertension. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lin, Brian M.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA.
[Lin, Brian M.; Curhan, Sharon G.; Wang, Molin; Curhan, Gary C.] Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA.
[Lin, Brian M.; Curhan, Sharon G.; Wang, Molin; Stankovic, Konstantina M.; Curhan, Gary C.] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Molin; Curhan, Gary C.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Eavey, Roland] Vanderbilt Univ, Sch Med, Vanderbilt Bill Wilkerson Ctr Otolaryngol & Commu, Nashville, TN 37212 USA.
[Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Div Renal, 75 Francis St, Boston, MA 02115 USA.
RP Lin, BM (reprint author), Brigham & Womens Hosp, Channing Div Network Med, 181 Longwood Ave, Boston, MA 02115 USA.
EM brian_lin@meei.harvard.edu
FU National Institutes of Health [U01 DC010811, UM1 CA176726]
FX This work was supported by Grants U01 DC010811 and UM1 CA176726 from the
National Institutes of Health. The sponsors of this study had no role in
the study design, data collection, data analysis, data interpretation,
or writing of the manuscript. This study was approved by the Partners
Healthcare Institutional Review Board. Completion of the
self-administered questionnaire was considered implied informed consent.
NR 50
TC 3
Z9 3
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD APR
PY 2016
VL 129
IS 4
BP 416
EP 422
DI 10.1016/j.amjmed.2015.11.014
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI4RH
UT WOS:000373486500028
PM 26656761
ER
PT J
AU Carbo, AR
Goodman, EB
Totte, C
Clardy, P
Feinbloom, D
Kim, H
Kriegel, G
Dierks, M
Weingart, SN
Sands, K
Aronson, M
Tess, A
AF Carbo, Alexander R.
Goodman, Elaine Besancon
Totte, Cheryle
Clardy, Peter
Feinbloom, David
Kim, Hans
Kriegel, Gila
Dierks, Meghan
Weingart, Saul N.
Sands, Ken
Aronson, Mark
Tess, Anjala
TI Resident Case Review at the Departmental Level: A Win-Win Scenario
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
ID QUALITY IMPROVEMENT; INTERNAL-MEDICINE; PATIENT SAFETY; EXPERIENCE;
MORBIDITY; PROGRAMS
AB Adverse event review using root cause analysis is a cornerstone of the peer review process. As stated in the landmark Institute of Medicine publication To Err is Human, "Adequate attention and resources must be devoted to analyzing reports and taking appropriate follow-up action to hold health care organizations accountable. Sufficient attention must be devoted to analyzing and understanding the causes of errors in order to make improvements." 1 In response to this call to action and to state regulatory requirements, hospitals have established internal processes to collect events, analyze them, and report findings as they occur. Given that residents and fellows are integral members of academic medical centers, the Accreditation Council for Graduate Medical Education (ACGME) has emphasized the importance of training the future workforce in safety science as well. Originally, this was codified indirectly within the framework of 6 core competencies and within milestone reporting. 2 Through the Clinical Learning Environment Review program, institutions are now also being asked to provide opportunities for trainees to participate in hands-on investigation of events.(3-5)
Despite these increased requirements for safety training, most published work in quality improvement and safety education tend to focus on resident integration into quality improvement work and medical morbidity conferences rather than event review or root cause analysis.(6-15) Few describe resident involvement in the peer review process itself.(16)
In this paper we describe the structured approach to event review by residents in our Department of Medicine and share descriptive outcomes over the past several years.
C1 [Carbo, Alexander R.; Totte, Cheryle; Clardy, Peter; Feinbloom, David; Kim, Hans; Kriegel, Gila; Dierks, Meghan; Sands, Ken; Aronson, Mark; Tess, Anjala] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Carbo, Alexander R.; Goodman, Elaine Besancon; Clardy, Peter; Feinbloom, David; Kim, Hans; Kriegel, Gila; Dierks, Meghan; Sands, Ken; Aronson, Mark; Tess, Anjala] Harvard Univ, Sch Med, Boston, MA USA.
[Goodman, Elaine Besancon] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Weingart, Saul N.] Tufts Med Ctr, Boston, MA USA.
[Weingart, Saul N.] Tufts Univ, Sch Med, Boston, MA 02111 USA.
RP Carbo, AR (reprint author), Beth Israel Deaconess Med Ctr, Hosp Med Program, Span 2nd Floor,330 Brookline Ave, Boston, MA 02215 USA.
EM acarbo@bidmc.harvard.edu
NR 22
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD APR
PY 2016
VL 129
IS 4
BP 448
EP 452
DI 10.1016/j.amjmed.2015.12.003
PG 5
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI4RH
UT WOS:000373486500035
PM 26721634
ER
PT J
AU Kempen, JH
Gewaily, DY
Newcomb, CW
Liesegang, TL
Kacmaz, RO
Levy-Clarke, GA
Nussenblatt, RB
Rosenbaum, JT
Sen, HN
Suhler, EB
Thorne, JE
Foster, CS
Jabs, DA
Payal, A
Fitzgerald, TD
AF Kempen, John H.
Gewaily, Dina Y.
Newcomb, Craig W.
Liesegang, Teresa L.
Kacmaz, R. Oktay
Levy-Clarke, Grace A.
Nussenblatt, Robert B.
Rosenbaum, James T.
Sen, H. Nida
Suhler, Eric B.
Thorne, Jennifer E.
Foster, C. Stephen
Jabs, Douglas A.
Payal, Abhishek
Fitzgerald, Tonetta D.
CA Systemic Immunosuppressive Therapy
TI Remission of Intermediate Uveitis: Incidence and Predictive Factors
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID PARS-PLANA VITRECTOMY; OCULAR INFLAMMATORY DISEASES; CLINICAL-FEATURES;
PLANITIS; THERAPY; PANUVEITIS; POSTERIOR; OUTCOMES; RISK; EYE
AB PURPOSE: To evaluate the incidence of remission among patients with intermediate uveitis; to identify factors potentially predictive of remission.
DESIGN: Retrospective cohort study.
METHODS: Involved eyes of patients with primary noninfectious intermediate uveitis at 4 academic ocular inflammation subspecialty practices, followed sufficiently long to meet the remission outcome definition, were studied retrospectively by standardized chart review data. Remission of intermediate uveitis was defined as a lack of inflammatory activity at >= 2 visits spanning >= 90 days in the absence of any corticosteroid or immunosuppressant medications. Factors potentially predictive of intermediate uveitis remission were evaluated using survival analysis.
RESULTS: Among 849 eyes (of 510 patients) with intermediate uveitis followed over 1934 eye-years, the incidence of intermediate uveitis remission was 8.6/100 eye-years (95% confidence interval [CI], 7.4-10.1). Factors predictive of disease remission included prior pars plana vitrectomy (PPV) (hazard ratio [HR] [vs no PPV] = 2.39; 95% CI, 1.42-4.00), diagnosis of intermediate uveitis within the last year (HR [vs diagnosis >5 years ago] = 3.82; 95% CI, 1.91-7.63), age >= 45 years (HR [vs age <45 years] = 1.79; 95% CI, 1.03-3.11), female sex (HR = 1.61; 95% CI, 1.04-2.49), and Hispanic race/ethnicity (HR [vs white race] = 2.81; 95% CI, 1.23-6.41). Presence/absence of a systemic inflammatory disease, laterality of uveitis, and smoking status, were not associated with differential incidence.
CONCLUSIONS: Our results suggest that intermediate uveitis is a chronic disease with an overall low rate of remission. Recently diagnosed patients and older, female, and Hispanic patients were more likely to remit. With regard to management, pars plana vitrectomy was associated with increased probability of remission. (C) 2016 by Elsevier Inc. All rights reserved.
C1 [Kempen, John H.; Gewaily, Dina Y.; Payal, Abhishek; Fitzgerald, Tonetta D.] Univ Penn, Perelman Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Kempen, John H.; Newcomb, Craig W.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Kempen, John H.; Newcomb, Craig W.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Gewaily, Dina Y.] Deglin & Greene Retinal Ctr, Wynnewood, PA USA.
[Liesegang, Teresa L.; Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA.
[Rosenbaum, James T.; Payal, Abhishek] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Waltham, MA USA.
[Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Dublin, Ireland.
[Levy-Clarke, Grace A.; Nussenblatt, Robert B.; Sen, H. Nida] NEI, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA.
[Levy-Clarke, Grace A.] Tampa Bay Uveitis Ctr, Tampa, FL USA.
[Rosenbaum, James T.] Devers Eye Inst, Portland, OR USA.
[Suhler, Eric B.; Payal, Abhishek] Portland VA Med Ctr, Portland, OR USA.
[Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA.
[Thorne, Jennifer E.; Jabs, Douglas A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Ophthalmol, New York, NY USA.
[Jabs, Douglas A.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
RP Kempen, JH (reprint author), Univ Penn, Dept Ophthalmol, Ctr Prevent Ophthalmol & Biostat, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM john.kempen@uphs.upenn.edu
OI Payal, Abhishek/0000-0002-4484-8279
FU NATIONAL EYE INSTITUTE (BETHESDA, MD, USA) [EY014943]; Research to
Prevent Blindness (New York, NY, USA); Paul and Evanina Mackall
Foundation (New York, NY, USA); Lois Pope Life Foundation (New York, NY,
USA); Veteran's Affairs Administration (Washington, DC, USA); National
Eye Institute; Research to Prevent Blindness
FX SUPPORTED PRIMARILY BY NATIONAL EYE INSTITUTE (BETHESDA, MD, USA) GRANT
EY014943 (JOHN H. Kempen). Additional support was provided by Research
to Prevent Blindness (New York, NY, USA), the Paul and Evanina Mackall
Foundation (New York, NY, USA), and the Lois Pope Life Foundation (New
York, NY, USA). During the course of the study, John H. Kempen was a
Research to Prevent Blindness James S. Adams Special Scholar Award
recipient, Jennifer E. Thorne was a Research to Prevent Blindness
Harrington Special Scholar Award recipient, and Douglas A. Jabs and
James T. Rosenbaum were Research to Prevent Blindness Senior Scientific
Investigator Award recipients. Eric B. Suhler receives support from the
Veteran's Affairs Administration (Washington, DC, USA). Grace A.
Levy-Clarke was previously supported by and Robert B. Nussenblatt and H.
Nida Sen continue to be supported by intramural funds of the National
Eye Institute. The funding organizations had no role in the design or
conduct of this research.
NR 34
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD APR
PY 2016
VL 164
BP 110
EP 117
DI 10.1016/j.ajo.2015.12.034
PG 8
WC Ophthalmology
SC Ophthalmology
GA DI7CS
UT WOS:000373657300014
PM 26772874
ER
PT J
AU Gao, S
Jakobs, TC
AF Gao, Shan
Jakobs, Tatjana C.
TI Mice Homozygous for a Deletion in the Glaucoma Susceptibility Locus INK4
Show Increased Vulnerability of Retinal Ganglion Cells to Elevated
Intraocular Pressure
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID OPEN-ANGLE GLAUCOMA; OPTIC-NERVE HEAD; GENOME-WIDE ASSOCIATION; INDUCED
OCULAR HYPERTENSION; MOUSE MODEL; NONCODING RNA; AQUEOUS-HUMOR;
TGF-BETA; COMMON VARIANTS; GENE-EXPRESSION
AB A genomic region Located on chromosome 9p21 is associated with primary open-angle glaucoma and normal tension glaucoma in genome-wide association studies. The genomic region contains the gene for a Long noncoding RNA called CDKN2B-AS, two genes that code for cyclin-dependent kinase inhibitors 2A and 2B (CDKN2A/p16(INK4A) and CDKN2B/p15(INK4B)) and an additional protein (p14(ARF)). We used a trans genic mouse model in which 70 kb of murine chromosome 4, syntenic to human chromosome 9p21, are deleted to study whether this deletion leads to a discernible phenotype in ocular structures implicated in glaucoma. Homozygous mice of this strain were previously reported to show persistent hyperplastic primary vitreous. Fundus photography and optical coherence tomography confirmed that finding but showed no abnormalities for heterozygous mice. Optokinetic response, eletroretinogram, and histology indicated that the heterozygous and mutant retinas were normal functionally and morphologically, whereas glial cells were activated in the retina and optic nerve head of mutant eyes. In quantitative PCR, CDKN2B expression was reduced by approximately 50% in the heterozygous mice and by 90% in the homozygous mice, which suggested that the CDKN2B knock down had no deleterious consequences for the retina under normal conditions. However, compared with wild-type and heterozygous animals, the homozygous mice are more vulnerable to retinal ganglion cell loss in response to elevated intraocular pressure.
C1 [Gao, Shan] Xi An Jiao Tong Univ, Hlth Sci Ctr, Affiliated Hosp 1, Dept Ophthalmol, Xian 710049, Shaanxi, Peoples R China.
[Gao, Shan; Jakobs, Tatjana C.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Schepens Eye Res Inst, Boston, MA USA.
RP Jakobs, TC (reprint author), Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA.
EM tatjana_jakobs@meei.harvard.edu
OI Jakobs, Tatjana/0000-0002-8104-9206
FU NIH [R01EY019703, R01EY022092, SP30EY003790-34]; Chinese Scholarship
Council; Massachusetts Lions Eye Research Fund; Ellison Foundation
FX Supported by NIH grants R01EY019703 and R01EY022092, a grant from the
Chinese Scholarship Council, and grants from the Massachusetts Lions Eye
Research Fund and the Ellison Foundation. The morphology core facility
at the Massachusetts Eye and Ear Infirmary/Schepens Eye Research
Institute is supported by the NIH core grant for vision research
SP30EY003790-34.
NR 99
TC 1
Z9 1
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD APR
PY 2016
VL 186
IS 4
BP 985
EP 1005
DI 10.1016/j.ajpath.2015.11.026
PG 21
WC Pathology
SC Pathology
GA DI3QP
UT WOS:000373413900022
PM 26883755
ER
PT J
AU Shahrabi-Farahani, S
Gallottini, M
Martins, F
Li, E
Mudge, DR
Nakayama, H
Hida, K
Panigrahy, D
D'Amore, PA
Bielenberg, DR
AF Shahrabi-Farahani, Shokoufeh
Gallottini, Marina
Martins, Fabiana
Li, Erik
Mudge, Dayna R.
Nakayama, Hironao
Hida, Kyoko
Panigrahy, Dipak
D'Amore, Patricia A.
Bielenberg, Diane R.
TI Neuropilin 1 Receptor Is Up-Regulated in Dysplastic Epithelium and Oral
Squamous Cell Carcinoma
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; SEMAPHORIN 3A; TUMOR-CELLS; PROSTATE-CANCER;
UNITED-STATES; SKIN-CANCER; LYMPH-NODE; EXPRESSION; ANGIOGENESIS;
IDENTIFICATION
AB Neuropilins are receptors for disparate ligands, including proangiogenic factors such as vascular endothelial growth factor and inhibitory class 3 semaphorin (SEMA3) family members. Differentiated cells in skin epithelium and cutaneous squamous ceLL carcinoma highly express the neuropilin-1 (NRP1) receptor. We examined the expression of NRP1 in human and mouse oral mucosa. NRP1 was significantly up-regulated in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). NRP1 receptor localized to the outer suprabasal epithelial layers in normal tongue, an expression pattern similar to the normal skin epidermis. However, dysplastic tongue epithelium and OSCC up regulated NRP1 in basal and proliferating epithelial layers, a profile unseen in cutaneous squamous cell carcinoma. NRP1 up-regulation is observed in a mouse carcinogen-induced OSCC model and in human tongue OSCC biopsies. Human OSCC cell Lines express NRP1 protein in vitro and in mouse tongue xenografts. Sites of capillary infiltration into orthotopic OSCC tumors correlate with high NRP1 expression. HSC3 xenografts, which express the highest NRP1 Levels of the cell lines examined, showed massive intratumoral lymphangiogenesis. SEMA3A inhibited OSCC cell migration, suggesting that the NRP1 receptor was bioactive in OSCC. In conclusion, NRP1 is regulated in the oral epithelium and is selectively up-regulated during epithelial dysplasia. NRP1 may function as a reservoir to sequester proangiogenic ligands within the neoplastic compartment, thereby recruiting neovessels toward tumor cells.
C1 [Shahrabi-Farahani, Shokoufeh; Li, Erik; Nakayama, Hironao; Bielenberg, Diane R.] Boston Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA.
[Gallottini, Marina; Martins, Fabiana] Univ Sao Paulo, Dept Stomatol, Sch Dent, BR-05508 Sao Paulo, Brazil.
[Mudge, Dayna R.; Panigrahy, Dipak] Beth Israel Deaconess Med Ctr, Ctr Vasc Biol Res, Boston, MA USA.
[Nakayama, Hironao; Bielenberg, Diane R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Panigrahy, Dipak] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA.
[D'Amore, Patricia A.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA.
[Hida, Kyoko] Hokkaido Univ, Inst Med Genet, Vasc Biol, Sapporo, Hokkaido, Japan.
[D'Amore, Patricia A.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Bielenberg, DR (reprint author), Boston Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
EM bielenberg@childrens.harvard.edu
RI gallottini, marina/B-8893-2011
OI gallottini, marina/0000-0001-6071-5110
FU Vascular Biology Program at Boston Children's Hospital; NIH National
Cancer Institute; National Eye Institute [K01CA118732, R21CA155728,
R01CA148633, R01EY015435]; L-Core, Center for Oral Health Research,
Medical University of South Carolina - NIH National Institute of General
Medical Sciences [P30GM103331]
FX Supported by the Vascular Biology Program at Boston Children's Hospital
and NIH National Cancer Institute and National Eye Institute grants
K01CA118732 and R21CA155728 (D.R.B.), R01CA148633 (D.P.), and
R01EY015435 (P.A.D.). Generation and production of the murine oral
cancer tissue microarray was supported in part by the L-Core, Center for
Oral Health Research, Medical University of South Carolina, funded by
NIH National Institute of General Medical Sciences grant P30GM103331.
NR 54
TC 1
Z9 1
U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD APR
PY 2016
VL 186
IS 4
BP 1055
EP 1064
DI 10.1016/j.ajpath.2015.11.021
PG 10
WC Pathology
SC Pathology
GA DI3QP
UT WOS:000373413900028
PM 26877262
ER
PT J
AU Capurso, NA
Petrakis, I
AF Capurso, Noah A.
Petrakis, Ismene
TI Dyslipidemia associated with heavy alcohol use
SO AMERICAN JOURNAL ON ADDICTIONS
LA English
DT Article
ID CORONARY-HEART-DISEASE; SEVERE HYPERTRIGLYCERIDEMIA; LIPOPROTEIN-LIPASE;
RISK; CONSUMPTION; MEN; MORTALITY; DRINKING
AB Background and ObjectivesAlcohol has many effects on lipid metabolism and has been associated with elevated triglycerides. The purpose of this paper is to report a case of globally dysregulated lipids secondary to alcohol use and to describe the natural history of this phenomenon after drinking cessation.
MethodsWe present a case of an otherwise healthy patient (N=1) who was admitted to our facility for alcohol detoxification and found to have extreme lipid dysregulation. He was treated with benzodiazepines for alcohol withdrawal but no hypolipidemic agents were given.
ResultsLipid indices self-corrected and were found to be normal following just several weeks of sobriety in the absence of treatment with any hypolipidemic agents.
DiscussionThe literature regarding the effects of alcohol on lipid metabolism is briefly reviewed followed by a discussion of how these findings might apply to this patient in particular as well as implications for broader clinical practice.
Conclusion and Scientific SignificanceAlcohol has the ability to dysregulate several lipid indices in addition to elevating triglycerides. The rapid resolution of dyslipidemia suggests that additional treatment may not be necessary for patients who are able to abstain from alcohol but that hypolipidemic agents may be indicated for those patients who continue to drink. Additionally, clinicians should consider checking lipid panels in patients who present with alcohol intoxication and are found to have other laboratory abnormalites or those who have risk factors for hyperlipidemia. (Am J Addict 2016;25:188-190)
C1 [Capurso, Noah A.; Petrakis, Ismene] Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA.
[Petrakis, Ismene] VA Connecticut Healthcare Syst, US Dept Vet Affairs, West Haven, CT USA.
RP Capurso, NA (reprint author), Yale Univ, Sch Med, Dept Psychiat, 300 George St,Suite 901, New Haven, CT 06511 USA.
EM noah.capurso@yale.edu
NR 19
TC 0
Z9 0
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1055-0496
EI 1521-0391
J9 AM J ADDICTION
JI Am. J. Addict.
PD APR
PY 2016
VL 25
IS 3
BP 188
EP 190
DI 10.1111/ajad.12347
PG 3
WC Substance Abuse
SC Substance Abuse
GA DI5UA
UT WOS:000373564800002
PM 26991470
ER
PT J
AU Freitas, CRD
Malbouisson, LMS
Benicio, A
Negri, EM
Bini, FM
Massoco, CO
Otsuki, DA
Melo, MFV
Carmona, MJC
AF da Costa Freitas, Claudia Regina
Sa Malbouisson, Luiz Marcelo
Benicio, Anderson
Negri, Elnara Marcia
Bini, Filipe Minussi
Massoco, Cristina Oliveira
Otsuki, Denise Aya
Vidal Melo, Marcos Francisco
Carvalho Carmona, Maria Jose
TI Lung Perfusion and Ventilation During Cardiopulmonary Bypass Reduces
Early Structural Damage to Pulmonary Parenchyma
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID MECHANICAL VENTILATION; INFLAMMATORY RESPONSE; GENERAL-ANESTHESIA;
ABDOMINAL-SURGERY; TIDAL-VOLUME; INJURY; ATELECTASIS; DYSFUNCTION;
HYPOTHERMIA; HYPOXEMIA
AB BACKGROUND: It is unclear whether maintaining pulmonary perfusion and ventilation during cardiopulmonary bypass (CPB) reduces pulmonary inflammatory tissue injury compared with standard CPB where the lungs are not ventilated and are minimally perfused. In this study, we tested the hypothesis that maintenance of lung perfusion and ventilation during CPB decreases regional lung inflammation, which may result in less pulmonary structural damage.
METHODS: Twenty-seven pigs were randomly allocated into a control group only submitted to sternotomy (n = 8), a standard CPB group (n = 9), or a lung perfusion group (n = 10), in which lung perfusion and ventilation were maintained during CPB. Hemodynamics, gas exchanges, respiratory mechanics, and systemic interleukins (ILs) were determined at baseline (T0), at the end of 90 minutes of CPB (T90), and 180 minutes after CPB (T180). Bronchoalveolar lavage (BAL) ILs were obtained at T0 and T180. Dorsal and ventral left lung tissue samples were examined for optical and electron microscopy.
RESULTS: At T90, there was a transient reduction in Pao(2)/Fio(2) in CPB (126 64 mm Hg) compared with the control and lung perfusion groups (296 +/- 46 and 244 +/- 57 mm Hg; P < 0.001), returning to baseline at T180. Serum ILs were not different among the groups throughout the study, whereas there were significant increases in BAL IL-6 (P < 0.001), IL-8 (P < 0.001), and IL-10 (P < 0.001) in both CPB and lung perfusion groups compared with the control group. Polymorphonuclear counts within the lung tissue were smaller in the lung perfusion group than in the CPB group (P = 0.006). Electron microscopy demonstrated extrusion of surfactant vesicles into the alveolar spaces and thickening of the alveolar septa in the CPB group, whereas alveolar and capillary histoarchitecture was better preserved in the lung perfusion group.
CONCLUSIONS: Maintenance of lung perfusion and ventilation during CPB attenuated early histologic signs of pulmonary inflammation and injury compared with standard CPB. Although increased compared with control animals, there were no differences in serum or BAL IL in animals receiving lung ventilation and perfusion during CPB compared with standard CPB.
C1 [da Costa Freitas, Claudia Regina; Sa Malbouisson, Luiz Marcelo; Bini, Filipe Minussi; Otsuki, Denise Aya; Carvalho Carmona, Maria Jose] Univ Sao Paulo, Discipline Anesthesiol, LIM Lab Anesthesiol 8, Fac Med, Sao Paulo, Brazil.
[Benicio, Anderson] Univ Sao Paulo, Dept Cardiothorac Surg, Inst Coracao, Fac Med,Hosp Clin, Sao Paulo, Brazil.
[Negri, Elnara Marcia] Univ Sao Paulo, Dept Pathol, Fac Med, Sao Paulo, Brazil.
[Massoco, Cristina Oliveira] Univ Sao Paulo, Dept Vet Pathol, Fac Med Vet, Sao Paulo, Brazil.
[Vidal Melo, Marcos Francisco] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA.
RP Carmona, MJC (reprint author), Ave Dr Eneas de Carvalho Aguiar 155,8 Andar, BR-05403001 Sao Paulo, SP, Brazil.
EM maria.carmona@incor.usp.br
RI Carmona, Maria Jose/G-3653-2014; massoco, cristina/N-2634-2015
OI Carmona, Maria Jose/0000-0002-3031-2924; massoco,
cristina/0000-0001-8030-0609
FU Brazilian National Council for Scientific and Technological Development
(CNPQ) [478485/2004-2]
FX This study was supported by grants from Brazilian National Council for
Scientific and Technological Development (CNPQ; grant number
478485/2004-2).
NR 43
TC 1
Z9 1
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2016
VL 122
IS 4
BP 943
EP 952
DI 10.1213/ANE.0000000000001118
PG 10
WC Anesthesiology
SC Anesthesiology
GA DG8OH
UT WOS:000372343000003
PM 26991612
ER
PT J
AU Eisenach, JC
Warner, DS
Houle, TT
AF Eisenach, James C.
Warner, David S.
Houle, Timothy T.
TI Reporting of Preclinical Research in Anesthesiology Transparency and
Enforcement
SO ANESTHESIOLOGY
LA English
DT Editorial Material
C1 [Eisenach, James C.] Wake Forest Sch Med, Dept Anesthesiol, Winston Salem, NC 27109 USA.
[Warner, David S.] Duke Univ, Sch Med, Dept Anesthesiol, Durham, NC USA.
[Houle, Timothy T.] Massachusetts Gen Hosp, Dept Anaesthesiol & Crit Care, Boston, MA 02114 USA.
RP Eisenach, JC (reprint author), Wake Forest Sch Med, Dept Anesthesiol, Winston Salem, NC 27109 USA.
EM editor-in-chief@anesthesiology.org
FU NIGMS NIH HHS [R37-GM48085, R37 GM048085]
NR 13
TC 2
Z9 2
U1 0
U2 2
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 APR
PY 2016
VL 124
IS 4
BP 763
EP 765
DI 10.1097/ALN.0000000000001044
PG 3
WC Anesthesiology
SC Anesthesiology
GA DI2TO
UT WOS:000373352000008
PM 26845144
ER
PT J
AU Yang, YS
Rivera, AJ
Fortier, CR
Abernathy, JH
AF Yang, Yushi
Rivera, Antonia Joy
Fortier, Christopher R.
Abernathy, James H., III
TI A Human Factors Engineering Study of the Medication Delivery Process
during an Anesthetic Self-filled Syringes versus Prefilled Syringes
SO ANESTHESIOLOGY
LA English
DT Article
ID PATIENT SAFETY; SYSTEMS; CARE; PERFORMANCE; WORKLOAD; QUALITY; DESIGN;
ERRORS
AB Background: Prefilled syringes (PFS) have been recommended by the Anesthesia Patient Safety Foundation. However, aspects in PFS systems compared with self-filled syringes (SFS) systems have never been explored. The aim of this study is to compare system vulnerabilities (SVs) in the two systems and understand the impact of PFS on medication safety and efficiency in the context of anesthesiology medication delivery in operating rooms.
Methods: This study is primarily qualitative research, with a quantitative portion. A work system analysis was conducted to analyze the complicated anesthesia work system using human factors principles and identify SVs. Anesthesia providers were shadowed: (1) during general surgery cases (n = 8) exclusively using SFS and (2) during general surgery cases (n = 9) using all commercially available PFS. A proactive risk assessment focus group was followed to understand the risk of each identified SV.
Results: PFS are superior to SFS in terms of the simplified work processes and the reduced number and associated risk of SVs. Eight SVs were found in the PFS system versus 21 in the SFS system. An SV example with high risk in the SFS system was a medication might need to be drawn-up during surgery while completing other requests simultaneously. This SV added cognitive complexity during anesthesiology medication delivery. However, it did not exist in the PFS system.
Conclusions: The inclusion of PFS into anesthesiology medication delivery has the potential to improve system safety and work efficiency. However, there were still opportunities for further improvement by addressing the remaining SVs and newly introduced complexity.
C1 [Yang, Yushi] Clemson Univ, Dept Ind Engn, Clemson, SC USA.
[Rivera, Antonia Joy] Childrens Hosp Wisconsin, Dept Informat Management Serv, Milwaukee, WI 53201 USA.
[Fortier, Christopher R.] Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA.
[Abernathy, James H., III] Med Univ S Carolina, Dept Anesthesia & Perioperat Med, Ashley River Tower, Charleston, SC 29425 USA.
RP Abernathy, JH (reprint author), Med Univ S Carolina, Dept Anesthesia & Perioperat Med, Ashley River Tower, Charleston, SC 29425 USA.
EM abernatj@musc.edu
FU Pharmedium (Lake Forest, Illinois)
FX Pharmedium (Lake Forest, Illinois) provided support in the form of an
unrestricted grant to the Medical University of South Carolina
(Charleston, South Carolina) to cover the costs of performing the study
and analyzing the results. This funding came at the request of our group
of researchers.
NR 33
TC 1
Z9 1
U1 5
U2 7
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 APR
PY 2016
VL 124
IS 4
BP 795
EP 803
DI 10.1097/ALN.0000000000001040
PG 9
WC Anesthesiology
SC Anesthesiology
GA DI2TO
UT WOS:000373352000013
PM 26845139
ER
PT J
AU Ladha, KS
Patorno, E
Huybrechts, KF
Liu, J
Rathmell, JP
Bateman, BT
AF Ladha, Karim S.
Patorno, Elisabetta
Huybrechts, Krista F.
Liu, Jun
Rathmell, James P.
Bateman, Brian T.
TI Variations in the Use of Perioperative Multimodal Analgesic Therapy
SO ANESTHESIOLOGY
LA English
DT Article
ID MAJOR NONCARDIAC SURGERY; POSTOPERATIVE PAIN; POSTSURGICAL PAIN; PATIENT
SATISFACTION; SURGICAL-PATIENTS; NATIONAL-SURVEY; ADVERSE EVENTS; OPEN
COLECTOMY; HIP FRACTURE; OUTCOMES
AB Background: Practice guidelines for perioperative pain management recommend that multimodal analgesic therapy should be used for all postsurgical patients. However, the proportion of patients who actually receive this evidence-based approach is unknown. The objective of this study was to describe hospital-level patterns in the utilization of perioperative multimodal analgesia.
Methods: Data for the study were obtained from the Premier Research Database. Patients undergoing below-knee amputation, open lobectomy, total knee arthroplasty, and open colectomy between 2007 and 2014 were included in the analysis. Patients were considered to have multimodal therapy if they received one or more nonopioid analgesic therapies. Mixed-effects logistic regression models were used to estimate the hospital-specific frequency of multimodal therapy use while adjusting for the case mix of patients and hospital characteristics and accounting for random variation.
Results: The cohort consisted of 799,449 patients who underwent a procedure at 1 of 315 hospitals. The mean probability of receiving multimodal therapy was 90.4%, with 95% of the hospitals having a predicted probability between 42.6 and 99.2%. A secondary analysis examined whether patients received two or more nonopioid analgesics, which gave an average predicted probability of 54.2%, with 95% of the hospitals having a predicted probability between 9.3 and 93.2%.
Conclusions: In this large nationwide sample of surgical admissions in the United States, the authors observed tremendous variation in the utilization of multimodal therapy not accounted for by patient or hospital characteristics. Efforts should be made to identify why there are variations in the use of multimodal analgesic therapy and to promote its adoption in appropriate patients.
C1 [Ladha, Karim S.; Patorno, Elisabetta; Huybrechts, Krista F.; Liu, Jun; Bateman, Brian T.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.
[Ladha, Karim S.; Bateman, Brian T.] Harvard Univ, Sch Med, Dept Anesthesiol Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Ladha, Karim S.] Toronto Gen Hosp, Dept Anesthesia, Toronto, ON, Canada.
[Ladha, Karim S.] Univ Toronto, Toronto, ON, Canada.
[Rathmell, James P.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA.
RP Ladha, KS (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.
EM karim.ladha@post.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development of the National Institutes of Health (Bethesda, Maryland)
[K08HD075831]; National Institute of Mental Health [K01MH099141]
FX This study was supported by the Eunice Kennedy Shriver National
Institute of Child Health & Human Development of the National Institutes
of Health (Bethesda, Maryland) under Award Number K08HD075831 (to Dr.
Bateman); a career development grant K01MH099141 from the National
Institute of Mental Health (to Dr. Huybrechts). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health or the National
Institute of Mental Health.
NR 45
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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 APR
PY 2016
VL 124
IS 4
BP 837
EP 845
DI 10.1097/ALN.0000000000001034
PG 9
WC Anesthesiology
SC Anesthesiology
GA DI2TO
UT WOS:000373352000017
PM 26835644
ER
PT J
AU Emery, MJ
Groves, CC
Kruse, TN
Shi, C
Terman, GW
AF Emery, Michael J.
Groves, Chase C.
Kruse, Timothy N.
Shi, Chen
Terman, Gregory W.
TI Ventilation and the Response to Hypercapnia after Morphine in
Opioid-naive and Opioid-tolerant Rats
SO ANESTHESIOLOGY
LA English
DT Article
ID INDUCED RESPIRATORY DEPRESSION; ADMINISTERED MORPHINE;
POSTNATAL-DEVELOPMENT; RECURRENT HYPOXIA; CHRONIC PAIN; RECEPTORS;
SLEEP; OVERDOSE; MECHANISMS; ANALGESIA
AB Background: Opioid-related deaths are a leading cause of accidental death, with most occurring in patients receiving chronic pain therapy. Respiratory arrest is the usual cause of death, but mechanisms increasing that risk with increased length of treatment remain unclear. Repeated administration produces tolerance to opioid analgesia, prompting increased dosing, but depression of ventilation may not gain tolerance to the same degree. This study addresses differences in the degree to which chronic morphine (1) produces tolerance to ventilatory depression versus analgesia and (2) alters the magnitude and time course of ventilatory depression.
Methods: Juvenile rats received subcutaneous morphine for 3 days (n = 116) or vehicle control (n = 119) and were then tested on day 4 following one of a range of morphine doses for (a) analgesia by paw withdraw from heat or (b) respiratory parameters by plethysmography-respirometry.
Results: Rats receiving chronic morphine showed significant tolerance to morphine sedation and analgesia (five times increased ED50). When sedation was achieved for all animals in a dose group (lowest effective doses: opioid-tolerant, 15 mg/kg; opioid-naive, 3 mg/kg), the opioid-tolerant showed similar magnitudes of depressed ventilation (-41.4 7.0%, mean +/- SD) and hypercapnic response (-80.9 +/- 15.7%) as found for morphine-naive (-35.5 +/- 16.9% and -67.7 +/- 15.1%, respectively). Ventilation recovered due to tidal volume without recovery of respiratory rate or hypercapnic sensitivity and more slowly in morphine-tolerant.
Conclusions: In rats, gaining tolerance to morphine analgesia does not reduce ventilatory depression effects when sedated and may inhibit recovery of ventilation.
C1 [Emery, Michael J.; Groves, Chase C.; Kruse, Timothy N.; Shi, Chen; Terman, Gregory W.] Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Emery, Michael J.] Vet Affairs Puget Sound Hlth Care Syst, Pulm & Crit Care Med, Seattle, WA USA.
RP Emery, MJ (reprint author), Univ Washington, Sch Med, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
EM mjemery@u.washington.edu
FU University of Washington Alcohol and Drug Abuse Institute (Seattle,
Washington)
FX This study was supported by the University of Washington Alcohol and
Drug Abuse Institute (Seattle, Washington).
NR 56
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U1 3
U2 4
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 APR
PY 2016
VL 124
IS 4
BP 945
EP 957
DI 10.1097/ALN.0000000000000997
PG 13
WC Anesthesiology
SC Anesthesiology
GA DI2TO
UT WOS:000373352000027
PM 26734964
ER
PT J
AU Datta, M
Via, LE
Chen, W
Baish, JW
Xu, L
Barry, CE
Jain, RK
AF Datta, Meenal
Via, Laura E.
Chen, Wei
Baish, James W.
Xu, Lei
Barry, Clifton E., III
Jain, Rakesh K.
TI Mathematical Model of Oxygen Transport in Tuberculosis Granulomas
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE Diffusion; Mycobacterium tuberculosis; Michaelis-Menten kinetics; Rabbit
model; Pimonidazole
ID MYCOBACTERIUM-BOVIS BCG; AVASCULAR TUMOR-GROWTH; IN-VITRO MODEL;
NONREPLICATING PERSISTENCE; IMMUNE-RESPONSE; HYPOXIA MARKER;
DRUG-DELIVERY; STRATEGIES; PIMONIDAZOLE; VASCULATURE
AB Pulmonary granulomas-the hallmark of Mycobacterium tuberculosis (MTB) infection-are dense cellular lesions that often feature regions of hypoxia and necrosis, partially due to limited transport of oxygen. Low oxygen in granulomas can impair the host immune response, while MTB are able to adapt and persist in hypoxic environments. Here, we used a physiologically based mathematical model of oxygen diffusion and consumption to calculate oxygen profiles within the granuloma, assuming Michaelis-Menten kinetics. An approximate analytical solution-using a priori and newly estimated parameters from experimental data in a rabbit model of tuberculosis-was able to predict the size of hypoxic and necrotic regions in agreement with experimental results from the animal model. Such quantitative understanding of transport limitations can inform future tuberculosis therapeutic strategies that may include adjunct host-directed therapies that facilitate oxygen and drug delivery for more effective treatment.
C1 [Datta, Meenal; Chen, Wei; Xu, Lei; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs, Cox 7,100 Blossom St, Boston, MA 02114 USA.
[Datta, Meenal; Chen, Wei; Xu, Lei; Jain, Rakesh K.] Harvard Univ, Sch Med, Cox 7,100 Blossom St, Boston, MA 02114 USA.
[Datta, Meenal] Tufts Univ, Dept Chem & Biol Engn, Medford, MA 02155 USA.
[Via, Laura E.; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Via, Laura E.; Barry, Clifton E., III] Univ Cape Town, Fac Hlth Sci, Dept Clin Lab Sci, ZA-7701 Cape Town, South Africa.
[Chen, Wei] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Pancreatobiliary Surg, Guangzhou 510080, Guangdong, Peoples R China.
[Baish, James W.] Bucknell Univ, Dept Biomed, Lewisburg, PA 17837 USA.
[Baish, James W.] Bucknell Univ, Dept Mech Engn, Lewisburg, PA 17837 USA.
RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Labs, Cox 7,100 Blossom St, Boston, MA 02114 USA.; Jain, RK (reprint author), Harvard Univ, Sch Med, Cox 7,100 Blossom St, Boston, MA 02114 USA.
EM jain@steele.mgh.harvard.edu
FU Bill and Melinda Gates Foundation; Imperial College; NIH, NIAID
FX We thank Drs. Jerry Meldon and Stephen Matson for their insightful
comments, and Drs. Vasileios Askoxylakis, Dai Fukumura, Giorgio Seano,
Triantafyllos Stylianopoulos, and Joshua Tam for their assistance in
manuscript editing. We would like to acknowledge Kathleen England,
Daniel Schimel, and Danielle Weiner (Tuberculosis Research Section,
Laboratory of Clinical Infectious Disease, National Institutes of
Health/National Institute of Allergy and Infectious Diseases) for their
technical assistance in the previously performed animal studies. Thanks
to Carolyn Smith (Edwin L. Steele Laboratories, Massachusetts General
Hospital/Harvard Medical School) for her support in the
immunohistochemistry studies. This study was supported in part by Grants
from the Bill and Melinda Gates Foundation (to R.K.J.), through the
Grand Challenges in Global Health Program to Douglas Young, Imperial
College (to C.E.B.), and from the Intramural Research Program of the
NIH, NIAID (to C.E.B).
NR 56
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U1 3
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
EI 1573-9686
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD APR
PY 2016
VL 44
IS 4
BP 863
EP 872
DI 10.1007/s10439-015-1415-3
PG 10
WC Engineering, Biomedical
SC Engineering
GA DI8HJ
UT WOS:000373741800003
PM 26253038
ER
PT J
AU MacGillivray, TE
AF MacGillivray, Thomas E.
TI How I Teach Hemi-Arch Replacement
SO ANNALS OF THORACIC SURGERY
LA English
DT Editorial Material
C1 [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA.
RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA.; MacGillivray, TE (reprint author), Massachusetts Gen Hosp, Div Cardiac Surg, 55 Fruit St,Cox 650, Boston, MA 02114 USA.
EM tmacgillivray@partners.org
NR 4
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP 1251
EP 1254
DI 10.1016/j.athoracsur.2016.02.047
PG 4
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700015
PM 27000566
ER
PT J
AU Sihag, S
Kosinski, AS
Gaissert, HA
Wright, CD
Schipper, PH
AF Sihag, Smita
Kosinski, Andrzej S.
Gaissert, Henning A.
Wright, Cameron D.
Schipper, Paul H.
TI Minimally Invasive Versus Open Esophagectomy for Esophageal Cancer: A
Comparison of Early Surgical Outcomes From The Society of Thoracic
Surgeons National Database
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID IVOR-LEWIS ESOPHAGECTOMY; SHORT-TERM OUTCOMES; PERIOPERATIVE OUTCOMES;
VOLUME; MORTALITY; LOBECTOMY
AB Background. Open esophagectomy results in significant morbidity and mortality. Minimally invasive esophagectomy (MIE) has become increasingly popular at specialized centers with the aim of improving perioperative outcomes. Numerous single-institution studies suggest MIE may offer lower short-term morbidity. The two approaches are compared using a large, multi institutional database.
Methods. The Society of Thoracic Surgeons (STS) National Database (v2.081) was queried for all resections performed for esophageal cancer between 2008 and 2011 (n = 3,780). Minimally invasive approaches included both transhiatal (n = 214) and Ivor Lewis (n = 600), and these were compared directly with open transhiatal (n = 1,065) and Ivor Lewis (n = 1,291) procedures, respectively. Thirty-day outcomes were examined using nonparametric statistical testing.
Results. Both open and MIE groups were similar in terms of preoperative risk factors. Morbidity and all cause mortality were equivalent at 62.2% and 3.8%. MIE was associated with longer median procedure times (443.0 versus 312.0 minutes; p < 0.001), but a shorter median length of hospital stay (9.0 versus 10.0 days; p < 0.001). Patients who underwent MIE had higher rates of reoperation (9.9% versus 4.4%; p < 0.001) and empyema (4.1% versus 1.8%; p < 0.001). Open technique led to an increased rate of wound infections (6.3% versus 2.3%; p < 0.001), postoperative transfusion (18.7% versus 14.1%; p = 0.002), and ileus (4.5% versus 2.2%; p = 0.002). Propensity score-matched analysis confirmed these findings. High-and low-volume centers had similar outcomes.
Conclusions. Early results from the STS National Database indicate that MIE is safe, with comparable rates of morbidity and mortality as open technique. Longer procedure times and a higher rate of reoperation following MIE may reflect a learning curve. (C) 2016 by The Society of Thoracic Surgeons
C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA.
Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA.
Duke Clin Res Inst, Durham, NC USA.
Oregon Hlth & Sci Univ, Med Ctr, Dept Cardiothorac Surg, Portland, OR 97201 USA.
RP Sihag, S (reprint author), 55 Fruit St,Blake 1570, Boston, MA 02114 USA.
EM ssihag@partners.org
FU TSFRE Research Fellowship
FX This work is partially supported by a TSFRE Research Fellowship (S.S.).
NR 24
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U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP 1281
EP 1289
DI 10.1016/j.athoracsur.2015.09.095
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700019
PM 26704412
ER
PT J
AU Kozower, BD
O'Brien, SM
Kosinski, AS
Magee, MJ
Dokholyan, R
Jacobs, JP
Shahian, DM
Wright, CD
Fernandez, FG
AF Kozower, Benjamin D.
O'Brien, Sean M.
Kosinski, Andrzej S.
Magee, Mitchell J.
Dokholyan, Rachel
Jacobs, Jeffery P.
Shahian, David M.
Wright, Cameron D.
Fernandez, Felix G.
TI The Society of Thoracic Surgeons Composite Score for Rating Program
Performance for Lobectomy for Lung Cancer
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID MEASUREMENT TASK-FORCE; DATABASE; OUTCOMES; MORTALITY; RESECTION;
QUALITY; RELIABILITY
AB Background. The Society of Thoracic Surgeons (STS) has developed multidimensional composite quality measures for common cardiac surgery procedures. This first composite measure for general thoracic surgery evaluates STS participant performance for lobectomy in lung cancer patients.
Methods. The STS lobectomy composite score is composed of two outcomes: risk-adjusted mortality; and any-or-none, risk-adjusted major complications. General Thoracic Surgery Database data were included from 2011 to 2014 to provide adequate sample size, and 95% Bayesian credible intervals were used to determine "star ratings." The STS participants were also compared with national benchmarks (including non-STS participants) using the National Inpatient Sample. Comparisons of discharge mortality, postoperative length of stay, and percent of stage I lung cancers resected using minimally invasive approaches are not included in star ratings but will be reported to participants in STS feedback reports.
Results. The study population included 20,657 lobectomy patients from 231 participating centers. Operative mortality was 1.5%, major complication rate was 9.6%, and median postoperative length of stay was 4 days. Risk-adjusted mortality and major complication rates varied threefold from highest performing (three-star) to lowest performing (one-star) programs. Approximately 5% of participants were one star, 7% were three-star, and 88% were two-star programs.
Conclusions. The STS has developed the first general thoracic surgery quality composite measure to compare programs performing lobectomy for lung cancer. This measure will be used for quality assessment and provider feedback, and will be made available for voluntary public reporting. (C) 2016 by The Society of Thoracic Surgeons
C1 [Kozower, Benjamin D.] Univ Virginia, Box 800679, Charlottesville, VA 22908 USA.
Duke Clin Res Inst, Durham, NC USA.
Med City Dallas Hosp, Dallas, TX USA.
Johns Hopkins Univ, All Childrens Hosp, St Petersburg, FL USA.
Massachusetts Gen Hosp, Boston, MA 02114 USA.
Emory Univ, Atlanta, GA 30322 USA.
RP Kozower, BD (reprint author), Univ Virginia, Box 800679, Charlottesville, VA 22908 USA.
EM bdk8g@virginia.edu
NR 22
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP 1379
EP 1387
DI 10.1016/j.athoracsur.2015.10.081
PG 9
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700032
PM 26785936
ER
PT J
AU Park, M
Shlipak, MG
Thiessen-Philbrook, H
Garg, AX
Koyner, JL
Coca, SG
Parikh, CR
AF Park, Meyeon
Shlipak, Michael G.
Thiessen-Philbrook, Heather
Garg, Amit X.
Koyner, Jay L.
Coca, Steven G.
Parikh, Chirag R.
CA TRIBE-AKI Consortium
TI Association of Peak Changes in Plasma Cystatin C and Creatinine With
Death After Cardiac Operations
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID GLOMERULAR-FILTRATION-RATE; ACUTE KIDNEY INJURY; SERUM CREATININE;
CARDIOTHORACIC SURGERY; RISK; BIOMARKERS; EQUATION; FAILURE; MARKER
AB Background. Acute kidney injury is a risk factor for death in cardiac surgical patients. Plasma cystatin C and creatinine have different temporal profiles in the postoperative setting, but the associations of simultaneous changes in both filtration markers compared with change in only one marker with prognosis after hospital discharge are not well described.
Methods. This is a longitudinal study of 1,199 high-risk adult cardiac surgical patients in the TRIBE-AM (Translational Research Investigating Biomarker Endpoints for Acute Kidney Injury) Consortium who survived hospitalization. We examined in-hospital peak changes of cystatin C and creatinine in the 3 days after cardiac operations. We evaluated associations of these filtration markers with death, adjusting for demographics, operative characteristics, medical comorbidities, preoperative estimated glomerular filtration rate, preoperative urinary albumin-to-creatinine ratio, and site.
Results. During the first 3 days of hospitalization, nearly twice as many patients had a 25% or higher rise in creatinine (30%) compared with a 25% or higher peak rise in cystatin C (15%). The risk of death was higher in those with elevations in cystatin C (adjusted hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.4 to 2.37) or creatinine (adjusted HR, 1.90; 95% CI, 1.32 to 2.72) compared with patients who experienced a postoperative decrease in either filtration marker. Patients who had simultaneous elevations of 25% or higher in cystatin C and creatinine were at similar adjusted risk for 3-year mortality (HR, 1.79; 95% CI, 1.03 to 3.1) as those with a 25% or higher increase in cystatin C alone (HR, 2.2; 95% CI, 1.09 to 4.47).
Conclusions. Elevations in creatinine postoperatively are more common than elevations in cystatin C. However, elevations in cystatin C appeared to be associated with a higher risk of death after hospital discharge. (C) 2016 by The Society of Thoracic Surgeons
C1 Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
Univ Calif San Francisco, Div Gen Internal Med, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
Univ Western Ontario, Dept Med, Div Nephrol, London, ON, Canada.
Inst Clin Evaluat Sci, Toronto, ON, Canada.
Univ Chicago, Dept Med, Nephrol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA.
Mt Sinai Sch Med, Div Nephrol, New York, NY USA.
Yale Univ, Sch Med, Nephrol Sect, New Haven, CT USA.
RP Park, M (reprint author), 521 Parnassus Ave,C443,Box 0532, San Francisco, CA 94143 USA.
EM meyeon.park@ucsf.edu
FU Institute for Clinical Evaluative Sciences; Ontario Ministry of Health
and Long-Term Care; National Institutes of Health (NIH) [R01-HL085757];
NIH National Institute of Diabetes and Digestive and Kidney Diseases
[K23-DK099238]; Adam Linton Chair in Kidney Health Analytics; NIH
[K23-DK081616, K23-DK080132, K24-DK090203, U01-DK082185]; Abbott
Diagnostics; Sekisui Diagnostics Inc
FX This study was supported by the Institute for Clinical Evaluative
Sciences, funded by an annual grant from the Ontario Ministry of Health
and Long-Term Care. The opinions, results, and conclusions reported in
this paper are those of the authors and are independent from the funding
sources. No endorsement by Institute for Clinical Evaluative Sciences or
the Ontario Ministry of Health and Long-Term Care is intended or should
be inferred. This study was supported by National Institutes of Health
(NIH) (R01-HL085757 C.R.P.) to fund the TRIBE-AKI Consortium to study
novel biomarkers of AKI in cardiac surgery. Other support: NIH National
Institute of Diabetes and Digestive and Kidney Diseases grant
K23-DK099238 (M.P.), Adam Linton Chair in Kidney Health Analytics
(A.X.G.), and NIH K23-DK081616 (J.L.K.), K23-DK080132 (S.G.C.), and
K24-DK090203 (C.R.P.). S.G.C., A.X.G., and C.R.P. are also members of
the NIH-sponsored Assess, Serial Evaluation, and Subsequent Sequelae in
Acute Kidney Injury Consortium (U01-DK082185). The granting agencies,
Abbott Diagnostics and Sekisui Diagnostics Inc, did not participate in
the design or conduct of the study, collection, management, analysis,
interpretation of data, or preparation, review, or approval of the
manuscript.
NR 21
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U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP 1395
EP 1401
DI 10.1016/j.athoracsur.2015.12.010
PG 7
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700034
PM 26921980
ER
PT J
AU Allen, MS
Calhoon, JH
Fullerton, D
Shemin, R
Naunheim, K
Verrier, E
Doty, J
Mathisen, DJ
AF Allen, Mark S.
Calhoon, John H.
Fullerton, David
Shemin, Richard
Naunheim, Keith
Verrier, Edward
Doty, John
Mathisen, Douglas J.
TI Outcome of the Joint Council of Thoracic Surgery Education's Early
Review Course Project
SO ANNALS OF THORACIC SURGERY
LA English
DT Article
ID PERFORMANCE
AB Background. The Joint Council on Thoracic Surgical Education was formed in 2008 to improve cardiothoracic education. Resident learning has been a concern as reflected in declining passing rates on the American Board of Thoracic Surgery examinations. The Joint Council on Thoracic Surgical Education piloted a program to determine whether early exposure to a cardiothoracic curriculum through participation in a board review course would improve learning. The purpose of this paper is to report the results of this project.
Methods. Residents from the incoming classes of traditional 5-2 or 5-3 cardiothoracic training programs were randomly selected to attend a 3-day board review course (University of Utah) in September of their first year. For the 2012 and 2013 classes of cardiothoracic residents, we asked all incoming residents to take the prior spring in-training examination in July of their first year and then take the in-training examination in the spring of their first year. We combined the results of the incoming class of 2012 and 2013 and analyzed the results.
Results. There were 171 residents who participated in either 2012 or 2013. There were 38 residents (78.9% were men) who attended the board review course and 133 (79.7% men) who did not. Questionnaires completed by the program directors and the residents who took the review course showed a favorable opinion of the program. The number of correct answers on the in-training examination, the percentage correct, and the percentile rank score increased more for the residents who took the review course, but was not statistically significant. When only the general thoracic surgery questions were analyzed, there was a statistically significant increase in the rank change between residents who attended the review course and residents who did not (8.4% increase versus 2.0% decrease, respectively; p = 0.042, Student t test).
Conclusions. This pilot study established for the first time the baseline level of knowledge of incoming residents assessed by the in-training examination. Participation in a board review type course early in the residency training program may increase learning by cardiothoracic residents, but there was not a clear statistical difference between the two groups. The program was viewed as favorable by both the participating residents and the program directors. (C) 2016 by The Society of Thoracic Surgeons
C1 Mayo Clin, Dept Surg, Div Gen Thorac Surg, Rochester, MN USA.
Univ Texas Hlth Sci Ctr San Antonio, Dept Cardiothorac Surg, San Antonio, TX 78229 USA.
Univ Colorado Denver, Aurora, CO USA.
Univ Calif Los Angeles, Div Cardiac Surg, Los Angeles, CA USA.
St Louis Univ, Hlth Sci Ctr, Div Thorac Surg, St Louis, MO 63103 USA.
Univ Washington, Div Cardiothorac Surg, Seattle, WA 98195 USA.
Intermt Med Ctr, Murray, UT USA.
Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
RP Allen, MS (reprint author), Mayo Clin, Div Gen Thorac Surg, 200 First St SW, Rochester, MN 55905 USA.
EM allen.mark@mayo.edu
FU Joint Council on Thoracic Surgical Education
FX This study was supported by a grant from the Joint Council on Thoracic
Surgical Education.
NR 8
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U1 1
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PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP 1564
EP 1568
DI 10.1016/j.athoracsur.2015.11.027
PG 5
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700057
PM 26897319
ER
PT J
AU Naqvi, M
Muniappan, A
Modest, V
Mathisen, DJ
Madapu, M
Bryant, A
Kaimal, A
AF Naqvi, Mariam
Muniappan, Ashok
Modest, Vicki
Mathisen, Douglas J.
Madapu, Manokanth
Bryant, Allison
Kaimal, Anjali
TI Tracheal Resection for Symptomatic Tracheal Stenosis During Pregnancy
SO ANNALS OF THORACIC SURGERY
LA English
DT Editorial Material
ID PARTURIENT
AB A 31-year-old multipara was diagnosed with tracheal stenosis that developed after intubation after an intentional benzodiazepine overdose in the first trimester of pregnancy. Tracheal dilations only temporarily improved her dyspnea at rest. A definitive repair by tracheal resection and reconstruction was performed at 28 weeks' gestation. Her symptoms resolved, and she delivered vaginally at 36 weeks' gestation after spontaneous labor. (C) 2016 by The Society of Thoracic Surgeons
C1 Massachusetts Gen Hosp, Dept Surg, Dept Obstet & Gynecol, Div Maternal Fetal Med,Div Thorac Surg, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA.
RP Naqvi, M (reprint author), 55 Fruit St,Founders 460, Boston, MA 02114 USA.
EM mnaqvi@partners.org
NR 8
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 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP 1589
EP 1591
DI 10.1016/j.athoracsur.2015.05.134
PG 4
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700068
PM 27000585
ER
PT J
AU Sng, GGR
Wright, CD
AF Sng, Gerald G. R.
Wright, Cameron D.
TI An Aneurysmal Abdominal Aortic Branch Supplying an Intralobar Pulmonary
Sequestration
SO ANNALS OF THORACIC SURGERY
LA English
DT Editorial Material
C1 [Sng, Gerald G. R.] Natl Univ Singapore, Yong Loo Lin Sch Med, 1E Kent Ridge Rd, Singapore 119228, Singapore.
Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA.
RP Sng, GGR (reprint author), Natl Univ Singapore, Yong Loo Lin Sch Med, 1E Kent Ridge Rd, Singapore 119228, Singapore.
EM geraldsng@gmail.com
NR 0
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 0003-4975
EI 1552-6259
J9 ANN THORAC SURG
JI Ann. Thorac. Surg.
PD APR
PY 2016
VL 101
IS 4
BP E123
EP E123
DI 10.1016/j.athoracsur.2015.11.012
PG 1
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery
SC Cardiovascular System & Cardiology; Respiratory System; Surgery
GA DH1CT
UT WOS:000372522700009
PM 27000616
ER
PT J
AU Sholl, LM
Aisner, DL
Allen, TC
Beasley, MB
Borczuk, AC
Cagle, PT
Capelozzi, V
Dacic, S
Hariri, L
Kerr, KM
Lantuejoul, S
Mino-Kenudson, M
Raparia, K
Rekhtman, N
Roy-Chowdhuri, S
Thunnissen, E
Tsao, MS
Yatabe, Y
AF Sholl, Lynette M.
Aisner, Dara L.
Allen, Timothy Craig
Beasley, Mary Beth
Borczuk, Alain C.
Cagle, Philip T.
Capelozzi, Vera
Dacic, Sanja
Hariri, Lida
Kerr, Keith M.
Lantuejoul, Sylvie
Mino-Kenudson, Mari
Raparia, Kirtee
Rekhtman, Natasha
Roy-Chowdhuri, Sinchita
Thunnissen, Eric
Tsao, Ming Sound
Yatabe, Yasushi
CA Pulm Pathology Soc
TI Programmed Death Ligand-1 Immunohistochemistry-A New Challenge for
Pathologists A Perspective From Members of the Pulmonary Pathology
Society
SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE
LA English
DT Article
ID CELL LUNG-CANCER; PD-1 BLOCKADE; ANTIBODY; IMMUNOTHERAPY; EXPRESSION;
NIVOLUMAB; DOCETAXEL
AB The binding of programmed death ligand-1 and ligand-2 (PD-L1 and PD-L2) to PD-1 blocks T-cell-mediated immune response to tumor. Antibodies that target programmed death receptor-1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non-small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non-small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay-one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.
C1 [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA.
[Sholl, Lynette M.; Hariri, Lida; Mino-Kenudson, Mari] Harvard Univ, Sch Med, Boston, MA USA.
[Aisner, Dara L.] Univ Colorado, Ctr Canc, Dept Pathol, Denver, CO 80262 USA.
[Allen, Timothy Craig] Univ Texas Med Branch, Dept Pathol, 301 Univ Blvd, Galveston, TX 77555 USA.
[Beasley, Mary Beth] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA.
[Borczuk, Alain C.; Cagle, Philip T.] Weill Cornell Med Coll, Dept Pathol, New York, NY USA.
[Cagle, Philip T.] Houston Methodist Hosp, Dept Pathol & Genom Med, Houston, TX USA.
[Capelozzi, Vera] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo, Brazil.
[Dacic, Sanja] Univ Pittsburgh, Med Ctr, Dept Pathol, Pittsburgh, PA USA.
[Hariri, Lida; Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Kerr, Keith M.] Univ Aberdeen, Sch Med, Dept Pathol, Aberdeen AB9 2ZD, Scotland.
[Kerr, Keith M.] Aberdeen Royal Infirm, Aberdeen, Scotland.
[Lantuejoul, Sylvie] Ctr Leon Berard, Dept Biopathol, F-69373 Lyon, France.
[Lantuejoul, Sylvie] Univ Grenoble 1, Inst Bonniot A, INSERM, U 823, Grenoble, France.
[Raparia, Kirtee] Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Rekhtman, Natasha] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
[Roy-Chowdhuri, Sinchita] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Thunnissen, Eric] Vrije Univ Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands.
[Tsao, Ming Sound] Princess Margaret Canc Ctr, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada.
[Tsao, Ming Sound] Univ Toronto, Toronto, ON, Canada.
[Yatabe, Yasushi] Aichi Canc Ctr, Dept Pathol & Mol Diagnost, Nagoya, Aichi 464, Japan.
RP Allen, TC (reprint author), Univ Texas Med Branch, Dept Pathol, 301 Univ Blvd, Galveston, TX 77555 USA.
EM tcallen@utmb.edu
FU Astra-Zeneca; Roche-Genentech; Bristol-Myers Squibb; Merck; Pfizer
FX Dr Sholl received consultancy honoraria from Genentech. Dr Rekhtman
received consultancy honoraria from Bristol-Myers Squibb. Dr Beasley is
a member of the Genentech Scientific Advisory Board. Dr Kerr receives
lecture fees and/or advisory fees from Astra-Zeneca, Roche-Genentech,
Bristol-Myers Squibb, Merck, and Pfizer. Dr Tsao received consultancy
honoraria from Pfizer, Merck Canada, AstraZeneca, and Roche-Genentech.
Dr Thunnissen is on the Global Advisory Board for Merck and only
receives cost for travel. The other authors have no relevant financial
interest in the products or companies described in this article.
NR 22
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U1 2
U2 8
PU COLL AMER PATHOLOGISTS
PI NORTHFIELD
PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA
SN 0003-9985
EI 1543-2165
J9 ARCH PATHOL LAB MED
JI Arch. Pathol. Lab. Med.
PD APR
PY 2016
VL 140
IS 4
BP 341
EP 344
DI 10.5858/arpa.2015-0506-SA
PG 4
WC Medical Laboratory Technology; Medicine, Research & Experimental;
Pathology
SC Medical Laboratory Technology; Research & Experimental Medicine;
Pathology
GA DI7TJ
UT WOS:000373704600010
PM 26780537
ER
PT J
AU Balasubramanian, CK
Li, CY
Bowden, MG
Duncan, PW
Kautz, SA
Velozo, CA
AF Balasubramanian, Chitralakshmi K.
Li, Chih-Ying
Bowden, Mark G.
Duncan, Pamela W.
Kautz, Steven A.
Velozo, Craig A.
TI Dimensionality and Item-Difficulty Hierarchy of the Lower Extremity
Fugl-Meyer Assessment in Individuals With Subacute and Chronic Stroke
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Lower extremity; Rehabilitation; Stroke
ID ASSESSMENT SCALE; HEMIPLEGIC PATIENT; OUTCOME MEASURES; MOTOR RECOVERY;
PERFORMANCE; POSTSTROKE; WALKING; REHABILITATION; COORDINATION;
RELIABILITY
AB Objective: To investigate the dimensionality and item-difficulty hierarchy of the Fugl-Meyer Assessment of the lower extremity (FMA-LE).
Design: Secondary analyses of data pooled from 4 existing datasets: a phase III randomized controlled trial investigating the effectiveness of body weight support and a treadmill for rehabilitation of walking poststroke, and 3 cross-sectional studies investigating the link between impaired motor performance poststroke and walking.
Setting: University research centers and rehabilitation centers.
Participants: A pooled sample of individuals with a stroke (N=535, men = 313; mean age +/- SD, 61.91 +/- 12.42y).
Interventions: Not applicable.
Main Outcome Measures: Confirmatory factor analyses (CFA) and Rasch residual principal component analysis (PCA) investigated the dimensionality of the FMA-LE. The Rasch analysis rating scale model investigated item-difficulty hierarchy of the FMA-LE.
Results: The CFA showed adequate fit of a 3-factor model, with 2 out of 3 indices (CFA=.95; Tucker-Lewis Index=.94; root mean square error of approximation=.124) showing good model fit. Rasch PCA showed that removal of the reflex and coordination items explained 90.8% of variance in the data, suggesting that the abnormal synergy items contributed to the measurement of a unidimensional construct. However, rating scale model results revealed deviations in the item-difficulty hierarchy of the unidimensional abnormal synergy items from the originally proposed stepwise sequence of motor recovery.
Conclusions: Our findings suggest that the FMA-LE might represent a multidimensional construct, challenging the use of a total score of the FMA-LE to predict lower extremity motor recovery. Removal of the misfit items resulted in creation of a unidimensional scale composed of the abnormal synergy items. However, this unidimensional scale deviates from the originally proposed hierarchical ordering. (C) 2016 by the American Congress of Rehabilitation Medicine
C1 [Balasubramanian, Chitralakshmi K.] Univ N Florida, Dept Clin & Appl Movement Sci, 1 UNF Dr, Jacksonville, FL 32224 USA.
[Li, Chih-Ying; Bowden, Mark G.; Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Dept Hlth Sci & Res, Charleston, SC 29425 USA.
[Li, Chih-Ying; Bowden, Mark G.; Kautz, Steven A.] Med Univ S Carolina, Coll Hlth Profess, Div Phys Therapy, Charleston, SC 29425 USA.
[Bowden, Mark G.; Kautz, Steven A.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA.
[Duncan, Pamela W.] Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA.
[Velozo, Craig A.] Med Univ S Carolina, Coll Hlth Profess, Div Occupat Therapy, Charleston, SC 29425 USA.
RP Balasubramanian, CK (reprint author), Univ N Florida, Dept Clin & Appl Movement Sci, 1 UNF Dr, Jacksonville, FL 32224 USA.
EM c.k-balasubramanian@unf.edu
FU National Institute of Neurologic Diseases and Stroke; National Center
for Medical Rehabilitation Research [RO1 NS050506]; National Institutes
of Health [HD46820]; Rehabilitation Research and Development Service of
the U.S. Department of Veterans Affairs [B2748R]; Institutional
Development Award from the National Institute of General Medical
Sciences of the National Institutes of Health [P20-GM109040]
FX Support for study 1 by the National Institute of Neurologic Diseases and
Stroke and the National Center for Medical Rehabilitation Research
(grant no. RO1 NS050506); for study 2, by the National Institutes of
Health (grant no. HD46820); for study 3, by the Rehabilitation Research
and Development Service of the U.S. Department of Veterans Affairs
(grant no. B2748R); and for study 4, by an Institutional Development
Award from the National Institute of General Medical Sciences of the
National Institutes of Health (grant no. P20-GM109040).
NR 47
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U1 0
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 APR
PY 2016
VL 97
IS 4
BP 582
EP 589
DI 10.1016/j.apmr.2015.12.012
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA DI5EM
UT WOS:000373521700012
PM 26740065
ER
PT J
AU Moreno, F
Dussel, V
Orellana, L
AF Moreno, Florencia
Dussel, Veronica
Orellana, Liliana
CA ROHA Network
TI Childhood cancer in Argentina: Survival 2000-2007 (vol 39, pg 505, 2015)
SO CANCER EPIDEMIOLOGY
LA English
DT Correction
C1 [Moreno, Florencia] Natl Canc Inst, Argentinean Oncopaediat Registry, Buenos Aires, DF, Argentina.
[Dussel, Veronica] Ctr Res & Implementat Palliat Care, Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina.
[Dussel, Veronica] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Orellana, Liliana] Natl Canc Inst, Buenos Aires, DF, Argentina.
[Orellana, Liliana] Deakin Univ, Fac Hlth, Biostat Unit, Burwood, Australia.
RP Moreno, F (reprint author), Natl Canc Inst, Argentinean Oncopaediat Registry ROHA, Av Julio A Roca 781 10th Floor, Buenos Aires, DF, Argentina.
EM roha@roha.org.ar; veronica_dussel@dfci.harvard.edu;
l.orellana@deakin.edu.au
RI Orellana, Liliana/S-3302-2016
OI Orellana, Liliana/0000-0003-3736-4337
NR 1
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 1877-7821
EI 1877-783X
J9 CANCER EPIDEMIOL
JI Cancer Epidemiol.
PD APR
PY 2016
VL 41
BP 165
EP 165
DI 10.1016/j.canep.2015.11.011
PG 1
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DI7ZZ
UT WOS:000373721800023
ER
PT J
AU Rebbeck, TR
AF Rebbeck, Timothy R.
TI Defining Priorities for Reducing Disparities in Cancer Mortality
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Editorial Material
C1 [Rebbeck, Timothy R.] Dana Farber Canc Inst, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02215 USA.
[Rebbeck, Timothy R.] Harvard Univ, TH Chan Sch Publ Hlth, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02215 USA.
RP Rebbeck, TR (reprint author), Dana Farber Canc Inst, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02215 USA.; Rebbeck, TR (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, 1101 Dana Bldg,450 Brookline Ave, Boston, MA 02215 USA.
EM Timothy_Rebbeck@dfci.harvard.edu
NR 2
TC 0
Z9 0
U1 0
U2 1
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 APR
PY 2016
VL 25
IS 4
BP 570
EP 572
DI 10.1158/1055-9965.EPI-15-1244
PG 3
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DI4RB
UT WOS:000373485900001
PM 27196088
ER
PT J
AU Nagler, RH
Bigman, CA
Ramanadhan, S
Ramamurthi, D
Viswanath, K
AF Nagler, Rebekah H.
Bigman, Cabral A.
Ramanadhan, Shoba
Ramamurthi, Divya
Viswanath, K.
TI Prevalence and Framing of Health Disparities in Local Print News:
Implications for Multilevel Interventions to Address Cancer Inequalities
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID NEWSPAPER CONTENT-ANALYSIS; SOCIAL DETERMINANTS; BLACK NEWSPAPERS;
COMMUNITY TIES; COVERAGE; MEDIA; JOURNALISTS; INTEGRATION; TELEVISION;
STRATEGIES
AB Background: Americans remain under-informed about cancer and other health disparities and the social determinants of health (SDH). The news media may be contributing to this knowledge deficit, whether by discussing these issues narrowly or ignoring them altogether. Because local media are particularly important in influencing public opinion and support for public policies, this study examines the prevalence and framing of disparities/SDH in local mainstream and ethnic print news.
Methods: We conducted a multi-method content analysis of local mainstream (English language) and ethnic (Spanish language) print news in two lower income cities in New England with substantial racial/ethnic minority populations. After establishing intercoder reliability (kappa = 0.63-0.88), coders reviewed the primary English and Spanish language newspaper in each city, identifying both disparities and non-disparities health stories published between February 2010 and January 2011.
Results: Local print news coverage of cancer and other health disparities was rare. Of 650 health stories published across four newspapers during the one-year study period, only 21 (3.2%) discussed disparities/SDH. Although some stories identified causes of and solutions for disparities, these were often framed in individual (e.g., poor dietary habits) rather than social contextual terms (e.g., lack of food availability/affordability). Cancer and other health stories routinely missed opportunities to discuss disparities/SDH.
Conclusion: Local mainstream and ethnic media may be ideal targets for multilevel interventions designed to address cancer and other health inequalities.
Impact: By increasing media attention to and framing of health disparities, we may observe important downstream effects on public opinion and support for structural solutions to disparities, particularly at the local level. (C) 2016 AACR.
C1 [Nagler, Rebekah H.] Univ Minnesota, Sch Journalism & Mass Commun, 111 Murphy Hall,206 Church St SE, Minneapolis, MN 55455 USA.
[Bigman, Cabral A.] Univ Illinois, Dept Commun, Urbana, IL 61801 USA.
[Ramanadhan, Shoba; Viswanath, K.] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA.
[Ramanadhan, Shoba; Viswanath, K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Ramamurthi, Divya] Stanford Sch Med, Stanford Res Impact Tobacco Advertising, Palo Alto, CA USA.
RP Nagler, RH (reprint author), Univ Minnesota, Sch Journalism & Mass Commun, 111 Murphy Hall,206 Church St SE, Minneapolis, MN 55455 USA.
EM nagle026@umn.edu
FU NCI at the NIH [5 P50-CA148596]; NCI through the Harvard Education
Program in Cancer Prevention [3 R25-CA057711]; Building
Interdisciplinary Research Careers in Women's Health Grant from the
Eunice Kennedy Shriver National Institutes of Child Health and Human
Development; Office of Research on Women's Health; National Institute on
Aging, administered by the University of Minnesota Deborah E. Powell
Center for Women's Health [2 K12-HD055887]; Yerby postdoctoral
fellowship at the Harvard T.H. Chan School of Public Health
FX This work was supported by the NCI at the NIH [grant number 5
P50-CA148596 to K. Viswanath (principal investigator for Project 1)].
Funding support for R.H. Nagler was provided by the NCI through the
Harvard Education Program in Cancer Prevention (grant number 3
R25-CA057711). R.H. Nagler also acknowledges support from the Building
Interdisciplinary Research Careers in Women's Health Grant from the
Eunice Kennedy Shriver National Institutes of Child Health and Human
Development, the Office of Research on Women's Health, and the National
Institute on Aging, administered by the University of Minnesota Deborah
E. Powell Center for Women's Health (grant number 2 K12-HD055887). C.A.
Bigman acknowledges support from the Yerby postdoctoral fellowship at
the Harvard T.H. Chan School of Public Health.
NR 55
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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 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD APR
PY 2016
VL 25
IS 4
BP 603
EP 612
DI 10.1158/1055-9965.EPI-15-1247
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA DI4RB
UT WOS:000373485900007
PM 27196094
ER
PT J
AU Yamashita, T
Koretsune, Y
Yang, YJ
Chen, SA
Chung, N
Shimada, YJ
Kimura, T
Miyazaki, K
Abe, K
Mercuri, M
Ruff, CT
Giugliano, RP
AF Yamashita, Takeshi
Koretsune, Yukihiro
Yang, Yuejin
Chen, Shih-Ann
Chung, Namsik
Shimada, Yuichi J.
Kimura, Tetsuya
Miyazaki, Koichi
Abe, Kenji
Mercuri, Michele
Ruff, Christian T.
Giugliano, Robert P.
TI Edoxaban vs. Warfarin in East Asian Patients With Atrial Fibrillation -
An ENGAGE AF-TIMI 48 Subanalysis -
SO CIRCULATION JOURNAL
LA English
DT Article
DE Anticoagulant; Asian; Atrial fibrillation; Edoxaban; Factor Xa inhibitor
ID FACTOR XA INHIBITOR; INTERNATIONAL NORMALIZED RATIO; J-RHYTHM REGISTRY;
JAPANESE PATIENTS; RISK-FACTORS; ROCKET AF; RIVAROXABAN; PREVALENCE;
STROKE; POPULATION
AB Background: In the multinational, double-blind, double-dummy ENGAGE AF-TIMI 48 phase 3 study, once-daily edoxaban was non-inferior to warfarin for prevention of stroke or systemic embolism event (SEE) in patients with non-valvular atrial fibrillation (AF). Here, we evaluated the efficacy and safety of edoxaban in patients from East Asia.
Methods and Results: Patients aged >= 21 years with documented AF and CHADS score >= 2 were randomized to receive once-daily edoxaban higher-dose (60 mg) or lower-dose (30 mg) regimen or warfarin dose-adjusted to an international normalized ratio of 2.0-3.0. Patients with a creatinine clearance of 30-50 ml/min, weighing <= 60 kg, or receiving strong p-glycoprotein inhibitors at randomization or during the study received a 50% dose reduction of edoxaban or matched placebo. This prespecified subanalysis included 1,943 patients from Japan, China, Taiwan, and South Korea. The annualized rate of stroke/SEE for higher-dose edoxaban was 1.34% vs. 2.62% for warfarin (hazard ratio [HR], 0.53; 95% confidence interval [CI]: 0.31-0.90, P=0.02) and 2.52% for lower-dose edoxaban (HR, 0.98; 95% CI: 0.63-1.54, P=0.93). Compared with warfarin (4.80%), major bleeding was significantly reduced for the higher-dose (2.86%; HR, 0.61; 95% CI: 0.41-0.89, P=0.011) and lower-dose regimens (1.59%; HR, 0.34; 95% CI: 0.21-0.54, P<0.001).
Conclusions: Once-daily edoxaban provided similar efficacy to warfarin while reducing major bleeding risk in the East Asian population.
C1 [Yamashita, Takeshi] Cardiovasc Inst, Tokyo, Japan.
[Koretsune, Yukihiro] Osaka Natl Hosp, Natl Hosp Org, Clin Res Inst, Osaka, Japan.
[Yang, Yuejin] Chinese Acad Med Sci, Cardiovasc Inst, Beijing 100730, Peoples R China.
[Yang, Yuejin] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Beijing 100730, Peoples R China.
[Yang, Yuejin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Chen, Shih-Ann] Taipei Vet Gen Hosp, Taipei, Taiwan.
[Chung, Namsik] Yonsei Univ, Coll Med, Severance Hosp, Seoul 120749, South Korea.
[Shimada, Yuichi J.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Kimura, Tetsuya; Miyazaki, Koichi; Abe, Kenji] Daiichi Sankyo Co Ltd, Tokyo, Japan.
[Mercuri, Michele] Daiichi Sankyo Pharma Dev, Edison, NJ USA.
[Ruff, Christian T.; Giugliano, Robert P.] Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA.
RP Yamashita, T (reprint author), Cardiovasc Inst, Minato Ku, 3-2-19 Nishiazabu, Tokyo 1060031, Japan.
EM yamt-tky@umin.ac.jp
OI Shimada, Yuichi/0000-0002-3494-307X
FU Daiichi Sankyo Co, Ltd (Tokyo, Japan); Daiichi Sankyo
FX This study was sponsored by Daiichi Sankyo Co, Ltd (Tokyo, Japan).
Medical writing and editorial support was provided by Terri Schochet,
PhD, and Meryl Gersh, PhD, of AlphaBioCom, LLC (King of Prussia, PA,
USA), and funded by Daiichi Sankyo.
NR 23
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U1 0
U2 1
PU JAPANESE CIRCULATION SOC
PI TOYKO
PA 18TH FLOOR IMPERIAL HOTEL TOWER, 1-1-1 UCHISAIWAI-CHO CHIYODA-KU, TOYKO,
100-0011, JAPAN
SN 1346-9843
EI 1347-4820
J9 CIRC J
JI Circ. J.
PD APR
PY 2016
VL 80
IS 4
BP 860
EP +
DI 10.1253/circj.CJ-15-1082
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DI3MD
UT WOS:000373401900016
PM 26888149
ER
PT J
AU Melanson, SEF
Griggs, D
Bixho, I
Khaliq, T
Flood, JG
AF Melanson, Stacy E. F.
Griggs, David
Bixho, Ida
Khaliq, Tahira
Flood, James G.
TI 7-Aminoclonazepam is superior to clonazepam for detection of clonazepam
use in oral fluid by LC-MS/MS
SO CLINICA CHIMICA ACTA
LA English
DT Article
DE Oral fluid; Clonazepam; 7-Aminoclonazepam; Addiction management;
Compliance
ID TANDEM MASS-SPECTROMETRY; MS-MS; DRUGS; ABUSE; BENZODIAZEPINES; URINE;
SAMPLES; MATRIX
AB Background: Clonazepam (CLON) is not only frequently prescribed in addiction management but is also commonly abused. Therefore many addiction clinics perform oral fluid (OF) testing, which unlike urine is not subject to adulteration, to monitor CLON compliance. However, CLON and other benzodiazepines can be challenging to detect in OF due to their weakly acidic nature and their presence in low concentrations. We determined the optimal technical and clinical approach for the detection of CLON use using OF.
Methods: We measured CLON and its primary metabolite 7-aminoclonazepam (7AC) by liquid chromatography tandem mass spectrometry in OF specimens over a 2 month period. The samples were collected using the Orasure Intercept OF sample collection device.
Results: One hundred samples were presumptive-positive for 7AC and/or CLON. 91(91.0%) confirmed positive for 7AC (median, range: 42, 0.5-316.7 ng/ml) using the ion ratio test, while only 44 of the 100 (44.0%) samples confirmed positive for CLON (median, range: 3.7, 0.5-217.2 ng/ml) using the ion ratio test. In OF the levels of 7AC were approximately 2.4-fold higher than CLON. The use of 7AC as an analyte for the detection of both CLON compliance and undisclosed use is also recommended.
Conclusions: 7AC should be the analyte measured in OF for the detection of CLON use. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Melanson, Stacy E. F.; Bixho, Ida] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Clin Labs Div, 75 Francis St, Boston, MA 02115 USA.
[Griggs, David; Khaliq, Tahira; Flood, James G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
RP Melanson, SEF (reprint author), Brigham & Womens Hosp, 75 Francis St,Amory 2, Boston, MA 02115 USA.
EM semelanson@partners.org
NR 20
TC 0
Z9 0
U1 2
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0009-8981
EI 1873-3492
J9 CLIN CHIM ACTA
JI Clin. Chim. Acta
PD APR 1
PY 2016
VL 455
BP 128
EP 133
DI 10.1016/j.cca.2016.01.027
PG 6
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA DI7BW
UT WOS:000373655100023
PM 26826393
ER
PT J
AU Freedman, RA
Kouri, EM
West, DW
Rosenberg, S
Partridge, AH
Lii, J
Keating, NL
AF Freedman, Rachel A.
Kouri, Elena M.
West, Dee W.
Rosenberg, Shoshana
Partridge, Ann H.
Lii, Joyce
Keating, Nancy L.
TI Higher Stage of Disease Is Associated With Bilateral Mastectomy Among
Patients With Breast Cancer: A Population-Based Survey
SO CLINICAL BREAST CANCER
LA English
DT Article
DE Bilateral mastectomy; Breast cancer; Contralateral prophylactic
mastectomy; Reconstruction; Stage
ID CONTRALATERAL PROPHYLACTIC MASTECTOMY; CARCINOMA-IN-SITU; YOUNG-WOMEN;
FOLLOW-UP; SURGICAL-TREATMENT; FAMILY-HISTORY; INCREASING USE;
RECONSTRUCTION; TRENDS; KNOWLEDGE
AB We examined factors that were associated with bilateral mastectomy and reconstruction in a population-based survey. In addition to other previously described factors, having stage III disease (vs. stage 0) was associated with bilateral mastectomy. Given the lack of clear medical benefit for this procedure, our findings highlight the need for interventions to assure women are making informed surgical decisions.
Background: The reasons for increasing rates of bilateral mastectomy for unilateral breast cancer are incompletely understood, and associations of disease stage with bilateral surgery have been inconsistent. We examined associations of clinical and sociodemographic factors, including stage, with surgery type and reconstruction receipt among women with breast cancer. Patients and Methods: We surveyed a diverse population-based sample of women from Northern California cancer registries with stage 0 to III breast cancer diagnosed during 2010-2011 (participation rate, 68.5%). Using multinomial logistic regression, we examined factors associated with bilateral and unilateral mastectomy (vs. breast-conserving surgery), adjusting for tumor and sociodemographic characteristics. In a second model, we examined factors associated with reconstruction for mastectomy-treated patients. Results: Among 487 participants, 58% had breast-conserving surgery, 32% had unilateral mastectomy, and 10% underwent bilateral mastectomy. In adjusted analyses, women with stage III (vs. stage 0) cancers had higher odds of bilateral mastectomy (odds ratio [OR], 8.28; 95% confidence interval, 2.32-29.50); women with stage II and III (vs. stage 0) disease had higher odds of unilateral mastectomy. Higher (vs. lower) income was also associated with bilateral mastectomy, while age >= 60 years (vs. < 50 years) was associated with lower odds of bilateral surgery. Among mastectomy-treated patients (n = 206), bilateral mastectomy, unmarried status, and higher education and income were all associated with reconstruction (P < .05). Conclusion: In this population-based cohort, women with the greatest risk of distant recurrence were most likely to undergo bilateral mastectomy despite a lack of clear medical benefit, raising concern for overtreatment. Our findings highlight the need for interventions to assure women are making informed surgical decisions. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Freedman, Rachel A.; Rosenberg, Shoshana; Partridge, Ann H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Kouri, Elena M.; Keating, Nancy L.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[West, Dee W.] Canc Registry Greater Calif, Inst Publ Hlth, Sacramento, CA USA.
[Lii, Joyce] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA.
[Keating, Nancy L.] Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA.
RP Freedman, RA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM rafreedman@partners.org
FU Susan G. Komen; National Cancer Institute [K24CA181510]; California
Department of Public Health [103885]; National Cancer Institute's
Surveillance, Epidemiology, and End Results Program [HHSN261201000140C,
HHSN261201000035C, HHSN261201000034C]; US Centers for Disease Control
and Prevention's National Program of Cancer Registries [U58DP003862-01]
FX We thank all women who participated in interviews, the Cancer Registry
of Greater California, and Ana Guerrero for assistance with interviews.
Supported in part by Susan G. Komen. Support was also received by an
American Cancer Society Mentored Research Scholar Grant (RAF) and a
K24CA181510 (NLK) from the National Cancer Institute.; The collection of
cancer incidence data used in this study was supported by the California
Department of Public Health as part of the statewide cancer reporting
program mandated by California Health and Safety Code Section 103885;
the National Cancer Institute's Surveillance, Epidemiology, and End
Results Program under contract HHSN261201000140C awarded to the Cancer
Prevention Institute of California, contract HHSN261201000035C awarded
to the University of Southern California, and contract HHSN261201000034C
awarded to the Public Health Institute; and the US Centers for Disease
Control and Prevention's National Program of Cancer Registries, under
agreement U58DP003862-01 awarded to the California Department of Public
Health. The ideas and opinions expressed herein are those of the
authors, 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.
NR 51
TC 2
Z9 2
U1 2
U2 2
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1526-8209
EI 1938-0666
J9 CLIN BREAST CANCER
JI Clin. Breast Cancer
PD APR
PY 2016
VL 16
IS 2
BP 105
EP 112
DI 10.1016/j.clbc.2015.08.004
PG 8
WC Oncology
SC Oncology
GA DI8LS
UT WOS:000373753100006
PM 26410475
ER
PT J
AU Bachireddy, P
Wu, CJ
AF Bachireddy, Pavan
Wu, Catherine J.
TI Arresting the Inflammatory Drive of Chronic Lymphocytic Leukemia with
Ibrutinib
SO CLINICAL CANCER RESEARCH
LA English
DT Editorial Material
ID INHIBITOR; THERAPY; CELLS; ITK
AB The clinical success of agents targeting the B-cell receptor signaling pathway in chronic lymphocytic leukemia (CLL) may also derive from disrupting the CLL microenvironment. Investigation of the immunomodulatory effects of these agents illuminates the unique immunobiology of CLL and highlights potential targets for dismantling the chronic inflammatory drive. (C) 2016 AACR.
C1 [Bachireddy, Pavan; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Bachireddy, Pavan; Wu, Catherine J.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Bachireddy, Pavan; Wu, Catherine J.] Harvard Univ, Sch Med, Boston, MA USA.
[Bachireddy, Pavan; Wu, Catherine J.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
RP Wu, CJ (reprint author), Dana Farber Canc Inst, Dana 540,44 Binney St, Boston, MA 02115 USA.
EM cwu@partners.org
FU NCI NIH HHS [R01 CA184922, U10 CA180861, R01 CA182461, R01 CA155010];
NHLBI NIH HHS [R01 HL116452, R01HL116452, R01HL103532, R01 HL103532]
NR 12
TC 2
Z9 2
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 APR 1
PY 2016
VL 22
IS 7
BP 1547
EP 1549
DI 10.1158/1078-0432.CCR-15-3106
PG 3
WC Oncology
SC Oncology
GA DI2WT
UT WOS:000373360600001
PM 26847060
ER
PT J
AU Andronesi, OC
Loebel, F
Bogner, W
Marjanska, M
Vander Heiden, MG
Iafrate, AJ
Dietrich, J
Batchelor, TT
Gerstner, ER
Kaelin, WG
Chi, AS
Rosen, BR
Cahill, DP
AF Andronesi, Ovidiu C.
Loebel, Franziska
Bogner, Wolfgang
Marjanska, Malgorzata
Vander Heiden, Matthew G.
Iafrate, A. John
Dietrich, Jorg
Batchelor, Tracy T.
Gerstner, Elizabeth R.
Kaelin, William G.
Chi, Andrew S.
Rosen, Bruce R.
Cahill, Daniel P.
TI Treatment Response Assessment in IDH-Mutant Glioma Patients by
Noninvasive 3D Functional Spectroscopic Mapping of 2-Hydroxyglutarate
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID MAGNETIC-RESONANCE-SPECTROSCOPY; DIFFUSION MAPS FDMS; LOW-GRADE GLIOMA;
ONCOMETABOLITE 2-HYDROXYGLUTARATE; VINCRISTINE CHEMOTHERAPY;
RANDOMIZED-TRIAL; IN-VIVO; GLIOBLASTOMA; MUTATIONS; SURVIVAL
AB Purpose: Measurements of objective response rates are critical to evaluate new glioma therapies. The hallmark metabolic alteration in gliomas with mutant isocitrate dehydrogenase (IDH) is the overproduction of oncometabolite 2-hydroxyglutarate (2HG), which plays a key role in malignant transformation. 2HG represents an ideal biomarker to probe treatment response in IDH-mutant glioma patients, and we hypothesized a decrease in 2HG levels would be measureable by in vivo magnetic resonance spectroscopy (MRS) as a result of antitumor therapy.
Experimental Design: We report a prospective longitudinal imaging study performed in 25 IDH-mutant glioma patients receiving adjuvant radiation and chemotherapy. A newly developed 3D MRS imaging was used to noninvasively image 2HG. Paired Student t test was used to compare pre- and posttreatment tumor 2HG values. Test-retest measurements were performed to determine the threshold for 2HG functional spectroscopic maps (fSM). Univariate and multivariate regression were performed to correlate 2HG changes with Karnofsky performance score (KPS).
Results: We found that mean 2HG (2HG/Cre) levels decreased significantly (median = 48.1%; 95% confidence interval = 27.3%-56.5%; P = 0.007) in the posttreatment scan. The volume of decreased 2HG correlates (R-2 = 0.88, P = 0.002) with clinical status evaluated by KPS.
Conclusions: We demonstrate that dynamic measurements of 2HG are feasible by 3D fSM, and the decrease of 2HG levels can monitor treatment response in patients with IDH-mutant gliomas. Our results indicate that quantitative in vivo 2HG imaging maybe used for precision medicine and early response assessment in clinical trials of therapies targeting IDH-mutant gliomas. (C) 2015 AACR.
C1 [Andronesi, Ovidiu C.; Loebel, Franziska; Bogner, Wolfgang; Rosen, Bruce R.] Harvard Univ, Sch Med, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging,Massachus, Boston, MA 02115 USA.
[Loebel, Franziska; Cahill, Daniel P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA USA.
[Loebel, Franziska] Charite, Dept Neurosurg, D-13353 Berlin, Germany.
[Bogner, Wolfgang] Med Univ Vienna, High Field MR Ctr, Dept Biomed Imaging & Imageguided Therapy, A-1090 Vienna, Austria.
[Marjanska, Malgorzata] Univ Minnesota, Ctr Magnet Resonance Res, Minneapolis, MN USA.
[Vander Heiden, Matthew G.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Iafrate, A. John] Harvard Univ, Sch Med, Dept Pathol, Ctr Integrated Diagnost,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Dietrich, Jorg; Batchelor, Tracy T.; Gerstner, Elizabeth R.; Chi, Andrew S.] Harvard Univ, Sch Med, Dept Neurol,Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol,Div H, Boston, MA 02115 USA.
[Kaelin, William G.] Dana Farber Harvard Canc Ctr, Boston, MA USA.
RP Andronesi, OC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA.
EM ovidiu@nmr.mgh.harvard.edu; cahill@mgh.harvard.edu
OI Cahill, Daniel/0000-0003-2552-6546; Bogner, Wolfgang/0000-0002-0130-3463
FU NCI/NIH K22 Career Award [1K22CA178269-01]; Burroughs-Wellcome Career
Award; DFHCC/MIT Koch Institute Bridge Foundation; NIH Brain Cancer
SPORE; NIH [R01CA129371, K24CA125440A, S10RR013026, S10RR021110,
S10RR023401]; Austrian Science Fund (FWF) [KLI-61]; Biotechnology
Research Center (BTRC) [P41 RR008079, P41 EB015894]; NCC [P30 NS057091]
FX This work was supported by NCI/NIH K22 Career Award 1K22CA178269-01 (to
O.C. Andronesi); Burroughs-Wellcome Career Award, DFHCC/MIT Koch
Institute Bridge Foundation and NIH Brain Cancer SPORE (to D.P. Cahill);
NIH R01CA129371 and K24CA125440A (to T.T. Batchelor); Austrian Science
Fund (FWF) KLI-61 (to W. Bogner); Biotechnology Research Center (BTRC)
grant P41 RR008079 and P41 EB015894 (NIBIB), and NCC P30 NS057091 (M.
Marjanska); NIH S10RR013026, S10RR021110, S10RR023401 (to B. Rosen).
NR 50
TC 12
Z9 13
U1 2
U2 9
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 APR 1
PY 2016
VL 22
IS 7
BP 1632
EP 1641
DI 10.1158/1078-0432.CCR-15-0656
PG 10
WC Oncology
SC Oncology
GA DI2WT
UT WOS:000373360600012
PM 26534967
ER
PT J
AU Ferreiro-Neira, I
Torres, NE
Liesenfeld, LF
Chan, CHF
Penson, T
Landesman, Y
Senapedis, W
Shacham, S
Hong, TS
Cusack, JC
AF Ferreiro-Neira, Isabel
Torres, Nancy E.
Liesenfeld, Lukas F.
Chan, Carlos H. F.
Penson, Tristan
Landesman, Yosef
Senapedis, William
Shacham, Sharon
Hong, Theodore S.
Cusack, James C.
TI XPO1 Inhibition Enhances Radiation Response in Preclinical Models of
Rectal Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID CRM1-MEDIATED NUCLEAR EXPORT; THERAPEUTIC TARGET; COLORECTAL-CANCER;
PREOPERATIVE RADIOCHEMOTHERAPY; SURVIVIN EXPRESSION; DRUG-RESISTANCE;
CRM1; APOPTOSIS; RADIOTHERAPY; PROTEINS
AB Purpose: Combination of radiation with radiosensitizing chemotherapeutic agents improves outcomes for locally advanced rectal cancer. Current treatment includes 5-fluorouracil-based chemoradiation prior to surgical resection; however pathologic complete response varies from 15% to 20%, prompting the need to identify new radiosensitizers. Exportin 1 (XPO1, also known as chromosome region 1, CRM1) mediates the nuclear export of critical proteins required for rectal cancer proliferation and treatment resistance. We hypothesize that inhibition of XPO1 may radiosensitize cancer cells by altering the function of these critical proteins resulting in decreased radiation resistance and enhanced antitumoral effects.
Experimental Design: To test our hypothesis, we used the selective XPO1 inhibitor, selinexor, to inhibit nuclear export in combination with radiation fractions similar to that given in clinical practice for rectal cancer: hypofractionated short-course radiation dosage of 5 Gy per fraction or the conventional long-course radiation dosage of 1 Gy fractions. Single and combination treatments were tested in colorectal cancer cell lines and xenograft tumor models.
Results: Combination treatment of radiotherapy and selinexor resulted in an increase of apoptosis and decrease of proliferation compared with single treatment, which correlated with reduced tumor size. We found that the combination promoted nuclear survivin accumulation and subsequent depletion, resulting in increased apoptosis and enhanced radiation antitumoral effects.
Conclusions: Our findings suggest a novel therapeutic option for improving radiation sensitivity in the setting of rectal cancer and provide the scientific rationale to evaluate this combination strategy for clinical trials. (C) 2015 AACR.
C1 [Ferreiro-Neira, Isabel; Torres, Nancy E.; Liesenfeld, Lukas F.; Chan, Carlos H. F.; Penson, Tristan; Hong, Theodore S.; Cusack, James C.] Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7,55 Fruit St, Boston, MA 02114 USA.
[Ferreiro-Neira, Isabel; Torres, Nancy E.; Liesenfeld, Lukas F.; Chan, Carlos H. F.; Penson, Tristan; Cusack, James C.] Harvard Univ, Sch Med, Boston, MA USA.
[Landesman, Yosef; Senapedis, William; Shacham, Sharon] Karyopharm Therapeut, Natick, MA USA.
[Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
RP Ferreiro-Neira, I; Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7,55 Fruit St, Boston, MA 02114 USA.; Ferreiro-Neira, I (reprint author), Harvard Univ, Sch Med, Boston, MA USA.
EM isabel.ferreironeira@gmail.com; jcusack@partners.org
FU Karyopharm Therapeutics Incorporated
FX The research was supported by Karyopharm Therapeutics Incorporated.
NR 50
TC 1
Z9 1
U1 0
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 APR 1
PY 2016
VL 22
IS 7
BP 1663
EP 1673
DI 10.1158/1078-0432.CCR-15-0978
PG 11
WC Oncology
SC Oncology
GA DI2WT
UT WOS:000373360600015
PM 26603256
ER
PT J
AU Zhao, SG
Evans, JR
Kothari, V
Sun, G
Larm, A
Mondine, V
Schaeffer, EM
Ross, AE
Klein, EA
Den, RB
Dicker, AP
Karnes, RJ
Erho, N
Nguyen, PL
Davicioni, E
Feng, FY
AF Zhao, Shuang G.
Evans, Joseph R.
Kothari, Vishal
Sun, Grace
Larm, Ashley
Mondine, Victor
Schaeffer, Edward M.
Ross, Ashley E.
Klein, Eric A.
Den, Robert B.
Dicker, Adam P.
Karnes, R. Jeffrey
Erho, Nicholas
Nguyen, Paul L.
Davicioni, Elai
Feng, Felix Y.
TI The Landscape of Prognostic Outlier Genes in High-Risk Prostate Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID AAA-ATPASE NVL2; CAPRA-S SCORE; RADICAL PROSTATECTOMY; TISSUE BIOMARKER;
CONSERVATIVE MANAGEMENT; BIOCHEMICAL RECURRENCE; GENOMIC CLASSIFIER;
DISEASE RECURRENCE; LIVER-CANCER; EXPRESSION
AB Purpose: There is a clear need to improve risk stratification and to identify novel therapeutic targets in aggressive prostate cancer. The goal of this study was to investigate genes with outlier expression with prognostic association in high-risk prostate cancer patients as potential biomarkers and drug targets.
Experimental Design: We interrogated microarray gene expression data from prostatectomy samples from 545 high-risk prostate cancer patients with long-term follow-up (mean 13.4 years). Three independent clinical datasets totaling an additional 545 patients were used for validation. Novel prognostic outlier genes were interrogated for impact on oncogenic phenotypes in vitro using siRNA-based knockdown. Association with clinical outcomes and comparison with existing prognostic instruments was assessed with multivariable models using a prognostic outlier score.
Results: Analysis of the discovery cohort identified 20 prognostic outlier genes. Three top prognostic outlier genes were novel prostate cancer genes; NVL, SMC4, or SQLE knockdown reduced migration and/or invasion and outlier expression was significantly associated with poor prognosis. Increased prognostic outlier score was significantly associated with poor prognosis independent of standard clinicopathologic variables. Finally, the prognostic outlier score prognostic association is independent of, and adds to existing genomic and clinical tools for prognostication in prostate cancer (Decipher, the cell-cycle progression signature, and CAPRA-S).
Conclusions: To our knowledge, this study represents the first unbiased high-throughput investigation of prognostic outlier genes in prostate cancer and demonstrates the potential biomarker and therapeutic importance of this previously unstudied class of cancer genes. (C) 2015 AACR.
C1 [Zhao, Shuang G.; Evans, Joseph R.; Kothari, Vishal; Sun, Grace; Larm, Ashley; Mondine, Victor; Feng, Felix Y.] Univ Michigan, Dept Radiat Oncol, UH B2C490,SPC 5010, Ann Arbor, MI 48109 USA.
[Zhao, Shuang G.] Beaumont Hosp, Transit Year Program, Dearborn, MI USA.
[Schaeffer, Edward M.; Ross, Ashley E.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44106 USA.
[Den, Robert B.; Dicker, Adam P.] Thomas Jefferson Univ, Dept Radiat Oncol, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
[Karnes, R. Jeffrey] Mayo Clin, Dept Urol, Rochester, MN USA.
[Erho, Nicholas; Davicioni, Elai] GenomeDx Biosci Inc, Vancouver, BC, Canada.
[Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
[Nguyen, Paul L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA.
[Feng, Felix Y.] Univ Michigan, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA.
[Feng, Felix Y.] Univ Michigan, Comprehens Canc Ctr, Ann Arbor, MI 48109 USA.
RP Feng, FY (reprint author), Univ Michigan, Dept Radiat Oncol, UH B2C490,SPC 5010, Ann Arbor, MI 48109 USA.
EM ffeng@med.umich.edu
FU Prostate Cancer Foundation; Evans Foundation
FX This research was supported by Challenge Grants awarded (to F.Y. Feng
and J.R. Evans) by the Prostate Cancer Foundation and the Evans
Foundation.
NR 52
TC 7
Z9 7
U1 1
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 APR 1
PY 2016
VL 22
IS 7
BP 1777
EP 1786
DI 10.1158/1078-0432.CCR-15-1250
PG 10
WC Oncology
SC Oncology
GA DI2WT
UT WOS:000373360600025
PM 26631616
ER
PT J
AU Johansen, KL
Dalrymple, LS
Glidden, D
Delgado, C
Kaysen, GA
Grimes, B
Chertow, GM
AF Johansen, Kirsten L.
Dalrymple, Lorien S.
Glidden, David
Delgado, Cynthia
Kaysen, George A.
Grimes, Barbara
Chertow, Glenn M.
TI Association of Performance-Based and Self-Reported Function-Based
Definitions of Frailty with Mortality among Patients Receiving
Hemodialysis
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID MAINTENANCE HEMODIALYSIS; CONSENSUS; DIALYSIS; DISEASE; HEALTH; OLDER
AB Background and objectives Frailty is common among patients on dialysis and increases vulnerability to dependency and death.
Design, setting, participants, & measurements We examined the predictive ability of frailty on the basis of physical performance and self-reported function in participants of a US Renal Data System special study that enrolled a convenience sample of 771 prevalent patients on hemodialysis from 14 facilities in the Atlanta and northern California areas from 2009 to 2011. Performance-based frailty was assessed using direct measures of grip strength (weakness) and gait speed along with weight loss, exhaustion, and low physical activity; poor self reported function was substituted for weakness and slow gait speed in the self reported function based definition. For both definitions, patients meeting three or more criteria were considered frail.
Results The mean age of 762 patients included in analyses was 57.1 +/- 14.2 years old; 240 patients (31%) met the physical performance-based definition of frailty, and 396 (52%) met the self reported function-based definition. There were 106 deaths during 1.7 (interquartile range, 1.4-2.4) years of follow-up. After adjusting for demographic and clinical characteristics, the hazard ratio (HR) for mortality for the performance-based definition (2.16; 95% confidence interval [95% CI], 1.41 to 3.29) was slightly higher than that of the self reported function based definition (HR, 1.93; 95% CI, 1.24 to 3.00). Patients who met the self-report based definition but not the physical performance definition of frailty (n=192) were not at statistically significantly higher risk of mortality than those who were not frail by either definition (n=330; HR, 1.41; 95% CI, 0.81 to 2.45), but those who met both definitions of frailty (n=204) were at significantly higher risk (HR, 2.46; 95% CI, 1.51 to 4.01).
Conclusions Frailty, defined using either direct tests of physical performance or self reported physical function, was associated with higher mortality among patients receiving hemodialysis. Future studies are needed to determine the utility of assessing frailty in clinical practice.
C1 [Johansen, Kirsten L.; Delgado, Cynthia] Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.; Glidden, David; Grimes, Barbara] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.; Delgado, Cynthia] San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA.
[Dalrymple, Lorien S.; Kaysen, George A.] Univ Calif Davis, Div Nephrol, Davis, CA 95616 USA.
[Chertow, Glenn M.] Stanford Univ, Sch Med, Div Nephrol, Stanford, CA 94305 USA.
RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA.
EM Kirsten.johansen@ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[N01-DK-7-005, K24DK085153, K23DK093584, K24DK085446]; Career
Development Award from US Department of Veterans Affairs [1K2CX000527];
Clinical Research and Development Program; National Center for Advancing
Translational Sciences, National Institutes of Health through University
of California; San Francisco-Clinical & Translational Science Institute
grant [UL1 TR000004]
FX This work was supported by National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) Contract N01-DK-7-005 and NIDDK Grants
K24DK085153 (to K.L.J.), K23DK093584 (to L.S.D.), and K24DK085446 (to
G.M.C.). In addition, C.D. was supported by Career Development Award
1K2CX000527 from the US Department of Veterans Affairs, Clinical
Research and Development Program. This publication was supported by the
National Center for Advancing Translational Sciences, National
Institutes of Health through University of California, San
Francisco-Clinical & Translational Science Institute grant UL1 TR000004.
NR 20
TC 3
Z9 3
U1 1
U2 3
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 APR
PY 2016
VL 11
IS 4
BP 626
EP 632
DI 10.2215/CJN.03710415
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DI5EV
UT WOS:000373522600013
PM 26792529
ER
PT J
AU Mueller, JL
King, LY
Johnson, KB
Gao, T
Nephew, LD
Kothari, D
Simpson, MA
Zheng, H
Wei, L
Corey, KE
Misdraji, J
Lee, JH
Lin, MV
Gogela, NA
Fuchs, BC
Tanabe, KK
Gordon, FD
Curry, MP
Chung, RT
AF Mueller, Jessica L.
King, Lindsay Y.
Johnson, Kara B.
Gao, Tian
Nephew, Lauren D.
Kothari, Darshan
Simpson, Mary Ann
Zheng, Hui
Wei, Lan
Corey, Kathleen E.
Misdraji, Joseph
Lee, Joon Hyoek
Lin, M. Valerie
Gogela, Neliswa A.
Fuchs, Bryan C.
Tanabe, Kenneth K.
Gordon, Fredric D.
Curry, Michael P.
Chung, Raymond T.
TI Impact of EGF, IL28B, and PNPLA3 polymorphisms on the outcome of
allograft hepatitis C: a multicenter study
SO CLINICAL TRANSPLANTATION
LA English
DT Article
DE cirrhosis; hepatitis C virus; single nucleotide polymorphism; sustained
virological response; transplantation
ID GROWTH-FACTOR GENE; LIVER-TRANSPLANTATION; HEPATOCELLULAR-CARCINOMA;
FIBROSIS PROGRESSION; ANTIVIRAL THERAPY; RECIPIENT IL28B; FUNCTIONAL
POLYMORPHISM; VIRUS; DONOR; ASSOCIATION
AB Hepatitis C virus (HCV) infection is accelerated following liver transplantation (LT). Single nucleotide polymorphisms (SNPs) near the epidermal growth factor (EGF) (rs4444903), IL28B (rs12979860), and PNPLA3 (rs738409) loci are associated with treatment response, fibrosis, and hepatocellular carcinoma in non-transplant hepatitis C, but allograft population data are limited. We sought to determine the role of these SNPs in 264 patients with HCV who underwent LT between 1990 and 2008. Genotypes were determined from donor wedge/allograft biopsies and recipient explants. Cox proportional hazards model was used to assess time to cirrhosis, liver-related death, and retransplantation, adjusting for donor age and sustained virological response (SVR). Over a median follow-up of 6.3 yr, a trend toward increased progression to graft cirrhosis was observed among recipients of an EGF non-AA vs. AA donor liver (adjusted HR 2.01; 95% CI 0.93-4.34; p = 0.08). No other genotypes predicted cirrhosis development or graft survival. The CC IL28B variant in both recipients and donors was associated with increased rate of SVR (R-CC/D-CC 8/12[67%], R-non-CC/D-CC or R-CC/D-non-CC 23/52[44%], R-non-CC/D-non-CC 12/45[27%], p linear trend = 0.009). Recipient EGF, IL28B, and PNPLA3, and donor IL28B and PNPLA3 genotypes do not predict adverse outcomes in HCV LT recipients. A potential association exists between donor EGF genotype and cirrhosis.
C1 [Mueller, Jessica L.; King, Lindsay Y.; Johnson, Kara B.; Corey, Kathleen E.; Lin, M. Valerie; Gogela, Neliswa A.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA.
[Mueller, Jessica L.; King, Lindsay Y.; Johnson, Kara B.; Kothari, Darshan; Corey, Kathleen E.; Lin, M. Valerie; Gogela, Neliswa A.; Fuchs, Bryan C.; Tanabe, Kenneth K.; Gordon, Fredric D.; Curry, Michael P.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA.
[Gao, Tian] Boston Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA.
[Nephew, Lauren D.] Univ Penn Hlth Syst, Dept Med, Div Gastroenterol, Philadelphia, PA USA.
[Kothari, Darshan; Curry, Michael P.] Beth Israel Deaconness Med Ctr, Dept Med, Div Gastroenterol, Boston, MA USA.
[Simpson, Mary Ann; Gordon, Fredric D.] Lahey Hosp & Med Ctr, Dept Med, Div Gastroenterol, Burlington, MA USA.
[Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, 55 Fruit St, Boston, MA 02114 USA.
[Wei, Lan; Fuchs, Bryan C.; Tanabe, Kenneth K.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 55 Fruit St, Boston, MA 02114 USA.
[Misdraji, Joseph] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
[Lee, Joon Hyoek] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Med, Seoul, South Korea.
RP Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, 55 Fruit St, Boston, MA 02114 USA.
EM rtchung@partners.org
FU NIDDK NIH HHS [K23 DK099422]
NR 30
TC 0
Z9 0
U1 0
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 APR
PY 2016
VL 30
IS 4
BP 452
EP 460
DI 10.1111/ctr.12710
PG 9
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DI7KT
UT WOS:000373679200015
PM 26854475
ER
PT J
AU Bitzer, C
AF Bitzer, Carolynn
TI Evidence-Based Practice Research on Pole- vs Patient-Mounted Transducer
Placement
SO CRITICAL CARE NURSE
LA English
DT Meeting Abstract
C1 [Bitzer, Carolynn] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC CRITICAL CARE NURSES
PI ALISO VIEJO
PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA
SN 0279-5442
EI 1940-8250
J9 CRIT CARE NURSE
JI Crit. Care Nurse
PD APR
PY 2016
VL 36
IS 2
MA EB66
BP E27
EP E28
PG 2
WC Critical Care Medicine; Nursing
SC General & Internal Medicine; Nursing
GA DI4CQ
UT WOS:000373448300030
ER
PT J
AU Scully, E
Alter, G
AF Scully, Eileen
Alter, Galit
TI NK Cells in HIV Disease
SO CURRENT HIV/AIDS REPORTS
LA English
DT Article
DE HIV; Innate immunity; NK cell; Antibody-dependent cellular cytotoxicity;
NK cell memory; Natural killer (NK); Viral immunity; HIV pathogenesis;
Review
ID NATURAL-KILLER-CELLS; DEPENDENT CELLULAR CYTOTOXICITY; HUMAN
CYTOMEGALOVIRUS-INFECTION; ANTIVIRAL T-CELLS; IN-VIVO; HLA-B; EPISTATIC
INTERACTION; PERSISTENT INFECTION; EFFECTOR FUNCTIONS; ADAPTIVE IMMUNITY
AB Natural killer (NK) cells play a critical role in viral immunity. In the setting of HIV infection, epidemiologic and functional evidence support a role for NK cells in both protection from new infection and in viral control. Specifically, NK cells directly mediate immune pressure leading to virus evolution, and NK cell receptor genotypic profiles, clonal repertoires, and functional capacity have all been implicated in virus containment. In addition, indirect NK cell-mediated antibody-dependent cellular cytotoxicity has been linked to vaccine-induced protective immunity against HIV infection. With recent advances in our understanding of NK cell deficiency, development, memory-like responses, and editing of the adaptive immune system, the opportunities to direct and exploit NK cell antiviral immunity to target HIV have exponentially grown. In this review, we seek to highlight the intersections between discoveries in basic NK cell biology and the challenges of HIV chronic infection, vaccine development, and cure/eradication strategies.
C1 [Scully, Eileen; Alter, Galit] MIT, Massachusetts Gen Hosp, Ragon Inst, 400 Technol Sq, Cambridge, MA 02139 USA.
[Scully, Eileen; Alter, Galit] Harvard Univ, 400 Technol Sq, Cambridge, MA 02139 USA.
[Scully, Eileen] Brigham & Womens Hosp, Dept Med, Div Infect Dis, Boston, MA 02130 USA.
RP Alter, G (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, 400 Technol Sq, Cambridge, MA 02139 USA.; Alter, G (reprint author), Harvard Univ, 400 Technol Sq, Cambridge, MA 02139 USA.
EM escully@partners.org; galter@partners.org
FU NIAID NIH HHS [P30 AI027763]
NR 98
TC 4
Z9 4
U1 4
U2 8
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1548-3568
EI 1548-3576
J9 CURR HIV-AIDS REP
JI Curr. Hiv/Aids Rep.
PD APR
PY 2016
VL 13
IS 2
BP 85
EP 94
DI 10.1007/s11904-016-0310-3
PG 10
WC Infectious Diseases
SC Infectious Diseases
GA DI6WI
UT WOS:000373640500002
PM 27002078
ER
PT J
AU Katz, IT
Bangsberg, DR
AF Katz, Ingrid T.
Bangsberg, David R.
TI Cascade of Refusal-What Does It Mean for the Future of Treatment as
Prevention in Sub-Saharan Africa?
SO CURRENT HIV/AIDS REPORTS
LA English
DT Article
DE Antiretroviral medications; Treatment refusal; Global epidemic;
HIV/AIDS; HIV prevention; Science of prevention; ART refusal; Point of
testing; Review
ID CLUSTER-RANDOMIZED-TRIAL; RURAL SOUTH-AFRICA; HIV-RELATED STIGMA;
ANTIRETROVIRAL THERAPY; FOLLOW-UP; CARE; UGANDA; INITIATION; RETENTION;
OUTCOMES
AB Recent recommendations by the World Health Organization support treatment for all people living with HIV (PLWH) globally to be initiated at the point of testing. While there has been marked success in efforts to identify and expand treatment for PLWH throughout sub-Saharan Africa, the goal of universal treatment may prove challenging to achieve. The pre-ART phase of the care cascade from HIV testing to HIV treatment initiation includes several social and structural barriers. One such barrier is antiretroviral therapy (ART) treatment refusal, a phenomenon in which HIV-infected individuals choose not to start treatment upon learning their ART eligibility. Our goal is to provide further understanding of why treatment-eligible adults may choose to present for HIV testing but not initiate ART when indicated. In this article, we will discuss factors driving pre-ART loss and present a framework for understanding the impact of decision-making on early losses in the care cascade, with a focus on ART refusal.
C1 [Katz, Ingrid T.] Brigham & Womens Hosp, Dept Med, Div Womens Hlth, 1620 Tremont St, Boston, MA 02120 USA.
[Katz, Ingrid T.; Bangsberg, David R.] Harvard Univ, Sch Med, Boston, MA USA.
[Katz, Ingrid T.; Bangsberg, David R.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
RP Katz, IT (reprint author), Brigham & Womens Hosp, Dept Med, Div Womens Hlth, 1620 Tremont St, Boston, MA 02120 USA.; Katz, IT (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Katz, IT (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA.
EM IKatz2@Partners.org
FU US National Institute for Mental Health [K23 MH097667]
FX This publication was made possible with funding from US National
Institute for Mental Health K23 MH097667 (Katz). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. The funders had no
role in the study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 77
TC 2
Z9 2
U1 3
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1548-3568
EI 1548-3576
J9 CURR HIV-AIDS REP
JI Curr. Hiv/Aids Rep.
PD APR
PY 2016
VL 13
IS 2
BP 125
EP 130
DI 10.1007/s11904-016-0309-9
PG 6
WC Infectious Diseases
SC Infectious Diseases
GA DI6WI
UT WOS:000373640500006
PM 26894487
ER
PT J
AU Dunn, EC
Wiste, A
Radmanesh, F
Almli, LM
Gogarten, SM
Sofer, T
Faul, JD
Kardia, SLR
Smith, JA
Weir, DR
Zhao, W
Soare, TW
Mirza, SS
Hek, K
Tiemeier, H
Goveas, JS
Sarto, GE
Snively, BM
Cornelis, M
Koenen, KC
Kraft, P
Purcell, S
Ressler, KJ
Rosand, J
Wassertheil-Smoller, S
Smoller, JW
AF Dunn, Erin C.
Wiste, Anna
Radmanesh, Farid
Almli, Lynn M.
Gogarten, Stephanie M.
Sofer, Tamar
Faul, Jessica D.
Kardia, Sharon L. R.
Smith, Jennifer A.
Weir, David R.
Zhao, Wei
Soare, Thomas W.
Mirza, Saira S.
Hek, Karin
Tiemeier, Henning
Goveas, Joseph S.
Sarto, Gloria E.
Snively, Beverly M.
Cornelis, Marilyn
Koenen, Karestan C.
Kraft, Peter
Purcell, Shaun
Ressler, Kerry J.
Rosand, Jonathan
Wassertheil-Smoller, Sylvia
Smoller, Jordan W.
TI GENOME-WIDE ASSOCIATION STUDY (GWAS) AND GENOME-WIDE BY ENVIRONMENT
INTERACTION STUDY (GWEIS) OF DEPRESSIVE SYMPTOMS IN AFRICAN AMERICAN AND
HISPANIC/LATINA WOMEN
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE genome-wide association study; gene-environment interaction; depression;
stressful life events; social support
ID STRESSFUL LIFE EVENTS; COMORBIDITY SURVEY REPLICATION; SEROTONIN
TRANSPORTER GENE; MAJOR DEPRESSION; POSTMENOPAUSAL WOMEN; POLYGENIC
RISK; SOCIAL SUPPORT; HEALTH; DISORDER; METAANALYSIS
AB BackgroundGenome-wide association studies (GWAS) have made little progress in identifying variants linked to depression. We hypothesized that examining depressive symptoms and considering gene-environment interaction (GxE) might improve efficiency for gene discovery. We therefore conducted a GWAS and genome-wide by environment interaction study (GWEIS) of depressive symptoms.
MethodsUsing data from the SHARe cohort of the Women's Health Initiative, comprising African Americans (n = 7,179) and Hispanics/Latinas (n = 3,138), we examined genetic main effects and GxE with stressful life events and social support. We also conducted a heritability analysis using genome-wide complex trait analysis (GCTA). Replication was attempted in four independent cohorts.
ResultsNo SNPs achieved genome-wide significance for main effects in either discovery sample. The top signals in African Americans were rs73531535 (located 20 kb from GPR139, P = 5.75 x 10(-8)) and rs75407252 (intronic to CACNA2D3, P = 6.99 x 10(-7)). In Hispanics/Latinas, the top signals were rs2532087 (located 27 kb from CD38, P = 2.44 x 10(-7)) and rs4542757 (intronic to DCC, P = 7.31 x 10(-7)). In the GEWIS with stressful life events, one interaction signal was genome-wide significant in African Americans (rs4652467; P = 4.10 x 10(-10); located 14 kb from CEP350). This interaction was not observed in a smaller replication cohort. Although heritability estimates for depressive symptoms and stressful life events were each less than 10%, they were strongly genetically correlated (rG = 0.95), suggesting that common variation underlying self-reported depressive symptoms and stressful life event exposure, though modest on their own, were highly overlapping in this sample.
ConclusionsOur results underscore the need for larger samples, more GEWIS, and greater investigation into genetic and environmental determinants of depressive symptoms in minorities.
C1 [Dunn, Erin C.; Radmanesh, Farid; Soare, Thomas W.; Rosand, Jonathan; Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,Simches Res Bldg 6th Floor, Boston, MA 02114 USA.
[Dunn, Erin C.; Soare, Thomas W.; Smoller, Jordan W.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Dunn, Erin C.; Soare, Thomas W.; Smoller, Jordan W.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Wiste, Anna] Massachusetts Gen Hosp, Ctr Expt Drugs & Diagnost, Dept Psychiat, 185 Cambridge St,Simches Res Bldg 6th Floor, Boston, MA 02114 USA.
[Radmanesh, Farid; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Div Neurocrit Care, 185 Cambridge St,Simches Res Bldg 6th Floor, Boston, MA 02114 USA.
[Radmanesh, Farid; Rosand, Jonathan] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Almli, Lynn M.; Ressler, Kerry J.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA.
[Gogarten, Stephanie M.; Sofer, Tamar] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Kardia, Sharon L. R.; Smith, Jennifer A.; Zhao, Wei] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Mirza, Saira S.; Hek, Karin; Tiemeier, Henning] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hek, Karin; Tiemeier, Henning] Erasmus MC, Dept Psychiat, Rotterdam, Netherlands.
[Goveas, Joseph S.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA.
[Sarto, Gloria E.] Univ Wisconsin, Dept Obstet & Gynecol, Sch Med & Publ Hlth, Ctr Womens Hlth & Hlth Dispar Res, Madison, WI 53706 USA.
[Snively, Beverly M.] Wake Forest Sch Med, Dept Biostat Sci, Div Publ Hlth Sci, Winston Salem, NC USA.
[Cornelis, Marilyn] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Koenen, Karestan C.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Kraft, Peter] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Purcell, Shaun] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
[Dunn, Erin C.; Wassertheil-Smoller, Sylvia] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
RP Dunn, EC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, 185 Cambridge St,Simches Res Bldg 6th Floor, Boston, MA 02114 USA.
EM edunn2@mgh.harvard.edu
OI Gogarten, Stephanie/0000-0002-7231-9745; Smith,
Jennifer/0000-0002-3575-5468; Sofer, Tamar/0000-0001-8520-8860
FU National Institute of Mental Health of the National Institutes of Health
[K01MH102403, K24MH094614]; NARSAD Young Investigator Grant from the
Brain & Behavior Research Foundation; National Heart, Lung, and Blood
Institute; U.S. Department of Health and Human Services
[HHSN268201100046C, HHSN268201100001C, HHSN 268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]; National
Institute on Aging [NIA U01AG009740, RC2 AG036495, RC4 AG039029]
FX Contract grant sponsor: National Institute of Mental Health of the
National Institutes of Health; Contract grant numbers: K01MH102403 and
K24MH094614; Contract grant sponsor: NARSAD Young Investigator Grant
from the Brain & Behavior Research Foundation. Contract grant sponsor:
the National Heart, Lung, and Blood Institute; Contract grant sponsor:
U.S. Department of Health and Human Services; Contract grant numbers:
HHSN268201100046C, HHSN268201100001C, HHSN 268201100002C,
HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C. Contract
grant sponsor: National Institute on Aging; Contract grant number: NIA
U01AG009740, RC2 AG036495, and RC4 AG039029.
NR 89
TC 3
Z9 3
U1 5
U2 12
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 APR
PY 2016
VL 33
IS 4
BP 265
EP 280
DI 10.1002/da.22484
PG 16
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DI7XS
UT WOS:000373715900001
PM 27038408
ER
PT J
AU Sadeh, N
Wolf, EJ
Logue, MW
Hayes, JP
Stone, A
Griffin, LM
Schichman, SA
Miller, MW
AF Sadeh, Naomi
Wolf, Erika J.
Logue, Mark W.
Hayes, Jasmeet P.
Stone, Annjanette
Griffin, L. Michelle
Schichman, Steven A.
Miller, Mark W.
TI EPIGENETIC VARIATION AT SKA2 PREDICTS SUICIDE PHENOTYPES AND
INTERNALIZING PSYCHOPATHOLOGY
SO DEPRESSION AND ANXIETY
LA English
DT Article
DE DNA methylation; PTSD; externalizing; suicide risk; trauma; veterans
ID POSTTRAUMATIC-STRESS-DISORDER; COMMON MENTAL-DISORDERS; EXTERNALIZING
PSYCHOPATHOLOGY; GENETIC-VARIATION; LIFE EVENTS; RISK; SAMPLE;
POPULATION; VETERANS; RECEPTOR
AB BackgroundDNA methylation of the SKA2 gene has recently been implicated as a biomarker of suicide risk and posttraumatic stress disorder (PTSD). To examine the specificity and reliability of these findings, we examined associations between SKA2 DNA methylation, broad dimensions of psychiatric symptoms, and suicide phenotypes in adults with high levels of trauma exposure.
MethodsA total of 466 White, non-Hispanic veterans and their intimate partners (65% male) underwent clinical assessment and had blood drawn for genotyping and methylation analysis. DNA methylation of the CpG locus cg13989295 and genotype at the methylation-associated single-nucleotide polymorphism (SNP) rs7208505 were examined in relation to current and lifetime PTSD, internalizing and externalizing psychopathology, and suicide phenotypes (ideation, plans, and attempts).
ResultsDNA methylation at the previously implicated SKA2 CpG locus (cg13989295) was associated with current and lifetime symptoms of internalizing (but not externalizing) disorders. SKA2 methylation levels also predicted higher rates of current suicidal thoughts and behaviors, even after including well-established psychiatric risk factors for suicide in the model. Associations between PTSD and SKA2 were not significant, and genetic variation at the methylation-associated SNP (rs7208505) was not related to any of the phenotypes examined.
ConclusionsSKA2 methylation may index a general propensity to experience stress-related psychopathology, including internalizing disorders and suicidal thoughts and behaviors. This study demonstrates that SKA2 methylation levels explain unique variance in suicide risk not captured by clinical symptom interviews, providing further evidence of its potential utility as a biomarker of suicide risk and stress-related psychopathology.
C1 [Sadeh, Naomi; Wolf, Erika J.; Hayes, Jasmeet P.; Miller, Mark W.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA.
[Sadeh, Naomi; Wolf, Erika J.; Hayes, Jasmeet P.; Miller, Mark W.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA.
[Logue, Mark W.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA.
[Logue, Mark W.] Boston Univ, Sch Med, Biomed Genet, Boston, MA 02118 USA.
[Logue, Mark W.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Stone, Annjanette; Griffin, L. Michelle; Schichman, Steven A.] Cent Arkansas Vet Healthcare Syst, Res Serv, Pharmacogen Anal Lab, Little Rock, AR USA.
RP Sadeh, N (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA.
EM Naomi.SamimiSadeh@va.gov
FU National Institute of Mental Health award
FX Contract grant sponsor: National Institute of Mental Health award.
NR 33
TC 2
Z9 2
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD APR
PY 2016
VL 33
IS 4
BP 308
EP 315
DI 10.1002/da.22480
PG 8
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DI7XS
UT WOS:000373715900005
PM 27038412
ER
PT J
AU Ito, N
Hendriks, WT
Dhakal, J
Vaine, CA
Liu, C
Shin, D
Shin, K
Wakabayashi-Ito, N
Dy, M
Multhaupt-Buell, T
Sharma, N
Breakefield, XO
Bragg, DC
AF Ito, Naoto
Hendriks, William T.
Dhakal, Jyotsna
Vaine, Christine A.
Liu, Christina
Shin, David
Shin, Kyle
Wakabayashi-Ito, Noriko
Dy, Marisela
Multhaupt-Buell, Trisha
Sharma, Nutan
Breakefield, Xandra O.
Bragg, D. Cristopher
TI Decreased N-TAF1 expression in X-linked dystonia-parkinsonism
patient-specific neural stem cells
SO DISEASE MODELS & MECHANISMS
LA English
DT Article
DE X-linked dystonia-parkinsonism; Induced pluripotent stem cells; TAF1
ID BILATERAL PALLIDAL STIMULATION; DOMINANT CEREBELLAR-ATAXIA; MULTIPLE
TRANSCRIPT SYSTEM; BINDING PROTEIN; SYNDROME XDP; SVA RETROTRANSPOSONS;
STRUCTURAL INSIGHTS; HUMAN TAF(II)250; PHILIPPINES XDP; SYNDROME LOCUS
AB X-linked dystonia-parkinsonism(XDP) is a hereditary neurodegenerative disorder involving a progressive loss of striatal medium spiny neurons. The mechanisms underlying neurodegeneration are not known, in part because there have been few cellular models available for studying the disease. The XDP haplotype consists of multiple sequence variations in a region of the X chromosome containing TAF1, a large gene with at least 38 exons, and a multiple transcript system (MTS) composed of five unconventional exons. A previous study identified an XDP-specific insertion of a SINE-VNTR-Alu (SVA)-type retrotransposon in intron 32 of TAF1, as well as a neural-specific TAF1 isoform, N-TAF1, which showed decreased expression in post-mortem XDP brain compared with control tissue. Here, we generated XDP patient and control fibroblasts and induced pluripotent stem cells (iPSCs) in order to further probe cellular defects associated with this disease. As initial validation of the model, we compared expression of TAF1 and MTS transcripts in XDP versus control fibroblasts and iPSC-derived neural stem cells (NSCs). Compared with control cells, XDP fibroblasts exhibited decreased expression of TAF1 transcript fragments derived from exons 32-36, a region spanning the SVA insertion site. N-TAF1, which incorporates an alternative exon (exon 34'), was not expressed in fibroblasts, but was detectable in iPSC-differentiated NSCs at levels that were similar to threefold lower in XDP cells than in controls. These results support the previous findings that N-TAF1 expression is impaired in XDP, but additionally indicate that this aberrant transcription might occur in neural cells at relatively early stages of development that precede neurodegeneration.
C1 [Ito, Naoto; Hendriks, William T.; Dhakal, Jyotsna; Vaine, Christine A.; Liu, Christina; Shin, David; Shin, Kyle; Wakabayashi-Ito, Noriko; Dy, Marisela; Multhaupt-Buell, Trisha; Sharma, Nutan; Breakefield, Xandra O.; Bragg, D. Cristopher] Massachusetts Gen Hosp, Dept Neurol, Collaborat Ctr X Linked Dystonia Parkinsonism, Boston, MA 02129 USA.
[Ito, Naoto; Hendriks, William T.; Dhakal, Jyotsna; Vaine, Christine A.; Liu, Christina; Shin, David; Shin, Kyle; Wakabayashi-Ito, Noriko; Breakefield, Xandra O.; Bragg, D. Cristopher] Harvard Univ, Sch Med, Harvard Brain Sci Initiat, Boston, MA 02114 USA.
[Breakefield, Xandra O.] Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
RP Breakefield, XO; Bragg, DC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Collaborat Ctr X Linked Dystonia Parkinsonism, Boston, MA 02129 USA.; Breakefield, XO; Bragg, DC (reprint author), Harvard Univ, Sch Med, Harvard Brain Sci Initiat, Boston, MA 02114 USA.; Breakefield, XO (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Charlestown, MA 02129 USA.
EM breakefield@hms.harvard.edu; bragg@helix.mgh.harvard.edu
OI Liu, Christina/0000-0001-7023-6578
FU Massachusetts General Hospital Collaborative Center for X-Linked
Dystonia-Parkinsonism
FX The study was supported by the Massachusetts General Hospital
Collaborative Center for X-Linked Dystonia-Parkinsonism (D.C.B., N.S.
and X.O.B.).
NR 74
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U1 4
U2 8
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD APR 1
PY 2016
VL 9
IS 4
BP 451
EP 462
DI 10.1242/dmm.022590
PG 12
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA DI4TA
UT WOS:000373491000009
PM 26769797
ER
PT J
AU Justice, AC
McGinnis, KA
Tate, JP
Braithwaite, RS
Bryant, KJ
Cook, RL
Edelman, EJ
Fiellin, LE
Freiberg, MS
Gordon, AJ
Kraemer, KL
Marshall, BDL
Williams, EC
Fiellin, DA
AF Justice, Amy C.
McGinnis, Kathleen A.
Tate, Janet P.
Braithwaite, R. Scott
Bryant, Kendall J.
Cook, Robert L.
Edelman, E. Jennifer
Fiellin, Lynn E.
Freiberg, Matthew S.
Gordon, Adam J.
Kraemer, Kevin L.
Marshall, Brandon D. L.
Williams, Emily C.
Fiellin, David A.
TI Risk of mortality and physiologic injury evident with lower alcohol
exposure among HIV infected compared with uninfected men
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Alcohol; Mortality; Morbidity; VACS Index; AUDIT-C; Veteran; HIV
ID VETERANS AGING COHORT; ALL-CAUSE MORTALITY; J-SHAPED CURVE;
ANTIRETROVIRAL THERAPY; PRIMARY-CARE; AUDIT-C; MEDICATION ADHERENCE;
ADMINISTRATIVE DATA; SCREENING SCORES; PROBLEM DRINKING
AB Background: HIV infected (HIV+) individuals may be more susceptible to alcohol-related harm than uninfected individuals.
Methods: We analyzed data on HIV+ and uninfected individuals in the Veterans Aging Cohort Study (VACS) with an Alcohol Use Disorders Identification Test-Consumption AUDIT-C score from 2008 to 2012. We used Cox proportional hazards models to examine the association between alcohol exposure and mortality through July, 2014; and linear regression models to assess the association between alcohol exposure and physiologic injury based on VACS Index Scores. Models were adjusted for age, race/ethnicity, smoking, and hepatitis C infection.
Results: The sample included 18,145 HIV+ and 42,228 uninfected individuals. Among HIV+ individuals, 76% had undetectable HIV-1 RNA (<500 copies/ml). The threshold for an association of alcohol use with mortality and physiologic injury differed by HIV status. Among HIV+ individuals, AUDIT-C score >= 4 (hazard ratio [HR] 1.25, 95% CI 1.09-1.44) and >= 30 drinks per month (HR, 1.30, 95% CI 1.14-1.50) were associated with increased risk of mortality. Among uninfected individuals, AUDIT-C score >= 5 (HR, 1.19, 95% CI 1.07-1.32) and >= 70 drinks per month (HR 1.13, 95% CI 1.00-1.28) were associated with increased risk. Similarly, AUDIT-C threshold scores of 5-7 were associated with physiologic injury among HIV+ individuals (beta 0.47, 95% CI 0.22, 0.73) and a score of 8 or more was associated with injury in uninfected (beta 0.29, 95% CI 0.16, 0.42) individuals.
Conclusions: Despite antiretroviral therapy, HIV+ individuals experienced increased mortality and physiologic injury at lower levels of alcohol use compared with uninfected individuals. Alcohol consumption limits should be lower among HIV+ individuals. Published by Elsevier Ireland Ltd.
C1 [Justice, Amy C.; Tate, Janet P.; Edelman, E. Jennifer; Fiellin, David A.] West Haven VA Healthcare Syst, Vet Aging Cohort Study Coordinating Ctr, 950 Campbell Ave, West Haven, CT 06516 USA.
[Justice, Amy C.; Tate, Janet P.; Edelman, E. Jennifer; Fiellin, Lynn E.; Fiellin, David A.] Yale Univ, Yale Sch Med, Dept Internal Med, 367 Cedar St, New Haven, CT 06510 USA.
[Justice, Amy C.; Tate, Janet P.; Edelman, E. Jennifer; Fiellin, Lynn E.; Fiellin, David A.] Yale Univ, Yale Sch Med, CIRA, 367 Cedar St, New Haven, CT 06510 USA.
[McGinnis, Kathleen A.; Gordon, Adam J.; Kraemer, Kevin L.] VA Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA.
[Braithwaite, R. Scott] NYU, Sch Med, Dept Populat Hlth, 227 East 30th St, New York, NY 10016 USA.
[Bryant, Kendall J.] NIAAA, 5635 Fishers Lane,MSC 9304, Bethesda, MD 20892 USA.
[Cook, Robert L.] Univ Florida, Dept Epidemiol, POB 100231, Gainesville, FL USA.
[Freiberg, Matthew S.] Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Nashville, TN 37212 USA.
[Freiberg, Matthew S.] Vet Affairs Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, 2525 West End Ave, Nashville, TN USA.
[Gordon, Adam J.; Kraemer, Kevin L.] Univ Pittsburgh, Sch Med, Div Gen Internal Med, Suite 600,230 McKee Pl, Pittsburgh, PA 15213 USA.
[Marshall, Brandon D. L.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, 121 South Main St, Providence, RI 02912 USA.
[Williams, Emily C.] Univ Washington, Sch Publ Hlth, 325 Ninth Ave,Box 359762, Seattle, WA 98195 USA.
RP Justice, AC (reprint author), Yale Univ, Sch Med, VA Connecticut Healthcare Syst, 950 Campbell Ave,Bldg 35a Room 2-212 11 ACSLG, West Haven, CT 06516 USA.
EM amy.Justice2@va.gov
OI Fiellin, David/0000-0002-4006-010X; Justice, Amy/0000-0003-0139-5502
FU NHLBI NIH HHS [R01 HL090342, R01 HL095136, R01-HL090342, R01-HL095136,
RC1 HL100347, RCI-HL100347]; NIA NIH HHS [R01 AG029154, R01-AG029154];
NIAAA NIH HHS [U10-AA13566, U10 AA013566, U13 AA022864, U24 AA022000,
U24 AA022002, U24AA02002]; PHS HHS [U01-A1069918]
NR 60
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U1 3
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD APR 1
PY 2016
VL 161
BP 95
EP 103
DI 10.1016/j.drugalcdep.2016.01.017
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DI3SP
UT WOS:000373419100013
PM 26861883
ER
PT J
AU Okita, K
Ghahremani, DG
Payer, DE
Robertson, CL
Dean, AC
Mandelkern, MA
London, ED
AF Okita, Kyoji
Ghahremani, Dara G.
Payer, Doris E.
Robertson, Chelsea L.
Dean, Andy C.
Mandelkern, Mark A.
London, Edythe D.
TI Emotion dysregulation and amygdala dopamine D2-type receptor
availability in methamphetamine users
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Methamphetamine; Amygdala; Emotion dysregulation; Dopamine;
[F-18]Fallypride; PET
ID BORDERLINE PERSONALITY-DISORDER; REFERENCE TISSUE MODEL; HUMAN BRAIN;
NEURAL MECHANISMS; IMPULSE CONTROL; ABSTINENCE; DEPENDENCE; CORTEX;
DIFFICULTIES; INHIBITION
AB Background: Individuals who use methamphetamine chronically exhibit emotional and dopaminergic neurochemical deficits. Although the amygdala has an important role in emotion processing and receives dopaminergic innervation, little is known about how dopamine transmission in this region contributes to emotion regulation. This investigation aimed to evaluate emotion regulation in subjects who met DSM-IV criteria for methamphetamine dependence, and to test for a relationship between self-reports of difficulty in emotion regulation and D2-type dopamine receptor availability in the amygdala.
Method: Ninety-four methamphetamine-using and 102 healthy-control subjects completed the Difficulties in Emotion Regulation Scale (DERS); 33 of those who used methamphetamine completed the Addiction Severity Index (ASI). A subset of 27 methamphetamine-group and 20 control-group subjects completed positron emission tomography with [F-18]fallypride to assay amygdala D2-type dopamine receptor availability, measured as binding potential (BPND).
Results: The methamphetamine group scored higher than the control group on the DERS total score (p < 0.001), with DERS total score positively correlated with the Drug Composite Score on the ASI (p = 0.02) in the methamphetamine group. The DERS total score was positively correlated with amygdala BPND in both groups and the combined group of participants (combined: r= 0.331, p= 0.02), and the groups did not differ in this relationship.
Conclusion: These findings highlight problems with emotion regulation linked to methamphetamine use, possibly contributing to personal and interpersonal behavioral problems. They also suggest that D2-type dopamine receptors in the amygdala contribute to emotion regulation in both healthy and methamphetamine-using subjects. (c) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Okita, Kyoji; Ghahremani, Dara G.; Dean, Andy C.; London, Edythe D.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA.
[Robertson, Chelsea L.; London, Edythe D.] Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA.
[London, Edythe D.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA.
[Payer, Doris E.] Ctr Addict & Mental Hlth, Addict Imaging Res Grp, Toronto, ON M5T 1R8, Canada.
[Payer, Doris E.] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada.
[Okita, Kyoji; Robertson, Chelsea L.; Mandelkern, Mark A.; London, Edythe D.] VA Greater Los Angeles Healthcare Syst, Dept Res, Los Angeles, CA 90073 USA.
[Mandelkern, Mark A.] Univ Calif Irvine, Dept Phys, Irvine, CA 92697 USA.
RP London, ED (reprint author), Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, 760 Westwood Plaza,POB 175919, Los Angeles, CA 90095 USA.
EM elondon@mednet.ucla.edu
OI Payer, Doris/0000-0001-9313-2587
FU National Institute on Drug Abuse [R01 DA015179, R01 DA020726, P20
DA022539, T32 DA024635, K23 DA027734, R21 DA034928]; National Center for
Research Resources [M01 RR00865]; Thomas P and Katherine K Pike Chair in
Addiction Studies; Marjorie M Greene Trust; Department of Psychiatry,
Chiba University, DOMONKAI fund
FX This research was supported, in part, by grants from the National
Institute on Drug Abuse (R01 DA015179, R01 DA020726, P20 DA022539, T32
DA024635, EDL; K23 DA027734, R21 DA034928, ACD) and the National Center
for Research Resources (M01 RR00865), and endowments from the Thomas P
and Katherine K Pike Chair in Addiction Studies and the Marjorie M
Greene Trust. KO was partly supported by Department of Psychiatry, Chiba
University, DOMONKAI fund.
NR 68
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U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD APR 1
PY 2016
VL 161
BP 163
EP 170
DI 10.1016/j.drugalcdep.2016.01.029
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DI3SP
UT WOS:000373419100021
PM 26880595
ER
PT J
AU Chavez, LJ
Bradley, K
Tefft, N
Liu, CF
Hebert, P
Devine, B
AF Chavez, Laura J.
Bradley, Katharine
Tefft, Nathan
Liu, Chuan-Fen
Hebert, Paul
Devine, Beth
TI Preference weights for the spectrum of alcohol use in the US Population
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Alcohol consumption; Health-related quality of life; preference weights
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; REPORTED HEALTH-STATUS;
USE DISORDER SEVERITY; UNITED-STATES; GENERAL-POPULATION; PRIMARY-CARE;
SCREENING SCORES; RISK-FACTORS; AUDIT-C
AB Background: Little is known about the cost-utility of population-based alcohol interventions. One barrier to research has been the lack of preference weights needed to calculate Quality Adjusted Life Years (QALYs). Preference weights can be estimated from measures of health-related quality of life (HRQOL). The objective of this study was to describe preference weights for the full spectrum of alcohol use.
Methods: This cross-sectional study included participants in both the National Health Interview Survey (NHIS; 1999-2002) and the Medical Expenditure Panel Survey (MEPS; 2000-2003). The AUDIT-C alcohol screen was derived from NHIS with scores categorized into 6 groups (0,1-3, 4-5, 6-7, 8-9,10-12 points), ranging from nondrinking (0) to very severe unhealthy alcohol use (10-12). AUDIT-C scores were mapped to EQ-5D and SF-6D preference weights using the linked datasets and analyses adjusted for demographics.
Results: Among 17,440 participants, mean EQ-5D and SF-6D preference weights were 0.82 (95% CI 0.82-0.83) and 0.79 (95% CI 0.79-0.80), respectively. Adjusted EQ-5D preference weights for nondrinking (0.80; 95% CI 0.79-0.81) and moderate unhealthy drinking (0.85; 95% CI 0.84-0.86) were significantly different from low-risk drinking (0.83; 95% CI 0.83-0.84), but no other differences were significant. Results for the SF-GD were similar.
Conclusions: This study provides EQ-5D and SF-6D preference weights for various alcohol use categories in a representative U.S. adult sample. However, neither measure suggested meaningful differences in HRQOL based on AUDIT-C categories. Self-reported alcohol consumption may not be associated with preference weights or generic instruments may not capture alcohol-related differences in HRQOL. (c) 2016 Elsevier Ireland Ltd. All rights reserved.
C1 [Chavez, Laura J.; Bradley, Katharine; Liu, Chuan-Fen; Hebert, Paul] Vet Affairs Puget Sound Hlth Care Syst, Seattle Ctr Innovat Vet Ctr & Value Driven Care, Hlth Serv Res & Dev, 1660 S Columbian Way, Seattle, WA 98108 USA.
[Bradley, Katharine] Vet Affairs Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, 1660 S Columbian Way, Seattle, WA 98108 USA.
[Chavez, Laura J.; Bradley, Katharine; Liu, Chuan-Fen; Hebert, Paul; Devine, Beth] Univ Washington, Dept Hlth Serv, 1959 NE Pacific St,Box 357660, Seattle, WA 98195 USA.
[Bradley, Katharine] Univ Washington, Dept Med, 1959 NE Pacific St, Seattle, WA 98195 USA.
[Devine, Beth] Univ Washington, Dept Pharm, 1959 NE Pacific St, Seattle, WA 98195 USA.
[Tefft, Nathan] Bates Coll, 2 Andrews Rd, Lewiston, ME 04240 USA.
[Bradley, Katharine] Grp Hlth Res Inst, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA.
RP Chavez, LJ (reprint author), Univ Washington, Dept Hlth Serv, 1959 NE Pacific St,Box 357660, Seattle, WA 98195 USA.
EM ljchavez@u.washington.edu
OI Bradley, Katharine/0000-0003-1933-4425; Tefft,
Nathan/0000-0002-2758-8700
FU Agency for Healthcare Research and Quality (AHRQ) [NIH 1R36HS022800-01];
University of Washington Center of Excellence in Comparative
Effectiveness Research; Pharmaceutical Researcher and Manufacturer's
Association (PhRMA) Foundation
FX Ms. Chavez's work on this study was supported by an Agency for
Healthcare Research and Quality (AHRQ) Dissertation Grant (NIH
1R36HS022800-01) and a predoctoral fellowship from the University of
Washington Center of Excellence in Comparative Effectiveness Research,
sponsored by the Pharmaceutical Researcher and Manufacturer's
Association (PhRMA) Foundation. Dr. Bradley's time on this study was
supported by the Center of Excellence for Substance Abuse Treatment and
Education (CESATE) at VA Puget Sound.
NR 50
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PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD APR 1
PY 2016
VL 161
BP 206
EP 213
DI 10.1016/j.drugalcdep.2016.02.004
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DI3SP
UT WOS:000373419100026
PM 26900145
ER
PT J
AU Ben-Shlomo, Y
Scharf, JM
Miller, LL
Mathews, CA
AF Ben-Shlomo, Y.
Scharf, J. M.
Miller, L. L.
Mathews, C. A.
TI Parental mood during pregnancy and post-natally is associated with
offspring risk of Tourette syndrome or chronic tics: prospective data
from the Avon Longitudinal Study of Parents and Children (ALSPAC)
SO EUROPEAN CHILD & ADOLESCENT PSYCHIATRY
LA English
DT Article
DE Tourette syndrome; Anxiety; Depression; Cohort studies; Risk factors;
ALSPAC
ID PRENATAL ANXIETY; COHORT; EPIDEMIOLOGY; DISORDER; DEPRESSION; CORTISOL;
SMOKING
AB Little is known about risk factors for Tourette syndrome (TS) and chronic tic disorders (CT) but maternal psychological morbidity in pregnancy may be associated with TS/CT. We examined whether pre- and post-natal parental anxiety and/or depression are associated with risk of TS/CT in the Avon Longitudinal Study of Parents and Children. We compared self-reported anxiety and depression measures collected prospectively at four time points (18 and 32 weeks prenatally, and 8 weeks and 8 months post-natally) among parents of children who subsequently met criteria for TS/CT at 13 years of age as compared to other children from the cohort. We adjusted for various socioeconomic measures and tested both for time period-specific exposure and chronic exposure using multivariable logistic regression models. 122 children had TS/CT (50 TS, 72 CT) and 5968 children had no tics. In crude analyses, both pre- and post-natal maternal anxiety and depression, but only post-natal paternal depression at 8 months, showed associations with TS/CT. In the final, adjusted multivariable models, chronic maternal anxiety (odds ratio 2.17, 95 % CI 1.23, 3.84, p = 0.007) and pre-natal maternal depression (odds ratio 1.86, 95 % CI 1.02, 3.39, p = 0.04) showed associations with TS/CT though the latter was consistent with chance (p = 0.07) after adjustment for past maternal depression. We find associations between maternal psychological morbidity pre- and post-natally and risk of future TS/CT in offspring. These associations may reflect either shared genetic susceptibility or a pre-natal exposure. Further work is required to see if these findings can be replicated in larger datasets.
C1 [Ben-Shlomo, Y.; Miller, L. L.] Univ Bristol, Sch Social & Community Med, 39 Whatley Rd, Bristol BS8 2PS, Avon, England.
[Scharf, J. M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Scharf, J. M.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Scharf, J. M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Scharf, J. M.] Brigham & Womens Hosp, Dept Neurol, Div Cognit & Behav Neurol, 75 Francis St, Boston, MA 02115 USA.
[Mathews, C. A.] Univ Calif San Francisco, Dept Psychiat, Program Genet & Epidemiol Neuropsychiat Symptoms, San Francisco, CA 94143 USA.
RP Ben-Shlomo, Y (reprint author), Univ Bristol, Sch Social & Community Med, 39 Whatley Rd, Bristol BS8 2PS, Avon, England.
EM y.ben-shlomo@bristol.ac.uk
FU Wellcome Trust [102215/2/13/2]; Tourette Syndrome Association (USA)
FX We are extremely grateful to all the families who took part in this
study, the midwives for their help in recruiting them, and the whole
ALSPAC team, which includes interviewers, computer and laboratory
technicians, clerical workers, research scientists, volunteers,
managers, receptionists and nurses. The UK Medical Research Council and
the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of
Bristol provided core support for ALSPAC. This publication is the work
of the authors and Yoav Ben-Shlomo will serve as guarantor for the
contents of this paper. This research was specifically funded by the
Tourette Syndrome Association (USA).
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1018-8827
EI 1435-165X
J9 EUR CHILD ADOLES PSY
JI Eur. Child Adolesc. Psych.
PD APR
PY 2016
VL 25
IS 4
BP 373
EP 381
DI 10.1007/s00787-015-0742-0
PG 9
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA DI6WU
UT WOS:000373641700005
PM 26174227
ER
PT J
AU Ovaska, MT
Madanat, R
Makinen, TJ
AF Ovaska, Mikko T.
Madanat, Rami
Maekinen, Tatu J.
TI Predictors of Postoperative Wound Necrosis Following Primary Wound
Closure of Open Ankle Fractures
SO FOOT & ANKLE INTERNATIONAL
LA English
DT Article
DE trauma; ankle fracture; open fracture; wound necrosis; wound closure
ID OPERATIVE TREATMENT; CANCELLOUS BONE; RISK-FACTORS; IRRIGATION;
COMPLICATIONS; INFECTION; PRESSURE; DEBRIDEMENT; MANAGEMENT; TRAUMA
AB Background: Most open malleolar ankle fracture wounds can be closed primarily after meticulous debridement. However, the development of wound necrosis following operative treatment of open malleolar ankle fractures can have catastrophic consequences. The aim of this study was to identify risk factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures.
Methods: A total of 137 patients with open malleolar ankle fractures were identified. The open fracture wound was primarily closed in 110 of 137 (80%) patients, and postoperative wound necrosis occurred in 18 (16%) of these patients. These patients were compared to the open fracture patients without wound necrosis. Twenty possible risk factors for the development of wound necrosis were studied with logistic regression analysis.
Results: The variables that were independently associated with an increased risk for postoperative wound necrosis included ASA class 2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery.
Conclusions: Our study showed that ASA class 2, Gustilo grade III open injury, and the use of pulsatile lavage at index surgery were the most important factors predisposing to postoperative wound necrosis following primary wound closure of open malleolar ankle fractures. The findings warrant a further study specifically comparing primary and delayed wound closure in patients with Gustilo grade III open malleolar ankle fractures and different ASA classes. Also, the role of pulsatile lavage should be re-evaluated.
Level of Evidence: Level III, retrospective comparative series.
C1 [Ovaska, Mikko T.] Helsinki Univ Hosp, Dept Orthopaed & Traumatol, Topeliuksenkatu 5, Helsinki 00260, Finland.
[Ovaska, Mikko T.] Univ Helsinki, Helsinki, Finland.
[Madanat, Rami] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Madanat, Rami] Harvard Univ, Sch Med, Boston, MA USA.
[Maekinen, Tatu J.] Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada.
[Maekinen, Tatu J.] Univ Toronto, Toronto, ON, Canada.
RP Ovaska, MT (reprint author), Helsinki Univ Hosp, Dept Orthopaed & Traumatol, Topeliuksenkatu 5, Helsinki 00260, Finland.
EM mikko.ovaska@hus.fi
FU HUS EVO; Maud Kuistila Memorial Foundation; Biomedicum Foundation;
Paivikki and Sakari Sohlberg Foundation
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This study
was supported by grants from the HUS EVO, the Maud Kuistila Memorial
Foundation, the Biomedicum Foundation, and the Paivikki and Sakari
Sohlberg Foundation. Mikko T. Ovaska, MD, PhD, reports grants from HUS
EVO, during the conduct of the study. Rami Madanat, MD, PhD, reports
grants from the Paivikki and Sakari Sohlberg Foundation and the
Biomedicum Foundation, during the conduct of the study. Tatu J. Makinen,
MD, PhD, reports grants from the Maud Kuistila Memorial Foundation and
the Biomedicum Foundation, during the conduct of the study.
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PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1071-1007
EI 1944-7876
J9 FOOT ANKLE INT
JI Foot Ankle Int.
PD APR
PY 2016
VL 37
IS 4
BP 401
EP 406
DI 10.1177/1071100715609182
PG 6
WC Orthopedics
SC Orthopedics
GA DI7GY
UT WOS:000373668700008
PM 26830839
ER
PT J
AU Gonzalez, TA
Watkins, C
Drummond, R
Wolf, JC
Toomey, EP
DiGiovanni, CW
AF Gonzalez, Tyler A.
Watkins, Colyn
Drummond, Rosa
Wolf, Jonathon C.
Toomey, E. Pepper
DiGiovanni, Christopher W.
TI Transfibular Approach to Posterior Malleolus Fracture Fixation:
Technique Tip
SO FOOT & ANKLE INTERNATIONAL
LA English
DT Editorial Material
DE ankle fracture; transfibular approach; posterior malleolus; ankle
fracture ORIF
ID POSTEROLATERAL APPROACH; ANKLE FRACTURES; OPERATIVE TREATMENT;
INTERNAL-FIXATION; OPEN REDUCTION
C1 [Gonzalez, Tyler A.; Watkins, Colyn] Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, 3F,Suite 3300,55 Fruit St, Boston, MA 02114 USA.
[Drummond, Rosa] Massachusetts Gen Hosp, Foot & Ankle Serv, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
[Drummond, Rosa] Massachusetts Gen Hosp, Fellowship Program, Dept Orthopaed Surg, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA.
[Wolf, Jonathon C.] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Harvard Combined Orthopaed Surg Prog, Boston, MA 02114 USA.
[Toomey, E. Pepper] Orthoped Phys Associates, Seattle, WA USA.
[DiGiovanni, Christopher W.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[DiGiovanni, Christopher W.] Newton Wellesley Hosp, Massachusetts Gen Hosp, MGH Comprehens Foot & Ankle Ctr, Foot & Ankle Serv, Waltham, MA USA.
[DiGiovanni, Christopher W.] Newton Wellesley Hosp, Massachusetts Gen Hosp, MGH Comprehens Foot & Ankle Ctr, Fellowship Program, Waltham, MA USA.
[DiGiovanni, Christopher W.] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Boston, MA USA.
RP Gonzalez, TA (reprint author), Massachusetts Gen Hosp, Harvard Combined Orthopaed Residency Program, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, 3F,Suite 3300,55 Fruit St, Boston, MA 02114 USA.
EM tagonzalez@partners.org
NR 14
TC 1
Z9 1
U1 0
U2 1
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1071-1007
EI 1944-7876
J9 FOOT ANKLE INT
JI Foot Ankle Int.
PD APR
PY 2016
VL 37
IS 4
BP 440
EP 445
DI 10.1177/1071100715617760
PG 6
WC Orthopedics
SC Orthopedics
GA DI7GY
UT WOS:000373668700014
PM 26596796
ER
PT J
AU Liang, JJ
Cade, BE
Wang, HM
Chen, H
Gleason, KJ
Larkin, EK
Saxena, R
Lin, XH
Redline, S
Zhu, XF
AF Liang, Jingjing
Cade, Brian E.
Wang, Heming
Chen, Han
Gleason, Kevin J.
Larkin, Emma K.
Saxena, Richa
Lin, Xihong
Redline, Susan
Zhu, Xiaofeng
TI Comparison of Heritability Estimation and Linkage Analysis for Multiple
Traits Using Principal Component Analyses
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE principal components; principal components of heritability;
heritability; estimation; linkage analysis; sleep apnea
ID OBSTRUCTIVE SLEEP-APNEA; GENOME-WIDE ASSOCIATION; BODY-MASS INDEX;
BLOOD-PRESSURE; RISK-FACTORS; PLEIOTROPY; PHENOTYPES; FAMILY; GENES;
POWER
AB A disease trait often can be characterized by multiple phenotypic measurements that can provide complementary information on disease etiology, physiology, or clinical manifestations. Given that multiple phenotypes may be correlated and reflect common underlying genetic mechanisms, the use of multivariate analysis of multiple traits may improve statistical power to detect genes and variants underlying complex traits. The literature, however, has been unclear as to the optimal approach for analyzing multiple correlated traits. In this study, heritability and linkage analysis was performed for six obstructive sleep apnea hypopnea syndrome (OSAHS) related phenotypes, as well as principal components of the phenotypes and principal components of the heritability (PCHs) using the data from Cleveland Family Study, which include both African and European American families. Our study demonstrates that principal components generally result in higher heritability and linkage evidence than individual traits. Furthermore, the PCHs can be transferred across populations, strongly suggesting that these PCHs reflect traits with common underlying genetic mechanisms for OSAHS across populations. Thus, PCHs can provide useful traits for using data on multiple phenotypes and for genetic studies of trans-ethnic populations.
C1 [Liang, Jingjing; Wang, Heming; Zhu, Xiaofeng] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
[Cade, Brian E.; Gleason, Kevin J.; Saxena, Richa; Redline, Susan] Brigham & Womens Hosp, Div Sleep & Circadian Disorders, 75 Francis St, Boston, MA 02115 USA.
[Cade, Brian E.; Gleason, Kevin J.; Saxena, Richa; Redline, Susan] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA.
[Lin, Xihong] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Larkin, Emma K.] Vanderbilt Univ, Med Ctr, Dept Med, Div Allergy Pulm & Crit Care, Nashville, TN USA.
[Saxena, Richa] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Saxena, Richa] Massachusetts Gen Hosp, Dept Anesthesia Pain & Crit Care Med, Boston, MA 02114 USA.
[Saxena, Richa] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Redline, Susan] Beth Israel Deaconess Med Ctr, Div Pulm Crit Care & Sleep Med, Boston, MA 02215 USA.
RP Zhu, XF (reprint author), Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
EM xiaofeng.zhu@case.edu
OI Chen, Han/0000-0002-9510-4923
FU NCRR NIH HHS [P41 RR003655, KL2 RR024990, RR024990, RR03655]; NHGRI NIH
HHS [HG003054, R01 HG003054]; NHLBI NIH HHS [HL046380, HL113338, R01
HL046380, R01 HL113338, T32 HL007567]; NIEHS NIH HHS [P30 ES000002]
NR 33
TC 1
Z9 1
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2016
VL 40
IS 3
BP 222
EP 232
DI 10.1002/gepi.21957
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA DI6HQ
UT WOS:000373600200005
PM 27027516
ER
PT J
AU Wang, S
Zhao, JH
An, P
Guo, XQ
Jensen, RA
Marten, J
Huffman, JE
Meidtner, K
Boeing, H
Campbell, A
Rice, KM
Scott, RA
Yao, J
Schulze, MB
Wareham, NJ
Borecki, IB
Province, MA
Rotter, JI
Hayward, C
Goodarzi, MO
Meigs, JB
Dupuis, J
AF Wang, Shuai
Zhao, Jing Hua
An, Ping
Guo, Xiuqing
Jensen, Richard A.
Marten, Jonathan
Huffman, Jennifer E.
Meidtner, Karina
Boeing, Heiner
Campbell, Archie
Rice, Kenneth M.
Scott, Robert A.
Yao, Jie
Schulze, Matthias B.
Wareham, Nicholas J.
Borecki, Ingrid B.
Province, Michael A.
Rotter, Jerome I.
Hayward, Caroline
Goodarzi, Mark O.
Meigs, James B.
Dupuis, Josee
TI General Framework for Meta-Analysis of Haplotype Association Tests
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE meta-analysis; haplotype association tests; family samples; linear mixed
effects model
ID GENOME-WIDE ASSOCIATION; FASTING GLUCOSE; EM ALGORITHM; TRAITS; LOCI;
SUSCEPTIBILITY; REGRESSION; LASSO
AB For complex traits, most associated single nucleotide variants (SNV) discovered to date have a small effect, and detection of association is only possible with large sample sizes. Because of patient confidentiality concerns, it is often not possible to pool genetic data from multiple cohorts, and meta-analysis has emerged as the method of choice to combine results from multiple studies. Many meta-analysis methods are available for single SNV analyses. As new approaches allow the capture of low frequency and rare genetic variation, it is of interest to jointly consider multiple variants to improve power. However, for the analysis of haplotypes formed by multiple SNVs, meta-analysis remains a challenge, because different haplotypes may be observed across studies. We propose a two-stage meta-analysis approach to combine haplotype analysis results. In the first stage, each cohort estimate haplotype effect sizes in a regression framework, accounting for relatedness among observations if appropriate. For the second stage, we use a multivariate generalized least square meta-analysis approach to combine haplotype effect estimates from multiple cohorts. Haplotype-specific association tests and a global test of independence between haplotypes and traits are obtained within our framework. We demonstrate through simulation studies that we control the type-I error rate, and our approach is more powerful than inverse variance weighted meta-analysis of single SNV analysis when haplotype effects are present. We replicate a published haplotype association between fasting glucose-associated locus (G6PC2) and fasting glucose in seven studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and we provide more precise haplotype effect estimates.
C1 [Wang, Shuai; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Zhao, Jing Hua] Univ Cambridge, MRC, Epidemiol Unit, Sch Clin Med,Inst Metab Sci, Box 285,Cambridge Biomed Campus, Cambridge, England.
[An, Ping; Borecki, Ingrid B.; Province, Michael A.] Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA.
[Guo, Xiuqing; Yao, Jie; Rotter, Jerome I.] Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Jensen, Richard A.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Jensen, Richard A.; Hayward, Caroline] Univ Washington, Dept Med, Seattle, WA USA.
[Marten, Jonathan; Huffman, Jennifer E.] Univ Edinburgh, Human Genet Unit, MRC, MRC IGMM, Edinburgh EH8 9YL, Midlothian, Scotland.
[Meidtner, Karina; Schulze, Matthias B.] German Inst Human Nutr Potsdam Rehbrucke, Dept Mol Epidemiol, Nuthetal, Germany.
[Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany.
[Campbell, Archie; Hayward, Caroline] Univ Edinburgh, Ctr Genom & Expt Med, Inst Genet & Mol Med, Generat Scotland,Western Gen Hosp, Edinburgh, Midlothian, Scotland.
[Rice, Kenneth M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Schulze, Matthias B.] German Ctr Diabet Res DZD, Munich, Germany.
[Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP Dupuis, J (reprint author), 3rd Floor,801 Massachusetts Ave, Boston, MA 02118 USA.
EM dupuis@bu.edu
OI Meidtner, Karina/0000-0001-5810-4062; Schulze, Matthias
B./0000-0002-0830-5277
FU Chief Scientist Office [CZD/16/6, CZD/16/6/4]; Intramural NIH HHS;
Medical Research Council [MC_PC_U127561128, MC_U106179471]; NCATS NIH
HHS [UL1 TR000040, UL1 TR000124, UL1 TR001079, UL1-TR-000040,
UL1-TR-001079, UL1TR000124]; NCRR NIH HHS [UL1-RR-025005, UL1 RR025005];
NHLBI NIH HHS [HHSN268200800007C, HHSN268201200036C, HL068986, HL080295,
HL087652, HL103612, N01-HC-95159, N01-HC-95160, N01-HC-95161,
N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166,
N01-HC-95167, N01-HC-95168, N01-HC-95169, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC95159,
N01HC95160, N01HC95161, N01HC95162, N01HC95163, N01HC95164, N01HC95165,
N01HC95166, N01HC95167, N01HC95168, N01HC95169, N02HL64278, R01
HL068986, R01 HL071205, R01 HL071250, R01 HL071252, R01 HL071258, R01
HL071259, R01 HL080295, R01 HL087652, R01 HL087700, R01 HL088215, R01
HL103612, R01-HL-071051, R01-HL-071205, R01-HL-071250, R01-HL-071251,
R01-HL-071252, R01-HL-071258, R01-HL-071259, R01-HL-087700,
R01-HL-088215, U01 HL080295]; NIA NIH HHS [AG023629, R01 AG023629, R56
AG023629]; NIDDK NIH HHS [DK063491, K24 DK080140, P30 DK063491, R01
DK075681, R01 DK078616, R01 DK089256, R01-DK-075681, R01-DK-8925601, U01
DK078616]; PHS HHS [HHSN268200800007C, HHSN268201200036C]; Wellcome
Trust
NR 26
TC 0
Z9 0
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD APR
PY 2016
VL 40
IS 3
BP 244
EP 252
DI 10.1002/gepi.21959
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA DI6HQ
UT WOS:000373600200007
PM 27027517
ER
PT J
AU Ananthakrishnan, AN
Cagan, A
Cai, TX
Gainer, VS
Shaw, SY
Savova, G
Churchill, S
Karlson, EW
Kohane, I
Liao, KP
Murphy, SN
AF Ananthakrishnan, Ashwin N.
Cagan, Andrew
Cai, Tianxi
Gainer, Vivian S.
Shaw, Stanley Y.
Savova, Guergana
Churchill, Susanne
Karlson, Elizabeth W.
Kohane, Isaac
Liao, Katherine P.
Murphy, Shawn N.
TI Comparative Effectiveness of Infliximab and Adalimumab in Crohn's
Disease and Ulcerative Colitis
SO INFLAMMATORY BOWEL DISEASES
LA English
DT Article
DE infliximab; ulcerative colitis; treatment response; biologic; Crohn's
disease
ID ELECTRONIC HEALTH RECORDS; ANTI-TNF AGENTS; NETWORK METAANALYSIS;
COMPARATIVE EFFICACY; MAINTENANCE THERAPY; CERTOLIZUMAB PEGOL;
CLINICAL-RESPONSE; TRIAL; GASTROENTEROLOGY; GOLIMUMAB
AB Background: The availability of monoclonal antibodies to tumor necrosis factor alpha has revolutionized management of Crohn's disease (CD) and ulcerative colitis. However, limited data exist regarding comparative effectiveness of these agents to inform clinical practice. Methods: This study consisted of patients with CD or ulcerative colitis initiation either infliximab (IFX) or adalimumab (ADA) between 1998 and 2010. A validated likelihood of nonresponse classification score using frequency of narrative mentions of relevant symptoms in the electronic health record was applied to assess comparative effectiveness at 1 year. Inflammatory bowel disease-related surgery, hospitalization, and use of steroids were determined during this period. Results: Our final cohort included 1060 new initiations of IFX (68% for CD) and 391 of ADA (79% for CD). In CD, the likelihood of nonresponse was higher in ADA than IFX (odds ratio, 1.62 and 95% CI, 1.21-2.17). Similar differences favoring efficacy of IFX were observed for the individual symptoms of diarrhea, pain, bleeding, and fatigue. However, there was no difference in inflammatory bowel disease-related surgery, hospitalizations, or prednisone use within 1 year after initiation of IFX or ADA in CD. There was no difference in narrative or codified outcomes between the 2 agents in ulcerative colitis. Conclusions: We identified a modestly higher likelihood of symptomatic nonresponse at 1 year for ADA compared with IFX in patients with CD. However, there were no differences in inflammatory bowel disease-related surgery or hospitalizations, suggesting these treatments are broadly comparable in effectiveness in routine clinical practice.
C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Karlson, Elizabeth W.; Kohane, Isaac; Liao, Katherine P.; Murphy, Shawn N.] Harvard Univ, Sch Med, Boston, MA USA.
[Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA.
[Cagan, Andrew; Gainer, Vivian S.] Partners HealthCare, Res IS & Comp, Charlestown, MA USA.
[Cai, Tianxi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA.
[Savova, Guergana] Boston Childrens Hosp, Childrens Hosp, Informat Program, Boston, MA USA.
[Churchill, Susanne; Kohane, Isaac; Murphy, Shawn N.] Harvard Univ, Sch Med, Ctr Biomed Informat, Boston, MA USA.
[Karlson, Elizabeth W.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA.
[Kohane, Isaac] Childrens Hosp Boston, Boston, MA USA.
[Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, Div Gastroenterol, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.
EM aananthakrishnan@mgh.harvard.edu
FU NIH [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01
AR049880]; US National Institutes of Health [K23 DK097142]; Amgen;
Harold and Duval Bowen Fund; Cubist
FX Supported by NIH U54-LM008748. A. N. Ananthakrishnan is supported by
funding from the US National Institutes of Health (K23 DK097142) and
Amgen. K. P. Liao is supported by NIH K08 AR060257 and the Harold and
Duval Bowen Fund. E. W. Karlson is supported by grants from the NIH (K24
AR052403, P60 AR047782, R01 AR049880).; A. N. Ananthakrishnan and S.
Churchill received funding from Amgen; A. N. Ananthakrishnan has
received research support from Cubist and has served on the scientific
advisory boards for Cubist, AbbVie, and Exact Sciences. The other
authors have no conflict of interest to disclose.
NR 31
TC 1
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1078-0998
EI 1536-4844
J9 INFLAMM BOWEL DIS
JI Inflamm. Bowel Dis.
PD APR
PY 2016
VL 22
IS 4
BP 880
EP 885
DI 10.1097/MIB.0000000000000754
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DH7VR
UT WOS:000373002500012
PM 26933751
ER
PT J
AU Adappa, ND
Workman, AD
Hadjiliadis, D
Dorgan, DJ
Frame, D
Brooks, S
Doghramji, L
Palmer, JN
Mansfield, C
Reed, DR
Cohen, NA
AF Adappa, Nithin D.
Workman, Alan D.
Hadjiliadis, Denis
Dorgan, Daniel J.
Frame, Danielle
Brooks, Steven
Doghramji, Laurel
Palmer, James N.
Mansfield, Corrine
Reed, Danielle R.
Cohen, Noam A.
TI T2R38 genotype is correlated with sinonasal quality of life in
homozygous F508 cystic fibrosis patients
SO INTERNATIONAL FORUM OF ALLERGY & RHINOLOGY
LA English
DT Article
DE chronic rhinosinusitis; cystic fibrosis; T2R38; SNOT-22; bitter taste
receptor; genetics
ID TASTE RECEPTOR T2R38; SINUS SURGERY; CHRONIC RHINOSINUSITIS;
PSEUDOMONAS-AERUGINOSA; PARANASAL SINUSES; INFECTION; DISEASE; NASAL;
MECHANISMS; PHENOTYPE
AB BackgroundChronic rhinosinusitis (CRS) is very prevalent in the cystic fibrosis (CF) patient population, and leads to high morbidity and markedly decreased quality of life (QOL). Identification of genetic markers that contribute to CRS symptoms in these patients can allow for risk stratification and tailoring of medical and surgical treatments. T2R38 is a bitter taste receptor expressed in the sinonasal tract, and nonfunctional alleles of this receptor have been implicated in treatment-refractory CRS in non-CF patients. The purpose of this study is to investigate the significance of T2R38 genotype in the variability of sinonasal QOL and CRS disease severity in a sample of CF patients.
MethodsF508 homozygous CF patients were recruited from the University of Pennsylvania Cystic Fibrosis Center and were genotyped for the TAS2R38 locus. To assess sinonasal symptom severity, a 22-item Sino-Nasal Outcome Test (SNOT-22) was collected from each patient. Additional demographic and medical history data was obtained at the time of patient enrollment.
ResultsA total of 49 F508 homozygous CF patients aged 18 to 32 years were included in the final SNOT-22 score analysis. Individuals with 2 functional T2R38 alleles (PAV/PAV) had significantly lower SNOT-22 scores (n = 49, p < 0.05). On further breakdown of SNOT-22 subcategories, rhinologic symptoms specifically were less severe in PAV/PAV patients than patients with other genotypes (n = 47, p < 0.05).
ConclusionOur investigation indicates that T2R38 genotype correlates both with SNOT-22 scores and rhinologic-specific QOL in F508 homozygous CF patients.
C1 [Adappa, Nithin D.; Workman, Alan D.; Brooks, Steven; Doghramji, Laurel; Palmer, James N.; Cohen, Noam A.] Univ Penn, Perelman Sch Med, Dept Otorhinolaryngol Head & Neck Surg, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA.
[Hadjiliadis, Denis; Dorgan, Daniel J.; Frame, Danielle] Univ Penn, Dept Med, Perelman Sch Med, Paul Harron Jr Lung Ctr, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA.
[Mansfield, Corrine; Reed, Danielle R.; Cohen, Noam A.] Monell Smell & Taste Ctr, Philadelphia, PA USA.
[Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Adappa, ND (reprint author), Univ Penn, Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, 5th Floor Ravdin Bldg,3400 Spruce St, Philadelphia, PA 19104 USA.
EM Nithin.Adappa@uphs.upenn.edu
FU American Rhinology Society; Cystic Fibrosis Foundation
FX American Rhinology Society (to N.D.A.); Cystic Fibrosis Foundation (to
N.D.A.).
NR 31
TC 6
Z9 6
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2042-6976
EI 2042-6984
J9 INT FORUM ALLERGY RH
JI Int. Forum Allergy Rhinol.
PD APR
PY 2016
VL 6
IS 4
BP 356
EP 361
DI 10.1002/alr.21675
PG 6
WC Otorhinolaryngology
SC Otorhinolaryngology
GA DI6OH
UT WOS:000373618500003
PM 26678226
ER
PT J
AU Bandyopadhaya, A
Constantinou, C
Psychogios, N
Ueki, R
Yasuhara, S
Martyn, JAJ
Wilhelmy, J
Mindrinos, M
Rahme, LG
Tzika, AA
AF Bandyopadhaya, Arunava
Constantinou, Caterina
Psychogios, Nikolaos
Ueki, Ryusuke
Yasuhara, Shingo
Martyn, J. A. Jeevendra
Wilhelmy, Julie
Mindrinos, Michael
Rahme, Laurence G.
Tzika, A. Aria
TI Bacterial-excreted small volatile molecule 2-aminoacetophenone induces
oxidative stress and apoptosis in murine skeletal muscle
SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
LA English
DT Article
DE Pseudomonas aeruginosa; 2-aminoacetophenone; skeletal muscle; oxidative
stress; apoptosis; mitochondria; nuclear magnetic resonance;
microarrays; genomics
ID PROGRAMMED CELL-DEATH; IN-VIVO DETECTION; PSEUDOMONAS-AERUGINOSA;
MITOCHONDRIAL DYSFUNCTION; CYSTIC-FIBROSIS; PROTEIN-METABOLISM;
VIRUS-INFECTION; BURN-TRAUMA; PATHWAYS; SPECTROSCOPY
AB Oxidative stress induces mitochondrial dysfunction and facilitates apoptosis, tissue damage or metabolic alterations following infection. We have previously discovered that the Pseudomonas aeruginosa (PA) quorum sensing (QS)-excreted small volatile molecule, 2-aminoacetophenone (2-AA), which is produced in infected human tissue, promotes bacterial phenotypes that favor chronic infection, while also compromising muscle function and dampens the pathogen-induced innate immune response, promoting host tolerance to infection. In this study, murine whole-genome expression data have demonstrated that 2-AA affects the expression of genes involved in reactive oxygen species (ROS) homeostasis, thus producing an oxidative stress signature in skeletal muscle. The results of the present study demonstrated that the expression levels of genes involved in apoptosis signaling pathways were upregulated in the skeletal muscle of 2-AA-treated mice. To confirm the results of our transcriptome analysis, we used a novel high-resolution magic-angle-spinning (HRMAS), proton (H-1) nuclear magnetic resonance (NMR) method and observed increased levels of bisallylic methylene fatty acyl protons and vinyl protons, suggesting that 2-AA induces skeletal muscle cell apoptosis. This effect was corroborated by our results demonstrating the downregulation of mitochondrial membrane potential in vivo in response to 2-AA. The findings of the present study indicate that the bacterial infochemical, 2-AA, disrupts mitochondrial functions by inducing oxidative stress and apoptosis signaling and likely promotes skeletal muscle dysfunction, which may favor chronic/persistent infection.
C1 [Bandyopadhaya, Arunava; Constantinou, Caterina; Rahme, Laurence G.] Harvard Univ, Sch Med, Dept Surg Microbiol & Immunobiol, Boston, MA 02114 USA.
[Bandyopadhaya, Arunava; Constantinou, Caterina; Rahme, Laurence G.] Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA.
[Bandyopadhaya, Arunava; Constantinou, Caterina; Rahme, Laurence G.] Shriners Burns Hosp, Boston, MA 02114 USA.
[Bandyopadhaya, Arunava; Constantinou, Caterina; Psychogios, Nikolaos; Rahme, Laurence G.; Tzika, A. Aria] Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA.
[Bandyopadhaya, Arunava; Constantinou, Caterina; Psychogios, Nikolaos; Rahme, Laurence G.; Tzika, A. Aria] Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA.
[Psychogios, Nikolaos; Tzika, A. Aria] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA.
[Psychogios, Nikolaos; Ueki, Ryusuke; Yasuhara, Shingo; Martyn, J. A. Jeevendra; Tzika, A. Aria] Harvard Univ, Sch Med, Boston, MA 02129 USA.
[Ueki, Ryusuke; Yasuhara, Shingo; Martyn, J. A. Jeevendra] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA.
[Wilhelmy, Julie; Mindrinos, Michael] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA.
RP Rahme, LG (reprint author), Harvard Univ, Sch Med, Dept Surg Microbiol & Immunobiol, Boston, MA 02114 USA.; Rahme, LG (reprint author), Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Dept Surg, Mol Surg Lab, Boston, MA 02114 USA.; Tzika, AA (reprint author), Massachusetts Gen Hosp, Ctr Surg Innovat & Bioengn, Dept Surg, NMR Surg Lab, Boston, MA 02114 USA.; Tzika, AA (reprint author), Harvard Univ, Sch Med, Shriners Burns Hosp, Boston, MA 02114 USA.
EM rahme@molbio.mgh.harvard.edu; atzika@hms.harvard.edu
OI Constantinou, Caterina/0000-0003-3589-0739
FU Shriner's Hospital for Children research grants [87100, 85200]; Basic
Research Award; US Army Medical Research Acquisition Act of US
Department of Defense, Congressionally Directed Medical Research
Programs (CDMRP) [W81XWH-10-DMRDP-BRA]; Defense Medical Research and
Development Program (DMRDP); Center grant of the National Institutes of
Health (NIH); NIH [AI105902]
FX This study was supported in part by Shriner's Hospital for Children
research grants (nos. 87100 and 85200), and Basic Research Award,
W81XWH-10-DMRDP-BRA from US Army Medical Research Acquisition Act of US
Department of Defense, Congressionally Directed Medical Research
Programs (CDMRP), Defense Medical Research and Development Program
(DMRDP) to Laurence G. Rahme, and by a Center grant of the National
Institutes of Health (NIH) to the Stanford Genome Technology Cente, as
well as by NIH grant AI105902. We acknowledge Dr Damien Maura at the
Massachusetts General Hospital and Harvard Medical School for his
insightful comments on the manuscript.
NR 85
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U1 1
U2 1
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1107-3756
EI 1791-244X
J9 INT J MOL MED
JI Int. J. Mol. Med.
PD APR
PY 2016
VL 37
IS 4
BP 867
EP 878
DI 10.3892/ijmm.2016.2487
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DI4TS
UT WOS:000373492900001
PM 26935176
ER
PT J
AU Schmid, M
Hanske, J
Ravi, P
Krishna, N
Reznor, G
Meyer, CP
Fisch, M
Noldus, J
Nguyen, PL
Trinh, QD
AF Schmid, Marianne
Hanske, Julian
Ravi, Praful
Krishna, Nandita
Reznor, Gally
Meyer, Christian P.
Fisch, Margit
Noldus, Joachim
Nguyen, Paul L.
Quoc-Dien Trinh
TI Relationship between androgen deprivation therapy and community-acquired
respiratory infections in patients with prostate cancer
SO INTERNATIONAL JOURNAL OF UROLOGY
LA English
DT Article
DE androgen deprivation therapy; pneumonia; prostate cancer; respiratory
infections; Surveillance; Epidemiology and End Results-Medicare
ID HORMONE AGONISTS; RISK; HOSPITALIZATIONS; POPULATION; FRACTURE; DISEASE;
MEN
AB Objectives: To investigate the dose-dependent effect of androgen deprivation therapy on community-acquired respiratory infections in patients with localized prostate cancer.
Methods: We identified 52 905 men diagnosed with localized prostate cancer within the Surveillance, Epidemiology and End Results-Medicare database between 1991 and 2006. We compared those who did not receive androgen deprivation therapy with those who received androgen deprivation therapy within 2 years of diagnosis, calculated as monthly equivalent doses (< 7, 7-11, > 11 doses), or orchiectomy. Adjusted Cox hazard models were fitted to predict the risk of community-acquired respiratory infections (acute sinusitis, acute bronchitis, [severe] pneumonia) in patients treated with medical androgen deprivation therapy versus orchiectomy versus none.
Results: Overall, 43.4% received medical androgen deprivation therapy. These patients more likely experienced respiratory events compared with those who did not receive androgen deprivation therapy or who underwent orchiectomy (62.2% vs 54.5% vs 47.8%, P < 0.001). The risk of experiencing any respiratory event increased with the number of doses received. For example, men receiving > 11 doses of androgen deprivation therapy were at greatest risk of acute sinusitis, acute bronchitis and pneumonia (HR 1.13, 1.26 and 1.15, respectively, all P < 0.001), except severe pneumonia. Furthermore, we did not detect any relationship between orchiectomy and respiratory events. Study limitations include the utilization of a retrospective population-based dataset.
Conclusions: Increased exposure to medical androgen deprivation therapy for men with localized prostate cancer is associated with a higher risk of community-acquired respiratory infections. Our results suggest that respiratory complications represent potentially underreported complications of medical androgen deprivation therapy.
C1 [Schmid, Marianne; Hanske, Julian; Krishna, Nandita; Reznor, Gally; Meyer, Christian P.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 45 Francis St,ASB II-3, Boston, MA 02115 USA.
[Schmid, Marianne; Hanske, Julian; Krishna, Nandita; Reznor, Gally; Meyer, Christian P.; Quoc-Dien Trinh] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Urol Surg, 45 Francis St,ASB II-3, Boston, MA 02115 USA.
[Schmid, Marianne; Meyer, Christian P.; Fisch, Margit] Univ Med Ctr Hamburg Eppendorf, Dept Urol, Hamburg, Germany.
[Hanske, Julian; Noldus, Joachim] Ruhr Univ Bochum, Marien Hosp, Dept Urol, Herne, Germany.
[Ravi, Praful] Mayo Clin, Dept Med, Rochester, MN USA.
[Nguyen, Paul L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, 45 Francis St,ASB II-3, Boston, MA 02115 USA.
RP Trinh, QD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Surg & Publ Hlth,Div Urol Surg, 45 Francis St,ASB II-3, Boston, MA 02115 USA.
EM qtrinh@partners.org
FU Vattikuti Urology Institute; Professor Walter Morris-Hale Distinguished
Chair in Urologic Oncology at Brigham and Women's Hospital; University
Medical Center Hamburg-Eppendorf; Heinrich Hertz-Stiftung
FX 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. Marianne Schmid is supported by the Equal Opportunity Grant
for Women of the University Medical Center Hamburg-Eppendorf. Julian
Hanske is supported by a grant from the Heinrich Hertz-Stiftung.
NR 30
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U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0919-8172
EI 1442-2042
J9 INT J UROL
JI Int. J. Urol.
PD APR
PY 2016
VL 23
IS 4
BP 305
EP 311
DI 10.1111/iju.13043
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA DI8TZ
UT WOS:000373776200003
PM 26763083
ER
PT J
AU Hemal, K
Pagidipati, NJ
Coles, A
Dolor, RJ
Mark, DB
Pellikka, PA
Hoffmann, U
Litwin, SE
Daubert, MA
Shah, SH
Ariani, K
Bullock-Palmer, RP
Martinez, B
Lee, KL
Douglas, PS
AF Hemal, Kshipra
Pagidipati, Neha J.
Coles, Adrian
Dolor, Rowena J.
Mark, Daniel B.
Pellikka, Patricia A.
Hoffmann, Udo
Litwin, Sheldon E.
Daubert, Melissa A.
Shah, Svati H.
Ariani, Kevin
Bullock-Palmer, Renee P.
Martinez, Beth
Lee, Kerry L.
Douglas, Pamela S.
TI Sex Differences in Demographics, Risk Factors, Presentation, and
Noninvasive Testing in Stable Outpatients With Suspected Coronary Artery
Disease
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE angina; CAD; risk factors; sex
ID AMERICAN-HEART-ASSOCIATION; GENDER-DIFFERENCES; MYOCARDIAL-INFARCTION;
SYMPTOM PRESENTATION; EXERCISE ECHOCARDIOGRAPHY; CARDIOVASCULAR RISK;
CHEST-PAIN; MANAGEMENT; DIAGNOSIS; OUTCOMES
AB OBJECTIVES The aim of this study was to determine whether presentation, risk assessment, testing choices, and results differ by sex in stable symptomatic outpatients with suspected coronary artery disease (CAD).
BACKGROUND Although established CAD presentations differ by sex, little is known about stable, suspected CAD.
METHODS The characteristics of 10,003 men and women in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial were compared using chi-square and Wilcoxon rank-sum tests. Sex differences in test selection and predictors of test positivity were examined using logistic regression.
RESULTS Women were older (62.4 years of age vs. 59.0 years of age) and were more likely to be hypertensive (66.6% vs. 63.2%), dyslipidemic (68.9% vs. 66.3%), and to have a family history of premature CAD (34.6% vs. 29.3) (all p values<0.005). Women were less likely to smoke (45.6% vs. 57.0%; p<0.001), although their prevalence of diabetes was similar to that in men(21.8% vs. 21.0%; p = 0.30). Chest pain was the primary symptomin 73.2% of women versus 72.3% of men (p = 0.30), and was characterized as "crushing/pressure/ squeezing/tightness" in 52.5% of women versus 46.2% of men (p<0.001). Compared with men, all risk scores characterized women as being at lower risk, and providers were more likely to characterize women as having a low (<30%) pre-test probability of CAD (40.7% vs. 34.1%; p < 0.001). Compared with men, women were more often referred to imaging tests (adjusted odds ratio: 1.21; 95% confidence interval: 1.01 to 1.44) than nonimaging tests. Women were less likely to have a positive test (9.7% vs. 15.1%; p < 0.001). Although univariate predictors of test positivity were similar, in multivariable models, age, body mass index, and Framingham risk score were predictive of a positive test in women, whereas Framingham and Diamond and Forrester risk scores were predictive in men.
CONCLUSIONS Patient sex influences the entire diagnostic pathway for possible CAD, from baseline risk factors and presentation to noninvasive test outcomes. These differences highlight the need for sex-specific approaches for the evaluation of CAD. (C) 2016 by the American College of Cardiology Foundation.
C1 [Hemal, Kshipra; Pagidipati, Neha J.; Coles, Adrian; Dolor, Rowena J.; Mark, Daniel B.; Daubert, Melissa A.; Shah, Svati H.; Martinez, Beth; Lee, Kerry L.; Douglas, Pamela S.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC 27715 USA.
[Dolor, Rowena J.; Shah, Svati H.] Duke Univ, Sch Med, Dept Med, Durham, NC 27715 USA.
[Pellikka, Patricia A.] Mayo Clin, Coll Med, Rochester, MN USA.
[Hoffmann, Udo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Litwin, Sheldon E.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA.
[Ariani, Kevin] Northridge Hosp, Med Ctr, Northridge, CA USA.
[Bullock-Palmer, Renee P.] Deborah Heart & Lung Ctr, Browns Mills, NJ USA.
RP Douglas, PS (reprint author), Duke Univ, Sch Med, 7022 North Pavil DUMC,POB 17969, Durham, NC 27715 USA.
EM pamela.douglas@duke.edu
FU National Heart, Lung, and Blood Institute [R01 HL098237, R01 HL098236,
R01 HL098305, R01 HL098235]; Medtronic; CardioDx; St. Jude Medical; Eli
Lilly; Bristol-Myers Squibb; Gilead Sciences; AGA Medical; Merck; Oxygen
Biotherapeutics; AstraZeneca; Siemens Healthcare; HeartFlow
FX From the aDuke Clinical Research Institute, Duke University
School of Medicine, Durham, North Carolina; bDepartment of
Medicine, Duke University School of Medicine, Durham, North Carolina;
cMayo Clinic College of Medicine, Rochester, Minnesota;
dMassachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts; eDepartment of Medicine, Medical
University of South Carolina, Charleston, South Carolina;
fNorthridge Hospital Medical Center, Northridge, California;
and the gDeborah Heart and Lung Center, Browns Mills, New
Jersey. The PROMISE trial was funded by National Heart, Lung, and Blood
Institute grants R01 HL098237, R01 HL098236, R01 HL098305, and R01
HL098235. The funding source 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. The views expressed in this
paper do not necessarily represent the official views of the National
Heart, Lung, and Blood Institute. Dr. Mark has received personal fees
from Medtronic, CardioDx, and St. Jude Medical; and grant support from
Eli Lilly, Bristol-Myers Squibb, Gilead Sciences, AGA Medical, Merck,
Oxygen Biotherapeutics, and AstraZeneca. Dr. Hoffmann has received grant
support from Siemens Healthcare and HeartFlow. Dr. Douglas has received
grant support from HeartFlow; and serves on a data and safety monitoring
board for General Electric Healthcare. All other authors have reported
that they have no relationships relevant to the contents of this paper
to disclose.
NR 35
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD APR
PY 2016
VL 9
IS 4
BP 337
EP 346
DI 10.1016/j.jcmg.2016.02.001
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DI8AE
UT WOS:000373722300001
PM 27017234
ER
PT J
AU Shi, L
Dorbala, S
Paez, D
Shaw, LJ
Zukotynski, KA
Pascual, TNB
Karthikeyan, G
Vitola, JV
Better, N
Bokhari, N
Rehani, MM
Kashyap, R
Dondi, M
Mercuri, M
Einstein, AJ
AF Shi, Lynn
Dorbala, Sharmila
Paez, Diana
Shaw, Leslee J.
Zukotynski, Katherine A.
Pascual, Thomas N. B.
Karthikeyan, Ganesan
Vitola, Joao V.
Better, Nathan
Bokhari, Nadia
Rehani, Madan M.
Kashyap, Ravi
Dondi, Maurizio
Mercuri, Mathew
Einstein, Andrew J.
CA INCAPS Investigators Grp
TI Gender Differences in Radiation Dose From Nuclear Cardiology Studies
Across the World Findings From the INCAPS Registry
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE gender; nuclear cardiology; radiation exposure
ID MYOCARDIAL-PERFUSION SPECT; RISK STRATIFICATION; PROGNOSTIC VALUE;
WOMEN; EXPOSURE; TOMOGRAPHY; MANAGEMENT; MEDICINE; DISEASE; SEX
AB OBJECTIVES The aim of this study was to investigate gender-based differences in nuclear cardiology practice globally, with a particular focus on laboratory volume, radiation dose, protocols, and best practices.
BACKGROUND It is unclear whether gender-based differences exist in radiation exposure for nuclear cardiology procedures.
METHODS In a large, multicenter, observational, cross-sectional study encompassing 7,911 patients in 65 countries, radiation effective dose was estimated for each examination. Patient-level best practices relating to radiation exposure were compared between genders. Analysis of covariance was used to determine any difference in radiation exposure according to gender, region, and the interaction between gender and region. Linear, logistic, and hierarchical regression models were developed to evaluate gender-based differences in radiation exposure and laboratory adherence to best practices. The study also included the United Nations Gender Inequality Index and Human Development Index as covariates in multivariable models.
RESULTS The proportion of myocardial perfusion imaging studies performed in women varied among countries; however, there was no significant correlation with the Gender Inequality Index. Globally, mean effective dose for nuclear cardiology procedures was only slightly lower in women (9.6 +/- 4.5 mSv) than in men (10.3 +/- 4.5 mSv; p < 0.001), with a difference of only 0.3 mSv in a multivariable model adjusting for patients' age and weight. Stress-only imaging was performed more frequently in women (12.5% vs. 8.4%; p < 0.001); however, camera-based dose reduction strategies were used less frequently in women (58.6% vs. 65.5%; p < 0.001).
\CONCLUSIONS Despite significant worldwide variation in best practice use and radiation doses from nuclear cardiology procedures, only small differences were observed between genders worldwide. Regional variations noted in myocardial perfusion imaging use and radiation dose offer potential opportunities to address gender-related differences in delivery of nuclear cardiology care. (C) 2016 by the American College of Cardiology Foundation.
C1 [Shi, Lynn] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Dorbala, Sharmila] Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiol, Boston, MA 02115 USA.
[Paez, Diana; Pascual, Thomas N. B.; Kashyap, Ravi; Dondi, Maurizio] IAEA, Div Human Hlth, Sect Nucl Med & Diagnost Imaging, A-1400 Vienna, Austria.
[Shaw, Leslee J.] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA.
[Shaw, Leslee J.] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Atlanta, GA USA.
[Zukotynski, Katherine A.] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Zukotynski, Katherine A.] McMaster Univ, Dept Radiol, Hamilton, ON, Canada.
[Karthikeyan, Ganesan] All India Inst Med Sci, Dept Cardiol, New Delhi, India.
[Vitola, Joao V.] Quanta Diagnost & Terapia, Curitiba, Parana, Brazil.
[Better, Nathan] Royal Melbourne Hosp, Dept Cardiol, Melbourne, Vic, Australia.
[Better, Nathan] Royal Melbourne Hosp, Dept Nucl Med, Melbourne, Vic, Australia.
[Bokhari, Nadia; Mercuri, Mathew; Einstein, Andrew J.] Columbia Univ, Med Ctr, Dept Med, Div Cardiol, New York, NY USA.
[Rehani, Madan M.] IAEA, Radiat Protect Patients Unit, A-1400 Vienna, Austria.
[Rehani, Madan M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
[Einstein, Andrew J.] New York Presbyterian Hosp, New York, NY USA.
[Einstein, Andrew J.] Columbia Univ, Dept Radiol, Med Ctr, New York, NY USA.
RP Einstein, AJ (reprint author), Columbia Univ, Med Ctr, Div Cardiol, 622 West 168th St PH 10-203, New York, NY 10032 USA.
EM andrew.einstein@columbia.edu
RI Lahoutte, Tony/O-6381-2016; Maffioli, Lorenzo Stefano/Q-4985-2016;
OI Maffioli, Lorenzo Stefano/0000-0002-8867-2447; Murthy,
Venkatesh/0000-0002-7901-1321; florimonte, luigia/0000-0002-5254-6852;
Al-Mallah, Mouaz/0000-0003-2348-0484
FU National Institutes of Health-National Heart, Lung, and Blood Institute
Summer Research Program at Columbia University [5T35HL007616-34];
International Atomic Energy Agency; Margaret Q. Landenberger Research
Foundation in memory of Professor A; Astellas; GE Healthcare; Philips
Healthcare; Spectrum Dynamics; Toshiba America Medical Systems
FX From the aCollege of Physicians and Surgeons, Columbia
University, New York, New York; bDivision of Cardiology,
Department of Medicine, Brigham and Women's Hospital, Harvard
University, Boston, Massachusetts; cSection of Nuclear
Medicine and Diagnostic Imaging, Division of Human Health, International
Atomic Energy Agency, Vienna, Austria; dDivision of
Cardiology, Department of Medicine, and Emory Clinical Cardiovascular
Research Institute, Emory University School of Medicine, Atlanta,
Georgia; eDepartments of Medicine and Radiology, McMaster
University, Hamilton, Ontario, Canada; fDepartment of
Cardiology, All India Institute of Medical Sciences, New Delhi, India;
gQuanta Diagnostico & Terapia, Curitiba, Brazil;
hDepartments of Cardiology and Nuclear Medicine, Royal
Melbourne Hospital, Melbourne, Australia; iDepartment of
Medicine, Cardiology Division, Columbia University Medical Center, New
York, New York; jRadiation Protection of Patients Unit,
International Atomic Energy Agency, Vienna, Austria;
kDepartment of Radiology, Massachusetts General Hospital,
Boston, Massachusetts; lDepartment of Medicine, Cardiology
Division, Columbia University Medical Center and New York-Presbyterian
Hospital, New York, New York; and the mDepartment of
Radiology, Columbia University Medical Center and New York-Presbyterian
Hospital, New York, New York. Funding was provided by the National
Institutes of Health-National Heart, Lung, and Blood Institute Summer
Research Program at Columbia University (5T35HL007616-34); the
International Atomic Energy Agency; and the Margaret Q. Landenberger
Research Foundation in memory of Professor A. Donny Strosberg; and the
Irving Scholars Program. Dr. Dorbala has received an institutional
research grant from Astellas; and owns stock in GE. Dr. Einstein has
received institutional research grants for other research from GE
Healthcare, Philips Healthcare, Spectrum Dynamics, and Toshiba America
Medical Systems. All other authors have reported that they have no
relationships relevant to the contents of this paper to disclose.
Heinrich Schelbert, MD, served as the Guest Editor for this article.
NR 26
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U1 0
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD APR
PY 2016
VL 9
IS 4
BP 376
EP 384
DI 10.1016/j.jcmg.2016.01.001
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA DI8AE
UT WOS:000373722300007
PM 27056156
ER
PT J
AU Reeves, GR
Forman, DE
AF Reeves, Gordon R.
Forman, Daniel E.
TI Gait Speed: Stepping Towards Improved Assessment of Heart Failure
Patients
SO JACC-HEART FAILURE
LA English
DT Editorial Material
DE frailty; gait speed; heart failure; hospitalization; prognosis
ID PRESERVED EJECTION FRACTION; CARDIOVASCULAR HEALTH; ELDERLY-PATIENTS;
OLDER PERSONS; RISK-FACTORS; ADULTS; OUTCOMES; IMPACT; CARE
C1 [Reeves, Gordon R.] Thomas Jefferson Univ, Dept Med, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
[Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Geriatr Cardiol Sect, Div Cardiol, Pittsburgh, PA 15213 USA.
[Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Geriatr Cardiol Sect, Div Geriatr, Pittsburgh, PA 15213 USA.
[Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA.
[Forman, Daniel E.] Univ Pittsburgh, Dept Med, 930 Scaife Hall, Pittsburgh, PA 15213 USA.
RP Forman, DE (reprint author), Univ Pittsburgh, Geriatr Cardiol Sect, 3471 Fifth Ave,Suite 500, Pittsburgh, PA 15213 USA.
EM formand@pitt.edu
NR 16
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U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2213-1779
EI 2213-1787
J9 JACC-HEART FAIL
JI JACC-Heart Fail.
PD APR
PY 2016
VL 4
IS 4
BP 299
EP 300
DI 10.1016/j.jchf.2016.02.002
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DI8KT
UT WOS:000373750600010
PM 27033017
ER
PT J
AU Auerbach, AD
Kripalani, S
Vasilevskis, EE
Sehgal, N
Lindenauer, PK
Metlay, JP
Fletcher, G
Ruhnke, GW
Flanders, SA
Kim, C
Williams, MV
Thomas, L
Giang, V
Herzig, SJ
Patel, K
Boscardin, WJ
Robinson, EJ
Schnipper, JL
AF Auerbach, Andrew D.
Kripalani, Sunil
Vasilevskis, Eduard E.
Sehgal, Neil
Lindenauer, Peter K.
Metlay, Joshua P.
Fletcher, Grant
Ruhnke, Gregory W.
Flanders, Scott A.
Kim, Christopher
Williams, Mark V.
Thomas, Larissa
Giang, Vernon
Herzig, Shoshana J.
Patel, Kanan
Boscardin, W. John
Robinson, Edmondo J.
Schnipper, Jeffrey L.
TI Preventability and Causes of Readmissions in a National Cohort of
General Medicine Patients
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID ADVERSE DRUG EVENTS; HOSPITAL READMISSIONS; PHARMACIST INTERVENTION;
RANDOMIZED-TRIAL; CARE; RISK; QUALITY; TRANSITIONS; STRATEGIES;
RATIONALE
AB IMPORTANCE Readmission penalties have catalyzed efforts to improve care transitions, but few programs have incorporated viewpoints of patients and health care professionals to determine readmission preventability or to prioritize opportunities for care improvement.
OBJECTIVES To determine preventability of readmissions and to use these estimates to prioritize areas for improvement.
DESIGN, SETTING, AND PARTICIPANTS An observational studywas conducted of 1000 general medicine patients readmitted within 30 days of discharge to 12 US academic medical centers between April 1, 2012, and March 31, 2013. We surveyed patients and physicians, reviewed documentation, and performed 2-physician case review to determine preventability of and factors contributing to readmission. We used bivariable statistics to compare preventable and nonpreventable readmissions, multivariable models to identify factors associated with potential preventability, and baseline risk factor prevalence and adjusted odds ratios (aORs) to determine the proportion of readmissions affected by individual risk factors.
MAIN OUTCOME AND MEASURE Likelihood that a readmission could have been prevented.
RESULTS The study cohort comprised 1000 patients (median age was 55 years). Of these, 269 (26.9%) were considered potentially preventable. In multivariable models, factors most strongly associated with potential preventability included emergency department decision making regarding the readmission (aOR, 9.13; 95% CI, 5.23-15.95), failure to relay important information to outpatient health care professionals (aOR, 4.19; 95% CI, 2.17-8.09), discharge of patients too soon (aOR, 3.88; 95% CI, 2.44-6.17), and lack of discussions about care goals among patients with serious illnesses (aOR, 3.84; 95% CI, 1.39-10.64). The most common factors associated with potentially preventable readmissions included emergency department decision making (affecting 9.0%; 95% CI, 7.1%-10.3%), inability to keep appointments after discharge (affecting 8.3%; 95% CI, 4.1%-12.0%), premature discharge from the hospital (affecting 8.7%; 95% CI, 5.8%-11.3%), and patient lack of awareness of whom to contact after discharge (affecting 6.2%; 95% CI, 3.5%-8.7%).
CONCLUSIONS AND RELEVANCE Approximately one-quarter of readmissions are potentially preventable when assessed using multiple perspectives. High-priority areas for improvement efforts include improved communication among health care teams and between health care professionals and patients, greater attention to patients' readiness for discharge, enhanced disease monitoring, and better support for patient self-management.
C1 [Auerbach, Andrew D.; Sehgal, Neil] Univ Calif San Francisco, Dept Med, Div Hosp Med, 505 Parnassus Ave,POB 0131, San Francisco, CA 94143 USA.
[Kripalani, Sunil; Vasilevskis, Eduard E.] Vanderbilt Univ, Dept Med, Sect Hosp Med Vanderbilt, Nashville, TN USA.
[Kripalani, Sunil; Vasilevskis, Eduard E.] Vanderbilt Univ, Ctr Clin Qual & Implementat Res, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Lindenauer, Peter K.] Tufts Univ, Sch Med, Dept Med, Ctr Qual Care Res,Baystate Med Ctr, Boston, MA 02111 USA.
[Metlay, Joshua P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Fletcher, Grant] Univ Washington, Harborview Med Ctr, Div Gen Internal Med, 325 9th Ave, Seattle, WA 98104 USA.
[Ruhnke, Gregory W.] Univ Chicago, Dept Med, Sect Hosp Med, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Flanders, Scott A.; Kim, Christopher] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Williams, Mark V.] Univ Kentucky, Coll Med, Ctr Hlth Serv Res, Louisville, KY USA.
[Thomas, Larissa] San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA.
[Giang, Vernon] Calif Pacific Med Ctr, Dept Med, San Francisco, CA USA.
[Herzig, Shoshana J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Patel, Kanan] Univ Calif San Francisco, Dept Med, Div Geriatr, 505 Parnassus Ave,POB 0131, San Francisco, CA 94143 USA.
[Boscardin, W. John] Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,POB 0131, San Francisco, CA 94143 USA.
[Boscardin, W. John] Univ Calif San Francisco, Dept Epidemiol & Biostat, 505 Parnassus Ave,POB 0131, San Francisco, CA 94143 USA.
[Robinson, Edmondo J.] Christiana Care Hlth Syst, Value Inst, Wilmington, DE USA.
[Robinson, Edmondo J.] Christiana Care Hlth Syst, Dept Med, Wilmington, DE USA.
[Schnipper, Jeffrey L.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Hosp Med Serv,Div Gen Med, Boston, MA 02115 USA.
RP Auerbach, AD (reprint author), Univ Calif San Francisco, Dept Med, Div Hosp Med, 505 Parnassus Ave,POB 0131, San Francisco, CA 94143 USA.
EM andrew.auerbach@ucsf.edu
OI Robinson, Edmondo/0000-0001-9625-6235
FU National Heart, Lung, and Blood Institute [K24HL098372]; American
Association of Medical Colleges; National Institute on Aging [2 UL1
TR000445-06]
FX Dr Auerbach is supported by grant K24HL098372 from the National Heart,
Lung, and Blood Institute. This work was supported by an unrestricted
research grant from the American Association of Medical Colleges and in
part by grant 2 UL1 TR000445-06 from the National Institute on Aging.
NR 38
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U1 2
U2 3
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 APR
PY 2016
VL 176
IS 4
BP 484
EP 493
DI 10.1001/jamainternmed.2015.7863
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EG
UT WOS:000373380600017
PM 26954564
ER
PT J
AU Atkins, D
Kansagara, D
AF Atkins, David
Kansagara, Devan
TI Reducing Readmissions-Destination or Journey?
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
ID CARE TRANSITIONS; RATES
C1 [Atkins, David] US Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev, 10P9H,810 Vermont Ave NW, Washington, DC 20420 USA.
[Kansagara, Devan] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA.
[Kansagara, Devan] Vet Affairs Portland Healthcare Syst, Portland, OR USA.
RP Atkins, D (reprint author), US Dept Vet Affairs, Off Res & Dev, Hlth Serv Res & Dev, 10P9H,810 Vermont Ave NW, Washington, DC 20420 USA.
EM David.atkins@va.gov
NR 8
TC 1
Z9 1
U1 0
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 APR
PY 2016
VL 176
IS 4
BP 493
EP 495
DI 10.1001/jamainternmed.2015.8603
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EG
UT WOS:000373380600018
PM 26954103
ER
PT J
AU Donze, JD
Williams, MV
Robinson, EJ
Zimlichman, E
Aujesky, D
Vasilevskis, EE
Kripalani, S
Metlay, JP
Wallington, T
Fletcher, GS
Auerbach, AD
Schnipper, JL
AF Donze, Jacques D.
Williams, Mark V.
Robinson, Edmondo J.
Zimlichman, Eyal
Aujesky, Drahomir
Vasilevskis, Eduard E.
Kripalani, Sunil
Metlay, Joshua P.
Wallington, Tamara
Fletcher, Grant S.
Auerbach, Andrew D.
Schnipper, Jeffrey L.
TI International Validity of the HOSPITAL Score to Predict 30-Day
Potentially Avoidable Hospital Readmissions
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID ATRIAL-FIBRILLATION; RISK PREDICTION; ANTICOAGULATED PATIENTS; MEDICAL
PATIENTS; BLEEDING RISK; VALIDATION; MODELS; CHADS(2); TRIAL
AB IMPORTANCE Identification of patients at a high risk of potentially avoidable readmission allows hospitals to efficiently direct additional care transitions services to the patients most likely to benefit.
OBJECTIVE To externally validate the HOSPITAL score in an international multicenter study to assess its generalizability.
DESIGN, SETTING, AND PARTICIPANTS International retrospective cohort study of 117 065 adult patients consecutively discharged alive from the medical department of 9 large hospitals across 4 different countries between January 2011 and December 2011. Patients transferred to another acute care facility were excluded.
EXPOSURES The HOSPITAL score includes the following predictors at discharge: hemoglobin, discharge from an oncology service, sodium level, procedure during the index admission, index type of admission (urgent), number of admissions during the last 12 months, and length of stay.
MAIN OUTCOMES AND MEASURES 30-day potentially avoidable readmission to the index hospital using the SQLape algorithm.
RESULTS Overall, 117 065 adults consecutively discharged alive from a medical department between January 2011 and December 2011 were studied. Of all medical discharges, 16 992 of 117 065 (14.5%) were followed by a 30-day readmission, and 11 307 (9.7%) were followed by a 30-day potentially avoidable readmission. The discriminatory power of the HOSPITAL score to predict potentially avoidable readmission was good, with a C statistic of 0.72 (95% CI, 0.72-0.72). As in the derivation study, patients were classified into 3 risk categories: low (n = 73 031 [62.4%]), intermediate (n = 27 612 [23.6%]), and high risk (n = 16 422 [14.0%]). The estimated proportions of potentially avoidable readmission for each risk category matched the observed proportion, resulting in an excellent calibration (Pearson.2 test P = .89).
CONCLUSIONS AND RELEVANCE The HOSPITAL score identified patients at high risk of 30-day potentially avoidable readmission with moderately high discrimination and excellent calibration when applied to a large international multicenter cohort of medical patients. This score has the potential to easily identify patients in need of more intensive transitional care interventions to prevent avoidable hospital readmissions.
C1 [Donze, Jacques D.; Aujesky, Drahomir] Univ Hosp Bern, Div Gen Internal Med, CH-3010 Bern, Switzerland.
[Donze, Jacques D.; Schnipper, Jeffrey L.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA.
[Donze, Jacques D.; Schnipper, Jeffrey L.] Harvard Univ, Sch Med, Boston, MA USA.
[Williams, Mark V.] Univ Kentucky, Ctr Hlth Serv Res, Lexington, KY 40506 USA.
[Robinson, Edmondo J.] Christiana Care Hlth Syst, Value Inst, Wilmington, DE USA.
[Zimlichman, Eyal] Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel.
[Vasilevskis, Eduard E.; Kripalani, Sunil] Vanderbilt Univ, Med Ctr, Sect Hosp Med, Nashville, TN USA.
[Vasilevskis, Eduard E.; Kripalani, Sunil] Vanderbilt Univ, Med Ctr, Ctr Clin Qual & Implementat Res, Nashville, TN USA.
[Vasilevskis, Eduard E.] Vet Affairs Tennessee Valley Geriatr Res Educ & C, Nashville, TN USA.
[Metlay, Joshua P.] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
[Wallington, Tamara] William Osler Hlth Syst, Toronto, ON, Canada.
[Fletcher, Grant S.] Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA.
[Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, San Francisco, CA 94143 USA.
RP Donze, JD (reprint author), Univ Hosp Bern, Inselspital, Univ Klin Allgemeine Innere Med, CH-3010 Bern, Switzerland.
EM donze.author@gmail.com
OI Robinson, Edmondo/0000-0001-9625-6235
FU Swiss National Science Foundation; Swiss Foundation for
Medical-Biological Scholarships [PASMP3-142734]; National Institute on
Aging of the National Institutes of Health [K23AG040157]; Veterans
Affairs Clinical Research Center of Excellence, the Geriatric Research,
Education, and Clinical Center (GRECC)
FX Dr Donze was supported by the Swiss National Science Foundation and the
Swiss Foundation for Medical-Biological Scholarships (grant No.
PASMP3-142734). Dr Vasilevskis was supported by the National Institute
on Aging of the National Institutes of Health (award No. K23AG040157)
and the Veterans Affairs Clinical Research Center of Excellence, the
Geriatric Research, Education, and Clinical Center (GRECC).
NR 28
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U1 2
U2 6
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 APR
PY 2016
VL 176
IS 4
BP 496
EP 502
DI 10.1001/jamainternmed.2015.8462
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EG
UT WOS:000373380600019
PM 26954698
ER
PT J
AU Blumenthal, D
Hsiao, W
Blumenthal, DM
AF Blumenthal, David
Hsiao, William
Blumenthal, Daniel M.
TI Caring for Coronary Artery Disease in China Managing Modernization
SO JAMA INTERNAL MEDICINE
LA English
DT Editorial Material
C1 [Blumenthal, David] Commonwealth Fund, One E 75th St, New York, NY 11201 USA.
[Hsiao, William] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Blumenthal, Daniel M.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA.
RP Blumenthal, D (reprint author), Commonwealth Fund, One E 75th St, New York, NY 11201 USA.
EM db@cmwf.org
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 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD APR
PY 2016
VL 176
IS 4
BP 521
EP 523
DI 10.1001/jamainternmed.2016.0198
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EG
UT WOS:000373380600023
PM 26974368
ER
PT J
AU McIlvennan, CK
Jones, J
Allen, LA
Swetz, KM
Nowels, C
Matlock, DD
AF McIlvennan, Colleen K.
Jones, Jacqueline
Allen, Larry A.
Swetz, Keith M.
Nowels, Carolyn
Matlock, Daniel D.
TI Bereaved Caregiver Perspectives on the End-of-Life Experience of
Patients With a Left Ventricular Assist Device
SO JAMA INTERNAL MEDICINE
LA English
DT Article
ID DESTINATION THERAPY; SUPPORT
AB IMPORTANCE For patients and their loved ones, decisions regarding the end of life in the setting of chronic progressive illness are among the most complex in health care. Complicating these decisions are increasingly available, invasive, and potentially life-prolonging technologies such as the left ventricular assist device (LVAD).
OBJECTIVE To understand the experience of bereaved caregivers and patients at the end of life who have an LVAD.
DESIGN, SETTING, AND PARTICIPANTS Semistructured, in-depth interviews were conducted between September 10 and November 21, 2014, with 8 bereaved caregivers of patients with an LVAD who were recruited from a single institution. Data were analyzed from December 13, 2014, to February 18, 2015, using a mixed inductive and deductive approach.
MAIN OUTCOMES AND MEASURES Themes from semistructured interviews.
RESULTS The 8 caregivers (6 females) described 3 main themes that coalesced around feelings of confusion in the final weeks with their loved ones: (1) the process of death with an LVAD, (2) the legal and ethically permissible care of patients with an LVAD approaching death, and (3) fragmented integration of palliative and hospice care.
CONCLUSIONS AND RELEVANCE Despite increasing use of LVADs in patients with advanced heart failure, bereaved caregivers of patients with an LVAD describe a high level of confusion at the end of life. There remains a need for the health care community to develop clear guidance on the management of patients with an LVAD at the end of life. Future work will focus on the educational process and the ideal timing and reiteration of such information to patients and families.
C1 [McIlvennan, Colleen K.; Allen, Larry A.] Univ Colorado, Sch Med, Div Cardiol, Sect Adv Heart Failure & Transplantat, 12631 E 17th Ave,Mail Code B130, Aurora, CO 80045 USA.
[McIlvennan, Colleen K.; Allen, Larry A.; Matlock, Daniel D.] Univ Colorado, Sch Med, Colorado Cardiovasc Outcomes Res Consortium, 12631 E 17th Ave,Mail Code B130, Aurora, CO 80045 USA.
[Jones, Jacqueline] Univ Colorado, Sch Nursing, 12631 E 17th Ave,Mail Code B130, Aurora, CO 80045 USA.
[Nowels, Carolyn; Matlock, Daniel D.] Univ Colorado, Sch Med, Div Gen Internal Med, 12631 E 17th Ave,Mail Code B130, Aurora, CO 80045 USA.
[Swetz, Keith M.] Birmingham VA Med Ctr, Dept Vet Affairs, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA.
[Swetz, Keith M.] Univ Alabama Birmingham, Ctr Palliat & Support Care, Birmingham, AL USA.
RP McIlvennan, CK (reprint author), Univ Colorado, Sch Med, Div Cardiol, Sect Adv Heart Failure & Transplantat, 12631 E 17th Ave,Mail Code B130, Aurora, CO 80045 USA.
EM colleen.mcilvennan@ucdenver.edu
NR 28
TC 5
Z9 5
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 APR
PY 2016
VL 176
IS 4
BP 534
EP 539
DI 10.1001/jamainternmed.2015.8528
PG 6
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EG
UT WOS:000373380600026
PM 26998594
ER
PT J
AU Kerlikowske, K
AF Kerlikowske, Karla
TI Progress Toward Consensus on Breast Cancer Screening Guidelines and
Reducing Screening Harms Reply
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
ID WOMEN
C1 [Kerlikowske, Karla] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Kerlikowske, Karla] Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA.
RP Kerlikowske, K (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect, 4150 Clement St,111A1, San Francisco, CA 94121 USA.
EM karla.kerlikowske@ucsf.edu
FU NCI NIH HHS [P01 CA154292, P01CA154292]
NR 6
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 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD APR
PY 2016
VL 176
IS 4
BP 562
EP 563
DI 10.1001/jamainternmed.2016.0225
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3EG
UT WOS:000373380600043
PM 27043108
ER
PT J
AU Silverberg, ND
Mannix, R
Iverson, GL
AF Silverberg, Noah D.
Mannix, Rebekah
Iverson, Grant L.
TI Attribution of Concussion-Like Symptoms and History of Collision Sports
Exposure Reply
SO JAMA PEDIATRICS
LA English
DT Letter
C1 [Silverberg, Noah D.] Univ British Columbia, Div Phys Med & Rehabil, Vancouver, BC V5Z 1M9, Canada.
[Silverberg, Noah D.] GF Strong Rehabil Ctr, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada.
[Mannix, Rebekah] Boston Childrens Hosp, Div Emergency Med, Boston, MA USA.
[Silverberg, Noah D.; Iverson, Grant L.] Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA.
[Iverson, Grant L.] Spaulding Rehabil Hosp, Boston, MA USA.
[Silverberg, Noah D.; Iverson, Grant L.] Massachusetts Gen Hosp, Children Sports Concuss Program, Boston, MA 02114 USA.
[Silverberg, Noah D.; Iverson, Grant L.] Red Sox Fdn, Boston, MA USA.
[Silverberg, Noah D.; Iverson, Grant L.] Massachusetts Gen Hosp, Home Base Program, Boston, MA 02114 USA.
RP Silverberg, ND (reprint author), GF Strong Rehabil Ctr, 4255 Laurel St, Vancouver, BC V5Z 2G9, Canada.
EM noah.silverberg@vch.ca
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 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD APR
PY 2016
VL 170
IS 4
BP 401
EP 401
PG 1
WC Pediatrics
SC Pediatrics
GA DI3EI
UT WOS:000373380800026
ER
PT J
AU Hauberg, ME
Roussos, P
Grove, J
Borglum, AD
Mattheisen, M
AF Hauberg, Mads Engel
Roussos, Panos
Grove, Jakob
Borglum, Anders Dupont
Mattheisen, Manuel
CA Psychiat Genomics Consortium
TI Analyzing the Role of MicroRNAs in Schizophrenia in the Context of
Common Genetic Risk Variants
SO JAMA PSYCHIATRY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SYNAPTIC PLASTICITY; TARGET GENES; BRAIN; LOCI;
NEUROGENESIS; ARCHITECTURE; ENRICHMENT; DATABASE; DISEASE
AB IMPORTANCE The recent implication of 108 genomic loci in schizophrenia marked a great advancement in our understanding of the disease. Against the background of its polygenic nature there is a necessity to identify how schizophrenia risk genes interplay. As regulators of gene expression, microRNAs (miRNAs) have repeatedly been implicated in schizophrenia etiology. It is therefore of interest to establish their role in the regulation of schizophrenia risk genes in disease-relevant biological processes.
OBJECTIVE To examine the role of miRNAs in schizophrenia in the context of disease-associated genetic variation.
DESIGN, SETTING, AND PARTICIPANTS The basis of this study was summary statistics from the largest schizophrenia genome-wide association study meta-analysis to date (83 550 individuals in a meta-analysis of 52 genome-wide association studies) completed in 2014 along with publicly available data for predicted miRNA targets. We examined whether schizophrenia risk genes were more likely to be regulated by miRNA. Further, we used gene set analyses to identify miRNAs that are regulators of schizophrenia risk genes.
MAIN OUTCOMES AND MEASURES Results from association tests for miRNA targetomes and related analyses.
RESULTS In line with previous studies, we found that similar to other complex traits, schizophrenia risk genes were more likely to be regulated by miRNAs (P < 2 x 10(-16)). Further, the gene set analyses revealed several miRNAs regulating schizophrenia risk genes, with the strongest enrichment for targets of miR-9-5p (P = .0056 for enrichment among the top 1% most-associated single-nucleotide polymorphisms, corrected for multiple testing). It is further of note that MIR9-2 is located in a genomic region showing strong evidence for association with schizophrenia (P = 7.1 x 10(-8)). The second and third strongest gene set signals were seen for the targets of miR-485-5p and miR-137, respectively.
CONCLUSIONS AND RELEVANCE This study provides evidence for a role of miR-9-5p in the etiology of schizophrenia. Its implication is of particular interest as the functions of this neurodevelopmental miRNA tie in with established disease biology: it has a regulatory loop with the fragile X mental retardation homologue FXR1 and regulates dopamine D-2 receptor density.
C1 [Hauberg, Mads Engel; Grove, Jakob; Borglum, Anders Dupont; Mattheisen, Manuel] Aarhus Univ, Dept Biomed, Wilhelm Meyers Alle 1, DK-8000 Aarhus C, Denmark.
[Hauberg, Mads Engel; Grove, Jakob; Borglum, Anders Dupont; Mattheisen, Manuel] Lundbeck Fdn Initiat Integrat Psychiat Res, Lundbeck, Denmark.
[Hauberg, Mads Engel; Grove, Jakob; Borglum, Anders Dupont; Mattheisen, Manuel] Aarhus Univ, Ctr Integrat Sequencing, DK-8000 Aarhus C, Denmark.
[Roussos, Panos] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA.
[Roussos, Panos] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Roussos, Panos] Icahn Sch Med Mt Sinai, Inst Genom & Multiscale Biol, New York, NY 10029 USA.
[Roussos, Panos] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA.
[Roussos, Panos] James J Peters VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Bronx, NY USA.
[Grove, Jakob] Aarhus Univ, Bioinformat Res Ctr, DK-8000 Aarhus C, Denmark.
[Borglum, Anders Dupont] Aarhus Univ Hosp, Res Dept P, Risskov, Denmark.
[Borglum, Anders Dupont] Aarhus Univ, Dept Clin Med, Translat Neuropsychiat Unit, DK-8000 Aarhus C, Denmark.
RP Mattheisen, M (reprint author), Aarhus Univ, Dept Biomed, Wilhelm Meyers Alle 1, DK-8000 Aarhus C, Denmark.
EM mm@biomed.au.dk
RI Roussos, Panos/J-7090-2013;
OI Roussos, Panos/0000-0002-4640-6239; Grove, Jakob/0000-0003-2284-5744
FU Lundbeck Foundation; Centre for Integrative Sequencing, Aarhus
University; Faculty of Health, Aarhus University
FX This work was supported by the Lundbeck Foundation; the Centre for
Integrative Sequencing, Aarhus University; and the Faculty of Health,
Aarhus University.
NR 47
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U1 1
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 APR
PY 2016
VL 73
IS 4
BP 369
EP 377
DI 10.1001/jamapsychiatry.2015.3018
PG 9
WC Psychiatry
SC Psychiatry
GA DI4BI
UT WOS:000373444700012
PM 26963595
ER
PT J
AU Camprodon, JA
Pascual-Leone, A
AF Camprodon, Joan A.
Pascual-Leone, Alvaro
TI Multimodal Applications of Transcranial Magnetic Stimulation for
Circuit-Based Psychiatry
SO JAMA PSYCHIATRY
LA English
DT Editorial Material
C1 [Camprodon, Joan A.] Harvard Univ, Massachusetts Gen Hosp, Lab Neuropsychiat & Neuromodulat, Dept Psychiat,Med Sch, 149 13th St,Ste 2654, Boston, MA 02129 USA.
[Camprodon, Joan A.] Harvard Univ, Massachusetts Gen Hosp, Transcranial Magnet Stimulat Clin Serv, Dept Psychiat,Med Sch, 149 13th St,Ste 2654, Boston, MA 02129 USA.
[Pascual-Leone, Alvaro] Harvard Univ, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Neuromodulat, Div Cognit Neurol,Dept Neurol,Med Sch, Boston, MA 02215 USA.
RP Camprodon, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Lab Neuropsychiat & Neuromodulat, Dept Psychiat,Med Sch, 149 13th St,Ste 2654, Boston, MA 02129 USA.; Camprodon, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Transcranial Magnet Stimulat Clin Serv, Dept Psychiat,Med Sch, 149 13th St,Ste 2654, Boston, MA 02129 USA.
EM jcamprodon@mgh.harvard.edu
NR 10
TC 1
Z9 1
U1 0
U2 2
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 APR
PY 2016
VL 73
IS 4
BP 407
EP 408
DI 10.1001/jamapsychiatry.2015.3127
PG 2
WC Psychiatry
SC Psychiatry
GA DI4BI
UT WOS:000373444700016
PM 26981644
ER
PT J
AU Pineles, SL
Nillni, YI
King, MW
Patton, SC
Bauer, MR
Mostoufi, SM
Gerber, MR
Hauger, R
Resick, PA
Rasmusson, AM
Orr, SP
AF Pineles, Suzanne L.
Nillni, Yael I.
King, Matthew W.
Patton, Samantha C.
Bauer, Margaret R.
Mostoufi, Sheeva M.
Gerber, Megan R.
Hauger, Richard
Resick, Patricia A.
Rasmusson, Ann M.
Orr, Scott P.
TI Extinction Retention and the Menstrual Cycle: Different Associations for
Women With Posttraumatic Stress Disorder
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Article
DE extinction retention; menstrual cycle; estradiol; progesterone; PTSD
ID SEX-DIFFERENCES; RECEPTOR; TRAUMA; PTSD
AB The propensity to acquire and retain conditioned fear responses may contribute to the risk of developing and maintaining posttraumatic stress disorder (PTSD) following a traumatic event. There is growing evidence that the gonadal hormones estrogen and progesterone are associated with how well women retain extinction of previously conditioned fear responses. Thus, sex steroid effects may contribute to the increased prevalence of PTSD in women. For the current study, 32 nonmedicated female trauma survivors with and without PTSD completed a differential fear conditioning task both during the early follicular phase of the menstrual cycle when estradiol and progesterone levels are low, and during the midluteal phase when estradiol and progesterone levels are high. Skin conductance served as the measure of conditioned fear. Women with PTSD, compared to those without, showed impaired retention of extinction learning in the midluteal phase of the menstrual cycle. Therefore, the impact of menstrual phase on extinction retention may differ between women with and without PTSD. These findings raise potential considerations regarding the coordination of psychopharmacologic and trauma exposure-based treatments for PTSD with specific phases of the menstrual cycle.
C1 [Pineles, Suzanne L.; Nillni, Yael I.] VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder PTSD, Boston, MA USA.
[Pineles, Suzanne L.; Nillni, Yael I.; Rasmusson, Ann M.] Boston Univ, Dept Psychiat, Sch Med, Boston, MA 02215 USA.
[King, Matthew W.; Rasmusson, Ann M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Patton, Samantha C.] Univ Louisville, Dept Psychol & Brain Sci, Louisville, KY 40292 USA.
[Bauer, Margaret R.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA USA.
[Mostoufi, Sheeva M.] Univ Calif San Diego, San Diego State Univ, Joint Doctoral Program Clin Psychol, San Diego, CA 92103 USA.
[Gerber, Megan R.] VA Boston Healthcare Syst, Women Vet Program, Boston, MA USA.
[Gerber, Megan R.] Boston Univ, Dept Med, Sch Med, Boston, MA 02215 USA.
[Hauger, Richard] San Diego VA Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA.
[Hauger, Richard] Univ Calif San Diego, Dept Psychiat, Sch Med, San Diego, CA 92103 USA.
[Resick, Patricia A.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC 27706 USA.
[Orr, Scott P.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Orr, Scott P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
RP Pineles, SL (reprint author), Vet Affairs Boston Healthcare Syst 116B 3, Boston, MA 02130 USA.
EM suzanne.pineles@va.gov
FU U.S. Department of Veterans Affairs Career Development Award
FX Support for this research was provided to Suzanne Pineles through a U.S.
Department of Veterans Affairs Career Development Award.
NR 21
TC 4
Z9 4
U1 6
U2 9
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 APR
PY 2016
VL 125
IS 3
BP 349
EP 355
DI 10.1037/abn0000138
PG 7
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA DI7XE
UT WOS:000373714500003
PM 26866677
ER
PT J
AU Painter, JM
Kring, AM
AF Painter, Janelle M.
Kring, Ann M.
TI Toward an Understanding of Anticipatory Pleasure Deficits in
Schizophrenia: Memory, Prospection, and Emotion Experience
SO JOURNAL OF ABNORMAL PSYCHOLOGY
LA English
DT Article
DE schizophrenia; memory; prospection; emotion; narratives
ID MENTAL TIME-TRAVEL; AUTOBIOGRAPHICAL MEMORY; NEGATIVE SYMPTOMS;
COGNITIVE NEUROSCIENCE; AFFECTIVE REACTIVITY; FUTURE; IMAGINE; THINKING;
EVENTS; BRAIN
AB Anticipatory pleasure deficits have been observed in people with schizophrenia. Less is known about the extent to which interrelated processes that comprise anticipatory pleasure, including memory, prospection, and emotion experience are disrupted. We asked people with (n = 32) and without (n = 29) schizophrenia or schizoaffective disorder to provide memory and prospection narratives in response to specific cues. Half of the prospections followed a memory task, and half followed a control task. People with schizophrenia generated memories similar in content and experience as controls even as they described them less clearly. However, people with schizophrenia were less likely to explicitly reference the past in their prospections, and their prospections were less detailed and richly experienced than controls, regardless of the task completed before prospection. People with schizophrenia reported similar levels of positive emotion (current and predicted) in positive prospections that followed the memory task, but less positive emotion than controls in positive prospections that followed the control task. Taken together, these results suggest that people with schizophrenia experience difficulties drawing from past experiences and generating detailed prospections. However, asking people with schizophrenia to recall and describe memories prior to prospection may increase the likelihood of drawing from the past in prospections, and may help boost current and predicted pleasure.
C1 [Painter, Janelle M.; Kring, Ann M.] Univ Calif Berkeley, Berkeley, CA 94720 USA.
[Painter, Janelle M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
RP Painter, JM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 South Columbian Way S-116, Seattle, WA 98108 USA.
EM janelle.painter@va.gov
FU National Institutes of Health Grant [1R01MH082890]
FX This study was supported in part by National Institutes of Health Grant
1R01MH082890 to Ann M. Kring.
NR 46
TC 0
Z9 0
U1 4
U2 5
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 APR
PY 2016
VL 125
IS 3
BP 442
EP 452
DI 10.1037/abn0000151
PG 11
WC Psychology, Clinical; Psychology, Multidisciplinary
SC Psychology
GA DI7XE
UT WOS:000373714500012
PM 26950753
ER
PT J
AU Moschetti, WE
Konopka, JF
Rubash, HE
Genuario, JW
AF Moschetti, Wayne E.
Konopka, Joseph F.
Rubash, Harry E.
Genuario, James W.
TI Can Robot-Assisted Unicompartmental Knee Arthroplasty Be Cost-Effective?
A Markov Decision Analysis
SO JOURNAL OF ARTHROPLASTY
LA English
DT Article
DE unicompartmental arthroplasty; robotic assistance; cost; economic
analysis; cost-effectiveness
ID UNITED-STATES; MEDICARE POPULATION; HOSPITAL-VOLUME; FOLLOW-UP;
REPLACEMENT; OSTEOARTHRITIS; PROSTHESIS; REVISION; HEALTH; REGISTER
AB Background: Unicompartmental knee arthroplasty (UKA) is a treatment option for single-compartment knee osteoarthritis. Robotic assistance may improve survival rates of UKA, but the cost-effectiveness of robot-assisted UKA is unknown. The purpose of this study was to delineate the revision rate, hospital volume, and robotic system costs for which this technology would be cost-effective.
Methods: We created a Markov decision analysis to evaluate the costs, outcomes, and incremental cost-effectiveness of robot-assisted UKA in 64-year-old patients with end-stage unicompartmental knee osteoarthritis.
Results: Robot-assisted UKA was more costly than traditional UKA, but offered a slightly better outcome with 0.06 additional quality-adjusted life-years at an incremental cost of $47,180 per quality-adjusted life-years, given a case volume of 100 cases annually. The system was cost-effective when case volume exceeded 94 cases per year, 2-year failure rates were below 1.2%, and total system costs were <$1.426 million.
Conclusion: Robot-assisted UKA is cost-effective compared with traditional UKA when annual case volume exceeds 94 cases per year. It is not cost-effective at low-volume or medium-volume arthroplasty centers. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Moschetti, Wayne E.] Dartmouth Hitchcock Med Ctr, Dept Orthopaed Surg, Lebanon, NH 03766 USA.
[Konopka, Joseph F.; Rubash, Harry E.] Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA.
[Genuario, James W.] Steadman Hawkins Clin, Denver, CO USA.
RP Konopka, JF (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 55 Fruit St, Boston, MA 02114 USA.
NR 46
TC 3
Z9 4
U1 0
U2 1
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0883-5403
EI 1532-8406
J9 J ARTHROPLASTY
JI J. Arthroplast.
PD APR
PY 2016
VL 31
IS 4
BP 759
EP 765
DI 10.1016/j.arth.2015.10.018
PG 7
WC Orthopedics
SC Orthopedics
GA DI6QS
UT WOS:000373625600004
PM 26706836
ER
PT J
AU Gromov, K
Greene, ME
Huddleston, JI
Emerson, R
Gebuhr, P
Malchau, H
Troelsen, A
AF Gromov, Kirill
Greene, Meridith E.
Huddleston, James I.
Emerson, Roger
Gebuhr, Peter
Malchau, Henrik
Troelsen, Anders
TI Acetabular Dysplasia and Surgical Approaches Other Than Direct Anterior
Increases Risk for Malpositioning of the Acetabular Component in Total
Hip Arthroplasty
SO JOURNAL OF ARTHROPLASTY
LA English
DT Article
DE total hip arthroplasty; component positioning; dysplasia; anteversion;
Martell analysis
ID OBESE-PATIENTS; ACCURACY; LIGAMENT; REPLACEMENT; POSITION;
OSTEOARTHRITIS; ORIENTATION; VARIABILITY; ANTEVERSION; WEAR
AB Background: Persistent acetabular dysplasia (AD) after periacetabular osteotomy has been hypothesized to increase the risk for malpositioning of the acetabular component. In this study, we investigate whether AD is an independent risk factor for cup malpositioning during primary total hip arthroplasty (THA).
Methods: Patient demographics, surgical approach, presence of AD assessed using the lateral center-edge angle, and acetabular cup positioning determined using Martell Hip Analysis Suite were investigated in 836 primary THA patients enrolled in a prospective multicenter study.
Results: We found that presence of AD, defined as the lateral center-edge angle of <25 degrees, is an independent risk factor for malpositioning of the acetabular component during primary THA. Surgical approach other than direct anterior was also independently associated with malpositioned cups.
Conclusions: Surgeons should therefore take special care during placement of the acetabular component in patients with AD. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Gromov, Kirill; Greene, Meridith E.; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA.
[Gromov, Kirill; Gebuhr, Peter; Troelsen, Anders] Copenhagen Hosp, Dept Orthopaed Surg, Copenhagen, Denmark.
[Huddleston, James I.] Stanford Univ, Med Ctr, Dept Orthopaed Surg, Stanford, CA 94305 USA.
[Emerson, Roger] Texas Ctr Joint Replacement, Plano, TX USA.
RP Gromov, K (reprint author), Univ Copenhagen Hosp, Dept Orthopaed Surg, DK-2100 Copenhagen, Denmark.
NR 35
TC 1
Z9 1
U1 0
U2 0
PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS
PI PHILADELPHIA
PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA
SN 0883-5403
EI 1532-8406
J9 J ARTHROPLASTY
JI J. Arthroplast.
PD APR
PY 2016
VL 31
IS 4
BP 835
EP 841
DI 10.1016/j.arth.2015.10.045
PG 7
WC Orthopedics
SC Orthopedics
GA DI6QS
UT WOS:000373625600018
PM 26706838
ER
PT J
AU Karmon, AE
Cardozo, ER
Souter, I
Gold, J
Petrozza, JC
Styer, AK
AF Karmon, Anatte E.
Cardozo, Eden R.
Souter, Irene
Gold, Julie
Petrozza, John C.
Styer, Aaron K.
TI Donor TSH level is associated with clinical pregnancy among oocyte
donation cycles
SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS
LA English
DT Article; Proceedings Paper
CT 70th Annual Scientific Meeting of the
American-Society-for-Reproductive-Medicine
CY OCT 18-22, 2014
CL Honolulu, HI
SP Amer Soc Reprod Med
DE Thyroid-stimulating hormone; Oocyte donation; Infertility; In vitro
fertilization
ID IN-VITRO FERTILIZATION; THYROID-HORMONE RECEPTORS; INFERTILE WOMEN;
HUMAN GRANULOSA; HYPOTHYROIDISM; CELLS
AB The purpose of the study is to evaluate the association between donor TSH level (independent of recipient TSH level) and recipient pregnancy outcome among fresh donor oocyte IVF cycles.
This is a retrospective cohort study investigating 232 consecutive fresh donor-recipient cycles (200 total oocyte donors) at an academic medical center. Main outcome measures include clinical pregnancy and live birth.
Cycles were categorized into two groups based on donor TSH level (< 2.5 and a parts per thousand yen 2.5 mIU/L). After controlling for multiple donor and recipient characteristics, the probability of clinical pregnancy was significantly lower among donors with TSH levels a parts per thousand yen2.5 mIU/L compared to those with TSH values < 2.5 mIU/L (43.1 %, 95 % CI 28.5-58.9, versus 66.7 %, 95 % CI 58.6-73.9, respectively, p = 0.01). The difference in live birth rates between the two groups did not achieve statistical significance (43.1 %, 95 % CI 28.8-58.6, versus 58.0 %, 95 % CI 50.0-65.6, respectively, p = 0.09).
Donor TSH level, independent of recipient TSH level, is associated with recipient clinical pregnancy. These findings suggest that thyroid function may impact the likelihood of pregnancy at the level of the oocyte.
C1 [Karmon, Anatte E.; Cardozo, Eden R.; Souter, Irene; Gold, Julie; Petrozza, John C.; Styer, Aaron K.] Massachusetts Gen Hosp, Vincent Reprod Med & IVF, Vincent Dept Obstet & Gynecol, Yawkey 10A 55 Fruit St, Boston, MA 02114 USA.
[Karmon, Anatte E.; Cardozo, Eden R.; Souter, Irene; Petrozza, John C.; Styer, Aaron K.] Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
RP Karmon, AE (reprint author), Massachusetts Gen Hosp, Vincent Reprod Med & IVF, Vincent Dept Obstet & Gynecol, Yawkey 10A 55 Fruit St, Boston, MA 02114 USA.; Karmon, AE (reprint author), Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
EM anatte@gmail.com
NR 22
TC 0
Z9 0
U1 0
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1058-0468
EI 1573-7330
J9 J ASSIST REPROD GEN
JI J. Assist. Reprod. Genet.
PD APR
PY 2016
VL 33
IS 4
BP 489
EP 494
DI 10.1007/s10815-016-0668-6
PG 6
WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology
GA DI5XG
UT WOS:000373573200010
PM 26847132
ER
PT J
AU Chamoto, K
Guo, TX
Imataki, O
Tanaka, M
Nakatsugawa, M
Ochi, T
Yamashita, Y
Saito, AM
Saito, TI
Butler, MO
Hirano, N
AF Chamoto, Kenji
Guo, Tingxi
Imataki, Osamu
Tanaka, Makito
Nakatsugawa, Munehide
Ochi, Toshiki
Yamashita, Yuki
Saito, Akiko M.
Saito, Toshiki I.
Butler, Marcus O.
Hirano, Naoto
TI CDR3 beta sequence motifs regulate autoreactivity of human invariant MKT
cell receptors
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Article
DE iNKT; Autoreactivity; TCR; CDR3 beta
ID KILLER T-CELLS; LIPID-ANTIGEN PRESENTATION; TCR ALPHA-CHAIN; NKT CELLS;
SELF-ANTIGENS; V-BETA; RECOGNITION; ACTIVATION; GLYCOSYLCERAMIDES;
IDENTIFICATION
AB Invariant natural killer T (INKT) cells are a subset of T lymphocytes that recognize lipid ligands presented by monomorphic CD1d. Human iNICT T cell receptor (TCR) is largely composed of invariant V alpha 24 (V alpha 24i) TCR alpha chain and semi-variant V beta 11 TCR beta chain, where complementarity-determining region (CDR)3 beta is the sole variable region. One of the characteristic features of iNKT cells is that they retain autoreactivity even after the thymic selection. However, the molecular features of human iNKT TCR CDR3 beta sequences that regulate autoreactivity remain unknown. Since the numbers of iNKT cells with detectable autoreactivity in peripheral blood is limited, we introduced the V alpha 24i gene into peripheral T cells and generated a de novo human iNKT TCR repertoire. By stimulating the transfected T cells with artificial antigen presenting cells (aAPCs) presenting self-ligands, we enriched strongly autoreactive iNKT TCRs and isolated a large panel of human iNKT TCRs with a broad range autoreactivity. From this panel of unique iNKT TCRs, we deciphered three CDR3 beta sequence motifs frequently encoded by strongly-autoreactive iNKT TCRs: a VD region with 2 or more acidic amino acids, usage of the J beta 2-5 allele, and a CDR beta region of 13 amino acids in length. iNKT TCRs encoding 2 or 3 sequence motifs also exhibit higher autoreactivity than those encoding 0 or 1 motifs. These data facilitate our understanding of the molecular basis for human iNKT cell autoreactivity involved in immune responses associated with human disease. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Chamoto, Kenji; Guo, Tingxi; Nakatsugawa, Munehide; Ochi, Toshiki; Yamashita, Yuki; Butler, Marcus O.; Hirano, Naoto] Princess Margaret Canc Ctr, Campbell Family Canc Res Inst, Campbell Family Inst Breast Canc Res, Univ Hlth Network,Tumor Immunotherapy Program, Toronto, ON M5G 2M9, Canada.
[Guo, Tingxi; Butler, Marcus O.; Hirano, Naoto] Univ Toronto, Dept Immunol, 100 Coll St, Toronto, ON M5S 1A8, Canada.
[Saito, Akiko M.; Saito, Toshiki I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Butler, Marcus O.] Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada.
RP Hirano, N (reprint author), Princess Margaret Canc Ctr, 610 Univ Ave, Toronto, ON M5G 2M9, Canada.
EM naoto.hirano@utoronto.ca
FU NIH [R01 CA148673]; Ontario Institute for Cancer Research Clinical
Investigator Award [IA-039]; Princess Margaret Cancer Foundation;
Knudson Postdoctoral Fellowship; Canadian Institutes of Health Research
Canada Graduate Scholarship; Guglietti Fellowship Award
FX This work was supported by NIH grant R01 CA148673 (NH); the Ontario
Institute for Cancer Research Clinical Investigator Award IA-039 (NH);
The Princess Margaret Cancer Foundation (MOB, NH); Knudson Postdoctoral
Fellowship (KC); Canadian Institutes of Health Research Canada Graduate
Scholarship (TG); and Guglietti Fellowship Award (TO).
NR 42
TC 3
Z9 3
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD APR
PY 2016
VL 68
BP 39
EP 51
DI 10.1016/j.jaut.2015.12.005
PG 13
WC Immunology
SC Immunology
GA DI5NP
UT WOS:000373546200005
PM 26748722
ER
PT J
AU Zappulli, V
Friis, KP
Fitzpatrick, Z
Maguire, CA
Breakefield, XO
AF Zappulli, Valentina
Friis, Kristina Pagh
Fitzpatrick, Zachary
Maguire, Casey A.
Breakefield, Xandra O.
TI Extracellular vesicles and intercellular communication within the
nervous system
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Review
ID MESENCHYMAL STEM-CELLS; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; L1
RETROTRANSPOSITION; AMYLOID-BETA; CEREBROSPINAL-FLUID; EXOSOME RELEASE;
IN-VIVO; GLIOBLASTOMA-MULTIFORME; TRANSPOSABLE ELEMENTS
AB Extracellular vesicles (EVs, including exosomes) are implicated in many aspects of nervous system development and function, including regulation of synaptic communication, synaptic strength, and nerve regeneration. They mediate the transfer of packets of information in the form. of nonsecreted proteins and DNA/RNA protected within a membrane compartment. EVs are essential for the packaging and transport of many cell-fate proteins during development as well as many neurotoxic misfolded proteins during pathogenesis. This form of communication provides another dimension of cellular crosstalk, with the ability to assemble a "kit" of directional instructions made up of different molecular entities and address it to specific recipient cells. This multidimensional form of communication has special significance in the nervous system. How EVs help to orchestrate the wiring of the brain while allowing for plasticity associated with learning and memory and contribute to regeneration and degeneration are all under investigation. Because they carry specific disease-related RNAs and proteins, practical applications of EVs include potential uses as biomarlcers and therapeutics. This Review describes our current understanding of EVs and serves as a springboard for future advances, which may reveal new important mechanisms by which EVs in coordinate brain and body function and dysfunction.
C1 [Zappulli, Valentina] Univ Padua, Dept Comparat Biomed & Food Sci, Legnaro, Italy.
[Friis, Kristina Pagh; Fitzpatrick, Zachary; Maguire, Casey A.; Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA.
[Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Radiol, Ctr Mol Imaging Res,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Breakefield, Xandra O.] Harvard Univ, Sch Med, NeuroDiscovery Ctr, Boston, MA USA.
RP Breakefield, XO (reprint author), Massachusetts Gen Hosp, CNY Bldg 149,Room 6203,149 13th St, Charlestown, MA 02129 USA.
EM xandra_breakefield@hms.harvard.edu
FU NIH Common Fund through the Office of Strategic Coordination/Office of
the NIH Director [NCI U19 CA179563, NIH/NCI P01 CA069246]; Alfred Benzon
Foundation; Fulbright Visiting Scholar Program Institute of
International Education; American Brain Tumor Association Discovery
Grant
FX We thank Suzanne McDavitt for skilled editorial assistance, Lawrence
Rajendran for insights into the role of EVs in neuro-degeneration, and
Sybren Maas for insights into the role of EVs in brain tumors. This work
was supported by the NIH Common Fund through the Office of Strategic
Coordination/Office of the NIH Director (NCI U19 CA179563 and NIH/NCI
P01 CA069246 to X.O. Breakefield); the Alfred Benzon Foundation (to K.P.
Friis); the Fulbright Visiting Scholar Program Institute of
International Education (to V. Zappulli); and an American Brain Tumor
Association Discovery Grant (to C.A. Maguire).
NR 148
TC 6
Z9 8
U1 3
U2 15
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 APR
PY 2016
VL 126
IS 4
BP 1198
EP 1207
DI 10.1172/JCI81134
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DI5ES
UT WOS:000373522300009
PM 27035811
ER
PT J
AU Lee, D
Wang, YH
Kalaitzidis, D
Ramachandran, J
Eda, H
Sykes, DB
Raje, N
Scadden, DT
AF Lee, Dongjun
Wang, Ying-Hua
Kalaitzidis, Demetrios
Ramachandran, Janani
Eda, Homare
Sykes, David B.
Raje, Noopur
Scadden, David T.
TI Endogenous transmembrane protein UT2 inhibits pSTAT3 and suppresses
hematological malignancy
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID MULTIPLE-MYELOMA CELLS; SIGNAL TRANSDUCER; STAT3 ACTIVATION; IN-VIVO;
CONSTITUTIVE EXPRESSION; LEUKEMIA-CELLS; GROWTH-HORMONE; CANCER;
INTERLEUKIN-6; TRANSCRIPTION-3
AB Regulation of STAT3 activation is critical for normal and malignant hematopoietic cell proliferation. Here, we have reported that the endogenous transmembrane protein upstream-of-mTORC2 (UT2) negatively regulates activation of STAT3. Specifically, we determined that UT2 interacts directly with GP130 and inhibits phosphorylation of STAT3 on tyrosine 705 (STAT3'05). This reduces cytokine signaling including IL6 that is implicated in multiple myeloma and other hematopoietic malignancies. Modulation of UT2 resulted in inverse effects on animal survival in myeloma models. Samples from multiple myeloma patients also revealed a decreased copy number of UT2 and decreased expression of UT2 in genomic and transcriptomic analyses, respectively. Together, these studies identify a transmembrane protein that functions to negatively regulate cytokine signaling through GP130 and pSTAT3(Y705) and is molecularly and mechanistically distinct from the suppressors of cytokine signaling (SOCS) family of genes. Moreover, this work provides evidence that perturbations of this activation-dampening molecule participate in hematologic malignancies and may serve as a key determinant of multiple myeloma pathophysiology. UT2 is a negative regulator shared across STAT3 and mTORC2 signaling cascades, functioning as a tumor suppressor in hematologic malignancies driven by those pathways.
C1 [Lee, Dongjun; Wang, Ying-Hua; Kalaitzidis, Demetrios; Sykes, David B.; Scadden, David T.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA.
[Lee, Dongjun; Wang, Ying-Hua; Kalaitzidis, Demetrios; Ramachandran, Janani; Eda, Homare; Sykes, David B.; Raje, Noopur; Scadden, David T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
[Lee, Dongjun; Wang, Ying-Hua; Kalaitzidis, Demetrios; Sykes, David B.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA.
[Lee, Dongjun; Wang, Ying-Hua; Kalaitzidis, Demetrios; Sykes, David B.; Scadden, David T.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA.
RP Scadden, DT (reprint author), 185 Cambridge St, Boston, MA 02114 USA.
EM david_scadden@harvard.edu
OI lee, dongjun/0000-0001-6828-401X
FU NIH NHLBI [U01HL100402, HL97794, HL044851]; Ellison Medical Foundation;
MGH Fund for Medical Discovery fellowship; MGH/HSCI CRM flow cytometry
core
FX We thank those who funded this work: NIH NHLBI U01HL100402, HL97794,
HL044851, and the Ellison Medical Foundation (to D. Lee and D.T.
Scadden); MGH Fund for Medical Discovery fellowship (D. Lee); and the
MGH/HSCI CRM flow cytometry core (L. Prickett, A. Galvin, M. Handley,
and M. Weglarz). We thank Scadden lab members for advice and helpful
comments and IH Oh (Catholic High Performance Cell Therapy Center,
Catholic University, Seoul, South Korea) for MIG-STAT3C plasmid. The
data reported in this manuscript are tabulated in the main paper and in
the supplementary materials.
NR 94
TC 0
Z9 0
U1 1
U2 2
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 APR
PY 2016
VL 126
IS 4
BP 1300
EP 1310
DI 10.1172/JCI84620
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DI5ES
UT WOS:000373522300022
PM 26927669
ER
PT J
AU Winnay, JN
Solheim, MH
Dirice, E
Sakaguchi, M
Noh, HL
Kang, HJ
Takahashi, H
Chudasama, KK
Kim, JK
Molven, A
Kahn, CR
Njolstad, PR
AF Winnay, Jonathon N.
Solheim, Marie H.
Dirice, Ercument
Sakaguchi, Masaji
Noh, Hye-Lim
Kang, Hee Joon
Takahashi, Hirokazu
Chudasama, Kishan K.
Kim, Jason K.
Molven, Anders
Kahn, C. Ronald
Njolstad, Pal R.
TI PI3-kinase mutation linked to insulin and growth factor resistance in
vivo
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID TYROSINE-PHOSPHATASE 1B; PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL
3-KINASE; RECEPTOR SUBSTRATE-1; SHORT STATURE; PARTIAL LIPODYSTROPHY;
POSTNATAL-GROWTH; MICE LACKING; BETA-CELLS; PROTEIN
AB The phosphatidylinositol 3-kinase (PI3K) signaling pathway is central to the action of insulin and many growth factors. Heterozygous mutations in the gene encoding the p85 alpha regulatory subunit of PI3K (PIK3R1) have been identified in patients with SHORT syndrome a disorder characterized by short stature, partial lipodystrophy, and insulin resistance. Here, we evaluated whether SHORT syndrome-associated PIK3R1 mutations account for the pathophysiology that underlies the abnormalities by generating knockin mice that are heterozygous for the Pik3r1(Arg649TrP) mutation, which is homologous to the mutation found in the majority of affected individuals. Similar to the patients, mutant mice exhibited a reduction in body weight and length, partial lipodystrophy, and systemic insulin resistance. These derangements were associated with a reduced capacity of insulin and other growth factors to activate PI3K in liver, muscle, and fat; marked insulin resistance in liver and fat of mutation-harboring animals; and insulin resistance in vitro in cells derived from these mice. In addition, mutant mice displayed defective insulin secretion and GLP-1 action on islets in vivo and in vitro. These data demonstrate the ability of this heterozygous mutation to alter PI3K activity in vivo and the central role of PI3K in insulin/growth factor action, adipocyte function, and glucose metabolism.
C1 [Winnay, Jonathon N.; Solheim, Marie H.; Dirice, Ercument; Sakaguchi, Masaji; Takahashi, Hirokazu; Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
[Solheim, Marie H.; Chudasama, Kishan K.; Molven, Anders; Njolstad, Pal R.] Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.
[Noh, Hye-Lim; Kang, Hee Joon; Kim, Jason K.] Univ Massachusetts, Sch Med, Div Endocrinol Metab & Diabet, Worcester, MA USA.
[Chudasama, Kishan K.] Oslo Univ Hosp, Inst Canc Res, Dept Canc Immunol, Oslo, Norway.
[Molven, Anders] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway.
[Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway.
[Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.
RP Kahn, CR (reprint author), Joslin Diabet Ctr, Sect Integrat Physiol & Metab, One Joslin Pl, Boston, MA 02215 USA.; Njolstad, PR (reprint author), Univ Bergen, Dept Clin Sci, Dept Pediat, Haukeland Univ Hosp, N-5021 Bergen, Norway.
EM c.ronald.kahn@joslin.harvard.edu; pal.njolstad@uib.no
RI Dirice, Ercument/B-2825-2017
FU National Institute of Digestive and Diabetes and Kidney Diseases [R01
DK055545]; NIH [U24-DK093000]; European Research Council [293574];
Research Council of Norway; University of Bergen; Western Regional
Health Authorities; KG Jebsen Foundation; Norwegian Society of
Endocrinology; Eckbo's Foundation; Tom Wilhelmsen Foundation; Norwegian
Diabetes Association
FX We would like to thank Rohit Kulkarni at the Joslin Diabetes Center for
helpful discussion. We would like to thank the Physiology Core at the
Joslin Diabetes Center for performing and interpreting the comprehensive
lab animal monitoring system and dual energy X-ray absorptiometry
analysis and the National Mouse Metabolic Phenotyping Center at the
University of Massachusetts Medical School for performing the
hyperinsulinemic-euglycemic clamp study. This work was supported by R01
DK055545 (to C.R. Kahn) from the National Institute of Digestive and
Diabetes and Kidney Diseases. The National Mouse Metabolic Phenotyping
Center at the University of Massachusetts is funded by NIH grant
U24-DK093000. This work was also supported by the European Research
Council (293574 to P.R. Njolstad), the Research Council of Norway (to
P.R. Njolstad), the University of Bergen, and the Western Regional
Health Authorities. M.H. Solheim was supported in part by funds from the
University of Bergen, the KG Jebsen Foundation, the Norwegian Society of
Endocrinology, Eckbo's Foundation, Tom Wilhelmsen Foundation, and the
Norwegian Diabetes Association.
NR 48
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Z9 2
U1 1
U2 1
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD APR
PY 2016
VL 126
IS 4
BP 1401
EP 1412
DI 10.1172/JCI84005
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DI5ES
UT WOS:000373522300029
PM 26974159
ER
PT J
AU Riedel, SS
Haladyna, JN
Bezzant, M
Stevens, B
Polyea, DA
Sinha, AU
Armstrong, SA
Wei, Q
Pollock, RM
Daigle, SR
Jordan, CT
Ernst, P
Neff, T
Bernt, KM
AF Riedel, Simone S.
Haladyna, Jessica N.
Bezzant, Matthew
Stevens, Brett
Polyea, Daniel A.
Sinha, Amit U.
Armstrong, Scott A.
Wei, Qi
Pollock, Roy M.
Daigle, Scott R.
Jordan, Craig T.
Ernst, Patricia
Neff, Tobias
Bernt, Kathrin M.
TI MLL1 and DOT1L cooperate with meningioma-1 to induce acute myeloid
leukemia
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID RXR-MEDIATED TRANSCRIPTION; H3K79 METHYLATION; GENE-EXPRESSION; MICRORNA
EXPRESSION; STEM-CELLS; MN1 GENE; AML; FUSION; TRANSFORMATION;
HEMATOPOIESIS
AB Meningioma-1 (MN1) overexpression is frequently observed in patients with acute myeloid leukemia (AML) and is predictive of poor prognosis. In murine models, forced expression of MN1 in hematopoietic progenitors induces an aggressive myeloid leukemia that is strictly dependent on a defined gene expression program in the cell of origin, which includes the homeobox genes Hoxa9 and Meis1 as key components. Here, we have shown that this program is controlled by two histone methyltransferases, MLL1 and DOT1L, as deletion of either MII1 or Dot1l in MN1-expressing cells abrogated the cell of origin derived gene expression program, including the expression of Hoxa cluster genes. In murine models, genetic inactivation of either Mill or Dot1l impaired MN1-mediated leukemogenesis. We determined that HOXA9 and MEIS1 are coexpressed with MN1 in a subset of clinical MN1(hi) leukemia, and human MN1(hi)/HOXA9(hi) leukemias were sensitive to pharmacologic inhibition of DOT1L. Together, these data point to DOT1L as a potential therapeutic target in MN1(hi) AML. In addition, our findings suggest that epigenetic modulation of the interplay between an oncogenic lesion and its cooperating developmental program has therapeutic potential in AML.
C1 [Riedel, Simone S.; Haladyna, Jessica N.; Bezzant, Matthew; Ernst, Patricia; Neff, Tobias; Bernt, Kathrin M.] Univ Colorado, Sch Med, Div Pediat Hematol Oncol BMT, Aurora, CO USA.
[Riedel, Simone S.; Haladyna, Jessica N.; Bezzant, Matthew; Ernst, Patricia; Neff, Tobias; Bernt, Kathrin M.] Childrens Hosp Colorado, Aurora, CO USA.
[Stevens, Brett; Polyea, Daniel A.; Jordan, Craig T.] Univ Colorado Denver, Div Hematol, Aurora, CO USA.
[Sinha, Amit U.; Armstrong, Scott A.] Harvard Univ, Childrens Hosp, Div Hematol Oncol, Sch Med,Dana Farber Canc Inst, Boston, MA 02115 USA.
[Sinha, Amit U.; Armstrong, Scott A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA.
[Wei, Qi] Childrens Hosp Colorado, Dept Pathol, Aurora, CO USA.
[Pollock, Roy M.; Daigle, Scott R.] Epizyme Inc, Cambridge, MA USA.
[Sinha, Amit U.] Basepair, New York, NY USA.
[Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Med, Dept Pediat, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA.
[Armstrong, Scott A.] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, 1275 York Ave, New York, NY 10021 USA.
RP Neff, T; Bernt, KM (reprint author), Univ Colorado, Ctr Canc & Blood Disorders, Childrens Hosp Colorado, 13123 East 16th Ave,Box B115, Aurora, CO 80045 USA.
EM Tobias.Neff@ucdenver.edu; Kathrin.Bernt@ucdenver.edu
RI Bernt, Kathrin/L-1826-2016;
OI Bernt, Kathrin/0000-0002-5400-0482; Neff, Tobias/0000-0002-0188-8393
FU University of Colorado Denver, Hematology/Oncology Section; Children's
Hospital Colorado Research Institute; NHLBI [K08HL102264]; Sidney-Kimmel
Foundation [141761]; Doris-Duke Charitable Foundation [2014104]; NCI
[K08CA154777, P30CA046934]; ASCO career development grant
FX We thank Ellen C. Zwarthoff (Erasmus University, Rotterdam, the
Netherlands) for providing the MN1 plasmid. We thank Karen Helm and the
staff at the flow cytometry core for assistance with cell sorting, and
we thank Katrina Diener, Bifeng Gao, Ted Shade, and Kenneth Jones from
the genomics and bioinformatics cores for assistance with the RNA-Seq
experiment. This work was supported by start-up funds from University of
Colorado Denver, Hematology/Oncology Section and the Children's Hospital
Colorado Research Institute (to K.M. Bernt), as well as NHLBI
K08HL102264 (to K.M. Bernt), Sidney-Kimmel Foundation 141761 (to K.M.
Bernt), Doris-Duke Charitable Foundation 2014104 (to K.M. Bernt, for
human cell line and patient sample work only; no funds from the Doris
Duke Charitable Foundation were used to support research that used
non-human animal models), NCI K08CA154777 (to T. Neff), ASCO career
development grant (to D.A. Pollyea), and NCI P30CA046934 (Shared
Resource of the University of Colorado Cancer Center).
NR 43
TC 0
Z9 0
U1 0
U2 5
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 APR
PY 2016
VL 126
IS 4
BP 1438
EP 1450
DI 10.1172/JCI80825
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DI5ES
UT WOS:000373522300032
PM 26927674
ER
PT J
AU Demehri, S
Cunningham, TJ
Manivasagam, S
Ngo, KH
Tuchayi, SM
Reddy, R
Meyers, MA
DeNardo, DG
Yokoyama, WM
AF Demehri, Shadmehr
Cunningham, Trevor J.
Manivasagam, Sindhu
Ngo, Kenneth H.
Tuchayi, Sara Moradi
Reddy, Rasika
Meyers, Melissa A.
DeNardo, David G.
Yokoyama, Wayne M.
TI Thymic stromal lymphopoietin blocks early stages of breast
carcinogenesis
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID CARCINOMA IN-SITU; CANCER-IMMUNOTHERAPY; PANCREATIC-CANCER;
ATOPIC-DERMATITIS; T-CELLS; MOUSE; SKIN; KERATINOCYTES; ALLERGY; RISK
AB Advances in the field of cancer immunology, including studies on tumor-infiltrating CD8(+) cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, CD4(+) Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers.
C1 [Demehri, Shadmehr; Cunningham, Trevor J.; Ngo, Kenneth H.; Tuchayi, Sara Moradi] Harvard Univ, Sch Med, Dept Dermatol, Ctr Canc Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Demehri, Shadmehr; Cunningham, Trevor J.; Ngo, Kenneth H.; Tuchayi, Sara Moradi] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Demehri, Shadmehr; Cunningham, Trevor J.; Ngo, Kenneth H.; Tuchayi, Sara Moradi] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA.
[Demehri, Shadmehr; Cunningham, Trevor J.; Reddy, Rasika] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA.
[Demehri, Shadmehr; Cunningham, Trevor J.; Manivasagam, Sindhu; Reddy, Rasika; Yokoyama, Wayne M.] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO USA.
[Meyers, Melissa A.; DeNardo, David G.] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA.
[Yokoyama, Wayne M.] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA.
RP Demehri, S (reprint author), Bldg 149 13th St,3rd Floor, Charlestown, MA 02129 USA.
EM sdemehri1@mgh.harvard.edu
FU Washington University Digestive Diseases Research Core Center (NIH)
[P30DK052574]; Washington University Rheumatic Diseases Core Center
(NIH) [P03AR048335]; NIH [S10-RR0227552, 1DP5OD021353]; American Skin
Association; Dermatology Foundation
FX We thank the Yokoyama and DeNardo laboratory members Emil R. Unanue and
Herbert W. Virgin for their critical reading of the manuscript. We thank
Andrew Farr for the K14-TSLPtg mice, Warren Leonard for the
Tslpr-/- mice, and Raphael Kopan and Ahu Turkoz for their
assistance with the early generation of the animal models used in this
study (NIH RO1 CA163353 and NIH P50 CA094056-07, to R. Kopan). We thank
the Washington University Digestive Diseases Research Core Center (NIH
grant P30DK052574) for assistance with IHC studies and the Washington
University Rheumatic Diseases Core Center (NIH grant P03AR048335) for
the Abs used in the depletion studies. The NanoZoomer imaging facility
is supported by NIH Shared Instrumentation grant S10-RR0227552. W.M.
Yokoyama is an Investigator of the Howard Hughes Medical Institute. S.
Demehri is supported by grants from the American Skin Association, the
Dermatology Foundation, and the NIH (1DP5OD021353).
NR 37
TC 6
Z9 7
U1 0
U2 2
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 APR
PY 2016
VL 126
IS 4
BP 1458
EP 1470
DI 10.1172/JCI83724
PG 13
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DI5ES
UT WOS:000373522300034
PM 26927668
ER
PT J
AU Grogg, KS
Toole, T
Ouyang, JS
Zhu, XP
Normandin, MD
Li, QZ
Johnson, K
Alpert, NM
El Fakhri, G
AF Grogg, Kira S.
Toole, Terrence
Ouyang, Jinsong
Zhu, Xuping
Normandin, Marc D.
Li, Quanzheng
Johnson, Keith
Alpert, Nathaniel M.
El Fakhri, Georges
TI National Electrical Manufacturers Association and Clinical Evaluation of
a Novel Brain PET/CT Scanner
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE PET/CT; instrumentation; NEMA standard
ID ECAT EXACT HR+; ATTENUATION COEFFICIENTS; PERFORMANCE; CT
AB The aim of this study was to determine the performance of a novel mobile human brain/small-animal PET/CT system. The scanner has a 35.7-cm-diameter bore and a 22-cm axial extent. The detector ring has 7 modules each with 3 x 4 cerium-doped lutetium yttrium orthosilicate crystal blocks, each consisting of 22 x 22 outer-layer and 21 x 21 inner-layer crystals, each layer 1-cm thick. Light is collected by 12 x 12 silicon photomultipliers. The integrated CT can be used for attenuation correction and anatomic localization. The scanner was designed as a low-cost device that nevertheless produces high-quality PET images with the unique capability of battery-powered propulsion, enabling use in many settings. Methods: Spatial resolution, sensitivity, and noise-equivalent counting rate were measured based on the National Electrical Manufacturers Association NU2-2012 procedures. Reconstruction was done with tight energy and timing cuts-400-650 keV and 7 ns-and loose cuts-350-700 keV and 10 ns. Additional image quality measurements were made from phantom, human, and animal studies. Performance was compared with a reference scanner with comparable imaging properties. Results: The full width at half maximum transverse resolution at a 1-cm (10-cm) radius was 3.2 mm (5.2-mm radial, 3.1-mm tangential), and the axial resolution was 3.5 mm (4.0 mm). A sensitivity of 7.5 and 11.7 kcps/MBq at the center for tight and loose cuts, respectively, increased to 8.8 and 13.9 kcps/MBq, respectively, at a 10-cm radial offset. The maximum noise-equivalent counting rate of 19.5 and 22.7 kcps for tight and loose cuts, respectively, was achieved for an activity concentration of 2.9 kBq/mL. Contrast recovery for 4: 1 hot cylinder to warm background was 76% for the 25-mm-diameter cylinder but decreased with decreasing cylinder size. The quantitation agreed within 2% of the known activity distribution and concentration. Brain phantom and human scans have shown agreement in SUVs and image quality with the reference scanner. Conclusion: We characterized the performance of the NeuroPET/CT and showed images from the first human studies. The study shows that this scanner achieves good performance when spatial resolution, sensitivity, counting rate, and image quality along with a low cost and unique mobile capabilities are considered.
C1 [Grogg, Kira S.; Ouyang, Jinsong; Zhu, Xuping; Normandin, Marc D.; Li, Quanzheng; Alpert, Nathaniel M.; El Fakhri, Georges] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gordon Ctr Med Imaging,Dept Radiol, Boston, MA USA.
[Toole, Terrence] Photo Diagnost Syst Inc, Boxboro, MA USA.
[Johnson, Keith] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA USA.
RP El Fakhri, G (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.
EM elfakhri.georges@mgh.harvard.edu
FU NIH [S10RR028110, T32EB013180, R21EB012823, R01EB019959, C06CA059267]
FX The costs of publication of this article were defrayed in part by the
payment of page charges. Therefore, and solely to indicate this fact,
this article is hereby marked "advertisement" in accordance with 18 USC
section 1734. This work was supported by NIH grants S10RR028110,
T32EB013180, R21EB012823, R01EB019959, and C06CA059267. Terrence Toole
is an employee of PDSi. No other potential conflict of interest relevant
to this article was reported.
NR 17
TC 0
Z9 0
U1 1
U2 4
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 APR 1
PY 2016
VL 57
IS 4
BP 646
EP 652
DI 10.2967/jnumed.115.159723
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DI6RN
UT WOS:000373627800036
PM 26697961
ER
PT J
AU Gaskins, AJ
Rich-Edwards, JW
Williams, PL
Toth, TL
Missmer, SA
Chavarro, JE
AF Gaskins, Audrey J.
Rich-Edwards, Janet W.
Williams, Paige L.
Toth, Thomas L.
Missmer, Stacey A.
Chavarro, Jorge E.
TI Prepregnancy Low to Moderate Alcohol Intake Is Not Associated with Risk
of Spontaneous Abortion or Stillbirth
SO JOURNAL OF NUTRITION
LA English
DT Article
DE alcohol; ethanol; miscarriage; pregnancy loss; stillbirth; spontaneous
abortion
ID BINGE DRINKING; CONSUMPTION; PREGNANCY; QUESTIONNAIRE; REPRODUCIBILITY;
MISCARRIAGE; RECALL; VALIDATION; CIGARETTE; CAFFEINE
AB Background: Numerous studies have documented the negative effects of maternal alcohol consumption during pregnancy on risk of pregnancy loss, yet whether prepregnancy alcohol intake affects the risk of spontaneous abortion is still unclear.
Objective: This study aimed to assess prepregnancy alcohol intake and risk of spontaneous abortion and stillbirth.
Methods: Our prospective cohort study included 27,580 pregnancies reported by 17,929 women in the Nurses' Health Study II between 1990 and 2009. Alcohol intake was assessed in 1989 and 1991 and every 4 y thereafter with the use of a validated questionnaire. Women were classified into 5 categories of consumption: 0, 0.1-1.9, 2-4.9, 5-9.9, and >= 10 g/d (1 serving = similar to 12 g). Pregnancies were self-reported, with case pregnancies lost spontaneously (spontaneous abortion after gestation of < 20 wk and stillbirth after gestation of >= 20 wk) and comparison pregnancies not ending in fetal loss (live birth, ectopic pregnancy, or induced abortion). Multivariable log-binomial regression models with generalized estimating equations were used to estimate RRs and 95% CIs.
Results: Incident spontaneous abortion and stillbirth were reported in 4326 (15.7%) and 205 (0.7%) pregnancies, respectively. Prepregnancy alcohol intake was not associated with spontaneous abortion. Compared with women who did not consume alcohol, the multivariable RRs (95% CIs) for increasing categories of alcohol intake among women who did consume alcohol were 1.04 (0.97, 1.12) for 0.1-1.9 g/d, 1.02 (0.94, 1.11) for 2-4.9 g/d, 1.01 (0.92, 1.10) for 5-9.9 g/d, and 0.98 (0.88, 1.09) for >= 10 g/d (P-trend = 0.45). Women who consumed >= 2 servings beer/wk before pregnancy had a 9% (95% CI: 1%, 17%) lower risk of spontaneous abortion than did women who consumed < 1 serving beer/mo; however, this association did not persist in various sensitivity analyses. Prepregnancy consumption of wine and liquor were not associated with spontaneous abortion. Total alcohol and specific alcohol beverage intake before pregnancy were not associated with stillbirth.
Conclusion: Prepregnancy alcohol intake was not related to risk of incident spontaneous abortion or stillbirth in women with no history of pregnancy loss. Our results provide reassuring evidence that low to moderate alcohol intake (<= 12 g/d) before pregnancy initiation does not affect risk of pregnancy loss.
C1 [Gaskins, Audrey J.; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Rich-Edwards, Janet W.; Williams, Paige L.; Missmer, Stacey A.; Chavarro, Jorge E.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Rich-Edwards, Janet W.; Missmer, Stacey A.; Chavarro, Jorge E.] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Rich-Edwards, Janet W.] Brigham & Womens Hosp, Dept Med, Connors Ctr Womens Hlth & Gender Biol, 75 Francis St, Boston, MA 02115 USA.
[Missmer, Stacey A.] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, 75 Francis St, Boston, MA 02115 USA.
[Toth, Thomas L.; Missmer, Stacey A.] Harvard Univ, Sch Med, Boston, MA USA.
[Toth, Thomas L.] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Boston, MA 02114 USA.
[Missmer, Stacey A.] Beth Israel Deaconess Med Ctr, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02215 USA.
RP Gaskins, AJ (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
EM agaskins@hsph.harvard.edu
FU NIH [T32DK007703-16, P30DK46200, UM1 CA176726]
FX Supported by NIH grants T32DK007703-16, P30DK46200, and UM1 CA176726.
NR 40
TC 0
Z9 0
U1 4
U2 8
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 APR
PY 2016
VL 146
IS 4
BP 799
EP 805
DI 10.3945/jn.115.226423
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DI3RA
UT WOS:000373415000019
ER
PT J
AU Langlois, J
Zaoui, A
Bichara, DA
Nich, C
Bensidhoum, M
Petite, H
Muratoglu, OK
Hamadouche, M
AF Langlois, Jean
Zaoui, Amine
Bichara, David A.
Nich, Christophe
Bensidhoum, Morad
Petite, Herve
Muratoglu, Orhun K.
Hamadouche, Moussa
TI Biological reaction to polyethylene particles in a murine calvarial
model is highly influenced by age
SO JOURNAL OF ORTHOPAEDIC RESEARCH
LA English
DT Article
DE orthopaedic implants; aging; bone histomorphometry; bone micro-CT;
luminescence
ID MICRO-COMPUTED TOMOGRAPHY; TOTAL HIP-ARTHROPLASTY; ALTERNATIVE
MACROPHAGE ACTIVATION; MOLECULAR-WEIGHT POLYETHYLENE; WEAR DEBRIS
PARTICLES; INNATE IMMUNE-SYSTEM; PERIPROSTHETIC OSTEOLYSIS;
BONE-FORMATION; IN-VIVO; RAT MODEL
AB Particle-induced osteolysis is driven by multiple factors including bone metabolism, inflammation, and age. The objective of this study was to determine the influence of age on polyethylene (PE) particle-induced osteolysis in a murine calvarial model comparing 2-month-old (young) versus 24-month-old (old) mice. After PE particle implantation, calvaria were assessed at days (D) 3, D7, D14, and D21 via chemoluminescent imaging for inflammation (L-012 probe). In addition micro-computed tomography (micro-CT) and histomorphometry end points addressed the bone reaction. Inflammation peaked at D7 in young mice and D14 in old mice. Using micro-CT, a nadir of mature bone was recorded at D7 for young mice, versus D21 for old mice. Besides, regenerating bone peaked at distinct timepoints: D7 for young mice versus D21 for old mice. In the young mice group, the histomorphometric findings correlated with micro-CT regenerating bone findings at D7, associated with ample osteoid deposition. No osteoid could be histologically quantified in the old mice group at D7. This study demonstrated that the biological reaction to polyethylene particles is highly influenced by age. (c) 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:574-580, 2016.
C1 [Langlois, Jean; Bichara, David A.; Muratoglu, Orhun K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, 55 Fruit St,GRJ 1231, Boston, MA 02114 USA.
[Langlois, Jean; Zaoui, Amine; Nich, Christophe; Bensidhoum, Morad; Petite, Herve; Hamadouche, Moussa] Paris 7 Denis Diderot, Fac Med, Lab Bioingn & Biomecan Osteoarticulaires, UMR CNRS 7052, 10 Ave Verdun, F-75010 Paris, France.
RP Langlois, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harris Orthopaed Lab, 55 Fruit St,GRJ 1231, Boston, MA 02114 USA.; Langlois, J (reprint author), Paris 7 Denis Diderot, Fac Med, Lab Bioingn & Biomecan Osteoarticulaires, UMR CNRS 7052, 10 Ave Verdun, F-75010 Paris, France.
EM jeangast@gmail.com
RI Petite, Herve/E-3478-2016
OI Petite, Herve/0000-0003-1694-5060
FU APHP; Fulbright Program; Arthur Sachs; Harvard French Scholarship Fund
grant
FX Grant sponsor: APHP (concours de la medaille); Grant sponsor: Fulbright
Program; Grant sponsor: Arthur Sachs; Grant sponsor: Harvard French
Scholarship Fund grant.
NR 55
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-0266
EI 1554-527X
J9 J ORTHOP RES
JI J. Orthop. Res.
PD APR
PY 2016
VL 34
IS 4
BP 574
EP 580
DI 10.1002/jor.23050
PG 7
WC Orthopedics
SC Orthopedics
GA DI4ST
UT WOS:000373490300004
PM 26375608
ER
PT J
AU Zhai, X
Sun, CL
Rong, PJ
Li, SY
McCabe, MF
Wang, X
Mao, JR
Wang, SX
AF Zhai, Xu
Sun, Chunli
Rong, Peijing
Li, Shaoyuan
McCabe, Michael F.
Wang, Xing
Mao, Jianren
Wang, Shuxing
TI A Correlative Relationship Between Chronic Pain and Insulin Resistance
in Zucker Fatty Rats: Role of Downregulation of Insulin Receptors
SO JOURNAL OF PAIN
LA English
DT Article
DE Chronic hypersensitivity; insulin resistance; type 2 diabetes;
constriction injury of a unilateral sciatic nerve; hemoglobiri Alc;
insulin receptor; Zucker Diabetic Fatty rats
ID PERIPHERAL MONONEUROPATHY; BETA-CELL; HYPERALGESIA; GLUCOSE; NERVE;
HYPERINSULINEMIA; PREVALENCE; NEUROPATHY; ALLODYNIA; SENSATION
AB Epidemiological studies and meta-analyses report a strong relationship between chronic pain and abnormalities in glucose metabolism, but the exact relationship between chronic pain and insulin resistance in type 2 diabetes (T2D) remains unknown. Using a model of neuropathic thermal and tactile hypersensitivity induced by chronic constriction injury (CCI) of the sciatic nerve in Zucker Diabetic Fatty (ZDF) and Zucker Lean (ZL) littermates, we compared the recovery period of hypersensitivity and the progression of T2D and studied the possible involvement of insulin receptors (IRs) in the comorbidity of these 2 conditions. We found that the nociceptive thresholds to thermal and mechanical stimulation in naive ZDF rats were lower than in ZL littermates at 6 weeks of age. Although ZDF and ZL rats developed thermal and tactile hypersensitivity after CCI, it took a longer time nociceptive sensitivity to be restored in ZDF rats. Nerve injury accelerated the progression of T2D in ZDF rats, shown by an earlier onset of hyperglycemia, more severe hyperinsulinemia, and a higher concentration of glycosylated hemoglobin Alc 6 weeks after CCI, compared with those in naive ZDF and ZL rats. IR-immunoreactive cells were located across the central nervous system and skeletal muscles. In the central nervous system, IR coexpressed with a neuronal marker (neuronal nuclei) but not a glial marker (glial fibrillary acidic protein). There was a low level of IR expression in skeletal muscles of naive ZDF rats. In contrast, CCI reduced the IR expression in skeletal muscles as well as the ipsilateral spinal cord, primarily in the dorsal horn. In conclusion, our data suggest that the relationship between insulin resistance and chronic pain in ZDF rats is bidirectional and an impaired IR signaling system might be implicated in this reciprocal relationship.
Perspective: Nerve injuries in genetically susceptible individuals might accelerate the development of insulin resistance as in T2D. A downregulated expression of IRs in the skeletal muscle innervated by the injured nerve is one of the underlying mechanisms. (C) 2016 The Authors. Published by Elsevier Inc. on behalf of the American Pain Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Zhai, Xu; Sun, Chunli; Wang, Xing] Xinxiang Med Univ, Dept Anat, Xinxiang, Henan Province, Peoples R China.
[Zhai, Xu; Rong, Peijing; Li, Shaoyuan] China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Dept Physiol, Beijing, Peoples R China.
[McCabe, Michael F.; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Ctr Translat Pain Res,Dept Anesthesia Crit Ca, Boston, MA USA.
[Wang, Shuxing] Guangdong Inst Appl Biol Resources, Guangzhou 510260, Guangdong, Peoples R China.
[Wang, Shuxing] Guangdong Publ Lab Wild Anim Conservat & Utilizat, Guangzhou, Guangdong, Peoples R China.
RP Rong, PJ (reprint author), China Acad Chinese Med Sci, Inst Acupuncture & Moxibust, Dept Physiol, Beijing, Peoples R China.; Wang, SX (reprint author), Guangdong Inst Appl Biol Resources, Guangzhou 510260, Guangdong, Peoples R China.
EM rongpj@hotmail.com; shuxingw@gmail.com
FU National Natural Science Foundation of China [81271243, 81571085,
81473780]; National Basic Research Program of China (973 Program)
[2012CB518503]; Project Supported National Science and Technology
Ministry [2012BAF14B10]; Guangdong Entomological Institute
[GDEI-gjrc201501]
FX This work was supported by the National Natural Science Foundation of
China-81271243 and 81571085 (S.W.), and 81473780 (P.R.); National Basic
Research Program of China (973 Program) - 2012CB518503 and Project
Supported National Science and Technology Ministry-2012BAF14B10 (ER.);
and Institutional fund of Guangdong Entomological
Institute-GDEI-gjrc201501 (S.W.). The funding sources had no role in the
experimental design, procedures, writing, and decision to submit the
work for publication.
NR 30
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U2 4
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
BP 404
EP 413
DI 10.1016/j.jpain.2015.12.003
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EY
UT WOS:000373522900002
PM 26705975
ER
PT J
AU Higgins, D
Buta, E
Heapy, A
Driscoll, M
Kerns, R
Masheb, R
Becker, W
Burgess, D
Hausmann, L
Bair, M
Justice, A
Wandner, L
Krein, S
Brandt, C
Goulet, J
AF Higgins, D.
Buta, E.
Heapy, A.
Driscoll, M.
Kerns, R.
Masheb, R.
Becker, W.
Burgess, D.
Hausmann, L.
Bair, M.
Justice, A.
Wandner, L.
Krein, S.
Brandt, C.
Goulet, J.
TI The relationship among BMI, pain intensity, and musculoskeletal
diagnoses
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Higgins, D.; Buta, E.; Heapy, A.; Driscoll, M.; Kerns, R.; Masheb, R.; Becker, W.; Burgess, D.; Hausmann, L.; Bair, M.; Justice, A.; Wandner, L.; Krein, S.; Brandt, C.; Goulet, J.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA.
NR 0
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Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 208
BP S28
EP S28
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000110
PM 28162438
ER
PT J
AU Jackson, W
Kulich, R
Malacarne, A
Lapidow, A
Vranceanu, A
AF Jackson, W.
Kulich, R.
Malacarne, A.
Lapidow, A.
Vranceanu, A.
TI Physical functioning and mindfulness based interventions in chronic
pain: a systematic review
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Jackson, W.; Kulich, R.; Malacarne, A.; Lapidow, A.; Vranceanu, A.] Tufts Univ, Sch Dent Med, Harvard Univ, Massachusetts Gen Hosp,Sch Med, Boston, MA 02111 USA.
NR 0
TC 0
Z9 0
U1 2
U2 3
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 497
BP S99
EP S99
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000395
PM 28162752
ER
PT J
AU Lonberger, C
McSheffrey, S
Allsup, K
Sluice, M
Driscoll, M
Higgins, D
Tyzik, A
Gerber, M
Scioli-Salter, E
AF Lonberger, C.
McSheffrey, S.
Allsup, K.
Sluice, M.
Driscoll, M.
Higgins, D.
Tyzik, A.
Gerber, M.
Scioli-Salter, E.
TI Potential barriers for achieving exercise maintenance among trauma
exposed female veterans with Fibromyalgia
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Lonberger, C.; McSheffrey, S.; Allsup, K.; Sluice, M.; Driscoll, M.; Higgins, D.; Tyzik, A.; Gerber, M.; Scioli-Salter, E.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 517
BP S104
EP S104
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000415
PM 28162324
ER
PT J
AU Mawla, I
Loggia, M
Schmithorst, V
Ortiz, A
Gerber, J
Protsenko, E
Lee, J
Kim, J
Kim, H
Berna, C
Kaptchuk, T
Kong, J
Gollub, R
Rosen, B
Edwards, R
Wasan, A
Napadow, V
AF Mawla, I.
Loggia, M.
Schmithorst, V.
Ortiz, A.
Gerber, J.
Protsenko, E.
Lee, J.
Kim, J.
Kim, H.
Berna, C.
Kaptchuk, T.
Kong, J.
Gollub, R.
Rosen, B.
Edwards, R.
Wasan, A.
Napadow, V.
TI Investigating the neural circuitry supporting clinical pain perception
in chronic low back pain - the importance of cardiorespiratory artifact
correction with arterial spin labeling fMRI
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Mawla, I.; Loggia, M.; Schmithorst, V.; Ortiz, A.; Gerber, J.; Protsenko, E.; Lee, J.; Kim, J.; Kim, H.; Berna, C.; Kaptchuk, T.; Kong, J.; Gollub, R.; Rosen, B.; Edwards, R.; Wasan, A.; Napadow, V.] Massachusetts Gen Hosp, Charlestown, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 336
BP S59
EP S60
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000236
PM 28162572
ER
PT J
AU Rudd-Barnard, G
Walbom, A
Pangarkar, S
Baria, A
AF Rudd-Barnard, G.
Walbom, A.
Pangarkar, S.
Baria, A.
TI A case study investigating opioid medication utilization in patients
with complex regional pain syndrome before and after ketamine infusion
therapy
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Rudd-Barnard, G.; Walbom, A.; Pangarkar, S.; Baria, A.] Univ Calif Los Angeles, Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 406
BP S76
EP S76
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000305
PM 28162651
ER
PT J
AU Rudd-Barnard, G
Pangarkar, S
Moaleji, N
Glassman, P
AF Rudd-Barnard, G.
Pangarkar, S.
Moaleji, N.
Glassman, P.
TI Epidemiology of naloxone use for opioid overdose in a tertiary care
medical center
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Rudd-Barnard, G.; Pangarkar, S.; Moaleji, N.; Glassman, P.] Greater Los Angeles VA Hlth Syst, Los Angeles, CA USA.
NR 0
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U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 141
BP S11
EP S11
PG 1
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000043
PM 28162348
ER
PT J
AU Stegner, A
Cook, D
AF Stegner, A.
Cook, D.
TI Resistance exercise training in Gulf War Veterans with chronic
unexplained muscle pain: impact on pain, fatigue, mood and global
impression of change
SO JOURNAL OF PAIN
LA English
DT Meeting Abstract
C1 [Stegner, A.; Cook, D.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD APR
PY 2016
VL 17
IS 4
SU 1
MA 484
BP S95
EP S96
PG 2
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI5EZ
UT WOS:000373523000382
PM 28162735
ER
PT J
AU Charidimou, A
AF Charidimou, Andreas
TI Cerebral Microbleeds Meta-analyses of Prospective Studies: The Need to
Consider Both Ischemic and Hemorrhagic Stroke Outcomes
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Letter
C1 [Charidimou, Andreas] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Res Ctr,Hemorrhag S, Boston, MA 02115 USA.
RP Charidimou, A (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Res Ctr,Hemorrhag S, Boston, MA 02115 USA.
EM andreas.charidimou.09@ucl.ac.uk
NR 5
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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 APR
PY 2016
VL 25
IS 4
BP 1007
EP 1007
DI 10.1016/j.jstrokecerebrovasdis.2015.12.012
PG 1
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DI7ZJ
UT WOS:000373720200045
PM 26794263
ER
PT J
AU Kennedy, JG
van Dijk, PAD
Murawski, CD
Duke, G
Newman, H
DiGiovanni, CW
Yasui, Y
AF Kennedy, John G.
van Dijk, Pim A. D.
Murawski, Christopher D.
Duke, Gavin
Newman, Hunter
DiGiovanni, Christopher W.
Yasui, Youichi
TI Functional outcomes after peroneal tendoscopy in the treatment of
peroneal tendon disorders
SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
LA English
DT Article
DE Peroneal tendon; Ankle; Tendoscopy; Tendon injury; Tendinosis; Magnetic
resonance imaging
ID LATERAL ANKLE INSTABILITY; PLATELET-RICH PLASMA; TEARS; RETINACULUM;
MANAGEMENT; INJURIES; FOOT; MRI; TENDINOPATHY; DISLOCATION
AB The primary purpose of this study was to evaluate clinical outcomes following peroneal tendoscopy for the treatment of peroneal pathology. Correlation between pre-operative magnetic resonance imaging (MRI) and peroneal tendoscopic diagnostic findings was also assessed.
Twenty-three patients with a mean age of 34 +/- A 8.8 years undergoing peroneal tendoscopy were pre- and post-operatively assessed with the foot and ankle outcome score (FAOS) and the Short Form-12 (SF-12) outcome questionnaires. Follow-up was over 24 months in all patients. The sensitivity and specificity of MRI were calculated in comparison with peroneal tendoscopy, including the positive predictive value (PPV).
Both the FAOS and the SF-12 improved significantly (p < 0.05) at a mean follow-up of 33 +/- A 7.3 months significantly. MRI showed an overall sensitivity of 0.90 (95 % confidence interval (CI) = 0.82-0.95) and specificity of 0.72 (95 % CI 0.62-0.80). The PPV for MRI diagnosis of peroneal tendon pathology was 0.76 (95 % CI 0.68-0.83).
The current study found good clinical outcomes in patients with peroneal tendon disorders, treated with peroneal tendoscopy. Although a relatively small number of patients were included, the study suggests good correlation between tendoscopic findings and pre-operative MRI findings of peroneal tendon pathology, supporting the use of MRI as a useful diagnostic modality for suspected peroneal tendon disorders.
Level IV, retrospective case series.
C1 [Kennedy, John G.; van Dijk, Pim A. D.; Newman, Hunter; Yasui, Youichi] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
[van Dijk, Pim A. D.] Univ Amsterdam, Acad Med Ctr, Dept Orthoped Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[van Dijk, Pim A. D.] ACHSS, Acad Ctr Evidence Based Sports Med ACES, Amsterdam, Netherlands.
[Duke, Gavin] East River Med Imaging, New York, NY USA.
[Murawski, Christopher D.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[DiGiovanni, Christopher W.] Harvard Univ, Dept Orthopaed Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA USA.
[Yasui, Youichi] Teikyo Univ, Sch Med, Dept Orthopaed Surg, Tokyo 173, Japan.
RP Kennedy, JG (reprint author), Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA.
EM KennedyJ@hss.edu
NR 40
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U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-2056
EI 1433-7347
J9 KNEE SURG SPORT TR A
JI Knee Surg. Sports Traumatol. Arthrosc.
PD APR
PY 2016
VL 24
IS 4
BP 1148
EP 1154
DI 10.1007/s00167-016-4012-6
PG 7
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA DI7SX
UT WOS:000373703400028
PM 26846655
ER
PT J
AU van Dijk, PAD
Lubberts, B
Verheul, C
DiGiovanni, CW
Kerkhoffs, GMMJ
AF van Dijk, Pim A. D.
Lubberts, Bart
Verheul, Claire
DiGiovanni, Christopher W.
Kerkhoffs, Gino M. M. J.
TI Rehabilitation after surgical treatment of peroneal tendon tears and
ruptures
SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
LA English
DT Article
DE Physical therapy; Rehabilitation; Peroneal tendon; Tear; Tendon;
Rupture; Tendon healing
ID CHRONIC ANKLE INSTABILITY; BREVIS TENDON; LONGUS TENDON; OS PERONEUM;
ALLOGRAFT RECONSTRUCTION; ACTIVE MOBILIZATION; SPLIT LESIONS; REPAIR;
INJURIES; FRACTURE
AB The purpose of this study was to provide an overview of the available evidence on rehabilitation programmes after operatively treated patients with peroneal tendon tearsand ruptures.
A systematic review was performed, and PubMed and EMBASE were searched for relevant studies. Information regarding the rehabilitation programme after surgical management of peroneal tendon tears and ruptures was extracted from all included studies.
In total, 49 studies were included. No studies were found with the primary purpose to report on rehabilitation of surgically treated peroneal tendon tears or ruptures. The median duration of the total immobilization period after primary repair was 6.0 weeks (range 0-12), 7.0 weeks (range 3.0-13) after tenodesis, 6.3 weeks (range 3.0-13) after grafting, and 8.0 weeks (range 6.0-11) after end-to-end suturing. Forty one percent of the studies that reported on the start of range of motion exercises initiated range of motion within 4 weeks after surgery. No difference was found in duration of immobilization or start of range of motion between different types of surgical treatment options.
Appropriate directed rehabilitation appears to be an important factor in the clinical success of surgically treated peroneal tendon tears and ruptures. There seems to be a trend towards shorter immobilization time and early range of motion, although there is no consensus in the literature on best practice recommendations for optimizing rehabilitation after surgical repair of peroneal tendon tears or ruptures. It is important to adjust the rehabilitation protocol to every specific patient for an optimal rehabilitation.
Level of evidence Systematic Review, Level IV.
C1 [van Dijk, Pim A. D.; Kerkhoffs, Gino M. M. J.] Univ Amsterdam, Acad Med Ctr, Orthopaed Res Ctr Amsterdam, Dept Orthopaed Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[van Dijk, Pim A. D.; Verheul, Claire; Kerkhoffs, Gino M. M. J.] Acad Ctr Evidence Based Sports Med ACES, Amsterdam, Netherlands.
[van Dijk, Pim A. D.; Verheul, Claire; Kerkhoffs, Gino M. M. J.] ACHSS, Amsterdam, Netherlands.
[van Dijk, Pim A. D.; Lubberts, Bart; DiGiovanni, Christopher W.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Foot & Ankle Serv, Boston, MA 02114 USA.
[Verheul, Claire] Orthopaed Manual Therapy & Sport Physiotherapy, Amsterdam, Netherlands.
RP van Dijk, PAD (reprint author), Univ Amsterdam, Acad Med Ctr, Orthopaed Res Ctr Amsterdam, Dept Orthopaed Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.; van Dijk, PAD (reprint author), Acad Ctr Evidence Based Sports Med ACES, Amsterdam, Netherlands.; van Dijk, PAD (reprint author), ACHSS, Amsterdam, Netherlands.; van Dijk, PAD (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Foot & Ankle Serv, Boston, MA 02114 USA.
EM p.a.vandijk@amc.uva.nl; g.m.kerkhoffs@amc.uva.nl
NR 69
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U1 1
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PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-2056
EI 1433-7347
J9 KNEE SURG SPORT TR A
JI Knee Surg. Sports Traumatol. Arthrosc.
PD APR
PY 2016
VL 24
IS 4
BP 1165
EP 1174
DI 10.1007/s00167-015-3944-6
PG 10
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA DI7SX
UT WOS:000373703400030
PM 26803783
ER
PT J
AU Claessen, FMAP
Meijer, DT
van den Bekerom, MPJ
Deynoot, BDJG
Mallee, WH
Doornberg, JN
van Dijk, CN
AF Claessen, Femke M. A. P.
Meijer, Diederik T.
van den Bekerom, Michel P. J.
Deynoot, Barend D. J. Gevers
Mallee, Wouter H.
Doornberg, Job N.
van Dijk, C. Niek
TI Reliability of classification for post-traumatic ankle osteoarthritis
SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
LA English
DT Article
DE Ankle trauma; Post-traumatic ankle fracture osteoarthritis;
Classification system; Interobserver study
ID PROXIMAL HUMERAL FRACTURES; OF-THE-LITERATURE; INTEROBSERVER
RELIABILITY; DECISION-MAKING; OSTEOCHONDRAL DEFECTS; PATIENT
PREFERENCES; 3-DIMENSIONAL CT; ARTHRITIS; PRIORITIES; OSTEOTOMY
AB The purpose of this study was to identify the most reliable classification system for clinical outcome studies to categorize post-traumatic-fracture-osteoarthritis.
A total of 118 orthopaedic surgeons and residents-gathered in the Ankle Platform Study Collaborative Science of Variation Group-evaluated 128 anteroposterior and lateral radiographs of patients after a bi- or trimalleolar ankle fracture on a Web-based platform in order to rate post-traumatic osteoarthritis according to the classification systems coined by (1) van Dijk, (2) Kellgren, and (3) Takakura. Reliability was evaluated with the use of the Siegel and Castellan's multirater kappa measure. Differences between classification systems were compared using the two-sample Z-test.
Interobserver agreement of surgeons who participated in the survey was fair for the van Dijk osteoarthritis scale (k = 0.24), and poor for the Takakura (k = 0.19) and the Kellgren systems (k = 0.18) according to the categorical rating of Landis and Koch. This difference in one categorical rating was found to be significant (p < 0.001, CI 0.046-0.053) with the high numbers of observers and cases available.
This study documents fair interobserver agreement for the van Dijk osteoarthritis scale, and poor interobserver agreement for the Takakura and Kellgren osteoarthritis classification systems. Because of the low interobserver agreement for the van Dijk, Kellgren, and Takakura classification systems, those systems cannot be used for clinical decision-making.
Development of diagnostic criteria on basis of consecutive patients, Level II.
C1 [Claessen, Femke M. A. P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, 55 Fruit St, Boston, MA 02114 USA.
[Claessen, Femke M. A. P.] Univ Amsterdam, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
[Meijer, Diederik T.; Deynoot, Barend D. J. Gevers; Mallee, Wouter H.; Doornberg, Job N.] Univ Amsterdam, Acad Med Ctr, Orthotrauma Res Ctr Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[van den Bekerom, Michel P. J.] Onze Lieve Vrouw Hosp, Shoulder & Elbow Unit, Amsterdam, Netherlands.
[van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
RP Claessen, FMAP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, 55 Fruit St, Boston, MA 02114 USA.; Claessen, FMAP (reprint author), Univ Amsterdam, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
EM femke__claessen@hotmail.com
FU Marti-Keuning Eckhart Foundation; Prins Bernhard Cultuur foundation;
Trust foundation; VSB foundation; Van Beek-Donner foundation
FX DT. Meijer and J. N. Doornberg have received an unrestricted research
grant from the Marti-Keuning Eckhart Foundation. F. M. A. P Claessen has
received a research grant from the Prins Bernhard Cultuur foundation,
Trust foundation, VSB foundation, and Van Beek-Donner foundation. For
the remaining authors, none were declared.
NR 36
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U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-2056
EI 1433-7347
J9 KNEE SURG SPORT TR A
JI Knee Surg. Sports Traumatol. Arthrosc.
PD APR
PY 2016
VL 24
IS 4
BP 1332
EP 1337
DI 10.1007/s00167-015-3871-6
PG 6
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA DI7SX
UT WOS:000373703400051
PM 26611896
ER
PT J
AU Claessen, FMAP
Meijer, DT
van den Bekerom, MPJ
Deynoot, BDJG
Mallee, WH
Doornberg, JN
van Dijk, CN
AF Claessen, Femke M. A. P.
Meijer, Diederik T.
van den Bekerom, Michel P. J.
Deynoot, Barend D. J. Gevers
Mallee, Wouter H.
Doornberg, Job N.
van Dijk, C. Niek
CA Ankle Platform Study Collaborative
TI Reliability of classification for post-traumatic ankle osteoarthritis
(vol 24, pg 1332, 2016)
SO KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY
LA English
DT Correction
C1 [Claessen, Femke M. A. P.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, 55 Fruit St, Boston, MA 02114 USA.
[Claessen, Femke M. A. P.] Univ Amsterdam, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
[Meijer, Diederik T.; Deynoot, Barend D. J. Gevers; Mallee, Wouter H.; Doornberg, Job N.] Univ Amsterdam, Acad Med Ctr, Orthotrauma Res Ctr Amsterdam, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
[van den Bekerom, Michel P. J.] Onze Lieve Vrouw Hosp, Shoulder & Elbow Unit, Amsterdam, Netherlands.
[van Dijk, C. Niek] Univ Amsterdam, Acad Med Ctr, Dept Orthopaed Surg, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands.
RP Claessen, FMAP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv,Yawkey Ctr, 55 Fruit St, Boston, MA 02114 USA.; Claessen, FMAP (reprint author), Univ Amsterdam, Sch Med, 55 Fruit St, Boston, MA 02114 USA.
EM femke__claessen@hotmail.com
NR 1
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0942-2056
EI 1433-7347
J9 KNEE SURG SPORT TR A
JI Knee Surg. Sports Traumatol. Arthrosc.
PD APR
PY 2016
VL 24
IS 4
BP 1338
EP 1338
DI 10.1007/s00167-016-3986-4
PG 1
WC Orthopedics; Sport Sciences; Surgery
SC Orthopedics; Sport Sciences; Surgery
GA DI7SX
UT WOS:000373703400052
PM 26814893
ER
PT J
AU Chan, AT
AF Chan, Andrew T.
TI Metformin for cancer prevention: a reason for optimism
SO LANCET ONCOLOGY
LA English
DT Editorial Material
ID DIABETIC-PATIENTS; RISK
C1 [Chan, Andrew T.] Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St,GRJ-825C, Boston, MA 02114 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, 55 Fruit St,GRJ-825C, Boston, MA 02114 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
RP Chan, AT (reprint author), Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, 55 Fruit St,GRJ-825C, Boston, MA 02114 USA.; Chan, AT (reprint author), Harvard Univ, Sch Med, 55 Fruit St,GRJ-825C, Boston, MA 02114 USA.; Chan, AT (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.; Chan, AT (reprint author), Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
EM achan@mgh.harvard.edu
NR 10
TC 2
Z9 2
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD APR
PY 2016
VL 17
IS 4
BP 407
EP 409
DI 10.1016/S1470-2045(16)00006-1
PG 4
WC Oncology
SC Oncology
GA DI4VN
UT WOS:000373497600033
PM 26947330
ER
PT J
AU Kim, DW
Mehra, R
Tan, DSW
Felip, E
Chow, LQM
Camidge, DR
Vansteenkiste, J
Sharma, S
De Pas, T
Riely, GJ
Solomon, BJ
Wolf, J
Thomas, M
Schuler, M
Liu, G
Santoro, A
Sutradhar, S
Li, SY
Szczudlo, T
Yovine, A
Shaw, AT
AF Kim, Dong-Wan
Mehra, Ranee
Tan, Daniel S. W.
Felip, Enriqueta
Chow, Laura Q. M.
Camidge, D. Ross
Vansteenkiste, Johan
Sharma, Sunil
De Pas, Tommaso
Riely, Gregory J.
Solomon, Benjamin J.
Wolf, Juergen
Thomas, Michael
Schuler, Martin
Liu, Geoffrey
Santoro, Armando
Sutradhar, Santosh
Li, Siyu
Szczudlo, Tomasz
Yovine, Alejandro
Shaw, Alice T.
TI Activity and safety of ceritinib in patients with ALK-rearranged
non-small-cell lung cancer (ASCEND-1): updated results from the
multicentre, open-label, phase 1 trial
SO LANCET ONCOLOGY
LA English
DT Article
ID TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; BRAIN METASTASES; CSF
CONCENTRATION; CLINICAL BENEFIT; CRIZOTINIB; CHEMOTHERAPY; DISEASE;
ALECTINIB; THERAPY
AB Background ALK-rearranged non-small-cell lung cancer (NSCLC) is sensitive to ALK tyrosine kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often with progression in the brain. Ceritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood-brain barrier in vivo, and shows clinical responses in patients with crizotinib-resistant disease. We aimed to assess whole-body activity of ceritinib in both ALK inhibitor-pretreated and ALK inhibitor-naive patients with ALK-rearranged NSCLC.
Methods ASCEND-1 was an open-label, phase 1 trial that recruited patients from 20 academic hospitals or cancer centres in 11 countries in Europe, North America, and Asia-Pacific. Eligible patients were aged 18 years or older with ALK-rearranged locally advanced or metastatic cancer that had progressed despite standard therapy (or for which no effective standard therapy existed), who had at least one measurable lesion at baseline. The primary objective (to determine the maximum tolerated dose) has been reported previously. This updated analysis includes all patients with ALK-rearranged NSCLC given oral ceritinib at the recommended dose of 750 mg/ day in the dose-escalation and expansion phases. Here we report the secondary outcomes of overall response, duration of response, and progression-free survival, analysed in all patients who received at least one 750 mg dose of ceritinib. Exploratory analyses included retrospective analysis of intracranial activity by independent neuroradiologists, in patients with untreated or locally treated neurologically stable brain metastases at baseline. Safety was assessed in all patients who received at least one dose of ceritinib. This study is no longer recruiting patients; however, treatment and follow-up are ongoing. This study is registered with ClinicalTrials.gov, number NCT01283516.
Findings Between Jan 24, 2011, and July 31, 2013, 255 patients were enrolled and received at least one dose of ceritinib 750 mg/ day, of whom 246 had ALK-rearranged NSCLC. At data cutoff (April 14, 2014), median follow-up was 11.1 months (IQR 6.7-15.2) and 147 (60%) patients had discontinued treatment, 98 (40%) as a result of disease progression. An overall response was reported in 60 (72% [95% CI 61-82]) of 83 ALK inhibitor-naive patients and 92 (56% [49-64]) of 163 ALK inhibitor-pretreated patients. Median duration of response was 17.0 months (95% CI 11.3-non-estimable [NE]) in ALK inhibitor-naive patients and 8.3 months (6.8-9.7) in ALK inhibitor-pretreated patients. Median progression-free survival was 18.4 months (95% CI 11.1-NE) in ALK inhibitor-naive patients and 6.9 months (5.6-8.7) in ALK inhibitor-pretreated patients. Of 94 patients with retrospectively confirmed brain metastases and at least one post-baseline MRI or CT tumour assessment, intracranial disease control was reported in 15 (79% [95% CI 54-94]) of 19 ALK inhibitor-naive patients and in 49 (65% [54-76]) of 75 ALK inhibitor-pretreated patients. Of these 94 patients, 11 had measurable brain lesions and no previous radiotherapy to the brain, six of whom achieved a partial intracranial response. Serious adverse events were recorded in 117 (48%) of 246 patients. The most common grade 3-4 laboratory abnormalities were increased alanine aminotransferase (73 [30%] patients) and increased aspartate aminotransferase (25 [10%]). The most common grade 3-4 non-laboratory adverse events were diarrhoea and nausea, both of which occurred in 15 (6%) patients. Two on-treatment deaths during the study were deemed to be related to study drug by the investigators, one due to interstitial lung disease and one as a result of multiorgan failure that occurred in the context of infection and ischaemic hepatitis.
Interpretation The durable whole-body responses reported, together with the intracranial activity, support a clinical benefit for treatment with ceritinib in patients with ALK-rearranged NSCLC who have received crizotinib, or as an alternative to crizotinib. A confi rmatory phase 2 clinical trial is ongoing to assess ceritinib activity in patients with ALK-rearranged NSCLC and brain or leptomeningeal metastases.
C1 [Kim, Dong-Wan] Seoul Natl Univ Hosp, Seoul 110744, South Korea.
[Mehra, Ranee] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA.
[Tan, Daniel S. W.] Natl Canc Ctr, Singapore, Singapore.
[Felip, Enriqueta] Vall dHebron Univ, Barcelona, Spain.
[Chow, Laura Q. M.] Univ Washington, Seattle, WA 98195 USA.
[Camidge, D. Ross] Univ Colorado, Denver, CO 80202 USA.
[Vansteenkiste, Johan] Univ Hosp KU Leuven, Leuven, Belgium.
[Sharma, Sunil] Huntsman Canc Inst, Salt Lake City, UT USA.
[De Pas, Tommaso] Ist Europeo Oncol, Milan, Italy.
[Riely, Gregory J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA.
[Solomon, Benjamin J.] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Wolf, Juergen] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Thomas, Michael] Univ Klinikum Heidelberg, Translat Lung Res Ctr Heidelberg TLRC H, Thoraxklin, Internist Onkol Thoraxtumoren, Heidelberg, Germany.
[Schuler, Martin] Univ Duisburg Essen, Univ Hosp Essen, German Canc Consortium DKTK, Partner Site Univ Hosp Essen, Essen, Germany.
[Liu, Geoffrey] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Santoro, Armando] IRCCS Inst Clin Humanitas, Milan, Italy.
[Sutradhar, Santosh; Li, Siyu; Szczudlo, Tomasz] Novartis Pharmaceut, E Hanover, NJ USA.
[Yovine, Alejandro] Novartis Pharma AG, Basel, Switzerland.
[Shaw, Alice T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM ashaw1@partners.org
RI Liu, Geoffrey/N-4421-2016
FU Novartis Pharmaceuticals Corporation
FX Novartis Pharmaceuticals Corporation.
NR 35
TC 19
Z9 22
U1 6
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD APR
PY 2016
VL 17
IS 4
BP 452
EP 463
DI 10.1016/S1470-2045(15)00614-2
PG 12
WC Oncology
SC Oncology
GA DI4VN
UT WOS:000373497600046
PM 26973324
ER
PT J
AU Garcia-Manero, G
Fenaux, P
Al-Kali, A
Baer, MR
Sekeres, MA
Roboz, GJ
Gaidano, G
Scott, BL
Greenberg, P
Platzbecker, U
Steensma, DP
Kambhampati, S
Kreuzer, KA
Godley, LA
Atallah, E
Collins, R
Kantarjian, H
Jabbour, E
Wilhelm, FE
Azarnia, N
Silverman, LR
AF Garcia-Manero, Guillermo
Fenaux, Pierre
Al-Kali, Aref
Baer, Maria R.
Sekeres, Mikkael A.
Roboz, Gail J.
Gaidano, Gianluca
Scott, Bart L.
Greenberg, Peter
Platzbecker, Uwe
Steensma, David P.
Kambhampati, Suman
Kreuzer, Karl-Anton
Godley, Lucy A.
Atallah, Ehab
Collins, Robert, Jr.
Kantarjian, Hagop
Jabbour, Elias
Wilhelm, Francois E.
Azarnia, Nozar
Silverman, Lewis R.
CA ONTIME Study Investigators
TI Rigosertib versus best supportive care for patients with high-risk
myelodysplastic syndromes after failure of hypomethylating drugs
(ONTIME): a randomised, controlled, phase 3 trial
SO LANCET ONCOLOGY
LA English
DT Article
ID MANTLE CELL LYMPHOMA; CLONAL HEMATOPOIESIS; SCORING SYSTEM; CYCLIN D1;
THERAPY; MDS; PROGNOSIS; 01910.NA
AB Background Hypomethylating drugs are the standard treatment for patients with high-risk myelodysplastic syndromes. Survival is poor after failure of these drugs; there is no approved second-line therapy. We compared the overall survival of patients receiving rigosertib and best supportive care with that of patients receiving best supportive care only in patients with myelodysplastic syndromes with excess blasts after failure of azacitidine or decitabine treatment.
Methods We did this randomised controlled trial at 74 hospitals and university medical centres in the USA and Europe. We enrolled patients with diagnosis of refractory anaemia with excess blasts (RAEB)-1, RAEB-2, RAEB-t, or chronic myelomonocytic leukaemia based on local site assessment, and treatment failure with a hypomethylating drug in the past 2 years. Patients were randomly assigned (2: 1) to receive rigosertib 1800 mg per 24 h via 72-h continuous intravenous infusion administered every other week or best supportive care with or without low-dose cytarabine. Randomisation was stratified by pretreatment bone marrow blast percentage. Neither patients nor investigators were masked to treatment assignment. The primary outcome was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT01241500.
Findings From Dec 13, 2010, to Aug 15, 2013, we enrolled 299 patients: 199 assigned to rigosertib, 100 assigned to best supportive care. Median follow-up was 19.5 months (IQR 11.9-27.3). As of Feb 1, 2014, median overall survival was 8.2 months (95% CI 6.1-10.1) in the rigosertib group and 5.9 months (4.1-9.3) in the best supportive care group (hazard ratio 0.87, 95% CI 0.67-1.14; p=0.33). The most common grade 3 or higher adverse events were anaemia (34 [18%] of 184 patients in the rigosertib group vs seven [8%] of 91 patients in the best supportive care group), thrombocytopenia (35 [19%] vs six [7%]), neutropenia (31 [17%] vs seven [8%]), febrile neutropenia (22 [12%] vs ten [11%]), and pneumonia (22 [12%] vs ten [11%]). 41 (22%) of 184 patients in the rigosertib group and 30 (33%) of 91 patients in the best supportive care group died due to adverse events and three deaths were attributed to rigosertib treatment.
Interpretation Rigosertib did not significantly improve overall survival compared with best supportive care. A randomised phase 3 trial of rigosertib (NCT 02562443) is underway in specific subgroups of patients deemed to be at high risk, including patients with very high risk per the Revised International Prognostic Scoring System criteria.
C1 [Garcia-Manero, Guillermo; Kantarjian, Hagop; Jabbour, Elias] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA.
[Fenaux, Pierre] Univ Paris 07, Hop St Louis, Paris, France.
[Al-Kali, Aref] Mayo Clin, Rochester, MN USA.
[Baer, Maria R.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA.
[Sekeres, Mikkael A.] Cleveland Clin, Leukemia Program, Cleveland, OH 44106 USA.
[Roboz, Gail J.] Weill Cornell Med Coll, New York, NY USA.
[Gaidano, Gianluca] Amedeo Avogadro Univ Eastern Piedmont, Dept Translat Med, Div Hematol, Novara, Italy.
[Scott, Bart L.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Greenberg, Peter] Stanford Canc Ctr, Stanford, CA USA.
[Platzbecker, Uwe] Univ Klinikum Dresden, Med Klin & Poliklin 1, Dresden, Germany.
[Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kambhampati, Suman] Univ Kansas, Med Ctr, Westwood, KS USA.
[Kreuzer, Karl-Anton] Univ Klinikum Koln, Klin Innere Med 1, Cologne, Nordhein Westfa, Germany.
[Godley, Lucy A.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
[Atallah, Ehab] Med Coll Wisconsin, Froedtert Mem Lutheran Hosp, Milwaukee, WI 53226 USA.
[Atallah, Ehab] Med Coll Wisconsin, Div Hematol & Oncol, Milwaukee, WI 53226 USA.
[Collins, Robert, Jr.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Wilhelm, Francois E.; Azarnia, Nozar] Onconova Therapeut, Newtown, PA USA.
[Silverman, Lewis R.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
RP Garcia-Manero, G (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, 1515 Holcombe Blvd,Unit 428, Houston, TX 77030 USA.
EM ggarciam@mdanderson.org
FU Onconova Therapeutics; Leukemia & Lymphoma Society
FX Onconova Therapeutics, Leukemia & Lymphoma Society.
NR 33
TC 10
Z9 10
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD APR
PY 2016
VL 17
IS 4
BP 496
EP 508
DI 10.1016/S1470-2045(16)00009-7
PG 13
WC Oncology
SC Oncology
GA DI4VN
UT WOS:000373497600050
PM 26968357
ER
PT J
AU Temel, JS
Abernethy, AP
Currow, DC
Friend, J
Duus, EM
Yan, Y
Fearon, KC
AF Temel, Jennifer S.
Abernethy, Amy P.
Currow, David C.
Friend, John
Duus, Elizabeth M.
Yan, Ying
Fearon, Kenneth C.
TI Anamorelin in patients with non-small-cell lung cancer and cachexia
(ROMANA 1 and ROMANA 2): results from two randomised, double-blind,
phase 3 trials
SO LANCET ONCOLOGY
LA English
DT Article
ID GHRELIN RECEPTOR AGONIST; WEIGHT-LOSS; FUNCTIONAL ASSESSMENT;
MEGESTROL-ACETATE; BODY-COMPOSITION; MUSCLE STRENGTH; CLINICAL-TRIAL;
SYNDROME CACS; OLDER-ADULTS; ANOREXIA
AB Background Patients with advanced cancer frequently experience anorexia and cachexia, which are associated with reduced food intake, altered body composition, and decreased functionality. We assessed anamorelin, a novel ghrelin-receptor agonist, on cachexia in patients with advanced non-small-cell lung cancer and cachexia.
Methods ROMANA 1 and ROMANA 2 were randomised, double-blind, placebo-controlled phase 3 trials done at 93 sites in 19 countries. Patients with inoperable stage III or IV non-small-cell lung cancer and cachexia (defined as >= 5% weight loss within 6 months or body-mass index < 20 kg/m(2)) were randomly assigned 2: 1 to anamorelin 100 mg orally once daily or placebo, with a computer-generated randomisation algorithm stratified by geographical region, cancer treatment status, and weight loss over the previous 6 months. Co-primary efficacy endpoints were the median change in lean body mass and handgrip strength over 12 weeks and were measured in all study participants (intention-to-treat population). Both trials are now completed and are registered with ClinicalTrials.gov, numbers NCT01387269 and NCT01387282.
Findings From July 8, 2011, to Jan 28, 2014, 484 patients were enrolled in ROMANA 1 (323 to anamorelin, 161 to placebo), and from July 14, 2011, to Oct 31, 2013, 495 patients were enrolled in ROMANA 2 (330 to anamorelin, 165 to placebo). Over 12 weeks, lean body mass increased in patients assigned to anamorelin compared with those assigned to placebo in ROMANA 1 (median increase 0.99 kg [95% CI 0.61 to 1.36] vs -0.47 kg [-1.00 to 0.21], p< 0.0001) and ROMANA 2 (0.65 kg [0.38 to 0.91] vs -0.98 kg [-1.49 to -0.41], p< 0.0001). We noted no difference in handgrip strength in ROMANA 1 (-1.10 kg [-1.69 to -0.40] vs -1.58 kg [-2.99 to -1.14], p=0.15) or ROMANA 2 (-1.49 kg [-2.06 to -0.58] vs -0.95 kg [-1.56 to 0.04], p= 0.65). There were no differences in grade 3-4 treatment-related adverse events between study groups; the most common grade 3-4 adverse event was hyperglycaemia, occurring in one (< 1%) of 320 patients given anamorelin in ROMANA 1 and in four (1%) of 330 patients given anamorelin in ROMANA 2.
Interpretation Anamorelin significantly increased lean body mass, but not handgrip, strength in patients with advanced non-small-cell lung cancer. Considering the unmet medical need for safe and effective treatments for cachexia, anamorelin might be a treatment option for patients with cancer anorexia and cachexia.
C1 [Temel, Jennifer S.] Massachusetts Gen Hosp, Ctr Canc, Dept Med, Boston, MA 02114 USA.
[Abernethy, Amy P.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Currow, David C.] Flinders Univ S Australia, Dept Palliat & Support Care, Adelaide, SA 5001, Australia.
[Friend, John; Duus, Elizabeth M.; Yan, Ying] Helsinn Therapeut US Inc, Iselin, NJ USA.
[Fearon, Kenneth C.] Royal Infirm, Dept Surg, Edinburgh, Midlothian, Scotland.
RP Temel, JS (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA.
EM jtemel@partners.org
OI Currow, David/0000-0003-1988-1250
FU Helsinn Therapeutics
FX Helsinn Therapeutics.
NR 33
TC 25
Z9 26
U1 8
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD APR
PY 2016
VL 17
IS 4
BP 519
EP 531
DI 10.1016/S1470-2045(15)00558-6
PG 13
WC Oncology
SC Oncology
GA DI4VN
UT WOS:000373497600052
PM 26906526
ER
PT J
AU Shaikh, F
Murray, MJ
Amatruda, JF
Coleman, N
Nicholson, JC
Hale, JP
Pashankar, F
Stoneham, SJ
Poynter, JN
Olson, TA
Billmire, DF
Stark, D
Rodriguez-Galindo, C
Frazier, AL
AF Shaikh, Furqan
Murray, Matthew J.
Amatruda, James F.
Coleman, Nicholas
Nicholson, James C.
Hale, Juliet P.
Pashankar, Farzana
Stoneham, Sara J.
Poynter, Jenny N.
Olson, Thomas A.
Billmire, Deborah F.
Stark, Daniel
Rodriguez-Galindo, Carlos
Frazier, A. Lindsay
TI Paediatric extracranial germ-cell tumours
SO LANCET ONCOLOGY
LA English
DT Review
ID CHILDRENS ONCOLOGY GROUP; HUMAN CHORIONIC-GONADOTROPIN;
MEDICAL-RESEARCH-COUNCIL; GENOME-WIDE ASSOCIATION; LONG-TERM SURVIVORS;
TESTICULAR-CANCER; STAGE-I; ALPHA-FETOPROTEIN; RANDOMIZED-TRIAL;
UNITED-KINGDOM
AB Management of paediatric extracranial germ-cell tumours carries a unique set of challenges. Germ-cell tumours are a heterogeneous group of neoplasms that present across a wide age range and vary in site, histology, and clinical behaviour. Patients with germ-cell tumours are managed by a diverse array of specialists. Thus, staging, risk stratification, and treatment approaches for germ-cell tumours have evolved disparately along several trajectories. Paediatric germ-cell tumours differ from the adolescent and adult disease in many ways, leading to complexities in applying age-appropriate, evidence-based care. Suboptimal outcomes remain for several groups of patients, including adolescents, and patients with extragonadal tumours, high tumour markers at diagnosis, or platinum-resistant disease. Survivors have significant long-term toxicities. The challenge moving forward will be to translate new insights from molecular studies and collaborative clinical data into improved patient outcomes. Future trials will be characterised by improved risk-stratification systems, biomarkers for response and toxic effects, rational reduction of therapy for low-risk patients and novel approaches for poor-risk patients, and improved international collaboration across paediatric and adult cooperative research groups.
C1 [Shaikh, Furqan] Hosp Sick Children, Div Haematol & Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
[Shaikh, Furqan] Univ Toronto, Toronto, ON M5G 1X8, Canada.
[Murray, Matthew J.; Coleman, Nicholas] Univ Cambridge, Dept Pathol, Tennis Court Rd, Cambridge CB2 1QP, England.
[Murray, Matthew J.; Nicholson, James C.] Addenbrookes Hosp, Dept Paediat Haematol & Oncol, Cambridge, England.
[Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dept Mol Biol, Dallas, TX 75390 USA.
[Amatruda, James F.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Amatruda, James F.] Childrens Hlth, Gill Ctr Canc & Blood Disorders, Dallas, TX USA.
[Coleman, Nicholas] Addenbrookes Hosp, Dept Histopathol, Hills Rd, Cambridge, England.
[Hale, Juliet P.] Royal Victoria Infirm NHS Fdn Trust, Newcastle Upon Tyne, Tyne & Wear, England.
[Pashankar, Farzana] Yale Univ, Sch Med, New Haven, CT USA.
[Stoneham, Sara J.] Univ Coll London Hosp NHS Fdn Trust, London, England.
[Poynter, Jenny N.] Univ Minnesota, Div Pediat Epidemiol & Clin Res, Minneapolis, MN USA.
[Poynter, Jenny N.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Olson, Thomas A.] Emory Univ, Aflac Canc & Blood Disorders Ctr, Atlanta, GA 30322 USA.
[Billmire, Deborah F.] Riley Hosp Children, Indianapolis, IN USA.
[Stark, Daniel] Univ Leeds, Inst Canc & Pathol, Leeds LS2 9JT, W Yorkshire, England.
[Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Boston Childrens Hosp, Boston, MA USA.
[Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Shaikh, F (reprint author), Hosp Sick Children, Div Haematol & Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.; Shaikh, F (reprint author), Univ Toronto, Toronto, ON M5G 1X8, Canada.
EM furqan.shaikh@sickkids.ca
FU Teenage Cancer Trust
FX DS received grants from the Teenage Cancer Trust during the conduct of
the study. ALF has served on the Germ Cell Tumor Advisory Board for
Seattle Genetics and has consulted for Decibel Therapeutics. All other
authors declare no competing interests.
NR 95
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1470-2045
EI 1474-5488
J9 LANCET ONCOL
JI Lancet Oncol.
PD APR
PY 2016
VL 17
IS 4
BP E149
EP E162
PG 14
WC Oncology
SC Oncology
GA DI4VN
UT WOS:000373497600026
PM 27300675
ER
PT J
AU Abuelkasem, E
Mazzeffi, MA
Lu, SY
Planinsic, RM
Sakai, T
Tanaka, KA
AF Abuelkasem, Ezeldeen
Mazzeffi, Michael A.
Lu, Shu Yang
Planinsic, Raymond M.
Sakai, Tetsuro
Tanaka, Kenichi A.
TI Ex vivo evaluation of 4 different viscoelastic assays for detecting
moderate to severe coagulopathy during liver transplantation
SO LIVER TRANSPLANTATION
LA English
DT Article
ID CONVENTIONAL COAGULATION TESTS; RANDOMIZED-CLINICAL-TRIAL;
CARDIAC-SURGERY; RISK-FACTORS; TRANSFUSION; THROMBOELASTOMETRY;
THROMBELASTOGRAPHY; TRAUMA; PLASMA; HYPOFIBRINOGENEMIA
AB Prolonged prothrombin time (PT) and its ratio are routinely used for the assessment of candidates for liver transplantation (LT), but intraoperative coagulation management of transfusion is hindered by its long turnaround time. Abnormal reaction time (R time) on thromboelastography (TEG) or clotting time (CT) of rotational thromboelastometry (ROTEM) are presumably an alternative, but there is a paucity of clinical data on abnormal R time/CT values compared to PT during LT. After receiving institutional review board approval and informed consent, we obtained blood samples from 36 LT patients for international normalized ratio (INR), factor (F) X level, and viscoelastic tests (EXTEM/INTEM and kaolin/rapid TEG) at baseline and 30 minutes after graft reperfusion. Receiver operating characteristic (ROC) curves were calculated for INR>1.5 and viscoelastic R time/CT thresholds to assess the ability to diagnose FX deficiency at the moderate (<50%) or severe (<35%) level. The FX deficiency data were calculated using cutoff values of INR (>1.5) and abnormal R time/CT for TEG and ROTEM. Tissue factor (TF)-activated INR and EXTEM-CT performed well in diagnosing FX below 50%, but rapid TEG with combined TF and kaolin activators failed. Improved performance of INTEM-CT in diagnosing FX below 35% underlies multifactorial deficiency involving both intrinsic and common pathways. In conclusion, the differences among different viscoelastic tests and clinical situations should be carefully considered when they are used to guide transfusion during LT.
C1 [Abuelkasem, Ezeldeen; Planinsic, Raymond M.; Sakai, Tetsuro] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA.
[Mazzeffi, Michael A.; Tanaka, Kenichi A.] Univ Maryland, Dept Anesthesiol, 22 South Greene St,Suite S8D12, Baltimore, MD 21201 USA.
[Lu, Shu Yang] Massachusetts Gen Hosp, Dept Anesthesiol, Boston, MA 02114 USA.
RP Tanaka, KA (reprint author), Univ Maryland, Dept Anesthesiol, 22 South Greene St,Suite S8D12, Baltimore, MD 21201 USA.
EM ktanaka@anes.umm.edu
FU University of Pittsburgh Medical Center; Department of Anesthesiology
(Pittsburgh, PA)
FX Financial support for this work was provided solely by the University of
Pittsburgh Medical Center and the Department of Anesthesiology
(Pittsburgh, PA). TEM Innovations (Munich, Germany) provided 2 ROTEM
devices for this study at the University of Pittsburgh Medical Center
(Pittsburgh, PA).
NR 27
TC 5
Z9 5
U1 3
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6465
EI 1527-6473
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD APR
PY 2016
VL 22
IS 4
BP 468
EP 475
DI 10.1002/lt.24379
PG 8
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA DI5UU
UT WOS:000373566800010
PM 26610182
ER
PT J
AU Adler, JT
Hyder, JA
Markmann, JF
Axelrod, DA
Yeh, H
AF Adler, Joel T.
Hyder, Joseph A.
Markmann, James F.
Axelrod, David A.
Yeh, Heidi
TI Socioeconomic gradients between locally transplanted and exported liver
donors and recipients
SO LIVER TRANSPLANTATION
LA English
DT Letter
ID GEOGRAPHIC DISPARITIES; QUALITATIVE LITERATURE; ORGAN DONATION
C1 [Adler, Joel T.; Markmann, James F.; Axelrod, David A.; Yeh, Heidi] Massachusetts Gen Hosp, Div Transplant Surg, 55 Fruit St,White 516, Boston, MA 02114 USA.
[Hyder, Joseph A.] Mayo Clin, Dept Anesthesiol, Rochester, MN USA.
[Axelrod, David A.] Dartmouth Hitchcock Med Ctr, Sect Transplant Surg, Lebanon, NH 03766 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
NR 10
TC 1
Z9 1
U1 5
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6465
EI 1527-6473
J9 LIVER TRANSPLANT
JI Liver Transplant.
PD APR
PY 2016
VL 22
IS 4
BP 557
EP 558
DI 10.1002/lt.24410
PG 2
WC Gastroenterology & Hepatology; Surgery; Transplantation
SC Gastroenterology & Hepatology; Surgery; Transplantation
GA DI5UU
UT WOS:000373566800020
PM 26845498
ER
PT J
AU Fukumura, D
Incio, J
Shankaraiah, RC
Jain, RK
AF Fukumura, Dai
Incio, Joao
Shankaraiah, Ram C.
Jain, Rakesh K.
TI Obesity and Cancer: An Angiogenic and Inflammatory Link
SO MICROCIRCULATION
LA English
DT Review
DE obesity; immune environment; desmoplasia; metformin; hypoxia; cytokines;
IL-6; IL-1; VEGFR-1
ID ANTIDIABETIC DRUG METFORMIN; ENDOTHELIAL GROWTH-FACTOR; WHITE
ADIPOSE-TISSUE; HUMAN BREAST-CANCER; BODY-MASS-INDEX; SP
TRANSCRIPTION-FACTORS; MAMMARY-TUMOR GROWTH; PANCREATIC-CANCER;
INSULIN-RESISTANCE; ENERGY-BALANCE
AB With the current epidemic of obesity, a large number of patients diagnosed with cancer are overweight or obese. Importantly, this excess body weight is associated with tumor progression and poor prognosis. The mechanisms for this worse outcome, however, remain poorly understood. We review here the epidemiological evidence for the association between obesity and cancer, and discuss potential mechanisms focusing on angiogenesis and inflammation. In particular, we will discuss how the dysfunctional angiogenesis and inflammation occurring in adipose tissue in obesity may promote tumor progression, resistance to chemotherapy, and targeted therapies such as anti-angiogenic and immune therapies. Better understanding of how obesity fuels tumor progression and therapy resistance is essential to improve the current standard of care and the clinical outcome of cancer patients. To this end, we will discuss how an anti-diabetic drug such as metformin can overcome these adverse effects of obesity on the progression and treatment resistance of tumors.
C1 [Fukumura, Dai; Incio, Joao; Shankaraiah, Ram C.; Jain, Rakesh K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Labs, Boston, MA USA.
[Incio, Joao] Univ Porto, Inst Innovat & Res Heath, Metab Nutr & Endocrinol Grp, Dept Biochem,Fac Med,I3S, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Incio, Joao] Hosp Sao Joao, Dept Internal Med, Oporto, Portugal.
[Shankaraiah, Ram C.] Univ Ferrara, Dept Morphol Surg & Expt Med, I-44100 Ferrara, Italy.
[Shankaraiah, Ram C.] Univ Ferrara, Lab Technol Adv Therapies LTTA, I-44100 Ferrara, Italy.
RP Fukumura, D (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 7, Boston, MA 02114 USA.
EM dai@steele.mgh.harvard.edu
FU Foundation for Science and Technology (Portugal, POPH/FSE funding
program); National Institutes of Health [CA080124, CA085140, CA096915,
CA115767, CA126642, CA197743]; US Department of Defense
[W81XWH-10-1-0016]; Lustgarten Foundation
FX The authors' work was supported by a fellowship from the Foundation for
Science and Technology (http://www.fct.pt/; Portugal, POPH/FSE funding
program) (JI) and funds from the National Institutes of Health
(http://nih.gov/; CA080124, CA085140, CA096915, CA115767, CA126642,
CA197743), the US Department of Defense (W81XWH-10-1-0016), and the
Lustgarten Foundation.
NR 181
TC 6
Z9 6
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1073-9688
EI 1549-8719
J9 MICROCIRCULATION
JI Microcirculation
PD APR
PY 2016
VL 23
IS 3
BP 191
EP 206
DI 10.1111/micc.12270
PG 16
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DI6NY
UT WOS:000373617500003
PM 26808917
ER
PT J
AU Katz, DA
Stewart, K
Paez, M
Holman, J
Adams, SL
Vander Weg, MW
Battaglia, CT
Joseph, AM
Titler, MG
Ono, S
AF Katz, David A.
Stewart, Kenda
Paez, Monica
Holman, John
Adams, Susan L.
Vander Weg, Mark W.
Battaglia, Catherine T.
Joseph, Anne M.
Titler, Marita G.
Ono, Sarah
TI "Let Me Get You a Nicotine Patch": Nurses' Perceptions of Implementing
Smoking Cessation Guidelines for Hospitalized Veterans
SO MILITARY MEDICINE
LA English
DT Article
ID CONTROLLED-TRIAL; STANDARDIZED PATIENTS; CARE; SERVICE; INTERVENTIONS;
PREVENTION; PROGRAM
AB Many hospitalized smokers do not receive guideline-recommended tobacco treatment, but little is known about the perceptions of inpatient nurses with regard to tobacco treatment. We used a sequential explanatory mixed methods design to help explain the findings of an academic detailing intervention trial on the inpatient medicine units of four Veterans Affairs (VA) hospitals. We surveyed 164 nurses and conducted semistructured interviews in a purposeful sample of 33 nurses with different attitudes toward cessation counseling. Content analysis was used to inductively characterize the issues raised by participants. Emerging themes were categorized using the knowledge-attitudes-behavior framework of guideline adherence. Knowledge-related and attitudinal barriers included perceived lack of skills in cessation counseling and skepticism about the effectiveness of cessation guidelines in hospitalized veterans. Nurses also reported multiple behavioral and organizational barriers to guideline adherence: resistance from patients, insufficient time and resources, the presence of smoking areas on VA premises, and lack of coordination with primary care. VA hospitals should train inpatient staff how to negotiate behavior change, integrate cessation counseling into nurses' workflow, develop alternative referral mechanisms for post-discharge cessation counseling, and adopt hospital policies to promote inpatient abstinence.
C1 [Katz, David A.; Stewart, Kenda; Paez, Monica; Holman, John; Adams, Susan L.; Vander Weg, Mark W.; Ono, Sarah] Iowa City VA Hlth Care Syst, Comprehens Access & Delivery Res & Evaluat CADRE, Iowa City, IA USA.
[Katz, David A.; Vander Weg, Mark W.] Univ Iowa, Dept Med, Iowa City, IA 52242 USA.
[Katz, David A.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Vander Weg, Mark W.] Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA.
[Battaglia, Catherine T.] VA Eastern Colorado Hlth Care Syst, Dept Med, Denver, CO USA.
[Battaglia, Catherine T.] Denver Seattle Ctr Vet Centr Value Based Res DiSC, Denver, CO USA.
Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA.
[Titler, Marita G.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA.
[Ono, Sarah] Portland VA Med Ctr, Ctr Improve Vet Involvement Care, Portland, OR USA.
RP Katz, DA (reprint author), Iowa City VA Hlth Care Syst, Comprehens Access & Delivery Res & Evaluat CADRE, Iowa City, IA USA.
FU Veterans Affairs Health Services Research and Development [IIR 07-113]
FX The authors acknowledge Jonathan Thomas for assistance with
transcription of in-depth interviews, George Bailey, MS and Ray Opiola
for assisting with database design and data management, Bonnie
Bootsmiller, PhD and Sue Kieffer for administrative support, and
Jennifer Reed for assistance with manuscript preparation. This work was
funded by the Veterans Affairs Health Services Research and Development
(IIR 07-113).
NR 41
TC 1
Z9 1
U1 4
U2 6
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 APR
PY 2016
VL 181
IS 4
BP 373
EP 382
DI 10.7205/MILMED-D-15-00101
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA DI3NO
UT WOS:000373405600015
PM 27046185
ER
PT J
AU van der Watt, PJ
Chi, A
Stelma, T
Stowell, C
Strydom, E
Carden, S
Angus, L
Hadley, K
Lang, D
Wei, W
Birrer, MJ
Trent, JO
Leaner, VD
AF van der Watt, Pauline J.
Chi, Alicia
Stelma, Tamara
Stowell, Catherine
Strydom, Erin
Carden, Sarah
Angus, Liselotte
Hadley, Kate
Lang, Dirk
Wei, Wei
Birrer, Michael J.
Trent, John O.
Leaner, Virna D.
TI Targeting the Nuclear Import Receptor Kpn beta 1 as an Anticancer
Therapeutic
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID SMALL-MOLECULE INHIBITOR; TRANSCRIPTION FACTOR; CERVICAL-CANCER;
CELL-LINES; RAN GTPASE; T-CELLS; BETA; TRANSPORT; EXPORT; LOCALIZATION
AB Karyopherin beta 1 (Kpn beta 1) is a nuclear transport receptor that imports cargoes into the nucleus. Recently, elevated Kpnb1 expression was found in certain cancers and Kpnb1 silencing with siRNA was shown to induce cancer cell death. This study aimed to identify novel small molecule inhibitors of Kpnb1, and determine their anticancer activity. An in silico screen identified molecules that potentially bind Kpnb1 and Inhibitor of Nuclear Import-43, INI-43 (3-(1H-benzimidazol-2-yl)-1-(3-dimethylaminopropyl) pyrrolo[5,4-b] quinoxalin-2-amine) was investigated further as it interfered with the nuclear localization of Kpn beta 1 and known Kpn beta 1 cargoes NFAT, NFkB, AP-1, and NFY and inhibited the proliferation of cancer cells of different tissue origins. Minimum effect on the proliferation of noncancer cells was observed at the concentration of INI-43 that showed a significant cytotoxic effect on various cervical and esophageal cancer cell lines. A rescue experiment confirmed that INI-43 exerted its cell killing effects, in part, by targeting Kpn beta 1. INI-43 treatment elicited a G2-M cell-cycle arrest in cancer cells and induced the intrinsic apoptotic pathway. Intraperitoneal administration of INI-43 significantly inhibited the growth of subcutaneously xenografted esophageal and cervical tumor cells. We propose that Kpn beta 1 inhibitors could have therapeutic potential for the treatment of cancer. (C) 2016 AACR.
C1 [van der Watt, Pauline J.; Chi, Alicia; Stelma, Tamara; Stowell, Catherine; Strydom, Erin; Carden, Sarah; Angus, Liselotte; Hadley, Kate; Leaner, Virna D.] Univ Cape Town, Inst Infect Dis & Mol Med, SAMRC UCT Gynaecol Canc Res Ctr, Div Med Biochem,Dept Integrat Biomed Sci,Fac Hlth, ZA-7925 Cape Town, South Africa.
[Lang, Dirk] Univ Cape Town, Confocal & Light Microscope Imaging Facil, Dept Human Biol, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
[Wei, Wei; Birrer, Michael J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc Res,Gillette Ctr Gynecol Oncol, Boston, MA USA.
[Trent, John O.] Univ Louisville, Dept Med, JG Brown Canc Ctr, Louisville, KY 40292 USA.
RP Leaner, VD (reprint author), Univ Cape Town, Div Med Biochem, Fac Hlth Sci, ZA-7925 Cape Town, South Africa.
EM Virna.Leaner@uct.ac.za
RI Lang, Dirk/I-2554-2015
OI Lang, Dirk/0000-0003-3901-2079
FU South African Medical Research Council; National Research Foundation;
Cancer Association of South Africa (CANSA); University of Cape Town
FX This work was supported by grants obtained by Virna D. Leaner from the
South African Medical Research Council, the National Research
Foundation, the Cancer Association of South Africa (CANSA), and the
University of Cape Town.
NR 50
TC 1
Z9 1
U1 5
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD APR
PY 2016
VL 15
IS 4
BP 560
EP 573
DI 10.1158/1535-7163.MCT-15-0052
PG 14
WC Oncology
SC Oncology
GA DI6GD
UT WOS:000373596300003
PM 26832790
ER
PT J
AU Ji, Z
Song, RS
Huang, HL
Regev, A
Struhl, K
AF Ji, Zhe
Song, Ruisheng
Huang, Hailiang
Regev, Aviv
Struhl, Kevin
TI Transcriptome-scale RNase-footprinting of RNA-protein complexes
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID LONG NONCODING RNAS; IN-VIVO; NUCLEOTIDE RESOLUTION; BINDING PROTEIN;
ELEMENTS; SITES; TRANSLATION; SPLICEOSOME; ANNOTATION; CLIP
AB Ribosome profiling is widely used to study translation in vivo, but not all sequence reads correspond to ribosome-protected RNA. Here we describe Rfoot, a computational pipeline that analyzes ribosomal profiling data and identifies native, nonribosomal RNA-protein complexes. We use Rfoot to precisely map RNase-protected regions within small nucleolar RNAs, spliceosomal RNAs, microRNAs, tRNAs, long noncoding (lnc) RNAs and 3' untranslated regions of mRNAs in human cells. We show that RNAs of the same class can show differential complex association. Although only a subset of lncRNAs show RNase footprints, many of these have multiple footprints, and the protected regions are evolutionarily conserved, suggestive of biological functions.
C1 [Ji, Zhe; Song, Ruisheng; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.
[Ji, Zhe; Huang, Hailiang; Regev, Aviv] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Huang, Hailiang] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Regev, Aviv] MIT, Dept Biol, Cambridge, MA USA.
[Regev, Aviv] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Regev, A (reprint author), Broad Inst MIT & Harvard, Cambridge, MA USA.; Regev, A (reprint author), MIT, Dept Biol, Cambridge, MA USA.; Regev, A (reprint author), Howard Hughes Med Inst, Chevy Chase, MD USA.
EM aregev@broadinstitute.org; kevin@hms.harvard.edu
FU National Institutes of Health [CA 107486]
FX This work was supported by grants to K.S. from the National Institutes
of Health (CA 107486). A.R. is a Howard Hughes Investigator.
NR 25
TC 7
Z9 7
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD APR
PY 2016
VL 34
IS 4
BP 410
EP +
DI 10.1038/nbt.3441
PG 5
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DI6NL
UT WOS:000373616100021
PM 26900662
ER
PT J
AU Yu, CN
Mannan, AM
Yvone, GM
Ross, KN
Zhang, YL
Marton, MA
Taylor, BR
Crenshaw, A
Gould, JZ
Tamayo, P
Weir, BA
Tsherniak, A
Wong, B
Garraway, LA
Shamji, AF
Palmer, MA
Foley, MA
Winckler, W
Schreiber, SL
Kung, AL
Golub, TR
AF Yu, Channing
Mannan, Aristotle M.
Yvone, Griselda Metta
Ross, Kenneth N.
Zhang, Yan-Ling
Marton, Melissa A.
Taylor, Bradley R.
Crenshaw, Andrew
Gould, Joshua Z.
Tamayo, Pablo
Weir, Barbara A.
Tsherniak, Aviad
Wong, Bang
Garraway, Levi A.
Shamji, Alykhan F.
Palmer, Michelle A.
Foley, Michael A.
Winckler, Wendy
Schreiber, Stuart L.
Kung, Andrew L.
Golub, Todd R.
TI High-throughput identification of genotype-specific cancer
vulnerabilities in mixtures of barcoded tumor cell lines
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID KINASE INHIBITOR SELECTIVITY; DRUG-SENSITIVITY; RESISTANCE; RESOURCE;
EFFICACY; GENE
AB Hundreds of genetically characterized cell lines are available for the discovery of genotype-specific cancer vulnerabilities. However, screening large numbers of compounds against large numbers of cell lines is currently impractical, and such experiments are often difficult to control(1-4). Here we report a method called PRISM that allows pooled screening of mixtures of cancer cell lines by labeling each cell line with 24-nucleotide barcodes. PRISM revealed the expected patterns of cell killing seen in conventional (unpooled) assays. In a screen of 102 cell lines across 8,400 compounds, PRISM led to the identification of BRD-7880 as a potent and highly specific inhibitor of aurora kinases B and C. Cell line pools also efficiently formed tumors as xenografts, and PRISM recapitulated the expected pattern of erlotinib sensitivity in vivo.
C1 [Yu, Channing; Mannan, Aristotle M.; Yvone, Griselda Metta; Ross, Kenneth N.; Zhang, Yan-Ling; Marton, Melissa A.; Taylor, Bradley R.; Crenshaw, Andrew; Gould, Joshua Z.; Tamayo, Pablo; Weir, Barbara A.; Tsherniak, Aviad; Wong, Bang; Garraway, Levi A.; Shamji, Alykhan F.; Palmer, Michelle A.; Foley, Michael A.; Winckler, Wendy; Schreiber, Stuart L.; Golub, Todd R.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Yu, Channing; Garraway, Levi A.; Kung, Andrew L.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Yu, Channing; Garraway, Levi A.; Kung, Andrew L.; Golub, Todd R.] Harvard Univ, Sch Med, Boston, MA USA.
[Schreiber, Stuart L.] Harvard Univ, Cambridge, MA 02138 USA.
[Schreiber, Stuart L.; Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Yvone, Griselda Metta] Univ Calif Los Angeles, Los Angeles, CA USA.
[Ross, Kenneth N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Palmer, Michelle A.] ImmunoGen, Waltham, MA USA.
[Foley, Michael A.] Triinst Therapeut Discovery Inst, New York, NY USA.
[Kung, Andrew L.] Columbia Univ, Med Ctr, New York, NY USA.
RP Golub, TR (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.; Golub, TR (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.; Golub, TR (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Golub, TR (reprint author), Howard Hughes Med Inst, Chevy Chase, MD USA.
EM golub@broadinstitute.org
OI Kung, Andrew/0000-0002-9091-488X
FU US National Institutes of Health (NIH) Genomics Based Drug Discovery
consortium grants [RL1-CA133834, RL1-GM084437, UL1DE019585]; US National
Cancer Institute Integrative Cancer Biology Program grant [U54CA112962];
Howard Hughes Medical Institute; Claudia Adams Barr Program in Cancer
Research Innovative Basic Science Research Program Grant; American
Society of Clinical Oncology Conquer Cancer Foundation Young
Investigator Award; Prostate Cancer Foundation; NIH grant [RL1-HG004671]
FX We thank S. Kim, G. Bonamy, J. (J.) Che, J. Thibault, T. Huynh, I.
Engels and A. Shipway at Novartis for sharing data before publication;
A. Christie and T. Davis for technical assistance in animal studies; C.
Hartland, S. Donovan, E. Rubin and E. Winchester for technical
assistance in compound assays; J. Bittker, J. McGrath and G. Wendel for
assistance in compound management; S. Le Quement and J. Duvall for
assistance in compound synthesis; J. Gale for technical assistance in
enzyme kinetic assays; S. Howell for assistance in curation of
computational data sets; A. Koehler, S. Dandapani, B. Munoz, C. Scherer,
D. Gray, D. Bachovchin, S. Santaguida and J. Elkins for expert
scientific guidance; J. Barretina, N. Stransky, S. Nijman, B. Julian, W.
Read-Button, J. Davis and D. Peck for technical advice; and members of
the Golub laboratory for critical review of the manuscript. This work
was supported in part by the US National Institutes of Health (NIH)
Genomics Based Drug Discovery consortium grants RL1-CA133834,
RL1-GM084437 and UL1DE019585 (administratively linked to NIH grant
RL1-HG004671), US National Cancer Institute Integrative Cancer Biology
Program grant U54CA112962, the Howard Hughes Medical Institute, the
Claudia Adams Barr Program in Cancer Research Innovative Basic Science
Research Program Grant, the American Society of Clinical Oncology
Conquer Cancer Foundation Young Investigator Award and the Prostate
Cancer Foundation.
NR 25
TC 3
Z9 3
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD APR
PY 2016
VL 34
IS 4
BP 419
EP +
DI 10.1038/nbt.3460
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DI6NL
UT WOS:000373616100023
PM 26928769
ER
PT J
AU Freyermuth, F
Rau, F
Kokunai, Y
Linke, T
Sellier, C
Nakamori, M
Kino, Y
Arandel, L
Jollet, A
Thibault, C
Philipps, M
Vicaire, S
Jost, B
Udd, B
Day, JW
Duboc, D
Wahbi, K
Matsumura, T
Fujimura, H
Mochizuki, H
Deryckere, F
Kimura, T
Nukina, N
Ishiura, S
Lacroix, V
Campan-Fournier, A
Navratil, V
Chautard, E
Auboeuf, D
Horie, M
Imoto, K
Lee, KY
Swanson, MS
de Munain, AL
Inada, S
Itoh, H
Nakazawa, K
Ashihara, T
Wang, E
Zimmer, T
Furling, D
Takahashi, MP
Charlet-Berguerand, N
AF Freyermuth, Fernande
Rau, Frederique
Kokunai, Yosuke
Linke, Thomas
Sellier, Chantal
Nakamori, Masayuki
Kino, Yoshihiro
Arandel, Ludovic
Jollet, Arnaud
Thibault, Christelle
Philipps, Muriel
Vicaire, Serge
Jost, Bernard
Udd, Bjarne
Day, John W.
Duboc, Denis
Wahbi, Karim
Matsumura, Tsuyoshi
Fujimura, Harutoshi
Mochizuki, Hideki
Deryckere, Francois
Kimura, Takashi
Nukina, Nobuyuki
Ishiura, Shoichi
Lacroix, Vincent
Campan-Fournier, Amandine
Navratil, Vincent
Chautard, Emilie
Auboeuf, Didier
Horie, Minoru
Imoto, Keiji
Lee, Kuang-Yung
Swanson, Maurice S.
Lopez de Munain, Adolfo
Inada, Shin
Itoh, Hideki
Nakazawa, Kazuo
Ashihara, Takashi
Wang, Eric
Zimmer, Thomas
Furling, Denis
Takahashi, Masanori P.
Charlet-Berguerand, Nicolas
TI Splicing misregulation of SCN5A contributes to cardiac-conduction delay
and heart arrhythmia in myotonic dystrophy
SO NATURE COMMUNICATIONS
LA English
DT Article
ID PRE-MESSENGER-RNA; BRUGADA-SYNDROME; MUSCULAR-DYSTROPHY; MUSCLEBLIND
PROTEINS; STRUCTURAL INSIGHTS; CHLORIDE CHANNEL; SKELETAL-MUSCLE; MOUSE
MODEL; CTG REPEAT; TYPE-1
AB Myotonic dystrophy (DM) is caused by the expression of mutant RNAs containing expanded CUG repeats that sequester muscleblind-like (MBNL) proteins, leading to alternative splicing changes. Cardiac alterations, characterized by conduction delays and arrhythmia, are the second most common cause of death in DM. Using RNA sequencing, here we identify novel splicing alterations in DM heart samples, including a switch from adult exon 6B towards fetal exon 6A in the cardiac sodium channel, SCN5A. We find that MBNL1 regulates alternative splicing of SCN5A mRNA and that the splicing variant of SCN5A produced in DM presents a reduced excitability compared with the control adult isoform. Importantly, reproducing splicing alteration of Scn5a in mice is sufficient to promote heart arrhythmia and cardiac-conduction delay, two predominant features of myotonic dystrophy. In conclusion, misregulation of the alternative splicing of SCN5A may contribute to a subset of the cardiac dysfunctions observed in myotonic dystrophy.
C1 [Freyermuth, Fernande; Sellier, Chantal; Thibault, Christelle; Philipps, Muriel; Vicaire, Serge; Jost, Bernard; Charlet-Berguerand, Nicolas] Univ Strasbourg, INSERM U964, CNRS UMR7104, Dept Translat Med & Neurogenet,IGBMC, F-67400 Illkirch Graffenstaden, France.
[Rau, Frederique; Arandel, Ludovic; Jollet, Arnaud; Furling, Denis] Univ Paris 06, Sorbonne Univ, INSERM, CNRS,Ctr Rech Myol,UMRS974,FRE3617,Inst Myol,GH P, F-75013 Paris, France.
[Kokunai, Yosuke; Nakamori, Masayuki; Mochizuki, Hideki; Takahashi, Masanori P.] Osaka Univ, Grad Sch Med, Dept Neurol, Osaka 5650871, Japan.
[Linke, Thomas; Zimmer, Thomas] Friedrich Schiller Univ Hosp, Dept Physiol, D-07743 Jena, Germany.
[Kino, Yoshihiro] Meiji Pharmaceut Univ, Dept Bioinformat & Mol Neuropathol, Kiyose 2058588, Japan.
[Udd, Bjarne] Tampere Univ, Neuromuscular Res Ctr, Tampere 33520, Finland.
[Udd, Bjarne] Tampere Univ Hosp, Tampere 33520, Finland.
[Udd, Bjarne] Univ Helsinki, Dept Med Genet, Folkhalsan Inst Genet, Helsinki 00250, Finland.
[Udd, Bjarne] Vaasa Cent Hosp, Dept Neurol, Vaasa 65130, Finland.
[Day, John W.] Stanford Univ, Dept Neurol, Stanford, CA 94304 USA.
[Duboc, Denis; Wahbi, Karim] Univ Paris 05, Hop Cochin, AP HP, Serv Cardiol, F-75014 Paris, France.
[Matsumura, Tsuyoshi; Fujimura, Harutoshi] Toneyama Natl Hosp, Dept Neurol, Toyonaka, Osaka 5608552, Japan.
[Deryckere, Francois] Ecole Super Biotechnol Strasbourg, CNRS, UMR7175, F-67400 Illkirch Graffenstaden, France.
[Kimura, Takashi] Hyogo Coll Med, Div Neurol, Nishinomiya, Hyogo 6638501, Japan.
[Nukina, Nobuyuki] Doshisha Univ, Grad Sch Brain Sci, Lab Struct Neuropathol, Kyoto 6100394, Japan.
[Ishiura, Shoichi] Univ Tokyo, Grad Sch Arts & Sci, Tokyo 1538902, Japan.
[Lacroix, Vincent] Univ Lyon 1, CNRS, LBBE UMR5558, F-69622 Villeurbanne, France.
[Campan-Fournier, Amandine] Hosp Civils Lyon, Lab Cytogenet Constitut, F-69500 Bron, France.
[Navratil, Vincent] Univ Lyon 1, Pole Rhone Alpes Bioinformat, Batiment Gregor Mendel, F-69100 Villeurbanne, France.
[Chautard, Emilie; Auboeuf, Didier] Ctr Rech Cancerol Lyon, F-69373 Lyon, France.
[Horie, Minoru; Itoh, Hideki; Ashihara, Takashi] Shiga Med Univ, Dept Cardiovasc & Resp Med, Otsu, Shiga 5202192, Japan.
[Imoto, Keiji] Natl Inst Nat Sci, Natl Inst Physiol Sci, Dept Informat Physiol, 38 Nishigonaka, Okazaki, Aichi 4448585, Japan.
[Lee, Kuang-Yung] Chang Gung Mem Hosp, Dept Neurol, Keelung 20401, Taiwan.
[Swanson, Maurice S.; Wang, Eric] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Ctr NeuroGenet, Gainesville, FL 32610 USA.
[Swanson, Maurice S.; Wang, Eric] Univ Florida, Coll Med, Genet Inst, Gainesville, FL 32610 USA.
[Lopez de Munain, Adolfo] Hosp Univ DONOSTIA, Inst Biodonostia CIBERNED, Neurosci Area, Dept Neurol, San Sebastian 20014, Spain.
[Lopez de Munain, Adolfo] Univ Basque Country UPV EHU, San Sebastian 20014, Spain.
[Inada, Shin; Nakazawa, Kazuo] Natl Cerebral & Cardiovasc Ctr, Res Inst, Lab Biomed Sci & Informat Management, Osaka 5658565, Japan.
[Freyermuth, Fernande] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA.
RP Charlet-Berguerand, N (reprint author), Univ Strasbourg, INSERM U964, CNRS UMR7104, Dept Translat Med & Neurogenet,IGBMC, F-67400 Illkirch Graffenstaden, France.; Furling, D (reprint author), Univ Paris 06, Sorbonne Univ, INSERM, CNRS,Ctr Rech Myol,UMRS974,FRE3617,Inst Myol,GH P, F-75013 Paris, France.; Takahashi, MP (reprint author), Osaka Univ, Grad Sch Med, Dept Neurol, Osaka 5650871, Japan.
EM denis.furling@upmc.fr; mtakahas@neurol.med.osaka-u.ac.jp;
ncharlet@igbmc.fr
RI Charlet-Berguerand, Nicolas/I-6727-2016; Auboeuf, Didier/M-4610-2014;
navratil, vincent/C-4193-2008
OI Charlet-Berguerand, Nicolas/0000-0002-4423-4920;
FU UPMC/INSERM/CNRS/AIM; AFM [18833]; ERC-StG [310659]; MEXT [25136705];
JSPS [25713034, 15K09314]; Intramural Research Grant of NCNP [26-8];
AMED; [ANR-10-LABX-0030-INRT]; [ANR-10-IDEX-0002-02];
[ANR-12-RARE-0005-01]
FX We thank Tom Cooper (Baylor College of Medicine, Houston, USA) for the
gift of the DT960 and tgCUGBP1 plasmids, Christiane Branlant (CNRS,
Nancy, France) for the gift of the pGEX-MBNL1 Delta101
vector, the Research Resource Network Japan and the Myobank of the
Institute of Myology for providing human heart tissue samples, Feriel
Azibani (UMRS974, Paris, France) and all members of the French DM
Network for fruitful discussion. We also deeply thank the IGBMC
Microarray and Sequencing platform, the informatics resources of the
PRABI, Nathalie Mougenot from the UPMC PECMV-CEF facility, the
Federation de Recherche en Imagerie Multimodalite
(www.bichat.inserm.fr), the AAV platform of the Centre de Recherche en
Myologie, the Penn Vector Core, Gene Therapy Program, University of
Pennsylvania (Philadelphia) for providing the pAAV2/9 plasmid
(p5E18-VD29), members of the France Genomique program for RNA sequencing
and all IGBMC common facilities for assistance. This work was supported
by UPMC/INSERM/CNRS/AIM (D.F.); ANR-12-RARE-0005-01 E-RARE 'HEART DM'
(N.C.-B. and D.F.); AFM #18833, ERC-2012-StG #310659 'RNA DISEASES' and
ANR-10-LABX-0030-INRT and ANR-10-IDEX-0002-02 (N.C.-B.); Research Grants
for Practical Research Project for Rare / Intractable Diseases and for
Comprehensive Research on Persons with Disabilities from AMED (H.M.,
M.P.T.); Grants-in-Aids from MEXT (25136705) (H.I.); Grants-in-Aids from
JSPS (25713034 (M.N.) and 15K09314 (M.P.T.)); and Intramural Research
Grant of NCNP 26-8 (M.P.T.).
NR 73
TC 7
Z9 7
U1 3
U2 11
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 APR
PY 2016
VL 7
AR 11067
DI 10.1038/ncomms11067
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI9JO
UT WOS:000373819100001
PM 27063795
ER
PT J
AU Gusev, A
Shi, H
Kichaev, G
Pomerantz, M
Li, F
Long, HW
Ingles, SA
Kittles, RA
Strom, SS
Rybicki, BA
Nemesure, B
Isaacs, WB
Zheng, W
Pettaway, CA
Yeboah, ED
Tettey, Y
Biritwum, RB
Adjei, AA
Tay, E
Truelove, A
Niwa, S
Chokkalingam, AP
John, EM
Murphy, AB
Signorello, LB
Carpten, J
Leske, MC
Wu, SY
Hennis, AJM
Neslund-Dudas, C
Hsing, AW
Chu, L
Goodman, PJ
Klein, EA
Witte, JS
Casey, G
Kaggwa, S
Cook, MB
Stram, DO
Blot, WJ
Eeles, RA
Easton, D
Kote-Jarai, Z
Al Olama, AA
Benlloch, S
Muir, K
Giles, GG
Southey, MC
Fitzgerald, LM
Gronberg, H
Wiklund, F
Aly, M
Henderson, BE
Schleutker, J
Wahlfors, T
Tammela, TLJ
Nordestgaard, BG
Key, TJ
Travis, RC
Neal, DE
Donovan, JL
Hamdy, FC
Pharoah, P
Pashayan, N
Khaw, KT
Stanford, JL
Thibodeau, SN
McDonnell, SK
Schaid, DJ
Maier, C
Vogel, W
Luedeke, M
Herkommer, K
Kibel, AS
Cybulski, C
Wokolorczyk, D
Kluzniak, W
Cannon-Albright, L
Teerlink, C
Brenner, H
Dieffenbach, AK
Arndt, V
Park, JY
Sellers, TA
Lin, HY
Slavov, C
Kaneva, R
Mitev, V
Batra, J
Spurdle, A
Clements, JA
Teixeira, MR
Pandha, H
Michael, A
Paulo, P
Maia, S
Kierzek, A
Conti, DV
Albanes, D
Berg, C
Berndt, SI
Campa, D
Crawford, ED
Diver, WR
Gapstur, SM
Gaziano, JM
Giovannucci, E
Hoover, R
Hunter, DJ
Johansson, M
Kraft, P
Le Marchand, L
Lindstrom, S
Navarro, C
Overvad, K
Riboli, E
Siddiq, A
Stevens, VL
Trichopoulos, D
Vineis, P
Yeager, M
Trynka, G
Raychaudhuri, S
Schumacher, FR
Price, AL
Freedman, ML
Haiman, CA
Pasaniuc, B
Cook, M
Guy, M
Govindasami, K
Leongamornlert, D
Sawyer, EJ
Wilkinson, R
Saunders, EJ
Tymrakiewicz, M
Dadaev, T
Morgan, A
Fisher, C
Hazel, S
Livni, N
Lophatananon, A
Pedersen, J
Hopper, JL
Adolfson, J
Stattin, P
Johansson, JE
Cavalli-Bjoerkman, C
Karlsson, A
Broms, M
Auvinen, A
Kujala, P
Maeaettaenen, L
Murtola, T
Taari, K
Weischer, M
Nielsen, SF
Klarskov, P
Roder, A
Iversen, P
Wallinder, H
Gustafsson, S
Cox, A
Brown, P
George, A
Marsden, G
Lane, A
Davis, M
Zheng, W
Signorello, LB
Blot, WJ
Tillmans, L
Riska, S
Wang, L
Rinckleb, A
Lubiski, J
Stegmaier, C
Pow-Sang, J
Park, H
Radlein, S
Rincon, M
Haley, J
Zachariah, B
Kachakova, D
Popov, E
Mitkova, A
Vlahova, A
Dikov, T
Christova, S
Heathcote, P
Wood, G
Malone, G
Saunders, P
Eckert, A
Yeadon, T
Kerr, K
Collins, A
Turner, M
Srinivasan, S
Kedda, MA
Alexander, K
Omara, T
Wu, HH
Henrique, R
Pinto, P
Santos, J
Barros-Silva, J
AF Gusev, Alexander
Shi, Huwenbo
Kichaev, Gleb
Pomerantz, Mark
Li, Fugen
Long, Henry W.
Ingles, Sue A.
Kittles, Rick A.
Strom, Sara S.
Rybicki, Benjamin A.
Nemesure, Barbara
Isaacs, William B.
Zheng, Wei
Pettaway, Curtis A.
Yeboah, Edward D.
Tettey, Yao
Biritwum, Richard B.
Adjei, Andrew A.
Tay, Evelyn
Truelove, Ann
Niwa, Shelley
Chokkalingam, Anand P.
John, Esther M.
Murphy, Adam B.
Signorello, Lisa B.
Carpten, John
Leske, M. Cristina
Wu, Suh-Yuh
Hennis, Anslem J. M.
Neslund-Dudas, Christine
Hsing, Ann W.
Chu, Lisa
Goodman, Phyllis J.
Klein, Eric A.
Witte, John S.
Casey, Graham
Kaggwa, Sam
Cook, Michael B.
Stram, Daniel O.
Blot, William J.
Eeles, Rosalind A.
Easton, Douglas
Kote-Jarai, ZSofia
Al Olama, Ali Amin
Benlloch, Sara
Muir, Kenneth
Giles, Graham G.
Southey, Melissa C.
Fitzgerald, Liesel M.
Gronberg, Henrik
Wiklund, Fredrik
Aly, Markus
Henderson, Brian E.
Schleutker, Johanna
Wahlfors, Tiina
Tammela, Teuvo L. J.
Nordestgaard, Borge G.
Key, Tim J.
Travis, Ruth C.
Neal, David E.
Donovan, Jenny L.
Hamdy, Freddie C.
Pharoah, Paul
Pashayan, Nora
Khaw, Kay-Tee
Stanford, Janet L.
Thibodeau, Stephen N.
McDonnell, Shannon K.
Schaid, Daniel J.
Maier, Christiane
Vogel, Walther
Luedeke, Manuel
Herkommer, Kathleen
Kibel, Adam S.
Cybulski, Cezary
Wokolorczyk, Dominika
Kluzniak, Wojciech
Cannon-Albright, Lisa
Teerlink, Craig
Brenner, Hermann
Dieffenbach, Aida K.
Arndt, Volker
Park, Jong Y.
Sellers, Thomas A.
Lin, Hui-Yi
Slavov, Chavdar
Kaneva, Radka
Mitev, Vanio
Batra, Jyotsna
Spurdle, Amanda
Clements, Judith A.
Teixeira, Manuel R.
Pandha, Hardev
Michael, Agnieszka
Paulo, Paula
Maia, Sofia
Kierzek, Andrzej
Conti, David V.
Albanes, Demetrius
Berg, Christine
Berndt, Sonja I.
Campa, Daniele
Crawford, E. David
Diver, W. Ryan
Gapstur, Susan M.
Gaziano, J. Michael
Giovannucci, Edward
Hoover, Robert
Hunter, David J.
Johansson, Mattias
Kraft, Peter
Le Marchand, Loic
Lindstrom, Sara
Navarro, Carmen
Overvad, Kim
Riboli, Elio
Siddiq, Afshan
Stevens, Victoria L.
Trichopoulos, Dimitrios
Vineis, Paolo
Yeager, Meredith
Trynka, Gosia
Raychaudhuri, Soumya
Schumacher, Frederick R.
Price, Alkes L.
Freedman, Matthew L.
Haiman, Christopher A.
Pasaniuc, Bogdan
Cook, Margaret
Guy, Michelle
Govindasami, Koveela
Leongamornlert, Daniel
Sawyer, Emma J.
Wilkinson, Rosemary
Saunders, Edward J.
Tymrakiewicz, Malgorzata
Dadaev, Tokhir
Morgan, Angela
Fisher, Cyril
Hazel, Steve
Livni, Naomi
Lophatananon, Artitaya
Pedersen, John
Hopper, John L.
Adolfson, Jan
Stattin, Paer
Johansson, Jan-Erik
Cavalli-Bjoerkman, Carin
Karlsson, Ami
Broms, Michael
Auvinen, Anssi
Kujala, Paula
Maeaettaenen, Liisa
Murtola, Teemu
Taari, Kimmo
Weischer, Maren
Nielsen, Sune F.
Klarskov, Peter
Roder, Andreas
Iversen, Peter
Wallinder, Hans
Gustafsson, Sven
Cox, Angela
Brown, Paul
George, Anne
Marsden, Gemma
Lane, Athene
Davis, Michael
Zheng, Wei
Signorello, Lisa B.
Blot, William J.
Tillmans, Lori
Riska, Shaun
Wang, Liang
Rinckleb, Antje
Lubiski, Jan
Stegmaier, Christa
Pow-Sang, Julio
Park, Hyun
Radlein, Selina
Rincon, Maria
Haley, James
Zachariah, Babu
Kachakova, Darina
Popov, Elenko
Mitkova, Atanaska
Vlahova, Aleksandrina
Dikov, Tihomir
Christova, Svetlana
Heathcote, Peter
Wood, Glenn
Malone, Greg
Saunders, Pamela
Eckert, Allison
Yeadon, Trina
Kerr, Kris
Collins, Angus
Turner, Megan
Srinivasan, Srilakshmi
Kedda, Mary-Anne
Alexander, Kimberly
Omara, Tracy
Wu, Huihai
Henrique, Rui
Pinto, Pedro
Santos, Joana
Barros-Silva, Joao
CA PRACTICAL Consortium
TI Atlas of prostate cancer heritability in European and African-American
men pinpoints tissue-specific regulation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; COMMON DISEASES; COMPLEX
TRAITS; RISK; SNPS; ENHANCERS; ELEMENTS; PITFALLS; ENCODE
AB Although genome-wide association studies have identified over 100 risk loci that explain similar to 33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
C1 [Gusev, Alexander; Signorello, Lisa B.; Gaziano, J. Michael; Giovannucci, Edward; Hunter, David J.; Kraft, Peter; Lindstrom, Sara; Trichopoulos, Dimitrios] Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Gusev, Alexander; Raychaudhuri, Soumya; Freedman, Matthew L.] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA.
[Shi, Huwenbo; Kichaev, Gleb; Pasaniuc, Bogdan] Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA 90095 USA.
[Pomerantz, Mark; Long, Henry W.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Pomerantz, Mark; Long, Henry W.; Freedman, Matthew L.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Li, Fugen; Long, Henry W.; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA.
[Li, Fugen] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Ingles, Sue A.; Casey, Graham; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Preventat Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Kittles, Rick A.] Univ Arizona, Coll Med, Tucson, AZ 85721 USA.
[Kittles, Rick A.] Univ Arizona, Ctr Canc, Tucson, AZ 85721 USA.
[Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Nemesure, Barbara; Leske, M. Cristina; Wu, Suh-Yuh; Hennis, Anslem J. M.] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
[Isaacs, William B.; Price, Alkes L.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Isaacs, William B.; Price, Alkes L.] Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Isaacs, William B.; Price, Alkes L.] Inst Med, Baltimore, MD 21205 USA.
[Zheng, Wei; Blot, William J.] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37232 USA.
[Pettaway, Curtis A.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn] Korle Bu Teaching Hosp, Accra, Ghana.
[Yeboah, Edward D.; Tettey, Yao; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn] Univ Ghana, Sch Med, Accra, Ghana.
[Truelove, Ann; Niwa, Shelley] Westat Corp, Rockville, MD 20850 USA.
[Chokkalingam, Anand P.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA.
[John, Esther M.; Hsing, Ann W.; Chu, Lisa] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[John, Esther M.; Hsing, Ann W.; Chu, Lisa] Stanford Univ, Sch Med, Palo Alto, CA 94305 USA.
[John, Esther M.; Hsing, Ann W.; Chu, Lisa] Stanford Canc Inst, Palo Alto, CA 94305 USA.
[Murphy, Adam B.] Northwestern Univ, Dept Urol, Chicago, IL 60611 USA.
[Signorello, Lisa B.; Blot, William J.] Int Epidemiol Inst, Rockville, MD 20850 USA.
[Carpten, John] Translat Genom Res Inst, Phoenix, AZ 85004 USA.
[Hennis, Anslem J. M.] Univ W Indies, Chron Dis Res Ctr, Bridgetown, Barbados.
[Hennis, Anslem J. M.] Univ W Indies, Fac Med Sci, Bridgetown, Barbados.
[Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98109 USA.
[Klein, Eric A.] Cleveland Clin, Glickman Urol & Kidney Inst, Cleveland, OH 44195 USA.
[Witte, John S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.
[Witte, John S.] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94118 USA.
[Kaggwa, Sam] Makerere Univ, Dept Surg, Coll Hlth Sci, Kampala 94118, Uganda.
[Cook, Michael B.; Berndt, Sonja I.; Hoover, Robert; Yeager, Meredith] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Eeles, Rosalind A.; Kote-Jarai, ZSofia; Guy, Michelle; Govindasami, Koveela; Leongamornlert, Daniel; Sawyer, Emma J.; Wilkinson, Rosemary; Saunders, Edward J.; Tymrakiewicz, Malgorzata; Dadaev, Tokhir; Morgan, Angela; Fisher, Cyril; Hazel, Steve; Livni, Naomi] Inst Canc Res, Sutton SM2 5NG, Surrey, England.
[Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, London, England.
[Eeles, Rosalind A.] Royal Marsden Natl Hlth Serv NHS Fdn Trust, Sutton, Surrey, England.
[Easton, Douglas; Al Olama, Ali Amin; Benlloch, Sara; Cook, Margaret] Univ Cambridge, Strangeways Lab, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge CB1 8RN, England.
[Muir, Kenneth; Lophatananon, Artitaya] Univ Manchester, Inst Populat Hlth, Manchester M13 9PL, Lancs, England.
[Muir, Kenneth; Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Giles, Graham G.; Fitzgerald, Liesel M.] Canc Council Victoria, Canc Epidemiol Ctr, 615 St Kilda Rd, Melbourne, Vic 3004, Australia.
[Giles, Graham G.; Hopper, John L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3004, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Grattan St, Melbourne, Vic 3010, Australia.
[Gronberg, Henrik; Wiklund, Fredrik; Aly, Markus; Adolfson, Jan; Stattin, Paer; Johansson, Jan-Erik; Cavalli-Bjoerkman, Carin; Karlsson, Ami; Broms, Michael] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Aly, Markus] Danderyd Hosp, Dept Clin Sci, S-17177 Stockholm, Sweden.
[Henderson, Brian E.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90007 USA.
[Schleutker, Johanna] Univ Turku, Inst Biomed, Dept Med Biochem & Genet, Kiinamyllynkatu 10, FI-20014 Turku, Finland.
[Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, BioMediTech, Tampere 33200, Finland.
[Schleutker, Johanna; Wahlfors, Tiina] FimLab Labs, Tampere 33200, Finland.
[Tammela, Teuvo L. J.] Univ Tampere, Dept Urol, Tampere Univ Hosp, Tampere 33200, Finland.
[Tammela, Teuvo L. J.] Univ Tampere, Sch Med, Tampere 33200, Finland.
[Nordestgaard, Borge G.; Weischer, Maren; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.
[Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen, Fac Hlth & Med Sci, DK-1165 Copenhagen, Denmark.
[Nordestgaard, Borge G.; Nielsen, Sune F.] Univ Copenhagen, Med Sci, DK-1165 Copenhagen, Denmark.
[Key, Tim J.; Travis, Ruth C.] Univ Oxford, Canc Epidemiol, Nuffield Dept Populat Hlth, Oxford OX3 7LF, England.
[Neal, David E.] Univ Cambridge, Dept Oncol, Addenbrookes Hosp, Cambridge CB2 0QQ, England.
[Neal, David E.] Li Ka Shing Ctr, Canc Res UK Cambridge Res Inst, Cambridge, England.
[Donovan, Jenny L.; Brown, Paul; George, Anne; Marsden, Gemma; Lane, Athene; Davis, Michael] Univ Bristol, Sch Social & Community Med, Canynge Hall,39Whatley Rd, Bristol BS8 2PS, Avon, England.
[Hamdy, Freddie C.] Aarhus Univ, Epidemiol Sect, Dept Publ Hlth, Aarhus OX1 3PN, Denmark.
[Hamdy, Freddie C.] Univ Oxford, John Radcliffe Hosp, Fac Med Sci, Oxford OX1 3PN, England.
[Pharoah, Paul; Pashayan, Nora] Univ Cambridge, Dept Oncol, Strangeways Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge CB1 8RN, England.
[Pashayan, Nora] UCL, Dept Appl Hlth Res, 1-19 Torrington Pl, London WC1E 7HB, England.
[Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge CB1 8RN, England.
[Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98109 USA.
[Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Tillmans, Lori; Riska, Shaun; Wang, Liang] Mayo Clin, Rochester, MN 55905 USA.
[Maier, Christiane; Vogel, Walther] Univ Hosp Ulm, Inst Human Genet, D-89081 Ulm, Germany.
[Luedeke, Manuel; Rinckleb, Antje] Univ Hosp Ulm, Dept Urol, D-89081 Ulm, Germany.
[Herkommer, Kathleen] Tech Univ Munich, Klinikum Rechts Isar, Dept Urol, D-81675 Munich, Germany.
[Kibel, Adam S.] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA.
[Cybulski, Cezary; Wokolorczyk, Dominika; Kluzniak, Wojciech; Lubiski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Cannon-Albright, Lisa; Teerlink, Craig] Univ Utah, Div Genet Epidemiol, Dept Med, Sch Med, Salt Lake City, UT 84132 USA.
[Cannon-Albright, Lisa; Teerlink, Craig] George E Wahlen Dept Vet Affairs, Med Ctr, Salt Lake City, UT 84132 USA.
[Brenner, Hermann; Dieffenbach, Aida K.; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
[Brenner, Hermann; Dieffenbach, Aida K.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
[Park, Jong Y.; Sellers, Thomas A.; Pow-Sang, Julio; Park, Hyun; Radlein, Selina; Rincon, Maria; Haley, James; Zachariah, Babu] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, 12902 Magnolia Dr, Tampa, FL 33612 USA.
[Lin, Hui-Yi] H Lee Moffitt Canc Ctr & Res Inst, Biostat Program, 12902 Magnolia Dr, Tampa, FL 33612 USA.
[Slavov, Chavdar; Popov, Elenko] Med Univ, Dept Urol, Sofia 1431, Bulgaria.
[Slavov, Chavdar; Popov, Elenko] Med Univ, Alexandrovska Univ Hosp, Sofia 1431, Bulgaria.
[Kaneva, Radka; Mitev, Vanio; Kachakova, Darina; Mitkova, Atanaska] Med Univ, Mol Med Ctr, Dept Med Chem & Biochem, 2 Zdrave Str, Sofia 1431, Bulgaria.
[Batra, Jyotsna; Clements, Judith A.; Vlahova, Aleksandrina; Heathcote, Peter; Wood, Glenn; Malone, Greg; Saunders, Pamela; Eckert, Allison; Yeadon, Trina; Kerr, Kris; Collins, Angus; Turner, Megan; Srinivasan, Srilakshmi; Kedda, Mary-Anne; Alexander, Kimberly; Omara, Tracy] Queensland Univ Technol, Australian Prostate Canc Res Ctr Qld, Inst Hlth & Biomed Innovat, Brisbane, Qld 4000, Australia.
[Batra, Jyotsna; Clements, Judith A.; Heathcote, Peter; Wood, Glenn; Malone, Greg; Saunders, Pamela; Eckert, Allison; Yeadon, Trina; Kerr, Kris; Collins, Angus; Turner, Megan; Srinivasan, Srilakshmi; Kedda, Mary-Anne; Alexander, Kimberly; Omara, Tracy] Queensland Univ Technol, Sch Biomed Sci, Brisbane, Qld 4000, Australia.
[Spurdle, Amanda] Queensland Inst Med Res, Mol Canc Epidemiol Lab, Brisbane, Qld 4000, Australia.
[Teixeira, Manuel R.; Paulo, Paula; Maia, Sofia; Henrique, Rui; Pinto, Pedro; Santos, Joana; Barros-Silva, Joao] Portuguese Oncol Inst, Dept Genet, P-4200 Oporto, Portugal.
[Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, P-4200 Oporto, Portugal.
[Pandha, Hardev; Michael, Agnieszka; Kierzek, Andrzej; Vlahova, Aleksandrina; Dikov, Tihomir; Christova, Svetlana] Univ Surrey, Guildford GU2 7XH, Surrey, England.
[Conti, David V.; Schumacher, Frederick R.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Norris Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Berg, Christine; Overvad, Kim] Johns Hopkins Med, Dept Radiat Oncol & Mol Radiat Sci, Baltimore, MD 21287 USA.
[Campa, Daniele] German Canc Res Ctr, Genom Epidemiol Grp, D-69121 Heidelberg, Germany.
[Crawford, E. David] Univ Colorado, Urol Oncol, Denver Hlth Sci Ctr, Denver, CO 80230 USA.
[Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Gaziano, J. Michael] Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69008 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, S-90736 Umea, Sweden.
[Kraft, Peter; Lindstrom, Sara] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96813 USA.
[Riboli, Elio] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London SW7 2AZ, England.
[Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis, London SW7 2AZ, England.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens 10679, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens 10679, Greece.
[Vineis, Paolo] HuGeF Fdn, I-10126 Turin, Italy.
[Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London SW7 2AZ, England.
[Trynka, Gosia; Raychaudhuri, Soumya] Brigham & Womens Hosp, Dept Med, Div Genet, 75 Francis St, Boston, MA 02115 USA.
[Trynka, Gosia; Raychaudhuri, Soumya] Brigham & Womens Hosp, Dept Med, Div Rheumatol, 75 Francis St, Boston, MA 02115 USA.
[Trynka, Gosia; Raychaudhuri, Soumya] Harvard Univ, Sch Med, Boston, MA USA.
[Trynka, Gosia] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England.
[Raychaudhuri, Soumya] Univ Manchester, Inst Inflammat & Repair, Manchester M13 9PT, Lancs, England.
[Pasaniuc, Bogdan] Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA.
[Pasaniuc, Bogdan] Univ Calif Los Angeles, Dept Lab Med, Los Angeles, CA USA.
[Pasaniuc, Bogdan] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA.
[Pedersen, John] Tissupath Pty Ltd, Melbourne, Vic 3122, Australia.
[Auvinen, Anssi] Univ Tampere, Sch Hlth Sci, Dept Epidemiol, Tampere 33014, Finland.
[Kujala, Paula] Tampere Univ Hosp, Fimlab Labs, Tampere, Finland.
[Maeaettaenen, Liisa] Finnish Canc Registry, FIN-00170 Helsinki, Finland.
[Murtola, Teemu] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Murtola, Teemu] Tampere Univ Hosp, Dept Urol, Tampere, Finland.
[Taari, Kimmo] Univ Helsinki, Cent Hosp, Dept Urol, SF-00100 Helsinki, Finland.
[Taari, Kimmo] Univ Helsinki, SF-00100 Helsinki, Finland.
[Klarskov, Peter] Copenhagen Univ Hosp, Herlev Hosp, Dept Urol, Ringvej 75, DK-230 Herlev, Denmark.
[Roder, Andreas; Iversen, Peter] Copenhagen Univ Hosp, Dept Urol, Rigshosp, Copenhagen Prostate Canc Ctr, DK-2200 Copenhagen, Denmark.
[Wallinder, Hans; Gustafsson, Sven] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.
[Cox, Angela] Univ Sheffield, CR UK YCR Sheffield Canc Res Ctr, Sheffield S10 2TN, S Yorkshire, England.
[Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, 2525 West End Ave, Nashville, TN 37232 USA.
[Signorello, Lisa B.] NCI, NIH, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
[Signorello, Lisa B.] NCI, NIH, Rockville, MD 20850 USA.
[Blot, William J.] Int Inst Epidemiol, 1555 Res Blvd,Suite 550, Rockville, MD 20850 USA.
[Blot, William J.] Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr,Vanderbilt Ingr, Nashville, TN 37232 USA.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Wu, Huihai] Univ Surrey, Guildford GU2 7XH, Surrey, England.
RP Gusev, A (reprint author), Harvard TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.; Pasaniuc, B (reprint author), Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA 90095 USA.
EM agusev@hsph.harvard.edu; pasaniuc@ucla.edu
RI Cook, Michael/A-5641-2009; Batra, Jyotsna/B-4130-2011; Campa,
Daniele/K-1617-2016; Zheng, Wei/O-3351-2013; Brenner,
Hermann/B-4627-2017;
OI Cook, Michael/0000-0002-0533-7302; Campa, Daniele/0000-0003-3220-9944;
Zheng, Wei/0000-0003-1226-070X; Brenner, Hermann/0000-0002-6129-1572;
Teerlink, Craig/0000-0002-1992-2326; albright, lisa/0000-0003-2602-3668;
Taari, Kimmo/0000-0002-0077-4896; Clements, Judith/0000-0001-6026-1964
FU NIH fellowship [F32 GM106584]; NIH [R01 MH101244, R01 CA188392, U01
CA194393, R01 GM107427, R01 CA193910, CA63464, CA54281, CA098758, R01
CA092447]; Prostate Cancer Foundation Challenge Award; Wellcome Trust
[076113]; European Commission's Seventh Framework Programme [223175
(HEALTH-F2-2009-223175)]; Cancer Research UK [C5047/A7357, C5047/A3354,
C16913/A6135, C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014,
C5047/A8384, C5047/A15007, C5047/A10692, C8197/A10123, C8197/A10865,
C522/A8649, C490/A10124]; National Institute of Health (NIH) Cancer
Post-Cancer GWAS initiative Grant [1 U19 CA 148537-01]; National
Institutes of Health [CA128978]; Post-Cancer GWAS initiative [1U19
CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defense
[W81XWH-10-1-0341]; Linneus Centre [70867902]; Swedish Research Council
[K2010-70X-20430-04-3]; Swedish Cancer Foundation [09-0677]; US National
Cancer Institute, National Institutes of Health [RO1CA056678,
RO1CA082664, RO1CA092579]; US National Cancer Institute [R01CA72818,
R01CA128813]; National Health and Medical Research Council, Australia
[126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204,
940394, 614296]; Bulgarian National Science Fund, Ministry of Education
and Science [DOO-119/2009, DUNK01/2-2009, DFNI-B01/28/2012]; NIHR Health
Technology Assessment Programme [96/20/06, 96/20/99]; Medical Research
Council of England [G0500966, 75466]; NCRI, UK; US Dept of Defense award
[W81XWH-04-1-0280]; Australia Project Grant [614296, 390130, 1009458];
Prostate Cancer Foundation of Australia; Vanderbilt-Ingram Cancer Center
[P30 CA68485]; UK National Institute for Health Research Biomedical
Research Centre at the University of Cambridge; Competitive Research
Funding of the Tampere University Hospital [9N069, X51003]; National
Cancer Institute [P30CA042014]; [G0500966/75466]
FX This work was supported by NIH fellowship F32 GM106584 (AG), NIH grants
R01 MH101244(A.G.), R01 CA188392 (B.P.), U01 CA194393(B.P.), R01
GM107427 (M.L.F.), R01 CA193910 (M.L.F./M.P.) and Prostate Cancer
Foundation Challenge Award (M.L.F./M.P.). This study makes use of data
generated by the Wellcome Trust Case Control Consortium and the Wellcome
Trust Sanger Institute. A full list of the investigators who contributed
to the generation of the Wellcome Trust Case Control Consortium data is
available on www.wtccc.org.uk. Funding for the Wellcome Trust Case
Control Consortium project was provided by the Wellcome Trust under
award 076113. This study makes use of data generated by the UK10K
Consortium. A full list of the investigators who contributed to the
generation of the data is available online (http://www.UK10K.org). The
PRACTICAL consortium was supported by the following grants: European
Commission's Seventh Framework Programme grant agreement no 223175
(HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357,
C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135 and The National
Institute of Health (NIH) Cancer Post-Cancer GWAS initiative Grant: no.
1 U19 CA 148537-01 (the GAME-ON initiative); Cancer Research UK
(C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384,
C5047/A15007 and C5047/A10692), the National Institutes of Health
(CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065
and 1U19 CA148112-the GAME-ON initiative), the Department of Defense
(W81XWH-10-1-0341), A Linneus Centre (Contract ID 70867902), Swedish
Research Council (grant no K2010-70X-20430-04-3), the Swedish Cancer
Foundation (grant no 09-0677), grants RO1CA056678, RO1CA082664 and
RO1CA092579 from the US National Cancer Institute, National Institutes
of Health; US National Cancer Institute (R01CA72818); support from The
National Health and Medical Research Council, Australia (126402, 209057,
251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394 and
614296); NIH grants CA63464, CA54281 and CA098758; US National Cancer
Institute (R01CA128813, PI: J.Y. Park); Bulgarian National Science Fund,
Ministry of Education and Science (contract DOO-119/2009; DUNK01/2-2009;
DFNI-B01/28/2012); Cancer Research UK grants [C8197/A10123] and
[C8197/A10865]; grant code G0500966/75466; NIHR Health Technology
Assessment Programme (projects 96/20/06 and 96/20/99); Cancer Research
UK grant number C522/A8649, Medical Research Council of England grant
number G0500966, ID 75466 and The NCRI, UK; The US Dept of Defense award
W81XWH-04-1-0280; Australia Project Grant [390130, 1009458] and Enabling
Grant [614296 to APCB]; the Prostate Cancer Foundation of Australia
(Project Grant [PG7] and Research infrastructure grant [to APCB]); NIH
grant R01 CA092447; Vanderbilt-Ingram Cancer Center (P30 CA68485);
Cancer Research UK [C490/A10124] and supported by the UK National
Institute for Health Research Biomedical Research Centre at the
University of Cambridge; Competitive Research Funding of the Tampere
University Hospital (9N069 and X51003); Award Number P30CA042014 from
the National Cancer Institute.
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PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2016
VL 7
AR 10979
DI 10.1038/ncomms10979
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI9EK
UT WOS:000373804700001
PM 27052111
ER
PT J
AU Ono, W
Sakagami, N
Nishimori, S
Ono, N
Kronenberg, HM
AF Ono, Wanida
Sakagami, Naoko
Nishimori, Shigeki
Ono, Noriaki
Kronenberg, Henry M.
TI Parathyroid hormone receptor signalling in osterix-expressing
mesenchymal progenitors is essential for tooth root formation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID OSTEOBLAST DIFFERENTIATION; PTH/PTHRP RECEPTOR; PRIMARY FAILURE; I
COLLAGEN; BONE; PROTEIN; ERUPTION; HEDGEHOG; CELLS; GENE
AB Dental root formation is a dynamic process in which mesenchymal cells migrate toward the site of the future root, differentiate and secrete dentin and cementum. However, the identities of dental mesenchymal progenitors are largely unknown. Here we show that cells expressing osterix are mesenchymal progenitors contributing to all relevant cell types during morphogenesis. The majority of cells expressing parathyroid hormone-related peptide (PTHrP) are in the dental follicle and on the root surface, and deletion of its receptor (PPR) in these progenitors leads to failure of eruption and significantly truncated roots lacking periodontal ligaments. The PPR-deficient progenitors exhibit accelerated cementoblast differentiation with upregulation of nuclear factor I/C (Nfic). Deletion of histone deacetylase-4 (HDAC4) partially recapitulates the PPR deletion root phenotype. These findings indicate that PPR signalling in dental mesenchymal progenitors is essential for tooth root formation, underscoring importance of the PTHrP-PPR system during root morphogenesis and tooth eruption.
C1 [Ono, Wanida; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.
[Ono, Wanida; Nishimori, Shigeki; Ono, Noriaki; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Ono, Wanida; Sakagami, Naoko; Ono, Noriaki] Univ Michigan, Dept Orthodont & Pediat Dent, Ann Arbor, MI 48109 USA.
RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA.; Kronenberg, HM (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
EM hkronenberg@mgh.harvard.edu
FU National Institutes of Health [DE022564, DK011794]; Japan Society for
the Promotion of Science [21689051]
FX The authors thank Eric Olson for HDAC4-null and HDAC4-floxed mice,
Arthur Broadus for PTHrP-LacZ mice and David Rowe for Col2.3-GFP and
Oc-GFP mice. This study was supported by National Institutes of Health
Grants DE022564 to N.O. and DK011794 to H.M.K., and Japan Society for
the Promotion of Science Grant-in-Aid for Young Scientists 21689051 to
N.O.
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U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD APR
PY 2016
VL 7
AR 11277
DI 10.1038/ncomms11277
PG 16
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI9NW
UT WOS:000373830600001
PM 27068606
ER
PT J
AU Vinegoni, C
Swisher, CL
Feruglio, PF
Giedt, RJ
Rousso, DL
Stapleton, S
Weissleder, R
AF Vinegoni, C.
Swisher, C. Leon
Feruglio, P. Fumene
Giedt, R. J.
Rousso, D. L.
Stapleton, S.
Weissleder, R.
TI Real-time high dynamic range laser scanning microscopy
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SINGLE-CELL; 2-PHOTON MICROSCOPY; LIGHT-MICROSCOPY; BRAIN; NEUROSCIENCE;
RECONSTRUCTION; ILLUMINATION; SENSITIVITY; IMAGES; SCALE
AB In conventional confocal/multiphoton fluorescence microscopy, images are typically acquired under ideal settings and after extensive optimization of parameters for a given structure or feature, often resulting in information loss from other image attributes. To overcome the problem of selective data display, we developed a new method that extends the imaging dynamic range in optical microscopy and improves the signal-to-noise ratio. Here we demonstrate how real-time and sequential high dynamic range microscopy facilitates automated three-dimensional neural segmentation. We address reconstruction and segmentation performance on samples with different size, anatomy and complexity. Finally, in vivo real-time high dynamic range imaging is also demonstrated, making the technique particularly relevant for longitudinal imaging in the presence of physiological motion and/or for quantification of in vivo fast tracer kinetics during functional imaging.
C1 [Vinegoni, C.; Swisher, C. Leon; Feruglio, P. Fumene; Giedt, R. J.; Stapleton, S.; Weissleder, R.] Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.
[Vinegoni, C.; Swisher, C. Leon; Feruglio, P. Fumene; Giedt, R. J.; Stapleton, S.; Weissleder, R.] Harvard Univ, Sch Med, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.
[Feruglio, P. Fumene] Univ Verona, Dept Neurol Biomed & Movement Sci, Str Le Grazie 8, I-37134 Verona, Italy.
[Rousso, D. L.] Harvard Univ, Ctr Brain Sci, Dept Mol & Cell Biol, 52 Oxford St, Cambridge, MA 02138 USA.
RP Vinegoni, C (reprint author), Massachusetts Gen Hosp, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA.; Vinegoni, C (reprint author), Harvard Univ, Sch Med, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA.
EM cvinegoni@mgh.harvard.edu
FU Federal funds from the National Heart, Lung, and Blood Institute,
National Institutes of Health, Department of Health and Human Services
[HHSN26820100004xC]; NRSA postdoctoral fellowship [F32-CA192531];
Natural Sciences and Engineering Research Council of Canada (NSERC);
CDMRP DOD BCRP postdoctoral fellowship [BC134081]; Institute of
Biomedical Engineering [R01EB006432]; EC [622182]
FX We thank Professor J.R. Sanes, Drs John Dubach, Kevin King, Nicolas De
Silva, Michael Cuccarese, Aaron Aguirre and Jonathan Carlson for helpful
discussions on applications of High Dynamic Range to fluorescence
microscopy as well as Yoshiko Guiles for help with sample preparation
and Dr Hunter Elliott for training with IMARIS. This project was funded
in part by Federal funds from the National Heart, Lung, and Blood
Institute, National Institutes of Health, Department of Health and Human
Services (under Contract No. HHSN26820100004xC), NRSA postdoctoral
fellowship F32-CA192531, the Natural Sciences and Engineering Research
Council of Canada (NSERC) postdoctoral fellowship, CDMRP DOD BCRP
postdoctoral fellowship BC134081 and from the Institute of Biomedical
Engineering (under R01EB006432). The research leading to these results
has also received funding from the EC Seventh Framework Programme under
the Grant Agreement nr. 622182.
NR 50
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U1 1
U2 10
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 APR
PY 2016
VL 7
AR 11077
DI 10.1038/ncomms11077
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI4NE
UT WOS:000373475800001
PM 27032979
ER
PT J
AU Spring, BQ
Sears, RB
Zheng, LZ
Mai, ZM
Watanabe, R
Sherwood, ME
Schoenfeld, DA
Pogue, BW
Pereira, SP
Villa, E
Hasan, T
AF Spring, Bryan Q.
Sears, R. Bryan
Zheng, Lei Zak
Mai, Zhiming
Watanabe, Reika
Sherwood, Margaret E.
Schoenfeld, David A.
Pogue, Brian W.
Pereira, Stephen P.
Villa, Elizabeth
Hasan, Tayyaba
TI A photoactivable multi-inhibitor nanoliposome for tumour control and
simultaneous inhibition of treatment escape pathways
SO NATURE NANOTECHNOLOGY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; ADVANCED PANCREATIC-CANCER; TARGETED
DRUG-DELIVERY; NEAR-INFRARED LIGHT; PHOTODYNAMIC THERAPY; IN-VIVO;
OVARIAN-CANCER; C-MET; ANTIANGIOGENIC THERAPY; METASTASIS
AB Nanoscale drug delivery vehicles can facilitate multimodal therapies of cancer by promoting tumour-selective drug release. However, few are effective because cancer cells develop ways to resist and evade treatment. Here, we introduce a photoactivable multi-inhibitor nanoliposome (PMIL) that imparts light-induced cytotoxicity in synchrony with a photoinitiated and sustained release of inhibitors that suppress tumour regrowth and treatment escape signalling pathways. The PMIL consists of a nanoliposome doped with a photoactivable chromophore (benzoporphyrin derivative, BPD) in the lipid bilayer, and a nanoparticle containing cabozantinib (XL184)-a multikinase inhibitor-encapsulated inside. Near-infrared tumour irradiation, following intravenous PMIL administration, triggers photodynamic damage of tumour cells and microvessels, and simultaneously initiates release of XL184 inside the tumour. A single PMIL treatment achieves prolonged tumour reduction in two mouse models and suppresses metastatic escape in an orthotopic pancreatic tumour model. The PMIL offers new prospects for cancer therapy by enabling spatiotemporal control of drug release while reducing systemic drug exposure and associated toxicities.
C1 [Spring, Bryan Q.; Sears, R. Bryan; Zheng, Lei Zak; Mai, Zhiming; Sherwood, Margaret E.; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Spring, Bryan Q.; Sears, R. Bryan; Zheng, Lei Zak; Mai, Zhiming; Sherwood, Margaret E.; Hasan, Tayyaba] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Spring, Bryan Q.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA.
[Sears, R. Bryan] Emmanuel Coll, Dept Chem, Boston, MA 02115 USA.
[Watanabe, Reika] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Schoenfeld, David A.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Schoenfeld, David A.] Harvard Univ, Biostat Unit, Boston, MA 02114 USA.
[Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.
[Pereira, Stephen P.] UCL, UCL Inst Liver & Digest Hlth, Royal Free Hosp Campus, London NW3 2QG, England.
[Hasan, Tayyaba] Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Hasan, Tayyaba] MIT, Cambridge, MA 02139 USA.
RP Hasan, T (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Hasan, T (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.; Hasan, T (reprint author), Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02139 USA.; Hasan, T (reprint author), MIT, Cambridge, MA 02139 USA.
EM thasan@mgh.harvard.edu
RI Villa, Elizabeth/D-1811-2010
OI Villa, Elizabeth/0000-0003-4677-9809
FU National Institutes of Health Grants [R01 CA156177, R01-CA160998,
P01-CA084203, F32-CA144210]
FX We thank N. Watson (W.M. Kreck Microscopy Facility at the Whitehead
Institute, Massachusetts Institute of Technology) for providing ionized
carbon coated grids; E. Oliva (Department of Pathology at Massachusetts
General Hospital) for expert histopathologic review of tissue sections;
G. Orbaid for a critical reading; and, A. Villanueva for assistance in
preparing a 3D render of a PMIL cryo-EM tomogram. This work was
supported by National Institutes of Health Grants R01 CA156177 (to
T.H.), R01-CA160998 (to T.H.), and P01-CA084203 (to B.W.P., S.P.P. and
T.H.) and F32-CA144210 (to B.Q.S.).
NR 50
TC 13
Z9 13
U1 25
U2 65
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1748-3387
EI 1748-3395
J9 NAT NANOTECHNOL
JI Nat. Nanotechnol.
PD APR
PY 2016
VL 11
IS 4
BP 378
EP +
DI 10.1038/NNANO.2015.311
PG 12
WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary
SC Science & Technology - Other Topics; Materials Science
GA DI4FJ
UT WOS:000373455500016
PM 26780659
ER
PT J
AU Notarangelo, LD
Kim, MS
Walter, JE
Lee, YN
AF Notarangelo, Luigi D.
Kim, Min-Sung
Walter, Jolan E.
Lee, Yu Nee
TI Human RAG mutations: biochemistry and clinical implications
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID SEVERE COMBINED IMMUNODEFICIENCY; COMBINED IMMUNE-DEFICIENCY;
RECOMBINATION-ACTIVATING GENE; HYPEREOSINOPHILIA OMENNS SYNDROME; COMMON
VARIABLE IMMUNODEFICIENCY; IMMUNOGLOBULIN-SECRETING CELLS; REGULATORY
T-CELLS; V(D)J RECOMBINATION; B-CELLS; GRANULOMATOUS-DISEASE
AB The recombination-activating gene 1 (RAG1) and RAG2 proteins initiate the V(D)J recombination process, which ultimately enables the generation of T cells and B cells with a diversified repertoire of antigen-specific receptors. Mutations of the RAG genes in humans are associated with a broad spectrum of clinical phenotypes, ranging from severe combined immunodeficiency to autoimmunity. Recently, novel insights into the phenotypic diversity of this disease have been provided by resolving the crystal structure of the RAG complex, by developing novel assays to test recombination activity of the mutant RAG proteins and by characterizing the molecular and cellular basis of immune dysregulation in patients with RAG deficiency.
C1 [Notarangelo, Luigi D.; Walter, Jolan E.; Lee, Yu Nee] Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA 02115 USA.
[Kim, Min-Sung] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Allergy & Immunol, Boston, MA 02114 USA.
[Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA.
RP Notarangelo, LD (reprint author), Harvard Univ, Sch Med, Div Immunol, Boston Childrens Hosp, Boston, MA 02115 USA.
EM luigi.notarangelo@childrens.harvard.edu
FU NIAID NIH HHS [5K08AI103035, 5R01AI100887, K08 AI103035]
NR 103
TC 9
Z9 9
U1 2
U2 3
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD APR
PY 2016
VL 16
IS 4
BP 234
EP 246
DI 10.1038/nri.2016.28
PG 13
WC Immunology
SC Immunology
GA DH7MD
UT WOS:000372977200009
PM 26996199
ER
PT J
AU Fu, ZL
Liu, M
Li, Z
Fan, Y
Zhang, JH
Zhang, XC
Li, Q
AF Fu, Zhanli
Liu, Meng
Li, Ziao
Fan, Yan
Zhang, Jianhua
Zhang, Xuchu
Li, Qian
TI Is the bullhead sign on bone scintigraphy really common in the patient
with SAPHO syndrome? A single-center study of a 16-year experience
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE bullhead sign; SAPHO syndrome; whole-body bone scintigraphy
ID PUSTULOTIC ARTHROOSTEITIS; FOLLOW-UP; SPECTRUM; HYPEROSTOSIS
AB ObjectiveThe aim of this study was to assess the bone lesion distribution and analyze the frequency of the bullhead sign in patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome using whole-body bone scintigraphy (WBBS) in a relatively populous study population.MethodsIn this study, the Nuclear Medicine Department's records of one center were retrospectively reviewed and the patients who fulfilled the diagnostic criteria for SAPHO syndrome and underwent Tc-99m-methylene diphosphonate WBBS were identified over a 16-year period. The following data were collected from patients, including age, sex, surgically proved pathology of the bone lesions, WBBS surveillance interval, and SAPHO syndrome components. The bone lesion distribution and the frequency of bullhead sign involving the manubrium and bilateral sternoclavicular junctions were analyzed.ResultsForty-eight patients were enrolled in this study. The initial WBBS indicated bone involvement in all of the 48 (100%) patients, in whom the most commonly affected region was the anterior chest wall (ACW) (100%, 48/48). The frequency of the upper costosternal junction involvement was the highest (38/48, 79.2%), and 28.9% (11/38) patients were found to show isolated involvement of the first rib in ACW. The frequency of the bullhead sign was only 22.9% (11/48, 95% CI: 12.0-37.3). In the eight (16.7%, 8/48) patients who were followed up using WBBS with an interval that ranged from 1 to 10 years, one patient with an initially single sternoclavicular junction lesion developed a typical bullhead sign over 10 years; other patients with or without the initial typical bullhead sign showed stable appearance over 1-4 years.ConclusionThis retrospective study shows that in patients with proposed SAPHO syndrome, the bone lesions are most likely located in ACW, and the configuration of the bullhead sign is characteristic, but not entirely sensitive. The value of upper costosternal junction involvement, especially the first rib, may be underevaluated.
C1 [Fu, Zhanli; Liu, Meng; Li, Ziao; Fan, Yan; Zhang, Jianhua; Zhang, Xuchu] Peking Univ, Hosp 1, Dept Nucl Med, Beijing 100871, Peoples R China.
[Li, Qian] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 55 Fruit St,White 270, Boston, MA 02114 USA.
RP Li, Q (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 55 Fruit St,White 270, Boston, MA 02114 USA.
EM qli14@mgh.harvard.edu
FU Seeding Grant for Medicine and Engineering Sciences of Peking University
[BMU20140398]
FX This work was supported, in part, by the Seeding Grant for Medicine and
Engineering Sciences of Peking University (BMU20140398).
NR 20
TC 3
Z9 4
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0143-3636
EI 1473-5628
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD APR
PY 2016
VL 37
IS 4
BP 387
EP 392
DI 10.1097/MNM.0000000000000451
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DI5GI
UT WOS:000373526500008
PM 26619395
ER
PT J
AU Bove, RM
Gerweck, AV
Mancuso, SM
Bredella, MA
Sherman, JC
Miller, KK
AF Bove, Riley M.
Gerweck, Anu V.
Mancuso, Sarah M.
Bredella, Miriam A.
Sherman, Janet C.
Miller, Karen K.
TI Association between adiposity and cognitive function in young men:
Hormonal mechanisms
SO OBESITY
LA English
DT Article
ID BODY-MASS INDEX; BINDING GLOBULIN; INSULIN SENSITIVITY; METABOLIC
SYNDROME; OBESITY; TESTOSTERONE; BRAIN; WOMEN; PERFORMANCE; MEMORY
AB ObjectiveTo determine the association between adiposity, hormones, and cognition in young men with abdominal obesity.
MethodsIn this cross-sectional observational study, 53 nondiabetic men with abdominal obesity (mean body mass index, 37.3 kg/m(2); age, 22-45 years) and normal intelligence underwent detailed measures of body composition, hormonal profiles, and cognition. Age- and education-adjusted performance in five cognitive domains was examined.
ResultsTotal fat percentage was negatively associated with visuospatial skills (P=0.002) and visual memory (P=0.012). Insulin resistance (homeostatic model assessment of insulin resistance) was also negatively associated with these domains (P=0.05 and trend, P=0.06, respectively). Total testosterone levels were negatively associated with executive function and verbal learning and memory (P=0.04 for each), but free testosterone was not. Sex hormone-binding globulin (SHBG) was also inversely associated with performance in these domains (P=0.015 and trend, P=0.09, respectively). In a stepwise regression model including percentage fat, homeostatic model assessment of insulin resistance, SHBG, and free testosterone, SHBG was the only variable selected for executive function (P=0.05) and showed a trend for verbal learning and memory (P=0.09).
ConclusionsAdiposity and insulin resistance were associated with worse function in visual domains. An unexpected negative association is reported between SHBG and cognitive measures, which seemed to be independent of free testosterone levels.
C1 [Bove, Riley M.] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
[Bove, Riley M.; Bredella, Miriam A.; Sherman, Janet C.; Miller, Karen K.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gerweck, Anu V.; Miller, Karen K.] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA.
[Mancuso, Sarah M.; Sherman, Janet C.] Massachusetts Gen Hosp, Dept Psychiat, Psychol Assessment Ctr, Boston, MA 02114 USA.
[Bredella, Miriam A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
RP Miller, KK (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA.; Miller, KK (reprint author), Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA.
EM kkmiller@partners.org; kkmiller@partners.org
FU National Institutes of Health [R01 HL-077674, K23 RR-23090, K24
HL092902-03, UL1 RR-025758]; Harvard Catalyst/The Harvard Clinical and
Translational Science Center (National Center for Research Resources);
Harvard Catalyst/The Harvard Clinical and Translational Science Center
(National Center for Advancing Translational Sciences, National
Institutes of Health) [UL1 TR001102]; Harvard University
FX This research was supported by National Institutes of Health awards: R01
HL-077674, K23 RR-23090, K24 HL092902-03, and UL1 RR-025758. This work
was conducted with support from Harvard Catalyst/The Harvard Clinical
and Translational Science Center (National Center for Research Resources
and the National Center for Advancing Translational Sciences, National
Institutes of Health Award UL1 TR001102) and financial contributions
from Harvard University and its affiliated academic health care centers.
NR 40
TC 2
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U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD APR
PY 2016
VL 24
IS 4
BP 954
EP 961
DI 10.1002/oby.21415
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA DI6MM
UT WOS:000373613200028
PM 26880680
ER
PT J
AU Hou, SS
Bacskai, BJ
Kumar, ATN
AF Hou, Steven S.
Bacskai, Brian J.
Kumar, Anand T. N.
TI Optimal estimator for tomographic fluorescence lifetime multiplexing
SO OPTICS LETTERS
LA English
DT Article
ID CONTRAST
AB We use the model resolution matrix to analytically derive an optimal Bayesian estimator for multiparameter inverse problems that simultaneously minimizes inter-parameter cross talk and the total reconstruction error. Application of this estimator to time-domain diffuse fluorescence imaging shows that the optimal estimator for lifetime multiplexing is identical to a previously developed asymptotic time-domain (ATD) approach, except for the inclusion of a diagonal regularization term containing decay amplitude uncertainties. We show that, while the optimal estimator and ATD provide zero cross talk, the optimal estimator provides lower reconstruction error, while ATD results in superior relative quantitation. The framework presented here is generally applicable to other multiplexing problems where the simultaneous and accurate relative quantitation of multiple parameters is of interest. (C) 2016 Optical Society of America
C1 [Hou, Steven S.; Kumar, Anand T. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
[Hou, Steven S.; Bacskai, Brian J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Unit, Charlestown, MA 02129 USA.
RP Kumar, ATN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA.
EM ankumar@nmr.mgh.harvard.edu
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB) [R01
EB000768, R01 EB015325]
FX National Institute of Biomedical Imaging and Bioengineering (NIBIB) (R01
EB000768, R01 EB015325).
NR 13
TC 1
Z9 1
U1 2
U2 3
PU OPTICAL SOC AMER
PI WASHINGTON
PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA
SN 0146-9592
EI 1539-4794
J9 OPT LETT
JI Opt. Lett.
PD APR 1
PY 2016
VL 41
IS 7
BP 1352
EP 1355
DI 10.1364/OL.41.001352
PG 4
WC Optics
SC Optics
GA DI0ZI
UT WOS:000373225400012
PM 27192234
ER
PT J
AU Crema, MD
Roemer, FW
Li, L
Rosen, LB
Dudley, A
Alexander, RC
Guermazi, A
AF Crema, M. D.
Roemer, F. W.
Li, L.
Rosen, L. B.
Dudley, A.
Alexander, R. C.
Guermazi, A.
TI SEMIQUANTITATIVE AND QUANTITATIVE METHODS FOR THE ASSESSMENT OF
SYNOVITIS IN KNEE OSTEOARTHRITIS USING NON ENHANCED AND
GADOLINIUM-ENHANCED MRI
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the Osteoarthritis-Research-Society-International
(OARSI) on Osteoarthritis
CY MAR 31-APR 03, 2016
CL Amsterdam, NETHERLANDS
SP Osteoarthritis Res Soc Int
C1 [Crema, M. D.; Roemer, F. W.; Guermazi, A.] Boston Univ, Boston, MA 02215 USA.
[Li, L.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Rosen, L. B.] Flex Pharma, Boston, MA USA.
[Dudley, A.] AstraZeneca NeuroSci Innovat Med, Cambridge, MA USA.
[Alexander, R. C.] Pfizer NeuroSci, Cambridge, MA USA.
NR 0
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 1063-4584
EI 1522-9653
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD APR
PY 2016
VL 24
SU S
MA 453
BP S269
EP S269
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA DI5KW
UT WOS:000373538800483
ER
PT J
AU Wink, AE
Niu, J
Felson, DT
Nevitt, MC
Lewis, CE
Torner, J
Brown, CA
Shakoor, N
Sharma, L
Gross, KD
AF Wink, A. E.
Niu, J.
Felson, D. T.
Nevitt, M. C.
Lewis, C. E.
Torner, J.
Brown, C. A.
Shakoor, N.
Sharma, L.
Gross, K. D.
TI STRUCTURAL AND SENSORIMOTOR CORRELATES OF VARUS KNEE THRUST DURING
WALKING: THE MULTICENTER OSTEOARTHRITIS STUDY
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the Osteoarthritis-Research-Society-International
(OARSI) on Osteoarthritis
CY MAR 31-APR 03, 2016
CL Amsterdam, NETHERLANDS
SP Osteoarthritis Res Soc Int
C1 [Wink, A. E.; Niu, J.; Felson, D. T.; Brown, C. A.; Gross, K. D.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Nevitt, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Lewis, C. E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Torner, J.] Univ Iowa, Iowa City, IA USA.
[Shakoor, N.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Sharma, L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gross, K. D.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
NR 0
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 1063-4584
EI 1522-9653
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD APR
PY 2016
VL 24
SU S
MA 140
BP S89
EP S90
PG 2
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA DI5KW
UT WOS:000373538800170
ER
PT J
AU Wink, AE
Gross, KD
Brown, CA
Niu, J
Torner, J
Lewis, CE
Nevitt, MC
Guermazi, A
Roemer, FW
Sharma, L
Felson, DT
AF Wink, A. E.
Gross, K. D.
Brown, C. A.
Niu, J.
Torner, J.
Lewis, C. E.
Nevitt, M. C.
Guermazi, A.
Roemer, F. W.
Sharma, L.
Felson, D. T.
TI RELATION OF VARUS KNEE THRUST DURING WALKING TO RISK OF INCIDENT AND
PROGRESSIVE MRI LESIONS: THE MULTICENTER OSTEOARTHRITIS STUDY
SO OSTEOARTHRITIS AND CARTILAGE
LA English
DT Meeting Abstract
CT World Congress of the Osteoarthritis-Research-Society-International
(OARSI) on Osteoarthritis
CY MAR 31-APR 03, 2016
CL Amsterdam, NETHERLANDS
SP Osteoarthritis Res Soc Int
C1 [Wink, A. E.; Gross, K. D.; Brown, C. A.; Niu, J.; Guermazi, A.; Roemer, F. W.; Felson, D. T.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Gross, K. D.] Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA.
[Torner, J.] Univ Iowa, Iowa City, IA USA.
[Lewis, C. E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Nevitt, M. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Sharma, L.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1063-4584
EI 1522-9653
J9 OSTEOARTHR CARTILAGE
JI Osteoarthritis Cartilage
PD APR
PY 2016
VL 24
SU S
MA 36
BP S29
EP S29
PG 1
WC Orthopedics; Rheumatology
SC Orthopedics; Rheumatology
GA DI5KW
UT WOS:000373538800066
ER
PT J
AU Bergroth, E
Aakula, M
Korppi, M
Remes, S
Kivisto, JE
Piedra, PA
Camargo, CA
Jartti, T
AF Bergroth, Eija
Aakula, Matilda
Korppi, Matti
Remes, Sami
Kivisto, Juho E.
Piedra, Pedro A.
Camargo, Carlos A., Jr.
Jartti, Tuomas
TI Post-bronchiolitis Use of Asthma Medication A Prospective 1-year
Follow-up Study
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE bronchiolitis; long-term; respiratory syncytial virus; rhinovirus;
treatment
ID RESPIRATORY SYNCYTIAL VIRUS; DAY-CARE ATTENDANCE; LENGTH-OF-STAY;
EARLY-LIFE; ALLERGIC SENSITIZATION; RHINOVIRUS ILLNESSES; CHILDHOOD
ASTHMA; WHEEZING EPISODE; YOUNG-CHILDREN; VIRAL-ETIOLOGY
AB Background: Our aim was to evaluate the association between viral findings during bronchiolitis and the use of asthma controller medication (primary outcome) and systemic corticosteroids (secondary outcome) during the first post-bronchiolitis year.
Methods: We enrolled 408 children hospitalized for bronchiolitis at <24 months of age in a prospective, 3-center, 1-year follow-up study in Finland. Viruses were detected with polymerase chain reaction in nasopharyngeal aspirates. The parents underwent a structured interview during hospitalization. Twelve months later, the use of asthma medication was asked in a structured questionnaire. Multivariable logistic regression was used for statistical analysis.
Results: In total, 365 (89%) children completed the 1-year follow-up. The use of long-term asthma controller medication was highest in the rhinovirus-positive group (61% vs. 15% in respiratory syncytial virus-positive group; adjusted odd ratios, 7.5; 95% confidence interval: 3.7-15.3), followed by children negative for both respiratory syncytial virus and rhinovirus (36%; adjusted odd ratios, 2.6; 95% confidence interval: 1.3-5.3). Likewise, rhinovirus etiology was associated with more courses of systemic corticosteroids during the follow-up. The main findings were similar in a subset of infants aged <12 months with first wheezing.
Conclusions: Children hospitalized for rhinovirus-positive bronchiolitis used long-term asthma controller medication more often than those hospitalized for rhinovirus-negative bronchiolitis during first year after hospitalization.
C1 [Bergroth, Eija; Remes, Sami] Kuopio Univ Hosp, Dept Pediat, SF-70210 Kuopio, Finland.
[Bergroth, Eija] Cent Hosp Cent Finland, Dept Pediat, Keskussairaalantie 19, Jyvaskyla 40620, Finland.
[Aakula, Matilda; Jartti, Tuomas] Turku Univ Hosp, Dept Pediat, FIN-20520 Turku, Finland.
[Korppi, Matti; Kivisto, Juho E.] Tampere Univ, Ctr Child Hlth Res, FIN-33101 Tampere, Finland.
[Korppi, Matti; Kivisto, Juho E.] Tampere Univ Hosp, Tampere, Finland.
[Kivisto, Juho E.] Tampere Univ Hosp, Allergy Ctr, Tampere, Finland.
[Kivisto, Juho E.] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA.
[Piedra, Pedro A.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA.
RP Bergroth, E (reprint author), Cent Hosp Cent Finland, Dept Pediat, Keskussairaalantie 19, Jyvaskyla 40620, Finland.
EM bergroth@student.uef.fi
FU Kerttu and Kalle Viik Foundation (Kuopio, Finland); EVO; Academy of
Finland (Helsinki, Finland); Finnish Medical Foundation (Helsinki,
Finland); Sigrid Juselius Foundation (Helsinki, Finland); Foundation for
pediatric research (Helsinki, Finland)
FX E.B. received funding from Kerttu and Kalle Viik Foundation (Kuopio,
Finland) and received EVO funding. T.J. received funding from the
Academy of Finland, the Finnish Medical Foundation, the Sigrid Juselius
Foundation and the Foundation for pediatric research (all in Helsinki,
Finland). The authors have no other funding or conflicts of interest to
disclose.
NR 46
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD APR
PY 2016
VL 35
IS 4
BP 363
EP 368
DI 10.1097/INF.0000000000001017
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA DH5PL
UT WOS:000372843600001
PM 26658529
ER
PT J
AU Eberlin, KR
Kobraei, EM
Upton, J
AF Eberlin, Kyle R.
Kobraei, Edward M.
Upton, Joseph, III
TI Reply: Salvage Palmar Fasciectomy following Initial Treatment with
Collagenase Clostridium Histolyticum
SO PLASTIC AND RECONSTRUCTIVE SURGERY
LA English
DT Letter
C1 [Eberlin, Kyle R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA.
[Kobraei, Edward M.; Upton, Joseph, III] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Plast Surg, Boston, MA 02215 USA.
RP Eberlin, KR (reprint author), Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Wang Ambulatory Care Ctr 435,15 Parkman St, Boston, MA 02114 USA.
EM keberlin@mgh.harvard.edu
NR 2
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 0032-1052
EI 1529-4242
J9 PLAST RECONSTR SURG
JI Plast. Reconstr. Surg.
PD APR
PY 2016
VL 137
IS 4
BP 761E
EP 762E
DI 10.1097/PRS.0000000000001997
PG 2
WC Surgery
SC Surgery
GA DI8XD
UT WOS:000373784800001
PM 26741890
ER
PT J
AU Mayer, VL
McDonough, K
Seligman, H
Mitra, N
Long, JA
AF Mayer, Victoria L.
McDonough, Kevin
Seligman, Hilary
Mitra, Nandita
Long, Judith A.
TI Food insecurity, coping strategies and glucose control in low-income
patients with diabetes
SO PUBLIC HEALTH NUTRITION
LA English
DT Article
DE Diabetes; Nutrition; Vulnerable populations; Socio-economic factors;
Disease management
ID NUTRITION ASSISTANCE PROGRAM; OF-THE-LITERATURE; GLYCEMIC CONTROL;
DIETARY QUALITY; ADULTS; HEALTH; MANAGEMENT; OBESITY; PARTICIPANTS;
SUFFICIENCY
AB Objective: To examine the relationship between food insecurity and coping strategies (actions taken to manage economic stress) hypothesized to worsen glucose control in patients with diabetes.
Design: Using a cross-sectional telephone survey and clinical data, we compared food-insecure and food-secure individuals in their use of coping strategies. Using logistic regression models, we then examined the association between poor glucose control (glycated Hb, HbA1c >= 8.0 %), food insecurity and coping strategies.
Setting: An urban medical centre, between June and December 2013.
Subjects: Four hundred and seven adults likely to be low income (receiving Medicaid or uninsured and/or residing in a zip code with >30 % of the population below the federal poverty level) with type 2 diabetes.
Results: Of respondents, 40.5 % were food insecure. A significantly higher percentage of the food-insecure group reported use of most examined coping strategies, including foregone medical care, participation in the Supplemental Nutrition Assistance Program (SNAP)) and use of emergency food programmes. Food insecurity was associated with poor glucose control (OR=2.23; 95 % CI 1.22, 4.10); coping strategies that were more common among the food insecure were not associated with poor glucose control. Among the food insecure, receipt of SNAP was associated with lower risk of poor glucose control (OR=0.27; 95 % CI 0.09, 0.80).
Conclusions: While food insecurity was associated with poor glucose control, most examined coping strategies did not explain this relationship. However, receipt of SNAP among food-insecure individuals was associated with better diabetes control, suggesting that such programmes may play a role in improving health.
C1 [Mayer, Victoria L.] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA.
[Mayer, Victoria L.] Icahn Sch Med Mt Sinai, Dept Med, Div Gen Internal Med, New York, NY 10029 USA.
[McDonough, Kevin] Univ Penn, Sch Arts & Sci, Philadelphia, PA 19104 USA.
[Seligman, Hilary] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Mitra, Nandita] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Mitra, Nandita; Long, Judith A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA.
[Long, Judith A.] Univ Penn, Dept Med, Perelman Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA.
[Long, Judith A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA.
RP Mayer, VL (reprint author), Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, 1 Gustave L Levy Pl,Box 1077, New York, NY 10029 USA.; Mayer, VL (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Gen Internal Med, New York, NY 10029 USA.
EM victoria.mayer@mountsinai.org
FU Division of General Internal Medicine Matt Slap Award from the Perelman
School of Medicine at the University of Pennsylvania; National
Institutes of Health Institutional Training Grant
[5-T32-HP-100296-20-00]; Empire Clinical Research Investigator Program
FX V.L.M. was supported with funding from the Division of General Internal
Medicine Matt Slap Award from the Perelman School of Medicine at the
University of Pennsylvania and the National Institutes of Health
Institutional Training Grant 5-T32-HP-100296-20-00. She is currently
supported by the Empire Clinical Research Investigator Program
(Investigator Dr Carol Horowitz). The funders had no role in the design,
analysis, or writing of this article.Principal
NR 52
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U1 3
U2 9
PU CAMBRIDGE UNIV PRESS
PI CAMBRIDGE
PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND
SN 1368-9800
EI 1475-2727
J9 PUBLIC HEALTH NUTR
JI Public Health Nutr.
PD APR
PY 2016
VL 19
IS 6
BP 1103
EP 1111
DI 10.1017/S1368980015002323
PG 9
WC Public, Environmental & Occupational Health; Nutrition & Dietetics
SC Public, Environmental & Occupational Health; Nutrition & Dietetics
GA DI7US
UT WOS:000373708100019
PM 26328922
ER
PT J
AU Jensen, M
Murphy, V
Mattes, J
Gibson, P
Carmargo, C
AF Jensen, M.
Murphy, V
Mattes, J.
Gibson, P.
Carmargo, Jr C.
TI MATERNAL SERUM VITAMIN D LEVELS >= 75 NMOL/L DURING PREGNANCY ARE
ASSOCIATED WITH FEWER ADVERSE RESPIRATORY OUTCOMES IN INFANTS AT 12
MONTHS OF AGE
SO RESPIROLOGY
LA English
DT Meeting Abstract
C1 [Jensen, M.; Murphy, V; Mattes, J.; Gibson, P.] Univ Newcastle, Ctr Asthma & Resp Dis, Callaghan, NSW 2308, Australia.
[Carmargo, Jr C.] Massachusetts Gen Hosp, Emergency Med Network, Boston, MA 02114 USA.
[Gibson, P.] John Hunter Hosp, Dept Resp & Sleep Med, New Lambton Hts, NSW, 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 1323-7799
EI 1440-1843
J9 RESPIROLOGY
JI Respirology
PD APR
PY 2016
VL 21
SU 2
SI SI
MA TO 061
BP 51
EP 51
PG 1
WC Respiratory System
SC Respiratory System
GA DH9FS
UT WOS:000373102400103
ER
PT J
AU Chan, A
Stewart, A
Foster, J
Mitchell, E
Camargo, C
Harrison, J
AF Chan, A.
Stewart, A.
Foster, J.
Mitchell, E.
Camargo, Jr C.
Harrison, J.
TI ETHNICITY AND AGE AT DIAGNOSIS PREDICT PREVENTER ADHERENCE IN CHILDREN
WITH ASTHMA
SO RESPIROLOGY
LA English
DT Meeting Abstract
C1 [Chan, A.; Harrison, J.] Univ Auckland, Sch Pharm, Fac Med & Hlth Sci, Auckland 1, New Zealand.
[Stewart, A.] Univ Auckland, Fac Med & Hlth Sci, Sch Populat Hlth, Epidemiol & Biostat, Auckland 1, New Zealand.
[Foster, J.] Univ Sydney, Woolcock Inst Med Res, Sydney, NSW 2006, Australia.
[Mitchell, E.] Univ Auckland, Sch Med, Fac Med & Hlth Sci, Dept Pediat Child & Youth Hlth, Auckland, New Zealand.
[Camargo, Jr C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, 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 1323-7799
EI 1440-1843
J9 RESPIROLOGY
JI Respirology
PD APR
PY 2016
VL 21
SU 2
SI SI
MA TO 140
BP 92
EP 92
PG 1
WC Respiratory System
SC Respiratory System
GA DH9FS
UT WOS:000373102400186
ER
PT J
AU Stone, WS
Mesholam-Gately, RI
Giuliano, AJ
Woodberry, KA
Addington, J
Bearden, CE
Cadenhead, KS
Cannon, TD
Cornblatt, BA
Mathalon, DH
McGlashan, TH
Perkins, DO
Tsuang, MT
Walker, EF
Woods, SW
McCarley, RW
Heinssen, R
Green, MF
Nuechterlein, K
Seidman, LJ
AF Stone, William S.
Mesholam-Gately, Raquelle I.
Giuliano, Anthony J.
Woodberry, Kristen A.
Addington, Jean
Bearden, Carrie E.
Cadenhead, Kristin S.
Cannon, Tyrone D.
Cornblatt, Barbara A.
Mathalon, Daniel H.
McGlashan, Thomas H.
Perkins, Diana O.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
McCarley, Robert W.
Heinssen, Robert
Green, Michael F.
Nuechterlein, Keith
Seidman, Larry J.
TI Healthy adolescent performance on the MATRICS Consensus Cognitive
Battery (MCCB): Developmental data from two samples of volunteers
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Healthy controls; Adolescents; MATRICS Consensus Cognitive Battery;
Psychosis; Clinical high risk; Schizophrenia; Cognition
ID IQ-ADJUSTED NORMS; ONSET SCHIZOPHRENIA; NEUROCOGNITIVE BATTERY; SPECTRUM
DISORDERS; CHILDHOOD-ONSET; ADULT-ONSET; FOLLOW-UP; PSYCHOSIS; MEMORY;
STANDARDIZATION
AB The MATRICS Consensus Cognitive Battery (MCCB) fills a significant need for a standardized battery of cognitive tests to use in clinical trials for schizophrenia in adults aged 20-59. A need remains, however, to develop norms for younger individuals, who also show elevated risks for schizophrenia. Toward this end, we assessed performance in healthy adolescents. Baseline MCCB, reading and IQ data were obtained from healthy controls (ages 12-19) participating in two concurrent NIMH-funded studies: North American Prodromal Longitudinal Study phase 2 (NAPLS-2; n = 126) and Boston Center for Intervention Development and Applied Research (CIDAR; n = 13). All MCCB tests were administered except the Managing Emotions subtest from the Mayer-Salovey-Caruso Emotional Intelligence Test. Data were collected from 8 sites across North America. MCCB scores were presented in four 2-year age cohorts as T-scores for each test and cognitive domain, and analyzed for effects of age and sex. Due to IQ differences between age-grouped subsamples, IQ served as a covariate in analyses. Overall and sex-based raw scores for individual MCCB tests are presented for each age-based cohort. Adolescents generally showed improvement with age in most MCCB cognitive domains, with the clearest linear trends in Attention/Vigilance and Working Memory. These control data show that healthy adolescence is a dynamic period for cognitive development that is marked by substantial improvement in MCCB performance through the 12-19 age range. They also provide healthy comparison raw scores to facilitate clinical evaluations of adolescents, including those at risk for developing psychiatric disorders such as schizophrenia-related conditions. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Stone, William S.; Mesholam-Gately, Raquelle I.; Woodberry, Kristen A.; Seidman, Larry J.] Massachusetts Mental Hlth Ctr, 75 Fenwood Rd, Boston, MA 02115 USA.
[Stone, William S.; Mesholam-Gately, Raquelle I.; Woodberry, Kristen A.; Seidman, Larry J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA.
[Giuliano, Anthony J.] Worcester Recovery Ctr & Hosp, Dept Psychol, Worcester, MA USA.
[Addington, Jean] Univ Calgary, Hotchkiss Brain Inst, Dept Psychiat, Calgary, AB T2N 1N4, Canada.
[Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Biobehavioral Sci & Psychol, Los Angeles, CA USA.
[Cadenhead, Kristin S.] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA.
[Cannon, Tyrone D.] Yale Univ, Dept Psychol, New Haven, CT USA.
[Cannon, Tyrone D.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
[Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, Ctr Behav Gen, Inst Genom Med, La Jolla, CA 92093 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychiat & Psychol, Atlanta, GA 30322 USA.
[McCarley, Robert W.] Harvard Univ, Sch Med, Brockton VA Med Ctr, Dept Psychiat, Brockton, MA 02401 USA.
[Heinssen, Robert] NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA.
[Green, Michael F.] Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehavioral Sci, Los Angeles, CA USA.
[Green, Michael F.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
[Nuechterlein, Keith] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA.
[Seidman, Larry J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA.
RP Stone, WS (reprint author), Massachusetts Mental Hlth Ctr, 75 Fenwood Rd, Boston, MA 02115 USA.
EM wstone@bidmc.Harvard.edu
FU National Institute of Mental Health [U01MH0818902, U01MH081984,
P50MH066286, U01MH082022, U01MH081857, U01MH082004, U01MH081928,
U01MH081988, U01MH066160, P50MH080272]; Commonwealth Research Center of
the Massachusetts Department of Mental Health [SCDMH82101008006];
Harvard Catalyst; Harvard Clinical and Translational Science Center
Harvard Catalyst Clinical Research Center at Beth Israel Deaconess
Medical Center; Harvard University Clinical and Translational Science
Center Research Unit (National Center for Research Resources and the
National Center for Advancing Translational Sciences, National
Institutes of Health) [1UL1 TR001102-01]
FX National Institute of Mental Health grants (U01MH0818902 to T.D.C.,
U01MH081984 to J.M.A., P50MH066286 to C.E.B., U01MH082022 to K.S.C.,
U01MH081857 to B.A.C., U01MH082004 to D.O.P., U01MH081928 to L.J.S.,
U01MH081988 to E.F.W., U01MH066160 to S.W.W., P50MH080272 to R.W.M.) and
the Commonwealth Research Center of the Massachusetts Department of
Mental Health (SCDMH82101008006 to L.J.S.). This work was also conducted
with support from Harvard Catalyst, The Harvard Clinical and
Translational Science Center Harvard Catalyst Clinical Research Center
at Beth Israel Deaconess Medical Center, A Harvard University Clinical
and Translational Science Center Research Unit (National Center for
Research Resources and the National Center for Advancing Translational
Sciences, National Institutes of Health Award 1UL1 TR001102-01 financial
contributions from Harvard University and its affiliated academic health
care centers). The content is solely the responsibility of the authors
and does not necessarily represent the official views of Harvard
Catalyst, Harvard University and its affiliated academic health care
centers, or the National Institutes of Health.
NR 60
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U1 4
U2 9
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 APR
PY 2016
VL 172
IS 1-3
BP 106
EP 113
DI 10.1016/j.schres.2016.02.003
PG 8
WC Psychiatry
SC Psychiatry
GA DI5GY
UT WOS:000373528100017
PM 26896388
ER
PT J
AU Pierre, JM
Gandal, M
Son, M
AF Pierre, Joseph M.
Gandal, Michael
Son, Maya
TI Cannabis-induced psychosis associated with high potency "wax dabs"
SO SCHIZOPHRENIA RESEARCH
LA English
DT Article
DE Marijuana; Tetrahydrocannabinol; Cannabis; Cannabis oil; Cannabis wax;
Cannabis-induced psychosis, catatonia
ID MARIJUANA; DANGERS; RISK
AB With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes. Published by Elsevier B.V.
C1 [Pierre, Joseph M.; Gandal, Michael] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Pierre, Joseph M.] VA Greater Los Angeles Healthcare Syst, Dept Vet Affairs, Los Angeles, CA USA.
[Son, Maya] Univ Vermont, Coll Med, Burlington, VT USA.
RP Pierre, JM (reprint author), 11301 Wilshire Blvd,Bldg 210 Room15, Los Angeles, CA 90073 USA.
EM joseph.pierre2@va.gov
NR 10
TC 2
Z9 2
U1 4
U2 11
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 APR
PY 2016
VL 172
IS 1-3
BP 211
EP 212
DI 10.1016/j.schres.2016.01.056
PG 2
WC Psychiatry
SC Psychiatry
GA DI5GY
UT WOS:000373528100034
PM 26876313
ER
PT J
AU Jain, IH
Zazzeron, L
Goli, R
Alexa, K
Schatzman-Bone, S
Dhillon, H
Goldberger, O
Peng, J
Shalem, O
Sanjana, NE
Zhang, F
Goessling, W
Zapol, WM
Mootha, VK
AF Jain, Isha H.
Zazzeron, Luca
Goli, Rahul
Alexa, Kristen
Schatzman-Bone, Stephanie
Dhillon, Harveen
Goldberger, Olga
Peng, Jun
Shalem, Ophir
Sanjana, Neville E.
Zhang, Feng
Goessling, Wolfram
Zapol, Warren M.
Mootha, Vamsi K.
TI Hypoxia as a therapy for mitochondrial disease
SO SCIENCE
LA English
DT Article
ID TUMOR-SUPPRESSOR PROTEIN; HIPPEL-LINDAU PROTEIN; COMPLEX-I DEFICIENCY;
INDUCIBLE FACTOR; OXYGEN-CONSUMPTION; LEIGH-SYNDROME; HUMAN-CELLS;
INHIBITION; ADAPTATION; DISORDERS
AB Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction.
C1 [Jain, Isha H.; Goli, Rahul; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Mootha, Vamsi K.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Jain, Isha H.; Goli, Rahul; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Mootha, Vamsi K.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.
[Jain, Isha H.; Goli, Rahul; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Mootha, Vamsi K.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.
[Jain, Isha H.; Goli, Rahul; Dhillon, Harveen; Goldberger, Olga; Peng, Jun; Shalem, Ophir; Sanjana, Neville E.; Zhang, Feng; Goessling, Wolfram; Mootha, Vamsi K.] Broad Inst Harvard & MIT, Cambridge, MA USA.
[Zazzeron, Luca; Zapol, Warren M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Alexa, Kristen; Schatzman-Bone, Stephanie; Goessling, Wolfram] Harvard Univ, Brigham & Womens Hosp, Div Genet, Sch Med, Boston, MA 02115 USA.
[Shalem, Ophir; Sanjana, Neville E.; Zhang, Feng] McGovern Inst Brain Res, Cambridge, MA USA.
[Shalem, Ophir; Sanjana, Neville E.; Zhang, Feng] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA.
[Shalem, Ophir; Sanjana, Neville E.; Zhang, Feng] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Goessling, Wolfram] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA.
[Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA USA.
RP Mootha, VK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Mootha, VK (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA.; Mootha, VK (reprint author), Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA.; Mootha, VK (reprint author), Broad Inst Harvard & MIT, Cambridge, MA USA.
EM vamsi@hms.harvard.edu
OI Goessling, Wolfram/0000-0001-9972-1569
FU Department of Energy Computational Science Graduate Fellowship Program
[DE-FG02-97ER25308]; National Institutes of Health (NIH) through a NHGRI
[K99-HG008171]; Simons Center for the Social Brain at the Massachusetts
Institute of Technology; NIH through NIMH [5DP1-MH100706,
1R01-MH110049]; NIDDK [5R01DK097768-03]; NSF; New York Stem Cell;
Simons, Paul G. Allen Family Foundation; Vallee Foundation; NIH
[R01DK090311, R24OD017870]
FX We thank W. Kaelin Jr. and members of the Mootha lab for valuable
feedback; R. Sharma, M. Ferrari, A. Rogers, and the MGH animal facility
for assistance with experiments; and F. van Eeden for Tg(phd3::EGFP)
zebrafish. I.H.J. is supported by the Department of Energy Computational
Science Graduate Fellowship Program (grant DE-FG02-97ER25308). N.E.S. is
supported by the National Institutes of Health (NIH) through a NHGRI
Pathway to Independence Award (K99-HG008171) and a postdoctoral
fellowship from the Simons Center for the Social Brain at the
Massachusetts Institute of Technology. F. Z. is supported by NIH through
NIMH (grants 5DP1-MH100706 and 1R01-MH110049) and NIDDK (grant
5R01DK097768-03); a Waterman Award from NSF; the New York Stem Cell,
Simons, Paul G. Allen Family, and Vallee Foundations; and B. Metcalfe.
F. Z. is a New York Stem Cell Foundation Robertson Investigator. W. G.
is supported by NIH grants R01DK090311 and R24OD017870 and is a Pew
Scholar in the Biomedical Sciences. This work was supported by a gift
from the Marriott Mitochondrial Disorders Research Fund (V. K. M.) and a
gift in memory of Daniel Garland (V. K. M.). V. K. M. is an Investigator
of the Howard Hughes Medical Institute. V. K. M. is a founder of and
paid scientific advisor for Raze Therapeutics. W. G. is a paid
consultant for FATE Therapeutics. F. Z. is a founder of and a scientific
advisor for Editas Medicine and a scientific advisor for Horizon
Discovery. V. K. M., I. H. J., L. Z., and W. M. Z. are listed as
inventors on a patent application filed by Massachusetts General
Hospital related to technology reported in this paper on the use of
hypoxia and the hypoxia response in the treatment of mitochondrial
dysfunction. F.Z., O.S., and N.E.S. are listed as inventors on a patent
application (PCT/US2013/074800) filed by The Broad Institute/MIT related
to the genome-scale CRISPR knockout screening technology used in this
study. The CRISPR knockout library is available through a Uniform
Biological Materials Transfer Agreement from Addgene. The Ndufs4 KO mice
were a kind gift of R. Palmiter and are available under a materials
transfer agreement with the University of Washington, Seattle.
NR 40
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U1 16
U2 45
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD APR 1
PY 2016
VL 352
IS 6281
BP 54
EP 61
DI 10.1126/science.aad9642
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DH8JP
UT WOS:000373039600033
PM 26917594
ER
PT J
AU Robinson, TM
O'Donnell, PV
Fuchs, EJ
Luznik, L
AF Robinson, Tara M.
O'Donnell, Paul V.
Fuchs, Ephraim J.
Luznik, Leo
TI Haploidentical bone marrow and stem cell transplantation: experience
with post-transplantation cyclophosphamide
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
DE Haploidentical; Bone marrow transplant; Post-transplant
cyclophosphamide; GVHD prophylaxis
ID TOTAL-BODY IRRADIATION; HLA-IDENTICAL SIBLINGS; UNRELATED DONOR
TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; VERSUS-HOST-DISEASE;
HEMATOLOGIC MALIGNANCIES; HIGH-RISK; PHASE-II; ALDEHYDE DEHYDROGENASE;
PROGENITOR CELLS
AB Allogeneic blood or bone marrow transplantation (BMT) is a potentially curative therapy for high-risk hematologic malignancies not curable by standard chemotherapy, but the procedure is limited by the availability of human leukocyte antigen-matched donors for many patients, as well as toxicities including graft-versus-host disease (GVHD). Our group has developed the use of high-dose post-transplantation cyclophosphamide (PTCy) to selectively remove alloreactive T cells without compromising engraftment. This protocol has allowed for successful transplantation of human leukocyte antigen (HLA)-haploidentical (haplo) grafts, thus expanding the donor pool for the many patients who would not otherwise be a candidate for this life-saving procedure. In this review we will summarize the data that led to the development of PTCy, then focus on the outcomes of haploBMT trials with PTCy across different transplant platforms for patients with malignant hematologic diseases, and finally we will discuss emerging evidence that suggests equivalency of haploBMT with PTCy compared with more traditional transplants. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Robinson, Tara M.; Fuchs, Ephraim J.; Luznik, Leo] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Robinson, Tara M.; Fuchs, Ephraim J.; Luznik, Leo] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[O'Donnell, Paul V.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Luznik, L (reprint author), 1650 Orleans St, Baltimore, MD 21287 USA.
EM luznile@jhmi.edu
FU NCI NIH HHS [P01 CA015396]
NR 60
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U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD APR
PY 2016
VL 53
IS 2
BP 90
EP 97
DI 10.1053/j.seminhematol.2016.01.005
PG 8
WC Hematology
SC Hematology
GA DI5QU
UT WOS:000373554500007
PM 27000732
ER
PT J
AU Kekre, N
Antin, JH
AF Kekre, Natasha
Antin, Joseph H.
TI Cord blood versus haploidentical stem cell transplantation for
hematological malignancies
SO SEMINARS IN HEMATOLOGY
LA English
DT Article
DE Umbilical cord blood; Haploidentical; Transplantation
ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; ALTERNATIVE DONOR
TRANSPLANTATION; 1ST COMPLETE REMISSION; UNRELATED DONORS; HIGH-RISK;
POSTTRANSPLANTATION CYCLOPHOSPHAMIDE; ADULTS; OUTCOMES; GRAFTS
AB Umbilical cord blood (UCB) and haploidentical donor stem cell sources represent common alternative donor strategies used when a matched sibling donor (MRD) or matched unrelated donor (MUD) is not available for hematopoietic stem cell transplantation (HSCT). Both donor sources require less stringent human leukocyte antigen (HLA) matching and thereby increase the donor pool for patients without a complete HLA-matched donor. Although a randomized trial comparing these donor sources is ongoing, currently available comparisons rely on observational data and small phase II trials. In hematologic malignancies, both donor sources offer the chance of eradicating disease, albeit with different results for engraftment time, graft failure, graft-versus-host disease (GVHD), transplant-related mortality (TRM), and relapse risk. This review focuses on comparing those outcomes and providing clinicians with evidence to help guide the decision between these alternative donor sources. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Kekre, Natasha] Ottawa Hosp, Div Hematol, Ottawa, ON, Canada.
[Antin, Joseph H.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
RP Antin, JH (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM jantin@partners.org
NR 37
TC 2
Z9 2
U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0037-1963
EI 1532-8686
J9 SEMIN HEMATOL
JI Semin. Hematol.
PD APR
PY 2016
VL 53
IS 2
BP 98
EP 102
DI 10.1053/j.seminhematol.2016.01.007
PG 5
WC Hematology
SC Hematology
GA DI5QU
UT WOS:000373554500008
PM 27000733
ER
PT J
AU Stowkowy, J
Liu, L
Cadenhead, KS
Cannon, TD
Cornblatt, BA
McGlashan, TH
Perkins, DO
Seidman, LJ
Tsuang, MT
Walker, EF
Woods, SW
Bearden, CE
Mathalon, DH
Addington, J
AF Stowkowy, Jacqueline
Liu, Lu
Cadenhead, Kristin S.
Cannon, Tyrone D.
Cornblatt, Barbara A.
McGlashan, Thomas H.
Perkins, Diana O.
Seidman, Larry J.
Tsuang, Ming T.
Walker, Elaine F.
Woods, Scott W.
Bearden, Carrie E.
Mathalon, Daniel H.
Addington, Jean
TI Early traumatic experiences, perceived discrimination and conversion to
psychosis in those at clinical high risk for psychosis
SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
LA English
DT Article
DE Clinical high risk; Psychosis; Trauma; Perceived discrimination;
Prodrome; Risk
ID ULTRA-HIGH-RISK; CHILDHOOD TRAUMA; PRODROMAL-SYMPTOMS; CANNABIS USE;
SCHIZOPHRENIA; INDIVIDUALS; HISTORY; COHORT; METAANALYSIS; NETHERLANDS
AB There is evidence to suggest that both early traumatic experiences and perceived discrimination are associated with later onset of psychosis. Less is known about the impact these two factors may have on conversion to psychosis in those who are at clinical high risk (CHR) of developing psychosis. The purpose of this study was to determine if trauma and perceived discrimination were predictors of conversion to psychosis.
The sample consisted of 764 individuals who were at CHR of developing psychosis and 280 healthy controls. All participants were assessed on past trauma, bullying and perceived discrimination.
Individuals at CHR reported significantly more trauma, bullying and perceived discrimination than healthy controls. Only perceived discrimination was a predictor of later conversion to psychosis.
Given that CHR individuals are reporting increased rates of trauma and perceived discrimination, these should be routinely assessed, with the possibility of offering interventions aimed at ameliorating the impact of past traumas as well as improving self-esteem and coping strategies in an attempt to reduce perceived discrimination.
C1 [Stowkowy, Jacqueline; Liu, Lu; Addington, Jean] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Dept Psychiat, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada.
[Cadenhead, Kristin S.; Tsuang, Ming T.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Cornblatt, Barbara A.] Zucker Hillside Hosp, Dept Psychiat, Long Isl City, NY USA.
[Cannon, Tyrone D.; McGlashan, Thomas H.; Woods, Scott W.] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA.
[Perkins, Diana O.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA.
[Seidman, Larry J.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Seidman, Larry J.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Walker, Elaine F.] Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Dept Psychiat & Psychol, Los Angeles, CA USA.
[Bearden, Carrie E.] Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA USA.
[Mathalon, Daniel H.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
RP Stowkowy, J (reprint author), Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Dept Psychiat, 3280 Hosp Dr NW, Calgary, AB T2N 4Z6, Canada.
EM stowkowy@ucalgary.ca; jmadding@ucalgary.ca
FU National Institute of Mental Health [U01MH081984, U01 MH081928, P50
MH080272, R01 MH60720, U01 MH082022, K24 MH76191, U01MH081902,
U01MH082004-01A1, U01MH081988, U01MH082022, UO1 MH081857-05]; National
Institute of Mental Health (Commonwealth of Massachusetts)
[SCDMH82101008006]
FX This study was supported by the National Institute of Mental Health
(Grant U01MH081984 to Dr Addington; Grants U01 MH081928; P50 MH080272;
Commonwealth of Massachusetts SCDMH82101008006 to Dr Seidman; Grants R01
MH60720, U01 MH082022 and K24 MH76191 to Dr Cadenhead; Grant U01MH081902
to Dr Cannon; Grant U01MH082004-01A1 to Dr Perkins; Grant U01MH081988 to
Dr Walker; Grant U01MH082022 to Dr Woods; and UO1 MH081857-05 Grant to
Dr Cornblatt. The NIMH had no further role in study design; in the
collection, analysis and interpretation of data; in the writing of the
report; and in the decision to submit the paper for publication.
NR 30
TC 3
Z9 3
U1 5
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0933-7954
EI 1433-9285
J9 SOC PSYCH PSYCH EPID
JI Soc. Psychiatry Psychiatr. Epidemiol.
PD APR
PY 2016
VL 51
IS 4
BP 497
EP 503
DI 10.1007/s00127-016-1182-y
PG 7
WC Psychiatry
SC Psychiatry
GA DI7UN
UT WOS:000373707600003
PM 26851943
ER
PT J
AU Guo, LN
Nagle, KF
Heaton, JT
AF Guo, Liana
Nagle, Kathleen F.
Heaton, James T.
TI Generating tonal distinctions in Mandarin Chinese using an electrolarynx
with preprogrammed tone patterns
SO SPEECH COMMUNICATION
LA English
DT Article
DE Electrolarynx; Mandarin Chinese; Tonal control; Speech intelligibility
ID NORMAL LARYNGEAL; PERCEPTIONS; ESOPHAGEAL; SPEECH; DESIGN
AB An electrolarynx (EL) is a valuable rehabilitative option for individuals who have undergone laryngectomy, but current monotone ELs do not support controlled variations in fundamental frequency for producing tonal languages. The present study examined the production and perception of Mandarin Chinese using a customized hand-held EL driven by computer software to generate tonal distinctions (tonal EL). Four native Mandarin speakers were trained to articulate their speech coincidentally with preprogrammed tonal patterns in order to produce mono and di-syllabic words with a monotone EL and tonal EL. Three native Mandarin speakers later transcribed and rated the speech samples for intelligibility and acceptability. Results indicated that words produced using the tonal EL were significantly more intelligible and acceptable than those produced using the monotone EL. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Guo, Liana; Heaton, James T.] Massachusetts Gen Hosp, Inst Hlth Profess, 36 1st Ave, Boston, MA 02129 USA.
[Guo, Liana; Nagle, Kathleen F.; Heaton, James T.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
RP Heaton, JT (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA.
EM james.heaton@mgh.harvard.edu
OI Nagle, Kathleen/0000-0001-8916-3639
FU Christopher Norman Education Fund at the MGH Institute of Health
Professions [R42DC011212-02]
FX We would like to thank Mark Robertson at Griffin Laboratories for
providing the modified TruTone (R) EL used in the study. This project
was supported by a grant from the Christopher Norman Education Fund at
the MGH Institute of Health Professions and R42DC011212-02 to Mark
Robertson and James Heaton, Multiple PI. We would also like to
acknowledge Anthony Guarino, PhD of the Massachusetts General Hospital
Institute of Health Professions for help with statistical analysis, and
Jie (Kingsley) Yang, PhD for invaluable assistance as a native speaker
of Mandarin.
NR 15
TC 0
Z9 0
U1 2
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0167-6393
EI 1872-7182
J9 SPEECH COMMUN
JI Speech Commun.
PD APR
PY 2016
VL 78
BP 34
EP 41
DI 10.1016/j.specom.2016.01.002
PG 8
WC Acoustics; Computer Science, Interdisciplinary Applications
SC Acoustics; Computer Science
GA DI3SR
UT WOS:000373419300004
PM 26951783
ER
PT J
AU Tofler, GH
Massarob, J
O'Donnell, CJ
Wilson, PWF
Vasan, RS
Sutherland, PA
Meigs, JB
Levy, D
D'Agostino, RB
AF Tofler, G. H.
Massarob, J.
O'Donnell, C. J.
Wilson, P. W. F.
Vasan, R. S.
Sutherland, P. A.
Meigs, J. B.
Levy, D.
D'Agostino, R. B., Sr.
TI Plasminogen activator inhibitor and the risk of cardiovascular disease:
The Framingham Heart Study
SO THROMBOSIS RESEARCH
LA English
DT Article
DE Plasminogen activator inhibitor 1; Tissue plasminogen activator;
Myocardial infarction; Cardiovascular diseases
ID LEFT-VENTRICULAR HYPERTROPHY; LINKED-IMMUNOSORBENT-ASSAY;
CORONARY-ARTERY-DISEASE; MYOCARDIAL-INFARCTION; FIBRINOLYTIC FACTORS;
PLASMA; EVENTS; PAI-1; PREDICTION; WOMEN
AB Introduction: Although plasminogen activator inhibitor (PAI-1) plays a key regulatory role in fibrinolysis, it has not been clearly shown to independently predict cardiovascular disease (CVD) among individuals without prior CVD. We investigated, in the Framingham Heart Study offspring cohort, whether PAI-1 predicted CVD risk among individuals without prior CVD.
Methods: Plasma PAI-1 antigen and tissue plasminogen activator (TPA) antigen were measured in 3203 subjects without prior CVD between 1991 and 1995; average follow-up of 10 years. PAI-1 was remeasured 4 years after baseline, to determine the effect of serial change on risk.
Results: PAI-1 levels (mean +/- SD) were 29.1 ng/ml (19.2) versus 22.1 (16.5) for those and without incident CVD; p < 0.001, and TPA levels were 12.0 ng/ml (5.7) versus 9.0 (4.7); p < 0.001. PAI-1 and TPA antigen levels had a strong unadjusted linear relation with incident CVD (p < 0.001). After adjustment for conventional risk factors, the hazard ratios (HRs) for higher quartiles of PAI-1, compared with the lowest, were 1.9, 1.9, 2.6 (linear trend p=0.006), and 1.6, 1.6, 2.9 (p < 0.001) for TPA antigen. The adjusted HRs for increasing quartiles of serial change in PAI-1 at 4 years, compared with the lowest, were 0.9, 0.8, 1.3 (p=0.050). C statistic assessment showed that adding PAI-1 or TPA to conventional risk factors resulted in small increases in discrimination and modest reclassification of risk, which was statistically significant for TPA (net reclassification 6.8%, p = 0.037) but not PAI-1 (4.8%, p = 0.113).
Conclusion: PAI-1 and TPA antigen levels are predictive of CVD events after accounting for established risk factors. A serial increase in PAI-1 is associated with a further increase in risk. These findings support the importance of fibrinolytic potential in CVD. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Tofler, G. H.] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia.
[Massarob, J.; D'Agostino, R. B., Sr.] Boston Univ, Boston, MA 02215 USA.
[O'Donnell, C. J.; Vasan, R. S.; Sutherland, P. A.; Levy, D.] NHLBI, Framingham Heart Study, NIH, Bethesda, MD USA.
[O'Donnell, C. J.; Sutherland, P. A.; Levy, D.] NHLBI, Populat Sci Branch, NIH, Bethesda, MD USA.
[O'Donnell, C. J.; Meigs, J. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Wilson, P. W. F.] Emory Univ, Atlanta, GA 30322 USA.
RP Tofler, GH (reprint author), Royal N Shore Hosp, Dept Cardiol, St Leonards, NSW 2065, Australia.
EM Geoffrey.Tofler@health.nsw.gov.au
OI Ramachandran, Vasan/0000-0001-7357-5970
FU AHA [92011960]; National Institutes of Health [RO1-HL-48157]; National
Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195];
Ducker Bequest and Heart Research Australia
FX This work was supported by an AHA Grant-in-Aid (92011960), the National
Institutes of Health (RO1-HL-48157), the National Heart, Lung and Blood
Institute's Framingham Heart Study (Contract No. N01-HC-25195), and the
Ducker Bequest and Heart Research Australia.
NR 35
TC 5
Z9 5
U1 2
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0049-3848
J9 THROMB RES
JI Thromb. Res.
PD APR
PY 2016
VL 140
BP 30
EP 35
DI 10.1016/j.thromres.2016.02.002
PG 6
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DI8DX
UT WOS:000373732600005
PM 26896607
ER
PT J
AU Kokoye, Y
Ivanov, I
Cheng, QF
Matafonov, A
Dickeson, SK
Mason, S
Sexton, DJ
Renne, T
McCrae, K
Feener, EP
Gailani, D
AF Kokoye, Yasin
Ivanov, Ivan
Cheng, Qiufang
Matafonov, Anton
Dickeson, S. Kent
Mason, Shauna
Sexton, Daniel J.
Renne, Thomas
McCrae, Keith
Feener, Edward P.
Gailani, David
TI A comparison of the effects of factor XII deficiency and prekallikrein
deficiency on thrombus formation
SO THROMBOSIS RESEARCH
LA English
DT Article
DE Factor XII; Factor XIIa; Prekallikrein; alpha-Kallikrein; Thrombosis
ID COAGULATION-FACTOR-XII; MOLECULAR-WEIGHT KININOGEN; HUMAN
HAGEMAN-FACTOR; IN-VIVO; CONTACT ACTIVATION; BLOOD-COAGULATION; PLASMA
KALLIKREIN; SELECTIVE DEPLETION; MICE; INHIBITION
AB Studies with animal models implicate the plasma proteases factor XIIa (FXIIa) and alpha-kallikrein in arterial and venous thrombosis. As congenital deficiencies of factor XII ( FXII) or prekallikrein (PK), the zymogens of FXIIa and alpha-kallikrein respectively, do not cause bleeding disorders, inhibition of these enzymesmay have therapeutic benefit without compromising hemostasis. The relative contributions of FXIIa and alpha-kallikrein to thrombosis in animal models are not clear. We compared mice lacking FXII or PK to wild type mice in established models of arterial thrombosis. Wild type mice developed carotid artery occlusion when the vessel was exposed to a 3.5% solution of ferric chloride (FeCl3). FXII-deficient mice were resistant to occlusion at 5% FeCl3 and partially resistant at 10% FeCl3. PK-deficient mice were resistant at 3.5% FeCl3 and partially resistant at 5% FeCl3. Mice lacking high molecular weight kininogen, a cofactor for PK activation and activity, were also partially resistant to thrombosis at 5% FeCl3. Induction of carotid artery thrombosis with Rose Bengal was delayed in FXII-deficient mice compared to wild type or PK-deficient animals. In human plasma supplemented with silica, DNA or collagen to induce contact activation, an antibody to the FXIIa active site was more effective at preventing thrombin generation than an antibody to the alpha-kallikrein active site. Similarly, the FXIIa antibody was more effective at reducing fibrin formation in human blood flowing through collagen coated-tubes. The findings suggest that inhibitors of FXIIa will have more potent anti-thrombotic effects than inhibitors of alpha-kallikrein. (C) 2016 Elsevier Ltd. All rights reserved.
C1 [Kokoye, Yasin; Ivanov, Ivan; Cheng, Qiufang; Matafonov, Anton; Dickeson, S. Kent; Gailani, David] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Matafonov, Anton] Tomsk Polytech Univ, Dept Bioengn & Organ Chem, Tomsk, Russia.
[Mason, Shauna; Sexton, Daniel J.] Dyax Corp, Burlington, MA USA.
[Renne, Thomas] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Renne, Thomas] Univ Hosp, Stockholm, Sweden.
[Renne, Thomas] Univ Med Ctr Hamburg Eppendorf, Inst Clin Chem & Lab Med, Hamburg, Germany.
[McCrae, Keith] Cleveland Clin, Dept Hematol & Oncol, Cleveland, OH 44106 USA.
[Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA.
RP Gailani, D (reprint author), Vanderbilt Univ, Hematol Oncol Div, 777 Preston Res Bldg,2220 Pierce Ave, Nashville, TN USA.
EM dave.gailani@vanderbilt.edu
FU National Heart, Lung, and Blood Institute [HL81326, HL58837, HL089796];
National Institute of Neurological Disorders and Stroke [NS077006];
Vetenskapsradet [K2013-65X-21462-014-5]; German Research Society
[SFB877, SFB841]; European Research Council [ERC-StG-2012-311575_F-12]
FX The authors wish to acknowledge support from awards HL81326 and HL58837
(D. Gailani) and HL089796 to (K. McCrae) from the National Heart, Lung,
and Blood Institute; award NS077006 (E.P. Feener) from the National
Institute of Neurological Disorders and Stroke; and awards
K2013-65X-21462-014-5 from Vetenskapsradet, SFB877, TP A11 and SFB841,
TP B8 from the German Research Society, and ERC-StG-2012-311575_F-12
from the European Research Council (T. Renne).
NR 42
TC 5
Z9 5
U1 1
U2 4
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0049-3848
J9 THROMB RES
JI Thromb. Res.
PD APR
PY 2016
VL 140
BP 118
EP 124
DI 10.1016/j.thromres.2016.02.020
PG 7
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DI8DX
UT WOS:000373732600019
PM 26950760
ER
PT J
AU Leung, AM
Korevaar, TIM
Peeters, RP
Zoeller, RT
Kohrle, J
Duntas, LH
Brent, GA
Demeneix, BA
AF Leung, Angela M.
Korevaar, Tim I. M.
Peeters, Robin P.
Zoeller, R. Thomas
Koehrle, Josef
Duntas, Leonidas H.
Brent, Gregory A.
Demeneix, Barbara A.
TI Exposure to Thyroid-Disrupting Chemicals: A Transatlantic Call for
Action
SO THYROID
LA English
DT Editorial Material
C1 [Leung, Angela M.; Brent, Gregory A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol, Los Angeles, CA 90095 USA.
[Leung, Angela M.; Brent, Gregory A.] VA Greater Los Angeles Healthcare Syst, Div Endocrinol, Los Angeles, CA USA.
[Korevaar, Tim I. M.; Peeters, Robin P.] Erasmus MC, Generat R Study Grp, Rotterdam, Netherlands.
[Korevaar, Tim I. M.; Peeters, Robin P.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Korevaar, Tim I. M.; Peeters, Robin P.] Erasmus MC, Rotterdam Thyroid Ctr, Rotterdam, Netherlands.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
[Zoeller, R. Thomas] Univ Massachusetts, Program Mol & Cellular Biol, Amherst, MA 01003 USA.
[Koehrle, Josef] Charite, Inst Expt Endokrinol, D-13353 Berlin, Germany.
[Duntas, Leonidas H.] Univ Athens, Thyroid Unit, Evgenid Hosp, Athens, Greece.
[Demeneix, Barbara A.] Museum Natl Hist Nat, Dept Regulat Dev & Diversite Mol, Evolut Regulat Endocriniennes, F-75231 Paris, France.
RP Leung, AM (reprint author), VA Greater Angeles Healthcare Syst, Div Endocrinol 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA.
EM amleung@mednet.ucla.edu
OI Kohrle, Josef/0000-0002-9187-9078
FU NICHD NIH HHS [K23HD068552]
NR 4
TC 3
Z9 3
U1 2
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD APR 1
PY 2016
VL 26
IS 4
BP 479
EP 480
DI 10.1089/thy.2016.0077
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DI1DY
UT WOS:000373237400001
PM 26906244
ER
PT J
AU Su, HK
Wenig, BM
Haser, GC
Rowe, ME
Asa, SL
Baloch, Z
Du, E
Faquin, WC
Fellegara, G
Giordano, T
Ghossein, R
LiVolsi, VA
Lloyd, R
Mete, O
Ozbek, U
Rosai, J
Suster, S
Thompson, LD
Turk, AT
Urken, ML
AF Su, Henry K.
Wenig, Bruce M.
Haser, Grace C.
Rowe, Meghan E.
Asa, Sylvia L.
Baloch, Zubair
Du, Eugenie
Faquin, William C.
Fellegara, Giovanni
Giordano, Thomas
Ghossein, Ronald
LiVolsi, Virginia A.
Lloyd, Ricardo
Mete, Ozgur
Ozbek, Umut
Rosai, Juan
Suster, Saul
Thompson, Lester D.
Turk, Andrew T.
Urken, Mark L.
TI Inter-Observer Variation in the Pathologic Identification of Minimal
Extrathyroidal Extension in Papillary Thyroid Carcinoma
SO THYROID
LA English
DT Article
ID EXTRANODAL EXTENSION; LYMPH-NODES; WELL; CANCER
AB Background: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases.
Methods: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE.
Results: The overall strength of agreement for identifying mETE was slight (=0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (=0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (=0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE.
Conclusions: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists' interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.
C1 [Su, Henry K.; Haser, Grace C.; Rowe, Meghan E.] Thyroid Head & Neck Canc THANC Fdn, Dept Otolaryngol Head & Neck Surg, New York, NY 10003 USA.
[Wenig, Bruce M.] Mt Sinai Beth Israel, Dept Pathol, New York, NY USA.
[Urken, Mark L.] Mt Sinai Beth Israel, Dept Otolaryngol Head & Neck Surg, New York, NY USA.
[Asa, Sylvia L.; Mete, Ozgur] Toronto Gen Hosp, Dept Pathol, Lab Med Program, Toronto, ON, Canada.
[Baloch, Zubair; LiVolsi, Virginia A.] Univ Penn, Dept Pathol & Lab Med, Hosp, Philadelphia, PA 19104 USA.
[Du, Eugenie] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Otorhinolaryngol Head & Neck Surg, Bronx, NY 10467 USA.
[Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Fellegara, Giovanni; Rosai, Juan] Ctr Diagnost Italiano, Ctr Consulenze Anat Patolog Oncolog, Milan, Italy.
[Giordano, Thomas] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA.
[Ghossein, Ronald] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA.
[Lloyd, Ricardo] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.
[Ozbek, Umut] Mt Sinai Hosp, Populat Hlth Sci & Policy, New York, NY 10029 USA.
[Suster, Saul] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
[Thompson, Lester D.] Woodland Hills Med Ctr, Dept Pathol, Woodland Hills, CA USA.
[Turk, Andrew T.] New York Presbyterian Columbia, Dept Pathol, New York, NY USA.
RP Haser, GC (reprint author), Thyroid Head & Neck Canc THANC Fdn, 10 Union Sq East,Suite 5B, New York, NY 10003 USA.
EM ghaser@thancfoundation.org
FU Mount Sinai Health System
FX The authors would like to acknowledge the Mount Sinai Health System for
its generous support of this research project.
NR 18
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD APR 1
PY 2016
VL 26
IS 4
BP 512
EP 517
DI 10.1089/thy.2015.0508
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DI1DY
UT WOS:000373237400006
PM 26953223
ER
PT J
AU Greiman, A
Shah, J
Bhavsar, R
Armeson, K
Caulder, S
Jones, R
Keane, TE
Clarke, HS
Savage, SJ
AF Greiman, Alyssa
Shah, Jaimin
Bhavsar, Robin
Armeson, Kent
Caulder, Susan
Jones, Rabun
Keane, Thomas E.
Clarke, Harry S.
Savage, Stephen J.
TI Six Weeks of Fluoroquinolone Antibiotic Therapy for Patients With
Elevated Serum Prostate-specific Antigen Is Not Clinically Beneficial: A
Randomized Controlled Clinical Trial
SO UROLOGY
LA English
DT Article
ID PSA LEVELS; CANCER; BIOPSY; BENIGN; MARKER
AB OBJECTIVE To evaluate asymptomatic men with elevated serum prostate-specific antigen (PSA) to determine whether a 6-week course of fluoroquinolone antibiotics lowers serum PSA and affects recommendations for prostate biopsy.
MATERIALS AND METHODS A randomized, single-center prospective trial of 150 men with an initial elevated PSA was conducted. Patients were randomized to 6 weeks of ciprofloxacin or observation. Those patients with persistently elevated PSA were recommended to proceed with transrectal ultrasound-guided 12-core biopsy. Those with reduced PSA were offered transrectal ultrasound-guided biopsy but could opt to continue serial digital rectal examination/PSA. Patients were followed an average of 4.6 years to assess trends in PSA and biopsy results.
RESULTS Of 136 men who completed the trial, 63 were in the treatment and 73 were in the observation group. The average PSA change from baseline was borderline statistically significant with a change of -0.68 ng/mL in the treatment arm and 0.01 ng/mL in the observation arm (P = .052). Of those who underwent biopsy, prostate cancer was diagnosed in the first biopsy in 24 (63%) of the treatment vs 27 (52%) of the observation group (P = .60) over follow-up.
CONCLUSION In a cohort of asymptomatic men with elevated PSA, there was only a borderline statistically significant change in serum PSA between patients randomized to a 6-week course of fluoroquinolones vs observation, and there was no difference in positive prostate biopsy results. Our clinical recommendation is one should not treat patients with elevated serum PSA with antibiotics in the absence of clinical symptoms of prostatitis. Published by Elsevier Inc.
C1 [Greiman, Alyssa; Shah, Jaimin; Bhavsar, Robin; Armeson, Kent; Caulder, Susan; Jones, Rabun; Keane, Thomas E.; Clarke, Harry S.; Savage, Stephen J.] Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Urol, Urol Sect, 96 Jonathan Lucas St,CSB 644, Charleston, SC 29425 USA.
RP Greiman, A (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Urol, Urol Sect, 96 Jonathan Lucas St,CSB 644, Charleston, SC 29425 USA.
EM greiman@musc.edu
NR 30
TC 1
Z9 1
U1 2
U2 3
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 APR
PY 2016
VL 90
BP 32
EP 37
DI 10.1016/j.urology.2015.11.046
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA DI4JT
UT WOS:000373466900017
PM 26802800
ER
PT J
AU Vasilevskis, EE
Kripalani, S
Ong, MK
Rosenthal, JT
Longnecker, DE
Harmon, B
Hohmann, SF
Wright, K
Black, JT
AF Vasilevskis, Eduard E.
Kripalani, Sunil
Ong, Michael K.
Rosenthal, J. Thomas
Longnecker, David E.
Harmon, Brian
Hohmann, Samuel F.
Wright, Kelly
Black, Jeanne T.
TI Variability in Implementation of Interventions Aimed at Reducing
Readmissions Among Patients With Heart
SO ACADEMIC MEDICINE
LA English
DT Article
ID HOSPITAL READMISSIONS; 30-DAY READMISSIONS; RANDOMIZED-TRIALS;
TRANSITIONAL CARE; FAILURE PATIENTS; PALLIATIVE CARE; HEALTH-CARE;
FOLLOW-UP; STRATEGIES; RATES
AB Purpose To highlight teaching hospitals' efforts to reduce readmissions by describing interventions implemented to improve care transitions for heart failure (HF) patients and the variability in implemented HF-specific and care transition interventions.
Method In 2012, the authors surveyed a network of 17 teaching hospitals to capture information about the number, type, stage of implementation, and structure of 4 HF-specific and 21 care transition (predischarge, bridging, and postdischarge) interventions implemented to reduce readmissions among patients with HF. The authors summarized data using descriptive statistics, including the mean number of interventions implemented and the frequency and stage of specific interventions, and descriptive plots of the structure of two common interventions (multidisciplinary rounds and follow-up telephone calls).
Results Sixteen hospitals (94%) responded. The number and stage of implementation of the HF-specific and care transition interventions implemented varied across institutions. The mean number of interventions at an advanced stage of implementation (i.e., implemented for 75% of HF patients on the cardiology service or on all services) was 10.9 (standard deviation = 4.3). Overall, predischarge interventions were more common than bridging or postdischarge interventions. There was variability in the personnel involved in multidisciplinary rounds and in the processes/content of follow-up telephone calls.
Conclusions Teaching hospitals have implemented a wide range of interventions aimed at reducing hospital readmissions, but there is substantial variability in the types, stages, and structure of their interventions. This heterogeneity highlights the need for collaborative efforts to improve understanding of intervention effectiveness.
C1 [Vasilevskis, Eduard E.] Vanderbilt Univ, Dept Med, Div Gen Internal Med & Publ Hlth, Med,Sect Hosp Med, Nashville, TN 37232 USA.
[Vasilevskis, Eduard E.] VA Tennessee Valley Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA.
[Kripalani, Sunil] Vanderbilt Univ, Dept Med, Div Gen Internal Med & Publ Hlth, Ctr Clin Qual & Implementat Res,Sect Hosp Med, Nashville, TN 37232 USA.
[Ong, Michael K.] Univ Calif Los Angeles, Dept Med, Med, Los Angeles, CA 90024 USA.
[Ong, Michael K.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Rosenthal, J. Thomas] Univ Calif Los Angeles Hlth Syst, Los Angeles, CA USA.
[Longnecker, David E.] Univ Penn, Anesthesiol, Philadelphia, PA 19104 USA.
[Longnecker, David E.] Coalit Transform Adv Care, Washington, DC USA.
[Harmon, Brian] Childrens Hosp & Clin Minnesota, Minneapolis, MN USA.
[Hohmann, Samuel F.] Univ HealthSyst Consortium, Comparat Data & Informat Res, Chicago, IL USA.
[Hohmann, Samuel F.] Rush Univ, Dept Hlth Syst Management, Chicago, IL 60612 USA.
[Wright, Kelly] Vanderbilt Univ, Div Gen Internal Med & Publ Hlth, Sect Hosp Med, Dept Med, Nashville, TN 37232 USA.
[Black, Jeanne T.] Cedars Sinai Hlth Syst, Hlth Policy & Program Evaluat, Los Angeles, CA USA.
RP Vasilevskis, EE (reprint author), Vanderbilt Univ, Med Ctr, 1215 21st Ave S,6006 Med Ctr East NT, Nashville, TN 37232 USA.
EM eduard.vasilevskis@vanderbilt.edu
FU National Institutes of Health [K23 AG040157]; Tennessee Valley Geriatric
Research, Education and Clinical Center (GRECC); Robert Wood Johnson
Foundation [RWJF 67627]
FX Funding for E.E. Vasilevskis was provided by the National Institutes of
Health (K23 AG040157) and the Tennessee Valley Geriatric Research,
Education and Clinical Center (GRECC). The Variations Collaborative
Study Group additionally received support from the Robert Wood Johnson
Foundation (RWJF 67627).
NR 40
TC 2
Z9 2
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1040-2446
EI 1938-808X
J9 ACAD MED
JI Acad. Med.
PD APR
PY 2016
VL 91
IS 4
BP 522
EP 529
PG 8
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA DH6XW
UT WOS:000372936400027
PM 26579793
ER
PT J
AU Hser, YI
Evans, E
Huang, D
Weiss, R
Saxon, A
Carroll, KM
Woody, G
Liu, D
Wakim, P
Matthews, AG
Hatch-Maillette, M
Jelstrom, E
Wiest, K
McLaughlin, P
Ling, W
AF Hser, Yih-Ing
Evans, Elizabeth
Huang, David
Weiss, Robert
Saxon, Andrew
Carroll, Kathleen M.
Woody, George
Liu, David
Wakim, Paul
Matthews, Abigail G.
Hatch-Maillette, Mary
Jelstrom, Eve
Wiest, Katharina
McLaughlin, Paul
Ling, Walter
TI Long-term outcomes after randomization to buprenorphine/naloxone versus
methadone in a multi-site trial
SO ADDICTION
LA English
DT Article
DE Buprenorphine; methadone; opioid dependence; longitudinal; outcomes;
opioid use; mortality
ID MAINTENANCE THERAPY; OPIOID DEPENDENCE; RETENTION; ADDICTION;
METHAMPHETAMINE; PERSPECTIVES; MEDICATION; HEALTH; ENTRY; USERS
AB AimsTo compare long-term outcomes among participants randomized to buprenorphine or methadone.
Design, Setting and ParticipantsFollow-up was conducted in 2011-14 of 1080 opioid-dependent participants entering seven opioid treatment programs in the United States between 2006 and 2009 and randomized (within each program) to receive open-label buprenorphine/naloxone or methadone for up to 24weeks; 795 participants completed in-person interviews (similar to 74% follow-up interview rate) covering on average 4.5years.
MeasurementsOutcomes were indicated by mortality and opioid use. Covariates included demographics, site, cocaine use and treatment experiences.
FindingsMortality was not different between the two randomized conditions, with 23 (3.6%) of 630 participants randomized to buprenorphine having died versus 26 (5.8%) of 450 participants randomized to methadone. Opioid use at follow-up was higher among participants randomized to buprenorphine relative to methadone [42.8 versus 31.7% positive opioid urine specimens, P<0.01, effect size (h)=0.23 (0.09, 0.38); 5.8days versus 4.4days of past 30-day heroin use, P<0.05, effect size (d)=0.14 (0.00, 0.28)]. Opioid use during the follow-up period by randomization condition was also significant (F-(7,F-39600)=3.16; P<0.001) due mainly to less treatment participation among participants randomized to buprenorphine than methadone. Less opioid use was associated with both buprenorphine and methadone treatment (relative to no treatment); no difference was found between the two treatments. Individuals who are white or used cocaine at baseline responded better to methadone than to buprenorphine.
ConclusionsThere are few differences in long-term outcomes between buprenorphine and methadone treatment for opioid dependence, and treatment with each medication is associated with a strong reduction in opioid use.
C1 [Hser, Yih-Ing; Evans, Elizabeth; Huang, David; Weiss, Robert; Ling, Walter] Univ Calif Los Angeles, Los Angeles, CA USA.
[Saxon, Andrew] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Carroll, Kathleen M.] Yale Univ, Sch Med, New Haven, CT USA.
[Woody, George] Univ Penn, Philadelphia, PA 19104 USA.
[Liu, David; Wakim, Paul] NIDA, Bethesda, MD 20892 USA.
[Matthews, Abigail G.; Jelstrom, Eve] Emmes Corp, Rockville, MD USA.
[Hatch-Maillette, Mary] Univ Washington, Seattle, WA 98195 USA.
[Wiest, Katharina] CODA Inc, Portland, OR USA.
[McLaughlin, Paul] Hartford Dispensary, Hartford, CT USA.
RP Hser, YI (reprint author), Univ Calif Los Angeles, Integrated Subst Abuse Programs, 11075 Santa Monica Blvd,Suite 200, Los Angeles, CA USA.
EM yhser@ucla.edu
FU National Institute on Drug Abuse (NIDA) through the Clinical Trials
Network (CTN) [U10 DA01714, U10 DA 015815, U10 DA13038, U10 DA13043, U10
DA13045]; NIDA [P30DA016383]
FX The corresponding author, Yih-Ing Hser, has full access to all of the
data in the study and takes responsibility for the integrity of the data
and the accuracy of the data analysis. Sincere appreciation to our
participating networks: the Pacific Northwest Node and Evergreen
Treatment Services; the Western States Node and CODA Inc. and Bi-Valley
Medical Clinic; the New England Node and Connecticut Counseling Centers
and Yale and Hartford Dispensary; the Delaware Valley Node and NET
Steps; the Pacific Region Node and Matrix Institute; and the EMMES
Corporation (CCC); the CCTN and NIDA. The main study funding was
provided by the National Institute on Drug Abuse (NIDA) through the
Clinical Trials Network (CTN) through a series of grants provided to
each participating node: the Pacific Northwest Node (U10 DA01714); the
Western States Node (U10 DA 015815); the New England Node (U10 DA13038);
the Delaware Valley Node (U10 DA13043); and he Pacific Region Node (U10
DA13045). Funding was also provided by NIDA through grant number
P30DA016383.
NR 29
TC 2
Z9 2
U1 5
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD APR
PY 2016
VL 111
IS 4
BP 695
EP 705
DI 10.1111/add.13238
PG 11
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA DH6NM
UT WOS:000372907400022
PM 26599131
ER
PT J
AU Kao, SY
Soares, VYR
Kristiansen, AG
Stankovic, KM
AF Kao, Shyan-Yuan
Soares, Vitor Y. R.
Kristiansen, Arthur G.
Stankovic, Konstantina M.
TI Activation of TRAIL-DR5 pathway promotes sensorineural degeneration in
the inner ear
SO AGING CELL
LA English
DT Article
DE TRAIL; DR5; OPG; cochlea; hair cells; spiral ganglion neuron
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; HEARING-LOSS; INDUCED APOPTOSIS;
LIGAND TRAIL; CELL-DEATH; COCHLEAR NERVE; HAIR-CELLS; EXPRESSION;
RECEPTOR
AB Tumor necrosis factor (TNF) family cytokines are important mediators of inflammation. Elevated levels of serum TNF- are associated with human sensorineural hearing loss via poorly understood mechanisms. We demonstrate, for the first time, expression of TNF-related apoptosis-inducing ligand (TRAIL) and its signaling death receptor 5 (DR5) in the murine inner ear and show that exogenous TRAIL can trigger hair cell and neuronal degeneration, which can be partly prevented with DR5-blocking antibodies.
C1 [Kao, Shyan-Yuan; Soares, Vitor Y. R.; Kristiansen, Arthur G.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA.
[Kao, Shyan-Yuan; Soares, Vitor Y. R.; Kristiansen, Arthur G.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Soares, Vitor Y. R.; Stankovic, Konstantina M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
[Stankovic, Konstantina M.] Harvard Univ, Sch Med, Program Speech & Hearing Biosci & Technol, Boston, MA 02115 USA.
RP Stankovic, KM (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA.
EM konstantina_stankovic@meei.harvard.edu
FU Department of Defense [W81XWH-15-1-0472]; Bertarelli Foundation; Nancy
Sayles Day Foundation; Lauer Tinnitus Research Center
FX This study was supported by grants from the Department of Defense grant
W81XWH-15-1-0472, the Bertarelli Foundation, the Nancy Sayles Day
Foundation, and the Lauer Tinnitus Research Center (all to K.M.S.).
NR 45
TC 2
Z9 2
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1474-9718
EI 1474-9726
J9 AGING CELL
JI Aging Cell
PD APR
PY 2016
VL 15
IS 2
BP 301
EP 308
DI 10.1111/acel.12437
PG 8
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DH6DF
UT WOS:000372880500011
PM 26791792
ER
PT J
AU Magidson, JF
Li, X
Mimiaga, MJ
Moore, AT
Srithanaviboonchai, K
Friedman, RK
Limbada, M
Hughes, JP
Cummings, V
Gaydos, CA
Elharrar, V
Celentano, D
Mayer, KH
Safren, SA
AF Magidson, Jessica F.
Li, Xin
Mimiaga, Matthew J.
Moore, Ayana T.
Srithanaviboonchai, Kriengkrai
Friedman, Ruth Khalili
Limbada, Mohammad
Hughes, James P.
Cummings, Vanessa
Gaydos, Charlotte A.
Elharrar, Vanessa
Celentano, David
Mayer, Kenneth H.
Safren, Steven A.
TI Antiretroviral Medication Adherence and Amplified HIV Transmission Risk
Among Sexually Active HIV-Infected Individuals in Three Diverse
International Settings
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Adherence; Treatment as prevention; HIV transmission; Amplified risk;
Alcohol use; MSM; Biomedical prevention
ID CARE; PREVALENCE; BEHAVIORS; THERAPY; SCALE; MEN
AB Successful biomedical prevention/treatment-as-prevention (TasP) requires identifying individuals at greatest risk for transmitting HIV, including those with antiretroviral therapy (ART) nonadherence and/or 'amplified HIV transmission risk,' defined as condomless sex with HIV-uninfected/unknown-status partners when infectious (i.e., with detectable viremia or STI diagnosis according to Swiss criteria for infectiousness). This study recruited sexually-active, HIV-infected patients in Brazil, Thailand, and Zambia to examine correlates of ART nonadherence and 'amplified HIV transmission risk'. Lower alcohol use (OR = .71, p < .01) and higher health-related quality of life (OR = 1.10, p < .01) were associated with greater odds of ART adherence over and above region. Of those with viral load data available (in Brazil and Thailand only), 40 % met Swiss criteria for infectiousness, and 29 % had 'amplified HIV transmission risk.' MSM had almost three-fold (OR = 2.89, p < .001) increased odds of 'amplified HIV transmission risk' (vs. heterosexual men) over and above region. TasP efforts should consider psychosocial and contextual needs, particularly among MSM with detectable viremia.
C1 [Magidson, Jessica F.; Mimiaga, Matthew J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
[Li, Xin; Hughes, James P.] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Mimiaga, Matthew J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Mimiaga, Matthew J.; Mayer, Kenneth H.; Safren, Steven A.] Fenway Hlth, Fenway Inst, Boston, MA USA.
[Moore, Ayana T.] FHI360, Durham, NC USA.
[Srithanaviboonchai, Kriengkrai] Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand.
[Srithanaviboonchai, Kriengkrai] Chiang Mai Univ, Fac Med, Chiang Mai 50000, Thailand.
[Friedman, Ruth Khalili] Inst Pesquisa Clin Evandro Chagas, Rio De Janeiro, Brazil.
[Limbada, Mohammad] Ctr Infect Dis Res Zambia, Lusaka, Zambia.
[Hughes, James P.] Univ Washington, Seattle, WA 98195 USA.
[Cummings, Vanessa; Gaydos, Charlotte A.] Johns Hopkins Sch Med, Div Infect Dis, Dept Pathol & Med, Baltimore, MD USA.
[Elharrar, Vanessa] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Celentano, David] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Mayer, Kenneth H.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
[Safren, Steven A.] Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA.
RP Magidson, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA.
EM jmagidson@mgh.harvard.edu
OI Srithanaviboonchai, Kriengkrai/0000-0002-1683-4259
FU NIH [T32MH093310, K24MH094214]; Harvard University Center for AIDS
Research (HU CFAR) NIH [P30AI060354]; Division of AIDS (DAIDS), National
Institute of Allergy and Infectious Disease (NIAID), National Institute
on Drug Abuse (NIDA); National Institute of Mental Health (NIMH)
[UM1AI068619]
FX HPTN 063 was funded by the Division of AIDS (DAIDS), National Institute
of Allergy and Infectious Disease (NIAID), National Institute on Drug
Abuse (NIDA), and the National Institute of Mental Health (NIMH) under
Cooperative Agreement # UM1AI068619. The content of this article is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institutes of Health or The
HIV Prevention Trials Network. The authors would also like to
acknowledge the staff at the HPTN 063 study sites for their
contributions to the study. Additionally, Dr. Magidson's work on this
manuscript was supported by NIH Grant T32MH093310, and Dr. Safren was
supported by NIH Grant K24MH094214. Dr. Mayer and Dr. Safren were also
supported by the Harvard University Center for AIDS Research (HU CFAR)
NIH P30AI060354. This manuscript was supported by consultation from
other members of the HU CFAR Social and Behavioral Sciences Core.
NR 20
TC 2
Z9 2
U1 1
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD APR
PY 2016
VL 20
IS 4
BP 699
EP 709
DI 10.1007/s10461-015-1142-7
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA DH7HF
UT WOS:000372962700001
PM 26246068
ER
PT J
AU Colby, DJ
Oldenburg, CE
Nguyen, T
Closson, EF
Biello, KB
Mayer, KH
Mimiaga, MJ
AF Colby, Donn J.
Oldenburg, Catherine E.
Thi Nguyen
Closson, Elizabeth F.
Biello, Katie B.
Mayer, Kenneth H.
Mimiaga, Matthew J.
TI HIV, Hepatitis C, and Other Sexually Transmitted Infections Among Male
Sex Workers in Ho Chi Minh City, Vietnam
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV; Hepatitis C; Prevalence; Male sex work; Vietnam
ID TRANSACTIONAL SEX; RISK; STREET; MEN; ENVIRONMENT; ENGAGE; USERS; HANOI
AB There is little data on the burden of HIV and other infections that affect male sex workers (MSW) in Vietnam. We conducted behavioral and biological sexual health surveys with 300 MSW in Ho Chi Minh City. Generalized estimating equation models were built to assess factors associated with HIV, hepatitis C, and other sexually transmitted infections (STI). Of 300 MSW, 19 (6.3 %) were diagnosed seropositive for HIV, 11 (3.7 %) had hepatitis C, and 26 (8.7 %) had at least one prevalent STI. In a multivariable model, opiate use was significantly associated with HIV infection (aOR 6.46, 95 % CI 1.28-32.7) and hepatitis C (aOR = 19.6, 95 % CI 2.35-163.6). Alcohol dependency was associated with increased odds of hepatitis C (aOR = 4.79, 95 % CI 1.02-22.5) and decreased odds of other STI (aOR = 0.30, 95 % CI 0.10-0.97). These findings suggest that MSW in Vietnam would benefit from regular HIV and STI testing, as well as linkage to care and substance use rehabilitation services.
C1 [Colby, Donn J.] Thai Red Cross AIDS Res Ctr, SEARCH, 104 Rajdamri Rd, Bangkok 10330, Thailand.
[Colby, Donn J.] Ctr Appl Res Men & Hlth, Ho Chi Minh City, Vietnam.
[Oldenburg, Catherine E.; Biello, Katie B.; Mimiaga, Matthew J.] Harvard Univ, Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Oldenburg, Catherine E.; Closson, Elizabeth F.; Biello, Katie B.; Mayer, Kenneth H.; Mimiaga, Matthew J.] Fenway Community Hlth, Fenway Inst, Boston, MA USA.
[Thi Nguyen] Harvard Univ, Med Sch AIDS Initiat Vietnam, Ho Chi Minh City, Vietnam.
[Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
[Mayer, Kenneth H.] Harvard Univ, Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA.
[Mimiaga, Matthew J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
RP Colby, DJ (reprint author), Thai Red Cross AIDS Res Ctr, SEARCH, 104 Rajdamri Rd, Bangkok 10330, Thailand.; Colby, DJ (reprint author), Ctr Appl Res Men & Hlth, Ho Chi Minh City, Vietnam.
EM doctordonn@gmail.com
OI colby, donn/0000-0003-3931-5926
FU Harvard Catalyst - the Harvard Clinical and Translational Science
Center; National Institute of Drug Abuse T32 NRSA Grant [T32 DA0131911];
Harvard Global Health Institute Fellowship
FX This study was conducted with the support of a pilot Grant from Harvard
Catalyst - the Harvard Clinical and Translational Science Center (PIs:
DJC and MJM). CEO is supported by a National Institute of Drug Abuse T32
NRSA Grant (T32 DA0131911; PI: Flanigan) and by a Harvard Global Health
Institute Fellowship.
NR 24
TC 0
Z9 0
U1 3
U2 3
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD APR
PY 2016
VL 20
IS 4
BP 768
EP 775
DI 10.1007/s10461-015-1247-z
PG 8
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA DH7HF
UT WOS:000372962700009
PM 26563761
ER
PT J
AU Adams, GL
Mustapha, J
Gray, W
Hargus, NJ
Martinsen, BJ
Ansel, G
Jaff, MR
AF Adams, George L.
Mustapha, Jihad
Gray, William
Hargus, Nick J.
Martinsen, Brad J.
Ansel, Gary
Jaff, Michael R.
TI The LIBERTY study: Design of a prospective, observational, multicenter
trial to evaluate the acute and long-term clinical and economic outcomes
of real-world endovascular device interventions in treating peripheral
artery disease
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID CRITICAL LIMB ISCHEMIA; LOWER-EXTREMITY AMPUTATION; SUPERVISED EXERCISE;
INTERMITTENT CLAUDICATION; REVASCULARIZATION; REHABILITATION; STANDARDS;
THERAPY; CLEVER; TRENDS
AB Background Most peripheral artery disease (PAD) clinical device trials are supported by commercial manufacturers and designed for regulatory device approval, with extensive inclusion/exclusion criteria to support homogeneous patient populations. High-risk patients with advanced disease, including critical limb ischemia (CLI), are often excluded leading to difficulty in translating trial results into real-world clinical practice. As a result, physicians have no direct guidance regarding the use of endovascular devices. There is a need for objectively assessed studies to evaluate clinical, functional, and economic outcomes in PAD patient populations.
Study Design LIBERTY is a prospective, observational, multicenter study sponsored by Cardiovascular Systems Inc (St Paul, MN) to evaluate procedural and long-term clinical and economic outcomes of endovascular device interventions in patients with symptomatic lower extremity PAD. Approximately 1,200 patients will be enrolled and followed up to 5 years: 500 patients in the "Claudicant Rutherford 2-3" arm, 600 in the "CLI Rutherford 4-5" arm, and 100 in the "CLI Rutherford6" arm. The study will use 4 core laboratories for independent analysis and will evaluate the following: procedural and lesion success, rates of major adverse events, duplex ultrasound interpretations, wound status, quality of life, 6-minute walk test, and economic analysis. The LIBERTY Patient Risk Score(s) will be developed as a clinical predictor of outcomes to provide guidance for interventions in this patient population.
Conclusion LIBERTY will investigate real-world PAD patients treated with endovascular revascularization with rigorous study guidelines and independent oversight of outcomes. This study will provide observational, all-comer patient clinical data to guide future endovascular therapy.
C1 [Adams, George L.] Rex Healthcare, 4414 Lake Boone Trail,Suite 402, Raleigh, NC 27607 USA.
[Mustapha, Jihad] Metro Hlth Hosp, Wyoming, MI USA.
[Gray, William] Columbia Univ, Med Ctr, New York, NY USA.
[Hargus, Nick J.; Martinsen, Brad J.] Cardiovasc Syst Inc, St Paul, MN USA.
[Ansel, Gary] Riverside Methodist Hosp, Columbus, OH 43214 USA.
[Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Adams, GL (reprint author), Rex Healthcare, 4414 Lake Boone Trail,Suite 402, Raleigh, NC 27607 USA.
EM George.Adams@rexhealth.com
FU Cardiovascular Systems Inc.
FX Financial support for the study is provided by Cardiovascular Systems
Inc. The authors thank Ann Behrens, BS, and Zsuzsanna Igyarto, PhD, of
Cardiovascular Systems Inc, for editing and critical review of this
manuscript.
NR 23
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 APR
PY 2016
VL 174
BP 14
EP 21
DI 10.1016/j.ahj.2015.12.013
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DH1IV
UT WOS:000372538500005
PM 26995365
ER
PT J
AU Axon, RN
Gebregziabher, M
Everett, CJ
Heidenreich, P
Hunt, KJ
AF Axon, R. Neal
Gebregziabher, Mulugeta
Everett, Charles J.
Heidenreich, Paul
Hunt, Kelly J.
TI Dual health care system use is associated with higher rates of
hospitalization and hospital readmission among veterans with heart
failure
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID GUIDELINES PROGRAM; AMBULATORY-CARE; MEDICARE; OUTCOMES; INPATIENT;
MORTALITY; ADMISSION; SERVICES; REGRESSION; PATIENT
AB Background Heart failure (HF) frequently causes hospital admission and readmission. Patients receiving care from multiple providers and facilities (dual users) may risk higher health care utilization and worse health outcomes.
Methods To determine rates of emergency department (ED) visits, hospitalizations, and hospital readmissions relative to dual use among HF patients, we analyzed a retrospective cohort of 13,977 veterans with HF hospitalized at the Veterans Affairs (VA) or non-VA facilities from 2007 to 2011; we analyzed rates of acute health care utilization using zero-inflated negative binomial regression.
Results Compared to VA-only users and dual users, individuals receiving all of their ED and hospital care outside the VA tended to be older, more likely to be non-Hispanic white and married, and less likely to have high levels of service connected disability. Compared to VA-only users, dual users had significantly higher rates of ED visits for HF as a primary diagnosis (adjusted rate ratio 1.15, 95% CI 1.04-1.27), hospitalization for HF (adjusted rate ratio 1.4, 95% CI 1.26-1.56), hospital readmission after HF hospitalization (all cause) (1.46, 95% CI 1.30-1.65), and HF-specific hospital readmission after HF hospitalization (1.46, 95% CI 1.31-1.63). With the exception of hospitalization for any primary diagnosis, non-VA-only users had significantly lower rates of ED visits, hospitalization, and readmission compared to VA-only users.
Conclusions Dual use is associated with higher rates of health care utilization among patients with HF. Interventions should be devised to encourage continuity of care where possible and to improve the effectiveness and safety of dual use in instances where it is necessary or desired.
C1 [Axon, R. Neal; Gebregziabher, Mulugeta; Everett, Charles J.; Hunt, Kelly J.] Ralph H Johnson VA Med Ctr, Charleston Hlth Equ & Rural Outreach Innovat Ctr, Charleston, SC USA.
[Axon, R. Neal] Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA.
[Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Heidenreich, Paul] Stanford Univ, Med Ctr, Div Cardiol, VA Palo Alto Healthcare Syst, Palo Alto, CA 94304 USA.
RP Axon, RN (reprint author), 109 Bee St,Mail Code 111, Charleston, SC 29401 USA.
EM axon@musc.edu
OI Gebregziabher, Mulugeta/0000-0002-4826-481X
FU VA Health Services Research and Development [IIR 12-331]
FX VA Health Services Research and Development (IIR 12-331, Axon-PI).
NR 40
TC 0
Z9 0
U1 0
U2 2
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 APR
PY 2016
VL 174
BP 157
EP 163
DI 10.1016/j.ahj.2015.09.023
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DH1IV
UT WOS:000372538500023
PM 26995383
ER
PT J
AU Alinari, L
Gru, A
Quinion, C
Huang, Y
Lozanski, A
Lozanski, G
Poston, J
Venkataraman, G
Oak, E
Kreisel, F
Park, SI
Matthews, S
Abramson, JS
Lim, HI
Martin, P
Cohen, JB
Evens, A
Al-Mansour, Z
Singavi, A
Fenske, TS
Blum, KA
AF Alinari, Lapo
Gru, Alejandro
Quinion, Carl
Huang, Ying
Lozanski, Arletta
Lozanski, Gerard
Poston, Jacqueline
Venkataraman, Girish
Oak, Eunhye
Kreisel, Friederike
Park, Steven I.
Matthews, Stephanie
Abramson, Jeremy S.
Lim, Hana Iris
Martin, Peter
Cohen, Jonathon B.
Evens, Andrew
Al-Mansour, Zeina
Singavi, Arun
Fenske, Timothy S.
Blum, Kristie A.
TI De novo CD5+diffuse large B-cell lymphoma: Adverse outcomes with and
without stem cell transplantation in a large, multicenter, rituximab
treated cohort
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID CHEMOTHERAPY; CHOP; THERAPY; EXPRESSION
AB De novo CD5+ diffuse large B-cell lymphomas (DLBCL) are a distinct subgroup of DLBCL with poor prognosis. However the role of rituximab-containing therapy and salvage stem cell transplantation in this patients' population remain to be defined. We retrospectively reviewed clinical features and outcomes of 102 patients with de novo CD5+ DLBCL treated with rituximab-containing therapy at nine different institutions. By Hans' criteria, 64 patients had activated B-cell (ABC) subtype, 24 germinal center B-cell (GCB) subtype, and 14 were not evaluated. No patients had a myc translocation. Eighty-three patients were treated with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), 7 with rituximab, etoposide, cyclophosphamide, doxorubicin, vincristine, prednisone (R-EPOCH), and 6 with R-CHOP with methotrexate, 3 g/m(2). The overall response rate to front-line therapy was 85%. The 3-year progression free survival (PFS) and overall survival (OS) for all patients were 40 and 65%, respectively. The 3-year PFS for ABC- and GCB-subtypes was 34 and 45%, respectively. The 3-year OS for ABC- and GCB-subtypes was 62 and 67%, respectively. The median time to second treatment failure was 3 months and 1 month for ABC- and GCB-subtypes, respectively. Twenty of 28 (71%) transplanted patients with autologous, allogeneic, or both, relapsed. This study confirms the poor prognosis of de novo CD5+ DLBCL in a large multi-center cohort despite initial rituximab-containing chemotherapy and suggests that stem cell transplantation fails to salvage the majority of these patients. Approaches to prevent recurrence and/or novel therapies for relapsed disease are needed for this subgroup of DLBCL patients. Am. J. Hematol. 91:395-399, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Alinari, Lapo; Quinion, Carl; Huang, Ying; Lozanski, Arletta; Blum, Kristie A.] Ohio State Univ, Wexner Med Ctr, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
[Gru, Alejandro; Lozanski, Gerard] Ohio State Univ, Wexner Med Ctr, Dept Pathol, Div Hematopathol, Columbus, OH 43210 USA.
[Poston, Jacqueline] Univ Chicago, Dept Internal Med, Div Hematol, Chicago, IL 60637 USA.
[Venkataraman, Girish] Univ Chicago, Dept Pathol, Div Hematopathol, 5841 S Maryland Ave, Chicago, IL 60637 USA.
[Oak, Eunhye] Washington Univ, Sch Med, Dept Internal Med, Div Hematol, St Louis, MO 63110 USA.
[Kreisel, Friederike] Washington Univ, Sch Med, Dept Pathol, Div Hematopathol, St Louis, MO 63110 USA.
[Park, Steven I.; Matthews, Stephanie] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Internal Med, Div Hematol, Chapel Hill, NC 27599 USA.
[Abramson, Jeremy S.] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Div Hematol,Dept Internal Med,Ctr Lymphoma,Med Sc, Boston, MA 02114 USA.
[Lim, Hana Iris; Martin, Peter] Weill Cornell Med Coll, Dept Internal Med, Div Hematol, New York, NY USA.
[Cohen, Jonathon B.] Emory Univ, Winship Canc Ctr, Dept Internal Med, Div Hematol, Atlanta, GA 30322 USA.
[Evens, Andrew] Tufts Univ, Sch Med, Tufts Med Ctr, Div Hematol,Dept Internal Med, Boston, MA 02111 USA.
[Al-Mansour, Zeina] Univ Massachusetts, Sch Med, Dept Internal Med, Div Hematol, Worcester, MA USA.
[Singavi, Arun; Fenske, Timothy S.] Med Coll Wisconsin, Dept Internal Med, Div Hematol, Milwaukee, WI 53226 USA.
RP Alinari, L (reprint author), Ohio State Univ, Dept Internal Med, Div Hematol, Med Ctr, 320 W 10th Ave,406C-1 Starling Loving Hall, Columbus, OH 43210 USA.
EM Lapo.alinari@osumc.edu
FU NCI NIH HHS [K24 CA201524, U10 CA180838]
NR 22
TC 2
Z9 2
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD APR
PY 2016
VL 91
IS 4
BP 395
EP 399
DI 10.1002/ajh.24299
PG 5
WC Hematology
SC Hematology
GA DH8CN
UT WOS:000373021200014
PM 26800311
ER
PT J
AU Ghobrial, IM
Siegel, DS
Vij, R
Berdeja, JG
Richardson, PG
Neuwirth, R
Patel, CG
Zohren, F
Wolf, JL
AF Ghobrial, Irene M.
Siegel, David S.
Vij, Ravi
Berdeja, Jesus G.
Richardson, Paul G.
Neuwirth, Rachel
Patel, Chirag G.
Zohren, Fabian
Wolf, Jeffrey L.
TI TAK-228 (formerly MLN0128), an investigational oral dual TORC1/2
inhibitor: A phase I dose escalation study in patients with relapsed or
refractory multiple myeloma, non-Hodgkin lymphoma, or Waldenstrom's
macroglobulinemia
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID MTOR KINASE INHIBITOR; ADVANCED SOLID TUMORS; MAMMALIAN TARGET;
HEMATOLOGIC MALIGNANCIES; INTERNATIONAL WORKSHOP; RESPONSE CRITERIA;
PI3K INHIBITOR; PATIENTS PTS; RAPAMYCIN; CANCER
AB The PI3K/AKT/mTOR signaling pathways are frequently dysregulated in multiple human cancers, including multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Waldenstrom's macroglobulinemia (WM). This was the first clinical study to evaluate the safety, tolerability, maximal-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetics, and preliminary clinical activity of TAK-228, an oral TORC1/2 inhibitor, in patients with MM, NHL, or WM. Thirty-nine patients received TAK-228 once daily (QD) at 2, 4, 6, or 7 mg, or QD for 3 days on and 4 days off each week (QDx3d QW) at 9 or 12 mg, in 28-day cycles. The overall median age was 61.0 years (range 46-85); 31 patients had MM, four NHL, and four WM. Cycle 1 DLTs occurred in five QD patients (stomatitis, urticaria, blood creatinine elevation, fatigue, and nausea and vomiting) and four QDx3d QW patients (erythematous rash, fatigue, asthenia, mucosal inflammation, and thrombocytopenia). The MTDs were determined to be 4 mg QD and 9 mg QDx3d QW. Thirty-six patients (92%) reported at least one drug-related toxicity; the most common grade 3 drug-related toxicities were thrombocytopenia (15%), fatigue (10%), and neutropenia (5%). TAK-228 exhibited a dose-dependent increase in plasma exposure and no appreciable accumulation with repeat dosing; mean plasma elimination half-life was 6-8 hr. Of the 33 response-evaluable patients, one MM patient had a minimal response, one WM patient achieved partial response, one WM patient had a minor response, and 18 patients (14 MM, two NHL, and two WM) had stable disease. These findings encourage further studies including combination strategies. Am. J. Hematol. 91:400-405, 2016. (c) 2016 Wiley Periodicals, Inc.
C1 [Ghobrial, Irene M.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Siegel, David S.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Vij, Ravi] Washington Univ, Sch Med, Div Hematol & Oncol, St Louis, MO USA.
[Berdeja, Jesus G.] Sarah Cannon Res Inst, Nashville, TN USA.
[Neuwirth, Rachel] Millennium Pharmaceut Inc, Global Biostat, Cambridge, MA USA.
[Patel, Chirag G.] Millennium Pharmaceut Inc, Clin Pharmacol, Cambridge, MA USA.
[Zohren, Fabian] Millennium Pharmaceut Inc, Oncol Clin Res, Cambridge, MA USA.
[Wolf, Jeffrey L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.
EM irene_ghobrial@dfci.harvard.edu
NR 47
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD APR
PY 2016
VL 91
IS 4
BP 400
EP 405
DI 10.1002/ajh.24300
PG 6
WC Hematology
SC Hematology
GA DH8CN
UT WOS:000373021200015
PM 26800393
ER
PT J
AU Hill, SY
Jones, BL
Steinhauer, SR
Zezza, N
Stiffler, S
AF Hill, Shirley Y.
Jones, Bobby L.
Steinhauer, Stuart R.
Zezza, Nicholas
Stiffler, Scott
TI Longitudinal predictors of cannabis use and dependence in offspring from
families at ultra high risk for alcohol dependence and in control
families
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS
LA English
DT Article
DE CNR1; D2; cannabis use; cannabis abuse; cannabis dependence
ID RECEPTOR GENE CNR1; EVENT-RELATED POTENTIALS; LINKAGE-PHYSICAL MAP;
SUBSTANCE USE; P300 AMPLITUDE; MARIJUANA USE; DEVELOPMENTAL
TRAJECTORIES; HAPLOTYPE RECONSTRUCTION; GENOTYPE DATA; HUMAN GENOME
AB Cannabis use is common among adolescents. Identification of the factors associated with continued heavy use into young adulthood and development of cannabis abuse and dependence is of considerable importance. The role of familial risk for addiction and an associated endophenotype, P300 amplitude, has not previously been related to cannabis use and dependence. A prospective longitudinal study spanning childhood and young adulthood provided the opportunity for exploring these factors, along with genetic variation, in the cannabis use behaviors of 338 young adult offspring from high and low familial risk for alcohol dependence families (ages 19-30). P300 data were collected multiple times in childhood. The association between young adult patterns of cannabis use or cannabis abuse/dependence was tested with genetic variation in the cannabinoid gene, CNR1, the ANKK1-DRD2 gene, and childhood developmental trajectories of P300. Young adult patterns of cannabis use was characterized by three patterns: (i) no use throughout; (ii) declining use from adolescence through young adulthood; and (iii) frequent use throughout. Following the low P300 trajectory in childhood predicted cannabis abuse and dependence by young adulthood. A four SNP ANKK1-DRD2 haplotype (G-G-G-C) was found to be significantly associated with the frequency of use patterns (P=0.0008). Although CNR1 variation overall was not significantly associated with these patterns, among individuals with cannabis abuse/dependence the presence of one or both copies of the rs806368 A>G minor allele conferred a 5.4-fold increase (P=0.003) in the likelihood that they would be in the frequent and persistent use group rather than the declining use group. (c) 2016 Wiley Periodicals, Inc.
C1 [Hill, Shirley Y.; Jones, Bobby L.; Zezza, Nicholas; Stiffler, Scott] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA.
[Steinhauer, Stuart R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
RP Hill, SY (reprint author), Univ Pittsburgh, Dept Psychiat, Med Ctr, 3811 O Hara St, Pittsburgh, PA 15213 USA.
EM syh50@imap.pitt.edu
FU NIAAA [AA018289, AA05909, AA08082, AA015168]
FX Grant sponsor: NIAAA; Grant numbers: AA018289, AA05909, AA08082,
AA015168.
NR 76
TC 0
Z9 0
U1 6
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4841
EI 1552-485X
J9 AM J MED GENET B
JI Am. J. Med. Genet. B
PD APR
PY 2016
VL 171
IS 3
BP 383
EP 395
DI 10.1002/ajmg.b.32417
PG 13
WC Genetics & Heredity; Psychiatry
SC Genetics & Heredity; Psychiatry
GA DH8FO
UT WOS:000373029100009
PM 26756393
ER
PT J
AU Hirsch, JA
Nicola, G
McGinty, G
Liu, RW
Barr, RM
Chittle, MD
Manchikanti, L
AF Hirsch, J. A.
Nicola, G.
McGinty, G.
Liu, R. W.
Barr, R. M.
Chittle, M. D.
Manchikanti, L.
TI ICD-10: History and Context
SO AMERICAN JOURNAL OF NEURORADIOLOGY
LA English
DT Article
ID CLASSIFICATIONS; GROWTH; FAMILY; READY
AB In recent months, organized medicine has been consumed by the anticipated transition to the 10th iteration of the International Classification of Disease system. Implementation has come and gone without the disruptive effects predicted by many. Despite the fundamental role the International Classification of Disease system plays in health care delivery and payment policy, few neuroradiologists are familiar with the history of its implementation and implications beyond coding for diseases.
C1 [Hirsch, J. A.; Liu, R. W.; Chittle, M. D.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 55 Fruit St,Gray Bldg 2nd Floor, Boston, MA 02114 USA.
[Nicola, G.] Univ Med Ctr, Dept Radiol, Hackensack Radiol Grp, River Edge, NJ USA.
[McGinty, G.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA.
[Barr, R. M.] Mecklenburg Radiol Associates, Charlotte, NC USA.
[Manchikanti, L.] Univ Louisville, Pain Management Ctr Paducah, Dept Anesthesiol & Perioperat Med, Paducah, KY USA.
RP Hirsch, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, 55 Fruit St,Gray Bldg 2nd Floor, Boston, MA 02114 USA.
EM jahirsch@mgh.harvard.edu
OI McGinty, Geraldine/0000-0001-6111-2514
NR 21
TC 1
Z9 1
U1 1
U2 2
PU AMER SOC NEURORADIOLOGY
PI DENVILLE
PA PO BOX 3000, DENVILLE, NJ 07834-9349 USA
SN 0195-6108
EI 1936-959X
J9 AM J NEURORADIOL
JI Am. J. Neuroradiol.
PD APR
PY 2016
VL 37
IS 4
BP 596
EP 599
DI 10.3174/ajnr.A4696
PG 4
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DI2RV
UT WOS:000373346900010
PM 26822730
ER
PT J
AU Das, F
Ghosh-Choudhury, N
Mariappan, MM
Kasinath, BS
Choudhury, GG
AF Das, Falguni
Ghosh-Choudhury, Nandini
Mariappan, Meenalakshmi M.
Kasinath, Balakuntalam S.
Choudhury, Goutam Ghosh
TI Hydrophobic motif site-phosphorylated protein kinase C beta II between
mTORC2 and Akt regulates high glucose-induced mesangial cell hypertrophy
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE diabetic nephropathy; signal transduction; mTOR complex; protein kinase
C
ID GROWTH-FACTOR-BETA; DIABETIC-NEPHROPATHY; RENAL HYPERTROPHY; IN-VIVO;
PHOSPHOINOSITIDE 3-KINASE; TRANSPLANT RECIPIENTS; RAPAMYCIN COMPLEXES;
DIACYLGLYCEROL MASS; ENDOTHELIAL-CELLS; BINDING PARTNER
AB PKC beta II controls the pathologic features of diabetic nephropathy, including glomerular mesangial cell hypertrophy. PKC beta II contains the COOH-terminal hydrophobic motif site Ser-660. Whether this hydrophobic motif phosphorylation contributes to high glucose-induced mesangial cell hypertrophy has not been determined. Here we show that, in mesangial cells, high glucose increased phosphorylation of PKC beta II at Ser-660 in a phosphatidylinositol 3-kinase (PI3-kinase)-dependent manner. Using siRNAs to downregulate PKC beta II, dominant negative PKC beta II, and PKC beta II hydrophobic motif phosphorylation-deficient mutant, we found that PKCbII regulates activation of mechanistic target of rapamycin complex 1 (mTORC1) and mesangial cell hypertrophy by high glucose. PKCbII via its phosphorylation at Ser-660 regulated phosphorylation of Akt at both catalytic loop and hydrophobic motif sites, resulting in phosphorylation and inactivation of its substrate PRAS40. Specific inhibition of mTORC2 increased mTORC1 activity and induced mesangial cell hypertrophy. In contrast, inhibition of mTORC2 decreased the phosphorylation of PKC beta II and Akt, leading to inhibition of PRAS40 phosphorylation and mTORC1 activity and prevented mesangial cell hypertrophy in response to high glucose; expression of constitutively active Akt or mTORC1 restored mesangial cell hypertrophy. Moreover, constitutively active PKC beta II reversed the inhibition of high glucose-stimulated Akt phosphorylation and mesangial cell hypertrophy induced by suppression of mTORC2. Finally, using renal cortexes from type 1 diabetic mice, we found that increased phosphorylation of PKC beta II at Ser-660 was associated with enhanced Akt phosphorylation and mTORC1 activation. Collectively, our findings identify a signaling route connecting PI3-kinase to mTORC2 to phosphorylate PKC beta II at the hydrophobic motif site necessary for Akt phosphorylation and mTORC1 activation, leading to mesangial cell hypertrophy.
C1 [Das, Falguni; Mariappan, Meenalakshmi M.; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
[Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Vet Affairs Res, San Antonio, TX USA.
[Choudhury, Goutam Ghosh] South Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Res, San Antonio, TX USA.
[Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA.
RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA.
EM choudhuryg@uthscsa.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[R01-DK-50190]; Veterans Affairs (VA) Research Service Merit Review
Grant [5I01BX000926]; VA Senior Research Career Scientist Award; VA
Merit Review Grants [5I01BX000150, 5I01BX001340]
FX This work was supported by National Institute of Diabetes and Digestive
and Kidney Diseases Grant R01-DK-50190 and Veterans Affairs (VA)
Research Service Merit Review Grant 5I01BX000926 (to G. G. Choudhury).
G. G. Choudhury is a recipient of VA Senior Research Career Scientist
Award. N. Ghosh-Choudhury and B. S. Kasinath are supported by VA Merit
Review Grants 5I01BX000150 and 5I01BX001340, respectively.
NR 87
TC 1
Z9 1
U1 0
U2 2
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD APR 1
PY 2016
VL 310
IS 7
BP C583
EP C596
DI 10.1152/ajpcell.00266.2015
PG 14
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA DI1RR
UT WOS:000373273900009
PM 26739493
ER
PT J
AU Wang, J
Han, L
Sinnett-Smith, J
Han, LL
Stevens, JV
Rozengurt, N
Young, SH
Rozengurt, E
AF Wang, Jia
Han, Liang
Sinnett-Smith, James
Han, Li-Li
Stevens, Jan V.
Rozengurt, Nora
Young, Steven H.
Rozengurt, Enrique
TI Positive cross talk between protein kinase D and beta-catenin in
intestinal epithelial cells: impact on beta-catenin nuclear localization
and phosphorylation at Ser552
SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
LA English
DT Article
DE G protein-coupled receptors; angiotensin II; IEC-18 cells; PKA; PKD
family inhibitors; CRT006610; kb NB 142-70; PKD1 transgenic mice
ID ACTIVATION LOOP SER(744); STEM-CELLS; IN-VIVO; ANG-II; G(Q)-COUPLED
RECEPTORS; SIGNALING PATHWAYS; COUPLED RECEPTOR; ANGIOTENSIN-II;
DNA-SYNTHESIS; LYSOPHOSPHATIDIC ACID
AB Given the fundamental role of beta-catenin signaling in intestinal epithelial cell proliferation and the growth-promoting function of protein kinase D1 (PKD1) in these cells, we hypothesized that PKDs mediate cross talk with beta-catenin signaling. The results presented here provide several lines of evidence supporting this hypothesis. We found that stimulation of intestinal epithelial IEC-18 cells with the G protein-coupled receptor (GPCR) agonist angiotensin II (ANG II), a potent inducer of PKD activation, promoted endogenous beta-catenin nuclear localization in a time-dependent manner. A significant increase was evident within 1 h of ANG II stimulation (P < 0.01), peaked at 4 h (P < 0.001), and declined afterwards. GPCR stimulation also induced a marked increase in beta-catenin-regulated genes and phosphorylation at Ser(552) in intestinal epithelial cells. Exposure to preferential inhibitors of the PKD family (CRT006610 or kb NB 142-70) or knockdown of the isoforms of the PKD family prevented the increase in beta-catenin nuclear localization and phosphorylation at Ser(552) in response to ANG II. GPCR stimulation also induced the formation of a complex between PKD1 and beta-catenin, as shown by coimmuno-precipitation that depended on PKD1 catalytic activation, as it was abrogated by cell treatment with PKD family inhibitors. Using transgenic mice that express elevated PKD1 protein in the intestinal epithelium, we detected a marked increase in the localization of beta-catenin in the nucleus of crypt epithelial cells in the ileum of PKD1 transgenic mice, compared with nontransgenic littermates. Collectively, our results identify a novel cross talk between PKD and beta-catenin in intestinal epithelial cells, both in vitro and in vivo.
C1 [Wang, Jia; Han, Liang; Sinnett-Smith, James; Han, Li-Li; Stevens, Jan V.; Young, Steven H.; Rozengurt, Enrique] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90095 USA.
[Sinnett-Smith, James; Rozengurt, Nora; Rozengurt, Enrique] Digest Dis Res Ctr, CURE, Los Angeles, CA USA.
[Rozengurt, Enrique] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA.
[Sinnett-Smith, James; Young, Steven H.; Rozengurt, Enrique] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
RP Rozengurt, E (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Warren Hall Rm 11-124,900 Vet Ave, Los Angeles, CA 90095 USA.
EM erozengurt@mednet.ucla.edu
FU National Institutes of Health [R01-DK-100405, P30-DK-41301,
P01-CA-163200]; Department of Veterans Affair Grant [1I01BX001473];
Chinese Scholarship Council
FX This work was supported by National Institutes of Health Grants
R01-DK-100405, P30-DK-41301, and P01-CA-163200 and by Department of
Veterans Affair Grant 1I01BX001473 (to E. Rozengurt). L. Han and L.-L.
Han were both supported by a scholarship from the Chinese Scholarship
Council.
NR 85
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PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6143
EI 1522-1563
J9 AM J PHYSIOL-CELL PH
JI Am. J. Physiol.-Cell Physiol.
PD APR 1
PY 2016
VL 310
IS 7
BP C542
EP C557
DI 10.1152/ajpcell.00302.2015
PG 16
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA DI1RR
UT WOS:000373273900005
PM 26739494
ER
PT J
AU Patterson, RE
Kalavalapalli, S
Williams, CM
Nautiyal, M
Mathew, JT
Martinez, J
Reinhard, MK
McDougall, DJ
Rocca, JR
Yost, RA
Cusi, K
Garrett, TJ
Sunny, NE
AF Patterson, Rainey E.
Kalavalapalli, Srilaxmi
Williams, Caroline M.
Nautiyal, Manisha
Mathew, Justin T.
Martinez, Janie
Reinhard, Mary K.
McDougall, Danielle J.
Rocca, James R.
Yost, Richard A.
Cusi, Kenneth
Garrett, Timothy J.
Sunny, Nishanth E.
TI Lipotoxicity in steatohepatitis occurs despite an increase in
tricarboxylic acid cycle activity
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE steatosis; hepatic insulin resistance; mitochondria; nonalcoholic
steatohepatitis
ID NONALCOHOLIC FATTY LIVER; HEPATIC INSULIN-RESISTANCE; TCA CYCLE;
MITOCHONDRIAL DYSFUNCTION; GLUCOSE-PRODUCTION; AMINO-ACIDS; DISEASE;
METABOLISM; MODEL; GLUCONEOGENESIS
AB The hepatic tricarboxylic acid (TCA) cycle is central to integrating macro-nutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by C-13-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry- based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P < 0.05) of mitochondrial fluxes (mu mol/min) through the TCA cycle (2.6 +/- 0.5 vs. 5.4 +/- 0.6), anaplerosis (9.1 +/- 1.2 vs. 16.9 +/- 2.2), and pyruvate cycling (4.9 +/- 1.0 vs. 11.1 +/- 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcar-nitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH.
C1 [Patterson, Rainey E.; McDougall, Danielle J.; Yost, Richard A.] Univ Florida, Dept Chem, Gainesville, FL 32610 USA.
[Kalavalapalli, Srilaxmi; Nautiyal, Manisha; Mathew, Justin T.; Martinez, Janie; Cusi, Kenneth; Sunny, Nishanth E.] Univ Florida, Dept Med, Div Endocrinol Diabet & Metab, 1600 SW Archer Rd, Gainesville, FL 32610 USA.
[Williams, Caroline M.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
[Reinhard, Mary K.] Univ Florida, Anim Care Serv, Gainesville, FL 32610 USA.
[Rocca, James R.] Univ Florida, McKnight Brain Inst, Adv Magnet Resonance Imaging & Spect Facil, Gainesville, FL 32610 USA.
[Cusi, Kenneth] Malcom Randall Vet Adm Med Ctr, Div Endocrinol Diabet & Metab, Gainesville, FL USA.
[Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA.
[Cusi, Kenneth] Audie L Murphy Vet Adm Med Ctr, Div Diabet, San Antonio, TX USA.
[Yost, Richard A.; Garrett, Timothy J.] Univ Florida, Dept Pathol, Gainesville, FL 32610 USA.
RP Sunny, NE (reprint author), Univ Florida, Dept Med, Div Endocrinol Diabet & Metab, 1600 SW Archer Rd, Gainesville, FL 32610 USA.
EM nishanth.sunny@medicine.ufl.edu
FU University of Florida [00089467]; Southeast Center for Integrated
Metabolomics National Institute of Diabetes and Digestive and Kidney
Diseases Grant [U24-DK-097209]; National Center for Research Resources
Clinical and Translational Science Award [UL1-TR-00064]; National
Institutes of Health
FX This work was supported by a University of Florida Research Opportunity
Seed Fund Award (00089467; to N. E. Sunny), a Southeast Center for
Integrated Metabolomics National Institute of Diabetes and Digestive and
Kidney Diseases Grant (U24-DK-097209), and a National Institutes of
Health and National Center for Research Resources Clinical and
Translational Science Award to the University of Florida (UL1-TR-00064).
NR 45
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U1 2
U2 8
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD APR 1
PY 2016
VL 310
IS 7
BP E484
EP E494
DI 10.1152/ajpendo.00492.2015
PG 11
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA DI1RJ
UT WOS:000373272900002
PM 26814015
ER
PT J
AU Blevins, JE
Thompson, BW
Anekonda, VT
Ho, JM
Graham, JL
Roberts, ZS
Hwang, BH
Ogimoto, K
Wolden-Hanson, T
Nelson, J
Kaiyala, KJ
Havel, PJ
Bales, KL
Morton, GJ
Schwartz, MW
Baskin, DG
AF Blevins, James E.
Thompson, Benjamin W.
Anekonda, Vishwanath T.
Ho, Jacqueline M.
Graham, James L.
Roberts, Zachary S.
Hwang, Bang H.
Ogimoto, Kayoko
Wolden-Hanson, Tami
Nelson, Jarrell
Kaiyala, Karl J.
Havel, Peter J.
Bales, Karen L.
Morton, Gregory J.
Schwartz, Michael W.
Baskin, Denis G.
TI Chronic CNS oxytocin signaling preferentially induces fat loss in
high-fat diet-fed rats by enhancing satiety responses and increasing
lipid utilization
SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE
PHYSIOLOGY
LA English
DT Article
DE obesity; food intake; energy expenditure; oxytocin
ID BROWN ADIPOSE-TISSUE; TYPE-2 DIABETIC-PATIENTS; CAUSES WEIGHT-LOSS;
NERVOUS-SYSTEM OUTFLOW; INDUCED OBESE RATS; FOOD-INTAKE;
ENERGY-EXPENDITURE; PARAVENTRICULAR NUCLEUS; METABOLIC SYNDROME;
BODY-WEIGHT
AB Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration
C1 [Blevins, James E.; Thompson, Benjamin W.; Anekonda, Vishwanath T.; Ho, Jacqueline M.; Roberts, Zachary S.; Hwang, Bang H.; Wolden-Hanson, Tami; Baskin, Denis G.] Vet Affairs Puget Sound Hlth Care Syst, Off Res & Dev Med Res Serv, Dept Vet Affairs Med Ctr, Seattle, WA 98108 USA.
[Blevins, James E.; Ho, Jacqueline M.; Morton, Gregory J.; Schwartz, Michael W.; Baskin, Denis G.] Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA.
[Ogimoto, Kayoko; Nelson, Jarrell; Morton, Gregory J.; Schwartz, Michael W.] Univ Washington, Sch Med, Diabet & Obes Ctr Excellence, Seattle, WA USA.
[Kaiyala, Karl J.] Univ Washington, Sch Dent, Dept Oral Hlth Sci, Seattle, WA 98195 USA.
[Graham, James L.; Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Nutr, Davis, CA 95616 USA.
[Graham, James L.; Havel, Peter J.] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA.
[Bales, Karen L.] Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA.
RP Blevins, JE (reprint author), VA Puget Sound Hlth Care Syst, Res 151, 1660 South Columbian Way, Seattle, WA 98108 USA.
EM jeblevin@u.washington.edu
FU Office of Research and Development, Medical Research Service, Department
of Veterans Affairs (VA); VA Puget Sound Health Care System Rodent
Metabolic and Behavioral Phenotyping Core; Cellular and Molecular
Imaging Core of the Diabetes Research Center at the University of
Washington; National Institutes of Health (NIH) [P30DK017047, P30
DK035816, P30DK017047-31689, 2T32DK007247]; Energy Balance and Glucose
Metabolism Core of the Nutrition Obesity Research Center at the
University of Washington; Department of Veterans Affairs Biomedical
Laboratory R&D Merit Review Program; NIH [DK-095980, HL-091333,
HL-107256]; University of California Office of the President; VA Senior
Research Career Scientist award
FX This material is based upon work supported by the Office of Research and
Development, Medical Research Service, Department of Veterans Affairs
(VA), the VA Puget Sound Health Care System Rodent Metabolic and
Behavioral Phenotyping Core, and the Cellular and Molecular Imaging Core
of the Diabetes Research Center at the University of Washington. This
study was supported by National Institutes of Health (NIH) Grant
P30DK017047. This work is also supported by the Energy Balance and
Glucose Metabolism Core of the Nutrition Obesity Research Center at the
University of Washington and supported by National Institutes of Health
(NIH) Grant P30 DK035816. The research in our laboratory has been
supported by the Department of Veterans Affairs Biomedical Laboratory
R&D Merit Review Program as well as National Institutes of Health Grants
P30DK017047-31689 and the Diabetes, Obesity, and Metabolism Training
Grant 2T32DK007247. P. J. Havel's research program also receives
research support from NIH Grants DK-095980, HL-091333, HL-107256,
HL-107256 and a Multi-campus grant from the University of California
Office of the President. D. G. Baskin is the recipient of a VA Senior
Research Career Scientist award.
NR 105
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U1 1
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6119
EI 1522-1490
J9 AM J PHYSIOL-REG I
JI Am. J. Physiol.-Regul. Integr. Comp. Physiol.
PD APR 1
PY 2016
VL 310
IS 7
BP R640
EP R658
DI 10.1152/ajpregu.00220.2015
PG 19
WC Physiology
SC Physiology
GA DI1PU
UT WOS:000373268800012
PM 26791828
ER
PT J
AU Stites, M
Pianykh, OS
AF Stites, Mark
Pianykh, Oleg S.
TI How Secure Is Your Radiology Department? Mapping Digital Radiology
Adoption and Security Worldwide
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE DICOM; firewall; networking; PACS; security
ID MEDICAL IMAGES; WATERMARKING
AB OBJECTIVE. Despite the long history of digital radiology, one of its most critical aspects-information security-still remains extremely underdeveloped and poorly standardized. To study the current state of radiology security, we explored the worldwide security of medical image archives.
MATERIALS AND METHODS. Using the DICOM data-transmitting standard, we implemented a highly parallel application to scan the entire World Wide Web of networked computers and devices, locating open and unprotected radiology servers. We used only legal and radiology-compliant tools. Our security-probing application initiated a standard DICOM handshake to remote computer or device addresses, and then assessed their security posture on the basis of handshake replies.
RESULTS. The scan discovered a total of 2774 unprotected radiology or DICOM servers worldwide. Of those, 719 were fully open to patient data communications. Geolocation was used to analyze and rank our findings according to country utilization. As a result, we built maps and world ranking of clinical security, suggesting that even the most radiology-advanced countries have hospitals with serious security gaps.
CONCLUSION. Despite more than two decades of active development and implementation, our radiology data still remains insecure. The results provided should be applied to raise awareness and begin an earnest dialogue toward elimination of the problem. The application we designed and the novel scanning approach we developed can be used to identify security breaches and to eliminate them before they are compromised.
C1 [Stites, Mark] Harvard Univ, Sch Med, Harvard Extens Sch, Grad Div, Boston, MA 02114 USA.
[Pianykh, Oleg S.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 25 New Chardon St,Off 470, Boston, MA 02114 USA.
[Pianykh, Oleg S.] Natl Res Univ Higher Sch Econ, Sch Data Anal & Artificial Intelligence, Moscow, Russia.
RP Pianykh, OS (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 25 New Chardon St,Off 470, Boston, MA 02114 USA.; Pianykh, OS (reprint author), Natl Res Univ Higher Sch Econ, Sch Data Anal & Artificial Intelligence, Moscow, Russia.
EM opiany@gmail.com
NR 12
TC 1
Z9 1
U1 3
U2 5
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD APR
PY 2016
VL 206
IS 4
BP 797
EP 804
DI 10.2214/AJR.15.15283
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DH5BJ
UT WOS:000372799700025
PM 26934387
ER
PT J
AU Morgan, TA
Chandran, S
Burger, IM
Zhang, CA
Goldstein, RB
AF Morgan, T. A.
Chandran, S.
Burger, I. M.
Zhang, C. A.
Goldstein, R. B.
TI Complications of Ultrasound-Guided Renal Transplant Biopsies
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
ID KIDNEY BIOPSY; CORE BIOPSY; SAFETY; NEEDLE; GUN; ALLOGRAFTS; ADEQUACY;
EFFICACY; YIELD; TRIAL
AB Renal transplant biopsies to diagnose transplant pathology are routinely performed using ultrasound guidance. Few large studies have assessed the rate and risk factors of major biopsy complications. This study is a single-center 5-year retrospective cohort analysis of 2514 biopsies. Major complications occurred in 47 of 2514 patients (1.9%) and included hospitalization, transfusion of blood products, operative exploration and interventional radiology procedures. The complication rate among cause biopsies was significantly higher than in protocol biopsies (2.7% vs. 0.33%, p < 0.001). Complications presented on postbiopsy days 0-14, with the majority diagnosed on the same day as the biopsy and manifested by hematocrit drop, although the presence of such delayed presentation of complications occurring >24 h after the biopsy on days 2-14 is previously unreported. Specific patient characteristics associated with increased risk of a complication were increased age and blood urea nitrogen, decreased platelet count, history of prior renal transplant, deceased donor transplant type and use of anticoagulant medications but not aspirin.
The authors review the incidence of major complications associated with ultrasound-guided renal transplant biopsies, including timing, presentation, and association with clinical factors, including patient demographics and prebiopsy laboratory values.
C1 [Morgan, T. A.; Zhang, C. A.; Goldstein, R. B.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Chandran, S.] Univ Calif San Francisco, Dept Med, Kidney Transplant Serv, Div Nephrol, San Francisco, CA USA.
[Burger, I. M.] Kaiser Permanente Los Angeles, VA Greater Angeles Healthcare Syst, Dept Radiol, Los Angeles, CA USA.
RP Morgan, TA (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
EM tara.morgan@ucsf.edu
NR 25
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Z9 2
U1 0
U2 2
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 APR
PY 2016
VL 16
IS 4
BP 1298
EP 1305
DI 10.1111/ajt.13622
PG 8
WC Surgery; Transplantation
SC Surgery; Transplantation
GA DH8VQ
UT WOS:000373075400031
PM 26601796
ER
PT J
AU Pejo, E
Liu, JF
Lin, XJ
Raines, DE
AF Pejo, Ervin
Liu, Jifeng
Lin, Xiangjie
Raines, Douglas E.
TI Distinct Hypnotic Recoveries After Infusions of Methoxycarbonyl
Etomidate and Cyclopropyl Methoxycarbonyl Metomidate: The Role of the
Metabolite
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID RETROMETABOLIC DRUG DESIGN; IN-VITRO; ENZYMATIC-HYDROLYSIS; ACID
METABOLITE; RENAL-FAILURE; PHARMACOKINETICS; PHARMACODYNAMICS;
REMIFENTANIL; ESMOLOL; ANALOG
AB BACKGROUND: Methoxycarbonyl etomidate (MOC-etomidate) and cyclopropyl methoxycarbonyl metomidate (CPMM) are rapidly metabolized soft etomidate analogs. CPMM's duration of hypnotic effect is context insensitive, whereas MOC-etomidate's is not. In this study, we tested the hypothesis that CPMM's effect is context insensitive because, unlike MOC-etomidate, its metabolite fails to reach physiologically important concentrations in vivo even with prolonged continuous infusion.
METHODS: We compared the potencies with which MOC-etomidate and CPMM activate (1)(L264T)(32) -aminobutyric acid type A receptors and induce loss-of-righting reflexes (i.e., produce hypnosis) in tadpoles with those of their metabolites (MOC-etomidate's carboxylic acid metabolite [MOC-ECA] and CPMM's carboxylic acid metabolite [CPMM-CA], respectively). We measured metabolite concentrations in the blood and cerebrospinal fluid of Sprague-Dawley rats on CPMM infusion and compared them with those achieved with MOC-etomidate infusion. We measured the rates with which brain tissue from Sprague-Dawley rats metabolize MOC-etomidate and CPMM.
RESULTS: Both analogs and their metabolites enhanced -aminobutyric acid type A receptor function and induced loss-of-righting reflexes in a concentration-dependent manner. However, in these 2 assays, CPMM-CA's potency relative to its parent hypnotic was approximately 1:4900 and 1:1900, respectively, whereas MOC-ECA's was only approximately 1:415 and 1:390, respectively. With 2-hour CPMM infusions, CPMM-CA reached respective concentrations in the blood and cerebrospinal fluid that were 2 and >3 orders of magnitude lower than that which produced hypnosis. CPMM was metabolized by the brain tissue at a rate that is approximately 1/15th that of MOC-etomidate.
CONCLUSIONS: Hypnotic recovery after CPMM administration is context insensitive because its metabolite does not accumulate to hypnotic levels in the central nervous system. This reflects the very large potency ratio between CPMM and CPMM-CA and the resistance of CPMM to metabolism by esterases present in the brain.
C1 [Pejo, Ervin; Raines, Douglas E.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
[Liu, Jifeng; Lin, Xiangjie] Aberjona Labs, Woburn, MA USA.
RP Raines, DE (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM draines@partners.org
FU Department of Anesthesia, Critical Care, and Pain Medicine,
Massachusetts General Hospital, Boston, Massachusetts; [R01-GM087316]
FX This research was supported by grant R01-GM087316 to DER and by the
Department of Anesthesia, Critical Care, and Pain Medicine,
Massachusetts General Hospital, Boston, Massachusetts.
NR 27
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2016
VL 122
IS 4
BP 1008
EP 1014
DI 10.1213/ANE.0000000000001146
PG 7
WC Anesthesiology
SC Anesthesiology
GA DG8OQ
UT WOS:000372343900001
PM 26991617
ER
PT J
AU Yuan, J
Cui, GY
Li, WL
Zhang, XL
Wang, XY
Zheng, H
Zhang, J
Xiang, SL
Xie, ZC
AF Yuan, Jing
Cui, Guiyun
Li, Wenlu
Zhang, Xiaoli
Wang, Xiaoying
Zheng, Hui
Zhang, Jian
Xiang, Shuanglin
Xie, Zhongcong
TI Propofol Enhances Hemoglobin-Induced Cytotoxicity in Neurons
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID PERMEABILITY TRANSITION PORE; CEREBRAL-ISCHEMIA; CORTICAL-NEURONS;
IN-VITRO; NEUROPROTECTION; ACTIVATION; INJURY; BRAIN; NEUROTOXICITY;
APOPTOSIS
AB BACKGROUND: It has been increasingly suggested that propofol protects against hypoxic-/ischemic-induced neuronal injury. As evidenced by hemorrhage-induced stroke, hemorrhage into the brain may also cause brain damage. Whether propofol protects against hemorrhage-induced brain damage remains unknown. Therefore, in this study, we investigated the effects of propofol on hemoglobin-induced cytotoxicity in cultured mouse cortical neurons. METHODS: Neurons were prepared from the cortex of embryonic 15-day-old mice. Hemoglobin was used to induce cytotoxicity in the neurons. The neurons were then treated with propofol for 4 hours. Cytotoxicity was determined by lactate dehydrogenase release assay. Caspase-3 activation was examined by Western blot analysis. Finally, the free radical scavenger U83836E was used to examine the potential involvement of oxidative stress in propofol's effects on hemoglobin-induced cytotoxicity. RESULTS: We found that treatment with hemoglobin induced cytotoxicity in the neurons. Propofol enhanced hemoglobin-induced cytotoxicity. Specifically, there was a significant difference in the amount of lactate dehydrogenase release between hemoglobin plus saline (19.84% +/- 5.38%) and hemoglobin plus propofol (35.79% +/- 4.41%) in mouse cortical neurons (P = 0.00058, Wilcoxon Mann-Whitney U test, n = 8 in the control group or the treatment group). U83836E did not attenuate the enhancing effects of propofol on hemoglobin-induced cytotoxicity in the neurons, and propofol did not significantly affect caspase-3 activation induced by hemoglobin. These data suggested that caspase-3 activation and oxidative stress might not be the underlying mechanisms by which propofol enhanced hemoglobin-induced cytotoxicity. Moreover, these data suggested that the neuroprotective effects of propofol would be dependent on the condition of the brain injury, which will need to be confirmed in future studies. CONCLUSIONS: These results from our current proof-of-concept study should promote more research in vitro and in vivo to develop better anesthesia care for patients with hemorrhagic stroke.
C1 [Yuan, Jing; Zhang, Jian; Xiang, Shuanglin] Hunan Normal Univ, Key Lab Prot Biochem & Dev Biol, State Educ Minist, Coll Life Sci, Changsha 410081, Hunan, Peoples R China.
[Yuan, Jing; Li, Wenlu; Zhang, Xiaoli; Wang, Xiaoying] Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA.
[Yuan, Jing; Li, Wenlu; Zhang, Xiaoli; Wang, Xiaoying] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA.
[Yuan, Jing; Li, Wenlu; Zhang, Xiaoli; Wang, Xiaoying] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA.
[Yuan, Jing; Li, Wenlu; Zhang, Xiaoli; Wang, Xiaoying] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02129 USA.
[Cui, Guiyun] Xuzhou Med Coll, Affiliated Hosp, Dept Neurol, Xuzhou, Jiangsu, Peoples R China.
[Cui, Guiyun; Xie, Zhongcong] Harvard Univ, Geriatr Anesthesia Res Unit, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med,Sch Med, 149,13th St,Room 4310, Charlestown, MA 02129 USA.
[Zheng, Hui] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Biostat, Charlestown, MA 02129 USA.
RP Xie, ZC (reprint author), Harvard Univ, Geriatr Anesthesia Res Unit, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med,Sch Med, 149,13th St,Room 4310, Charlestown, MA 02129 USA.; Xiang, SL (reprint author), Hunan Normal Univ, Coll Life Sci, State Educ Minist, Key Lab Prot Chem & Dev Biol, Changsha 410081, Hunan, Peoples R China.
EM xshlin@hunnu.edu.cn; zxie@mgh.harvard.edu
FU National Institutes of Health, Bethesda, MD [R01 GM088801, R01
AG041274]; Alzheimer's Association, Chicago, IL; Cure Alzheimer's Fund,
Wellesley, MA
FX This research was supported by R01 GM088801 and R01 AG041274 from the
National Institutes of Health, Bethesda, MD; the Investigator-initiated
research grant from Alzheimer's Association, Chicago, IL; and Cure
Alzheimer's Fund, Wellesley, MA (to ZX).
NR 26
TC 2
Z9 2
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2016
VL 122
IS 4
BP 1024
EP 1030
DI 10.1213/ANE.0000000000001123
PG 7
WC Anesthesiology
SC Anesthesiology
GA DG8OQ
UT WOS:000372343900003
PM 26771264
ER
PT J
AU Aplin, AC
Nicosia, RF
AF Aplin, Alfred C.
Nicosia, Roberto F.
TI Hypoxia paradoxically inhibits the angiogenic response of isolated
vessel explants while inducing overexpression of vascular endothelial
growth factor
SO ANGIOGENESIS
LA English
DT Article
DE Endothelial cells; Pericytes; Neovessels; Vascular endothelial growth
factor; Aorta; Vein; Collagen; Neovascularization
ID AORTIC RING MODEL; SOLUBLE VEGF RECEPTOR-1; RAT AORTA; IN-VITRO; OXYGEN;
CELLS; PERMEABILITY; EXPRESSION; SYSTEM; PHOSPHORYLATION
AB This study was designed to investigate how changes in O-2 levels affected angiogenesis in vascular organ culture. Although hypoxia is a potent inducer of angiogenesis, aortic rings cultured in collagen paradoxically failed to produce an angiogenic response in 1-4 % O-2. Additionally, aortic neovessels preformed in atmospheric O-2 lost pericytes and regressed at a faster rate than control when exposed to hypoxia. Aortic explants remained viable in hypoxia and produced an angiogenic response when returned to atmospheric O-2. Hypoxic aortic rings were unresponsive to VEGF, while increased oxygenation of the system dose-dependently enhanced VEGF-induced angiogenesis. Hypoxia-induced refractoriness to angiogenic stimulation was not restricted to the aorta because similar results were obtained with vena cava explants or isolated endothelial cells. Unlike endothelial cells, aorta-derived mural cells were unaffected by hypoxia. Hypoxia downregulated expression in aortic explants of key signaling molecules including VEGFR2, NRP1 and Prkc-beta while upregulating expression of VEGFR1. Medium conditioned by hypoxic cultures exhibited angiostatic and anti-VEGF activities likely mediated by sVEGFr1. Hypoxia reduced expression of VEGFR1 and VEGFR2 in endothelial cells while upregulating VEGFR1 in macrophages and VEGF in both macrophages and mural cells. Thus, changes in O-2 levels profoundly affect the endothelial response to angiogenic stimuli. These results suggest that hypoxia-induced angiogenesis is fine-tuned by complex regulatory mechanisms involving not only production of angiogenic factors including VEGF but also differential regulation of VEGFR expression in different cell types and production of inhibitors of VEGF function such as sVEGFR1.
C1 [Aplin, Alfred C.; Nicosia, Roberto F.] Univ Washington, Dept Pathol, Seattle, WA 98195 USA.
[Nicosia, Roberto F.] VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv S Lab 113, Seattle, WA USA.
RP Nicosia, RF (reprint author), Univ Washington, Dept Pathol, Seattle, WA 98195 USA.; Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv S Lab 113, Seattle, WA USA.
EM Roberto.Nicosia@va.gov
FU United States (U.S.) Department of Veterans Affairs Biomedical
Laboratory Research and Development Service; American Heart Association
FX This work was supported in part by a Merit Review Award from the United
States (U.S.) Department of Veterans Affairs Biomedical Laboratory
Research and Development Service. The contents do not represent the
views of the U.S. Department of Veteran Affairs or the United States
Government. In addition, we gratefully acknowledge the support of a
grant-in-aid from the American Heart Association.
NR 55
TC 2
Z9 2
U1 1
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0969-6970
EI 1573-7209
J9 ANGIOGENESIS
JI Angiogenesis
PD APR
PY 2016
VL 19
IS 2
BP 133
EP 146
DI 10.1007/s10456-015-9493-2
PG 14
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DI0IK
UT WOS:000373178900003
PM 26748649
ER
PT J
AU Wang, RC
Rodriguez, RM
Moghadassi, M
Noble, V
Bailitz, J
Mallin, M
Corbo, J
Kang, TL
Chu, P
Shiboski, S
Smith-Bindman, R
AF Wang, Ralph C.
Rodriguez, Robert M.
Moghadassi, Michelle
Noble, Vicki
Bailitz, John
Mallin, Mike
Corbo, Jill
Kang, Tarina L.
Chu, Phillip
Shiboski, Steve
Smith-Bindman, Rebecca
TI External Validation of the STONE Score, a Clinical Prediction Rule for
Ureteral Stone: An Observational Multi-institutional Study
SO ANNALS OF EMERGENCY MEDICINE
LA English
DT Article
ID ACUTE FLANK PAIN; UNENHANCED HELICAL CT; COMPUTED-TOMOGRAPHY; DECISION
RULES; METHODOLOGIC STANDARDS; EMERGENCY-MEDICINE; CALCULI; US;
ULTRASONOGRAPHY; NEPHROLITHIASIS
AB Study objective: The STONE score is a clinical decision rule that classifies patients with suspected nephrolithiasis into low-, moderate-, and high-score groups, with corresponding probabilities of ureteral stone. We evaluate the STONE score in a multi-institutional cohort compared with physician gestalt and hypothesize that it has a sufficiently high specificity to allow clinicians to defer computed tomography (CT) scan in patients with suspected nephrolithiasis.
Methods: We assessed the STONE score with data from a randomized trial for participants with suspected nephrolithiasis who enrolled at 9 emergency departments between October 2011 and February 2013. In accordance with STONE predictors, we categorized participants into low-, moderate-, or high-score groups. We determined the performance of the STONE score and physician gestalt for ureteral stone.
Results: Eight hundred forty-five participants were included for analysis; 331 (39%) had a ureteral stone. The global performance of the STONE score was superior to physician gestalt (area under the receiver operating characteristic curve=0.78 [95% confidence interval (CI) 0.74 to 0.81] versus 0.68 [95% CI 0.64 to 0.71]). The prevalence of ureteral stone on CTscan ranged from 14% (95% CI 9% to 19%) to 73% (95% CI 67% to 78%) in the low-, moderate-, and high-score groups. The sensitivity and specificity of a high score were 53% (95% CI 48% to 59%) and 87% (95% CI 84% to 90%), respectively.
Conclusion: The STONE score can successfully aggregate patients into low-, medium-, and high-risk groups and predicts ureteral stone with a higher specificity than physician gestalt. However, in its present form, the STONE score lacks sufficient accuracy to allow clinicians to defer CTscan for suspected ureteral stone.
C1 [Wang, Ralph C.; Rodriguez, Robert M.] Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA.
[Moghadassi, Michelle; Chu, Phillip; Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Shiboski, Steve; Smith-Bindman, Rebecca] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Noble, Vicki] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Bailitz, John] John H Stroger Jr Hosp Cook Cty, Dept Emergency Med, Chicago, IL USA.
[Mallin, Mike] Univ Utah, Div Emergency Med, Salt Lake City, UT USA.
[Corbo, Jill] Albert Einstein Coll Med, Dept Emergency Med, Jacobi Med Ctr, New York, NY USA.
[Kang, Tarina L.] Univ So Calif, Dept Emergency Med, Los Angeles, CA USA.
RP Wang, RC (reprint author), Univ Calif San Francisco, Dept Emergency Med, San Francisco, CA 94143 USA.
EM ralph.wang@ucsf.edu
FU Agency for Healthcare Research and Quality (AHRQ) [K08 HS02181];
National Center for Advancing Translational Sciences (NCATS) [8 KL2
TR000143-08]; American Recovery and Reinvestment Act through AHRQ grant
[R01HS019312]; K24 award [NIH K24 CA125036]
FX By Annals policy, all authors are required to disclose any and all
commercial, financial, and other relationships in any way related to the
subject of this article as per ICMJE conflict of interest guidelines
(see www.icmje.org). The authors have stated that no such relationships
exist and provided the following details: This study was supported by
funding from Agency for Healthcare Research and Quality (AHRQ) grant K08
HS02181 and National Center for Advancing Translational Sciences (NCATS)
grant 8 KL2 TR000143-08. The Study of Ultrasonography Versus Computed
Tomography for Suspected Nephrolithiasis was supported by the American
Recovery and Reinvestment Act of 2009 through AHRQ grant R01HS019312.
Rebecca Smith-Bindman received a K24 award (NIH K24 CA125036).
NR 30
TC 8
Z9 8
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-0644
J9 ANN EMERG MED
JI Ann. Emerg. Med.
PD APR
PY 2016
VL 67
IS 4
BP 423
EP 432
DI 10.1016/j.annemergmed.2015.08.019
PG 10
WC Emergency Medicine
SC Emergency Medicine
GA DI1FK
UT WOS:000373241800003
PM 26440490
ER
PT J
AU Domsic, RT
Nihtyanova, SI
Wisniewski, SR
Fine, MJ
Lucas, M
Kwoh, CK
Denton, CP
Medsger, TA
AF Domsic, Robyn T.
Nihtyanova, Svetlana I.
Wisniewski, Stephen R.
Fine, Michael J.
Lucas, Mary
Kwoh, C. Kent
Denton, Christopher P.
Medsger, Thomas A., Jr.
TI Derivation and External Validation of a Prediction Rule for Five-Year
Mortality in Patients With Early Diffuse Cutaneous Systemic Sclerosis
SO ARTHRITIS & RHEUMATOLOGY
LA English
DT Article
ID CLINICAL-PREDICTION; EUSTAR DATABASE; SCLERODERMA; SURVIVAL; FEATURES;
DEATH; EMPHASIS; DISEASE; COHORT; MODEL
AB ObjectiveAlthough diffuse cutaneous systemic sclerosis (dcSSc) is associated with a reduction in life expectancy, there are no validated prognostic models for determining 5-year mortality in patients with dcSSc. The objective of this study was to derive and validate a rule for predicting 5-year mortality in patients with early dcSSc.
MethodsWe studied an inception cohort of 388 US Caucasian patients with early dcSSc (<2 years from the appearance of the first symptom). Predefined baseline variables were analyzed in a stepwise logistic regression model in order to identify factors independently associated with 5-year all-cause mortality. We rounded the beta weights to the nearest integer and summed the points assigned to each variable in order to stratify patients into low-risk (<0 points), moderate-risk (1-2 points), and high-risk (3 points) groups. We then applied this rule to an external validation cohort of 144 Caucasian patients with early dcSSc from the Royal Free Hospital cohort and compared stratum-specific 5-year mortality.
ResultsSix independent predictors (rounded beta weight) comprised the model: age at first visit (points allotted: -1, 0, or 1), male sex (points allotted: 0 or 1), tendon friction rubs (points allotted: 0 or 1), gastrointestinal involvement (points allotted: 0 or 1), RNA polymerase III antibodies (points allotted: 0 or 1), and anemia (points allotted: 0 or 1). The 3-level risk stratification model performed well, with no significant differences between the US derivation cohort and the UK validation cohort.
ConclusionWe derived and externally validated, in US and UK cohorts, an easy-to-use 6-variable prediction rule that assigns low-risk, moderate-risk, and high-risk categories for 5-year mortality in patients with early dcSSc. Only history, physical examination, and basic laboratory assessments are required.
C1 [Domsic, Robyn T.; Wisniewski, Stephen R.; Lucas, Mary; Medsger, Thomas A., Jr.] Univ Pittsburgh, Pittsburgh, PA USA.
[Nihtyanova, Svetlana I.; Denton, Christopher P.] UCL, Sch Med, Royal Free Hosp, Mortimer St, London W1N 8AA, England.
[Fine, Michael J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Fine, Michael J.] Vet Affairs Pittsburgh Healthcare, Vet Affairs Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
[Kwoh, C. Kent] Univ Arizona, Arthrit Ctr, Tucson, AZ USA.
RP Domsic, RT (reprint author), Univ Pittsburgh, S724 Biomed Sci Tower,3500 Terrace St, Pittsburgh, PA 15261 USA.
EM rtd4@pitt.edu
OI Wisniewski, Stephen/0000-0002-3877-9860
FU NIH (National Institute of Arthritis and Musculoskeletal and Skin
Diseases) [K23-AR-057845]
FX Dr. Domsic's work was supported by the NIH (National Institute of
Arthritis and Musculoskeletal and Skin Diseases grant K23-AR-057845).
NR 40
TC 2
Z9 2
U1 0
U2 1
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 APR
PY 2016
VL 68
IS 4
BP 993
EP 1003
DI 10.1002/art.39490
PG 11
WC Rheumatology
SC Rheumatology
GA DH9QH
UT WOS:000373130300026
PM 26554637
ER
PT J
AU Williams, KM
Cheng, GS
Pusic, I
Jagasia, M
Burns, L
Ho, VT
Pidala, J
Palmer, J
Johnston, L
Mayer, S
Chien, JW
Jacobsohn, DA
Pavletic, SZ
Martin, PJ
Storer, BE
Inamoto, Y
Chai, XY
Flowers, MED
Lee, SJ
AF Williams, Kirsten M.
Cheng, Guang-Shing
Pusic, Iskra
Jagasia, Madan
Burns, Linda
Ho, Vincent T.
Pidala, Joseph
Palmer, Jeanne
Johnston, Laura
Mayer, Sebastian
Chien, Jason W.
Jacobsohn, David A.
Pavletic, Steven Z.
Martin, Paul J.
Storer, Barry E.
Inamoto, Yoshihiro
Chai, Xiaoyu
Flowers, Mary E. D.
Lee, Stephanie J.
TI Fluticasone, Azithromycin, and Montelukast Treatment for New-Onset
Bronchiolitis Obliterans Syndrome after Hematopoietic Cell
Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Bronchiolitis obliterans syndrome; Fluticasone; Azithromycin;
Montelukast; Hematopoietic cell transplantation; Lung chronic
graft-versus-host disease; Leukotrienes
ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; CONSENSUS DEVELOPMENT
PROJECT; AIR-FLOW OBSTRUCTION; WORKING GROUP-REPORT; MEASURING
THERAPEUTIC RESPONSE; RECEPTOR ENBREL ETANERCEPT; PLACEBO-CONTROLLED
TRIAL; LONG-TERM SURVIVORS; LUNG TRANSPLANTATION
AB Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study (NCT01307462). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BUS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BUS despite FAM. (C) 2016 American Society for Blood and Marrow Transplantation.
C1 [Williams, Kirsten M.; Jacobsohn, David A.] Childrens Natl Hlth Syst, Childrens Res Inst, Div Blood & Marrow Transplantat, Washington, DC USA.
[Williams, Kirsten M.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Cheng, Guang-Shing; Martin, Paul J.; Storer, Barry E.; Chai, Xiaoyu; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA.
[Pusic, Iskra] Washington Univ, Div Med & Oncol, St Louis, MO USA.
[Jagasia, Madan] Vandebilt Univ, Div Hematol Oncol, Nashville, TN USA.
[Burns, Linda] Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN USA.
[Ho, Vincent T.] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Blood & Marrow Transplantat, Tampa, FL 33682 USA.
[Palmer, Jeanne] Mayo Clin, Div Hematol Oncol, Scottsdale, AZ USA.
[Johnston, Laura] Stanford Univ, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Mayer, Sebastian] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Chien, Jason W.] Gilead Sci Inc, Seattle, WA USA.
[Inamoto, Yoshihiro] Natl Canc Ctr, Div Hematopoiet Stem Cell Transplantat, 1-1 Tsukiji 5 chome, Tokyo, Japan.
RP Williams, KM (reprint author), George Washington Univ, Med Ctr, Childrens Natl Med Ctr, Div Blood & Marrow Transplantat,Ctr Canc & Blood, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM kmwillia@cnmc.org
FU NCATS; National Cancer Institute; GlaxoSmithKline [113611]
FX The Chronic GVHD Consortium (U54 CA163438) is part of the 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.
GlaxoSmithKline provided fluticasone propionate under grant number
113611, and Merck provided montelukast.
NR 50
TC 9
Z9 9
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD APR
PY 2016
VL 22
IS 4
BP 710
EP 716
DI 10.1016/j.bbmt.2015.10.009
PG 7
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA DH9CH
UT WOS:000373093500017
PM 26475726
ER
PT J
AU Yu, EW
Carmody, JS
Brooks, DJ
LaJoie, S
Kaplan, LM
Bouxsein, ML
AF Yu, Elaine W.
Carmody, Jill S.
Brooks, Daniel J.
LaJoie, Scott
Kaplan, Lee M.
Bouxsein, Mary L.
TI Cortical and trabecular deterioration in mouse models of Roux-en-Y
gastric bypass
SO BONE
LA English
DT Article
DE Bariatric surgery; Gastric bypass; Weight loss; Obesity; Bone loss; Bone
microarchitecture; Mouse models
ID BONE-MINERAL DENSITY; VERTICAL SLEEVE GASTRECTOMY; WEIGHT-LOSS;
BARIATRIC SURGERY; METABOLIC-ACIDOSIS; MORBID-OBESITY; ANIMAL-MODELS;
RATS; RESTRICTION; TURNOVER
AB Roux-en-Y gastric bypass (RYGB) is a profoundly effective treatment for severe obesity, but results in significant bone loss in patients. Developing a murine model that recapitulates this skeletal phenotype will provide a robust tool with which to study the physiologic mechanisms of this bone loss. We studied adult male C57BL/6J mice who underwent either RYGB or sham operation. Twelve weeks after surgery, we characterized biochemical bone markers (parathyroid hormone, PTH; C-telopeptide, CTX; and type 1 procollagen, P1NP) and bone microarchitectural parameters as measured by microcomputed tomography. RYGB-treated mice had significant trabecular and cortical bone deficits compared with sham-operated controls. Although adjustment for final body weight eliminated observed cortical differences, the trabecular bone volume fraction remained significantly lower in RYGB mice even after weight adjustment. PTH levels were similar between groups, but RYGB mice had significantly higher indices of bone turnover than sham controls. These data demonstrate that murine models of RYGB recapitulate patterns of bone loss and turnover that have been observed in human clinical studies. Future studies that exploit this murine model will help delineate the alterations in bone metabolism and mechanisms of bone loss after RYGB. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Yu, Elaine W.; Brooks, Daniel J.; Bouxsein, Mary L.] Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1041, Boston, MA 02114 USA.
[Carmody, Jill S.; LaJoie, Scott; Kaplan, Lee M.] Massachusetts Gen Hosp, Obes Metab & Nutr Inst, Boston, MA 02114 USA.
[Carmody, Jill S.; LaJoie, Scott; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.
[Brooks, Daniel J.; Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA USA.
RP Yu, EW (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,Thier 1041, Boston, MA 02114 USA.
FU NIH [DK093713, DK088661]; Ethicon, Inc.
FX This work was supported by NIH grants DK093713 (E.W.Y.), DK088661
(L.M.K.) and a research grant from Ethicon, Inc.
NR 40
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD APR
PY 2016
VL 85
BP 23
EP 28
DI 10.1016/j.bone.2016.01.017
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DH4QJ
UT WOS:000372770200004
PM 26806052
ER
PT J
AU Paluch-Shimon, S
Pagani, O
Partridge, AH
Bar-Meir, E
Fallowfield, L
Fenlon, D
Friedman, E
Gelmon, K
Gentilini, O
Geraghty, J
Harbeck, N
Higgins, S
Loibl, S
Moser, E
Peccatori, F
Raanani, H
Kaufman, B
Cardoso, F
AF Paluch-Shimon, Shani
Pagani, Olivia
Partridge, Ann H.
Bar-Meir, Eran
Fallowfield, Lesley
Fenlon, Deborah
Friedman, Eitan
Gelmon, Karen
Gentilini, Oreste
Geraghty, James
Harbeck, Nadia
Higgins, Stephen
Loibl, Sibylle
Moser, Elizabeth
Peccatori, Fedro
Raanani, Hila
Kaufman, Bella
Cardoso, Fatima
TI Second international consensus guidelines for breast cancer in young
women (BCY2)
SO BREAST
LA English
DT Article
DE Breast cancer; Young women; Guidelines; Consensus
ID ADJUVANT ENDOCRINE THERAPY; BRCA MUTATION CARRIERS; OVARIAN-FUNCTION
SUPPRESSION; NIPPLE-SPARING MASTECTOMY; BONE-MINERAL DENSITY;
QUALITY-OF-LIFE; PREMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ZOLEDRONIC ACID;
HOT FLASHES
AB The 2nd International Consensus Conference for Breast Cancer in Young Women (BCY2) took place in November 2014, in Dublin, Ireland organized by the European School of Oncology (ESO). Consensus recommendations for the management of breast cancer in young women (BCYW) were updated from BCY1 with incorporation of new evidence to inform the guidelines, and areas of research priorities were identified. This manuscript summarizes these international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA). (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Paluch-Shimon, Shani; Friedman, Eitan; Raanani, Hila; Kaufman, Bella] Sheba Med Ctr, Ramat Gan, Israel.
[Pagani, Olivia] Oncol Inst Southern Switzerland, Bellinzona, Switzerland.
[Pagani, Olivia] Breast Unit Southern Switzerland, Bellinzona, Switzerland.
[Partridge, Ann H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA.
[Bar-Meir, Eran] Bar Ilan Univ, Fac Med, IL-52100 Ramat Gan, Israel.
[Fallowfield, Lesley] Univ Sussex, Brighton & Sussex Med Sch, SHORE C, Falmer, England.
[Fenlon, Deborah] Univ Southampton, Southampton, Hants, England.
[Gelmon, Karen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
[Gentilini, Oreste] Hosp San Raffaele, Breast Surg Unit, I-20132 Milan, Italy.
[Geraghty, James] St Vincent Hosp, Dublin, Ireland.
[Harbeck, Nadia] Univ Munich LMU, Dept OB&GYN, Breast Ctr, Munich, Germany.
[Higgins, Stephen] Tallaght Hosp, Dublin, Ireland.
[Higgins, Stephen] Our Ladys Hosp Sick Children, Dublin, Ireland.
[Loibl, Sibylle] German Breast Grp, Neu Isenburg, Germany.
[Loibl, Sibylle] Sana Klinikum Offenbach, Sana, Germany.
[Moser, Elizabeth; Cardoso, Fatima] Champalimaud Canc Ctr, Breast Unit, Av Brasilia S-N, P-1400038 Lisbon, Portugal.
[Peccatori, Fedro] European Inst Oncol, Milan, Italy.
[Cardoso, Fatima] European Sch Oncol, Rome, Italy.
RP Cardoso, F (reprint author), Champalimaud Canc Ctr, Breast Unit, Av Brasilia S-N, P-1400038 Lisbon, Portugal.
EM fatimacardoso@fundacaochampalimaud.pt
OI Cardoso, Fatima/0000-0002-6692-2249; Fenlon, Deborah/0000-0001-7347-8919
NR 142
TC 8
Z9 8
U1 3
U2 7
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 0960-9776
EI 1532-3080
J9 BREAST
JI Breast
PD APR
PY 2016
VL 26
BP 87
EP 99
DI 10.1016/j.breast.2015.12.010
PG 13
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DH9JO
UT WOS:000373112600012
PM 27017247
ER
PT J
AU Chapman, JAW
Shepherd, LE
Ingle, JN
Muss, HB
Pritchard, KI
Gelmon, KA
Whelan, TJ
Elliott, C
Goss, PE
AF Chapman, Judith-Anne W.
Shepherd, Lois E.
Ingle, James N.
Muss, Hyman B.
Pritchard, Kathleen I.
Gelmon, Karen A.
Whelan, Timothy J.
Elliott, Catherine
Goss, Paul E.
TI Competing risks of death in women treated with adjuvant aromatase
inhibitors for early breast cancer on NCIC CTG MA.27
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Competing risks; Breast cancer death; Cardiovascular death; Elderly
ID THERAPY; TRIAL
AB Baseline patient and tumor characteristics differentially affected type of death in the MA.17 placebo-controlled letrozole trial where cardiovascular death was not separately identified. The MA.27 trial allowed competing risks analysis of breast cancer (BC), cardiovascular, and other type (OT) of death. MA.27 was a phase III adjuvant breast cancer trial of exemestane versus anastrozole. Effects of baseline patient and tumor characteristics were tested for whether factors were associated with (1) all cause mortality and (2) cause-specific mortality. We also fit step-wise forward cause-specific-adjusted models. 7576 women (median age 64 years; 5417 (72 %) < 70 years and 2159 (28 %) a parts per thousand yen 70 years) were enrolled and followed for median 4.1 years. The 432 deaths comprised 187 (43 %) BC, 66 (15 %) cardiovascular, and 179 (41 %) OT. Five baseline factors were differentially associated with type of death. Older patients had greater BC (p = 0.03), cardiovascular (p < 0.001), and other types (p < 0.001) of mortality. Patients with pre-existing cardiovascular history had worse cardiovascular mortality (p < 0.001); those with worse ECOG performance status had worse OT mortality (p < 0.001). Patients with T1 tumors (p < 0.001) and progesterone receptor positive had less BC mortality (p < 0.001). Fewer BC deaths occurred with node-negative disease (p < 0.001), estrogen receptor-positive tumors (p = 0.001), and without adjuvant chemotherapy (p = 0.005); worse cardiovascular mortality (p = 0.01), with trastuzumab; worse OT mortality, for non-whites (p = 0.03) and without adjuvant radiotherapy (p = 0.003). Overall, 57 % of deaths in MA.27 AI-treated patients were non-breast cancer related. Baseline patient and tumor characteristics differentially affected type of death with women 70 or older experiencing more non-breast cancer death.
C1 [Chapman, Judith-Anne W.; Shepherd, Lois E.; Elliott, Catherine] Queens Univ, Canadian Canc Trials Grp, NCIC Clin Trials Grp, Kingston, ON, Canada.
[Ingle, James N.] Mayo Clin, Rochester, MN USA.
[Muss, Hyman B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Pritchard, Kathleen I.] Univ Toronto, Sunnybrook Odette Canc Ctr, Toronto, ON, Canada.
[Gelmon, Karen A.] British Columbia Canc Agcy, Vancouver Ctr, Vancouver, BC V5Z 4E6, Canada.
[Whelan, Timothy J.] McMaster Univ, Juravinski Canc Ctr Hamilton Hlth Sci, Hamilton, ON, Canada.
[Goss, Paul E.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA.
RP Chapman, JAW (reprint author), Queens Univ, Canadian Canc Trials Grp, NCIC Clin Trials Grp, Kingston, ON, Canada.
EM jachapma@aol.com; Lshepherd@ctg.queensu.ca; ingle.james@mayo.edu;
hyman_muss@med.unc.edu; kathy.pritchard@sunnybrook.ca;
kgelmon@bccancer.bc.ca; twhelan@hhsc.ca; CElliott@ctg.queensu.ca;
pgoss@mgh.harvard.edu
RI Whelan, Timothy/D-3185-2017
FU Canadian Cancer Society Research Institute [015761, 015764]; United
States National Cancer Institute at the National Institutes of Health
[CA77202]; Pfizer (New York, Canada); Avon Foundation
FX This work was supported by the Canadian Cancer Society Research
Institute [grant numbers 015761,015764]; the United States National
Cancer Institute at the National Institutes of Health [grant number
CA77202]; and Pfizer (New York, Canada). Dr. Goss is supported by the
Avon Foundation.
NR 10
TC 1
Z9 1
U1 0
U2 3
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 APR
PY 2016
VL 156
IS 2
BP 343
EP 349
DI 10.1007/s10549-016-3761-8
PG 7
WC Oncology
SC Oncology
GA DI0DI
UT WOS:000373164800013
PM 27006189
ER
PT J
AU Abuelkasem, E
Lu, S
Tanaka, K
Planinsic, R
Sakai, T
AF Abuelkasem, E.
Lu, S.
Tanaka, K.
Planinsic, R.
Sakai, T.
TI Comparison between thrombelastography and thromboelastometry in
hyperfibrinolysis detection during adult liver transplantation
SO BRITISH JOURNAL OF ANAESTHESIA
LA English
DT Article
DE clinical laboratory techniques; fibrinolysis; liver transplantation;
thrombelastography
ID PLASMINOGEN-ACTIVATOR; CLOT RETRACTION; FACTOR-XIII; FIBRINOLYSIS;
BLOOD; DISEASE; LYSIS; ACID
AB Background: Hyperfibrinolysis is one of the main causes of non-surgical bleeding during liver transplantation (LT). Viscoelastic haemostatic assays, including thromboelastometry (ROTEM (R)) and thrombelastography (TEG (R)), can detect hyperfibrinolysis at the bedside. No study has yet demonstrated which device or assay is more suitable for detecting hyperfibrinolysis.
Methods: This prospective observational study compared ROTEM (R) and TEG (R) in isolated adult LT. ROTEM (R) (EXTEM (R) [tissue factor activation], FIBTEM (R) [tissue factor activation with platelet inhibition], and APTEM (R) [tissue factor activation with tranexamic acid/aprotinin]) and TEG (R) (kaolin-TEG (R)) were simultaneously performed using arterial blood samples at eight time-points during LT: induction of general anaesthesia, 60 min after skin incision, 10 and 45 min after portal vein clamp, 15 min before graft reperfusion, and five, 30, and 90 min after graft reperfusion. Hyperfibrinolysis was identified per the manufacturers' definitions (maximum lysis >15% in ROTEM (R) or Lysis30>8% in TEG (R)) and confirmed with APTEM (R); incidence was compared between assays McNemar's test.
Results: Among 296 possible measurement points from 376 consecutive LT recipients, 250 underwent final analysis: 46 measurement points were excluded because of missing assays or flat line. Hyperfibrinolysis was confirmed at 89 (36%) of 250 measurement points: FIBTEM (R), EXTEM (R), and kaolin-TEG (R) detected 84 (94%), 41 (46%), and 21 (24%) hyperfibrinolysis, respectively. These hyperfibrinolysis detection rates significantly differed from each other (P<0.001).
Conclusions: Tissue factor-triggered ROTEM (R) tests were more sensitive than contact-activated k-TEG (R) in identifying hyperfibrinolysis in LT patients. Inhibition of platelet-fibrin interaction in FIBTEM (R) enhanced sensitivity to hyperfibrinolysis detection compared with EXTEM (R).
C1 [Abuelkasem, E.; Planinsic, R.; Sakai, T.] Univ Pittsburgh, Dept Anesthesiol, Med Ctr, 200 Lothrop St, Pittsburgh, PA 15213 USA.
[Lu, S.] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesiol, Sch Med, Boston, MA 02114 USA.
[Tanaka, K.] Univ Maryland, Dept Anesthesiol, Med Ctr, Baltimore, MD 21201 USA.
[Sakai, T.] Univ Pittsburgh, Clin & Translat Sci Inst, Atwood & Sennott St, Pittsburgh, PA 15260 USA.
RP Sakai, T (reprint author), Univ Pittsburgh, Dept Anesthesiol, Med Ctr, 200 Lothrop St, Pittsburgh, PA 15213 USA.; Sakai, T (reprint author), Univ Pittsburgh, Clin & Translat Sci Inst, Atwood & Sennott St, Pittsburgh, PA 15260 USA.
EM sakait@upmc.edu
FU Tem International
FX K.A.T. is currently participating in a clinical study sponsored by Tem
International. The other authors declare no conflicts of interest.
NR 22
TC 3
Z9 3
U1 1
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0007-0912
EI 1471-6771
J9 BRIT J ANAESTH
JI Br. J. Anaesth.
PD APR
PY 2016
VL 116
IS 4
BP 507
EP 512
DI 10.1093/bja/aew023
PG 6
WC Anesthesiology
SC Anesthesiology
GA DH2BB
UT WOS:000372588000012
PM 26934942
ER
PT J
AU Ballen, KK
Lazarus, H
AF Ballen, Karen K.
Lazarus, Hillard
TI Cord blood transplant for acute myeloid leukaemia
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE umbilical cord blood; allogeneic haematopoietic cell transplantation
ID STEM-CELL TRANSPLANTATION; MYELOABLATIVE CONDITIONING REGIMEN;
ALTERNATIVE DONOR TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; ANTI-HLA
ANTIBODIES; HEMATOLOGIC MALIGNANCIES; UNRELATED DONOR; BONE-MARROW;
ADULT PATIENTS; PROSPECTIVE MULTICENTER
AB Umbilical cord blood is a haematopoietic progenitor cell source for patients with acute myeloid leukaemia (AML), other haematological malignancies and metabolic diseases who can be cured by allogeneic haematopoietic cell transplantation, but who do not have a human leucocyte antigen compatible related or unrelated donor. Although the first cord blood transplants were done in children, there are currently more cord blood transplants performed in adults. In this review, we explore the history of umbilical cord blood transplantation, paediatric and adult outcome results, and novel trends to improve engraftment and reduce infection. Umbilical cord blood transplantation cures approximately 30-40% of adults and 60-70% of children with AML. Controversial issues, including the use of double versus single cord blood units for transplantation, optimal cord blood unit selection, infection prophylaxis, conditioning regimens and graft versus host disease prophylaxis, will be reviewed. Finally, comparison to other graft sources, cost, access to care, and the ideal graft source are discussed.
C1 [Ballen, Karen K.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA.
[Lazarus, Hillard] Case Western Reserve Univ, Seidman Canc Ctr, Cleveland, OH 44106 USA.
RP Ballen, KK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Div Hematol Oncol, Zero Emerson,Suite 118, Boston, MA 02114 USA.
EM kballen@partners.org
NR 86
TC 0
Z9 0
U1 3
U2 7
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 APR
PY 2016
VL 173
IS 1
BP 25
EP 36
DI 10.1111/bjh.13926
PG 12
WC Hematology
SC Hematology
GA DH9TL
UT WOS:000373138700002
PM 26766286
ER
PT J
AU Ting, KR
Brady, JJ
Hameed, A
Le, G
Meiller, J
Verburgh, E
Bayers, C
Benjamin, D
Anderson, KC
Richardson, PG
Dowling, P
Clynes, M
Fitzgibbon, MC
O'Gorman, P
AF Ting, Kay R.
Brady, Jennifer J.
Hameed, Abdul
Le, Giao
Meiller, Justine
Verburgh, Estelle
Bayers, Christopher
Benjamin, Dalia
Anderson, Kenneth C.
Richardson, Paul G.
Dowling, Paul
Clynes, Martin
Fitzgibbon, Maria C.
O'Gorman, Peter
TI Clinical utility of C-terminal telopeptide of type 1 collagen in
multiple myeloma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE multiple myeloma; CTX-1; myeloma bone disease; bone markers; bone
resorption
ID GROUP CONSENSUS STATEMENT; BONE-DISEASE; BIOCHEMICAL MARKERS; WORKING
GROUP; PATHOLOGICAL FRACTURES; IMAGING TECHNIQUES; MANAGEMENT;
RESORPTION; CHEMISTRY; DIAGNOSIS
AB Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P<005), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6months prior to relapse (P=0007), and in 608% up to 3months before relapse (P=0015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0771 +/- 0400g/l), and lowest in the remission group (0099 +/- 0070g/l) (P<00001). P1NP levels were not statistically different across the patient groups. We conclude that CTX-1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.
C1 [Ting, Kay R.; Hameed, Abdul; Le, Giao; Verburgh, Estelle; Bayers, Christopher; Benjamin, Dalia; O'Gorman, Peter] Mater Misericordiae Univ Hosp, Dept Haematol, Dublin 7, Ireland.
[Ting, Kay R.; Hameed, Abdul; Le, Giao; Meiller, Justine; Dowling, Paul; Clynes, Martin; O'Gorman, Peter] Dublin City Univ, Natl Inst Cellular Biotechnol, Dublin 9, Ireland.
[Brady, Jennifer J.; Fitzgibbon, Maria C.] Mater Misericordiae Univ Hosp, Dept Clin Chem & Diagnost Endocrinol, Dublin 7, Ireland.
[Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Anderson, Kenneth C.; Richardson, Paul G.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.
[Dowling, Paul] Maynooth Univ, Dept Biol, Maynooth, Kildare, Ireland.
[O'Gorman, Peter] Univ Coll Dublin, Sch Med & Med Sci, Dublin 4, Ireland.
RP O'Gorman, P (reprint author), 8 Berkeley Rd, Dublin 7, Ireland.
EM pogorman@mater.ie
OI Dowling, Paul/0000-0002-9290-9267
NR 30
TC 0
Z9 1
U1 1
U2 4
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 APR
PY 2016
VL 173
IS 1
BP 82
EP 88
DI 10.1111/bjh.13928
PG 7
WC Hematology
SC Hematology
GA DH9TL
UT WOS:000373138700007
PM 26787413
ER
PT J
AU Armand, P
Redd, R
Bsat, J
Mayuram, S
Giardino, A
Fisher, DC
LaCasce, AS
Jacobson, C
Davids, MS
Brown, JR
Weng, L
Wilkins, J
Faham, M
Freedman, AS
Joyce, R
Jacobsen, ED
AF Armand, Philippe
Redd, Robert
Bsat, Jad
Mayuram, Sangeetha
Giardino, Angela
Fisher, David C.
LaCasce, Ann S.
Jacobson, Caron
Davids, Matthew S.
Brown, Jennifer R.
Weng, Li
Wilkins, Jennifer
Faham, Malek
Freedman, Arnold S.
Joyce, Robin
Jacobsen, Eric D.
TI A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for
transplant-eligible patients with mantle cell lymphoma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE malignant lymphomas; clinical trials; chemotherapy
ID NON-HODGKIN-LYMPHOMA; PROSPECTIVE RANDOMIZED-TRIAL; ACUTE
LYMPHOBLASTIC-LEUKEMIA; RESIDUAL DISEASE DETECTION; PROGRESSION-FREE
SURVIVAL; CIRCULATING TUMOR DNA; SEQUENCING APPROACH; FOLLOW-UP;
IMMUNOCHEMOTHERAPY; REMISSION
AB Chemoimmunotherapy followed by autologous stem cell transplantation (ASCT) is a standard therapy for transplant-eligible patients with newly diagnosed mantle cell lymphoma (MCL). The achievement of complete remission (CR) and minimal residual disease (MRD) negativity are associated with better outcomes. We tested an induction regimen of rituximab/bendamustine followed by rituximab/high-dose cytarabine (RB/RC). This phase 2 study (NCT01661881) enrolled 23 transplant-eligible patients aged 42-69, of whom 70% were MCL international prognostic index low-risk. Patients received three cycles of RB followed by three cycles of RC. The primary endpoint of the trial was the rate of CR after six cycles of therapy, with a rate of 75% considered promising. 96% of patients achieved a CR/unconfirmed CR after treatment, meeting the primary objective. One patient progressed on study, one declined ASCT in CR, and the remaining 21 underwent successful stem cell collection and ASCT. After a median follow-up of 13months, the progression-free survival rate was 96%. Among 15 MRD-evaluable patients who completed treatment, 93% achieved MRD negativity after RB/RC. In conclusion, RB/RC achieves very high CR and MRD negativity rates in transplant-eligible patients, with a favourable safety profile. RB/RC warrants further comparative studies, and may become a useful alternative to RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)-based induction regimens in this patient population.
C1 [Armand, Philippe; Bsat, Jad; Mayuram, Sangeetha; Fisher, David C.; LaCasce, Ann S.; Jacobson, Caron; Davids, Matthew S.; Brown, Jennifer R.; Freedman, Arnold S.; Jacobsen, Eric D.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Redd, Robert] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Giardino, Angela] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA.
[Weng, Li; Wilkins, Jennifer; Faham, Malek] Sequenta Inc, San Francisco, CA USA.
[Joyce, Robin] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA.
RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM parmand@partners.org
FU ASH Scholar Award; ASCO Career Development Award; ASBMT/Genentech Young
Investigator Award; Dunkin Donuts Rising Star award
FX P.A. was supported by an ASH Scholar Award, an ASCO Career Development
Award, an ASBMT/Genentech Young Investigator Award, and a Dunkin Donuts
Rising Star award. We are also indebted to the nursing and research
staff who were involved in this study, and to all of the participants
and their families.
NR 28
TC 5
Z9 5
U1 1
U2 4
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 APR
PY 2016
VL 173
IS 1
BP 89
EP 95
DI 10.1111/bjh.13929
PG 7
WC Hematology
SC Hematology
GA DH9TL
UT WOS:000373138700008
PM 26729345
ER
PT J
AU Armand, P
Kim, HT
Sainvil, MM
Lange, PB
Giardino, AA
Bachanova, V
Devine, SM
Waller, EK
Jagirdar, N
Herrera, AF
Cutler, C
Ho, VT
Koreth, J
Alyea, EP
McAfee, SL
Soiffer, RJ
Chen, YB
Antin, JH
AF Armand, Philippe
Kim, Haesook T.
Sainvil, Marie-Michele
Lange, Paulina B.
Giardino, Angela A.
Bachanova, Veronika
Devine, Steven M.
Waller, Edmund K.
Jagirdar, Neera
Herrera, Alex F.
Cutler, Corey
Ho, Vincent T.
Koreth, John
Alyea, Edwin P.
McAfee, Steven L.
Soiffer, Robert J.
Chen, Yi-Bin
Antin, Joseph H.
TI The addition of sirolimus to the graft-versus-host disease prophylaxis
regimen in reduced intensity allogeneic stem cell transplantation for
lymphoma: a multicentre randomized trial
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE clinical trials; lymphomas; stem cell transplantation; GVHD
ID PHASE-II TRIAL; LOW-DOSE METHOTREXATE; UNRELATED DONOR TRANSPLANTATION;
SINGLE-AGENT TEMSIROLIMUS; GVHD PROPHYLAXIS; CLINICAL-TRIALS;
TACROLIMUS; COMBINATION; BLOOD; EVEROLIMUS
AB Inhibition of the mechanistic target of rapamycin (mTOR) pathway has clinical activity in lymphoma. The mTOR inhibitor sirolimus has been used in the prevention and treatment of graft-versus-host disease (GVHD) after allogeneic haematopoietic stem cell transplantation (HSCT). A retrospective study suggested that patients with lymphoma undergoing reduced intensity conditioning (RIC) HSCT who received sirolimus as part of their GVHD prophylaxis regimen had a lower rate of relapse. We therefore performed a multicentre randomized trial comparing tacrolimus, sirolimus and methotrexate to standard regimens in adult patients undergoing RIC HSCT for lymphoma in order to assess the possible benefit of sirolimus on HSCT outcome. 139 patients were randomized. There was no difference overall in 2-year overall survival, progression-free survival, relapse, non-relapse mortality or chronic GVHD. However, the sirolimus-containing arm had a significantly lower incidence of grade II-IV acute GVHD (9% vs. 25%, P=0015), which was more marked for unrelated donor grafts. In conclusion, the addition of sirolimus for GVHD prophylaxis in RIC HSCT is associated with no increased overall toxicity and a lower risk of acute GVHD, although it does not improve survival; this regimen is an acceptable option for GVHD prevention in RIC HSCT. This trial is registered at clinicaltrials.gov (NCT00928018).
C1 [Armand, Philippe; Sainvil, Marie-Michele; Lange, Paulina B.; Cutler, Corey; Ho, Vincent T.; Koreth, John; Alyea, Edwin P.; Soiffer, Robert J.; Antin, Joseph H.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Kim, Haesook T.] Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA.
[Giardino, Angela A.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
[Bachanova, Veronika] Univ Minnesota, Dept Med Oncol, Minneapolis, MN USA.
[Devine, Steven M.] Ohio State Univ, Ctr Comprehens Canc, Dept Med, Columbus, OH 43210 USA.
[Waller, Edmund K.; Jagirdar, Neera] Emory Univ, Winship Canc Inst, Dept Hematol Oncol, Atlanta, GA 30322 USA.
[Herrera, Alex F.] City Hope Canc Ctr, Duarte, CA USA.
[McAfee, Steven L.; Chen, Yi-Bin] Massachusetts Gen Hosp, Div Hematol Oncol, Bone Marrow Transplant Unit, Boston, MA 02114 USA.
RP Armand, P (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM parmand@partners.org
FU ASH Scholar Award; ASCO Career Development Award; ASBMT/Genentech Young
Investigator Award; Dunkin Donuts Rising Star award; NIAID [U19 AI
29530]; NCI [P01 CA142106]; Jock and Bunny Adams Research and Education
Endowment
FX P.A. was supported by an ASH Scholar Award, an ASCO Career Development
Award, an ASBMT/Genentech Young Investigator Award, and a Dunkin Donuts
Rising Star award for this work. This work was also supported by NIAID
U19 AI 29530, NCI P01 CA142106, and the Jock and Bunny Adams Research
and Education Endowment. We are also indebted to the nursing and
research staff who were involved in this study, and to all of the
participants and their families.
NR 35
TC 8
Z9 8
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD APR
PY 2016
VL 173
IS 1
BP 96
EP 104
DI 10.1111/bjh.13931
PG 9
WC Hematology
SC Hematology
GA DH9TL
UT WOS:000373138700009
PM 26729448
ER
PT J
AU Van Dyke, DL
Werner, L
Rassenti, LZ
Neuberg, D
Ghia, E
Heerema, NA
Dal Cin, P
Dell Aquila, M
Sreekantaiah, C
Greaves, AW
Kipps, TJ
Kay, NE
AF Van Dyke, Daniel L.
Werner, Lillian
Rassenti, Laura Z.
Neuberg, Donna
Ghia, Emanuella
Heerema, Nyla A.
Dal Cin, Paola
Dell Aquila, Marie
Sreekantaiah, Chandrika
Greaves, Andrew W.
Kipps, Thomas J.
Kay, Neil E.
TI The Dohner fluorescence insitu hybridization prognostic classification
of chronic lymphocytic leukaemia (CLL): the CLL Research Consortium
experience
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE chronic lymphocytic leukaemia; cytogenetics; leukaemia; fluorescence
insitu hybridization
ID GENOMIC ABERRATIONS; DISEASE PROGRESSION; CLONAL EVOLUTION; FOLLOW-UP;
HETEROGENEITY; MUTATIONS; REVEALS; ZAP-70; IMPACT; COHORT
AB This study revisited the Dohner prognostic hierarchy in a cohort of 1585 well-documented patients with chronic lymphocytic leukaemia. The duration of both time to first treatment (TTFT) and overall survival (OS) were significantly longer than observed previously, and this is at least partly due to improved therapeutic options. Deletion 13q remains the most favourable prognostic group with median TTFT and OS from fluorescence insitu hybridization (FISH) testing of 72months and >12years, respectively. Deletion 11q had the poorest median TTFT (22months) and 17p deletion the poorest median OS (5years). The percentages of abnormal nuclei were significantly associated with differential TTFT for the trisomy 12, 13q and 17p deletion cohorts but not for the 11q deletion cohort. From the date of the first FISH study, patients with >85% 13q deletion nuclei had a notably shorter TTFT (24months). Patients with 20% 17p deletion nuclei had longer median TTFT and OS from the date of the first FISH study (44months and 11years), and were more likely to be IGHV mutated.
C1 [Van Dyke, Daniel L.; Kay, Neil E.] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55902 USA.
[Van Dyke, Daniel L.; Kay, Neil E.] Mayo Clin, Dept Internal Med, Rochester, MN USA.
[Werner, Lillian; Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Rassenti, Laura Z.; Ghia, Emanuella; Dell Aquila, Marie; Greaves, Andrew W.; Kipps, Thomas J.] Moores Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA.
[Heerema, Nyla A.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA.
[Dal Cin, Paola] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA.
[Sreekantaiah, Chandrika] North Shore LIJ Hlth Syst, Long Isl City, NY USA.
RP Van Dyke, DL (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55902 USA.
EM vandyke.daniel@mayo.edu
FU National Institutes of Health [PO1-CA81534]
FX 'This work was supported by a grant (PO1-CA81534) from the National
Institutes of Health to T. J. Kipps for the CLL Research Consortium'. We
appreciate the technical support and cytogenetic data from C
Sreekantaiah and SA Smoley.
NR 25
TC 6
Z9 7
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1048
EI 1365-2141
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD APR
PY 2016
VL 173
IS 1
BP 105
EP 113
DI 10.1111/bjh.13933
PG 9
WC Hematology
SC Hematology
GA DH9TL
UT WOS:000373138700010
PM 26848054
ER
PT J
AU Fisher, MB
Belkin, NS
Milby, AH
Henning, EA
Soegaard, N
Kim, M
Pfeifer, C
Saxena, V
Dodge, GR
Burdick, JA
Schaer, TP
Steinberg, DR
Mauck, RL
AF Fisher, Matthew B.
Belkin, Nicole S.
Milby, Andrew H.
Henning, Elizabeth A.
Soeegaard, Nicole
Kim, Minwook
Pfeifer, Christian
Saxena, Vishal
Dodge, George R.
Burdick, Jason A.
Schaer, Thomas P.
Steinberg, David R.
Mauck, Robert L.
TI Effects of Mesenchymal Stem Cell and Growth Factor Delivery on Cartilage
Repair in a Mini-Pig Model
SO CARTILAGE
LA English
DT Article
DE cartilage; repair; mesenchymal stem cells; TGF-3; animal models
ID HYALURONIC-ACID HYDROGELS; AUTOLOGOUS CHONDROCYTE IMPLANTATION;
ENGINEERED CARTILAGE; IN-VIVO; OSTEOCHONDRAL DEFECTS;
ARTICULAR-CARTILAGE; CHONDROGENIC DIFFERENTIATION; ALGINATE
MICROSPHERES; STROMAL CELLS; MATRIX
AB Objective We have recently shown that mesenchymal stem cells (MSCs) embedded in a hyaluronic acid (HA) hydrogel and exposed to chondrogenic factors (transforming growth factor-3 [TGF-3]) produce a cartilage-like tissue in vitro. The current objective was to determine if these same factors could be combined immediately prior to implantation to induce a superior healing response in vivo relative to the hydrogel alone.
Design Trochlear chondral defects were created in Yucatan mini-pigs (6 months old). Treatment groups included an HA hydrogel alone and hydrogels containing allogeneic MSCs, TGF-3, or both. Six weeks after surgery, micro-computed tomography was used to quantitatively assess defect fill and subchondral bone remodeling. The quality of cartilage repair was assessed using the ICRS-II histological scoring system and immunohistochemistry for type II collagen.
Results Treatment with TGF-3 led to a marked increase in positive staining for collagen type II within defects (P < 0.05), while delivery of MSCs did not (P > 0.05). Neither condition had an impact on other histological semiquantitative scores (P > 0.05), and inclusion of MSCs led to significantly less defect fill (P < 0.05). For all measurements, no synergistic interaction was found between TGF-3 and MSC treatment when they were delivered together (P > 0.05).
Conclusions At this early healing time point, treatment with TGF-3 promoted the formation of collagen type II within the defect, while allogeneic MSCs had little benefit. Combination of TGF-3 and MSCs at the time of surgery did not produce a synergistic effect. An in vitro precultured construct made of these components may be required to enhance in vivo repair in this model system.
C1 [Fisher, Matthew B.; Belkin, Nicole S.; Milby, Andrew H.; Henning, Elizabeth A.; Soeegaard, Nicole; Kim, Minwook; Pfeifer, Christian; Saxena, Vishal; Dodge, George R.; Steinberg, David R.; Mauck, Robert L.] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA 19104 USA.
[Fisher, Matthew B.; Belkin, Nicole S.; Milby, Andrew H.; Henning, Elizabeth A.; Soeegaard, Nicole; Kim, Minwook; Pfeifer, Christian; Saxena, Vishal; Dodge, George R.; Burdick, Jason A.; Steinberg, David R.; Mauck, Robert L.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA.
[Fisher, Matthew B.] Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC USA.
[Fisher, Matthew B.] N Carolina State Univ, Raleigh, NC 27695 USA.
[Pfeifer, Christian] Univ Regensburg, Med Ctr, Dept Trauma Surg, D-93053 Regensburg, Germany.
[Burdick, Jason A.; Mauck, Robert L.] Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA.
[Schaer, Thomas P.] Univ Penn, Sch Vet Med, Comparat Orthopaed Res Lab, Philadelphia, PA 19104 USA.
RP Mauck, RL (reprint author), Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA.; Mauck, RL (reprint author), Univ Penn, Perelman Sch Med, Dept Bioengn, 424 Stemmler Hall,36th St & Hamilton Walk, Philadelphia, PA 19104 USA.
EM lemauck@mail.med.upenn.edu
FU National Institutes of Health [R01 EB008722, F32 AR062971]; Department
of Veterans Affairs [I01 RX000700]; AO Foundation; Orthopaedic Research
and Education Foundation
FX The authors thank Liming Bian, Megan Farrell, Tristan Driscoll, Sylvia
Qu, and Marc Bostrom for their technical assistance. This work was
supported by the National Institutes of Health (R01 EB008722 and F32
AR062971), the Department of Veterans Affairs (I01 RX000700), the AO
Foundation, and the Orthopaedic Research and Education Foundation
(Resident Clinician Scientist Training Grant).
NR 52
TC 1
Z9 1
U1 7
U2 18
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1947-6035
EI 1947-6043
J9 CARTILAGE
JI Cartilage
PD APR
PY 2016
VL 7
IS 2
BP 174
EP 184
DI 10.1177/1947603515623030
PG 11
WC Orthopedics
SC Orthopedics
GA DH6LG
UT WOS:000372901500006
PM 27047640
ER
PT J
AU Cormier, AC
Drapek, L
Fahey, J
Rowen, B
Burns-Britton, BA
Lavadinho-Lemos, M
Hultman, T
AF Cormier, Aurelie C.
Drapek, Lorraine
Fahey, Jean
Rowen, Brenna
Burns-Britton, Betty Ann
Lavadinho-Lemos, Maria
Hultman, Todd
TI When the Patient Seeks Cure: Challenging Chemotherapy and Radiation Side
Effects Requiring Creative Solutions
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Editorial Material
DE rectal cancer; concomitant chemoradiotherapy; radiation dermatitis; pain
AB When undergoing concomitant chemotherapy and radiation therapy for anal cancer, patients often experience significant side effects, including grade 1 or 2 radiation dermatitis, pain, exudate, and diarrhea. This case study presents a grade 3 reaction complicated by complex medical conditions. In addition to an evidence-based skin care treatment and side effect management plan that support patients during this intense period, this article offers creative strategies to provide a cost-effective healing option.
C1 [Cormier, Aurelie C.; Fahey, Jean; Rowen, Brenna; Burns-Britton, Betty Ann; Lavadinho-Lemos, Maria] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Drapek, Lorraine] Massachusetts Gen Hosp, Gastrointestinal Radiat Oncol, Boston, MA 02114 USA.
[Hultman, Todd] HealthONE, Denver, CO USA.
RP Cormier, AC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.
EM acormier@partners.org
NR 7
TC 0
Z9 0
U1 1
U2 3
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
EI 1538-067X
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD APR
PY 2016
VL 20
IS 2
BP 117
EP 120
DI 10.1188/16.CJON.117-120
PG 4
WC Oncology; Nursing
SC Oncology; Nursing
GA DH8ID
UT WOS:000373035800002
PM 26991702
ER
PT J
AU Sullivan, CM
Dalby, C
Gross, AH
Chesnulevich, K
Lilienfeld, CW
Hooper, C
Rizzo, P
Kochanek, T
AF Sullivan, Clare M.
Dalby, Carole
Gross, Anne H.
Chesnulevich, Kaitlin
Lilienfeld, Christine W.
Hooper, Catherine
Rizzo, Patricia
Kochanek, Thomas
TI Oral Chemotherapy Education: Using Innovation to Ensure Broad Access
SO CLINICAL JOURNAL OF ONCOLOGY NURSING
LA English
DT Editorial Material
DE oral chemotherapy; audiovisual education; social media
AB The purpose of this article is to share one institution's intervention to improve oral chemotherapy patient education. The overall aim was to provide clinicians with a single source of educational materials that would meet a diverse group of patients' educational needs and be consistent with published guidelines.
C1 [Sullivan, Clare M.] Dana Farber Canc Inst, Patient Educ, Boston, MA 02115 USA.
[Sullivan, Clare M.] Dana Farber Canc Inst, Patient Educ, Boston, MA 02115 USA.
[Dalby, Carole] Dana Farber Canc Inst, Clin Qual Improvement, Boston, MA 02115 USA.
[Gross, Anne H.] Dana Farber Canc Inst, Adult Nursing & Clin Serv, Boston, MA 02115 USA.
[Chesnulevich, Kaitlin; Hooper, Catherine] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Lilienfeld, Christine W.; Rizzo, Patricia] Dana Farber Canc Inst, Ctr Gastrointestinal Canc, Boston, MA 02115 USA.
[Kochanek, Thomas] Rhode Isl Coll, Feinstein Sch Educ & Human Dev, Providence, RI 02908 USA.
RP Sullivan, CM (reprint author), Dana Farber Canc Inst, Patient Educ, Boston, MA 02115 USA.; Sullivan, CM (reprint author), Dana Farber Canc Inst, Patient Educ, Boston, MA 02115 USA.
EM clare_sullivan@dfci.harvard.edu
NR 7
TC 0
Z9 0
U1 1
U2 4
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 1092-1095
EI 1538-067X
J9 CLIN J ONCOL NURS
JI Clin. J. Oncol. Nurs.
PD APR
PY 2016
VL 20
IS 2
BP 126
EP 128
DI 10.1188/16.CJON.126-128
PG 3
WC Oncology; Nursing
SC Oncology; Nursing
GA DH8ID
UT WOS:000373035800003
PM 26991703
ER
PT J
AU Post, RM
Leverich, GS
Kupka, R
Keck, PE
McElroy, SL
Altshuler, LL
Frye, MA
Rowe, M
Grunze, H
Suppes, T
Nolen, WA
AF Post, Robert M.
Leverich, Gabriele S.
Kupka, Ralph
Keck, Paul E., Jr.
McElroy, Susan L.
Altshuler, Lori L.
Frye, Mark A.
Rowe, Michael
Grunze, Heinz
Suppes, Trisha
Nolen, Willem A.
TI Clinical correlates of sustained response to individual drugs used in
naturalistic treatment of patients with bipolar disorder
SO COMPREHENSIVE PSYCHIATRY
LA English
DT Article
ID LIFE-CHART METHOD; I DISORDER; ANTIDEPRESSANT TREATMENT;
CONTROLLED-TRIAL; DOUBLE-BLIND; EARLY-ONSET; STEP-BD; LITHIUM;
OUTPATIENTS; DEPRESSION
AB Objective: To report use and treatment success rates of medications for bipolar disorder as a function of patients' clinical characteristics.
Method: Outpatients with bipolar illness diagnosed by SCID were rated by research assistants on the NIMH-LCM and those who had an good response for at least 6 months (much or very much improved on the CGI-BP) were considered responders (treatment "success"). Clinical characteristics associated with treatment response in the literature were examined for how often a drug was in a successful regimen when a given characteristic was either present or absent.
Results: Lithium was less successful in those with histories of rapid cycling, substance abuse, or (surprisingly) a positive parental history of mood disorders. Valproate was less successful in those with >= 20 prior episodes. Lamotrigine (LTG) was less successful in those with a parental history of mood disorders or in BP-I compared to BP-II disorder. Antidepressants (ADs) had low success rates, especially in those with a history of anxiety disorders. Benzodiazepines had low success rates in those with child abuse, substance use, or >= 20 episodes. Atypical antipsychotics were less successful in the presence of rapid cycling, >= 20 prior episodes, or a greater number of poor prognosis factors.
Conclusion: Success rates reflect medications used in combination with an average of two other drugs during naturalistic treatment and thus should be considered exploratory. However, the low long-term success rates of drugs (even when used in combination with others) that occurred in the presence of many very common clinical characteristics of bipolar illness speak to the need for the development of alternative treatment strategies. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Post, Robert M.; Leverich, Gabriele S.; Rowe, Michael] 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, Coll Med, Dept Psychiat & Behav Neurosci, Cincinnati, OH USA.
[Keck, Paul E., Jr.; McElroy, Susan L.] Lindner Ctr HOPE, Mason, OH USA.
[McElroy, Susan L.] Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA.
[Altshuler, Lori L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA.
[Altshuler, Lori L.] West Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA.
[Frye, Mark A.] Mayo Clin, Dept Psychiat, Rochester, MI USA.
[Grunze, Heinz] Newcastle Univ, Acad Psychiat, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, 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, Groningen, Netherlands.
RP Post, RM (reprint author), Bipolar Collaborat Network, 5415 West Cedar Lane,Suite 201-B, Bethesda, MD 20814 USA.
EM robert.post@speakeasy.net
OI Grunze, Heinz/0000-0003-4712-8979
NR 43
TC 2
Z9 2
U1 2
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0010-440X
EI 1532-8384
J9 COMPR PSYCHIAT
JI Compr. Psychiat.
PD APR
PY 2016
VL 66
BP 146
EP 156
DI 10.1016/j.comppsych.2016.01.009
PG 11
WC Psychiatry
SC Psychiatry
GA DH4ML
UT WOS:000372760000020
PM 26995248
ER
PT J
AU Lynch, CP
Williams, JS
Voronca, D
Walker, RJ
Egede, LE
AF Lynch, Cheryl P.
Williams, Joni Strom
Voronca, Delia
Walker, Rebekah J.
Egede, Leonard E.
TI Meaning of Illness and Cardiovascular Risk Factors in Patients With Type
2 Diabetes
SO DIABETES EDUCATOR
LA English
DT Article
ID SELF-MANAGEMENT; DEPRESSION; MELLITUS; ADULTS; HEALTH; QUESTIONNAIRE;
RELIABILITY; ASSOCIATION; DISTRESS; VALIDITY
AB Purpose The purpose of this study was to examine the relationship between meaning of illness and cardiovascular disease risk factors in patients with type 2 diabetes.
Methods The sample population was recruited from primary care clinics in the southeastern United States. The meaning of illness was assessed by a validated questionnaire with 5 subscales. The primary outcomes were cardiovascular disease (CVD) risk factors, assessed by A1C, systolic and diastolic blood pressure (SBP and DBP, respectively), and low-density lipoprotein cholesterol (LDL-C). Multivariate linear regression models investigated associations between the clinical outcomes and the 5 MIQ factors, controlling for possible confounders.
Results The sample comprised 302 black and white participants of whom more than half were elderly (65+ years) and the vast majority were male (98%). Systolic blood pressure was positively associated with non-anticipated vulnerability. Diastolic blood pressure was negatively associated with degree of stress/change in commitments and positively associated with challenge/motivation/hope and non-anticipated vulnerability. Low-density lipoprotein cholesterol was significantly and negatively associated with degree of stress/change in commitments.
Conclusions Meaning of illness had a significant effect on measured outcomes of CVD risk. The specific factor included in the overarching concept of meaning of illness differed in its influence, with more positive views of stress/commitments associated with lower blood pressure and LDL but more positive views of the challenge/hope/motivation and negative views of non-anticipated vulnerability associated with diabetes associated with higher systolic and diastolic blood pressure.
C1 [Lynch, Cheryl P.; Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, HEROIC, Charleston, SC USA.
[Lynch, Cheryl P.; Williams, Joni Strom; Voronca, Delia; Walker, Rebekah J.; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Ctr Hlth Dispar Res, Charleston, SC 29425 USA.
[Lynch, Cheryl P.; Williams, Joni Strom; Voronca, Delia; Egede, Leonard E.] Med Univ S Carolina, Dept Med, Div Gen Internal Med & Geriatr, Charleston, SC 29425 USA.
RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Hlth Equ & Rural Outreach Innovat Ctr, 135 Rutledge Ave,Room 280G,POB 250593, Charleston, SC 29425 USA.
EM egedel@musc.edu
FU VHA Health Services Research and Development (HSRD) program [TRP 04-038]
FX This study was supported by grant No. TRP 04-038 funded by the VHA
Health Services Research and Development (HSR&D) program. The funding
agency did not participate in the design and conduct of the study;
collection, management, analysis, and interpretation of the data; or
preparation, review, or approval of the manuscript. The manuscript
represents the views of the authors and not those of the VA or HSR&D.
NR 29
TC 0
Z9 0
U1 0
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0145-7217
EI 1554-6063
J9 DIABETES EDUCATOR
JI Diabetes Educ.
PD APR
PY 2016
VL 42
IS 2
BP 220
EP 227
DI 10.1177/0145721716631430
PG 8
WC Endocrinology & Metabolism; Public, Environmental & Occupational Health
SC Endocrinology & Metabolism; Public, Environmental & Occupational Health
GA DH6DV
UT WOS:000372882100007
PM 26879460
ER
PT J
AU Iezzoni, LI
Wint, AJ
Kuhlthau, KA
Boudreau, AA
AF Iezzoni, Lisa I.
Wint, Amy J.
Kuhlthau, Karen A.
Boudreau, Alexy Arauz
TI Adults' recollections and perceptions of childhood caregiving to a
parent with significant physical disability
SO DISABILITY AND HEALTH JOURNAL
LA English
DT Article
DE Disability; Caregiving; Child; Parent
ID YOUNG CARERS; MULTIPLE-SCLEROSIS; FAMILY-MEMBERS; CHILDREN; IMPACT
AB Background: Caregiving roles of children < 18 years of age living with parents with health conditions or disability have been studied extensively abroad, but little U.S. research has examined the caregiving activities and perceptions of children with parents with significant physical disability.
Objective: To examine children's caregiving activities for their disabled parent, childhood perceptions of these activities, and adult views of this caregiving.
Methods: We conducted 1-h, semi-structured, open-ended interviews with 20 persons age >= 21 years who as children (age < 18 years) had a parent with significant mobility disability. We used conventional content analysis to identify themes.
Results: Interviewees' mean (standard deviation) age was 36.7 (13.8) years; 4 were male. As children, most interviewees assisted their disabled parent with activities of daily living (ADLs) and instrumental ADLs; some children provided more medical supports. Several parents, especially of older interviewees, did not seek their children's care. Interviewees reported both positive and negative childhood attitudes about caregiving. Roughly half recalled as children feeling proud, special, or otherwise positively toward caregiving activities, while about one-third viewed caregiving as just part of their daily reality (i.e., simply needing to be done). Approximately half remembered also feeling resentful, primarily from time demands, insufficient appreciation, and being different from their peers. Interviewees reported gender and cultural factors affecting their caregiving roles and perceptions.
Conclusions: Children can provide significant care to parents with physical disability. Understanding better their roles and perceptions could suggest ways to improve these experiences for both child and parent. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Iezzoni, Lisa I.; Wint, Amy J.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
[Kuhlthau, Karen A.; Boudreau, Alexy Arauz] Massachusetts Gen Hosp Children, Dept Pediat, Boston, MA USA.
[Iezzoni, Lisa I.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA.
[Kuhlthau, Karen A.; Boudreau, Alexy Arauz] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA.
RP Iezzoni, LI (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Room 901B, Boston, MA 02114 USA.
EM liezzoni@mgh.harvard.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [R21HD073553-01A2]
FX The Eunice Kennedy Shriver National Institute of Child Health and Human
Development funded this study (Grant No. R21HD073553-01A2). The authors
have no financial conflicts of interest.
NR 36
TC 0
Z9 0
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-6574
EI 1876-7583
J9 DISABIL HEALTH J
JI Disabil. Health J.
PD APR
PY 2016
VL 9
IS 2
BP 208
EP 217
DI 10.1016/j.dhjo.2015.10.009
PG 10
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health; Rehabilitation
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Rehabilitation
GA DH3WT
UT WOS:000372718200007
PM 26712460
ER
PT J
AU Tritos, NA
AF Tritos, Nicholas A.
TI Skeletal health in adult growth hormone deficiency
SO ENDOCRINE
LA English
DT Editorial Material
ID BONE-MINERAL DENSITY; GH DEFICIENCY; REPLACEMENT THERAPY; PREVALENCE
C1 [Tritos, Nicholas A.] Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA.
[Tritos, Nicholas A.] Harvard Univ, Sch Med, Zero Emerson Pl 112, Boston, MA 02114 USA.
RP Tritos, NA (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Zero Emerson Pl 112, Boston, MA 02114 USA.; Tritos, NA (reprint author), Harvard Univ, Sch Med, Zero Emerson Pl 112, Boston, MA 02114 USA.
EM ntritos@partners.org
NR 10
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD APR
PY 2016
VL 52
IS 1
BP 1
EP 2
DI 10.1007/s12020-016-0859-z
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DH9XA
UT WOS:000373148100001
PM 26767651
ER
PT J
AU Svensson, E
Farkas, DK
Gradus, JL
Lash, TL
Sorensen, HT
AF Svensson, E.
Farkas, D. K.
Gradus, J. L.
Lash, T. L.
Sorensen, H. T.
TI Adjustment disorder and risk of Parkinson's disease
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE adjustment disorder; Parkinson's disease; psychological stress
ID SEVERE STRESS; REGISTER; DEPRESSION; EPIDEMIOLOGY; DIAGNOSES; SYMPTOMS;
SMOKING; COHORT; SYSTEM
AB Background and purposeIt has been postulated that stress is part of the etiological process of Parkinson's disease (PD). The risk of PD was examined in a cohort of patients with adjustment disorders, a diagnosis made in the presence of a severe response to a stressful life event.
MethodsUsing Danish medical registries, PD occurrence was examined in a nationwide population-based cohort of patients with adjustment disorder diagnosed between 1995 and 2011. The standardized incidence ratio of PD was calculated as the ratio of observed to expected cases, stratified by time and potential risk factors, including depression and anxiety.
ResultsOur adjustment disorder cohort (67 786 patients) was followed for a median of 8 years (interquartile range 4, 12.6 years). During follow-up, 119 patients developed PD, versus 64 expected, corresponding to a standardized incidence ratio of 1.84 (95% confidence interval 1.53, 2.20). Consistent results were observed after stratification on potential risk factors, including depression and anxiety.
ConclusionAdjustment disorder, a diagnosis made in the presence of severe response to stressful life events, was associated with an increased risk of PD.
C1 [Svensson, E.; Farkas, D. K.; Gradus, J. L.; Lash, T. L.; Sorensen, H. T.] Aarhus Univ Hosp, Dept Clin Epidemiol, Olof Palmes Alle 43-45, DK-8000 Aarhus N, Denmark.
[Gradus, J. L.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA.
[Gradus, J. L.] Boston Univ, Dept Psychiat, Boston, MA 02215 USA.
[Gradus, J. L.] Boston Univ, Dept Epidemiol, Boston, MA 02215 USA.
[Lash, T. L.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
RP Svensson, E (reprint author), Aarhus Univ Hosp, Dept Clin Epidemiol, Olof Palmes Alle 43-45, DK-8000 Aarhus N, Denmark.
EM Elisabeth.svensson@clin.au.dk
FU National Institute of Mental Health [1R21MH094551-01A1]; Program for
Clinical Research Infrastructure
FX This work was supported by a National Institute of Mental Health grant
'Constructing a Danish Reaction to Severe Stress Cohort'
(1R21MH094551-01A1), Jaimie Gradus, Principal Investigator, the Program
for Clinical Research Infrastructure established by Lundbeck and Novo
Nordisk Foundations, Aarhus University Research Foundation.
NR 30
TC 0
Z9 0
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD APR
PY 2016
VL 23
IS 4
BP 751
EP 756
DI 10.1111/ene.12933
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DH7KK
UT WOS:000372972300017
PM 26756302
ER
PT J
AU Robles, AI
Traverso, G
Zhang, M
Roberts, NJ
Khan, MA
Joseph, C
Lauwers, GY
Selaru, FM
Popoli, M
Pittman, ME
Ke, XQ
Hruban, RH
Meltzer, SJ
Kinzler, KW
Vogelstein, B
Harris, CC
Papadopoulos, N
AF Robles, Ana I.
Traverso, Giovanni
Zhang, Ming
Roberts, Nicholas J.
Khan, Mohammed A.
Joseph, Christine
Lauwers, Gregory Y.
Selaru, Florin M.
Popoli, Maria
Pittman, Meredith E.
Ke, Xiquan
Hruban, Ralph H.
Meltzer, Stephen J.
Kinzler, Kenneth W.
Vogelstein, Bert
Harris, Curtis C.
Papadopoulos, Nickolas
TI Whole-Exome Sequencing Analyses of Inflammatory Bowel Disease-Associated
Colorectal Cancers
SO GASTROENTEROLOGY
LA English
DT Article
DE Exome; Sequencing; Ulcerative Colitis; Crohn's Disease
ID C-KI-RAS; COLITIS-ASSOCIATED NEOPLASMS; SPORADIC COLON-CARCINOMA;
ULCERATIVE-COLITIS; MICROSATELLITE INSTABILITY; GENE-MUTATIONS;
GASTRIC-CANCER; NITRIC-OXIDE; ESOPHAGEAL ADENOCARCINOMA; ABERRANT
METHYLATION
AB BACKGROUND & AIMS: A long duration of inflammatory bowel disease (IBD) increases the risk for colorectal cancer. Mutation analysis of limited numbers of genes has indicated that colorectal tumors that develop in patients with IBD differ from those of patients without IBD. We performed whole-exome sequencing analyses to characterize the genetic landscape of these tumors. METHODS: We collected colorectal tumor and non-neoplastic tissues from 31 patients with IBD and colorectal cancer (15 with ulcerative colitis, 14 with Crohn's disease, and 2 with indeterminate colitis) and performed whole-exome sequencing analyses of the micro-dissected tumor and matched nontumor tissues. We identified somatic alterations by comparing matched specimens. The prevalence of mutations in sporadic colorectal tumors was obtained from previously published exome-sequencing studies. RESULTS: Two specimens had somatic mutations in the DNA proofreading or mismatch repair genes POLE, MLH1, and MSH6 and the tumor cells had a hypermutable phenotype. The remaining tumors had, on average, 71 alterations per sample. TP53 was the most commonly mutated gene, with prevalence similar to that of sporadic colorectal tumors (63% of cases). However, tumors from the patients with IBD had a different mutation spectrum. APC and KRAS were mutated at significantly lower rates in tumors from patients with IBD than in sporadic colorectal tumors (13% and 20% of cases, respectively). Several genes were mutated more frequently or uniquely in tumors from patients with IBD, including SOX9 and EP300 (which encode proteins in the WNT pathway), NRG1 (which encodes an ERBB ligand), and IL16 (which encodes a cytokine). Our study also revealed recurrent mutations in components of the Rho and Rac GTPase network, indicating a role for noncanonical WNT signaling in development of colorectal tumors in patients with IBD. CONCLUSIONS: Colorectal tumors that develop in patients with IBD have distinct genetic features from sporadic colorectal tumors. These findings could be used to develop disease-specific markers for diagnosis and treatment of patients with IBD and colorectal cancer.
C1 [Robles, Ana I.; Khan, Mohammed A.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 3068A,MSC 4258, Bethesda, MD 20892 USA.
[Traverso, Giovanni] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA.
[Traverso, Giovanni] MIT, Dept Chem Engn, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA.
[Zhang, Ming; Roberts, Nicholas J.; Joseph, Christine; Popoli, Maria; Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas] Ludwig Ctr Johns Hopkins, Baltimore, MD 21287 USA.
[Roberts, Nicholas J.; Pittman, Meredith E.; Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21205 USA.
[Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Selaru, Florin M.; Ke, Xiquan; Meltzer, Stephen J.] Johns Hopkins Univ, Sch Med, Div Gastroenterol, Baltimore, MD USA.
[Vogelstein, Bert] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Kinzler, Kenneth W.; Vogelstein, Bert; Papadopoulos, Nickolas] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 3068A,MSC 4258, Bethesda, MD 20892 USA.; Vogelstein, B; Papadopoulos, N (reprint author), Ludwig Ctr Johns Hopkins, Dept Oncol, 1650 Orleans St,CRB1 Room 585, Baltimore, MD 21287 USA.
EM bertvog@gmail.com; harrisc@mail.nih.gov; npapado1@jhmi.edu
FU Intramural NIH HHS; NCI NIH HHS [R01 CA133012, CA057345, CA133012,
CA152753, CA190040, CA43460, CA62924, P50 CA062924, R01 CA057345, R01
CA190040, R37 CA043460, R37 CA057345, U01 CA152753]; NIDDK NIH HHS [P30
DK089502, T32 DK007191, T32-DK007191-38-S1]
NR 98
TC 14
Z9 14
U1 6
U2 12
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2016
VL 150
IS 4
BP 931
EP 943
DI 10.1053/j.gastro.2015.12.036
PG 13
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DH4BH
UT WOS:000372730000032
PM 26764183
ER
PT J
AU Francis, FF
Kulich, SM
Hashash, JG
AF Francis, Fadi F.
Kulich, Scott M.
Hashash, Jana G.
TI Diarrhea, Ascites, and Eosinophilia Image 3: Hypereosinophilic Syndrome
SO GASTROENTEROLOGY
LA English
DT Editorial Material
C1 [Francis, Fadi F.] VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Francis, Fadi F.; Hashash, Jana G.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Kulich, Scott M.] VA Pittsburgh Hlth Care Syst, Dept Pathol, Pittsburgh, PA USA.
[Kulich, Scott M.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA.
RP Francis, FF (reprint author), VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.; Francis, FF (reprint author), Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
NR 3
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 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD APR
PY 2016
VL 150
IS 4
BP E6
EP E8
DI 10.1053/j.gastro.2015.10.019
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DH4BH
UT WOS:000372730000003
PM 26930018
ER
PT J
AU Coleman, RL
Matulonis, UA
AF Coleman, Robert L.
Matulonis, Ursula A.
TI Precision medicine
SO GYNECOLOGIC ONCOLOGY
LA English
DT Editorial Material
C1 [Coleman, Robert L.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA.
[Matulonis, Ursula A.] Dana Farber Canc Inst, Gynecol Oncol Program, Dept Med Oncol, Boston, MA 02215 USA.
RP Matulonis, UA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA.
EM Ursula_Matulonis@dfci.harvard.edu
NR 0
TC 0
Z9 0
U1 1
U2 7
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 APR
PY 2016
VL 141
IS 1
SI SI
BP 1
EP 1
DI 10.1016/j.ygyno.2016.03.017
PG 1
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DI1HG
UT WOS:000373246600001
PM 27016221
ER
PT J
AU Myers, AP
Filiaci, VL
Zhang, YP
Pearl, M
Behbakht, K
Makker, V
Hanjani, P
Zweizig, S
Burke, JJ
Downey, G
Leslie, KK
Van Hummelen, P
Birrer, MJ
Fleming, GF
AF Myers, Andrea P.
Filiaci, Virginia L.
Zhang, Yuping
Pearl, Michael
Behbakht, Kian
Makker, Vicky
Hanjani, Parviz
Zweizig, Susan
Burke, James J., II
Downey, Gordon
Leslie, Kimberly K.
Van Hummelen, Paul
Birrer, Michael J.
Fleming, Gini F.
TI Tumor mutational analysis of GOG248, a phase II study of temsirolimus or
temsirolimus and alternating megestrol acetate and tamoxifen for
advanced endometrial cancer (EC): An NRG Oncology/Gynecologic Oncology
Group study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
ID TUBEROUS SCLEROSIS COMPLEX; MAMMALIAN TARGET; RAPAMYCIN INHIBITION;
CARCINOMA; EVEROLIMUS; RECURRENT; TRIAL; RIDAFOROLIMUS; WOMEN; PTEN
AB Objective. Rapamycin analogs have reproducible but modest efficacy in endometrial cancer (EC). Identification of molecular biomarkers that predict benefit could guide clinical development.
Methods. Fixed primary tissue and whole blood were collected prospectively from patients enrolled on GOG 248. DNA was isolated from macro-dissected tumors and blood; next-generation sequence analysis was performed on a panel of cancer related genes. Associations between clinical outcomes [response rate (RR) 20%; progression-free survival (PFS) median 4.9 months] and mutations (PTEN, PIK3CA, PIK3R1, KRAS, CTNNB1, AKT1, TSC1, TSC2, NF1, FBXW7) were explored.
Results. Sequencing data was obtained from tumors of 55 of the 73 enrolled pts. Mutation rates were consistent with published reports: mutations in PTEN (45%), PIK3CA (29%), PIK3R1 (24%), K-RAS (16%), CTNNB1 (18%) were common and mutations in AKT1 (4%), TSC1 (2%), TSC2 (2%), NF1 (9%) and FBXW7 (4%) were less common. Increased PFS (HR 0.16; 95% CI 0.01-0.78) and RR (response difference 0.83; 95% CI 0.03-0.99) were noted for AKT1 mutation. An increase in PFS (HR 0.46; 95% CI 0.20-0.97) but not RR (response difference 0.00, 95% CI-0.34-0.34) was identified for CTNNB1 mutation. Both patients with TSC mutations had an objective response. There were no statistically significant associations between mutations in PIK3CA, PTEN, PIK3R1, or KRAS and PFS or RR.
Conclusions. Mutations in AKT1, TSC1 and TSC2 are rare, but may predict clinical benefit from temsirolimus. CTNNB1 mutations were associated with longer PFS on temsirolimus. (C) 2016 Published by Elsevier Inc.
C1 [Myers, Andrea P.; Van Hummelen, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Filiaci, Virginia L.] NRG Oncol Stat & Data Management Ctr, Buffalo, NY USA.
[Zhang, Yuping; Leslie, Kimberly K.] Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA.
[Pearl, Michael] SUNY Stony Brook, Stony Brook, NY 11794 USA.
[Behbakht, Kian] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Makker, Vicky] Mem Sloan Kettering Canc Ctr, Weill Cornell Med Coll, 1275 York Ave, New York, NY 10021 USA.
[Hanjani, Parviz] Abington Mem Hosp, Gladwyne, PA USA.
[Zweizig, Susan] Univ Massachusetts Mem Hlth Care, Worcester, MA USA.
[Burke, James J., II] Mercer Univ, Sch Med, Savannah, GA USA.
[Downey, Gordon] Gynecol Oncol West Michigan, Grand Rapids, MI USA.
[Birrer, Michael J.] Massachusetts Gen Hosp, Dana Farber Canc Ctr, Boston, MA 02114 USA.
[Fleming, Gini F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA.
RP Myers, AP (reprint author), Novartis Inst BioMed Res, 220 Massachusetts Ave, Cambridge, MA 02139 USA.
EM andrea.myers@novartis.com
FU NCI grants [CA 27469]; GOG Statistical and Data Center [CA 37517]; NRG
Oncology [1 U10CA180822]; Susan Smith Executive Council
FX NCI grants to the GOG Administrative Office (CA 27469), the GOG
Statistical and Data Center (CA 37517), and the NRG Oncology 1
U10CA180822. Molecular analysis was funded by a Susan Smith Executive
Council Grant to A. M.
NR 38
TC 1
Z9 1
U1 0
U2 2
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 APR
PY 2016
VL 141
IS 1
SI SI
BP 43
EP 48
DI 10.1016/j.ygyno.2016.02.025
PG 6
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DI1HG
UT WOS:000373246600008
PM 27016228
ER
PT J
AU Liu, J
Westin, SN
AF Liu, Joyce
Westin, Shannon N.
TI Rational selection of biomarker driven therapies for gynecologic
cancers: The more we know, the more we know we don't know
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Gynecologic cancer; Biomarkers; Personalized medicine; Targeted therapy;
Precision medicine
ID RECURRENT EPITHELIAL OVARIAN; PHASE-II TRIAL; METASTATIC ENDOMETRIAL
CANCER; OLAPARIB MAINTENANCE THERAPY; PRIMARY PERITONEAL CANCER; GRADE
SEROUS CARCINOMA; FALLOPIAN-TUBE CANCER; CELL LUNG-CANCER;
ONCOLOGY-GROUP; BRAF MUTATION
AB Precision medicine is a rapidly evolving area in the treatment of gynecologic malignancies. Advances in sequencing technology have resulted in an increasing wealth of data regarding the genomic characteristics of ovarian, endometrial, and cervical cancers. These vast new datasets of information have led to novel insights into potential vulnerabilities and therapeutic targets for these cancers. However, unraveling the complex molecular changes within cancer cells to determine how best to attack these targets and to identify effective biomarkers of response remains a significant challenge. In this article, we review the current status of biomarker-driven targeted therapy in gynecologic malignancies. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Liu, Joyce] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Westin, Shannon N.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA.
RP Westin, SN (reprint author), Univ Texas MD Anderson Canc Ctr, 1155 Herman Pressler Blvd,Unit 1362, Houston, TX 77030 USA.
EM swestin@mdanderson.org
OI Westin, Shannon/0000-0002-1922-0156
FU Calabresi Scholar Award [K12 CA088084 K12]; NIH SPORE in Uterine Cancer
[2P50 CA098258-06]; NIH SPORE in Ovarian Cancer [2P50CA083639]
FX K12 CA088084 K12 Calabresi Scholar Award (SW).; NIH 2P50 CA098258-06
SPORE in Uterine Cancer (SW).; NIH 2P50CA083639 SPORE in Ovarian Cancer
(SW).
NR 97
TC 2
Z9 2
U1 0
U2 5
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 APR
PY 2016
VL 141
IS 1
SI SI
BP 65
EP 71
DI 10.1016/j.ygyno.2016.01.003
PG 7
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DI1HG
UT WOS:000373246600011
PM 27016231
ER
PT J
AU Penson, RT
Sales, E
Sullivan, L
Borger, DR
Krasner, CN
Goodman, AK
del Carmen, MG
Growdon, WB
Schorge, JO
Boruta, DM
Castro, CM
Dizon, DS
Birrer, MJ
AF Penson, R. T.
Sales, E.
Sullivan, L.
Borger, D. R.
Krasner, C. N.
Goodman, A. K.
del Carmen, M. G.
Growdon, W. B.
Schorge, J. O.
Boruta, D. M.
Castro, C. M.
Dizon, D. S.
Birrer, M. J.
TI A SNaPshot of potentially personalized care: Molecular diagnostics in
gynecologic cancer
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Personalized targeted therapy genotyping
ID MUTATIONS; CARCINOMA; INHIBITORS; MEDICINE; BREAST
AB Background. Genetic abnormalities underlie the development and progression of cancer, and represent potential opportunities for personalized cancer therapy in Gyn malignancies.
Methods. We identified Gyn oncology patients at the MGH Cancer Center with tumors genotyped for a panel of mutations by SNaPshot, a CLIA approved assay, validated in lung cancer, that uses SNP genotyping in degraded DNA from FFPE tissue to identify 160 described mutations across 15 cancer genes (AKT1, APC, BRAF, CTNNB1, EGFR, ERBB2, IDH1, KIT, KRAS, MAP2KI, NOTCH1, NRAS, PIK3CA, PTEN, TP53).
Results. Between 5/17/10 and 8/8/13, 249 pts consented to SNaPshot analysis. Median age 60 (29-84) yrs. Tumors were ovarian 123 (49%), uterine 74(30%), cervical 14(6%), fallopian 9(4%), primary peritoneal 13(5%), or rare 16(6%) with the incidence of testing high grade serous ovarian cancer (HGSOC) halving over time. SNaPshot was positive in 75 (30%), with 18 of these (24%) having 2 or 3 (n = 5) mutations identified. TP53 mutations are most common in high-grade serous cancers yet a low detection rate (17%) was likely related to the assay. However, 4 of the 7 purely endometrioid ovarian tumors (57%) harbored a p53 mutation. Of the 38 endometrioid uterine tumors, 18 mutations (47%) in the PI3Kinase pathway were identified. Only 9 of 122 purely serous (7%) tumors across all tumor types harbored a 'drugable' mutation, compared with 20 of 45 (44%) of endometrioid tumors (p < 0.0001). 17 pts subsequently enrolled on a clinical trial; all but 4 of whom had PIK3CA pathway mutations. Eight of 14 (47%) cervical tumors harbored a 'drugable' mutation.
Conclusion. Although SNaPshot can identify potentially important therapeutic targets, the incidence of 'drugable' targets in ovarian cancer is low. In this cohort, only 7% of subjects eventually were treated on a relevant clinical trial. Geneotyping should be used judiciously and reflect histologic subtype and available platform. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Penson, R. T.; Sales, E.; Sullivan, L.; Borger, D. R.; Krasner, C. N.; Goodman, A. K.; del Carmen, M. G.; Growdon, W. B.; Schorge, J. O.; Boruta, D. M.; Castro, C. M.; Dizon, D. S.; Birrer, M. J.] Massachusetts Gen Hosp, Div Hematol Oncol, Yawkey 9-064,32 Fruit St, Boston, MA 02114 USA.
RP Penson, RT (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Yawkey 9-064,32 Fruit St, Boston, MA 02114 USA.
EM rpenson@partners.org
NR 19
TC 0
Z9 0
U1 1
U2 2
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 APR
PY 2016
VL 141
IS 1
SI SI
BP 108
EP 112
DI 10.1016/j.ygyno.2016.02.032
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA DI1HG
UT WOS:000373246600017
PM 27016236
ER
PT J
AU Nunes, MCP
Nascimento, BR
Lodi-Junqueira, L
Tan, TC
Athayde, GRS
Hung, J
AF Nunes, Maria Carmo P.
Nascimento, Bruno Ramos
Lodi-Junqueira, Lucas
Tan, Timothy C.
Sant'Anna Athayde, Guilherme Rafael
Hung, Judy
TI Update on percutaneous mitral commissurotomy
SO HEART
LA English
DT Review
ID RHEUMATIC HEART-DISEASE; TERM-FOLLOW-UP; BALLOON VALVOTOMY; TRICUSPID
REGURGITATION; ATRIAL-FIBRILLATION; ECHOCARDIOGRAPHIC ASSESSMENT; VALVE
CALCIFICATION; INOUE-BALLOON; VALVULOPLASTY; STENOSIS
AB Percutaneous mitral commissurotomy (PMC) is the first-line therapy for managing rheumatic mitral stenosis. Over the past two decades, the indications of the procedure have expanded to include patients with unfavourable valve anatomy as a consequence of epidemiological changes in patient population. The procedure is increasingly being performed in patients with increased age, more deformed valves and associated comorbidities. Echocardiography plays a crucial role in patient selection and to guide a more efficient procedure. The main echocardiographic predictors of immediate results after PMC are mitral valve area, subvalvular thickening and valve calcification, especially at the commissural level. However, procedural success rate is not only dependent on valve anatomy, but a number of other factors including patient characteristics, interventional management strategies and operator expertise. Severe mitral regurgitation continues to be the most common immediate procedural complication with unchanged incidence rates over time. The long-term outcome after PMC is mainly determined by the immediate procedural results. Postprocedural parameters associated with late adverse events include mitral valve area, mitral regurgitation severity, mean gradient and pulmonary artery pressure. Mitral restenosis is an important predictor of event-free survival rates after successful PMC, and repeat procedure can be considered in cases with commissural refusion. PMC can be performed in special situations, which include high-risk patients, during pregnancy and in the presence of left atrial thrombus, especially in centres with specialised expertise. Therefore, procedural decision-making should take into account the several determinant factors of PMC outcomes. This paper provides an overview and update of PMC techniques, complications, immediate and long-term results over time, and assessment of suitability for the procedure.
C1 [Nunes, Maria Carmo P.; Nascimento, Bruno Ramos; Lodi-Junqueira, Lucas; Sant'Anna Athayde, Guilherme Rafael] Univ Fed Minas Gerais, Sch Med, Hosp Clin, Ave Prof Alfredo Balena,190,Room 246, BR-30130100 Belo Horizonte, MG, Brazil.
[Tan, Timothy C.] Univ Western Sydney, Blacktown Hosp, Dept Cardiol, Sydney, NSW, Australia.
[Hung, Judy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02115 USA.
RP Nunes, MCP (reprint author), Univ Fed Minas Gerais, Sch Med, Hosp Clin, Ave Prof Alfredo Balena,190,Room 246, BR-30130100 Belo Horizonte, MG, Brazil.
EM mcarmo@waymail.com.br
OI Nascimento, Bruno/0000-0002-5586-774X
NR 63
TC 0
Z9 0
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1355-6037
EI 1468-201X
J9 HEART
JI Heart
PD APR 1
PY 2016
VL 102
IS 7
BP 500
EP 507
DI 10.1136/heartjnl-2015-308091
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DI2EM
UT WOS:000373308500005
PM 26743926
ER
PT J
AU Baker, MA
Huang, SS
Letourneau, AR
Kaganov, RE
Peeples, JR
Drees, M
Platt, R
Yokoe, DS
AF Baker, Meghan A.
Huang, Susan S.
Letourneau, Alyssa R.
Kaganov, Rebecca E.
Peeples, Jennifer R.
Drees, Marci
Platt, Richard
Yokoe, Deborah S.
CA Ctr Dis Control Prevention Epictr
TI Lack of Comprehensive Outbreak Detection in Hospitals
SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY
LA English
DT Article
ID CARE-ASSOCIATED INFECTIONS; STAPHYLOCOCCUS-AUREUS; PREVENTION
AB Timely identification of outbreaks of hospital-associated infections is needed to implement control measures and minimize impact. Survey results from 33 hospitals indicated that most hospitals lacked a formal cluster definition and all targeted a very limited group of prespecified pathogens. Standardized, statistically based outbreak detection could greatly improve current practice.
C1 [Baker, Meghan A.; Kaganov, Rebecca E.; Platt, Richard] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Baker, Meghan A.; Kaganov, Rebecca E.; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA.
[Baker, Meghan A.; Yokoe, Deborah S.] Brigham & Womens Hosp, Dept Med, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA.
[Huang, Susan S.] Univ Calif Irvine, Sch Med, Div Infect Dis, Dept Med, Orange, CA 92668 USA.
[Letourneau, Alyssa R.] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA.
[Peeples, Jennifer R.] Premier, Charlotte, NC USA.
[Drees, Marci] Christiana Care Hlth Syst, Div Infect Dis, Dept Med, Newark, DE USA.
RP Baker, MA (reprint author), Harvard Pilgrim Hlth Care Inst, Dept Populat Med, 133 Brookline Ave,6th Fl, Boston, MA 02215 USA.
EM meghan_baker@harvardpilgrim.org
FU Centers for Disease Control and Prevention Epicenters Program [1U54
CK000172-01]
FX Centers for Disease Control and Prevention Epicenters Program (grant
1U54 CK000172-01).
NR 12
TC 1
Z9 1
U1 1
U2 2
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0899-823X
EI 1559-6834
J9 INFECT CONT HOSP EP
JI Infect. Control Hosp. Epidemiol.
PD APR
PY 2016
VL 37
IS 4
BP 466
EP 468
DI 10.1017/ice.2015.325
PG 3
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA DH5AD
UT WOS:000372796200014
PM 26996060
ER
PT J
AU Charidimou, A
Shams, S
AF Charidimou, Andreas
Shams, Sara
TI Introducing @microbleeds: A pilot Twitter space for cerebral microbleeds
research
SO INTERNATIONAL JOURNAL OF STROKE
LA English
DT Letter
C1 [Charidimou, Andreas] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program,Stroke Res Ctr, Boston, MA 02115 USA.
[Shams, Sara] Karolinska Inst, Div Med Imaging & Technol, Dept Clin Sci Intervent & Technol, Stockholm, Sweden.
[Shams, Sara] Karolinska Univ Hosp, Dept Radiol, Stockholm, Sweden.
RP Charidimou, A (reprint author), Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program, 175 Cambridge St,Suite 300, Boston, MA 02114 USA.
EM andreas.charidimou.09@ucl.ac.uk
NR 2
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 1747-4930
EI 1747-4949
J9 INT J STROKE
JI Int. J. Stroke
PD APR
PY 2016
VL 11
IS 3
BP NP40
EP NP41
DI 10.1177/1747493016632251
PG 2
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DH5FL
UT WOS:000372811200006
PM 26865156
ER
PT J
AU Helenius, IT
Nair, A
Bittar, HET
Sznajder, JI
Sporn, PHS
Beitel, GJ
AF Helenius, Iiro Taneli
Nair, Aisha
Bittar, Humberto E. Trejo
Sznajder, Jacob I.
Sporn, Peter H. S.
Beitel, Greg J.
TI Focused Screening Identifies Evoxine as a Small Molecule That
Counteracts CO2-Induced Immune Suppression
SO JOURNAL OF BIOMOLECULAR SCREENING
LA English
DT Article
DE anti-infective drugs; cell-based assays; immune system diseases;
reporter gene assays
ID DROSOPHILA-MELANOGASTER; FUROQUINOLINE ALKALOIDS; ACUTE EXACERBATION;
HUMAN-DISEASE; CO2; CELLS; EXPRESSION; PROTEIN; MACROPHAGES; MORTALITY
AB Patients with severe lung disease may develop hypercapnia, elevation of the levels of CO2 in the lungs and blood, which is associated with increased risk of death, often from infection. To identify compounds that ameliorate the adverse effects of hypercapnia, we performed a focused screen of 8832 compounds using a CO2-responsive luciferase reporter in Drosophila S2* cells. We found that evoxine, a plant alkaloid, counteracts the CO2-induced transcriptional suppression of antimicrobial peptides in S2* cells. Strikingly, evoxine also inhibits hypercapnic suppression of interleukin-6 and the chemokine CCL2 expression in human THP-1 macrophages. Evoxine's effects are selective, since it does not prevent hypercapnic inhibition of phagocytosis by THP-1 cells or CO2-induced activation of AMPK in rat ATII pulmonary epithelial cells. The results suggest that hypercapnia suppresses innate immune gene expression by definable pathways that are evolutionarily conserved and demonstrate for the first time that specific CO2 effects can be targeted pharmacologically.
C1 [Helenius, Iiro Taneli; Beitel, Greg J.] Northwestern Univ, Dept Mol Biosci, Evanston, IL USA.
[Nair, Aisha; Bittar, Humberto E. Trejo; Sznajder, Jacob I.; Sporn, Peter H. S.] Northwestern Univ, Feinberg Sch Med, Div Pulm & Crit Care Med, Evanston, IL USA.
[Sporn, Peter H. S.] Jesse Brown Vet Affairs Med Ctr, Chicago, IL USA.
[Helenius, Iiro Taneli] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA.
RP Beitel, GJ (reprint author), Northwestern Univ, Hogan Hall,Rm 2-100,22015 Tech Dr, Evanston, IL 60208 USA.
EM beitel@northwestern.edu
FU NIH [NHLBI/R01-HL107629, NHLBI/R01-HL-85534, NERCE/NSRB U54-AI057159,
NIGMS/R01-GM067761]; American Heart Association [0855686G, 0715562Z];
Chicago Biomedical Consortium; Searle Funds at The Chicago Community
Trust; Northwestern University Robert H. Lurie Comprehensive Cancer
Center
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This work was
supported by grants from the NIH to GJB and PHSS (NHLBI/R01-HL107629),
to JIS (NHLBI/R01-HL-85534), to ICCB-Longwood (NERCE/NSRB U54-AI057159),
and to DRSC (NIGMS/R01-GM067761); from the American Heart Association to
GJB (grant-in-aid award, 0855686G) and to ITH (predoctoral fellowship,
0715562Z); from the Chicago Biomedical Consortium with support from The
Searle Funds at The Chicago Community Trust to NU CMIDD; and from the
Northwestern University Robert H. Lurie Comprehensive Cancer Center to
the NU HTA core facility.
NR 30
TC 1
Z9 1
U1 3
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1087-0571
EI 1552-454X
J9 J BIOMOL SCREEN
JI J. Biomol. Screen
PD APR
PY 2016
VL 21
IS 4
BP 363
EP 371
DI 10.1177/1087057115624091
PG 9
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Chemistry
GA DH6EG
UT WOS:000372883200005
PM 26701099
ER
PT J
AU Hayakawa, K
Pham, LDD
Seo, JH
Miyamoto, N
Maki, T
Terasaki, Y
Sakadzic, S
Boas, D
van Leyen, K
Waeber, C
Kim, KW
Arai, K
Lo, EH
AF Hayakawa, Kazuhide
Pham, Loc-Duyen D.
Seo, Ji Hae
Miyamoto, Nobukazu
Maki, Takakuni
Terasaki, Yasukazu
Sakadzic, Sava
Boas, David
van Leyen, Klaus
Waeber, Christian
Kim, Kyu-Won
Arai, Ken
Lo, Eng H.
TI CD200 restrains macrophage attack on oligodendrocyte precursors via
toll-like receptor 4 downregulation
SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
LA English
DT Article
DE CD200; macrophage; phagocytosis; oligodendrocyte precursors; white
matter injury
ID SPINAL-CORD-INJURY; MICROGLIA/MACROPHAGE POLARIZATION DYNAMICS;
WHITE-MATTER INJURY; ISCHEMIC-STROKE; BRAIN; CELLS; MECHANISMS;
PHAGOCYTOSIS; ACTIVATION; DISEASE
AB There are numerous barriers to white matter repair after central nervous system injury and the underlying mechanisms remain to be fully understood. In this study, we propose the hypothesis that inflammatory macrophages in damaged white matter attack oligodendrocyte precursor cells via toll-like receptor 4 signaling thus interfering with this endogenous progenitor recovery mechanism. Primary cell culture experiments demonstrate that peritoneal macrophages can attack and digest oligodendrocyte precursor cells via toll-like receptor 4 signaling, and this phagocytosis of oligodendrocyte precursor cells can be inhibited by using CD200-Fc to downregulate toll-like receptor 4. In an in vivo model of white matter ischemia induced by endothelin-1, treatment with CD200-Fc suppressed toll-like receptor 4 expression in peripherally circulating macrophages, thus restraining macrophage phagocytosis of oligodendrocyte precursor cells and leading to improved myelination. Taken together, these findings suggest that deleterious macrophage effects may occur after white matter ischemia, whereby macrophages attack oligodendrocyte precursor cells and interfere with endogenous recovery responses. Targeting this pathway with CD200 may offer a novel therapeutic approach to amplify endogenous oligodendrocyte precursor cell-mediated repair of white matter damage in mammalian brain.
C1 [Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Seo, Ji Hae; Miyamoto, Nobukazu; Maki, Takakuni; Terasaki, Yasukazu; van Leyen, Klaus; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA.
[Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Seo, Ji Hae; Miyamoto, Nobukazu; Maki, Takakuni; Terasaki, Yasukazu; van Leyen, Klaus; Arai, Ken; Lo, Eng H.] Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA.
[Hayakawa, Kazuhide; Pham, Loc-Duyen D.; Seo, Ji Hae; Miyamoto, Nobukazu; Maki, Takakuni; Terasaki, Yasukazu; Sakadzic, Sava; Boas, David; van Leyen, Klaus; Arai, Ken; Lo, Eng H.] Harvard Univ, Sch Med, Charlestown, MA USA.
[Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, NeuroVasc Protect Res Ctr, Coll Pharm, Seoul, South Korea.
[Seo, Ji Hae; Kim, Kyu-Won] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea.
[Sakadzic, Sava; Boas, David] Massachusetts Gen Hosp, Opt Div, MHG MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA.
[Waeber, Christian] Natl Univ Ireland Univ Coll Cork, Sch Pharm, Dept Pharmacol & Therapeut, Cork, Ireland.
[Kim, Kyu-Won] Seoul Natl Univ, Dept Mol Med & Biopharmaceut Sci, Grad Sch Convergence Sci & Technol, Seoul, South Korea.
[Kim, Kyu-Won] Seoul Natl Univ, Coll Med, Seoul, South Korea.
[Kim, Kyu-Won] Seoul Natl Univ, Coll Pharm, Seoul, South Korea.
RP Hayakawa, K; Lo, EH (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA.
EM Khayakawa1@mgh.harvard.edu; Lo@helix.mgh.harvard.edu
FU National Institutes of Health; National Research Foundation of Korea;
World Class University Program; Global Research Laboratory Program
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: This study
is supported in part by National Institutes of Health, National Research
Foundation of Korea, the World Class University Program, and the Global
Research Laboratory Program.
NR 48
TC 1
Z9 1
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0271-678X
EI 1559-7016
J9 J CEREBR BLOOD F MET
JI J. Cereb. Blood Flow Metab.
PD APR
PY 2016
VL 36
IS 4
BP 781
EP 793
DI 10.1177/0271678X15606148
PG 13
WC Endocrinology & Metabolism; Hematology; Neurosciences
SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology
GA DI2VA
UT WOS:000373355900012
PM 26661156
ER
PT J
AU McGrath, LM
Braaten, EB
Doty, ND
Willoughby, BL
Wilson, HK
O'Donnell, EH
Colvin, MK
Ditmars, HL
Blais, JE
Hill, EN
Metzger, A
Perlis, RH
Willcutt, EG
Smoller, JW
Waldman, ID
Faraone, SV
Seidman, LJ
Doyle, AE
AF McGrath, Lauren M.
Braaten, Ellen B.
Doty, Nathan D.
Willoughby, Brian L.
Wilson, H. Kent
O'Donnell, Ellen H.
Colvin, Mary K.
Ditmars, Hillary L.
Blais, Jessica E.
Hill, Erin N.
Metzger, Aaron
Perlis, Roy H.
Willcutt, Erik G.
Smoller, Jordan W.
Waldman, Irwin D.
Faraone, Stephen V.
Seidman, Larry J.
Doyle, Alysa E.
TI Extending the "cross-disorder' relevance of executive functions to
dimensional neuropsychiatric traits in youth
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Executive functions; mania; psychosis; social responsiveness;
cross-disorder; dimensional traits
ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; INDIVIDUAL-DIFFERENCES;
PSYCHIATRIC-DISORDERS; BIPOLAR DISORDER; COGNITIVE DEFICITS;
SCHIZOPHRENIA; METAANALYSIS; AUTISM; PSYCHOPATHOLOGY; INTELLIGENCE
AB BackgroundEvidence that different neuropsychiatric conditions share genetic liability has increased interest in phenotypes with cross-disorder' relevance, as they may contribute to revised models of psychopathology. Cognition is a promising construct for study; yet, evidence that the same cognitive functions are impaired across different forms of psychopathology comes primarily from separate studies of individual categorical diagnoses versus controls. Given growing support for dimensional models that cut across traditional diagnostic boundaries, we aimed to determine, within a single cohort, whether performance on measures of executive functions (EFs) predicted dimensions of different psychopathological conditions known to share genetic liability.
MethodsData are from 393 participants, ages 8-17, consecutively enrolled in the Longitudinal Study of Genetic Influences on Cognition (LOGIC). This project is conducting deep phenotyping and genomic analyses in youth referred for neuropsychiatric evaluation. Using structural equation modeling, we examined whether EFs predicted variation in core dimensions of the autism spectrum disorder, bipolar illness, and schizophrenia (including social responsiveness, mania/emotion regulation, and positive symptoms of psychosis, respectively).
ResultsWe modeled three cognitive factors (working memory, shifting, and executive processing speed) that loaded on a second-order EF factor. The EF factor predicted variation in our three target traits, but not in a negative control (somatization). Moreover, this EF factor was primarily associated with the overlapping (rather than unique) variance across the three outcome measures, suggesting that it related to a general increase in psychopathology symptoms across those dimensions.
ConclusionsFindings extend support for the relevance of cognition to neuropsychiatric conditions that share underlying genetic risk. They suggest that higher-order cognition, including EFs, relates to the dimensional spectrum of each of these disorders and not just the clinical diagnoses. Moreover, results have implications for bottom-up models linking genes, cognition, and a general psychopathology liability.
C1 [McGrath, Lauren M.] Amer Univ, Sch Educ, Washington, DC 20016 USA.
[Braaten, Ellen B.; Doty, Nathan D.; Willoughby, Brian L.; Wilson, H. Kent; O'Donnell, Ellen H.; Colvin, Mary K.; Perlis, Roy H.; Smoller, Jordan W.; Seidman, Larry J.; Doyle, Alysa E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA.
[Ditmars, Hillary L.; Blais, Jessica E.; Hill, Erin N.; Perlis, Roy H.; Smoller, Jordan W.; Doyle, Alysa E.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Metzger, Aaron] W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA.
[Perlis, Roy H.; Smoller, Jordan W.; Doyle, Alysa E.] Broad Inst Harvard & MIT, Stanley Ctr Psychiat Res, Cambridge, MA USA.
[Willcutt, Erik G.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Waldman, Irwin D.] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA.
[Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Neurosci & Physiol, Syracuse, NY 13210 USA.
[Seidman, Larry J.] Harvard Univ, Sch Med, Commonwealth Res Ctr, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA.
RP Doyle, AE (reprint author), MGH Ctr Human Genet Res, 185 Cambridge St,CPZN 6240, Boston, MA 02114 USA.
EM doylea@helix.mgh.harvard.edu
FU Stanley Center for Psychiatric Research; American University faculty
research support grant; David Judah Foundation; Akili Interactive Labs;
Alcobra; VAYA Pharma; SynapDx; National Institutes of Health (NIH);
Shire; Otsuka; McNeil; Janssen; Novartis; Pfizer; Eli Lilly; K.G. Jebsen
Centre for Research on Neuropsychiatric Disorders, University of Bergen,
Bergen, Norway; European Union's Seventh Framework Programme [602805];
NIMH [R13MH059126, R01MH094469]; NIMH; Massachusetts Department of
Mental Health; Sidney R. Baer, Jr. Foundation; [R03 MH106862]
FX This research was supported in part by the Stanley Center for
Psychiatric Research and R03 MH106862 (to A. E. D.), an American
University faculty research support grant (to L. M. M.), and the David
Judah Foundation (to A. E. D. and E. B. B.). The authors wish to thank
Pieter Vuijk for his comments on this manuscript. Author R.P. consults
to or serves on scientific advisory boards for Genomind, Healthrageous,
Pamlab, Perfect Health, Pfizer, Proteus Biomedical, Psybrain, and
RIDVentures. The author receives royalties from UBC, a Medco subsidiary.
In the past year, author S.F. received consulting income, travel
expenses, and/or research support from Akili Interactive Labs, Alcobra,
VAYA Pharma, and SynapDx and research support from the National
Institutes of Health (NIH). The author's institution is seeking a patent
for the use of sodium-hydrogen exchange inhibitors in the treatment of
ADHD. In previous years, the author received consulting fees or was on
Advisory Boards or participated in continuing medical education programs
sponsored by Shire, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer
and Eli Lilly. The author receives royalties from books published by
Guilford Press: Straight Talk about Your Child's Mental Health and
Oxford University Press: Schizophrenia: The Facts. He is supported by
the K.G. Jebsen Centre for Research on Neuropsychiatric Disorders,
University of Bergen, Bergen, Norway, the European Union's Seventh
Framework Programme for research, technological development and
demonstration under grant agreement no 602805 and NIMH grants
R13MH059126 and R01MH094469. Author J.S. serves on the scientific
advisory board of PsyBrain. Author L.S. reports no competing interests.
The author receives support from NIMH, the Massachusetts Department of
Mental Health, and the Sidney R. Baer, Jr. Foundation. All other authors
declare that they have no competing or potential conflicts of interests.
NR 48
TC 2
Z9 2
U1 5
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD APR
PY 2016
VL 57
IS 4
BP 462
EP 471
DI 10.1111/jcpp.12463
PG 10
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DH9JU
UT WOS:000373113200004
PM 26411927
ER
PT J
AU Michalska, KJ
Zeffiro, TA
Decety, J
AF Michalska, Kalina J.
Zeffiro, Thomas A.
Decety, Jean
TI Brain response to viewing others being harmed in children with conduct
disorder symptoms
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Conduct disorder; callousness; affective arousal; emotional empathy;
insula; anterior cingulate cortex
ID CALLOUS-UNEMOTIONAL TRAITS; ANTISOCIAL-BEHAVIOR; NEURAL RESPONSES;
PSYCHOPATHIC TENDENCIES; OPPOSITIONAL DEFIANT; PROACTIVE AGGRESSION;
AMYGDALA RESPONSE; COMMUNITY SAMPLE; EARLY-ONSET; EMPATHY
AB BackgroundDeficient empathic processing is thought to foster conduct disorder (CD). It is important to determine the extent to which neural response associated with perceiving harm to others predicts CD symptoms and callous disregard for others.
MethodsA total of 107 9- to 11-year-old children (52 female) were recruited from pediatric and mental health clinics, representing a wide range of CD symptoms. Children were scanned with functional magnetic resonance imaging while viewing brief video clips of persons being harmed intentionally or accidentally.
ResultsPerceiving harm evoked increased hemodynamic response in the anterior insula (aINS), anterior cingulate cortex (ACC), amygdala, periaqueductal gray (PAG), caudate, and inferior parietal lobe (IPL) across all participants. Intentionally caused, relative to unintentional harm was associated with greater activity in the aINS, amygdala, and temporal pole. There was an inverse association of number of CD symptoms with right posterior insula in both the Harm>No Harm and the Intentional>Unintentional Harm contrasts. Furthermore, an inverse association between callousness and posterior insula activation was found in the Harm>No Harm contrast, with the opposite pattern for reactive aggression scores. An interaction revealed a stronger association in girls between CD symptoms and the right posterior superior temporal sulcus (pSTS) in the Intentional Harm versus Unintentional Harm contrast.
ConclusionsChildren with greater CD and callousness exhibit dampened hemodynamic response to viewing others being harmed in the insula, a region which plays a key role in empathy and emotional awareness. Sex differences in the neural correlates of CD were observed.
C1 [Michalska, Kalina J.; Decety, Jean] Univ Chicago, Dept Psychol, 5848 S Univ Ave, Chicago, IL 60637 USA.
[Michalska, Kalina J.] NIMH, Bethesda, MD 20892 USA.
[Michalska, Kalina J.] Univ Maryland, Dept Human Dev, College Pk, MD 20742 USA.
[Zeffiro, Thomas A.] Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA USA.
[Decety, Jean] Univ Chicago Med, Dept Psychiat & Behav Neurosci, Chicago, IL USA.
RP Decety, J (reprint author), Univ Chicago, Child Neurosuite, 5848 S Univ Ave, Chicago, IL 60637 USA.
EM decety@uchicago.edu
FU NIMH [R01-MH084934]
FX This study was supported by NIMH grant R01-MH084934 to J.D. The authors
are grateful to Jason M. Cowell for helpful suggestions and to Carrie
Swetlik and Talia Reiter for their help with data collection and entry.
The authors have declared that they have no competing or potential
conflicts of interests.
NR 49
TC 6
Z9 6
U1 18
U2 20
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD APR
PY 2016
VL 57
IS 4
BP 510
EP 519
DI 10.1111/jcpp.12474
PG 10
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA DH9JU
UT WOS:000373113200009
PM 26472591
ER
PT J
AU Qian, QF
Urman, G
Cederroth, T
Najarian, R
Kirby, JE
AF Qian, Qinfang
Urman, Grigoriy
Cederroth, Terra
Najarian, Robert
Kirby, James E.
TI A Man with Fever and Cough
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Editorial Material
ID PULMONARY BLASTOMYCOSIS
C1 [Qian, Qinfang] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Qian, Qinfang] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
RP Qian, QF (reprint author), Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA.; Qian, QF (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
EM qqian@mgh.harvard.edu
NR 8
TC 0
Z9 0
U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2016
VL 54
IS 4
BP 825
EP +
DI 10.1128/JCM.00852-14
PG 2
WC Microbiology
SC Microbiology
GA DI2OX
UT WOS:000373337100001
PM 27016589
ER
PT J
AU White, PL
Wiederhold, NP
Loeffler, J
Najvar, LK
Melchers, W
Herrera, M
Bretagne, S
Wickes, B
Kirkpatrick, WR
Barnes, RA
Donnelly, JP
Patterson, TF
AF White, P. Lewis
Wiederhold, Nathan P.
Loeffler, Juergen
Najvar, Laura K.
Melchers, Willem
Herrera, Monica
Bretagne, Stephane
Wickes, Brian
Kirkpatrick, William R.
Barnes, Rosemary A.
Donnelly, J. Peter
Patterson, Thomas F.
TI Comparison of Nonculture Blood-Based Tests for Diagnosing Invasive
Aspergillosis in an Animal Model
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID HIGH-RISK HEMATOLOGY; RANDOMIZED CONTROLLED-TRIAL; GUINEA-PIG MODEL;
REAL-TIME PCR; FUNGAL DISEASE; PULMONARY ASPERGILLOSIS; AMPHOTERICIN-B;
FUMIGATUS DNA; GALACTOMANNAN; SERUM
AB The European Aspergillus PCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and beta-D-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and beta-D-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and beta-D-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and beta-D-glucan proved optimal (area under the curve [AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests.
C1 [White, P. Lewis] PHW Microbiol, Cardiff, S Glam, Wales.
[Wiederhold, Nathan P.; Najvar, Laura K.; Herrera, Monica; Wickes, Brian; Kirkpatrick, William R.; Patterson, Thomas F.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio Ctr Med Mycol, San Antonio, TX 78229 USA.
[Loeffler, Juergen] Univ Wurzburg, D-97070 Wurzburg, Germany.
[Melchers, Willem; Donnelly, J. Peter] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Bretagne, Stephane] Hop St Louis, Paris, France.
[Barnes, Rosemary A.] Cardiff Univ, UHW, Cardiff CF10 3AX, S Glam, Wales.
[Patterson, Thomas F.] South Texas Vet Hlth Care Syst, San Antonio, TX USA.
RP White, PL (reprint author), PHW Microbiol, Cardiff, S Glam, Wales.
EM lewis.white@wales.nhs.uk
OI Bretagne, Stephane/0000-0001-6870-3800; Wiederhold,
Nathan/0000-0002-2225-5122; Donnelly, J Peter/0000-0002-8521-335X
FU HHS\ NIH\ National Institute of Allergy and Infectious Diseases (NIAID)
[N01-AI-30041]
FX HHS vertical bar NIH vertical bar National Institute of Allergy and
Infectious Diseases (NIAID) provided funding to Nathan P. Wiederhold,
Laura K. Najvar, Monica L. Herrera, Brian L. Wickes, William R.
Kirkpatrick, and Thomas F. Patterson under grant number N01-AI-30041.
NR 30
TC 2
Z9 2
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2016
VL 54
IS 4
BP 960
EP 966
DI 10.1128/JCM.03233-15
PG 7
WC Microbiology
SC Microbiology
GA DI2OX
UT WOS:000373337100015
PM 26791366
ER
PT J
AU Jelden, KC
Iwen, PC
Herstein, JJ
Biddinger, PD
Kraft, CS
Saiman, L
Smith, PW
Hewlett, AL
Gibbs, SG
Lowe, JJ
AF Jelden, Katelyn C.
Iwen, Peter C.
Herstein, Jocelyn J.
Biddinger, Paul D.
Kraft, Colleen S.
Saiman, Lisa
Smith, Philip W.
Hewlett, Angela L.
Gibbs, Shawn G.
Lowe, John J.
TI US Ebola Treatment Center Clinical Laboratory Support
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID UNITED-STATES; VIRUS
AB Fifty-five hospitals in the United States have been designated Ebola treatment centers (ETCs) by their state and local health authorities. Designated ETCs must have appropriate plans to manage a patient with confirmed Ebola virus disease (EVD) for the full duration of illness and must have these plans assessed through a CDC site visit conducted by an interdisciplinary team of subject matter experts. This study determined the clinical laboratory capabilities of these ETCs. ETCs were electronically surveyed on clinical laboratory characteristics. Survey responses were returned from 47 ETCs (85%). Forty-one (87%) of the ETCs planned to provide some laboratory support (e.g., point-of-care [POC] testing) within the room of the isolated patient. Forty-four (94%) ETCs indicated that their hospital would also provide clinical laboratory support for patient care. Twenty-two (50%) of these ETC clinical laboratories had biosafety level 3 (BSL-3) containment. Of all respondents, 34 (72%) were supported by their jurisdictional public health laboratory (PHL), all of which had available BSL-3 laboratories. Overall, 40 of 44 (91%) ETCs reported BSL-3 laboratory support via their clinical laboratory and/or PHL. This survey provided a snapshot of the laboratory support for designated U.S. ETCs. ETCs have approached high-level isolation critical care with laboratory support in close proximity to the patient room and by distributing laboratory support among laboratory resources. Experts might review safety considerations for these laboratory testing/diagnostic activities that are novel in the context of biocontainment care.
C1 [Jelden, Katelyn C.; Herstein, Jocelyn J.; Gibbs, Shawn G.; Lowe, John J.] Univ Nebraska Med Ctr, Dept Environm Agr & Occupat Hlth, Omaha, NE USA.
[Iwen, Peter C.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Coll Med, Omaha, NE USA.
[Iwen, Peter C.] Nebraska Publ Hlth Lab, Omaha, NE USA.
[Biddinger, Paul D.] Massachusetts Gen Hosp, Dept Emergency Med, Div Emergency Preparedness, Boston, MA 02114 USA.
[Biddinger, Paul D.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA.
[Kraft, Colleen S.] Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA.
[Kraft, Colleen S.] Emory Univ, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA.
[Saiman, Lisa] Columbia Univ, Dept Pediat, Med Ctr, New York, NY 10027 USA.
[Saiman, Lisa] New York Presbyterian Hosp, Dept Infect Prevent & Control, New York, NY USA.
[Smith, Philip W.; Hewlett, Angela L.] Univ Nebraska Med Ctr, Dept Internal Med, Div Infect Dis, Omaha, NE USA.
[Gibbs, Shawn G.] Indiana Univ, Sch Publ Hlth, Dept Environm Hlth, Bloomington, IN USA.
RP Lowe, JJ (reprint author), Univ Nebraska Med Ctr, Dept Environm Agr & Occupat Hlth, Omaha, NE USA.
EM jjlowe@unmc.edu
NR 17
TC 1
Z9 1
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD APR
PY 2016
VL 54
IS 4
BP 1031
EP 1035
DI 10.1128/JCM.02905-15
PG 5
WC Microbiology
SC Microbiology
GA DI2OX
UT WOS:000373337100025
PM 26842705
ER
PT J
AU Moldovan, M
Calin, A
Kumaraswamy, VM
Braver, D
Simon, MV
AF Moldovan, Mihai
Calin, Alexandru
Kumaraswamy, Vishakhadatta M.
Braver, Diana
Simon, Mirela V.
TI Burst-Suppression Ratio on Electrocorticography Depends on
Interelectrode Distance
SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE asynchrony; distance; EEG burst-suppression
ID BISPECTRAL INDEX; ANESTHESIA; PROPOFOL; EEG; ISOFLURANE; BRAIN;
ELECTROENCEPHALOGRAM; PROTECTION; MODEL; COMA
AB Introduction:
With deepening of anesthesia-induced comatose states, the EEG becomes fragmented by increasing periods of suppression. When measured from conventional EEG recordings, the binary burst-suppression signal (BS) appears similar across the scalp. As such, the BS ratio (BSR), quantifying the fraction of time spent in suppression, is clinically considered a global index of brain function in sedation monitoring. Recent studies indicate that BS may be considerably asynchronous when measured with higher spatial resolution such as on electrocorticography. The authors investigated the magnitude of BSR changes with cortical recording interelectrode distance.
Methods:
The authors selected fronto-parietal electrocorticography recordings showing propofol-induced BS recorded via 8-electrode strips (1-cm interelectrode distance) during cortical motor mapping in 31 patients. For 1-minute epochs, bipolar recordings were computed between each electrode pair. The median BSR, burst duration (BD), and bursting frequency were derived for each interelectrode distance.
Results:
At 1-cm interelectrode distance, with increasing BSR, BD decreased exponentially. For a BSR between 50% and 80%, BD reached a plateau of 2.1 seconds while the bursting frequency decreased from 14 to 6 bursts per minute. With increasing interelectrode distance, BD increased at a rate of 0.2 seconds per cm. This correlated with a decrease in BSR with distance that reached the rate of -4.4 percentage per centimeters during deepest anesthesia.
Conclusions:
With increasing cortical interelectrode recording distance, burst summation leads to an increasing BD associated with a reduction in BSR. Standardization of interelectrode distance is important for cortical BSR measurements.
C1 [Moldovan, Mihai; Calin, Alexandru] Carol Davila Univ Med & Pharm, Dept Funct Sci, Div Physiol & Neurosci, Bucharest, Romania.
[Moldovan, Mihai] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen, Denmark.
[Calin, Alexandru; Kumaraswamy, Vishakhadatta M.; Braver, Diana; Simon, Mirela V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Intraoperat Neurophysiol Unit,Dept Neurol, Boston, MA USA.
[Calin, Alexandru] Univ Oxford, Dept Pharmacol, S Parks Rd, Oxford OX1 3QT, England.
[Kumaraswamy, Vishakhadatta M.] Univ Hosp Case Med Ctr, Dept Neurol, Cleveland, OH USA.
RP Simon, MV (reprint author), Massachusetts Gen Hosp, WACC 739G,55 Fruit St, Boston, MA 02114 USA.
EM mvsimon@mgh.harvard.edu
RI Moldovan, Mihai/C-4215-2011
OI Moldovan, Mihai/0000-0003-2512-3499
FU Romanian National Authority for Scientific Research, CNCS-UEFISCDI
[PN-II-ID-PCE-2011-3-0847, PN-II-PT-PCCA-2011-3.2-1290]
FX This study was supported by grants of the Romanian National Authority
for Scientific Research, CNCS-UEFISCDI, project number
PN-II-ID-PCE-2011-3-0847, and PN-II-PT-PCCA-2011-3.2-1290 to M.M.
NR 31
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 0736-0258
EI 1537-1603
J9 J CLIN NEUROPHYSIOL
JI J. Clin. Neurophysiol.
PD APR
PY 2016
VL 33
IS 2
BP 127
EP 132
DI 10.1097/WNP.0000000000000248
PG 6
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI0YP
UT WOS:000373223500008
PM 26690549
ER
PT J
AU Lee, JW
LaRoche, S
Choi, H
Ruiz, AAR
Fertig, E
Politsky, JM
Herman, ST
Loddenkemper, T
Sansevere, AJ
Korb, PJ
Abend, NS
Goldstein, JL
Sinha, SR
Dombrowski, KE
Ritzl, EK
Westover, MB
Gavvala, JR
Gerard, EE
Schmitt, SE
Szaflarski, JP
Ding, K
Haas, KF
Buchsbaum, R
Hirsch, LJ
Wusthoff, CJ
Hopp, JL
Hahn, CD
AF Lee, Jong Woo
LaRoche, Suzette
Choi, Hyunmi
Ruiz, Andres A. Rodriguez
Fertig, Evan
Politsky, Jeffrey M.
Herman, Susan T.
Loddenkemper, Tobias
Sansevere, Arnold J.
Korb, Pearce J.
Abend, Nicholas S.
Goldstein, Joshua L.
Sinha, Saurabh R.
Dombrowski, Keith E.
Ritzl, Eva K.
Westover, Michael B.
Gavvala, Jay R.
Gerard, Elizabeth E.
Schmitt, Sarah E.
Szaflarski, Jerzy P.
Ding, Kan
Haas, Kevin F.
Buchsbaum, Richard
Hirsch, Lawrence J.
Wusthoff, Courtney J.
Hopp, Jennifer L.
Hahn, Cecil D.
CA Critical Care EEG Monitoring Res C
TI Development and Feasibility Testing of a Critical Care EEG Monitoring
Database for Standardized Clinical Reporting and Multicenter
Collaborative Research
SO JOURNAL OF CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Clinical reporting tool; Research database; Continuous EEG monitoring
ID NONCONVULSIVE STATUS EPILEPTICUS; REFRACTORY STATUS EPILEPTICUS;
CONSENSUS STATEMENT; ILL ADULTS; TERMINOLOGY; SEIZURES; DISCHARGES;
PATTERNS; EPILEPSY; CHILDREN
AB Purpose:
The rapid expansion of the use of continuous critical care electroencephalogram (cEEG) monitoring and resulting multicenter research studies through the Critical Care EEG Monitoring Research Consortium has created the need for a collaborative data sharing mechanism and repository. The authors describe the development of a research database incorporating the American Clinical Neurophysiology Society standardized terminology for critical care EEG monitoring. The database includes flexible report generation tools that allow for daily clinical use.
Methods:
Key clinical and research variables were incorporated into a Microsoft Access database. To assess its utility for multicenter research data collection, the authors performed a 21-center feasibility study in which each center entered data from 12 consecutive intensive care unit monitoring patients. To assess its utility as a clinical report generating tool, three large volume centers used it to generate daily clinical critical care EEG reports.
Results:
A total of 280 subjects were enrolled in the multicenter feasibility study. The duration of recording (median, 25.5 hours) varied significantly between the centers. The incidence of seizure (17.6%), periodic/rhythmic discharges (35.7%), and interictal epileptiform discharges (11.8%) was similar to previous studies. The database was used as a clinical reporting tool by 3 centers that entered a total of 3,144 unique patients covering 6,665 recording days.
Conclusions:
The Critical Care EEG Monitoring Research Consortium database has been successfully developed and implemented with a dual role as a collaborative research platform and a clinical reporting tool. It is now available for public download to be used as a clinical data repository and report generating tool.
C1 [Lee, Jong Woo] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[LaRoche, Suzette; Ruiz, Andres A. Rodriguez] Emory Univ Hosp, Dept Neurol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA.
[Choi, Hyunmi] Columbia Univ, Dept Neurol, New York, NY USA.
[Fertig, Evan; Politsky, Jeffrey M.] Atlantic Hlth Systems Northeast Reg Epilepsy Grp, Hackensack, NJ USA.
[Herman, Susan T.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA.
[Loddenkemper, Tobias; Sansevere, Arnold J.] Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA.
[Korb, Pearce J.] Univ Colorado, Sch Med, Dept Neurol, Aurora, CO USA.
[Abend, Nicholas S.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Goldstein, Joshua L.] Northwestern Univ, Dept Pediat, Sect Pediat Neurocrit Care, Chicago, IL 60611 USA.
[Sinha, Saurabh R.; Dombrowski, Keith E.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA.
[Ritzl, Eva K.] Johns Hopkins Univ, Baltimore, MD USA.
[Westover, Michael B.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gavvala, Jay R.; Gerard, Elizabeth E.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Schmitt, Sarah E.] Hosp Univ Penn, 3400 Spruce St, Philadelphia, PA 19104 USA.
[Szaflarski, Jerzy P.] Univ Alabama Birmingham, Birmingham, AL USA.
[Ding, Kan] UT Southwestern Med Ctr, Dallas, TX USA.
[Haas, Kevin F.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Buchsbaum, Richard] Columbia Univ, Dept Biostat, New York, NY USA.
[Hirsch, Lawrence J.] Yale Med Ctr, New Haven, CT USA.
[Wusthoff, Courtney J.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Hopp, Jennifer L.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Hahn, Cecil D.] Univ Toronto, Hosp Sick Children, Div Neurol, Toronto, ON M5G 1X8, Canada.
RP Hahn, CD (reprint author), Hosp Sick Children, Div Neurol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada.
EM cecil.hahn@sickkids.ca
RI Hahn, Cecil/J-3372-2016;
OI Hahn, Cecil/0000-0002-0887-8761; Gavvala, Jay/0000-0002-9392-6608
FU UCB-Pharma; Upsher-Smith; Lundbeck; Eisai; Sunovion; Neuropace; GSK;
Sage Therapeutics; UCB; Acorda Therapeutics Inc; Marinus
Pharmaceuticals; NINDS; Canadian Institutes of Health Research;
Physicians' Services Incorporated Foundation; Hospital for Sick Children
Foundation; UCB Pharma; Lundbeck, Inc; National Institutes of Health
(NIH)/National Institute of Neurological Disorders and Stroke (NINDS);
Fidelity Biosciences Research Initiative; Epilepsy Therapy Development
Project; T. Loddenkemper American Epilepsy Society; Epilepsy Foundation
of America; Epilepsy Therapy Project; PCORI; Pediatric Epilepsy Research
Foundation; CURE; Danny-Did Foundation; HHV-6 Foundation; Biogen;
Cyberonics Inc; NIH; Shor Foundation for Epilepsy Research; AES; EFA;
FDA; State of AL General Funds; DoD; Epilepsy Study Consortium (HEP);
UAB; American Brain Foundation; NIH-NINDS [1K23NS090900]; Rappaport
Foundation
FX L. J. Hirsch: Research support to Yale for investigator initiated
studies from UCB-Pharma, Upsher-Smith, Lundbeck, Eisai and Sunovion,
consultation fees for advising from Lundbeck, Upsher-Smith, Neuropace,
and GSK, honoraria for speaking from Neuropace (last 12/2014), royalties
for authoring chapters for UpToDate-Neurology, chapters for
Medlink-Neurology, and from Wiley for coauthoring the book "Atlas of EEG
in Critical Care," by Hirsch and Brenner, 2010; Dr. Hirsch spends about
25% of his clinically billable time implementing and interpreting
critical care EEG studies.; N. S. Abend: NINDS (NIH NS076550); H. Choi:
UCB-Pharma, Lundbeck, Sunovion, and Eisai (research support); K. E.
Dombrowski: Sage Therapeutics (salary support); E. Fertig: UCB (research
funding), Acorda Therapeutics Inc (research funding), and Marinus
Pharmaceuticals (research funding); Gerard: NINDS (research funding),
SAGE pharmaceuticals (site-PI), and UCB/Duke (research consultant work);
C. D. Hahn: Canadian Institutes of Health Research, the Physicians'
Services Incorporated Foundation, and The Hospital for Sick Children
Foundation (research support); S. Herman: Biotie, Inc (consultant), UCB
Pharma, Lundbeck, Inc, National Institutes of Health (NIH)/National
Institute of Neurological Disorders and Stroke (NINDS), Fidelity
Biosciences Research Initiative, and Epilepsy Therapy Development
Project (research support); L. J. Hirsch: Research support to Yale for
investigator-initiated studies from UCB-Pharma, Upsher-Smith, Lundbeck,
Eisai and Sunovion, consultation fees for advising from Lundbeck,
Upsher-Smith, Neuropace, and GSK, honoraria for speaking from Natus
(last 1/2014) and Neuropace (last 12/2014), royalties for authoring
chapters for UpToDate-Neurology, chapters for Medlink-Neurology, and
from Wiley for coauthoring the book "Atlas of EEG in Critical Care," by
Hirsch and Brenner, 2010, spends about 25% of his clinically billable
time implementing and interpreting critical care EEG studies; J. L.
Hopp: NETT study member, UpToDate (royalties); S. LaRoche: Demos
Publishing (royalties); J. W. Lee: NINDS (research funding), Advance
Medical and SleepMed/DigiTrace (consultant/contract work), UCB (research
funding), and Sunovion (research funding); T. Loddenkemper: T.
Loddenkemper American Epilepsy Society, Epilepsy Foundation of America,
Epilepsy Therapy Project, PCORI, Pediatric Epilepsy Research Foundation,
CURE, Danny-Did Foundation, HHV-6 Foundation, Lundbeck, Eisai, and
Upsher-Smith (research support); S.R. Sinha: UCB (research funding),
Acorda Therapeutics Inc (research funding), Biogen (research funding),
Sage Therapeutics (research funding), and Cyberonics Inc (research
funding, speakers bureau); J. P. Szaflarski: Funding: NIH, Shor
Foundation for Epilepsy Research, AES, EFA, FDA, State of AL General
Funds, DoD, Epilepsy Study Consortium (HEP), UAB; Editorial Boards:
Associate Editor, Journal of Epileptology; Associate Editor: Restorative
Neurology and Neuroscience; Editorial Board Member: Folia Medica
Copernicana, Journal of Medical Science; Epilepsy and Behavior;
Consultant: Sage Pharmaceuticals; Biomedical Systems, Inc, Medico-legal
expert; and M. B. Westover: American Brain Foundation, NIH-NINDS
(1K23NS090900), and the Rappaport Foundation (research support).
NR 23
TC 3
Z9 3
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0736-0258
EI 1537-1603
J9 J CLIN NEUROPHYSIOL
JI J. Clin. Neurophysiol.
PD APR
PY 2016
VL 33
IS 2
BP 133
EP 140
DI 10.1097/WNP.0000000000000230
PG 8
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DI0YP
UT WOS:000373223500009
PM 26943901
ER
PT J
AU Bankoff, SM
Marks, AK
Swenson, LP
Pantalone, DW
AF Bankoff, Sarah M.
Marks, Amy K.
Swenson, Lance P.
Pantalone, David W.
TI Examining Associations of Sexual Attraction and Attitudes on Women's
Disordered Eating Behavior
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE disordered eating; sexual attractions; women; implicit attitudes;
heterosexism
ID INTERNALIZED HETEROSEXISM; ORIENTATION; SYMPTOMS; PATTERNS; WEIGHT;
SCALE; RISK; QUESTIONNAIRE; PREVALENCE; VALIDATION
AB ObjectiveWe aimed to expand the scant research on disordered eating in women identifying same-sex sexual attractions.
MethodWe used multiple linear regressions to explore potential mechanisms driving disordered eatingboth explicit and implicit weight bias and heterosexismin a cross-sectional, online-recruited community sample of women (N = 437). Participants endorsed a range of sexual attractions from exclusively opposite-sex (21.1%) to exclusively same-sex (19.5%) attraction.
ResultsFindings revealed no associations between sexual attraction and disordered eating. Awareness of sociocultural norms valuing thinness accounted for disordered eating for all women, regardless of sexual attraction, and was influenced by attitudes regarding weight. Among women endorsing same-sex attractions, self-reported internalized heterosexism influenced disordered eating.
DiscussionFindings contradict long-held beliefs that same-sex attracted women are protected from disordered eating. They emphasize a universal risk, for all women, of sociocultural norms valuing thinness, as well as the risk of internalized heterosexism among same-sex attracted women.
C1 [Bankoff, Sarah M.] VA Boston Healthcare Syst, Boston, MA 02130 USA.
[Marks, Amy K.; Swenson, Lance P.] Suffolk Univ, Boston, MA USA.
[Pantalone, David W.] Univ Massachusetts Boston, Boston, MA USA.
[Pantalone, David W.] Fenway Hlth, Fenway Inst, Boston, MA USA.
RP Bankoff, SM (reprint author), VA Boston Healthcare Syst, Primary Care Serv, 11PC,150 South Huntington Ave, Boston, MA 02130 USA.
EM sarah.bankoff@va.gov
NR 50
TC 0
Z9 0
U1 3
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 APR
PY 2016
VL 72
IS 4
BP 350
EP 364
DI 10.1002/jclp.22244
PG 15
WC Psychology, Clinical
SC Psychology
GA DH7KX
UT WOS:000372973800004
PM 26613200
ER
PT J
AU Wahbeh, H
Goodrich, E
Goy, E
Oken, BS
AF Wahbeh, Helane
Goodrich, Elena
Goy, Elizabeth
Oken, Barry S.
TI Mechanistic Pathways of Mindfulness Meditation in Combat Veterans With
Posttraumatic Stress Disorder
SO JOURNAL OF CLINICAL PSYCHOLOGY
LA English
DT Article
DE meditation; mindfulness; veteran; combat; posttraumatic stress disorder
ID AUTONOMIC NERVOUS-SYSTEM; HEART-RATE-VARIABILITY; PSYCHOMETRIC
PROPERTIES; CLINICAL-TRIAL; WAR VETERANS; METAANALYSIS; PTSD; SYMPTOMS;
EEG; QUESTIONNAIRE
AB ObjectiveThis study's objective was to evaluate the effect of two common components of meditation (mindfulness and slow breathing) on potential mechanistic pathways.
MethodsA total of 102 combat veterans with posttraumatic stress disorder (PTSD) were randomized to (a) the body scan mindfulness meditation (MM), (b) slow breathing (SB) with a biofeedback device, (c) mindful awareness of the breath with an intention to slow the breath (MM+SB), or (d) sitting quietly (SQ). Participants had 6 weekly one-on-one sessions with 20 minutes of daily home practice. The mechanistic pathways and measures were as follows: (a) autonomic nervous system (hyperarousal symptoms, heart rate [HR], and heart rate variability [HRV]); (b) frontal cortex activity (attentional network task [ANT] conflict effect and event-related negativity and intrusive thoughts); and (c) hypothalamic-pituitary-adrenal axis (awakening cortisol). PTSD measures were also evaluated.
ResultsMeditation participants had significant but modest within-group improvement in PTSD and related symptoms, although there were no effects between groups. Perceived impression of PTSD symptom improvement was greater in the meditation arms compared with controls. Resting respiration decreased in the meditation arms compared with SQ. For the mechanistic pathways, (a) subjective hyperarousal symptoms improved within-group (but not between groups) for MM, MM+SB, and SQ, while HR and HRV did not; (b) intrusive thoughts decreased in MM compared with MM+SB and SB, while the ANT measures did not change; and (c) MM had lower awakening cortisol within-group (but not between groups).
ConclusionTreatment effects were mostly specific to self-report rather than physiological measures. Continued research is needed to further evaluate mindfulness meditation's mechanism in people with PTSD.
C1 [Wahbeh, Helane; Goodrich, Elena; Oken, Barry S.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Wahbeh, Helane] Natl Coll Nat Med, Portland, OR USA.
[Goy, Elizabeth] Portland VA Med Ctr, Portland, OR USA.
RP Wahbeh, H (reprint author), 3181 SW Sam Jackson Pk Rd CR120, Portland, OR 97239 USA.
EM wahbehh@ohsu.edu
FU National Center for Advancing Translational Sciences of the National
Institutes of Health [UL1TR000128]; National Center for Complementary
and Alternative Medicine of the National Institutes of Health
[T32AT002688, K01AT004951, K24AT005121]
FX Research reported in this publication was supported by National Center
for Advancing Translational Sciences of the National Institutes of
Health under award number UL1TR000128 and the National Center for
Complementary and Alternative Medicine of the National Institutes of
Health [grant numbers T32AT002688, K01AT004951, K24AT005121].
NR 81
TC 0
Z9 0
U1 13
U2 22
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 APR
PY 2016
VL 72
IS 4
BP 365
EP 383
DI 10.1002/jclp.22255
PG 19
WC Psychology, Clinical
SC Psychology
GA DH7KX
UT WOS:000372973800005
PM 26797725
ER
PT J
AU Nasser, AF
Henderson, DC
Fava, M
Fudala, PJ
Twumasi-Ankrah, P
Kouassi, A
Heidbreder, C
AF Nasser, Azmi F.
Henderson, David C.
Fava, Maurizio
Fudala, Paul J.
Twumasi-Ankrah, Philip
Kouassi, Alex
Heidbreder, Christian
TI Efficacy, Safety, and Tolerability of RBP-7000 Once-Monthly Risperidone
for the Treatment of Acute Schizophrenia An 8-Week, Randomized,
Double-Blind, Placebo-Controlled, Multicenter Phase 3 Study
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Article
DE RBP-7000; schizophrenia; ATRIGEL; long-acting risperidone
ID ACTING INJECTABLE RISPERIDONE; POPULATION PHARMACOKINETICS; FORMULATION;
DISORDERS; RELAPSE; TRIAL; OCCUPANCY; PROLACTIN; INJECTION; MORTALITY
AB RBP-7000 is a sustained-release formulation of risperidone for the treatment of schizophrenia, designed to be administered by once-monthly subcutaneous injection using the ATRIGEL delivery system. This study assessed the efficacy, safety, and tolerability of RBP-7000 compared with placebo in subjects with acute exacerbation of schizophrenia. Inpatients were randomly assigned to 8 weeks of double-blind treatment with subcutaneous 90 or 120 mg of RBP-7000 or placebo. Efficacy was evaluated using a mixed-model repeated-measures analysis of the change from baseline (the last nonmissing value before the first dose of RBP-7000 or placebo on day 1) to end of the study in Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure) and Clinical Global Impression-Severity score (secondary efficacy measure). The least-squares means from the repeated-measures analysis for the change from baseline in the PANSS total scores for placebo was -9.219 (SE, 1.2162). RBP-7000 produced statistically and clinically significant differences in mean reductions from baseline in PANSS total scores (90-mg RBP-7000 compared with placebo, -6.148 [-9.982 to -2.314], P = 0.0004; 120-mg RBP-7000 compared with placebo, -7.237 [-11.045 to -3.429], P < 0.0001) and significantly improved Clinical Global Impression-Severity scores (90-mg RBP-7000 compared with placebo, -0.350 [-0.557 to -0.143], P = 0.0002; 120-mg RBP-7000 compared with placebo, -0.396 [-0.602 to -0.190], P < 0.0001). Both RBP-7000 dosages were generally well tolerated. The most frequently reported treatment-emergent adverse events in RBP-7000 groups compared with placebo were somnolence, weight gain, and akathisia. The overall incidence of extrapyramidal syndrome-related effects was low and similar across groups. RBP-7000 may provide a new, long-acting alternative treatment for use in adults with acute schizophrenia.
C1 [Nasser, Azmi F.; Fudala, Paul J.; Twumasi-Ankrah, Philip; Kouassi, Alex; Heidbreder, Christian] Indivior Inc, Global Res & Dev, Richmond, VA 23235 USA.
[Henderson, David C.] Massachusetts Gen Hosp, Schizophrenia Clin & Res Program, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA.
[Henderson, David C.] Harvard Univ, Sch Med, Dept Psychiat, Harvard Sch Publ Hlth, Boston, MA 02115 USA.
[Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Div Clin Res, Clin Trials Network & Inst, Boston, MA 02114 USA.
[Fava, Maurizio] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
RP Heidbreder, C (reprint author), Indivior Inc, 10710 Midlothian Turnpike,Suite 430, Richmond, VA 23235 USA.
EM christian.heidbreder@indivior.com
FU Indivior, Inc.
FX This study was sponsored and supported by Indivior, Inc. At the time,
this manuscript was submitted for publication, A.F. Nasser, P.J. Fudala,
P. Twumasi-Ankrah, A. Kouassi, and C. Heidbreder were full-time
employees of Indivior, Inc. D.C. Henderson and M. Fava were full-time
employees of the Massachusetts General Hospital, Harvard Medical School,
and were paid consultants for Indivior, Inc.
NR 43
TC 1
Z9 1
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD APR
PY 2016
VL 36
IS 2
BP 130
EP 140
DI 10.1097/JCP.0000000000000479
PG 11
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA DG5FG
UT WOS:000372100800006
PM 26862829
ER
PT J
AU Gurrera, RJ
Parlee, AC
Perry, NL
AF Gurrera, Ronald J.
Parlee, Anne C.
Perry, Nicole L.
TI Aspiration Pneumonia An Underappreciated Risk of Clozapine Treatment
SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY
LA English
DT Letter
ID ANTIPSYCHOTIC-DRUG USE; SALIVARY FLOW-RATE; ESOPHAGEAL DYSFUNCTION;
SCHIZOPHRENIA; SIALORRHEA; SMOKING; REASONS
C1 [Gurrera, Ronald J.; Perry, Nicole L.] VA Boston Healthcare Syst, Boston, MA USA.
[Gurrera, Ronald J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Parlee, Anne C.] Boston Med Ctr, Boston, MA USA.
RP Gurrera, RJ (reprint author), VA Boston Healthcare Syst, Boston, MA USA.; Gurrera, RJ (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
EM ronald.gurrera@va.gov
NR 25
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0271-0749
EI 1533-712X
J9 J CLIN PSYCHOPHARM
JI J. Clin. Psychopharmacol.
PD APR
PY 2016
VL 36
IS 2
BP 174
EP 176
DI 10.1097/JCP.0000000000000458
PG 3
WC Pharmacology & Pharmacy; Psychiatry
SC Pharmacology & Pharmacy; Psychiatry
GA DG5FG
UT WOS:000372100800014
PM 26848787
ER
PT J
AU Turner, AP
Hartoonian, N
Sloan, AP
Benich, M
Kivlahan, DR
Hughes, C
Hughes, AJ
Haselkorn, JK
AF Turner, Aaron P.
Hartoonian, Narineh
Sloan, Alicia P.
Benich, Marisa
Kivlahan, Daniel R.
Hughes, Christina
Hughes, Abbey J.
Haselkorn, Jodie K.
TI Improving Fatigue and Depression in Individuals With Multiple Sclerosis
Using Telephone-Administered Physical Activity Counseling
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE fatigue; depression; physical activity; motivational interviewing;
self-management
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; DISABILITY STATUS SCALE;
SELF-REPORT; MAJOR DEPRESSION; CLINICAL-TRIALS; MENTAL-HEALTH;
PRIMARY-CARE; MS PATIENTS; EXERCISE
AB Objective: To evaluate the impact of a physical activity intervention consisting of telephone counseling with home-based monitoring to improve fatigue and depression in individuals with multiple sclerosis (MS). Method: Single-blind randomized controlled trial. Sixty-four individuals with MS received either telephone counseling (N = 31), or self-directed physical activity education (N = 33). The education condition (EC) consisted of advice to increase physical activity and a DVD with examples of in-home exercises for multiple physical ability levels. The telephone counseling condition (TC) included EC as well as mailed graphic feedback, 6 telephone counseling sessions using principles of motivational interviewing, and telehealth home monitoring to track progress on physical activity goals. Booster sessions were provided when participants indicated they did not meet their goals. Assessment was conducted at baseline, 3-month, and 6-month follow-up. Results: TC participants reported significantly reduced fatigue (d = -.70), reduced depression (d = -.72) and increased physical activity (d =.92) relative to EC participants. Of individuals receiving TC, 33.3% experienced clinically significant improvement in fatigue (vs. 18.2% in EC) and 53.3% experienced clinically significant improvement in depression (vs. 9.1% in EC). Improvements in physical activity mediated improvements in fatigue with a similar trend for depression. TC was highly feasible (participants completed 99.5% of schedule telephone sessions) and well tolerated (100% rated it highly successful). Conclusion: Telephone-based counseling with home monitoring is a promising modality to improve physical activity and treat fatigue and depression.
C1 [Turner, Aaron P.; Benich, Marisa; Hughes, Abbey J.] VA Puget Sound Hlth Care Syst, VA Multiple Sclerosis Ctr Excellence, Seattle, WA USA.
[Turner, Aaron P.; Hughes, Abbey J.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Hartoonian, Narineh; Sloan, Alicia P.; Haselkorn, Jodie K.] VA Multiple Sclerosis Ctr Excellence West, Seattle, WA USA.
[Kivlahan, Daniel R.] Vet Hlth Adm, Mental Hlth Serv, Washington, DC USA.
[Kivlahan, Daniel R.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
[Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117 RCS,1660 South Columbian Way, Seattle, WA 98108 USA.
EM Aaron.Turner@med.va.gov
OI Turner, Aaron/0000-0001-6897-8003
FU Department of Veterans Affairs Rehabilitation Research and Development
Service Career Development Award [B4927W]; VA Multiple Sclerosis Center
of Excellence West; VA Center of Excellence for Limb Loss Prevention and
Prosthetic Engineering; VA Center of Excellence in Substance Abuse
Treatment and Education
FX This research was supported by Department of Veterans Affairs
Rehabilitation Research and Development Service Career Development Award
B4927W to Aaron P. Turner. Additional support was provided by the VA
Multiple Sclerosis Center of Excellence West, the VA Center of
Excellence for Limb Loss Prevention and Prosthetic Engineering, and the
VA Center of Excellence in Substance Abuse Treatment and Education.
Trial Registration clinicaltrials.gov Identifier: NCT01198977. Special
thanks to Charles Bombardier who provided mentorship and consultation on
this project.
NR 75
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U1 10
U2 17
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
EI 1939-2117
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD APR
PY 2016
VL 84
IS 4
BP 297
EP 309
DI 10.1037/ccp0000086
PG 13
WC Psychology, Clinical
SC Psychology
GA DH8PP
UT WOS:000373057100002
PM 26913621
ER
PT J
AU Jarrett, RB
Minhajuddin, A
Vittengl, JR
Clark, LA
Thase, ME
AF Jarrett, Robin B.
Minhajuddin, Abu
Vittengl, Jeffrey R.
Clark, Lee Anna
Thase, Michael E.
TI Quantifying and Qualifying the Preventive Effects of Acute-Phase
Cognitive Therapy: Pathways to Personalizing Care
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE depression; cognitive therapy; relapse; recurrence; predictors of
outcomes
ID MAJOR DEPRESSIVE DISORDER; ATTRIBUTIONAL STYLE QUESTIONNAIRE; RECURRENT
DEPRESSION; CONTINUATION PHASE; FOLLOW-UP; SOCIAL-ADJUSTMENT;
RANDOMIZED-TRIAL; PILL PLACEBO; SELF-CONTROL; RELAPSE
AB Objective: To determine the extent to which prospectively identified responders to cognitive therapy (CT) for recurrent major depressive disorder (MDD) hypothesized to be lower risk show significantly less relapse or recurrence than treated higher risk counterparts across 32 months. Method: Outpatients (N = 523), aged 18-70, with recurrent MDD received 12-14 weeks of CT. The last 7 consecutive scores from the Hamilton Rating Scale for Depression (HRSD-17) were used to stratify or define responders (n = 290) into lower (7 HRSD-17 scores of less than or equal to 6; n = 49; 17%) and higher risk (n = 241; 83%). The lower risk patients entered the 32-month follow-up. Higher risk patients were randomized to 8 months of continuation-phase CT or clinical management plus double-blind fluoxetine or pill placebo, with a 24-month follow-up. Results: Lower risk patients were significantly less likely to relapse over the first 8 months compared to higher risk patients (Kaplan-Meier [KM] estimates; i.e., 4.9% = lower risk; 22.1% = higher risk; log-rank chi(2) = 6.83, p = .009). This increased risk was attenuated, but not completely neutralized, by active continuation-phase therapy. Over the subsequent 24 months, the lower and higher risk groups did not differ in relapse or recurrence risk. Conclusions: Rapid and sustained acute-phase CT remission identifies responders who do not require continuation-phase treatment to prevent relapse (i.e., return of an index episode). To prevent recurrence (i.e., new episodes), however, strategic allocation and more frequent "dosing" of CT and/or targeted maintenance-phase treatments may be required. Longitudinal follow-up is recommended.
C1 [Jarrett, Robin B.] Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
[Minhajuddin, Abu] Univ Texas SW Med Ctr Dallas, Dept Clin Sci, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
[Vittengl, Jeffrey R.] Truman State Univ, Dept Psychol, Kirksville, MO USA.
[Clark, Lee Anna] Univ Notre Dame, Dept Psychol, Notre Dame, IN 46556 USA.
[Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
RP Jarrett, RB (reprint author), Univ Texas SW Med Ctr Dallas, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM robin.jarrett@utsouthwestern.edu
FU Alkermes; Assurerx; AstraZeneca; Avenir; Eli Lilly and Company; Forest
Laboratories; Janssen/Johnson Johnson; Otsuka; Roche; Agency for
Healthcare Research and Quality; National Institute of Mental Health
(NIMH); NIMH [K24 MH001571, R01 MH058397, R01 MH069619, R01 MH058356,
R01 MH069618]
FX During the past 3 years, Michael E. Thase has consulted with and/or
served on advisory boards for Advir, Alkermes, Allergan, AstraZeneca,
Avenir, Bristol-Myers Squibb Company, Cerecor, Cerenex, Eli Lilly and
Company, Forest Laboratories, Janssen Pharmaceutica, Johnson & Johnson,
Lundbeck, MedAvante, Merck, Moksha8, Naurex, Neuronetics, Novartis,
Otsuka, Nestle (formerly Pamlab), Pfizer Pharmaceuticals, Roche, Shire,
Sunovion, Takeda, and Teva. During this time, he has received grant
support from Alkermes, Assurerx, AstraZeneca, Avenir, Eli Lilly and
Company, Forest Laboratories, Janssen/Johnson & Johnson, Otsuka, and
Roche, as well as funding from the Agency for Healthcare Research and
Quality and the National Institute of Mental Health (NIMH). He has
equity holdings for MedAvante, Inc., and has received royalties from
American Psychiatric Publishing, Inc. (APPI), Guilford Publications,
Herald House, and W. W. Norton & Company, Inc. Two books currently
promoted by the APPI specifically pertain to cognitive therapy. Michael
E. Thase also discloses that his spouse is an employee of Peloton
Advantage, which does business with several pharmaceutical companies
that market medications used to treat depression. Robin B. Jarrett's
medical center collects the payments from the cognitive therapy she
provides to patients. Jarrett is a paid consultant to the NIMH and the
National Institutes of Health (NIH). Robin B. Jarrett and Jeffrey R.
Vittengl are paid reviewers for UpToDate.; This report was supported by
Grants K24 MH001571, R01 MH058397, and R01 MH069619 (to Robin B.
Jarrett) and R01 MH058356 and R01 MH069618 (to Michael E. Thase) from
the NIMH. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the NIMH or the
NIH. We also wish to acknowledge the unrestricted support of Eli Lilly
and Company, which provided fluoxetine and matched pill placebo for the
first 6 years of the study. Thereafter, study materials were purchased
and prepared to appear identical for both sites by the pharmacy at The
University of Texas Southwestern Medical Center. We are grateful to our
patients, research teams, and colleagues at The University of Texas
Southwestern Medical Center, the University of Pittsburgh, and the
University of Pennsylvania who made this trial possible. We appreciate
the assistance of Lauren Singer, M. S. and Joanne Sanders, M. S. for
their research support.
NR 47
TC 1
Z9 1
U1 8
U2 11
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0022-006X
EI 1939-2117
J9 J CONSULT CLIN PSYCH
JI J. Consult. Clin. Psychol.
PD APR
PY 2016
VL 84
IS 4
BP 365
EP 376
DI 10.1037/ccp0000069
PG 12
WC Psychology, Clinical
SC Psychology
GA DH8PP
UT WOS:000373057100008
PM 26654211
ER
PT J
AU Lopez, L
Tan-McGrory, A
Horner, G
Betancourt, JR
AF Lopez, Lenny
Tan-McGrory, Aswita
Horner, Gabrielle
Betancourt, Joseph R.
TI Eliminating disparities among Latinos with type 2 diabetes: Effective
eHealth strategies
SO JOURNAL OF DIABETES AND ITS COMPLICATIONS
LA English
DT Review
DE Disparities; Diabetes; eHealth; Interventions; Latino
ID RANDOMIZED CONTROLLED-TRIALS; SELF-MANAGEMENT EDUCATION; BEHAVIOR-CHANGE
INTERVENTIONS; ETHNIC-MINORITY GROUPS; PHYSICAL-ACTIVITY;
HEALTH-EDUCATION; DIVERSE BACKGROUNDS; MEXICAN-AMERICANS;
AFRICAN-AMERICAN; GLYCEMIC CONTROL
AB Latinos are at increased risk for obesity and type 2 diabetes (T2D). Well-designed information technology (IT) interventions have been shown to be generally efficacious in improving diabetes self-management. However, there are very few published IT intervention studies focused on Latinos. With the documented close of the digital divide, Latinos stand to benefit from such advances. There are limited studies on how best to address the unique socio-cultural-linguistic characteristics that would optimize adoption, use and benefit among Latinos. Successful e-health programs involve frequent communication, bidirectionality including feedback, and multimodal delivery of the intervention. The use of community health workers (CHWs) has been shown consistently to improve T2D outcomes in Latinos. Incorporating CHWs into eHealth interventions is likely to address barriers with technology literacy and improve patient activation, satisfaction and adherence. Additionally, tailored interventions are more successful in improving patient activation. It is important to note that tailoring is more than linguistic translation; tailoring interventions to the Latino population will need to address educational, language, literacy and acculturation levels, along with unique illness beliefs and attitudes about T2D found among Latinos. Interventions will need to go beyond the lone participant and include shared decision making models that incorporate family members and friends. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Lopez, Lenny; Tan-McGrory, Aswita; Betancourt, Joseph R.] Massachusetts Gen Hosp, Dispar Solut Ctr, Boston, MA 02114 USA.
[Lopez, Lenny; Tan-McGrory, Aswita; Horner, Gabrielle; Betancourt, Joseph R.] Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA.
[Lopez, Lenny] Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA.
[Lopez, Lenny] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
RP Lopez, L (reprint author), Massachusetts Gen Hosp, Mongan Inst Hlth Policy, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA.; Lopez, L (reprint author), Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA.
EM lopezlenny77@gmail.com
FU Robert Wood Johnson Foundation Harold Amos Medical Faculty Development
Program; [NIDDK1K23DK098280-01]
FX Dr. Lenny Lopez acknowledges the support of the Robert Wood Johnson
Foundation Harold Amos Medical Faculty Development Program and
NIDDK1K23DK098280-01. This funding body was not involved in the design,
data collection, analysis, interpretation or the preparation of the
manuscript.
NR 70
TC 0
Z9 0
U1 7
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1056-8727
EI 1873-460X
J9 J DIABETES COMPLICAT
JI J. Diabetes Complications
PD APR
PY 2016
VL 30
IS 3
BP 554
EP 560
DI 10.1016/j.jdiacomp.2015.12.003
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DH6ZJ
UT WOS:000372940300028
PM 26774790
ER
PT J
AU Gomes, CBF
Treisten, NS
Millen, B
Armand, P
Friedland, B
AF Ferreira Gomes, Camilla Borges
Treisten, Nathaniel Simon
Millen, Brian
Armand, Philippe
Friedland, Bernard
TI Pulp Obliteration in a Patient with Sclerodermatous Chronic
Graft-versus-Host Disease
SO JOURNAL OF ENDODONTICS
LA English
DT Article
DE Allogeneic hematopoietic cell transplantation; dental pulp obliteration;
oral chronic graft-versus-host disease; pulp calcification
ID SYSTEMIC-SCLEROSIS; CALCIFICATIONS; PATHOGENESIS; PREVALENCE; DIAGNOSIS;
THERAPY; STONES
AB Dental pulp calcification is a common finding associated with localized dental trauma, genetic disorders, and systemic inflammatory diseases. Chronic graft-versus-host disease (cGVHD) is a frequent complication after allogeneic hematopoietic cell transplantation (allo-HCT) characterized by immune-mediated injury to the skin, mouth, eyes, liver, and other tissues, resulting in significant disability and reduced quality of life. We report a patient with sclerodermatous cGVHD who presented with general pulp calcification in all teeth 5 years after allo-HCT. A review of full mouth dental radiographs obtained just before allo-HCT revealed normal-appearing pulp chambers. Based on prior reports of generalized pulp calcification associated with progressive systemic sclerosis, we hypothesized that the etiology was likely related to the presence of cGVHD with associated vascular and fibrotic tissue changes within the pulp vasculature. Clinicians should consider cGVHD in the differential diagnosis of generalized pulp calcification.
C1 [Ferreira Gomes, Camilla Borges] Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Sao Paulo, Brazil.
[Ferreira Gomes, Camilla Borges; Treisten, Nathaniel Simon] Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA.
[Ferreira Gomes, Camilla Borges; Treisten, Nathaniel Simon] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Treisten, Nathaniel Simon; Armand, Philippe] Dana Farber Canc Inst, Dept Med Oncol Hematol Malignancies, Boston, MA 02115 USA.
[Millen, Brian] Miller Lung Dent Grp, South Attleboro, MA USA.
[Friedland, Bernard] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA.
RP Gomes, CBF (reprint author), Univ Estadual Campinas, Sch Dent, Dept Oral Diag, Av Limeira 901, BR-13414018 Piracicaba, SP, Brazil.
EM camillabfgomes@hotmail.com
NR 23
TC 0
Z9 0
U1 3
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0099-2399
EI 1878-3554
J9 J ENDODONT
JI J. Endod.
PD APR
PY 2016
VL 42
IS 4
BP 678
EP 680
DI 10.1016/j.joen.2016.01.009
PG 3
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DI1FL
UT WOS:000373241900029
PM 26906241
ER
PT J
AU Lightner, AL
Shannon, E
Gibbons, MM
Russell, MM
AF Lightner, Amy L.
Shannon, Evan
Gibbons, Melinda Maggard
Russell, Marcia M.
TI Primary Gastrointestinal Non-Hodgkin's Lymphoma of the Small and Large
Intestines: a Systematic Review
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Review
DE Lymphoma; Small intestine; Large intestine; Surgery; Outcomes
ID B-CELL LYMPHOMA; PRIMARY COLONIC LYMPHOMA; FOLLICULAR LYMPHOMA;
CLINICAL-FEATURES; CLINICOPATHOLOGICAL ANALYSIS; MALT LYMPHOMA;
POPULATION; MANAGEMENT; RITUXIMAB; TRACT
AB Primary gastrointestinal non-Hodgkin's lymphoma (PGINHL) of small and large intestines is a group of heterogeneous, rare malignancies. Optimal treatment practices remain undefined.
A systematic review (2003-2015) was performed to assess tumor characteristics, treatment practices, and treatment outcomes of PGINHL of small and large intestines.
Twenty-eight studies (1658 patients) were included; five focused on follicular lymphoma subtype. Of the non-follicular patients, 59.3 % presented with abdominal pain, 37.2 % were located in ileocecum, and 53.6 % were diffuse large B cell lymphoma subtype. The majority of patients (60.7 %) were treated with a combination of surgery and chemotherapy. Forty-three percent of studies concluded an overall survival benefit with surgery; none reported increased postoperative morbidity or mortality. Survival outcomes were not typically stratified by emergent versus elective surgery. Multivariate analysis within individual studies associated B cell lymphoma and ileocecum location with higher survival, while advanced stage and B symptoms were associated with poorer survival. Patients with asymptomatic follicular lymphoma had no progression with a watchful waiting approach.
The majority of patients with non-follicular small and large intestinal PGINHLs are treated with both chemotherapy and surgery. Although surgery appears to be an important part of the treatment algorithm, definitive statements regarding its survival benefit remain limited due to lack of patient stratification based on timing and indication for surgery.
C1 [Lightner, Amy L.; Gibbons, Melinda Maggard; Russell, Marcia M.] Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, 200 1st St SW Rochester, Los Angeles, MN 55905 USA.
[Shannon, Evan] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
[Russell, Marcia M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA.
RP Lightner, AL (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, 200 1st St SW Rochester, Los Angeles, MN 55905 USA.
EM Lightner.amy@mayo.edu
NR 57
TC 2
Z9 2
U1 2
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
EI 1873-4626
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD APR
PY 2016
VL 20
IS 4
BP 827
EP 839
DI 10.1007/s11605-015-3052-4
PG 13
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA DI0BB
UT WOS:000373158700021
PM 26676930
ER
PT J
AU Alvino, DML
Chang, DC
Fong, ZV
AF Alvino, Donna Marie L.
Chang, David C.
Fong, Zhi Ven
TI How Does Outcomes Research Help Advance Our Knowledge of Patient
Outcomes in Hepatopancreaticobiliary Surgery?
SO JOURNAL OF GASTROINTESTINAL SURGERY
LA English
DT Editorial Material
DE Health services research; Outcomes; Pancreas; Hepatopancreaticobiliary
surgery
ID INSTRUMENTAL-VARIABLE-ANALYSIS; PANCREATIC FISTULA;
PANCREATICODUODENECTOMY; CANCER; MORTALITY; TRENDS
AB Randomized controlled trials have historically been regarded as the gold standard of modern clinical research tools, allowing us to elucidate the efficacy of novel therapeutics in an unparalleled manner. However, when attempting to generalize trial results to broader populations, it becomes apparent that the unexplained outcome variability exists among treatment recipients, suggesting that randomized controlled trials harbor inherent limitations. Herein, we explore the benefits of health services (outcomes) research utilization in addressing variation in patient outcomes following surgical intervention in the non-randomized setting, with a specific focus on hepatopancreaticobiliary surgery outcomes. To achieve this, we have constructed a framework that outlines the complex interactions existing between therapeutic, patient, and provider factors that subsequently lead to variation in outcomes. By exploring examples in the current literature, we have highlighted the areas where the knowledge is currently lacking and can be further strengthened through the application of outcomes research. Furthermore, we have attempted to demonstrate the utility of alternative study designs in the investigation of novel clinical questions currently unanswered in the field of hepatopancreaticobiliary surgery.
C1 [Alvino, Donna Marie L.; Chang, David C.; Fong, Zhi Ven] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Codman Ctr Clin Effectiveness Surg, 165 Cambridge St, Boston, MA 02114 USA.
RP Fong, ZV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Codman Ctr Clin Effectiveness Surg, 165 Cambridge St, Boston, MA 02114 USA.
EM zfong@partners.org
NR 25
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1091-255X
EI 1873-4626
J9 J GASTROINTEST SURG
JI J. Gastrointest. Surg.
PD APR
PY 2016
VL 20
IS 4
BP 871
EP 877
DI 10.1007/s11605-015-3072-0
PG 7
WC Gastroenterology & Hepatology; Surgery
SC Gastroenterology & Hepatology; Surgery
GA DI0BB
UT WOS:000373158700027
PM 26861969
ER
PT J
AU Harris, AHS
Chen, C
Rubinsky, AD
Hoggatt, KJ
Neuman, M
Vanneman, ME
AF Harris, Alex H. S.
Chen, Cheng
Rubinsky, Anna D.
Hoggatt, Katherine J.
Neuman, Matthew
Vanneman, Megan E.
TI Are Improvements in Measured Performance Driven by Better Treatment or
"Denominator Management"?
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE quality measurement; measurement reactivity; performance contracts
ID PREVENTING UNINTENDED CONSEQUENCES; QUALITY MEASUREMENT; REPORT CARDS;
INFORMATION
AB Process measures of healthcare quality are usually formulated as the number of patients who receive evidence-based treatment (numerator) divided by the number of patients in the target population (denominator). When the systems being evaluated can influence which patients are included in the denominator, it is reasonable to wonder if improvements in measured quality are driven by expanding numerators or contracting denominators.
In 2003, the US Department of Veteran Affairs (VA) based executive compensation in part on performance on a substance use disorder (SUD) continuity-of-care quality measure. The first goal of this study was to evaluate if implementing the measure in this way resulted in expected improvements in measured performance. The second goal was to examine if the proportion of patients with SUD who qualified for the denominator contracted after the quality measure was implemented, and to describe the facility-level variation in and correlates of denominator contraction or expansion.
Using 40 quarters of data straddling the implementation of the performance measure, an interrupted time series design was used to evaluate changes in two outcomes.
All veterans with an SUD diagnosis in all VA facilities from fiscal year 2000 to 2009.
The two outcomes were 1) measured performance-patients retained/patients qualified and 2) denominator prevalence-patients qualified/patients with SUD program contact.
Measured performance improved over time (P < 0.001). Notably, the proportion of patients with SUD program contact who qualified for the denominator decreased more rapidly after the measure was implemented (p = 0.02). Facilities with higher pre-implementation denominator prevalence had steeper declines in denominator prevalence after implementation (p < 0.001).
These results should motivate the development of measures that are less vulnerable to denominator management, and also the exploration of "shadow measures" to monitor and reduce undesirable denominator management.
C1 [Harris, Alex H. S.; Chen, Cheng; Rubinsky, Anna D.; Neuman, Matthew; Vanneman, Megan E.] VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd, Menlo Pk, CA 94025 USA.
[Hoggatt, Katherine J.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA.
[Hoggatt, Katherine J.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Vanneman, Megan E.] Stanford Univ, Ctr Hlth Policy Primary Care & Outcomes Res, Sch Med, Stanford, CA 94305 USA.
RP Harris, AHS (reprint author), VA Palo Alto Hlth Care Syst, Ctr Innovat Implementat, 795 Willow Rd, Menlo Pk, CA 94025 USA.
EM Alexander.Harris2@va.gov
FU VA Health Services Research and Development (HSRD) Service [IIR
10-370-2]; VA Substance Use Disorder Quality Enhancement Research
Initiative (SUD QUERI) [SUDQ-LIP-1208, SUDQ-LIP-1314]; VA HSR&D/QUERI
Career Development Award; VA HSR&D Postdoctoral Fellowship; VA HSR&D
Research Career Scientist Award [RCS-14-232]
FX This study was funded by the VA Health Services Research and Development
(HSR&D) Service (IIR 10-370-2), VA Substance Use Disorder Quality
Enhancement Research Initiative (SUD QUERI; SUDQ-LIP-1208;
SUDQ-LIP-1314), a VA HSR&D/QUERI Career Development Award to Dr.
Hoggatt, a VA HSR&D Postdoctoral Fellowship to Dr. Vanneman, and a VA
HSR&D Research Career Scientist Award (RCS-14-232) to Dr. Harris. The
views expressed herein are not necessarily those of the Department of
Veterans Affairs.
NR 21
TC 2
Z9 2
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
SU 1
BP 21
EP 27
DI 10.1007/s11606-015-3558-1
PG 7
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BN
UT WOS:000373159900006
PM 26951270
ER
PT J
AU Farmer, MM
Rubenstein, LV
Sherbourne, CD
Huynh, A
Chu, K
Lam, CA
Fickel, JJ
Lee, ML
Metzger, ME
Verchinina, L
Post, EP
Chaney, EF
AF Farmer, Melissa M.
Rubenstein, Lisa V.
Sherbourne, Cathy D.
Huynh, Alexis
Chu, Karen
Lam, Christine A.
Fickel, Jacqueline J.
Lee, Martin L.
Metzger, Maureen E.
Verchinina, Lilia
Post, Edward P.
Chaney, Edmund F.
TI Depression Quality of Care: Measuring Quality over Time Using VA
Electronic Medical Record Data
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE performance measurement; depression; Veterans; measurement; quality
assessment
ID RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE CARE; PERFORMANCE-MEASURES;
CHRONIC DISEASE; MENTAL-HEALTH; IMPROVEMENT; OUTCOMES; IMPACT
AB The Veterans Health Administration (VA) has invested substantially in evidence-based mental health care. Yet no electronic performance measures for assessing the level at which the population of Veterans with depression receive appropriate care have proven robust enough to support rigorous evaluation of the VA's depression initiatives.
Our objectives were to develop prototype longitudinal electronic population-based measures of depression care quality, validate the measures using expert panel judgment by VA and non-VA experts, and examine detection, follow-up and treatment rates over a decade (2000-2010). We describe our development methodology and the challenges to creating measures that capture the longitudinal course of clinical care from detection to treatment.
Data come from the National Patient Care Database and Pharmacy Benefits Management Database for primary care patients from 1999 to 2011, from nine Veteran Integrated Service Networks.
We developed four population-based quality metrics for depression care that incorporate a 6-month look back and 1-year follow-up: detection of a new episode of depression, 84 and 180 day follow-up, and minimum appropriate treatment 1-year post detection. Expert panel techniques were used to evaluate the measure development methodology and results. Key challenges to creating valid longitudinal measures are discussed.
Over the decade, the rates for detection of new episodes of depression remained stable at 7-8 %. Follow-up at 84 and 180 days were 37 % and 45 % in 2000 and increased to 56 % and 63 % by 2010. Minimum appropriate treatment remained relatively stable over the decade (82-84 %).
The development of valid longitudinal, population-based quality measures for depression care is a complex process with numerous challenges. If the full spectrum of care from detection to follow-up and treatment is not captured, performance measures could actually mask the clinical areas in need of quality improvement efforts.
C1 [Farmer, Melissa M.; Rubenstein, Lisa V.; Huynh, Alexis; Chu, Karen; Lam, Christine A.; Fickel, Jacqueline J.; Lee, Martin L.] VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 16111 Plummer St 152, Sepulveda, CA 91343 USA.
[Rubenstein, Lisa V.; Sherbourne, Cathy D.] RAND Corp, Santa Monica, CA USA.
[Rubenstein, Lisa V.; Lee, Martin L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Rubenstein, Lisa V.; Lee, Martin L.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA.
[Metzger, Maureen E.; Verchinina, Lilia; Post, Edward P.] HSR&D Ctr Clin Management Res, VA Ann Arbor, Ann Arbor, MI USA.
[Post, Edward P.] Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA.
[Chaney, Edmund F.] Univ Washington, Sch Med, Seattle, WA 98195 USA.
RP Farmer, MM (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Study Healthcare Innovat Implementat, 16111 Plummer St 152, Sepulveda, CA 91343 USA.
EM Melissa.Farmer@va.gov
FU VA Health Services Research Development [IIR 11-326]
FX Funding for this research was supported by a grant from VA Health
Services Research & Development (Project #IIR 11-326; PI: Farmer). We
would like to acknowledge the expert panelists for their contribution as
well as Britney Chow, MPH and Ismelda Canelo, MPA for administrative
support.
NR 33
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U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
SU 1
BP 36
EP 45
DI 10.1007/s11606-015-3563-4
PG 10
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BN
UT WOS:000373159900008
PM 26951274
ER
PT J
AU Saini, SD
Powell, AA
Dominitz, JA
Fisher, DA
Francis, J
Kinsinger, L
Pittman, KS
Schoenfeld, P
Moser, SE
Vijan, S
Kerr, EA
AF Saini, Sameer D.
Powell, Adam A.
Dominitz, Jason A.
Fisher, Deborah A.
Francis, Joseph
Kinsinger, Linda
Pittman, Kathleen S.
Schoenfeld, Philip
Moser, Stephanie E.
Vijan, Sandeep
Kerr, Eve A.
TI Developing and Testing an Electronic Measure of Screening Colonoscopy
Overuse in a Large Integrated Healthcare System
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE performance measurement; colorectal cancer; screening; health services
research
ID SOCIETY TASK-FORCE; COLORECTAL-CANCER; MEDICARE POPULATION; QUALITY
MEASURES; GUIDELINES
AB Most existing performance measures focus on underuse of care, but there is growing interest in identifying and reducing overuse.
We aimed to develop a valid and reliable electronic performance measure of overuse of screening colonoscopy in the Veterans Affairs Health Care System (VA), and to quantify overuse in VA.
This was a cross-sectional study with multiple cross-sections.
U.S. Veterans who underwent screening colonoscopy between 2011 and 2013.
Overuse of screening colonoscopy, using a validated electronic measure developed by an expert workgroup.
Compared to results obtained from manual record review, the electronic measure was highly specific (97 %) for overuse, but not sensitive (20 %). After exclusion of diagnostic and high-risk screening or surveillance procedures, the validated electronic measure identified 88,754 average-risk screening colonoscopies performed in VA during 2013. Of these, 20,530 (23 %) met the definition for probable (17 %) or possible (6 %) overuse. Substantial variation in colonoscopy overuse was noted between Veterans Integrated Care Networks (VISNs) and between facilities, with a nearly twofold difference between the maximum and minimum rates of overuse at the VISN level and a nearly eightfold difference at the facility level. Overuse at the VISN and facility level was relatively stable over time.
Overuse of screening colonoscopy can be measured reliably and with high specificity using electronic data, and is common in a large integrated healthcare system. Overuse measures, such as those we have specified through a consensus workgroup process, could be combined with underuse measures to improve the appropriateness of colorectal cancer screening.
C1 [Saini, Sameer D.; Schoenfeld, Philip; Moser, Stephanie E.; Vijan, Sandeep; Kerr, Eve A.] Vet Affairs Ctr Clin Management Res CCMR, 2215 Fuller Rd,111D, Ann Arbor, MI 48105 USA.
[Saini, Sameer D.; Schoenfeld, Philip; Vijan, Sandeep; Kerr, Eve A.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Saini, Sameer D.; Schoenfeld, Philip; Vijan, Sandeep; Kerr, Eve A.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA.
[Powell, Adam A.] Minneapolis VA HealthCare Syst, CCDOR, Minneapolis, MN USA.
[Powell, Adam A.] Anthem Inc, Minneapolis, MN USA.
[Dominitz, Jason A.] VA Puget Sound Hlth Care Syst, Seattle, WA USA.
[Fisher, Deborah A.] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Fisher, Deborah A.] Duke Univ, Dept Med, Durham, NC USA.
[Francis, Joseph] VHA Off Analyt & Business Intelligence, Washington, DC USA.
[Kinsinger, Linda; Pittman, Kathleen S.] VHA Natl Ctr Hlth Promot & Dis Prevent, Durham, NC USA.
[Vijan, Sandeep] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA.
RP Saini, SD (reprint author), Vet Affairs Ctr Clin Management Res CCMR, 2215 Fuller Rd,111D, Ann Arbor, MI 48105 USA.
EM sdsaini@umich.edu
FU VA Health Services Research and Development [CDA 09-213-2, RRP 12-184];
Veterans Health Administration (VHA) Office of Informatics and Analytics
(OIA)
FX This work was funded by VA Health Services Research and Development (CDA
09-213-2 and RRP 12-184). Partial funding for this work was provided by
the Veterans Health Administration (VHA) Office of Informatics and
Analytics (OIA). These funding agencies had no role in the design and
conduct of the study. VHA OIA reviewed the manuscript prior to
submission. The opinions expressed in this paper are of the authors and
do not necessarily reflect those of the Department of Veterans Affairs.
NR 22
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U2 1
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PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
SU 1
BP 53
EP 60
DI 10.1007/s11606-015-3569-y
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BN
UT WOS:000373159900010
PM 26951277
ER
PT J
AU Kondo, KK
Damberg, CL
Mendelson, A
Motu'apuaka, M
Freeman, M
O'Neil, M
Relevo, R
Low, A
Kansagara, D
AF Kondo, Karli K.
Damberg, Cheryl L.
Mendelson, Aaron
Motu'apuaka, Makalapua
Freeman, Michele
O'Neil, Maya
Relevo, Rose
Low, Allison
Kansagara, Devan
TI Implementation Processes and Pay for Performance in Healthcare: A
Systematic Review
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Review
DE pay for performance; financial incentives; implementation; performance
metrics; systematic review
ID FOR-PERFORMANCE; OUTCOMES-FRAMEWORK; GENERAL PRACTICES; DIABETES CARE;
PRACTICE SIZE; QUALITY; PROGRAM; INCENTIVES; IMPACT; CONTRACT
AB Over the last decade, various pay-for-performance (P4P) programs have been implemented to improve quality in health systems, including the VHA. P4P programs are complex, and their effects may vary by design, context, and other implementation processes. We conducted a systematic review and key informant (KI) interviews to better understand the implementation factors that modify the effectiveness of P4P.
We searched PubMed, PsycINFO, and CINAHL through April 2014, and reviewed reference lists. We included trials and observational studies of P4P implementation. Two investigators abstracted data and assessed study quality. We interviewed P4P researchers to gain further insight.
Among 1363 titles and abstracts, we selected 509 for full-text review, and included 41 primary studies. Of these 41 studies, 33 examined P4P programs in ambulatory settings, 7 targeted hospitals, and 1 study applied to nursing homes. Related to implementation, 13 studies examined program design, 8 examined implementation processes, 6 the outer setting, 18 the inner setting, and 5 provider characteristics. Results suggest the importance of considering underlying payment models and using statistically stringent methods of composite measure development, and ensuring that high-quality care will be maintained after incentive removal. We found no conclusive evidence that provider or practice characteristics relate to P4P effectiveness. Interviews with 14 KIs supported limited evidence that effective P4P program measures should be aligned with organizational goals, that incentive structures should be carefully considered, and that factors such as a strong infrastructure and public reporting may have a large influence.
There is limited evidence from which to draw firm conclusions related to P4P implementation. Findings from studies and KI interviews suggest that P4P programs should undergo regular evaluation and should target areas of poor performance. Additionally, measures and incentives should align with organizational priorities, and programs should allow for changes over time in response to data and provider input.
C1 [Kondo, Karli K.; Motu'apuaka, Makalapua; Freeman, Michele; O'Neil, Maya; Relevo, Rose; Low, Allison; Kansagara, Devan] Evidence Based Synth Program, Portland Vet Affairs Med Ctr, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
[Damberg, Cheryl L.] RAND Corp, Santa Monica, CA USA.
[Kondo, Karli K.; Mendelson, Aaron; O'Neil, Maya; Kansagara, Devan] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
RP Kondo, KK (reprint author), Evidence Based Synth Program, Portland Vet Affairs Med Ctr, Mailcode RD71,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA.
EM karli.kondo@va.gov
RI haron, suhaila/E-9360-2017;
OI Low, Allison/0000-0003-2088-2429
FU U.S. Department of Veterans Affairs, Veterans Health Administration
(VHA) ESP [05-225]
FX This project was funded by the U.S. Department of Veterans Affairs,
Veterans Health Administration (VHA) ESP Project #05-225.
NR 49
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U1 9
U2 19
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
SU 1
BP 61
EP 69
DI 10.1007/s11606-015-3567-0
PG 9
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BN
UT WOS:000373159900011
PM 26951276
ER
PT J
AU Prentice, JC
Frakt, AB
Pizer, SD
AF Prentice, Julia C.
Frakt, Austin B.
Pizer, Steven D.
TI Metrics That Matter
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE metric validation; metric implementation; access to care metrics; mental
health metrics; veterans
ID HEALTH-CARE; QUALITY MEASURES; ACCESS; CONSEQUENCES; MEDICARE; OUTCOMES
AB Increasingly, performance metrics are seen as key components for accurately measuring and improving health care value. Disappointment in the ability of chosen metrics to meet these goals is exemplified in a recent Institute of Medicine report that argues for a consensus-building process to determine a simplified set of reliable metrics. Overall health care goals should be defined and then metrics to measure these goals should be considered. If appropriate data for the identified goals are not available, they should be developed. We use examples from our work in the Veterans Health Administration (VHA) on validating waiting time and mental health metrics to highlight other key issues for metric selection and implementation. First, we focus on the need for specification and predictive validation of metrics. Second, we discuss strategies to maintain the fidelity of the data used in performance metrics over time. These strategies include using appropriate incentives and data sources, using composite metrics, and ongoing monitoring. Finally, we discuss the VA's leadership in developing performance metrics through a planned upgrade in its electronic medical record system to collect more comprehensive VHA and non-VHA data, increasing the ability to comprehensively measure outcomes.
C1 [Prentice, Julia C.; Frakt, Austin B.; Pizer, Steven D.] VA Boston Healthcare Syst, Hlth Care Financing & Econ, 150 S Huntington Ave,Mailstop 152H, Boston, MA 02130 USA.
[Prentice, Julia C.; Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Prentice, Julia C.; Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Frakt, Austin B.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[Pizer, Steven D.] Northeastern Univ, Boston, MA 02115 USA.
RP Prentice, JC (reprint author), VA Boston Healthcare Syst, Hlth Care Financing & Econ, 150 S Huntington Ave,Mailstop 152H, Boston, MA 02130 USA.
EM Julia.Prentice@va.gov
FU VHA Access & Clinic Administration Program; Health Services Research and
Development Service, Department of Veterans Affairs [CREATE 12023]
FX Funding for this research was provided by the VHA Access & Clinic
Administration Program and CREATE 12023 from the Health Services
Research and Development Service, Department of Veterans Affairs. The
views expressed in this article are those of the authors and do not
necessarily represent the views of the Department of Veterans Affairs,
Boston University, Havard University or Northeastern University.
NR 31
TC 1
Z9 1
U1 5
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
SU 1
BP 70
EP 73
DI 10.1007/s11606-015-3559-0
PG 4
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BN
UT WOS:000373159900012
PM 26951272
ER
PT J
AU Wagner, TH
Burstin, H
Frakt, AB
Krein, SL
Lorenz, K
Maciejewski, ML
Pizer, SD
Weiner, M
Yoon, J
Zulman, DM
Asch, SM
AF Wagner, Todd H.
Burstin, Helen
Frakt, Austin B.
Krein, Sarah L.
Lorenz, Karl
Maciejewski, Matthew L.
Pizer, Steven D.
Weiner, Michael
Yoon, Jean
Zulman, Donna M.
Asch, Steven M.
TI Opportunities to Enhance Value-Related Research in the US Department of
Veterans Affairs
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
ID COST-EFFECTIVENESS ANALYSIS; HEALTH-CARE; QUALITY IMPROVEMENT;
TECHNOLOGY; TRIAL; ORGANIZATIONS; INTERVENTIONS; PERSPECTIVES;
CHALLENGES; SURGERY
C1 [Wagner, Todd H.; Yoon, Jean] Hlth Econ Resource Ctr, Menlo Pk, CA USA.
[Wagner, Todd H.; Lorenz, Karl; Yoon, Jean; Zulman, Donna M.; Asch, Steven M.] Ctr Innovat Implementat, Menlo Pk, CA USA.
[Wagner, Todd H.] Stanford Univ, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Burstin, Helen] Natl Qual Forum, Washington, DC USA.
[Burstin, Helen] George Washington Univ, Washington, DC USA.
[Frakt, Austin B.; Pizer, Steven D.] VA Boston Hlth Care Syst, Hlth Care Financing & Econ, Boston, MA USA.
[Frakt, Austin B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Frakt, Austin B.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Krein, Sarah L.] VA Ann Arbor Ctr Clin Management Res, Ann Arbor, MI USA.
[Krein, Sarah L.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Lorenz, Karl] VA Palliat Care Qual Improvement Resource Ctr QuI, Menlo Pk, CA USA.
[Lorenz, Karl; Zulman, Donna M.; Asch, Steven M.] Stanford Univ, Div Gen Med Disciplines, Stanford, CA 94305 USA.
[Maciejewski, Matthew L.] Durham VA Med Ctr, Ctr Innovat, Durham, NC USA.
[Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA.
[Pizer, Steven D.] Northeastern Univ, Dept Pharm Practice, Boston, MA 02115 USA.
[Pizer, Steven D.] Northeastern Univ, Dept Econ, Boston, MA 02115 USA.
[Weiner, Michael] VA Ctr Hlth Informat & Commun, Indianapolis, IN USA.
[Weiner, Michael] Regenstrief Inst Inc, Indianapolis, IN USA.
[Weiner, Michael] Indiana Univ, Ctr Hlth Serv & Outcomes Res, Indianapolis, IN 46204 USA.
RP Wagner, TH (reprint author), VA Palo Alto, Hlth Econ Resource Ctr, 795 Willow Rd,152-MPD, Menlo Pk, CA 94025 USA.
EM todd.wagner@va.gov
FU VA Health Services Research and Development Service
FX The VA State of the Art Conference was funded by the VA Health Services
Research and Development Service. All commentary and conclusions are our
own and do not represent the opinions of the Health Services Research
and Development Service or the Department of Veterans Affairs. The
committee presented its findings at the Performance Measurement SOTA
Plenary on May 6, 2015.
NR 47
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U2 2
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PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
SU 1
BP 78
EP 83
DI 10.1007/s11606-015-3538-5
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BN
UT WOS:000373159900014
PM 26951279
ER
PT J
AU Tosteson, ANA
Beaber, EF
Tiro, J
Kim, J
McCarthy, AM
Quinn, VP
Doria-Rose, VP
Wheeler, CM
Barlow, WE
Bronson, M
Garcia, M
Corley, DA
Haas, JS
Halm, EA
Kamineni, A
Rutter, CM
Tosteson, TD
Trentham-Dietz, A
Weaver, DL
AF Tosteson, Anna N. A.
Beaber, Elisabeth F.
Tiro, Jasmin
Kim, Jane
McCarthy, Anne Marie
Quinn, Virginia P.
Doria-Rose, V. Paul
Wheeler, Cosette M.
Barlow, William E.
Bronson, Mackenzie
Garcia, Michael
Corley, Douglas A.
Haas, Jennifer S.
Halm, Ethan A.
Kamineni, Aruna
Rutter, Carolyn M.
Tosteson, Tor D.
Trentham-Dietz, Amy
Weaver, Donald L.
CA PROSPR Consortium
TI Variation in Screening Abnormality Rates and Follow-Up of Breast,
Cervical and Colorectal Cancer Screening within the PROSPR Consortium
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Article
DE breast cancer screening; colorectal cancer screening; cervical cancer
screening; practice variation
ID FORCE RECOMMENDATION STATEMENT; EARLY-DETECTION PROGRAM; PERSONALIZED
REGIMENS; CONCEPTUAL-MODEL; NATIONAL BREAST; UNITED-STATES;
PRIMARY-CARE; TIMELINESS; WOMEN; MAMMOGRAPHY
AB Primary care providers and health systems have prominent roles in guiding effective cancer screening.
To characterize variation in screening abnormality rates and timely initial follow-up for common cancer screening tests.
Population-based cohort undergoing screening in 2011, 2012, or 2013 at seven research centers comprising the National Cancer Institute-sponsored Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium.
Adults undergoing mammography with or without digital breast tomosynthesis (n = 97,683 ages 40-75 years), fecal occult blood or fecal immunochemical tests (n = 759,553 ages 50-75 years), or Papanicolaou with or without human papillomavirus tests (n = 167,330 ages 21-65 years).
Breast, colorectal, or cervical cancer screening.
Abnormality rates per 1000 screens; percentage with timely initial follow-up (within 90 days, except 9-month window for BI-RADS 3). Primary care clinic-level variation in percentage with screening abnormality and percentage with timely initial follow-up.
There were 10,248/97,683 (104.9 per 1000) abnormal breast cancer screens, 35,847/759,553 (47.2 per 1000) FOBT/FIT-positive colorectal cancer screens, and 13,266/167,330 (79.3 per 1000) abnormal cervical cancer screens. The percentage with timely follow-up was 93.2 to 96.7 % for breast centers, 46.8 to 68.7 % for colorectal centers, and 46.6 % for the cervical cancer screening center (low-grade squamous intraepithelial lesions or higher). The primary care clinic variation (25th to 75th percentile) was smaller for the percentage with an abnormal screen (breast, 8.5-10.3 %; colorectal, 3.0-4.8 %; cervical, 6.3-9.9 %) than for the percentage with follow-up within 90 days (breast, 90.2-95.8 %; colorectal, 43.4-52.0 %; cervical, 29.6-61.4 %).
Variation in both the rate of screening abnormalities and their initial follow-up was evident across organ sites and primary care clinics. This highlights an opportunity for improving the delivery of cancer screening through focused study of patient, provider, clinic, and health system characteristics associated with timely follow-up of screening abnormalities.
C1 [Tosteson, Anna N. A.; Bronson, Mackenzie; Tosteson, Tor D.] Geisel Sch Med Dartmouth, Lebanon, NH USA.
[Tosteson, Anna N. A.; Tosteson, Tor D.] Norris Cotton Canc Ctr, Lebanon, NH USA.
[Beaber, Elisabeth F.; Garcia, Michael] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA.
[Tiro, Jasmin] Univ Texas Southwestern, Dallas, TX USA.
[Kim, Jane] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.
[McCarthy, Anne Marie] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Quinn, Virginia P.] Kaiser Permanente So Calif, Pasadena, CA 91101 USA.
[Doria-Rose, V. Paul] NCI, Bethesda, MD 20892 USA.
[Wheeler, Cosette M.] Univ New Mexico, Albuquerque, NM 87131 USA.
[Barlow, William E.] Canc Res & Biostat, Seattle, WA USA.
[Corley, Douglas A.] Kaiser Permanente No Calif, Oakland, CA USA.
[Haas, Jennifer S.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA.
[Halm, Ethan A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Kamineni, Aruna] Grp Hlth, Seattle, WA USA.
[Rutter, Carolyn M.] RAND Corp, Santa Monica, CA USA.
[Trentham-Dietz, Amy] Univ Wisconsin, Madison, WI USA.
[Weaver, Donald L.] Univ Vermont, Burlington, VT USA.
RP Tosteson, ANA (reprint author), Geisel Sch Med Dartmouth, Lebanon, NH USA.
EM Anna.Tosteson@Dartmouth.edu
OI Doria-Rose, Vincent/0000-0002-8802-5143
FU National Cancer Institute (NCI) [U01CA163304, U54CA163303, U54CA163307,
U54CA163313, U54CA163308, U54CA163308-04S1, U54CA163261,
U54CA163261-04S1, U54CA163262, U54CA163262-04S1, U54CA164336]
FX This work was supported by the National Cancer Institute (NCI)-funded
Population-based Research Optimizing Screening through Personalized
Regimens (PROSPR) consortium (grant numbers U01CA163304 to M.T., W.B.;
U54CA163303 to D.L.W., B.S.; U54CA163307 to A.N.A.T., T.O., J.H.;
U54CA163313 to K.A., M.S.; U54CA163308 to C.S.S., E.H.; U54CA163308-04S1
to C.S.S., J.A.T.; U54CA163261 to C.R.; U54CA163261-04S1 to J.C., A.K.;
U54CA163262 to A.G.Z., D.C., C.D., T.L.; U54CA163262-04S1 to D.C., M.S.;
and U54CA164336 to C.W.). The content of this manuscript is solely the
responsibility of the authors and does not necessarily represent the
official views of the Department of Veterans Affairs or the United
States government.
NR 41
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Z9 5
U1 3
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
IS 4
BP 372
EP 379
DI 10.1007/s11606-015-3552-7
PG 8
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BR
UT WOS:000373160300005
PM 26658934
ER
PT J
AU Linsky, A
AF Linsky, Amy
TI Capsule Commentary on Genoff et al., Navigating Language Barriers: A
Systematic Review of Patient Navigators' Impact on Cancer Screening for
Limited English Proficient Patients
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Editorial Material
ID CONCORDANCE
C1 [Linsky, Amy] VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA.
[Linsky, Amy] Boston Univ, Sch Med, Gen Internal Med, Boston, MA 02215 USA.
RP Linsky, A (reprint author), VA Boston Healthcare Syst, Gen Internal Med Sect, Boston, MA 02130 USA.
EM amy.linsky@va.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
IS 4
BP 415
EP 415
DI 10.1007/s11606-016-3602-9
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BR
UT WOS:000373160300014
PM 26857729
ER
PT J
AU Oslin, DW
Lynch, KG
Maisto, SA
Lantinga, LJ
Mckay, JR
Possemato, K
Ingram, E
Wierzbicki, M
AF Oslin, David W.
Lynch, Kevin G.
Maisto, Stephen A.
Lantinga, Larry J.
McKay, James R.
Possemato, Kyle
Ingram, Erin
Wierzbicki, Michael
TI A Randomized Clinical Trial of Alcohol Care Management Delivered in
Department of Veterans Affairs Primary Care Clinics Versus Specialty
Addiction Treatment (vol 29, pg 162, 2014)
SO JOURNAL OF GENERAL INTERNAL MEDICINE
LA English
DT Correction
C1 [Oslin, David W.; McKay, James R.; Ingram, Erin] Univ Penn, Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA.
[Oslin, David W.; Lynch, Kevin G.; McKay, James R.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Maisto, Stephen A.; Lantinga, Larry J.; Possemato, Kyle] Syracuse Univ, Dept Psychol, Syracuse, NY USA.
[Maisto, Stephen A.; Lantinga, Larry J.; Possemato, Kyle] VISN2, Dept Vet Affairs, Ctr Integrated Healthcare, Syracuse, NY USA.
[Wierzbicki, Michael] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
RP Oslin, DW (reprint author), Univ Penn, Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA 19104 USA.; Oslin, DW (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
NR 1
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0884-8734
EI 1525-1497
J9 J GEN INTERN MED
JI J. Gen. Intern. Med.
PD APR
PY 2016
VL 31
IS 4
BP 449
EP 449
DI 10.1007/s11606-015-3419-y
PG 1
WC Health Care Sciences & Services; Medicine, General & Internal
SC Health Care Sciences & Services; General & Internal Medicine
GA DI0BR
UT WOS:000373160300023
PM 26055225
ER
PT J
AU Ghosh, A
Leahy, KP
Singhal, S
Einhorn, E
Howlett, P
Cohen, NA
Mirza, N
AF Ghosh, A.
Leahy, K. P.
Singhal, S.
Einhorn, E.
Howlett, P.
Cohen, N. A.
Mirza, N.
TI A murine model of subglottic granulation
SO JOURNAL OF LARYNGOLOGY AND OTOLOGY
LA English
DT Article
DE Subglottic Stenosis, Acquired; Airway Obstruction; Granulation Tissue;
Animal Model
ID RABBIT MODEL; STENOSIS; INJURY
AB Objective: This study aimed to develop a functional model of subglottic stenosis by inducing direct airway irritation in transplanted mouse laryngotracheal complexes.
Methods: Laryngotracheal complexes from C57BL/6 mice were harvested and divided into three groups: uninjured, mechanically injured and chemically injured. Donor laryngotracheal complexes from each group were placed in dorsal subcutaneous pockets of recipient mice. Each week, the transplanted laryngotracheal complexes were harvested, and tissues were fixed, sectioned, and stained with haematoxylin and eosin. Representative slides were reviewed by a blinded pathologist, to determine the formation of granulation tissue, and graded as to the degree of granulation formation.
Results: Direct airway irritation induced granulation tissue formation under the disrupted epithelium of airway mucosa; this was seen as early as two weeks after chemical injury.
Conclusion: Results indicate that granulation tissue formation in a murine model may be an efficient tool for investigating the development and treatment of subglottic stenosis.
C1 [Ghosh, A.; Leahy, K. P.; Cohen, N. A.; Mirza, N.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, 3400 Spruce St,5 Ravdin, Philadelphia, PA 19104 USA.
[Singhal, S.] Univ Penn, Dept Thorac Surg, 3400 Spruce St,5 Ravdin, Philadelphia, PA 19104 USA.
[Einhorn, E.; Howlett, P.] Philadelphia Vet Affairs Med Ctr, Dept Pathol, Philadelphia, PA USA.
RP Ghosh, A (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, 3400 Spruce St,5 Ravdin, Philadelphia, PA 19104 USA.
EM ankona.ghosh@uphs.upenn.edu
OI Cohen, Noam/0000-0002-9462-3932
NR 9
TC 0
Z9 0
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 APR
PY 2016
VL 130
IS 4
BP 380
EP 387
DI 10.1017/S0022215116000049
PG 8
WC Otorhinolaryngology
SC Otorhinolaryngology
GA DH9PJ
UT WOS:000373127800013
PM 26991876
ER
PT J
AU Panych, LP
Chiou, YG
Qin, L
Kimbrell, VL
Bussolari, L
Mulkern, RV
AF Panych, Lawrence P.
Chiou, Jr-Yuan George
Qin, Lei
Kimbrell, Vera L.
Bussolari, Lisa
Mulkern, Robert V.
TI On replacing the manual measurement of ACR phantom images performed by
MRI technologists with an automated measurement approach
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE ACR phantom imaging; quality control; quality assurance; accreditation
ID QUALITY-ASSURANCE; MULTICENTER; VALIDATION
AB PurposeTo assess whether measurements on American College of Radiology (ACR) phantom images performed by magnetic resonance imaging (MRI) technologists as part of a weekly quality control (QC) program could be performed exclusively using an automated system without compromising the integrity of the QC program.
Materials and MethodsACR phantom images are acquired on 15 MRI scanners at a number of ACR-accredited sites to fulfill requirements of a weekly QC program. MRI technologists routinely perform several measurements on these images. Software routines are also used to perform the measurements. A set of geometry measurements made by technologists over a five week period and those made using software routines were compared to reference-standard measurements made by two MRI physicists.
ResultsThe geometry measurements performed by software routines had a very high positive correlation (0.92) with the reference-standard measurements. Technologist measurements also had a high positive correlation (0.63), although the correlation was less than for the automated measurements. Bland-Altman analysis revealed overall good agreement between the automated and reference-standard measurements, with the 95% limits of agreement being within 0.62mm. Agreement between the technologist and the reference-standard measurements was demonstratively poorer, with 95% limits of agreement being +/- 1.46mm. Some of the technologist measurements differed from the reference standard by as much as 2mm.
ConclusionThe technologists' geometry measurements may be able to be replaced by automated measurement without compromising the weekly QC program required by the ACR. J. Magn. Reson. Imaging 2016;43:843-852
C1 [Panych, Lawrence P.; Chiou, Jr-Yuan George; Kimbrell, Vera L.; Bussolari, Lisa; Mulkern, Robert V.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
[Panych, Lawrence P.; Chiou, Jr-Yuan George; Qin, Lei; Mulkern, Robert V.] Harvard Univ, Sch Med, Boston, MA USA.
[Qin, Lei] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA.
[Mulkern, Robert V.] Childrens Hosp Boston, Dept Radiol, Boston, MA USA.
RP Panych, LP (reprint author), 75 Francis St, Boston, MA 02115 USA.
EM panych@bwh.harvard.edu
NR 16
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD APR
PY 2016
VL 43
IS 4
BP 843
EP 852
DI 10.1002/jmri.25052
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DH7UY
UT WOS:000373000500007
PM 26395366
ER
PT J
AU Mansouri, M
Aran, S
Harvey, HB
Shaqdan, KW
Abujudeh, HH
AF Mansouri, Mohammad
Aran, Shima
Harvey, Harlan B.
Shaqdan, Khalid W.
Abujudeh, Hani H.
TI Rates of safety incident reporting in MRI in a large academic medical
center
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE patient safety; incident report; safety report; MRI safety; quality and
safety; safety incident reporting system
ID ADVERSE EVENTS; INTENSIVE-CARE; ERRORS; FALLS; EXPERIENCE; INJECTIONS;
HOSPITALS; RADIOLOGY; SYSTEMS; CONSEQUENCES
AB PurposeTo describe our multiyear experience in incident reporting related to magnetic resonance imaging (MRI) in a large academic medical center.
Materials and MethodsThis was an Institutional Review Board (IRB)-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant study. Incident report data were collected during the study period from April 2006 to September 2012. The incident reports filed during the study period were searched for all reports related to MRI. Incident reports were classified with regard to the patient type (inpatient vs. outpatient), primary reason for the incident report, and the severity of patient harm resulting from the incident.
ResultsA total of 362,090 MRI exams were performed during the study period, resulting in 1290 MRI-related incident reports. The rate of incident reporting was 0.35% (1290/362,090). MRI-related incident reporting was significantly higher in inpatients compared to outpatients (0.74% [369/49,801] vs. 0.29% [921/312,288], P < 0.001). The most common reason for incident reporting was diagnostic test orders (31.5%, 406/1290), followed by adverse drug reactions (19.1%, 247/1290) and medication/IV safety (14.3%, 185/1290). Approximately 39.6% (509/1290) of reports were associated with no patient harm and did not affect the patient, followed by no patient harm but did affect the patient (35.8%, 460/1290), temporary or minor patient harm (23.9%, 307/1290), permanent or major patient harm (0.6%, 8/1290) and patient death (0.2%, 2/1290).
ConclusionMRI-related incident reports are relatively infrequent, occur at significantly higher rates in inpatients, and usually do not result in patient harm. Diagnostic test orders, adverse drug reactions, and medication/IV safety were the most frequent safety incidents. J. Magn. Reson. Imaging 2016;43:998-1007
C1 [Mansouri, Mohammad; Aran, Shima; Harvey, Harlan B.; Shaqdan, Khalid W.; Abujudeh, Hani H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders Bldg,Room 210, Boston, MA 02114 USA.
RP Abujudeh, HH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders Bldg,Room 210, Boston, MA 02114 USA.
EM Habujudeh@partners.org
RI Mansouri, Mohammad/M-4774-2016
OI Mansouri, Mohammad/0000-0002-7472-1287
NR 37
TC 0
Z9 0
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD APR
PY 2016
VL 43
IS 4
BP 998
EP 1007
DI 10.1002/jmri.25055
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DH7UY
UT WOS:000373000500025
PM 26483127
ER
PT J
AU Manchikanti, L
Atluri, S
Kaye, AD
Hirsch, JA
AF Manchikanti, Laxmaiah
Atluri, Sairam
Kaye, Alan David
Hirsch, Joshua A.
TI A report of spinal subdural abscess provides incomplete and inaccurate
information
SO JOURNAL OF NEUROSURGERY-SPINE
LA English
DT Letter
ID LONG-TERM RELIEF; 2-YEAR FOLLOW-UP; EPIDURAL INJECTIONS;
RANDOMIZED-TRIAL; DOUBLE-BLIND; STENOSIS; PAIN
C1 [Manchikanti, Laxmaiah] Univ Louisville, Louisville, KY 40292 USA.
[Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Murray, KY 42071 USA.
[Atluri, Sairam] Tri State Spine Care Inst, Cincinnati, OH USA.
[Kaye, Alan David] LSU Sch Med, New Orleans, LA USA.
[Hirsch, Joshua A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
RP Manchikanti, L (reprint author), Univ Louisville, Louisville, KY 40292 USA.; Manchikanti, L (reprint author), Pain Management Ctr Paducah, Murray, KY 42071 USA.
NR 18
TC 0
Z9 0
U1 0
U2 0
PU AMER ASSOC NEUROLOGICAL SURGEONS
PI ROLLING MEADOWS
PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA
SN 1547-5654
EI 1547-5646
J9 J NEUROSURG-SPINE
JI J. Neurosurg.-Spine
PD APR
PY 2016
VL 24
IS 4
BP 675
EP 676
DI 10.3171/2015.7.SPINE15846
PG 2
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA DH3DZ
UT WOS:000372669000026
PM 26722958
ER
PT J
AU Schreibeis-Baum, HC
Xenakis, LE
Chen, EK
Hanson, M
Ahluwalia, S
Ryan, G
Lorenz, KA
AF Schreibeis-Baum, Hannah C.
Xenakis, Lea E.
Chen, Emily K.
Hanson, Mark
Ahluwalia, Sangeeta
Ryan, Gery
Lorenz, Karl A.
TI A Qualitative Inquiry on Palliative and End-of-Life Care Policy Reform
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID TOBACCO CONTROL; HEALTH; OPPORTUNITIES; SMOKING
AB Background: There is increasing recognition of the role of palliative care (PC) in health care delivery, but priorities for state and federal policy to support PC are unclear and have sometimes engendered controversy. We canvassed experts to shed light on general recommendations for improving PC.
Objective: The study objective was to identify challenges to and potential solutions for promoting, adopting, and implementing policies that would support or expand high-quality PC.
Methods: Semistructured telephone interviews were used to solicit challenges to and potential solutions for promoting, adopting, and implementing policies that would support or expand high-quality PC. Interviews were analyzed using qualitative methods. The subjects were a purposive sample of 22 professional state and federal-level advocates who work in the field of aging and/or PC.
Results: Respondents identified four central challenges to advancing PC policies: (1) knowledge about PC in the health care setting, (2) cultural beliefs about PC, (3) payment/reimbursement for PC services, and (4) public understanding of PC. Of the wide range of solutions proposed by respondents, we present the eight most frequently discussed solutions to these challenges targeted towards policymakers, health care professionals, research, and the general public. Respondents' understanding of the relationships between problems and solutions revealed many dependencies and interconnectedness.
Conclusions: A qualitative approach of querying experts identified multiple significant challenges to improving and expanding PC, most of which are acknowledged in existing consensus statements. Proposed solutions were more numerous and diffuse than descriptions of the problems, signaling the need for further consensus building around actionable policy, and better understanding of how to advance a PC policy agenda.
C1 [Schreibeis-Baum, Hannah C.] VA Greater Angeles, Ctr Healthcare Innovat Implementat & Policy, Hlth Serv Res & Dev, Los Angeles, CA USA.
[Xenakis, Lea E.; Chen, Emily K.; Hanson, Mark; Ahluwalia, Sangeeta; Ryan, Gery; Lorenz, Karl A.] RAND Corp, RAND Hlth, Santa Monica, CA USA.
[Lorenz, Karl A.] VA Palo Alto, Ctr Innovat Implementat Ci2i, Palo Alto, CA USA.
[Lorenz, Karl A.] Stanford Univ, Sch Med, Sect Palliat Med, Stanford, CA 94305 USA.
RP Lorenz, KA (reprint author), Stanford Univ, Sch Med, Div Gen Med Disciplines, Sch Med, Off Bldg,1265 Welch Rd,Room X3c46,MC 5411, Stanford, CA 94305 USA.
EM kalorenz@stanford.edu
FU National Institute of Nursing Research [NINR R01NR013372]; California
Healthcare Foundation [CHCF 17173]
FX The Trajectories and Palliation Study (TAPS) was funded by a grant from
the National Institute of Nursing Research (NINR R01NR013372), and the
TAPS Policy Project was funded by the California Healthcare Foundation
(CHCF 17173).
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 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD APR 1
PY 2016
VL 19
IS 4
BP 400
EP 407
DI 10.1089/jpm.2015.0296
PG 8
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DI1DZ
UT WOS:000373237500013
PM 27035522
ER
PT J
AU Sadeghi, B
Walling, AM
Romano, PS
Ahluwalia, SC
Ong, MK
AF Sadeghi, Bahman
Walling, Anne M.
Romano, Patrick S.
Ahluwalia, Sangeeta C.
Ong, Michael K.
TI A Hospital-Based Advance Care Planning Intervention for Patients with
Heart Failure: A Feasibility Study
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; LIFE-SUSTAINING TREATMENT; DECISION-MAKING;
PREFERENCES; ADULTS
AB Background: Early discussions about advance care planning (ACP) have been associated with improved patient and caregiver outcomes for patients with serious illness. Many patients with heart failure (HF) may benefit from more timely ACP, in part due to the unpredictable trajectory of the disease.
Objectives: The purpose of this study was to evaluate the feasibility of implementing a multiple-component hospital-based intervention on completion of ACP forms among HF patients.
Methods: A brief hospital-based ACP intervention was led by a nonclinician health educator that included (1) an educational video about shared decision making and (2) a protocol to engage HF providers in patients' ACP decision making after the hospitalization. We surveyed patients regarding attitudes toward the ACP intervention and studied completion rates of advance directives (ADs) or physician orders for life sustaining treatment (POLST) forms six months following discharge.
Results: The educational video component of this intervention was considered helpful by 92% of participants, and 70% said they were more likely to talk with their physician about their end-of-life preferences after watching the video and interacting with the health educator. Of 37 participants, 49% had evidence of completion of an AD or POLST in their medical records six months after the index hospitalization compared to 32% before the intervention. The number of patients having a signed scanned POLST form increased from 10 (27%) before the intervention to 16 (43%) six months after the intervention (p = 0.03).
Conclusions: A hospital-based ACP intervention using nonclinician health educators is feasible to implement and has the potential to facilitate the ACP process.
C1 [Sadeghi, Bahman; Walling, Anne M.; Ong, Michael K.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, 10940 Wilshire Blvd, Los Angeles, CA 90024 USA.
[Walling, Anne M.; Ong, Michael K.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA.
[Romano, Patrick S.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA.
[Romano, Patrick S.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA.
[Ahluwalia, Sangeeta C.] RAND Corp, Santa Monica, CA USA.
[Ahluwalia, Sangeeta C.] Univ Calif Los Angeles, UCLA Fielding Sch Publ Hlth, Dept Hlth Policy & Management, Los Angeles, CA 90024 USA.
RP Ong, MK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, 10940 Wilshire Blvd, Los Angeles, CA 90024 USA.
EM mong@mednet.ucla.edu
FU California Healthcare Foundation [15666]; Agency for Healthcare Research
and Quality [R01 HS019311]; NIH National Center for Advancing
Translational Science UCLA Clinical and Translational Science Institute
(CTSI) [UL1TR000124]; NIH Loan Repayment Program; Foundation for
Informed Medical Decision Making
FX This study was supported by a grant from the California Healthcare
Foundation (#15666). The authors would like to acknowledge the work of
Kymberly Aoki, Jennifer Matsui, Wern Ong, and Matt Tiacharoen at the
UCLA Medical Center and Mauricio Rodriguez and Meghan Soulsby at the UCD
Medical Center. We acknowledge the support we received for the patient
screening process from the BEAT-HF study funded by a grant from the
Agency for Healthcare Research and Quality (#R01 HS019311). Dr. Walling
was also supported by the NIH National Center for Advancing
Translational Science UCLA Clinical and Translational Science Institute
(CTSI) (#UL1TR000124) and the NIH Loan Repayment Program. We appreciate
the support from the Foundation for Informed Medical Decision Making
with regards to the videos used in this study.
NR 15
TC 1
Z9 1
U1 3
U2 6
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD APR 1
PY 2016
VL 19
IS 4
BP 451
EP 455
DI 10.1089/jpm.2015.0269
PG 5
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DI1DZ
UT WOS:000373237500019
PM 26862682
ER
PT J
AU Bekelman, DB
Rabin, BA
Nowels, CT
Sahay, A
Heidenreich, PA
Fischer, SM
Main, DS
AF Bekelman, David B.
Rabin, Borsika A.
Nowels, Carolyn T.
Sahay, Anju
Heidenreich, Paul A.
Fischer, Stacy M.
Main, Deborah S.
TI Barriers and Facilitators to Scaling Up Outpatient Palliative Care
SO JOURNAL OF PALLIATIVE MEDICINE
LA English
DT Article
ID CHRONIC HEART-FAILURE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE;
IMPLEMENTATION SCIENCE; INTERVENTION; CONSULTATION; PROGRAMS; OUTCOMES;
FRAMEWORK; ADOPTION
AB Background: The Institute of Medicine recommends people with serious advanced illness have access to skilled palliative care. However, the predominant delivery model of nonhospice palliative care is inpatient, consultative care focused on the end of life, with a small specialist palliative care workforce.
Objective: The study objective was to understand organizational factors that could influence the adoption and scale-up of outpatient palliative care in chronic advanced illness, using the example of heart failure.
Methods: This was a cross-sectional qualitative study. Participants were 17 health care providers and local, regional, and national health system leaders from the Veterans Health Administration (VHA) who were considering whether and how to adopt and sustain outpatient palliative care. Individual interviews using semistructured questions assessed domains of the Consolidated Framework for Implementation Science.
Results: Most providers and leaders perceived outpatient palliative care as high priority in the VHA given its patient-centeredness and potential to decrease health care use and costs associated with conditions like heart failure. They also supported a collaborative care team model of outpatient palliative care delivery where a palliative care specialist collaborates with medical nurses and social workers. They reported lack of performance measures/incentives for patient-centered care processes and outcomes as a potential barrier to implementation. Features of outpatient palliative care viewed as important for successful adoption and scale-up included coordination and communication with other providers, ease of integration into existing programs, and evidence of improving quality of care while not substantially increasing overall health care costs.
Conclusion: Incentives such as performance measures and collaboration with local VHA providers and leaders could improve adoption and scale-up of outpatient palliative care.
C1 [Bekelman, David B.] Eastern Colorado Hlth Care Syst, Dept Vet Affairs, Denver, CO USA.
[Bekelman, David B.; Nowels, Carolyn T.; Fischer, Stacy M.] Univ Colorado, Sch Med, Dept Med, Anschutz Med Campus, Aurora, CO USA.
[Rabin, Borsika A.] Univ Colorado, Sch Med, Dept Family Med, Anschutz Med Campus, Aurora, CO USA.
[Rabin, Borsika A.] Univ Colorado, Sch Med, Colorado Hlth Outcomes Program, Anschutz Med Campus, Aurora, CO USA.
[Sahay, Anju; Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Main, Deborah S.] Univ Colorado, Dept Hlth & Behav Sci, Denver, CO 80202 USA.
RP Bekelman, DB (reprint author), Denver VA Med Ctr, 1055 Clermont St,Res 151, Denver, CO 80220 USA.
EM david.bekelman@va.gov
FU VA HSR&D Quality Enhancement Research Initiative (QUERI) Rapid Response
Project [11-239]
FX This study was funded by VA HSR&D Quality Enhancement Research
Initiative (QUERI) Rapid Response Project #11-239. The views expressed
in this article are those of the authors and do not necessarily reflect
the position or policy of the Department of Veterans Affairs or the
United States government.
NR 28
TC 1
Z9 1
U1 5
U2 9
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1096-6218
EI 1557-7740
J9 J PALLIAT MED
JI J. Palliat. Med.
PD APR 1
PY 2016
VL 19
IS 4
BP 456
EP 459
DI 10.1089/jpm.2015.0280
PG 4
WC Health Care Sciences & Services
SC Health Care Sciences & Services
GA DI1DZ
UT WOS:000373237500020
PM 26974489
ER
PT J
AU Yoshida, N
Miyoshi, H
Kato, T
Sakata-Yanagimoto, M
Niino, D
Taniguchi, H
Moriuchi, Y
Miyahara, M
Kurita, D
Sasaki, Y
Shimono, J
Kawamoto, K
Utsunomiya, A
Imaizumi, Y
Seto, M
Ohshima, K
AF Yoshida, Noriaki
Miyoshi, Hiroaki
Kato, Takeharu
Sakata-Yanagimoto, Mamiko
Niino, Daisuke
Taniguchi, Hiroaki
Moriuchi, Yukiyoshi
Miyahara, Masaharu
Kurita, Daisuke
Sasaki, Yuya
Shimono, Joji
Kawamoto, Keisuke
Utsunomiya, Atae
Imaizumi, Yoshitaka
Seto, Masao
Ohshima, Koichi
TI CCR4 frameshift mutation identifies a distinct group of adult T cell
leukaemia/lymphoma with poor prognosis
SO JOURNAL OF PATHOLOGY
LA English
DT Article
DE adult T cell leukaemia/lymphoma; CCR4 mutation; clinicopathological
analyses; prognostic impact; tissue array
ID WALDENSTROM MACROGLOBULINEMIA; LEUKEMIA/LYMPHOMA; LYMPHOMA; EXPRESSION;
SURVIVAL; LEUKEMIA; CXCR4
AB Adult T cell leukaemia/lymphoma (ATLL) is an intractable T cell neoplasm caused by human T cell leukaemia virus type 1. Next-generation sequencing-based comprehensive mutation studies have revealed recurrent somatic CCR4 mutations in ATLL, although clinicopathological findings associated with CCR4 mutations remain to be delineated. In the current study, 184 cases of peripheral T cell lymphoma, including 113 cases of ATLL, were subjected to CCR4 mutation analysis. This sequence analysis identified mutations in 27% (30/113) of cases of ATLL and 9% (4/44) of cases of peripheral T cell lymphoma not otherwise specified. Identified mutations included nonsense (NS) and frameshift (FS) mutations. No significant differences in clinicopathological findings were observed between ATLL cases stratified by presence of CCR4 mutation. All ATLL cases with CCR4 mutations exhibited cell-surface CCR4 positivity. Semi-quantitative CCR4 protein analysis of immunohistochemical sections revealed higher CCR4 expression in cases with NS mutations of CCR4 than in cases with wild-type (WT) CCR4. Furthermore, among ATLL cases, FS mutation was significantly associated with a poor prognosis, compared with NS mutation and WTCCR4. These results suggest that CCR4 mutation is an important determinant of the clinical course in ATLL cases, and that NS and FS mutations of CCR4 behave differently with respect to ATLL pathophysiology. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
C1 [Yoshida, Noriaki; Miyoshi, Hiroaki; Kato, Takeharu; Niino, Daisuke; Kurita, Daisuke; Sasaki, Yuya; Shimono, Joji; Kawamoto, Keisuke; Seto, Masao; Ohshima, Koichi] Kururne Univ, Dept Pathol, Sch Med, 67 Asahi Machi, Kurume, Fukuoka 8300011, Japan.
[Kato, Takeharu; Imaizumi, Yoshitaka] Nagasaki Univ, Atom Bomb Dis Inst, Dept Haematol, Atom Bomb Dis & Hibakusha Med Unit, Nagasaki, Japan.
[Sakata-Yanagimoto, Mamiko] Univ Tsukuba, Fac Med, Dept Haematol, Tsukuba, Ibaraki 305, Japan.
[Taniguchi, Hiroaki; Moriuchi, Yukiyoshi] Sasebo City Gen Hosp, Dept Haematol, Sasebo, Japan.
[Miyahara, Masaharu] Karatsu Red Cross Hosp, Dept Internal Med, Fukushima, Japan.
[Utsunomiya, Atae] Imamura Bun In Hosp, Dept Haematol, Kagoshima, Japan.
[Yoshida, Noriaki] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
[Niino, Daisuke] Nagasaki Univ, Grad Sch Biomed Sci, Dept Pathol, Nagasaki 852, Japan.
RP Ohshima, K (reprint author), Kururne Univ, Dept Pathol, Sch Med, 67 Asahi Machi, Kurume, Fukuoka 8300011, Japan.
EM ohshima_kouichi@med.kurume-u.ac.jp
OI Yoshida, Noriaki/0000-0001-7001-0106
NR 20
TC 2
Z9 2
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3417
EI 1096-9896
J9 J PATHOL
JI J. Pathol.
PD APR
PY 2016
VL 238
IS 5
BP 621
EP 626
DI 10.1002/path.4699
PG 6
WC Oncology; Pathology
SC Oncology; Pathology
GA DH7QE
UT WOS:000372988100004
PM 26847489
ER
PT J
AU Scharf, JM
AF Scharf, Jeremiah M.
TI Parity in Tourette Syndrome: Reproducible Risk Factors for an
Underrecognized Neurodevelopmental Disorder
SO JOURNAL OF PEDIATRICS
LA English
DT Editorial Material
ID AUTISM SPECTRUM DISORDER; POPULATION-BASED COHORT; TIC DISORDERS;
PREVALENCE; AGE; METAANALYSIS
C1 [Scharf, Jeremiah M.] Brigham & Womens Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res,Div Cognit & Behav Neurol, Div Movement Disorders,Dept Neurol,Massachusetts, 75 Francis St, Boston, MA 02115 USA.
[Scharf, Jeremiah M.] Brigham & Womens Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res,Div Cognit & Behav Neurol,Dep, Div Movement Disorders,Dept Neurol,Massachusetts, 75 Francis St, Boston, MA 02115 USA.
RP Scharf, JM (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat Neurodev Genet Unit, 185 Cambridge St,6th Floor, Boston, MA 02114 USA.
EM jscharf@partners.org
FU NIMH NIH HHS [R01 MH096767]; NINDS NIH HHS [K02 NS085048]
NR 22
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 0022-3476
EI 1097-6833
J9 J PEDIATR-US
JI J. Pediatr.
PD APR
PY 2016
VL 171
BP 17
EP 19
DI 10.1016/j.jpeds.2015.12.048
PG 4
WC Pediatrics
SC Pediatrics
GA DH4KC
UT WOS:000372753600008
PM 26778098
ER
PT J
AU Wu, XM
Hu, XQ
Hamblin, MR
AF Wu, Ximing
Hu, Xiaoqing
Hamblin, Michael R.
TI Ultraviolet blood irradiation: Is it time to remember "the cure that
time forgot"?
SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
LA English
DT Review
DE Ultraviolet irradiation of blood; Systemic infections; DNA repair; Blood
cells; Phagocytes; Lymphocytes; Extracorporeal photopheresis; Bone
marrow; Cytokines
ID T-CELL LYMPHOMA; ANTIGEN-PRESENTING CELLS; UV-C IRRADIATION;
EXTRACORPOREAL PHOTOCHEMOTHERAPY; DRUG DEVELOPMENT; CONTROLLED TRIAL; B
IRRADIATION; DNA-REPAIR; IN-VITRO; LYMPHOCYTES
AB Ultraviolet blood irradiation (UBI) was extensively used in the 1940s and 1950s to treat many diseases including septicemia, pneumonia, tuberculosis, arthritis, asthma, and even poliomyelitis. The early studies were carried out by several physicians in USA and published in the American Journal of Surgery. However, with the development of antibiotics, the use of UBI declined and it has now been called "the cure that time forgot." Later studies were mostly performed by Russian workers, and in other Eastern countries, and the modern view in Western countries is that UBI remains highly controversial. This review discusses the potential of UBI as an alternative approach to current methods used to treat infections, as an immune-modulating therapy and as a method for normalizing blood parameters. Low and mild doses of UV kill microorganisms by damaging the DNA, while any DNA damage in host cells can be rapidly repaired by DNA repair enzymes. However, the use of UBI to treat septicemia cannot be solely due to UV-mediated killing of bacteria in the bloodstream, as only 5-7% of blood volume needs to be treated with UV to produce the optimum benefit, and higher doses can be damaging. There may be some similarities to extracorporeal photopheresis (ECP) using psoralens and UVA irradiation. However, there are differences between UBI and ECP in that UBI tends to stimulate the immune system, while ECP tends to be immunosuppressive. With the recent emergence of bacteria that are resistant to all known antibiotics, UBI should be more investigated as an alternative approach to infections, and as an immune-modulating therapy. (C) 2016 Elsevier B.V. All rights reserved.
C1 [Wu, Ximing] Guangxi Med Univ, Dept Emergency, Affiliated Coll & Hosp 1, Nanning 530021, Peoples R China.
[Wu, Ximing; Hu, Xiaoqing; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
[Wu, Ximing; Hu, Xiaoqing; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA.
[Hu, Xiaoqing] Jiangnan Univ, State Key Lab Food Sci & Technol, Wuxi 214122, Peoples R China.
[Hamblin, Michael R.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.
EM Hamblin@helix.mgh.harvard.edu
FU US NIH [R01AI050875]
FX Research in the Hamblin laboratory is supported by US NIH grant
R01AI050875.
NR 92
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Z9 0
U1 3
U2 8
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1011-1344
J9 J PHOTOCH PHOTOBIO B
JI J. Photochem. Photobiol. B-Biol.
PD APR
PY 2016
VL 157
BP 89
EP 96
DI 10.1016/j.jphotobiol.2016.02.007
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DH3KV
UT WOS:000372686800009
PM 26894849
ER
PT J
AU Sapkota, BR
Hopkins, R
Bjonnes, A
Ralhan, S
Wander, GS
Mehra, NK
Singh, JR
Blackett, PR
Saxena, R
Sanghera, DK
AF Sapkota, Bishwa R.
Hopkins, Ruth
Bjonnes, Andrew
Ralhan, Sarju
Wander, Gurpreet S.
Mehra, Narinder K.
Singh, Jai Rup
Blackett, Piers R.
Saxena, Richa
Sanghera, Dharambir K.
TI Genome-wide association study of 25(OH) Vitamin D concentrations in
Punjabi Sikhs: Results of the Asian Indian diabetic heart study
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE Vitamin D deficiency; 25(OH)D levels (ELISA); Type 2 diabetes;
Genome-wide association study; Punjabi Sikhs
ID PARATHYROID-HORMONE; ENERGY-METABOLISM; GENE; POLYMORPHISMS;
METAANALYSIS; OSTEOBLASTS; VARIANTS; RISK; EXPRESSION; CAUCASIANS
AB Vitamin D deficiency is implicated in multiple disease conditions and accumulating evidence supports that the variation in serum vitamin D (25(OH)D) levels, including deficiency, is under strong genetic control. However, the underlying genetic mechanism associated with vitamin 25(OH)D concentrations is poorly understood. We earlier reported a very high prevalence of vitamin D deficiency associated with an increased risk for type 2 diabetes and obesity in a Punjabi Sikh diabetic cohort as part of the Asian Indian diabetic heart study (AIDHS). Here we have performed the first genome-wide association study (GWAS) of serum 25(OH)D on 3538 individuals from this Punjabi Sikh population. Our discovery GWAS comprised of 1387 subjects followed by validation of 24 putative SNPs (P < 10(-4)) using an independent replication sample (n = 2151) from the same population by direct genotyping. A novel locus at chromosome 20p11.21 represented by rs2207173 with minor allele frequency (MAF) 0.29, [beta = -0.13, p = 4.47 x 10(-9)] between FOXA2 and SSTR4 was identified to be associated with 25(OH)D levels. Another suggestive association signal at rs11586313 (MAF 0.54) [beta = 0.90; p = 1.36 x 10(-6)] was found within the regulatory region of the IVL gene on chromosome 1q21.3. Additionally, our study replicated 3 of 5 known GWAS genes associated with 25(OH)D concentrations including GC (p = 0.007) and CYP2R1 (p = 0.019) reported in Europeans and the DAB1 (p = 0.003), reported in Hispanics. Identification of novel association signals in biologically plausible regions with 25(OH)D metabolism will provide new molecular insights on genetic drivers of vitamin D status and its implications in health disparities. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Sapkota, Bishwa R.; Hopkins, Ruth; Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat,Sect Genet, Oklahoma City, OK 73104 USA.
[Blackett, Piers R.] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat,Sect Endocrinol, Oklahoma City, OK 73104 USA.
[Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73104 USA.
[Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Neurosci, Oklahoma City, OK 73104 USA.
[Ralhan, Sarju; Wander, Gurpreet S.] Hero DMC Heart Inst, Ludhiana, Punjab, India.
[Mehra, Narinder K.] All India Inst Med Sci & Res, New Delhi, India.
[Singh, Jai Rup] Cent Univ Punjab, Bathinda, Punjab, India.
[Bjonnes, Andrew; Saxena, Richa] Broad Inst Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Cambridge, MA USA.
RP Sanghera, DK (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, 940 Stanton L Young Blvd,Rm 317 BMSB, Oklahoma City, OK 73104 USA.
EM Dharambir-sanghera@ouhsc.edu
FU NIH - National Institute of Health (NIDDK) [-R01DK082766]; NHGRI
[NOT-HG-11-009]; VPR Bridge Grant from University of Oklahoma Health
Sciences Center
FX This work was supported by NIH grants -R01DK082766 funded by the
National Institute of Health (NIDDK) and NOT-HG-11-009 funded by NHGRI,
and a VPR Bridge Grant from University of Oklahoma Health Sciences
Center. Technical support provided by Timothy Braun and Praveen Natt is
duly acknowledged. Authors thank all the participants of AIDHS/SDS and
PhenX RISING consortium (NHGRI), and are grateful for their contribution
in this study.
NR 44
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U1 4
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD APR
PY 2016
VL 158
BP 149
EP 156
DI 10.1016/j.jsbmb.2015.12.014
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA DH3MD
UT WOS:000372690200016
PM 26704534
ER
PT J
AU Kougias, P
Tiwari, V
Berger, DH
AF Kougias, Panos
Tiwari, Vikram
Berger, David H.
TI Use of simulation to assess a statistically driven surgical scheduling
system
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE Simulation; Statistical modeling; Effectiveness
ID OPERATING-ROOM EFFICIENCY; TIMES; EXPENDITURES; VARIABILITY; PREDICTION;
SURGERY; THEATER; LENGTH; MODEL
AB Background: To maximize operating room (OR) utilization, better estimates of case duration lengths are needed. We used computerized simulation to determine whether scheduling OR cases using a statistically driven system that incorporates patient and surgery-specific factors in the process of case duration prediction improves OR throughput and utilization.
Methods: We modeled surgical and anesthetic length of vascular surgical procedures as a function of patient and operative characteristics using a multivariate linear regression approach (Predictive Modeling System [PMS]). Mean historical operative time per surgeon (HMS) and mean anesthetic time were also calculated for each procedure type. A computerized simulation of scheduling in a single OR performing vascular operations was then created using either the PMS or the HMS.
Results: Compared to HMS, scheduling the operating room using the PMS increased throughput by a minimum of 15% (99.8% cumulative probability, P < 0.001). The PMS was slightly more likely to lead to overtime (mean 13% versus 11% of operative days during a calendar year, P < 0.001). However, the overtime lasted longer in the HMS group (mean 140 versus 95 min per day of overtime, P < 0.001). PMS was associated with lower OR underutilization rate (mean 23% versus 34% of operative days, P < 0.001) and less lengthy OR underutilization (mean 120 versus 193 min per day of underutilization, P < 0.001).
Conclusions: This computerized simulation demonstrates that using the PMS for scheduling in a single operating room increases throughput and other measures of surgical efficiency. Published by Elsevier Inc.
C1 [Kougias, Panos; Berger, David H.] Michael E DeBakey VA Med Ctr, Houston, TX USA.
[Kougias, Panos] Baylor Coll Med, Div Vasc Surg, Houston, TX 77030 USA.
[Kougias, Panos; Berger, David H.] Ctr Innovat Qual Effectiveness & Safety, Houston, TX USA.
[Tiwari, Vikram] Vanderbilt Univ, Dept Anesthesiol, 221 Kirkland Hall, Nashville, TN 37235 USA.
[Berger, David H.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA.
RP Kougias, P (reprint author), Houston VAMC, Michael E DeBakey Dept Surg, 2002 Holcombe Blvd OCL 112, Houston, TX 77030 USA.
EM pkougias@bcm.edu
NR 17
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U1 4
U2 8
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 APR
PY 2016
VL 201
IS 2
BP 306
EP 312
DI 10.1016/j.jss.2015.10.043
PG 7
WC Surgery
SC Surgery
GA DH8VS
UT WOS:000373075600010
PM 27020812
ER
PT J
AU Urban, LE
Weber, JL
Heyman, MB
Schichtl, RL
Verstraete, S
Lowery, NS
Das, SK
Schleicher, MM
Rogers, G
Economos, C
Masters, WA
Roberts, SB
AF Urban, Lorien E.
Weber, Judith L.
Heyman, Melvin B.
Schichtl, Rachel L.
Verstraete, Sofia
Lowery, Nina S.
Das, Sai Krupa
Schleicher, Molly M.
Rogers, Gail
Economos, Christina
Masters, William A.
Roberts, Susan B.
TI Energy Contents of Frequently Ordered Restaurant Meals and Comparison
with Human Energy Requirements and US Department of Agriculture Database
Information: A Multisite Randomized Study
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
DE Dietary energy; Restaurants; Obesity; Fast food; Weight gain
ID FAST-FOOD RESTAURANTS; UNITED-STATES; PORTION SIZES; TEMPORAL TRENDS;
DIETARY-INTAKE; OBESITY; MENU; CONSUMPTION; SODIUM; ADULTS
AB Background Excess energy intake from meals consumed away from home is implicated as a major contributor to obesity, and similar to 50% of US restaurants are individual or small-chain (non-chain) establishments that do not provide nutrition information.
Objective To measure the energy content of frequently ordered meals in non-chain restaurants in three US locations, and compare with the energy content of meals from large-chain restaurants, energy requirements, and food database information.
Design A multisite random-sampling protocol was used to measure the energy contents of the most frequently ordered meals from the most popular cuisines in non-chain restaurants, together with equivalent meals from large-chain restaurants.
Setting Meals were obtained from restaurants in San Francisco, CA; Boston, MA; and Little Rock, AR, between 2011 and 2014.
Main outcome measures Meal energy content determined by bomb calorimetry.
Statistical analysis performed Regional and cuisine differences were assessed using a mixed model with restaurant nested within region x cuisine as the random factor. Paired t tests were used to evaluate differences between non-chain and chain meals, human energy requirements, and food database values.
Results Meals from non-chain restaurants contained 1,205 +/- 465 kcal/meal, amounts that were not significantly different from equivalent meals from large-chain restaurants (+5.1%; P=0.41). There was a significant effect of cuisine on non-chain meal energy, and three of the four most popular cuisines (American, Italian, and Chinese) had the highest mean energy (1,495 kcal/meal). Ninety-two percent of meals exceeded typical energy requirements for a single eating occasion.
Conclusions Non-chain restaurants lacking nutrition information serve amounts of energy that are typically far in excess of human energy requirements for single eating occasions, and are equivalent to amounts served by the large-chain restaurants that have previously been criticized for providing excess energy. Restaurants in general, rather than specific categories of restaurant, expose patrons to excessive portions that induce overeating through established biological mechanisms.
C1 [Urban, Lorien E.] Gelesis Inc, Boston, MA USA.
[Urban, Lorien E.; Lowery, Nina S.; Das, Sai Krupa; Schleicher, Molly M.; Roberts, Susan B.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Energy Metab Lab, 711 Washington St, Boston, MA 02111 USA.
[Weber, Judith L.] Univ Arkansas Med Sci, Coll Med, Dept Pediat, Pediat, Little Rock, AR 72205 USA.
[Schichtl, Rachel L.] Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72205 USA.
[Heyman, Melvin B.] Univ Calif San Francisco, Dept Pediat, Pediat Clin, San Francisco, CA USA.
[Verstraete, Sofia] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Lowery, Nina S.] Massachusetts Gen Hosp, Phys Assistant Program, Boston, MA 02114 USA.
[Rogers, Gail] Tufts Univ, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Nutr Epidemiol Program, Boston, MA 02111 USA.
[Economos, Christina; Masters, William A.] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[Schleicher, Molly M.] Broad Inst, Off Res Subject Protect, Cambridge, MA USA.
RP Roberts, SB (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Energy Metab Lab, 711 Washington St, Boston, MA 02111 USA.
EM susan.roberts@tufts.edu
RI Masters, William/A-4796-2017
OI Masters, William/0000-0002-4546-7291
FU USDA [58-1950-0-0014, 1950-51000-072-02S]; Tufts University; Arkansas
Children's Hospital Research Institute; National Institutes of Health
[DK00776]
FX Supported by the USDA under agreement nos. 58-1950-0-0014 and
1950-51000-072-02S with Tufts University. Any opinions, findings,
conclusions, or recommendations expressed in this publication are those
of the authors and do not necessarily reflect the views of the USDA.
This research was supported, in part, with funding from the Arkansas
Children's Hospital Research Institute and in part by National
Institutes of Health grant no. DK00776.
NR 46
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U1 4
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
EI 2212-2680
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD APR
PY 2016
VL 116
IS 4
BP 590
EP +
DI 10.1016/j.jand.2015.11.009
PG 15
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DH4KJ
UT WOS:000372754500006
PM 26803805
ER
PT J
AU Friedlander, AH
Chang, TI
Aghazadehsanai, N
Graves, LL
AF Friedlander, Arthur H.
Chang, Tina I.
Aghazadehsanai, Nona
Graves, Lindsay L.
TI COST-EFFECTIVENESS OF ANTIBIOTIC PROPHYLAXIS
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Letter
C1 [Friedlander, Arthur H.] Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA.
[Friedlander, Arthur H.] Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Qual Assurance, Los Angeles, CA USA.
[Friedlander, Arthur H.; Chang, Tina I.] Univ Calif Los Angeles, Sch Dent, Dept Oral & Maxillofacial Surg, Los Angeles, CA 90024 USA.
[Chang, Tina I.] Vet Affairs Greater Los Angeles Healthcare Syst, Inpatient Oral & Maxillofacial Surg, Los Angeles, CA USA.
[Aghazadehsanai, Nona; Graves, Lindsay L.] Vet Affairs Greater Los Angeles Healthcare Syst, Oral & Maxillofacial Surg Sect, Dent Serv, Los Angeles, CA USA.
RP Friedlander, AH (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Grad Med Educ, Los Angeles, CA USA.; Friedlander, AH (reprint author), Ronald Reagan UCLA Med Ctr, Hosp Dent Serv, Qual Assurance, Los Angeles, CA USA.; Friedlander, AH (reprint author), Univ Calif Los Angeles, Sch Dent, Dept Oral & Maxillofacial Surg, Los Angeles, CA 90024 USA.
NR 1
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U1 0
U2 0
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
EI 1943-4723
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD APR
PY 2016
VL 147
IS 4
BP 229
EP 230
DI 10.1016/j.adaj.2016.02.004
PG 3
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA DH9LD
UT WOS:000373116700003
PM 27017589
ER
PT J
AU Wrocklage, KM
Schweinsburg, BC
Krystal, JH
Trejo, M
Roy, A
Weisser, V
Moore, TM
Southwick, SM
Scott, JC
AF Wrocklage, Kristen M.
Schweinsburg, Brian C.
Krystal, John H.
Trejo, Marcia
Roy, Alicia
Weisser, Valerie
Moore, Tyler M.
Southwick, Steven M.
Scott, J. Cobb
TI Neuropsychological Functioning in Veterans with Posttraumatic Stress
Disorder: Associations with Performance Validity, Comorbidities, and
Functional Outcomes
SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY
LA English
DT Article
DE Posttraumatic stress disorder; Neuropsychology; Cognitive abilities;
Memory; Executive functions; Quality of life; Occupational functioning
ID TRAUMATIC BRAIN-INJURY; TERM BENZODIAZEPINE USE; MEMORY PERFORMANCE;
COMBAT EXPOSURE; VERBAL MEMORY; ARMY SOLDIERS; WAR VETERANS; FOLLOW-UP;
PTSD; HEALTH
AB Objectives: Numerous studies have shown that individuals with posttraumatic stress disorder (PTSD) display reduced performances on neuropsychological tests, although most prior research has not adequately accounted for comorbidities or performance validity concerns that are common in this population and could partially account for the observed neurocognitive findings. Moreover, few studies have examined the functional implications of neuropsychological results in PTSD. Methods: We examined neuropsychological functioning in 44 veterans with PTSD and 40 veteran trauma comparison (TC) participants with combat exposure and no PTSD. Results: After excluding four veterans with PTSD for performance validity concerns, multivariate analyses of variance by neurocognitive domain revealed significantly worse performance by the PTSD group in the domains of speed of information processing (p = .035) and executive functions (p = .017), but no group differences in attention/working memory, verbal/language functioning, visuoconstruction, or episodic memory. Group differences by PTSD status were still present after covarying for depression, a history of head injuries, and substance use disorders. Executive functioning performance was associated with poorer self-reported occupational functioning and physical health-related quality of life, while speed of information processing performance was associated with poorer physical health-related quality of life. Discussion: These results are generally consistent with a fronto-limbic conceptualization of PTSD-associated neuropsychological dysfunction and show that cognitive functioning may be associated with critical functional outcomes. Taken together, results suggest that consideration of neurocognitive functioning may enhance the clinical management of individuals with PTSD.
C1 [Wrocklage, Kristen M.; Schweinsburg, Brian C.; Krystal, John H.; Trejo, Marcia; Roy, Alicia; Weisser, Valerie; Southwick, Steven M.] Natl Ctr PTSD, Clin Neurosci Div, West Haven, CT USA.
[Wrocklage, Kristen M.; Schweinsburg, Brian C.; Krystal, John H.; Trejo, Marcia; Roy, Alicia; Weisser, Valerie; Southwick, Steven M.] VA Connecticut Healthcare Syst, West Haven, CT USA.
[Schweinsburg, Brian C.; Krystal, John H.; Roy, Alicia; Southwick, Steven M.] 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.
[Moore, Tyler M.; Scott, J. Cobb] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Scott, J. Cobb] Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr VISN4, Philadelphia, PA 19104 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]
FX 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
National Institute on Alcohol Abuse and Alcoholism (P50AA12870,
M01RR00125), and the Yale Center for Clinical Investigation (UL1
RR024139). Portions of this research were presented at the 2014 Annual
Meeting of the American Psychological Association (APA). 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 92
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U1 6
U2 12
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 APR
PY 2016
VL 22
IS 4
BP 399
EP 411
DI 10.1017/S1355617716000059
PG 13
WC Clinical Neurology; Neurosciences; Psychiatry; Psychology
SC Neurosciences & Neurology; Psychiatry; Psychology
GA DI1ZK
UT WOS:000373295300003
PM 26892753
ER
PT J
AU Streiff, MB
Agnelli, G
Connors, JM
Crowther, M
Eichinger, S
Lopes, RD
McBane, RD
Moll, S
Ansell, J
AF Streiff, Michael B.
Agnelli, Giancarlo
Connors, Jean M.
Crowther, Mark
Eichinger, Sabine
Lopes, Renato D.
McBane, Robert D.
Moll, Stephan
Ansell, Jack
TI Guidance for the treatment of deep vein thrombosis and pulmonary
embolism (vol 41, pg 32, 2016)
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Correction
C1 [Streiff, Michael B.] Johns Hopkins Univ, Sch Med, Dept Pathol & Med, Div Hematol, Baltimore, MD USA.
[Agnelli, Giancarlo] Univ Perugia, Dept Internal Med, Stroke Unit, I-06100 Perugia, Italy.
[Connors, Jean M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Hematol Div,Brigham & Womens Hosp, 44 Binney St, Boston, MA 02115 USA.
[Crowther, Mark] McMaster Univ, Dept Med, Hamilton, ON, Canada.
[Crowther, Mark] McMaster Univ, Dept Pathol, Hamilton, ON, Canada.
[Crowther, Mark] McMaster Univ, Dept Mol Med, Hamilton, ON, Canada.
[Eichinger, Sabine] Med Univ Vienna, Dept Med, Vienna, Austria.
[Lopes, Renato D.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA.
[McBane, Robert D.] Mayo Clin, Dept Med, Cardiovasc Div, Rochester, MN USA.
[Moll, Stephan] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Ansell, Jack] Hofstra North Shore LIJ Sch Med, Dept Med, Hempstead, NY USA.
RP Streiff, MB (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol & Med, Div Hematol, Baltimore, MD USA.
EM mstreif@jhmi.edu
NR 1
TC 0
Z9 0
U1 2
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
EI 1573-742X
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD APR
PY 2016
VL 41
IS 3
BP 548
EP 548
DI 10.1007/s11239-016-1345-4
PG 1
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DH8CF
UT WOS:000373020400026
PM 26945859
ER
PT J
AU Sammon, JD
Dalela, D
Abdollah, F
Choueiri, TK
Han, PK
Hansen, M
Nguyen, PL
Sood, A
Menon, M
Trinh, QD
AF Sammon, Jesse D.
Dalela, Deepansh
Abdollah, Firas
Choueiri, Toni K.
Han, Paul K.
Hansen, Moritz
Nguyen, Paul L.
Sood, Akshay
Menon, Mani
Trinh, Quoc-Dien
TI Determinants of Prostate Specific Antigen Screening among Black Men in
the United States in the Contemporary Era
SO JOURNAL OF UROLOGY
LA English
DT Article
DE prostate; prostate specific antigen; mass screening; African American;
education
ID AFRICAN-AMERICAN MEN; DECISION-MAKING; FOLLOW-UP; US MEN; CANCER;
TRENDS; MORTALITY; RISK
AB Purpose: Although black men represent a high risk population for prostate specific antigen screening for prostate cancer, recommendations in black men are unclear. To our knowledge the resultant effect of conflicting recommendations and disparities in access to care on prostate specific antigen screening in black men is unknown.
Materials and Methods: We compared the rate of self-reported prostate specific antigen screening in black men relative to that in nonHispanic white men. The BRFSS (Behavioral Risk Factor Surveillance System) 2012 data set was used to identify asymptomatic men 40 to 99 years old who reported undergoing prostate specific antigen screening in the last 12 months. Age, education, income, residence location, marital status, health insurance, regular access to a health care provider and a health care provider recommendation to undergo screening were extracted. Subgroup analyses by race and age were performed using complex samples logistic regression models to assess the odds of undergoing prostate specific antigen screening.
Results: In 2012 there were 122,309 survey respondents (weighted estimate 54.5 million) in the study population, of whom 29% of black and 32% of nonHispanic white men reported undergoing prostate specific antigen screening. Younger black males had higher rates and odds of screening than nonHispanic white men of a similar age (ages 45 to 49, 50 to 54 and 55 to 59 years OR 1.66, 1.58 and 1.36, respectively). Among black men only a higher education level (graduates vs nongraduates OR 2.12), regular access to a health care provider (OR 2.05) and a health care provider recommendation for screening (OR 8.43) were independently associated with prostate specific antigen screening.
Conclusions: Despite long-standing disparities in health care access black males 45 to 60 years old have a higher rate and probability of prostate specific antigen screening than nonHispanic white men. Among black men educational attainment had a more pronounced association. In contrast the association with health care provider recommendations was less pronounced relative to that in nonHispanic white men. Future research may shed more light on the gamut of factors that influence the decision making process for prostate specific antigen testing.
C1 [Sammon, Jesse D.; Trinh, Quoc-Dien] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Surg & Publ Hlth, Boston, MA 02115 USA.
[Sammon, Jesse D.; Han, Paul K.; Hansen, Moritz] Tufts Univ, Sch Med, Medford, MA USA.
[Choueiri, Toni K.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA.
[Nguyen, Paul L.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA.
[Sammon, Jesse D.; Han, Paul K.; Hansen, Moritz] Maine Med Ctr, Res Inst, Portland, ME 04102 USA.
[Sammon, Jesse D.; Dalela, Deepansh; Abdollah, Firas; Sood, Akshay; Menon, Mani; Trinh, Quoc-Dien] Henry Ford Hlth Syst, Vattikuti Urol Inst, Ctr Outcomes Res Analyt & Evaluat, Detroit, MI USA.
RP Sammon, JD (reprint author), Brigham & Womens Hosp, Ctr Surg & Publ Hlth, 45 Francis St,ASB 2-3, Boston, MA 02115 USA.
EM jsammon79@gmail.com
OI Han, Paul/0000-0003-0165-1940
FU Vattikuti Urology Institute
FX Supported by the Professor Walter MorrisHale Distinguished Chair in
Urologic Oncology at Brigham and Women's Hospital and an unrestricted
educational grant from the Vattikuti Urology Institute (QDT).
NR 29
TC 2
Z9 2
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD APR
PY 2016
VL 195
IS 4
BP 913
EP 918
DI 10.1016/j.juro.2015.11.023
PN 1
PG 6
WC Urology & Nephrology
SC Urology & Nephrology
GA DI3LW
UT WOS:000373401200030
PM 26598427
ER
PT J
AU Sorensen, MD
AF Sorensen, Mathew D.
TI A Prospective Randomized Controlled Trial of the Efficacy of External
Physical Vibration Lithecbole after Extracorporeal Shock Wave
Lithotripsy for a Lower Pole Renal Stone Less Than 2 cm EDITORIAL
COMMENT
SO JOURNAL OF UROLOGY
LA English
DT Editorial Material
C1 [Sorensen, Mathew D.] Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
RP Sorensen, MD (reprint author), Univ Washington, Dept Urol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD APR
PY 2016
VL 195
IS 4
BP 970
EP 970
PN 1
PG 1
WC Urology & Nephrology
SC Urology & Nephrology
GA DI3LW
UT WOS:000373401200048
PM 26812396
ER
PT J
AU Lo, RC
Buck, DB
Herrmann, J
Hamdan, AD
Wyers, M
Patel, VI
Fillinger, M
Schermerhorn, ML
AF Lo, Ruby C.
Buck, Dominique B.
Herrmann, Jeremy
Hamdan, Allen D.
Wyers, Mark
Patel, Virendra I.
Fillinger, Mark
Schermerhorn, Marc L.
CA Vasc Study Grp New England
TI Risk factors and consequences of persistent type II endoleaks
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 41st Annual Symposium of the Society-for-Clinical-Vascular-Surgery
CY MAR 12-16, 2013
CL Miami Beach, FL
SP Soc Clin Vasc Surg
ID ABDOMINAL AORTIC-ANEURYSM; ENDOVASCULAR REPAIR; SELECTIVE INTERVENTION;
RANDOMIZED-TRIAL; OUTCOMES; EMBOLIZATION; SAFE
AB Objective: Type II endoleaks are common after endovascular aneurysm repair (EVAR), but their clinical significance remains undefined and their management controversial. We determined risk factors for type II endoleaks and associations with adverse outcomes.
Methods: We identified all EVAR patients in the Vascular Study Group of New England abdominal aortic aneurysm database. Patients were subdivided into two groups: (1) those with no endoleak or transient type II endoleak and (2) persistent type II endoleak or new type II endoleak (no endoleak at completion of case). Patients with other endoleak types and follow-up shorter than 6 months were excluded. Multivariable analysis was used to evaluate predictors of persistent or new type II endoleaks. Kaplan-Meier and Cox regression analysis were used to evaluate predictors of reintervention and survival.
Results: Two thousand three hundred sixty-seven EVAR patients had information on endoleaks: 1977 (84%) were in group 1, of which 79% had no endoleaks at all, and 21% had transient endoleaks that resolved at follow-up. The other 390 (16%) were in group 2, of which 31% had a persistent leak, and 69% had a new leak at follow-up that was not seen at the time of surgery. Group 2 was older (mean age, 75 vs 73 years; P < .001) and less likely to have chronic obstructive pulmonary disease (COPD; 24% vs 34%; P < .001) or elevated creatinine levels (2.6% vs 5.3%; P = .027). Coil embolization of one or both hypogastric arteries was associated with a higher rate of persistent type II endoleaks (12 vs 8%; P = .024), as was distal graft extension (12% vs 8%; P = .008). In multivariable analysis, COPD (odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5-0.9; P = .017) was protective against persistent type II endoleak, while hypogastric artery coil embolization (OR, 1.5; 95% CI, 1.0-2.2; P = .044), distal graft extension (OR, 1.6; 95% CI, 1.1-2.3; P = .025), and age >= 80 (OR, 2.7; 95% CI, 1.4-5.3; P = .004) were predictive. Graft type was also associated with endoleak development. Persistent type II endoleaks were predictive of postdischarge reintervention (OR, 15.3; 95% CI, 9.7-24.3; P < .001); however, they were not predictive of long-term survival (OR, 1.1; 95% CI, 0.9-1.6; P = .477).
Conclusions: Persistent type II endoleak is associated with hypogastric artery coil embolization, distal graft extension, older age, the absence of COPD, and graft type, but not with aneurysm size. Persistent type II endoleaks are associated with an increased risk of reinterventions, but not rupture or survival. This reinforces the need for continued surveillance of patients with persistent type II endoleaks and the importance of follow-up to detect new type II endoleaks over time.
C1 [Lo, Ruby C.; Buck, Dominique B.; Herrmann, Jeremy; Hamdan, Allen D.; Wyers, Mark; Schermerhorn, Marc L.] Beth Israel Deaconess Med Ctr, Div Vasc & Endovasc Surg, Boston, MA 02215 USA.
[Patel, Virendra I.] Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA.
[Fillinger, Mark] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03766 USA.
RP Schermerhorn, ML (reprint author), 110 Francis St,Ste 5B, Boston, MA USA.
EM mscherme@bidmc.harvard.edu
FU NHLBI NIH HHS [R01 HL105453, 5R01HL105453-03, T32 HL007734]
NR 25
TC 2
Z9 2
U1 1
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD APR
PY 2016
VL 63
IS 4
BP 895
EP 901
DI 10.1016/j.jvs.2015.10.088
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA DH7FR
UT WOS:000372958200008
PM 26796291
ER
PT J
AU Daniel, VT
Gupta, N
Raffetto, JD
McPhee, JT
AF Daniel, Vijaya T.
Gupta, Naren
Raffetto, Joseph D.
McPhee, James T.
TI Impact of coexisting aneurysms on open revascularization for aortoiliac
occlusive disease
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT 43rd Annual Symposium of the Society-for-Clinical-Vascular-Surgery on
Vascular Surgery
CY MAR 29-APR 02, 2015
CL Miami, FL
SP Soc Clin Vasc Surg
ID ABDOMINAL AORTIC-ANEURYSM; PREDICTING 1-YEAR MORTALITY; RISK-FACTORS;
REPAIR
AB Objective: National data evaluating outcomes for occlusive abdominal aortic reconstructions are well described. The relative effect of operative indication as well as the presence of concomitant abdominal aortic aneurysm (AAA) on in-hospital mortality is not well defined.
Methods: The Nationwide Inpatient Sample was queried to identify patients who underwent open aortic surgery (2003-2010). Indication for surgery was classified by International Classification of Diseases, Ninth Revision diagnostic codes to identify isolated occlusive indications as well as combined occlusive disease and AAA. Primary outcome was in-hospital mortality. Secondary outcomes were complications and discharge disposition.
Results: Overall, 56,374 underwent aortic reconstruction, 48,591 for occlusive disease (86.2%) and 7783 for combined occlusive disease with AAA (13.8%). Intermittent claudication was the most common indication for intervention (60.9%), whereas 39.7% underwent intervention for critical limb ischemia (22.2% rest pain, 17.6% gangrene). Patients with intermittent claudication had more concomitant AAAs (17.3%) than did patients with critical limb ischemia (8.4%). The baseline characteristics for those with occlusive disease and combined occlusive with AAA disease were similar in terms of obesity (4.8% vs 4.2%; P=.27) and congestive heart failure (6.6% vs 6.3%; P = .65) but differed by age (62.2 years vs 68.4 years; P < .0001) and hypertension (65.4% vs 69.1%; P = .005). Patients with combined occlusive and AAA disease had higher mortality than those with occlusive disease alone (3.9% vs 2.7%; P = .01). On multivariable regression, factors associated with in-hospital mortality included gangrene with AAA compared with gangrene alone (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.6-4.7; P < .0002), age > 65 years age (OR, 3.1; 95% CI, 2.4-4.1; P <.0001), renal failure (OR, 2.7; 95% CI, 1.9-3.8; P < .0001), and concurrent lower extremity revascularization (OR, 1.3; 95% CI, 1.1-1.7; P < .02).
Conclusions: Intermittent claudication or critical limb ischemia with concomitant AAA carries a higher mortality than intermittent claudication or critical limb ischemia alone, especially in older patients with gangrene requiring revascularization and renal insufficiency. Preoperative risk stratification strategies should focus on the indication for surgery as well as the presence of concomitant
C1 [Daniel, Vijaya T.] Univ Massachusetts, Sch Med, Dept Surg, Worcester, MA USA.
[Gupta, Naren; Raffetto, Joseph D.; McPhee, James T.] VA Boston Healthcare Syst, Div Vasc Surg, West Roxbury, MA USA.
[Gupta, Naren; Raffetto, Joseph D.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Gupta, Naren; Raffetto, Joseph D.] Brigham & Womens Hosp, Div Vasc & Endovasc Surg, 75 Francis St, Boston, MA 02115 USA.
[McPhee, James T.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA.
RP Daniel, VT (reprint author), Univ Massachusetts, Dept Surg, 55 N Lake Ave, Worcester, MA 01655 USA.
EM v.m.thomas@gmail.com
NR 18
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 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD APR
PY 2016
VL 63
IS 4
BP 944
EP 948
DI 10.1016/j.jvs.2015.10.062
PG 5
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA DH7FR
UT WOS:000372958200016
PM 26843353
ER
PT J
AU Corey, MR
Ergul, EA
Cambria, RP
English, SJ
Patel, VI
Lancaster, RT
Kwolek, CJ
Conrad, MF
AF Corey, Michael R.
Ergul, Emel A.
Cambria, Richard P.
English, Sean J.
Patel, Virendra I.
Lancaster, R. Todd
Kwolek, Christopher J.
Conrad, Mark F.
TI The natural history of splanchnic artery aneurysms and outcomes after
operative intervention
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article; Proceedings Paper
CT Vascular Annual Meeting of the Society-for-Vascular-Surgery
CY JUN 17-20, 2015
CL Chicago, IL
SP Soc Vasc Surg
ID ABDOMINAL AORTIC-ANEURYSMS; CELIAC ARTERY; PANCREATICODUODENAL ARTERIES;
CLINICAL IMPORTANCE; CURRENT MANAGEMENT; EXPERIENCE; PSEUDOANEURYSMS;
RUPTURE
AB Objective: Splanchnic artery aneurysms (SAAs) are uncommon, and standards for surveillance and intervention are lacking. The goal of this study was to review our 20-year experience with managing SAAs.
Methods: The Research Patient Data Registry at the Massachusetts General Hospital was queried, and all patients with SAAs identified by axial imaging from 1994 to 2014 were included. Aneurysms were stratified into two cohorts: those that underwent early intervention (<6 months after lesion discovery) and those that received surveillance. Primary study end points included aneurysm growth or rupture during surveillance and patient 30-day morbidity or mortality after aneurysm repair.
Results: There were 264 SAAs identified in 250 patients. In 166 patients, 176 SAAs (66.6%) were placed into the surveillance cohort; 38 SAAs (21.6%) did not have subsequent axial imaging and were considered lost to follow-up. Mean aneurysm size in the surveillance cohort at first imaging study was 16.28 mm (8-41 mm), and mean surveillance time was 36.1 months (2-155 months); 126 SAAs (91.3%) remained stable in size over time, and 8 SAAs (5.8%) required intervention for aneurysm growth after a mean of 24 months. There were no ruptures in the surveillance cohort. There were 88 SAAs (33.3%) repaired early. Mean size of SAAs that were repaired early was 31.1 mm (10-140 mm). For intact SAAs, 30-day morbidity and mortality rates after repair were 13% and 3%, respectively. In the early repair cohort, 13 SAAs (14.7%) were ruptured at presentation. The 30-day morbidity and mortality rates after rupture were 54% and 8%, respectively. Five ruptured SAAs (38%) were anatomically located in the pancreaticoduodenal arcade. On univariate analysis, pancreaticoduodenal aneurysms were strongly associated with rupture (P = .0002).
Conclusions: Small SAAs (<= 25 mm) are not prone to significant expansion and do not require frequent surveillance imaging. Imaging every 3 years for small SAAs is adequate. Aneurysms of the pancreaticoduodenal arcade and gastroduodenal aneurysms are more likely to rupture and therefore warrant a more aggressive interventional approach.
C1 [Corey, Michael R.; Ergul, Emel A.; Cambria, Richard P.; English, Sean J.; Patel, Virendra I.; Lancaster, R. Todd; Kwolek, Christopher J.; Conrad, Mark F.] Massachusetts Gen Hosp, Dept Vasc & Endovasc Surg, Boston, MA 02114 USA.
RP Conrad, MF (reprint author), 15 Parkman St,WACC 440, Boston, MA 02114 USA.
EM mconrad@partners.org
NR 31
TC 3
Z9 3
U1 2
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD APR
PY 2016
VL 63
IS 4
BP 949
EP 957
DI 10.1016/j.jvs.2015.10.066
PG 9
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA DH7FR
UT WOS:000372958200017
PM 26792545
ER
PT J
AU Kikuchi, S
Kenagy, RD
Gao, L
Wight, TN
Azuma, N
Sobel, M
Clowes, AW
AF Kikuchi, Shinsuke
Kenagy, Richard D.
Gao, Lu
Wight, Thomas N.
Azuma, Nobuyoshi
Sobel, Michael
Clowes, Alexander W.
TI Surgical marking pen dye inhibits saphenous vein cell proliferation and
migration in saphenous vein graft tissue
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID LOWER-EXTREMITY BYPASS; SMOOTH-MUSCLE; INTIMAL HYPERPLASIA;
RANDOMIZED-TRIAL; PROGENITOR CELLS; METHYLENE-BLUE; NEOINTIMA; INSITU;
MYOFIBROBLASTS; APOPTOSIS
AB Objective: Markers containing dyes such as crystal violet (CAS 548-62-9) are routinely used on the adventitia of vein bypass grafts to avoid twisting during placement. Because little is known about how these dyes affect vein graft healing and function, we determined the effect of crystal violet on cell migration and proliferation, which are responses to injury after grafting.
Methods: Fresh human saphenous veins were obtained as residual specimens from leg bypass surgeries. Portions of the vein that had been surgically marked with crystal violet were analyzed separately from those that had no dye marking. In the laboratory, they were split into easily dissected inner and outer layers after removal of endothelium. This cleavage plane was within the circular muscle layer of the media. Cell migration from explants was measured daily as either (1) percentage of migration-positive explants, which exclusively measures migration, or (2) number of cells on the plastic surrounding each explant, which measures migration plus proliferation. Cell proliferation and apoptosis (Ki67 and TUNEL staining, respectively) were determined in dye-marked and unmarked areas of cultured vein rings. The dose-dependent effects of crystal violet were measured for cell migration from explants as well as for proliferation, migration, and death of cultured outer layer cells. Dye was extracted from explants with ethanol and quantified by spectrophotometry.
Results: There was significantly less cell migration from visibly blue compared with unstained outer layer explants by both methods. There was no significant difference in migration from inner layer explants adjacent to blue-stained or unstained sections of vein because dye did not penetrate to the inner layer. Ki67 staining of vein in organ culture, which is a measure of proliferation, progressively increased up to 6 days in nonblue outer layer and was abolished in the blue outer layer. Evidence of apoptosis (TUNEL staining) was present throughout the wall and not different in blue-stained and unstained vein wall segments. Blue outer layer explants had 65.9 +/- 8.0 ng dye/explant compared with 2.1 +/- 1.3 for nonblue outer layer explants. Dye applied in vitro to either outer or inner layer explants dose dependently inhibited migration (IC50 similar to 10 ng/explant). The IC(50)s of crystal violet for outer layer cell proliferation and migration were 0.1 and 1.2 mg/mL, whereas the EC50 for death was between 1 and 10 mg/mL.
Conclusions: Crystal violet inhibits venous cell migration and proliferation, indicating that alternative methods should be considered for marking vein grafts.
C1 [Kikuchi, Shinsuke; Kenagy, Richard D.; Gao, Lu; Sobel, Michael; Clowes, Alexander W.] Univ Washington, Dept Surg, Seattle, WA 98195 USA.
[Kikuchi, Shinsuke; Azuma, Nobuyoshi] Asahikawa Med Univ, Dept Vasc Surg, Asahikawa, Hokkaido, Japan.
[Wight, Thomas N.] Virginia Mason, Benaroya Res Inst, Matrix Biol Program, Seattle, WA USA.
[Sobel, Michael] VA Puget Sound Hlth Care Syst, Div Vasc Surg, Seattle, WA USA.
[Sobel, Michael] Univ Washington, Seattle, WA 98195 USA.
RP Kenagy, RD (reprint author), Univ Washington, Ctr Cardiovasc Biol, POB 358050,850 Republican St, Seattle, WA 98109 USA.
EM rkenagy@u.washington.edu
FU CSRD VA [I01 CX000712]; NHLBI NIH HHS [R41 HL106967, R01 HL030946, R01
HL30946]
NR 34
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD APR
PY 2016
VL 63
IS 4
BP 1044
EP 1050
DI 10.1016/j.jvs.2014.10.017
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA DH7FR
UT WOS:000372958200031
PM 25935273
ER
PT J
AU Rosales, IA
Colvin, RB
AF Rosales, Ivy A.
Colvin, Robert B.
TI Glomerular disease with idiopathic linear immunoglobulin deposition: a
rose by any other name would be atypical
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID ANTI-GBM DISEASE; BASEMENT-MEMBRANE; AUTOANTIBODIES; GLOMERULONEPHRITIS
AB Nasr et al. (2016) report 20 cases of "atypical anti-GBM disease," characterized by bright, linear glomerular basement membrane (GBM) immunoglobulin deposition in patients who lacked anti-GBM antibodies by conventional testing and who had a relatively benign course. Half had light chain restriction. The term " idiopathic linear immunoglobulin deposition" may be preferable until anti-GBM activity is demonstrable, since there are alternative mechanisms of linear deposition in the GBM, including physicochemical affinity for GBM components and alterations of the GBM itself. (C) 2016 International Society of Nephrology
C1 [Rosales, Ivy A.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA.
EM colvin@helix.mgh.harvard.edu
NR 9
TC 1
Z9 1
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD APR
PY 2016
VL 89
IS 4
BP 750
EP 752
DI 10.1016/j.kint.2016.01.018
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA DH1CD
UT WOS:000372521100007
PM 26994573
ER
PT J
AU Nasr, SH
Collins, AB
Alexander, MP
Schraith, DF
Hernandez, LH
Fidler, ME
Sethi, S
Leung, N
Fervenza, FC
Cornell, LD
AF Nasr, Samih H.
Collins, A. Bernard
Alexander, Mariam Priya
Schraith, Daniel F.
Hernandez, Loren Herrera
Fidler, Mary E.
Sethi, Sanjeev
Leung, Nelson
Fervenza, Fernando C.
Cornell, Lynn D.
TI The clinicopathologic characteristics and outcome of atypical
anti-glomerular basement membrane nephritis
SO KIDNEY INTERNATIONAL
LA English
DT Article
DE anti-GBM disease; glomerulonephritis; kidney biopsy; nephrotic syndrome;
renal pathology
ID NORMAL RENAL-FUNCTION; IMMUNOGLOBULIN DEPOSITION DISEASE; LINKED
IMMUNOSORBENT ASSAYS; ANTIBODY-MEDIATED DISEASE; GOODPASTURES-SYNDROME;
GLOMERULONEPHRITIS; AUTOANTIBODIES; AUTOANTIGEN; IGG; NEPHROPATHY
AB Classic anti-glomerular basement membrane (GBM) disease presents with rapidly progressive glomerulonephritis (GN) with or without pulmonary hemorrhage. On biopsy typical disease displays bright polytypic linear GBM staining for IgG by immunofluorescence and diffuse crescentic/necrotizing GN on light microscopy. Here, we studied 20 patients with atypical anti-GBM nephritis typified by bright linear GBM staining for immunoglobulins but without a diffuse crescentic phenotype. Patients had hematuria, proteinuria, and mild renal insufficiency, without pulmonary hemorrhage. Light microscopy showed endocapillary proliferative GN in 9 patients, mesangial proliferative GN in 6, membranoproliferative GN in 3, and focal segmental glomerulosclerosis with mesangial hypercellularity in 2. Eight of the 20 showed features of microangiopathy. Crescents/necrosis were absent in 12 and were focal in 8 patients. Bright linear GBM staining for IgG was seen in 17 patients, IgM in 2, and IgA in 1 patient, which was polytypic in 10 patients and monotypic in 10 patients. No circulating alpha 3NC1 antibodies were detected by commercial ELISA. The 1-year patient and renal survival rates were 93% and 85%, respectively. Thus, atypical anti-GBM nephritis is a rare variant of anti-GBM disease characterized clinically by an indolent course, no pulmonary involvement, and undetectable circulating a3NC1 antibodies. Further studies are needed to characterize the molecular architecture of GBM autoantigens in these patients and establish optimal therapy.
C1 [Nasr, Samih H.; Alexander, Mariam Priya; Hernandez, Loren Herrera; Fidler, Mary E.; Sethi, Sanjeev; Cornell, Lynn D.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Collins, A. Bernard] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA.
[Schraith, Daniel F.] Gundersen Hlth Syst, Dept Pathol & Lab Med, La Crosse, WI USA.
[Leung, Nelson; Fervenza, Fernando C.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN 55905 USA.
RP Cornell, LD (reprint author), Mayo Clin, Div Anat Pathol, 200 First St SW, Rochester, MN 55905 USA.
EM cornell.lynn@mayo.edu
NR 46
TC 4
Z9 4
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD APR
PY 2016
VL 89
IS 4
BP 897
EP 908
DI 10.1016/j.kint.2016.02.001
PG 12
WC Urology & Nephrology
SC Urology & Nephrology
GA DH1CD
UT WOS:000372521100020
PM 26994577
ER
PT J
AU Healy, DY
Chhabra, N
Metson, R
Holbrook, EH
Gray, ST
AF Healy, David Y., Jr.
Chhabra, Nipun
Metson, Ralph
Holbrook, Eric H.
Gray, Stacey T.
TI Surgical risk factors for recurrence of inverted papilloma
SO LARYNGOSCOPE
LA English
DT Article
DE Inverted papilloma; Schneiderian papilloma; paranasal sinus tumor;
endoscopic sinus surgery; risk factors
ID STAGING SYSTEM; MANAGEMENT
AB Objectives/HypothesisTo identify variations in surgical technique that impact the recurrence of inverted papilloma following endoscopic excision.
Study DesignRetrospective cohort.
MethodsData from 127 consecutive patients who underwent endoscopic excision of inverted papilloma and oncocytic papilloma at a tertiary care medical center from 1998 to 2011 were reviewed. Patient demographics, comorbidities, tumor stage, and intraoperative details, including tumor location and management of the base, were evaluated to identify factors associated with tumor recurrence.
ResultsRecurrence of papilloma occurred in 16 patients (12.6%). Mean time to recurrence was 31.0 months (range, 5.2-110.0 months). Mucosal stripping alone was associated with a recurrence rate of 52.2% (12/23 patients), compared to 4.9% (3/61 patients) when the tumor base was drilled, 4.7% (1/21 patients) when it was cauterized, and 0.0% (0/22 patients) when it was completely excised (P = .001). Increased recurrence rate was associated with tumors located in the maxillary sinus (P = .03), as well as the performance of endoscopic medial maxillectomy (P = .001) and external frontal approaches (P = .02).
ConclusionsDrilling, cauterizing, or completely excising the bone underlying the tumor base during endoscopic resection reduces the recurrence rate of inverted and oncocytic papilloma, when compared to mucosal stripping alone. Surgeons who perform endoscopic resection of these tumors should consider utilization of these techniques when possible.
Level of Evidence4 Laryngoscope, 126:796-801, 2016
C1 [Healy, David Y., Jr.] Naval Med Ctr Portsmouth, Dept Otolaryngol, 620 John Paul Jones Circle, Portsmouth, VA 23708 USA.
[Chhabra, Nipun] Univ Illinois, Coll Med, Dept Surg, St Anthony Med Ctr, Rockford, IL 61107 USA.
[Metson, Ralph; Holbrook, Eric H.; Gray, Stacey T.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA.
[Metson, Ralph; Holbrook, Eric H.; Gray, Stacey T.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA.
RP Healy, DY (reprint author), Naval Med Ctr Portsmouth, Dept Otolaryngol, 620 John Paul Jones Circle, Portsmouth, VA 23708 USA.
EM dyhealy@hotmail.com
NR 14
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD APR
PY 2016
VL 126
IS 4
BP 796
EP 801
DI 10.1002/lary.25663
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA DI3EV
UT WOS:000373382100010
PM 26372045
ER
PT J
AU Lu, IC
Wu, CW
Chang, PY
Chen, HY
Tseng, KY
Randolph, GW
Cheng, KI
Chiang, FY
AF Lu, I-Cheng
Wu, Che-Wei
Chang, Pi-Ying
Chen, Hsiu-Ya
Tseng, Kuang-Yi
Randolph, Gregory W.
Cheng, Kuang-I
Chiang, Feng-Yu
TI Reversal of rocuronium-induced neuromuscular blockade by sugammadex
allows for optimization of neural monitoring of the recurrent laryngeal
nerve
SO LARYNGOSCOPE
LA English
DT Article
DE Intraoperative neuromonitoring; neuromuscular blocking agent;
sugammadex; recurrent laryngeal nerve; thyroid surgery; anesthesia
ID PROSPECTIVE PORCINE MODEL; RELAXANT BINDING-AGENT; THYROID-SURGERY;
ENDOTRACHEAL-TUBE; INJURY; IDENTIFICATION; VECURONIUM; SUCCINYLCHOLINE;
STIMULATION; RLN
AB Objectives/HypothesisThe use of neuromuscular blocking agent may effect intraoperative neuromonitoring (IONM) during thyroid surgery. An enhanced neuromuscular-blockade (NMB) recovery protocol was investigated in a porcine model and subsequently clinically applied during human thyroid neural monitoring surgery.
Study DesignProspective animal and retrospective clinical study.
MethodsIn the animal experiment, 12 piglets were injected with rocuronium 0.6 mg/kg and randomly allocated to receive normal saline, sugammadex 2 mg/kg, or sugammadex 4mg/kg to compare the recovery of laryngeal electromyography (EMG). In a subsequent clinical application study, 50 patients who underwent thyroidectomy with IONM followed an enhanced NMB recovery protocolrocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at the operation start. The train-of-four (TOF) ratio was used for continuous quantitative monitoring of neuromuscular transmission.
ResultsIn our porcine model, it took 49 15, 13.2 5.6, and 4.2 +/- 1.5 minutes for the 80% recovery of laryngeal EMG after injection of saline, sugammadex 2 mg/kg, and sugammadex 4 mg/kg, respectively. In subsequent clinical human application, the TOF ratio recovered from 0 to >0.9 within 5 minutes after administration of sugammadex 2 mg/kg at the operation start. All patients had positive and high EMG amplitude at the early stage of the operation, and intubation was without difficulty in 96% of patients.
ConclusionsBoth porcine modeling and clinical human application demonstrated that sugammadex 2 mg/kg allows effective and rapid restoration of neuromuscular function suppressed by rocuronium. Implementation of this enhanced NMB recovery protocol assures optimal conditions for tracheal intubation as well as IONM in thyroid surgery.
Level of EvidenceNA Laryngoscope, 126:1014-1019, 2016
C1 [Lu, I-Cheng; Wu, Che-Wei; Cheng, Kuang-I; Chiang, Feng-Yu] Kaohsiung Med Univ, Coll Med, Grad Inst Med, 100 TzYou First Rd, Kaohsiung 807, Taiwan.
[Lu, I-Cheng; Wu, Che-Wei; Cheng, Kuang-I; Chiang, Feng-Yu] Kaohsiung Med Univ, Coll Med, Fac Med, 100 TzYou First Rd, Kaohsiung 807, Taiwan.
[Lu, I-Cheng] Kaohsiung Med Univ, Kaohsiung Municipal Hsiao Kang Hosp, Dept Anesthesiol, 100 TzYou First Rd, Kaohsiung 807, Taiwan.
[Chang, Pi-Ying; Chen, Hsiu-Ya; Tseng, Kuang-Yi; Cheng, Kuang-I] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Anesthesiol, 100 TzYou First Rd, Kaohsiung 807, Taiwan.
[Wu, Che-Wei; Chiang, Feng-Yu] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Otolaryngol Head & Neck Surg, 100 TzYou First Rd, Kaohsiung 807, Taiwan.
[Randolph, Gregory W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Div Thyroid & Parathyroid Surg, Massachusetts Eye & Ear Infirm,Dept Laryn & Otol, Boston, MA USA.
[Randolph, Gregory W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Surg Oncol, Boston, MA USA.
RP Cheng, KI (reprint author), Kaohsiung Med Univ, Coll Med, 100 TzYou First Rd, Kaohsiung 807, Taiwan.
EM fychiang@kmu.edu.tw
OI Wu, Che-Wei/0000-0003-1052-5348
FU Kaohsiung Medical University Hospital (KMUH) [103-3T07, 103-3R36];
Ministry of Science and Technology, Taiwan (MOST)
[103-2314-B-037-037-MY2]
FX This study was supported by grants from the Kaohsiung Medical University
Hospital (KMUH 103-3T07, 103-3R36) and the Ministry of Science and
Technology, Taiwan (MOST 103-2314-B-037-037-MY2).
NR 33
TC 4
Z9 4
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD APR
PY 2016
VL 126
IS 4
BP 1014
EP 1019
DI 10.1002/lary.25577
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA DI3EV
UT WOS:000373382100048
PM 26748952
ER
PT J
AU Salari, B
Ren, Y
Kamani, D
Randolph, GW
AF Salari, Behzad
Ren, Yin
Kamani, Dipti
Randolph, Gregory W.
TI Revision neural monitored surgery for recurrent thyroid cancer: Safety
and thyroglobulin response
SO LARYNGOSCOPE
LA English
DT Article
DE Revision thyroid surgery; thyroglobulin; Tg; safety; complications
ID CENTRAL COMPARTMENT DISSECTION; LYMPH-NODE DISSECTION; NECK DISSECTION;
PAPILLARY; CARCINOMA; EFFICACY; REOPERATION; OUTCOMES; ULTRASOUND;
MORBIDITY
AB Objectives/HypothesisTo evaluate the quantitative biochemical response, recurrence rate, and rate of surgical complications for thyroid cancer revision surgery.
Study DesignRetrospective review.
MethodsThis is a single institution analysis of a prospective database of 181 patients undergoing reoperation for local recurrent thyroid cancer by the same surgeon from 2004 to 2013 with intraoperative neural monitoring. Main outcome measures included pathologic findings, surgical complications, effect of reoperation on thyroglobulin (Tg) levels, and recurrence rate. We defined biochemical complete remission as postoperative stimulated Tg of 0.2 ng/mL or less.
ResultsFourteen percent of the patients presented with permanent vocal cord palsy (VCP), and 20% of the patients presented with hypocalcemia prior to surgery. Among them, 70% of the patients underwent first revision surgery; whereas in 30% the surgery represented second or higher revision surgery, with 8% being a third or higher revision. None developed temporary or permanent VCP. Temporary hypocalcemia occurred in 9% of the patients, and permanent hypocalcemia occurred in 4.2%. The rate of cervical node recurrence was 5% at a median follow-up of 3.4 years. There were no disease-specific deaths. Mean preoperative basal Tg was 22.3 ng/mL and mean postoperative Tg was 5.7 ng/mL, a decline of 74% (P = 0.023, paired t test). Biochemical complete remission was achieved in 58% of all revision cases.
ConclusionReoperative neural monitored surgery for recurrent thyroid cancer is a safe and effective procedure with limited morbidity in experienced hands, even in the setting of multiple prior revision surgeries and existing comorbidities such as VCP and hypocalcemia.
Level of Evidence4. Laryngoscope, 126:1020-1025, 2016
C1 [Salari, Behzad; Ren, Yin; Kamani, Dipti; Randolph, Gregory W.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol,Div Thyroid & Parathyroid Surg, Boston, MA USA.
[Randolph, Gregory W.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.
[Randolph, Gregory W.] Harvard Univ, Sch Med, Boston, MA USA.
RP Randolph, GW (reprint author), Dept Otolaryngol, Thyroid & Parathyroid Endocrine Surg Div, 243 Charles St, Boston, MA 02114 USA.
EM gregory_randolph@meei.harvard.edu
FU John and Claire Bertucci Thyroid Research
FX The authors thank The John and Claire Bertucci Thyroid Research fund for
supporting this research.
NR 34
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD APR
PY 2016
VL 126
IS 4
BP 1020
EP 1025
DI 10.1002/lary.25796
PG 6
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA DI3EV
UT WOS:000373382100049
PM 26608969
ER
PT J
AU Torrado-Carvajal, A
Herraiz, JL
Hernandez-Tamames, JA
Jose-Estepar, RS
Eryaman, Y
Rozenholc, Y
Adalsteinsson, E
Wald, LL
Malpica, N
AF Torrado-Carvajal, Angel
Herraiz, Joaquin L.
Hernandez-Tamames, Juan A.
Jose-Estepar, Raul San
Eryaman, Yigitcan
Rozenholc, Yves
Adalsteinsson, Elfar
Wald, Lawrence L.
Malpica, Norberto
TI Multi-Atlas and Label Fusion Approach for Patient-Specific MRI Based
Skull Estimation
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE atlas-based; label fusion; MRI; skull segmentation; tissue models
ID MULTIMODALITY IMAGE REGISTRATION; ATTENUATION CORRECTION;
MUTUAL-INFORMATION; HUMAN-BODY; SEGMENTATION; PERFORMANCE; MODELS;
MAXIMIZATION
AB Purpose: MRI-based skull segmentation is a useful procedure for many imaging applications. This study describes a methodology for automatic segmentation of the complete skull from a single T1-weighted volume.
Methods: The skull is estimated using a multi-atlas segmentation approach. Using a whole head computed tomography (CT) scan database, the skull in a new MRI volume is detected by nonrigid image registration of the volume to every CT, and combination of the individual segmentations by label-fusion. We have compared Majority Voting, Simultaneous Truth and Performance Level Estimation (STAPLE), Shape Based Averaging (SBA), and the Selective and Iterative Method for Performance Level Estimation (SIMPLE) algorithms.
Results: The pipeline has been evaluated quantitatively using images from the Retrospective Image Registration Evaluation database (reaching an overlap of 72.46 +/- 6.99%), a clinical CT-MR dataset (maximum overlap of 78.31 +/- 6.97%), and a whole head CT-MRI pair (maximum overlap 78.68%). A qualitative evaluation has also been performed on MRI acquisition of volunteers.
Conclusion: It is possible to automatically segment the complete skull from MRI data using a multi-atlas and label fusion approach. This will allow the creation of complete MRI-based tissue models that can be used in electromagnetic dosimetry applications and attenuation correction in PET/MR. (C) 2015 Wiley Periodicals, Inc.
C1 [Torrado-Carvajal, Angel; Hernandez-Tamames, Juan A.; Malpica, Norberto] Univ Rey Juan Carlos, Med Image Anal & Biometry Lab, Madrid, Spain.
[Torrado-Carvajal, Angel; Herraiz, Joaquin L.; Hernandez-Tamames, Juan A.; Jose-Estepar, Raul San; Eryaman, Yigitcan; Adalsteinsson, Elfar; Malpica, Norberto] Madrid MIT M Vis Consortium, Madrid, Spain.
[Herraiz, Joaquin L.; Eryaman, Yigitcan] MIT, Elect Res Lab, Inst Technol, Cambridge, MA 02139 USA.
[Jose-Estepar, Raul San] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA.
[Eryaman, Yigitcan; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA.
[Rozenholc, Yves] Univ Paris 05, CNRS, MAP5, UMR 8145, Paris, France.
[Rozenholc, Yves] INRIA Saclay Ile de France SELECT, Paris, France.
[Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA.
[Adalsteinsson, Elfar; Wald, Lawrence L.] MIT, Harvard MIT Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Adalsteinsson, Elfar] MIT, Inst Med Engn & Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
RP Torrado-Carvajal, A (reprint author), Univ Rey Juan Carlos, Med Image Anal & Biometry Lab, Biomed Engn, Madrid, Spain.
EM angel.torrado@urjc.es
RI Wald, Lawrence/D-4151-2009; Hernandez-Tamames, Juan /N-5319-2014; LOPEZ
HERRAIZ, JOAQUIN/E-9234-2010; Malpica, Norberto/I-2090-2015
OI Hernandez-Tamames, Juan /0000-0003-0027-9518; LOPEZ HERRAIZ,
JOAQUIN/0000-0001-7208-8863; Malpica, Norberto/0000-0003-4618-7459
FU Comunidad de Madrid; Madrid-MIT M+Vision Consortium
FX Grant sponsor: Comunidad de Madrid; Grant sponsor: Madrid-MIT M+Vision
Consortium.
NR 36
TC 2
Z9 2
U1 3
U2 7
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 APR
PY 2016
VL 75
IS 4
BP 1797
EP 1807
DI 10.1002/mrm.25737
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DH6OR
UT WOS:000372910900042
PM 25981161
ER
PT J
AU Di Stefano, B
Collombet, S
Jakobsen, JS
Wierer, M
Sardina, JL
Lackner, A
Stadhouders, R
Segura-Morales, C
Francesconi, M
Limone, F
Mann, M
Porse, B
Thieffry, D
Graf, T
AF Di Stefano, Bruno
Collombet, Samuel
Jakobsen, Janus Schou
Wierer, Michael
Luis Sardina, Jose
Lackner, Andreas
Stadhouders, Ralph
Segura-Morales, Carolina
Francesconi, Mirko
Limone, Francesco
Mann, Matthias
Porse, Bo
Thieffry, Denis
Graf, Thomas
TI C/EBP alpha creates elite cells for iPSC reprogramming by upregulating
Klf4 and increasing the levels of Lsd1 and Brd4
SO NATURE CELL BIOLOGY
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; ACUTE MYELOID-LEUKEMIA; MLL-REARRANGED AML;
TRANSCRIPTION FACTORS; SUPER-ENHANCERS; HEMATOPOIETIC DIFFERENTIATION;
SELECTIVE-INHIBITION; SIGNALING PATHWAYS; HIGHLY EFFICIENT;
SOMATIC-CELLS
AB Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) is typically inefficient and has been explained by elite-cell and stochastic models. We recently reported that B cells exposed to a pulse of C/EBP alpha (B alpha' cells) behave as elite cells, in that they can be rapidly and efficiently reprogrammed into iPSCs by the Yamanaka factors OSKM. Here we show that C/EBP alpha post-transcriptionally increases the abundance of several hundred proteins, including Lsd1, Hdac1, Brd4, Med1 and Cdk9, components of chromatin-modifying complexes present at super-enhancers. Lsd1 was found to be required for B cell gene silencing and Brd4 for the activation of the pluripotency program. C/EBP alpha also promotes chromatin accessibility in pluripotent cells and upregulates Klf4 by binding to two haematopoietic enhancers. B alpha' cells share many properties with granulocyte/macrophage progenitors, naturally occurring elite cells that are obligate targets for leukaemic transformation, whose formation strictly requires C/EBP alpha.
C1 [Di Stefano, Bruno; Luis Sardina, Jose; Lackner, Andreas; Stadhouders, Ralph; Segura-Morales, Carolina; Francesconi, Mirko; Limone, Francesco; Graf, Thomas] Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain.
[Di Stefano, Bruno; Luis Sardina, Jose; Lackner, Andreas; Stadhouders, Ralph; Segura-Morales, Carolina; Francesconi, Mirko; Limone, Francesco; Graf, Thomas] Univ Pompeu Fabra, Barcelona 08003, Spain.
[Collombet, Samuel; Thieffry, Denis] PSL Res Univ, Ecole Normale Super, IBENS, CNRS,INSERM,U1024,UMR8197, F-75005 Paris, France.
[Jakobsen, Janus Schou; Porse, Bo] Univ Copenhagen, Fac Hlth Sci, Rigshosp, Finsen Lab, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark.
[Jakobsen, Janus Schou; Porse, Bo] Univ Copenhagen, BRIC, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark.
[Jakobsen, Janus Schou; Porse, Bo] Univ Copenhagen, Fac Hlth Sci, Danish Stem Cell Ctr DanStem, 3B Blegdamsvej, DK-2200 Copenhagen, Denmark.
[Wierer, Michael; Mann, Matthias] Max Planck Inst Biochem, D-82152 Munich, Germany.
[Di Stefano, Bruno] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Di Stefano, Bruno] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Lackner, Andreas] Univ Vienna, Max F Perutz Labs, Vienna Bioctr VBC, Dr Bohr Gasse 9-3, A-1030 Vienna, Austria.
RP Di Stefano, B; Graf, T (reprint author), Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Dr Aiguader 88, Barcelona 08003, Spain.; Di Stefano, B; Graf, T (reprint author), Univ Pompeu Fabra, Barcelona 08003, Spain.; Di Stefano, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.; Di Stefano, B (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA.
EM distefano@molbio.mgh.harvard.edu; thomas.graf@crg.eu
RI francesconi, mirko/O-8080-2015;
OI francesconi, mirko/0000-0002-8702-0877; Di Stefano,
Bruno/0000-0003-2532-3087
FU Ministerio de Educacion y Ciencia [SAF.2012-37167]; Fundacio La Marato
[TV3 120410]; AGAUR [SGR 1136]; European Research Council Synergy Grant
(4D-Genome); EMBO Long-term Fellowship (ALTF) [1201-2014]; Marie Curie
Individual Fellowship (H2020-MSCA-IF); MINECO [IJCI-2014-21872];
NovoNordisk Foundation (Section for Stem Cell Biology in Human Disease)
[R179-A1513]
FX We thank J. E. Bradner (Dana Farber Cancer Institute, Harvard Medical
School, USA) for the JQ1 compound, J. Zuber (Research Institute of
Molecular Pathology (IMP), Vienna Biocenter (VBC), Austria) for the Brd4
shRNA construct, R. Levine (Memorial Sloan Kettering Cancer Center, USA)
for the Tet2 shRNA construct, L. de Andres for help with GMP isolations,
L. Batlle for help with the chimaeric mice, the Genomics Facility and
the Biomolecular Screening & Protein Technologies Facility of the CRG
for technical assistance and members of the Graf laboratory for
discussions. This work was supported by Ministerio de Educacion y
Ciencia, SAF.2012-37167, Fundacio La Marato TV3 120410, AGAUR SGR 1136
and European Research Council Synergy Grant (4D-Genome). R.S. was
supported by an EMBO Long-term Fellowship (ALTF 1201-2014) and a Marie
Curie Individual Fellowship (H2020-MSCA-IF-2014). J.L.S. was supported
by MINECO (IJCI-2014-21872). Work in the Porse laboratory was supported
through a Centre grant from the NovoNordisk Foundation (Section for Stem
Cell Biology in Human Disease and R179-A1513).
NR 69
TC 7
Z9 7
U1 8
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1465-7392
EI 1476-4679
J9 NAT CELL BIOL
JI Nat. Cell Biol.
PD APR
PY 2016
VL 18
IS 4
BP 371
EP +
DI 10.1038/ncb3326
PG 25
WC Cell Biology
SC Cell Biology
GA DH7LX
UT WOS:000372976600005
PM 26974661
ER
PT J
AU Boettger, LM
Salem, RM
Handsaker, RE
Peloso, GM
Kathiresan, S
Hirschhorn, JN
McCarroll, SA
AF Boettger, Linda M.
Salem, Rany M.
Handsaker, Robert E.
Peloso, Gina M.
Kathiresan, Sekar
Hirschhorn, Joel N.
McCarroll, Steven A.
TI Recurring exon deletions in the HP (haptoglobin) gene contribute to
lower blood cholesterol levels
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; APOLIPOPROTEIN-E; COPY NUMBER; GENOTYPE
IMPUTATION; NATURAL-SELECTION; POPULATION; HEMOGLOBIN; PROTEINS;
BINDING; HUMANS
AB One of the first protein polymorphisms identified in humans involves the abundant blood protein haptoglobin. Two exons of the HP gene (encoding haptoglobin) exhibit copy number variation that affects HP protein structure and multimerization. The evolutionary origins and medical relevance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from many recurring deletions, more specifically, reversions of an ancient hominin-specific duplication of these exons. Although this polymorphism has been largely invisible to genome-wide genetic studies thus far, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We further show that these deletions, and a SNP that affects HP expression, appear to drive the strong association of cholesterol levels with SNPs near HP. Recurring exonic deletions in HP likely enhance human health by lowering cholesterol levels in the blood.
C1 [Boettger, Linda M.; Salem, Rany M.; Handsaker, Robert E.; Hirschhorn, Joel N.; McCarroll, Steven A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Boettger, Linda M.; Salem, Rany M.; Handsaker, Robert E.; Peloso, Gina M.; Kathiresan, Sekar; Hirschhorn, Joel N.; McCarroll, Steven A.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.
[Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.
[Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP McCarroll, SA (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.; McCarroll, SA (reprint author), Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
EM mccarroll@genetics.med.harvard.edu
FU National Human Genome Research Institute [R01HG006855]; Yerkes Center
[P51OD011132]; US National Institutes of Health/National Heart, Lung,
and Blood Institute K99 award [1K99HL122515-01A1]; Juvenile Diabetes
Research Foundation [JDRF 3-APF-2014-111-A-N]; National Heart, Lung, and
Blood Institute of the US National Institutes of Health [K01HL125751]
FX We thank C. Usher for comments on the manuscript and work on the
figures. This work was supported by a grant from the National Human
Genome Research Institute (R01HG006855 to S.A.M.). The Yerkes Center
(grant P51OD011132) provided primate DNA samples. R.M.S. was supported
by a US National Institutes of Health/National Heart, Lung, and Blood
Institute K99 award (1K99HL122515-01A1) and an advanced postdoctoral
fellowship award from the Juvenile Diabetes Research Foundation (JDRF
3-APF-2014-111-A-N). G.M.P. was supported by the National Heart, Lung,
and Blood Institute of the US National Institutes of Health under award
K01HL125751.
NR 50
TC 3
Z9 3
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2016
VL 48
IS 4
BP 359
EP +
DI 10.1038/ng.3510
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA DH6NZ
UT WOS:000372908800007
PM 26901066
ER
PT J
AU Dunning, AM
Michailidou, K
Kuchenbaecker, KB
Thompson, D
French, JD
Beesley, J
Healey, CS
Kar, S
Pooley, KA
Lopez-Knowles, E
Dicks, E
Barrowdale, D
Sinnott-Armstrong, NA
Sallari, RC
Hillman, KM
Kaufmann, S
Sivakumaran, H
Marjaneh, MM
Lee, JS
Hills, M
Jarosz, M
Drury, S
Canisius, S
Bolla, MK
Dennis, J
Wang, Q
Hopper, JL
Southey, MC
Broeks, A
Schmidt, MK
Lophatananon, A
Muir, K
Beckmann, MW
Fasching, PA
dos-Santos-Silva, I
Peto, J
Sawyer, EJ
Tomlinson, I
Burwinkel, B
Marme, F
Guenel, P
Truong, T
Bojesen, SE
Flyger, H
Gonzalez-Neira, A
Perez, JIA
Anton-Culver, H
Eunjung, L
Arndt, V
Brenner, H
Meindl, A
Schmutzler, RK
Brauch, H
Hamann, U
Aittomaki, K
Blomqvist, C
Ito, H
Matsuo, K
Bogdanova, N
Dork, T
Lindblom, A
Margolin, S
Kosma, VM
Mannermaa, A
Tseng, CC
Wu, AH
Lambrechts, D
Wildiers, H
Chang-Claude, J
Rudolph, A
Peterlongo, P
Radice, P
Olson, JE
Giles, GG
Milne, RL
Haiman, CA
Henderson, BE
Goldberg, MS
Teo, SH
Yip, CH
Nord, S
Borresen-Dale, AL
Kristensen, V
Long, J
Zheng, W
Pylkas, K
Winqvist, R
Andrulis, IL
Knight, JA
Devilee, P
Seynaeve, C
Figueroa, J
Sherman, ME
Czene, K
Darabi, H
Hollestelle, A
van den Ouweland, AMW
Humphreys, K
Gao, YT
Shu, XO
Cox, A
Cross, SS
Blot, W
Cai, Q
Ghoussaini, M
Perkins, BJ
Shah, M
Choi, JY
Kang, D
Lee, SC
Hartman, M
Kabisch, M
Torres, D
Jakubowska, A
Lubinski, J
Brennan, P
Sangrajrang, S
Ambrosone, CB
Toland, AE
Shen, CY
Wu, PE
Orr, N
Swerdlow, A
McGuffog, L
Healey, S
Lee, A
Kapuscinski, M
John, EM
Terry, MB
Daly, MB
Goldgar, DE
Buys, SS
Janavicius, R
Tihomirova, L
Tung, N
Dorfling, CM
van Rensburg, EJ
Neuhausen, SL
Ejlertsen, B
Hansen, TVO
Osorio, A
Benitez, J
Rando, R
Weitzel, JN
Bonanni, B
Peissel, B
Manoukian, S
Papi, L
Ottini, L
Konstantopoulou, I
Apostolou, P
Garber, J
Rashid, MU
Frost, D
Izatt, L
Ellis, S
Godwin, AK
Arnold, N
Niederacher, D
Rhiem, K
Bogdanova-Markov, N
Sagne, C
Stoppa-Lyonnet, D
Damiola, F
Sinilnikova, OM
Mazoyer, S
Isaacs, C
Claes, KBM
De Leeneer, K
De la Hoya, M
Caldes, T
Nevanlinna, H
Khan, S
Mensenkamp, AR
Hooning, MJ
Rookus, MA
Kwong, A
Olah, E
Diez, O
Brunet, J
Pujana, MA
Gronwald, J
Huzarski, T
Barkardottir, RB
Laframboise, R
Soucy, P
Montagna, M
Agata, S
Teixeira, MR
Park, SK
Lindor, N
Couch, FJ
Tischkowitz, M
Foretova, L
Vijai, J
Offit, K
Singer, CF
Rappaport, C
Phelan, CM
Greene, MH
Mai, PL
Rennert, G
Imyanitov, EN
Hulick, PJ
Phillips, KA
Piedmonte, M
Mulligan, AM
Glendon, G
Bojesen, A
Thomassen, M
Caligo, MA
Yoon, SY
Friedman, E
Laitman, Y
Borg, A
Von Wachenfeldt, A
Ehrencrona, H
Rantala, J
Olopade, OI
Ganz, PA
Nussbaum, RL
Gayther, SA
Nathanson, KL
Domchek, SM
Arun, BK
Mitchell, G
Karlan, BY
Lester, J
Maskarinec, G
Woolcott, C
Scott, C
Stone, J
Apicella, C
Tamimi, R
Luben, R
Khaw, KT
Helland, A
Haakensen, V
Dowsett, M
Pharoah, PDP
Simard, J
Hall, P
Garcia-Closas, M
Vachon, C
Chenevix-Trench, G
Antoniou, AC
Easton, DF
Edwards, SL
AF Dunning, Alison M.
Michailidou, Kyriaki
Kuchenbaecker, Karoline B.
Thompson, Deborah
French, Juliet D.
Beesley, Jonathan
Healey, Catherine S.
Kar, Siddhartha
Pooley, Karen A.
Lopez-Knowles, Elena
Dicks, Ed
Barrowdale, Daniel
Sinnott-Armstrong, Nicholas A.
Sallari, Richard C.
Hillman, Kristine M.
Kaufmann, Susanne
Sivakumaran, Haran
Marjaneh, Mahdi Moradi
Lee, Jason S.
Hills, Margaret
Jarosz, Monika
Drury, Suzie
Canisius, Sander
Bolla, Manjeet K.
Dennis, Joe
Wang, Qin
Hopper, John L.
Southey, Melissa C.
Broeks, Annegien
Schmidt, Marjanka K.
Lophatananon, Artitaya
Muir, Kenneth
Beckmann, Matthias W.
Fasching, Peter A.
dos-Santos-Silva, Isabel
Peto, Julian
Sawyer, Elinor J.
Tomlinson, Ian
Burwinkel, Barbara
Marme, Frederik
Guenel, Pascal
Truong, Therese
Bojesen, Stig E.
Flyger, Henrik
Gonzalez-Neira, Anna
Perez, Jose I. A.
Anton-Culver, Hoda
Eunjung, Lee
Arndt, Volker
Brenner, Hermann
Meindl, Alfons
Schmutzler, Rita K.
Brauch, Hiltrud
Hamann, Ute
Aittomaki, Kristiina
Blomqvist, Carl
Ito, Hidemi
Matsuo, Keitaro
Bogdanova, Natasha
Dork, Thilo
Lindblom, Annika
Margolin, Sara
Kosma, Veli-Matti
Mannermaa, Arto
Tseng, Chiu-chen
Wu, Anna H.
Lambrechts, Diether
Wildiers, Hans
Chang-Claude, Jenny
Rudolph, Anja
Peterlongo, Paolo
Radice, Paolo
Olson, Janet E.
Giles, Graham G.
Milne, Roger L.
Haiman, Christopher A.
Henderson, Brian E.
Goldberg, Mark S.
Teo, Soo H.
Yip, Cheng Har
Nord, Silje
Borresen-Dale, Anne-Lise
Kristensen, Vessela
Long, Jirong
Zheng, Wei
Pylkas, Katri
Winqvist, Robert
Andrulis, Irene L.
Knight, Julia A.
Devilee, Peter
Seynaeve, Caroline
Figueroa, Jonine
Sherman, Mark E.
Czene, Kamila
Darabi, Hatef
Hollestelle, Antoinette
van den Ouweland, Ans M. W.
Humphreys, Keith
Gao, Yu-Tang
Shu, Xiao-Ou
Cox, Angela
Cross, Simon S.
Blot, William
Cai, Qiuyin
Ghoussaini, Maya
Perkins, Barbara J.
Shah, Mitul
Choi, Ji-Yeob
Kang, Daehee
Lee, Soo Chin
Hartman, Mikael
Kabisch, Maria
Torres, Diana
Jakubowska, Anna
Lubinski, Jan
Brennan, Paul
Sangrajrang, Suleeporn
Ambrosone, Christine B.
Toland, Amanda E.
Shen, Chen-Yang
Wu, Pei-Ei
Orr, Nick
Swerdlow, Anthony
McGuffog, Lesley
Healey, Sue
Lee, Andrew
Kapuscinski, Miroslav
John, Esther M.
Terry, Mary Beth
Daly, Mary B.
Goldgar, David E.
Buys, Saundra S.
Janavicius, Ramunas
Tihomirova, Laima
Tung, Nadine
Dorfling, Cecilia M.
van Rensburg, Elizabeth J.
Neuhausen, Susan L.
Ejlertsen, Bent
Hansen, Thomas V. O.
Osorio, Ana
Benitez, Javier
Rando, Rachel
Weitzel, Jeffrey N.
Bonanni, Bernardo
Peissel, Bernard
Manoukian, Siranoush
Papi, Laura
Ottini, Laura
Konstantopoulou, Irene
Apostolou, Paraskevi
Garber, Judy
Rashid, Muhammad Usman
Frost, Debra
Izatt, Louise
Ellis, Steve
Godwin, Andrew K.
Arnold, Norbert
Niederacher, Dieter
Rhiem, Kerstin
Bogdanova-Markov, Nadja
Sagne, Charlotte
Stoppa-Lyonnet, Dominique
Damiola, Francesca
Sinilnikova, Olga M.
Mazoyer, Sylvie
Isaacs, Claudine
Claes, Kathleen B. M.
De Leeneer, Kim
De la Hoya, Miguel
Caldes, Trinidad
Nevanlinna, Heli
Khan, Sofia
Mensenkamp, Arjen R.
Hooning, Maartje J.
Rookus, Matti A.
Kwong, Ava
Olah, Edith
Diez, Orland
Brunet, Joan
Pujana, Miquel Angel
Gronwald, Jacek
Huzarski, Tomasz
Barkardottir, Rosa B.
Laframboise, Rachel
Soucy, Penny
Montagna, Marco
Agata, Simona
Teixeira, Manuel R.
Park, Sue Kyung
Lindor, Noralane
Couch, Fergus J.
Tischkowitz, Marc
Foretova, Lenka
Vijai, Joseph
Offit, Kenneth
Singer, Christian F.
Rappaport, Christine
Phelan, Catherine M.
Greene, Mark H.
Mai, Phuong L.
Rennert, Gad
Imyanitov, Evgeny N.
Hulick, Peter J.
Phillips, Kelly-Anne
Piedmonte, Marion
Mulligan, Anna Marie
Glendon, Gord
Bojesen, Anders
Thomassen, Mads
Caligo, Maria A.
Yoon, Sook-Yee
Friedman, Eitan
Laitman, Yael
Borg, Ake
Von Wachenfeldt, Anna
Ehrencrona, Hans
Rantala, Johanna
Olopade, Olufunmilayo I.
Ganz, Patricia A.
Nussbaum, Robert L.
Gayther, Simon A.
Nathanson, Katherine L.
Domchek, Susan M.
Arun, Banu K.
Mitchell, Gillian
Karlan, Beth Y.
Lester, Jenny
Maskarinec, Gertraud
Woolcott, Christy
Scott, Christopher
Stone, Jennifer
Apicella, Carmel
Tamimi, Rulla
Luben, Robert
Khaw, Kay-Tee
Helland, Aslaug
Haakensen, Vilde
Dowsett, Mitch
Pharoah, Paul D. P.
Simard, Jacques
Hall, Per
Garcia-Closas, Montserrat
Vachon, Celine
Chenevix-Trench, Georgia
Antoniou, Antonis C.
Easton, Douglas F.
Edwards, Stacey L.
CA EMBRACE
GEMO Study Collaborators
HEBON
KConFab Investigators
TI Breast cancer risk variants at 6q25 display different phenotype
associations and regulate ESR1, RMND1 and CCDC170
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; BRCA2 MUTATION CARRIERS; BONE-MINERAL DENSITY;
MAMMOGRAPHIC DENSITY; SUSCEPTIBILITY LOCUS; METAANALYSIS; EXPRESSION;
MODIFIERS; REVEALS; DISEASE
AB We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor a) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER+ or ER-) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER-tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.
C1 [Dunning, Alison M.; Healey, Catherine S.; Kar, Siddhartha; Dicks, Ed; Ghoussaini, Maya; Perkins, Barbara J.; Shah, Mitul; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Michailidou, Kyriaki; Kuchenbaecker, Karoline B.; Thompson, Deborah; Pooley, Karen A.; Barrowdale, Daniel; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; McGuffog, Lesley; Lee, Andrew; Frost, Debra; Ellis, Steve; Pharoah, Paul D. P.; Antoniou, Antonis C.; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[French, Juliet D.; Beesley, Jonathan; Hillman, Kristine M.; Kaufmann, Susanne; Sivakumaran, Haran; Marjaneh, Mahdi Moradi; Lee, Jason S.; Healey, Sue; Chenevix-Trench, Georgia; Edwards, Stacey L.] QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia.
[Lopez-Knowles, Elena; Jarosz, Monika; Drury, Suzie; Dowsett, Mitch] Breakthrough Breast Canc Res Ctr, Breast Canc Res, London, England.
[Lopez-Knowles, Elena; Hills, Margaret; Jarosz, Monika; Drury, Suzie; Dowsett, Mitch] Royal Marsden Hosp, Acad Biochem, London SW3 6JJ, England.
[Sinnott-Armstrong, Nicholas A.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
[Sallari, Richard C.] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
[Canisius, Sander; Broeks, Annegien; Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Hopper, John L.; Giles, Graham G.; Milne, Roger L.; Apicella, Carmel] Univ Melbourne, Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Lophatananon, Artitaya; Muir, Kenneth] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England.
[Muir, Kenneth] Univ Manchester, Inst Populat Hlth, Manchester, Lancs, England.
[Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Comprehens Canc Ctr Erlangen Nuremberg Metropolit, D-91054 Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol & Oncol, Dept Med, Los Angeles, CA 90095 USA.
[dos-Santos-Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1, England.
[Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Div Canc Studies, Res Oncol, London, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Burwinkel, Barbara] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Grp, Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Marme, Frederik] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Guenel, Pascal; Truong, Therese] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France.
[Guenel, Pascal; Truong, Therese] Univ Paris Sud, Villejuif, France.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Herlev, Denmark.
[Bojesen, Stig E.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Herlev, Denmark.
[Bojesen, Stig E.] Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Herlev, Denmark.
[Gonzalez-Neira, Anna] Spanish Natl Canc Ctr CNIO, Human Canc Genet Program, Madrid, Spain.
[Perez, Jose I. A.] Hosp Monte Naranco, Serv Cirugia Gen & Especialidades, Oviedo, Spain.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Eunjung, Lee; Tseng, Chiu-chen; Wu, Anna H.; Haiman, Christopher A.; Henderson, Brian E.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann; Brauch, Hiltrud] German Canc Res Ctr, German Canc Consortium, Heidelberg, Germany.
[Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynaecol, D-80290 Munich, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Dept Obstet & Gynaecol, Div Mol Gynecooncol, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp, Ctr Integrated Oncol, Cologne, Germany.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Auerbachstr 112, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Hamann, Ute; Kabisch, Maria; Torres, Diana; Rashid, Muhammad Usman] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Aittomaki, Kristiina] Helsinki Univ Cent Hosp, Dept Clin Genet, Helsinki, Finland.
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[Ito, Hidemi] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Aichi, Japan.
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[Bogdanova, Natasha] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany.
[Dork, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara; Von Wachenfeldt, Anna] Karolinska Univ Hosp, Dept Oncol Pathol, Stockholm, Sweden.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland.
[Lambrechts, Diether] Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Wildiers, Hans] Univ Hosp Leuven, Dept Gen Med Oncol, Multidisciplinary Breast Ctr, Leuven, Belgium.
[Chang-Claude, Jenny; Rudolph, Anja] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Chang-Claude, Jenny] Univ Med Ctr Hamburg Eppendorf, UCCH, Hamburg, Germany.
[Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol, IFOM, Milan, Italy.
[Radice, Paolo] Fdn IRCCS Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Basis Genet Risk & Genet Testing, Milan, Italy.
[Olson, Janet E.; Lindor, Noralane; Couch, Fergus J.; Scott, Christopher; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
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[Teo, Soo H.; Yip, Cheng Har] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia.
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[Borresen-Dale, Anne-Lise; Kristensen, Vessela] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway.
[Long, Jirong; Zheng, Wei; Shu, Xiao-Ou; Blot, William; Cai, Qiuyin] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
[Pylkas, Katri; Winqvist, Robert] Univ Oulu, NordLab Oulu Univ Hosp, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Pylkas, Katri; Winqvist, Robert] Univ Oulu, NordLab Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland.
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[Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
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[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
[Devilee, Peter] Leiden Univ Med Ctr, Dept Pathol, Leiden, Netherlands.
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[Figueroa, Jonine; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
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[van den Ouweland, Ans M. W.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
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[Cox, Angela] Univ Sheffield, Sheffield Canc Res, Dept Oncol, Sheffield, S Yorkshire, England.
[Cross, Simon S.] Univ Sheffield, Dept Neurosci, Acad Unit Pathol, Sheffield, S Yorkshire, England.
[Blot, William] Int Epidemiol Inst, Rockville, MD USA.
[Choi, Ji-Yeob; Park, Sue Kyung] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
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[Brennan, Paul] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France.
[Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand.
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[Swerdlow, Anthony; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
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[Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark.
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[Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain.
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[Weitzel, Jeffrey N.] City Hope Natl Med Ctr, Clin Canc Genet, Duarte, CA USA.
[Bonanni, Bernardo] Ist Europeo Oncol, Div Canc Prevent & Genet, Milan, Italy.
[Peissel, Bernard; Manoukian, Siranoush] Ist Nazl Tumori, Fdn Ist Ricovero & Cura Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, Via Venezian 1, I-20133 Milan, Italy.
[Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Florence, Italy.
[Ottini, Laura] Univ Roma La Sapienza, Dept Mol Med, Piazzale Aldo Moro 5, I-00185 Rome, Italy.
[Konstantopoulou, Irene; Apostolou, Paraskevi] Aghia Paraskevi Attikis, Natl Ctr Sci Res Demokritos, INRASTES Inst Nucl & Radiol Sci & Technol, Mol Diagnost Lab, Athens, Greece.
[Garber, Judy] Dana Farber Canc Inst, Canc Risk & Prevent Clin, Boston, MA 02115 USA.
[Rashid, Muhammad Usman] Shaukat Khanum Mem Canc Hosp & Res Ctr, Dept Basic Sci, Lahore, Pakistan.
[Izatt, Louise] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Clin Genet, London, England.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Arnold, Norbert] Univ Kiel, Univ Hosp Schleswig Holstein, Dept Gynaecol & Obstet, Campus Kiel, Kiel, Germany.
[Niederacher, Dieter] Univ Dusseldorf, Dusseldorf, Germany.
[Rhiem, Kerstin] Univ Hosp Cologne, Ctr Mol Med Cologne, Dept Obstet & Gynaecol, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Rhiem, Kerstin] Univ Hosp Cologne, Ctr Mol Med Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Bogdanova-Markov, Nadja] Univ Munster, Inst Human Genet, D-48149 Munster, Germany.
[Sagne, Charlotte; Damiola, Francesca; Sinilnikova, Olga M.; Mazoyer, Sylvie] Univ Lyon 1, CNRS UMR 5286, INSERM U1052, Ctr Rech Cancerol Lyon, F-69365 Lyon, France.
[Stoppa-Lyonnet, Dominique] Inst Curie, Dept Tumour Biol, Paris, France.
[Stoppa-Lyonnet, Dominique] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Sinilnikova, Olga M.] Hosp Civils Lyon, Ctr Leon Berard, Unite Mixte Genet Constitutionnelle Canc Frequent, Lyon, France.
[Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA.
[Claes, Kathleen B. M.; De Leeneer, Kim] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
[De la Hoya, Miguel; Caldes, Trinidad] Hosp Clin San Carlos, IdISSC, Mol Oncol Lab, Madrid, Spain.
[Nevanlinna, Heli; Khan, Sofia] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Nevanlinna, Heli; Khan, Sofia] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Mensenkamp, Arjen R.] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6525 ED Nijmegen, Netherlands.
[Hooning, Maartje J.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Kwong, Ava] Hong Kong Sanat & Hosp, Canc Genet Ctr, Hong Kong Hereditary Breast Canc Family Registry, Hong Kong, Hong Kong, Peoples R China.
[Kwong, Ava] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary.
[Diez, Orland] Vall dHebron Univ Hosp, VHIO, Oncogenet Lab, Barcelona, Spain.
[Brunet, Joan] Catalan Inst Oncol, IDIBGI, Hereditary Canc Program, Genet Counseling Unit, Girona, Spain.
[Pujana, Miquel Angel] Catalan Inst Oncol, IDIBELL Bellvitge Biomed Res Inst, Breast Canc & Syst Biol Unit, Barcelona, Spain.
[Barkardottir, Rosa B.] Univ Iceland, Fac Med, Landspitali Univ Hosp, Dept Pathol, Reykjavik, Iceland.
[Barkardottir, Rosa B.] Univ Iceland, Fac Med, Biomed Ctr BMC, Reykjavik, Iceland.
[Laframboise, Rachel] Ctr Hosp Univ Quebec, Div Med Genet, Quebec City, PQ, Canada.
[Laframboise, Rachel; Soucy, Penny; Simard, Jacques] Univ Laval, Quebec City, PQ, Canada.
[Soucy, Penny; Simard, Jacques] Ctr Hosp Univ Quebec, Quebec City, PQ, Canada.
[Montagna, Marco; Agata, Simona] IRCCS, IOV, Immunol & Mol Oncol Unit, Padua, Italy.
[Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Oporto, Portugal.
[Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Rua Campo Alegre 823, P-4100 Oporto, Portugal.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Tischkowitz, Marc] McGill Univ, Program Canc Genet, Montreal, PQ, Canada.
[Foretova, Lenka] Masaryk Univ, Masaryk Mem Canc Inst, Brno, Czech Republic.
[Foretova, Lenka] Masaryk Univ, Fac Med, Brno, Czech Republic.
[Vijai, Joseph; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA.
[Singer, Christian F.; Rappaport, Christine] Med Univ Vienna, Ctr Comprehens Canc, Dept Obstet & Gynecol, Vienna, Austria.
[Phelan, Catherine M.] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Tampa, FL 33682 USA.
[Greene, Mark H.; Mai, Phuong L.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, US NIH, Rockville, MD USA.
[Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel.
[Rennert, Gad] Technion Israel Inst Technol, Bruce Rappaport Fac Med, POB 9649, IL-31096 Haifa, Israel.
[Rennert, Gad] Clalit Natl Israeli Canc Control Ctr, Haifa, Israel.
[Imyanitov, Evgeny N.] NN Petrov Oncol Res Inst, St Petersburg, Russia.
[Hulick, Peter J.] NorthShore Univ Hlth Syst, Ctr Med Genet, Evanston, IL USA.
[Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Div Canc Med, East Melbourne, Vic, Australia.
[Piedmonte, Marion] Roswell Pk Canc Inst, Stat & Data Management Ctr, NRG Oncol, Buffalo, NY 14263 USA.
[Mulligan, Anna Marie] Univ Hlth Network, Lab Med Program, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Bojesen, Anders] Vejle Hosp, Dept Clin Genet, Vejle, Denmark.
[Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense, Denmark.
[Caligo, Maria A.] Univ Pisa, Dept Lab Med, Sect Genet Oncol, Pisa, Italy.
[Caligo, Maria A.] Univ Hosp Pisa, Pisa, Italy.
[Yoon, Sook-Yee] Univ Malaya, Univ Malaya Med Ctr, Fac Med, Univ Malaya Canc Res Inst, Kuala Lumpur, Malaysia.
[Friedman, Eitan; Laitman, Yael] Chaim Sheba Med Ctr, Susanne Levy Gertner Oncogenet Unit, IL-52621 Tel Hashomer, Israel.
[Borg, Ake] Lund Univ, Dept Oncol, Lund, Sweden.
[Ehrencrona, Hans] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Ehrencrona, Hans] Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden.
[Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Stockholm, Sweden.
[Olopade, Olufunmilayo I.] Univ Chicago, Med Ctr, Ctr Clin Canc Genet & Global Hlth, Chicago, IL 60637 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Publ Hlth, Johnsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA USA.
[Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, San Francisco, CA 94143 USA.
[Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Abramson Canc Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Mitchell, Gillian] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic, Australia.
[Mitchell, Gillian] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia.
[Karlan, Beth Y.; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, Los Angeles, CA 90048 USA.
[Maskarinec, Gertraud] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Woolcott, Christy] Dalhousie Univ, Dept Obstet Gynaecol & Pediat, Halifax, NS, Canada.
[Stone, Jennifer] Univ Western Australia, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia.
[Tamimi, Rulla] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Tamimi, Rulla] Harvard Univ, Sch Med, Boston, MA USA.
[Tamimi, Rulla] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Tamimi, Rulla] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, 665 Huntington Ave, Boston, MA 02115 USA.
[Luben, Robert; Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Clin Gerontol, Cambridge, England.
RP Dunning, AM; Easton, DF; Edwards, SL (reprint author), Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.; Easton, DF (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.; Edwards, SL (reprint author), QIMR Berghofer Med Res Inst, Canc Div, Brisbane, Qld, Australia.
EM amd24@medschl.cam.ac.uk; dfe20@medschl.cam.ac.uk;
stacey.edwards@qimrberghofer.edu.au
RI Gronwald, Jacek/A-4576-2017; Brenner, Hermann/B-4627-2017; manoukian,
siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; montagna,
marco/E-2225-2012; Zheng, Wei/O-3351-2013; Nord, Silje/R-5212-2016;
Helland, Aslaug/H-3910-2015; Andrulis, Irene/E-7267-2013; Edwards,
Stacey/A-4980-2011; Arnold, Norbert/E-3012-2010; Jansen van Rensburg,
Elizabeth (Lizette)/B-9104-2011; Osorio, Ana/I-4324-2014; Lee,
Jason/M-7522-2016; Dork, Thilo/J-8620-2012; Yip, Cheng-Har/B-1909-2010;
Teo, Soo-hwang/H-2353-2014; Knight, Julia/A-6843-2012
OI Dunning, Alison Margaret/0000-0001-6651-7166; Matsuo,
Keitaro/0000-0003-1761-6314; Evans, Gareth/0000-0002-8482-5784;
Gronwald, Jacek/0000-0002-3643-2871; Brenner,
Hermann/0000-0002-6129-1572; manoukian, siranoush/0000-0002-6034-7562;
Peissel, Bernard/0000-0001-9233-3571; montagna,
marco/0000-0002-4929-2150; Ehrencrona, Hans/0000-0002-5589-3622;
Phillips, Kelly-Anne/0000-0002-0475-1771; Barrowdale,
Daniel/0000-0003-1661-3939; Khan, Sofia/0000-0003-4185-8882; Brunet,
Joan/0000-0003-1945-3512; Sivakumaran, Haran/0000-0002-4691-4989;
Dowsett, Mitch/0000-0003-4122-744X; Zheng, Wei/0000-0003-1226-070X;
Nord, Silje/0000-0002-3271-5356; Helland, Aslaug/0000-0002-5520-0275;
Arnold, Norbert/0000-0003-4523-8808; Osorio, Ana/0000-0001-8124-3984;
Lee, Jason/0000-0003-0879-934X;
FU National Institute for Health Research (NIHR); European Community
[223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C1287/A10118,
C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007,
C5047/A10692, C8197/A16565]; US National Institutes of Health (NIH)
[CA128978, CA192393, CA116167, CA176785]; US National Institutes of
Health (NIH Specialized Program of Research Excellence (SPORE) in Breast
Cancer) [CA116201]; Post-Cancer GWAS initiative [1U19 CA148537, 1U19
CA148065, 1U19 CA148112]; Post-Cancer GWAS initiative (GAME-ON
initiative); US Department of Defense [W81XWH-10-1-0341]; Canadian
Institutes of Health Research (CIHR); Komen Foundation for the Cure;
Breast Cancer Research Foundation; Ovarian Cancer Research Fund
FX We thank all the individuals who took part in these studies and all the
researchers, clinicians, technicians and administrative staff who have
enabled this work to be carried out. This study would not have been
possible without the contributions of the following: A. Berchuck (OCAC),
R.A. Eeles, A. A. Al Olama, Z. Kote-Jarai and S. Benlloch (PRACTICAL),
C. Luccarini and the staff of the Centre for Genetic Epidemiology
Laboratory, the staff of the CNIO genotyping unit, D.C. Tessier, F.
Bacot, D. Vincent, S. LaBoissiere, F. Robidoux and the staff of the
McGill University and Genome Quebec Innovation Centre, S. F. Nielsen,
B.G. Nordestgaard and the staff of the Copenhagen DNA laboratory, and
J.M. Cunningham, S. A. Windebank, C. A. Hilker, J. Meyer and the staff
of the Mayo Clinic Genotyping Core Facility. Normal human tissues from
the Susan G. Komen for the Cure Tissue Bank at the Indiana University
Simon Cancer Center (Indianapolis) were used in this study. We thank the
contributors, including Indiana University who collected samples used in
this study, as well as the donors and their families, whose help and
participation made this work possible. We also acknowledge National
Institute for Health Research (NIHR) support to the Royal Marsden
Biomedical Research Centre. Funding for the iCOGS infrastructure came
from the European Community's Seventh Framework Programme under grant
agreement 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK
(C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384,
C5047/A15007, C5047/A10692 and C8197/A16565), the US National Institutes
of Health (NIH; CA128978, CA192393, CA116167, CA176785 and an NIH
Specialized Program of Research Excellence (SPORE) in Breast Cancer
(CA116201)) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19
CA148065 and 1U19 CA148112, the GAME-ON initiative), the US Department
of Defense (W81XWH-10-1-0341), the Canadian Institutes of Health
Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer,
the Komen Foundation for the Cure, the Breast Cancer Research Foundation
and the Ovarian Cancer Research Fund. Full acknowledgments are given in
the Supplementary Note.
NR 46
TC 7
Z9 7
U1 6
U2 27
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD APR
PY 2016
VL 48
IS 4
BP 374
EP +
DI 10.1038/ng.3521
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA DH6NZ
UT WOS:000372908800009
PM 26928228
ER
PT J
AU Jang, C
Oh, SF
Wada, S
Rowe, GC
Liu, L
Chan, MC
Rhee, J
Hoshino, A
Kim, B
Ibrahim, A
Baca, LG
Kim, E
Ghosh, CC
Parikh, SM
Jiang, AH
Chu, QW
Forman, DE
Lecker, SH
Krishnaiah, S
Rabinowitz, JD
Weljie, AM
Baur, JA
Kasper, DL
Arany, Z
AF Jang, Cholsoon
Oh, Sungwhan F.
Wada, Shogo
Rowe, Glenn C.
Liu, Laura
Chan, Mun Chun
Rhee, James
Hoshino, Atsushi
Kim, Boa
Ibrahim, Ayon
Baca, Luisa G.
Kim, Esl
Ghosh, Chandra C.
Parikh, Samir M.
Jiang, Aihua
Chu, Qingwei
Forman, Daniel E.
Lecker, Stewart H.
Krishnaiah, Saikumari
Rabinowitz, Joshua D.
Weljie, Aalim M.
Baur, Joseph A.
Kasper, Dennis L.
Arany, Zoltan
TI A branched-chain amino acid metabolite drives vascular fatty acid
transport and causes insulin resistance
SO NATURE MEDICINE
LA English
DT Article
ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; SKELETAL-MUSCLE; IN-VIVO;
EXPRESSION; CAPACITY; DISEASE; FIBERS; PLASMA; RISK
AB Epidemiological and experimental data implicate branched-chain amino acids (BCAAs) in the development of insulin resistance, but the mechanisms that underlie this link remain unclear(1-3). Insulin resistance in skeletal muscle stems from the excess accumulation of lipid species(4), a process that requires blood-borne lipids to initially traverse the blood vessel wall. How this trans-endothelial transport occurs and how it is regulated are not well understood. Here we leveraged PPARGC1a (also known as PGC-1 alpha; encoded by Ppargc1a), a transcriptional coactivator that regulates broad programs of fatty acid consumption, to identify 3-hydroxyisobutyrate (3-HIB), a catabolic intermediate of the BCAA valine, as a new paracrine regulator of trans-endothelial fatty acid transport. We found that 3-HIB is secreted from muscle cells, activates endothelial fatty acid transport, stimulates muscle fatty acid uptake in vivo and promotes lipid accumulation in muscle, leading to insulin resistance in mice. Conversely, inhibiting the synthesis of 3-HIB in muscle cells blocks the ability of PGC-1 alpha to promote endothelial fatty acid uptake. 3-HIB levels are elevated in muscle from db/db mice with diabetes and from human subjects with diabetes, as compared to those without diabetes. These data unveil a mechanism in which the metabolite 3-HIB, by regulating the trans-endothelial flux of fatty acids, links the regulation of fatty acid flux to BCAA catabolism, providing a mechanistic explanation for how increased BCAA catabolic flux can cause diabetes.
C1 [Jang, Cholsoon; Wada, Shogo; Hoshino, Atsushi; Kim, Boa; Ibrahim, Ayon; Chu, Qingwei; Krishnaiah, Saikumari; Weljie, Aalim M.; Baur, Joseph A.; Arany, Zoltan] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Jang, Cholsoon; Rowe, Glenn C.; Liu, Laura; Chan, Mun Chun; Rhee, James; Baca, Luisa G.; Kim, Esl; Ghosh, Chandra C.; Parikh, Samir M.; Jiang, Aihua; Lecker, Stewart H.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA.
[Oh, Sungwhan F.; Kasper, Dennis L.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Rhee, James] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA.
[Forman, Daniel E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Rabinowitz, Joshua D.] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
[Rowe, Glenn C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
RP Arany, Z (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM zarany@mail.med.upenn.edu
RI Krishnaiah, Saikumari/I-7140-2016;
OI Rowe, Glenn/0000-0002-8195-9605
FU Lotte Scholarship; American Heart Association (AHA); Crohn's and Colitis
Foundation of America (Research Fellowship Award); Toyobo Biotechnology
Foundation; US National Institute of Arthritis and Musculoskeletal and
Skin Diseases [AR062128]; US National Institutes of Health [5 T32
GM7592-35]; US National Heart, Lung, and Blood Institute (NHLBI)
[HL093234, HL125275]; US National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK) [DK095072]; NIDDK [DK098656, DK049210];
NHLBI [HL094499]; AHA; Geis Realty Group Emerging Initiatives Fund
FX Human endothelial colony forming cells (ECFCs) were kindly provided by
J. Bischoff (Boston Children's Hospital). Fatp4-/- and
Cd36-/- mice were kindly provided by J. Miner (Washington
University School of Medicine) and J. Lawler (Harvard Medical School),
respectively. Flt1flox/flox and Kdrflox/flox mice
were kindly provided by Genentech. C.J. is supported by the Lotte
Scholarship and American Heart Association (AHA). S.F.O. is supported by
the Crohn's and Colitis Foundation of America (Research Fellowship
Award). S.W. is supported by the Toyobo Biotechnology Foundation. G.C.R.
is supported by the US National Institute of Arthritis and
Musculoskeletal and Skin Diseases (AR062128). J.R. is supported by the
US National Institutes of Health (5 T32 GM7592-35). S.M.P. is supported
by the US National Heart, Lung, and Blood Institute (NHLBI) (HL093234;
HL125275) and the US National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK) (DK095072). Q.C. and J.A.B. are supported by the
NIDDK (DK098656; DK049210). Z.A. is supported by the NHLBI (HL094499),
the AHA and the Geis Realty Group Emerging Initiatives Fund and Dean and
Ann Geis.
NR 25
TC 17
Z9 17
U1 15
U2 32
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 APR
PY 2016
VL 22
IS 4
BP 421
EP +
DI 10.1038/nm.4057
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA DI4GF
UT WOS:000373457700018
PM 26950361
ER
PT J
AU Baumann, M
Krause, M
Overgaard, J
Debus, J
Bentzen, SM
Daartz, J
Richter, C
Zips, D
Bortfeld, T
AF Baumann, Michael
Krause, Mechthild
Overgaard, Jens
Debus, Juergen
Bentzen, Soren M.
Daartz, Juliane
Richter, Christian
Zips, Daniel
Bortfeld, Thomas
TI Radiation oncology in the era of precision medicine
SO NATURE REVIEWS CANCER
LA English
DT Review
ID SQUAMOUS-CELL CARCINOMA; RELATIVE BIOLOGICAL EFFECTIVENESS;
INTENSITY-MODULATED RADIOTHERAPY; RANDOMIZED CONTROLLED-TRIAL;
GENOME-WIDE ASSOCIATION; GROWTH-FACTOR RECEPTOR; DOUBLE-STRAND BREAKS;
NECK-CANCER PATIENTS; LOCAL TUMOR-CONTROL; 3-DIMENSIONAL CONFORMAL
RADIOTHERAPY
AB Technological advances and clinical research over the past few decades have given radiation oncologists the capability to personalize treatments for accurate delivery of radiation dose based on clinical parameters and anatomical information. Eradication of gross and microscopic tumours with preservation of health-related quality of life can be achieved in many patients. Two major strategies, acting synergistically, will enable further widening of the therapeutic window of radiation oncology in the era of precision medicine: technology-driven improvement of treatment conformity, including advanced image guidance and particle therapy, and novel biological concepts for personalized treatment, including biomarker-guided prescription, combined treatment modalities and adaptation of treatment during its course.
C1 [Baumann, Michael; Krause, Mechthild; Richter, Christian] Tech Univ Dresden, Fac Med, Dept Radiat Oncol, D-01307 Dresden, Germany.
[Baumann, Michael; Krause, Mechthild; Richter, Christian] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Fetscherstr 74, D-01307 Dresden, Germany.
[Baumann, Michael; Krause, Mechthild; Richter, Christian] Tech Univ Dresden, Fac Med, Natl Ctr Radiat Res Oncol NCRO, OncoRay, Fetscherstr 74, D-01307 Dresden, Germany.
[Baumann, Michael; Krause, Mechthild; Richter, Christian] Helmholtz Zentrum Dresden Rossendorf, Fetscherstr 74, D-01307 Dresden, Germany.
[Baumann, Michael; Krause, Mechthild; Richter, Christian] Natl Ctr Tumor Dis NCT, Fetscherstr 74, D-01307 Dresden, Germany.
[Baumann, Michael; Krause, Mechthild; Richter, Christian] German Canc Consortium DKTK, Dresden, Germany.
[Baumann, Michael; Krause, Mechthild; Debus, Juergen; Richter, Christian; Zips, Daniel] German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
[Baumann, Michael; Krause, Mechthild] Helmholtz Zentrum Dresden Rossendorf, Inst Radiat Oncol, Bautzner Landstr 400, D-01328 Dresden, Germany.
[Overgaard, Jens] Aarhus Univ Hosp, Dept Expt Clin Oncol, Norrebrogade 44, DK-8000 Aarhus C, Denmark.
[Debus, Juergen] Heidelberg Univ, Sch Med, Natl Ctr Radiat Res Oncol NCRO, HIRO, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
[Debus, Juergen] Natl Ctr Tumor Dis NCT, Neuenheimer Feld 460, D-69120 Heidelberg, Germany.
[Debus, Juergen] Heidelberg Univ, Sch Med, Dept Radiat Oncol, Heidelberg Ion Therapy Ctr HIT, Neuenheimer Feld 400, D-69120 Heidelberg, Germany.
[Debus, Juergen] German Canc Consortium DKTK, Heidelberg, Germany.
[Bentzen, Soren M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, 22 S Greene St S9a03, Baltimore, MD 21201 USA.
[Bentzen, Soren M.] Univ Maryland, Sch Med, Greenebaum Canc Ctr, 22 S Greene St S9a03, Baltimore, MD 21201 USA.
[Daartz, Juliane; Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Div Phys, 1000 Blossom St Cox 362, Boston, MA 02114 USA.
[Daartz, Juliane; Bortfeld, Thomas] Harvard Univ, Sch Med, 1000 Blossom St Cox 362, Boston, MA 02114 USA.
[Zips, Daniel] German Canc Consortium Tubingen, Postfach 2669, D-72016 Tubingen, Germany.
[Zips, Daniel] Univ Tubingen, Fac Med, Dept Radiat Oncol, Hoppe Seyler Str 3, D-72016 Tubingen, Germany.
[Zips, Daniel] Univ Tubingen, Univ Hosp Tubingen, Hoppe Seyler Str 3, D-72016 Tubingen, Germany.
RP Baumann, M (reprint author), Tech Univ Dresden, Fac Med, Dept Radiat Oncol, D-01307 Dresden, Germany.; Baumann, M (reprint author), Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Fetscherstr 74, D-01307 Dresden, Germany.; Baumann, M (reprint author), Tech Univ Dresden, Fac Med, Natl Ctr Radiat Res Oncol NCRO, OncoRay, Fetscherstr 74, D-01307 Dresden, Germany.; Baumann, M (reprint author), Helmholtz Zentrum Dresden Rossendorf, Fetscherstr 74, D-01307 Dresden, Germany.; Baumann, M (reprint author), Natl Ctr Tumor Dis NCT, Fetscherstr 74, D-01307 Dresden, Germany.; Baumann, M (reprint author), German Canc Consortium DKTK, Dresden, Germany.; Baumann, M (reprint author), German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.; Baumann, M (reprint author), Helmholtz Zentrum Dresden Rossendorf, Inst Radiat Oncol, Bautzner Landstr 400, D-01328 Dresden, Germany.
EM michael.baumann@uniklinikum-dresden.de
RI Bentzen, Soren/E-3997-2012
OI Bentzen, Soren/0000-0002-7444-7564
NR 227
TC 15
Z9 15
U1 6
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
EI 1474-1768
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD APR
PY 2016
VL 16
IS 4
BP 234
EP 249
DI 10.1038/nrc.2016.18
PG 16
WC Oncology
SC Oncology
GA DH5AI
UT WOS:000372796700006
PM 27009394
ER
PT J
AU Bates, SE
Fojo, T
AF Bates, Susan E.
Fojo, Tito
TI New drug for pancreatic cancer highlights the dual effect of regulatory
approvals
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID PACLITAXEL PLUS GEMCITABINE; FOLFIRINOX; TRIALS
AB The recent FDA approval of MM-398 as a second-line treatment of metastatic pancreatic cancer, based on a 1.9-month overall survival benefit observed in the NAPOLI-1 trial, adds a new therapeutic option for this notoriously difficult-to-treat disease; however, by discouraging clinical trial enrolment, this approval might have negative consequences for the development of novel agents, which remain an essential unmet need.
C1 [Bates, Susan E.; Fojo, Tito] Columbia Univ, Med Ctr, Dept Med, Div Hematol Oncol, Herbert Irving Pavil,9th Floor, New York, NY 10032 USA.
[Bates, Susan E.; Fojo, Tito] James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA.
RP Bates, SE (reprint author), Columbia Univ, Med Ctr, Dept Med, Div Hematol Oncol, Herbert Irving Pavil,9th Floor, New York, NY 10032 USA.; Bates, SE (reprint author), James J Peters VA Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA.
EM seb2227@cumc.columbia.edu
NR 9
TC 0
Z9 0
U1 7
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD APR
PY 2016
VL 13
IS 4
BP 205
EP 206
DI 10.1038/nrclinonc.2016.22
PG 2
WC Oncology
SC Oncology
GA DH4DF
UT WOS:000372735000002
PM 26902963
ER
PT J
AU Banks, WA
AF Banks, William A.
TI From blood-brain barrier to blood-brain interface: new opportunities for
CNS drug delivery
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Review
ID AMYLOID-BETA-PROTEIN; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE
ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS;
MICROVASCULAR ENDOTHELIAL-CELLS; RECEPTOR-RELATED PROTEIN-1;
CEREBRAL-ARTERY OCCLUSION; NECROSIS-FACTOR-ALPHA; SPINAL-CORD BARRIER;
ALZHEIMERS-DISEASE
AB One of the biggest challenges in the development of therapeutics for central nervous system (CNS) disorders is achieving sufficient blood-brain barrier (BBB) penetration. Research in the past few decades has revealed that the BBB is not only a substantial barrier for drug delivery to the CNS but also a complex, dynamic interface that adapts to the needs of the CNS, responds to physiological changes, and is affected by and can even promote disease. This complexity confounds simple strategies for drug delivery to the CNS, but provides a wealth of opportunities and approaches for drug development. Here, I review some of the most important areas that have recently redefined the BBB and discuss how they can be applied to the development of CNS therapeutics.
C1 [Banks, William A.] Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA.
[Banks, William A.] Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, 1660 S Columbian Way, Seattle, WA 98108 USA.
RP Banks, WA (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA.; Banks, WA (reprint author), Univ Washington, Sch Med, Dept Med, Div Gerontol & Geriatr Med, 1660 S Columbian Way, Seattle, WA 98108 USA.
EM wabanks1@uw.edu
FU US Department of Veterans Affairs; US National Institute on Aging [R01
AG046619]
FX The author is supported by the US Department of Veterans Affairs and a
grant from the US National Institute on Aging (grant R01 AG046619).
NR 174
TC 18
Z9 18
U1 15
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD APR
PY 2016
VL 15
IS 4
BP 275
EP +
DI 10.1038/nrd.2015.21
PG 18
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA DI0ZM
UT WOS:000373225800017
PM 26794270
ER
PT J
AU McCarthy, MS
Warren, M
Roberts, PR
AF McCarthy, Mary S.
Warren, Malissa
Roberts, Pamela R.
TI Recent Critical Care Nutrition Trials and the Revised Guidelines: Do
They Reconcile?
SO NUTRITION IN CLINICAL PRACTICE
LA English
DT Editorial Material
ID SUPPLEMENTAL PARENTERAL-NUTRITION; IMMUNE-MODULATING NUTRIENTS; OIL
LIPID EMULSIONS; ILL PATIENT SOCIETY; ACUTE LUNG INJURY; CLINICAL-TRIAL;
GASTROINTESTINAL SURGERY; ENTERAL NUTRITION; RANDOMIZED-TRIAL;
NOSOCOMIAL INFECTIONS
C1 [McCarthy, Mary S.] Madigan Army Med Ctr, Ctr Nursing Sci & Clin Inquiry, 9040 Jackson Ave, Tacoma, WA 98431 USA.
[Warren, Malissa] Portland VA Med Ctr, Portland, OR USA.
[Roberts, Pamela R.] Univ Oklahoma, Coll Med, Dept Anesthesiol, Oklahoma City, OK 73190 USA.
RP McCarthy, MS (reprint author), Madigan Army Med Ctr, Ctr Nursing Sci & Clin Inquiry, 9040 Jackson Ave, Tacoma, WA 98431 USA.
EM Mary.s.mccarthy1.civ@mail.mil
NR 34
TC 1
Z9 1
U1 2
U2 2
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0884-5336
EI 1941-2452
J9 NUTR CLIN PRACT
JI Nutr. Clin. Pract.
PD APR
PY 2016
VL 31
IS 2
BP 150
EP 154
DI 10.1177/0884533616630301
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DH6LS
UT WOS:000372902700002
PM 26915509
ER
PT J
AU Curtis, CS
Busch, RA
Crass, RL
Webb, AP
Kudsk, KA
AF Curtis, Caitlin S.
Busch, Rebecca A.
Crass, Ryan L.
Webb, Aaron P.
Kudsk, Kenneth A.
TI Use of Premixed Parenteral Nutrition During a Phosphate Shortage in a
Non-Critically Ill Population
SO NUTRITION IN CLINICAL PRACTICE
LA English
DT Article
DE parenteral nutrition; nutritional support; dietary phosphorus;
phosphates
ID DRUG SHORTAGES; IMPACT
AB Background: Drug shortages pose prescribing problems to clinicians. During fiscal year (FY) 2014, an acute shortage of intravenous potassium phosphate (K-Phos IV), a common supplement in parenteral nutrition (PN), prompted the use of premixed instead of individualized PN to conserve K-Phos IV. Here we quantify the K-Phos IV conserved by using premixed PN and the associated cost differences. Materials and Methods: Costs of preparing premixed PN vs individualized PN of equivalent composition were calculated for FY 2014 at a single-center tertiary care facility. Quantity and cost of K-Phos IV saved were calculated based on the number of premixed PN prescriptions. Costs for FY 2015 were projected based on drug costs from July 2014. Results: During FY 2014, prescribing premixed in lieu of individualized PN conserved 16,440 mmol K-Phos IV but increased the cost of PN by $4080.45. However, increases in K-Phos IV cost at the end of FY 2014 resulted in premixed PN as a relatively less expensive therapy than individualized PN for our institution. Cost savings of $7092.20 due to use of premixed PN is projected for FY 2015. Conclusions: Prescribing premixed PN conserves K-Phos IV during shortages, but it increased direct drug spending in non-critically ill patients at our institution during FY 2014. Persistent shortages can drive market costs of K-Phos IV, however, necessitating frequent reconsideration of resource utilization.
C1 [Kudsk, Kenneth A.] William S Middleton Mem Vet Adm Med Ctr, Veteran Adm Surg Serv, Madison, WI USA.
[Curtis, Caitlin S.; Webb, Aaron P.] Univ Wisconsin Hosp & Clin, Dept Pharm, Madison, WI 53792 USA.
[Busch, Rebecca A.; Kudsk, Kenneth A.] Univ Wisconsin, Sch Med & Publ Hlth, Dept Surg, Madison, WI USA.
[Crass, Ryan L.] Univ Wisconsin, Sch Pharm, 425 N Charter St, Madison, WI 53706 USA.
RP Kudsk, KA (reprint author), G5 341 Clin Sci Ctr, 600 Highland Ave, Madison, WI 53792 USA.
EM kudsk@surgery.wisc.edu
FU Surgical Oncology Research Training Program [T32 CA090217]; William S.
Middleton Memorial Veterans Hospital, Madison, Wisconsin
FX This material is the result of work supported with the resources and use
of facilities at the William S. Middleton Memorial Veterans Hospital,
Madison, Wisconsin. The contents of this article do not represent the
views of the Department of Veterans Affairs or the United States
government. The project described was supported in part by the Surgical
Oncology Research Training Program T32 CA090217.
NR 9
TC 0
Z9 0
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0884-5336
EI 1941-2452
J9 NUTR CLIN PRACT
JI Nutr. Clin. Pract.
PD APR
PY 2016
VL 31
IS 2
BP 218
EP 222
DI 10.1177/0884533615583093
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA DH6LS
UT WOS:000372902700012
PM 25896971
ER
PT J
AU Holland, CL
Rubio, D
Rodriguez, KL
Kraemer, KL
Day, N
Arnold, RM
Tarr, JA
Chang, JC
AF Holland, Cynthia L.
Rubio, Doris
Rodriguez, Keri L.
Kraemer, Kevin L.
Day, Nancy
Arnold, Robert M.
Tarr, Jill A.
Chang, Judy C.
TI Obstetric Health Care Providers' Counseling Responses to Pregnant
Patient Disclosures of Marijuana Use
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article; Proceedings Paper
CT International Conference on Communication in Healthcare
CY OCT 25-28, 2015
CL New Orleans, LA
ID EXPOSURE; ATTENTION; BEHAVIOR; ALCOHOL; ABUSE; DRUG; AGE
AB OBJECTIVE:
To describe obstetric health care providers' responses and counseling approaches to patients' disclosures of marijuana use during first prenatal visits.
METHODS:
We performed a content analysis of audio-recorded patient-health care provider first prenatal visits for obstetrics health care providers' responses to patients' disclosure of marijuana use. The study was conducted at five urban outpatient clinics located in Pittsburgh, Pennsylvania.
RESULTS:
Among 468 audio-recorded first obstetric encounters, 90 patients (19%) disclosed marijuana use to 47 health care providers; mean number of recoded encounters containing marijuana disclosures for participating health providers was 1.8 +/- 1.4. In 48% of these 90 visits, obstetric health care providers did not respond to marijuana use disclosures or offer counseling. When counseling was offered, it consisted of general statements without specific information on the risks or outcomes related to marijuana use in pregnancy, discussions regarding the need for urine toxicology testing, and warnings that use detected at the time of delivery would initiate child protective services involvement.
CONCLUSION:
Obstetric health care provider responses to disclosure of marijuana use occurred in approximately half of patient encounters when marijuana use was disclosed and focused on legal and procedural consequences with less focus on health or medical implications. Our results suggest a need for health care provider training on potential consequences of perinatal marijuana use and communication skills for counseling patients about perinatal marijuana.
C1 Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
Univ Pittsburgh, Dept Internal Med, Ctr Res Hlth Care, Div Gen Internal Med,Clin & Translat Sci Inst, Pittsburgh, PA USA.
Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA.
Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
Ctr Res Hlth Care, Inst Enhance Palliat Care, Sect Palliat Care & Med Eth, Inst Doctor Patient Commun, Pittsburgh, PA USA.
RP Chang, JC (reprint author), 300 Halket St, Pittsburgh, PA 15213 USA.
EM jchang@mail.magee.edu
RI Day, Nancy/H-3171-2016
FU NCATS NIH HHS [UL1 TR000005, UL1TR000005]; NIDA NIH HHS
[1R01DA026410-01A1, R01 DA026410]
NR 24
TC 2
Z9 2
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD APR
PY 2016
VL 127
IS 4
BP 681
EP 687
DI 10.1097/AOG.0000000000001343
PG 7
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DH4YF
UT WOS:000372791000009
PM 26959210
ER
PT J
AU Tracy, EE
Bortoletto, P
AF Tracy, Erin E.
Bortoletto, Pietro
TI The Role of Social Networks, Medical-Legal Climate, and Patient Advocacy
on Surgical Options A New Era
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Article
ID ESSURE; STERILIZATION; MESH
AB The dissemination of information online and resultant public discourse through social media and other online channels has influenced the practice of medicine in dramatic ways. Physicians have historically worked to develop new techniques and devices for the benefit of their patients. It is only a more recent phenomenon, however, that these tools are either removed or their use is curtailed largely driven by anecdotal reports; passionate, vocal, often media-savvy advocates; and plaintiff attorneys. The use of power morcellation, hysteroscopic tubal sterilization, and mesh in urogynecologic procedures all have been victims of these societal pressures. It is important for health care professionals to be involved in the debate to ensure that public outcry does not unduly influence what we, as clinicians, are able to safely offer our patients. By being better advocates for our field, our instruments, and our patients, we can ensure medical decision-making is driven by good science and not public fervor.
C1 [Tracy, Erin E.; Bortoletto, Pietro] Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 55 Fruit St,406 Founders House, Boston, MA 02114 USA.
RP Bortoletto, P (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol, 55 Fruit St,406 Founders House, Boston, MA 02114 USA.
EM pbortoletto@partners.org
NR 23
TC 3
Z9 3
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD APR
PY 2016
VL 127
IS 4
BP 758
EP 762
DI 10.1097/AOG.0000000000001335
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DH4YU
UT WOS:000372792600003
PM 26959205
ER
PT J
AU Schorge, JO
AF Schorge, John O.
TI What Is New in Prevention of Ovarian Cancer? Best Articles From the Past
Year
SO OBSTETRICS AND GYNECOLOGY
LA English
DT Editorial Material
AB This month we focus on current research in preventing ovarian cancer. Dr. Schorge discusses four recent publications, which are concluded with a bottom line that is the take-home message. The complete reference for each can be found in Box 1 on this page, along with direct links to the abstracts.
C1 [Schorge, John O.] Massachusetts Gen Hosp, Dept OB GYN Gynecol Oncol, Boston, MA 02114 USA.
RP Schorge, JO (reprint author), Massachusetts Gen Hosp, Dept OB GYN Gynecol Oncol, Boston, MA 02114 USA.
EM jschorge@partners.org
NR 2
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7844
J9 OBSTET GYNECOL
JI Obstet. Gynecol.
PD APR
PY 2016
VL 127
IS 4
BP 795
EP 796
DI 10.1097/AOG.0000000000001380
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA DH4ZC
UT WOS:000372793500004
PM 26959218
ER
PT J
AU McCarrier, KP
Deal, LS
Abraham, L
Blum, SI
Bush, EN
Martin, ML
Thase, ME
Coons, SJ
AF McCarrier, Kelly P.
Deal, Linda S.
Abraham, Lucy
Blum, Steven I.
Bush, Elizabeth Nicole
Martin, Mona L.
Thase, Michael E.
Coons, Stephen Joel
CA PRO Consortium's Depression Workin
TI Patient-Centered Research to Support the Development of the Symptoms of
Major Depressive Disorder Scale (SMDDS): Initial Qualitative Research
SO PATIENT-PATIENT CENTERED OUTCOMES RESEARCH
LA English
DT Article
ID OUTCOMES PRO INSTRUMENTS; INTERRATER RELIABILITY; RATING-SCALE;
SELF-REPORT; MELANCHOLIA; VALIDATION; SEVERITY
AB Content valid, patient-reported outcome (PRO) measures of major depressive disorder (MDD) symptoms are needed to assess MDD treatment benefit. While a range of questionnaires are currently available to evaluate aspects of depression from the patient's perspective, their comprehensiveness and qualitative development histories are unclear.
The objective of this study was to describe the process and results of the preliminary qualitative development of a new symptom-based PRO measure intended to assess treatment benefit in MDD clinical trials.
Qualitative interviews were conducted with adult MDD patients in the USA who recently experienced a major depressive episode. Experienced interviewers conducted concept elicitation (CE) and cognitive interviews using semi-structured interview guides. The CE interview guide was used to elicit spontaneous reports of symptom experiences along with probing to further explore and confirm concepts. The cognitive interview guide was developed to evaluate concept relevance, understandability, and structure of the draft items, and to facilitate further instrument refinement.
Forty patients participated in the CE interviews. A total of 3022 symptom codes, representing 84 different concepts were derived from the transcripts. Data from the CE interviews were considered alongside existing literature and clinical expert opinion during an item-generation process, leading to development of a preliminary version of the Symptoms of Major Depressive Disorder Scale (SMDDS). Fifteen patients participated in three waves of cognitive interviews, during which the SMDDS was further refined.
The SMDDS is a 35-item PRO measure intended for use as an endpoint in MDD clinical trials to support medical product labeling. The SMDDS uses a 7-day recall period and verbal rating scales. It was developed in accordance with the US Food and Drug Administration (FDA)'s PRO Guidance and best practices. Qualitative interviews have provided evidence for content validity. Future quantitative studies will confirm the SMDDS's measurement properties and support FDA qualification.
C1 [McCarrier, Kelly P.; Martin, Mona L.] Hlth Res Associates Inc, 6505 216th St SW Suite 105, Mountlake Terrace, WA 98043 USA.
[Deal, Linda S.] Shire, Clin Outcomes Assessment, Wayne, PA USA.
[Abraham, Lucy] Pfizer Ltd, Outcomes & Evidence, Tadworth, Surrey, England.
[Blum, Steven I.] GlaxoSmithKline, Patient Reported Outcomes, King Of Prussia, PA USA.
[Bush, Elizabeth Nicole] Eli Lilly & Co, PRO Ctr Expertise, Indianapolis, IN 46285 USA.
[Thase, Michael E.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Thase, Michael E.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
[Coons, Stephen Joel] Crit Path Inst, Patient Reported Outcome Consortium, Tucson, AZ USA.
RP McCarrier, KP (reprint author), Hlth Res Associates Inc, 6505 216th St SW Suite 105, Mountlake Terrace, WA 98043 USA.
EM mccarrier@hrainc.net
FU AbbVie; Bristol-Myers Squibb; Eli Lilly and Company; Forest Research
Institute; Janssen; Pfizer; Roche Products Limited; Shire; Sunovion;
Takeda; United States Food and Drug Administration [U01FD003865]
FX This research was funded by the following members of the PRO Consortium:
AbbVie, Bristol-Myers Squibb, Eli Lilly and Company, Forest Research
Institute, Janssen, Pfizer, Roche Products Limited, Shire, Sunovion, and
Takeda. The PRO Consortium receives support through Grant U01FD003865
from the United States Food and Drug Administration to the Critical Path
Institute.
NR 28
TC 1
Z9 1
U1 0
U2 1
PU ADIS INT LTD
PI NORTHCOTE
PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND
SN 1178-1653
EI 1178-1661
J9 PATIENT
JI Patient
PD APR
PY 2016
VL 9
IS 2
BP 117
EP 134
DI 10.1007/s40271-015-0132-1
PG 18
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA DH6EL
UT WOS:000372883700003
PM 26113249
ER
PT J
AU Rowan, CM
Gertz, SJ
McArthur, J
Fitzgerald, JC
Nitu, ME
Loomis, A
Hsing, DD
Duncan, CN
Mahadeo, KM
Smith, LS
Moffet, J
Hall, MW
Pinos, EL
Cheifetz, IM
Tamburro, RF
AF Rowan, Courtney M.
Gertz, Shira J.
McArthur, Jennifer
Fitzgerald, Julie C.
Nitu, Mara E.
Loomis, Ashley
Hsing, Deyin D.
Duncan, Christine N.
Mahadeo, Kris M.
Smith, Lincoln S.
Moffet, Jerelyn
Hall, Mark W.
Pinos, Emily L.
Cheifetz, Ira M.
Tamburro, Robert F.
CA Investigators Pediat Acute Lung In
TI Invasive Mechanical Ventilation and Mortality in Pediatric Hematopoietic
Stem Cell Transplantation: A Multicenter Study*
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE critical care; hematopoietic stem cell transplantation; respiratory
insufficiency; artificial respiration; mortality
ID RESPIRATORY-DISTRESS-SYNDROME; BONE-MARROW-TRANSPLANTATION; ACUTE LUNG
INJURY; FREQUENCY OSCILLATORY VENTILATION; RENAL REPLACEMENT THERAPY;
REQUIRING INTENSIVE-CARE; CRITICALLY-ILL CHILDREN; INHALED NITRIC-OXIDE;
PERMISSIVE HYPOXEMIA; FLUID OVERLOAD
AB Objective:
To establish the current respiratory practice patterns in pediatric hematopoietic stem cell transplant patients and investigate their associations with mortality across multiple centers.
Design:
Retrospective cohort between 2009 and 2014.
Setting:
Twelve children's hospitals in the United States.
Patients:
Two hundred twenty-two pediatric allogeneic hematopoietic stem cell transplant recipients with acute respiratory failure using invasive mechanical ventilation.
Interventions:
None.
Measurements and Main Results:
PICU mortality of our cohort was 60.4%. Mortality at 180 days post PICU discharge was 74%. Length of PICU stay prior to initiation of invasive mechanical ventilation was significantly lower in survivors, and the odds of mortality increased for longer length of PICU stay prior to intubation. A total of 91 patients (41%) received noninvasive ventilation at some point during their PICU stay prior to intubation. Noninvasive ventilation use preintubation was associated with increased mortality (odds ratio, 2.1; 95% CI, 1.2-3.6; p = 0.010). Patients ventilated longer than 15 days had higher odds of death (odds ratio, 2.4; 95% CI, 1.3-4.2; p = 0.004). Almost 40% of patients (n = 85) were placed on high-frequency oscillatory ventilation with a mortality of 76.5% (odds ratio, 3.3; 95% CI, 1.7-6.5; p = 0.0004). Of the 20 patients who survived high-frequency oscillatory ventilation, 18 were placed on high-frequency oscillatory ventilation no later than the third day of invasive mechanical ventilation. In this subset of 85 patients, transition to high-frequency oscillatory ventilation within 2 days of the start of invasive mechanical ventilation resulted in a 76% decrease in the odds of death compared with those who transitioned to high-frequency oscillatory ventilation later in the invasive mechanical ventilation course.
Conclusions:
This study suggests that perhaps earlier more aggressive critical care interventions in the pediatric hematopoietic stem cell transplant patient with respiratory failure requiring invasive mechanical ventilation may offer an opportunity to improve outcomes.
C1 [Rowan, Courtney M.; Nitu, Mara E.] Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA.
[Gertz, Shira J.] Hackensack Univ, Med Ctr, Joseph M Sanzari Childrens Hosp, Dept Pediat, Hackensack, NJ USA.
[McArthur, Jennifer] Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
[Fitzgerald, Julie C.] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Dept Anesthesia, Philadelphia, PA 19104 USA.
[Loomis, Ashley] Univ Minnesota, Masonic Childrens Hosp, Dept Pediat, Minneapolis, MN USA.
[Hsing, Deyin D.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Pediat, New York, NY USA.
[Duncan, Christine N.] Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA.
[Mahadeo, Kris M.] Childrens Hosp Montefiore, Albert Einstein Coll Med, Dept Pediat, Bronx, NY USA.
[Smith, Lincoln S.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Smith, Lincoln S.] Seattle Childrens Hosp, Seattle, WA USA.
[Moffet, Jerelyn; Cheifetz, Ira M.] Duke Childrens Hosp, Dept Pediat, Durham, NC USA.
[Hall, Mark W.] Nationwide Childrens Hosp, Dept Pediat, Columbus, OH USA.
[Pinos, Emily L.; Tamburro, Robert F.] Penn State Univ, Coll Med, Penn State Hershey Childrens Hosp, Dept Pediat, Hershey, PA USA.
[Tamburro, Robert F.] Penn State Univ, Coll Med, Penn State Hershey Childrens Hosp, Dept Publ Hlth, Hershey, PA USA.
RP Rowan, CM (reprint author), Indiana Univ Sch Med, Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA.
EM coujohns@iu.edu
FU Riley Children's Foundation; NIH; Philips; CareFusion; Covidien;
Teleflex; Ikaria; U.S. FDA Office of Orphan Product Development
FX Dr. Rowan received grant support from the Riley Children's Foundation.
Dr. Gertz is employed by Hackensack University Medical Center. Her
institution received support for travel from Baxter Pharmaceuticals
(investigator start up meeting for ongoing clinical trial). Dr. Moffet
is employed by Duke University. Dr. Hall's institution received grant
support from the NIH (Dr. Hall is NIH-funded for work unrelated to this
project). Dr. Cheifetz consulted for Philips and Hill-Rom (Medical
Advisor) and provided expert testimony for various entities. His
institution received grant support from Philips, CareFusion, Covidien,
Teleflex, and Ikaria. Dr. Tamburro received royalties from
Verlag-Springer (textbook and study guide that he helped prepare as an
associate editor). His institution received grant support (Dr. Tamburro
received a grant from the U.S. FDA Office of Orphan Product Development
to study the use of exogenous surfactant [calfactant] in pediatric
hematopoietic stem cell transplant patients with acute lung injury. The
medication for the trial was donated by the manufacturer [Ony, LLC]).
The remaining authors have disclosed that they do not have any potential
conflicts of interest.
NR 39
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Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1529-7535
EI 1947-3893
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD APR
PY 2016
VL 17
IS 4
BP 294
EP 302
DI 10.1097/PCC.0000000000000673
PG 9
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA DI0UA
UT WOS:000373211600003
PM 26910477
ER
PT J
AU Berg, AT
Baca, CB
Rychlik, K
Vickrey, BG
Caplan, R
Testa, FM
Levy, SR
AF Berg, Anne T.
Baca, Christine B.
Rychlik, Karen
Vickrey, Barbara G.
Caplan, Rochelle
Testa, Francine M.
Levy, Susan R.
TI Determinants of Social Outcomes in Adults With Childhood-onset Epilepsy
SO PEDIATRICS
LA English
DT Article
ID LONG-TERM PROGNOSIS; ABSENCE EPILEPSY; 2 DECADES; CHILDREN; SEIZURES;
DIAGNOSIS; BEHAVIOR; DUTCH; LIFE
AB BACKGROUND: Adults with childhood-onset epilepsy experience poorer adult social outcomes than their peers. The relative roles of seizures over time versus learning and psychiatric problems are unclear.
METHODS: We examined independent influences of psychiatric and learning disorders and of seizure course in 241 young adults (22-35 years old) with uncomplicated epilepsy in a longitudinal community-based cohort study. Social outcomes were ascertained throughout the study. A history of psychiatric and learning problems was ascertained similar to 9 years after study entry. Seizure course was: "Excellent," no seizures after the first year, in complete remission at last contact (N = 95, 39%); " Good, " seizures occurred 1 to 5 years after diagnosis, in complete remission at last contact (N = 56, 23%); " Fluctuating, " more complicated trajectories, but never pharmacoresistant (N = 70, 29%); " Pharmacoresistant, " long-term pharmacoresistant (N = 20, 8%). Multiple logistic regression was used to identify contributors to each social outcome.
RESULTS: Better seizure course predicted college completion, being either employed or pursuing a degree, and driving, but was not substantially associated with other social outcomes. Poorer seizure course was associated with a greater likelihood of having offspring, particularly in women without partners. Learning problems, psychiatric disorders, or both negatively influenced all but 2 of the social outcomes.
CONCLUSIONS: In young adults with uncomplicated epilepsy, the course of seizures contributed primarily to education, employment, and driving. A history of learning problems and psychiatric disorders adversely influenced most adult outcomes. These findings identify potential reasons for vocational and social difficulties encountered by young adults with childhood epilepsy and areas to target for counseling and transition planning.
C1 [Berg, Anne T.] Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Box 29,225 East Chicago Ave, Chicago, IL 60611 USA.
[Rychlik, Karen] Ann & Robert H Lurie Childrens Hosp Chicago, Stanley Manne Childrens Res Inst, Biostat Res Core, Chicago, IL 60611 USA.
[Berg, Anne T.] Northwestern Feinberg Sch Med, Dept Pediat, Chicago, IL USA.
[Baca, Christine B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Dept Neurol, Los Angeles, CA 90024 USA.
[Caplan, Rochelle] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Los Angeles, CA 90024 USA.
[Baca, Christine B.] VA Greater Los Angeles Hlth Care Syst, Dept Neurol, Los Angeles, CA USA.
[Vickrey, Barbara G.] Icahn Sch Med Mt Sinai, Dept Neurol, New York, NY 10029 USA.
[Testa, Francine M.; Levy, Susan R.] Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA.
[Testa, Francine M.; Levy, Susan R.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
RP Berg, AT (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Epilepsy Ctr, Box 29,225 East Chicago Ave, Chicago, IL 60611 USA.
EM atberg@luriechildrens.org
FU National Institute of Neurologic Disorders and Stroke [R37-NS31146];
National Institutes of Health (NIH)
FX This study was funded by grant R37-NS31146 from the National Institute
of Neurologic Disorders and Stroke. Funded by the National Institutes of
Health (NIH).
NR 37
TC 1
Z9 1
U1 1
U2 4
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 APR
PY 2016
VL 137
IS 4
AR e20153944
DI 10.1542/peds.2015-3944
PG 10
WC Pediatrics
SC Pediatrics
GA DI0OU
UT WOS:000373197500049
ER
PT J
AU Treister, NS
London, WB
Guo, DJ
Malsch, M
Verrill, K
Brewer, J
Margossian, S
Duncan, C
AF Treister, Nathaniel S.
London, Wendy B.
Guo, Dongjing
Malsch, Maggie
Verrill, Kelly
Brewer, Jennifer
Margossian, Steven
Duncan, Christine
TI A Feasibility Study Evaluating Extraoral Photobiomodulation Therapy for
Prevention of Mucositis in Pediatric Hematopoietic Cell Transplantation
SO PHOTOMEDICINE AND LASER SURGERY
LA English
DT Article
ID LEVEL LASER THERAPY; ORAL MUCOSITIS; CANCER; LLLT; METAANALYSIS; SCT
AB Objective: The objective of this study was to determine the feasibility, safety, and tolerability of providing extraoral photobiomodulation therapy (PBT) for prevention of oral mucositis (OM) in pediatric hematopoietic cell transplantation (HCT). Background data: OM is a frequent complication in pediatric HCT. Methods: Patients 4-21 years of age scheduled for myeloablative HCT were eligible to participate. PBT was delivered using a THOR Model LX2M with a 69 Diode LED Cluster Probe (34 x 660 nm 10 mW, 35 x 850 nm 30 mW; 1390 mW total power output) at an irradiance of 50 mW/cm(2). Daily treatment exposed six sites (right, left, and midline face and neck) for 60 sec each, for a total dose of 3.0 J/cm(2). Treatment was initiated on the 1st day of conditioning, through day +20. OM assessments were completed at baseline then daily, from day -1 through day +20. Feasibility assessment included both qualitative and quantitative measures and outcomes from patients and providers. Results: Thirteen patients with a median age of 15 years (range, 4.8-21.6) were consented and enrolled, and completed the protocol. The incidence of severe OM [World Health Organization (WHO) Grade >= 3] was 77%, with a median duration of 4 days (range, 1-14). Of 355 attempted PBT administrations, there were six refusals, and the mean proportion of days with data submitted was 96.2% [95% confidence interval (CI): 78.5-97.2%]. The 10 trained nurses all reported that the device was accessible, maneuverable, and lightweight, and that training was effective. There was no reported toxicity attributed to the PBT. Conclusions: Daily delivery of external PBT and completion of OM evaluations is feasible in children undergoing HCT.
C1 [Treister, Nathaniel S.; Brewer, Jennifer] Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA.
[Treister, Nathaniel S.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA.
[London, Wendy B.; Guo, Dongjing; Margossian, Steven; Duncan, Christine] Boston Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA USA.
[London, Wendy B.; Margossian, Steven; Duncan, Christine] Harvard Univ, Sch Med, Boston, MA USA.
[Malsch, Maggie; Verrill, Kelly] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA.
RP Treister, NS (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA.
EM ntreister@partners.org
NR 13
TC 0
Z9 0
U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1549-5418
EI 1557-8550
J9 PHOTOMED LASER SURG
JI Photomed. Laser Surg.
PD APR 1
PY 2016
VL 34
IS 4
BP 178
EP 184
DI 10.1089/pho.2015.4021
PG 7
WC Surgery
SC Surgery
GA DI1TD
UT WOS:000373277800007
PM 26982624
ER
PT J
AU Fleseriu, M
Pivonello, R
Young, J
Hamrahian, AH
Molitch, ME
Shimizu, C
Tanaka, T
Shimatsu, A
White, T
Hilliard, A
Tian, C
Sauter, N
Biller, BMK
Bertagna, X
AF Fleseriu, Maria
Pivonello, Rosario
Young, Jacques
Hamrahian, Amir H.
Molitch, Mark E.
Shimizu, Chikara
Tanaka, Tomoaki
Shimatsu, Akira
White, Tracy
Hilliard, Annie
Tian, Chuan
Sauter, Nicholas
Biller, Beverly M. K.
Bertagna, Xavier
TI Osilodrostat, a potent oral 11 beta-hydroxylase inhibitor: 22-week,
prospective, Phase II study in Cushing's disease
SO PITUITARY
LA English
DT Article
DE LCI699; Osilodrostat; 11 beta-hydroxylase; Cushing's; Cortisol
ID GLUCOCORTICOID-RECEPTOR ANTAGONIST; PROSPECTIVE MULTICENTER;
MEDICAL-MANAGEMENT; MIFEPRISTONE; PEGVISOMANT; THERAPY
AB In a 10-week proof-of-concept study (LINC 1), the potent oral 11 beta-hydroxylase inhibitor osilodrostat (LCI699) normalized urinary free cortisol (UFC) in 11/12 patients with Cushing's disease. The current 22-week study (LINC 2; NCT01331239) further evaluated osilodrostat in patients with Cushing's disease.
Phase II, open-label, prospective study of two patient cohorts. Follow-up cohort: 4/12 patients previously enrolled in LINC 1, offered re-enrollment if baseline mean UFC was above ULN. Expansion cohort: 15 newly enrolled patients with baseline UFC > 1.5 x ULN. In the follow-up cohort, patients initiated osilodrostat twice daily at the penultimate efficacious/tolerable dose in LINC 1; dose was adjusted as needed. In the expansion cohort, osilodrostat was initiated at 4 mg/day (10 mg/day if baseline UFC > 3 x ULN), with dose escalated every 2 weeks to 10, 20, 40, and 60 mg/day until UFC a parts per thousand currency sign ULN. Main efficacy endpoint was the proportion of responders (UFC a parts per thousand currency sign ULN or a parts per thousand yen50 % decrease from baseline) at weeks 10 and 22.
Overall response rate was 89.5 % (n/N = 17/19) at 10 weeks and 78.9 % (n/N = 15/19) at 22 weeks; at week 22, all responding patients had UFC a parts per thousand currency sign ULN. The most common AEs observed during osilodrostat treatment were nausea, diarrhea, asthenia, and adrenal insufficiency (n = 6 for each). New or worsening hirsutism (n = 2) and/or acne (n = 3) were reported among four female patients, all of whom had increased testosterone levels.
Osilodrostat treatment reduced UFC in all patients; 78.9 % (n/N = 15/19) had normal UFC at week 22. Treatment with osilodrostat was generally well tolerated.
C1 [Fleseriu, Maria] Oregon Hlth & Sci Univ, Dept Med, Northwest Pituitary Ctr, Portland, OR 97201 USA.
[Fleseriu, Maria] Oregon Hlth & Sci Univ, Dept Neurol Surg, Northwest Pituitary Ctr, Portland, OR 97201 USA.
[Pivonello, Rosario] Univ Naples Federico II, Dipartimento Med Clin & Chirurg, Sez Endocrinol, Naples, Italy.
[Young, Jacques] Univ Paris 11, Hop Bicetre, AP HP, Dept Endocrinol, Paris, France.
[Hamrahian, Amir H.] Cleveland Clin Fdn, Dept Diabet Endocrinol & Metab, 9500 Euclid Ave, Cleveland, OH 44195 USA.
[Molitch, Mark E.] Northwestern Univ, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA.
[Shimizu, Chikara] Hokkaido Univ Hosp, Div Lab & Transfus Med, Sapporo, Hokkaido 060, Japan.
[Tanaka, Tomoaki] Chiba Univ Hosp, Div Endocrinol & Metab, Chiba, Japan.
[Shimatsu, Akira] Natl Hosp Org, Kyoto Med Ctr, Clin Res Inst, Kyoto, Japan.
[White, Tracy; Hilliard, Annie; Tian, Chuan; Sauter, Nicholas] Novartis Pharmaceut, E Hanover, NJ USA.
[Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA.
[Bertagna, Xavier] Univ Paris 05, Hop Cochin, Ctr Reference Malad Rares Surrenale, Dept Endocrinol,Fac Med Paris Descartes, Paris, France.
RP Fleseriu, M (reprint author), Oregon Hlth & Sci Univ, Dept Med, Northwest Pituitary Ctr, Portland, OR 97201 USA.; Fleseriu, M (reprint author), Oregon Hlth & Sci Univ, Dept Neurol Surg, Northwest Pituitary Ctr, Portland, OR 97201 USA.
EM fleseriu@ohsu.edu
FU Novartis Pharma AG; Novartis Pharmaceuticals Corporation
FX This study was funded by Novartis Pharma AG. Financial support for
medical editorial assistance was provided by Novartis Pharmaceuticals
Corporation. We thank Peter Unge, Albert Kandra, and Michael Roughton
for their support with the development of this manuscript. We thank
Andrew Jones PhD for medical editorial assistance with this manuscript.
We thank the sub-investigators and the study coordinators/nurses
involved in this study, and give special thanks to the patients who made
this study possible.
NR 25
TC 4
Z9 4
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1386-341X
EI 1573-7403
J9 PITUITARY
JI Pituitary
PD APR
PY 2016
VL 19
IS 2
BP 138
EP 148
DI 10.1007/s11102-015-0692-z
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DH6WI
UT WOS:000372932400004
PM 26542280
ER
PT J
AU Green, JD
Jakupcak, M
AF Green, Jonathan D.
Jakupcak, Matthew
TI Masculinity and Men's Self-Harm Behaviors: Implications for Non-Suicidal
Self-Injury Disorder
SO PSYCHOLOGY OF MEN & MASCULINITY
LA English
DT Article
DE gender; masculinity; nonsuicidal self-injury disorder; self-harm;
self-injury
ID BORDERLINE PERSONALITY-DISORDER; COLLEGE POPULATION; SEX-DIFFERENCES;
MUTILATION; PSYCHOPATHOLOGY; ADOLESCENTS; AGGRESSION; INVENTORY;
THOUGHTS; FEATURES
AB A composite of clinical cases treated by the authors is presented to illustrate the complexity of understanding nonsuicidal self-harm as it occurs in men, particularly in the context of Non-Suicidal Self-Injury (NSSI) disorder, a condition for further study in the fifth edition of Diagnostic and Statistical Manual of Mental Disorders. As a function of adherence to masculine norms, intentionality, social acceptability, and functions of self-harm behaviors common among men do not appear to be in line with diagnostic criteria for NSSI disorder, despite these behaviors resulting in serious tissue damage worthy of clinical and research attention. Suggestions for novel approaches to the assessment and treatment of self-harm, particularly in light of men's difficulty identifying and discussing intentionality of self-harm behaviors, are presented along with specific recommendations clinical practice.
C1 [Green, Jonathan D.] VA Boston Healthcare Syst, 116B-4,150 South Huntington Ave, Boston, MA 02130 USA.
[Green, Jonathan D.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA.
[Jakupcak, Matthew] VA Puget Sound Healthcare Syst, Northwest Mental Illness Res Educ & Clin Ctr MIRE, Seattle, WA USA.
[Jakupcak, Matthew] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.
RP Green, JD (reprint author), VA Boston Healthcare Syst, 116B-4,150 South Huntington Ave, Boston, MA 02130 USA.
EM Green.JonathanD@gmail.com
NR 61
TC 1
Z9 1
U1 4
U2 8
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 1524-9220
EI 1939-151X
J9 PSYCHOL MEN MASCULIN
JI Psychol. Men Masculinity
PD APR
PY 2016
VL 17
IS 2
BP 147
EP 155
DI 10.1037/a0039691
PG 9
WC Psychology, Social
SC Psychology
GA DI0RJ
UT WOS:000373204400004
ER
PT J
AU Commissariat, PV
Kenowitz, JR
Trast, J
Heptulla, RA
Gonzalez, JS
AF Commissariat, Persis V.
Kenowitz, Joslyn R.
Trast, Jeniece
Heptulla, Rubina A.
Gonzalez, Jeffrey S.
TI Developing a Personal and Social Identity With Type 1 Diabetes During
Adolescence: A Hypothesis Generative Study
SO QUALITATIVE HEALTH RESEARCH
LA English
DT Article
DE diabetes; adolescents; youth; young adults; lived experience; health;
self; stigma; qualitative; thematic analysis; USA
ID SELF-CARE; METABOLIC-CONTROL; MELLITUS; ILLNESS; GENDER; ASSOCIATION;
SUPPORT; HEALTH; YOUTH; LIFE
AB This study explored the incorporation of type 1 diabetes mellitus (T1DM) into self-identity among adolescents. Guided interviews explored 40 adolescents' views of T1DM in relation to their sense of self and relationships with others. Responses were analyzed using thematic analysis. Results revealed that the entire sample described T1DM as a significant burden; many described how T1DM made them feel less normal. Adolescents described both positive and negative aspects of self-management in social relationships, though most reported benefits in sharing T1DM with friends. Females were more likely to share information about T1DM and to describe positive changes in self-perception as a result of T1DM. The psychosocial processes related to integration of T1DM into self-identity described in these qualitative data provide hypothesis-generating findings that can guide future quantitative research examining incorporation of T1DM into adolescent self-identity in relation to measures of self-esteem, peer orientation, self-management, and glycemic control.
C1 [Commissariat, Persis V.] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Kenowitz, Joslyn R.; Gonzalez, Jeffrey S.] Yeshiva Univ, Ferkauf Grad Sch Psychol, Bronx, NY USA.
[Heptulla, Rubina A.] Yeshiva Univ, Albert Einstein Coll Med, Pediat & Med, Bronx, NY USA.
[Trast, Jeniece; Heptulla, Rubina A.; Gonzalez, Jeffrey S.] Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA.
[Gonzalez, Jeffrey S.] Yeshiva Univ, Albert Einstein Coll Med, Diabet Res Ctr, 1300 Morris Pk Ave,Rousso Bldg, Bronx, NY 10461 USA.
RP Gonzalez, JS (reprint author), Yeshiva Univ, Albert Einstein Coll Med, Diabet Res Ctr, 1300 Morris Pk Ave,Rousso Bldg, Bronx, NY 10461 USA.
EM jeffrey.gonzalez@einstein.yu.edu
FU National Institutes of Health [P60 DK020541, R18 DK098742]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: Dr. Gonzalez's
time and effort were partially supported by Grants P60 DK020541 and R18
DK098742 from the National Institutes of Health.
NR 50
TC 0
Z9 0
U1 4
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1049-7323
EI 1552-7557
J9 QUAL HEALTH RES
JI Qual. Health Res.
PD APR
PY 2016
VL 26
IS 5
SI SI
BP 672
EP 684
DI 10.1177/1049732316628835
PG 13
WC Information Science & Library Science; Social Sciences,
Interdisciplinary; Social Sciences, Biomedical
SC Information Science & Library Science; Social Sciences - Other Topics;
Biomedical Social Sciences
GA DH5KE
UT WOS:000372825900008
PM 26893304
ER
PT J
AU Hong, JX
Zhong, TL
Li, HL
Xu, JM
Ye, XF
Mu, Z
Lu, Y
Mashaghi, A
Zhou, Y
Tan, MX
Li, QY
Sun, XH
Liu, ZG
Xu, JJ
AF Hong, Jiaxu
Zhong, Taoling
Li, Huili
Xu, Jianming
Ye, Xiaofang
Mu, Zhe
Lu, Yi
Mashaghi, Alireza
Zhou, Ying
Tan, Mengxi
Li, Qiyuan
Sun, Xinghuai
Liu, Zuguo
Xu, Jianjiang
TI Ambient air pollution, weather changes, and outpatient visits for
allergic conjunctivitis: A retrospective registry study
SO SCIENTIFIC REPORTS
LA English
DT Article
ID CLIMATE-CHANGE; PARTICULATE MATTER; ARMA MODEL; HEALTH; CHINA; SYMPTOMS;
CHILDREN; ASTHMA; PREVALENCE; EPITHELIUM
AB Allergic conjunctivitis is a common problem that significantly impairs patients' quality of life. Whether air pollution serves as a risk factor for the development of allergic conjunctivitis remains elusive. In this paper, we assess the relationship between air pollutants and weather conditions with outpatient visits for allergic conjunctivitis. By using a time-series analysis based on the largest dataset ever assembled to date, we found that the number of outpatient visits for allergic conjunctivitis was significantly correlated with the levels of NO2, O-3, and temperature, while its association with humidity was statistically marginal. No associations between PM10, PM2.5, SO2, or wind velocity and outpatient visits were seen. Subgroup analyses showed that sex seemed to modify the effects of humidity on outpatient visits for allergic conjunctivitis, but not for NO2, O-3, or temperature. People younger than 40 were found to be susceptible to changes of all four parameters, while those older than 40 were only consistently affected by NO2 levels. Our findings revealed that higher levels of ambient NO2, O-3, and temperature increase the chances of outpatient visits for allergic conjunctivitis. Ambient air pollution and weather changes may contribute to the worsening of allergic conjunctivitis.
C1 [Hong, Jiaxu; Lu, Yi; Sun, Xinghuai; Xu, Jianjiang] Fudan Univ, Shanghai Med Coll, Dept Ophthalmol & Visual Sci, Eye & ENT Hosp, 83 Rd Fenyang, Shanghai 200433, Peoples R China.
[Hong, Jiaxu; Zhong, Taoling; Li, Huili; Zhou, Ying; Li, Qiyuan; Liu, Zuguo] Xiamen Univ, Inst Eye, Rd Xiangan Nan, Xiamen, Peoples R China.
[Xu, Jianming; Ye, Xiaofang; Mu, Zhe] Shanghai Key Lab Meteorol & Hlth, 951 Rd Jinxiu, Shanghai, Peoples R China.
[Hong, Jiaxu; Mashaghi, Alireza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA.
[Sun, Xinghuai] Fudan Univ, Inst Brain Sci, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China.
[Sun, Xinghuai] Minist Hlth China, Myopia Key Lab, Shanghai, Peoples R China.
[Tan, Mengxi] Westminster Coll, Dept Environm Sci, Fulton, MO 65251 USA.
RP Xu, JJ (reprint author), Fudan Univ, Shanghai Med Coll, Dept Ophthalmol & Visual Sci, Eye & ENT Hosp, 83 Rd Fenyang, Shanghai 200433, Peoples R China.; Liu, ZG (reprint author), Xiamen Univ, Inst Eye, Rd Xiangan Nan, Xiamen, Peoples R China.
EM zuguoliu@126.com; jianjiangxu@126.com
FU Key Clinic Medicine Research Program, the Ministry of Health, China
[201302015]; National Science and Technology Research Program, the
Ministry of Science and Technology, China [2012BAI08B01]; National
Natural Science Foundation of China [81170817, 81200658, 81300735,
81270978, U1205025, 81330022]; Scientific Research Program, Science and
Technology Commission of Shanghai Municipality, Shanghai [13441900900,
13430720400]; Chinese Postdoctoral Fund [XMU135890]; New Technology
Joint Research Project in Shanghai Hospitals [SHDC12014114]
FX The authors thank Prof. Reza Dana and Prof. David A. Sullivan from
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary,
Harvard Medical School, for their constructive critique and suggestions.
The authors were supported by grants from the Key Clinic Medicine
Research Program, the Ministry of Health, China (201302015); the
National Science and Technology Research Program, the Ministry of
Science and Technology, China (2012BAI08B01); the National Natural
Science Foundation of China (81170817, 81200658, 81300735, 81270978,
U1205025, and 81330022); the Scientific Research Program, Science and
Technology Commission of Shanghai Municipality, Shanghai (13441900900,
13430720400); the Chinese Postdoctoral Fund (XMU135890); and the New
Technology Joint Research Project in Shanghai Hospitals (SHDC12014114).
The sponsor or funding organization had no role in the design or conduct
of this research.
NR 32
TC 0
Z9 0
U1 7
U2 22
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 APR 1
PY 2016
VL 6
AR 23858
DI 10.1038/srep23858
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DI0RG
UT WOS:000373204100001
PM 27033635
ER
PT J
AU Munn, LL
Jain, RK
AF Munn, Lance L.
Jain, Rakesh K.
TI The Forces of Cancer
SO SCIENTIST
LA English
DT Article
ID TUMOR-GROWTH; PRESSURE; CELLS; MICROENVIRONMENT; INVASION; THERAPY;
VESSELS; FLOW
C1 [Munn, Lance L.] Harvard Univ, Med Sch, Radiat Oncol, Cambridge, MA 02138 USA.
[Jain, Rakesh K.] Harvard Univ, Med Sch, Tumor Biol Radiat Oncol, Cambridge, MA 02138 USA.
[Jain, Rakesh K.] Massachusetts Gen Hosp, EL Steele Labs Tumor Biol, Boston, MA 02114 USA.
RP Munn, LL (reprint author), Harvard Univ, Med Sch, Radiat Oncol, Cambridge, MA 02138 USA.
RI Munn, Lance/L-3950-2016
OI Munn, Lance/0000-0003-0698-7232
NR 17
TC 0
Z9 0
U1 2
U2 7
PU LABX MEDIA GROUP
PI MIDLAND
PA PO BOX 216, 478 BAY ST, MIDLAND, ONTARIO L4R 1K9, CANADA
SN 0890-3670
EI 1547-0806
J9 SCIENTIST
JI Scientist
PD APR
PY 2016
VL 30
IS 4
BP 52
EP 57
PG 6
WC Information Science & Library Science; Multidisciplinary Sciences
SC Information Science & Library Science; Science & Technology - Other
Topics
GA DH7BS
UT WOS:000372946800014
ER
PT J
AU Gremmel, T
Frelinger, AL
Michelson, AD
AF Gremmel, Thomas
Frelinger, Andrew L., III
Michelson, Alan D.
TI Platelet Physiology
SO SEMINARS IN THROMBOSIS AND HEMOSTASIS
LA English
DT Article
DE platelet function; platelet structure; platelet granules; platelet
surface glycoproteins; platelet activation pathways; platelet
physiology; review
ID ACUTE CORONARY SYNDROMES; GLYCOPROTEIN-IIB-IIIA; IB-IX-V; OPEN
CANALICULAR SYSTEM; LYSOSOME-RELATED ORGANELLES; ELECTRON MICROSCOPIC
OBSERVATIONS; PROTEASE-ACTIVATED RECEPTORS; HERMANSKY-PUDLAK-SYNDROME;
STORAGE POOL-DEFICIENCY; HUMAN-BLOOD PLATELETS
AB Platelets are the smallest blood cells, numbering 150 to 350 x 10(9)/L in healthy individuals. The ability of activated platelets to adhere to an injured vessel wall and form aggregates was first described in the 19th century. Besides their long-established roles in thrombosis and hemostasis, platelets are increasingly recognized as pivotal players in numerous other pathophysiological processes including inflammation and atherogenesis, antimicrobial host defense, and tumor growth and metastasis. Consequently, profound knowledge of platelet structure and function is becoming more important in research and in many fields of modern medicine. This review provides an overview of platelet physiology focusing particularly on the structure, granules, surface glycoproteins, and activation pathways of platelets.
C1 [Gremmel, Thomas; Frelinger, Andrew L., III; Michelson, Alan D.] Dana Farber Canc Inst, Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.
[Gremmel, Thomas] Med Univ Vienna, Dept Internal Med 2, Vienna, Austria.
RP Gremmel, T (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Ctr Platelet Res Studies, 300 Longwood Ave, Boston, MA USA.
EM thomas.gremmel@childrens.harvard.edu
OI Gremmel, Thomas/0000-0001-9554-7292
NR 226
TC 8
Z9 8
U1 5
U2 11
PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0094-6176
EI 1098-9064
J9 SEMIN THROMB HEMOST
JI Semin. Thromb. Hemost.
PD APR
PY 2016
VL 42
IS 3
BP 191
EP 204
DI 10.1055/s-0035-1564835
PG 14
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA DH9TR
UT WOS:000373139300003
PM 26926581
ER
PT J
AU Shindo, A
Maki, T
Mandeville, ET
Liang, AC
Egawa, N
Itoh, K
Itoh, N
Borlongan, M
Holder, JC
Chuang, TT
McNeish, JD
Tomimoto, H
Lok, J
Lo, EH
Arai, K
AF Shindo, Akihiro
Maki, Takakuni
Mandeville, Emiri T.
Liang, Anna C.
Egawa, Naohiro
Itoh, Kanako
Itoh, Naoki
Borlongan, Mia
Holder, Julie C.
Chuang, Tsu Tshen
McNeish, John D.
Tomimoto, Hidekazu
Lok, Josephine
Lo, Eng H.
Arai, Ken
TI Astrocyte-Derived Pentraxin 3 Supports Blood-Brain Barrier Integrity
Under Acute Phase of Stroke
SO STROKE
LA English
DT Article
DE astrocyte; blood-brain barrier; cell-cell interaction; endothelium;
stroke
ID ACUTE MYOCARDIAL-INFARCTION; LONG PENTRAXIN; ENDOTHELIAL-CELLS; PTX3;
INJURY; ANGIOGENESIS; EXPRESSION; PROTEIN; GROWTH; DISRUPTION
AB Background and Purpose Pentraxin 3 (PTX3) is released on inflammatory responses in many organs. However, roles of PTX3 in brain are still mostly unknown. Here we asked whether and how PTX3 contributes to blood-brain barrier dysfunction during the acute phase of ischemic stroke.
Methods In vivo, spontaneously hypertensive rats were subjected to focal cerebral ischemia by transient middle cerebral artery occlusion. At day 3, brains were analyzed to evaluate the cellular origin of PTX3 expression. Correlations with blood-brain barrier breakdown were assessed by IgG staining. In vitro, rat primary astrocytes and rat brain endothelial RBE.4 cells were cultured to study the role of astrocyte-derived PTX3 on vascular endothelial growth factor-mediated endothelial permeability.
Results During the acute phase of stroke, reactive astrocytes in the peri-infarct area expressed PTX3. There was negative correlation between gradients of IgG leakage and PTX3-positive astrocytes. Cell culture experiments showed that astrocyte-conditioned media increased levels of tight junction proteins and reduced endothelial permeability under normal conditions. Removing PTX3 from astrocyte-conditioned media by immunoprecipitation increased endothelial permeability. PTX3 strongly bound vascular endothelial growth factor in vitro and was able to decrease vascular endothelial growth factor-induced endothelial permeability.
Conclusions Astrocytes in peri-infarct areas upregulate PTX3, which may support blood-brain barrier integrity by regulating vascular endothelial growth factor-related mechanisms. This response in astrocytes may comprise a compensatory mechanism for maintaining blood-brain barrier function after ischemic stroke.
C1 [Shindo, Akihiro; Maki, Takakuni; Mandeville, Emiri T.; Liang, Anna C.; Egawa, Naohiro; Itoh, Kanako; Itoh, Naoki; Borlongan, Mia; Lok, Josephine; Lo, Eng H.; Arai, Ken] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Radiol, Charlestown, MA USA.
[Shindo, Akihiro; Maki, Takakuni; Mandeville, Emiri T.; Liang, Anna C.; Egawa, Naohiro; Itoh, Kanako; Itoh, Naoki; Borlongan, Mia; Lok, Josephine; Lo, Eng H.; Arai, Ken] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA.
[Lok, Josephine] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Charlestown, MA USA.
[Holder, Julie C.; Chuang, Tsu Tshen; McNeish, John D.] GlaxoSmithKline, Dept Vasc Biol, Harlow, Essex, England.
[Shindo, Akihiro; Tomimoto, Hidekazu] Mie Univ, Grad Sch Med, Dept Neurol, Tsu, Mie, Japan.
RP Arai, K (reprint author), Neuroprotect Res Lab, MGH East 149-2401, Charlestown, MA 02129 USA.
EM karai@partners.org
FU National Institutes of Health [P01-NS55104, R01-NS065089];
Glaxo-Smith-Kline-Harvard-Stem-Cell-Institute consortium
FX This study was supported, in part, by grants from National Institutes of
Health (P01-NS55104 and R01-NS065089) and the
Glaxo-Smith-Kline-Harvard-Stem-Cell-Institute consortium.
NR 34
TC 5
Z9 5
U1 5
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD APR
PY 2016
VL 47
IS 4
BP 1094
EP 1100
DI 10.1161/STROKEAHA.115.012133
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DH5SX
UT WOS:000372853200028
PM 26965847
ER
PT J
AU Raffeld, MR
Debette, S
Woo, D
AF Raffeld, Miriam R.
Debette, Stephanie
Woo, Daniel
TI International Stroke Genetics Consortium Update
SO STROKE
LA English
DT Article
DE epidemiology; genetics; stroke
ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; AMERICAN-HEART-ASSOCIATION
C1 [Raffeld, Miriam R.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Debette, Stephanie] Univ Paris 07, DHU Neurovasc Sorbonne Paris Cite, Dept Neurol, Lariboisiere Hosp, Paris, France.
[Debette, Stephanie] Bordeaux Univ, Inserm U897, Talence, France.
[Woo, Daniel] Univ Cincinnati, Med Ctr, Dept Neurol, 222 Piedmont Ave,3200, Cincinnati, OH 45219 USA.
RP Woo, D (reprint author), Univ Cincinnati, Med Ctr, Dept Neurol, 222 Piedmont Ave,3200, Cincinnati, OH 45219 USA.
EM daniel.woo@Uc.edu
FU Wellcome Trust; National Institute of Neurological Diseases and Stroke;
National Institutes of Health
FX This work was funded by Wellcome Trust awards, The National Institute of
Neurological Diseases and Stroke awards, and The National Institutes of
Health.
NR 4
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD APR
PY 2016
VL 47
IS 4
BP 1144
EP 1145
DI 10.1161/STROKEAHA.116.012682
PG 2
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DH5SX
UT WOS:000372853200038
PM 26906919
ER
PT J
AU Gurol, ME
AF Gurol, M. Edip
TI Molecular Neuroimaging in Vascular Cognitive Impairment
SO STROKE
LA English
DT Review
DE cerebral amyloid angiopathy; cerebral small vessel disease;
leukoaraiosis; magnetic resonance imaging; magnetic resonance
spectroscopy; Pittsburgh Compound B; positron emission tomography
ID CEREBRAL AMYLOID ANGIOPATHY; PITTSBURGH COMPOUND-B; SMALL VESSEL
DISEASE; ALZHEIMERS-DISEASE; WHITE-MATTER; INTRACEREBRAL HEMORRHAGE;
LOBAR MICROBLEEDS; MR SPECTROSCOPY; IMAGING AGENTS; POTENTIAL USE
C1 [Gurol, M. Edip] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
RP Gurol, ME (reprint author), MGH Stroke Res, 175 Cambridge St 300, Boston, MA 02114 USA.
EM edip@mail.harvard.edu
RI Gurol, Edip/J-2279-2014
OI Gurol, Edip/0000-0002-2169-4457
FU National Institutes of Health [K23 NS 083711]
FX This work was made possible through research grant support from National
Institutes of Health (K23 NS 083711).
NR 48
TC 3
Z9 3
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD APR
PY 2016
VL 47
IS 4
BP 1146
EP 1152
DI 10.1161/STROKEAHA.115.007958
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA DH5SX
UT WOS:000372853200039
PM 26883497
ER
PT J
AU Wise, SS
Holmes, AL
Liou, L
Adam, RM
Wise, JP
AF Wise, Sandra S.
Holmes, Arnie L.
Liou, Louis
Adam, Rosalyn M.
Wise, John Pierce, Sr.
TI Hexavalent chromium induces chromosome instability in human urothelial
cells
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Chromium; Chromate; Urothelial; Bladder cancer; Aneuploidy; Genotoxicity
ID HUMAN LUNG-CELLS; HUMAN BRONCHIAL CELLS; TOTAL HIP REPLACEMENTS;
DOUBLE-STRAND BREAKS; LOWER URINARY-TRACT; CHRONIC EXPOSURE; INDUCED
CYTOTOXICITY; GENOTOXICITY; PARTICULATE; CANCER
AB Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. (C) 2016 Published by Elsevier Inc.
C1 [Wise, Sandra S.; Holmes, Arnie L.; Wise, John Pierce, Sr.] Univ So Maine, Wise Lab Environm & Genet Toxicol, Maine Ctr Toxicol & Environm Hlth, Dept Appl Sci Med, Sci Bldg,96 Falmouth St, Portland, ME 04103 USA.
[Holmes, Arnie L.] Dana Farber Canc Inst, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
[Liou, Louis] Boston Univ, Dept Pathol, Sch Med, 670 Albany St, Boston, MA 02118 USA.
[Adam, Rosalyn M.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA.
[Wise, Sandra S.] Univ Louisville, Wise Lab Environm & Genet Toxicol, Dept Pharmacol & Toxicol, 505 S Prescott St, Louisville, KY 40292 USA.
RP Wise, JP (reprint author), Univ Louisville, Wise Lab Environm & Genet Toxicol, Dept Pharmacol & Toxicol, 505 S Prescott St, Louisville, KY 40292 USA.
EM john.wise@louisville.edu
FU National Institute of Environmental Health Sciences (NIEHS) [ES016893];
Army Research Office (ARO) Grant [W911NF-09-1-0296]; Maine Center for
Toxicology and Environmental Health
FX The authors would like to thank Melanie Hebert and Christy Gianios, Jr
for the technical assistance. This work was supported by the National
Institute of Environmental Health Sciences (NIEHS) grant ES016893
(J.P.W.), Army Research Office (ARO) Grant #W911NF-09-1-0296 (J.P.W.),
and the Maine Center for Toxicology and Environmental Health.
NR 37
TC 0
Z9 0
U1 2
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD APR 1
PY 2016
VL 296
BP 54
EP 60
DI 10.1016/j.taap.2016.02.015
PG 7
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA DH3IV
UT WOS:000372681600006
PM 26908176
ER
PT J
AU Rago, AP
Sharma, U
Duggan, M
King, DR
AF Rago, Adam P.
Sharma, Upma
Duggan, Michael
King, David R.
TI Percutaneous damage control with self-expanding foam: pre-hospital
rescue from abdominal exsanguination
SO TRAUMA-ENGLAND
LA English
DT Review
DE Non-compressible hemorrhage; bleeding; foam; pre-hospital; abdominal
ID ENDOVASCULAR BALLOON OCCLUSION; SMALL-BOWEL INJURIES; PRIMARY REPAIR;
PRIMARY ANASTOMOSIS; HEMORRHAGE CONTROL; IMPROVES SURVIVAL;
CLOSED-ABDOMEN; COLON INJURIES; OUTCOMES; TRAUMA
AB Non-compressible intra-abdominal hemorrhage results in significant morbidity and mortality in contemporary trauma medicine. Regrettably, many deaths from non-compressible hemorrhage are attributable to potentially survivable injuries. A self-expanding polyurethane foam has been developed for rapid, percutaneous damage control of exsanguinating abdominal hemorrhage, for patients not expected to survive to definitive surgical care. Foam intervention creates a temporary, commensal, hemostatic environment within the abdominal cavity. This tropism away from exsanguination physiology creates a hemostatic bridge such that the patient may reach definitive surgical intervention. This review article summarizes the existing literature characterizing the safety and efficacy of this intervention, along with a study in recently deceased patients that enables dose translation from animal models to human beings.
C1 [Rago, Adam P.; Sharma, Upma] Arsenal Med Inc, Watertown, MA USA.
[Duggan, Michael; King, David R.] Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA.
EM dking3@mgh.harvard.edu
NR 30
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 1460-4086
EI 1477-0350
J9 TRAUMA
JI Trauma
PD APR
PY 2016
VL 18
IS 2
BP 85
EP 91
DI 10.1177/1460408615617790
PG 7
WC Emergency Medicine
SC Emergency Medicine
GA DH5KC
UT WOS:000372825600002
ER
PT J
AU Henderson, MX
Wirak, GS
Zhang, YQ
Dai, F
Ginsberg, SD
Dolzhanskaya, N
Staropoli, JF
Nijssen, PCG
Lam, TT
Roth, AF
Davis, NG
Dawson, G
Velinov, M
Chandra, SS
AF Henderson, Michael X.
Wirak, Gregory S.
Zhang, Yong-quan
Dai, Feng
Ginsberg, Stephen D.
Dolzhanskaya, Natalia
Staropoli, John F.
Nijssen, Peter C. G.
Lam, TuKiet T.
Roth, Amy F.
Davis, Nicholas G.
Dawson, Glyn
Velinov, Milen
Chandra, Sreeganga S.
TI Neuronal ceroid lipofuscinosis with DNAJC5/CSP alpha mutation has PPT1
pathology and exhibit aberrant protein palmitoylation
SO ACTA NEUROPATHOLOGICA
LA English
DT Article
DE Neuronal ceroid lipofuscinosis (NCL); Cysteine-string protein alpha (CSP
alpha); Palmitoyl-protein thioesterase 1 (PPT1); Palmitoylation;
Neurodegeneration
ID CYSTEINE-STRING PROTEIN; HUMAN NEUROBLASTOMA-CELLS; AUTOSOMAL-DOMINANT;
CSP-ALPHA; THIOESTERASE-1 DEFICIENCY; SYNAPTIC VESICLES; CLN3 PROTEIN;
KUFS-DISEASE; REVEALS; MICE
AB Neuronal ceroid lipofuscinoses (NCL) are a group of inherited neurodegenerative disorders with lysosomal pathology (CLN1-14). Recently, mutations in the DNAJC5/CLN4 gene, which encodes the presynaptic co-chaperone CSP alpha were shown to cause autosomal-dominant NCL. Although 14 NCL genes have been identified, it is unknown if they act in common disease pathways. Here we show that two disease-associated proteins, CSP alpha and the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1/CLN1) are biochemically linked. We find that in DNAJC5/CLN4 patient brains, PPT1 is massively increased and mis-localized. Surprisingly, the specific enzymatic activity of PPT1 is dramatically reduced. Notably, we demonstrate that CSP alpha is depalmitoylated by PPT1 and hence its substrate. To determine the consequences of PPT1 accumulation, we compared the palmitomes from control and DNAJC5/CLN4 patient brains by quantitative proteomics. We discovered global changes in protein palmitoylation, mainly involving lysosomal and synaptic proteins. Our findings establish a functional link between two forms of NCL and serve as a springboard for investigations of NCL disease pathways.
C1 [Henderson, Michael X.; Wirak, Gregory S.; Zhang, Yong-quan; Chandra, Sreeganga S.] Yale Univ, Program Cellular Neurosci Neurodegenerat & Regene, New Haven, CT USA.
[Henderson, Michael X.; Wirak, Gregory S.; Zhang, Yong-quan; Chandra, Sreeganga S.] Yale Univ, Dept Neurol, New Haven, CT USA.
[Henderson, Michael X.; Chandra, Sreeganga S.] Yale Univ, Interdept Neurosci Program, New Haven, CT USA.
[Dai, Feng] Yale Ctr Analyt Serv, New Haven, CT USA.
[Ginsberg, Stephen D.] Nathan S Kline Inst Psychiat Res, Orangeburg, NY USA.
[Ginsberg, Stephen D.] NYU, Langone Med Ctr, Dept Psychiat, New York, NY USA.
[Ginsberg, Stephen D.] NYU, Langone Med Ctr, Dept Neurosci & Physiol, New York, NY USA.
[Staropoli, John F.] Massachusetts Gen Hosp, Ctr Human Genet Res, Dept Neurol, Boston, MA 02114 USA.
[Staropoli, John F.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.
[Nijssen, Peter C. G.] St Elizabeth Hosp, Dept Neurol, NL-5022 GC Tilburg, Netherlands.
[Lam, TuKiet T.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA.
[Roth, Amy F.; Davis, Nicholas G.] Wayne State Univ, Dept Pharmacol, Detroit, MI 48201 USA.
[Dawson, Glyn] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA.
[Velinov, Milen] Albert Einstein Coll Med, Dept Pediat, New York, NY USA.
[Velinov, Milen] New York State Inst Basic Res Dev Disabil, Dept Human Genet, 1050 Forest Hill Rd, Staten Isl, NY 10314 USA.
[Chandra, Sreeganga S.] Yale Univ, Dept Mol Cell & Dev Biol, New Haven, CT USA.
[Staropoli, John F.] Biogen Idec Inc, Cambridge, MA 02142 USA.
RP Chandra, SS (reprint author), Yale Univ, Program Cellular Neurosci Neurodegenerat & Regene, New Haven, CT USA.; Chandra, SS (reprint author), Yale Univ, Dept Neurol, New Haven, CT USA.; Chandra, SS (reprint author), Yale Univ, Interdept Neurosci Program, New Haven, CT USA.; Chandra, SS (reprint author), Yale Univ, Dept Mol Cell & Dev Biol, New Haven, CT USA.
EM sreeganga.chandra@yale.edu
RI di Ronza, Alberto/H-7674-2016;
OI di Ronza, Alberto/0000-0002-9813-5143; Henderson,
Michael/0000-0001-9710-0726; Ginsberg, Stephen/0000-0002-1797-4288
FU Battens Disease Research and Support Association; NIH [R01NS083846,
R01NS064963]; NIDA Neuroproteomic Center [5 P30 DA018343-07]; NRSA
[NS078861-02]; CTSA Grant from the National Center for Research
Resources (NCRR) [UL1 RR024139]; National Center for Advancing
Translational Science (NCATS)
FX We thank Dr. Katherine Sims for contributing pathologic material from
the Massachusetts General Hospital NCL Biorepository. We also thank Ted
Voss, Jean Kanyo, and Kathrin Wilczak for assistance with sample prep,
data collection, and LFQ analysis, respectively. We would like to thank
Art Horwich, Shawn Ferguson, Pietro De Camilli, Thomas Biederer, and
members of our laboratories for critical discussions related to this
paper. We would also like to thank Zack Gomez for data analysis. This
work was supported by the Battens Disease Research and Support
Association Grant, NIH R01NS083846, R01NS064963 (to S.S.C.), NIDA
Neuroproteomic Center Grant (5 P30 DA018343-07) and by a NRSA
NS078861-02 (to M.X.H) as well as CTSA Grant UL1 RR024139 from the
National Center for Research Resources (NCRR) and the National Center
for Advancing Translational Science (NCATS).
NR 42
TC 3
Z9 3
U1 1
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-6322
EI 1432-0533
J9 ACTA NEUROPATHOL
JI Acta Neuropathol.
PD APR
PY 2016
VL 131
IS 4
BP 621
EP 637
DI 10.1007/s00401-015-1512-2
PG 17
WC Clinical Neurology; Neurosciences; Pathology
SC Neurosciences & Neurology; Pathology
GA DG7XR
UT WOS:000372297500009
PM 26659577
ER
PT J
AU Kittiskulnam, P
Chertow, GM
Kaysen, GA
Delgado, C
Dalrymple, LS
Johansen, KL
AF Kittiskulnam, Piyawan
Chertow, Glenn M.
Kaysen, George A.
Delgado, Cynthia
Dalrymple, Lorien S.
Johansen, Kirsten L.
TI Misclassification of Obesity by Body Mass Index Among Patients Receiving
Hemodialysis
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Letter
ID WAIST CIRCUMFERENCE; DIAGNOSING OBESITY; POPULATION; MORTALITY; DISEASE
C1 [Kittiskulnam, Piyawan; Delgado, Cynthia; Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Kittiskulnam, Piyawan; Delgado, Cynthia; Johansen, Kirsten L.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Kittiskulnam, Piyawan] Chulalongkorn Univ, Bangkok, Thailand.
[Kittiskulnam, Piyawan] King Chulalongkorn Mem Hosp, Thai Red Cross Soc, Bangkok, Thailand.
[Chertow, Glenn M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Kaysen, George A.; Dalrymple, Lorien S.] Univ Calif Davis, Sacramento, CA 95817 USA.
[Johansen, Kirsten L.] Univ Calif San Francisco, US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA 94143 USA.
RP Johansen, KL (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.; Johansen, KL (reprint author), San Francisco VA Med Ctr, San Francisco, CA USA.; Johansen, KL (reprint author), Univ Calif San Francisco, US Renal Data Syst Nutr Special Studies Ctr, San Francisco, CA 94143 USA.
EM kirsten.johansen@ucsf.edu
FU CSRD VA [IK2 CX000527]; NIDDK NIH HHS [K24DK085153, N01-DK-7-0005,
K23DK093584]; PHS HHS [KD-7-5004]
NR 10
TC 1
Z9 1
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 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD APR
PY 2016
VL 67
IS 4
BP 709
EP 711
DI 10.1053/j.ajkd.2015.09.028
PG 3
WC Urology & Nephrology
SC Urology & Nephrology
GA DH3XO
UT WOS:000372720300027
PM 26612278
ER
PT J
AU Boudreaux, ED
Camargo, CA
Arias, SA
Sullivan, AF
Allen, MH
Goldstein, AB
Manton, AP
Espinola, JA
Miller, IW
AF Boudreaux, Edwin D.
Camargo, Carlos A., Jr.
Arias, Sarah A.
Sullivan, Ashley F.
Allen, Michael H.
Goldstein, Amy B.
Manton, Anne P.
Espinola, Janice A.
Miller, Ivan W.
TI Improving Suicide Risk Screening and Detection in the Emergency
Department
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID FOLLOW-UP; IDEATION; MULTICENTER; PREVENTION; VISITS; TRENDS
AB Introduction: The Emergency Department Safety Assessment and Follow-up Evaluation Screening Outcome Evaluation examined whether universal suicide risk screening is feasible and effective at improving suicide risk detection in the emergency department (ED).
Methods: A three-phase interrupted time series design was used: Treatment as Usual (Phase 1), Universal Screening (Phase 2), and Universal Screening + Intervention (Phase 3). Eight EDs from seven states participated from 2009 through 2014. Data collection spanned peak hours and 7 days of the week. Chart reviews established if screening for intentional self-harm ideation/behavior (screening) was documented in the medical record and whether the individual endorsed intentional self-harm ideation/behavior (detection). Patient interviews determined if the documented intentional self-harm was suicidal. In Phase 2, universal suicide risk screening was implemented during routine care. In Phase 3, improvements were made to increase screening rates and fidelity. Chi-square tests and generalized estimating equations were calculated. Data were analyzed in 2014.
Results: Across the three phases (N=236,791 ED visit records), documented screenings rose from 26% (Phase 1) to 84% (Phase 3) (chi(2) [2, n=236,789]=71,000, p < 0.001). Detection rose from 2.9% to 5.7% (chi(2) [2, n=236,789]=902, p < 0.001). The majority of detected intentional self-harm was confirmed as recent suicidal ideation or behavior by patient interview.
Conclusions: Universal suicide risk screening in the ED was feasible and led to a nearly twofold increase in risk detection. If these findings remain true when scaled, the public health impact could be tremendous, because identification of risk is the first and necessary step for preventing suicide. (C) 2016 American Journal of Preventive Medicine
C1 [Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA 01655 USA.
[Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA.
[Boudreaux, Edwin D.] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA 01655 USA.
[Camargo, Carlos A., Jr.; Sullivan, Ashley F.; Espinola, Janice A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Arias, Sarah A.; Miller, Ivan W.] Brown Univ, Dept Psychiat & Human Behav, Butler Hosp, Providence, RI 02912 USA.
[Arias, Sarah A.; Miller, Ivan W.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Allen, Michael H.] Univ Colorado, Depress Ctr, Aurora, CO USA.
[Allen, Michael H.] Rocky Mt Crisis Partners, Aurora, CO USA.
[Goldstein, Amy B.] NIMH, Div Serv & Intervent Res, NIH, Bethesda, MD 20892 USA.
[Manton, Anne P.] Cape Cod Hosp, Ctr Behav Hlth, Cape Cod, MA USA.
RP Boudreaux, ED (reprint author), Univ Massachusetts, Sch Med, Emergency Med, LA-189,55 Lake Ave North, Worcester, MA 01655 USA.
EM edwin.boudreaux@umassmed.edu
RI Allen, Michael/A-8776-2011
FU NIMH [U01MH088278]; NIMH
FX The project described was supported by Award Number U01MH088278 from
NIMH. This grant was funded as a cooperative award by NIMH. NIMH was
represented on the Emergency Department Safety Assessment and Follow-up
Evaluation (ED-SAFE) Steering Committee by Amy Goldstein, PhD. She
collaborated with the other committee members and investigators to
oversee the conduct of the study, data collection, analysis, and
interpretation. NIMH provided Data and Safety Monitoring Board (DSMB)
oversight of the study. The NIMH DSMB liaison was Adam Haim, PhD.
NR 25
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U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD APR
PY 2016
VL 50
IS 4
BP 445
EP 453
DI 10.1016/j.amepre.2015.09.029
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA DH1RP
UT WOS:000372562900003
PM 26654691
ER
PT J
AU Havens, JM
Do, WS
Kaafarani, H
Mesar, T
Reznor, G
Cooper, Z
Askari, R
Kelly, E
Columbus, AB
Gates, JD
Haider, AH
Salim, A
AF Havens, Joaquim M.
Do, Woo S.
Kaafarani, Haytham
Mesar, Tomaz
Reznor, Gally
Cooper, Zara
Askari, Reza
Kelly, Edward
Columbus, Alexandra B.
Gates, Jonathan D.
Haider, Adil H.
Salim, Ali
TI Explaining the excess morbidity of emergency general surgery: packed red
blood cell and fresh frozen plasma transfusion practices are associated
with major complications in nonmassively transfused patients
SO AMERICAN JOURNAL OF SURGERY
LA English
DT Article
DE Emergency general surgery; Transfusion; Surgical outcomes
ID IMPROVEMENT PROGRAM ANALYSIS; CLINICAL DECISION-SUPPORT; I TRAUMA
CENTER; LAST 60 YEARS; APGAR SCORE; MULTIPLE IMPUTATION; RISK-FACTORS;
MORTALITY; HANDWRITTEN; PERFORMANCE
AB BACKGROUND: Intraoperative blood product transfusions carry risk but are often necessary in emergency general surgery (EGS).
METHODS: We queried the American College of Surgery-National Surgical Quality Improvement Program database for EGS patients (2008 to 2012) at 2 tertiary academic hospitals. Outcomes included rates of high packed red blood cell (pRBC) use (estimated blood loss: pRBC, 350: 1) and high fresh frozen plasma (FFP) use (FFP: pRBC >1:1.5). Patients were then stratified by exposure to high blood product use. Stepwise logistic regression was performed.
RESULTS: Of 992 patients, 33% underwent EGS. Estimated blood loss was similar between EGS and non-EGS (282 vs 250 cc, P = .288). EGS patients were more often exposed to high pRBC use (adjusted odds ratio [OR] = 2.01, 95% confidence interval [CI] = 1.11 to 3.66) and high-FFP use (OR = 2.75, 95% CI: = 1.10 to 6.84). High blood product use was independently associated with major nonbleeding complications (high pRBC: OR = 1.73, 95% CI = 1.04 to 2.91; high FFP: OR = 2.15, 95% CI = 1.15 to 4.02).
CONCLUSIONS: Despite similar blood loss, EGS patients received higher rates of intraoperative blood product transfusion, which was independently associated with major complication. (C) 2016 Elsevier Inc. All rights reserved.
C1 [Havens, Joaquim M.; Do, Woo S.; Cooper, Zara; Askari, Reza; Kelly, Edward; Columbus, Alexandra B.; Gates, Jonathan D.; Salim, Ali] Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA.
[Havens, Joaquim M.; Reznor, Gally; Cooper, Zara; Haider, Adil H.; Salim, Ali] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Dept Surg, 75 Francis St, Boston, MA 02115 USA.
[Kaafarani, Haytham; Mesar, Tomaz] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.
RP Do, WS (reprint author), Brigham & Womens Hosp, Div Trauma Burns & Surg Crit Care, 75 Francis St, Boston, MA 02115 USA.
EM wdo@post.harvard.edu
NR 34
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U1 1
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 APR
PY 2016
VL 211
IS 4
BP 656
EP U219
DI 10.1016/j.amjsurg.2015.11.031
PG 12
WC Surgery
SC Surgery
GA DG9WH
UT WOS:000372434000003
PM 26860622
ER
PT J
AU Pace, MM
Sharma, B
Anderson-Dam, J
Fleischmann, K
Warren, L
Stefanovich, P
AF Pace, Meredith M.
Sharma, Balram
Anderson-Dam, John
Fleischmann, Katherine
Warren, Lisa
Stefanovich, Peter
TI Ultrasound-Guided Thoracic Paravertebral Blockade: A Retrospective Study
of the Incidence of Complications
SO ANESTHESIA AND ANALGESIA
LA English
DT Article
ID BREAST SURGERY; NERVE BLOCK; INTERCOSTAL APPROACH; CHRONIC PAIN; SPREAD;
BUPIVACAINE; METAANALYSIS; ANESTHESIA; INJECTION
AB BACKGROUND:
The benefits of thoracic paravertebral block (TPVB) have been demonstrated for patients undergoing surgery for breast cancer. However, pleural puncture resulting in pneumothorax is a serious complication associated with traditional approaches using guidance from anatomic landmarks and nerve stimulation and may contribute to the low utilization of this block. An ultrasound-guided technique has the potential to reduce complications by providing direct visualization of the paravertebral space during needle manipulation. We evaluated the complications using a single-injection, transverse, in-plane ultrasound-guided technique for paravertebral blockade in patients undergoing mastectomy with immediate reconstruction for breast cancer treatment or prophylaxis.
METHODS:
Data from all patients who underwent TPVB between January 1, 2010, and December 3, 2013, at Massachusetts General Hospital was prospectively recorded in a computerized database. All blocks were placed for postoperative analgesia after unilateral or bilateral mastectomy with immediate breast reconstruction. Medical records were retrospectively reviewed for any patient who developed complications including accidental pleural puncture, symptomatic pneumothorax, hypotension, or bradycardia, as well as signs and symptoms of toxicity or effects of local anesthetic outside of the paravertebral space.
RESULTS:
Eight hundred fifty-six patients underwent a total of 1427 thoracic paravertebral injections (285 unilateral and 571 bilateral TPVB). There were 6 complications (0.70%; 99.2% confidence interval, 0.17%-1.86%) including symptomatic bradycardia and hypotension (n = 3), vasovagal episode (n = 1), and evidence of possible local anesthetic toxicity (n = 2). There was no incidence of suspected accidental pleural puncture or symptomatic pneumothorax identified in our study population.
CONCLUSIONS:
The routine use of a single-injection, transverse, in-plane ultrasound-guided technique for TPVB in patients undergoing mastectomy with immediate breast reconstruction is associated with very few complications.
C1 [Pace, Meredith M.; Sharma, Balram; Anderson-Dam, John; Fleischmann, Katherine; Warren, Lisa; Stefanovich, Peter] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA.
RP Stefanovich, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Gray Bigelow 444, Boston, MA 02114 USA.
EM pstefanovich@mgh.harvard.edu
NR 25
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Z9 6
U1 4
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2016
VL 122
IS 4
BP 1186
EP 1191
DI 10.1213/ANE.0000000000001117
PG 6
WC Anesthesiology
SC Anesthesiology
GA DG8PA
UT WOS:000372344900008
PM 26756911
ER
PT J
AU Meyer, MJ
Hyder, JA
Cole, DJ
Kamdar, NV
AF Meyer, Matthew J.
Hyder, Joseph A.
Cole, Daniel J.
Kamdar, Nirav V.
TI The Mandate to Measure Patient Experience: How Can Patients "Value"
Anesthesia Care?
SO ANESTHESIA AND ANALGESIA
LA English
DT Editorial Material
ID PERIOPERATIVE SURGICAL HOME; HEALTH-CARE; SATISFACTION; OUTCOMES
C1 [Meyer, Matthew J.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
[Hyder, Joseph A.] Mayo Clin, Ctr Sci Hlth Care Delivery, Dept Anesthesiol, Rochester, MN USA.
[Cole, Daniel J.; Kamdar, Nirav V.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol & Perioperat Med, Los Angeles, CA 90095 USA.
RP Meyer, MJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St, Boston, MA 02114 USA.
EM mjmeyer@mgh.harvard.edu
NR 36
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Z9 1
U1 1
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2016
VL 122
IS 4
BP 1211
EP 1215
DI 10.1213/ANE.0000000000001198
PG 5
WC Anesthesiology
SC Anesthesiology
GA DG8PA
UT WOS:000372344900011
PM 26991623
ER
PT J
AU Xie, ZC
Wang, H
AF Xie, Zhongcong
Wang, Hui
TI Regarding "2-Deoxy-D-Glucose Enhances Anesthetic Effects in Mice"
Response
SO ANESTHESIA AND ANALGESIA
LA English
DT Letter
ID P-31 MAGNETIC-RESONANCE; SPECTROSCOPY; BRAIN
C1 [Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA.
[Xie, Zhongcong] Harvard Univ, Sch Med, Charlestown, MA USA.
[Wang, Hui] Capital Med Univ, Dept Anesthesia, Beijing Chaoyang Hosp, Beijing, Peoples R China.
RP Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Charlestown, MA USA.
EM zxie@mgh.harvard.edu
NR 6
TC 1
Z9 1
U1 2
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-2999
J9 ANESTH ANALG
JI Anesth. Analg.
PD APR
PY 2016
VL 122
IS 4
BP 1225
EP 1225
DI 10.1213/ANE.0000000000001177
PG 1
WC Anesthesiology
SC Anesthesiology
GA DG8PA
UT WOS:000372344900018
PM 26991630
ER
PT J
AU Thomas, KM
Wright, AGC
Lukowitsky, MR
Donnellan, MB
Hopwood, CJ
AF Thomas, Katherine M.
Wright, Aidan G. C.
Lukowitsky, Mark R.
Donnellan, M. Brent
Hopwood, Christopher J.
TI Correction to "Evidence for the Criterion Validity and Clinical Utility
of the Pathological Narcissism Inventory"
SO ASSESSMENT
LA English
DT Article
DE correction; narcissism; validity; clinical utility
AB In our article Evidence for the Criterion Validity and Clinical Utility of the Pathological Narcissism Inventory (2012), we provided incorrect values for the r(contrast-cv) coefficients we presented in Table 1. In the current report, we provide correct r(contrast-cv) values in Table 1 and discuss the implications of our updated results, particularly with respect to how these results differ from our initial report.
C1 [Thomas, Katherine M.; Hopwood, Christopher J.] Michigan State Univ, E Lansing, MI 48824 USA.
[Thomas, Katherine M.] San Francisco VA Med Ctr, Bldg 8 Behav Hlth, San Francisco, CA 94118 USA.
[Wright, Aidan G. C.] Univ Pittsburgh, Pittsburgh, PA USA.
[Lukowitsky, Mark R.] Albany Med Ctr, Albany, NY USA.
[Donnellan, M. Brent] Texas A&M Univ, College Stn, TX USA.
RP Thomas, KM (reprint author), San Francisco VA Med Ctr, Bldg 8 Behav Hlth, San Francisco, CA 94118 USA.
EM thomas.kate.m@gmail.com
NR 5
TC 1
Z9 1
U1 0
U2 3
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1073-1911
EI 1552-3489
J9 ASSESSMENT
JI Assessment
PD APR
PY 2016
VL 23
IS 2
BP 262
EP 263
DI 10.1177/1073191115584971
PG 2
WC Psychology, Clinical
SC Psychology
GA DG8CO
UT WOS:000372310200011
PM 26019298
ER
PT J
AU Kammerdiener, LL
Speiser, JL
Aquavella, JV
Harissi-Dagher, M
Dohlman, CH
Chodosh, J
Ciolino, JB
AF Kammerdiener, Leah L.
Speiser, Jaime Lynn
Aquavella, James V.
Harissi-Dagher, Mona
Dohlman, Claes H.
Chodosh, James
Ciolino, Joseph B.
TI Protective effect of soft contact lenses after Boston keratoprosthesis
SO BRITISH JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
AB Purpose To evaluate associations between preoperative diagnosis, soft contact lens (SCL) retention and complications.
Methods A retrospective chart review was conducted of 92 adult patients (103 eyes) who received a Boston keratoprosthesis type I at the Massachusetts's Eye and Ear Infirmary or the Flaum Eye Institute. Records were reviewed for preoperative diagnosis, SCL retention and subsequent complications. Preoperative categories included 16 autoimmune (Stevens-Johnson syndrome, ocular cicatricial pemphigoid, rheumatoid arthritis and uveitis), 9 chemical injury and 67 'other' (aniridia, postoperative infection, dystrophies, keratopathies) patients.
Results 50% of the lenses had been lost the first time after about a year. A subset (n= 17) experienced more than 2 SCL losses per year; this group is comprised of 1 patient with autoimmune diseases, 2 patients with chemical injuries and 14 patients with 'other' diseases. The preoperative diagnosis was not predictive of contact lens retention. However, multivariate analysis demonstrated that the absence of a contact lens was an independent risk factor for postoperative complications, such as corneal melts with or without aqueous humour leak/extrusion and infections.
Conclusions Presence of a contact lens after Boston keratoprosthesis implantation decreases the risk of postoperative complications; this has been clinically experienced by ophthalmologists, but never before has the benefit of contact lens use in this patient population been statistically documented.
C1 [Kammerdiener, Leah L.; Aquavella, James V.] Univ Rochester, Dept Ophthalmol, Flaum Eye Inst, Rochester, NY USA.
[Kammerdiener, Leah L.] Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA.
[Speiser, Jaime Lynn] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Harissi-Dagher, Mona] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada.
[Dohlman, Claes H.; Chodosh, James; Ciolino, Joseph B.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA.
RP Kammerdiener, LL (reprint author), Med Univ S Carolina, Storm Eye Inst, Dept Ophthalmol, Charleston, SC 29425 USA.
EM lkammerdiener@gmail.com
FU Research to Prevent Blindness, New York, New York, USA
FX Supported in part by an unrestricted grant to the Department of
Ophthalmology-Harvard Medical School from Research to Prevent Blindness,
New York, New York, USA.
NR 9
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Z9 3
U1 4
U2 8
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0007-1161
EI 1468-2079
J9 BRIT J OPHTHALMOL
JI Br. J. Ophthalmol.
PD APR
PY 2016
VL 100
IS 4
BP 549
EP 552
DI 10.1136/bjophthalmol-2014-306396
PG 4
WC Ophthalmology
SC Ophthalmology
GA DH0JA
UT WOS:000372469300021
PM 26276169
ER
PT J
AU Kim, AE
Lundgreen, A
Wolff, RK
Fejerman, L
John, EM
Torres-Mejia, G
Ingles, SA
Boone, SD
Connor, AE
Hines, LM
Baumgartner, KB
Giuliano, A
Joshi, AD
Slattery, ML
Stern, MC
AF Kim, Andre E.
Lundgreen, Abbie
Wolff, Roger K.
Fejerman, Laura
John, Esther M.
Torres-Mejia, Gabriela
Ingles, Sue A.
Boone, Stephanie D.
Connor, Avonne E.
Hines, Lisa M.
Baumgartner, Kathy B.
Giuliano, Anna
Joshi, Amit D.
Slattery, Martha L.
Stern, Mariana C.
TI Red meat, poultry, and fish intake and breast cancer risk among Hispanic
and Non-Hispanic white women: The Breast Cancer Health Disparities Study
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Breast cancer; Meat; Hispanics; Processed meat
ID POLYUNSATURATED FATTY-ACIDS; MULTIETHNIC POPULATION; POSTMENOPAUSAL
WOMEN; PROSPECTIVE COHORT; SOUTHERN FRANCE; US LATINAS; CONSUMPTION;
METAANALYSIS; FOOD; ASSOCIATION
AB There is suggestive but limited evidence for a relationship between meat intake and breast cancer (BC) risk. Few studies included Hispanic women. We investigated the association between meats and fish intake and BC risk among Hispanic and NHW women.
The study included NHW (1,982 cases and 2,218 controls) and the US Hispanics (1,777 cases and 2,218 controls) from two population-based case-control studies. Analyses considered menopausal status and percent Native American ancestry. We estimated pooled ORs combining harmonized data from both studies, and study- and race-/ethnicity-specific ORs that were combined using fixed or random effects models, depending on heterogeneity levels.
When comparing highest versus lowest tertile of intake, among NHW we observed an association between tuna intake and BC risk (pooled OR 1.25; 95 % CI 1.05-1.50; trend p = 0.006). Among Hispanics, we observed an association between BC risk and processed meat intake (pooled OR 1.42; 95 % CI 1.18-1.71; trend p < 0.001), and between white meat (OR 0.80; 95 % CI 0.67-0.95; trend p = 0.01) and BC risk, driven by poultry. All these findings were supported by meta-analysis using fixed or random effect models and were restricted to estrogen receptor-positive tumors. Processed meats and poultry were not associated with BC risk among NHW women; red meat and fish were not associated with BC risk in either race/ethnic groups.
Our results suggest the presence of ethnic differences in associations between meat and BC risk that may contribute to BC disparities.
C1 [Kim, Andre E.; Ingles, Sue A.; Stern, Mariana C.] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,Room 5421A, Los Angeles, CA 90089 USA.
[Lundgreen, Abbie; Wolff, Roger K.; Slattery, Martha L.] Univ Utah, Dept Internal Med, Hlth Sci Ctr, Salt Lake City, UT 84112 USA.
[Fejerman, Laura] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Fejerman, Laura] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[John, Esther M.] Canc Prevent Inst Calif, Epidemiol, Fremont, CA USA.
[John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Epidemiol, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA.
[Torres-Mejia, Gabriela] Ctr Invest Salud Poblac, Inst Nacl Salud Publ, Cuernavaca, Morelos, Mexico.
[Boone, Stephanie D.; Baumgartner, Kathy B.] Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA.
[Connor, Avonne E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Connor, Avonne E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Oncol, Baltimore, MD USA.
[Connor, Avonne E.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Hines, Lisa M.] Univ Colorado, Dept Biol, Colorado Springs, CO 80907 USA.
[Giuliano, Anna] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Dept Immunol, Tampa, FL 33612 USA.
[Joshi, Amit D.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA.
RP Stern, MC (reprint author), Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,Room 5421A, Los Angeles, CA 90089 USA.
EM marianas@usc.edu
OI Fejerman, Laura/0000-0003-3179-1151
FU National Cancer Institute [CA14002, CA63446, CA77305, CA078682,
CA078762, CA078552, CA078802, P30CA014089]; US Department of Defense
[DAMD17-96-1-6071]; California Breast Cancer Research Program
[7PB-0068]; National Cancer Institute's Surveillance, Epidemiology and
End Results Program [HHSN261201000036C]; Centers for Disease Control and
Prevention's National Program of Cancer Registries [1U58 DP000807-01];
Utah Cancer Registry from the National Cancer Institute [N01-PC-67000];
State of Utah Department of Health; New Mexico Tumor Registry; Arizona
and Colorado cancer registries; Centers for Disease Control and
Prevention National Program of Cancer Registries; Consejo Nacional de
Ciencia y Tecnologia (CONACyT) [SALUD-2002-C01-7462]; American Cancer
Society [RSF-09-020-01-CNE]; National Institute of Environmental Health
Sciences [5P30 ES07048, 5T32 ES013678]
FX The Breast Cancer Health Disparities Study was funded by Grant CA14002
from the National Cancer Institute to Dr. Slattery. The San Francisco
Bay Area Breast Cancer Study was supported by Grants CA63446 and CA77305
from the National Cancer Institute, Grant DAMD17-96-1-6071 from the US
Department of Defense, and Grant 7PB-0068 from the California Breast
Cancer Research Program. The collection of cancer incidence data used in
this study was supported by the California Department of Public Health
as part of the statewide cancer reporting program mandated by California
Health and Safety Code Section 103885; the National Cancer Institute's
Surveillance, Epidemiology and End Results Program under contract
HHSN261201000036C awarded to the Cancer Prevention Institute of
California; and the Centers for Disease Control and Prevention's
National Program of Cancer Registries, under agreement #1U58 DP000807-01
awarded to the Public Health Institute. The 4-Corners Breast Cancer
Study was funded by Grants CA078682, CA078762, CA078552, and CA078802
from the National Cancer Institute. The research also was supported by
the Utah Cancer Registry, which is funded by contract N01-PC-67000 from
the National Cancer Institute, with additional support from the State of
Utah Department of Health, the New Mexico Tumor Registry, and the
Arizona and Colorado cancer registries, funded by the Centers for
Disease Control and Prevention National Program of Cancer Registries and
additional state support. The contents of this manuscript are solely the
responsibility of the authors and do not necessarily represent the
official view of the National Cancer Institute or endorsement by the
State of California Department of Public Health, the National Cancer
Institute, and the Centers for Disease Control and Prevention or their
Con