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 TC 4 Z9 4 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 TC 2 Z9 2 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 TC 3 Z9 3 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 TC 9 Z9 11 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 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 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 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 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 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 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 TC 12 Z9 13 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 TC 1 Z9 1 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 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 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 TC 11 Z9 11 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 TC 0 Z9 0 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 TC 13 Z9 13 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 TC 0 Z9 0 U1 8 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 TC 0 Z9 0 U1 0 U2 0 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). NR 22 TC 2 Z9 2 U1 5 U2 8 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. NR 25 TC 3 Z9 3 U1 1 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 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 TC 2 Z9 2 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 TC 2 Z9 2 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 TC 7 Z9 7 U1 0 U2 0 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 TC 2 Z9 2 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 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD 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 TC 19 Z9 19 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 TC 11 Z9 11 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 TC 4 Z9 4 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 TC 2 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 TC 0 Z9 0 U1 0 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 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 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 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 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 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1052-3057 EI 1532-8511 J9 J STROKE CEREBROVASC JI J. Stroke Cerebrovasc. Dis. PD 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 TC 1 Z9 1 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 TC 1 Z9 1 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 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 TC 0 Z9 0 U1 1 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. NR 39 TC 4 Z9 4 U1 1 U2 6 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 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. NR 47 TC 2 Z9 2 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 TC 3 Z9 3 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 Z9 2 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 TC 3 Z9 3 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 TC 0 Z9 0 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 TC 1 Z9 1 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 TC 18 Z9 19 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 TC 11 Z9 11 U1 0 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 TC 0 Z9 0 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 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 TC 4 Z9 4 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 TC 6 Z9 6 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 TC 2 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 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 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 TC 1 Z9 1 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 TC 3 Z9 3 U1 0 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 TC 2 Z9 2 U1 0 U2 1 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 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 TC 4 Z9 4 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 TC 1 Z9 1 U1 0 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 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 TC 5 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 TC 0 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 TC 0 Z9 0 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 TC 2 Z9 2 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 TC 0 Z9 0 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 TC 0 Z9 0 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 TC 5 Z9 5 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. [Blomqvist, Carl] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Oncol, Helsinki, Finland. [Ito, Hidemi] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Aichi, Japan. [Matsuo, Keitaro] Aichi Canc Ctr Res Inst, Div Mol Med, Nagoya, Aichi, Japan. [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. [Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada. [Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. [Teo, Soo H.; Yoon, Sook-Yee] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia. [Teo, Soo H.; Yip, Cheng Har] Univ Malaya, Med Ctr, Canc Res Inst, Breast Canc Res Unit, Kuala Lumpur, Malaysia. [Nord, Silje; Borresen-Dale, Anne-Lise; Kristensen, Vessela; Helland, Aslaug; Haakensen, Vilde] Radiumhospitalet, Oslo Univ Hosp, Inst Canc Res, Dept Genet, Oslo, Norway. [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. [Pylkas, Katri; Winqvist, Robert] Northern Finland Lab Ctr NordLab, Lab Canc Genet & Tumor Biol, Oulu, Finland. [Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada. [Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [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. [Devilee, Peter] Leiden Univ Med Ctr, Dept Human Genet, Leiden, Netherlands. [Seynaeve, Caroline; Hollestelle, Antoinette] Erasmus MC, Dept Med Oncol, Rotterdam, Netherlands. [Figueroa, Jonine; Sherman, Mark E.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Czene, Kamila; Darabi, Hatef; Humphreys, Keith; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [van den Ouweland, Ans M. W.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. [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. [Choi, Ji-Yeob; Park, Sue Kyung] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul, South Korea. [Park, Sue Kyung] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul, South Korea. [Kang, Daehee; Lee, Soo Chin] Natl Univ Hlth Syst, Dept Haematol Oncol, Singapore, Singapore. [Kang, Daehee; Lee, Soo Chin] Natl Univ Singapore, Canc Sci Inst Singapore, Singapore 117548, Singapore. [Hartman, Mikael] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore. [Hartman, Mikael] Natl Univ Hlth Syst, Dept Surg, Singapore, Singapore. [Torres, Diana] Pontificia Univ Javerianar, Inst Human Genet, Bogota, Colombia. [Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Huzarski, Tomasz] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland. [Brennan, Paul] Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. [Sangrajrang, Suleeporn] Natl Canc Inst, Bangkok, Thailand. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. [Shen, Chen-Yang] China Med Univ, Sch Publ Hlth, Taichung, Taiwan. [Shen, Chen-Yang; Wu, Pei-Ei] Acad Sinica, Inst Biomed Sci, Taiwan Biobank, Taipei, Taiwan. [Orr, Nick; Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Canc Studies, London SW3 6JB, England. [Swerdlow, Anthony; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England. [Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England. [Kapuscinski, Miroslav] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, Fremont, CA USA. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Daly, Mary B.] Fox Chase Canc Ctr, Dept Clin Genet, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Goldgar, David E.] Univ Utah, Sch Med, Dept Dermatol, Huntsman Canc Inst, Salt Lake City, UT USA. [Buys, Saundra S.] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT USA. [Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Vilnius, Lithuania. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Riga, Latvia. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, ZA-0002 Pretoria, South Africa. [Neuhausen, Susan L.] Beckman Res Inst City Hope, Dept Populat Sci, Duarte, CA USA. [Ejlertsen, Bent] Copenhagen Univ Hosp, Rigshosp, Dept Oncol, Copenhagen, Denmark. [Hansen, Thomas V. O.] Copenhagen Univ Hosp, Rigshosp, Ctr Genom Med, Copenhagen, Denmark. [Osorio, Ana; Benitez, Javier] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. [Osorio, Ana; Benitez, Javier] Biomed Network Rare Dis CIBERER, Madrid, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain. [Rando, Rachel] City Hope Clin Canc Genom Community Res Network, Duarte, CA USA. [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 TC 5 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 TC 5 Z9 5 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 TC 1 Z9 1 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 TC 6 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 TC 1 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 TC 3 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