FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gvilia, I Suntsova, N Kostin, A Kalinchuk, A McGinty, D Basheer, R Szymusiak, R AF Gvilia, Irma Suntsova, Natalia Kostin, Andrey Kalinchuk, Anna McGinty, Dennis Basheer, Radhika Szymusiak, Ronald TI The role of adenosine in the maturation of sleep homeostasis in rats SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article DE sleep homeostasis; postweaning development; rats; adenosine; preoptic hypothalamus ID PREOPTIC AREA NEURONS; WAKING DISCHARGE PATTERNS; BASAL FOREBRAIN NEURONS; EYE-MOVEMENT SLEEP; CHOLINERGIC NEURONS; INFANT RATS; PROLONGED WAKEFULNESS; GABAERGIC NEURONS; A(2A) RECEPTORS; C-FOS AB Sleep homeostasis in rats undergoes significant maturational changes during postweaning development, but the underlying mechanisms of this process are unknown. In the present study we tested the hypothesis that the maturation of sleep is related to the functional emergence of adenosine (AD) signaling in the brain. We assessed postweaning changes in 1) wake-related elevation of extracellular AD in the basal forebrain (BF) and adjacent lateral preoptic area (LPO), and 2) the responsiveness of median preoptic nucleus (MnPO) sleep-active cells to increasing homeostatic sleep drive. We tested the ability of exogenous AD to augment homeostatic responses to sleep deprivation (SD) in newly weaned rats. In groups of postnatal day (P) 22 and P30 rats, we collected dialysate from the BF/LPO during baseline (BSL) wake-sleep, SD, and recovery sleep (RS). HPLC analysis of micro-dialysis samples revealed that SD in P30 rats results in significant increases in AD levels compared with BSL. P22 rats do not exhibit changes in AD levels in response to SD. We recorded neuronal activity in the MnPO during BSL, SD, and RS at P22/P30. MnPO neurons exhibited adult-like increases in waking neuronal discharge across SD on both P22 and P30, but discharge rates during enforced wake were higher on P30 vs. P22. Central administration of AD (1 nmol) during SD on P22 resulted in increased sleep time and EEG slow-wave activity during RS compared with saline control. Collectively, these findings support the hypothesis that functional reorganization of an adenosinergic mechanism of sleep regulation contributes to the maturation of sleep homeostasis. NEW & NOTEWORTHY Brain mechanisms that regulate the maturation of sleep are understudied. The present study generated first evidence about a potential mechanistic role for adenosine in the maturation of sleep homeostasis. Specifically, we demonstrate that early postweaning development in rats, when homeostatic response to sleep loss become adult like, is characterized by maturational changes in wake-related production/release of adenosine in the brain. Pharmacologically increased adenosine signaling in developing brain facilitates homeostatic responses to sleep deprivation. C1 [Gvilia, Irma; Suntsova, Natalia; Kostin, Andrey; McGinty, Dennis; Szymusiak, Ronald] Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91344 USA. [Gvilia, Irma; Suntsova, Natalia; Szymusiak, Ronald] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [McGinty, Dennis] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Gvilia, Irma] Ilia State Univ, Tbilisi, Rep of Georgia. [Kalinchuk, Anna; Basheer, Radhika] Harvard Med Sch, Dept Psychiat, Boston, MA USA. RP Gvilia, I (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv 151A3, 16111 Plummer St, North Hills, CA 91344 USA. EM igvilia@ucla.edu FU Department of Veterans Affairs Medical Research Service Award [BX001556, 2I01BX001404]; National Institute of Mental Health Grant [MH-63323]; Shota Rustaveli National Science Foundation Grant [31/61]; National Institute of Neurological Disorders and Stroke Grant [NS-079866] FX This work was supported by the Department of Veterans Affairs Medical Research Service Award BX001556 (to R. Szymusiak), National Institute of Mental Health Grant MH-63323 (to R. Szymusiak), Shota Rustaveli National Science Foundation Grant 31/61 (to I. Gvilia), Department of Veterans Affairs Medical Research Service Award 2I01BX001404 (to R. Basheer), and National Institute of Neurological Disorders and Stroke Grant NS-079866 (to R. Basheer). NR 48 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN 1 PY 2017 VL 117 IS 1 BP 327 EP 335 DI 10.1152/jn.00675.2016 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA EK3WZ UT WOS:000393860400029 PM 27784808 ER PT J AU Wang, L Djousse, L Song, YQ Akinkuolie, AO Matsumoto, C Manson, JE Gaziano, JM Sesso, HD AF Wang, Lu Djousse, Luc Song, Yiqing Akinkuolie, Akintunde O. Matsumoto, Chisa Manson, JoAnn E. Gaziano, J. Michael Sesso, Howard D. TI Associations of Diabetes and Obesity with Risk of Abdominal Aortic Aneurysm in Men SO JOURNAL OF OBESITY LA English DT Article ID LIFE-STYLE FACTORS; CARDIOVASCULAR-DISEASE; HEALTH; COHORT; POPULATION; GROWTH; ATHEROSCLEROSIS; MORTALITY; SURVEILLANCE; METAANALYSIS AB Background. The associations of diabetes and obesity with the risk of abdominal aortic aneurysm (AAA) are inconclusive in previous studies. Subjects/Methods. We conducted prospective analysis in the Physicians' Health Study. Among 25,554 male physicians aged >= 50 years who reported no AAA at baseline, 471 reported a newly diagnosed AAA during a mean of 10.4 years' follow-up. Results. Compared with men who had baseline body mass index (BMI) <25 kg/m(2), the multivariable hazard ratio (HR[ 95% CI]) of newly diagnosed AAA was 1.30 [1.06-1.59] for BMI 25-<30 kg/m(2) and 1.69 [1.24-2.30] for BMI >= 30 kg/m(2). The risk of diagnosed AAA was significantly higher by 6% with each unit increase in baseline BMI. This association was consistent regardless of the other known AAA risk factors and preexisting vascular diseases. Overall, baseline history of diabetes tended to be associated with a lower risk of diagnosed AAA (HR = 0.79 [0.57-1.11]); this association appeared to vary by follow-up time (HR = 1.56 and 0.63 during <= and > 2 years' follow-up, resp.). Conclusion. In a large cohort of middle-aged and older men, obesity was associated with a higher risk, while history of diabetes tended to associate with a lower risk of diagnosed AAA, particularly over longer follow-up. C1 [Wang, Lu; Akinkuolie, Akintunde O.; Manson, JoAnn E.; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Djousse, Luc; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, 75 Francis St, Boston, MA 02115 USA. [Djousse, Luc; Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Djousse, Luc; Gaziano, J. Michael] VA Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Boston, MA USA. [Song, Yiqing] Indiana Univ, Dept Epidemiol, Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN 46204 USA. [Matsumoto, Chisa] Tokyo Med Univ Hosp, Div Cardiol, Dept Clin Epidemiol, Tokyo, Japan. [Manson, JoAnn E.; Sesso, Howard D.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Wang, L (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. EM luwang@rics.bwh.harvard.edu FU National Institutes of Health (Bethesda, MD) [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF Corporation (Florham Park, NJ) FX The authors are deeply indebted to the 22,071 participants of PHS I and 14,641 participants of PHS II for their long-standing dedication and conscientious collaboration. They also acknowledge the contributions of Gregory Kotler and Natalya Gomelskaya to the statistical analysis of this study. This work was supported by grants (CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595) from the National Institutes of Health (Bethesda, MD) and an investigator-initiated grant from BASF Corporation (Florham Park, NJ). Study agents and packaging in the PHS were provided by BASF Corporation, Pfizer (formerly Wyeth, American Home Products, and Lederle) (New York, NY), and DSM Nutritional Products, Inc. (formerly RocheVitamins) (Parsippany, NJ). NR 47 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2090-0708 EI 2090-0716 J9 J OBES JI J. Obes. PY 2017 AR 3521649 DI 10.1155/2017/3521649 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EL5FR UT WOS:000394647500001 ER PT J AU Kim, EL Tran, J Toteberg-Harms, M Chahal, J Rhee, D Chopra, V Francis, B AF Kim, Esther Lee Tran, Jeffrey Toteberg-Harms, Marc Chahal, Jasdeep Rhee, Douglas Chopra, Vikas Francis, Brian TI Vision Loss and Recovery after Baerveldt Aqueous Tube Shunt Implantation SO JOURNAL OF OPHTHALMOLOGY LA English DT Article ID TREATMENT-OUTCOMES; VISUAL-LOSS; REFRACTORY GLAUCOMA; FOLLOW-UP; TRABECULECTOMY; RISK; SURGERY AB This study aims to determine the course of vision loss after Baerveldt aqueous tube shunt placement and identify risk factors associated with unexplained severe long-term vision loss, or snuff-out. We retrospectively reviewed 247 eyes of 222 patients who underwent Baerveldt implantations at one of two academic institutions. Postoperative vision loss at 6 months following surgery was categorized as mild-to-moderate versus severe and long-term versus transient. Long-term vision loss, defined as 3 or more lines of Snellen visual acuity (VA) loss compared with preoperative VA, occurred in 63 of 247 eyes (25.5%), and 39 had mild-to-moderate and 24 had severe loss. Of these 63 eyes, 18 had no identifiable cause of vision loss. On multivariate analysis, poorer Snellen VA on postoperative day 1 (POD1) was found to be a significant risk factor for long-term vision loss (p = 0.005). In addition, the negative change in preoperative versus POD1 Snellen VA (p = 0.021) and the presence of split fixation involving the inferonasal quadrant on preoperative Humphrey visual field (p = 0.044) were significant risk factors for snuff-out. Transient vision loss occurred in 76 of 242 eyes (30.8%). In conclusion, vision loss is not uncommon after Baerveldt surgery, with snuff-out occurring in 2.4% of cases in this study. C1 [Kim, Esther Lee; Tran, Jeffrey; Chahal, Jasdeep] Univ Southern Calif, Keck Sch Med, Inst Eye, Dept Ophthalmol, Los Angeles, CA USA. [Kim, Esther Lee; Toteberg-Harms, Marc; Rhee, Douglas] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Kim, Esther Lee; Chopra, Vikas; Francis, Brian] Univ Calif Los Angeles, David Geffen Sch Med, Doheny Eye Inst, Los Angeles, CA 90095 USA. [Toteberg-Harms, Marc] Univ Zurich Hosp, Dept Ophthalmol, Zurich, Switzerland. [Rhee, Douglas] Case Western Med Ctr, Dept Ophthalmol & Visual Sci, Cleveland, OH USA. RP Francis, B (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Doheny Eye Inst, Los Angeles, CA 90095 USA. EM bfrancis@doheny.org FU Research to Prevent Blindness; NEI Core Grant [EY03040] FX The authors are supported by an unrestricted grant from Research to Prevent Blindness as well as the NEI Core Grant EY03040. NR 24 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2090-004X EI 2090-0058 J9 J OPHTHALMOL JI J. Ophthalmol. PY 2017 AR 4140305 DI 10.1155/2017/4140305 PG 12 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA EL9UT UT WOS:000394966300001 ER PT J AU Treister, R Eaton, TA Trudeau, JJ Elder, H Katz, NP AF Treister, Roi Eaton, Thomas A. Trudeau, Jeremiah J. Elder, Harrison Katz, Nathaniel P. TI Development and preliminary validation of the focused analgesia selection test to identify accurate pain reporters SO JOURNAL OF PAIN RESEARCH LA English DT Article DE pain assessment; pain variability; analgesic clinical trials; pain psychophysics ID CLINICAL-TRIALS; NEUROPATHIC PAIN; VARIABILITY AB Clinical trials of analgesics have been plagued with poor assay sensitivity due, in part, to variability in subjects' pain reporting. Herein, we develop and evaluate the focused analgesia selection test (FAST), a method to measure patients' pain reporting skills. Subjects with osteoarthritis of the hip, knee, and/or ankle with pain intensity of >= 3/10 on a 0-10 numerical rating scale were enrolled. Subjects underwent the FAST procedure, which consists of recording subjects' pain reports in response to repeated administration of thermal noxious stimuli of various intensities applied on the arm with the Medoc (R) Thermal Sensory Analyzer II. Subjects also rated non-noxious stimuli consisting of visual contrast rating. After performing an exercise task, subjects also rated clinical pain and were asked to report whether their pain had increased, decreased, or stayed the same. Overall, 88 subjects were enrolled, and 83 were included in the analyses. FAST's outcomes including the R-2, intraclass correlation coefficient (ICC), and coefficient of variation (CoV) indicated that subjects' pain reporting skills were widely distributed. Higher FAST ICC significantly predicted greater changes in clinical pain following exercise (p=0.017), whereas the visual contrast test did not predict postexercise pain. FAST is the first method that measures subjects' pain reporting skills. Using FAST to enrich clinical trials with "good" pain reporters (with high FAST ICC) could increase assay sensitivity. Further evaluation of FAST is ongoing. C1 [Treister, Roi] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Treister, Roi; Elder, Harrison; Katz, Nathaniel P.] Analges Solut, 232 Pond St, Natick, MA 01760 USA. [Eaton, Thomas A.] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Trudeau, Jeremiah J.] Boehringer Ingelheim GmbH & Co KG, Ridgefield, CT USA. [Katz, Nathaniel P.] Tufts Univ, Sch Med, Anesthesiol & Perioperat Med, Boston, MA 02111 USA. RP Katz, NP (reprint author), Analges Solut, 232 Pond St, Natick, MA 01760 USA. EM NKatz@analgesicsolutions.com FU Pfizer, Inc. FX The authors wish to thank Pfizer, Inc. for funding this project. NR 9 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7090 J9 J PAIN RES JI J. Pain Res. PY 2017 VL 10 BP 319 EP 326 DI 10.2147/JPR.S121455 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA EM2NE UT WOS:000395152000001 PM 28243138 ER PT J AU Harrington, LB Marck, BT Wiggins, KL McKnight, B Heckbert, SR Woods, NF LaCroix, AZ Blondon, M Psaty, BM Rosendaal, FR Matsumoto, AM Smith, NL AF Harrington, L. B. Marck, B. T. Wiggins, K. L. McKnight, B. Heckbert, S. R. Woods, N. F. LaCroix, A. Z. Blondon, M. Psaty, B. M. Rosendaal, F. R. Matsumoto, A. M. Smith, N. L. TI Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE epidemiology; hemostasis; hormones; postmenopause; women ID VENOUS THROMBOSIS; REPLACEMENT THERAPY; ORAL-CONTRACEPTIVES; COAGULATION-FACTORS; EQUINE ESTROGEN; S LEVELS; RISK; PROTEIN; THROMBOEMBOLISM; PLASMA AB Background Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 g mL(-1) higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nmxmin lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin. C1 [Harrington, L. B.; Heckbert, S. R.; LaCroix, A. Z.; Blondon, M.; Psaty, B. M.; Smith, N. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Harrington, L. B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2,Room 302, Boston, MA 02115 USA. [Marck, B. T.; Matsumoto, A. M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Wiggins, K. L.; Psaty, B. M.] Univ Washington, Dept Med, Seattle, WA USA. [McKnight, B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Heckbert, S. R.; LaCroix, A. Z.; Psaty, B. M.; Smith, N. L.] Univ Washington, Grp Hlth Res Inst, Seattle, WA 98195 USA. [Woods, N. F.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. [LaCroix, A. Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, San Diego, CA 92103 USA. [Blondon, M.] Geneva Univ Hosp & Fac Med, Div Angiol & Hemostasis, Geneva, Switzerland. [Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Rosendaal, F. R.] Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands. [Matsumoto, A. M.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Smith, N. L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off Res & Dev, Seattle, WA USA. RP Harrington, LB (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Nutr, 655 Huntington Ave,Bldg 2,Room 302, Boston, MA 02115 USA. EM lharring@hsph.harvard.edu FU National Institutes of Health [HL007902, HL098048, HL043201, HL060739, HL068986, HL073410, HL074745, HL085251, HL095080] FX This work was supported by National Institutes of Health grants HL007902 (D. S. Siscovick), HL098048 (E. B. Rimm), HL043201 (B. M. Psaty), HL060739 (B. M. Psaty), HL068986 (S. R. Heckbert), HL073410 (N. L. Smith), HL074745 (B. M. Psaty), HL085251 (B. M. Psaty), and HL095080 (N. L. Smith). NR 37 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JAN PY 2017 VL 15 IS 1 BP 80 EP 90 DI 10.1111/jth.13554 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA EK5OI UT WOS:000393975300012 PM 27797446 ER PT J AU Lin, JJ Shaw, AT AF Lin, Jessica J. Shaw, Alice T. TI Raising the bar on first-line immunotherapy in lung cancer SO LANCET ONCOLOGY LA English DT Editorial Material ID OPEN-LABEL; PEMBROLIZUMAB; DOCETAXEL; NIVOLUMAB C1 [Lin, Jessica J.; Shaw, Alice T.] Massachusetts Gen Hosp, Ctr Canc, Dept Thorac Oncol, Boston, MA 02114 USA. RP Shaw, AT (reprint author), Massachusetts Gen Hosp, Ctr Canc, Dept Thorac Oncol, Boston, MA 02114 USA. EM ashaw1@mgh.harvard.edu NR 9 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2017 VL 18 IS 1 BP 2 EP 3 DI 10.1016/S1470-2045(16)30594-0 PG 2 WC Oncology SC Oncology GA EN9SX UT WOS:000396341000017 PM 27932066 ER PT J AU Steensma, DP AF Steensma, David P. TI Predicting therapy-related myeloid neoplasms-and preventing them? SO LANCET ONCOLOGY LA English DT Editorial Material ID ACUTE MYELOGENOUS LEUKEMIA; MYELODYSPLASTIC SYNDROMES; TRANSPLANTATION C1 [Steensma, David P.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Steensma, DP (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM david_steensma@dfci.harvard.edu FU Celgene; Amgen; Genoptix; Takeda; Edward P Evans Foundation FX I report fees from Celgene for being a registry lead, fees from Amgen for being DSMC chair, fees from Genoptix for consulting on the biology of myelodysplastic syndromes, and fees from Takeda for being a DSMC member; I own common stock in Ariad and serve on an advisory board for a platelet drug for Novartis. I am supported by the Edward P Evans Foundation. NR 10 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2017 VL 18 IS 1 BP 11 EP 13 DI 10.1016/s1470-2045(16)30622-2 PG 4 WC Oncology SC Oncology GA EN9SX UT WOS:000396341000023 PM 27927581 ER PT J AU Rosenberg, SM Partridge, AH AF Rosenberg, Shoshana M. Partridge, Ann H. TI Looking back, moving forward: the evolution of cancer survivorship care SO LANCET ONCOLOGY LA English DT Editorial Material ID BREAST-CANCER; TRIAL; PLANS C1 [Partridge, Ann H.] Dana Farber Canc Inst, Boston, MA 02215 USA. Harvard Med Sch, Boston, MA USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Boston, MA 02215 USA. EM ann_partridge@dfci.harvard.edu FU Agency for Healthcare Research and Quality [AHRQ K01 HS023680] FX SMR is supported in part by a grant from the Agency for Healthcare Research and Quality (AHRQ K01 HS023680). We declare no other competing interests. 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2017 VL 18 IS 1 BP 18 EP 19 PG 3 WC Oncology SC Oncology GA EN9SX UT WOS:000396341000027 PM 28049568 ER PT J AU Guinney, J Wang, T Laajala, TD Winner, KK Bare, JC Neto, EC Khan, SA Peddinti, G Airola, A Pahikkala, T Mirtti, T Yu, T Bot, BM Shen, L Abdallah, K Norman, T Friend, S Stolovitzky, G Soule, H Sweeney, CJ Ryan, CJ Scher, HI Sartor, O Xie, Y Aittokallio, T Zhou, FL Costello, JC AF Guinney, Justin Wang, Tao Laajala, Teemu D. Winner, Kimberly Kanigel Bare, J. Christopher Neto, Elias Chaibub Khan, Suleiman A. Peddinti, Gopal Airola, Antti Pahikkala, Tapio Mirtti, Tuomas Yu, Thomas Bot, Brian M. Shen, Liji Abdallah, Kald Norman, Thea Friend, Stephen Stolovitzky, Gustavo Soule, Howard Sweeney, Christopher J. Ryan, Charles J. Scher, Howard I. Sartor, Oliver Xie, Yang Aittokallio, Tero Zhou, Fang Liz Costello, James C. CA Prostate Canc Challenge DREAM Comm TI Prediction of overall survival for patients with metastatic castration-resistant prostate cancer: development of a prognostic model through a crowdsourced challenge with open clinical trial data SO LANCET ONCOLOGY LA English DT Article ID SIPULEUCEL-T IMMUNOTHERAPY; BIOMEDICAL-RESEARCH; DOUBLE-BLIND; PHASE-III; CHEMOTHERAPY; DOCETAXEL; PREDNISONE; PLACEBO; MEN; ENZALUTAMIDE AB Background Improvements to prognostic models in metastatic castration-resistant prostate cancer have the potential to augment clinical trial design and guide treatment strategies. In partnership with Project Data Sphere, a not-for-profit initiative allowing data from cancer clinical trials to be shared broadly with researchers, we designed an open-data, crowdsourced, DREAM (Dialogue for Reverse Engineering Assessments and Methods) challenge to not only identify a better prognostic model for prediction of survival in patients with metastatic castration-resistant prostate cancer but also engage a community of international data scientists to study this disease. Methods Data from the comparator arms of four phase 3 clinical trials in first-line metastatic castration-resistant prostate cancer were obtained from Project Data Sphere, comprising 476 patients treated with docetaxel and prednisone from the ASCENT2 trial, 526 patients treated with docetaxel, prednisone, and placebo in the MAINSAIL trial, 598 patients treated with docetaxel, prednisone or prednisolone, and placebo in the VENICE trial, and 470 patients treated with docetaxel and placebo in the ENTHUSE 33 trial. Datasets consisting of more than 150 clinical variables were curated centrally, including demographics, laboratory values, medical history, lesion sites, and previous treatments. Data from ASCENT2, MAINSAIL, and VENICE were released publicly to be used as training data to predict the outcome of interest-namely, overall survival. Clinical data were also released for ENTHUSE 33, but data for outcome variables (overall survival and event status) were hidden from the challenge participants so that ENTHUSE 33 could be used for independent validation. Methods were evaluated using the integrated time-dependent area under the curve (iAUC). The reference model, based on eight clinical variables and a penalised Cox proportional-hazards model, was used to compare method performance. Further validation was done using data from a fifth trial-ENTHUSE M1-in which 266 patients with metastatic castration-resistant prostate cancer were treated with placebo alone. Findings 50 independent methods were developed to predict overall survival and were evaluated through the DREAM challenge. The top performer was based on an ensemble of penalised Cox regression models (ePCR), which uniquely identified predictive interaction effects with immune biomarkers and markers of hepatic and renal function. Overall, ePCR outperformed all other methods (iAUC 0.791; Bayes factor >5) and surpassed the reference model (iAUC 0.743; Bayes factor >20). Both the ePCR model and reference models stratified patients in the ENTHUSE 33 trial into high-risk and low-risk groups with significantly different overall survival (ePCR: hazard ratio 3.32, 95% CI 2.39-4.62, p<0.0001; reference model: 2.56, 1.85-3.53, p<0.0001). The new model was validated further on the ENTHUSE M1 cohort with similarly high performance (iAUC 0.768). Meta-analysis across all methods confirmed previously identified predictive clinical variables and revealed aspartate aminotransferase as an important, albeit previously under-reported, prognostic biomarker. Interpretation Novel prognostic factors were delineated, and the assessment of 50 methods developed by independent international teams establishes a benchmark for development of methods in the future. The results of this effort show that data-sharing, when combined with a crowdsourced challenge, is a robust and powerful framework to develop new prognostic models in advanced prostate cancer. C1 [Guinney, Justin; Bare, J. Christopher; Neto, Elias Chaibub; Yu, Thomas; Bot, Brian M.; Norman, Thea; Friend, Stephen] Sage Bionetworks, Seattle, WA USA. [Wang, Tao; Xie, Yang] Univ Texas Southwestern Med Ctr, Quantitat Biomed Res Ctr, Dept Clin Sci, Dallas, TX USA. [Wang, Tao] Univ Texas Southwestern Med Ctr, Ctr Genet Host Def, Dallas, TX USA. [Xie, Yang] Univ Texas Southwestern Med Ctr, Simmons Comprehens Canc Ctr, Dallas, TX USA. [Xie, Yang] Univ Texas Southwestern Med Ctr, Lyda Hill Dept Bioinformat, Dallas, TX USA. [Laajala, Teemu D.; Aittokallio, Tero] Turku Univ, Dept Math & Stat, Turku, Finland. [Laajala, Teemu D.; Airola, Antti; Pahikkala, Tapio] Turku Univ, Dept Informat Technol, Turku, Finland. [Laajala, Teemu D.; Khan, Suleiman A.; Peddinti, Gopal; Mirtti, Tuomas; Aittokallio, Tero] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland. [Mirtti, Tuomas] Helsinki Univ Hosp, Dept Pathol HUSLAB, Helsinki, Finland. [Winner, Kimberly Kanigel; Costello, James C.] Univ Colorado, Dept Pharmacol & Computat Biosci Program, Anschutz Med Campus, Aurora, CO 80045 USA. [Costello, James C.] Univ Colorado Comprehens Canc Ctr, Anschutz Med Campus, Aurora, CO USA. [Abdallah, Kald] AstraZeneca, Gaithersburg, MD USA. [Stolovitzky, Gustavo] IBM Corp, IBM TJ Watson Res Ctr, Yorktown Hts, NY USA. [Soule, Howard] Prostate Canc Fdn, Santa Monica, CA USA. [Sweeney, Christopher J.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Ryan, Charles J.] Univ Calif San Francisco, Div Hematol & Oncol, Genitourinary Med Oncol Program, San Francisco, CA USA. [Scher, Howard I.] Sidney Kimmel Ctr Prostate, Dept Med, Genitourinary Oncol Serv, Sidney, BC, Canada. [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, Urol Canc, New York, NY USA. [Scher, Howard I.] Weill Cornell Med Coll, New York, NY USA. [Sartor, Oliver] Tulane Univ, Tulane Canc Ctr, New Orleans, LA USA. [Shen, Liji; Zhou, Fang Liz] Sanofi, Bridgewater, NJ USA. RP Costello, JC (reprint author), Univ Colorado Anschutz Med Campus, Aurora, CO 80045 USA. EM james.costello@ucdenver.edu RI Khan, Suleiman/F-3472-2017; Aittokallio, Tero/B-6583-2009; OI Khan, Suleiman/0000-0002-0823-4042; Aittokallio, Tero/0000-0002-0886-9769; Ballester, Pedro/0000-0002-4078-743X FU Sanofi US Services; Project Data Sphere FX Sanofi US Services, Project Data Sphere. NR 33 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2017 VL 18 IS 1 BP 132 EP 142 DI 10.1016/S1470-2045(16)30560-5 PG 11 WC Oncology SC Oncology GA EN9SX UT WOS:000396341000054 PM 27864015 ER PT J AU Wilkerson, J Abdallah, K Hugh-Jones, C Curt, G Rothenberg, M Simantov, R Murphy, M Morrell, J Beetsch, J Sargent, DJ Scher, HI Lebowitz, P Simon, R Stein, WD Bates, SE Fojo, T AF Wilkerson, Julia Abdallah, Kald Hugh-Jones, Charles Curt, Greg Rothenberg, Mace Simantov, Ronit Murphy, Martin Morrell, Joseph Beetsch, Joel Sargent, Daniel J. Scher, Howard I. Lebowitz, Peter Simon, Richard Stein, Wilfred D. Bates, Susan E. Fojo, Tito TI Estimation of tumour regression and growth rates during treatment in patients with advanced prostate cancer: a retrospective analysis SO LANCET ONCOLOGY LA English DT Article ID CELL LUNG-CANCER; DOCETAXEL PLUS PREDNISONE; PHASE-III TRIAL; OPEN-LABEL; RATE CONSTANTS; DOUBLE-BLIND; SURVIVAL; CHEMOTHERAPY; MITOXANTRONE; PLACEBO AB Background We applied mathematical models to clinical trial data available at Project Data Sphere LLC (Cary, NC, USA), a non-profit universal access data-sharing warehouse. Our aim was to assess the rates of cancer growth and regression using the comparator groups of eight randomised clinical trials that enrolled patients with metastatic castration-resistant prostate cancer. Methods In this retrospective analysis, we used data from eight randomised clinical trials with metastatic castration-resistant prostate cancer to estimate the growth (g) and regression (d) rates of disease burden over time. Rates were obtained by applying mathematical models to prostate-specific antigen levels as the representation of tumour quantity. Rates were compared between study interventions (prednisone, mitoxantrone, and docetaxel) and off-treatment data when on-study treatment had been discontinued to understand disease behaviour during treatment and after discontinuation. Growth (g) was examined for association with a traditional endpoint (overall survival) and for its potential use as an endpoint to reduce sample size in clinical trials. Findings Estimates for g, d, or both were obtained in 2353 (88%) of 2678 patients with data available for analysis; g differentiated docetaxel (a US Food and Drug Administration-approved therapy) from prednisone and mitoxantrone and was predictive of overall survival in a landmark analysis at 8 months. A simulated sample size analysis, in which g was used as the endpoint, compared docetaxel data with mitoxantrone data and showed that small sample sizes were sufficient to achieve 80% power (16, 47, and 25 patients, respectively, in the three docetaxel comparator groups). Similar results were found when the mitoxantrone data were compared with the prednisone data (41, 39, and 41 patients in the three mitoxantrone comparator groups). Finally, after discontinuation of docetaxel therapy, median tumour growth (g) increased by nearly five times. Interpretation The application of mathematical models to existing clinical data allowed estimation of rates of growth and regression that provided new insights in metastatic castration-resistant prostate cancer. The availability of clinical data through initiatives such as Project Data Sphere, when combined with innovative modelling techniques, could greatly enhance our understanding of how cancer responds to treatment, and accelerate the productivity of clinical development programmes. C1 [Wilkerson, Julia] NCI, Genitourinary Malignancies Branch, NIH, Bethesda, MD USA. [Abdallah, Kald; Curt, Greg] AstraZeneca, Gaithersburg, MD USA. [Hugh-Jones, Charles] Sanofi US, Bridgewater, NJ USA. [Rothenberg, Mace; Simantov, Ronit] Pfizer Inc, New York, NY USA. [Murphy, Martin; Morrell, Joseph] Project Data Sphere LLC, Cary, NC USA. [Beetsch, Joel] Celgene Corp, Summit, NJ USA. [Sargent, Daniel J.] Mayo Med Ctr, Rochester, MN USA. [Scher, Howard I.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Lebowitz, Peter] Johnson & Johnson, Janssen Pharmaceut Co, New Brunswick, NJ USA. [Simon, Richard] NCI, Biometr Res Program, NIH, Bethesda, MD USA. [Stein, Wilfred D.] Hebrew Univ Jerusalem, Silberman Inst Life Sci, Jerusalem, Israel. [Bates, Susan E.; Fojo, Tito] Columbia Univ, New York Presbyterian Hosp, Dept Med, Div Med Oncol, New York, NY USA. [Bates, Susan E.; Fojo, Tito] James J Peters VA Med Ctr, Bronx, NY USA. RP Fojo, T (reprint author), Univ Colombia, Div Med Oncol, Dept Med, Herbert Irving Pavil,9th Floor, New York, NY 10032 USA. EM atf2116@cumc.columbia.edu NR 35 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 JAN PY 2017 VL 18 IS 1 BP 143 EP 154 DI 10.1016/S1470-2045(16)30633-7 PG 12 WC Oncology SC Oncology GA EN9SX UT WOS:000396341000055 PM 27979599 ER PT J AU Recklitis, CJ Syrjala, KL AF Recklitis, Christopher J. Syrjala, Karen L. TI Provision of integrated psychosocial services for cancer survivors post-treatment SO LANCET ONCOLOGY LA English DT Article ID PRIMARY-CARE PHYSICIANS; SELF-MANAGEMENT; GUIDELINE ADAPTATION; AMERICAN SOCIETY; CHRONIC DISEASE; ROUTINE CANCER; UNITED-STATES; OLDER-ADULTS; MEDICAL HOME; CHRONIC PAIN AB Meeting the psychosocial needs of patients with cancer has been recognised as a priority within oncology care for several decades. Many approaches that address these needs have been developed and described; however, until recently much of this work had focused on patients during treatment and end-of-life care. With continued improvement in therapies, the population of cancer survivors who can expect to live for 5 or more years after cancer diagnosis has increased dramatically, as have associated concerns about how to meet their medical, psychosocial, and health behaviour needs after treatment. Guidelines and models for general survivorship care routinely address psychosocial needs, and similar guidelines for psychosocial care of patients with cancer are being extended to address the needs of survivors. In this Series paper, we summarise the existing recommendations for the provision of routine psychosocial care to survivors, as well as the challenges present in providing this care. We make specific recommendations for the integration of psychosocial services into survivorship care. C1 [Recklitis, Christopher J.] Dana Farber Canc Inst, Perini Family Survivors Ctr, 450 Brookline Ave, Boston, MA 02215 USA. [Recklitis, Christopher J.] Harvard Med Sch, Boston, MA USA. [Syrjala, Karen L.] Fred Hutchinson Canc Res Ctr, Biobehav Sci Dept, 1124 Columbia St, Seattle, WA 98104 USA. [Syrjala, Karen L.] Univ Washington, Sch Med, Seattle, WA USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, 450 Brookline Ave, Boston, MA 02215 USA. EM christopher_recklitis@dfci.harvard.edu NR 96 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 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JAN PY 2017 VL 18 IS 1 BP E39 EP E50 PG 12 WC Oncology SC Oncology GA EN9SX UT WOS:000396341000014 PM 28049576 ER PT J AU Petrova-Drus, K Hasserjian, R Pozdnyakova, O Dal Cin, P Mathew, S Margolskee, E Orazi, A Geyer, JT AF Petrova-Drus, Kseniya Hasserjian, Robert Pozdnyakova, Olga Dal Cin, Paola Mathew, Susan Margolskee, Elizabeth Orazi, Attilio Geyer, Julia T. TI Clinicopathologic evaluation of cytopenic patients with isolated trisomy 8: a detailed comparison between idiopathic cytopenia of unknown significance and low-grade myelodysplastic syndrome SO LEUKEMIA & LYMPHOMA LA English DT Article DE Idiopathic cytopenia of undetermined significance; isolated trisomy 8 (+8); myelodysplastic syndrome; myeloid neoplasms ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; IN-SITU HYBRIDIZATION; CHROMOSOME-ABNORMALITIES; CYTOGENETIC MARKERS; SYNDROMES MDS; DISEASE; DIAGNOSIS; LYMPHOMA AB The significance of an isolated trisomy 8 (+8) in the diagnosis of myelodysplastic syndrome (MDS) is not well established. It is common in MDS, but is not considered as an MDS-defining abnormality in the absence of morphologic dysplasia. We evaluated two groups of patients with isolated +8 and either low-grade MDS (LG-MDS) or idiopathic cytopenia of undetermined significance (ICUS). At presentation, ICUS patients had a lower platelet count (85.0 vs 163.5 x 10(9) cells/L; p = 0.02), while MDS patients had more frequent incidence of isolated anemia (64% vs 0%, p = 0.007). A subset (36%) of ICUS patients progressed to MDS or AML. These patients presented with more severe neutropenia (0.9 vs 3.1 x 10(3)/mu L, p = 0.01) and a trend toward a higher proportion (> 50%) of+8 metaphases compared to those that did not progress (p = 0.05). Thus, ICUS patients with isolated +8 may progress to MDS and AML and deserve close clinical follow-up. C1 [Petrova-Drus, Kseniya; Mathew, Susan; Margolskee, Elizabeth; Orazi, Attilio; Geyer, Julia T.] New York Presbyterian Hosp, Weill Cornell Med, Dept Pathol & Lab Med, New York, NY USA. [Hasserjian, Robert] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Pozdnyakova, Olga] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Dal Cin, Paola] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, Boston, MA 02115 USA. RP Petrova-Drus, K (reprint author), New York Presbyterian Hosp, Weill Cornell Med, Dept Pathol & Lab Med, Div Hematopathol, Starr 711A,525 East 68th St, New York, NY 10065 USA. EM ksp9004@nyp.org NR 48 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2017 VL 58 IS 3 BP 569 EP 577 DI 10.1080/10428194.2016.1203432 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA EK4IW UT WOS:000393891300009 PM 27389864 ER PT J AU Castillo, JJ Gertz, MA AF Castillo, Jorge J. Gertz, Morie A. TI Secondary malignancies in patients with multiple myeloma, Waldenstrom macroglobulinemia and monoclonal gammopathy of undetermined significance SO LEUKEMIA & LYMPHOMA LA English DT Review DE Myeloma; Waldenstrom macroglobulinemia; MGUS; secondary malignancies ID STEM-CELL TRANSPLANTATION; 2ND PRIMARY MALIGNANCIES; MYELODYSPLASTIC SYNDROMES; PRIMARY CANCERS; ACUTE-LEUKEMIA; SEER DATABASE; LONG-TERM; RISK; LENALIDOMIDE; MELPHALAN AB In recent years, the survival of patients with plasma cell dyscrasias has improved due to improvements in anticancer and supportive therapy. However, the risk of secondary malignancies has increased, thought to be due to a combination of environmental and disease-related factors, as well as treatment. In the present review, we evaluate the risk of secondary malignancies in patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and Waldenstrom macroglobulinemia (WM). Patients with MGUS appear to have a higher risk of developing myeloid malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). In patients with MM, the risk of AML, acute lymphoblastic leukemia and some solid tumors appears increased. Finally, in WM patients, there seems to be increased risk of AML, diffuse large B-cell lymphoma, thyroid cancer and melanoma. C1 [Castillo, Jorge J.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA. [Gertz, Morie A.] Mayo Clin, Div Hematol, Rochester, MN USA. RP Castillo, JJ (reprint author), 450 Brookline Ave,Mayer 221, Boston, MA 02215 USA. EM Jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532 NR 39 TC 1 Z9 1 U1 2 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2017 VL 58 IS 4 BP 773 EP 780 DI 10.1080/10428194.2016.1217527 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA EK4JG UT WOS:000393892300005 PM 27546465 ER PT J AU Zeidan, AM Wang, R Gross, CP Gore, SD Huntington, SF Prebet, T Abel, GA Davidoff, AJ Ma, XM AF Zeidan, Amer M. Wang, Rong Gross, Cary P. Gore, Steven D. Huntington, Scott F. Prebet, Thomas Abel, Gregory A. Davidoff, Amy J. Ma, Xiaomei TI Modest improvement in survival of patients with refractory anemia with excess blasts in the hypomethylating agents era in the United States SO LEUKEMIA & LYMPHOMA LA English DT Letter ID RISK MYELODYSPLASTIC SYNDROMES; PHASE-III; AZACITIDINE; REGIMENS; LEUKEMIA; OUTCOMES; REGISTRY; CANCER C1 [Zeidan, Amer M.; Gore, Steven D.; Huntington, Scott F.; Prebet, Thomas] Yale Sch Med, Dept Internal Med, Sect Hematol, 333 Cedar St,POB 208028, New Haven, CT 06250 USA. [Zeidan, Amer M.; Wang, Rong; Gross, Cary P.; Gore, Steven D.; Huntington, Scott F.; Davidoff, Amy J.; Ma, Xiaomei] Yale Univ, COPPER, New Haven, CT USA. [Wang, Rong; Ma, Xiaomei] Yale Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA. [Abel, Gregory A.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Davidoff, Amy J.] Yale Sch Publ Hlth, Dept Hlth Policy & Management, New Haven, CT USA. RP Zeidan, AM (reprint author), Yale Sch Med, Dept Internal Med, Sect Hematol, 333 Cedar St,POB 208028, New Haven, CT 06250 USA. EM amer.zeidan@yale.edu NR 18 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2017 VL 58 IS 4 BP 982 EP 985 DI 10.1080/10428194.2016.1214954 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA EK4JG UT WOS:000393892300030 PM 27558206 ER PT J AU Xiao, Y Liu, ZZ Liao, CN Mao, XX Cai, JX Xia, K Qi, J Huang, H Yang, TL Duan, Q AF Xiao, Yi Liu, Zhenzhen Liao, Chaonan Mao, Xiaoxiao Cai, Jinxing Xia, Ke Qi, Jun Huang, He Yang, Tianlun Duan, Qiong TI Inhibition of BET bromodomain improves anemia in APC(min) mice SO LEUKEMIA & LYMPHOMA LA English DT Letter ID HEMATOPOIETIC STEM; MOUSE; MODEL; WNT C1 [Xiao, Yi; Liu, Zhenzhen; Mao, Xiaoxiao; Xia, Ke; Yang, Tianlun; Duan, Qiong] Cent S Univ, Xiangya Hosp, Div Cardiovasc, 87 Xiangya Rd, Changsha 410078, Hunan, Peoples R China. [Liao, Chaonan; Cai, Jinxing; Huang, He] Cent S Univ, Xiangya Sch Med, Dept Histol & Embryol, 172 Tongzipo Rd, Changsha 410008, Hunan, Peoples R China. [Mao, Xiaoxiao] Brigham & Womens Hosp, Harvard Med Sch, Div Cardiovasc, Boston, MA 02115 USA. [Qi, Jun] Dana Farber Canc Inst, Harvard Med Sch, Dept Med Oncol, Boston, MA 02115 USA. RP Yang, TL; Duan, Q (reprint author), Cent S Univ, Xiangya Hosp, Div Cardiovasc, 87 Xiangya Rd, Changsha 410078, Hunan, Peoples R China.; Huang, H (reprint author), Cent S Univ, Xiangya Sch Med, Dept Histol & Embryol, 172 Tongzipo Rd, Changsha 410008, Hunan, Peoples R China. EM huanghe@csu.edu.cn; tianluny@163.com; qiongorwu@163.com FU National Natural Science Foundation of China [81370320, 81570334, 81141068, 31571241]; Xiangya Eminent Doctor Project [013]; Zijing Foundation FX We thank Fan Xia for technical support and Xiong Xiao for the assistance with picture editing. This work was supported by the National Natural Science Foundation of China [81370320, 81570334] (TL Yang), and [81141068, 31571241] (H Huang), Xiangya Eminent Doctor Project #013 (TL Yang), and Zijing Foundation (Q Duan). NR 14 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2017 VL 58 IS 4 BP 989 EP 992 DI 10.1080/10428194.2016.1219907 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA EK4JG UT WOS:000393892300032 PM 27545270 ER PT J AU Castillo, JJ Gustine, JN Meid, K Dubeau, T Yang, G Xu, L Hunter, ZR Treon, SP AF Castillo, Jorge J. Gustine, Joshua N. Meid, Kirsten Dubeau, Toni Yang, Guang Xu, Lian Hunter, Zachary R. Treon, Steven P. TI Idelalisib in Waldenstrom macroglobulinemia: high incidence of hepatotoxicity SO LEUKEMIA & LYMPHOMA LA English DT Letter ID CONSENSUS PANEL RECOMMENDATIONS; 2ND INTERNATIONAL WORKSHOP; LYMPHOMA; THERAPY C1 [Castillo, Jorge J.; Gustine, Joshua N.; Meid, Kirsten; Dubeau, Toni; Yang, Guang; Xu, Lian; Hunter, Zachary R.; Treon, Steven P.] Harvard Med Sch, Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. RP Castillo, JJ (reprint author), 450 Brookline Ave, Boston, MA 02215 USA. EM Jorgej_castillo@dfci.harvard.edu OI Castillo, Jorge/0000-0001-9490-7532; Hunter, Zachary/0000-0002-1689-1691 FU Gilead [10.13039/100005564, IN-US-313-1609] FX Gilead, 10.13039/100005564 [IN-US-313-1609]. NR 11 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1042-8194 EI 1029-2403 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2017 VL 58 IS 4 BP 1002 EP 1004 DI 10.1080/10428194.2016.1222380 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA EK4JG UT WOS:000393892300036 PM 27562445 ER PT J AU Riggs, KR Knight, SJ AF Riggs, Kevin R. Knight, Sara J. TI The Language of Stewardship: Is the "Low-Value" Label Overused? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID TOP 5 LISTS; PROSTATE-CANCER; HEALTH-CARE; COST; CLINICIAN; MEDICINE; NEED C1 [Riggs, Kevin R.] Univ Alabama Birmingham, Div Prevent Med, MT 610,1720 2nd Ave S, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Riggs, KR (reprint author), Univ Alabama Birmingham, Div Prevent Med, MT 610,1720 2nd Ave S, Birmingham, AL 35294 USA. EM kriggs@uab.edu FU National Institutes of Health [T32HL007180] FX This work was supported in part by grant T32HL007180 (K.R.R.) from the National Institutes of Health. NR 24 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 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2017 VL 92 IS 1 BP 11 EP 14 DI 10.1016/j.mayocp.2016.09.011 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA EK4QQ UT WOS:000393912300008 PM 27842705 ER PT J AU Doufas, AG Panagiotou, OA Panousis, P Wong, SS Ioannidis, JPA AF Doufas, Anthony G. Panagiotou, Orestis A. Panousis, Periklis Wong, Shane Shucheng Ioannidis, John P. A. TI Insomnia From Drug Treatments: Evidence From Meta-analyses of Randomized Trials and Concordance With Prescribing Information SO MAYO CLINIC PROCEEDINGS LA English DT Article ID SLEEP FOUNDATION SURVEY; PSYCHIATRIC-DISORDERS; UNITED-STATES; DEPRESSION; HETEROGENEITY; EPIDEMIOLOGY; PERFORMANCE; PREVALENCE; SYMPTOMS; ADULTS AB Objective: To determine whether drugs used to treat diverse conditions cause insomnia symptoms and whether their prescription information is concordant with this evidence. Methods: We conducted a survey of meta-analyses (Cochrane Database of Systematic Reviews) and comparisons with package inserts compiled in the Physicians' Desk Reference (PDR). We identified randomized controlled trials (RCTs) in which any drug had been evaluated vs placebo and sleep had been assessed. We collectively referred to insomnia-related outcomes as sleep disturbance. We also searched the PDR to identify any insomnia symptoms listed for drugs with RCT evidence available. Results: Seventy-four Cochrane systematic reviews corresponding to 274 RCTs assessed 88 drugs in 27 different conditions, providing evidence on 109 drug-condition pairs. Of these 88 drugs, 5 decreased sleep problems and 19 increased sleep problems; 64 drugs had no nominally statistically significant effect on sleep. Acetylcholinesterase inhibitors, dopamine agonists, and selective serotonin reuptake inhibitors were the drug classes most importantly associated with sleep disturbance. Of 35 drugs that included disturbed sleep as an adverse effect in the PDR, only 14 had RCT evidence supporting such effect, and 2 had evidence of increasing and decreasing sleep problems in RCTs, although this was not shown in the PDR. We identified weak concordance between the PDR and RCTs (weighted k = 0.31; P<. 001). Conclusion: The RCTs offer substantial evidence about the common effects of drugs on the risk of sleep disturbance; currently, prescription information only partially agrees with the available randomized evidence. (C) 2016 Mayo Foundation for Medical Education and Research C1 [Doufas, Anthony G.; Panousis, Periklis] Stanford Univ, Sch Med, Stanford Prevent Res Ctr, Dept Anesthesiol Perioperat & Pain Med, Stanford, CA 94305 USA. [Wong, Shane Shucheng] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, MD Program, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. [Ioannidis, John P. A.] Stanford Univ, Sch Med, Meta Res Innovat Ctr Stanford, Stanford, CA 94305 USA. [Doufas, Anthony G.] Outcomes Res Consortium, Cleveland, OH USA. [Panagiotou, Orestis A.] Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Panagiotou, Orestis A.] Brown Univ, Sch Publ Hlth, Ctr Gerontol & Healthcare Res, Providence, RI 02912 USA. [Ioannidis, John P. A.] Stanford Univ, Sch Humanities & Sci, Dept Stat, Stanford, CA 94305 USA. [Wong, Shane Shucheng] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Ioannidis, JPA (reprint author), Stanford Univ, Stanford Prevent Res Ctr, Sch Med, MSOB X306,1265 Welch Rd, Stanford, CA 94305 USA. EM jioannid@stanford.edu NR 38 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 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2017 VL 92 IS 1 BP 72 EP 87 DI 10.1016/j.mayocp.2016.09.005 PG 16 WC Medicine, General & Internal SC General & Internal Medicine GA EK4QQ UT WOS:000393912300015 PM 27842706 ER PT J AU Steensma, DP Kyle, RA AF Steensma, David P. Kyle, Robert A. TI The Medical Doctors of Star Trek: Leonard "Bones" McCoy and Beverly Crusher SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kyle, Robert A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. 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 0025-6196 EI 1942-5546 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD JAN PY 2017 VL 92 IS 1 BP E9 EP E10 DI 10.1016/j.mayocp.2016.10.025 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA EK4QQ UT WOS:000393912300003 PM 28062069 ER PT J AU Cai, SY Kong, XY Yan, CR Liu, Y Zhou, X Qiu, GX AF Cai, Siyi Kong, Xiangyi Yan, Chengrui Liu, Yong Zhou, Xi Qiu, Guixing TI Successful treatment of metastatic pheochromocytoma in the spine with cement augmentation SO MEDICINE LA English DT Article DE cement; metastatic pheochromocytoma; osteoplasty; spine ID INTRAOSSEOUS PARAGANGLIOMA; LOCAL TUMOR; CRYOABLATION; RESECTION; SACRUM AB Metastatic pheochromocytoma in the spine is rare, and there is no standard curative management. Treatment via open surgery is often risky in the perioperative period, while osteoplasty by cement augmentation is a less invasive option. We describe 2 patients with recurrence of pheochromocytoma involving the spine and the pelvis who were successfully treated with osteoplasty by cement augmentation. A 31-year-old female underwent cement augmentation for a pelvic lesion 6 months after the resection and screw fixation of an L3 lesion. A 58-year-old male underwent cement augmentation to directly destroy the functional tumor, with a surgical decompression 6 months later. Both patients showed appropriate destruction of the tumor, adequate pain relief, and the decreased release of catecholamine from metastatic lesions. Osteoplasty by cement augmentation may be a treatment option for patients with metastatic pheochromocytoma who cannot undergo appropriate surgery or decline surgery. This represents a safe approach to sustainably relieve pain and stabilize vertebral bodies with metastatic malignant pheochromocytoma. C1 [Cai, Siyi; Liu, Yong; Zhou, Xi; Qiu, Guixing] Beijing Union Med Coll Hosp, Peking Union Med Coll, Dept Orthopaed Surg, 1 Shuaifuyuan Wangfujing, Beijing 100730, Peoples R China. [Kong, Xiangyi; Yan, Chengrui] Beijing Union Med Coll Hosp, Peking Union Med Coll, Dept Neurosurg, Beijing, Peoples R China. [Kong, Xiangyi; Yan, Chengrui] Chinese Acad Med Sci, 1 Shuaifuyuan Wangfujing, Beijing 100730, Peoples R China. [Kong, Xiangyi] Harvard Univ, Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Liu, Y (reprint author), Beijing Union Med Coll Hosp, Peking Union Med Coll, Dept Orthopaed Surg, 1 Shuaifuyuan Wangfujing, Beijing 100730, Peoples R China.; Liu, Y (reprint author), Chinese Acad Med Sci, 1 Shuaifuyuan Wangfujing, Beijing 100730, Peoples R China. EM liuyong_pumch@126.com FU Peking Union Medical College Youth Research Funds [3332016010]; Peking Union Medical College Graduate Student Innovation Fund [2015-1002-02-09] FX This study was supported by Peking Union Medical College Youth Research Funds (2016) (Project No. 3332016010; to XK) and Peking Union Medical College Graduate Student Innovation Fund (2015) (Project No. 2015-1002-02-09; to XK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2017 VL 96 IS 4 AR e5892 DI 10.1097/MD.0000000000005892 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA EK1WT UT WOS:000393717200024 PM 28121933 ER PT J AU Kong, XY Li, DM Kong, YG Zhong, DR AF Kong, Xiangyi Li, Dongmei Kong, Yanguo Zhong, Dingrong TI Malignant adenohypophysis spindle cell oncocytoma with repeating recurrences and a high Ki-67 index SO MEDICINE LA English DT Article DE adenohypophysis spindle cell oncocytoma; Ki-67 index; malignant; recurrent ID OF-THE-LITERATURE; PITUICYTOMA; PITUITARY; TUMORS AB Adenohypophysis spindle cell oncocytoma (ASCO) is a rare tumor recently reported by Roncaroli et al in 2002. This tumor is considered a grade I tumor by the World Health Organization. We report a rare case of malignant ASCO with repeating recurrences and a high Ki-67 index-a challenging diagnosis guided by clinical presentations, radiological signs, and postoperative pathological tests. We represent a 30-year-old man who had suffered from headaches, diplopia, and impaired visual field and acuity. His magnetic resonance imaging revealed an abnormal sellar mass and was originally misdiagnosed as a pituitary macroadenoma. We present detailed analysis of the patient's disease course and review relevant literature. When surgically treated, the specimen revealed a typical histopathology pattern of ASCO. The tumor recurred for several times and the patient underwent 3 surgeries and 1 g-knife treatment, which was accompanied by a continuously increasing Ki-67 index. This is the first reported case of malignant ASCO (WHO III-IV grade). Despite its rarity, ASCO should be considered in the differential diagnosis of sellar lesions that mimic pituitary adenomas. Abbreviations: ACTH = adrenocorticotropic hormone, ASCO = adenohypophysis spindle cell oncocytoma, EMA = epithelial membrane antigen, FSH = follicle-stimulating hormone, GFAP = glial fibrillary acidic protein, H & E = hematoxylin and eosin, LH = luteinizing hormone, MAPK = mitogen-activated protein kinase, MEN1 = multiple endocrine neoplasia 1, MRI = magnetic resonance imaging, NeuN = neuron-specific nuclear protein, NSE = neuron-specific enolase, PUMCH = Peking Union Medical College Hospital, SMA = smooth muscle actin, TSH = thyroid stimulating hormone, WHO = World Health Organization. C1 [Kong, Xiangyi; Kong, Yanguo] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, 1 Shuaifuyuan, Beijing 100730, Peoples R China. [Kong, Xiangyi] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Harvard Med Sch, Boston, MA 02115 USA. [Li, Dongmei; Zhong, Dingrong] Chinese Acad Med Sci, Dept Pathol, Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China. RP Kong, YG (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, 1 Shuaifuyuan, Beijing 100730, Peoples R China.; Zhong, DR (reprint author), Chinese Acad Med Sci, Dept Pathol, Peking Union Med Coll Hosp, 1 Shuaifuyuan, Beijing 100730, Peoples R China. EM kong0126@126.com; 748803069@qq.com FU Peking Union Medical College Youth Research Funds [3332016010]; Peking Union Medical College Graduate Student Innovation Fund [2015-1002-02-09] FX This study was supported by Peking Union Medical College Youth Research Funds (2016) (Project No. 3332016010; Grant recipient: XK) and Peking Union Medical College Graduate Student Innovation Fund (2015) (Project No. 2015-1002-02-09; Grant recipient: XK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 19 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2017 VL 96 IS 4 AR e5657 DI 10.1097/MD.0000000000005657 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA EK1WT UT WOS:000393717200012 PM 28121922 ER PT J AU Tang, K Kong, XY Mao, GS Qiu, M Zhu, HB Zhou, L Nie, QB Xu, Y Du, SW AF Tang, Kai Kong, Xiangyi Mao, Gengsheng Qiu, Ming Zhu, Haibo Zhou, Lei Nie, Qingbin Xu, Yi Du, Shiwei TI Primary cerebral malignant melanoma A case report with literature review SO MEDICINE LA English DT Article DE case presentation; differential diagnosis; primary cerebral malignant melanoma ID METASTATIC MELANOMA; BRAIN METASTASES; DIAGNOSIS AB Primary intracranial melanomas are uncommon and constitute approximately 1% of all melanoma cases and 0.07% of all brain tumors. In nature, these primary melanomas are very aggressive and can spread to other organs. We report an uncommon case of primary cerebral malignant melanoma-a challenging diagnosis guided by clinical presentations, radiological features, and surgical biopsy results, aiming to emphasize the importance of considering primary melanoma when making differential diagnoses of intracranial lesions. We present a rare case of a primary cerebral melanoma in the left temporal lobe. The mass appeared iso-hypodense on brain computed tomography (CT), short signal on T1-weighted magnetic resonance images (T1WI) and long signal on T2WI. It was not easy to make an accurate diagnosis before surgery. We showed the patient's disease course and reviewed related literatures, for readers' reference. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Because of this, there is no need to conduct special ethic review and the ethical approval is not necessary. After surgery, the pathological examination confirmed the diagnosis of melanoma. The patient was discharged without any complications and went on to receive adjuvant radiochemotherapy. It is difficult to diagnose primary cerebral melanoma in the absence of any cutaneous melanosis. A high index of clinical suspicion along with good pathology reporting is the key in diagnosing these extremely rare tumors. C1 [Tang, Kai] Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Beijing, Peoples R China. [Kong, Xiangyi] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, Beijing, Peoples R China. [Kong, Xiangyi] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Harvard Med Sch, Boston, MA 02115 USA. [Mao, Gengsheng; Qiu, Ming; Zhu, Haibo; Zhou, Lei; Nie, Qingbin; Xu, Yi] Chinese Armed Police Gen Hosp, Dept Neurovasc Surg, Haidian Dist, Peoples R China. [Du, Shiwei] Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, 45 Changchun St, Beijing 100053, Peoples R China. RP Du, SW (reprint author), Capital Med Univ, Xuanwu Hosp, Dept Neurosurg, 45 Changchun St, Beijing 100053, Peoples R China. EM dusw1981@163.com FU Peking Union Medical College Youth Research Funds [3332016010]; Peking Union Medical College Graduate Student Innovation Fund [2015-1002-02-09] FX This study was supported by Peking Union Medical College Youth Research Funds (2016) (Project No. 3332016010; to XK) and Peking Union Medical College Graduate Student Innovation Fund (2015) (Project No. 2015-1002-02-09; to XK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2017 VL 96 IS 4 AR e5805 DI 10.1097/MD.0000000000005805 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA EK1WT UT WOS:000393717200017 PM 28121927 ER PT J AU Hahn, T Nierenberg, AA Whitfield-Gabrieli, S AF Hahn, T. Nierenberg, A. A. Whitfield-Gabrieli, S. TI Predictive analytics in mental health: applications, guidelines, challenges and perspectives SO MOLECULAR PSYCHIATRY LA English DT Review ID QUALITY-OF-LIFE; PSYCHIATRIC-DISORDERS; DEPRESSIVE-DISORDERS; TREATMENT OUTCOMES; FAMILY-MEMBERS; MECHANISMS; MEDICINE; BIPOLAR; BURDEN; NEUROSCIENCE AB The emerging field of 'predictive analytics in mental health' has recently generated tremendous interest with the bold promise to revolutionize clinical practice in psychiatry paralleling similar developments in personalized and precision medicine. Here, we provide an overview of the key questions and challenges in the field, aiming to (1) propose general guidelines for predictive analytics projects in psychiatry, (2) provide a conceptual introduction to core aspects of predictive modeling technology, and (3) foster a broad and informed discussion involving all stakeholders including researchers, clinicians, patients, funding bodies and policymakers. C1 [Hahn, T.] Goethe Univ Frankfurt, Dept Cognit Psychol 2, Theodor W Adorno Pl 6, Frankfurt, Germany. [Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Bipolar Clin, Boston, MA 02114 USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Res Program, Boston, MA 02114 USA. [Nierenberg, A. A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Whitfield-Gabrieli, S.] MIT, McGovern Inst Brain Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, S.] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. RP Hahn, T (reprint author), Goethe Univ Frankfurt, Dept Cognit Psychol 2, Theodor W Adorno Pl 6, Frankfurt, Germany. EM Hahn@psych.uni-frankfurt.de FU American Foundation for Suicide Prevention; AHRQ; Brain and Behavior Research Foundation; Bristol-Myers Squibb; Cederroth; Cephalon; Cyberonics; Elan; Eli Lilly; Forest; GlaxoSmithKline; Janssen Pharmaceutica; IntraCellular Therapies; Lichtwer Pharma; Marriott Foundation; Mylan; NIMH; PamLabs; PCORI; Pfizer Pharmaceuticals; Shire; Stanley Foundation; Takeda; Wyeth-Ayerst FX TH and SW-G declare no conflicts of interest. AAN is a consultant for the Abbott Laboratories, Alkermes, American Psychiatric Association, Appliance Computing Inc. (Mindsite), Basliea, Brain Cells, Inc., Brandeis University, Bristol Myers Squibb, Clintara, Corcept, Dey Pharmaceuticals, Dainippon Sumitomo (now Sunovion), Eli Lilly and Company, EpiQ, L. P./Mylan Inc., Forest, Genaissance, Genentech, GlaxoSmithKline, Hoffman LaRoche, Infomedic, Intra-Cellular Therapies, Lundbeck, Janssen Pharmaceutica, Jazz Pharmaceuticals, Medavante, Merck, Methylation Sciences, Naurex, NeuroRx, Novartis, Otsuka, PamLabs, Parexel, Pfizer, PGx Health, Ridge Diagnostics Shire, Schering-Plough, Somerset, Sunovion, Takeda Pharmaceuticals, Targacept, and Teva; consulted through the MGH Clinical Trials Network and Institute (CTNI) for Astra Zeneca, Brain Cells, Inc, Dianippon Sumitomo/Sepracor, Johnson and Johnson, Labopharm, Merck, Methylation Science, Novartis, PGx Health, Shire, Schering-Plough, Targacept and Takeda/Lundbeck Pharmaceuticals. He receives grant/research support from American Foundation for Suicide Prevention, AHRQ, Brain and Behavior Research Foundation, Bristol-Myers Squibb, Cederroth, Cephalon, Cyberonics, Elan, Eli Lilly, Forest, GlaxoSmithKline, Janssen Pharmaceutica, IntraCellular Therapies, Lichtwer Pharma, Marriott Foundation, Mylan, NIMH, PamLabs, PCORI, Pfizer Pharmaceuticals, Shire, Stanley Foundation, Takeda and Wyeth-Ayerst. Honoraria include Belvoir Publishing, University of Texas Southwestern Dallas, Brandeis University, Bristol-Myers Squibb, Hillside Hospital, American Drug Utilization Review, American Society for Clinical Psychopharmacology, Baystate Medical Center, Columbia University, CRICO, Dartmouth Medical School, Health New England, Harold Grinspoon Charitable Foundation, IMEDEX, Israel Society for Biological Psychiatry, Johns Hopkins University, MJ Consulting, New York State, Medscape, MBL Publishing, MGH Psychiatry Academy, National Association of Continuing Education, Physicians Postgraduate Press, SUNY Buffalo, University of Wisconsin, University of Pisa, University of Michigan, University of Miami, University of Wisconsin at Madison, World Congress of Brain Behavior and Emotion, APSARD, ISBD, SciMed, Slack Publishing and Wolters Klower Publishing ASCP, NCDEU, Rush Medical College, Yale University School of Medicine, NNDC, Nova Southeastern University, NAMI, Institute of Medicine, CME Institute, ISCTM. He was currently or formerly on the advisory boards of Appliance Computing, Inc., Brain Cells, Inc., Eli Lilly and Company, Genentech, Johnson and Johnson, Takeda/Lundbeck, Targacept, and InfoMedic. He owns stock options in Appliance Computing, Inc., Brain Cells, Inc, and Medavante; has copyrights to the Clinical Positive Affect Scale and the MGH Structured Clinical Interview for the Montgomery Asberg Depression Scale exclusively licensed to the MGH Clinical Trials Network and Institute (CTNI). NR 56 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2017 VL 22 IS 1 BP 37 EP 43 DI 10.1038/mp.2016.201 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA EK7JD UT WOS:000394101200005 PM 27843153 ER PT J AU Ho, NF Iglesias, JE Sum, MY Kuswanto, CN Sitoh, YY De Souza, J Hong, Z Fischl, B Roffman, JL Zhou, J Sim, K Holt, DJ AF Ho, N. F. Iglesias, J. E. Sum, M. Y. Kuswanto, C. N. Sitoh, Y. Y. De Souza, J. Hong, Z. Fischl, B. Roffman, J. L. Zhou, J. Sim, K. Holt, D. J. TI Progression from selective to general involvement of hippocampal subfields in schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article ID MEDIAL TEMPORAL-LOBE; SURFACE-BASED ANALYSIS; IN-VIVO MRI; 1ST-EPISODE SCHIZOPHRENIA; PATTERN SEPARATION; DENTATE GYRUS; BRAIN MORPHOLOGY; PSYCHOTIC DISORDERS; AMYGDALA VOLUMES; BIPOLAR DISORDER AB Volume deficits of the hippocampus in schizophrenia have been consistently reported. However, the hippocampus is anatomically heterogeneous; it remains unclear whether certain portions of the hippocampus are affected more than others in schizophrenia. In this study, we aimed to determine whether volume deficits in schizophrenia are confined to specific subfields of the hippocampus and to measure the subfield volume trajectories over the course of the illness. Magnetic resonance imaging scans were obtained from Data set 1: 155 patients with schizophrenia (mean duration of illness of 7 years) and 79 healthy controls, and Data set 2: an independent cohort of 46 schizophrenia patients (mean duration of illness of 18 years) and 46 healthy controls. In addition, follow-up scans were collected for a subset of Data set 1. A novel, automated method based on an atlas constructed from ultra-high resolution, post-mortem hippocampal tissue was used to label seven hippocampal subfields. Significant cross-sectional volume deficits in the CA1, but not of the other subfields, were found in the schizophrenia patients of Data set 1. However, diffuse cross-sectional volume deficits across all subfields were found in the more chronic and ill schizophrenia patients of Data set 2. Consistent with this pattern, the longitudinal analysis of Data set 1 revealed progressive illness-related volume loss (similar to 2-6% per year) that extended beyond CA1 to all of the other subfields. This decline in volume correlated with symptomatic worsening. Overall, these findings provide converging evidence for early atrophy of CA1 in schizophrenia, with extension to other hippocampal subfields and accompanying clinical sequelae over time. C1 [Ho, N. F.; Sum, M. Y.; Kuswanto, C. N.; Sim, K.] Inst Mental Hlth, Div Res, 10 Buangkok View, Singapore 539747, Singapore. [Ho, N. F.; De Souza, J.; Hong, Z.; Zhou, J.] Duke Natl Univ Singapore, Neurosci & Behav Disorders Program, Ctr Cognit Neurosci, Grad Sch Med, Singapore, Singapore. [Iglesias, J. E.] Basque Ctr Cognit Brain & Language, San Sebastian, Spain. [Iglesias, J. E.; Fischl, B.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Sitoh, Y. Y.] Natl Inst Neurosci, Dept Neuroradiol, Singapore, Singapore. [Fischl, B.] Harvard Med Sch, Dept Radiol, Boston, MA USA. [Roffman, J. L.; Holt, D. J.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Roffman, J. L.; Holt, D. J.] Harvard Med Sch, Boston, MA USA. [Sim, K.] Inst Mental Hlth, Dept Gen Psychiat, Gen Psychiat, Singapore, Singapore. RP Ho, NF (reprint author), Inst Mental Hlth, Div Res, 10 Buangkok View, Singapore 539747, Singapore. EM new_fei_HO@imh.com.sg FU National Medical Research Council under the Centre Grant Programme (Institute of Mental Health, Singapore) [NMRC/CG/004/2013]; National Healthcare Group, Singapore [SIG/05004, SIG/05028]; Singapore Bioimaging Consortium [RP C-009/2006]; National Institute of Mental Health [K23MH076054, K23MH084059]; Howard Hughes Medical Institute Physician Scientist Early Career Award; Biomedical Research Council, Singapore [BMRC 04/1/36/372]; Agency for Science, Technology, and Research (A*STAR); Duke-NUS Graduate Medical School Signature Research Program - Ministry of Health, Singapore; Pamlab FX This study was supported by the National Medical Research Council under the Centre Grant Programme (Institute of Mental Health, Singapore) (NMRC/CG/004/2013) (NFH) and by the National Healthcare Group, Singapore (SIG/05004; SIG/05028), and the Singapore Bioimaging Consortium (RP C-009/2006) research grants awarded to KS, as well grants from the National Institute of Mental Health (DJH: K23MH076054; JLR: K23MH084059) and a Howard Hughes Medical Institute Physician Scientist Early Career Award and grant from Pamlab (JLR). This research was also supported by the Biomedical Research Council, Singapore (awarded to JZ, BMRC 04/1/36/372), the Agency for Science, Technology, and Research (A*STAR) and Duke-NUS Graduate Medical School Signature Research Program funded by Ministry of Health, Singapore. We thank Dr. Jean Augustinack for her valuable comments on the manuscript. We NR 85 TC 3 Z9 3 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 EI 1476-5578 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2017 VL 22 IS 1 BP 142 EP 152 DI 10.1038/mp.2016.4 PG 11 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA EK7JD UT WOS:000394101200017 PM 26903271 ER PT J AU Campbell, MG Mercier, J Genicot, C Gouverneur, V Hooker, JM Ritter, T AF Campbell, Michael G. Mercier, Joel Genicot, Christophe Gouverneur, Veronique Hooker, Jacob M. Ritter, Tobias TI Bridging the gaps in F-18 PET tracer development SO NATURE CHEMISTRY LA English DT Editorial Material ID FLUORINATION; CATALYSIS; ARENES C1 [Campbell, Michael G.; Ritter, Tobias] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Mercier, Joel; Genicot, Christophe] UCB Biopharma SPRL, UCB NewMed, Global Chem, B-1420 Braine Lalleud, Belgium. [Gouverneur, Veronique] Univ Oxford, Chem Res Lab, 12 Mansfield Rd, Oxford OX1 3TA, England. [Hooker, Jacob M.; Ritter, Tobias] Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA. [Hooker, Jacob M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Hooker, Jacob M.] Harvard Med Sch, Charlestown, MA 02129 USA. [Ritter, Tobias] Max Planck Inst Kohlenforsch, Kaiser Wilhelm Pl 1, D-45470 Mulheim, Germany. [Campbell, Michael G.] Barnard Coll, Dept Chem, 3009 Broadway, New York, NY 10027 USA. RP Ritter, T (reprint author), Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA.; Ritter, T (reprint author), Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Dept Radiol, Boston, MA 02114 USA.; Ritter, T (reprint author), Max Planck Inst Kohlenforsch, Kaiser Wilhelm Pl 1, D-45470 Mulheim, Germany. EM ritter@mpi-muelheim.mpg.de NR 14 TC 0 Z9 0 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1755-4330 EI 1755-4349 J9 NAT CHEM JI Nat. Chem. PD JAN PY 2017 VL 9 IS 1 BP 1 EP 3 DI 10.1038/nchem.2693 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA EL3SU UT WOS:000394540400001 ER PT J AU Avila, EK Chamberlain, M Schiff, D Reijneveld, JC Armstrong, TS Ruda, R Wen, PY Weller, M Koekkoek, JAF Mittal, S Arakawa, Y Choucair, A Gonzalez-Martinez, J MacDonald, DR Nishikawa, R Shah, A Vecht, CJ Warren, P van den Bent, MJ DeAngelis, LM AF Avila, Edward K. Chamberlain, Marc Schiff, David Reijneveld, Jaap C. Armstrong, Terri S. Ruda, Roberta Wen, Patrick Y. Weller, Michael Koekkoek, Johan A. F. Mittal, Sandeep Arakawa, Yoshiki Choucair, Ali Gonzalez-Martinez, Jorge MacDonald, David R. Nishikawa, Ryo Shah, Aashit Vecht, Charles J. Warren, Paula van den Bent, Martin J. DeAngelis, Lisa M. TI Seizure control as a new metric in assessing efficacy of tumor treatment in low-grade glioma trials SO NEURO-ONCOLOGY LA English DT Article DE glioma; low-grade; metric; scale; seizures ID QUALITY-OF-LIFE; SEVERITY SCALE; TEMOZOLOMIDE CHEMOTHERAPY; INTRACTABLE EPILEPSY; BRAIN-TUMORS; RADIOTHERAPY; ADULTS; ASTROCYTOMAS; RESECTION; OUTCOMES AB Patients with low-grade glioma frequently have brain tumor-related epilepsy, which is more common than in patients with high-grade glioma. Treatment for tumor-associated epilepsy usually comprises a combination of surgery, anti-epileptic drugs (AEDs), chemotherapy, and radiotherapy. Response to tumor-directed treatment is measured primarily by overall survival and progression-free survival. However, seizure frequency has been observed to respond to tumor-directed treatment with chemotherapy or radiotherapy. A review of the current literature regarding seizure assessment for low-grade glioma patients reveals a heterogeneous manner in which seizure response has been reported. There is a need for a systematic approach to seizure assessment and its influence on health-related quality-of-life outcomes in patients enrolled in low-grade glioma therapeutic trials. In view of the need to have an adjunctive metric of tumor response in these patients, a method of seizure assessment as a metric in brain tumor treatment trials is proposed. C1 [Avila, Edward K.; DeAngelis, Lisa M.] Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. [Chamberlain, Marc] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Schiff, David] Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Reijneveld, Jaap C.] VUmc Canc Ctr, Dept Neurol, Amsterdam, Netherlands. [Armstrong, Terri S.] Univ Texas Hlth Sci Ctr Houston, Dept Family Hlth, Houston, TX 77030 USA. [Ruda, Roberta] City Hlth & Sci Hosp, Dept Neurooncol, Turin, Italy. [Warren, Paula] Brigham & Womens Ctr, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA. [Weller, Michael] Univ Zurich Hosp, Dept Neurol, Zurich, Switzerland. [Koekkoek, Johan A. F.] Leiden Univ, Dept Neurol, Med Ctr, The Hague, Netherlands. [Mittal, Sandeep] Wayne State Univ, Dept Neurosurg, Detroit, MI USA. [Arakawa, Yoshiki] Kyoto Univ, Grad Sch Med, Dept Neurosurg, Kyoto, Japan. [Choucair, Ali] Southern Illinois Univ, Sch Med, Dept Neurol, Springfield, IL USA. [Gonzalez-Martinez, Jorge] Cleveland Clin, Dept Epilepsy, Cleveland, OH 44106 USA. [Gonzalez-Martinez, Jorge] Cleveland Clin, Surg Ctr, Cleveland, OH 44106 USA. [MacDonald, David R.] London Hlth Sci Ctr, Dept Neurol, London, ON, Canada. [Nishikawa, Ryo] Saitama Med Univ, Dept Neurosurg, Saitama, Japan. [Shah, Aashit] Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA. [Vecht, Charles J.] CHU Pitie Salpetriere, Serv Neurol Mazarin, Paris, France. [Warren, Paula] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA. [van den Bent, Martin J.] Erasmus MC Canc Inst, Brain Tumor Ctr, Dept Neurooncol, Rotterdam, Netherlands. RP Avila, EK (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10065 USA. EM avilae@mskcc.org FU NIH/NCI Cancer Center Support [P30 CA008748] FX This research was funded through the NIH/NCI Cancer Center Support Grant P30 CA008748. NR 62 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2017 VL 19 IS 1 BP 12 EP 21 DI 10.1093/neuonc/now190 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EK4JL UT WOS:000393892800010 PM 27651472 ER PT J AU Ni, J Xie, SZ Ramkissoon, SH Luu, V Sun, Y Bandopadhayay, P Beroukhim, R Roberts, TM Stiles, CD Segal, RA Ligon, KL Hahn, WC Zhao, JJ AF Ni, Jing Xie, Shaozhen Ramkissoon, Shakti H. Luu, Victor Sun, Yu Bandopadhayay, Pratiti Beroukhim, Rameen Roberts, Thomas M. Stiles, Charles D. Segal, Rosalind A. Ligon, Keith L. Hahn, William C. Zhao, Jean J. TI Tyrosine receptor kinase B is a drug target in astrocytomas SO NEURO-ONCOLOGY LA English DT Article DE astrocytoma; CCL2; NTRK2; STAT3; QKI-NTRK2 ID NEUROTROPHIC FACTOR; HUMAN GLIOBLASTOMA; JAK/STAT PATHWAY; GROWTH-FACTOR; LUNG-CANCER; CELL; INHIBITOR; TRKB; ALK; AZD1480 AB Background. Astrocytomas are the most common primary human brain tumors. Receptor tyrosine kinases (RTKs), including tyrosine receptor kinase B (TrkB, also known as tropomyosin-related kinase B; encoded by neurotrophic tyrosine kinase receptor type 2 [NTRK2]), are frequently mutated by rearrangement/fusion in high-grade and lowgrade astrocytomas. We found that activated TrkB can contribute to the development of astrocytoma and might serve as a therapeutic target in this tumor type. Methods. To identify RTKs capable of inducing astrocytoma formation, a library of human tyrosine kinases was screened for the ability to transform murine Ink4a(-/-)/Arf(-/-) astrocytes. Orthotopic allograft studies were conducted to evaluate the effects of RTKs on the development of astrocytoma. Since TrkB was identified as a driver of astrocytoma formation, the effect of the Trk inhibitors AZD1480 and RXDX-101 was assessed in astrocytoma cells expressing activated TrkB. RNA sequencing, real-time PCR, western blotting, and enzyme-linked immunosorbent assays were conducted to characterize NTRK2 in astrocytomas. Results. Activated TrkB cooperated with Ink4a/Arf loss to induce the formation of astrocytomas through a mechanism mediated by activation of signal transducer and activator of transcription 3 (STAT3). TrkB activation positively correlated with Ccl2 expression. TrkB-induced astrocytomas remained dependent on TrkB signaling for survival, highlighting a role of NTRK2 as an addictive oncogene. Furthermore, the QKI-NTRK2 fusion associated with human astrocytoma transformed Ink4a(-/-)/Arf(-/-) astrocytes, and this process was also mediated via STAT3 signaling. Conclusions. Our findings provide evidence that constitutively activated NTRK2 alleles, notably the human tumor-associated QKI-NTRK2 fusion, can cooperate with Ink4a/Arf loss to drive astrocytoma formation. Therefore, we propose NTRK2 as a potential therapeutic target in the subset of astrocytoma patients defined by QKI-NTRK2 fusion. C1 [Ni, Jing; Xie, Shaozhen; Luu, Victor; Sun, Yu; Bandopadhayay, Pratiti; Beroukhim, Rameen; Roberts, Thomas M.; Stiles, Charles D.; Segal, Rosalind A.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,SM 970, Boston, MA 02115 USA. [Ni, Jing; Xie, Shaozhen; Luu, Victor; Roberts, Thomas M.; Zhao, Jean J.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Ramkissoon, Shakti H.; Beroukhim, Rameen; Ligon, Keith L.; Hahn, William C.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Bandopadhayay, Pratiti; Beroukhim, Rameen; Hahn, William C.] Broad Inst, Boston, MA USA. [Ramkissoon, Shakti H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave,SM 970, Boston, MA 02115 USA. EM jean_zhao@dfci.harvard.edu FU NIH [P01 CA142536, P50 CA165962, R01 CA188288, K08 NS]; DFCI Medical Oncology Grant; Pediatric Low-Grade Astrocytoma Foundation FX This work was supported by NIH grants P01 CA142536 (C.D.S., R.A.S., K.L.L., W.C.H., and J.J.Z.), P50 CA165962 (C.D.S., T.M.R., K.L.L., and J.J.Z.), R01 CA188288 (K.L.L.), and K08 NS (S.H.R.); Pediatric Low-Grade Astrocytoma Foundation (C.D.S.); and DFCI Medical Oncology Grant (S.H.R. and K.L.L.). NR 48 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2017 VL 19 IS 1 BP 22 EP 30 DI 10.1093/neuonc/now139 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EK4JL UT WOS:000393892800011 PM 27402815 ER PT J AU Raleigh, DR Solomon, DA Lloyd, SA Lazar, A Garcia, MA Sneed, PK Clarke, JL McDermott, MW Berger, MS Tihan, T Haas-Kogan, DA AF Raleigh, David R. Solomon, David A. Lloyd, Shane A. Lazar, Ann Garcia, Michael A. Sneed, Penny K. Clarke, Jennifer L. McDermott, Michael W. Berger, Mitchel S. Tihan, Tarik Haas-Kogan, Daphne A. TI Histopathologic review of pineal parenchymal tumors identifies novel morphologic subtypes and prognostic factors for outcome SO NEURO-ONCOLOGY LA English DT Article DE DICER1; pineal parenchymal tumor; pineal parenchymal tumor of intermediate differentiation; pineoblastoma; pineocytoma ID STEREOTACTIC RADIOSURGERY; HISTOLOGICAL FEATURES; ADULT PATIENTS; REGION TUMORS; MANAGEMENT; DIAGNOSIS; PINEALOBLASTOMA; PINEOCYTOMAS; PATTERNS; DIFFERENTIATION AB Background. Pineal parenchymal tumors (PPTs) are rare neoplasms of the central nervous system, and data concerning clinical outcomes are limited. The purpose of this study was to define the clinical behavior of PPT according to current histopathologic criteria and identify prognostic factors to guide therapeutic decisions. Methods. Seventy-five patients treated for PPT at a single institution between 1992 and 2015 were retrospectively identified. Forty-five resection specimens were available and re-reviewed. Freedom from progression (FFP) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using log-rank tests. Results. Median follow-up was 4.1 years. All patients initially underwent surgery; 78% of patients with PPT of intermediate differentiation (PPTID) and all patients with pineoblastoma received adjuvant therapy. Pathologic re-review refined classification in 27% of cases, with the majority of these being adult patients with pineal tumors originally classified as pineoblastomas that more accurately resembled PPTID based on the 2007 WHO classification. Classification. Our histologic review also identified that PPTIDs can be classified into small-cell and large-cell morphologic subtypes, which have distinct clinical outcomes. Tumor grade, extent of resection, and neuraxis spread were prognostic for FFP. PPTID subtype, extent of resection, and neuraxis spread were prognostic for OS. Genetic analysis of a pineoblastoma case identified somatic mutations of DICER1, ARID1A, and KDM5C genes. Conclusions. PPTIDs can be classified into 1 of 2 novel morphologic subtypes that are associated with distinct clinical outcomes. Tumor grade, neuraxis spread, and extent of resection also influence outcome for patients with PPT. C1 [Raleigh, David R.; Lloyd, Shane A.; Lazar, Ann; Garcia, Michael A.; Sneed, Penny K.; Haas-Kogan, Daphne A.] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA USA. [Solomon, David A.; Tihan, Tarik] Univ Calif San Francisco, Dept Pathol, Div Neuropathol, San Francisco, CA 94140 USA. [Clarke, Jennifer L.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Clarke, Jennifer L.; McDermott, Michael W.; Berger, Mitchel S.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA. RP Haas-Kogan, DA (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol,Boston Childrens Hosp, 450 Brookline Ave,D1622, Boston, MA 02215 USA. EM dhaas-kogan@lroc.harvard.edu FU V Foundation for Cancer Research Pediatric Brain Cancer Research Award; American Brain Tumor Society Basic Research Fellowship; Rally Foundation for Childhood Cancer Research Collaborative Pediatric Research Award; American Society of Clinical Oncology Young Investigator Award; UCSF Brain Tumor SPORE [P50 CA097257]; NIH Director's Early Independence Award [DP5 OD021403]; National Institute of Neurological Disorders and Stroke grant [1R01NS091620]; Nancy and Stephen Grand Philanthropic Fund; Pediatric Low-Grade Astrocytoma Foundation FX The authors are supported in part by a V Foundation for Cancer Research Pediatric Brain Cancer Research Award (D.R.R.), an American Brain Tumor Society Basic Research Fellowship (D.R.R.), a Rally Foundation for Childhood Cancer Research Collaborative Pediatric Research Award (D.R.R.), and an American Society of Clinical Oncology Young Investigator Award (D.R.R.), a Career Development Award from the UCSF Brain Tumor SPORE (D.A.S., P50 CA097257), an NIH Director's Early Independence Award (D.A.S., DP5 OD021403), a National Institute of Neurological Disorders and Stroke grant 1R01NS091620 (D.H.K.), The Nancy and Stephen Grand Philanthropic Fund (D.H.K.), and the Pediatric Low-Grade Astrocytoma Foundation (D.H.K.). Portions of this work were presented at the annual meeting of the American Society for Therapeutic Radiation Oncology in San Antonio, Texas, in October 2015. NR 44 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2017 VL 19 IS 1 BP 78 EP 88 DI 10.1093/neuonc/now105 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EK4JL UT WOS:000393892800016 PM 27282397 ER PT J AU Ellingson, BM Harris, RJ Woodworth, DC Leu, K Zaw, O Mason, WP Sahebjam, S Abrey, LE Aftab, DT Schwab, GM Hessel, C Lai, A Nghiemphu, PL Pope, WB Wen, PY Cloughesy, TF AF Ellingson, Benjamin M. Harris, Robert J. Woodworth, Davis C. Leu, Kevin Zaw, Okkar Mason, Warren P. Sahebjam, Solmaz Abrey, Lauren E. Aftab, Dana T. Schwab, Gisela M. Hessel, Colin Lai, Albert Nghiemphu, Phioanh L. Pope, Whitney B. Wen, Patrick Y. Cloughesy, Timothy F. TI Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single- and multicenter trials SO NEURO-ONCOLOGY LA English DT Article DE bevacizumab; cabozantinib; glioblastoma; recurrent; T1 subtraction; tumor volume ID GLIAL NEOPLASMS; RESECTION; SURVIVAL; EXTENT; BEVACIZUMAB; CHEMOTHERAPY; MULTIFORME; SURGERY; GLIOMA; MR AB Background. The prognostic significance of baseline contrast enhancing tumor prior to second-or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM. Methods. Included were 497 patients with recurrent GBM from 4 data sources: 2 single-center sites (University of Toronto, University of California Los Angeles) and 2 phase II multicenter trials (AVF3708G, Bevacizumab +/- Irinotecan, NCT00345163; XL184-201, Cabozantinib, NCT00704288). T1 subtraction maps were used to define volume of contrast enhancing tumor, including central necrosis. Cox multivariable and univariate analyses were used to evaluate the relationship between tumor volume prior to second-or third-line therapy and OS. Results. Both continuous measures of baseline tumor volume and tumors dichotomized into large (>= 15cc) and small (<15cc) tumors were significant predictors of OS (P<.0001), independently of age and treatment. Univariate analysis demonstrated significant OS differences (P<.05) between large (>= 15cc) and small (<15cc) tumors in patients under all therapeutic scenarios. Only patients treated with cabozantinib who previously failed anti-angiogenic therapy did not show an OS dependence on baseline tumor volume. Conclusions. Baseline tumor volume is a significant prognostic factor in recurrent GBM. Clinical trial treatment arms must have a balanced distribution of tumor size, and tumor size should be considered when interpreting therapeutic efficacy. C1 [Ellingson, Benjamin M.; Harris, Robert J.; Woodworth, Davis C.; Leu, Kevin; Zaw, Okkar] Univ Calif Los Angeles, David Geffen Sch Med, Ctr Comp Vis & Imaging Biomarkers, Brain Tumor Imaging Lab, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.; Harris, Robert J.; Woodworth, Davis C.; Leu, Kevin; Zaw, Okkar; Pope, Whitney B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90095 USA. [Ellingson, Benjamin M.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Phys & Biol Med, Los Angeles, CA 90095 USA. [Mason, Warren P.] Univ Toronto, Princess Margaret Hosp, Dept Med, Toronto, ON, Canada. [Sahebjam, Solmaz] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Abrey, Lauren E.] F Hoffman La Roche Ltd, Basel, Switzerland. [Aftab, Dana T.; Schwab, Gisela M.; Hessel, Colin] Exelixis, San Francisco, CA USA. [Lai, Albert; Nghiemphu, Phioanh L.; Cloughesy, Timothy F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Wen, Patrick Y.] Harvard Med Sch, Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. RP Ellingson, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Radiol, 924 Westwood Blvd,Suite 615, Los Angeles, CA 90024 USA.; Ellingson, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Brain Tumor Imaging Lab, Dept Radiol Sci, 924 Westwood Blvd,Suite 615, Los Angeles, CA 90024 USA.; Ellingson, BM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Brain Tumor Imaging Lab, Dept Psychiat, 924 Westwood Blvd,Suite 615, Los Angeles, CA 90024 USA. EM bellingson@mednet.ucla.edu FU American Cancer Society (ACS) Research Scholar Grant [RSG-15-003-01-CCE]; National Brain Tumor Society (NBTS) Research Grant; Art of the Brain; Singleton Family Foundation FX This work was supported by American Cancer Society (ACS) Research Scholar Grant (RSG-15-003-01-CCE) (B.M.E.); National Brain Tumor Society (NBTS) Research Grant (B.M.E., T.F.C.); Art of the Brain (T.F.C.); Ziering Family Foundation in memory of Sigi Ziering (T.F.C.); Singleton Family Foundation (T.F.C.). NR 24 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2017 VL 19 IS 1 BP 89 EP 98 DI 10.1093/neuonc/now187 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EK4JL UT WOS:000393892800017 PM 27580889 ER PT J AU Zhang, BQ Chang, K Ramkissoon, S Tanguturi, S Bi, WL Reardon, DA Ligon, KL Alexander, BM Wen, PY Huang, RY AF Zhang, Biqi Chang, Ken Ramkissoon, Shakti Tanguturi, Shyam Bi, Wenya Linda Reardon, David A. Ligon, Keith L. Alexander, Brian M. Wen, Patrick Y. Huang, Raymond Y. TI Multimodal MRI features predict isocitrate dehydrogenase genotype in high-grade gliomas SO NEURO-ONCOLOGY LA English DT Article DE high-grade glioma; isocitrate dehydrogenase; machine learning; MRI; prediction ID MAGNETIC-RESONANCE-SPECTROSCOPY; CENTRAL-NERVOUS-SYSTEM; IDH1 MUTATION STATUS; GLIOBLASTOMA-MULTIFORME; MALIGNANT GLIOMAS; PATIENT SURVIVAL; RANDOM FORESTS; CLASSIFICATION; IMAGE; BRAIN AB Background. High-grade gliomas with mutations in the isocitrate dehydrogenase (IDH) gene family confer longer overall survival relative to their IDH-wild-type counterparts. Accurate determination of the IDH genotype preoperatively may have both prognostic and diagnostic value. The current study used a machine-learning algorithm to generate a model predictive of IDH genotype in high-grade gliomas based on clinical variables and multimodal features extracted from conventional MRI. Methods. Preoperative MRIs were obtained for 120 patients with primary grades III (n = 35) and IV (n = 85) glioma in this retrospective study. IDH genotype was confirmed for grade III (32/35, 91%) and IV (22/85, 26%) tumors by immunohistochemistry, spectrometry-based mutation genotyping (OncoMap), or multiplex exome sequencing (OncoPanel). IDH1 and IDH2 mutations were mutually exclusive, and all mutated tumors were collapsed into one IDH-mutated cohort. Cases were randomly assigned to either the training (n = 90) or validation cohort (n = 30). A total of 2970 imaging features were extracted from pre- and postcontrast T1-weighted, T2-weighted, and apparent diffusion coefficient map. Using a random forest algorithm, nonredundant features were integrated with clinical data to generate a model predictive of IDH genotype. Results. Our model achieved accuracies of 86% (area under the curve [AUC] = 0.8830) in the training cohort and 89% (AUC = 0.9231) in the validation cohort. Features with the highest predictive value included patient age as well as parametric intensity, texture, and shape features. Conclusion. Using a machine-learning algorithm, we achieved accurate prediction of IDH genotype in high-grade gliomas with preoperative clinical and MRI features. C1 [Zhang, Biqi; Chang, Ken; Huang, Raymond Y.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02445 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Ramkissoon, Shakti; Ligon, Keith L.] Harvard Med Sch, Dept Pathol, Boston, MA USA. [Ramkissoon, Shakti; Ligon, Keith L.] Boston Childrens Hosp, Dept Pathol, Boston, MA USA. [Ramkissoon, Shakti; Reardon, David A.; Ligon, Keith L.; Wen, Patrick Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Tanguturi, Shyam] Harvard Radiat Oncol Program, Boston, MA USA. [Bi, Wenya Linda] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. [Reardon, David A.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA USA. [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. RP Huang, RY (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02445 USA. EM ryhuang@partners.org NR 56 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JAN PY 2017 VL 19 IS 1 BP 109 EP 117 DI 10.1093/neuonc/now121 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EK4JL UT WOS:000393892800019 PM 27353503 ER PT J AU Sadaka, A Durand, ML Sisk, R Gilmore, MS AF Sadaka, Ama Durand, Marlene L. Sisk, Robert Gilmore, Michael S. TI Staphylococcus aureus and its Bearing on Ophthalmic Disease SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Review DE Antibiotic resistance; endophthalmitis; methicillin; Staphylococcus aureus; virulence ID ENDOGENOUS BACTERIAL ENDOPHTHALMITIS; ONSET POSTOPERATIVE ENDOPHTHALMITIS; FIBRONECTIN-BINDING PROTEINS; INTRAOCULAR FOREIGN-BODIES; AQUEOUS-HUMOR PENETRATION; CATARACT-SURGERY; GLYCEROL MONOLAURATE; METHICILLIN RESISTANCE; UNITED-STATES; POSTTRAUMATIC ENDOPHTHALMITIS AB Purpose: To review antibiotic resistance associated with S. aureus endophthalmitis and the virulence of S. aureus. Methods: Review of the current and prospective approaches for treating S. aureus endophthalmitis. Results: Bacterial endophthalmitis remains to be a major threat for vision. S. aureus endophthalmitis specifically, carries a poor visual prognosis making early diagnosis and treatment crucial. Methicillin resistant Staphylococcus aureus (MRSA) endophthalmitis represents a significant number of S. aureus endophthalmitis cases. MRSA with reduced susceptibility to glycopeptide antibiotics such as vancomycin (vancomycin intermediate S. aureus, VISA) have also emerged in the ocular infections, and there has been a rise in S. aureus resistance to new and old generation fluoroquinolones that are commonly used for prophylaxis after intravitreal injections and intraocular surgeries. Conclusions: With the rise in the number of penetrating procedures in the ophthalmology practice and the parallel rise in antibiotic resistance, prophylaxis and awareness of the antimicrobial resistance profiles remain crucial and the identification of novel antimicrobials is essential. C1 [Sadaka, Ama; Sisk, Robert] Univ Cincinnati, Coll Med, Dept Ophthalmol, Cincinnati Eye Inst, Cincinnati, OH USA. [Sadaka, Ama; Durand, Marlene L.; Gilmore, Michael S.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Gilmore, Michael S.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. [Gilmore, Michael S.] Harvard Med Sch, Dept Microbiol & Mol Genet, Boston, MA USA. RP Gilmore, MS (reprint author), 243 Charles St, Boston, MA 02114 USA. EM michael_gilmore@meei.harvard.edu NR 152 TC 2 Z9 2 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0927-3948 EI 1744-5078 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PY 2017 VL 25 IS 1 BP 111 EP 121 DI 10.3109/09273948.2015.1075559 PG 11 WC Ophthalmology SC Ophthalmology GA EK4NY UT WOS:000393905000017 PM 26679534 ER PT J AU Fagoonee, S Picco, G Orso, F Arrigoni, A Longo, DL Forni, M Scarfo, I Cassenti, A Piva, R Cassoni, P Silengo, L Tolosano, E Aime, S Taverna, D Pandolfi, PP Brancaccio, M Medico, E Altruda, F AF Fagoonee, Sharmila Picco, Gabriele Orso, Francesca Arrigoni, Arrigo Longo, Dario L. Forni, Marco Scarfo, Irene Cassenti, Adele Piva, Roberto Cassoni, Paola Silengo, Lorenzo Tolosano, Emanuela Aime, Silvio Taverna, Daniela Pandolfi, Pier Paolo Brancaccio, Mara Medico, Enzo Altruda, Fiorella TI The RNA-binding protein ESRP1 promotes human colorectal cancer progression SO ONCOTARGET LA English DT Article DE ESRP1; RNA binding protein; proto-oncogene; human colorectal cancer ID EPITHELIAL-MESENCHYMAL TRANSITION; SPLICING REGULATORY PROTEIN-1; MESSENGER-RNA; PANCREATIC-CANCER; TUMOR-SUPPRESSOR; COLON-CANCER; IN-VIVO; CELL; EXPRESSION; SNAIL AB Epithelial splicing regulatory protein 1 (ESRP1) is an epithelial cell-specific RNA binding protein that controls several key cellular processes, like alternative splicing and translation. Previous studies have demonstrated a tumor suppressor role for this protein. Recently, however, a pro-metastatic function of ESRP1 has been reported. We thus aimed at clarifying the role of ESRP1 in Colorectal Cancer (CRC) by performing loss- and gain-of-function studies, and evaluating tumorigenesis and malignancy with in vitro and in vivo approaches. We found that ESRP1 plays a role in anchorage-independent growth of CRC cells. ESRP1-overexpressing cells grown in suspension showed enhanced fibroblast growth factor receptor ( FGFR1/2) signalling, Akt activation, and Snail upregulation. Moreover, ESRP1 promoted the ability of CRC cells to generate macrometastases in mice livers. High ESRP1 expression may thus stimulate growth of cancer epithelial cells and promote colorectal cancer progression. Our findings provide mechanistic insights into a previously unreported, pro-oncogenic role for ESRP1 in CRC, and suggest that fine-tuning the level of this RNA-binding protein could be relevant in modulating tumor growth in a subset of CRC patients. C1 [Fagoonee, Sharmila; Longo, Dario L.; Silengo, Lorenzo; Altruda, Fiorella] Univ Turin, Dept Mol Biotechnol & Hlth Sci, CNR, Inst Biostruct & Bioimaging, I-10124 Turin, Italy. [Fagoonee, Sharmila; Orso, Francesca; Longo, Dario L.; Silengo, Lorenzo; Tolosano, Emanuela; Aime, Silvio; Taverna, Daniela; Pandolfi, Pier Paolo; Brancaccio, Mara; Altruda, Fiorella] Univ Turin, Dept Mol Biotechnol & Hlth Sci, Mol Biotechnol Ctr, I-10124 Turin, Italy. [Picco, Gabriele; Medico, Enzo] Univ Turin, IRCCS, Candiolo Canc Inst, I-10124 Turin, Italy. [Arrigoni, Arrigo] Azienda Citta Salute & Sci Torino, Endoscopia San Giovanni AS, SC Gastroenterol U, Turin, Italy. [Forni, Marco] Univ Turin, Ctr Mol Biotechnol, EuroClone SpA Res Lab, I-10124 Turin, Italy. [Scarfo, Irene; Piva, Roberto] Univ Turin, Ctr Expt Res & Med Studies, I-10124 Turin, Italy. [Cassenti, Adele; Cassoni, Paola] Univ Turin, Dept Med Sci, I-10124 Turin, Italy. [Pandolfi, Pier Paolo] Harvard Med Sch, BIDMC, Canc Res Inst, Boston, MA USA. [Picco, Gabriele] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England. RP Fagoonee, S; Altruda, F (reprint author), Univ Turin, Dept Mol Biotechnol & Hlth Sci, CNR, Inst Biostruct & Bioimaging, I-10124 Turin, Italy.; Fagoonee, S; Altruda, F (reprint author), Univ Turin, Dept Mol Biotechnol & Hlth Sci, Mol Biotechnol Ctr, I-10124 Turin, Italy. EM sharmila.fagoonee@unito.it; fiorella.altruda@unito.it FU Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG12944, 9970-2010, IG2013-14201, IG 15880]; Fondazione Piemontese per la Ricerca sul Cancro Ministero della Salute; Fondazione Cassa di Risparmio Torino CRT [2014.1085]; Progetti di ricerca di interesse nazionale (PRIN); Telethon; Prometeo; Advanced Life Science in Italy (Alisei) FX to FA: Progetti di ricerca di interesse nazionale (PRIN) 2010, Telethon 2014, Prometeo, Advanced Life Science in Italy (Alisei); to EM: Associazione Italiana per la Ricerca sul Cancro (AIRC) investigator grants (IG12944), Associazione Italiana per la Ricerca sul Cancro (AIRC) 9970-2010 Special Program Molecular Clinical Oncology 5x1000, Fondazione Piemontese per la Ricerca sul Cancro 5x1000 Ministero della Salute 2010 and 2011; to DT: Associazione Italiana per la Ricerca sul Cancro (AIRC) 2013 (IG2013-14201), Fondazione Cassa di Risparmio Torino CRT (2014.1085); to MB: Associazione Italiana per la Ricerca sul Cancro AIRC 2014 (IG 15880) NR 52 TC 0 Z9 0 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 6 BP 10007 EP 10024 DI 10.18632/oncotarget.14318 PG 18 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EK8NX UT WOS:000394181800090 PM 28052020 ER PT J AU Kong, XY Kong, YG AF Kong, Xiangyi Kong, Yanguo TI Evidence from a meta-analysis: is nivolumab neurotoxic in cancer patients? SO ONCOTARGETS AND THERAPY LA English DT Article DE PD-1 inhibitor; nivolumab; neurotoxicity; cancer ID CELL LUNG-CANCER; UNTREATED MELANOMA; ANTIBODY; SAFETY; PD-1; DOCETAXEL; ANTI-PD-1 AB The aim of this study was to summarize the findings of previous studies focusing on whether the risks of certain neurotoxicities are correlated to the programmed death 1 (PD-1) inhibitor nivolumab versus other chemotherapy or immunotherapy drugs. Six eligible studies, including 3,023 patients, were considered in the meta-analysis. The risk ratios (RRs) of fatigue, headache, dysgeusia, vertigo, paresthesia, anxiety or malaise and peripheral neuropathy were 0.908 (95% confidence interval [95% CI]: 0.724, 1.138; P= 0.402), 0.841 (95% CI: 0.606, 1.168; P= 0.302), 0.423 (95% CI: 0.132, 1.357; P= 0.148), 0.762 (95% CI: 0.475, 1.223; P= 0.261), 0.411 (95% CI: 0.232, 0.730; P= 0.002), 1.049 (95% CI: 0.094, 11.752; P= 0.969) and 0.192 (95% CI: 0.039, 0.935; P= 0.041), respectively. Our analysis supported that the PD-1 inhibitor nivolumab did not cause increased or decreased risks of fatigue, headache, dysgeusia, vertigo and anxiety or malaise and was associated with decreased risks of paresthesia and peripheral neuropathy as compared with controls. These outcomes indicated that although clinicians should be attentive of the side effects of nivolumab, in terms of nervous system side effects, nivolumab is generally safe. C1 [Kong, Xiangyi; Kong, Yanguo] Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, 1 Shuaifuyuan, Beijing 100730, Peoples R China. [Kong, Xiangyi] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Kong, YG (reprint author), Chinese Acad Med Sci, Peking Union Med Coll Hosp, Dept Neurosurg, 1 Shuaifuyuan, Beijing 100730, Peoples R China. EM kong0126@126.com FU Peking Union Medical College Youth Research Funds [3332016010]; Peking Union Medical College Graduate Student Innovation Fund [2015-1002-02-09] FX We would like to thank our colleagues at the Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. This study was supported by Peking Union Medical College Youth Research Funds (2016) (Project No 3332016010; Grant recipient: Xiangyi Kong) and Peking Union Medical College Graduate Student Innovation Fund (2015) (Project No 2015-1002-02-09; Grant recipient: Xiangyi Kong). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 19 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER JI OncoTargets Ther. PY 2017 VL 10 BP 1335 EP 1344 DI 10.2147/OTT.S120341 PG 10 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA EM3SZ UT WOS:000395236200001 PM 28280368 ER PT J AU Ali, MA Lacin, S Abdel-Wahab, R Uemura, M Hassan, M Rashid, A Duda, DG Kaseb, AO AF Ali, Mahmoud A. Lacin, Sahin Abdel-Wahab, Reham Uemura, Mark Hassan, Manal Rashid, Asif Duda, Dan G. Kaseb, Ahmed O. TI Nonalcoholic steatohepatitis-related hepatocellular carcinoma: is there a role for the androgen receptor pathway? SO ONCOTARGETS AND THERAPY LA English DT Review DE hepatocellular carcinoma; nonalcoholic steatohepatitis; androgen receptor; flutamide; sorafenib ID FATTY LIVER-DISEASE; POLYCYSTIC-OVARY-SYNDROME; HEPATITIS-B-VIRUS; BEVACIZUMAB PLUS ERLOTINIB; HORMONE-BINDING GLOBULIN; SEX-STEROID-RECEPTORS; PHASE-II TRIAL; METABOLIC SYNDROME; UNITED-STATES; INSULIN-RESISTANCE AB The epidemic of insulin resistance, obesity, and metabolic syndrome has led to the emergence of nonalcoholic steatohepatitis (NASH) as the most common cause of liver disease in the US. Patients with NASH are at an increased risk for hepatic disease-related morbidity and death, and chronic inflammation in NASH patients can lead to hepatocellular carcinoma (HCC). The prevalence of HCC is higher in males than in females, and genetic studies have identified androgen and androgen receptors (ARs) as partially responsible for the gender disparity in the development of liver disease and HCC. Although many factors are known to play important roles in the progression of inflammation in NASH patients, the role of androgen and AR in the progression of NASH to HCC has been understudied. This review summarizes the evidence for a potential role of androgen and the AR pathway in the development of NASH-related HCC and in the treatment of HCC. It has been proposed that AR plays a role in the progression of HCC: inhibitory roles in early stages of hepatocarcinogenesis and tumor-promoting roles in advanced stages. AR can be activated by several pathways, even in the absence of androgen. While AR has been explored as a potential therapeutic target in HCC, several clinical trials have failed to demonstrate a clinical benefit of antiandrogen drugs in HCC. This review discusses the potential reason for these observations and discuss the potential future trials design in this important setting. C1 [Ali, Mahmoud A.; Lacin, Sahin; Abdel-Wahab, Reham; Uemura, Mark; Hassan, Manal; Kaseb, Ahmed O.] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. [Abdel-Wahab, Reham] Assiut Univ, Dept Clin Oncol, Assiut, Egypt. [Rashid, Asif] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Duda, Dan G.] Harvard Med Sch, Boston, MA USA. RP Kaseb, AO (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM akaseb@mdanderson.org FU MD Anderson Cancer Center FX This work was supported by MD Anderson Cancer Center (to AOK). NR 111 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-6930 J9 ONCOTARGETS THER JI OncoTargets Ther. PY 2017 VL 10 BP 1403 EP 1412 DI 10.2147/OTT.S111681 PG 10 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA EM3TP UT WOS:000395237800001 ER PT J AU Lee, R Khoueir, Z Tsikata, E Chodosh, J Dohlman, CH Chen, TC AF Lee, Ramon Khoueir, Ziad Tsikata, Edem Chodosh, James Dohlman, Claes H. Chen, Teresa C. TI Long-term Visual Outcomes and Complications of Boston Keratoprosthesis Type II Implantation SO OPHTHALMOLOGY LA English DT Article ID OSTEO-ODONTO-KERATOPROSTHESIS; UNIVERSITY-OF-CALIFORNIA; CORNEAL BLINDNESS; EXPERIENCE; SURGERY; MULTICENTER; GLAUCOMA; EYES; PREVENTION; MANAGEMENT AB Purpose: To report the long-term visual outcomes and complications after Boston keratoprosthesis type II implantation in the largest single-center case series with the longest average follow-up. Design: Retrospective review of consecutive clinical case series. Participants: Between January 1992 and April 2015 at the Massachusetts Eye and Ear Infirmary, 48 eyes of 44 patients had keratoprosthesis type II implanted by 2 surgeons (C. H. D. and J. C.). Methods: For each eye, data were collected and analyzed on the preoperative characteristics, intraoperative procedures, and postoperative course. Main Outcome Measures: Visual acuity outcomes, postoperative complications, and device retention. Results: The most common indications for surgery were StevenseJohnson syndrome in 41.7% (20 of 48 eyes) and mucous membrane pemphigoid in 41.7% (20 of 48 eyes). Mean follow-up duration was 70.2 months (standard deviation, 61.8 months; median, 52 months; range, 6 months to 19.8 years). Almost all patients (95.8%, 46 of 48 eyes) had a preoperative visual acuity of 20/200 or worse. Postoperative visual acuity improved to 20/200 or better in 37.5% (18 of 48 eyes) and to 20/100 or better in 33.3% (16 of 48 eyes) at the last follow-up visit. The most common postoperative complication was retroprosthetic membrane formation in over half (60.4%, 29 of 48 eyes). The most pressing postoperative complication was glaucoma onset or progression in about a third. Preexisting glaucoma was present in 72.9% (35 of 48 eyes). Glaucoma progressed in 27.1% (13 of 48 eyes) and was newly diagnosed in 8.3% (4 of 48 eyes) after surgery. Other postoperative complications were tarsorrhaphy revision in 52.1% (25 of 48 eyes), retinal detachment in 18.8% (9 of 48 eyes), infectious endophthalmitis in 6.3% (3 of 48 eyes), and choroidal detachment or hemorrhage in 8.3% (4 of 48 eyes). Half of eyes retained their initial keratoprosthesis at the last follow-up (50.0%, 24 of 48 eyes). Conclusions: The Boston keratoprosthesis type II is a viable option to salvage vision in patients with poor prognosis for other corneal procedures. Retroprostheticmembranes, keratoprosthesis retention, and glaucoma are major challenges in the postoperative period; however, the keratoprosthesis can still provide improved vision in a select group of patients. (C) 2016 by the American Academy of Ophthalmology. C1 [Lee, Ramon] Harvard Med Sch, Boston, MA USA. [Khoueir, Ziad; Tsikata, Edem; Chen, Teresa C.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Glaucoma Serv, Dept Ophthalmol, Boston, MA USA. [Chodosh, James; Dohlman, Claes H.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Cornea Serv, Dept Ophthalmol, Boston, MA USA. RP Chen, TC (reprint author), Massachusetts Eye & Ear Infirm, Glaucoma Serv, 243 Charles St, Boston, MA 02114 USA. EM teresa_chen@meei.harvard.edu FU National Eye Institute/National Institutes of Health; Novartis (Basel, Switzerland) FX The authors have made the following disclosures: J.C.: Grant - National Eye Institute/National Institutes of Health; Personal consultant fees - Novartis (Basel, Switzerland); Travel costs for teaching - Reliance, which are all unrelated to this manuscript. NR 45 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 0161-6420 EI 1549-4713 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2017 VL 124 IS 1 BP 27 EP 35 DI 10.1016/j.ophtha.2016.07.011 PG 9 WC Ophthalmology SC Ophthalmology GA EK4KZ UT WOS:000393896900019 PM 27538795 ER PT J AU Warnhoff, K Roh, HC Kocsisova, Z Tan, CH Morrison, A Croswell, D Schneider, DL Kornfeld, K AF Warnhoff, Kurt Roh, Hyun C. Kocsisova, Zuzana Tan, Chieh-Hsiang Morrison, Andrew Croswell, Damari Schneider, Daniel L. Kornfeld, Kerry TI The Nuclear Receptor HIZR-1 Uses Zinc as a Ligand to Mediate Homeostasis in Response to High Zinc SO PLOS BIOLOGY LA English DT Article ID FACTOR-I MTF-1; CAENORHABDITIS-ELEGANS; TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; C. ELEGANS; METALLOTHIONEIN GENES; DIETARY ZINC; IDENTIFICATION; EXPRESSION; BINDING AB Nuclear receptors were originally defined as endocrine sensors in humans, leading to the identification of the nuclear receptor superfamily. Despite intensive efforts, most nuclear receptors have no known ligand, suggesting new ligand classes remain to be discovered. Furthermore, nuclear receptors are encoded in the genomes of primitive organisms that lack endocrine signaling, suggesting the primordial function may have been environmental sensing. Here we describe a novel Caenorhabditis elegans nuclear receptor, HIZR-1, that is a high zinc sensor in an animal and the master regulator of high zinc homeostasis. The essential micronutrient zinc acts as a HIZR-1 ligand, and activated HIZR-1 increases transcription of genes that promote zinc efflux and storage. The results identify zinc as the first inorganic molecule to function as a physiological ligand for a nuclear receptor and direct environmental sensing as a novel function of nuclear receptors. C1 [Warnhoff, Kurt; Roh, Hyun C.; Kocsisova, Zuzana; Tan, Chieh-Hsiang; Morrison, Andrew; Croswell, Damari; Schneider, Daniel L.; Kornfeld, Kerry] Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA. [Warnhoff, Kurt] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Roh, Hyun C.] Beth Israel Deaconess Med Ctr, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Kornfeld, K (reprint author), Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO 63130 USA. EM kornfeld@wustl.edu FU National Institute of Health [2R01GM068598-09] FX National Institute of Health https://www.nigms.nih.gov/Pages/default.aspx (grant number 2R01GM068598-09).Received by KK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 0 Z9 0 U1 2 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JAN PY 2017 VL 15 IS 1 AR e2000094 DI 10.1371/journal.pbio.2000094 PG 27 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA EK2WL UT WOS:000393787500016 ER PT J AU Boland, MR Karczewski, KJ Tatonetti, NP AF Boland, Mary Regina Karczewski, Konrad J. Tatonetti, Nicholas P. TI Ten Simple Rules to Enable Multi-site Collaborations through Data Sharing SO PLOS COMPUTATIONAL BIOLOGY LA English DT Editorial Material ID EMERGE NETWORK; GENETIC-VARIATION; CHALLENGES; SCIENCE C1 [Boland, Mary Regina; Tatonetti, Nicholas P.] Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA. [Boland, Mary Regina; Tatonetti, Nicholas P.] Columbia Univ, Dept Syst Biol, New York, NY 10027 USA. [Boland, Mary Regina; Tatonetti, Nicholas P.] Columbia Univ, Dept Med, New York, NY 10027 USA. [Boland, Mary Regina; Tatonetti, Nicholas P.] Columbia Univ, Observat Hlth Data Sci & Informat, New York, NY 10027 USA. [Karczewski, Konrad J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Karczewski, Konrad J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. RP Boland, MR (reprint author), Columbia Univ, Dept Biomed Informat, New York, NY 10027 USA.; Boland, MR (reprint author), Columbia Univ, Dept Syst Biol, New York, NY 10027 USA.; Boland, MR (reprint author), Columbia Univ, Dept Med, New York, NY 10027 USA.; Boland, MR (reprint author), Columbia Univ, Observat Hlth Data Sci & Informat, New York, NY 10027 USA. EM mary.boland@columbia.edu FU NLM [T15 LM00707]; NCATS; NIH [TL1 TR000082]; NCRR [TL1 RR024158] FX MRB was supported by NLM T15 LM00707 from Jul 2014-Jun2016 and by the NCATS, NIH, through TL1 TR000082, formerly the NCRR, TL1 RR024158 from Jul 2016-Jun 2017. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2017 VL 13 IS 1 AR e1005278 DI 10.1371/journal.pcbi.1005278 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA EK7ZT UT WOS:000394144400019 ER PT J AU Heitmann, S Rule, M Truccolo, W Ermentrout, B AF Heitmann, Stewart Rule, Michael Truccolo, Wilson Ermentrout, Bard TI Optogenetic Stimulation Shifts the Excitability of Cerebral Cortex from Type Ito Type II: Oscillation Onset and Wave Propagation SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID NEURONAL NETWORKS; NEURAL-NETWORK; DYNAMICS; PULSES; MODEL AB Constant optogenetic stimulation targeting both pyramidal cells and inhibitory interneurons has recently been shown to elicit propagating waves of gamma-band (40-80 Hz) oscillations in the local field potential of non-human primate motor cortex. The oscillations emerge with non-zero frequency and small amplitude the hallmark of a type II excitable medium yet they also propagate far beyond the stimulation site in the manner of a type I excitable medium. How can neural tissue exhibit both type I and type II excitability? We investigated the apparent contradiction by modeling the cortex as a Wilson-Cowan neural field in which optogenetic stimulation was represented by an external current source. In the absence of any external current, the model operated as a type I excitable medium that supported propagating waves of gamma oscillations similar to those observed in vivo. Applying an external current to the population of inhibitory neurons transformed the model into a type II excitable medium. The findings suggest that cortical tissue normally operates as a type I excitable medium but it is locally transformed into a type II medium by optogenetic stimulation which predominantly targets inhibitory neurons. The proposed mechanism accounts for the graded emergence of gamma oscillations at the stimulation site while retaining propagating waves of gamma oscillations in the non-stimulated tissue. It also predicts that gamma waves can be emitted on every second cycle of a 100 Hz oscillation. That prediction was subsequently confirmed by re-analysis of the neurophysiological data. The model thus offers a theoretical account of how optogenetic stimulation alters the excitability of cortical neural fields. C1 [Heitmann, Stewart; Ermentrout, Bard] Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. [Rule, Michael; Truccolo, Wilson] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Truccolo, Wilson] US Dept Vet Affairs, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. RP Heitmann, S; Ermentrout, B (reprint author), Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. EM heitmann@pitt.edu; bard@pitt.edu FU USA National Science Fund (NSF) [1219753]; National Institute of Neurological Disorders and Stroke (NINDS) [R01 NS25074]; K01 Career Award [NS057389]; Defense Advanced Research Projects Agency (DARPA REPAIR) [N66001-10-C-2010]; U.S. Department of Veterans Affairs, Merit Review Award [101RX000668]; Pablo J. Salame '88 Goldman Sachs endowed Assistant Professorship of Computational Neuroscience; National Science Foundation Graduate Research Fellowships Program (NSFGRFP) FX BE and SH were funded by USA National Science Fund (NSF) award 1219753. WT was supported by the National Institute of Neurological Disorders and Stroke (NINDS), R01 NS25074, K01 Career Award NS057389; Defense Advanced Research Projects Agency (DARPA REPAIR N66001-10-C-2010); U.S. Department of Veterans Affairs, Merit Review Award 101RX000668, and the Pablo J. Salame '88 Goldman Sachs endowed Assistant Professorship of Computational Neuroscience. MR was supported by National Science Foundation Graduate Research Fellowships Program (NSFGRFP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-734X EI 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD JAN PY 2017 VL 13 IS 1 AR e1005349 DI 10.1371/journal.pcbi.1005349 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA EK7ZT UT WOS:000394144400054 PM 28118355 ER PT J AU Cui, Y Yu, HS Zheng, X Peng, R Wang, Q Zhou, Y Wang, R Wang, JH Qu, B Shen, N Guo, Q Liu, X Wang, C AF Cui, Ye Yu, Huansha Zheng, Xin Peng, Rui Wang, Qiang Zhou, Yi Wang, Rui Wang, Jiehua Qu, Bo Shen, Nan Guo, Qiang Liu, Xing Wang, Chen TI SENP7 Potentiates cGAS Activation by Relieving SUMO-Mediated Inhibition of Cytosolic DNA Sensing SO PLOS PATHOGENS LA English DT Article ID CYCLIC GMP-AMP; SYSTEMIC-LUPUS-ERYTHEMATOSUS; INNATE IMMUNITY; MYCOBACTERIUM-TUBERCULOSIS; IMMUNOGENIC TUMORS; SENSOR CGAS; SELF-DNA; SYNTHASE; DISEASE; VIRUS AB Cyclic GMP-AMP (cGAMP) synthase (cGAS, a.k.a. MB21D1), a cytosolic DNA sensor, catalyzes formation of the second messenger 2'3'-cGAMP that activates the stimulator of interferon genes (STING) signaling. How the cGAS activity is modulated remains largely unknown. Here, we demonstrate that sentrin/SUMO-specific protease 7 (SENP7) interacted with and potentiated cGAS activation. The small ubiquitin-like modifier (SUMO) was conjugated onto the lysine residues 335, 372 and 382 of cGAS, which suppressed its DNA-binding, oligomerization and nucleotidyl-transferase activities. SENP7 reversed this inhibition via catalyzing the cGAS de-SUMOylation. Consistently, silencing of SENP7 markedly impaired the IRF3-responsive gene expression induced by cGAS-STING axis. SENP7-knockdown mice were more susceptible to herpes simplex virus 1 (HSV-1) infection. SENP7 was significantly up-regulated in patients with SLE. Our study highlights the temporal modulation of the cGAS activity via dynamic SUMOylation, uncovering a novel mechanism for fine-tuning the STING signaling in innate immunity. C1 [Cui, Ye; Yu, Huansha; Zheng, Xin; Peng, Rui; Wang, Qiang; Zhou, Yi; Wang, Rui; Wang, Chen] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai, Peoples R China. [Wang, Jiehua; Qu, Bo; Shen, Nan; Guo, Qiang] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Rheumatol, Shanghai, Peoples R China. [Liu, Xing] Harvard Med Sch, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Liu, Xing] Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. [Wang, Chen] China Pharmaceut Univ, State Key Lab Nat Med, Nanjing, Jiangsu, Peoples R China. [Wang, Chen] China Pharmaceut Univ, Sch Life Sci & Technol, Nanjing, Jiangsu, Peoples R China. RP Liu, X (reprint author), Harvard Med Sch, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. EM xing.liu@childrens.harvard.edu; cwang01@sibcb.ac.cn FU National Natural Science Foundation of China [31030021, 31300735, 81161120542, 81401331]; Ministry of Science and Technology of China [2012CB910200, 2011CB910904, 2014CB541902, 2014CB541906]; 111 Project [111-2-07] FX This work was supported by grants from National Natural Science Foundation of China (31030021, 31300735, 81161120542, 81401331), Ministry of Science and Technology of China (2012CB910200, 2011CB910904, 2014CB541902, 2014CB541906). CW was supported by the 111 Project (No. 111-2-07). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 0 Z9 0 U1 1 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2017 VL 13 IS 1 AR e1006156 DI 10.1371/journal.ppat.1006156 PG 24 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA EN1AV UT WOS:000395743500054 ER PT J AU Ellett, F Jorgensen, J Frydman, GH Jones, CN Irimia, D AF Ellett, Felix Jorgensen, Julianne Frydman, Galit H. Jones, Caroline N. Irimia, Daniel TI Neutrophil Interactions Stimulate Evasive Hyphal Branching by Aspergillus fumigatus SO PLOS PATHOGENS LA English DT Article ID EXTRACELLULAR TRAPS; INVASIVE ASPERGILLOSIS; ALVEOLAR MACROPHAGES; CANDIDA-ALBICANS; RISK-FACTORS; CELL-DEATH; CONIDIA; GROWTH; DIAGNOSIS; EPIDEMIOLOGY AB Invasive aspergillosis (IA), primarily caused by Aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that is difficult to treat and results in high mortality. Investigations of neutrophil-hypha interaction in vitro and in animal models of IA are limited by lack of temporal and spatial control over interactions. This study presents a new approach for studying neutrophil- hypha interaction at single cell resolution over time, which revealed an evasive fungal behavior triggered by interaction with neutrophils: Interacting hyphae performed de novo tip formation to generate new hyphal branches, allowing the fungi to avoid the interaction point and continue invasive growth. Induction of this mechanism was independent of neutrophil NADPH oxidase activity and neutrophil extracellular trap (NET) formation, but could be phenocopied by iron chelation and mechanical or physiological stalling of hyphal tip extension. The consequence of branch induction upon interaction outcome depends on the number and activity of neutrophils available: In the presence of sufficient neutrophils branching makes hyphae more vulnerable to destruction, while in the presence of limited neutrophils the interaction increases the number of hyphal tips, potentially making the infection more aggressive. This has direct implications for infections in neutrophil- deficient patients and opens new avenues for treatments targeting fungal branching. C1 [Ellett, Felix; Jorgensen, Julianne; Frydman, Galit H.; Jones, Caroline N.; Irimia, Daniel] Harvard Med Sch, Shriners Burns Hosp, Massachusetts Gen Hosp,Dept Surg, BioMEMS Resource Ctr,Div Surg Innovat & Bioengn, Boston, MA 02115 USA. [Frydman, Galit H.] MIT, Div Comparat Med, Dept Biol Engn, Cambridge, MA 02139 USA. RP Irimia, D (reprint author), Harvard Med Sch, Shriners Burns Hosp, Massachusetts Gen Hosp,Dept Surg, BioMEMS Resource Ctr,Div Surg Innovat & Bioengn, Boston, MA 02115 USA. EM dirimia@hms.harvard.edu FU Cidara Therapeutics; National Institute of Health [EB002503, GM092804] FX Funding support for this project was provided in part by Cidara Therapeutics and grants from the National Institute of Health: EB002503 and GM092804. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 62 TC 0 Z9 0 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2017 VL 13 IS 1 AR e1006154 DI 10.1371/journal.ppat.1006154 PG 22 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA EN1AV UT WOS:000395743500053 ER PT J AU Wibmer, CK Gorman, J Ozorowski, G Bhiman, JN Sheward, DJ Elliott, DH Rouelle, J Smira, A Joyce, MG Ndabambi, N Druz, A Asokan, M Burton, DR Connors, M Karim, SSA Mascola, JR Robinson, JE Ward, AB Williamson, C Kwong, PD Morris, L Moore, PL AF Wibmer, Constantinos Kurt Gorman, Jason Ozorowski, Gabriel Bhiman, Jinal N. Sheward, Daniel J. Elliott, Debra H. Rouelle, Julie Smira, Ashley Joyce, M. Gordon Ndabambi, Nonkululeko Druz, Aliaksandr Asokan, Mangai Burton, Dennis R. Connors, Mark Karim, Salim S. Abdool Mascola, John R. Robinson, James E. Ward, Andrew B. Williamson, Carolyn Kwong, Peter D. Morris, Lynn Moore, Penny L. TI Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape SO PLOS PATHOGENS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BROADLY NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN TRIMERS; HUMAN MONOCLONAL-ANTIBODIES; MUCOSAL SHIV CHALLENGE; B-CELL RESPONSES; CONFORMATIONAL EPITOPE; GLYCOSYLATION PROFILES; TYPE-1 INFECTION; VACCINE DESIGN AB A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagene-sis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epi-topes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N-or O-linked glyco-sylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design. C1 [Wibmer, Constantinos Kurt; Bhiman, Jinal N.; Morris, Lynn; Moore, Penny L.] NHLS, NICD, Ctr HIV & STIs, Johannesburg, South Africa. [Wibmer, Constantinos Kurt; Bhiman, Jinal N.; Morris, Lynn; Moore, Penny L.] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa. [Gorman, Jason; Joyce, M. Gordon; Druz, Aliaksandr; Asokan, Mangai; Mascola, John R.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Ozorowski, Gabriel; Ward, Andrew B.] Scripps Res Inst, Dept Integrat Struct & Computat Biol, CHAVI ID, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Ozorowski, Gabriel; Ward, Andrew B.] Scripps Res Inst, CAVD, La Jolla, CA 92037 USA. [Sheward, Daniel J.; Ndabambi, Nonkululeko; Williamson, Carolyn] Univ Cape Town, Inst Infect Dis & Mol Med IDM, Cape Town, South Africa. [Sheward, Daniel J.; Ndabambi, Nonkululeko; Williamson, Carolyn] Univ Cape Town, Div Med Virol, Cape Town, South Africa. [Sheward, Daniel J.; Ndabambi, Nonkululeko; Williamson, Carolyn] NHLS, Cape Town, South Africa. [Elliott, Debra H.; Rouelle, Julie; Smira, Ashley; Robinson, James E.] Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70118 USA. [Burton, Dennis R.] Scripps Res Inst, CHAVI ID, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp MIT & Harvard, Cambridge, MA USA. [Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. [Karim, Salim S. Abdool; Williamson, Carolyn; Morris, Lynn; Moore, Penny L.] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Durban, South Africa. [Karim, Salim S. Abdool] Columbia Univ, Dept Epidemiol, New York, NY USA. RP Morris, L; Moore, PL (reprint author), NHLS, NICD, Ctr HIV & STIs, Johannesburg, South Africa.; Morris, L; Moore, PL (reprint author), Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.; Morris, L; Moore, PL (reprint author), Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Durban, South Africa. EM lynnm@nicd.ac.za; pennym@nicd.ac.za OI Wibmer, Constantinos Kurt/0000-0003-2329-2280 FU Centre for the AIDS Programme of Research (CAPRISA); South African Medical Research Council (MRC) SHIP program; NIH [A1116086-01]; Vaccine Research Center; National Institute of Allergy and Infectious Diseases (NIAID); HIVRAD NIH grant [AI088610]; South African HIV/AIDS Research and Innovation Platform of the South African Department of Science and Technology; US NIAID; NIH; US Department of Health and Human Services [U19 AI51794]; Columbia University Southern African Fogarty AIDS International Training and Research Program through the Fogarty International Center, NIH [5 D43 TW000231]; Poliomyelitis Research Foundation PhD Bursary; National Research Foundation of South Africa PhD Bursary; Collaboration for AIDS Vaccine Discovery [OPP1115782]; South African Research Chairs Initiative of the Department of Science and Technology; National Research Foundation of South Africa [98341] FX We acknowledge research funding from the Centre for the AIDS Programme of Research (CAPRISA) (SSAK), the South African Medical Research Council (MRC) SHIP program (P.L.M.), the NIH through a U01 grant (A1116086-01) (PLM, LM, JRM and PDK), the intramural research programs of the Vaccine Research Center and the National Institute of Allergy and Infectious Diseases (NIAID) (JRM and PDK) and a HIVRAD NIH grant (JER, CW and LM, AI088610). CAPRISA is funded by the South African HIV/AIDS Research and Innovation Platform of the South African Department of Science and Technology, and was initially supported by the US NIAID, NIH, US Department of Health and Human Services grant U19 AI51794 (SSAK). Funding was received by CKW and JNB from the Columbia University Southern African Fogarty AIDS International Training and Research Program through the Fogarty International Center, NIH grant 5 D43 TW000231 (to Quarraisha Abdool Karim). CKW and JNB are supported by a Poliomyelitis Research Foundation PhD Bursary and a National Research Foundation of South Africa PhD Bursary. Funding for ABW was provided by Collaboration for AIDS Vaccine Discovery grant OPP1115782. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa (Grant No 98341). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 88 TC 0 Z9 0 U1 3 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD JAN PY 2017 VL 13 IS 1 DI 10.1371/journal.ppat.1006074 PG 30 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA EN1AV UT WOS:000395743500012 ER PT J AU Clark, MA Ott, M Rogers, ML Politi, MC Miller, SC Moynihan, L Robison, K Stuckey, A Dizon, D AF Clark, Melissa A. Ott, Miles Rogers, Michelle L. Politi, Mary C. Miller, Susan C. Moynihan, Laura Robison, Katina Stuckey, Ashley Dizon, Don TI Advance care planning as a shared endeavor: completion of ACP documents in a multidisciplinary cancer program SO PSYCHO-ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; LIFE CARE; CARDIOPULMONARY-RESUSCITATION; DECISION-MAKING; ONCOLOGY PATIENTS; END; DIRECTIVES; INFORMATION; DISCUSSIONS; PHYSICIANS AB Objective: We examined the roles of oncology providers in advance care planning (ACP) delivery in the context of a multidisciplinary cancer program. Methods: Semi-structured interviews were conducted with 200 women with recurrent and/or metastatic breast or gynecologic cancer. Participants were asked to name providers they deemed important in their cancer care and whether they had discussed and/or completed ACP documentation. Evidence of ACP documentation was obtained from chart reviews. Results: Fifty percent of participants self-reported completing an advance directive (AD) and 48.5% had named a healthcare power of attorney (HPA), 38.5% had completed both, and 39.0% had completed neither document. Among women who self-reported completion of the documents, only 24.0% and 14.4% of women respectively had documentation of an AD and HPA in their chart. Completion of an AD was associated with number (adjusted odds ratio [AOR] = 1.49) and percentage (AOR=6.58) of providers with whom the participant had a conversation about end-of-life decisions. Participants who named a social worker or nurse practitioner were more likely to report having completed an AD. Participants who named at least one provider in common (e.g., named the same oncologist) were more likely to have comparable behaviors related to naming a HPA (AOR=1.13, p = 0.011) and completion of an AD (AOR=1.06, p = 0.114). Conclusions: Despite the important role of physicians in facilitating ACP discussions, involvement of other staff was associated with a greater likelihood of completion of ACP documentation. Patients may benefit from opportunities to discuss ACP with multiple members of their cancer care team. Copyright (C) 2015 John Wiley & Sons, Ltd. C1 [Clark, Melissa A.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Box G-121-6, Providence, RI 02912 USA. [Clark, Melissa A.; Rogers, Michelle L.] Brown Univ, Ctr Populat Hlth & Clin Epidemiol, Box G-121-6, Providence, RI 02912 USA. [Clark, Melissa A.; Robison, Katina; Stuckey, Ashley] Brown Univ, Warren Alpert Med Sch, Dept Obstet & Gynecol, Box G-121-6, Providence, RI 02912 USA. [Ott, Miles] Augsburg Coll, Dept Math, Minneapolis, MN USA. [Politi, Mary C.] Washington Univ, Dept Surg, Div Publ Hlth Sci, St Louis, MO USA. [Miller, Susan C.] Brown Univ, Dept Hlth Serv Policy & Practice, Box G-121-6, Providence, RI 02912 USA. [Miller, Susan C.] Brown Univ, Ctr Gerontol & Hlth Care Res, Box G-121-6, Providence, RI 02912 USA. [Moynihan, Laura] Brown Univ, Box G-121-6, Providence, RI 02912 USA. [Robison, Katina; Stuckey, Ashley] Women & Infants Hosp Rhode Isl, Program Womens Oncol, Providence, RI USA. [Dizon, Don] Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. [Dizon, Don] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Clark, MA (reprint author), Brown Univ, Sch Publ Hlth, Dept Epidemiol, Box G-121-6, Providence, RI 02912 USA. EM melissa_clark@brown.edu FU National Cancer Institute [R21CA137290] FX This work was supported by the National Cancer Institute [R21CA137290]. NR 39 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1057-9249 EI 1099-1611 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD JAN PY 2017 VL 26 IS 1 BP 67 EP 73 DI 10.1002/pon.4010 PG 7 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA EK7VN UT WOS:000394133400010 PM 26489363 ER PT J AU Barrett, LF AF Barrett, Lisa Feldman TI Categories and Their Role in the Science of Emotion SO PSYCHOLOGICAL INQUIRY LA English DT Editorial Material ID PSYCHOLOGICAL CONSTRUCTION; BRAIN; DEGENERACY; NETWORKS; SYSTEMS; ARCHITECTURE; EXPERIENCE; COMPLEXITY; MODELS C1 [Barrett, Lisa Feldman] Northeastern Univ, Dept Psychol, 125 Nightingale Hall, Boston, MA 02115 USA. [Barrett, Lisa Feldman] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Cambridge, MA USA. [Barrett, Lisa Feldman] Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Cambridge, MA USA. RP Barrett, LF (reprint author), Northeastern Univ, Dept Psychol, 125 Nightingale Hall, Boston, MA 02115 USA. EM l.barrett@neu.edu FU National Cancer Institute [U01 CA193632]; National Institute on Aging [R01 AG030311]; U.S. Army Research Institute [W911NF-15-1-0647, W911NF-16-1-0191] FX This article received funding from the National Cancer Institute (U01 CA193632), the National Institute on Aging (R01 AG030311), and the U.S. Army Research Institute (W911NF-15-1-0647; W911NF-16-1-0191). NR 69 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1047-840X EI 1532-7965 J9 PSYCHOL INQ JI Psychol. Inq. PY 2017 VL 28 IS 1 BP 20 EP 26 DI 10.1080/1047840X.2017.1261581 PG 7 WC Psychology, Multidisciplinary SC Psychology GA EM3VW UT WOS:000395243700002 ER PT J AU LaMotte, AD Taft, CT Weatherill, RP Casement, MD Creech, SK Milberg, WP Fortier, CB McGlinchey, RE AF LaMotte, Adam D. Taft, Casey T. Weatherill, Robin P. Casement, Melynda D. Creech, Suzannah K. Milberg, William P. Fortier, Catherine B. McGlinchey, Regina E. TI Sleep Problems and Physical Pain as Moderators of the Relationship Between PTSD Symptoms and Aggression in Returning Veterans SO PSYCHOLOGICAL TRAUMA-THEORY RESEARCH PRACTICE AND POLICY LA English DT Article DE posttraumatic stress disorder; violence; sleep; pain; veteran ID POSTTRAUMATIC-STRESS-DISORDER AB Objective: This study investigated sleep problems and physical pain as moderators of the relationship between PTSD symptoms and aggression among returning veterans. Prior research has demonstrated associations between PTSD symptoms and aggression, but little work has sought to identify moderators of this relationship. Sleep problems and physical pain are both common clinical problems among veterans and have theoretical links to aggression. Method: Participants were 103 returning service members and veterans recruited from the greater Boston area and enrolled in the VA Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS). Aggression outcomes included physical and psychological intimate partner aggression (IPA), as well as physical and psychological general aggression (GA). Variables were measured via self-report questionnaires, with the exception of PTSD symptoms, which were assessed via clinician interview. Results: Bivariate correlations revealed significant associations between PTSD symptoms, sleep problems, physical pain, and aggression outcomes. Both sleep problems and physical pain significantly moderated the relationship between PTSD symptoms and physical GA, such that this relationship became stronger at higher levels of these moderator variables. However, moderation was not found for the other aggression outcomes. Conclusions: Findings suggest that sleep problems and physical pain strengthen the relationship between veterans' PTSD symptoms and physical aggression toward others. Although further replication and elucidation is needed, these factors may disinhibit aggression among those at higher risk due to their PTSD symptoms. C1 [LaMotte, Adam D.; Taft, Casey T.; Weatherill, Robin P.] VA Boston Healthcare Syst, Natl Ctr PTSD, 116B 4,150 South Huntington Ave, Boston, MA 02130 USA. [Taft, Casey T.; Weatherill, Robin P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Casement, Melynda D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Creech, Suzannah K.] Cent Texas Vet Healthcare Syst, VHA VISN Ctr Excellence Res Returning War Vet 17, Waco, TX USA. [Creech, Suzannah K.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat, Providence, RI 02912 USA. [Milberg, William P.; Fortier, Catherine B.; McGlinchey, Regina E.] Harvard Med Sch, Translat Res Ctr Traumat Brain Injury & Stress Di, Natl Network Res Ctr, Boston, MA USA. [Milberg, William P.; Fortier, Catherine B.; McGlinchey, Regina E.] Harvard Med Sch, GRECC, Boston, MA USA. [Milberg, William P.; Fortier, Catherine B.; McGlinchey, Regina E.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B 4,150 South Huntington Ave, Boston, MA 02130 USA. EM casey.taft@va.gov FU TRACTS, a VA Rehabilitation Research and Development Service Traumatic Brain Injury National Network Research Center [B9254-C] FX This research was supported by TRACTS, a VA Rehabilitation Research and Development Service Traumatic Brain Injury National Network Research Center (B9254-C). The contents of this article do not represent the views of the United States Department of Veterans Affairs or the United States Government. NR 16 TC 0 Z9 0 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1942-9681 EI 1942-969X J9 PSYCHOL TRAUMA-US JI Psychol. Trauma PD JAN PY 2017 VL 9 IS 1 BP 113 EP 116 DI 10.1037/tra0000178 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EK1HL UT WOS:000393676300016 PM 27732020 ER PT J AU Loya, F Novakovic-Agopian, T Binder, D Rossi, A Rome, S Murphy, M Chen, AJW AF Loya, Fred Novakovic-Agopian, Tatjana Binder, Deborah Rossi, Annemarie Rome, Scott Murphy, Michelle Chen, Anthony J. -W. TI Long-Term Use and Perceived Benefits of Goal-Oriented Attentional Self-Regulation Training in Chronic Brain Injury SO REHABILITATION RESEARCH AND PRACTICE LA English DT Article ID EXECUTIVE DYSFUNCTION; REHABILITATION; INTERVENTIONS; MANAGEMENT; DISORDERS; AWARENESS; EFFICACY; BEHAVIOR; DEFICITS; PEOPLE AB Primary Objective. To investigate the long-term use and perceived benefit(s) of strategies included in Goal-Oriented Attentional Self-Regulation (GOALS) training (Novakovic-Agopian et al., 2011) by individuals with acquired brain injury (ABI) and chronic executive dysfunction. Research Design. Longitudinal follow-up of training. Methods and Procedures. Sixteen participants with chronic ABI participated in structured telephone interviews 20 months (range 11 to 31 months) following completion of GOALS training. Participants responded to questions regarding the range of strategies they continued to utilize, perceived benefit(s) of strategy use, situations in which strategy use was found helpful, and functional changes attributed to training. Results. Nearly all participants (94%) reported continued use of at least one trained strategy in their daily lives, with 75% of participants also reporting improved functioning resulting from training. However, there was considerable variability with respect to the specific strategies individuals found helpful as well as the perceived impact of training on overall functioning. Conclusions. GOALS training shows promising long-term benefits for individuals in the chronic phase of brain injury. Identifying individual-and injury-level factors that account for variability in continued strategy use and the perceived long-termbenefits of training will help with ongoing intervention development. C1 [Loya, Fred; Novakovic-Agopian, Tatjana; Chen, Anthony J. -W.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Loya, Fred; Novakovic-Agopian, Tatjana; Binder, Deborah; Chen, Anthony J. -W.] VA Northern Calif Hlth Care Syst, Martinez, CA 94553 USA. [Loya, Fred; Novakovic-Agopian, Tatjana; Chen, Anthony J. -W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Loya, Fred; Chen, Anthony J. -W.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Novakovic-Agopian, Tatjana; Rossi, Annemarie; Rome, Scott] Calif Pacific Med Ctr, San Francisco, CA USA. [Murphy, Michelle] Laguna Honda Hosp, San Francisco, CA USA. RP Loya, F (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA.; Loya, F (reprint author), VA Northern Calif Hlth Care Syst, Martinez, CA 94553 USA.; Loya, F (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA.; Loya, F (reprint author), Univ Calif Berkeley, Berkeley, CA 94720 USA. EM fred.loya@va.gov FU VA Rehabilitation and Research Development Merit Awards (VANCHCS Project) [VA 1IO1RX001111-01A1, B7467I]; CPMC Foundation; Veterans Affairs Office of Academic Affiliations Advanced Postdoctoral Training Grant, Polytrauma/TBI Rehabilitation FX Aspects of this research were supported by the VA Rehabilitation and Research Development Merit Awards (VA 1IO1RX001111-01A1 and VANCHCS Project no. B7467I), CPMC Foundation Grant, and Veterans Affairs Office of Academic Affiliations Advanced Postdoctoral Training Grant, Polytrauma/TBI Rehabilitation. The authors thank Gary Abrams, MD, and Mark D'Esposito, MD, for their support and mentorship and their participants for contributing their time to their research program. NR 39 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2090-2867 EI 2090-2875 J9 REHABIL RES PRACT JI Rehabil. Res. Pract. PY 2017 AR 8379347 DI 10.1155/2017/8379347 PG 8 WC Rehabilitation SC Rehabilitation GA EL8OQ UT WOS:000394880000001 ER PT J AU Ford, JM AF Ford, Judith M. TI Current Approaches to Studying Hallucinations: Overcoming Barriers to Progress SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material ID AUDITORY VERBAL HALLUCINATIONS; RDOC FRAMEWORK; SCHIZOPHRENIA C1 [Ford, Judith M.] San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. [Ford, Judith M.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. RP Ford, JM (reprint author), San Francisco VA Med Ctr, Psychiat Serv 116D, 4150 Clement St, San Francisco, CA 94121 USA. EM judith.ford@ucsf.edu FU NIMH [MH058262]; Veterans Administration [I01 CX000497] FX This work was supported by grants from NIMH (MH058262) and the Veterans Administration (I01 CX000497). NR 23 TC 1 Z9 1 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 EI 1745-1701 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2017 VL 43 IS 1 BP 21 EP 23 DI 10.1093/schbul/sbw149 PG 3 WC Psychiatry SC Psychiatry GA EK4LC UT WOS:000393897200008 PM 27872264 ER PT J AU Chang, JS Kushel, M Miaskowski, C Ceasar, R Zamora, K Hurstak, E Knight, KR AF Chang, Jamie Suki Kushel, Margot Miaskowski, Christine Ceasar, Rachel Zamora, Kara Hurstak, Emily Knight, Kelly R. TI Provider Experiences With the Identification, Management, and Treatment of Co-occurring Chronic Noncancer Pain and Substance Use in the Safety Net SO SUBSTANCE USE & MISUSE LA English DT Article DE Chronic noncancer pain; prescription opioids; safety net; primary care; provider-patient interactions; substance use treatment; qualitative research ID CHRONIC OPIOID THERAPY; UNITED-STATES; USE DISORDERS; PRIMARY-CARE; PATIENT; ABUSE; GUIDELINES; MEDICAID; HEALTH; TRENDS AB Background: In the United States and internationally, providers have adopted guidelines on the management of prescription opioids for chronic noncancer pain (CNCP). For high-risk patients with co-occurring CNCP and a history of substance use, guidelines advise that providers monitor patients using urine toxicology screening tests, develop opioid management plans, and refer patients to substance use treatment. Objective: We report primary care provider experiences in the safety net interpreting and implementing prescription opioid guideline recommendations for patients with CNCP and substance use. Methods: We interviewed primary care providers who work in safety net settings (N = 23) on their experiences managing CNCP and substance use. We analyzed interviews using a content analysis method. Results: Providers found management plans and urine toxicology screening tests useful for informing patients about clinic expectations of opioid therapy and substance use. However, they described that guideline-based clinic policies had unintended consequences, such as raising barriers to open, honest dialogue about substance use and treatment. While substance use treatment was recommended for high-risk patients, providers described lack of integration with and availability of substance use treatment programs. Conclusions: Our findings indicate that clinicians in the safety net found guideline-based clinic policies helpful. However, effective implementation was challenged by barriers to open dialogue about substance use and limited linkages with treatment programs. Further research is needed to examine how the context of safety net settings shapes the management and treatment of co-occurring CNCP and substance use. C1 [Chang, Jamie Suki] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Psychiat, 1001 Potrero Ave,Bldg 20,Suite 2100, San Francisco, CA 94110 USA. [Kushel, Margot; Hurstak, Emily] Univ Calif San Francisco, Div Gen Internal Med, San Francisco Gen Hosp, San Francisco, CA 94143 USA. [Miaskowski, Christine] Univ Calif San Francisco, Physiol Nursing, San Francisco, CA 94143 USA. [Ceasar, Rachel] Univ Witwatersrand, Sch Publ Hlth, Johannesburg, South Africa. [Zamora, Kara] San Francisco VA Med Ctr, San Francisco, CA USA. [Knight, Kelly R.] Univ Calif San Francisco, Dept Anthropol Hist & Social Med, San Francisco, CA 94143 USA. RP Chang, JS (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Dept Psychiat, 1001 Potrero Ave,Bldg 20,Suite 2100, San Francisco, CA 94110 USA. EM jamie.chang@ucsf.edu FU National Institute of Drug Abuse [RO1DA034625]; Postdoctoral Training Program in Drug Abuse Treatment/Services Research [T32DA007250]; Career Investigator Award in Patient-Oriented Research [K24AG046372] FX This research was funded by a grant from the National Institute of Drug Abuse, RO1DA034625. Dr. Chang was supported in part by T32DA007250, Postdoctoral Training Program in Drug Abuse Treatment/Services Research. Dr. Kushel is supported in part by K24AG046372, Career Investigator Award in Patient-Oriented Research. NR 21 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6084 EI 1532-2491 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2017 VL 52 IS 2 BP 251 EP 255 DI 10.1080/10826084.2016.1223138 PG 5 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA EK3GL UT WOS:000393814400013 PM 27754719 ER PT J AU Kazak, AE Nash, JM Hiroto, K Kaslow, NJ AF Kazak, Anne E. Nash, Justin M. Hiroto, Kimberly Kaslow, Nadine J. TI Psychologists in Patient-Centered Medical Homes (PCMHs): Roles, Evidence, Opportunities, and Challenges SO AMERICAN PSYCHOLOGIST LA English DT Article DE patient-centered medical home; psychology; health care delivery ID MENTAL-HEALTH-SERVICES; PRIMARY-CARE; BEHAVIORAL HEALTH; PROFESSIONAL PSYCHOLOGY; UNITED-STATES; ADULTS; PREFERENCES; COMPETENCES; DEPRESSION; MANAGEMENT AB The patient-centered medical home (PCMH) is an increasingly common model of health care delivery with many exciting opportunities for psychologists. The PCMH reflects a philosophy and model of care that is highly consistent with psychological science and practice. It strives to provide patient-centered, comprehensive, team-based, coordinated, accessible, and quality and safety-oriented health care delivery to individuals and families. Moreoever, in keeping with changes in the health care system more broadly, the PCMH model prioritizes the integration of behavioral and physical health care, and this emphasis lays the foundation for active and full engagement of psychologists in this context. This article provides an overview of the PCMH and the evidence and roles for psychologists across a range of pediatric, adult, and geriatric health care populations and settings. Current challenges to the necessary expansion of psychology in the PCMH are discussed, with particular attention to the needs for training and advocacy to support the contributions of behavioral health care in the PCMH. Psychology must embrace its rightful place as a health profession and appreciate and highlight the ways in which psychologists can play unique and critical roles in transforming present and future health care delivery models. C1 [Kazak, Anne E.] Nemours Childrens Hlth Syst, Nemours Ctr Healthcare Delivery Sci, Wilmington, DE USA. [Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Sch, Dept Pediat, Philadelphia, PA 19107 USA. [Nash, Justin M.] Brown Univ, Warren Alpert Med Sch, Dept Family Med, Pawtucket, RI USA. [Nash, Justin M.] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Pawtucket, RI USA. [Nash, Justin M.] Mem Hosp Rhode Isl, Pawtucket, RI USA. [Hiroto, Kimberly] VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Tacoma, WA USA. [Kaslow, Nadine J.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP Kazak, AE (reprint author), Nemours Ctr Healthcare Delivery Sci, 1701 Rockland Rd,Suite 160, Wilmington, DE 19803 USA. EM anne.kazak@nemours.org NR 68 TC 3 Z9 3 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X EI 1935-990X J9 AM PSYCHOL JI Am. Psychol. PD JAN PY 2017 VL 72 IS 1 BP 1 EP 12 DI 10.1037/a0040382 PG 12 WC Psychology, Multidisciplinary SC Psychology GA EK1GQ UT WOS:000393674200001 PM 26766761 ER PT J AU Brown, JC Harhay, MO Harhay, MN AF Brown, Justin C. Harhay, Michael O. Harhay, Meera N. TI Anthropometrically-predicted visceral adipose tissue and mortality among men and women in the third national health and nutrition examination survey (NHANES III) SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Article DE anthropometrics; waist circumference; body mass index; population-based ID ABDOMINAL ADIPOSITY; CONTROLLED-TRIAL; OBESITY; REDUCTION; DESIGN; INDEX; DEATH; RISK AB ObjectiveThis study seeks to quantify the relationship between anthropometrically-predicted visceral adipose tissue (apVAT) and all-cause and cause-specific mortality among individuals of European descent in a population-based prospective cohort study of 10,624 participants. MethodsThe apVAT with a validated regression equation that included age, body mass index, and waist and thigh circumferences were predicted. ResultsDuring a median of 18.8 years, 3531 participants died with 1153 and 741 deaths attributable to cardiovascular disease and cancer, respectively. In multivariable-adjusted analyses that accounted for demographic, clinical, and behavioral characteristics, higher apVAT was associated with an increased risk of all-cause (P-trend<.001), cardiovascular-specific (P-trend<.001), and cancer-specific mortality (P-trend=.007). Excluding participants with a history of cancer, myocardial infarction, heart failure, or diabetes at baseline did not substantively alter effect estimates. apVAT more accurately predicted all-cause, cardiovascular-specific, and cancer-specific mortality than body mass index (P<.001), waist circumference (P<.001), or the combination of body mass index and waist circumference (P<.001). ConclusionsThese data provide evidence that apVAT is associated with all-cause and cause-specific mortality in a large population-based sample of men and women of European descent. These results support the use of apVAT to risk-stratify individuals for premature mortality when imaging data are not available such as in routine clinical practice or in large clinical trials. C1 [Brown, Justin C.] Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. [Brown, Justin C.; Harhay, Michael O.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Harhay, Meera N.] Drexel Univ, Dept Med, Coll Med, Div Nephrol, Philadelphia, PA 19104 USA. RP Brown, JC (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM justinc_brown@dfci.harvard.edu FU National Cancer Institute [F31-CA192560, R21-CA182726]; National Heart, Lung, and Blood Institute [F31-HL127947]; National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [K23-DK105207] FX Research reported in this publication was supported by the National Cancer Institute (F31-CA192560, R21-CA182726), National Heart, Lung, and Blood Institute (F31-HL127947) and the National Institute of Diabetes and Digestive and Kidney Diseases (K23-DK105207) of the National Institutes of Health. NR 25 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1042-0533 EI 1520-6300 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD JAN-FEB PY 2017 VL 29 IS 1 AR UNSP e22898 DI 10.1002/ajhb.22898 PG 7 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA EK0KI UT WOS:000393614900008 ER PT J AU Cooper, CA Jain, N Gallagher, MD Weintraub, D Xie, SX Berlyand, Y Espay, AJ Quinn, J Edwards, KL Montine, T Van Deerlin, VM Trojanowski, J Zabetian, CP Chen-Plotkin, AS AF Cooper, Christine A. Jain, Nimansha Gallagher, Michael D. Weintraub, Daniel Xie, Sharon X. Berlyand, Yosef Espay, Alberto J. Quinn, Joseph Edwards, Karen L. Montine, Thomas Van Deerlin, Vivianna M. Trojanowski, John Zabetian, Cyrus P. Chen-Plotkin, Alice S. TI Common variant rs356182 near SNCA defines a Parkinson's disease endophenotype SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY LA English DT Article ID GENOME-WIDE ASSOCIATION; ALPHA-SYNUCLEIN; RATING-SCALE; CLINICAL HETEROGENEITY; COGNITIVE IMPAIRMENT; GENETIC-VARIABILITY; PROSPECTIVE COHORT; CLUSTER-ANALYSIS; MOTOR SUBTYPE; ONSET AB Objective: Parkinson's disease (PD) presents clinically with several motor subtypes that exhibit variable treatment response and prognosis. Here, we investigated genetic variants for their potential association with PD motor phenotype and progression. Methods: We screened 10 SNPs, previously associated with PD risk, for association with tremor-dominant (TD) versus postural-instability gait disorder (PIGD) motor subtypes. SNPs that correlated with the TD/PIGD ratio in a discovery cohort of 251 PD patients were then evaluated in a multi-site replication cohort of 559 PD patients. SNPs associated with motor phenotype in both cross-sectional cohorts were next evaluated for association with (1) rates of motor progression in a longitudinal subgroup of 230 PD patients and (2) brain alpha-synuclein (SNCA) expression in the GTEx (Genotype-Tissue Expression project) consortium database. Results: Genotype at rs356182, near SNCA, correlated with the TD/PIGD ratio in both the discovery (Bonferroni-corrected P = 0.04) and replication cohorts (P = 0.02). The rs356182 GG genotype was associated with a more tremor-predominant phenotype and predicted a slower rate of motor progression (1-point difference in annual rate of UPDRS-III motor score change, P = 0.01). The rs356182 genotype was associated with SNCA expression in the cerebellum (P = 0.005). Interpretation: Our study demonstrates that the GG genotype at rs356182 provides molecular definition for a clinically important endophenotype associated with (1) more tremor-predominant motor phenomenology, (2) slower rates of motor progression, and (3) decreased brain expression of SNCA. Such molecularly defined endophenotyping in PD may benefit both clinical trial design and tailoring of clinical care as we enter the era of precision medicine. C1 [Cooper, Christine A.] Med Univ South Carolina, Dept Neurol, Charleston, SC 29425 USA. [Cooper, Christine A.; Jain, Nimansha; Gallagher, Michael D.; Berlyand, Yosef; Chen-Plotkin, Alice S.] Univ Penn, Dept Neurol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Xie, Sharon X.] Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Berlyand, Yosef] Harvard Med Sch, Boston, MA USA. [Espay, Alberto J.] Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. [Quinn, Joseph] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Edwards, Karen L.] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA. [Montine, Thomas] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Van Deerlin, Vivianna M.; Trojanowski, John] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Philadelphia, PA 19104 USA. [Zabetian, Cyrus P.] Univ Washington, VA Puget Sound Hlth Care Syst, Dept Neurol, Seattle, WA 98195 USA. RP Chen-Plotkin, AS (reprint author), Dept Neurol, 3W Gates,3400 Spruce St, Philadelphia, PA 19104 USA. EM chenplot@mail.med.upenn.edu RI Gallagher, Michael/G-7113-2015 OI Gallagher, Michael/0000-0002-2109-1293 FU NIH [U01 NS082134, P50 NS062684, P50 NS053488, AG10124]; Burroughs Wellcome Fund; Pechenik Montague Award Fund; Benaroya Fund FX We thank Xiaoyan Han for her help with the statistical programming for Figure 2B. This work was supported by grants from the NIH (U01 NS082134, P50 NS062684, and P50 NS053488, and AG10124). Dr. Chen-Plotkin also receives research support from the Burroughs Wellcome Fund, the Pechenik Montague Award Fund, and the Benaroya Fund. NR 52 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2328-9503 J9 ANN CLIN TRANSL NEUR JI Ann. Clin. Transl. Neurol. PD JAN PY 2017 VL 4 IS 1 BP 15 EP 25 DI 10.1002/acn3.371 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EK1CY UT WOS:000393664600002 PM 28078311 ER PT J AU Marquie, M Normandin, MD Meltzer, AC Chong, MST Andrea, NV Anton-Fernandez, A Klunk, WE Mathis, CA Ikonomovic, MD Debnath, M Bien, EA Vanderburg, CR Costantino, I Makaretz, S DeVos, SL Oakley, DH Gomperts, SN Growdon, JH Domoto-Reilly, K Lucente, D Dickerson, BC Frosch, MP Hyman, BT Johnson, KA Gomez-Isla, T AF Marquie, Marta Normandin, Marc D. Meltzer, Avery C. Chong, Michael Siao Tick Andrea, Nicolas V. Anton-Fernandez, Alejandro Klunk, William E. Mathis, Chester A. Ikonomovic, Milos D. Debnath, Manik Bien, Elizabeth A. Vanderburg, Charles R. Costantino, Isabel Makaretz, Sara DeVos, Sarah L. Oakley, Derek H. Gomperts, Stephen N. Growdon, John H. Domoto-Reilly, Kimiko Lucente, Diane Dickerson, Bradford C. Frosch, Matthew P. Hyman, Bradley T. Johnson, Keith A. Gomez-Isla, Teresa TI Pathological correlations of [F-18]-AV-1451 imaging in non-alzheimer tauopathies SO ANNALS OF NEUROLOGY LA English DT Article ID FRONTOTEMPORAL LOBAR DEGENERATION; PROGRESSIVE SUPRANUCLEAR PALSY; EMISSION-TOMOGRAPHY TRACER; TAU PET; CORTICOBASAL DEGENERATION; DISEASE; CRITERIA; DEMENTIA; MUTATION; DIAGNOSIS AB ObjectiveRecent studies have shown that positron emission tomography (PET) tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases. MethodsWe quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays, and quantitative tau measurements in postmortem brain samples from two progressive supranuclear palsy (PSP) cases and a MAPT P301L mutation carrier. They all underwent [F-18]-AV-1451 PET imaging before death. ResultsThe three subjects exhibited [F-18]-AV-1451 in vivo retention predominantly in basal ganglia and midbrain. Neuropathological examination confirmed the PSP diagnosis in the first two subjects; the MAPT P301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in gray and white matter with heaviest burden in basal ganglia. In all three cases, autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined, with the exception of entorhinal cortex (reflecting incidental age-related neurofibrillary tangles) and neuromelanin-containing neurons in the substantia nigra (off-target binding). The lack of a consistent significant correlation between in vivo [F-18]-AV-1541 retention and postmortem in vitro binding and tau measures in these cases suggests that this ligand has low affinity for tau lesions primarily made of straight tau filaments. InterpretationAV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in these non-Alzheimer tauopathies. ANN NEUROL 2017;81:117-128 C1 [Marquie, Marta; Meltzer, Avery C.; Chong, Michael Siao Tick; Andrea, Nicolas V.; Bien, Elizabeth A.; Vanderburg, Charles R.; Makaretz, Sara; DeVos, Sarah L.; Gomperts, Stephen N.; Growdon, John H.; Domoto-Reilly, Kimiko; Dickerson, Bradford C.; Hyman, Bradley T.; Johnson, Keith A.; Gomez-Isla, Teresa] Massachusetts Gen Hosp, Dept Neurol, WACC Suite 715,15 Parkman St, Boston, MA 02114 USA. [Marquie, Marta; Meltzer, Avery C.; Chong, Michael Siao Tick; Anton-Fernandez, Alejandro; Bien, Elizabeth A.; Vanderburg, Charles R.; Costantino, Isabel; DeVos, Sarah L.; Oakley, Derek H.; Gomperts, Stephen N.; Frosch, Matthew P.; Hyman, Bradley T.; Gomez-Isla, Teresa] MassGen Inst NeuroDegenerat Dis, Charlestown, MA USA. [Normandin, Marc D.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Klunk, William E.; Debnath, Manik] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. [Mathis, Chester A.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Ikonomovic, Milos D.] VA Pittsburgh Clin Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Bien, Elizabeth A.; Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard Neurodiscovery Ctr, Boston, MA 02114 USA. [Oakley, Derek H.; Frosch, Matthew P.] Massachusetts Gen Hosp, CS Kubik Neuropathol Ctr, Boston, MA 02114 USA. [Lucente, Diane] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Gomez-Isla, T (reprint author), Massachusetts Gen Hosp, Dept Neurol, WACC Suite 715,15 Parkman St, Boston, MA 02114 USA. EM tgomezisla@mgh.harvard.edu OI Marquie, Marta/0000-0002-0660-0950 FU ASISA Foundation, Madrid, Spain; NIH National Institute of Neurological Disorders and Stroke [U01NS086659]; NIH National Institute of Mental Health [R01MH100350]; Ministry of Economy and Competitiveness-State Secretariat for Research, Development and Innovation of Spain; NIH National Institute on Aging [AG005133, AG025204, AG014449, AG005134, AG036694]; Harvard NeuroDiscovery Center, Boston, MA FX Marta Marquie received research funding from the ASISA Foundation, Madrid, Spain. Marc D. Normandin received research funding from NIH National Institute of Neurological Disorders and Stroke (U01NS086659) and NIH National Institute of Mental Health (R01MH100350). Alejandro Anton-Fernandez received research funding from the Ministry of Economy and Competitiveness-State Secretariat for Research, Development and Innovation of Spain. William E. Klunk and Chester A. Mathis both received research funding from NIH National Institute on Aging (AG005133 and AG025204). Milos D. Ikonomovic received research funding from NIH National Institute on Aging (AG025204 and AG014449). Charles Vanderburg received research funding from the Harvard NeuroDiscovery Center, Boston, MA. Teresa Gomez-Isla received research funding from NIH National Institute on Aging (AG005134 and AG036694).; This study was funded by NIH National Institute on Aging (AG005134 and AG036694). NR 54 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2017 VL 81 IS 1 BP 117 EP 128 DI 10.1002/ana.24844 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EJ9QV UT WOS:000393562300011 PM 27997036 ER PT J AU Fasano, A Laganiere, SE Lam, S Fox, MD AF Fasano, Alfonso Laganiere, Simon E. Lam, Susy Fox, Michael D. TI Lesions causing freezing of gait localize to a cerebellar functional network SO ANNALS OF NEUROLOGY LA English DT Article ID UNILATERAL PARASAGITTAL LESION; PARKINSONS-DISEASE; PEDUNCULOPONTINE NUCLEUS; BRAIN-STEM; LOCOMOTOR REGION; MIDBRAIN ATAXIA; CEREBRAL-CORTEX; STIMULATION; CONNECTIVITY; APRAXIA AB ObjectiveFreezing of gait is a disabling symptom in Parkinson disease and related disorders, but the brain regions involved in symptom generation remain unclear. Here we analyze brain lesions causing acute onset freezing of gait to identify regions causally involved in symptom generation. MethodsFourteen cases of lesion-induced freezing of gait were identified from the literature, and lesions were mapped to a common brain atlas. Because lesion-induced symptoms can come from sites connected to the lesion location, not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has been recently shown to identify regions involved in symptom generation across a variety of lesion-induced disorders. ResultsLesion location was heterogeneous, and no single region could be considered necessary for symptom generation. However,>90% (13 of 14) of lesions were functionally connected to a focal area in the dorsal medial cerebellum. This cerebellar area overlapped previously recognized regions that are activated by locomotor tasks, termed the cerebellar locomotor region. Connectivity to this region was specific to lesions causing freezing of gait compared to lesions causing other movement disorders (hemichorea or asterixis). InterpretationLesions causing freezing of gait are located within a common functional network characterized by connectivity to the cerebellar locomotor region. These results based on causal brain lesions complement prior neuroimaging studies in Parkinson disease patients, advancing our understanding of the brain regions involved in freezing of gait. ANN NEUROL 2017;81:129-141 C1 [Fasano, Alfonso] Toronto Western Hosp, Morton & Gloria Shulman Movement Disorders Clin, Toronto, ON, Canada. [Fasano, Alfonso] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON, Canada. [Fasano, Alfonso] Univ Toronto, Div Neurol, Toronto, ON, Canada. [Fasano, Alfonso] Krembil Res Inst, Toronto, ON, Canada. [Laganiere, Simon E.; Fox, Michael D.] Harvard Med Sch, Dept Neurol, Div Cognit Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02115 USA. [Laganiere, Simon E.; Fox, Michael D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Lam, Susy] Univ Toronto, Fac Med, Inst Med Sci, Toronto, ON, Canada. [Fox, Michael D.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Fox, Michael D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Fasano, A (reprint author), Toronto Western Hosp, Movement Disorders Ctr, 399 Bathurst St,7 Mc412, Toronto, ON M5T 2S8, Canada.; Fox, MD (reprint author), Harvard Med Sch, Dept Neurol, Div Cognit Neurol, Berenson Allen Ctr Noninvas Brain Stimulat, Boston, MA 02115 USA.; Fox, MD (reprint author), Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.; Fox, MD (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.; Fox, MD (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. EM alfonso.fasano@gmail.com; mfox3@bidmc.harvard.edu FU Sidney R. Baer Jr. research foundation; NIH [K23NS083741]; Dystonia Medical Research Foundation; National Parkinson Foundation; NIH; National Center for Research Resources: Harvard Clinical and Translational Science Center [UL1 RR025758] FX S.E.L. was supported by a fellowship grant from the Sidney R. Baer Jr. research foundation. M.D.F. was supported by NIH grant K23NS083741, by the Dystonia Medical Research Foundation and by the National Parkinson Foundation. Work on this study was also supported by grants from the NIH and National Center for Research Resources: Harvard Clinical and Translational Science Center (UL1 RR025758). NR 49 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2017 VL 81 IS 1 BP 129 EP 141 DI 10.1002/ana.24845 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EJ9QV UT WOS:000393562300012 PM 28009063 ER PT J AU Chang, YC Wang, HF Zheng, YJ Lin, H AF Chang, Yuchou Wang, Haifeng Zheng, Yuanjie Lin, Hong TI Instrument Variables for Reducing Noise in Parallel MRI Reconstruction SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID GRAPPA RECONSTRUCTION; LINEAR-SYSTEMS; INPUT; IDENTIFICATION AB Generalized autocalibrating partially parallel acquisition (GRAPPA) has been a widely used parallel MRI technique. However, noise deteriorates the reconstructed image when reduction factor increases or even at low reduction factor for some noisy datasets. Noise, initially generated from scanner, propagates noise-related errors during fitting and interpolation procedures of GRAPPA to distort the final reconstructed image quality. The basic idea we proposed to improve GRAPPA is to remove noise from a system identification perspective. In this paper, we first analyze the GRAPPA noise problem from a noisy input-output system perspective; then, a new framework based on errors-in-variables (EIV) model is developed for analyzing noise generation mechanism in GRAPPA and designing a concrete method-instrument variables (IV) GRAPPA to remove noise. The proposed EIV framework provides possibilities that noiseless GRAPPA reconstruction could be achieved by existing methods that solve EIV problem other than IV method. Experimental results show that the proposed reconstruction algorithm can better remove the noise compared to the conventional GRAPPA, as validated with both of phantom and in vivo brain data. C1 [Chang, Yuchou; Lin, Hong] Univ Houston Downtown, Comp Sci & Engn Technol Dept, Houston, TX 77002 USA. [Wang, Haifeng] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Wang, Haifeng] Harvard Med Sch, Boston, MA 02115 USA. [Zheng, Yuanjie] Shandong Normal Univ, Key Lab Intelligent Informat Proc, Inst Life Sci, Sch Informat Sci & Engn, Jinan 250014, Peoples R China. RP Zheng, YJ (reprint author), Shandong Normal Univ, Key Lab Intelligent Informat Proc, Inst Life Sci, Sch Informat Sci & Engn, Jinan 250014, Peoples R China. EM zheng.vision@gmail.com FU Natural Science Foundation of China (NSFC) [61572300]; Natural Science Foundation of Shandong Province in China [ZR2014FM001]; Taishan Scholar Program of Shandong Province in China [TSHW201502038] FX This work was made possible through support from Natural Science Foundation of China (NSFC) (61572300), Natural Science Foundation of Shandong Province in China (ZR2014FM001), and Taishan Scholar Program of Shandong Province in China (TSHW201502038). NR 22 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2017 AR 9016826 DI 10.1155/2017/9016826 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA EK6BO UT WOS:000394010200001 ER PT J AU Brown, FC Cifani, P Drill, E He, J Still, E Zhong, S Balasubramanian, S Pavlick, D Yilmazel, B Knapp, KM Alonzo, TA Meshinchi, S Stone, RM Kornblau, SM Marcucci, G Gamis, AS Byrd, JC Gonen, M Levine, RL Kentsis, A AF Brown, Fiona C. Cifani, Paolo Drill, Esther He, Jie Still, Eric Zhong, Shan Balasubramanian, Sohail Pavlick, Dean Yilmazel, Bahar Knapp, Kristina M. Alonzo, Todd A. Meshinchi, Soheil Stone, Richard M. Kornblau, Steven M. Marcucci, Guido Gamis, Alan S. Byrd, John C. Gonen, Mithat Levine, Ross L. Kentsis, Alex TI Genomics of primary chemoresistance and remission induction failure in paediatric and adult acute myeloid leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE primary chemoresistance; paediatric leukaemia; cytogenetically normal acute myeloid leukaemia; targeted deep sequencing genomics; induction failure ID ACUTE LYMPHOBLASTIC-LEUKEMIA; AML; EXPRESSION AB Cure rates of children and adults with acute myeloid leukaemia (AML) remain unsatisfactory partly due to chemotherapy resistance. We investigated the genetic basis of AML in 107 primary cases by sequencing 670 genes mutated in haematological malignancies. SETBP1, ASXL1 and RELN mutations were significantly associated with primary chemoresistance. We identified genomic alterations not previously described in AML, together with distinct genes that were significantly overexpressed in therapy-resistant AML. Defined gene mutations were sufficient to explain primary induction failure in only a minority of cases. Thus, additional genetic or molecular mechanisms must cause primary chemoresistance in paediatric and adult AML. C1 [Brown, Fiona C.; Cifani, Paolo; Still, Eric; Kentsis, Alex] Mem Sloan Kettering Canc Ctr, Mol Pharmacol Program, Sloan Kettering Inst, 1275 York Ave, New York, NY 10021 USA. [Drill, Esther; Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Biostat & Epidemiol, 1275 York Ave, New York, NY 10021 USA. [He, Jie; Zhong, Shan; Balasubramanian, Sohail; Pavlick, Dean; Yilmazel, Bahar] Fdn Med, Cambridge, MA USA. [Knapp, Kristina M.] Mem Sloan Kettering Canc Ctr, Leukemia Ctr, 1275 York Ave, New York, NY 10021 USA. [Alonzo, Todd A.; Meshinchi, Soheil; Gamis, Alan S.] Childrens Oncol Grp, Monrovia, CA USA. [Alonzo, Todd A.] Univ Southern Calif, Dept Biostat, Los Angeles, CA USA. [Meshinchi, Soheil] Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USA. [Meshinchi, Soheil] Univ Washington, Sch Med, Seattle, WA USA. [Stone, Richard M.] Harvard Med Sch, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA USA. [Kornblau, Steven M.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Marcucci, Guido] City Hope Natl Med Ctr, Ctr Comprehens Canc, Gehr Family Leukemia Ctr, Duarte, CA USA. [Gamis, Alan S.] Childrens Mercy Hosp & Clin, Div Hematol Oncol, Kansas City, MO USA. [Byrd, John C.] Ohio State Univ, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Levine, Ross L.] Cornell Univ, Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. [Levine, Ross L.; Kentsis, Alex] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Kentsis, Alex] Cornell Univ, Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Kentsis, A (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10065 USA. EM kentsisresearchgroup@gmail.com FU NIH [R21 CA188881, K08 CA160660, P30 CA008748, U10 CA180899]; Burroughs Wellcome Fund; Alex's Lemonade Stand Foundation; Gabrielle's Angel Foundation; Josie Robertson Investigator Program FX We thank Alejandro Gutierrez for critical discussions. This work was supported by the NIH R21 CA188881, K08 CA160660, P30 CA008748, U10 CA180899, Burroughs Wellcome Fund, Alex's Lemonade Stand Foundation, Gabrielle's Angel Foundation, and the Josie Robertson Investigator Program. AK is the Damon Runyon-Richard Lumsden Foundation Clinical Investigator. NR 15 TC 1 Z9 1 U1 5 U2 5 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 JAN PY 2017 VL 176 IS 1 BP 86 EP 91 DI 10.1111/bjh.14413 PG 6 WC Hematology SC Hematology GA EK0JE UT WOS:000393611900010 PM 27766616 ER PT J AU Meyerhardt, JA Kroenke, CH Prado, CM Kwan, ML Castillo, A Weltzien, E Feliciano, EMC Xiao, JJ Caan, BJ AF Meyerhardt, Jeffrey A. Kroenke, Candyce H. Prado, Carla M. Kwan, Marilyn L. Castillo, Adrienne Weltzien, Erin Feliciano, Elizabeth M. Cespedes Xiao, Jingjie Caan, Bette J. TI Association of Weight Change after Colorectal Cancer Diagnosis and Outcomes in the Kaiser Permanente Northern California Population SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; STAGE BREAST-CANCER; TREATMENT-RELATED TOXICITY; COLON-CANCER; PHYSICAL-ACTIVITY; ADJUVANT CHEMOTHERAPY; RADICAL CYSTECTOMY; PROGNOSTIC-FACTOR; LIVER METASTASES; SKELETAL-MUSCLE AB Background: Higher body mass index (BMI) is associated with incident colorectal cancer but not consistently with colorectal cancer survival. Whether weight gain or loss is associated with colorectal cancer survival is largely unknown. Methods: Weidentified 2,781 patients from Kaiser Permanente Northern California diagnosed with stages I-III colorectal cancer between 2006 and 2011 with weight and height measurements within 3 months of diagnosis and approximately 18 months after diagnosis. We evaluated associations between weight change and colorectal cancer-specific and overall mortality, adjusted for sociodemographics, disease severity, and treatment. Results: After completion of treatment and recovery from stage I-III colorectal cancer, loss of at least 10% of baseline weight was associated with significantly worse colorectal cancer-specific mortality (HR 3.20; 95% confidence interval [CI], 2.3-34.39; P-trend < 0.0001) and overall mortality (HR 3.27; 95% CI, 2.56-4.18; P-trend < 0.0001). For every 5% loss of baseline weight, there was a 41% increased risk of colorectal cancer-specific mortality (95% CI, 29%-56%). Weight gain was not significantly associated with colorectal cancer-specific mortality (P-trend = 0.54) or overall mortality (P-trend = 0.27). The associations were largely unchanged after restricting analyses to exclude patients who died within 6 months and 12 months of the second weight measurement. No significant interactions were demonstrated for weight loss or gain by gender, stage, primary tumor location, or baseline BMI. Conclusions: Weight loss after diagnosis was associated with worse colorectal cancer-specific mortality and overall mortality. Reverse causation does not appear to explain our findings. Impact: Understanding mechanistic underpinnings for the association of weight to worse mortality is important to improving patient outcomes. (C) 2016 AACR. C1 [Meyerhardt, Jeffrey A.] Dana Farber Canc Inst, 450 Brookline Ave,D1220, Boston, MA 02215 USA. [Kroenke, Candyce H.; Kwan, Marilyn L.; Castillo, Adrienne; Weltzien, Erin; Feliciano, Elizabeth M. Cespedes; Caan, Bette J.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Prado, Carla M.; Xiao, Jingjie] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB, Canada. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D1220, Boston, MA 02215 USA. EM jeffrey_meyerhardt@dfci.harvard.edu OI Cespedes Feliciano, Elizabeth/0000-0003-1192-4017 FU NIH [R01 CA175011, R01 CA149222] FX This work was supported by the NIH (R01 CA175011 to B.J. Caan and R01 CA149222 to J.A. Meyerhardt). NR 63 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2017 VL 26 IS 1 BP 30 EP 37 DI 10.1158/1055-9965.EPI-16-0145 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EK2JN UT WOS:000393753700006 PM 27986654 ER PT J AU Kinsey, CM Estepar, RS van der Velden, J Cole, BF Christiani, DC Washko, GR AF Kinsey, C. Matthew Estepar, Raul San Jose van der Velden, Jos Cole, Bernard F. Christiani, David C. Washko, George R. TI Lower Pectoralis Muscle Area Is Associated with a Worse Overall Survival in Non-Small Cell Lung Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID EMPHYSEMA; POLYMORPHISMS; CACHEXIA; SMOKERS; COPD; CHEMOTHERAPY; SARCOPENIA; SMOKING; IMPACT; TUMORS AB Background: Muscle wasting is a component of the diagnosis of cancer cachexia and has been associated with poor prognosis. However, recommended tools to measure sarcopenia are limited by poor sensitivity or the need to perform additional scans. We hypothesized that pectoralis muscle area (PMA) measured objectively on chest CT scan may be associated with overall survival (OS) in non-small cell lung cancer (NSCLC). Methods: We evaluated 252 cases from a prospectively enrolling lung cancer cohort. Eligible cases had CT scans performed prior to the initiation of surgery, radiation, or chemotherapy. PMA was measured in a semi-automated fashion while blinded to characteristics of the tumor, lung, and patient outcomes. Results: Men had a significantly greater PMA than women (37.59 vs. 26.19 cm(2), P < 0.0001). In univariate analysis, PMA was associated with age and body mass index (BMI). A Cox proportional hazards model was constructed to account for confounders associated with survival. Lower pectoralis area (per cm(2)) at diagnosis was associated with an increased hazard of death of 2%(HRadj, 0.98; confidence interval, 0.96-0.99; P = 0.044) while adjusting for age, sex, smoking, chronic bronchitis, emphysema, histology, stage, chemotherapy, radiation, surgery, BMI, and ECOG performance status. Conclusions: Lower PMA measured from chest CT scans obtained at the time of diagnosis of NSCLC is associated with a worse OS. Impact: PMA may be a valuable CT biomarker for sarcopenia-associated lung cancer survival. Impact: PMA may be a valuable CT biomarker for sarcopenia-associated lung cancer survival.(C) 2016 AACR. C1 [Kinsey, C. Matthew] Univ Vermont, Med Ctr, Div Pulm & Crit Care, Burlington, VT USA. [Estepar, Raul San Jose] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [van der Velden, Jos] Univ Vermont, Dept Pathol, Med Ctr, Burlington, VT 05405 USA. [Cole, Bernard F.] Univ Vermont, Coll Engn & Math, Burlington, VT USA. [Christiani, David C.] Harvard Sch Publ Hlth, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Environm Hlth & Epidemiol, Boston, MA USA. [Washko, George R.] Brigham & Womens Hosp, Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. RP Kinsey, CM (reprint author), Univ Vermont, Coll Med, Div Pulm & Crit Care, 89 Beaumont Ave,Given D208, Burlington, VT 05401 USA. EM Matt.Kinsey@uvmhealth.org FU University of Vermont Cancer Cancer/Lake Champlain Cancer Center [RO1 CA092824, RO1 CA074386, RO1 CA090578, K25 HL104085, R01HL116931, R01 HL122464] FX This study was supported by grants from the University of Vermont Cancer Cancer/Lake Champlain Cancer Center (to C.M. Kinsey), RO1 CA092824 (to D.C. Christiani), RO1 CA074386 (to D.C. Christiani), RO1 CA090578 (to D.C Christiani), K25 HL104085 (to R. San Jose Estepar), R01HL116931(to R. San Jose Estepar), and R01 HL122464 (G.R. Washko). NR 26 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2017 VL 26 IS 1 BP 38 EP 43 DI 10.1158/1055-9965.EPI-15-1067 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EK2JN UT WOS:000393753700007 PM 27197281 ER PT J AU Feliciano, EMC Kroenke, CH Bradshaw, PT Chen, WY Prado, CM Weltzien, EK Castillo, AL Caan, BJ AF Feliciano, Elizabeth M. Cespedes Kroenke, Candyce H. Bradshaw, Patrick T. Chen, Wendy Y. Prado, Carla M. Weltzien, Erin K. Castillo, Adrienne L. Caan, Bette J. TI Postdiagnosis Weight Change and Survival Following a Diagnosis of Early-Stage Breast Cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CARDIOVASCULAR-DISEASE MORTALITY; BODY-MASS INDEX; LIFE-STYLE; CHEMOTHERAPY; PROGNOSIS; WOMEN AB Background: Achieving a healthy weight is recommended for all breast cancer survivors. Previous research on postdiagnosis weight change and mortality had conflicting results. Methods: We examined whether change in body weight in the 18 months following diagnosis is associated with overall and breast cancer-specific mortality in a cohort of n - 12,590 stage I-III breast cancer patients at Kaiser Permanente using multivariable-adjusted Cox regression models. Follow-up was from the date of the postdiagnosis weight at 18 months until death or June 2015 [median follow-up (range): 3 (0-9) years]. We divided follow-up into earlier (18-54 months) and later (> 54 months) postdiagnosis periods. Results: Mean (SD) age-at-diagnosis was 59 (11) years. A total of 980 women died, 503 from breast cancer. Most women maintained weight within 5% of diagnosis body weight; weight loss and gain were equally common at 19% each. Compared with weight maintenance, large losses (>= 10%) were associated with worse survival, with HRs and 95% confidence intervals (CI) for all-cause death of 2.63 (2.12-3.26) earlier and 1.60 (1.14-2.25) later in follow-up. Modest losses (> 5%-< 10%) were associated with worse survival earlier [1.39 (1.11-1.74)] but not later in follow-up [0.77 (0.54-1.11)]. Weight gain was not related to survival. Results were similar for breast cancer-specific death. Conclusion: Large postdiagnosis weight loss is associated with worse survival in both earlier and later postdiagnosis periods, independent of treatment and prognostic factors. Impact: Weight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk. Impact: Weight loss and gain are equally common after breast cancer, and weight loss is a consistent marker of mortality risk. (C) 2016 AACR. C1 [Feliciano, Elizabeth M. Cespedes; Kroenke, Candyce H.; Weltzien, Erin K.; Castillo, Adrienne L.; Caan, Bette J.] Kaiser Permanente Northern Calif, Div Res, 2000 Broadway,5th Floor, Oakland, CA 94612 USA. [Bradshaw, Patrick T.] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. [Chen, Wendy Y.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Chen, Wendy Y.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Prado, Carla M.] Univ Alberta, Dept Agr Food & Nutr Sci, Edmonton, AB, Canada. RP Feliciano, EMC (reprint author), Kaiser Permanente Northern Calif, Div Res, 2000 Broadway,5th Floor, Oakland, CA 94612 USA. EM elizabeth.m.cespedes@kp.org OI Cespedes Feliciano, Elizabeth/0000-0003-1192-4017 FU National Cancer Institute [5R01CA184953-02] FX This work was supported by National Cancer Institute Grant 5R01CA184953-02 (to B.J. Caan, C.H. Kroenke, W.Y. Chen, C.M. Prado, E.M. Cespedes Feliciano, E.K. Weltzien, and A.L. Castillo). NR 32 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2017 VL 26 IS 1 BP 44 EP 50 DI 10.1158/1055-9965.EPI-16-0150 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA EK2JN UT WOS:000393753700008 ER PT J AU Mayer, IA Abramson, VG Formisano, L Balko, JM Estrada, MV Sanders, ME Juric, D Solit, D Berger, MF Won, HH Li, YS Cantley, LC Winer, E Arteaga, CL AF Mayer, Ingrid A. Abramson, Vandana G. Formisano, Luigi Balko, Justin M. Estrada, Monica V. Sanders, Melinda E. Juric, Dejan Solit, David Berger, Michael F. Won, Helen H. Li, Yisheng Cantley, Lewis C. Winer, Eric Arteaga, Carlos L. TI A Phase Ib Study of Alpelisib (BYL719), a PI3K alpha-Specific Inhibitor, with Letrozole in ER+/HER2(-) Metastatic Breast Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; PIK3CA MUTATIONS; ESTROGEN DEPRIVATION; RESISTANCE; GROWTH; PI3K; ACTIVATION; ALPHA; NVP-BYL719; TUMORS AB Purpose: Alpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit p110 alpha, has shown synergistic antitumor activity with endocrine therapy againstER(+)/PIK3CA-mutated breast cancer cells. This phase Ib study evaluated alpelisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER- breast cancer refractory to endocrine therapy. Experimental Design: Twenty-six patients received letrozole and alpelisib daily. Outcomes were assessed by standard solid-tumor phase I methods. Tumor blocks were collected for DNA extraction and next-generation sequencing. Results: Alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression >= 6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment >= 12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER+/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro. Conclusions: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER+ breast cancer are ongoing. (C) 2016 AACR. C1 [Mayer, Ingrid A.; Abramson, Vandana G.; Formisano, Luigi; Balko, Justin M.; Estrada, Monica V.; Sanders, Melinda E.; Arteaga, Carlos L.] Vanderbilt Univ, VICC, 221 Kirkland Hall, Nashville, TN 37235 USA. [Juric, Dejan] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Solit, David; Berger, Michael F.; Won, Helen H.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Li, Yisheng] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Cantley, Lewis C.] Weill Cornell Med Coll, New York, NY USA. [Winer, Eric] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mayer, IA (reprint author), Vanderbilt Univ, Div Hematol Oncol, Sch Med, 2220 Pierce Ave,777 PRB, Nashville, TN 37232 USA. EM ingrid.mayer@vanderbilt.edu; carlos.arteaga@vanderbilt.edu FU Stand Up to Cancer Dream Team Translational Research Grant - Stand Up To Cancer is a program of the Entertainment Industry Foundation [SU2CAACR-DT0209]; Breast SPORE [P50 CA098131]; VICC [P30 CA68485]; Breast Cancer Research Foundation; Susan G. Komen for the Cure Foundation SAC grant [SAC100013]; Novartis Pharmaceuticals; [K23 CA127469-01A2]; [R01 GM041890] FX This work was funded by Stand Up to Cancer Dream Team Translational Research Grant (SU2CAACR-DT0209) - Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research, Breast SPORE P50 CA098131, VICC Support Grant P30 CA68485, a Breast Cancer Research Foundation grant (C.L. Arteaga), Susan G. Komen for the Cure Foundation SAC grant (SAC100013), K23 CA127469-01A2 (I.A. Mayer), and by R01 GM041890 (L.C. Cantley). This study was sponsored by Novartis Pharmaceuticals. NR 34 TC 4 Z9 4 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2017 VL 23 IS 1 BP 26 EP 34 DI 10.1158/1078-0432.CCR-16-0134 PG 9 WC Oncology SC Oncology GA EK4DC UT WOS:000393876300006 PM 27126994 ER PT J AU Schneider, BP Shen, F Gardner, L Radovich, M Li, L Miller, KD Jiang, GL Lai, DB O'Neill, A Sparano, JA Davidson, NE Cameron, D Gradus-Pizlo, I Mastouri, RA Suter, TM Foroud, T Sledge, GW AF Schneider, Bryan P. Shen, Fei Gardner, Laura Radovich, Milan Li, Lang Miller, Kathy D. Jiang, Guanglong Lai, Dongbing O'Neill, Anne Sparano, Joseph A. Davidson, Nancy E. Cameron, David Gradus-Pizlo, Irmina Mastouri, Ronald A. Suter, Thomas M. Foroud, Tatiana Sledge, George W., Jr. TI Genome-Wide Association Study for Anthracycline-Induced Congestive Heart Failure SO CLINICAL CANCER RESEARCH LA English DT Article ID INDUCED CARDIOTOXICITY; BREAST-CANCER; GENETIC POLYMORPHISMS; CHILDHOOD-CANCER; LEUKEMIA; CARDIOMYOPATHY; PARAMETERS; CHILDREN; THERAPY; VARIANT AB Purpose: Anthracycline-induced congestive heart failure (CHF) is a rare but serious toxicity associated with this commonly employed anticancer therapy. The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk-to-benefit ratio for each patient. Herein, we present a genome-wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive anthracycline. Experimental Design: We performed a genome-wide association study in 3,431 patients from the randomized phase III adjuvant breast cancer trial E5103 to identify single nucleotide polymorphism (SNP) genotypes associated with an increased risk of anthracycline-induced CHF. We further attempted candidate validation in two independent phase III adjuvant trials, E1199 and BEATRICE. Results: When evaluating for cardiologist-adjudicated CHF, 11 SNPs had a P value <10(-5), of which nine independent chromosomal regions were associated with increased risk. Validation of the top two SNPs in E1199 revealed one SNP rs28714259 that demonstrated a borderline increased CHF risk (P = 0.04, OR = 1.9). rs28714259 was subsequently tested in BEATRICE and was significantly associated with a decreased left ventricular ejection fraction (P = 0.018, OR = 4.2). Conclusions: rs28714259 represents a validated SNP that is associated with anthracycline-induced CHF in three independent, phase III adjuvant breast cancer clinical trials. (C) 2016 AACR. C1 [Schneider, Bryan P.; Shen, Fei; Gardner, Laura; Radovich, Milan; Li, Lang; Miller, Kathy D.; Jiang, Guanglong; Lai, Dongbing; Gradus-Pizlo, Irmina; Mastouri, Ronald A.; Foroud, Tatiana] Indiana Univ Sch Med, Indianapolis, IN 46202 USA. [O'Neill, Anne] Dana Farber Canc Inst, ECOG ACRIN Biostat Ctr, Boston, MA 02115 USA. [Sparano, Joseph A.] Albert Einstein Univ, Montefiore Med Ctr, Bronx, NY USA. [Davidson, Nancy E.] Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. [Cameron, David] Edinburgh Canc Res Ctr, Edinburgh, Midlothian, Scotland. [Suter, Thomas M.] Inselspital Bern, Univ Hosp Bern, Swiss Cardiovasc Ctr, Bern, Switzerland. [Sledge, George W., Jr.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Schneider, BP (reprint author), Indiana Univ, Dept Med, Div Hematol Oncol, 535 Barnhill Dr Rt473, Indianapolis, IN 46202 USA. EM bpschnei@iupui.edu FU Public Health Service [CA180820, CA180794, CA180795, CA180867, CA189859, CA180844, CA180816]; Susan G. Komen for the Cure; Conquer Cancer Foundation; Breast Cancer Research Foundation; NCI, NIH; Department of Health and Human Services FX This study was conducted by the ECOG-ACRIN Cancer Research Group (Robert L. Comis, MD and Mitchell D. Schnall, MD, PhD, Group Co-Chairs) and supported in part by Public Health Service grants (CA180820, CA180794, CA180795, CA180867, CA189859, CA180844, and CA180816) Susan G. Komen for the Cure(to B.P. Schneider), Conquer Cancer Foundation(to B.P. Schneider), Breast Cancer Research Foundation(to K.D. Miller), and from the NCI, NIH, and the Department of Health and Human Services(to B.P. Schneider). NR 30 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2017 VL 23 IS 1 BP 43 EP 51 DI 10.1158/1078-0432.CCR-16-0908 PG 9 WC Oncology SC Oncology GA EK4DC UT WOS:000393876300008 PM 27993963 ER PT J AU Sinnott, JA Peisch, SF Tyekucheva, S Gerke, T Lis, R Rider, JR Fiorentino, M Stampfer, MJ Mucci, LA Loda, M Penney, KL AF Sinnott, Jennifer A. Peisch, Sam F. Tyekucheva, Svitlana Gerke, Travis Lis, Rosina Rider, Jennifer R. Fiorentino, Michelangelo Stampfer, Meir J. Mucci, Lorelei A. Loda, Massimo Penney, Kathryn L. TI Prognostic Utility of a New mRNA Expression Signature of Gleason Score SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC PROSTATE-CANCER; GENE-EXPRESSION; TRANSITION ZONE; PERIPHERAL ZONE; VARIANTS; TISSUE; MEN; PSA AB Purpose: Gleason score strongly predicts prostate cancer mortality; however, scoring varies among pathologists, and many men are diagnosed with intermediate-risk Gleason score 7. We previously developed a 157-gene signature for Gleason score using a limited gene panel. Using a new whole-transcriptome expression dataset, we verified the previous signature's performance and developed a new Gleason signature to improve lethal outcome prediction among men with Gleason score 7. Experimental Design: We generated mRNA expression data from prostate tumor tissue from men in the Physicians' Health Study and Health Professionals Follow-Up Study (N = 404) using the Affymetrix Human Gene 1.0 ST microarray. The Prediction Analysis for Microarrays method was used to develop a signature to distinguish high (>= 8) versus low (<= 6) Gleason score. We evaluated the signature's ability to improve prediction of lethality among men with Gleason score 7, adjusting for 3+4/4+3 status, by quantifying the area under the receiver operating characteristic (ROC) curve (AUC). Results: We identified a 30-gene signature that best distinguished Gleason score <= 6 from >= 8. The AUC to predict lethal disease among Gleason score 7 men was 0.76 [95% confidence interval (CI), 0.67-0.84] compared with 0.68 (95% CI, 0.59-0.76) using 3 + 4/4 + 3 status alone (P = 0.0001). This signature was a nonsignificant (P = 0.09) improvement over our previous signature (AUC = 0.72). Conclusions: Our new 30-gene signature improved prediction of lethality among men with Gleason score 7. This signature can potentially become a useful prognostic tool for physicians to improve treatment decision making. (C) 2016 AACR. C1 [Sinnott, Jennifer A.] Ohio State Univ, Dept Stat, Columbus, OH 43210 USA. [Sinnott, Jennifer A.; Peisch, Sam F.; Rider, Jennifer R.; Stampfer, Meir J.; Mucci, Lorelei A.; Penney, Kathryn L.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Tyekucheva, Svitlana] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Tyekucheva, Svitlana] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Gerke, Travis] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL USA. [Lis, Rosina] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Rider, Jennifer R.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Fiorentino, Michelangelo; Loda, Massimo] St Orsola Marcello Malpighi Hosp, Addarii Inst, Pathol Unit, Bologna, Italy. [Stampfer, Meir J.; Mucci, Lorelei A.; Penney, Kathryn L.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Stampfer, Meir J.; Mucci, Lorelei A.; Loda, Massimo; Penney, Kathryn L.] Harvard Med Sch, Boston, MA USA. [Stampfer, Meir J.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RP Penney, KL (reprint author), Harvard Med Sch, Brigham & Womens Hosp, 181 Longwood Ave, Boston, MA 02115 USA. EM kpenney@hsph.harvard.edu FU A. David Mazzone Career Development Award; Prostate Cancer Foundation; [CA34944]; [CA40360]; [CA097193]; [HL26490]; [HL34595]; [CA133891]; [UM1CA167552]; [CA136578]; [CA141298]; [CA131945]; [P50CA090381]; [CA09001] FX The Physicians' Health Study was supported by grants CA34944, CA40360, CA097193, HL26490 and HL34595. The Health Professionals Follow-Up Study was supported by grants CA133891 and UM1CA167552. This study was supported by CA136578, CA141298, CA131945, and P50CA090381. J.A. Sinnott was supported by CA09001 and the A. David Mazzone Career Development Award. J.P. Rider, L.A. Mucci, and K.L. Penney were supported by Prostate Cancer Foundation Young Investigator Awards. NR 31 TC 1 Z9 1 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 JAN PY 2017 VL 23 IS 1 BP 81 EP 87 DI 10.1158/1078-0432.CCR-16-1245 PG 7 WC Oncology SC Oncology GA EK4DC UT WOS:000393876300012 PM 27663590 ER PT J AU Chong, CR Bahcall, M Capelletti, M Kosaka, T Ercan, D Sim, T Sholl, LM Nishino, M Johnson, BE Gray, NS Janne, PA AF Chong, Curtis R. Bahcall, Magda Capelletti, Marzia Kosaka, Takayuki Ercan, Dalia Sim, Taebo Sholl, Lynette M. Nishino, Mizuki Johnson, Bruce E. Gray, Nathanael S. Janne, Pasi A. TI Identification of Existing Drugs That Effectively Target NTRK1 and ROS1 Rearrangements in Lung Cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CRIZOTINIB RESISTANCE; CABOZANTINIB; INHIBITOR; CHEMOTHERAPY; ONCOGENE; PROTEINS AB Purpose: Efforts to discover drugs that overcome resistance to targeted therapies in patients with rare oncogenic alterations, such as NTRK1 and ROS1 rearrangements, are complicated by the cost and protracted timeline of drug discovery. Experimental Design: In an effort to identify inhibitors of NTRK1 and ROS1, which are aberrantly activated in some patients with non-small cell lung cancer (NSCLC), we created and screened a library of existing targeted drugs against Ba/F3 cells transformed with these oncogenes. Results: This screen identified the FDA-approved drug cabozantinib as a potent inhibitor of CD74-ROS1-transformed Ba/F3, including the crizotinib-resistant mutants G2032R and L2026M (IC50 = 9, 26, and 11 nmol/L, respectively). Cabozantinib inhibited CD74-ROS1-transformed Ba/F3 cells more potently than brigatinib (wild-type/G2032R/L2026M IC50 = 30/170/200 nmol/L, respectively), entrectinib (IC50 = 6/2,200/3,500 nmol/L), and PF-06463922 (IC50 = 1/270/2 nmol/L). Cabozantinib inhibited ROS1 autophosphorylation and downstream ERK activation in transformed Ba/F3 cells and in patient-derived tumor cell lines. The IGF-1R inhibitor BMS-536924 potently inhibited CD74-NTRK1-transformed compared with parental Ba/F3 cells (IC50 = 19 nmol/L vs. > 470 nmol/L). A patient with metastatic ROS1-rearranged NSCLC with progression on crizotinib was treated with cabozantinib and experienced a partial response. Conclusions: While acquired resistance to targeted therapies is challenging, this study highlights that existing agents may be repurposed to overcome drug resistance and identifies cabozantinib as a promising treatment of ROS1-rearranged NSCLC after progression on crizotinib. (C) 2016 AACR. C1 [Chong, Curtis R.; Bahcall, Magda; Capelletti, Marzia; Kosaka, Takayuki; Ercan, Dalia; Johnson, Bruce E.; Janne, Pasi A.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,LC4114, Boston, MA 02215 USA. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul, South Korea. [Sim, Taebo] KU KIST Grad Sch Converging Sci & Technol, Seoul, South Korea. [Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Nishino, Mizuki] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. [Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Janne, Pasi A.] Dana Farber Canc Inst, Belfer Ctr Appl Canc Sci, Boston, MA 02115 USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 450 Brookline Ave,LC4114, Boston, MA 02215 USA.; Gray, NS (reprint author), Longwood Ctr, Dept Biol Chem & Mol Pharmacol, 360 Longwood Ave,Room 2209, Boston, MA 02215 USA. EM Nathanael_Gray@dfci.harvard.edu; pasi_janne@dfci.harvard.edu FU NIH [RO1CA136851, R01CA135257, 1K23CA157631, 1 U54 HL127365-01]; Cammarata Family Foundation; Nirenberg Fellowship at Dana-Farber Cancer Institute; Uniting Against Lung Cancer; Conquer Cancer Foundation/ASCO; American Cancer Society [PF-14-020-01-CDD] FX This study is supported by grants from the NIH RO1CA136851 (P.A. Janne and N.S. Gray), R01CA135257 (P.A. Janne), 1K23CA157631 (M. Nishino) and 1 U54 HL127365-01 (N.S. Gray), the Cammarata Family Foundation Research Fund (M. Capelletti and P.A. Janne), and the Nirenberg Fellowship at Dana-Farber Cancer Institute (M. Capelletti and P.A. Janne). C.R. Chong is the recipient of funding from Uniting Against Lung Cancer, a Conquer Cancer Foundation/ASCO Young Investigator Award, and a post-doctoral fellowship from the American Cancer Society (PF-14-020-01-CDD). NR 31 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2017 VL 23 IS 1 BP 204 EP 213 DI 10.1158/1078-0432.CCR-15-1601 PG 10 WC Oncology SC Oncology GA EK4DC UT WOS:000393876300024 PM 27370605 ER PT J AU Liu, HW Yang, J Wang, LT Xu, YG Zhang, SY Lv, J Ran, CZ Li, YY AF Liu, Hongwu Yang, Jian Wang, Letian Xu, Yungen Zhang, Siyuan Lv, Jie Ran, Chongzhao Li, Yuyan TI Targeting beta-amyloid plaques and oligomers: development of near-IR fluorescence imaging probes SO FUTURE MEDICINAL CHEMISTRY LA English DT Review DE Alzheimer's disease; amyloid cascade hypothesis; near-IR fluorescence imaging ID MODERATE ALZHEIMERS-DISEASE; IN-VIVO DETECTION; BODIPY DYES; CROSS-LINKING; THIOFLAVIN-T; STYRYL DYES; CONGO RED; TAU; CURCUMIN; DEPOSITS AB Evidence indicated that shifting treatment to a presymptomatic stage may produce significant benefits to prevent/alleviate the progression of Alzheimer's disease (AD); in particular, early incorporation of noninvasive imaging and biomarker testing will be significantly beneficial for AD drug development. Based on amyloid cascade hypothesis and its revised version, both beta-amyloid deposition and soluble oligomeric species could be good diagnostic biomarkers for AD. Near-IR fluorescence (NIRF) imaging, which so far is limited to animal studies, is a promising method for its incomparable advantages such as low cost, high-throughput and easy operation. This review focuses on recent reported NIRF probes that showed excellent binding to plaques and oligomers. We hope that this review will shed light on the future of NIRF probes' discovery. C1 [Liu, Hongwu; Yang, Jian; Wang, Letian; Xu, Yungen; Zhang, Siyuan; Lv, Jie; Li, Yuyan] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China. [Yang, Jian; Ran, Chongzhao] Harvard Med Sch, Massachusetts Gen Hosp, Mol Imaging Lab,MIT, Athinoula Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. RP Li, YY (reprint author), China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China. EM yuyanli@cpu.edu.cn FU Outstanding Scientific and Technological Innovation Team of Jiangsu Province of China FX The authors of this review were supported by Outstanding Scientific and Technological Innovation Team of Jiangsu Province of China in 2015. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript. NR 99 TC 0 Z9 0 U1 6 U2 6 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PD JAN PY 2017 VL 9 IS 2 BP 179 EP 198 DI 10.4155/fmc-2016-0185 PG 20 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA EK1KF UT WOS:000393683500005 PM 28127995 ER PT J AU McCoy, LE Burton, DR AF McCoy, Laura E. Burton, Dennis R. TI Identification and specificity of broadly neutralizing antibodies against HIV SO IMMUNOLOGICAL REVIEWS LA English DT Review DE B cells; HIV; monoclonal antibody isolation; neutralization ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; HIGH-MANNOSE PATCH; CD4 BINDING-SITE; IG KNOCKIN MICE; HIV-1-NEUTRALIZING ANTIBODIES; CONFORMATIONAL EPITOPE; POTENT NEUTRALIZATION; VACCINE DESIGN AB Beginning in 2009, studies of the humoral responses of HIV-positive individuals have led to the identification of scores, if not hundreds, of antibodies that are both broadly reactive and potently neutralizing. This development has provided renewed impetus toward an HIV vaccine and led directly to the development of novel immunogens. Advances in identification of donors with the most potent and broad anti-HIV serum neutralizing responses were crucial in this effort. Equally, development of methods for the rapid generation of human antibodies from these donors was pivotal. Primarily these methods comprise single B-cell culture coupled to high-throughput neutralization screening and flow cytometry-based sorting of single B cells using HIV envelope protein baits. In this review, the advantages and disadvantages of these methodologies are discussed in the context of the specificities targeted by individual antibodies and the need for further improvements to evaluate HIV vaccine candidates. C1 [McCoy, Laura E.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA. [McCoy, Laura E.] UCL, Div Infect & Immun, London, England. [Burton, Dennis R.] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, IAVI Neutralizing Antibody Ctr, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA.; McCoy, LE (reprint author), UCL, Div Infect & Immun, London, England. EM l.mccoy@ucl.ac.uk; burton@scripps.edu FU Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant [UM1AI100663]; Collaboration for AIDS Vaccine Discovery [OPP1084519, OPP1115782]; European Union Marie-Curie Fellowship [FP7-PEOPLE-2013-IOF]; IAVI; USAID; Bill & Melinda Gates Foundation FX Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery Grant, Grant/Award Number: UM1AI100663; Collaboration for AIDS Vaccine Discovery, Grant/Award Number: OPP1084519 and OPP1115782; European Union Marie-Curie Fellowship, Grant/Award Number: FP7-PEOPLE-2013-IOF; IAVI; USAID and the Bill & Melinda Gates Foundation. NR 103 TC 2 Z9 2 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2017 VL 275 IS 1 BP 11 EP 20 DI 10.1111/imr.12484 PG 10 WC Immunology SC Immunology GA EK5LX UT WOS:000393969000002 PM 28133814 ER PT J AU Verkoczy, L Alt, FW Tian, M AF Verkoczy, Laurent Alt, Frederick W. Tian, Ming TI Human Ig knockin mice to study the development and regulation of HIV-1 broadly neutralizing antibodies SO IMMUNOLOGICAL REVIEWS LA English DT Review DE B-cell lineages; B-cell tolerance controls; broadly neutralizing antibodies (bnAbs); CD4-binding site (CD4bs); knockin (KI) mice; sequential immunization ID AUTOREACTIVE B-CELLS; IMMUNODEFICIENCY-VIRUS TYPE-1; SYSTEMIC-LUPUS-ERYTHEMATOSUS; N-GLYCAN RECOGNITION; TRANSGENIC MICE; AFFINITY MATURATION; POTENT NEUTRALIZATION; VACCINE DEVELOPMENT; ENVELOPE GLYCOPROTEINS; MONOCLONAL-ANTIBODIES AB A major challenge for HIV-1 vaccine research is developing a successful immunization approach for inducing broadly neutralizing antibodies (bnAbs). A key shortcoming in meeting this challenge has been the lack of animal models capable of identifying impediments limiting bnAb induction and ranking vaccine strategies for their ability to promote bnAb development. Since 2010, immunoglobulin knockin (KI) technology, involving inserting functional rearranged human variable exons into the mouse IgH and IgL loci has been used to express bnAbs in mice. This approach has allowed immune tolerance mechanisms limiting bnAb production to be elucidated and strategies to overcome such limitations to be evaluated. From these studies, along with the wealth of knowledge afforded by analyses of recombinant Ig-based bnAb structures, it became apparent that key functional features of bnAbs often are problematic for their elicitation in mice by classic vaccine paradigms, necessitating more iterative testing of new vaccine concepts. In this regard, bnAb KI models expressing deduced precursor V(D)J rearrangements of mature bnAbs or unrearranged germline V, D, J segments (that can be assembled into variable region exons that encode bnAb precursors), have been engineered to evaluate novel immunogens/regimens for effectiveness in driving bnAb responses. One promising approach emerging from such studies is the ability of sequentially administered, modified immunogens (designed to bind progressively more mature bnAb precursors) to initiate affinity maturation. Here, we review insights gained from bnAb KI studies regarding the regulation and induction of bnAbs, and discuss new Ig KI methodologies to manipulate the production and/or expression of bnAbs in vivo, to further facilitate vaccine-guided bnAb induction studies. C1 [Verkoczy, Laurent] Duke Univ, Sch Med, Dept Med, Human Vaccine Inst, Durham, NC 27706 USA. [Verkoczy, Laurent] Duke Univ, Sch Med, Dept Pathol, Human Vaccine Inst, Durham, NC 27706 USA. [Alt, Frederick W.; Tian, Ming] Harvard Med Sch, Howard Hughes Med Inst, Program Cellular & Mol Med, Boston Childrens Hosp, Boston, MA USA. [Alt, Frederick W.; Tian, Ming] Harvard Med Sch, Dept Genet, Boston, MA USA. RP Verkoczy, L (reprint author), Duke Univ, Med Ctr, Durham, NC 27708 USA. EM laurent.verkoczy@duke.edu FU NIH/NIAID [R01AI087202, R01AI118571]; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery [5UMI-AI100645]; NIH [R01AI077595] FX NIH/NIAID, Grant/Award Number: R01AI087202 and R01AI118571; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, Grant/Award Number: 5UMI-AI100645; NIH, Grant/Award Number: R01AI077595 NR 147 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2017 VL 275 IS 1 BP 89 EP 107 DI 10.1111/imr.12505 PG 19 WC Immunology SC Immunology GA EK5LX UT WOS:000393969000008 PM 28133799 ER PT J AU Ackerman, ME Barouch, DH Alter, G AF Ackerman, Margaret E. Barouch, Dan H. Alter, Galit TI Systems serology for evaluation of HIV vaccine trials SO IMMUNOLOGICAL REVIEWS LA English DT Review DE antibody; effector function; Fc receptor; machine learning; vaccine ID EFFECTOR FUNCTION; RHESUS-MONKEYS; IN-VIVO; SIVMAC251 ACQUISITION; REVERSE VACCINOLOGY; PROTECTIVE EFFICACY; PHAGOCYTIC-ACTIVITY; HUMORAL IMMUNITY; NEURAL-NETWORKS; HIGH-THROUGHPUT AB The scale and scope of the global epidemic, coupled to challenges with traditional vaccine development approaches, point toward a need for novel methodologies for HIV vaccine research. While the development of vaccines able to induce broadly neutralizing antibodies remains the ultimate goal, to date, vaccines continue to fail to induce these rare humoral immune responses. Conversely, growing evidence across vaccine platforms in both non-human primates and humans points to a role for polyclonal vaccine-induced antibody responses in protection from infection. These candidate vaccines, despite employing disparate viral vectors and immunization strategies, consistently identify a role for functional or non-traditional antibody activities as correlates of immunity. However, the precise mechanism(s) of action of these binding antibodies, their specific characteristics, and their ability to be selectively induced and/or potentiated to result in complete protection merits parallel investigation to neutralizing antibody-based vaccine design approaches. Ultimately, while neutralizing and functional antibody-based vaccine strategies need not be mutually exclusive, defining the specific characteristics of protective functional antibodies may provide a target immune profile to potentially induce more robust immunity against HIV. Specifically, one approach to guide the development of functional antibody-based vaccine strategies, termed systems serology, offers an unbiased and comprehensive approach to systematically survey humoral immune responses, capturing the array of functions and humoral response characteristics that may be induced following vaccination with high resolution. Coupled to machine learning tools, large datasets that explore the antibody-ome offer a means to step back from anticipated correlates and mechanisms of protection and toward a more fundamental understanding of coordinated aspects of humoral immune responses, to more globally differentiate among vaccine candidates, and most critically, to identify the features of humoral immunity that distinguish protective from non-protective responses. Overall, the systematic serological approach described here aimed at broadly capturing the enormous biodiversity in antibody profiles that may emerge following vaccination, complements the existing cutting edge tools in the cellular immunology space that survey vaccine-induced polyfunctional cellular activity by flow cytometry, transcriptional profiling, epigenetic, and metabolomic analysis to offer a means to develop both a more nuanced and a more complete understanding of correlates of protection to support the design of functional vaccine strategies. C1 [Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Barouch, Dan H.; Alter, Galit] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. [Barouch, Dan H.] Beth Israel Deaconness Med Ctr, Boston, MA USA. RP Ackerman, ME (reprint author), Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA.; Alter, G (reprint author), Ragon Inst MGH MIT & Harvard, Cambridge, MA USA. EM margaret.e.ackerman@dartmouth.edu; galter@mgh.harvard.edu FU NIH [AI060354, AI078526, AI080289, AI084794, AI095985, AI096040, AI102660, AI102691, OD011170, HHSN261200800001E]; Bill and Melinda Gates Foundation [OPP1032817, OPP1114729]; Ragon Institute of MGH; MIT; Harvard FX NIH, Grant/Award Number: AI060354, AI078526, AI080289, AI084794, AI095985, AI096040, AI102660, AI102691, OD011170 and HHSN261200800001E; Bill and Melinda Gates Foundation, Grant/Award Number: OPP1032817 and OPP1114729; Ragon Institute of MGH, MIT, and Harvard NR 66 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-2896 EI 1600-065X J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2017 VL 275 IS 1 BP 262 EP 270 DI 10.1111/imr.12503 PG 9 WC Immunology SC Immunology GA EK5LX UT WOS:000393969000018 PM 28133810 ER PT J AU Mitchell, SB Lucente, D Larvie, M Cobos, MI Frosch, M Dickerson, BC AF Mitchell, Sara B. Lucente, Diane Larvie, Mykol Cobos, M. I. Frosch, Matthew Dickerson, Bradford C. TI A 63-Year-Old Man With Progressive Visual Symptoms SO JAMA NEUROLOGY LA English DT Article ID POSTERIOR CORTICAL ATROPHY; PHENOTYPE; MUTATIONS AB A 63-year-old man presented with a 4-year history of insidious onset and gradual progression of visual symptoms including right homonymous hemianopsia, alexia, and simultanagnosia with preserved memory. Magnetic resonance imaging, perfusion single-photon emission computed tomography, and fluorodeoxyglucose positron emission tomographic scans revealed strikingly asymmetric left parieto-occipital abnormality. Neuropsychological testing was performed. The differential diagnosis, pathologic findings, genetic testing results, and diagnosis are discussed. C1 [Mitchell, Sara B.] Univ Toronto, Dept Neurol, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Lucente, Diane] Harvard Med Sch, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA USA. [Larvie, Mykol] Harvard Med Sch, Dept Radiol, Massachusetts Gen Hosp, Boston, MA USA. [Cobos, M. I.; Frosch, Matthew] Harvard Med Sch, Massachusetts Gen Hospital, Dept Pathol, Boston, MA USA. [Dickerson, Bradford C.] Harvard Med Sch, Massachusetts Gen Hospital, Frontotemporal Disorders Unit, Dept Neurol, Boston, MA USA. RP Dickerson, BC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Frontotemporal Disorders Unit, 149 13th St,Ste 2691, Charlestown, MA 02129 USA. EM brad.dickerson@mgh.harvard.edu FU National Institutes of Health [R21NS084156] FX This investigation was supported by grant R21NS084156 from the National Institutes of Health. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN 1 PY 2017 VL 74 IS 1 BP 114 EP 118 DI 10.1001/jamaneurol.2016.2210 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA EK1IK UT WOS:000393678800020 PM 27842190 ER PT J AU Boulouis, G Charidimou, A Van Veluw, S Greenberg, SM AF Boulouis, Gregoire Charidimou, Andreas Van Veluw, Susanne Greenberg, Steven M. TI Imaging the Acute Formation of a Cortical Microbleed in Cerebral Amyloid Angiopathy SO JAMA NEUROLOGY LA English DT Editorial Material ID INTRACEREBRAL HEMORRHAGE C1 [Boulouis, Gregoire; Charidimou, Andreas; Van Veluw, Susanne; Greenberg, Steven M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program,Stroke Res Ctr, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. RP Boulouis, G (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Program,Stroke Res Ctr, 175 Cambridge St,Ste 300, Boston, MA 02114 USA. EM gregoireboulouis@gmail.com NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6149 EI 2168-6157 J9 JAMA NEUROL JI JAMA Neurol. PD JAN 1 PY 2017 VL 74 IS 1 BP 120 EP 121 DI 10.1001/jamaneurol.2016.3445 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA EK1IK UT WOS:000393678800021 PM 27893876 ER PT J AU Hinman, JD Rost, NS Leung, TW Montaner, J Muir, KW Brown, S Arenillas, JF Feldmann, E Liebeskind, DS AF Hinman, Jason D. Rost, Natalia S. Leung, Thomas W. Montaner, Joan Muir, Keith W. Brown, Scott Arenillas, Juan F. Feldmann, Edward Liebeskind, David S. TI Principles of precision medicine in stroke SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Review DE CEREBRAL BLOOD FLOW; CEREBROVASCULAR; IMAGE ANALYSIS; NEUROGENETICS; STATISTICS ID ACUTE ISCHEMIC-STROKE; RANDOMIZED CLINICAL-TRIAL; COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; WHITE-MATTER; PERFUSION; THERAPY; THROMBOLYSIS; DIAGNOSIS; REPERFUSION AB The era of precision medicine has arrived and conveys tremendous potential, particularly for stroke neurology. The diagnosis of stroke, its underlying aetiology, theranostic strategies, recurrence risk and path to recovery are populated by a series of highly individualised questions. Moreover, the phenotypic complexity of a clinical diagnosis of stroke makes a simple genetic risk assessment only partially informative on an individual basis. The guiding principles of precision medicine in stroke underscore the need to identify, value, organise and analyse the multitude of variables obtained from each individual to generate a precise approach to optimise cerebrovascular health. Existing data may be leveraged with novel technologies, informatics and practical clinical paradigms to apply these principles in stroke and realise the promise of precision medicine. Importantly, precision medicine in stroke will only be realised once efforts to collect, value and synthesise the wealth of data collected in clinical trials and routine care starts. Stroke theranostics, the ultimate vision of synchronising tailored therapeutic strategies based on specific diagnostic data, demand cerebrovascular expertise on big data approaches to clinically relevant paradigms. This review considers such challenges and delineates the principles on a roadmap for rational application of precision medicine to stroke and cerebrovascular health. C1 [Hinman, Jason D.; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Neurovasc Imaging Res Core, Los Angeles, CA 90095 USA. [Hinman, Jason D.; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Stroke Ctr, Los Angeles, CA 90095 USA. [Rost, Natalia S.] Massachusetts Gen Hosp, Dept Neurol, Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Rost, Natalia S.] Harvard Med Sch, Boston, MA USA. [Leung, Thomas W.] Chinese Univ Hong Kong, Dept Med & Therapeut, Div Neurol, Shatin, Hong Kong, Peoples R China. [Montaner, Joan] VHIR, Neurovasc Res Lab, Barcelona, Spain. [Montaner, Joan] Hosp Virgen Macarena Rocio, IBIS Stroke Programme, Seville, Spain. [Muir, Keith W.] Inst Neurosci & Psychol, Glasgow, Lanark, Scotland. [Brown, Scott] Altair Biostat, St Louis Pk, MN USA. [Arenillas, Juan F.] Univ Valladolid, Hosp Clin Univ, Dept Neurol & Med, Stroke Unit, Valladolid, Spain. [Feldmann, Edward] Baystate Med Ctr, Springfield, MA USA. RP Liebeskind, DS (reprint author), Dept Neurol, Neurosci Res Bldg,Suite 225, Los Angeles, CA 90095 USA. EM davidliebeskind@yahoo.com RI Montaner, Joan/D-3063-2015; Leung, Thomas /O-8567-2015 FU UCLA Cardiovascular Theme Discovery Award [CVTDA-0001-2016]; NIH [NS083740]; USA Department of Veterans Affairs Greater Los Angeles Healthcare System; NIH-NINDS [R01 NS082285, NS086905, K24 NS072272] FX JDH is supported by the UCLA Cardiovascular Theme Discovery Award (CVTDA-0001-2016), Partners in Discovery Pilot Stroke Research Award, NIH NS083740, and the USA Department of Veterans Affairs Greater Los Angeles Healthcare System. NSR is in supported in part by NIH-NINDS R01 NS082285 & NS086905. DSL is supported by NIH-NINDS K24 NS072272. NR 57 TC 2 Z9 2 U1 4 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 EI 1468-330X J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JAN PY 2017 VL 88 IS 1 BP 54 EP 61 DI 10.1136/jnnp-2016-314587 PG 8 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA EK2HD UT WOS:000393747500010 PM 27919057 ER PT J AU Eisen, A Cannon, CP Braunwald, E Steen, DL Zhou, J Goodrich, EL Im, K Dalby, AJ Spinar, J Daga, S Lukas, MA O'Donoghue, ML AF Eisen, Alon Cannon, Christopher P. Braunwald, Eugene Steen, Dylan L. Zhou, Jing Goodrich, Erica L. Im, KyungAh Dalby, Anthony J. Spinar, Jindrich Daga, Shruti Lukas, Mary Ann O'Donoghue, Michelle L. TI Predictors of Nonuse of a High-Potency Statin After an Acute Coronary Syndrome: Insights From the Stabilization of Plaques Using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) Trial SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE acute coronary syndrome; guideline; secondary prevention; statin therapy ID ARTERY-DISEASE; TASK-FORCE; GUIDELINES; THERAPY; PREVENTION; MANAGEMENT; INTENSITY; PATTERNS AB Background- High-potency statins reduce cardiovascular events after acute coronary syndromes but remain underused in clinical practice. We examined predictors of nonuse of high-potency statins after acute coronary syndromes. Methods and Results- The Stabilization of pLaques usIng Darapladib-Thrombolysis in Myocardial Infarction (SOLID-TIMI 52) trial enrolled patients after an acute coronary syndrome in 36 countries between 2009 and 2011. Statin use was strongly encouraged throughout the trial, and statin potency was at the discretion of the treating physician. A high-potency statin was defined as >= 40 mg atorvastatin, >= 20 mg rosuvastatin, or 80 mg simvastatin daily. Predictors of nonuse of high-potency statins were examined using logistic regression. Of the patients included (n = 12 446), 11 850 (95.2%) were treated with a statin at baseline after acute coronary syndrome (median 14 days), but only 5212 (41.9%) were on a high-potency statin. Selected patient factors associated with nonuse of high-potency statins included age >= 75 years (odds ratio 1.39, 95% CI 1.24-1.56), female sex (odds ratio 1.11, 95% CI 1.02-1.22), renal dysfunction (odds ratio 1.17, 95% CI 1.03-1.32), and heart failure during hospital admission (odds ratio 1.43, 95% CI 1.27-1.62). At 3 months after baseline, only 49% of patients had low-density lipoprotein cholesterol < 70 mg/dL. Among the 5490 patients (59%) who were not on a high-potency statin at 3 months, lower low-density lipoprotein cholesterol was a predictor of nonuse of a high-potency statin after a median of 2.3 years (odds ratio 1.15 for 10 mg/dL decrease, 95% CI 1.11-1.19). Conclusion- Despite the widespread use of statins after acute coronary syndromes, most patients are not treated with highpotency statins early and late after the event, including patients at the highest risk of recurrent cardiovascular events. C1 [Eisen, Alon; Cannon, Christopher P.; Braunwald, Eugene; Zhou, Jing; Goodrich, Erica L.; Im, KyungAh; O'Donoghue, Michelle L.] Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. [Steen, Dylan L.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Dalby, Anthony J.] Milpark Hosp, Johannesburg, South Africa. [Spinar, Jindrich] Univ Hosp Brno, Brno, Czech Republic. [Daga, Shruti; Lukas, Mary Ann] GlaxoSmithKline, Philadelphia, PA USA. RP O'Donoghue, ML (reprint author), TIMI Study Grp, 60 Fenwood Rd,7th Floor, Boston, MA 02115 USA. EM modonoghue@partners.org FU Amgen; Arisaph; Boehringer-Ingelheim; Bristol-Myers Squibb; Daiichi Sankyo; Janssen; Merck; Takeda; Alnylam; Astra Zeneca; Bristol-Myers; GlaxoSmithKline; Kowa; Lipimedix; Pfizer; Regeneron; Sanofi; Novartis; Duke University; Menarini International; Bayer; Medscape; Eisai; Sanofi/Regeneron FX Cannon discloses research grants (all >10K) from Amgen, Arisaph, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Janssen, Merck, and Takeda and consulting fees from Alnylam, Amgen, Arisaph, Astra Zeneca, Bristol-Myers, Bristol-Myers Squibb, GlaxoSmithKline, Kowa, Merck, Takeda, Lipimedix*, Pfizer, Regeneron* and Sanofi* (* denotes >10K). Braunwald discloses grant support to his institution from GlaxoSmithKline, Astra Zeneca, Novartis, Duke University, Merck, and Daiichi Sankyo; uncompensated consultancies and lectures with Merck and Novartis; consultancies with The Medicines Company, Sanofi Aventis and Theravance; and personal fees for lectures from Daiichi Sankyo, Menarini International, Bayer and Medscape. Steen discloses moderate compensation from Sanofi/Regeneron. Dalby is on advisory boards for Aspen, Astra Zeneca, Bayer, Boehringer-Ingelheim, Novartis, Sanofi, and Servier. He has received honoraria from Astra Zeneca and Servier and travel sponsorships from Bayer, Boehringer-Ingelheim, Novartis, and Sanofi. Daga is an employee and shareholder of GlaxoSmithKline. Lukas is an employee and shareholder of GlaxoSmithKline. O'Donoghue discloses grants from Eisai, GlaxoSmithKline, Astra Zeneca, Merck, and Janssen. The remaining authors have no disclosures to report. NR 20 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JAN PY 2017 VL 6 IS 1 AR e004332 DI 10.1161/JAHA.116.004332 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EK0CE UT WOS:000393593300009 ER PT J AU Heidenreich, PA Zhao, X Hernandez, AF Schwamm, LH Smith, E Reeves, M Peterson, ED Fonarow, GC AF Heidenreich, Paul A. Zhao, Xin Hernandez, Adrian F. Schwamm, Lee H. Smith, Eric Reeves, Mat Peterson, Eric D. Fonarow, Gregg C. TI Impact of an Expanded Hospital Recognition Program for Stroke Quality of Care SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE awards; health care quality assessment; health care quality indicators; hospital performance; performance measure; stroke ID GUIDELINES-STROKE; ISCHEMIC-STROKE; OUTCOMES; TRENDS; DOCUMENTATION; IMPROVEMENT; TIMES AB Background-In 2009, the Get With The Guidelines-Stroke (GWTG-Stroke) program offered additional recognition if hospitals performed well on certain stroke quality measures. We sought to determine whether quality of care for all hospitals participating in GWTG- Stroke improved with this expanded recognition program. Methods and Results-We examined hospital- level performance on 6 quality of care (process) measures and 1 defect- free composite quality measure for stroke following expansion of the existing performance measure recognition program. Compliance with all measures improved following launch of the expanded program, and this rate increased significantly for all 9 measures. When evaluated as the relative rate of increase in use over time, process improvement slowed significantly (P< 0.05) following launch of the program for 2 measures, and accelerated significantly for 1 measure. However, when evaluated as a gap in care, the decrease in the quality gap was greater following launch of the program for 5 of 6 (83%) measures. There was no evidence that other processes of stroke care suffered as the result of the increase in measures and expanded recognition program. Conclusions-While care for stroke continues to improve in this country, expanded hospital process performance recognition had mixed results in accelerating this improvement. However, the quality gap continues to shrink among those participating in provider performance programs. C1 [Heidenreich, Paul A.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Zhao, Xin; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Smith, Eric] Univ Calgary, Calgary, AB, Canada. [Reeves, Mat] Michigan State Univ, Lansing, MI USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. RP Heidenreich, PA (reprint author), 3801 Miranda Ave, Palo Alto, CA 94306 USA. EM heiden@stanford.edu FU Medtronic; GlaxoSmithKline; Ortho-McNeil; American Heart Association Pharmaceutical Roundtable; Veteran Administration's Quality Enhancement and Research Initiative [04-326] FX The Get With The Guidelines-Stroke (GWTG-Stroke) program is provided by the American Heart Association. GWTG-Stroke has been funded in the past through support from Medtronic, GlaxoSmithKline, Ortho-McNeil, and the American Heart Association Pharmaceutical Roundtable. Dr Heidenreich is supported by a grant from the Veteran Administration's Quality Enhancement and Research Initiative 04-326. NR 16 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JAN PY 2017 VL 6 IS 1 AR e004278 DI 10.1161/JAHA.116.004278 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EK0CE UT WOS:000393593300026 ER PT J AU Manstein, D AF Manstein, Dieter TI Special dermatology/plastic surgery issue 2017 Introduction SO LASERS IN SURGERY AND MEDICINE LA English DT Editorial Material ID PHOTOTHERMOLYSIS C1 [Manstein, Dieter] Harvard Med Sch, Res Inst, Massachusetts Gen Hosp, Dermatol, Boston, MA 02115 USA. RP Manstein, D (reprint author), Harvard Med Sch, Res Inst, Massachusetts Gen Hosp, Dermatol, Boston, MA 02115 USA. EM dmanstein@mgh.harvard.edu NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD JAN PY 2017 VL 49 IS 1 BP 3 EP 6 DI 10.1002/lsm.22623 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA EK5QD UT WOS:000393980000001 PM 28129437 ER PT J AU Wat, H Wu, DC Chan, HHL AF Wat, Heidi Wu, Douglas C. Chan, Henry Hin Lee TI Fractional resurfacing in the Asian patient: Current state of the art SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE fractional laser; acne scarring; hypertrophic scarring; melasma; erbium glass; thulium fiber; Asian skin; fractional photothermolysis; photorejuvenation; resurfacing ID CARBON-DIOXIDE LASER; ATROPHIC ACNE SCARS; YTTRIUM-ALUMINUM-GARNET; THULIUM FIBER LASER; ERBIUM-GLASS LASER; RADIOFREQUENCY MICRONEEDLE SYSTEM; INTENSE PULSED-LIGHT; PATTERN HAIR LOSS; SPLIT-FACE; BIPOLAR RADIOFREQUENCY AB Background and ObjectiveFractionated photothermolysis (FP) has revolutionized modern laser technology. By creating selective columns of microthermal damage, fractionated devices allows for greater treatment depths to be achieved without the prolonged downtime and risk of complications seen in traditional fully ablative laser resurfacing. Fractional resurfacing is a proven method to treat a variety of cutaneous conditions. In the Caucasian patient, a wide range of devices and treatment settings can be utilized safely and effectively. However, ethnic skin requires special consideration due to its unique pigmentary characteristics and clinical presentations. In this review article, we detail the current indications and strategies to optimize results and mitigate complications when utilizing fractional resurfacing for the Asian patient. MethodsA review of the MEDLINE English literature was conducted on fractionated laser devices studied in the Asian population. Articles included describe non-ablative devices including fractionated erbium glass, thulium fiber, diode, and radiofrequency devices; and ablative devices including fractionated carbon dioxide (CO2) laser, erbium yttrium aluminum garnet and yttrium scandium gallium garnet (YSGG) laser. These data were integrated with the expert opinion of the authors. ConclusionTaking into account the unique characteristics and cosmetic concerns of the Asian population, fractional resurfacing can be considered a safe and effective option for the treatment of atrophic and hypertrophic scarring, and photorejuvenation in ethnic skin types. Select cases of melasma may be treated with fractionated non-ablative devices, but utilized with caution. The predominant complication associated with fractional resurfacing for these conditions is post-inflammatory hyperpigmentation (PIH) and rebound worsening of melasma. A greater number of treatments at lower density settings and wider treatment intervals typically produce the lowest risks of PIH without compromising treatment efficacy. Lasers Surg. Med. 49:45-59, 2017. (c) 2016 Wiley Periodicals, Inc. C1 [Wat, Heidi] Univ Alberta, Dept Med, Div Dermatol, 8-112 Clin Sci Bldg,11350-83 Ave, Edmonton, AB T6G 2G3, Canada. [Wu, Douglas C.] Goldman Butterwick Groff Fabi & Wu Cosmet Laser D, San Diego, CA 92121 USA. [Chan, Henry Hin Lee] Univ Hong Kong, Div Dermatol, Dept Med, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry Hin Lee] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Wat, H (reprint author), Univ Alberta, Dept Med, Div Dermatol, 8-112 Clin Sci Bldg,11350-83 Ave, Edmonton, AB T6G 2G3, Canada. EM heidiwat1@gmail.com NR 103 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0196-8092 EI 1096-9101 J9 LASER SURG MED JI Lasers Surg. Med. PD JAN PY 2017 VL 49 IS 1 BP 45 EP 59 DI 10.1002/lsm.22579 PG 15 WC Dermatology; Surgery SC Dermatology; Surgery GA EK5QD UT WOS:000393980000006 PM 27605303 ER PT J AU Merritt, FW Noble, MN Prochazka, AV Aagaard, EM Stickrath, CR AF Merritt, Frank W. Noble, Melissa N. Prochazka, Allan V. Aagaard, Eva M. Stickrath, Chad R. TI Attending rounds: What do the all-star teachers do? SO MEDICAL TEACHER LA English DT Article ID LEARNER-CENTERED MODEL; DUTY-HOUR REGULATIONS; INTERNAL-MEDICINE; TEACHING ROUNDS; BEDSIDE; EDUCATION; RESIDENT; CARE; ERA AB Aim: To examine differences in the types of teaching activities performed during rounds between the most effective and least effective inpatient teaching attendings.Methods: Participants included 56 attending physicians supervising 279 trainees. Trained observers accompanied teams during rounds and recorded the frequencies of educational activities that occurred. Students and residents then rated their satisfaction with the teaching on rounds.Results: Attending physicians with the highest learner satisfaction scores performed significantly more teaching activities per patient than attending physicians who were rated as average or less-effective (2.1 vs. 1.4 vs. 1.5; p=.03). There were significant differences in the frequencies of 3 out of the 9 specific teaching activities observed, including answering specific patient-care related questions (77% vs. 66% vs. 47%; p=.003), teaching on learner chosen topics (8% vs. 2% vs. 2%; p=.02), and providing feedback (31% vs. 10% vs. 0.1%; p=.001).Conclusions: Specific categories of teaching activitiespatient-specific teaching, teaching on learner-identified topics, and providing real-time feedbackare performed more frequently by the highest-rated attending physicians, which can guide faculty development. C1 [Merritt, Frank W.; Aagaard, Eva M.] Univ Colorado, Sch Med, Med, Aurora, CO USA. [Noble, Melissa N.; Stickrath, Chad R.] Univ Colorado, Sch Med, Aurora, CO USA. [Prochazka, Allan V.] Univ Colorado, Sch Med, Med, Div Gen Internal Med, Aurora, CO USA. [Prochazka, Allan V.] Univ Colorado, Sch Med, Mentored Scholarly Act, Aurora, CO USA. [Prochazka, Allan V.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Merritt, FW (reprint author), Hosp Med Grp, Leprino Bldg,4th Floor,12401 East 17th Ave, Aurora, CO 80045 USA. EM frank.merritt@ucdenver.edu NR 26 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0142-159X EI 1466-187X J9 MED TEACH JI Med. Teach. PD JAN PY 2017 VL 39 IS 1 BP 100 EP 104 DI 10.1080/0142159X.2017.1248914 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EK4GT UT WOS:000393885800016 PM 27841061 ER PT J AU Wu, M Huang, JY Zhang, JM Benes, C Jiao, B Ren, RB AF Wu, Min Huang, Jinyan Zhang, Jianming Benes, Cyril Jiao, Bo Ren, Ruibao TI N-Arachidonoyl Dopamine Inhibits NRAS Neoplastic Transformation by Suppressing Its Plasma Membrane Translocation SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; RAS ONCOGENES; CANNABINOID-RECEPTOR; PROTEIN TRANSFERASE; TARGETING MOTIF; CELL-DEATH; IN-VITRO; CANCER; PALMITOYLATION; ONCOSIS AB RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block RAS oncogenic signaling by a distinct mechanism. Because the biological activity of RAS proteins relies upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS-specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers. (C) 2016 AACR. C1 [Wu, Min; Huang, Jinyan; Jiao, Bo; Ren, Ruibao] Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Hematol, Collaborat Innovat Ctr Syst Biol,Ruijin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol,Sch, Shanghai, Peoples R China. [Zhang, Jianming] Massachusetts Gen Hosp, Dept Dermatol, Charlestown, MA USA. [Benes, Cyril] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Ren, Ruibao] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. RP Jiao, B (reprint author), Shanghai Jiao Tong Univ, Collaborat Innovat Ctr Hematol, Collaborat Innovat Ctr Syst Biol,Ruijin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol,Sch, Shanghai, Peoples R China.; Ren, RB (reprint author), Brandeis Univ, 415 South St, Waltham, MA 02454 USA. EM bjiao@sibs.ac.cn; ren@brandeis.edu FU National Natural Science Foundation of China [81230055, 81300402]; Shanghai Outstanding Academic Leader Program [12XD1403500]; Doctoral Innovation Fund from Shanghai Jiao Tong University School of Medicine FX This work was supported by the National Natural Science Foundation of China (81230055 to R. Ren; 81300402 to B. Jiao), Shanghai Outstanding Academic Leader Program (12XD1403500 to R. Ren), and the Doctoral Innovation Fund from Shanghai Jiao Tong University School of Medicine to M. Wu. NR 50 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 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2017 VL 16 IS 1 BP 57 EP 67 DI 10.1158/1535-7163.MCT-16-0419 PG 11 WC Oncology SC Oncology GA EK1OP UT WOS:000393695500006 PM 27760835 ER PT J AU Oudin, MJ Barbier, L Schafer, C Kosciuk, T Miller, MA Han, S Jonas, O Lauffenburger, DA Gertler, FB AF Oudin, Madeleine J. Barbier, Lucie Schafer, Claudia Kosciuk, Tatsiana Miller, Miles A. Han, Sangyoon Jonas, Oliver Lauffenburger, Douglas A. Gertler, Frank B. TI MENA Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TUMOR PROGRESSION; PROTEIN-KINASE; MICROTUBULE DYNAMICS; PROGNOSTIC MARKER; TAXOL RESISTANCE; CELL-LINES; METASTASIS; APOPTOSIS; CHEMOTHERAPY; ISOFORM AB Taxane therapy remains the standard of care for triple-negative breast cancer. However, high frequencies of recurrence and progression in treated patients indicate that metastatic breast cancer cells can acquire resistance to this drug. The actin regulatory protein MENA and particularly its invasive isoform, MENA(INV), are established drivers of metastasis. MENA(INV) expression is significantly correlated with metastasis and poor outcome in human patients with breast cancer. We investigated whether MENA isoforms might play a role in driving resistance to chemotherapeutics. We find that both MENA and MENA(INV) confer resistance to the taxane paclitaxel, but not to the widely used DNA-damaging agents doxorubicin or cisplatin. Furthermore, paclitaxel treatment does not attenuate growth of MENA(INV)-driven metastatic lesions. Mechanistically, MENA isoform expression alters the ratio of dynamic and stable microtubule populations in paclitaxel-treated cells. MENA expression also increases MAPK signaling in response to paclitaxel treatment. Decreasing ERK phosphorylation by cotreatment with MEK inhibitor restored paclitaxel sensitivity by driving microtubule stabilization in MENA isoform-expressing cells. Our results reveal a novel mechanism of taxane resistance in highly metastatic breast cancer cells and identify a combination therapy to overcome such resistance. (C) 2016 AACR. C1 [Oudin, Madeleine J.; Barbier, Lucie; Schafer, Claudia; Kosciuk, Tatsiana; Jonas, Oliver; Lauffenburger, Douglas A.; Gertler, Frank B.] MIT, David H Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Barbier, Lucie] ENS Cachan, Cachan, France. [Miller, Miles A.; Lauffenburger, Douglas A.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Miller, Miles A.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Miller, Miles A.] Harvard Med Sch, Boston, MA USA. [Han, Sangyoon] UT Southwestern Med Ctr, Lydia Hill Dept Bioinformat, Dallas, TX USA. [Gertler, Frank B.] MIT, Dept Biol, Cambridge, MA USA. RP Gertler, FB (reprint author), Koch Inst Integrat Canc Res, MIT 76-361a,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM fgertler@mit.edu FU DoD Breast Cancer Research Program post-doctoral fellowship [W81XWH-12-1-0031]; Ludwig post-doctoral fellowship [K99-CA207866-01]; ENS-Cachan funds; Ludwig Center at MIT; NIH [U54-CA112967]; Koch Institute Frontier Research Program award from the Kathy and Curt Marble Cancer Research Fund; Koch Institute NCI core grant [P30-CA14051] FX This work was supported by a DoD Breast Cancer Research Program post-doctoral fellowship (W81XWH-12-1-0031), a Ludwig post-doctoral fellowship and K99-CA207866-01 to M.J. Oudin; ENS-Cachan funds to L. Barbier; funds from the Ludwig Center at MIT to F.B. Gertler; NIH grant U54-CA112967 to F.B. Gertler and D.A. Lauffenburger; a Koch Institute Frontier Research Program award from the Kathy and Curt Marble Cancer Research Fund to F.B. Gertler and O. Jonas; and the Koch Institute NCI core grant P30-CA14051 to all authors. payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 53 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 EI 1538-8514 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JAN PY 2017 VL 16 IS 1 BP 143 EP 155 DI 10.1158/1535-7163.MCT-16-0413 PG 13 WC Oncology SC Oncology GA EK1OP UT WOS:000393695500014 PM 27811011 ER PT J AU Hopkin, RJ Brand, E Rasmussen, UF Germain, DP Guffon, N Jovanovic, A Kantola, I Karaa, A Lemay, R Martins, AM Wilcox, WR Yoo, HW AF Hopkin, Robert J. Brand, Eva Rasmussen, Ulla F. Germain, Dominique P. Guffon, Nathalie Jovanovic, Ana Kantola, Ilkka Karaa, Amel Lemay, Roberta Martins, Ana M. Wilcox, William R. Yoo, Han-Wook TI Burden of Fabry disease in young patients (<= 30 years of age) who were initiated on enzyme replacement therapy with agalsidase beta: a Fabry Registry analysis SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 13th Annual Research Meeting on We're Organizing Research for Lysosomal Diseases (WORLD) CY FEB 13-17, 2017 CL San Diego, CA C1 [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA. [Hopkin, Robert J.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Brand, Eva] Univ Hosp Munster, Interdisciplinary Fabry Ctr Munster, Munster, Germany. [Rasmussen, Ulla F.] Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark. [Germain, Dominique P.] Paris Saclay Univ, Univ Versailles, Montigny, France. [Guffon, Nathalie] Femme Mere Enfant Hosp, Reference Ctr Inherited Metab Disorders, Lyon, France. [Jovanovic, Ana] Salford Royal NHS Fdn Trust, Mark Holland Metab Unit, Salford, Lancs, England. [Kantola, Ilkka] Turku Univ Hosp, Turku, Finland. [Karaa, Amel] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Lemay, Roberta] Sanofi Genzyme, Cambridge, MA USA. [Martins, Ana M.] Univ Fed Sao Paulo, Reference Ctr Inborn Errors Metab, Sclo Paulo, Brazil. [Wilcox, William R.] Emory Univ, Sch Med, Atlanta, GA USA. [Yoo, Han-Wook] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. FU Sanofi Genzyme FX Funding by Sanofi Genzyme (Fabry Registry and abstract). NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN-FEB PY 2017 VL 120 IS 1-2 MA 142 BP S65 EP S66 DI 10.1016/j.ymgme.2016.11.151 PG 2 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA EK2CC UT WOS:000393734000144 ER PT J AU Hughes, D Boyd, S Giraldo, P Gonzalez, D Holida, M Goker-Alpan, O Maegawa, G Atta, M Nicholls, K Schiffmann, R Tuffaha, A Barisoni, L Colvin, R Jannette, JC Krupko, J Szlaifer, M Brill-Almon, E Chertkoff, R AF Hughes, Derralynn Boyd, Simeon Giraldo, Pilar Gonzalez, Derlis Holida, Myrl Goker-Alpan, Ozlem Maegawa, Gustavo Atta, Mohamed Nicholls, Kathy Schiffmann, Raphael Tuffaha, Ahmad Barisoni, Laura Colvin, Robert Jannette, J. Charles Krupko, Jenny Szlaifer, Mali Brill-Almon, Einat Chertkoff, Raul TI One-year follow up of Fabry disease patients treated by IV administration of a plant derived alpha-Gal-A enzyme: safety and efficacy SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 13th Annual Research Meeting on We're Organizing Research for Lysosomal Diseases (WORLD) CY FEB 13-17, 2017 CL San Diego, CA C1 [Hughes, Derralynn] Univ Colege London, London, England. [Boyd, Simeon] Univ Calif Davis, Med Ctr, Sacramento, CA USA. [Giraldo, Pilar] Hosp Dia Quiron, Zaragoza, Spain. [Gonzalez, Derlis] Inst Privado Hematol Invest Clin, Asuncion, Paraguay. [Holida, Myrl] Univ Iowa, Iowa City, IA USA. [Goker-Alpan, Ozlem] O&O Alpan LLC, Fairfax, VA USA. [Maegawa, Gustavo] Univ Florida, Gainesville, FL USA. [Atta, Mohamed] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Nicholls, Kathy] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Nicholls, Kathy] Univ Melbourne, Parkville, Vic, Australia. [Schiffmann, Raphael] Baylor Univ, Dallas, TX USA. [Tuffaha, Ahmad] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Barisoni, Laura] Univ Miami, Miami, FL USA. [Colvin, Robert] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Jannette, J. Charles] Univ N Carolina, Chapel Hill, NC USA. [Krupko, Jenny; Szlaifer, Mali; Brill-Almon, Einat; Chertkoff, Raul] Protalix, Carmiel, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN-FEB PY 2017 VL 120 IS 1-2 MA 149 BP S68 EP S68 DI 10.1016/j.ymgme.2016.11.158 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA EK2CC UT WOS:000393734000151 ER PT J AU Mehta, A Salek, S Kuter, DJ AF Mehta, Atul Salek, Sam Kuter, David J. TI A global Delphi consensus initiative to facilitate early diagnosis of type 1 and type 3 Gaucher disease: what are the phenotypic commonalities? SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 13th Annual Research Meeting on We're Organizing Research for Lysosomal Diseases (WORLD) CY FEB 13-17, 2017 CL San Diego, CA C1 [Mehta, Atul] UCL Sch Med, Royal Free Hosp, Dept Haematol, London, England. [Salek, Sam] Univ Hertfordshire, Sch Life & Med Sci, Hatfield, Herts, England. [Kuter, David J.] Massachusetts Gen Hosp, Ctr Hematol, Boston, MA 02114 USA. FU Shire International GmbH FX Administration of the GED-C initiative was funded by an unrestricted educational grant from Shire International GmbH. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN-FEB PY 2017 VL 120 IS 1-2 MA 226 BP S95 EP S95 DI 10.1016/j.ymgme.2016.11.235 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA EK2CC UT WOS:000393734000228 ER PT J AU Rolfs, A Oprea, G Kramp, G Giese, AK Zielke, S Lukas, J Cozma, C AF Rolfs, Arndt Oprea, Gabriela Kramp, Guido Giese, Anne-Katrin Zielke, Susanne Lukas, Jan Cozma, Claudia TI Glucosylsphingosine concentration in the blood of Gaucher patients reflects the severity of GBA mutations SO MOLECULAR GENETICS AND METABOLISM LA English DT Meeting Abstract CT 13th Annual Research Meeting on We're Organizing Research for Lysosomal Diseases (WORLD) CY FEB 13-17, 2017 CL San Diego, CA C1 [Rolfs, Arndt; Giese, Anne-Katrin; Zielke, Susanne; Lukas, Jan] Univ Rostock, Rostock, Germany. [Rolfs, Arndt; Oprea, Gabriela; Kramp, Guido; Cozma, Claudia] Centogene AG, Rostock, Germany. [Giese, Anne-Katrin] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN-FEB PY 2017 VL 120 IS 1-2 MA 290 BP S116 EP S116 DI 10.1016/j.ymgme.2016.11.299 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA EK2CC UT WOS:000393734000291 ER PT J AU Mainero, C Granberg, T AF Mainero, Caterina Granberg, Tobias TI Visualization of cortical MS lesions with MRI need not be further improved - No SO MULTIPLE SCLEROSIS JOURNAL LA English DT Article ID MULTIPLE-SCLEROSIS LESIONS; CRITERIA; 7T C1 [Mainero, Caterina; Granberg, Tobias] Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA. [Mainero, Caterina; Granberg, Tobias] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Mainero, Caterina; Granberg, Tobias] Harvard Med Sch, Boston, MA USA. RP Mainero, C (reprint author), Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA. EM caterina@nmr.mgh.harvard.edu NR 10 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 1352-4585 EI 1477-0970 J9 MULT SCLER J JI Mult. Scler. J. PD JAN PY 2017 VL 23 IS 1 BP 17 EP 19 DI 10.1177/1352458516666336 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EK4OH UT WOS:000393906000005 PM 27566449 ER PT J AU Bianchi, MT Russo, K Gabbidon, H Smith, T Goparaju, B Westover, MB AF Bianchi, Matt T. Russo, Kathryn Gabbidon, Harriett Smith, Tiaundra Goparaju, Balaji Westover, M. Brandon TI Big data in sleep medicine: prospects and pitfalls in phenotyping SO NATURE AND SCIENCE OF SLEEP LA English DT Article DE polysomnography; sleep disorders; subjective symptoms; correlation; plotting; statistics ID PERIODIC LEG MOVEMENTS; HEART-RATE-VARIABILITY; APNEA-HYPOPNEA INDEX; RESPIRATORY EVENTS; STAGE TRANSITIONS; SPECTRAL-ANALYSIS; INSOMNIA; FRAGMENTATION; DURATION; TIME AB Clinical polysomnography (PSG) databases are a rich resource in the era of "big data" analytics. We explore the uses and potential pitfalls of clinical data mining of PSG using statistical principles and analysis of clinical data from our sleep center. We performed retrospective analysis of self-reported and objective PSG data from adults who underwent overnight PSG (diagnostic tests, n=1835). Self-reported symptoms overlapped markedly between the two most common categories, insomnia and sleep apnea, with the majority reporting symptoms of both disorders. Standard clinical metrics routinely reported on objective data were analyzed for basic properties (missing values, distributions), pairwise correlations, and descriptive phenotyping. Of 41 continuous variables, including clinical and PSG derived, none passed testing for normality. Objective findings of sleep apnea and periodic limb movements were common, with 51% having an apnea-hypopnea index (AHI) >5 per hour and 25% having a leg movement index >15 per hour. Different visualization methods are shown for common variables to explore population distributions. Phenotyping methods based on clinical databases are discussed for sleep architecture, sleep apnea, and insomnia. Inferential pitfalls are discussed using the current dataset and case examples from the literature. The increasing availability of clinical databases for large-scale analytics holds important promise in sleep medicine, especially as it becomes increasingly important to demonstrate the utility of clinical testing methods in management of sleep disorders. Awareness of the strengths, as well as caution regarding the limitations, will maximize the productive use of big data analytics in sleep medicine. C1 [Bianchi, Matt T.; Russo, Kathryn; Gabbidon, Harriett; Smith, Tiaundra; Goparaju, Balaji; Westover, M. Brandon] Massachusetts Gen Hosp, Dept Neurol, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA. [Bianchi, Matt T.] Harvard Med Sch, Div Sleep Med, Boston, MA USA. RP Bianchi, MT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang 7 Neurol,55 Fruit St, Boston, MA 02114 USA. EM mtbianchi@partners.org OI Russo, Kathryn/0000-0002-1782-2508 FU Department of Neurology, Massachusetts General Hospital; Center for Integration of Medicine and Innovative Technology; Milton Family Foundation; MGH-MIT Grand Challenge; American Sleep Medicine Foundation; MC10 Inc; Insomnisolv Inc; NIH-NINDS [1K23NS090900]; Rappaport Foundation; Andrew David Heitman Neuroendovascular Research Fund FX Dr Matt T Bianchi has received funding from the Department of Neurology, Massachusetts General Hospital, the Center for Integration of Medicine and Innovative Technology, the Milton Family Foundation, the MGH-MIT Grand Challenge, and the American Sleep Medicine Foundation. He has a pending patent on a sleep wearable device, received research funding from MC10 Inc and Insomnisolv Inc, has a consulting agreement with McKesson Health and International Flavors and Fragrances, serves as a medical monitor for Pfizer, and has provided expert testimony in sleep medicine. Dr M Brandon Westover receives funding from NIH-NINDS (1K23NS090900), the Rappaport Foundation, and the Andrew David Heitman Neuroendovascular Research Fund. The authors report no other conflicts of interest in this work. NR 93 TC 0 Z9 0 U1 4 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1608 J9 NAT SCI SLEEP JI NAT. SCI. SLEEP PY 2017 VL 9 BP 11 EP 29 DI 10.2147/NSS.S130141 PG 19 WC Clinical Neurology SC Neurosciences & Neurology GA EL4NR UT WOS:000394598400001 PM 28243157 ER PT J AU Simao, S Costa, MA Sun, JK Cunha-Vaz, J Simo, R AF Simao, Silvia Costa, Miguel Angelo Sun, Jennifer K. Cunha-Vaz, Jose Simo, Rafael CA European Consortium Early Treatmen TI Development of a Normative Database for Multifocal Electroretinography in the Context of a Multicenter Clinical Trial SO OPHTHALMIC RESEARCH LA English DT Article DE Multifocal electroretinography; Retina; Normative database; Retinal function ID OPTICAL COHERENCE TOMOGRAPHY; DIABETIC-RETINOPATHY; MACULAR THICKNESS; TOPOGRAPHY; COMPONENTS; DELAYS; MODEL; EYES; SEX; AGE AB Purpose: The aim of this study is to present the largest normative database using nnultifocal electroretinography (mfERG) in the context of a multicenter clinical trial. Methods: This investigational study included 156 eyes from 78 Caucasian subjects aged 45-70 years without known ophthalmic disease or diabetes mellitus; the subjects were recruited from 11 clinical sites in the setting of the EUROCONDOR project. Standardized mfERG acquisition (103 hexagons per eye) was established based on the International Society of Clinical Electrophysiology in Vision. At least one technician per site received both specialized training and certification. The main variables that could have influenced the results were considered in the analyses. Results: The normative database was based on 111 eyes. The overall mean P1-implicit time (IT) was 33.94 +/- 1.70 ms, and the mean P1 amplitude was 30.58 +/- 5.20 nV/deg(2). Age and gender were independently related to predictors of P1-IT but not of P1 amplitude. The responses that were averaged for the 6 rings showed a longer P1-ITtime in the fovea, decreasing progressively to the parafovea and perifovea. By contrast, P1 amplitude values sharply decreased with retinal eccentricity. Conclusions: This normative database can be used as a comparative index of expected normal values in the clinical setting and for examining the effect of studies testing neuroprotective agents. (C) 2017 S. Karger AG, Basel C1 [Simao, Silvia; Costa, Miguel Angelo; Cunha-Vaz, Jose] Assoc Innovat & Biomed Res Light & Image AIBILI, Coimbra, Portugal. [Sun, Jennifer K.] Harvard Med Sch, Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. [Simo, Rafael] Inst Salud Carlos III, Vall dHebron Res Inst VHIR, Barcelona, Spain. [Simo, Rafael] Inst Salud Carlos III, CIBERDEM, Barcelona, Spain. AIBILI, P-3000548 Coimbra, Portugal. Hosp Univ Vall dHebron, Inst Recerca, ES-08035 Barcelona, Spain. RP Simo, R (reprint author), AIBILI, P-3000548 Coimbra, Portugal. EM silvia@aibili.pt; rafael.simo@vhir.org NR 27 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0030-3747 EI 1423-0259 J9 OPHTHALMIC RES JI Ophthalmic Res. PY 2017 VL 57 IS 2 BP 107 EP 117 DI 10.1159/000450958 PG 11 WC Ophthalmology SC Ophthalmology GA EK2BY UT WOS:000393733500005 PM 28052266 ER PT J AU Koutroumpakis, E Slivka, A Furlan, A Dasyam, AK Dudekula, A Greer, JB Whitcomb, DC Yadav, D Papachristou, GI AF Koutroumpakis, Efstratios Slivka, Adam Furlan, Alessandro Dasyam, Anil K. Dudekula, Anwar Greer, Julia B. Whitcomb, David C. Yadav, Dhiraj Papachristou, Georgios I. TI Management and outcomes of acute pancreatitis patients over the last decade: A US tertiary-center experience SO PANCREATOLOGY LA English DT Article DE Acute pancreatitis; Management; Outcomes; Revised Atlanta classification ID DETERMINANT-BASED CLASSIFICATION; REVISED ATLANTA CLASSIFICATION; PERSISTENT ORGAN FAILURE; NECROTIZING PANCREATITIS; PROSPECTIVE COHORT; UNITED-STATES; INFLAMMATORY RESPONSE; INVASIVE-APPROACH; SEVERITY; MORTALITY AB Background/objectives: Acute pancreatitis (AP) management remains largely supportive and can be challenging in patients with severe disease. This study aims to describe a ten-year US tertiary-center experience in managing AP patients. Methods: Clinical management and outcomes of 400 prospectively enrolled AP patients stratified by the Revised Atlanta Classification were analyzed; trends in management between early (2004-2008) and late enrollment phase (2009-2014) were assessed. Results: Fifty-two% of patients were classified as mild AP (MAP); moderately severe (MoAP) and severe (SAP) grades contained 23.5% and 24.5% of participants. Intravenous fluid administration during the first 24 h (MAP 3.7, MoAP 4.7, and SAP 4.8 L), need for ICU (6%, 23%, 93%), and nutritional support (7%, 51%, 90%) increased significantly with greater AP severity (p < 0.001). One hundred fifty five (39%) patients developed necrotizing AP, of which 41% received prophylactic antibiotics, and 44% underwent pancreatic drainage/debridement. Prophylactic antibiotics (58% vs. 27%) and interventions (63% vs. 27%) were noted more frequently in SAP than MoAP (p < 0.001). Enteral nutrition (18% vs. 30%) and minimally invasive pancreatic interventions (19% vs. 41%) were more commonly used in the late phase (p < 0.05). The overall median length of hospitalization was 7 days reaching 29 days in SAP group. Mortality was 5%; all deaths occurred in SAP group. Conclusions: This study provides an extensive report on clinical management of AP and its trends overtime. Pancreatic intervention is required in less than 50% of patients with necrotizing pancreatitis. Utilization of enteral nutrition and minimally invasive pancreatic interventions has been increasing over time. Published by Elsevier B.V. on behalf of IAP and EPC. C1 [Koutroumpakis, Efstratios; Slivka, Adam; Greer, Julia B.; Whitcomb, David C.; Yadav, Dhiraj; Papachristou, Georgios I.] Univ Pittsburgh, Med Ctr, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15260 USA. [Furlan, Alessandro; Dasyam, Anil K.] Univ Pittsburgh, Med Ctr, Dept Radiol, Div Abdominal Imaging, Pittsburgh, PA 15260 USA. [Dudekula, Anwar] Univ Pittsburgh, Med Ctr, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. [Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Dept Med, Div Gastroenterol, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), UPMC Presbyterian, 200 Lothrop St,3rd Floor, Pittsburgh, PA 15212 USA. EM papachri@pitt.edu FU Veterans Affairs Merit Review Award [PRO00000496] FX The study was supported by a Veterans Affairs Merit Review Award (PRO00000496; PI: G.I.P.). NR 31 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1424-3903 EI 1424-3911 J9 PANCREATOLOGY JI Pancreatology PD JAN-FEB PY 2017 VL 17 IS 1 BP 32 EP 40 DI 10.1016/j.pan.2016.10.011 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EK0RG UT WOS:000393634200008 PM 28341116 ER PT J AU Mukherjee, K Chio, TI Gu, H Banerjee, A Sorrentino, AM Sackett, DL Bane, SL AF Mukherjee, Kamalika Chio, Tak Ian Gu, Han Banerjee, Abhijit Sorrentino, Anthony M. Sackett, Dan L. Bane, Susan L. TI Benzocoumarin Hydrazine: A Large Stokes Shift Fluorogenic Sensor for Detecting Carbonyls in Isolated Biomolecules and in Live Cells SO ACS SENSORS LA English DT Article DE fluorophore; hydrazone; coumarin; bioconjugation; carbonylation; oxidative stress; live cells; microscopy ID OXIDATIVE STRESS; HYDROGEN-PEROXIDE; INTRACELLULAR ACIDIFICATION; PROTEIN CARBONYLATION; PYRUVATE; DYES; AGGREGATION; MECHANISM; PROBES; STATE AB Detection and quantification of biomolecule carbonylation, a critical manifestation of oxidative stress, allows better understanding of associated disease states. Existing approaches for such analyses require further processing of cells and tissues, which leads to loss of both spatial and temporal information about carbonylated biomolecules in cells. Live cell detection of these species requires sensors that are nontoxic, sufficiently reactive with the biocarbonyl in the intracellular milieu, and detectable with commonly available instrumentation. Presented here is a new fluorescent sensor for biomolecule carbonyl detection: a hydrazine derivative of a benzocoumarin, 7-hydrazinyl-4-methyl-2H-benzo[h]chromen-2-one (BzCH), which meets these requirements. This probe is especially well suited for live cell studies. It can be excited by a laser line common to many fluorescence microscopes. The emission maximum of BzCH undergoes a substantial red shift upon hydrazone formation (from similar to 430 to similar to 550 nm), which is the result of fluorophore disaggregation. Additionally, the hydrazone exhibits an exceptionally large Stokes shift (similar to 195 nm). The latter properties eliminate self-quenching of the probe and the need to remove unreacted fluorophore for reliable carbonyl detection. Thus, biomolecule carbonylation can be detected and quantified in cells and in cell extracts in a one-step procedure using this probe. C1 [Mukherjee, Kamalika; Chio, Tak Ian; Gu, Han; Banerjee, Abhijit; Sorrentino, Anthony M.; Bane, Susan L.] SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA. [Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Mukherjee, Kamalika] Harvard Med Sch, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. [Banerjee, Abhijit] Thermax Ltd, Chem Div, 97-E,Gen Block, Pune 411026, Maharashtra, India. RP Bane, SL (reprint author), SUNY Binghamton, Dept Chem, Binghamton, NY 13902 USA. EM sbane@binghamton.edu FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development; NIH [R15 GM-102867]; NSF [CHE-0922815] FX This work was supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and by NIH Grant R15 GM-102867. The Regional NMR Facility (600 MHz instrument) at Binghamton University is supported by NSF(CHE-0922815). The authors thank Mr. David Tuttle for photographing the gels and for expert assistance with image processing, Professor Rebecca Kissling for scientific discussion and assistance with organic synthesis, and Professor Ming An for the generous gift of A549 cells. NR 26 TC 0 Z9 0 U1 9 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 2379-3694 J9 ACS SENSORS JI ACS Sens. PD JAN PY 2017 VL 2 IS 1 BP 128 EP 134 DI 10.1021/acssensors.6b00616 PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Chemistry; Science & Technology - Other Topics GA EJ3CF UT WOS:000393088300017 ER PT J AU Domian, IJ Yu, H Mittal, N AF Domian, Ibrahim J. Yu, Hanry Mittal, Nikhil TI On Materials for Cardiac Tissue Engineering SO ADVANCED HEALTHCARE MATERIALS LA English DT Editorial Material DE cardiac; chamber pressure; materials; stiffness; tissue engineering ID BLOOD-PRESSURE; DILATED CARDIOMYOPATHY; MYOCARDIAL STIFFNESS; PASSIVE STIFFNESS; HEART-DISEASE; WALL STRESS; MODULATION; MECHANICS; VENTRICLE; PRELOAD C1 [Domian, Ibrahim J.; Mittal, Nikhil] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Domian, Ibrahim J.] Harvard Med Sch, Boston, MA 02115 USA. [Yu, Hanry; Mittal, Nikhil] Inst Bioengn & Nanotechnol, Singapore 138669, Singapore. [Yu, Hanry] Singapore MIT Alliance Res & Technol, 1 CREATE Way,10-01 CREATE Tower, Singapore 138602, Singapore. [Yu, Hanry] Natl Univ Hlth Syst, Yong Loo Lin Sch Med, Dept Physiol, Singapore 117597, Singapore. RP Mittal, N (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.; Mittal, N (reprint author), Inst Bioengn & Nanotechnol, Singapore 138669, Singapore. EM nikhil.v.mittal@gmail.com RI Yu, Hanry/C-1031-2013 OI Yu, Hanry/0000-0002-0339-3685 FU Institute of Bioengineering and Nanotechnology (Biomedical Research Council, AstarSTAR, Singapore); Massachusetts General Hospital (Boston, USA) FX This work was supported by the Institute of Bioengineering and Nanotechnology (Biomedical Research Council, AstarSTAR, Singapore) and the Massachusetts General Hospital (Boston, USA). NR 27 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2192-2640 EI 2192-2659 J9 ADV HEALTHC MATER JI Adv. Healthc. Mater. PD JAN PY 2017 VL 6 IS 2 AR UNSP 1600768 DI 10.1002/adhm.201600768 PG 3 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials SC Engineering; Science & Technology - Other Topics; Materials Science GA EK0BC UT WOS:000393590400007 ER PT J AU Butt, H Yetisen, AK Khan, AA Knowles, KM Qasim, MM Yun, SH Wilkinson, TD AF Butt, Haider Yetisen, Ali K. Khan, Ammar A. Knowles, Kevin M. Qasim, Malik M. Yun, Seok Hyun Wilkinson, Timothy D. TI Electrically Tunable Scattering from Devitrite-Liquid Crystal Hybrid Devices SO ADVANCED OPTICAL MATERIALS LA English DT Article ID HOLOGRAPHIC SENSORS; PHOTONIC NANOSENSOR; LIGHT-SCATTERING; LASER-ABLATION; NANOSTRUCTURES; GLASS AB Devitrite is normally an unwanted crystalline impurity in the soda-lime-silica glass making process. Thin needles formed by heterogeneous nucleation of devitrite on the glass surface provide unique birefringence properties for potential applications in tunable optical devices. Here, devitrite and a liquid crystal are combined to create an electrically variable optical diffuser. The magnitude and scattering angle of the transmitted light propagating through the diffuser are tuned by varying the voltage between the graphene and indium tin oxide electrodes on either side of the liquid crystal. The threshold voltage to switch the transmitted light from a predominantly horizontal diffusion to a random order is 3.5 V. Angle-resolved measurements show broad diffusion angles of transmitted light with a maximum deflection of +/- 60 degrees. The dynamically tunable devitrite-liquid crystal hybrid devices may advance the development of currently less viable technologies including beam shaping and automatic light transmission control. C1 [Butt, Haider] Univ Birmingham, Sch Engn, Birmingham B15 2TT, W Midlands, England. [Yetisen, Ali K.; Yun, Seok Hyun] Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.; Yun, Seok Hyun] MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Khan, Ammar A.; Qasim, Malik M.; Wilkinson, Timothy D.] Univ Cambridge, Dept Engn, Ctr Mol Mat Photon & Elect, 9 JJ Thomson Ave, Cambridge CB3 0FA, England. [Knowles, Kevin M.] Univ Cambridge, Dept Mat Sci & Met, 27 Charles Babbage Rd, Cambridge CB3 0FS, England. RP Butt, H (reprint author), Univ Birmingham, Sch Engn, Birmingham B15 2TT, W Midlands, England. EM h.butt@bham.ac.uk OI Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust; Royal Society; EPSRC IAA Follow on Fund FX H.B. and A.K.Y. thank the Leverhulme Trust for research funding. The authors also thank the Royal Society and EPSRC IAA Follow on Fund for supporting this research. The authors thank Dr. Aydin Sabouri, Chern Wong, and Prof. Stephan Hoffman for discussions and research assistance. NR 33 TC 0 Z9 0 U1 2 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA POSTFACH 101161, 69451 WEINHEIM, GERMANY SN 2195-1071 J9 ADV OPT MATER JI Adv. Opt. Mater. PD JAN PY 2017 VL 5 IS 1 AR UNSP 1600414 DI 10.1002/adom.201600414 PG 7 WC Materials Science, Multidisciplinary; Optics SC Materials Science; Optics GA EJ4RD UT WOS:000393203600016 ER PT J AU Roh, MR Park, KH Chung, KY Shin, SJ Rha, SY Tsao, H AF Roh, Mi Ryung Park, Kyu-Hyun Chung, Kee Yang Shin, Sang Joon Rha, Sun Young Tsao, Hensin TI Telomerase reverse transcriptase (TERT) promoter mutations in Korean melanoma patients SO AMERICAN JOURNAL OF CANCER RESEARCH LA English DT Article DE TERT mutation; Korean; melanoma; survival; prognosis AB Telomerase reverse transcriptase (TERT) is the reverse transcriptase component of the telomeric complex, which synthesizes terminal DNA to protect chromosomal ends and to maintain genomic integrity. In melanoma, mutation in TERT promoter region is a common event and theses promoter variants have been shown to be associated with increased gene expression, decreased telomere length and poorer outcome. In this study, we determined the frequency of TERT promoter mutation in 88 Korean primary melanoma patients and aimed to see the association of TERT promoter mutation status to other major molecular features, such as BRAF, NRAS, KIT mutations and correlate with clinicopathological features. In our study, acral melanoma (n=46, 52.3%) was the most common type. Overall, TERT promoter mutation was observed in 15 cases (17%) with ten c. -124C>T altertions and five c. -146C>T alterations. None of our samples showed CC>TT mutation which is considered pathognomonic of UV induction. Among the 46 acral melanoma patients, 5 patients (10.9%) harbored TERT promoter mutation. Tumors with TERT promoter mutation showed significantly greater Breslow thickness compared to WT tumors (P=0.039). A combined analysis for the presence of TERT promoter and BRAF mutations showed that patients with both TERT promoter and BRAF mutation showed decreased survival compared with those with only TERT promoter mutation, only BRAF mutation, or without mutations in either TERT promoter or BRAF (P=0.035). Our data provides additional evidence that UV-induced TERT promoter mutation frequencies vary depending on melanoma subtype, but preserves its prognostic value. C1 [Roh, Mi Ryung; Tsao, Hensin] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA USA. [Roh, Mi Ryung; Chung, Kee Yang] Yonsei Univ, Cutaneous Biol Res Inst, Dept Dermatol, Coll Med, Seoul, South Korea. [Park, Kyu-Hyun; Shin, Sang Joon; Rha, Sun Young] Yonsei Univ, Songdang Inst Canc Res, Yonsei Canc Ctr, Coll Med, Seoul, South Korea. [Shin, Sang Joon; Rha, Sun Young] Yonsei Univ, Dept Internal Med, Div Med Oncol, Coll Med, 50 Yonsei Ro, Seoul 03722, South Korea. RP Rha, SY (reprint author), Yonsei Univ, Dept Internal Med, Div Med Oncol, Coll Med, 50 Yonsei Ro, Seoul 03722, South Korea.; Tsao, H (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. EM RHA7655@yuhs.ac; htsao@mgh.harvard.edu FU NIH [K24 CA149202]; Basic Science Research Program through National Research Foundation of Korea; Ministry of Education, Science, and Technology [2011-0022376]; grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI13C2096] FX This work was made possible by a grant from the NIH (K24 CA149202 to HT), a grant from the Basic Science Research Program through the National Research Foundation of Korea, which is funded by the Ministry of Education, Science, and Technology (2011-0022376 to MRR), a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI13C2096 to SYR) and the generous donors to the MGH Millennium Melanoma Fund and Innovations in Melanoma Care Fund. NR 10 TC 0 Z9 0 U1 0 U2 0 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 2156-6976 J9 AM J CANCER RES JI Am. J. Cancer Res. PY 2017 VL 7 IS 1 BP 134 EP + PG 7 WC Oncology SC Oncology GA EJ4RZ UT WOS:000393205800012 PM 28123854 ER PT J AU Sethi, N Manesh, RS Sperling, A Bresler, SC Connell, NT Tierney, LM AF Sethi, Nilay Manesh, Reza Sedighi Sperling, Adam Bresler, Scott C. Connell, Nathan T. Tierney, Lawrence M. TI Factoring in the missing link SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID LIGHT-CHAIN AMYLOIDOSIS; FACTOR-X DEFICIENCY; SYSTEMIC AMYLOIDOSIS; AL AMYLOIDOSIS; DIAGNOSIS; IMMUNOHISTOCHEMISTRY; BIOPSY C1 [Sethi, Nilay; Sperling, Adam] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. [Manesh, Reza Sedighi] Johns Hopkins Univ, Dept Med, Baltimore, MD USA. [Bresler, Scott C.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Connell, Nathan T.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Connell, Nathan T.] Harvard Med Sch, Dept Med, Boston, MA USA. [Tierney, Lawrence M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Tierney, Lawrence M.] San Francisco Vet Affair Med Ctr, Med Dept, San Francisco, CA USA. RP Sethi, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. EM nilay_sethi@dfci.harvard.edu OI Connell, Nathan/0000-0003-4100-7826 NR 20 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 EI 1096-8652 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2017 VL 92 IS 1 BP 110 EP 113 DI 10.1002/ajh.24501 PG 4 WC Hematology SC Hematology GA EJ7TK UT WOS:000393425300027 PM 27486087 ER PT J AU Fitzsimmons, C Johnstone, D Conant, K St Hillaire, C Parsons, CH Stins, M Moir, R Milward, EA AF Fitzsimmons, Chantel Johnstone, Daniel Conant, Katherine St Hillaire, Coryse Parsons, Carl H. Stins, Monique Moir, Robert Milward, Elizabeth A. TI Soluble lipoprotein receptor-related protein immunoreactive species in cell culture media and serum replacement supplements SO ANALYTICAL METHODS LA English DT Article ID BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; LRP; ENDOCYTOSIS; CLEARANCE; GROWTH; FORM AB The low-density lipoprotein receptor-related protein (LRP) is a large multifunctional cell surface membrane receptor capable of binding over 50 ligands. These include molecules important in Alzheimer's disease such as the amyloid beta-protein precursor (A beta PP), the beta-amyloid (A beta) peptide and apolipoprotein E (ApoE). Full length LRP consists of a 515 kDa extracellular ligand binding alpha-chain and an 85 kDa membrane spanning beta-chain. A soluble form of LRP (sLRP) present in human plasma retains the ability to bind ligands, including A beta. This soluble form is an ectodomain fragment generated from the membrane bound form of the receptor by proteolytic cleavage. Here we report data demonstrating that some commercial 'serum-free' supplements and 'serum-free' media contain unlisted sLRP immunoreactive species that may reflect the presence of undefined serum protein extracts in these 'serum-free' preparations. This has the potential to interfere with experimental results and interpretation in a range of cell culture studies involving LRP or any of its ligands and possibly also other serum proteins. C1 [Fitzsimmons, Chantel; Johnstone, Daniel; Milward, Elizabeth A.] Univ Newcastle, Sch Biomed Sci, Univ Dr, Callaghan, NSW 2308, Australia. [Fitzsimmons, Chantel; Johnstone, Daniel; Milward, Elizabeth A.] Sch Biomed Sci MSB 615, Hunter Med Res Inst, Dept Mol Neurobiol, Univ Dr, Callaghan, NSW 2308, Australia. [Fitzsimmons, Chantel; Conant, Katherine; St Hillaire, Coryse; Stins, Monique] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. [Parsons, Carl H.] Univ Western Sydney, Sch Med, Campbelltown, NSW 2560, Australia. [Moir, Robert] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Fitzsimmons, C (reprint author), Univ Newcastle, Sch Biomed Sci, Univ Dr, Callaghan, NSW 2308, Australia.; Fitzsimmons, C (reprint author), Sch Biomed Sci MSB 615, Hunter Med Res Inst, Dept Mol Neurobiol, Univ Dr, Callaghan, NSW 2308, Australia.; Fitzsimmons, C (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. EM fitzsimmons@newcastle.edu.au NR 15 TC 0 Z9 0 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1759-9660 EI 1759-9679 J9 ANAL METHODS-UK JI Anal. Methods PY 2017 VL 9 IS 1 BP 110 EP 116 DI 10.1039/c6ay02438f PG 7 WC Chemistry, Analytical; Food Science & Technology; Spectroscopy SC Chemistry; Food Science & Technology; Spectroscopy GA EJ3GZ UT WOS:000393101900013 ER PT J AU Toschi, N Kim, J Sclocco, R Duggento, A Barbieri, R Kuo, B Napadow, V AF Toschi, Nicola Kim, Jieun Sclocco, Roberta Duggento, Andrea Barbieri, Riccardo Kuo, Braden Napadow, Vitaly TI Motion sickness increases functional connectivity between visual motion and nausea-associated brain regions SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Article; Proceedings Paper CT Conference on Biology and Control of Nausea and Vomiting CY OCT 23-24, 2015 CL Univ Pittsburgh, Pittsburgh, PA HO Univ Pittsburgh DE Brain-gut interactions; MT+/V5; Brain connectivity; Heart rate variability; Sympathovagal balance ID HEART-RATE-VARIABILITY; SUSCEPTIBILITY; INTEROCEPTION; PAIN AB The brain networks supporting nausea not yet understood. We previously found that while visual stimulation activated primary (V1) and extrastriate visual cortices (MT+/V5, coding for visual motion), increasing nausea was associated with increasing sustained activation in several brain areas, with significant co-activation for anterior insula (aIns) and mid-cingulate (MCC) cortices. Here, we hypothesized that motion sickness also alters functional connectivity between visual motion and previously identified nausea-processing brain regions. Subjects prone to motion sickness and controls completed a motion sickness provocation task during fMRI/ECG acquisition. We studied changes in connectivity between visual processing areas activated by the stimulus (MT +/V5, V1), right alns and MCC when comparing rest (BASELINE) to peak nausea state (NAUSEA). Compared to BASELINE, NAUSEA reduced connectivity between right and left V1 and increased connectivity between right MT +/V5 and alns and between left MT +/V5 and MCC Additionally, the change in MT +/V5 to insula connectivity was significantly associated with a change in sympathovagal balance, assessed by heart rate variability analysis. No state-related connectivity changes were noted for the control group. Increased connectivity between a visual motion processing region and nausea/salience brain regions may reflect increased transfer of visual/vestibular mismatch information to brain regions supporting nausea perception and autonomic processing. We conclude that vection-induced nausea increases connectivity between nausea-processing regions and those activated by the nauseogenic stimulus. This enhanced low-frequency coupling may support continual, slowly evolving nausea perception and shifts toward sympathetic dominance. Disengaging this coupling may be a target for biobehavioral interventions aimed at reducing motion sickness severity. (C) 2016 Elsevier B.V. All rights reserved. C1 [Toschi, Nicola; Kim, Jieun; Sclocco, Roberta; Duggento, Andrea; Napadow, Vitaly] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Toschi, Nicola] Univ Roma Tor Vergata, Dept Biomed & Prevent, Rome, Italy. [Kim, Jieun] KIOM, Daejeon, South Korea. [Sclocco, Roberta; Napadow, Vitaly] Logan Univ, Dept Radiol, Chesterfield, MO USA. [Barbieri, Riccardo] Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. [Barbieri, Riccardo] Politecn Milan, Dept Biomed Engn, Milan, Italy. [Kuo, Braden] Massachusetts Gen Hosp, Ctr Neurointestinal Hlth, GI Unit, Boston, MA 02114 USA. RP Toschi, N (reprint author), Univ Roma Tor Vergata, Dept Biomed & Prevent, Med Phys Sect, Via Montpellier 1, I-00133 Rome, Italy. EM toschi@med.uniroma2.it OI Toschi, Nicola/0000-0003-1929-5833 FU National Institutes of Health [P01-AT006663, R01-AT007550, R01-AR064367, K23-DK069614, R21-AR057920]; National Center for Research Resources [P41RR14075]; Harvard Clinical and Translational Science Center [CRC 1 UL1 RR025758]; MGH Department of Anesthesia, Critical Care and Pain Medicine; International Foundation of Functional Gastrointestinal Disorders FX This work was supported by the National Institutes of Health (grant numbers P01-AT006663, R01-AT007550, and R01-AR064367 to VN, K23-DK069614 to BK, and R21-AR057920 to VN, BK and RB); the National Center for Research Resources (P41RR14075); CRC 1 UL1 RR025758, Harvard Clinical and Translational Science Center; the MGH Department of Anesthesia, Critical Care and Pain Medicine and the International Foundation of Functional Gastrointestinal Disorders. NR 27 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 EI 1872-7484 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD JAN PY 2017 VL 202 SI SI BP 108 EP 113 DI 10.1016/j.autneu.2016.10.003 PG 6 WC Neurosciences SC Neurosciences & Neurology GA EJ5GD UT WOS:000393244900015 PM 28245927 ER PT J AU Mayer, M Ortmaier, R Koller, H Koller, J Hitzl, W Auffarth, A Resch, H von Keudell, A AF Mayer, M. Ortmaier, R. Koller, H. Koller, J. Hitzl, W. Auffarth, A. Resch, H. von Keudell, A. TI Impact of Sagittal Balance on Clinical Outcomes in Surgically Treated T12 and L1 Burst Fractures: Analysis of Long-Term Outcomes after Posterior-Only and Combined Posteroanterior Treatment SO BIOMED RESEARCH INTERNATIONAL LA English DT Article ID MORRIS DISABILITY QUESTIONNAIRE; SHORT-SEGMENT FIXATION; THORACOLUMBAR FRACTURES; FOLLOW-UP; NEUROLOGICAL DEFICIT; DEFORMITY SURGERY; COMBINED ANTERIOR; SPINAL DEFORMITY; LUMBAR SPINE; BACK-PAIN AB Objective. Long-term radiological and clinical outcome retrospective study of surgical treatment for T12 and L1 burst fractures in perspective of sagittal balance measures. Methods. Patients with age of 16-60 years, complete radiographs, early surgical treatment surgery, and follow-up (F/U) > 18 months were included and strict exclusion criteria applied. Regional and thoracolumbar kyphosis angles (RKA and TLA) were measured preoperatively and at final F/U, as were parameters of the spinopelvic sagittal alignment. Clinical outcomes were assessed using validated measures. Results. 36 patients with age mean age of 39 years and F/U of 69 months were included. 61% of patients were treated with bisegmental posterior instrumentation (POST-I) and 39% with combined posteroanterior instrumented fusion (PA-F). At F/U, several indicators for clinical outcomes showed a significant correlation with radiographic measures in the overall cohort with inferior clinical outcomes corresponding with increasing residual deformity and sagittal malalignment. Statistical analysis failed to reach level of significance for the differences between POST-I and PA-F group at final F/U. Only a strong trend towards better restoration of the thoracolumbar alignment was observed for the PA-F group in terms of the RKA and TLA. Conclusions. Results in a surgically treated cohort of T12 and L1 burst fracture patients indicate that superior clinical outcomes depend on restoration of sagittal alignment. C1 [Mayer, M.; Koller, H.; Koller, J.] Schoen Clin Nuernberg Fuerth, Spinal Surg Ctr, Europa Allee 1, D-90763 Furth, Germany. [Ortmaier, R.; Auffarth, A.; Resch, H.] Paracelsus Med Univ Salzburg, Dept Traumatol & Sports Injuries, Muellner Hauptstr 48, A-5020 Salzburg, Austria. [Hitzl, W.] Paracelsus Med Univ Salzburg, Res Off & Biostat, Strubergasse 21, A-5020 Salzburg, Austria. [von Keudell, A.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Combined Orthopaed Surg Program, 55 Fruit St, Boston, MA 02114 USA. RP Mayer, M (reprint author), Schoen Clin Nuernberg Fuerth, Spinal Surg Ctr, Europa Allee 1, D-90763 Furth, Germany. EM mayermichi@yahoo.de NR 51 TC 0 Z9 0 U1 0 U2 0 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2314-6133 EI 2314-6141 J9 BIOMED RES INT JI Biomed Res. Int. PY 2017 AR 1568258 DI 10.1155/2017/1568258 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA EK6IT UT WOS:000394029000001 ER PT J AU San-Juan, D Lopez, DAE Gregorio, RV Trenado, C Aragon, MFG Morales-Quezada, L Ruiz, AH Hernandez-Gonzalez, F Alcaraz-Guzman, A Anschel, DJ Fregni, F AF San-Juan, Daniel Espinoza Lopez, Dulce Anabel Vazquez Gregorio, Rafael Trenado, Carlos Fernandez-Gonzalez Aragon, Maricarmen Morales-Quezada, Leon Hernandez Ruiz, Axel Hernandez-Gonzalez, Flavio Alcaraz-Guzman, Alejandro Anschel, David J. Fregni, Felipe TI Transcranial Direct Current Stimulation in Mesial Temporal Lobe Epilepsy and Hippocampal Sclerosis SO BRAIN STIMULATION LA English DT Article DE Transcranial direct current stimulation (tDCS); Mesial temporal lobe epilepsy (MTLE); Hippocampal sclerosis (HS) ID HUMAN MOTOR CORTEX; EXCITABILITY SHIFTS; DC POLARIZATION; CLINICAL-TRIAL; HUMAN BRAIN; MECHANISMS; MODULATION; HUMANS; PLASTICITY; DISEASE AB Background: Transcranial direct current stimulation (tDCS) has been evaluated in medication refractory epilepsy patients. The results have been inconclusive and protocols have varied between studies. Objective: To evaluate the safety and efficacy of two protocols of tDCS in adult patients with mesial temporal lobe epilepsy and hippocampal sclerosis (MTLE-HS). Methods: This is a randomized placebo-controlled, double-blinded clinical trial, with 3 arms, 3 sessions, 5 sessions and placebo stimulation. Frequency of seizures(SZs), interictal epileptiform discharges (IEDs) and adverse effects (AEs) were registered before and after treatment, and at 30 and 60 days follow-up. Descriptive statistics, k-related samples, Friedman's test, and relative risk (RR) estimation were used for analysis. Results: We included twenty-eight subjects (3d n = 12, 5d n = 8, placebo n = 8), 16/28 (57%) men, age 37.8(+/- 10.9) years old. There was a significant reduction of the frequency of SZs at one (p = 0.001) and two (p = 0.0001) months following cathodal tDCS compared to baseline in the 3 arms (p = 0.0001). The mean reduction of SZ frequency at two months in both active groups was significantly higher than placebo (-48% vs. -6.25%, p < 0.008). At 3 days (-43.4% vs. -6.25%, p < 0.007) and 5 days (-54.6% vs. -6.25%, p < 0.010) individual groups showed a greater reduction of SZs. A significant IED reduction effect was found between baseline and immediately after interventions (p = 0.041) in all groups. Side effects were minor. Conclusions: Cathodal tDCS technique of 3 and 5 sessions decreased the frequency of SZs and IEDs (between baseline and immediately post-tDCS) in adult patients with MTLE-HS compared to placebo tDCS. (C) 2016 Elsevier Inc. All rights reserved. C1 [San-Juan, Daniel; Espinoza Lopez, Dulce Anabel; Vazquez Gregorio, Rafael; Fernandez-Gonzalez Aragon, Maricarmen] Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Clin Neurophysiol, Av Insurgentes 3877, Tlalpan 14269, Ciudad De Mexic, Mexico. [San-Juan, Daniel] Dresden Int Univ, Div Hlth Care Sci, Ctr Clin Res & Management Educ, Freiberger Str 37, D-01067 Dresden, Germany. [Trenado, Carlos] Univ Hosp Dusseldorf, Inst Clin Neurosci & Med Psychol, Moorenstr 5, D-40225 Dusseldorf, Germany. [Morales-Quezada, Leon; Fregni, Felipe] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Lab Neuromodulat, 125 Nashua St, Boston, MA 02114 USA. [Morales-Quezada, Leon; Fregni, Felipe] Harvard Med Sch, Massachusetts Gen Hosp, 125 Nashua St, Boston, MA 02114 USA. [Morales-Quezada, Leon] Harvard Med Sch, Program Placebo Studies, Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. [Hernandez Ruiz, Axel] Natl Polytech Inst, Super Sch Med, Av Salvador Diaz Miron Esq, Miguel Hidalgo 11340, Ciudad De Mexic, Mexico. [Hernandez-Gonzalez, Flavio] Autonomous Univ Aguascalientes, Super Sch Med, Av Univ 940,Ciudad Univ, Aguascalientes 20131, Aguascalientes, Mexico. [Alcaraz-Guzman, Alejandro] Univ Colima, Super Sch Med, Av Univ 333, Colima 28040, Colima, Mexico. [Anschel, David J.] St Charles Hosp, Comprehens Epilepsy Ctr Long Isl, Port Jefferson, NY USA. RP San-Juan, D (reprint author), Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Clin Neurophysiol, Av Insurgentes 3877, Tlalpan 14269, Ciudad De Mexic, Mexico.; San-Juan, D (reprint author), Dresden Int Univ, Div Hlth Care Sci, Ctr Clin Res & Management Educ, Freiberger Str 37, D-01067 Dresden, Germany. EM pegaso31@yahoo.com NR 43 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2017 VL 10 IS 1 BP 28 EP 35 DI 10.1016/j.brs.2016.08.013 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EJ5JO UT WOS:000393254500003 PM 27693237 ER PT J AU Caulfield, KA Bernstein, MH Stern, AP Pascual-Leone, A Press, DZ Fox, MD AF Caulfield, Kevin A. Bernstein, Margo H. Stern, Adam P. Pascual-Leone, Alvaro Press, Daniel Z. Fox, Michael D. TI Antidepressant Effect of Low-Frequency Right-Sided rTMS in Two Patients with Left Frontal Stroke SO BRAIN STIMULATION LA English DT Letter ID TRANSCRANIAL MAGNETIC STIMULATION; DEPRESSION C1 [Caulfield, Kevin A.] Med Univ South Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. [Caulfield, Kevin A.; Bernstein, Margo H.; Stern, Adam P.; Pascual-Leone, Alvaro; Press, Daniel Z.; Fox, Michael D.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Brain Stimulat, Dept Neurol, Boston, MA USA. [Stern, Adam P.; Pascual-Leone, Alvaro; Press, Daniel Z.; Fox, Michael D.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Neurol, Div Cognit Neurol, Boston, MA USA. [Fox, Michael D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Fox, Michael D.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Fox, MD (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,KS-158, Boston, MA 02215 USA. EM foxmdphd@gmail.com NR 11 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2017 VL 10 IS 1 BP 150 EP 151 DI 10.1016/j.brs.2016.10.002 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EJ5JO UT WOS:000393254500018 PM 28104083 ER PT J AU Badran, BW Austelle, CW Smith, NR Glusman, CE Froeliger, B Garland, EL Borckardt, JJ George, MS Short, B AF Badran, Bashar W. Austelle, Chris W. Smith, Nicole R. Glusman, Chloe E. Froeliger, Brett Garland, Eric L. Borckardt, Jeffrey J. George, Mark S. Short, Baron TI A Double-Blind Study Exploring the Use of Transcranial Direct Current Stimulation (tDCS) to Potentially Enhance Mindfulness Meditation (E-Meditation) SO BRAIN STIMULATION LA English DT Letter C1 [Badran, Bashar W.; Austelle, Chris W.; Smith, Nicole R.; Glusman, Chloe E.; Borckardt, Jeffrey J.; George, Mark S.; Short, Baron] Med Univ South Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. [Badran, Bashar W.; Austelle, Chris W.; Froeliger, Brett; George, Mark S.] Med Univ South Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ South Carolina, Coll Med, Charleston, SC 29425 USA. [Froeliger, Brett] MUSC, Hollings Canc Ctr, Charleston, SC USA. [Garland, Eric L.] Univ Utah, Salt Lake City, UT USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Badran, BW (reprint author), MUSC Inst Psychiat, 67 President St,504N, Charleston, SC 29425 USA. EM basharwbadran@gmail.com FU MUSC Brain Stimulation Laboratory FX BWB is supported by the MUSC Brain Stimulation Laboratory and would like to thank Huda Nassori, William Stubbeman, and Zoe Fan for their early support and inspiration. NR 10 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 1935-861X EI 1876-4754 J9 BRAIN STIMUL JI Brain Stimul. PD JAN-FEB PY 2017 VL 10 IS 1 BP 152 EP 154 DI 10.1016/j.brs.2016.09.009 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EJ5JO UT WOS:000393254500019 PM 27839723 ER PT J AU Mashaghi, A Hong, JX Chauhan, SK Dana, R AF Mashaghi, Alireza Hong, Jiaxu Chauhan, Sunil K. Dana, Reza TI Ageing and ocular surface immunity SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Review ID DRY EYE DISEASE; AGE-RELATED-CHANGES; REGULATORY T-CELLS; VIVO CONFOCAL MICROSCOPY; INTERFERON-GAMMA; DESICCATING STRESS; SJOGRENS-SYNDROME; DENDRITIC CELLS; LACRIMAL KERATOCONJUNCTIVITIS; PROINFLAMMATORY CYTOKINES AB The prevalence of ocular surface immunopathologies is enhanced in the elderly. This increased prevalence has been attributed to age-related dysregulation of innate and adaptive immune system responses. Age-related changes in ocular surface immunity have similar and distinct characteristics to those changes seen in other mucosal tissues. This mini review provides a brief outline of key findings in the field of ocular ageing, draws comparisons with other mucosal tissues and, finally, discusses age-related changes in the context of immunopathogenesis of infectious keratitis and dry eye disease, two of the most common inflammatory disorders of the ocular surface. C1 [Mashaghi, Alireza; Hong, Jiaxu; Chauhan, Sunil K.; Dana, Reza] Harvard Med Sch, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, 20 Staniford St, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Med Sch, Schepens Eye Res Inst, Massachusetts Eye & Ear Infirm, 20 Staniford St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu FU National Institute of Health [EY020889, EY024602] FX Supported in part by National Institute of Health grants EY020889 (RD) and EY024602 (SKC). NR 89 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 EI 1468-2079 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JAN PY 2017 VL 101 IS 1 BP 1 EP 5 DI 10.1136/bjophthalmol-2015-307848 PG 5 WC Ophthalmology SC Ophthalmology GA EJ6BP UT WOS:000393303800001 PM 27378485 ER PT J AU Izar, B Regan, MM McDermott, DF AF Izar, Benjamin Regan, Meredith M. McDermott, David F. TI Clinical Trial Design and Endpoints for Stage IV Melanoma in the Modern Era SO CANCER JOURNAL LA English DT Review DE Clinical trial design; immunotherapy; melanoma; targeted therapy; treatment-free interval; treatment-free survival ID RENAL-CELL CARCINOMA; PHASE-III TRIAL; METASTATIC MELANOMA; MEK INHIBITION; UNTREATED MELANOMA; IMPROVED SURVIVAL; COMBINED BRAF; IPILIMUMAB; NIVOLUMAB; CANCER AB Immunotherapies and targeted therapies for the treatment of metastatic or advancedmelanoma produce unique patterns of antitumor response. Conventional outcome measures, such as median progression-free and overall survival, may not be ideally suited to identify all patients who derive a benefit from such therapies. Therefore, the introduction of additional endpoint measures, such as milestone comparisons, may be necessary to characterize the potential benefit of such treatment approaches. Immune checkpoint inhibitors induce durable responses in a portion of patients that may continue after treatment cessation. Measuring the associated treatment-free interval, treatment-free survival, and associated patientreported outcomes could provide important information when implemented in prospective clinical trials. In this article, we discuss the limitations of current endpoint measures and the potential advantage of using novel endpoints and how these might be used in designing clinical trials to address critical unanswered questions for patients with metastatic melanoma. C1 [Izar, Benjamin; McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Izar, Benjamin; Regan, Meredith M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Izar, Benjamin; Regan, Meredith M.; McDermott, David F.] Dana Farber Harvard Canc Ctr, Boston, MA USA. [Izar, Benjamin] Broad Inst MIT & Harvard, Cambridge, MA USA. [Regan, Meredith M.] Harvard Med Sch, Boston, MA USA. RP McDermott, DF (reprint author), Beth Israel Deaconess Med Ctr, Cutaneous Oncol Programs, MASCO Bldg,375 Longwood Ave, Boston, MA 02215 USA. EM dmcdermo@bidmc.harvard.edu FU Veridex; OncoGenex; Novartis; Pfizer; Ipsen; Merck; Ferring; Celgene; AstraZeneca; Pierre-Fabre; Kidney Cancer Research, Prometheus FX M.M.R. has received research funding from Veridex, OncoGenex. She is a consultant and an advisor of Ipsen, Merck, BMS. Member of the International Breast Cancer Study Group receiving research funding and/or provision of drug supply for clinical trials from Novartis, Pfizer, Ipsen, Merck, Ferring, Celgene, AstraZeneca, Pierre-Fabre. D.F.M. is a consultant for Kidney Cancer Research of BMS, Pfizer, Merck, Novartis, Eisai, Exelixis, Array BioPharm, Genentech BioOncology; has received research support from Kidney Cancer Research, Prometheus. The remaining author have no conflict of interest and nothing to disclose. NR 37 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 1528-9117 EI 1540-336X J9 CANCER J JI Cancer J. PD JAN-FEB PY 2017 VL 23 IS 1 BP 63 EP 67 PG 5 WC Oncology SC Oncology GA EJ7RC UT WOS:000393418900009 PM 28114257 ER PT J AU Jiang, J Gui, F He, ZX Li, L Li, YZ Li, SY Wu, XR Deng, Z Sun, XH Huang, XX Huang, W Han, S Zhang, T Wang, Z Jiao, B Song, SY Wang, HR Chen, LF Zhou, DW Liu, Q Ren, RB Zhang, JM Deng, XM AF Jiang, Jie Gui, Fu He, Zhixiang Li, Li Li, Yunzhan Li, Shunying Wu, Xinrui Deng, Zhou Sun, Xihuan Huang, Xiaoxing Huang, Wei Han, Shang Zhang, Ting Wang, Zheng Jiao, Bo Song, Siyang Wang, Hongrui Chen, Lanfen Zhou, Dawang Liu, Qiang Ren, Ruibao Zhang, Jianming Deng, Xianming TI Targeting BRK-Positive Breast Cancers with Small-Molecule Kinase Inhibitors SO CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; TYROSINE KINASE; BCR-ABL; TUMOR KINASE; LUNG-CANCER; DISCOVERY; MUTATION; RESISTANCE; EXPRESSION; MUTANT AB Approximately 80% of breast cancers overexpress the kinase breast tumor kinase ( BRK)/protein tyrosine kinase 6, which has various oncogenic roles in breast cancer cell proliferation, survival, and migration. However, BRK inhibitors have yet to be explored as possible therapeutic tools. In this study, we used a parallel compound-centric approach to discover a new class of pharmaceutical agents, exemplified by XMU-MP-2, as potent and selective BRK inhibitors. XMU-MP-2 exhibited target-specific inhibition of BRK kinase activity and disrupted signaling path-ways mediated by this activity, thereby reducing proliferation in BRK-positive breast cancer cells. In mouse xenograft models, XMU-MP-2 repressed the growth of tumors driven by oncogenic BRK, including BRK-transformed Ba/F3 cells and BRK-positive breast cancer cells. Notably, XMU-MP-2 cooperated strongly with HER2 inhibitor or ER blockade to block breast cancer cell proliferation in vitro and in vivo. Overall, our findings offer a preclinical proof of concept for therapeutic targeting of the BRK kinase in breast cancer. (C) 2016 AACR. C1 [Jiang, Jie; Gui, Fu; He, Zhixiang; Li, Li; Li, Yunzhan; Wu, Xinrui; Deng, Zhou; Sun, Xihuan; Huang, Xiaoxing; Huang, Wei; Han, Shang; Zhang, Ting; Wang, Zheng; Song, Siyang; Wang, Hongrui; Chen, Lanfen; Zhou, Dawang; Deng, Xianming] Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen, Fujian, Peoples R China. [Li, Shunying; Liu, Qiang] Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou, Guangdong, Peoples R China. [Jiao, Bo; Ren, Ruibao] Shanghai Jiao Tong Univ, State Key Lab Med Genom, Collaborat Innovat Ctr Hematol,Ruijin Hosp,Sch Me, Shanghai Inst Hematol,Collaborat Innovat Ctr Syst, Shanghai, Peoples R China. [Ren, Ruibao] Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. [Zhang, Jianming] Harvard Med Sch, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA USA. RP Deng, XM (reprint author), Xiamen Univ, South Xiangan Rd, Xiamen 361102, Peoples R China.; Zhang, JM (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02129 USA.; Ren, RB (reprint author), Brandeis Univ, Waltham, MA 02453 USA. EM ren@brandeis.edu; Jzhang14@mgh.harvard.edu; xmdeng@xmu.edu.cn FU National Natural Science Foundation of China [81422045, U1405223, 21272195, 81230055, 21402165, 81603131]; China's 1000 Young Talents Program; Fundamental Research Funds for the Central Universities of China [2013121032, 20720160064] FX This work was supported by grants from the National Natural Science Foundation of China (nos. 81422045, U1405223, and 21272195 to X. Deng, 81230055 to R. Ren, 21402165 to W. Huang, and 81603131 to L. Li), the China's 1000 Young Talents Program to X. Deng, and the Fundamental Research Funds for the Central Universities of China (nos. 2013121032 and 20720160064 to X. Deng). NR 50 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2017 VL 77 IS 1 BP 175 EP 186 DI 10.1158/0008-5472.CAN-16-1038 PG 12 WC Oncology SC Oncology GA EJ4LF UT WOS:000393187900016 PM 27758886 ER PT J AU Eisfeld, AK Kohlschmidt, J Mrozek, K Volinia, S Blachly, JS Nicolet, D Oakes, C Kroll, K Orwick, S Carroll, AJ Stone, RM Byrd, JC de la Chapelle, A Bloomfield, CD AF Eisfeld, Ann-Kathrin Kohlschmidt, Jessica Mrozek, Krzysztof Volinia, Stefano Blachly, James S. Nicolet, Deedra Oakes, Christopher Kroll, Karl Orwick, Shelley Carroll, Andrew J. Stone, Richard M. Byrd, John C. de la Chapelle, Albert Bloomfield, Clara D. TI Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR; GROUP-B; CYTOGENETIC ABNORMALITIES; RECURRENT MUTATIONS; CANCER; MALIGNANCIES; CHROMOSOME-7; SPECTRUM; THERAPY; DISORDERS AB Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressors. Gene mutations in the chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had less mutations in the methylation and spliceosome groups compared with patients >= 60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients >= 60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate ( P = 0.03). RNA sequencing revealed distinct gene and miRNA expression patterns between the sole - 7 and non -7 AML cases, with reduced expression, as expected, of many genes and miRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients. (C) 2016 AACR. C1 [Eisfeld, Ann-Kathrin; Kohlschmidt, Jessica; Mrozek, Krzysztof; Nicolet, Deedra; de la Chapelle, Albert; Bloomfield, Clara D.] Ohio State Univ, Ctr Comprehens Canc, Biomed Res Tower,Room 850G,460 West 12th Ave, Columbus, OH 43210 USA. [Kohlschmidt, Jessica; Nicolet, Deedra] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. [Volinia, Stefano] Univ Ferrara, Dept Morphol Surg & Expt Med, Ferrara, Italy. [Blachly, James S.; Oakes, Christopher; Kroll, Karl; Orwick, Shelley; Byrd, John C.] Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Carroll, Andrew J.] Univ Alabama Birmingham, Birmingham, AL USA. [Stone, Richard M.] Dana Farber Partners CancerCare, Boston, MA USA. RP Eisfeld, AK; Bloomfield, CD (reprint author), Ohio State Univ, Ctr Comprehens Canc, Biomed Res Tower,Room 850G,460 West 12th Ave, Columbus, OH 43210 USA. EM ann-kathrin.eisfeld@osumc.edu; clara.bloomfield@osumc.edu FU NCI [CA101140, CA140158, CA180861, CA196171, CA016058, CA180821, CA180882, CA077658]; Coleman Leukemia Research Foundation; Pelotonia Fellowship Program FX This work was supported in part by the NCI (grants CA101140, CA140158, CA180861, CA196171, CA016058, CA180821, CA180882, and CA077658), the Coleman Leukemia Research Foundation, the Pelotonia Fellowship Program (A.-K. Eisfeld), and by an allocation of computing resources from The Ohio Supercomputer Center. NR 51 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2017 VL 77 IS 1 BP 207 EP 218 DI 10.1158/0008-5472.CAN-16-1386 PG 12 WC Oncology SC Oncology GA EJ4LF UT WOS:000393187900019 PM 27784745 ER PT J AU Chatterjee, NA Shah, RV Murthy, VL Praestgaard, A Shah, SJ Ventetuolo, CE Barr, RG Kronmal, R Lima, JAC Bluemke, DA Jerosch-Herold, M Alonso, A Kawut, SM AF Chatterjee, Neal A. Shah, Ravi V. Murthy, Venkatesh L. Praestgaard, Amy Shah, Sanjiv J. Ventetuolo, Corey E. Barr, R. Graham Kronmal, Richard Lima, Joao A. C. Bluemke, David A. Jerosch-Herold, Michael Alonso, Alvaro Kawut, Steven M. TI Right Ventricular Structure and Function Are Associated With Incident Atrial Fibrillation MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle) SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; heart failure; heart ventricles; magnetic resonance imaging ID PULMONARY ARTERIAL-HYPERTENSION; SUCCESSFUL CATHETER ABLATION; PRESERVED EJECTION FRACTION; C-REACTIVE PROTEIN; HEART-FAILURE; SYSTOLIC FUNCTION; SEX-HORMONES; RISK-FACTORS; SLEEP-APNEA; PREVALENCE AB Background-Right ventricular (RV) morphology has been associated with drivers of atrial fibrillation (AF) risk, including left ventricular and pulmonary pathology, systemic inflammation, and neurohormonal activation. The aim of this study was to investigate the association between RV morphology and risk of incident AF. Methods and Results-We interpreted cardiac magnetic resonance imaging in 4204 participants free of clinical cardiovascular disease in the MESA (Multi-Ethnic Study of Atherosclerosis). Incident AF was determined using hospital discharge records, study electrocardiograms, and Medicare claims data. The study sample (n=3819) was 61 +/- 10 years old and 47% male with 47.2% current/former smokers. After adjustment for demographics and clinical factors, including incident heart failure, higher RV ejection fraction (hazard ratio, 1.16 per SD; 95% confidence interval, 1.03-1.32; P=0.02) and greater RV mass (hazard ratio, 1.25 per SD; 95% confidence interval, 1.08-1.44; P=0.002) were significantly associated with incident AF. After additional adjustment for the respective left ventricular parameter, higher RV ejection fraction remained significantly associated with incident AF (hazard ratio, 1.15 per SD; 95% confidence interval, 1.01-1.32; P=0.04), whereas the association was attenuated for RV mass (hazard ratio, 1.16 per SD; 95% confidence interval, 0.99-1.35; P=0.07). In a subset of patients with available spirometry (n=2540), higher RV ejection fraction and mass remained significantly associated with incident AF after additional adjustment for lung function (P=0.02 for both). Conclusions-Higher RV ejection fraction and greater RV mass were associated with an increased risk of AF in a multiethnic population free of clinical cardiovascular disease at baseline. C1 [Jerosch-Herold, Michael] Brigham & Womens Hosp, Div Radiol, 75 Francis St, Boston, MA 02115 USA. [Chatterjee, Neal A.; Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Nucl Med & Mol Imaging, Ann Arbor, MI 48109 USA. [Praestgaard, Amy; Kawut, Steven M.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kawut, Steven M.] Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA. [Kawut, Steven M.] Univ Penn, Perelman Sch Med, Pulm Allergy & Crit Care Div, Dept Med, Philadelphia, PA 19104 USA. [Shah, Sanjiv J.] Northwestern Univ, Feinberg Sch Med, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Ventetuolo, Corey E.] Brown Univ, Alpert Med Sch, Dept Med & Hlth Serv Policy & Practice, Providence, RI 02912 USA. [Barr, R. Graham] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA. [Kronmal, Richard] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA. [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA. [Alonso, Alvaro] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. RP Kawut, SM (reprint author), Univ Penn, Pulm Vasc Dis Program, Perelman Sch Med, 718 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kawut@upenn.edu FU National Heart, Lung, and Blood Institute [T-32 HL-007575]; National Institutes of Health [R01-HL086719, R01-HL077612, K24-HL103844, N01-HC95159, N01-HC95160, N01-HC95161, N01-HC95162, N01-HC95163, N01-HC95164, N01-HC95165, N01-HC95166, N01-HC95167, N01-HC95168, N01-HC95169] FX Dr Chatterjee was supported by National Heart, Lung, and Blood Institute T-32 HL-007575 which does not represent a relevant disclosure but does support time for writing. This study was funded by National Institutes of Health R01-HL086719, R01-HL077612, K24-HL103844, and N01-HC95159 through N01-HC95169. NR 49 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JAN PY 2017 VL 10 IS 1 AR e004738 DI 10.1161/CIRCEP.116.004738 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EJ4IF UT WOS:000393179400010 ER PT J AU Link, MS Giugliano, RP Ruff, CT Scirica, BM Huikuri, H Oto, A Crompton, AE Murphy, SA Lanz, H Mercuri, MF Antman, EM Braunwald, E AF Link, Mark S. Giugliano, Robert P. Ruff, Christian T. Scirica, Benjamin M. Huikuri, Heikke Oto, Ali Crompton, Andrea E. Murphy, Sabina A. Lanz, Hans Mercuri, Michele F. Antman, Elliott M. Braunwald, Eugene CA ENGAGE AF-TIMI 48 Investigators TI Stroke and Mortality Risk in Patients With Various Patterns of Atrial Fibrillation Results From the ENGAGE AF-TIMI 48 Trial (Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) SO CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; bleeding; mortality; stroke; thromboembolism ID ASSOCIATION TASK-FORCE; PRACTICE GUIDELINES; AMERICAN-COLLEGE; WARFARIN; PERSISTENT; MANAGEMENT; EDOXABAN; THERAPY; UPDATE AB Background-Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial. In ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48), the factor Xa inhibitor edoxaban was noninferior to warfarin in preventing stroke or systemic embolic events and significantly reduced bleeding and cardiovascular mortality. However, detailed analyses by AF pattern have not been reported. Methods and Results-The 21 105 patients were categorized as having paroxysmal (<7 days duration), persistent (>= 7 days but <1 year), or permanent (>= 1 year or failed cardioversion) AF patterns at randomization. Efficacy and safety outcomes were evaluated during the 2.8 years median follow-up and compared by AF pattern. The primary end point of stroke/systemic embolic event was lower in those patients with paroxysmal AF (1.49%/year), compared with persistent (1.83%/year; P-adj =0.015) and permanent AF (1.95%/year; P-adj =0.004). Overall, all-cause mortality also was lower with paroxysmal (3.0%/year) compared with persistent (4.4%/year; P-adj <0.001) and permanent AF (4.4%/year; P-adj <0.001). Annualized major bleeding rates were similar across AF patterns (2.86% versus 2.65% versus 2.73%). There was no effect modification by treatment assignment. Conclusions-In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF. The efficacy and safety profile of edoxaban as compared with warfarin was consistent across the 3 patterns of AF. C1 [Link, Mark S.] UTSouthwestern Med Ctr, Dept Med, Dallas, TX USA. [Giugliano, Robert P.; Ruff, Christian T.; Scirica, Benjamin M.; Crompton, Andrea E.; Murphy, Sabina A.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. [Huikuri, Heikke] Univ Oulu, Dept Med, Oulu, Finland. [Huikuri, Heikke] Oulu Univ Hosp, Oulu, Finland. [Oto, Ali] Heart & Hlth Fdn Turkey, Ankara, Turkey. [Lanz, Hans] Daiichi Sankyo Pharma Dev, Munich, Germany. [Mercuri, Michele F.] Daiichi Sankyo Pharma Dev, Edison, NJ USA. RP Link, MS (reprint author), UTSouthwestern Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM mark.link@UTSouthwestern.edu FU Daiichi-Sankyo Pharma Inc FX Daiichi-Sankyo Pharma Inc funded the ENGAGE AF-TIMI 48 trial. NR 23 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1941-3149 EI 1941-3084 J9 CIRC-ARRHYTHMIA ELEC JI Circ.-Arrhythmia Electrophysiol. PD JAN PY 2017 VL 10 IS 1 AR e004267 DI 10.1161/CIRCEP.116.004267 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EJ4IF UT WOS:000393179400003 ER PT J AU Davey, RA Russell, PK Fam, BC Mangiafico, S Clarke, MV Andrikopoulos, S Wiren, KM Zajac, JD AF Davey, Rachel A. Russell, Patricia K. Fam, Barbara C. Mangiafico, Salvatore Clarke, Michele V. Andrikopoulos, Sof Wiren, Kristine M. Zajac, Jeffrey D. TI Androgens act via the Androgen Receptor (AR) in progenitor cells residing within the bone marrow to reduce fat mass in male mice SO CLINICAL ENDOCRINOLOGY LA English DT Meeting Abstract C1 [Davey, Rachel A.; Russell, Patricia K.; Fam, Barbara C.; Mangiafico, Salvatore; Clarke, Michele V.; Andrikopoulos, Sof; Zajac, Jeffrey D.] Univ Melbourne, Dept Med, Austin Hlth, Heidelberg, Vic, Australia. [Wiren, Kristine M.] Portland VA Med Ctr, Bone & Mineral Res Unit, Portland, OR USA. [Wiren, Kristine M.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 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 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2017 VL 86 SU S1 MA 74 BP 6 EP 6 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EJ8DB UT WOS:000393453600017 ER PT J AU Haddad, R Schlumberger, M Wirth, LJ Sherman, EJ Shah, MH Robinson, B Dutcus, CE Young, L Teng, A Gianoukakis, A Sherman, SI AF Haddad, Robert Schlumberger, Martin Wirth, Lori J. Sherman, Eric J. Shah, Manisha H. Robinson, Bruce Dutcus, Corina E. Young, Louise Teng, Angela Gianoukakis, Andrew Sherman, Steven I. TI Incidence and timing of common adverse events in lenvatinib-treated patients with radioiodine-refractory thyroid cancer from the SELECT trial SO CLINICAL ENDOCRINOLOGY LA English DT Meeting Abstract C1 [Haddad, Robert] Harvard Med Sch, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA USA. [Schlumberger, Martin] Gustave Roussy & Univ Paris Sud, Dept Nucl Med & Endocrine Oncol, Villejuif, France. [Wirth, Lori J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Sherman, Eric J.] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Shah, Manisha H.] Ohio State Univ, Dept Internal Med, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Robinson, Bruce] Univ Sydney, Kolling Inst Med Res, Sydney, NSW, Australia. [Dutcus, Corina E.; Teng, Angela] Eisai Inc, Dept Med, Woodcliff Lake, NJ USA. [Young, Louise] Eisai Australia Pty Ltd, Dept Med, Melbourne, Vic, Australia. [Gianoukakis, Andrew] Harbor UCLA Med Ctr, Div Endocrinol & Metab, Torrance, CA 90509 USA. [Sherman, Steven I.] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Div Internal Med, Houston, TX 77030 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 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2017 VL 86 SU S1 MA 427 BP 68 EP 68 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EJ8DB UT WOS:000393453600174 ER PT J AU Dichtel, LE Schorr, M Gill, CM Economopoulos, KP Gerweck, AV Swearingen, B Hodin, R Bredella, MA Miller, KK AF Dichtel, Laura E. Schorr, Melanie Gill, Corey M. Economopoulos, Konstantinos P. Gerweck, Anu V. Swearingen, Brooke Hodin, Richard Bredella, Miriam A. Miller, Karen K. TI Body composition in pituitary, adrenal and iatrogenic Cushing's syndrome and effects of DHEAS levels SO CLINICAL ENDOCRINOLOGY LA English DT Letter ID TISSUE DISTRIBUTION; DISEASE; FAT C1 [Dichtel, Laura E.; Schorr, Melanie; Miller, Karen K.] Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02115 USA. [Gill, Corey M.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Economopoulos, Konstantinos P.; Hodin, Richard] Harvard Med Sch, Massachusetts Gen Hosp, Dept Gen Surg, Boston, MA USA. [Gerweck, Anu V.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. [Swearingen, Brooke] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Bredella, Miriam A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Dichtel, LE (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02115 USA. EM ldichtel@partners.org FU National Institutes of Health [R01 HL077674, K24 HL092902, K23 RR023090, T32 DK007028]; Harvard Clinical and Translational Science Center (CTSC) [UL1 RR025758]; KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Research Resources) [KL2 TR001100]; KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst \ The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health) FX This work was supported by National Institutes of Health grants R01 HL077674, K24 HL092902, K23 RR023090 and T32 DK007028 as well as the Harvard Clinical and Translational Science Center (CTSC) grant UL1 RR025758. This work was also conducted with the support of a KL2/Catalyst Medical Research Investigator Training award (an appointed KL2 award) from Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award KL2 TR001100). 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 healthcare centers, or the National Institutes of Health. NR 5 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0300-0664 EI 1365-2265 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JAN PY 2017 VL 86 IS 1 BP 160 EP 162 DI 10.1111/cen.13251 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EJ8CZ UT WOS:000393453400022 PM 27696526 ER PT J AU Fazio, RL Denning, JH Denney, RL AF Fazio, Rachel L. Denning, John H. Denney, Robert L. TI TOMM Trial 1 as a performance validity indicator in a criminal forensic sample SO CLINICAL NEUROPSYCHOLOGIST LA English DT Article DE Forensic neuropsychology; malingering; performance validity; response bias; Test of Memory Malingering ID TRAUMATIC BRAIN-INJURY; MALINGERED NEUROCOGNITIVE DYSFUNCTION; ALBANY CONSISTENCY INDEX; RESPONSE BIAS SCALE; CLASSIFICATION ACCURACY; MENTAL-RETARDATION; COLLEGE-STUDENTS; RETENTION TRIAL; TEST FAILURE; WORD MEMORY AB Objective: To determine the effectiveness of the Test of Memory Malingering Trial 1 (TOMM1) as a freestanding Performance Validity Test (PVT) as compared to the full TOMM in a criminal forensic sample. Method: Participants included 119 evaluees in a Midwestern forensic hospital. Criterion groups were formed based on passing/failing scores on other freestanding PVTs. This resulted in three groups: +MND (Malingered Neurocognitive Dysfunction), who failed two or more freestanding PVTs; possible MND (pMND), who failed one freestanding PVT; and -MND, who failed no other freestanding PVTs. All three groups were compared initially, but only+MND and -MND groups were retained for final analyses. TOMM1 performance was compared to standard TOMM performance using Receiver Operating Characteristic (ROC) analyses. Results: TOMM1 was highly predictive of the standard TOMM decision rules (AUC=.92). Overall accuracy rate for TOMM1 predicting failure on 2 PVTs was quite robust as well (AUC=.80), and TOMM139 provided acceptable diagnostic statistics (Sensitivity=.68, Specificity=.89). These results were essentially no different from the standard TOMM accuracy statistics. In addition, by adjusting for those strongly suspected of being inaccurately placed into the -MND group (e.g. false negatives), TOMM1 diagnostics slightly improved (AUC=.84) at a TOMM140 (sensitivity=.71, specificity=.94). Conclusions: Results support use of TOMM1 in a criminal forensic setting where accuracy, shorter evaluation times, and more efficient use of resources are often critical in informing legal decision-making. C1 [Fazio, Rachel L.] Carter Psychol Ctr, Bradenton, FL 34207 USA. [Denning, John H.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Denning, John H.] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Denney, Robert L.] Neuropsychol Associates Southwest Missouri, Springfield, MO USA. RP Fazio, RL (reprint author), Carter Psychol Ctr, Bradenton, FL 34207 USA. EM rlfazio@gmail.com NR 78 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1385-4046 EI 1744-4144 J9 CLIN NEUROPSYCHOL JI Clin. Neuropsychol. PY 2017 VL 31 IS 1 BP 251 EP 267 DI 10.1080/13854046.2016.1213316 PG 17 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA EK2VR UT WOS:000393785300016 PM 27456971 ER PT J AU Kadayifci, A Atar, M Wang, JL Forcione, DG Casey, BW Pitman, MB Brugge, WR AF Kadayifci, Abdurrahman Atar, Mustafa Wang, Jessica L. Forcione, David G. Casey, Brenna W. Pitman, Martha B. Brugge, William R. TI Value of adding GNAS testing to pancreatic cyst fluid KRAS and carcinoembryonic antigen analysis for the diagnosis of intraductal papillary mucinous neoplasms SO DIGESTIVE ENDOSCOPY LA English DT Article DE carcinoembryonic antigen; GNAS; intraductal papillary mucinous neoplasms; KRAS; pancreas cyst ID MANAGEMENT; MUTATIONS; IPMN; EUS AB Background and Aim: Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novelmethod for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN). Methods: Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated. Results: The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P < 0.05). Conclusion: GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved. C1 [Kadayifci, Abdurrahman] Gaziantep Univ, Sch Med, Div Gastroenterol, Gaziantep, Turkey. [Kadayifci, Abdurrahman; Atar, Mustafa; Forcione, David G.; Casey, Brenna W.; Brugge, William R.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, 3-H GI Associates,Zero Emerson Pl,Blossom St, Boston, MA 02114 USA. [Wang, Jessica L.; Pitman, Martha B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Kadayifci, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, 3-H GI Associates,Zero Emerson Pl,Blossom St, Boston, MA 02114 USA. EM kadayifci@hotmail.com NR 16 TC 2 Z9 2 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0915-5635 EI 1443-1661 J9 DIGEST ENDOSC JI Dig. Endosc. PD JAN PY 2017 VL 29 IS 1 BP 111 EP 117 DI 10.1111/den.12710 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA EK0AS UT WOS:000393589300015 PM 27514845 ER PT J AU Joshi, RS Quadros, R Drumm, M Ain, R Panicker, MM AF Joshi, Radhika S. Quadros, Rolen Drumm, Michael Ain, Rupasri Panicker, Mitradas M. TI Sedative effect of Clozapine is a function of 5-HT2A and environmental novelty SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE 5-HT2A; Clozapine; Environmental; novelty; Knockout ID SEROTONIN 2A RECEPTORS; ANXIETY-LIKE BEHAVIORS; ANTIPSYCHOTIC-DRUGS; IN-VIVO; LOCOMOTOR SUPPRESSION; MICE LACKING; RATS; SCHIZOPHRENIA; HALOPERIDOL; OLANZAPINE AB Antipsychotic drugs are the mainstay in the treatment of schizophrenia and bipolar disorder. However, antipsychotics often exhibit sedation or activity suppression among many other side effects, and the factors that influence them remain poorly understood. We now show, using a 5-HT2A knockout (Htr2a(-/-)) mouse, that environmental circumstances can affect suppression of activity induced by the atypical antipsychotic-Clozapine. We observed that Htr2a(-/-) mice were more resistant to Clozapine-induced suppression of activity (CISA) and this behaviour was dependent on the environment being 'novel'. In their 'home' environment, at identical doses the mice exhibited CISA. Interestingly, the effect of genotype and environmental novelty on CISA could not be extended to the other antipsychotics that were tested, i.e. Haloperidol and Risperidone. Haloperidol-induced activity suppression was independent of context and genotype. Whereas context affected Risperidone-induced activity suppression only in the Htr2a(+/+) mice. Furthermore, we observed that caffeine, a stimulant, elicited resistance to CISA similar to that seen in the 'novel' context. Our study establishes a previously unknown interaction between the environmental context, 5-HT2A and CISA and emphasises the role of non-pharmacological factors such as environment on the effects of the drug, which seem antipsychotic-specific. Our findings should advance the understanding of the side effects of individual antipsychotics and the role of environment to overcome side effects such as sedation. (C) 2016 Elsevier B.V. and ECNP. All rights reserved. C1 [Joshi, Radhika S.; Quadros, Rolen; Drumm, Michael; Ain, Rupasri; Panicker, Mitradas M.] Natl Ctr Biol Sci, TIFR, GKVK Campus,Bellary Rd, Bengaluru 560065, India. [Drumm, Michael] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Ain, Rupasri] Indian Inst Chem Biol, CSIR, Div Cell Biol & Physiol, Kolkata, India. RP Joshi, RS; Panicker, MM (reprint author), Natl Ctr Biol Sci, TIFR, GKVK Campus,Bellary Rd, Bengaluru 560065, India. EM radhikasj@ncbs.res.in; panic@ncbs.res.in FU Department of Biotechnology, Government of India; National Centre for Biological Sciences FX Funding for this study was provided by grants from Department of Biotechnology, Government of India, and intramural funding from the National Centre for Biological Sciences; the funding sources 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 69 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X EI 1873-7862 J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD JAN PY 2017 VL 27 IS 1 BP 70 EP 81 DI 10.1016/j.euroneuro.2016.10.007 PG 12 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA EJ5FZ UT WOS:000393244500008 PM 27955831 ER PT J AU Matlasz, TM Brylski, JL Leidenfrost, CM Scalco, M Sinclair, SJ Schoelerman, RM Tsang, V Antonius, D AF Matlasz, Tatiana M. Brylski, Jamie L. Leidenfrost, Corey M. Scalco, Matt Sinclair, Samuel J. Schoelerman, Ronald M. Tsang, Valerie Antonius, Daniel TI Cognitive status and profile validity on the Personality Assessment Inventory (PAI) in offenders with serious mental illness SO INTERNATIONAL JOURNAL OF LAW AND PSYCHIATRY LA English DT Article DE Personality Assessment Inventory; PAI validity scales; Serious mental illness; Cognitive status; Competency to stand trial ID NEUROPSYCHIATRIC INTERVIEW MINI; WORKING-MEMORY CAPACITY; COMPETENCE RESTORATION; FORENSIC EVALUATION; PSYCHOLOGICAL TEST; PCL-R; DEFENDANTS; INMATES; INTELLIGENCE; RELIABILITY AB Cognitive impairment among seriously mentally ill offenders has implications for legal matters (e.g., competency to stand trial), as well as clinical treatment and care. Thus, being able to identify potential cognitive concerns early in the adjudication process can be important when deciding on further interventions. In this study, we examined the validity scales of the Personality Assessment Inventory (PAI), scores on the Wechsler Adult Intelligence Scale-IV (WAIS-IV), and competency findings in male inmates (n = 61) diagnosed with a serious mental illness. Lower scores on the WAIS-IV significantly (p = 0.001) predicted invalid, versus valid, PAI profiles, with working memory impairment being the most significant (p = 0.004) predictor of an invalid profile. Ancillary analyses on a smaller sample (n = 18) indicate that those with invalid PAI profiles were more likely to be deemed legally incompetent (p = 0.03). These findings suggest that the PAI validity scales may be informative in detecting cognitive concerns and help clinicians make determinations about competency restoration and treatment. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Matlasz, Tatiana M.; Leidenfrost, Corey M.; Antonius, Daniel] Univ Buffalo State Univ New York, Dept Psychiat, 462 Grider St, Buffalo, NY 14215 USA. [Matlasz, Tatiana M.; Brylski, Jamie L.; Leidenfrost, Corey M.; Scalco, Matt; Schoelerman, Ronald M.; Antonius, Daniel] Forens Mental Hlth Serv, Erie Cty Dept Mental Hlth, 120 West Eagle St, Buffalo, NY 14202 USA. [Brylski, Jamie L.; Tsang, Valerie] Medaille Coll, Dept Psychol, 18 Agassiz Circle, Buffalo, NY 14215 USA. [Scalco, Matt] Univ Buffalo State Univ New York, Dept Psychol, Pk Hall,Room 204, Buffalo, NY 14260 USA. [Sinclair, Samuel J.] Massachusetts Gen Hosp, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. [Sinclair, Samuel J.] Harvard Med Sch, Dept Psychiat, One Bowdoin Sq,7th Floor, Boston, MA 02114 USA. [Antonius, Daniel] NYU, Sch Med, Dept Psychiat, 462 First Ave,8th Floor, New York, NY 10016 USA. RP Matlasz, TM (reprint author), Louisiana State Univ, 307 Audubon Hall, Baton Rouge, LA 70803 USA. EM tmmatlasz92@gmail.com NR 63 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-2527 EI 1873-6386 J9 INT J LAW PSYCHIAT JI Int. J. Law Psychiatr. PD JAN-FEB PY 2017 VL 50 BP 38 EP 44 DI 10.1016/j.ijlp.2016.10.003 PG 7 WC Law; Psychiatry SC Government & Law; Psychiatry GA EJ5LD UT WOS:000393258600006 PM 27802872 ER PT J AU Grassberger, C Scott, JG Paganetti, H AF Grassberger, Clemens Scott, Jacob G. Paganetti, Harald TI Biomathematical Optimization of Radiation Therapy in the Era of Targeted Agents SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID LUNG-CANCER; EGFR; CHEMOTHERAPY; CARE C1 [Grassberger, Clemens; Paganetti, Harald] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Grassberger, Clemens; Paganetti, Harald] Harvard Med Sch, Boston, MA 02114 USA. [Scott, Jacob G.] H Lee Moffitt Canc Ctr & Res Inst, Integrated Math Oncol Dept, Tampa, FL USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.; Paganetti, H (reprint author), Harvard Med Sch, Boston, MA 02114 USA. EM hpaganetti@mgh.harvard.edu OI Paganetti, Harald/0000-0002-6257-2413 NR 14 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 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JAN 1 PY 2017 VL 97 IS 1 BP 13 EP 17 DI 10.1016/j.ijrobp.2016.09.008 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA EJ5XW UT WOS:000393293300009 PM 27979444 ER PT J AU Madden, JM Lakoma, MD Lynch, FL Rusinak, D Owen-Smith, AA Coleman, KJ Quinn, VP Yau, VM Qian, YX Croen, LA AF Madden, Jeanne M. Lakoma, Matthew D. Lynch, Frances L. Rusinak, Donna Owen-Smith, Ashli A. Coleman, Karen J. Quinn, Virginia P. Yau, Vincent M. Qian, Yinge X. Croen, Lisa A. TI Psychotropic Medication Use among Insured Children with Autism Spectrum Disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism spectrum disorder; Medications; Antipsychotics; Comorbidities; Epidemiological studies ID HEALTH-CARE; PSYCHIATRIC-DISORDERS; ADOLESCENTS; PREVALENCE; DIAGNOSIS; GENDER; ADULTS; COSTS; MODEL AB This study examined psychotropic medication use among 7901 children aged 1-17 with autism spectrum disorder (ASD) in five health systems, comparing to matched cohorts with no ASD. Nearly half (48.5 %) of children with ASD received psychotropics in the year observed; the most common classes were stimulants, alpha-agonists, or atomoxetine (30.2 %), antipsychotics (20.5 %), and antidepressants (17.8 %). Psychotropic treatment was far more prevalent among children with ASD, as compared to children with no ASD (7.7 % overall), even within strata defined by the presence or absence of other psychiatric diagnoses. The widespread use of psychotropics we observed, particularly given weak evidence supporting the effectiveness of these medications for most children with ASD, highlights challenges in ASD treatment and the need for greater investment in its evaluation. C1 [Madden, Jeanne M.] Northeastern Univ, Sch Pharm, Dept Pharm & Hlth Syst Sci, Bouve Coll Hlth Sci, 360 Huntington Ave R218X TF, Boston, MA 02115 USA. [Madden, Jeanne M.; Lakoma, Matthew D.; Rusinak, Donna] Harvard Med Sch, Dept Populat Med, Boston, MA 02115 USA. [Madden, Jeanne M.; Lakoma, Matthew D.; Rusinak, Donna] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Lynch, Frances L.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Owen-Smith, Ashli A.] Georgia State Univ, Sch Publ Hlth, Atlanta, GA 30303 USA. [Owen-Smith, Ashli A.] Kaiser Permanente Georgia, Ctr Clin & Outcomes Res, Atlanta, GA USA. [Coleman, Karen J.; Quinn, Virginia P.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. [Yau, Vincent M.; Qian, Yinge X.; Croen, Lisa A.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Rusinak, Donna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yau, Vincent M.] McKesson Corp, San Francisco, CA USA. RP Madden, JM (reprint author), Northeastern Univ, Sch Pharm, Dept Pharm & Hlth Syst Sci, Bouve Coll Hlth Sci, 360 Huntington Ave R218X TF, Boston, MA 02115 USA.; Madden, JM (reprint author), Harvard Med Sch, Dept Populat Med, Boston, MA 02115 USA.; Madden, JM (reprint author), Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. EM j.madden@northeastern.edu FU National Institutes of Health [U19MH092201] FX This study was funded by the National Institutes of Health (Grant U19MH092201). NR 44 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JAN PY 2017 VL 47 IS 1 BP 144 EP 154 DI 10.1007/s10803-016-2946-7 PG 11 WC Psychology, Developmental SC Psychology GA EI9GU UT WOS:000392816700013 PM 27817163 ER PT J AU Mody, M Shui, AM Nowinski, LA Golas, SB Ferrone, C O'Rourke, JA McDougle, CJ AF Mody, M. Shui, A. M. Nowinski, L. A. Golas, S. B. Ferrone, C. O'Rourke, J. A. McDougle, C. J. TI Communication Deficits and the Motor System: Exploring Patterns of Associations in Autism Spectrum Disorder (ASD) SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE Autism; Motor deficits; Language; Social interactions ID LANGUAGE IMPAIRMENT; SPEECH; CHILDREN; INFANT; SKILLS; COORDINATION; PERCEPTION; RISK; SIBLINGS; DELAY AB Many children with autism spectrum disorder (ASD) have notable difficulties in motor, speech and language domains. The connection between motor skills (oral-motor, manual-motor) and speech and language deficits reported in other developmental disorders raises important questions about a potential relationship between motor skills and speech-language deficits in ASD. To this end, we examined data from children with ASD (n = 1781), 2-17 years of age, enrolled in the Autism Speaks-Autism Treatment Network (AS-ATN) registry who completed a multidisciplinary evaluation that included diagnostic, physical, cognitive and behavioral assessments as part of a routine standard of care protocol. After adjusting for age, non-verbal IQ, Attention Deficit Hyperactivity Disorder (ADHD) medication use, and muscle tone, separate multiple linear regression analyses revealed significant positive associations of fine motor skills (FM) with both expressive language (EL) and receptive language (RL) skills in an impaired FM subgroup; in contrast, the impaired gross motor (GM) subgroup showed no association with EL but a significant negative association with RL. Similar analyses between motor skills and interpersonal relationships across the sample found both GM skills and FM skills to be associated with social interactions. These results suggest potential differences in the contributions of fine versus gross motor skills to autistic profiles and may provide another lens with which to view communication differences across the autism spectrum for use in treatment interventions. C1 [Mody, M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. [Mody, M.] Harvard Med Sch, Boston, MA 02129 USA. [Shui, A. M.] Massachusetts Gen Hosp East, Biostat Ctr, Boston, MA 02129 USA. [Mody, M.; Nowinski, L. A.; Golas, S. B.; Ferrone, C.; O'Rourke, J. A.; McDougle, C. J.] Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA. [Mody, M.; Nowinski, L. A.; Golas, S. B.; Ferrone, C.; O'Rourke, J. A.; McDougle, C. J.] Harvard Med Sch, Lexington, MA 02421 USA. RP Mody, M (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA.; Mody, M (reprint author), Harvard Med Sch, Boston, MA 02129 USA.; Mody, M (reprint author), Massachusetts Gen Hosp, Lurie Ctr Autism, Lexington, MA 02421 USA.; Mody, M (reprint author), Harvard Med Sch, Lexington, MA 02421 USA. EM maria@nmr.mgh.harvard.edu; ASHUI@mgh.harvard.edu; LNOWINSKI@mgh.harvard.edu; SGOLAS@mgh.harvard.edu; CFERRONE2@mgh.harvard.edu; JOOROURKE@mgh.harvard.edu; CMCDOUGLE@mgh.harvard.edu FU Autism Treatment Network/AIR-P [ATN-AIR-14-06]; U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program [UA3 MC 11054]; Autism Speaks FX This work was supported by funding from the Autism Treatment Network/AIR-P (in response to RFA #: ATN-AIR-14-06) a cooperative agreement UA3 MC 11054 through the U.S. Department of Health and Human Services, Health Resources and Services Administration, Maternal and Child Health Research Program. The AS ATN Registry is supported by Autism Speaks. We would also like to thank the Nancy Lurie Marks Family Foundation for their ongoing support of our research efforts. NR 40 TC 0 Z9 0 U1 8 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 EI 1573-3432 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD JAN PY 2017 VL 47 IS 1 BP 155 EP 162 DI 10.1007/s10803-016-2934-y PG 8 WC Psychology, Developmental SC Psychology GA EI9GU UT WOS:000392816700014 PM 27785593 ER PT J AU De Cecco, CN Schoepf, UJ Steinbach, L Boll, DT Foley, WD Kaza, RK Bolus, DN Morgan, DE Sahani, DV Shuman, WP Siegel, MJ Vrtiska, TJ Yeh, BM Berland, LL AF De Cecco, Carlo N. Schoepf, U. Joseph Steinbach, Lynne Boll, Daniel T. Foley, W. Dennis Kaza, Ravi K. Bolus, David N. Morgan, Desiree E. Sahani, Dushyant V. Shuman, William P. Siegel, Marilyn J. Vrtiska, Terri J. Yeh, Benjamin M. Berland, Lincoln L. TI White Paper of the Society of Computed Body Tomography and Magnetic Resonance on Dual-Energy CT, Part 3: Vascular, Cardiac, Pulmonary, and Musculoskeletal Applications SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE dual-energy CT; CT angiography; cardiac CT; musculoskeletal CT ID PERFUSED-BLOOD-VOLUME; REPERFUSED CHRONIC INFARCTION; PATIENTS INITIAL-EXPERIENCE; ANTERIOR CRUCIATE LIGAMENT; METAL ARTIFACT REDUCTION; CORONARY-ARTERY-DISEASE; BONE-MARROW LESIONS; MULTIDETECTOR CT; IMAGE-QUALITY; MYOCARDIAL-INFARCTION AB This is the third of a series of 4 white papers that represent Expert Consensus Documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its Task Force on dual-energy computed tomography. This paper, part 3, describes computed tomography angiography and thoracic, cardiac, vascular, and musculoskeletal clinical applications. At the end of the discussion of each application category (vascular, cardiac, pulmonary, and musculoskeletal), we present our consensus opinions on the current clinical utility of the application and opportunities for further research. C1 [De Cecco, Carlo N.; Schoepf, U. Joseph] Med Univ South Carolina, Dept Radiol & Radiol Sci, Div Cardiovasc Imaging, Charleston, SC 29425 USA. [Steinbach, Lynne; Yeh, Benjamin M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. [Boll, Daniel T.] Univ Basel Hosp, Dept Radiol, Basel, Switzerland. [Foley, W. Dennis] Med Coll Wisconsin, Dept Radiol, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA. [Kaza, Ravi K.] Univ Michigan Hosp, Dept Radiol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. [Bolus, David N.; Morgan, Desiree E.; Berland, Lincoln L.] Univ Alabama Birmingham, Dept Radiol, 619S 19th St,N454, Birmingham, AL 35249 USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA USA. [Shuman, William P.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Siegel, Marilyn J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Vrtiska, Terri J.] Mayo Clin, Coll Med, Dept Radiol, Rochester, MN USA. RP Berland, LL (reprint author), Univ Alabama Birmingham, Dept Radiol, 619S 19th St,N454, Birmingham, AL 35249 USA. EM lberland@uabmc.edu OI De Cecco, Carlo N./0000-0002-2956-3101 FU Astellas; Bayer; Bracco; GE Healthcare; Guerbet; Medrad; Nextrast, Inc.; NIH; Nuance Communications, Inc.; Oxford University Press; Siemens Healthcare FX The authors of this article declare relationships with the following companies: Astellas, Bayer, Bracco, GE Healthcare, Guerbet, Medrad, Nextrast, Inc., NIH, Nuance Communications, Inc., Oxford University Press, and Siemens Healthcare. The authors state that this work has not received any funding. NR 126 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN PY 2017 VL 41 IS 1 BP 1 EP 7 DI 10.1097/RCT.0000000000000538 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI9HV UT WOS:000392819500001 PM 28081050 ER PT J AU De Cecco, CN Boll, DT Bolus, DN Foley, WD Kaza, RK Morgan, DE Rofsky, NM Sahani, DV Schoepf, UJ Shuman, WP Siegel, MJ Vrtiska, TJ Yeh, BM Berland, LL AF De Cecco, Carlo N. Boll, Daniel T. Bolus, David N. Foley, W. Dennis Kaza, Ravi K. Morgan, Desiree E. Rofsky, Neil M. Sahani, Dushyant V. Schoepf, U. Joseph Shuman, William P. Siegel, Marilyn J. Vrtiska, Terri J. Yeh, Benjamin M. Berland, Lincoln L. TI White Paper of the Society of Computed Body Tomography and Magnetic Resonance on Dual-Energy CT, Part 4: Abdominal and Pelvic Applications SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE dual-energy CT; hepatic CT; pancreatic CT; renal CT ID GASTROINTESTINAL-STROMAL-TUMOR; VIRTUAL NONENHANCED IMAGES; SPECTRAL MULTIDETECTOR CT; IODINE OVERLAY TECHNIQUE; RENAL STONE COMPOSITION; IN-VIVO EVALUATION; INITIAL-EXPERIENCE; URINARY CALCULI; PANCREATIC ADENOCARCINOMA; MATERIAL DENSITY AB This is the fourth of a series of 4 white papers that represent expert consensus documents developed by the Society of Computed Body Tomography and Magnetic Resonance through its task force on dual-energy computed tomography. This article, part 4, discusses DECT for abdominal and pelvic applications and, at the end of each, will offer our consensus opinions on the current clinical utility of the application and opportunities for further research. C1 [De Cecco, Carlo N.; Schoepf, U. Joseph] Med Univ South Carolina, Dept Radiol & Radiol Sci, Div Cardiovasc Imaging, Charleston, SC 29425 USA. [Boll, Daniel T.] Univ Basel Hosp, Dept Radiol, Basel, Switzerland. [Bolus, David N.; Morgan, Desiree E.; Berland, Lincoln L.] Univ Alabama Birmingham, Dept Radiol, 619 S,19th St,N454, Birmingham, AL 35249 USA. [Foley, W. Dennis] Med Coll Wisconsin, Dept Radiol, 8700 W Wisconsin Ave, Milwaukee, WI 53226 USA. [Kaza, Ravi K.] Univ Michigan Hosp, Dept Radiol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. [Rofsky, Neil M.] UT Southwestern Med Ctr, Dept Radiol, Dallas, TX USA. [Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA USA. [Shuman, William P.] Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. [Siegel, Marilyn J.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Vrtiska, Terri J.] Mayo Clin, Coll Med, Dept Radiol, Rochester, MN USA. [Yeh, Benjamin M.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA. RP Berland, LL (reprint author), Univ Alabama Birmingham, Dept Radiol, 619 S,19th St,N454, Birmingham, AL 35249 USA. EM lberland@uabmc.edu OI De Cecco, Carlo N./0000-0002-2956-3101 NR 93 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 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN PY 2017 VL 41 IS 1 BP 8 EP 14 DI 10.1097/RCT.0000000000000546 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI9HV UT WOS:000392819500002 PM 27824670 ER PT J AU Ghani, MU Ren, LQ Wong, M Li, YH Zheng, B Rong, XJJ Yang, K Liu, H AF Ghani, Muhammad U. Ren, Liqiang Wong, Molly Li, Yuhua Zheng, Bin Rong, Xiujiang John Yang, Kai Liu, Hong TI Noise Power Characteristics of a Micro-Computed Tomography System SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE noise power spectrum; micro-CT; spatial frequency; cone beam ID CONE-BEAM CT; PHOTON-COUNTING STATISTICS; BREAST CT; SPECTRUM; RECONSTRUCTION; MAMMOGRAPHY; PERFORMANCE; EXPERIENCE; ALGORITHM; IMAGES AB Objective: The aim of this study was to investigate the noise power properties of amicro-computed tomography (micro-CT) system under different operating conditions. Methods: A commercial micro-CTwas used in the study that used a flat panel detector with a 127-mu m-pixel pitch and a micro-focus x-ray tube. Conical tubes of various diameters were used under different acquisition conditions. Multidimensional noise power spectrums were used as a metric to investigate the noise properties of the system. Noise power spectrum was calculated from the difference data generated by subtraction of 2 identical scans. The noise properties with respect to various parameters that include the impact of number of projections, x-ray spectra, milliampere-second, slice location, object diameter, voxel size, geometricmagnification (M), back-projection filters, and reconstruction magnification (M-recon) were studied. Results: At a same isocentric exposure rate of 270 mR/s, the noise power was much lower for the image reconstructed with 3672 views (122 seconds) as compared with the 511 views (17 seconds), whereas at a fixed isocentric exposure of 4600 mR, the noise power levels were almost similar. Image noise with a 50-kV beam was higher as compared with the 90-kV beam at a same isocentric exposure. Image noise from a 16-mm-diameter conical tube was much lower as compared with the 28and 56-mm tubes under identical isocentric exposures. The choice of back-projection filter influences noise power spectrum curves in terms of width and amplitudes. Reconstruction magnification applied during the reconstruction process increased the noise power at lower spatial frequencies but reduced the noise power at higher spatial frequencies. It can be established that, for small details corresponding to high spatial frequencies, reconstruction magnification can provide an improved signal-to-noise ratio. At all spatial frequencies, the in-plane images had lower noise power levels as compared with the z-plane images. Conclusions: The noise power properties investigated in this study provide important image quality references for refined cone beam system development, optimization, and operations. C1 [Ghani, Muhammad U.; Ren, Liqiang; Wong, Molly; Li, Yuhua; Zheng, Bin; Liu, Hong] Univ Oklahoma, Ctr Biomed Engn, 101 David L Boren Blvd, Norman, OK 73019 USA. [Ghani, Muhammad U.; Ren, Liqiang; Wong, Molly; Li, Yuhua; Zheng, Bin; Liu, Hong] Univ Oklahoma, Sch Elect & Comp Engn, 101 David L Boren Blvd, Norman, OK 73019 USA. [Rong, Xiujiang John] Univ Texas MD Anderson Canc Ctr, Dept Imaging Phys, Houston, TX 77030 USA. [Yang, Kai] Massachusetts Gen Hosp, Radiat Dept, Boston, MA 02114 USA. RP Liu, H (reprint author), Univ Oklahoma, Ctr Biomed Engn, 101 David L Boren Blvd, Norman, OK 73019 USA.; Liu, H (reprint author), Univ Oklahoma, Sch Elect & Comp Engn, 101 David L Boren Blvd, Norman, OK 73019 USA. EM liu@ou.edu RI Ghani, Muhammad/P-5473-2016 FU Charles and Jean Smith Chair endowment fund FX We would like to acknowledge the support of Charles and Jean Smith Chair endowment fund. NR 30 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 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN PY 2017 VL 41 IS 1 BP 82 EP 89 DI 10.1097/RCT.0000000000000483 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI9HV UT WOS:000392819500014 PM 27680419 ER PT J AU Knipp, D Lane, BF Mitchell, JW Daly, BD AF Knipp, David Lane, Barton F. Mitchell, Jason W. Daly, Barry D. TI Computed Tomographic Angiography of the Abdomen and Pelvis in Azotemic Patients Utilizing 80-kV(p) Technique and Reduced Dose Iodinated Contrast: Comparison With Routine 120-kV(p) Technique SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE CT angiography; low kV; iodinated contrast; iterative reconstruction; image quality ID LOW-TUBE VOLTAGE; 256-DETECTOR ROW CT; IMAGE QUALITY; DYNAMIC CT; VENOUS ENHANCEMENT; LOW-KILOVOLTAGE; ABDOMINAL CT; THIN ADULTS; SETTINGS; VENOGRAPHY AB Objective: To evaluate image quality (IQ) of a reduced contrast volume, low kilovolt (peak) [kV(p)] abdominopelvic computed tomographic angiography (AP-CTA) protocol compared to a standard 120-kV(p) AP-CTA protocol. Methods: A retrospective image analysis was performed on 103 patients with end-stage renal disease who underwent AP-CTA. Forty-nine patients were scanned at 80 kV(p) with amean of 48mL of contrast, and 54 patients were scanned at 120 kV(p) with a mean of 98 mL of contrast. Objective comparison of arterial attenuation, noise, and contrast-to-noise ratio was obtained, in addition to radiation dose. Subjective assessment of IQ, enhancement intensity, and image noise (IN) was scored on a 3-point scale. Results: The 6-level aggregate contrast-to-noise ratio for the 80-kV (p) group was 11.8 +/- 7.0, compared to 12.4 +/- 4.6 in the 120-kV(p) group (P = 0.210). Radiation exposure was significantly lower in the 80-kV (p) group versus the 120-kV(p) group, as measured by average CT dose index (mGy) of 9.0 +/- 3.1 and 15.8 +/- 5.8 (P < 0.0001), respectively; and average dose length product (mGy x cm) of 490.0 +/- 214.1 and 863.1 +/- 344.4 (P < 0.0001), respectively. The 120-kV(p) technique scored better for subjective IQ (P = 0.042) and IN (P = 0.004) but not for enhancement intensity (P = 0.205). Conclusions: A 50% reduced iodinated contrast dose coupled with 80-kV(p) technique with iterative reconstruction allows for satisfactory AP-CTA studies at a 43% mean radiation dose reduction compared to a standard protocol. Negative but potentially reversible sequelae of this drop in radiation dose include increased IN and reduced subjective IQ. C1 [Knipp, David] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Lane, Barton F.; Mitchell, Jason W.; Daly, Barry D.] Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, 22 S Greene St, Baltimore, MD 21201 USA. RP Lane, BF (reprint author), Univ Maryland, Sch Med, Dept Diagnost Radiol & Nucl Med, 22 S Greene St, Baltimore, MD 21201 USA. EM blane@umm.edu NR 24 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 0363-8715 EI 1532-3145 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN PY 2017 VL 41 IS 1 BP 141 EP 147 DI 10.1097/RCT.0000000000000478 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI9HV UT WOS:000392819500023 PM 27560016 ER PT J AU Zhao, G Lee, KC Peacock, S Reisch, LM Knezevich, SR Elder, DE Piepkorn, MW Elmore, JG Barnhill, RL AF Zhao, Ge Lee, Kachiu C. Peacock, Sue Reisch, Lisa M. Knezevich, Stevan R. Elder, David E. Piepkorn, Michael W. Elmore, Joann G. Barnhill, Raymond L. TI The utilization of spitz-related nomenclature in the histological interpretation of cutaneous melanocytic lesions by practicing pathologists: results from the M-Path study SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article DE dermatopathology; melanocytic nevus; melanoma; Spitz terminology ID RISK-ASSESSMENT; TUMORS; MELANOMA; NEVUS; NEOPLASMS AB Background: Spitz nevi, atypical Spitz tumors and spitzoid melanomas ('spitzoid lesions') represent controversial and poorly understood cutaneous melanocytic lesions that are difficult to diagnose histologically. It is unknown how these terms are used by pathologists. Methods: We describe use of Spitz-related terminology using data from the Melanoma Pathology (M-Path) study database comprising pathologists'interpretations of biopsy slides, a nation-wide study evaluating practicing US pathologists' (N=187) diagnoses of melanocytic lesions (8976 independent diagnostic assessments on 240 total test cases, with 1 slide per case). Results: Most pathologists (90%) used the Spitz-related terminology. However, significant variation exists in which specific lesions were diagnosed as spitzoid and in the corresponding treatment recommendations. Recommendations ranged from 'no further treatment' to 'wide excision of 10mm or greater' with no category capturing more than 50% of responses. For spitzoid melanoma diagnoses, 90% of pathologists recommended excision with = 10 mm margin. Pathologists report less confidence in diagnosing these lesions compared with other melanocytic proliferations and are more likely to request second opinions and additional clinical information (all p < 0.05). Conclusions: Spitzoid lesions are often not classified in any standardized way, evoke uncertainty in diagnosis by pathologists, and elicit variability in treatment recommendations. C1 [Zhao, Ge] Univ Washington, Div Dermatol, Dept Med, Seattle, WA 98195 USA. [Lee, Kachiu C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Dermatol, Boston, MA USA. [Peacock, Sue; Reisch, Lisa M.; Elmore, Joann G.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Knezevich, Stevan R.] Pathol Associates Inc, Clovis, CA USA. [Elder, David E.] Hosp Univ Penn, Dept Pathol & Lab Med, 3400 Spruce St, Philadelphia, PA 19104 USA. [Piepkorn, Michael W.] Univ Washington, Sch Med, Dept Med, Div Dermatol, Seattle, WA 98195 USA. [Piepkorn, Michael W.] Dermatopathol Northwest, Bellevue, WA USA. [Barnhill, Raymond L.] Univ Paris 05, Inst Curie, Dept Pathol, Paris, France. [Barnhill, Raymond L.] Univ Paris 05, Fac Med, Paris, France. RP Elmore, JG (reprint author), Univ Washington, Sch Med, Harborview Med Ctr, 325 Ninth Ave,Box 359780, Seattle, WA 98104 USA. EM jelmore@u.washington.edu FU NCI NIH HHS [K05 CA104699, R01 CA151306]; NIAMS NIH HHS [T32 AR056969] NR 22 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0303-6987 EI 1600-0560 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD JAN PY 2017 VL 44 IS 1 BP 5 EP 14 DI 10.1111/cup.12826 PG 10 WC Dermatology; Pathology SC Dermatology; Pathology GA EJ0BF UT WOS:000392872900002 PM 27686456 ER PT J AU Wagner, M Wagner, L Wagner, C Bell, SJ Nicholson, BW Strauss, DG Warren, S Pahlm, O Bacharova, L Lipton, J Eisenstein, E Kudaiberdieva, G Hakacova, N AF Wagner, Marilyn Wagner, Laura Wagner, Chris Bell, Samuel J. Nicholson, Brit W. Strauss, David G. Warren, Stafford Pahlm, Olle Bacharova, Ljuba Lipton, Jonathan Eisenstein, Eric Kudaiberdieva, Gulmira Hakacova, Nina TI In memory of Professor Galen S. Wagner MD, Ph.D. (1939-2016): our mentor, colleague and friend SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Biographical-Item C1 [Bell, Samuel J.] IRIS, Boston, MA 02116 USA. [Nicholson, Brit W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Strauss, David G.] US FDA, Washington, DC 20204 USA. [Warren, Stafford] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Pahlm, Olle; Hakacova, Nina] Lund Univ, Lund, Sweden. [Bacharova, Ljuba] Ctr Int Laser, Ilkovicova 3, Bratislava 84104, Slovakia. [Lipton, Jonathan] Royal Hobart Hosp, Hobart, Tas, Australia. [Lipton, Jonathan] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Eisenstein, Eric] Duke Univ, Durham, NC USA. RP Bacharova, L (reprint author), Ctr Int Laser, Ilkovicova 3, Bratislava 84104, Slovakia. NR 1 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD JAN-FEB PY 2017 VL 50 IS 1 BP 3 EP 4 DI 10.1016/j.jelectrocard.2016.11.001 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EJ9GL UT WOS:000393534500002 PM 27889056 ER PT J AU Russell, RG Davidson, H Rhoads, C Petrusa, ER AF Russell, Regina G. Davidson, Heather Rhoads, Celia Petrusa, Emil R. TI How do we understand the determinants of health? An exploration of distributed knowledge and interprofessional health sciences education SO JOURNAL OF INTERPROFESSIONAL CARE LA English DT Article DE Determinants of health; distributed knowledge; interprofessional education; medical students; nursing students; pharmacy students ID TEAMS AB It is acknowledged that interprofessional communication and teamwork are foundational for high-quality, safe medical practice. The theory of distributed knowledge posits that each person has unique knowledge and experiences that can contribute to a broader group perspective. Patient care can be positively influenced by a robust and interprofessionally shared understanding of the complexities of health and illness. One would expect a variety of perspectives to be evident in all healthcare providers, including incoming health science students from different professional fields. To examine this notion, medical, nursing, and pharmacy students (n = 24) at the start of an interprofessional training experience were asked to write an essay on factors that contribute to health and/or illness. Their essays were thematically coded to generate a list of factors considered key to health/illness and compare responses across fields to better understand how knowledge is distributed across entering learners. Results show that students from different professional backgrounds emphasise some shared and some divergent factors. This distributed knowledge can be a rich source of understanding and shared thinking across professions. It is also a critical source of individual power to contribute to the construction of an ongoing, collaborative discourse about health. C1 [Russell, Regina G.; Rhoads, Celia; Petrusa, Emil R.] Vanderbilt Univ, Sch Med, Off Teaching & Learning Med, Nashville, TN 37212 USA. [Davidson, Heather] Vanderbilt Univ, Sch Med, VPIL, Nashville, TN 37212 USA. [Petrusa, Emil R.] Harvard Med Sch, Boston, MA USA. [Petrusa, Emil R.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Russell, RG (reprint author), Vanderbilt Univ, Sch Med, Off Undergrad Med Educ, 201 Light Hall, Nashville, TN 37232 USA. EM regina.russell@vanderbilt.edu FU Josiah Macy Jr. Foundation, New York City FX The interprofessional educational experience was partially funded by the Josiah Macy Jr. Foundation, New York City (2010-2013). NR 8 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1356-1820 EI 1469-9567 J9 J INTERPROF CARE JI J. Interprofessional Care PY 2017 VL 31 IS 1 BP 118 EP 121 DI 10.1080/13561820.2016.1233391 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA EI9JY UT WOS:000392825300019 PM 27849415 ER PT J AU Heaven, S de Sa, D Simunovic, N Bedair, H Naudie, D Ayeni, OR AF Heaven, Sebastian de Sa, Darren Simunovic, Nicole Bedair, Hany Naudie, Douglas Ayeni, Olufemi R. TI Knee Arthroscopy in the Setting of Knee Arthroplasty SO JOURNAL OF KNEE SURGERY LA English DT Article DE knee arthroscopy; painful knee arthroplasty; systematic review; patellar clunk syndrome; arthrofibrosis ID RETAINED CEMENT; REPLACEMENT AB Knee arthroplasty is an effective and reproducible way of treating advanced knee arthritis; however, results are not always favorable. Knee arthroscopy has been described in symptomatic knee arthroplasty, but opinion is divided over its utility. The purpose of this systematic review is to examine existing evidence supporting knee arthroscopy in the setting of knee arthroplasty. Predetermined inclusion criteria were used to search the databases EMBASE, MEDLINE, and PubMed for articles addressing knee arthroplasty patients who subsequently underwent arthroscopy. Inclusion criteria limited our search to human and English language studies with clearly described surgical indications. Article screening was conducted in duplicate. Before duplicate screening, 2,179 studies were retrieved and 52 ultimately satisfied the inclusion criteria. A total of 609 patients underwent knee arthroscopy of a symptomatic knee arthroplasty and 120 patients went on to require further surgery post-arthroscopy. Peripatellar fibrosis and pain with no clear diagnosis were the most commonly described indications for surgery. Knee arthroscopy is a safe diagnostic and therapeutic tool in symptomatic knee arthroplasty with variable efficacy depending on indication. It has diagnostic utility in painful knee arthroplasty patients and is a reliable therapeutic option for those with post-arthroplasty diagnoses; although 20% of the patients go on to require further surgery. This is a systematic review of level IV studies. C1 [Heaven, Sebastian; de Sa, Darren; Ayeni, Olufemi R.] McMaster Univ, Dept Orthopaed Surg, 1200 Main St West,4E15, Hamilton, ON L8N 3Z5, Canada. [Simunovic, Nicole] McMaster Univ, Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Bedair, Hany] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA USA. [Naudie, Douglas] Univ Hosp, Dept Orthopaed Surg, London Hlth Sci Ctr, London, ON, Canada. RP Ayeni, OR (reprint author), McMaster Univ, Dept Orthopaed Surg, 1200 Main St West,4E15, Hamilton, ON L8N 3Z5, Canada. EM femiayeni@gmail.com NR 18 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 1538-8506 EI 1938-2480 J9 J KNEE SURG JI J. Knee Surg. PD JAN PY 2017 VL 30 IS 1 BP 51 EP 56 DI 10.1055/s-0036-1579669 PG 6 WC Orthopedics SC Orthopedics GA EJ2HD UT WOS:000393029800010 PM 26963069 ER PT J AU Wang, HZ Zhao, M Ackerman, JL Song, YQ AF Wang, Hongzhi Zhao, Ming Ackerman, Jerome L. Song, Yiqiao TI Saturation-inversion-recovery: A method for T-1 measurement SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Spin-lattice relaxation; Saturation inversion recovery; T(1)contrast; T(1)dispersion ID NMR RELAXATION DATA; COHERENCE PATHWAYS; LAPLACE INVERSION; UNCERTAINTY AB Spin-lattice relaxation (Ti) has always been measured by inversion-recovery (IR), saturation-recovery (SR), or related methods. These existing methods share a common behavior in that the function describing Ti sensitivity is the exponential, e.g., exp( -tau/T-1), where is the recovery time. In this paper, we describe a saturation-inversion-recovery (SIR) sequence for T-1 measurement with considerably sharper T-1-dependence than those of the IR and SR sequences, and demonstrate it experimentally. The SIR method could be useful in improving the contrast between regions of differing T-1 in T-1-weighted MRI. (C) 2016 Elsevier Inc. All rights reserved. C1 [Wang, Hongzhi] Shanghai Univ Med & Hlth Sci, Shanghai 201318, Peoples R China. [Wang, Hongzhi] East China Normal Univ, Shanghai Key Lab Magnet Resonance, Shanghai 200062, Peoples R China. [Wang, Hongzhi; Zhao, Ming; Ackerman, Jerome L.; Song, Yiqiao] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Zhao, Ming] Univ Massachusetts Lowell, Dept Phys, Lowell, MA 01854 USA. [Ackerman, Jerome L.] Harvard Med Sch, Boston, MA 02115 USA. [Song, Yiqiao] Schlumberger Doll Res Ctr, Cambridge, MA 02143 USA. RP Wang, HZ (reprint author), Shanghai Univ Med & Hlth Sci, Shanghai 201318, Peoples R China. EM wanghzhi2000@sina.com OI Ackerman, Jerome/0000-0001-5176-7496 FU China National Ministry of Science and Technology [2013YQ170406]; National Institutes of Health [S10RR013026, P41EB015896] FX The work was supported by the Special Project for the Major Scientific Instrument Grant from China National Ministry of Science and Technology 2013YQ170406. Spectrometer laboratory support was provided by the Martinos Center and National Institutes of Health Grants S10RR013026 and P41EB015896. We thank Drs. Sara Sprinkhuizen and Jeffrey Paulsen for informative discussions. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 EI 1096-0856 J9 J MAGN RESON JI J. Magn. Reson. PD JAN PY 2017 VL 274 BP 137 EP 143 DI 10.1016/j.jmr.2016.11.015 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA EJ8BA UT WOS:000393446000016 PM 27918897 ER PT J AU McCloskey, LA Doran, KA Gerber, MR AF McCloskey, Laura Ann Doran, Kelly A. Gerber, Megan R. TI Intimate Partner Violence is Associated with Voluntary Sterilization in Women SO JOURNAL OF WOMENS HEALTH LA English DT Article DE sterilization; intimate partner violence; reproductive health ID DOMESTIC VIOLENCE; CONTRACEPTIVE USE; UNINTENDED PREGNANCY; SEXUAL ABUSE; NEW-ZEALAND; HEALTH; PREVALENCE; ABORTION; COERCION; RISK AB Background: Intimate partner violence (IPV) may interfere with women's use of preferred forms of contraception, resulting in unwanted pregnancies forcing women to seek permanent sterilization. A history of child sexual abuse (CSA) presages the risk for IPV in adulthood setting the stage for adverse reproductive outcomes. Objective: To determine whether CSA and IPV are associated with women's voluntary sterilization when adjusting for demographics and reproductive health history. Methods: This cross-sectional study is based on in-person interviews of women (N= 278) drawn from outpatients surveyed in more than 10 different clinics (N = 2465). Women's history of gender-based violence and bilateral tubal ligation (BTL) were assessed. Results: About half of the women had a past history of IPV and 29% disclosed CSA. CSA predicted later entry into an abusive relationship (odds ratio [OR] = 6.7). Sterilization was reported by 19.6%. Parity (3+ children), having had an abortion, and receipt of welfare were associated with sterilization in univariate tests. Among those women receiving a BTL, 74% had violent partners. Adjusted multivariate logistic regressions, adjusted for demographics and reproductive history, indicated that having had an abusive partner increased the odds of sterilization; parity was also highly associated. CSA exerted only an indirect influence on sterilization via entry into violent relationships. Conclusion: IPV raises the likelihood that women will choose sterilization. Despite the importance of women's access to permanent contraception, priority should be given to screening for gender-based violence and promoting interventions. C1 [McCloskey, Laura Ann] Indiana Univ, Sch Publ Hlth, 1025 E 7th St, Bloomington, IN 47408 USA. [Doran, Kelly A.] Indiana Univ, Sch Educ, Bloomington, IN 47405 USA. [Gerber, Megan R.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. RP McCloskey, LA (reprint author), Indiana Univ, Sch Publ Hlth, 1025 E 7th St, Bloomington, IN 47408 USA. EM lmcclosk@indiana.edu FU Agency for Healthcare Research Quality (AHRQ) [R01-HS011088] FX The research was funded by the Agency for Healthcare Research Quality (AHRQ) (R01-HS011088). NR 43 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 EI 1931-843X J9 J WOMENS HEALTH JI J. Womens Health PD JAN PY 2017 VL 26 IS 1 BP 64 EP 70 DI 10.1089/jwh.2015.5595 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA EJ0FP UT WOS:000392884300012 PM 27661288 ER PT J AU Ramaiya, NH AF Ramaiya, Nikhil H. TI Expanding Horizons in Cancer Imaging SO KOREAN JOURNAL OF RADIOLOGY LA English DT Editorial Material C1 [Ramaiya, Nikhil H.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ramaiya, NH (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 4 EP 5 DI 10.3348/kjr.2017.18.1.4 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900001 PM 28096713 ER PT J AU O'Neill, AC Jagannathan, JP Ramaiya, NH AF O'Neill, Ailbhe C. Jagannathan, Jyothi P. Ramaiya, Nikhil H. TI Evolving Cancer Classification in the Era of Personalized Medicine: A Primer for Radiologists SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Lung cancer; NSCLC; Adenocarcinoma; EGFR mutation; ALK rearrangement ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; ANAPLASTIC LYMPHOMA KINASE; INFLAMMATORY MYOFIBROBLASTIC TUMOR; MOLECULAR TARGETED THERAPIES; PHASE-II TRIAL; BREAST-CANCER; ACQUIRED-RESISTANCE; BRAIN METASTASES; COLORECTAL-CANCER AB Traditionally tumors were classified based on anatomic Location but now specific genetic mutations in cancers are leading to treatment of tumors with molecular targeted therapies. This has Led to a paradigm shift in the classification and treatment of cancer. Tumors treated with molecular targeted therapies often show morphological changes rather than change in size and are associated with class specific and drug specific toxicities, different from those encountered with conventional chemotherapeutic agents. It is important for the radiologists to be familiar with the new cancer classification and the various treatment strategies employed, in order to effectively communicate and participate in the multi-disciplinary care. In this paper we will focus on lung cancer as a prototype of the new molecular classification. C1 [O'Neill, Ailbhe C.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. RP O'Neill, AC (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ailbheconeill@yahoo.co.uk NR 63 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 6 EP 17 DI 10.3348/kjr.2017.18.1.6 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900002 PM 28096714 ER PT J AU DiPiro, PJ Krajewski, KM Giardino, AA Braschi-Amirfarzan, M Ramaiya, NH AF DiPiro, Pamela J. Krajewski, Katherine M. Giardino, Angela A. Braschi-Amirfarzan, Marta Ramaiya, Nikhil H. TI Radiology Consultation in the Era of Precision Oncology: A Review of Consultation Models and Services in the Tertiary Setting SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Radiology consultation; Radiology services; Precision medicine; Tertiary cancer center ID CANCER CENTER; REFERRING CLINICIAN; IMAGING FINDINGS; BREAST-CANCER; NECK-CANCER; IMPACT; COMMUNICATION; PREFERENCES; MANAGEMENT; IMPLEMENTATION AB The purpose of the article is to describe the various radiology consultation models in the Era of Precision Medicine. Since the inception of our specialty, radiologists have served as consultants to physicians of various disciplines. A variety of radiology consultation services have been described in the literature, including clinical decision support, patient-centric, subspecialty interpretation, and/or some combination of these. In oncology care in particular, case complexity often merits open dialogue with clinical providers. To explore the utility and impact of radiology consultation services in the academic setting, this article will further describe existing consultation models and the circumstances that precipitated their development. The hybrid model successful at our tertiary cancer center is discussed. In addition, the contributions of a consultant radiologist in breast cancer care are reviewed as the archetype of radiology consultation services provided to oncology practitioners. C1 [DiPiro, Pamela J.; Krajewski, Katherine M.; Giardino, Angela A.; Braschi-Amirfarzan, Marta; Ramaiya, Nikhil H.] Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [DiPiro, Pamela J.; Krajewski, Katherine M.; Giardino, Angela A.; Braschi-Amirfarzan, Marta; Ramaiya, Nikhil H.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA. RP DiPiro, PJ (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. EM pdipiro@partners.org NR 42 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 18 EP 27 DI 10.3348/kjr.2017.18.1.18 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900003 PM 28096715 ER PT J AU Krajewski, KM Braschi-Amirfarzan, M DiPiro, PJ Jagannathan, JP Shinagare, AB AF Krajewski, Katherine M. Braschi-Amirfarzan, Marta DiPiro, Pamela J. Jagannathan, Jyothi P. Shinagare, Atul B. TI Molecular Targeted Therapy in Modern Oncology: Imaging Assessment of Treatment Response and Toxicities SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Vascular endothelial growth factor; Response Evaluation Criteria in Solid Tumors; Epidermal growth factor receptor; Anaplastic lymphoma kinase; Mammalian target of rapamycin; Human epidermal growth factor receptor 2 ID CELL LUNG-CANCER; METASTATIC BREAST-CANCER; DRUG-RELATED PNEUMONITIS; RAPAMYCIN INHIBITOR THERAPY; MESSENGER-RNA EXPRESSION; RECEPTOR GENE-MUTATIONS; PATTERN-BASED APPROACH; PHASE-III TRIAL; MAMMALIAN TARGET; TUMOR RESPONSE AB Oncology is a rapidly evolving field with a shift toward personalized cancer treatment. The use of therapies targeted to the molecular features of individual tumors and the tumor microenvironment has become much more common. In this review, anti-angiogenic and other molecular targeted therapies are discussed, with a focus on typical and atypical response patterns and imaging manifestations of drug toxicities. C1 [Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B.] Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. [Krajewski, Katherine M.; Braschi-Amirfarzan, Marta; DiPiro, Pamela J.; Jagannathan, Jyothi P.; Shinagare, Atul B.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Krajewski, KM (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM kmkrajewski@partners.org NR 92 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 28 EP 41 DI 10.3348/kjr.2017.18.1.28 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900004 PM 28096716 ER PT J AU Braschi-Amirfarzan, M Tirumani, SH Hodi, FS Nishino, M AF Braschi-Amirfarzan, Marta Tirumani, Sree Harsha Hodi, Frank Stephen Jr. Nishino, Mizuki TI Immune-Checkpoint Inhibitors in the Era of Precision Medicine: What Radiologists Should Know SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Immune-checkpoint inhibitor; Toxicity; Response; Immune-related Response Criteria ID CELL LUNG-CANCER; CLASSICAL HODGKIN LYMPHOMA; GUIDELINE VERSION 1.1; ADVERSE EVENTS; RESPONSE CRITERIA; ADVANCED MELANOMA; TUMOR RESPONSE; SOLID TUMORS; METASTATIC MELANOMA; COMMON LANGUAGE AB Over the past five years immune-checkpoint inhibitors have dramatically changed the therapeutic landscape of advanced solid and hematologic malignancies. The currently approved immune-checkpoint inhibitors include antibodies to cytotoxic T-lymphocyte antigen-4, programmed cell death (PD-1), and programmed cell death ligand (PD-L1 and PD-L2). Response to immune-checkpoint inhibitors is evaluated on imaging using the immune-related response criteria. Activation of immune system results in a unique toxicity profile termed immune-related adverse events. This article will review the molecular mechanism, clinical applications, imaging of immune-related response patterns and adverse events associated with immune-checkpoint inhibitors. C1 [Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Nishino, Mizuki] Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA. [Braschi-Amirfarzan, Marta; Tirumani, Sree Harsha; Nishino, Mizuki] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Hodi, Frank Stephen Jr.] Dana Farber Canc Inst, Dept Med Oncol & Med, Boston, MA 02215 USA. RP Braschi-Amirfarzan, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 450 Brookline Ave, Boston, MA 02215 USA.; Braschi-Amirfarzan, M (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM mbraschi@partners.org FU Merck; Canon; Bristol-Myers Squibb; Merck Sharp Dohme; Genentech; Novartis FX Merck (Inst), Canon (Inst); Bristol-Myers Squibb (Inst), Merck Sharp & Dohme (Inst), Genentech (Inst), Novartis (Inst) NR 63 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 42 EP 53 DI 10.3348/kjr.2017.18.1.42 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900005 PM 28096717 ER PT J AU Shah, HJ Keraliya, AR Jagannathan, JP Tirumani, SH Lele, VR DiPiro, PJ AF Shah, Hina J. Keraliya, Abhishek R. Jagannathan, Jyothi P. Tirumani, Sree Harsha Lele, Vikram R. DiPiro, Pamela J. TI Diffuse Large B-Cell Lymphoma in the Era of Precision Oncology: How Imaging Is Helpful SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Lymphoma; Diffuse large B cell lymphoma; FDG-positron emission tomography/CT; MRI ID POSITRON-EMISSION-TOMOGRAPHY; NERVOUS-SYSTEM LYMPHOMA; NON-HODGKIN-LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; PRIMARY CNS LYMPHOMA; FDG-PET; PROGNOSTIC VALUE; DIAGNOSTIC PERFORMANCE; RESPONSE ASSESSMENT; CHOP CHEMOTHERAPY AB Diffuse large B cell lymphoma (DLBCL) is the most common histological subtype of Non-Hodgkin's lymphoma. As treatments continues to evolve, so do imaging strategies, and positron emission tomography (PET) has emerged as the most important imaging tool to guide oncologists in the diagnosis, staging, response assessment, relapse/recurrence detection,and therapeutic decision making of DLBCL. Other imaging modalities including magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, and conventional radiography are also used in the evaluation of lymphoma. MRI is useful for nervous system and musculoskeletal system involvement and is emerging as a radiation free alternative to PET/CT. This article provides a comprehensive review of both the functional and morphological imaging modalities, available in the management of DLBCL. C1 [Shah, Hina J.; Keraliya, Abhishek R.; Jagannathan, Jyothi P.; Tirumani, Sree Harsha; DiPiro, Pamela J.] Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. [Shah, Hina J.; Keraliya, Abhishek R.; Jagannathan, Jyothi P.; Tirumani, Sree Harsha; DiPiro, Pamela J.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Lele, Vikram R.] Jaslok Hosp & Res Ctr, Dept Nucl Med, Bombay 400026, Maharashtra, India. [Lele, Vikram R.] Jaslok Hosp & Res Ctr, PET CT, Bombay 400026, Maharashtra, India. RP Keraliya, AR (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM akeraliya@partners.org NR 91 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 54 EP 70 DI 10.3348/kjr.2017.18.1.54 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900006 PM 28096718 ER PT J AU Park, HS McIntosh, L Braschi-Amirfarzan, M Shinagare, AB Krajewski, KM AF Park, Hye Sun McIntosh, Lacey Braschi-Amirfarzan, Marta Shinagare, Atul B. Krajewski, Katherine M. TI T-Cell Non-Hodgkin Lymphomas: Spectrum of Disease and the Role of Imaging in the Management of Common Subtypes SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE T-cell lymphoma; Non-Hodgkin lymphoma; CT; MRI; PET-CT ID NATURAL KILLER/T-CELL; ACUTE LYMPHOBLASTIC-LEUKEMIA; MYCOSIS-FUNGOIDES; UNITED-STATES; PROGNOSTIC-FACTORS; CUTANEOUS LYMPHOMAS; CLINICAL-FEATURES; F-18-FDG PET/CT; SEZARY-SYNDROME; FDG-PET/CT AB T-cell non-Hodgkin Lymphomas (NHLs) are biologically diverse, uncommon malignancies characterized by a spectrum of imaging findings according to subtype. The purpose of this review is to describe the common subtypes of T-cell NHL, highlight important differences between cutaneous, various peripheral and precursor subtypes, and summarize imaging features and the role of imaging in the management of this diverse set of diseases. C1 [Park, Hye Sun] Univ Ulsan, Coll Med, Dept Radiol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea. [Park, Hye Sun] Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea. [McIntosh, Lacey; Braschi-Amirfarzan, Marta; Shinagare, Atul B.; Krajewski, Katherine M.] Harvard Med Sch, Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [McIntosh, Lacey; Braschi-Amirfarzan, Marta; Shinagare, Atul B.; Krajewski, Katherine M.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Park, HS (reprint author), Univ Ulsan, Coll Med, Dept Radiol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea.; Park, HS (reprint author), Univ Ulsan, Coll Med, Asan Med Ctr, Res Inst Radiol, 88 Olymp Ro 43 Gil, Seoul 05505, South Korea. EM hesoni86@gmail.com NR 73 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 71 EP 83 DI 10.3348/kjr.2017.18.1.71 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900007 PM 28096719 ER PT J AU Tirumani, SH Baheti, AD Tirumani, H O'Neill, A Jagannathan, JP AF Tirumani, Sree Harsha Baheti, Akshay D. Tirumani, Harika O'Neill, Ailbhe Jagannathan, Jyothi P. TI Update on Gastrointestinal Stromal Tumors for Radiologists SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Gastrointestinal stromal tumor; Imatinib; Risk stratification; Choi criteria ID IMATINIB MESYLATE; RISK STRATIFICATION; RESPONSE CRITERIA; SINGLE-INSTITUTION; MUTATION ANALYSIS; PHASE-3 TRIAL; GIST; VALIDATION; PATHOLOGY; THERAPY AB The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters. Surveillance of patients with GIST in the adjuvant setting is important for timely detection of recurrences. C1 [Tirumani, Sree Harsha; O'Neill, Ailbhe; Jagannathan, Jyothi P.] Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. [Tirumani, Sree Harsha; O'Neill, Ailbhe; Jagannathan, Jyothi P.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Baheti, Akshay D.] Tata Mem Hosp, Dept Radiol, Bombay 400012, Maharashtra, India. [Tirumani, Harika] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. RP Tirumani, SH (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM stirumani@partners.org NR 52 TC 0 Z9 0 U1 0 U2 0 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 84 EP 93 DI 10.3348/kjr.2017.18.1.84 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900008 PM 28096720 ER PT J AU Baheti, AD Jagannathan, JP O'Neill, A Tirumani, H Tirumani, SH AF Baheti, Akshay D. Jagannathan, Jyothi P. O'Neill, Ailbhe Tirumani, Harika Tirumani, Sree Harsha TI Current Concepts in Non-Gastrointestinal Stromal Tumor Soft Tissue Sarcomas: A Primer for Radiologists SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Soft tissue sarcomas; World Health Organization classification; Liposarcoma; Leiomyosarcoma ID EPITHELIOID CELL TUMORS; MR-IMAGING FEATURES; PHASE-II TRIAL; DEDIFFERENTIATED LIPOSARCOMA; DERMATOFIBROSARCOMA PROTUBERANS; PATHOLOGICAL CORRELATION; VILLONODULAR SYNOVITIS; RETROPERITONEAL MASSES; UTERINE LEIOMYOSARCOMA; RETROSPECTIVE ANALYSIS AB Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely Liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist. C1 [Baheti, Akshay D.] Tata Mem Hosp, Dept Radiol, Bombay 400012, Maharashtra, India. [Jagannathan, Jyothi P.; O'Neill, Ailbhe; Tirumani, Sree Harsha] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Jagannathan, Jyothi P.; O'Neill, Ailbhe; Tirumani, Sree Harsha] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02215 USA. [Tirumani, Harika] Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72205 USA. RP Baheti, AD (reprint author), Tata Mem Hosp, Dept Radiol, Bombay 400012, Maharashtra, India. EM akshaybaheti@gmail.com NR 82 TC 0 Z9 0 U1 1 U2 1 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 94 EP 106 DI 10.3348/kjr.2017.18.1.94 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900009 PM 28096721 ER PT J AU Shinagare, AB Khorasani, R AF Shinagare, Atul B. Khorasani, Ramin TI Evidence-Based Cancer Imaging SO KOREAN JOURNAL OF RADIOLOGY LA English DT Review DE Evidence-based imaging; Cancer imaging; Computerized physician order entry; Clinical decision support ID MANAGING INCIDENTAL FINDINGS; CLINICAL DECISION-SUPPORT; GASTROINTESTINAL STROMAL TUMOR; FOLLOW-UP; WHITE PAPER; OVARIAN-CANCER; COMMITTEE II; PELVIC CT; EMERGENCY-DEPARTMENT; THORACIC METASTASES AB With the advances in the field of oncology, imaging is increasingly used in the follow-up of cancer patients, Leading to concerns about over-utilization. Therefore, it has become imperative to make imaging more evidence-based, efficient, cost-effective and equitable. This review explores the strategies and tools to make diagnostic imaging more evidence-based, mainly in the context of follow-up of cancer patients. C1 [Shinagare, Atul B.] Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. [Shinagare, Atul B.; Khorasani, Ramin] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Shinagare, Atul B.; Khorasani, Ramin] Brigham & Womens Hosp, Ctr Evidence Based Imaging, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02215 USA. EM ashinagare@partners.org NR 52 TC 0 Z9 0 U1 1 U2 1 PU KOREAN RADIOLOGICAL SOC PI SEOUL PA 121-8 YANGJAE-DONG, SEOCHO-GU, SEOUL 137-130, SOUTH KOREA SN 1229-6929 EI 2005-8330 J9 KOREAN J RADIOL JI Korean J. Radiol. PD JAN-FEB PY 2017 VL 18 IS 1 BP 107 EP 112 DI 10.3348/kjr.2017.18.1.107 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EJ3YX UT WOS:000393149900010 PM 28096722 ER PT J AU Bradley, CJ Yabroff, KR Warren, JL Zeruto, C Chawla, N Lamont, EB AF Bradley, Cathy J. Yabroff, K. Robin Warren, Joan L. Zeruto, Christopher Chawla, Neetu Lamont, Elizabeth B. TI Use of High-cost Systemic Treatments in Elderly mCRC Patients In Reply SO MEDICAL CARE LA English DT Letter ID MEDICARE MANAGED CARE; TRADITIONAL MEDICARE; CANCER C1 [Bradley, Cathy J.] Univ Colorado, Colorado Comprehens Canc Ctr, Dept Hlth Syst Management & Policy, Aurora, CO 80045 USA. [Yabroff, K. Robin; Warren, Joan L.; Chawla, Neetu] NCI, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. [Zeruto, Christopher] Informat Management Serv Inc, Rockville, MD USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Lamont, Elizabeth B.] Massachusetts Gen Hosp, Ctr Canc, Dept Hlth Care Policy, Boston, MA USA. [Lamont, Elizabeth B.] Harvard Med Sch, Boston, MA USA. RP Bradley, CJ (reprint author), Univ Colorado, Colorado Comprehens Canc Ctr, Dept Hlth Syst Management & Policy, Aurora, CO 80045 USA. FU National Cancer Institute FX The authors declare no conflict of interest. Bradley's work for the original manuscript was partially supported by a contract from the National Cancer Institute. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JAN PY 2017 VL 55 IS 1 BP 86 EP 87 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EJ0RO UT WOS:000392918200015 PM 27547951 ER PT J AU Offodile, AC Aherrera, A Wenger, J Rajab, TK Guo, LF AF Offodile, Anaeze C., II Aherrera, Andrew Wenger, Julia Rajab, Taufiek K. Guo, Lifei TI Impact of increasing operative time on the incidence of early failure and complications following free tissue transfer? A risk factor analysis of 2,008 patients from the ACS-NSQIP database SO MICROSURGERY LA English DT Article ID FREE-FLAP FAILURE; QUALITY IMPROVEMENT PROGRAM; BREAST RECONSTRUCTION; MICROVASCULAR RECONSTRUCTION; NECK DEFECTS; HEAD; SURGERY; OUTCOMES; PREDICTORS; THROMBOSIS AB BackgroundThere is a scarcity of externally valid data that investigate the utility of operative time, a common clinical parameter, as a predictor of free flap failures. Our aim was to assess whether prolonged operative time correlates with early flap failure following free tissue transfer in the acute care setting using the American College of Surgeons National Surgical Quality Improvement Program database. MethodsThe 2005-2011 American College of Surgeons National Surgical Quality Improvement Program databases were reviewed for encounters that entailed a free tissue transfer via a CPT algorithm. Patients identified as having a flap loss were compared with people who did not with regards to operative time and patient comorbidities. Patients were subdivided into the following cohort groups with regards to operative time: <6 hours, 6-12 hours, and >12 hours. Secondary outcome was association between increasing operative time and postoperative complications. ResultsOf the 2,008 patients identified, 62 (3.1%) had early flap failure. After multivariable analysis, it was found that progressive operative time was associated with an increased risk of flap failure; 6-12 hours odds ratio was 4.64 and >12 hours odds ratio was 5.65 (P=0.0140). Higher American Society of Anesthesiologists class (P=0.0042) was also shown to be significantly associated with flap failure. On secondary analysis, increasing operative time was correlated with the following complications: pneumonia, blood transfusions, prolonged ventilation, wound dehiscence, and wound complications. ConclusionOur results, one of the largest series in the literature, revealed that prolonged operative time was associated with a stepwise increase in the likelihood of early flap failure as well certain postoperative complications. (c) 2014 Wiley Periodicals, Inc. Microsurgery 37:12-20, 2017. C1 [Offodile, Anaeze C., II; Aherrera, Andrew; Guo, Lifei] Lahey Hosp & Med Ctr, Dept Plast Surg, 41 Mall Rd, Burlington, MA 01805 USA. [Wenger, Julia] Massachusetts Gen Hosp, Dept Nephrol, Boston, MA 02114 USA. [Rajab, Taufiek K.] Brigham & Womens Hosp, Dept Gen Surg, 75 Francis St, Boston, MA 02115 USA. RP Guo, LF (reprint author), Lahey Hosp & Med Ctr, Dept Plast Surg, 41 Mall Rd, Burlington, MA 01805 USA. EM Lifei.guo@lahey.org NR 42 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0738-1085 EI 1098-2752 J9 MICROSURG JI Microsurgery PD JAN PY 2017 VL 37 IS 1 BP 12 EP 20 DI 10.1002/micr.22387 PG 9 WC Surgery SC Surgery GA EJ8EQ UT WOS:000393458400002 PM 25752264 ER PT J AU Okondo, MC Johnson, DC Sridharan, R Bin Go, E Chui, AJ Wang, MS Poplawski, SE Wu, WG Liu, YX Lai, JH Sanford, DG Arciprete, MO Golub, TR Bachovchin, WW Bachovchin, DA AF Okondo, Marian C. Johnson, Darren C. Sridharan, Ramya Bin Go, Eun Chui, Ashley J. Wang, Mitchell S. Poplawski, Sarah E. Wu, Wengen Liu, Yuxin Lai, Jack H. Sanford, David G. Arciprete, Michael O. Golub, Todd R. Bachovchin, William W. Bachovchin, Daniel A. TI DPP8 and DPP9 inhibition induces pro-caspase-1-dependent monocyte and macrophage pyroptosis SO NATURE CHEMICAL BIOLOGY LA English DT Article ID PROLYL DIPEPTIDASE DPP8; INFLAMMASOME ACTIVATION; PEPTIDASES 8; GASDERMIN D; CANCER; EXPRESSION; POTENT; IMMUNOSURVEILLANCE; LOCALIZATION; CASPASE-11 AB Val-boroPro (Talabostat, PT-100), a nonselective inhibitor of post-proline cleaving serine proteases, stimulates mammalian immune systems through an unknown mechanism of action. Despite this lack of mechanistic understanding, Val-boroPro has attracted substantial interest as a potential anticancer agent, reaching phase 3 trials in humans. Here we show that Val-boroPro stimulates the immune system by triggering a proinflammatory form of cell death in monocytes and macrophages known as pyroptosis. We demonstrate that the inhibition of two serine proteases, DPP8 and DPP9, activates the pro-protein form of caspase-1 independent of the inflammasome adaptor ASC. Activated pro-caspase-1 does not efficiently process itself or IL-113 but does cleave and activate gasdermin D to induce pyroptosis. Mice lacking caspase-1 do not show immune stimulation after treatment with Val-boroPro. Our data identify what is to our knowledge the first small molecule that induces pyroptosis and reveals a new checkpoint that controls the activation of the innate immune system. C1 [Okondo, Marian C.; Bachovchin, Daniel A.] Mem Sloan Kettering Canc Ctr, Chem Biol Program, 1275 York Ave, New York, NY 10021 USA. [Johnson, Darren C.; Bin Go, Eun; Chui, Ashley J.; Bachovchin, Daniel A.] Mem Sloan Kettering Canc Ctr, Triinst PhD Program Chem Biol, 1275 York Ave, New York, NY 10021 USA. [Sridharan, Ramya; Wang, Mitchell S.; Bachovchin, Daniel A.] Weill Cornell Grad Sch Med Sci, Grad Program Pharmacol, New York, NY 10065 USA. [Poplawski, Sarah E.; Wu, Wengen; Liu, Yuxin; Lai, Jack H.; Sanford, David G.; Arciprete, Michael O.; Bachovchin, William W.] Tufts Univ, Sackler Sch Grad Biomed Sci, Dept Dev Chem & Mol Biol, Boston, MA 02111 USA. [Golub, Todd R.] Eli & Edythe L Broad Inst, Cambridge, MA USA. [Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Golub, Todd R.] Harvard Med Sch, Boston, MA USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Bachovchin, William W.] Arisaph Pharmaceut, Boston, MA USA. RP Bachovchin, DA (reprint author), Mem Sloan Kettering Canc Ctr, Chem Biol Program, 1275 York Ave, New York, NY 10021 USA.; Bachovchin, DA (reprint author), Mem Sloan Kettering Canc Ctr, Triinst PhD Program Chem Biol, 1275 York Ave, New York, NY 10021 USA.; Bachovchin, DA (reprint author), Weill Cornell Grad Sch Med Sci, Grad Program Pharmacol, New York, NY 10065 USA. EM bachovcd@mskcc.org FU Josie Robertson Foundation; MSKCC Core Grant [P30 CA008748]; NCI [U54CA112962]; HHMI; NIH [CA174008-01A1, NIH NIGMS T32 GM115327-Tan] FX We thank S. Fujisawa for microscopy assistance, E. De Stanchina and B. Qeriqi for assistance harvesting mEMDMs, C. Taabazuing for helpful comments and A. Kentsis and F. Brown (Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center) for the HL-60 cell line. This work was supported by the Josie Robertson Foundation (D.A.B.), the MSKCC Core Grant (P30 CA008748), the NCI (grant no. U54CA112962 to T.R.G.), HHMI (T.R.G.) and the NIH (CA174008-01A1 to W.W.B. and NIH NIGMS T32 GM115327-Tan to D.C.J.). NR 42 TC 2 Z9 2 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 EI 1552-4469 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JAN PY 2017 VL 13 IS 1 BP 46 EP 53 DI 10.1038/NCHEMBIO.2229 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EJ5OI UT WOS:000393267200012 PM 27820798 ER PT J AU Ponde, PH de Sena, EP Camprodon, JA de Araujo, AN Neto, MF DiBiasi, M Baptista, AF Moura, LMVR Cosmo, C AF Ponde, Pedro H. de Sena, Eduardo P. Camprodon, Joan A. de Araujo, Arao Nogueira Neto, Mario F. DiBiasi, Melany Baptista, Abrahao Fontes Moura, Lidia M. V. R. Cosmo, Camila TI Use of transcranial direct current stimulation for the treatment of auditory hallucinations of schizophrenia - a systematic review SO NEUROPSYCHIATRIC DISEASE AND TREATMENT LA English DT Review DE auditory hallucinations; tDCS; schizophrenia; non-invasive brain stimulation ID NONINVASIVE BRAIN-STIMULATION; NEGATIVE SYNDROME SCALE; MAGNETIC STIMULATION; FUNCTIONAL CONNECTIVITY; VERBAL HALLUCINATIONS; TDCS; SYMPTOMS; METAANALYSIS; ACTIVATION; SMOKING AB Introduction: Auditory hallucinations are defined as experiences of auditory perceptions in the absence of a provoking external stimulus. They are the most prevalent symptoms of schizophrenia with high capacity for chronicity and refractoriness during the course of disease. The transcranial direct current stimulation (tDCS) - a safe, portable, and inexpensive neuromodulation technique has emerged as a promising treatment for the management of auditory hallucinations. Objective: The aim of this study is to analyze the level of evidence in the literature available for the use of tDCS as a treatment for auditory hallucinations in schizophrenia. Methods: A systematic review was performed, searching in the main electronic databases including the Cochrane Library and MEDLINE/PubMed. The searches were performed by combining descriptors, applying terms of the Medical Subject Headings (MeSH) of Descriptors of Health Sciences and descriptors contractions. PRISMA protocol was used as a guide and the terms used were the clinical outcomes ("Schizophrenia" OR "Auditory Hallucinations" OR "Auditory Verbal Hallucinations" OR "Psychosis") searched together ("AND") with interventions ("transcranial Direct Current Stimulation" OR "tDCS" OR "Brain Polarization"). Results: Six randomized controlled trials that evaluated the effects of tDCS on the severity of auditory hallucinations in schizophrenic patients were selected. Analysis of the clinical results of these studies pointed toward incongruence in the information with regard to the therapeutic use of tDCS with a view to reducing the severity of auditory hallucinations in schizophrenia. Only three studies revealed a therapeutic benefit, manifested by reductions in severity and frequency of auditory verbal hallucinations in schizophrenic patients. Conclusion: Although tDCS has shown promising results in reducing the severity of auditory hallucinations in schizophrenic patients, this technique cannot yet be used as a therapeutic alternative due to lack of studies with large sample sizes that portray the positive effects that have been described. C1 [Ponde, Pedro H.] Univ Fed Bahia, Dynam Neuromusculoskeletal Syst Lab, Bahiana Sch Med & Publ Hlth, Salvador, BA, Brazil. [de Sena, Eduardo P.; de Araujo, Arao Nogueira; Cosmo, Camila] Univ Fed Bahia, Postgrad Program Interact Proc Organs & Syst, Salvador, BA, Brazil. [Camprodon, Joan A.; Cosmo, Camila] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Lab Neuropsychiat & Neuromodulat, Boston, MA USA. [Camprodon, Joan A.; Cosmo, Camila] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Transcranial Magnet Stimulat Clin Serv, Boston, MA USA. [Neto, Mario F.] Univ Fed Bahia, Sci Training Ctr Dept, Sch Med Bahia, Salvador, BA, Brazil. [DiBiasi, Melany] Harvard Med Sch, Neuromodulat Ctr, Spaulding Rehabil Hosp, Boston, MA USA. [Baptista, Abrahao Fontes; Cosmo, Camila] Univ Fed Bahia, Funct Electrostimulat Lab, Biomorphol Dept, Salvador, BA, Brazil. [Baptista, Abrahao Fontes] Univ Fed Bahia, Postgrad Program Med & Human Hlth, Sch Med, Salvador, BA, Brazil. [Moura, Lidia M. V. R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Cosmo, Camila] Univ Fed Bahia, Ctr Technol Innovat Rehabil, Salvador, BA, Brazil. [Cosmo, Camila] Bahia State Hlth Dept SESAB, Salvador, BA, Brazil. RP Cosmo, C (reprint author), Univ Fed Bahia, Inst Hlth Sci, Ave Reitor Miguel Calmon S-N, BR-40110100 Salvador, BA, Brazil. EM ccosmo@ufba.br NR 48 TC 0 Z9 0 U1 0 U2 0 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2021 J9 NEUROPSYCH DIS TREAT JI Neuropsychiatr. Dis. Treat. PY 2017 VL 13 BP 347 EP 355 DI 10.2147/NDT.S122016 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA EJ5DE UT WOS:000393235900004 PM 28203084 ER PT J AU Khoury, CC Steele, DJR AF Khoury, Charbel C. Steele, David J. R. TI The Challenges of Treating Cancer Patients on Hemodialysis, or With Chronic Kidney Disease SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID CRITICALLY-ILL PATIENTS; RENAL-FAILURE; HEMATOLOGICAL MALIGNANCIES; ANEMIA; DIALYSIS; ESRD; INJURY; ALPHA; KDIGO; CKD C1 [Khoury, Charbel C.; Steele, David J. R.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Steele, David J. R.] Harvard Med Sch, Med, Boston, MA USA. RP Khoury, CC (reprint author), Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JAN PY 2017 VL 31 IS 1 BP 40 EP 44 PG 5 WC Oncology SC Oncology GA EJ6XE UT WOS:000393363300005 ER PT J AU Oh, E Choi, IK Hong, J Yun, CO AF Oh, Eonju Choi, Il-Kyu Hong, JinWoo Yun, Chae-Ok TI Oncolytic adenovirus coexpressing interleukin-12 and decorin overcomes Treg-mediated immunosuppression inducing potent antitumor effects in a weakly immunogenic tumor model SO ONCOTARGET LA English DT Article DE oncolytic adenovirus; IL-12; decorin; TGF-beta; Treg ID GROWTH-FACTOR-BETA; REGULATORY T-CELLS; GENE-THERAPY; TGF-BETA; HEPATOCELLULAR-CARCINOMA; EXPRESSING IL-12; CLINICAL-TRIALS; LUNG METASTASES; CANCER-THERAPY; IMMUNE CELLS AB Interleukin (IL)-12 is a potent antitumor cytokine. However, immunosuppressive tumor microenvironments containing transforming growth factor-beta (TGF-beta) attenuate cytokine-mediated antitumor immune responses. To enhance the efficacy of IL-12-mediated cancer immunotherapy, decorin (DCN) was explored as an adjuvant for overcoming TGF-beta-mediated immunosuppression. We designed and generated a novel oncolytic adenovirus (Ad) coexpressing IL-12 and DCN (RdB/IL12/DCN). RdB/IL12/DCN-treated tumors showed significantly greater levels of interferon (IFN)-gamma, tumor necrosis factor-a, monocyte chemoattractant protein-1, and IFN-gamma-secreting immune cells than tumors treated with cognate control oncolytic Ad expressing a single therapeutic gene (RdB/DCN or RdB/IL12). Moreover, RdB/IL12/DCN attenuated intratumoral TGF-beta expression, which positively correlated with reduction of Treg cells in draining lymph nodes and tumor tissues. Furthermore, tumor tissue treated with RdB/IL12/DCN showed increases infiltration of CD8(+) T cells and proficient viral spreading within tumor tissues. These results demonstrated that an oncolytic Ad co-expressing IL-12 and DCN induces a potent antitumor immune response via restoration of antitumor immune function in a weakly immunogenic murine 4T1 orthotopic breast cancer model. These findings provide new insights into the therapeutic mechanisms of IL-12 plus DCN, making it a promising cancer immunotherapeutic agent for overcoming tumor-induced immunosuppression. C1 [Oh, Eonju; Hong, JinWoo; Yun, Chae-Ok] Hanyang Univ, Coll Engn, Dept Bioengn, Seoul 133791, South Korea. [Choi, Il-Kyu] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA. RP Yun, CO (reprint author), Hanyang Univ, Coll Engn, Dept Bioengn, Seoul 133791, South Korea. EM chaeok@hanyang.ac.kr OI Hong, JinWoo/0000-0003-2137-7846 FU National Research Foundation of Korea [2015R1A2A1A13027811, 2013M3A9D3045879, 2016M3A9B5942352] FX This work was supported by grants from the National Research Foundation of Korea (2015R1A2A1A13027811, 2013M3A9D3045879, and 2016M3A9B5942352). NR 78 TC 0 Z9 0 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 3 BP 4730 EP 4746 DI 10.18632/oncotarget.13972 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EJ5AH UT WOS:000393228400080 PM 28002796 ER PT J AU Wu, LP Fu, JF Wan, L Pan, J Lai, SC Zhong, J Chung, DC Wang, LJ AF Wu, Lunpo Fu, Jianfei Wan, Li Pan, Jie Lai, Sanchuan Zhong, Jing Chung, Daniel C. Wang, Liangjing TI Survival outcomes and surgical intervention of small intestinal neuroendocrine tumors: a population based retrospective study SO ONCOTARGET LA English DT Article DE small intestine; neuroendocrine tumors; prognostic factors; surgical management; SEER ID CARCINOID-TUMORS; PROGNOSTIC-FACTORS; CONSENSUS GUIDELINES; ENDOCRINE TUMORS; GRADING SYSTEM; UNITED-STATES; GEP-NETS; MANAGEMENT; MIDGUT; EPIDEMIOLOGY AB Background: Small intestinal neuroendocrine tumors (SiNETs) without distant metastasis typically behave in an indolent manner, but there can be heterogeneity. We aimed to define the survival outcomes and impacts of surgical intervention. Methods: A retrospective cohort study was conducted by using data from the Surveillance, Epidemiology, and End Results (SEER) database. Clinicopathologic features were analyzed in 4407 patients between 2000 and 2012. The cancer specific survival (CSS) was calculated by the Kaplan-Meier method. Multivariable Cox regression models with hazard ratios (HRs) were constructed to analyze survival outcomes and risk factors. Results: The adjusted incidence of early SiNETs is 1.3/100,000. Tumors are most commonly located in the ileum and are small (<= 2 cm). The 5-year and 10-year CSS rates were 95.0% and 88.5%, respectively. Age > 50 years, large tumor size (> 2cm), poor differentiation, advanced T classification, and absence of surgical treatment were independent predictors of poor survival. Stratified analysis indicated that surgery significantly improved survival in patients that were white (HR, 0.45), > 50 years old (HR, 0.61), had duodenal tumors (HR, 0.43), large tumors (> 2cm) (HR, 0.32), advanced T classification (T3: HR, 0.29; T4: HR, 0.18) or well differentiation (HR, 0.55). There was no significant survival difference between local resection and radical resection (P = 0.884). Conclusions: Early SiNETs have a favorable prognosis. Surgical resection may improve outcomes, particularly in older patients and those with large tumors. More aggressive resections couldn't improve outcomes. C1 [Wu, Lunpo; Wan, Li; Zhong, Jing; Wang, Liangjing] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Gastroenterol, Hangzhou, Zhejiang, Peoples R China. [Wu, Lunpo; Wan, Li; Lai, Sanchuan; Zhong, Jing; Wang, Liangjing] Zhejiang Univ, Inst Gastroenterol, Hangzhou, Zhejiang, Peoples R China. [Fu, Jianfei] Zhejiang Univ, Jinhua Hosp, Dept Oncol, Jinhua, Zhejiang, Peoples R China. [Pan, Jie] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Endocrinol, Hangzhou, Zhejiang, Peoples R China. [Lai, Sanchuan] Zhejiang Univ, Sir Run Run Shaw Hosp, Dept Gastroenterol, Hangzhou, Zhejiang, Peoples R China. [Chung, Daniel C.] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. RP Wang, LJ (reprint author), Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Gastroenterol, Hangzhou, Zhejiang, Peoples R China.; Wang, LJ (reprint author), Zhejiang Univ, Inst Gastroenterol, Hangzhou, Zhejiang, Peoples R China. EM Wanglj76@hotmail.com FU National Natural Science Foundation of China [81472214, 81302070]; Science and Technology Innovation Team of Zhejiang Province in China [2013TD13]; Natural Science Foundation of Zhejiang Province in China [LY13H160019]; Public Technology Application Research of Zhejiang Province [2016YFC0107003]; National Key Research and Development Program of China [2015C37085] FX The research was supported by the National Natural Science Foundation of China (81472214, 81302070), Science and Technology Innovation Team of Zhejiang Province in China (2013TD13) and Natural Science Foundation of Zhejiang Province in China (LY13H160019), the Public Technology Application Research of Zhejiang Province (2016YFC0107003) and National Key Research and Development Program of China (2015C37085). NR 44 TC 0 Z9 0 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 3 BP 4935 EP 4947 DI 10.18632/oncotarget.13632 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EJ5AH UT WOS:000393228400095 PM 27903960 ER PT J AU Feng, S Shao, LJ Castro, P Coleman, I Nelson, PS Smith, PD Davies, BR Ittmann, M AF Feng, Shu Shao, Longjiang Castro, Patricia Coleman, Ilsa Nelson, Peter S. Smith, Paul D. Davies, Barry R. Ittmann, Michael TI Combination treatment of prostate cancer with FGF receptor and AKT kinase inhibitors SO ONCOTARGET LA English DT Article DE prostate cancer; signal transduction; fibroblast growth factors; kinase inhibitor; AKT ID LUNG-CANCER; PI3K/AKT PATHWAY; GROWTH; PROGRESSION; EXPRESSION; PTEN; AZD5363; SENSITIVITY; PREDICT; MODELS AB Activation of the PI3K/AKT pathway occurs in the vast majority of advanced prostate cancers (PCas). Activation of fibroblast growth factor receptor (FGFR) signaling occurs in a wide variety of malignancies, including PCa. RNA-Seq of castration resistant PCa revealed expression of multiple FGFR signaling components compatible with FGFR signaling in all cases, with multiple FGF ligands expressed in 90% of cases. Immunohistochemistry confirmed FGFR signaling in the majority of xenografts and advanced PCas. AZD5363, an AKT kinase inhibitor and AZD4547, a FGFR kinase inhibitor are under active clinical development. We therefore sought to determine if these two drugs have additive effects in PCa models. The effect of both agents, singly and in combination was evaluated in a variety of PCa cell lines in vitro and in vivo. All cell lines tested responded to both drugs with decreased invasion, soft agar colony formation and growth in vivo, with additive effects seen with combination treatment. Activation of the FGFR, AKT, ERK and STAT3 pathways was examined in treated cells. AZD5363 inhibited AKT signaling and increased FGFR1 signaling, which partially compensated for decreased AKT kinase activity. While AZD4547 could effectively block the ERK pathway, combination treatment was needed to completely block STAT3 activation. Thus combination treatment with AKT and FGFR kinase inhibitors have additive effects on malignant phenotypes in vitro and in vivo by inhibiting multiple signaling pathways and mitigating the compensatory upregulation of FGFR signaling induced by AKT kinase inhibition. Our studies suggest that co-targeting these pathways may be efficacious in advanced PCa. C1 [Feng, Shu; Shao, Longjiang; Castro, Patricia; Ittmann, Michael] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Feng, Shu; Shao, Longjiang; Castro, Patricia; Ittmann, Michael] Baylor Coll Med, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. [Coleman, Ilsa; Nelson, Peter S.] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. [Smith, Paul D.; Davies, Barry R.] AstraZeneca, Oncol iMED, Macclesfield, Cheshire, England. RP Ittmann, M (reprint author), Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA.; Ittmann, M (reprint author), Baylor Coll Med, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. EM mittmann@bcm.edu FU Dept of Defense Prostate Cancer Research Program [W81XWH-13-1-0367]; Prostate Cancer Foundation; Dept of Veterans Affairs Merit Review program; National Cancer Institute [P50CA097186, R01CA165573]; Dan L. Duncan Cancer [P30 CA125123] FX This work was supported by grants from the Dept of Defense Prostate Cancer Research Program (W81XWH-13-1-0367; MI); the Prostate Cancer Foundation (PSN and MI); the Dept of Veterans Affairs Merit Review program (MI); the National Cancer Institute (P50CA097186 and R01CA165573; PSN) and to the Dan L. Duncan Cancer (P30 CA125123) supporting the Human Tissue Acquisition and Pathology Shared Resource and by the use of the facilities of the Michael E. DeBakey VAMC. NR 44 TC 0 Z9 0 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 4 BP 6179 EP 6192 DI 10.18632/oncotarget.14049 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EJ5WG UT WOS:000393289000065 PM 28008155 ER PT J AU Timerman, D McEnery-Stonelake, M Joyce, CJ Nambudiri, VE Hodi, FS Claus, EB Ibrahim, N Lin, JY AF Timerman, Dmitriy McEnery-Stonelake, Melissa Joyce, Cara J. Nambudiri, Vinod E. Hodi, F. Stephen Claus, Elizabeth B. Ibrahim, Nageatte Lin, Jennifer Y. TI Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma SO ONCOTARGET LA English DT Article DE vitamin D deficiency; melanoma; 25(OH)D3 ID D SUPPLEMENTATION; UNITED-STATES; CANCER RISK; PREVENTION; MORTALITY; METAANALYSIS; NUTRITION; TRIAL AB Vitamin D deficiency (<= 20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome. A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH) D3 level were identified. 252 individuals with a 25(OH) D3 level recorded within one year after diagnosis were included in the study and the individual and melanoma characteristics such as age, sex, Breslow thickness, ulceration, stage, mitotic rate, and LDH were obtained from the medical record. A worse melanoma prognosis was associated with vitamin D deficiency (P=0.012), higher stage (P<0.001), ulceration (P=0.001), and higher mitotic rate (P=0.001) (HR 1.93, 95% CI 1.15-3.22). In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality (adjusted HR 2.06, 95% CI 1.10-3.87). Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or <= 20 ng/mL increase in their 25(OH) D3 concentration had significantly worse outcomes (HR 4.68, 95% CI 1.05-20.88) compared to non-deficient patients who had a > 20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma. C1 [Timerman, Dmitriy] Harvard Med Sch, HST, Harvard MIT Hlth Sci & Technol, Boston, MA USA. [McEnery-Stonelake, Melissa] Univ Alabama Birmingham, Dept Dermatol, Birmingham, AL 35294 USA. [Joyce, Cara J.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA USA. [Nambudiri, Vinod E.; Lin, Jennifer Y.] Harvard Med Sch, Brigham & Womens Hosp, Dept Dermatol, Boston, MA USA. [Hodi, F. Stephen; Ibrahim, Nageatte; Lin, Jennifer Y.] Harvard Med Sch, Dana Farber Canc Inst, Melanoma Program, Boston, MA USA. [Claus, Elizabeth B.] Harvard Med Sch, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA USA. [Ibrahim, Nageatte] Merck Res Labs, Clin Oncol, North Wales, PA USA. RP Lin, JY (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Dermatol, Boston, MA USA.; Lin, JY (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Melanoma Program, Boston, MA USA. EM jylin@partners.org FU James R. Fitzgerald, Jr. Melanoma Research Fund FX The authors would like to thank James R. Fitzgerald, Jr. Melanoma Research Fund for support of this project. NR 25 TC 0 Z9 0 U1 1 U2 1 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 4 BP 6873 EP 6882 DI 10.18632/oncotarget.14316 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EJ5WG UT WOS:000393289000120 PM 28036288 ER PT J AU Bajwa, P Nielsen, S Lombard, JM Rassam, L Nahar, P Rueda, BR Wilkinson, JE Miller, RA Tanwar, PS AF Bajwa, Preety Nielsen, Sarah Lombard, Janine M. Rassam, Loui Nahar, Pravin Rueda, Bo R. Wilkinson, J. Erby Miller, Richard A. Tanwar, Pradeep S. TI Overactive mTOR signaling leads to endometrial hyperplasia in aged women and mice SO ONCOTARGET LA English DT Article DE endometrial; mTOR; rapalogs; aging; PI3K; Pten; Gerotarget ID EXTENDS LIFE-SPAN; FOLLICLE POOL; RAPAMYCIN; CANCER; PATHWAY; TUMORIGENESIS; ACTIVATION; MOUSE; MECHANISMS; INHIBITOR AB During aging, uncontrolled epithelial cell proliferation in the uterus results in endometrial hyperplasia and/or cancer development. The mTOR signaling pathway is one of the major regulators of aging as suppression of this pathway prolongs lifespan in model organisms. Genetic alterations in this pathway via mutations and/or amplifications are often encountered in endometrial cancers. However, the exact contribution of mTOR signaling and uterine aging to endometrial pathologies is currently unclear. This study examined the role of mTOR signaling in uterine aging and its implications in the development of endometrial hyperplasia. The hyperplastic endometrium of both postmenopausal women and aged mice exhibited elevated mTOR activity as seen with increased expression of the pS6 protein. Analysis of uteri from Pten heterozygous and Pten overexpressing mice further confirmed that over-activation of mTOR signaling leads to endometrial hyperplasia. Pharmacological inhibition of mTOR signaling using rapamycin treatment suppressed endometrial hyperplasia in aged mice. Furthermore, treatment with mTOR inhibitors reduced colony size and proliferation of a PTEN negative endometrial cancer cell line in 3D culture. Collectively, this study suggests that hyperactivation of the mTOR pathway is involved in the development of endometrial hyperplasia in aged women and mice. C1 [Bajwa, Preety; Tanwar, Pradeep S.] Sch Biomed Sci & Pharm, Gynaecol Oncol Grp, Callaghan, NSW, Australia. [Nielsen, Sarah; Rassam, Loui] Hunter Canc Biobank, Callaghan, NSW, Australia. [Lombard, Janine M.; Rassam, Loui; Nahar, Pravin] Univ Newcastle, Sch Med & Publ Hlth, Callaghan, NSW, Australia. [Lombard, Janine M.] Calvary Mater Newcastle, Dept Med Oncol, Gynaecol Oncol, Waratah, NSW, Australia. [Nahar, Pravin] John Hunter Hosp, Gynaecol & Obstet, New Lambton, NSW, Australia. [Rueda, Bo R.] Harvard Med Sch, Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA USA. [Rueda, Bo R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA USA. [Rueda, Bo R.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA USA. [Wilkinson, J. Erby] Univ Michigan, Sch Med, Dept Pathol, Unit Lab Anim Med, Ann Arbor, MI USA. [Miller, Richard A.] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. [Miller, Richard A.] Univ Michigan, Geriatr Ctr, Ann Arbor, MI USA. RP Tanwar, PS (reprint author), Sch Biomed Sci & Pharm, Gynaecol Oncol Grp, Callaghan, NSW, Australia. EM pradeep.tanwar@newcastle.edu.au FU National Health and Medical Research Council; Australian Research Council; Cancer Institute NSW; National Institute of Health [AG022303]; Glenn Foundation for Medical Research; University of Newcastle Postgraduate Research Fellowship FX This work in part was supported by funding from the National Health and Medical Research Council, the Australian Research Council, and the Cancer Institute NSW (P.S.T). Work in the Miller lab was supported by the National Institute of Health grant AG022303 and the Glenn Foundation for Medical Research. The Hunter Cancer Biobank is supported by the Cancer Institute NSW. P.B. is a recipient of the University of Newcastle Postgraduate Research Fellowship. NR 46 TC 1 Z9 1 U1 2 U2 2 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 5 BP 7265 EP 7275 DI 10.18632/oncotarget.13919 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EJ5YP UT WOS:000393295500011 PM 27980219 ER PT J AU Feng, ZY Xu, WD Zhang, CG Liu, MR Wen, HW AF Feng, Zhaoyi Xu, Wandong Zhang, Chenguang Liu, Mengran Wen, Hongwu TI Inhibition of gamma-secretase in Notch1 signaling pathway as a novel treatment for ovarian cancer SO ONCOTARGET LA English DT Article DE epithelial ovarian carcinoma; Notch; Jagged1; NICD; gamma-secretase ID HUMAN BREAST-CANCER; JAGGED1 EXPRESSION; ESTROGEN-RECEPTOR; ALZHEIMER-DISEASE; LEUKEMIA CELLS; POOR; CARCINOMA; APOPTOSIS; CLEAVAGE AB Epithelial ovarian cancer (EOC) is the leading cause of death for gynecological cancer. Most patients are not diagnosed until the cancer is at an advanced stage with poor prognosis. Notch1 signaling pathway plays an oncogenic role in EOC. There have been few studies on enzymatic activity of gamma-secretase and the mechanism of how gamma-secretase inhibitor works on cancer cell. Here, we show that Jagged1 and NICD were highly expressed in ovarian carcinoma. The expressions of Notch1, Jagged1 and NICD in Notch1 pathway did not correlate with outcome in ovarian cancer. The enzymatic activity of g-secretase in ovarian cancer cell lines SKOV3, CAOV3 and ES2 is significantly higher than in normal ovarian epithelial cell line T29. DAPT (a gamma-secretase inhibitor) reduced the enzymatic activity of gamma-secretase, inhibited the proliferation, and increased the apoptosis in ovarian cancer cell lines. Hence, g-secretase inhibitor may become a highly promising novel therapeutic strategy against ovarian cancer in the field of precision medicine. C1 [Feng, Zhaoyi; Xu, Wandong; Liu, Mengran; Wen, Hongwu] Peking Univ, Dept Obstet & Gynecol, Hosp 1, Beijing 100034, Peoples R China. [Feng, Zhaoyi] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc Immunol, Charlestown, MA 02129 USA. [Feng, Zhaoyi] Harvard Med Sch, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Zhang, Chenguang] Capital Med Univ, Dept Med Genet, Beijing 100069, Peoples R China. RP Wen, HW (reprint author), Peking Univ, Dept Obstet & Gynecol, Hosp 1, Beijing 100034, Peoples R China. EM wenhongwu3184@sohu.com NR 32 TC 0 Z9 0 U1 0 U2 0 PU IMPACT JOURNALS LLC PI ORCHARD PARK PA 6666 E QUAKER ST, STE 1, ORCHARD PARK, NY 14127 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PY 2017 VL 8 IS 5 BP 8215 EP 8225 DI 10.18632/oncotarget.14152 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EJ5YP UT WOS:000393295500088 PM 28030808 ER PT J AU Sinha, S Puram, SV Sethi, RKV Goyal, N Emerick, KS Lin, D Durand, ML Deschler, DG AF Sinha, Sumi Puram, Sidharth V. Sethi, Rosh K. V. Goyal, Neerav Emerick, Kevin S. Lin, Derrick Durand, Marlene L. Deschler, Daniel G. TI Perioperative Deep Vein Thrombosis Risk Stratification: A Comparative Analysis of Free and Pedicled Flap Patients SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE deep vein thrombosis; free flap; pedicled flap; head and neck; microvascular reconstruction ID VENOUS THROMBOEMBOLISM; PULMONARY-EMBOLISM; NECK-CANCER; HEAD; SURGERY; RECONSTRUCTION; OTOLARYNGOLOGY; MALIGNANCY AB Patients with head and neck cancer who undergo reconstructive surgery are at risk for deep venous thrombosis (DVT), but the risk profile for patients undergoing major flap reconstruction is highly variable. Herein, we report our findings from a retrospective analysis of head and neck cancer patients (n = 517) who underwent free (n = 384) or pedicled (n = 133) flap reconstructive operations at a major tertiary care center from 2011 to 2014. DVTs developed perioperatively in 9 (1.7%) patients. Compared with pedicled flap patients, free flap patients had a longer mean operative time (421.4 +/- 4.4 vs 332.7 +/- 10.7 min, P < .0001), but the DVT incidence did not differ significantly between free and pedicled flap patients (1.6% vs 2.2%, respectively, P = .28). These data suggest that perioperative DVT risk in head and neck oncology patients may be largely similar regardless of the reconstructive strategy pursued. C1 [Sinha, Sumi; Puram, Sidharth V.; Sethi, Rosh K. V.; Emerick, Kevin S.; Lin, Derrick; Deschler, Daniel G.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Goyal, Neerav] Penn State Hershey Med Ctr, Dept Otolaryngol, Hershey, PA USA. [Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Daniel_deschler@meei.harvard.edu NR 17 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 EI 1097-6817 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 2017 VL 156 IS 1 BP 118 EP 121 DI 10.1177/0194599816667399 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA EJ0DH UT WOS:000392878300017 PM 27600631 ER PT J AU Hu, QH Cho, MS Thiagarajan, P Aung, FM Sood, AK Afshar-Kharghan, V AF Hu, Qianghua Cho, Min Soon Thiagarajan, Perumal Aung, Fleur M. Sood, Anil K. Afshar-Kharghan, Vahid TI A small amount of cyclooxygenase 2 (COX2) is constitutively expressed in platelets SO PLATELETS LA English DT Article DE COX2; Platelets; COX1COX2; expression ID OVARIAN-CANCER CELLS; MEGAKARYOPOIESIS; INHIBITION; ASSAY AB Cyclooxygenase (COX) is the rate-limiting enzyme in conversion of arachidonic acid to prostanoids, COX2, Platelets, COX1C0X2, expression and has two isoforms, COX1 and COX2, which share similar to 65% amino acid homology. COX1 is universally expressed in many cell types including platelets; however, expression of COX2 is known to be more limited. We examined expression of COX2 mRNA and protein in platelets and platelet-derived microparticles (MPs); using quantitative RT-PCR, immunostaining, and Western blotting. We have detected a significant amount of COX2 in platelets, both at mRNA and protein levels. We found that COX1/COX2 mRNA and protein ratios in platelets were 370:1 and 17:1, respectively. Expression level of COX2 in platelets was less than COX1, but comparable to the expression of COX2 in malignant epithelial cells. Considering the important role of COX2 in tumorigenesis and thrombosis, and the large number of circulating platelets, we propose that platelet COX2 may play an important role in physiologic and pathologic conditions. C1 [Hu, Qianghua; Cho, Min Soon; Afshar-Kharghan, Vahid] Univ Texas MD Anderson Canc Ctr, Sect Benign Hematol, Houston, TX 77030 USA. [Thiagarajan, Perumal] Baylor Coll Med, Ctr Translat Res Inflammatory Dis, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Aung, Fleur M.] Univ Texas MD Anderson Canc Ctr, Lab Med, Houston, TX 77030 USA. [Sood, Anil K.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA. RP Sood, AK (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol & Reprod Med, Houston, TX 77030 USA.; Afshar-Kharghan, V (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Benign Hematol, Houston, TX 77030 USA. EM asood@mdanderson.org; vakharghan@mdanderson.org OI Thiagarajan, Perumal/0000-0003-2186-7036 FU NIH grant [CA177909]; Ovarian Cancer Research Fund Program Project Development Grant FX This work is supported in part by NIH grant CA177909 (V. Afshar-Kharghan and A.K. Sood) and Ovarian Cancer Research Fund Program Project Development Grant (V. Afshar-Kharghan and A.K. Sood). NR 18 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0953-7104 EI 1369-1635 J9 PLATELETS JI Platelets PD JAN PY 2017 VL 28 IS 1 BP 99 EP 102 DI 10.1080/09537104.2016.1203406 PG 4 WC Cell Biology; Hematology SC Cell Biology; Hematology GA EJ5OZ UT WOS:000393268900016 PM 27534811 ER PT J AU Tenke, CE Kayser, J Pechtel, P Webb, CA Dillon, DG Goer, F Murray, L Deldin, P Kurian, BT McGrath, PJ Parsey, R Trivedi, M Fava, M Weissman, MM Mcinnis, M Abraham, K Alvarenga, JE Alschuler, DM Cooper, C Pizzagalli, DA Bruder, GE AF Tenke, Craig E. Kayser, Jurgen Pechtel, Pia Webb, Christian A. Dillon, Daniel G. Goer, Franziska Murray, Laura Deldin, Patricia Kurian, Benji T. McGrath, Patrick J. Parsey, Ramin Trivedi, Madhukar Fava, Maurizio Weissman, Myrna M. Mcinnis, Melvin Abraham, Karen Alvarenga, Jorge E. Alschuler, Daniel M. Cooper, Crystal Pizzagalli, Diego A. Bruder, Gerard E. TI Demonstrating test-retest reliability of electrophysiological measures for healthy adults in a multisite study of biomarkers of antidepressant treatment response SO PSYCHOPHYSIOLOGY LA English DT Article DE EEG; Evoked potentials; Surface Laplacian; LORETA; Biomarkers; Reliability ID PRINCIPAL-COMPONENTS-ANALYSIS; CURRENT SOURCE DENSITY; AUDITORY-EVOKED-POTENTIALS; ANTERIOR CINGULATE CORTEX; EEG ALPHA ASYMMETRY; RESOLUTION ELECTROMAGNETIC TOMOGRAPHY; EVENT-RELATED POTENTIALS; ERP GENERATOR PATTERNS; LAPLACIAN WAVE-FORMS; MAJOR DEPRESSION AB Growing evidence suggests that loudness dependency of auditory evoked potentials (LDAEP) and resting EEG alpha and theta may be biological markers for predicting response to antidepressants. In spite of this promise, little is known about the joint reliability of these markers, and thus their clinical applicability. New standardized procedures were developed to improve the compatibility of data acquired with different EEG platforms, and used to examine test-retest reliability for the three electrophysiological measures selected for a multisite project-Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care (EMBARC). Thirty-nine healthy controls across four clinical research sites were tested in two sessions separated by about 1 week. Resting EEG (eyes-open and eyes-closed conditions) was recorded and LDAEP measured using binaural tones (1000 Hz, 40 ms) at five intensities (60-100 dB SPL). Principal components analysis of current source density waveforms reduced volume conduction and provided reference-free measures of resting EEG alpha and N1 dipole activity to tones from auditory cortex. Low-resolution electromagnetic tomography (LORETA) extracted resting theta current density measures corresponding to rostral anterior cingulate (rACC), which has been implicated in treatment response. There were no significant differences in posterior alpha, N1 dipole, or rACC theta across sessions. Test-retest reliability was.84 for alpha, .87 for N1 dipole, and .70 for theta rACC current density. The demonstration of good-to-excellent reliability for these measures provides a template for future EEG/ERP studies from multiple testing sites, and an important step for evaluating them as biomarkers for predicting treatment response. C1 [Tenke, Craig E.; Kayser, Jurgen; McGrath, Patrick J.; Weissman, Myrna M.; Abraham, Karen; Alvarenga, Jorge E.; Alschuler, Daniel M.; Bruder, Gerard E.] Columbia Univ Coll Phys & Surg, Dept Psychiat, 722 W 168th St, New York, NY 10032 USA. [Tenke, Craig E.; Kayser, Jurgen; McGrath, Patrick J.; Weissman, Myrna M.; Abraham, Karen; Alvarenga, Jorge E.; Alschuler, Daniel M.; Bruder, Gerard E.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. [Pechtel, Pia; Webb, Christian A.; Dillon, Daniel G.; Fava, Maurizio; Pizzagalli, Diego A.] Harvard Med Sch, Dept Psychiat, Belmont, MA USA. [Pechtel, Pia; Webb, Christian A.; Dillon, Daniel G.; Fava, Maurizio; Pizzagalli, Diego A.] McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. [Goer, Franziska; Murray, Laura] McLean Hosp, Ctr Depress Anxiety & Stress Res, 115 Mill St, Belmont, MA 02178 USA. [Deldin, Patricia; Mcinnis, Melvin] Univ Michigan Hlth Syst, Dept Psychol, Ann Arbor, MI USA. [Deldin, Patricia; Mcinnis, Melvin] Univ Michigan Hlth Syst, Dept Psychiat, Ann Arbor, MI USA. [Kurian, Benji T.; Trivedi, Madhukar; Cooper, Crystal] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA. [Parsey, Ramin] SUNY Stony Brook, Dept Psychiat, Stony Brook, NY 11794 USA. [Fava, Maurizio] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Tenke, CE (reprint author), New York State Psychiat Inst & Hosp, Div Cognit Neurosci, Unit 50,1051 Riverside Dr, New York, NY 10032 USA. EM cet2103@columbia.edu OI Kayser, Jurgen/0000-0001-5309-1573 FU National Institute of Mental Health of the National Institutes of Health [U01MH092221, U01MH092250]; EMBARC National Coordinating Center at UT Southwestern Medical Center; Data Center at Columbia; Stony Brook Universities; Targacept, Inc.; Pfizer, Inc.; Johnson Johnson; Evotec; Rexahn; Naurex; Forest Pharmaceuticals; Agency for Healthcare Research and Quality (AHRQ); Corcept Therapeutics, Inc.; Cyberonics, Inc.; National Alliance for Research in Schizophrenia and Depression; National Institute of Mental Health; National Institute on Drug Abuse; Novartis; Pharmacia Upjohn; Predix Pharmaceuticals (Epix); Solvay Pharmaceuticals, Inc.; Forest Research; Sunovion; [MH36295] FX The authors would like to thank the reviewers for their helpful comments. The EMBARC study was supported by the National Institute of Mental Health of the National Institutes of Health under award numbers U01MH092221 (MHT) and U01MH092250 (PGMcG, RVP, MMW). The CSD methods were funded by MH36295.; The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Valeant Pharmaceuticals donated the Wellbutrin XL that will be used in the clinical trial. This work was supported by the EMBARC National Coordinating Center at UT Southwestern Medical Center, Madhukar H. Trivedi, M.D., Coordinating PI, and the Data Center at Columbia and Stony Brook Universities. Dr. Kurian has received grant support from the following additional sources: Targacept, Inc.; Pfizer, Inc.; Johnson & Johnson; Evotec; Rexahn; Naurex; and Forest Pharmaceuticals. Dr. Trivedi is or has been an advisor/consultant to Abbott Laboratories, Inc., Abdi Ibrahim, Akzo (Organon Pharmaceuticals Inc.), Alkermes, AstraZeneca, Axon Advisors, Bristol-Myers Squibb Company, Cephalon, Inc., Cerecor, Concert Pharmaceuticals, Inc., Eli Lilly & Company, Evotec, Fabre Kramer Pharmaceuticals, Inc., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Global Services, LLC, Janssen Pharmaceutica Products, LP, Johnson & Johnson PRD, Libby, Lundbeck, Meade Johnson, MedAvante, Medtronic, Merck, Mitsubishi Tanabe Pharma Development America, Inc., Naurex, Neuronetics, Otsuka Pharmaceuticals, Pamlab, Parke-Davis Pharmaceuticals, Inc., Pfizer Inc., PgxHealth, Phoenix Marketing Solutions, Rexahn Pharmaceuticals, Ridge Diagnostics, Roche Products Ltd., Sepracor, SHIRE Development, Sierra, SK Life and Science, Sunovion, Takeda, Tal Medical/Puretech Venture, Targacept, Transcept, VantagePoint, Vivus, and Wyeth-Ayerst Laboratories. In addition, he has received research support from Agency for Healthcare Research and Quality (AHRQ), Corcept Therapeutics, Inc., Cyberonics, Inc., National Alliance for Research in Schizophrenia and Depression, National Institute of Mental Health, National Institute on Drug Abuse, Novartis, Pharmacia & Upjohn, Predix Pharmaceuticals (Epix), and Solvay Pharmaceuticals, Inc. For a comprehensive list of lifetime disclosures of Dr. Fava, see http://mghcme.org/faculty/faculty-detail/maurizio_fava. Dr. McGrath has received research grant support from Forest Research, Naurex, and Sunovion. Over the past 3 years, Dr. Pizzagalli has received honoraria/consulting fees from BlackThorn Therapeutics, Otsuka America Pharmaceutical, and Pfizer for activities unrelated to this project. All other authors have no biomedical financial interests or potential conflicts of interest. NR 108 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD JAN PY 2017 VL 54 IS 1 BP 34 EP 50 DI 10.1111/psyp.12758 PG 17 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA EJ9MI UT WOS:000393549800005 PM 28000259 ER PT J AU Pham, XH Lee, M Shim, S Jeong, S Kim, HM Hahm, E Lee, SH Lee, YS Jeong, DH Jun, BH AF Pham, Xuan-Hung Lee, Minwoo Shim, Seongbo Jeong, Sinyoung Kim, Hyung-Mo Hahm, Eunil Lee, Sang Hun Lee, Yoon-Sik Jeong, Dae Hong Jun, Bong-Hyun TI Highly sensitive and reliable SERS probes based on nanogap control of a Au-Ag alloy on silica nanoparticles SO RSC ADVANCES LA English DT Article ID ENHANCED-RAMAN-SCATTERING; SILVER NANOPARTICLES; GOLD NANOPARTICLES; OPTICAL-PROPERTIES; NANOSHELLS; NANOSTRUCTURES; SPECTROSCOPY; NANOSPHERES; FABRICATION; NANOPROBES AB We developed highly sensitive surface-enhanced Raman scattering (SERS) probes based on SiO2@Au@Ag nanoparticles (NPs) using the Ag growth onto Au NP seeds method. The SiO2@Au@Ag NPs were synthesized by reducing Ag ions under mild conditions (ascorbic acid) and using the structure-directing agent polyvinylpyrrolidone (PVP). SERS activities of the NPs were tuned by adjusting AgNO3 concentration, resulting in the growth of the Ag shell on the surface of the Au NP seeds and the formation of narrow gaps between two Ag NPs on the surface of the probes. The NPs exhibited strong Raman signals originating from a highly enhanced E-field at the gaps. The SiO2@Au@Ag NPs exhibited a low limit of detection (LOD) value of 2.4 nM for ATP, which proves that they are highly sensitive probes. Moreover, reproducible Raman signals of the SiO2@Au@ Ag NPs toward ATP were obtained in batch-to-batch experiments which is very promising for potential use in on-site detection. C1 [Pham, Xuan-Hung; Shim, Seongbo; Kim, Hyung-Mo; Hahm, Eunil; Jun, Bong-Hyun] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea. [Lee, Minwoo; Jeong, Sinyoung; Jeong, Dae Hong] Seoul Natl Univ, Dept Chem Educ, Seoul 151742, South Korea. [Lee, Sang Hun; Lee, Yoon-Sik] Seoul Natl Univ, Sch Chem & Biol Engn, Seoul 151742, South Korea. [Jeong, Sinyoung] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, 149 13th St, Charlestown, MA 02129 USA. RP Jun, BH (reprint author), Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea. EM bjun@konkuk.ac.kr FU Bio & Medical Technology Development Program of the National Research Foundation (NRF); Korean government (MSIP MOHW) [2016-A423-0045] FX This work was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) & funded by the Korean government (MSIP & MOHW) (2016-A423-0045). NR 50 TC 0 Z9 0 U1 10 U2 10 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2046-2069 J9 RSC ADV JI RSC Adv. PY 2017 VL 7 IS 12 BP 7015 EP 7021 DI 10.1039/c6ra26213a PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA EK2KK UT WOS:000393756000027 ER PT J AU Jan, M Ebert, BL Jaiswal, S AF Jan, Max Ebert, Benjamin L. Jaiswal, Siddhartha TI Clonal hematopoiesis SO SEMINARS IN HEMATOLOGY LA English DT Article DE Aging; Pre-leukemia; Hematopoietic stem cell ID ACUTE MYELOID-LEUKEMIA; ACQUIRED APLASTIC-ANEMIA; ACUTE NONLYMPHOCYTIC LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; IDENTIFIES SOMATIC MUTATIONS; OF-FUNCTION MUTATIONS; B-CELL LYMPHOCYTOSIS; STEM-CELL; MYELODYSPLASTIC SYNDROMES; UNDETERMINED SIGNIFICANCE AB Cancer results from multistep pathogenesis, yet the pre-malignant states that precede the development of many hematologic malignancies have been difficult to identify. Recent genomic studies of blood DNA from tens of thousands of people have revealed the presence of remarkably common, age-associated somatic mutations in genes associated with hematologic malignancies. These somatic mutations drive the expansion from a single founding cell to a detectable hematopoietic clone. Owing to the admixed nature of blood that provides a sampling of blood cell production throughout the body, clonal hematopoiesis is a rare view into the biology of pre-malignancy and the direct effects of pre cancerous lesions on organ dysfunction. Indeed, clonal hematopoiesis is associated not only with increased risk of hematologic malignancy, but also with cardiovascular disease and overall mortality. Here we review rapid advances in the genetic understanding of clonal hematopoiesis and nascent evidence implicating clonal hematopoiesis in malignant and non-malignant age-related disease. (C) 2017 Elsevier Inc. All rights reserved. C1 [Jan, Max] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Ebert, Benjamin L.; Jaiswal, Siddhartha] Harvard Med Sch, Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. [Ebert, Benjamin L.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Ebert, BL; Jaiswal, S (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. EM Benjamin_Ebert@dfci.harvard.edu; sjaiswal@partners.org FU NIH [R01 HL082945, R24 DK099808]; Department of Defense; Edward P. Evans Foundation; Leukemia and Lymphoma Society; Training Program in Molecular Hematology T32 training grant (Brigham and Women's Hospital); Burroughs Wellcome Fund Career Award for Medical Scientists FX This work was supported by grants from the NIH (R01 HL082945, R24 DK099808), the Department of Defense, the Edward P. Evans Foundation, and the Leukemia and Lymphoma Society. SJ is supported by the Training Program in Molecular Hematology T32 training grant (Brigham and Women's Hospital) and the Burroughs Wellcome Fund Career Award for Medical Scientists. NR 105 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0037-1963 EI 1532-8686 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2017 VL 54 IS 1 BP 43 EP 50 DI 10.1053/j.seminhematol.2016.10.002 PG 8 WC Hematology SC Hematology GA EJ8AY UT WOS:000393445800008 PM 28088988 ER PT J AU Koo, EB Gilbert, AL VanderVeen, DK AF Koo, Euna B. Gilbert, Aubrey L. VanderVeen, Deborah K. TI Treatment of Amblyopia and Amblyopia Risk Factors Based on Current Evidence SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Amblyopia; PEDIG ID CONGENITAL UNILATERAL CATARACT; ANISOMETROPIC AMBLYOPIA; INFANTILE ESOTROPIA; ACCOMMODATIVE ESOTROPIA; REFRACTIVE CORRECTION; STRABISMIC AMBLYOPIA; OPTICAL CORRECTION; SURGICAL-TREATMENT; RANDOMIZED-TRIAL; BOTULINUM TOXIN AB Purpose: Amblyopia is a leading cause of low vision and warrants timely management during childhood. We performed a literature review of the management of amblyopia and potential risk factors for amblyopia. Methods: Literature review of the management of amblyopia and risk factors for amblyopia. Results: Common amblyopia risk factors include anisometropic or high refractive error, strabismus, cataract, and ptosis. Often a conservative approach with spectacles is enough to prevent amblyopia. However, surgery may be necessary to clear the visual axis or align the eyes. Conclusion: Amblyopia risk factors should be managed early. Though amblyopia treatment is more likely to be successful at a younger age, those who are older but treatment-naive may still respond to treatment. Promoting binocular or dichoptic experiences may be the future direction of amblyopia management. C1 [Koo, Euna B.; Gilbert, Aubrey L.; VanderVeen, Deborah K.] Boston Childrens Hosp, Boston, MA USA. [Gilbert, Aubrey L.; VanderVeen, Deborah K.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Koo, Euna B.] Stanford Sch Med, 2452 Watson Ct, Palo Alto, CA 94303 USA. [VanderVeen, Deborah K.] Harvard Med Sch, Boston, MA USA. RP Koo, EB (reprint author), Stanford Sch Med, 2452 Watson Ct, Palo Alto, CA 94303 USA. EM kooeuna@gmail.com NR 60 TC 0 Z9 0 U1 6 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 1 EP 7 DI 10.1080/08820538.2016.1228408 PG 7 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700001 PM 27748640 ER PT J AU Gilbert, AL Koo, EB Heidary, G AF Gilbert, Aubrey L. Koo, Euna B. Heidary, Gena TI Evaluation and Management of Acute Acquired Comitant Esotropia in Children SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Chiari malformation; pediatric strabismus ID CHIARI-I-MALFORMATION; ONSET CONCOMITANT ESOTROPIA; SERIOUS NEUROLOGICAL DISEASE; BINOCULAR CONTROL; BOTULINUM-TOXIN; EYE-MOVEMENTS; SIGN; CLASSIFICATION; STRABISMUS AB Acute acquired comitant esotropia (AACE) is characterized by a sudden-onset eye misalignment with an equal angle of deviation in all fields of gaze. This form of esotropia is distinct from common forms of childhood esotropia, such as infantile esotropia and accommodative esotropia, in the rapid tempo and typically later timing of onset; further, AACE is distinct from restrictive or paretic strabismus, which usually results in an incomitant angle of deviation that varies with the direction of gaze. The underlying etiologies for AACE are broad but, in some cases, it may be associated with significant neurologic disease. Therefore, the purpose of this article is to examine and summarize the current literature on AACE to provide a framework for the evaluation and management of this form of acquired strabismus. C1 Harvard Med Sch, Boston Childrens Hosp, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gilbert, AL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Educ Off, 243 Charles St,3rd Floor, Boston, MA 02114 USA. EM aubrey_gilbert@meei.harvard.edu OI Heidary, Gena/0000-0002-3557-0420 NR 34 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 8 EP 13 DI 10.1080/08820538.2016.1228398 PG 6 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700002 PM 27726470 ER PT J AU Gupta, A Cavallerano, J Sun, JK Silva, PS AF Gupta, Aditi Cavallerano, Jerry Sun, Jennifer K. Silva, Paolo S. TI Evidence for Telemedicine for Diabetic Retinal Disease SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Diabetic macular edema; diabetic retinopathy; digital; remote; retinal imaging ID RETINOPATHY SCREENING EXAMINATIONS; SCANNING LASER OPHTHALMOSCOPY; ANNUAL EYE EXAMINATIONS; FUNDUS PHOTOGRAPHY; ECONOMIC-ANALYSIS; UNITED-STATES; DIGITAL PHOTOGRAPHY; COST-EFFECTIVENESS; CARE; TELEOPHTHALMOLOGY AB According to current projections, the number of Americans with diabetes mellitus will increase from 27.8 million in 2007 to 60.7 million in 2030. With the increasing gap between demand for eye care and supply of ophthalmologists and optometrists, and the non-uniform distribution of eye care providers in US counties, barriers to eye examinations will likely increase. Telemedicine assessment of diabetic retinal disease through remote retinal imaging and diagnosis has the potential to meet these growing demands. To establish evidence for a telemedicine program as an effective modality for diabetic retinopathy (DR) assessment, the interpretation of teleretinal images should compare favorably with Early Treatment Diabetic Retinopathy Study film or digital photographs. We review the current evidence on the critical features and characteristics of ocular telehealth programs for DR in the following categories: image gradability, mydriasis, sensitivity and specificity, cost-effectiveness, long-term effectiveness, patient comfort and satisfaction, and improvement of patient related outcomes. C1 [Gupta, Aditi; Cavallerano, Jerry; Sun, Jennifer K.; Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. [Cavallerano, Jerry; Sun, Jennifer K.; Silva, Paolo S.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu NR 57 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 22 EP 28 DI 10.1080/08820538.2016.1228403 PG 7 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700004 PM 27748634 ER PT J AU Chee, YE Eliott, D AF Chee, Yewlin E. Eliott, Dean TI The Role of Vitrectomy in the Management of Fungal Endophthalmitis SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Fungal endophthalmitis; vitrectomy ID ENDOGENOUS CANDIDA ENDOPHTHALMITIS; POLYMERASE-CHAIN-REACTION; VISUAL-ACUITY OUTCOMES; CHOROIDAL NEOVASCULARIZATION SECONDARY; TERTIARY REFERRAL CENTER; TERM-FOLLOW-UP; AMPHOTERICIN-B; ASPERGILLUS ENDOPHTHALMITIS; CLINICAL-FEATURES; ALBICANS ENDOPHTHALMITIS AB Fungal endophthalmitis is an important cause of vision loss worldwide with a large body of literature describing the treatment of the disease. The evidence supporting the use of pars plana vitrectomy in the management of fungal endophthalmitis is largely comprised of case reports and case series and demonstrates the important role of vitrectomy surgery. Vitrectomy can improve the likelihood of establishing the diagnosis, enhance the treatment of infection by removing fungal elements in the vitreous, aid in the removal of other inoculated intraocular structures, and is an important tool in the management of vision-threatening post-infectious sequelae like retinal detachment and epiretinal membrane. C1 [Chee, Yewlin E.] Univ Washington, Dept Ophthalmol, Seattle, WA 98195 USA. [Eliott, Dean] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Eliott, D (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA.; Eliott, D (reprint author), Harvard Med Sch, 243 Charles St, Boston, MA 02114 USA. EM dean_eliott@meei.harvard.edu NR 82 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 29 EP 35 DI 10.1080/08820538.2016.1228396 PG 7 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700005 PM 27792412 ER PT J AU Yang, D Eliott, D AF Yang, Dong Eliott, Dean TI Systemic Mineralocorticoid Antagonists in the Treatment of Central Serous Chorioretinopathy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Chronic central serous chorioretinopathy; eplerenone; mineralocorticoid-receptor antagonist; spironolactone ID RETINAL-DETACHMENT; ORAL EPLERENONE; CASE SERIES; RECEPTOR; PATHOGENESIS; CORTICOSTEROIDS; SPIRONOLACTONE; DEXAMETHASONE; FIBROBLASTS; EXPERIENCE AB Central serous chorioretinopathy (CSCR) is a challenging disease characterized by subretinal serous fluid accumulation. The complex pathogenesis is still not fully understood, but is thought to be multifactorial and involves exogenous and endogenous factors affecting the choroid and retinal pigment epithelium. The involvement of corticosteroids is undisputed, while the contribution of mineralocorticoid pathways is under investigation. This review addresses the proposed pathogenesis models and the evidence for systemic treatment of CSCR with mineralocorticoid antagonists. C1 [Yang, Dong; Eliott, Dean] Harvard Med Sch, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Yang, D (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dong_yang@meei.harvard.edu NR 60 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 36 EP 42 DI 10.1080/08820538.2016.1228418 PG 7 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700006 PM 27929707 ER PT J AU Shaikh, M Miller, JB Papakostas, TD Husain, D AF Shaikh, Mehrine Miller, John B. Papakostas, Thanos D. Husain, Deeba TI The Efficacy and Safety Profile of Ocriplasmin in Vitreomacular Interface Disorders SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Cystoid macular edema; epiretinal membrane; full-thickness macular hole; jetrea; ocriplasmin; posterior vitreous detachment; vitreomacular adhesion; vitreomacular traction ID OPTICAL COHERENCE TOMOGRAPHY; MACULAR HOLE SURGERY; INTRAVITREAL OCRIPLASMIN; PHARMACOLOGICAL VITREOLYSIS; VISION LOSS; TRACTION; ADHESION; OUTCOMES AB Vitreomacular adhesion (VMA) describes the adhesion of the posterior hyaloid face to the inner retina in any part of the macula. This can arise after incomplete separation of the posterior vitreous cortex from the macula during vitreous liquefaction. While the VMA may resolve spontaneously, a strong and persistent adhesion can lead to a variety of anatomical changes, including vitreomacular traction (VMT) and macular hole (MH). Both conditions can present with metamorphopsia and decreased vision. In cases of symptomatic VMT and full-thickness macular hole, pars plana vitrectomy has long been the standard of care. However, due to the possible surgical complications and need for postoperative care, many have searched for non-surgical options via pharmacologic vitreolysis. Ocriplasmin (Jetrea, Thrombogenics USA, Alcon/Novartis EU) is a recombinant protease approved in October 2012 for the treatment of symptomatic vitreomacular adhesion (VMA). There have been conflicting views on the safety of Ocriplasmin with changes in the ellipsoid zone seen on OCT and changes seen on ERG indicating photoreceptor damage. This publication reviews the efficacy and safety of ocriplasmin injection for VMA based on previously published data. C1 [Shaikh, Mehrine; Miller, John B.; Papakostas, Thanos D.; Husain, Deeba] Harvard Med Sch, Dept Ophthalmol, Retina Serv, Massachusetts Eye & Ear Infirm, 243 Charles St,12th Floor, Boston, MA 02114 USA. RP Shaikh, M (reprint author), Harvard Med Sch, Dept Ophthalmol, Retina Serv, Massachusetts Eye & Ear Infirm, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM mehrineshaikh@gmail.com NR 19 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 52 EP 55 DI 10.1080/08820538.2016.1228416 PG 4 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700008 PM 27786583 ER PT J AU Barham, R El Rami, H Sun, JK Silva, PS AF Barham, Rasha El Rami, Hala Sun, Jennifer K. Silva, Paolo S. TI Evidence-Based Treatment of Diabetic Macular Edema SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE Clinical trials; diabetic macular edema; vascular endothelial growth factor inhibitors ID DEXAMETHASONE INTRAVITREAL IMPLANT; RANDOMIZED CONTROLLED-TRIAL; ACETONIDE VITREOUS INSERTS; RANIBIZUMAB PLUS PROMPT; LONG-TERM-BENEFIT; DEFERRED LASER; CLINICAL-TRIAL; COMPLICATIONS TRIAL/EPIDEMIOLOGY; BARRIER PERMEABILITY; HARD EXUDATE AB Diabetes mellitus is a chronic disease that affects 415 million people worldwide. Despite treatment advances, diabetic eye disease remains a leading cause of vision loss worldwide. Diabetic macular edema (DME) is a common cause of vision loss in diabetic patients. The pathophysiology is complex and involves multiple pathways that ultimately lead to central retinal thickening and, if untreated, visual loss. First-line treatment of DME has evolved from focal/grid laser established by the Early Treatment of Diabetic Retinopathy Study (ETDRS) to intravitreous pharmacologic therapy. Landmark prospective clinical trials examining the effect of intravitreous injections of vascular endothelial growth factor (VEGF) inhibitors in the treatment of DME have demonstrated improved visual outcomes over focal grid laser. This review focuses on the scientific evidence treatment of DME, disease pathophysiology, clinical disease course, current treatment standards, and emerging novel therapeutic approaches. C1 [Barham, Rasha; El Rami, Hala; Sun, Jennifer K.; Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. [Sun, Jennifer K.; Silva, Paolo S.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu NR 81 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 56 EP 66 DI 10.1080/08820538.2016.1228388 PG 11 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700009 PM 28060586 ER PT J AU El Rami, H Barham, R Sun, JK Silva, PS AF El Rami, Hala Barham, Rasha Sun, Jennifer K. Silva, Paolo S. TI Evidence-Based Treatment of Diabetic Retinopathy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Diabetes mellitus; panretinal photocoagulation; vascular endothelial growth factor; vitrectomy ID INTRAVITREAL BEVACIZUMAB AVASTIN; POSTERIOR VITREOUS DETACHMENT; TRACTION RETINAL-DETACHMENT; RANDOMIZED CONTROLLED-TRIAL; BLOOD-PRESSURE CONTROL; PARS-PLANA VITRECTOMY; PANRETINAL PHOTOCOAGULATION; LASER PHOTOCOAGULATION; MACULAR EDEMA; SERUM-LIPIDS AB Diabetic retinopathy (DR) is the most frequent microvascular complication from diabetes and requires annual screening and at least annual follow-up. A systemic approach to optimize blood glucose and blood pressure may halt progression to severe stages of DR and obviate the need for ocular treatment. Although there is evidence of benefit from fenofibrate or intravitreous antiVEGF treatment for eyes with nonproliferative DR (NPDR), these therapies are not standard care for NPDR at this time. Some patients with severe NPDR, especially those with type 2 diabetes, benefit from early panretinal photocoagulation (PRP). Once DR progresses to proliferative DR (PDR), treatment is often necessary to prevent visual loss. PRP remains mainstay treatment for PDR with high-risk characteristics. However, intravitreous antiVEGF injections appear to be a safe and effective treatment alternative for PDR through at least two years. Vitreoretinal surgery is indicated for PDR cases with non-clearing vitreous hemorrhage and/or tractional retinal detachment. C1 [El Rami, Hala; Barham, Rasha; Sun, Jennifer K.; Silva, Paolo S.] Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. [Sun, Jennifer K.; Silva, Paolo S.] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. RP Silva, PS (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM paoloantonio.silva@joslin.harvard.edu NR 74 TC 0 Z9 0 U1 3 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 67 EP 74 DI 10.1080/08820538.2016.1228397 PG 8 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700010 PM 27700224 ER PT J AU Grotting, LA Papaliodis, GN AF Grotting, Lindsay A. Papaliodis, George N. TI A Review of the Course and Treatment of Non-Infectious Uveitis during Pregnancy SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Autoimmune disease; biologics; lactation; ocular inflammatory disease ID INFLAMMATORY-BOWEL-DISEASE; COLLAGEN-INDUCED ARTHRITIS; NECROSIS FACTOR AGENTS; TNF-ALPHA; POSTPARTUM EXACERBATION; LIVER-TRANSPLANTATION; RHEUMATOID-ARTHRITIS; CONGENITAL-ANOMALIES; AUTOIMMUNE-DISEASES; BIRTH OUTCOMES AB Inflammatory conditions such as autoimmune uveitis often occur in women of childbearing age. During pregnancy, women may experience exacerbations of their disease in the first trimester. In the later stages of pregnancy, however, the uveitis tends to remain less active. The management of uveitis during pregnancy is a challenging task, forcing the physician to re-evaluate the patient's current therapy and offer alternative options that pose the least risk to the patient and fetus. This article will review treatments widely used for uveitis, including corticosteroid therapy, anti-metabolites, calcineurin inhibitors, and biologic therapy. It will evaluate the use of these medications in pregnancy and the postpartum state. C1 [Grotting, Lindsay A.; Papaliodis, George N.] Massachusetts Eye & Ear Infirm, Uveitis & Immunol Serv, Boston, MA 02114 USA. RP Grotting, LA (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St,12th Floor, Boston, MA 02114 USA. EM Lindsay.Ambrecht@gmail.com NR 68 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 75 EP 81 DI 10.1080/08820538.2016.1228402 PG 7 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700011 PM 27805464 ER PT J AU Anwar, F Turalba, A AF Anwar, Farihah Turalba, Angela TI An Overview of Treatment Methods for Primary Angle Closure SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Glaucoma; primary angle closure ID GLAUCOMA; MANAGEMENT AB Background: Glaucoma is the second leading cause of blindness in the world. Angle closure glaucoma accounts for 25% of all glaucoma, with Asia having the highest rate. Angle closure is an anatomical variation, making the Inuit, Chinese, and other Asians more susceptible. Current treatments include medical, laser, and surgical modalities.Purpose: To identify the current treatment protocols for primary angle closure. Discussion: The current general protocol to treat angle closure is to lower the intraocular pressure with medications and perform laser iridotomy. However, cataract surgery, laser iridoplasty, goniosynechiolysis, diode cyclophotocoagulation, and filtering surgery are additional treatment modalities used for primary angle closure. Conclusion: Primary angle closure occurs due to various anatomical angle variations. Laser iridotomy is not the sole method of treatment. Specifically, cataract surgery can be particularly effective in the treatment and prevention of angle closure. Recalcitrant cases can be treated with trabeculectomy and shunt implants, although these are not usually first-line treatments. C1 [Anwar, Farihah; Turalba, Angela] Massachussetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02140 USA. RP Anwar, F (reprint author), Massachussetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02140 USA. EM fanwar130@gmail.com NR 21 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 82 EP 85 DI 10.1080/08820538.2016.1228386 PG 4 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700012 PM 27686782 ER PT J AU Joseph, A Pasquale, LR AF Joseph, Arun Pasquale, Louis R. TI Attributes Associated with Adherence to Glaucoma Medical Therapy and its Effects on Glaucoma Outcomes: An Evidence-Based Review and Potential Strategies to Improve Adherence SO SEMINARS IN OPHTHALMOLOGY LA English DT Review DE Adherence; evidence-based; glaucoma ID COUNTY HOSPITAL POPULATION; PATIENT COMMUNICATION; DAILY-LIFE; TIMOLOL; DORZOLAMIDE; PILOCARPINE; COMBINATION; PERSISTENCE; PREFERENCE; BARRIERS AB The treatment paradigm in glaucoma classically starts with exhausting all medical therapy prior to proceeding with laser or incisional surgery, although laser-first and surgery-first strategies have been explored in randomized clinical trials. Although glaucoma drops are proven to work well to lower intraocular pressure, slow the conversion from ocular hypertension, and slow the progression of disease in early open angle glaucoma, adherence to treatment is likely optimum in the randomized clinical trials that support these claims. In real-world scenarios, medical therapy often fails and practitioners are forced to proceed with more invasive treatment modalities to slow the progression of this blinding disease. This review aims to take an evidence-based approach to study the risk factors for poor adherence in glaucoma patients, to determine whether poor adherence is, in fact, associated with worse outcomes, and to seek potential strategies to improve adherence in these patients. C1 [Joseph, Arun; Pasquale, Louis R.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Pasquale, Louis R.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. RP Joseph, A (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02118 USA. EM arunjoseph41@gmail.com NR 33 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 86 EP 90 DI 10.1080/08820538.2016.1228406 PG 5 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700013 PM 27792450 ER PT J AU Bovee, CE Pasquale, LR AF Bovee, Courtney E. Pasquale, Louis R. TI Evolving Surgical Interventions in the Treatment of Glaucoma SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE MIGS; iStent; trabectome; glaucoma ID OPEN-ANGLE GLAUCOMA; AB-INTERNO TRABECULECTOMY; MICRO-BYPASS STENT; COMBINED CATARACT; SURGERY; OUTCOMES; PHACOEMULSIFICATION; TRABECTOME AB Interventions in the treatment of mild to moderate glaucoma have evolved to include a group of procedures collectively named Minimally Invasive Glaucoma Surgery (MIGS). These procedures are less invasive than traditional filtering surgery and setons and offer the benefit of an improved side-effect profile. A review of current published literature has shown that these procedures offer lower intraocular pressure, decrease reliance on topical medications, have no negative effect on refractive outcomes, and can be safely done following failed tube surgery. C1 [Bovee, Courtney E.; Pasquale, Louis R.] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. [Pasquale, Louis R.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. RP Bovee, CE (reprint author), Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM courtneybovee@gmail.com NR 28 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 91 EP 95 DI 10.1080/08820538.2016.1228393 PG 5 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700014 PM 27686565 ER PT J AU Liu, SH Veldman, P AF Liu, Shaohui Veldman, Peter TI Evidence-Based Endothelial Rehabilitation SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Descemet membrane; DMEK; DSAEK; DSEK; endothelial keratoplasty; keratoplasty ID POSTERIOR LAMELLAR KERATOPLASTY; OPTICAL COHERENCE TOMOGRAPHY; GRAFT-REJECTION EPISODES; FUCHS CORNEAL-DYSTROPHY; 5-YEAR FOLLOW-UP; DESCEMET MEMBRANE; PENETRATING KERATOPLASTY; CELL-LOSS; CONFOCAL MICROSCOPY; LEARNING-CURVE AB Endothelial keratoplasty (EK) has replaced penetrating keratoplasty (PKP) as the preferred surgical therapy for corneal endothelial dysfunction. However, recent nationwide corneal graft registry data showed few advantages to EK relative to PKP with respect to graft survival and visual outcomes. This article compares the published outcomes and complications of EK to those of PKP. EK demonstrates superior spectacle corrected visual outcomes, fast recovery, less graft rejection, and higher patient satisfaction, particularly in studies performed by high-volume surgeons/centers. Endothelial cell loss in EK, while higher at early time points, was equivalent or superior at five-years' follow-up and graft survival was equivalent to or superior to PKP in these centers/studies. Continued standardization and simplification of EK procedures may allow surgeons who perform a lower volume of EK to achieve results that mirror those of high-volume centers/surgeons and close the potential gap in outcomes demonstrated in the registry data. C1 [Liu, Shaohui] Indiana Univ Sch Med, Dept Ophthalmol, Glick Eye Inst, Indianapolis, IN 46202 USA. [Liu, Shaohui; Veldman, Peter] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Liu, SH (reprint author), Glick Eye Inst, 1160 W Michigan St, Indianapolis, IN 46202 USA. EM liu486@iu.edu NR 78 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 96 EP 103 DI 10.1080/08820538.2016.1228409 PG 8 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700015 PM 27754721 ER PT J AU Rapoport, Y Veldman, P AF Rapoport, Yuna Veldman, Peter TI A Comprehensive Review of Postoperative Management of Descemet's Membrane Endothelial Keratoplasty SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Corneal; Descemet Membrane Endothelial Keratoplasty (DMEK); endothelial; lamellar; postoperative; surgery ID PREDNISOLONE ACETATE 1-PERCENT; OPTICAL COHERENCE TOMOGRAPHY; SULFUR-HEXAFLUORIDE SF6; ALLOGRAFT-REJECTION; GRAFT ATTACHMENT; DMEK GRAFTS; CELL-LOSS; RISK; SURVIVAL; DSAEK AB Introduction: As Descemet's Membrane Endothelial Keratoplasty (DMEK) continues to gain in popularity, the postoperative management of DMEK surgery is becoming increasingly important, as these management strategies may affect postoperative success rates. Materials and Methods: This article reviews the current evidence for postoperative management in DMEK. Results: There are variable strategies in the postoperative management of DMEK as it relates to postoperative positioning, need for and timing of rebubble, tamponade agent utilized (both primarily and at rebubble), steroid agent and tapering schedule, timing of secondary regraft when required, and postoperative monitoring. Discussion: While a great deal of attention is rightly devoted to developing better surgical techniques for DMEK, we believe it is also crucial to develop a better understanding of and evidence-based best practice in the postoperative management of DMEK, as this may have important implications for outcomes. C1 [Rapoport, Yuna; Veldman, Peter] Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Rapoport, Y (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM yuna.rapoport@gmail.com NR 31 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 104 EP 110 DI 10.1080/08820538.2016.1228414 PG 7 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700016 PM 27780445 ER PT J AU Greenstein, S Pineda, R AF Greenstein, Steven Pineda, Roberto TI The Quest for Spectacle Independence: A Comparison of Multifocal Intraocular Lens Implants and Pseudophakic Monovision for Patients with Presbyopia SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Mini-monovision; monovision; multifocal; presbyopia; spectacle independence ID OPTICAL-PERFORMANCE; REFRACTIVE SURGERY; CATARACT-SURGERY; VISUAL FUNCTION; MINI-MONOVISION; ADDITION POWER; SATISFACTION; OUTCOMES; IOL AB We performed a literature review comparing multifocal intraocular lens (IOL) implantation with pseudophakic monovision to treat presbyopia. Multifocal IOLs utilize refractive or diffractive principles to treat both distance and near vision, with a single lens implant. Monovision uses traditional monofocal lens implants to treat the dominant eye for emmotropia, and the non-dominant eye for myopia. This planned anisometropia is designed to enhance intermediate or near vision. Generally, distance vision was similar with both types of lens implantation, near vision was better with multifocal IOLs, and intermediate vision appeared to be better in the monovision group. For patients requiring cataract surgery, both multifocal IOLs and monovision appear to address presbyopia with a high level of patient satisfaction. More patients reported complete spectacle independence with multifocal IOLs, but more glare and halos were reported by multifocal IOL patients as well. C1 [Greenstein, Steven; Pineda, Roberto] Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Greenstein, S (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM steven.greenstein327@gmail.com NR 34 TC 0 Z9 0 U1 4 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 111 EP 115 DI 10.1080/08820538.2016.1228400 PG 5 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700017 PM 27792408 ER PT J AU Jimenez-Perez, JC Yoon, MK AF Jimenez-Perez, Juan C. Yoon, Michael K. TI Natural Killer T-Cell Lymphoma of the Orbit: An Evidence-Based Approach SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Extranodal natural killer T-cell; natural killer cell; orbital lymphoma ID NASAL-TYPE; CLINICAL-FEATURES; DIAGNOSIS; CHEMOTHERAPY; INVOLVEMENT; SMILE AB Natural killer T-cell lymphoma (NKTCL) is a rare and aggressive condition with a high mortality rate. It is most commonly seen in the nasal sinuses, generally affecting the orbit by direct extension. Primary orbital NKTCL is even more rare, with only a few published cases with occasional secondary nasal involvement. This malignancy can present as a masquerade syndrome, delaying proper diagnosis and treatment. Biopsy is required for diagnosis, which shows specific histopathological characteristics. Radiation and chemotherapy are the mainstay of treatment. Newer chemotherapies show improved prognosis. C1 [Jimenez-Perez, Juan C.; Yoon, Michael K.] Harvard Med Sch, Ophthalm Plast & Reconstruct Surg Serv, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Jimenez-Perez, JC (reprint author), Massachusetts Eye & Ear Infirm, Ophthalm Plast & Reconstruct Surg Serv, 243 Charles St, Boston, MA 02114 USA. EM juan_jimenez@meei.harvard.edu NR 34 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 116 EP 124 DI 10.1080/08820538.2016.1228405 PG 9 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700018 PM 27740876 ER PT J AU Vodopivec, I Cestari, DM Rizzo, JF AF Vodopivec, Ivana Cestari, Dean M. Rizzo, Joseph F. TI Management of Transient Monocular Vision Loss and Retinal Artery Occlusions SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Branch retinal artery occlusion; central retinal artery occlusion; embolism; giant cell arteritis; retinal vasospasm; transient monocular vision loss ID GIANT-CELL ARTERITIS; VASOSPASTIC AMAUROSIS FUGAX; ASSOCIATION/AMERICAN STROKE ASSOCIATION; LOCAL INTRAARTERIAL FIBRINOLYSIS; HEALTH-CARE PROFESSIONALS; ACUTE ISCHEMIC-STROKE; VISUAL-LOSS; OCULAR NEOVASCULARIZATION; CAROTID STENOSIS; VEIN OCCLUSION AB Acute transient or permanent retinal occlusive disease requires prompt medical attention and can be an ophthalmological emergency. Central retinal artery occlusion leads to permanent and severe monocular visual loss in the majority of patients. Transient monocular vision loss leaves no permanent deficits, but requires the same level of clinical vigilance, as it portends possible future adverse events, including loss of vision and stroke. Acute treatment options remain limited, and secondary prevention of cerebral ischemic events is the mainstay of management. This article reviews the current evidence for managing patients with retinal ischemia. C1 [Vodopivec, Ivana; Cestari, Dean M.; Rizzo, Joseph F.] Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. RP Vodopivec, I (reprint author), Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, 243 Charles St, Boston, MA 02114 USA. EM ivodopivec@partners.org NR 80 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 125 EP 133 DI 10.1080/08820538.2016.1228417 PG 9 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700019 PM 27780399 ER PT J AU Thon, OR Gittinger, JW AF Thon, Olga R. Gittinger, John W. TI Medication-Related Pseudotumor Cerebri Syndrome SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Medication-related intracranial hypertension; papilledema; pseudotumor cerebri ID IDIOPATHIC INTRACRANIAL HYPERTENSION; HUMAN GROWTH-HORMONE; TRANS-RETINOIC ACID; VITAMIN-A; DIAGNOSTIC-CRITERIA; CEREBROSPINAL-FLUID; CYCLOSPORINE USE; SECONDARY; THERAPY; LITHIUM AB Pseudotumor cerebri syndrome refers to elevated intracranial pressure associated with papilledema without an identified etiology for intracranial hypertension. Over the past few decades, several medications have been described to be associated with this syndrome. We searched the literature for those case reports and series and evaluated the evidence for the association of such medications with pseudotumor cerebri syndrome. C1 [Thon, Olga R.; Gittinger, John W.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Thon, OR (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Div Neuroophthalmol, Neuroophthalmol, 243 Charles St, Boston, MA 02114 USA. EM olga.rosenvald@gmail.com NR 56 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 134 EP 143 DI 10.1080/08820538.2016.1228415 PG 10 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700020 PM 27786584 ER PT J AU Pillai, C Gittinger, JW AF Pillai, Cinthi Gittinger, John W., Jr. TI Vision Testing in the Evaluation of Concussion SO SEMINARS IN OPHTHALMOLOGY LA English DT Article DE Brain; injury; neurology; neuro-ophthalmology; technology; traumatic ID TRAUMATIC BRAIN-INJURY; SPORTS-RELATED CONCUSSION; CLOSED-HEAD INJURY; TEST-RETEST RELIABILITY; VISUAL SCREENING TOOL; BASE-LINE; FOOTBALL PLAYERS; KING-DEVICK; OCULOMOTOR REHABILITATION; TEST-PERFORMANCE AB Traumatic brain injury results from an acute impact to the head causing brain dysfunction. Concussion is a form of mild traumatic brain injury. There are significant short- and long-term sequelae of concussion, and early diagnosis and management are key to recovery. Visual system symptoms and signs are common following concussion and have been shown to be a useful feature of concussion testing. Neuro-ophthalmic findings include abnormalities in the pupillary light reflex, accommodation, convergence, extraocular motility, steroacuity, as well as pursuit and saccades. Concussion generally occurs out of the medical setting, and access to a trained examiner or equipment to assist in diagnosis is limited. For this reason, much research is focused on developing a concussion test that is practical and reliable, and technology is likely to play an important role in this. Ultimately, no single test is a substitute for clinical judgment and multifaceted testing. C1 [Pillai, Cinthi; Gittinger, John W., Jr.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RP Pillai, C (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM cpillaimd@gmail.com OI Pillai, Cinthi/0000-0002-7662-443X NR 103 TC 0 Z9 0 U1 7 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0882-0538 EI 1744-5205 J9 SEMIN OPHTHALMOL JI Semin. Ophthalmol. PY 2017 VL 32 IS 1 SI SI BP 144 EP 152 DI 10.1080/08820538.2016.1228412 PG 9 WC Ophthalmology SC Ophthalmology GA EJ6HS UT WOS:000393320700021 PM 27805468 ER PT J AU Park, YI Kim, E Huang, CH Park, KS Castro, CM Lee, H Weissleder, R AF Park, Yong Il Kim, Eunha Huang, Chen-Han Park, Ki Soo Castro, Cesar M. Lee, Hakho Weissleder, Ralph TI Facile Coating Strategy to Functionalize Inorganic Nanoparticles for Biosensing SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MAGNETIC NANOPARTICLES; BIOLOGICAL-SYSTEMS; SURFACE; SENSITIVITY; NANOPROBES; DESIGN; DNA AB The use of inorganic nanoparticles (NPs) for biosensing requires that they exhibit high colloidal stability under various physiological conditions. Here, we report on a general approach to render hydrophobic NPs into hydrophilic ones that are ready for bioconjugation. The method uses peglyated polymers conjugated with multiple dopamines, which results in multidentate coordination. As proof-of concept, we applied the coating to stabilize ferrite and lanthanide NPs synthesized by thermal decomposition. Both polymer coated NPs showed excellent water solubility and were stable at high salt concentrations under physiological conditions. We used these NPs as molecular-sensing agents to detect exosomes and bacterial nucleic acids. C1 [Park, Yong Il; Kim, Eunha; Huang, Chen-Han; Park, Ki Soo; Castro, Cesar M.; Lee, Hakho; Weissleder, Ralph] Harvard Med Sch, Ctr Syst Biol, Boston, MA 02114 USA. [Park, Yong Il; Kim, Eunha; Huang, Chen-Han; Park, Ki Soo; Lee, Hakho; Weissleder, Ralph] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Castro, Cesar M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Weissleder, Ralph] Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA. [Park, Yong Il] Chonnam Natl Univ, Sch Chem Engn, 77 Yongbong Ro, Gwangju 61186, South Korea. [Kim, Eunha] Ajou Univ, Dept Mol Sci & Technol, Suwon 16499, South Korea. RP Lee, H; Weissleder, R (reprint author), Harvard Med Sch, Ctr Syst Biol, Boston, MA 02114 USA.; Lee, H; Weissleder, R (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Weissleder, R (reprint author), Harvard Med Sch, Dept Syst Biol, Boston, MA 02115 USA. EM hlee@mgh.harvard.edu; rweissleder@mgh.harvard.edu FU NIH [R01HL113156, R21CA205322, R01EB004626, R01EB010011, HHSN268201000044C, U54-CA119349, T32-CA79443]; Department of Defense OCRP Program Award [W81XWH-14-1-0279] FX This work was supported in part by NIH Grants R01HL113156, R21CA205322, R01EB004626, R01EB010011, HHSN268201000044C, U54-CA119349, and T32-CA79443 and by the Department of Defense OCRP Program Award W81XWH-14-1-0279. NR 23 TC 0 Z9 0 U1 4 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN PY 2017 VL 28 IS 1 BP 33 EP 37 DI 10.1021/acs.bioconjchem.6b00524 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA EI4JG UT WOS:000392459200005 PM 27792877 ER PT J AU Xie, X Pascual, C Lieu, C Oh, S Wang, J Zou, BD Xie, JL Li, ZH Xie, J Yeomans, DC Wu, MX Xie, XS AF Xie, Xi Pascual, Conrado Lieu, Christopher Oh, Seajin Wang, Ji Zou, Bende Xie, Julian Li, Zhaohui Xie, James Yeomans, David C. Wu, Mei X. Xie, Xinmin Simon TI Analgesic Microneedle Patch for Neuropathic Pain Therapy SO ACS NANO LA English DT Article DE microneedle; CGRP antagonist peptide; neuropathic pain; analgesia; drug delivery ID TRANSDERMAL DRUG-DELIVERY; GENE-RELATED PEPTIDE; ORAL OPIOID THERAPY; LOCAL-ANESTHETICS; RIGHTING REFLEX; SUBSTANCE-P; MODEL; LIDOCAINE; ANTAGONIST; MIGRAINE AB Neuropathic pain caused by nerve injury is debilitating and difficult to treat. Current systemic pharmacological therapeutics for neuropathic pain produce limited pain relief and have undesirable side effects, while current local anesthetics tend to nonspecifically block both sensory and motor functions. Calcitonin gene related peptide (CGRP), a neuropeptide released from sensory nerve endings, appears to play a significant role in chronic neuropathic pain. In this study, an analgesic microneedle (AMN) patch was developed using dissolvable microneedles to transdermally deliver selective CGRP antagonist peptide in a painless manner for the treatment of localized neuropathic pain. Local analgesic effects were evaluated in rats by testing behavioral pain sensitivity in response to thermal and mechanical stimuli using neuropathic pain models such as spared-nerve injury and diabetic neuropathy pain, as well as neurogenic inflammatory pain model induced by ultraviolet B (UVB) radiation. Unlike several conventional therapies, the AMN patches produced effective analgesia on neuropathic pain without disturbing the normal nociception and motor function of the rat, resulting from the high specificity of the delivered peptide against CGRP receptors. The AMN patches did not cause skin irritation or systemic side effects. These results demonstrate that dissolvable microneedle patches delivering CGRP antagonist peptide provide an effective, safe, and simple approach to mitigate neuropathic pain with significant advantages over current treatments. C1 [Xie, Xi; Pascual, Conrado; Lieu, Christopher; Oh, Seajin; Zou, Bende; Xie, Julian; Li, Zhaohui; Xie, James; Xie, Xinmin Simon] AfaSci Res Labs, Redwood City, CA 94063 USA. [Xie, Xi] Sun Yat Sen Univ, Sch Elect & Informat Technol, Guangzhou 510275, Guangdong, Peoples R China. [Xie, Xi] Sun Yat Sen Univ, State Key Lab Optoelect Mat & Technol, Guangzhou 510275, Guangdong, Peoples R China. [Pascual, Conrado; Yeomans, David C.; Xie, Xinmin Simon] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Wang, Ji; Wu, Mei X.] Harvard Med Sch, Dept Dermatol, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02115 USA. RP Xie, X; Xie, XS (reprint author), AfaSci Res Labs, Redwood City, CA 94063 USA.; Xie, X (reprint author), Sun Yat Sen Univ, Sch Elect & Informat Technol, Guangzhou 510275, Guangdong, Peoples R China.; Xie, X (reprint author), Sun Yat Sen Univ, State Key Lab Optoelect Mat & Technol, Guangzhou 510275, Guangdong, Peoples R China.; Xie, XS (reprint author), Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. EM xiexi27@mail.sysu.edu.cn; simonxie@afasci.com FU National Institute of Health [R44DA026363, R44 NS086343]; 100 Talents Program of Sun Yat-Sen University [76120-18821104] FX The authors wish to thank Dr. Sung-Yun Kwon, TheraJect, Inc., Fremont, CA, USA, for the use of equipment and experimental advice. This work was supported by the National Institute of Health grants R44DA026363 and R44 NS086343. X.X. would like to thank the 100 Talents Program of Sun Yat-Sen University (76120-18821104) for support. NR 60 TC 0 Z9 0 U1 12 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JAN PY 2017 VL 11 IS 1 BP 395 EP 406 DI 10.1021/acsnano.6b06104 PG 12 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA EJ0GL UT WOS:000392886500040 PM 28001346 ER PT J AU Smith, BN Wang, JM Vaughn-Coaxum, RA Di Leone, BAL Vogt, D AF Smith, Brian N. Wang, Joyce M. Vaughn-Coaxum, Rachel A. Di Leone, Brooke A. L. Vogt, Dawne TI The role of postdeployment social factors in linking deployment experiences and current posttraumatic stress disorder symptomatology among male and female veterans SO ANXIETY STRESS AND COPING LA English DT Article DE Stress; risk and resilience; social support; reintegration; veterans ID MILITARY SEXUAL TRAUMA; MENTAL-HEALTH PROBLEMS; MALE VIETNAM VETERANS; WAR-ZONE STRESSORS; RISK-FACTORS; COMMUNITY REINTEGRATION; PSYCHOMETRIC PROPERTIES; RESILIENCE INVENTORY; PTSD CHECKLIST; IRAQI FREEDOM AB Background and Objectives: The postdeployment social context is likely highly salient in explaining mental health symptoms following deployment. The aim of this study was to examine the role of postdeployment social factors (social support and social reintegration difficulty) in linking deployment-related experiences (warfare exposure, sexual harassment, concerns about relationship disruptions, and deployment social support) and posttraumatic stress disorder (PTSD) symptomatology in male and female veterans. Design: A survey was administered to 998 potential participants (after accounting for undeliverable mail) who had returned from deployment to Afghanistan or Iraq. Completed surveys were received from 469 veterans, yielding a response rate of 47%. Methods: Hypotheses were examined using structural equation modeling. Results: For male and female veterans, deployment factors predicted later PTSD symptoms through postdeployment social support and social reintegration, with lower support and higher social reintegration difficulty both associated with higher PTSD symptomatology. While the final models for women and men indicated similar risk mechanisms, some differences in pathways were observed. Sexual harassment presented more of a risk for women, whereas lower social support was a greater risk factor for men. Conclusions: Postdeployment social factors appear to represent potentially important targets for interventions aiming to reduce the potential impact of stressful deployment experiences. C1 [Smith, Brian N.; Vogt, Dawne] VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. [Smith, Brian N.; Vogt, Dawne] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Wang, Joyce M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Wang, Joyce M.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Vaughn-Coaxum, Rachel A.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Di Leone, Brooke A. L.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Wang, Joyce M.] RTI Int, Aging Disabil & Long Term Care Program, Waltham, MA USA. [Di Leone, Brooke A. L.] Childrens Literacy Initiat, Philadelphia, PA USA. RP Smith, BN (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA.; Smith, BN (reprint author), Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. EM brian.smith12@va.gov FU Department of Veterans Affairs, Health Services Research and Development Service [DHI 09-086] FX This study was supported by a Department of Veterans Affairs, Health Services Research and Development Service grant ("Validation of Modified DRRI Scales in a National Sample of OEF/OIF Veterans," Project DHI 09-086, Dawne Vogt, Principal Investigator). NR 56 TC 0 Z9 0 U1 4 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1061-5806 EI 1477-2205 J9 ANXIETY STRESS COPIN JI Anxiety Stress Coping PY 2017 VL 30 IS 1 BP 39 EP 51 DI 10.1080/10615806.2016.1188201 PG 13 WC Neurosciences; Psychiatry; Psychology, Multidisciplinary SC Neurosciences & Neurology; Psychiatry; Psychology GA EI9MM UT WOS:000392832200004 PM 27232981 ER PT J AU Harkenrider, MM Block, AM Alektiar, KM Gaffney, DK Jones, E Klopp, A Viswanathan, AN Small, W AF Harkenrider, Matthew M. Block, Alec M. Alektiar, Kaled M. Gaffney, David K. Jones, Ellen Klopp, Ann Viswanathan, Akila N. Small, William, Jr. TI American Brachytherapy Task Group Report: Adjuvant vaginal brachytherapy for early-stage endometrial cancer: A comprehensive review SO BRACHYTHERAPY LA English DT Article DE Endometrial cancer; Vaginal brachytherapy; Vaginal cuff brachytherapy; Vaginal cuff; Vaginal cylinder; Gynecologic brachytherapy ID HIGH-DOSE-RATE; GYNECOLOGIC-ONCOLOGY-GROUP; PELVIC RADIATION-THERAPY; QUALITY-OF-LIFE; PAPILLARY SEROUS CARCINOMA; PHASE-III TRIAL; CUFF BRACHYTHERAPY; HIGH-RISK; CLEAR-CELL; POSTOPERATIVE RADIOTHERAPY AB This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the postoperative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early-stage endometrial cancer patients results in very low rates of vaginal recurrence (0-3.1%) with low rates of late toxicity which are primarily vaginal in nature. Post-Operative Radiation Therapy in Endometrial Cancer 2 (PORTEC-2) supports that VBT results in noninferior rates of vaginal recurrence compared to external beam radiotherapy for the treatment of high-intermediate risk patients. VBT as a boost after external beam radiotherapy, in combination with chemotherapy, and for high risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians prefer joint decision making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multidisciplinary setting, and patients should be counseled properly regarding the risks and benefits of adjuvant therapy. (C) 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved. C1 [Harkenrider, Matthew M.; Block, Alec M.; Small, William, Jr.] Loyola Univ Chicago, Stritch Sch Med, Dept Radiat Oncol, 2160 S First Ave,Maguire Bldg,Room 2944, Maywood, IL 60153 USA. [Alektiar, Kaled M.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY USA. [Gaffney, David K.] Univ Utah, Dept Radiat Oncol, Huntsman Canc Inst, Salt Lake City, UT USA. [Jones, Ellen] Univ N Carolina, Sch Med, Dept Radiat Oncol, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Klopp, Ann] Univ Texas Houston, MD Anderson Canc Ctr, Dept Radiat Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. [Viswanathan, Akila N.] Dana Farber Canc Inst, Dept Radiat Oncol, Brigham & Womens Hosp, Boston, MA 02115 USA. RP Harkenrider, MM (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Radiat Oncol, 2160 S First Ave,Maguire Bldg,Room 2944, Maywood, IL 60153 USA. EM mharkenrider@lumc.edu FU NIH/NCI [R21 167800] FX Dr. Viswanathan receives support through NIH/NCI R21 167800. NR 110 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 1538-4721 EI 1873-1449 J9 BRACHYTHERAPY JI Brachytherapy PD JAN-FEB PY 2017 VL 16 IS 1 BP 95 EP 108 DI 10.1016/j.brachy.2016.04.005 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA EI8YK UT WOS:000392793900009 PM 27260082 ER PT J AU Sun, PZ Ayata, C Lo, EH AF Sun, Phillip Zhe Ayata, Cenk Lo, Eng H. TI Fleeting footprints: finding MRI biomarkers of transient ischaemic attack SO BRAIN LA English DT Editorial Material ID SPREADING DEPRESSION; PITFALLS; MODELS; STROKE; PEARLS C1 [Lo, Eng H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lo@helix.mgh.harvard.edu NR 13 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 EI 1460-2156 J9 BRAIN JI Brain PD JAN PY 2017 VL 140 BP 8 EP 10 DI 10.1093/brain/aww306 PN 1 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA EI7UZ UT WOS:000392710500010 PM 28031217 ER PT J AU Rich, T Zhao, FM Cruciani, RA Cella, D Manola, J Fisch, MJ AF Rich, Tyvin Zhao, Fengmin Cruciani, Ricardo A. Cella, David Manola, Judith Fisch, Michael J. TI Association of fatigue and depression with circulating levels of proinflammatory cytokines and epidermal growth factor receptor ligands: a correlative study of a placebo-controlled fatigue trial SO CANCER MANAGEMENT AND RESEARCH LA English DT Article DE fatigue; depression; proinflammatory cytokine; circadian-signaling pathways; cancer; placebo effect ID CANCER-RELATED FATIGUE; CELL LUNG-CANCER; DOUBLE-BLIND; PROSTATE-CANCER; FACTOR-ALPHA; SYMPTOMS; BEHAVIOR; IMPROVEMENT; MECHANISMS; BIOMARKERS AB Context: The biology of fatigue and depression in cancer patients is poorly understood. Hypotheses regarding cytokines and growth factors related to sickness behavior and disruption of circadian signaling have been proposed. Objectives: We prospectively examined proinflammatory cytokines (e.g., sickness behavior model) and epidermal growth factor receptor (EGFR) ligands (e.g., circadian disruption model) in the serum of cancer patients enrolled in a clinical trial testing levocarnitine for fatigue. Methods: Serum samples were collected at baseline and week 4. Cytokine/growth factor analyses were performed with a Luminex analyzer. The Brief Fatigue Index and the Center for Epidemiologic Studies Depression Index were used to measure fatigue and depression severity. The association between cytokine and symptoms was examined using logistic models. Results: Among 101 analyzable patients, all ten cytokines/growth factors examined were highly elevated at baseline and all significantly decreased at week 4 (p<0.001) regardless of treatment intervention. At baseline, the odds of severe fatigue significantly increased for patients with higher level of interleukin-1 receptor antagonist (IL-1Ra), whereas patients with higher levels of IL-1Ra, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, interferon-gamma, transforming growth factor alpha, and vascular endothelial growth factor had higher odds of severe depression. At week 4, fatigue (p=0.023) and depression (p=0.007) responders had less decrease in IL-1 level than the corresponding non-responders. Conclusion: In this correlative analysis of a fatigue clinical trial, levels of fatigue were significantly associated with levels of IL-1 and IL-1Ra. Circadian-signaling pathways related to EGFR signaling were correlated with depression as were other cytokines. A major placebo effect was associated with a global decrease in cytokine and growth factors. These data provide further basis for testing hypotheses regarding the mechanisms of fatigue and depression in cancer patients. C1 [Rich, Tyvin] Hampton Univ Proton, Inst Therapy, 40 Enterprise Pkwy, Hampton, VA 23666 USA. [Zhao, Fengmin; Manola, Judith] Dana Farber Canc Inst, Boston, MA USA. [Cruciani, Ricardo A.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Cella, David] Northwestern Univ Feinberg, Sch Med, Chicago, IL USA. [Fisch, Michael J.] Univ Texas Houston, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. RP Rich, T (reprint author), Hampton Univ Proton, Inst Therapy, 40 Enterprise Pkwy, Hampton, VA 23666 USA. EM Tar4d@virginia.edu FU National Cancer Institute, National Institutes of Health [CA23318, CA66636, CA21115, CA49957, CA39229, CA104362]; Department of Health and Human Services FX This study was conducted by the Eastern Cooperative Oncology Group and supported in part by Public Health Service Grants CA23318, CA66636, CA21115, CA49957, CA39229, and CA104362 from the National Cancer Institute, National Institutes of Health, and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 33 TC 0 Z9 0 U1 1 U2 1 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1322 J9 CANCER MANAG RES JI Cancer Manag. Res. PY 2017 VL 9 BP 1 EP 10 DI 10.2147/CMAR.S115835 PG 10 WC Oncology SC Oncology GA EJ7JY UT WOS:000393399200001 PM 28203105 ER PT J AU Minalyan, A Benhammou, JN Artashesyan, A Lewis, MS Pisegna, JR AF Minalyan, Artem Benhammou, Jihane N. Artashesyan, Aida Lewis, Michael S. Pisegna, Joseph R. TI Autoimmune atrophic gastritis: current perspectives SO CLINICAL AND EXPERIMENTAL GASTROENTEROLOGY LA English DT Review DE autoimmune gastritis; pernicious anemia; gastric carcinoid ID HELICOBACTER-PYLORI INFECTION; IRON-DEFICIENCY ANEMIA; POLYPEPTIDE-EXPRESSING METAPLASIA; SUBACUTE COMBINED DEGENERATION; PARIETAL-CELL ANTIBODIES; PERNICIOUS-ANEMIA; INTESTINAL METAPLASIA; COBALAMIN DEFICIENCY; CHROMOGRANIN-A; ANTIGASTRIC AUTOANTIBODIES AB At present there is no universally accepted classification for gastritis. The first successful classification (The Sydney System) that is still commonly used by medical professionals was first introduced by Misiewicz et al in Sydney in 1990. In fact, it was the first detailed classification after the discovery of Helicobacter pylori by Warren and Marshall in 1982. In 1994, the Updated Sydney System was proposed during the International Workshop on the Histopathology of Gastritis followed by the publication in The American Journal of Surgical Pathology by Dixon et al. Using the new classification, distinction between atrophic and nonatrophic gastritis was revised, and the visual scale grading was incorporated. According to the Updated Sydney System Classification, atrophic gastritis is categorized into multifocal (H. pylori, environmental factors, specific diet) and corpus-predominant (autoimmune). Since metaplasia is a key histological characteristic in patients with atrophic gastritis, it has been recommended to use the word "metaplastic" in both variants of atrophic gastritis: autoimmune metaplastic atrophic gastritis (AMAG) and environmental metaplastic atrophic gastritis. Although there are many overlaps in the course of the disease and distinction between those two entities may be challenging, the aim of this review article was to describe the etiology, epidemiology, pathogenesis, diagnosis, clinical manifestations and treatment in patients with AMAG. However, it is important to mention that H. pylori is the most common etiologic factor for the development of gastritis in the world. C1 [Minalyan, Artem; Benhammou, Jihane N.; Artashesyan, Aida; Pisegna, Joseph R.] VA Greater Los Angeles Healthcare Syst, Div Gastroenterol Hepatol & Parenteral Nutr, Los Angeles, CA USA. [Lewis, Michael S.] VA Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. RP Pisegna, JR (reprint author), VA Greater Los Angeles Healthcare Syst 691 111C, Div Gastroenterol Hepatol & Parenteral Nutr, Dept Vet Affairs, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jpisegna@ucla.edu FU Department of Veterans Affairs RRD [I01 RX000194]; Human Studies CORE through CURE: Digestive Diseases Research Center by NIH [P30DK41301]; NIH NIDDK [T32 NIH5T32DK07180] FX This work received grant support from Department of Veterans Affairs RR&D Merit Review (JRP) I01 RX000194; Human Studies CORE through CURE: Digestive Diseases Research Center supported by NIH grant P30DK41301 and NIH NIDDK T32 NIH5T32DK07180 (JNB). NR 101 TC 0 Z9 0 U1 4 U2 4 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-7023 J9 CLIN EXP GASTROENTER JI Clin. Exp. Gastroenterol. PY 2017 VL 10 BP 19 EP 27 DI 10.2147/CEG.S109123 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EJ7ZQ UT WOS:000393441600001 PM 28223833 ER PT J AU Rodriguez-Salas, N Dominguez, G Barderas, R Mendiola, M Garcia-Albeniz, X Maurel, J Batlle, JF AF Rodriguez-Salas, Nuria Dominguez, Gema Barderas, Rodrigo Mendiola, Marta Garcia-Albeniz, Xabier Maurel, Juan Feliu Batlle, Jaime TI Clinical relevance of colorectal cancer molecular subtypes SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE Colorectal cancer; Molecular subtypes; Personalized treatment ID III COLON-CANCER; ISLAND METHYLATOR PHENOTYPE; MICROSATELLITE-INSTABILITY STATUS; TO-MESENCHYMAL TRANSITION; MISMATCH REPAIR STATUS; STAGE-II; ADJUVANT THERAPY; GENE-MUTATIONS; CELL-LINES; TUMOR-SUPPRESSOR AB Colorectal cancer (CRC) is characterized by alteration of critical pathways such TP53 inactivation, BRAF, PI3CA mutations, APC inactivation, ICRAS, TGF-beta, CTNNB mutations, disregulation of Epithelial to mesnechymal transition (EMT) genes, WNT signaling activation, MYC amplification, and others. Differences in these molecular events results in differences in phenotypic characteristics of CRC, that have been studied and classified by different models of molecular subtypes. It could have potential applications to prognosis, but also to therapeutical approaches of the CRC patients. We review and summarized the different molecular classifications and try to clarify their clinical and therapeutical relevance. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Rodriguez-Salas, Nuria; Feliu Batlle, Jaime] Univ Autonoma Madrid, La Paz Univ Hosp, Dept Med Oncol, Paseo La Castellana 261, Madrid 28046, Spain. [Dominguez, Gema] CSIC UAM, Inst Invest Biomed Alberto Sols, Sch Med, Dept Med, Calle Arturo Duperier 4, Madrid 28029, Spain. [Barderas, Rodrigo] Univ Complutense Madrid, Fac Ciencias Quim, Biochem & Mol Biol Dept, E-28040 Madrid, Spain. [Mendiola, Marta] La Paz Hosp Res Inst IdiPAZ, Mol Pathol Canc & Therapeut Targets Grp, Paseo La Castellana 261, Madrid 28046, Spain. [Garcia-Albeniz, Xabier] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Garcia-Albeniz, Xabier] Massachusetts Gen Hosp, Mongan Inst, Boston, MA USA. [Maurel, Juan] Univ Barcelona, Hosp Clin Barcelona, Translat Genom & Targeted Therapeut Solid Tumors, IDIBAPS,Dept Med Oncol, Barcelona, Spain. [Feliu Batlle, Jaime] Inst Salud Carlos III, CIBER Canc, Madrid, Spain. RP Rodriguez-Salas, N (reprint author), La Paz Univ Hosp, Dept Med Oncol, Paseo La Castellana 261, Madrid 28046, Spain. EM nuria.rodriguez@salud.madrid.org FU Instituto de Salud Carlos III, Ministerio de Economia, Industria y Competitividad [PI13-01659, PI 13/01278, PI15-00246] FX Grants sponsor, PI13-01659, PI 13/01278 and PI15-00246, from Instituto de Salud Carlos III, Ministerio de Economia, Industria y Competitividad. NR 92 TC 0 Z9 0 U1 9 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 EI 1879-0461 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD JAN PY 2017 VL 109 BP 9 EP 19 DI 10.1016/j.critrevonc.2016.11.007 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA EI8WO UT WOS:000392789100002 PM 28010901 ER PT J AU Yarlagadda, BB Meier, JC Lin, DT Emerick, KS Deschler, DG AF Yarlagadda, Bharat B. Meier, Josh C. Lin, Derrick T. Emerick, Kevin S. Deschler, Daniel G. TI Locoregional control of tongue base adenoid cystic carcinoma with primary resection and radial forearm free flap reconstruction SO ENT-EAR NOSE & THROAT JOURNAL LA English DT Article ID MINOR SALIVARY-GLANDS; PROGNOSTIC-FACTORS; SPEECH; TUMORS; HEAD; NECK AB Adenoid cystic carcinoma of the minor salivary glands can be challenging and marked by high rates of local recurrence despite appropriate surgical resection. Management of this pathology in the base of the tongue is particularly difficult given the poor functional outcomes traditionally associated with an aggressive surgical approach. This article presents a case series of patients who underwent up-front surgical resection followed by free tissue transfer reconstruction. A retrospective analysis was performed of patients with adenoid cystic carcinoma of the base of the tongue who underwent composite resection and reconstruction with a radial forearm free flap. Three patients met inclusion criteria and underwent analysis. All patients achieved locoregional control after at least 4 years of surveillance. In addition, all patients were decannulated and were swallowing without the need for gastrostomy tube feeding. This series demonstrates that for select patients with adenoid cystic carcinoma of the base of the tongue, excellent locoregional control can be achieved with acceptable functional outcomes and prolonged survival when appropriate reconstructive measures are employed. C1 [Yarlagadda, Bharat B.] Lahey Clin Fdn, Dept Otolaryngol, Boston, MA USA. [Meier, Josh C.; Lin, Derrick T.; Emerick, Kevin S.; Deschler, Daniel G.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. RP Deschler, DG (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Div Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM Daniel_deschler@meei.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 6 EAST 32 ST, 8 FLOOR, NEW YORK, NY 10016 USA SN 0145-5613 EI 1942-7522 J9 ENT-EAR NOSE THROAT JI ENT-Ear Nose Throat J. PD JAN PY 2017 VL 96 IS 1 BP 37 EP 40 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA EJ3CA UT WOS:000393087800010 PM 28122103 ER PT J AU Herrmann, B Parthasarathy, A Bartlett, EL AF Herrmann, Bjoern Parthasarathy, Aravindakshan Bartlett, Edward L. TI Ageing affects dual encoding of periodicity and envelope shape in rat inferior colliculus neurons SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ageing; amplitude modulation; inferior colliculus; neural synchronisation; rats ID AGE-RELATED-CHANGES; AMPLITUDE-MODULATED SOUNDS; CENTRAL AUDITORY-SYSTEM; STEADY-STATE RESPONSES; DORSAL COCHLEAR NUCLEUS; FALSE DISCOVERY RATE; AWAKE GUINEA-PIGS; HEARING-LOSS; BRAIN-STEM; GABAERGIC INHIBITION AB Extracting temporal periodicities and envelope shapes of sounds is important for listening within complex auditory scenes but declines behaviorally with age. Here, we recorded local field potentials (LFPs) and spikes to investigate how ageing affects the neural representations of different modulation rates and envelope shapes in the inferior colliculus of rats. We specifically aimed to explore the input-output (LFP-spike) response transformations of inferior colliculus neurons. Our results show that envelope shapes up to 256-Hz modulation rates are represented in the neural synchronisation phase lags in younger and older animals. Critically, ageing was associated with (i) an enhanced gain in onset response magnitude from LFPs to spikes; (ii) an enhanced gain in neural synchronisation strength from LFPs to spikes for a low modulation rate (45Hz); (iii) a decrease in LFP synchronisation strength for higher modulation rates (128 and 256Hz) and (iv) changes in neural synchronisation strength to different envelope shapes. The current age-related changes are discussed in the context of an altered excitation-inhibition balance accompanying ageing. C1 [Herrmann, Bjoern] Univ Western Ontario, Dept Psychol, London, ON N6A 3K7, Canada. [Herrmann, Bjoern] Univ Western Ontario, Brain & Mind Inst, London, ON N6A 3K7, Canada. [Parthasarathy, Aravindakshan; Bartlett, Edward L.] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. [Parthasarathy, Aravindakshan; Bartlett, Edward L.] Purdue Univ, Dept Biomed Engn, W Lafayette, IN 47907 USA. [Parthasarathy, Aravindakshan] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. [Parthasarathy, Aravindakshan] Massachusetts Eye & Ear Infirm, Eaton Peabody Labs, Boston, MA 02114 USA. RP Herrmann, B (reprint author), Univ Western Ontario, Dept Psychol, London, ON N6A 3K7, Canada.; Herrmann, B (reprint author), Univ Western Ontario, Brain & Mind Inst, London, ON N6A 3K7, Canada. EM herrmann.b@gmail.com FU NIDCD [DC-011580]; Brain and Mind Institute at the University of Western Ontario FX This study was supported by NIDCD DC-011580 to ELB and the Brain and Mind Institute at the University of Western Ontario (postdoctoral fellowship award to BH). NR 106 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0953-816X EI 1460-9568 J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2017 VL 45 IS 2 BP 299 EP 311 DI 10.1111/ejn.13463 PG 13 WC Neurosciences SC Neurosciences & Neurology GA EJ4HF UT WOS:000393176800010 PM 27813207 ER PT J AU Zhou, XH Ramke, M Chintakuntlawar, AV Lee, JY Rajaiya, J Chodosh, J AF Zhou, Xiaohong Ramke, Mirja Chintakuntlawar, Ashish V. Lee, Jeong Yoon Rajaiya, Jaya Chodosh, James TI Role of MyD88 in adenovirus keratitis SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article ID INNATE IMMUNE-RESPONSE; IN-VIVO; INFLAMMATORY RESPONSE; PATHOGEN RECOGNITION; REGULATORY FACTOR-3; SIGNALS ACTIVATION; EPITHELIAL-CELLS; DENDRITIC CELLS; CORNEAL STROMA; RECEPTOR AB Pattern recognition receptors (PRRs) are critical to the early detection and innate immune responses to pathogens. In particular, the toll-like receptor (TLR) system and its associated adaptor proteins have essential roles in early host responses to infection. Epidemic keratoconjunctivitis, caused by the human adenovirus, is a severe ocular surface infection associated with corneal inflammation (stromal keratitis). We previously showed that adenovirus capsid was a key molecular pattern in adenovirus keratitis, with viral DNA having a lesser role. We have now investigated the role of the adaptor molecule MyD88 in a mouse model of adenovirus keratitis in which there is no viral replication. In MyD88(-/-)mice infected with human adenovirus type 37, clinical keratitis was markedly reduced, along with infiltration of CD45(+) cells, and expression of inflammatory cytokines. Reduction of inflammatory cytokines was also observed in infected primary human corneal fibroblasts pretreated with a MyD88 inhibitory peptide. Keratitis similar to wild type mice was observed in TLR2, TLR9 and IL-1R knockout mice, but was reduced in TLR2/9 double knockout mice, consistent with synergy of TLR2 and TLR9 in the response to adenovirus infection. MyD88 co-immunoprecipitated with Src kinase in mice corneas and in human corneal fibroblasts infected with adenovirus, and MyD88 inhibitory peptide reduced Src phosphorylation, linking MyD88 activation to inflammatory gene expression through a signaling cascade previously shown to be directed by Src. Our findings reveal a critical role for the PRRs TLR2 and 9, and their adaptor protein MyD88, in corneal inflammation upon adenovirus infection. C1 [Zhou, Xiaohong; Ramke, Mirja; Chintakuntlawar, Ashish V.; Lee, Jeong Yoon; Rajaiya, Jaya; Chodosh, James] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Howe Lab, 243 Charles St, Boston, MA 02114 USA. RP Rajaiya, J; Chodosh, J (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Howe Lab, 243 Charles St, Boston, MA 02114 USA. EM james_chodosh@meei.harvard.edu FU NIH [EY013124, EY021558, P30EY014104]; Research to Prevent Blindness, New York, NY; Falk Foundation; Massachusetts Lions Eye Research Fund FX We thank Shizuo Akira, Michelle Callegan and Paul Kincade for TLR9-/-, TLR2-/- and Myd88-/-mice, and Beth Benas for technical support. This work was supported by NIH Grants EY013124, EY021558 and P30EY014104, a Senior Scientific Investigator Award (to JC) from Research to Prevent Blindness, New York, NY, the Falk Foundation and the Massachusetts Lions Eye Research Fund. NR 60 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 EI 1440-1711 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JAN PY 2017 VL 95 IS 1 BP 108 EP 116 DI 10.1038/icb.2016.73 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA EI8WG UT WOS:000392788300014 PM 27528076 ER PT J AU Gillespie, CD O'Reilly, MK Allen, GN McDermott, S Chan, VO Ridge, CA AF Gillespie, C. D. O'Reilly, M. K. Allen, G. N. McDermott, S. Chan, V. O. Ridge, C. A. TI Imaging the Abdominal Manifestations of Cystic Fibrosis SO INTERNATIONAL JOURNAL OF HEPATOLOGY LA English DT Review ID NONALCOHOLIC FATTY LIVER; ADULT PATIENTS; RISK-FACTORS; STONE FORMATION; DISEASE; CIRRHOSIS; BIOPSY; FIBROGENESIS; PROGRESSION; MANAGEMENT AB Cystic fibrosis (CF) is a multisystem disease with a range of abdominal manifestations including those involving the liver, pancreas, and kidneys. Recent advances in management of the respiratory complications of the disease has led to a greater life expectancy in patients with CF. Subsequently, there is increasing focus on the impact of abdominal disease on quality of life and survival. Liver cirrhosis is the most important extrapulmonary cause of death in CF, yet significant challenges remain in the diagnosis of CF related liver disease. The capacity to predict those patients at risk of developing cirrhosis remains a significant challenge. We review representative abdominal imaging findings in patients with CF selected from the records of two academic health centres, with a view to increasing familiarity with the abdominal manifestations of the disease. We review their presentation and expected imaging findings, with a focus on the challenges facing diagnosis of the hepatic manifestations of the disease. An increased familiarity with these abdominal manifestations will facilitate timely diagnosis and management, which is paramount to further improving outcomes for patients with cystic fibrosis. C1 [Gillespie, C. D.] Mater Misericordiae Univ Hosp, Dept Med, Dublin, Ireland. [O'Reilly, M. K.; Chan, V. O.; Ridge, C. A.] Mater Misericordiae Univ Hosp, Dept Radiol, Dublin, Ireland. [Allen, G. N.] Univ Coll Dublin, Sch Med, Dublin, Ireland. [McDermott, S.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. RP Gillespie, CD (reprint author), Mater Misericordiae Univ Hosp, Dept Med, Dublin, Ireland. EM ciaragill@gmail.com NR 45 TC 0 Z9 0 U1 1 U2 1 PU HINDAWI LTD PI LONDON PA ADAM HOUSE, 3RD FLR, 1 FITZROY SQ, LONDON, WIT 5HE, ENGLAND SN 2090-3448 EI 2090-3456 J9 INT J HEPATOL JI Int. J. Hepatol. PY 2017 AR 5128760 DI 10.1155/2017/5128760 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EJ5TD UT WOS:000393280100001 ER PT J AU Falavarjani, KG Iafe, NA Hubschman, JP Tsui, I Sadda, SR Sarraf, D AF Falavarjani, Khalil Ghasemi Iafe, Nicholas A. Hubschman, Jean-Pierre Tsui, Irena Sadda, Srinivas R. Sarraf, David TI Optical Coherence Tomography Angiography Analysis of the Foveal Avascular Zone and Macular Vessel Density After Anti-VEGF Therapy in Eyes With Diabetic Macular Edema and Retinal Vein Occlusion SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE aflibercept; anti-VEGF; bevacizumab; diabetic retinopathy; foveal avascular zone; macular edema; optical coherence tomography angiography; retinal vein occlusion; ranibizumab; vessel density ID ENDOTHELIAL GROWTH-FACTOR; INTRAVITREAL BEVACIZUMAB; FLUORESCEIN ANGIOGRAPHY; RANDOMIZED-TRIAL; VISUAL-ACUITY; NONPERFUSION; PROGRESSION; ISCHEMIA; RANIBIZUMAB; MANAGEMENT AB PURPOSE. To evaluate the changes in foveal avascular zone (FAZ) area and the retinal capillary density after a single intravitreal anti-VEGF injection for macular edema secondary to diabetic retinopathy or retinal vein occlusion. METHODS. In this prospective noncomparative case series, 18 eyes of 15 patients with diabetic macular edema (13 eyes) or macular edema secondary to central retinal vein occlusion (5 eyes) were included. Optical coherence tomography angiography (OCTA) images were obtained, and retinal capillary vessel density and FAZ area were measured in the foveal and parafoveal regions at the level of the superficial (SCP) and deep retinal capillary plexus (DCP) before and at the first visit after intravitreal injection. RESULTS. The mean interval between baseline and follow up OCTA was 32.5+/-9.4 (range, 2150) days. Foveal and parafoveal vessel density in the SCP and DCP were not significantly different before and after intravitreal injection (all P > 0.1), nor was FAZ area (P = 0.48 and P = 0.42, respectively). No significant difference was found between eyes with diabetic macular edema and those with retinal vein occlusion with respect to the mean change of vessel density and FAZ area (all P > 0.05). CONCLUSIONS. In this pilot study, retinal capillary density and FAZ area remained statistically unchanged in the short-term after a single intravitreal injection of an anti-VEGF agent. C1 [Falavarjani, Khalil Ghasemi; Iafe, Nicholas A.; Hubschman, Jean-Pierre; Tsui, Irena; Sadda, Srinivas R.; Sarraf, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. [Falavarjani, Khalil Ghasemi; Sadda, Srinivas R.] Univ Calif Los Angeles, Doheny Eye Inst, Los Angeles, CA USA. [Falavarjani, Khalil Ghasemi] Iran Univ Med Sci, Rassoul Akram Hosp, Eye Res Ctr, Tehran, Iran. [Iafe, Nicholas A.; Hubschman, Jean-Pierre; Tsui, Irena; Sarraf, David] Univ Calif Los Angeles, Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. EM sarraf@jsei.ucla.edu NR 25 TC 0 Z9 0 U1 2 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2017 VL 58 IS 1 BP 30 EP 34 DI 10.1167/iovs.16-20579 PG 5 WC Ophthalmology SC Ophthalmology GA EJ1EW UT WOS:000392954300004 ER PT J AU Zhou, CX Robert, MC Kapoulea, V Lei, FY Stagner, AM Jakobiec, FA Dohlman, CH Paschalis, EI AF Zhou, Chengxin Robert, Marie-Claude Kapoulea, Vassiliki Lei, Fengyang Stagner, Anna M. Jakobiec, Frederick A. Dohlman, Claes H. Paschalis, Eleftherios I. TI Sustained Subconjunctival Delivery of Infliximab Protects the Cornea and Retina Following Alkali Burn to the Eye SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE polydimethylsiloxane; tumor necrosis factor alpha; drug delivery system; antibody therapy; corneal wound healing; retinal protection; burn ID PERIPHERAL ULCERATIVE KERATITIS; TOPICAL INFLIXIMAB; IN-VIVO; TRANSPLANTATION; GLAUCOMA; DISEASE; KERATOPROSTHESIS; SYSTEM AB PURPOSE. Tumor necrosis factor (TNF)-alpha is upregulated in eyes following corneal alkali injury and contributes to corneal and also retinal damage. Prompt TNF-alpha inhibition by systemic infliximab ameliorates retinal damage and improves corneal wound healing. However, systemic administration of TNF-alpha inhibitors carries risk of significant complications, whereas topical eye-drop delivery is hindered by poor ocular bioavailability and the need for patient adherence. This study investigates the efficacy of subconjunctival delivery of TNF-alpha antibodies using a polymer-based drug delivery system (DDS). METHODS. The drug delivery system was prepared using porous polydimethylsiloxane/polyvinyl alcohol composite fabrication and loaded with 85 lg of infliximab. Six Dutch-belted pigmented rabbits received ocular alkali burn with NaOH. Immediately after the burn, subconjunctival implantation of anti-TNF-alpha DDS was performed in three rabbits while another three received sham DDS (without antibody). Rabbits were followed with photography for 3 months. RESULTS. After 3 months, the device was found to be well tolerated by the host and the eyes exhibited less corneal damage as compared to eyes implanted with a sham DDS without drug. The low dose treatment suppressed CD45 and TNF-alpha expression in the burned cornea and inhibited retinal ganglion cell apoptosis and optic nerve degeneration, as compared to the sham DDS treated eyes. Immunolocalization revealed drug penetration in the conjunctiva, cornea, iris, and choroid, with residual infliximab in the DDS 3 months after implantation. CONCLUSIONS. This reduced-risk biologic DDS improves corneal wound healing and provides retinal neuroprotection, and may be applicable not only to alkali burns but also to other inflammatory surgical procedures such as penetrating keratoplasty and keratoprosthesis implantation. C1 [Zhou, Chengxin; Kapoulea, Vassiliki; Lei, Fengyang; Dohlman, Claes H.; Paschalis, Eleftherios I.] Massachusetts Eye & Ear, Dept Ophthalmol, Boston Keratoprosthesis Lab, Boston, MA USA. [Zhou, Chengxin; Kapoulea, Vassiliki; Lei, Fengyang; Dohlman, Claes H.; Paschalis, Eleftherios I.] Schepens Eye Res Inst, Boston, MA USA. [Zhou, Chengxin; Kapoulea, Vassiliki; Lei, Fengyang; Stagner, Anna M.; Jakobiec, Frederick A.; Dohlman, Claes H.; Paschalis, Eleftherios I.] Harvard Med Sch, Boston, MA 02114 USA. [Robert, Marie-Claude] Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada. [Robert, Marie-Claude] Notre Dame Hosp, Ctr Hosp Univ Montreal, Montreal, PQ, Canada. [Stagner, Anna M.; Jakobiec, Frederick A.] Massachusetts Eye & Ear, David G Cogan Ophthalm Pathol Lab, Boston, MA USA. [Paschalis, Eleftherios I.] Harvard Med Sch, DTL, Massachusetts Eye & Ear, Dept Ophthalmol, Boston, MA 02114 USA. RP Paschalis, EI (reprint author), Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston Keratoprosthesis Lab, Dept Ophthalmol, Boston, MA 02114 USA.; Paschalis, EI (reprint author), Harvard Med Sch, Schepens Eye Res Inst, Boston, MA 02114 USA. EM eleftherios_paschalis@meei.harvard.edu FU Boston Keratoprosthesis Fund of Massachusetts Eye and Ear; Eleanor and Miles Shore Fund; National Eye Institute; Core Grant [P30EY003790]; National Science Foundation under NSF [1541959] FX Supported by Boston Keratoprosthesis Fund of Massachusetts Eye and Ear; the Eleanor and Miles Shore Fund; National Eye Institute, and Core Grant #P30EY003790. This work was performed in part at the Harvard University Center for Nanoscale Systems (CNS), a member of the National Nanotechnology Coordinated Infrastructure Network (NNCI), which is supported by the National Science Foundation under NSF award no. 1541959. NR 35 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2017 VL 58 IS 1 BP 96 EP 105 DI 10.1167/iovs.16-20339 PG 10 WC Ophthalmology SC Ophthalmology GA EJ1EW UT WOS:000392954300012 PM 28114570 ER PT J AU Zhu, H Kochevar, IE Behlau, I Zhao, J Wang, FH Wang, YC Sun, XD Hamblin, MR Dai, TH AF Zhu, Hong Kochevar, Irene E. Behlau, Irmgard Zhao, Jie Wang, Fenghua Wang, Yucheng Sun, Xiaodong Hamblin, Michael R. Dai, Tianhong TI Antimicrobial Blue Light Therapy for Infectious Keratitis: Ex Vivo and In Vivo Studies SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE antimicrobial blue light; keratitis; Pseudomonas aeruginosa; mouse model; rabbit model; bioluminescence imaging ID PSEUDOMONAS-AERUGINOSA KERATITIS; BACTERIAL KERATITIS; RISK-FACTORS; STAPHYLOCOCCUS-AUREUS; MICROBIAL KERATITIS; WOUND INFECTIONS; RESISTANCE; ENDOPHTHALMITIS; ANTIBIOTICS; MANAGEMENT AB PURPOSE. To investigate the effectiveness of antimicrobial blue light (aBL) as an alternative or adjunctive therapeutic for infectious keratitis. METHODS. We developed an ex vivo rabbit model and an in vivo mouse model of infectious keratitis. A bioluminescent strain of Pseudomonas aeruginosa was used as the causative pathogen, allowing noninvasive monitoring of the extent of infection in real time via bioluminescence imaging. Quantitation of bacterial luminescence was correlated to colonyforming units (CFU). Using the ex vivo and in vivo models, the effectiveness of aBL (415 nm) for the treatment of keratitis was evaluated as a function of radiant exposure when aBL was delivered at 6 or 24 hours after bacterial inoculation. The aBL exposures calculated to reach the retina were compared to the American National Standards Institute standards to estimate aBL retinal safety. RESULTS. Pseudomonas aeruginosa keratitis fully developed in both the ex vivo and in vivo models at 24 hours post inoculation. Bacterial luminescence in the infected corneas correlated linearly to CFU (R-2 = 0.921). Bacterial burden in the infected corneas was rapidly and significantly reduced (>2-log(10)) both ex vivo and in vivo after a single exposure of aBL. Recurrence of infection was observed in the aBL-treated mice at 24 hours after aBL exposure. The aBL toxicity to the retina is largely dependent on the aBL transmission of the cornea. CONCLUSIONS. Antimicrobial blue light is a potential alternative or adjunctive therapeutic for infectious keratitis. Further studies of corneal and retinal safety using large animal models, in which the ocular anatomies are similar to that of humans, are warranted. C1 [Zhu, Hong; Kochevar, Irene E.; Zhao, Jie; Wang, Yucheng; Hamblin, Michael R.; Dai, Tianhong] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Zhu, Hong; Wang, Fenghua; Sun, Xiaodong] Shanghai Jiao Tong Univ, Shanghai Peoples Hosp 1, Dept Ophthalmol, Shanghai, Peoples R China. [Behlau, Irmgard] Harvard Med Sch, Mt Auburn Hosp, Dept Med, Cambridge, MA USA. [Behlau, Irmgard] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Wang, Yucheng] Chinese Peoples Liberat Army Gen Hosp, Dept Laser Med, Beijing, Peoples R China. RP Sun, XD (reprint author), Shanghai First Peoples Hosp, Dept Ophthalmol, 85 Wujin Rd, Shanghai 200080, Peoples R China.; Dai, TH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR 404B,55 Fruit St, Boston, MA 02114 USA. EM xdsun@sjtu.edu.cn; tdai@mgh.harvard.edu FU Smith Infectious Diseases Foundation; Air Force Office of Scientific Research [FA9550-16-1-0479]; National Institutes of Health [1R21AI109172, 1R01AI123312] FX Supported in part by the Smith Infectious Diseases Foundation (Research Grant Award to TD), the Air Force Office of Scientific Research (FA9550-16-1-0479 to TD), and the National Institutes of Health (1R21AI109172 and 1R01AI123312 to TD). NR 34 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 2017 VL 58 IS 1 BP 586 EP 593 DI 10.1167/iovs.16-20272 PG 8 WC Ophthalmology SC Ophthalmology GA EJ1EW UT WOS:000392954300064 PM 28129422 ER PT J AU Armour, C Fried, EI Deserno, MK Tsai, J Pietrzak, RH AF Armour, Cherie Fried, Eiko I. Deserno, Marie K. Tsai, Jack Pietrzak, Robert H. TI A network analysis of DSM-5 posttraumatic stress disorder symptoms and correlates in US military veterans SO JOURNAL OF ANXIETY DISORDERS LA English DT Article DE PTSD; Depression; DSM-5; Veterans; Network analysis; Functioning; Quality of life (QoL); Suicide ID PTSD SYMPTOMS; LATENT STRUCTURE; DEPRESSION SYMPTOMS; SUICIDAL IDEATION; PRIMARY-CARE; COMORBIDITY; AFGHANISTAN; RISK; IRAQ; PREDICTORS AB Objective: Recent developments in psychometrics enable the application of network models to analyze psychological disorders, such as PTSD. Instead of understanding symptoms as indicators of an underlying common cause, this approach suggests symptoms co-occur in syndromes due to causal interactions. The current study has two goals: (1) examine the network structure among the 20 DSM-5 PTSD symptoms, and (2) incorporate clinically relevant variables to the network to investigate whether PTSD symptoms exhibit differential relationships with suicidal ideation, depression, anxiety, physical functioning/quality of life (QoL), mental functioning(QoL, age, and sex. Method: We utilized a nationally representative U.S. military veteran's sample; and analyzed the data from a subsample of 221 veterans who reported clinically significant DSM-5 PTSD symptoms. Networks were estimated using state-of-the-art regularized partial correlation models. Data and code are published along with the paper. Results: The 20-item DSM-5 PTSD network revealed that symptoms were positively connected within the network. Especially strong connections emerged between nightmares and flashbacks; blame of self or others and negative trauma-related emotions, detachment and restricted affect; and hypervigilance and exaggerated startle response. The most central symptoms were negative trauma-related emotions, flashbacks, detachment, and physiological cue reactivity. Incorporation of clinically relevant covariates into the network revealed paths between self-destructive behavior and suicidal ideation; concentration difficulties and anxiety, depression, and mental QoL; and depression and restricted affect. Conclusion: These results demonstrate the utility of a network approach in modeling the structure of DSM-5 PTSD symptoms, and suggest differential associations between specific DSM-5 PTSD symptoms and clinical outcomes in trauma survivors. Implications of these results for informing the assessment and treatment of this disorder, are discussed. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Armour, Cherie] Univ Ulster, Psychol Res Inst, Coleraine Campus, Coleraine BT52 1SA, Londonderry, North Ireland. [Fried, Eiko I.] Univ Leuven, Fac Psychol & Educ Sci, Leuven, Belgium. [Deserno, Marie K.] Univ Amsterdam, Dept Psychol, Amsterdam, Netherlands. [Tsai, Jack; Pietrzak, Robert H.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Tsai, Jack] US Dept Vet Affairs, New England Mental Illness Res Educ & Clin Ctr, West Haven, CT USA. [Pietrzak, Robert H.] Natl Ctr Posttraumat Stress Disorder, US Dept Vet Affairs, Clin Neurosci Div, West Haven, CT USA. RP Armour, C (reprint author), Univ Ulster, Psychol Res Inst, Coleraine Campus, Coleraine BT52 1SA, Londonderry, North Ireland. EM armour.cherie@gmail.com FU U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder; European Research Council Consolidator Grant [647209] FX The National Health and Resilience in Veterans Study is supported by the U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder. Dr. Fried is supported by the European Research Council Consolidator Grant no. 647209. NR 73 TC 1 Z9 1 U1 11 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-6185 EI 1873-7897 J9 J ANXIETY DISORD JI J. Anxiety Disord. PD JAN PY 2017 VL 45 BP 49 EP 59 DI 10.1016/j.janxdis.2016.11.008 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA EI8YM UT WOS:000392794100007 PM 27936411 ER PT J AU Gilbert, MR Pugh, SL Aldape, K Sorensen, AG Mikkelsen, T Penas-Prado, M Bokstein, F Kwok, Y Lee, RJ Mehta, M AF Gilbert, Mark R. Pugh, Stephanie L. Aldape, Ken Sorensen, A. Gregory Mikkelsen, Tom Penas-Prado, Marta Bokstein, Felix Kwok, Young Lee, R. Jeffrey Mehta, Minesh TI NRG oncology RTOG 0625: a randomized phase II trial of bevacizumab with either irinotecan or dose-dense temozolomide in recurrent glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Anti-angiogenic treatment; Randomized trial; Combination therapy ID NEWLY-DIAGNOSED GLIOBLASTOMA; SINGLE-AGENT BEVACIZUMAB; CLINICAL-TRIALS; MALIGNANT GLIOMA; TUMORS; CRITERIA; THERAPY AB Angiogenesis, a hallmark of glioblastoma, can potentially be targeted by inhibiting the VEGF pathway using bevacizumab, a humanized monoclonal antibody against VEGF-A. This study was designed to determine the efficacy and safety of these regimens in the cooperative group setting. Eligibility included age 18, recurrent or progressive GBM after standard chemoradiation. Treatment was intravenous bevacizumab 10 mg/kg and either irinotecan (CPT) 125 mg/m(2) every 2 weeks or temozolomide (TMZ) 75-100 mg/m(2) day 1-21 of 28 day cycle. Accrual goal was 57 eligible patients per arm. Primary endpoint was 6 month progression-free survival (6-m PFS); a predetermined rate of 35 % to declare efficacy. 60 eligible patients were enrolled on TMZ arm and 57 patients on CPT arm. Median age was 56, median KPS was 80. For TMZ arm, the 6-m-PFS rate was 39 % (23/59); for the CPT arm, the 6-m-PFS rate was 38.6 % (22/57). Objective responses: TMZ arm had 2 (3 %) CR, 9 (16 %) PR; CPT arm had 2 (4 %) CR, 13 (24 %) PR. Overall there was moderate toxicity: TMZ arm with 33 (55 %) grade 3, 11 (18 %) grade 4, and 1 (2 %) grade 5 (fatal) toxicities; CPT arm had 22 (39 %) grade 3, 7 (12 %) grade 4, and 3 (5 %) grade 5 toxicities. The 6-m-PFS surpassed the predetermined efficacy threshold for both arms, corroborating the efficacy of bevacizumab and CPT and confirming activity for bevacizumab and protracted TMZ for recurrent/progressive GBM, even after prior temozolomide exposure. Toxicities were within anticipated frequencies with a moderately high rate of venous thrombosis, moderate hypertension and one intracranial hemorrhage. C1 [Gilbert, Mark R.] NCI, Neurooncol Branch, NIH, Bloch Bldg 82,Rm 235,9030 Old George Town Rd, Bethesda, MD 20892 USA. [Pugh, Stephanie L.] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Aldape, Ken] Univ Toronto, Toronto, ON, Canada. [Sorensen, A. Gregory] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mikkelsen, Tom] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Penas-Prado, Marta] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bokstein, Felix] Tel Aviv Med Ctr & Sch Med, Tel Aviv, Israel. [Kwok, Young; Mehta, Minesh] Univ Maryland, Baltimore, MD 21201 USA. [Lee, R. Jeffrey] Intermt Med Ctr, Murray, UT USA. RP Gilbert, MR (reprint author), NCI, Neurooncol Branch, NIH, Bloch Bldg 82,Rm 235,9030 Old George Town Rd, Bethesda, MD 20892 USA. EM mark.gilbert@nih.gov OI mehta, minesh/0000-0002-4812-5713 FU National Cancer Institute (NCI) [U10CA21661, U10CA180868, U10CA180822, U10CA37422, U24CA180803] FX This project was supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and U24CA180803 from the National Cancer Institute (NCI). NR 24 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X EI 1573-7373 J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2017 VL 131 IS 1 BP 193 EP 199 DI 10.1007/s11060-016-2288-5 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA EJ2TX UT WOS:000393065400021 PM 27770279 ER PT J AU Kaiser, AP Wang, J Davison, EH Park, CL Stellman, JM AF Kaiser, Anica Pless Wang, Joyce Davison, Eve H. Park, Crystal L. Stellman, Jeanne Mager TI Stressful and positive experiences of women who served in Vietnam SO JOURNAL OF WOMEN & AGING LA English DT Article DE Older women; qualitative; stressful and positive experiences; Vietnam ID POSTTRAUMATIC-STRESS; AMERICAN LEGIONNAIRES; VETERANS; WAR; COMBAT; DISORDER; MILITARY; EXPOSURE; NURSES; TRAUMA AB Experiences of women who served during the Vietnam War have been described in interviews/anecdotal reports but rarely in empirical literature. Potential positive (versus negative) aspects of service or its impact on well-being are seldom considered. We describe stressful and positive experiences reported by approximately 1,300 female military personnel, Red Cross workers, and others deployed to Vietnam. Prominent stressful (e.g., negative living/working conditions) and positive (e.g., interpersonal relationships) themes and differences based on trauma history, Vietnam experiences, and group membership are explored. We evaluate associations between themes and psychological well-being. Findings provide insight into experiences of this understudied group of women. C1 [Kaiser, Anica Pless; Davison, Eve H.] VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B 2, Boston, MA 02130 USA. [Kaiser, Anica Pless; Davison, Eve H.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Wang, Joyce] VA Boston Healthcare Syst, MAVERIC, Boston, MA USA. [Wang, Joyce] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Wang, Joyce] RTI Int, Waltham, MA USA. [Park, Crystal L.] Univ Connecticut, Dept Psychol, Storrs, CT USA. [Stellman, Jeanne Mager] Columbia Univ, Mailman Sch Publ Hlth, Hlth Policy & Management, New York, NY USA. RP Kaiser, AP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B 2, Boston, MA 02130 USA. EM anica.plesskaiser@va.gov FU National Academy of Sciences [NAS-VA-5124-98-001] FX This research was supported in part by the National Academy of Sciences Subcontract NAS-VA-5124-98-001. NR 34 TC 0 Z9 0 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0895-2841 EI 1540-7322 J9 J WOMEN AGING JI J. Women Aging PY 2017 VL 29 IS 1 BP 26 EP 38 DI 10.1080/08952841.2015.1019812 PG 13 WC Gerontology; Women's Studies SC Geriatrics & Gerontology; Women's Studies GA EJ1SP UT WOS:000392990800004 ER PT J AU Goncalves, OF Rego, G Oliveira-Silva, P Leite, J Carvalho, S Fregni, F Amaro, E Boggio, PS AF Goncalves, Oscar F. Rego, Gabriel Oliveira-Silva, Patricia Leite, Jorge Carvalho, Sandra Fregni, Felipe Amaro, Edson, Jr. Boggio, Paulo S. TI Mind wandering and the attention network system SO ACTA PSYCHOLOGICA LA English DT Article DE Mind wandering; Attention; Alerting; Orienting; Conflict; Executive control ID EXTERNAL DISTRACTION; CONTROL ABILITIES; EXECUTIVE-CONTROL; DEFAULT NETWORK; HUMAN BRAIN; REVEALS; THOUGHT AB Attention and mind wandering are often seen as anticorrelated. However, both attention and mind wandering are multi-component processes, and their relationship may be more complex than previously thought. In this study, we tested the interference of different types of thoughts as measured by a Thought Identification Task TIT (on task thoughts, task related interference thoughts, external distractions, stimulus independent and task unrelated thoughts) on different components of the attention network system - ANT (alerting, orienting, executive). Results show that, during the ANT, individuals were predominantly involved in task related interference thoughts which, along with external distractors, significantly impaired their performance accuracy. However, mind wandering (i.e., stimulus independent and task unrelated thoughts) did not significantly interfere with accuracy in the ANT. No significant relationship was found between type of thoughts and alerting, orienting, or executive effects in the ANT. While task related interference thoughts and external distractions seemed to impair performance on the attention task, mind wandering was still compatible with satisfactory performance in the ANT. The present results confirmed the importance of differentiating type of "out of task" thoughts in studying the relationship between though distractors and attention. (C) 2016 Elsevier B.V. All rights reserved. C1 [Goncalves, Oscar F.; Oliveira-Silva, Patricia; Leite, Jorge; Carvalho, Sandra] Univ Minho, Sch Psychol, Neuropsychophysiol Lab CIPsi, Braga, Portugal. [Goncalves, Oscar F.; Leite, Jorge; Carvalho, Sandra; Fregni, Felipe] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Spaulding Neuromodulat Ctr, Boston, MA USA. [Goncalves, Oscar F.; Leite, Jorge; Carvalho, Sandra; Fregni, Felipe] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Goncalves, Oscar F.; Rego, Gabriel; Boggio, Paulo S.] Univ Prebiteriana Mackenzie, Ctr Hlth & Biol Sci, Social & Cognit Neurosci Lab, Sao Paulo, Brazil. [Oliveira-Silva, Patricia] UCP, Ctr Studies Human Dev CEDH, Human Neurobehav Lab, FEP, Oporto, Portugal. [Amaro, Edson, Jr.] Univ Sao Paulo, Sch Med, Clin Hosp, Dept Radiol, Sao Paulo, Brazil. RP Goncalves, OF (reprint author), Northeastern Univ, Counseling & Appl Educ Psychol, 360 Huntington Ave, Boston, MA 02115 USA. EM o.goncalves@neu.edu RI Leite, Jorge/E-4404-2013; OI Leite, Jorge/0000-0002-0323-9012; Amaro Jr, Edson/0000-0002-5889-1382; Goncalves, Oscar/0000-0003-2735-9155 FU Brazilian National Counsel for Scientific and Technological Development (CNPq) as a Special Visiting Researcher of the Science Without Borders program [401143/2014-7]; Portuguese Foundation for Science and Technology; Portuguese Ministry of Science, Technology and Higher Education; FEDER [POCI-01-0145-FEDER-007653]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [311641/2015-6, FAPESP - 2015/18713-9]; Portuguese Foundation for Science and Technology (FCT); European Union (FSE-POPH) [SFRH/BPD/86041/2012, SFRH/BPD/86027/2012] FX Oscar F. Goncalves was funded by the Brazilian National Counsel for Scientific and Technological Development (CNPq) as a Special Visiting Researcher of the Science Without Borders program (grant number: 401143/2014-7). This study was partially conducted at the Neuropsychophysiology Lab from the Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). Paulo S Boggio is a CNPq researcher fellow (311641/2015-6) Gabriel Gaudencio Rego was supported by a PhD grant from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP - 2015/18713-9). This work was also supported by the Portuguese Foundation for Science and Technology (FCT) and European Union (FSE-POPH) with two individual grants (SFRH/BPD/86041/2012 and SFRH/BPD/86027/2012). NR 31 TC 0 Z9 0 U1 6 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-6918 EI 1873-6297 J9 ACTA PSYCHOL JI Acta Psychol. PD JAN PY 2017 VL 172 BP 49 EP 54 DI 10.1016/j.actpsy.2016.11.008 PG 6 WC Psychology, Experimental SC Psychology GA EI8QS UT WOS:000392773200006 PM 27886519 ER PT J AU Wertheim, BM Aguirre, AJ Bhattacharyya, RP Chorba, J Jadhav, AP Kerry, VB Macklin, EA Motyckova, G Raju, S Lewandrowski, K Hunt, DP Wright, DE AF Wertheim, Bradley M. Aguirre, Andrew J. Bhattacharyya, Roby P. Chorba, John Jadhav, Ashutosh P. Kerry, Vanessa B. Macklin, Eric A. Motyckova, Gabriela Raju, Shveta Lewandrowski, Kent Hunt, Daniel P. Wright, Douglas E. TI An Educational and Administrative Intervention to Promote Rational Laboratory Test Ordering on an Academic General Medicine Service SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Diagnostic tests; Medical education; Resource use ID ANEMIA; PHLEBOTOMY; BEHAVIOR AB BACKGROUND: Overuse of clinical laboratory testing in the inpatient setting is a common problem. The objective of this project was to develop an inexpensive and easily implemented intervention to promote rational laboratory use without compromising resident education or patient care. METHODS: The study comprised of a cluster-randomized, controlled trial to assess the impact of a multifaceted intervention of education, guideline development, elimination of recurring laboratory orders, unbundling of laboratory panels, and redesign of the daily progress note on laboratory test ordering. The population included all patients hospitalized " general medicine" was duplicated during 2 consecutive months on a general medicine teaching service within a 999-bed tertiary care hospital in Boston, Massachusetts. The primary outcome was the total number of commonly used laboratory tests per patient day during 2 months in 2008. Secondary outcomes included a subgroup analysis of each individual test per patient day, adverse events, and resident and nursing satisfaction. RESULTS: A total of 5392 patient days were captured. The intervention produced a 9% decrease in aggregate laboratory use (rate ratio, 0.91; P = .021; 95% confidence interval, 0.84-0.98). Six instances of delayed diagnosis of acute kidney injury and 11 near misses were reported in the intervention arm. CONCLUSIONS: A bundled educational and administrative intervention promoting rational ordering of laboratory tests on a single academic general medicine service led to a modest but significant decrease in laboratory use. To our knowledge, this was the first study to examine the daily progress note as a tool to limit excessive test ordering. Unadjudicated near misses and possible harm were reported with this intervention. This finding warrants further study. (C) 2016 Elsevier Inc. All rights reserved. C1 [Wertheim, Bradley M.; Aguirre, Andrew J.; Chorba, John; Jadhav, Ashutosh P.; Motyckova, Gabriela; Raju, Shveta; Hunt, Daniel P.; Wright, Douglas E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wertheim, Bradley M.; Aguirre, Andrew J.; Bhattacharyya, Roby P.; Kerry, Vanessa B.; Lewandrowski, Kent; Wright, Douglas E.] Harvard Med Sch, Boston, MA USA. [Bhattacharyya, Roby P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Kerry, Vanessa B.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Raju, Shveta] Georgia Regents Univ, Med Coll Georgia, Augusta, GA USA. [Lewandrowski, Kent] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Hunt, Daniel P.] Emory Univ, Sch Med, Atlanta, GA USA. [Wertheim, Bradley M.] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA. [Aguirre, Andrew J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Chorba, John] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Cardiol, San Francisco, CA USA. [Jadhav, Ashutosh P.] Univ Pittsburgh, Med Ctr, Dept Neurol & Neurol Surg, Pittsburgh, PA 15260 USA. [Motyckova, Gabriela] LDS Hosp, Intermt Blood & Marrow Transplant Acute Leukemia, Salt Lake City, UT USA. [Raju, Shveta] Gwinnett Clin, Lawrenceville, GA USA. [Hunt, Daniel P.] Emory Univ, Div Hosp Med, Atlanta, GA 30322 USA. EM bwertheim@partners.org OI Jadhav, Ashutosh/0000-0002-9454-0678 FU Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institutes of Health) [UL1 TR001102]; 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 work was conducted with support from Harvard Catalyst, the Harvard Clinical and Translational Science Center (National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR001102), and financial contributions from Harvard University and its affiliated academic healthcare 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 healthcare centers, or the National Institutes of Health. NR 18 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 JAN PY 2017 VL 130 IS 1 BP 47 EP 53 DI 10.1016/j.amjmed.2016.08.021 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA EI6QS UT WOS:000392621500026 PM 27619354 ER PT J AU Mahmood, SS Abtahian, F Fogerty, AE Cefalo, P MacKay, C Jaff, MR Weinberg, I AF Mahmood, Syed S. Abtahian, Farhad Fogerty, Annemarie E. Cefalo, Philip MacKay, Cheryl Jaff, Michael R. Weinberg, Ido TI Anticoagulation Is Associated with Decreased Inferior Vena Cava Filter-Related Complications in Patients with Metastatic Carcinoma SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Anticoagulants; Carcinoma; Inferior vena cava filters; Metastatic cancer; Venous thromboembolism ID DEEP-VEIN THROMBOSIS; TERM-FOLLOW-UP; VENOUS THROMBOEMBOLISM; CANCER-PATIENTS; RETRIEVAL; PREVENTION; PLACEMENT; SURVIVAL AB OBJECTIVES: Patients with metastatic carcinoma and venous thromboembolism commonly have contraindications to anticoagulation that prompt the use of retrievable inferior vena cava filters. The aim of this study was to compare the pattern of inferior vena cava filter use, anticoagulation management, and development of inferior vena cava filter-related complications in patients with localized versus metastatic carcinoma. METHODS: We conducted a retrospective cohort study of inferior vena cava filter use at a tertiary referral hospital between January 1, 2009, and December 31, 2011. Including only patients with cancer and carcinomas, both metastatic and localized, we recorded the indications for inferior vena cava filter, postfilter practices including anticoagulation use, filter retrieval rates, and filter-related complications. RESULTS: Overall, 154 patients with carcinoma underwent inferior vena cava filter placement. Basic demographics and indication for filter placement were similar between the metastatic and localized groups. Metastatic patients had more filter-related complications (25% vs 11%, P = .03) and underwent filter retrieval less often (31% vs 58%, P = .01). Time to reinitiating anticoagulation was longer in metastatic patients (5.5 vs 2 days, P = .05). In multivariate analysis, metastatic disease was associated with reduced inferior vena cava filter retrieval (odds ratio, 0.3; P = .003). Anticoagulation use was associated with a lower rate of filter-related complications (odds ratio, 0.3; P = .005). CONCLUSIONS: Patients with metastatic carcinoma with an indwelling inferior vena cava filter had a higher rate of filter-related complications, a lower filter retrieval rate, and a greater median time to initiating anticoagulation. When possible, early reinitiation of anticoagulation may reduce inferior vena cava filter-related complications. (C) 2016 Elsevier Inc. All rights reserved. C1 [Mahmood, Syed S.] Massachusetts Gen Hosp, Dept Med, 55 Fruit St, Boston, MA 02114 USA. [Mahmood, Syed S.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. [Abtahian, Farhad] Rochester Reg Hlth Ctr, Cardiol, Rochester, NY USA. [Fogerty, Annemarie E.] Massachusetts Gen Hosp, Dept Hematol & Oncol, 55 Fruit St, Boston, MA 02114 USA. [Cefalo, Philip] Massachusetts Gen Hosp, Dept Med & Phys Med & Rehabil, 55 Fruit St, Boston, MA 02114 USA. [MacKay, Cheryl; Jaff, Michael R.; Weinberg, Ido] Massachusetts Gen Hosp, Fireman Vasc Ctr, 55 Fruit St, Boston, MA 02114 USA. EM iweinberg@mgh.harvard.edu OI MacKay, Cheryl/0000-0003-2220-4226 NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2017 VL 130 IS 1 BP 77 EP + DI 10.1016/j.amjmed.2016.06.048 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA EI6QS UT WOS:000392621500030 PM 27477669 ER PT J AU Panosian, J Ding, SA Wewalka, M Simonson, DC Goebel-Fabbri, A Foster, K Halperin, F Vernon, A Goldfine, AB AF Panosian, Jennifer Ding, Su-Ann Wewalka, Marlene Simonson, Donald C. Goebel-Fabbri, Ann Foster, Kathleen Halperin, Florencia Vernon, Ashley Goldfine, Allison B. TI Physical Activity in Obese Type 2 Diabetes After Gastric Bypass or Medical Management SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Bariatric surgery; Obesity; Physical activity; Physical fitness; Roux-en-Y gastric bypass; Type 2 diabetes ID LIFE-STYLE INTERVENTION; BARIATRIC SURGERY; ACTIVITY QUESTIONNAIRE; EXERCISE CAPACITY; BLOOD-PRESSURE; RISK ENGINE; MORTALITY; DISEASE; REPRODUCIBILITY; METAANALYSIS AB BACKGROUND: The purpose of this study was to compare effects of Roux-en-Y gastric bypass versus a multidisciplinary, group-based medical diabetes and weight management program on physical fitness and behaviors. METHODS: Physical behavior and fitness were assessed in participants of the study Surgery or Lifestyle With Intensive Medical Management in the Treatment of Type 2 Diabetes (SLIMM-T2D) (NCT01073020), a randomized, parallel-group trial conducted at a US academic hospital and diabetes clinic with 18- to 24-month follow-up. Thirty-eight type 2 diabetes patients with hemoglobin A(1c) >= 6.5% and body mass index 30-42 kg/m(2) were randomized to Roux-en-Y gastric bypass or the medical program. A 6-minute walk test to evaluate fitness, self-reported physical activity, standardized physical surveys, and cardiometabolic risk assessment were performed at baseline and after intervention. RESULTS: Both groups similarly improved 6-minute walk test distance, with greater improvements in oxygen saturation and reduced heart rate after surgery. Self-reported physical activity improved similarly at 18-24 months after interventions, although exercise increased gradually after surgery, whereas early substantial increases in the medical group were not fully sustained. Self-reported total and physical health were similar by Short Form-36 but improved more in the Impact of Weight on Quality of Life survey after surgery. Improvement in cardiovascular risk scores, HbA(1c), and body mass index were greater after surgery. CONCLUSION: In this small, randomized study, both interventions led to therapeutic lifestyle changes and improved objective and self-reported physical fitness. Greater improvements in heart rate, oxygen saturation, and perceived impact of weight on health were seen after surgery, which could be attributable to greater weight loss. The clinical importance of these improvements with greater weight loss warrants further investigation. (C) 2016 Elsevier Inc. All rights reserved. C1 [Panosian, Jennifer; Ding, Su-Ann; Wewalka, Marlene; Goebel-Fabbri, Ann; Foster, Kathleen; Halperin, Florencia; Goldfine, Allison B.] Joslin Diabet Ctr, Div Res, Sect Clin Behav & Outcomes Res, One Joslin Pl, Boston, MA 02215 USA. [Ding, Su-Ann; Wewalka, Marlene; Simonson, Donald C.; Goebel-Fabbri, Ann; Halperin, Florencia; Vernon, Ashley; Goldfine, Allison B.] Harvard Med Sch, Boston, MA USA. [Simonson, Donald C.; Halperin, Florencia; Vernon, Ashley; Goldfine, Allison B.] Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA. [Vernon, Ashley] Brigham & Womens Hosp, Dept Surg, Div Gen & Gastrointestinal Surg, 75 Francis St, Boston, MA 02115 USA. EM Allison.Goldfine@Joslin.Harvard.Edu FU National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases (Bethesda, Md) [RC-DK086918, R56-DK095451]; Covidien (Mansfield, Mass); Herbert Graetz Fund; Osterreichischer Austausdienst, Lifescan (Milpitas, Calif); Nestle Medical Nutrition (Florham Park, Fla); Novo Nordisk (Bagsvaerd, Denmark); [P30-DK036836]; [PCORI CE1304-6756] FX The National Institutes of Health and National Institute of Diabetes and Digestive and Kidney Diseases (Bethesda, Md) (RC-DK086918, R56-DK095451) principally supported the trial, with additional support from P30-DK036836, PCORI CE1304-6756; and Covidien (Mansfield, Mass) for surgery in patients with body mass index <35 kg/m2, the Herbert Graetz Fund, the Marietta Blau Grant from the Osterreichischer Austausdienst, Lifescan (Milpitas, Calif), Nestle Medical Nutrition (Florham Park, Fla), and Novo Nordisk (Bagsvaerd, Denmark). No funding source had a role in trial design, conduct, data analysis, or manuscript preparation. NR 32 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JAN PY 2017 VL 130 IS 1 BP 83 EP 92 DI 10.1016/j.amjmed.2016.07.019 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA EI6QS UT WOS:000392621500031 PM 27555097 ER PT J AU Shah, J Patel, M Elias, N Navarro-Alvarez, N Hertl, M Cosimi, A Markmann, J Sachs, D Vagefi, P AF Shah, J. Patel, M. Elias, N. Navarro-Alvarez, N. Hertl, M. Cosimi, A. Markmann, J. Sachs, D. Vagefi, P. TI Progress Towards Liver Xenotransplantation Serving as a Bridge to Allotransplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT ASTS 17th Annual State of the Art Water Symposiam CY JAN 26-29, 2017 CL Miami Beach, FL SP Amer Soc Transplant Surg, Novartis Pharmeceut Corp, Astellas, Sanofi Genzyme C1 [Shah, J.; Patel, M.; Elias, N.; Navarro-Alvarez, N.; Hertl, M.; Cosimi, A.; Markmann, J.; Sachs, D.; Vagefi, P.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 SU 2 SI SI MA MO-7 BP 21 EP 21 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA EI6QP UT WOS:000392621100022 ER PT J AU Loupy, A Haas, M Solez, K Racusen, L Glotz, D Seron, D Nankivell, BJ Colvin, RB Afrouzian, M Akalin, E Alachkar, N Bagnasco, S Becker, JU Cornell, L Drachenberg, C Dragun, D de Kort, H Gibson, IW Kraus, ES Lefaucheur, C Legendre, C Liapis, H Muthukumar, T Nickeleit, V Orandi, B Park, W Rabant, M Randhawa, P Reed, EF Roufosse, C Seshan, SV Sis, B Singh, HK Schinstock, C Tambur, A Zeevi, A Mengel, M AF Loupy, A. Haas, M. Solez, K. Racusen, L. Glotz, D. Seron, D. Nankivell, B. J. Colvin, R. B. Afrouzian, M. Akalin, E. Alachkar, N. Bagnasco, S. Becker, J. U. Cornell, L. Drachenberg, C. Dragun, D. de Kort, H. Gibson, I. W. Kraus, E. S. Lefaucheur, C. Legendre, C. Liapis, H. Muthukumar, T. Nickeleit, V. Orandi, B. Park, W. Rabant, M. Randhawa, P. Reed, E. F. Roufosse, C. Seshan, S. V. Sis, B. Singh, H. K. Schinstock, C. Tambur, A. Zeevi, A. Mengel, M. TI The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE clinical research; practice; translational research; science; kidney transplantation; nephrology; pathology; histopathology; organ transplantation in general; rejection; rejection: antibody-mediated (ABMR); rejection: subclinical; rejection: T cell mediated (TCMR) ID ANTIBODY-MEDIATED REJECTION; DONOR-SPECIFIC ANTIBODIES; TRANSPLANTATION BIFQUIT REPRODUCIBILITY; RENAL-ALLOGRAFT REJECTION; NON-HLA ANTIBODIES; MICROARRAY DIAGNOSIS; COMPLEMENT-BINDING; QUALITY-ASSURANCE; GRAFT FAILURE; BIOPSIES AB The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next-generation clinical trials. In this article, the Banff consortium presents the most updated version of the kidney, pancreas, and VCA transplant rejection classification and prospects for implementing intragraft molecular assessment. See the companion report on page 42. C1 [Loupy, A.; Legendre, C.; Rabant, M.] Univ Paris 05, INSERM, U970, Paris Translat Res Ctr Organ Transplantat, Paris, France. [Loupy, A.; Legendre, C.; Rabant, M.] Univ Paris 05, Necker Hosp, Paris, France. [Haas, M.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Solez, K.; Sis, B.; Mengel, M.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Racusen, L.; Bagnasco, S.] Johns Hopkins Univ, Sch Med, Dept Lab Med & Pathol, Baltimore, MD USA. [Glotz, D.; Lefaucheur, C.] Univ Paris VII, Paris Translat Res Ctr Organ Transplantat, Paris, France. [Glotz, D.; Lefaucheur, C.] Univ Paris VII, Hop St Louis, Dept Nephrol & Transplantat, Paris, France. [Glotz, D.; Lefaucheur, C.] INSERM, U 1160, Paris, France. [Seron, D.] Autonomous Univ Barcelona, Hosp Vall Hebron, Dept Nephrol, Barcelona, Spain. [Nankivell, B. J.] Westmead Hosp, Dept Renal Med, Sydney, NSW, Australia. [Colvin, R. B.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Afrouzian, M.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Afrouzian, M.] Univ Texas Med Branch, Dept Internal Med, Galveston, TX 77555 USA. [Akalin, E.] Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. [Alachkar, N.; Kraus, E. S.; Orandi, B.] Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA. [Becker, J. U.] Univ Hosp Cologne, Inst Pathol, Cologne, Germany. [Cornell, L.; Park, W.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Drachenberg, C.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Dragun, D.] Charite, Berlin Inst Hlth, Berlin, Germany. [Dragun, D.] Charite, Dept Nephrol & Crit Care Med, Berlin, Germany. [de Kort, H.] Leiden Univ, Med Ctr, Dept Nephrol, Leiden, Netherlands. [Gibson, I. W.] Univ Manitoba, Dept Pathol, Winnipeg, MB, Canada. [Liapis, H.] Washington Univ, Dept Pathol & Immunol, St Louis, MO USA. [Muthukumar, T.] New York Presbyterian Hosp Weill Cornell Med, Dept Med, Div Nephrol & Hypertens, New York, NY USA. [Nickeleit, V.; Singh, H. K.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Randhawa, P.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Div Transplantat Pathol, Pittsburgh, PA USA. [Reed, E. F.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Roufosse, C.] Hammersmith Hosp, Dept Cellular Pathol, London, England. [Seshan, S. V.] Weill Cornell Med, Dept Pathol, New York, NY USA. [Schinstock, C.] Mayo Clin, Div Nephrol, Rochester, MN USA. [Tambur, A.] Northwestern Univ, Transplant Immunol Lab, Comprehens Transplant Ctr, Chicago, IL 60611 USA. [Zeevi, A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. EM alexandreloupy@gmail.com RI de Kort, Hanneke/N-3898-2014 OI de Kort, Hanneke/0000-0003-3601-532X FU Roche Organ Transplantation Research Foundation [608390948]; Astellas; Alexion; Novartis; One Lambda; Renal Pathology Society; American Society of Transplantation; Wiley; Qiagen; Canadian Institute for Health Research; Immucor; Bridge to Life; Organ Recovery Systems; Transplant Connect; Glycorex Transplantation; Transpath Inc.; University of Alberta FX We would like to acknowledge the instrumental support from the Roche Organ Transplantation Research Foundation Grant 608390948 awarded to Dr. Kim Solez, which allowed establishing the Banff Foundation for Allograft Pathology. The joint 2015 Banff and Canadian Transplant Society meeting acknowledges the receipt of sponsorship from Astellas, Alexion, Novartis, One Lambda, Renal Pathology Society, American Society of Transplantation, Wiley, Qiagen, Canadian Institute for Health Research, Immucor, Bridge to Life, Organ Recovery Systems, Transplant Connect, Glycorex Transplantation, Transpath Inc., and the University of Alberta. NR 62 TC 1 Z9 1 U1 5 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 IS 1 BP 28 EP 41 DI 10.1111/ajt.14107 PG 14 WC Surgery; Transplantation SC Surgery; Transplantation GA EI5BK UT WOS:000392508200008 PM 27862883 ER PT J AU Adler, J Chang, D Yeh, H AF Adler, Joel Chang, David Yeh, Heidi TI Greater Access to Kidney Transplantation in Competitive DSAs: Due to Improved Referral? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT ASTS 17th Annual State of the Art Water Symposiam CY JAN 26-29, 2017 CL Miami Beach, FL SP Amer Soc Transplant Surg, Novartis Pharmeceut Corp, Astellas, Sanofi Genzyme C1 [Adler, Joel; Chang, David; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 SU 2 SI SI MA P-37 BP 42 EP 43 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA EI6QP UT WOS:000392621100065 ER PT J AU Bruneval, P Angelini, A Miller, D Potena, L Loupy, A Zeevi, A Reed, EF Dragun, D Reinsmoen, N Smith, RN West, L Tebutt, S Thum, T Haas, M Mengel, M Revelo, P Fedrigo, M Huyen, JPDV Berry, GJ AF Bruneval, P. Angelini, A. Miller, D. Potena, L. Loupy, A. Zeevi, A. Reed, E. F. Dragun, D. Reinsmoen, N. Smith, R. N. West, L. Tebutt, S. Thum, T. Haas, M. Mengel, M. Revelo, P. Fedrigo, M. Huyen, J. P. Duong Van Berry, G. J. TI The XIIIth Banff Conference on Allograft Pathology: The Banff 2015 Heart Meeting Report: Improving Antibody-Mediated Rejection Diagnostics: Strengths, Unmet Needs, and Future Directions SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE clinical research; practice; heart transplantation; cardiology; rejection; rejection: antibody-mediated (ABMR); rejection: subclinical; translational research; science ID NON-HLA-ANTIBODIES; ANGIOTENSIN TYPE-1 RECEPTOR; DONOR-SPECIFIC ANTIBODIES; S6 RIBOSOMAL-PROTEIN; CARDIAC ALLOGRAFT; TRANSPLANT RECIPIENTS; ENDOMYOCARDIAL BIOPSIES; KIDNEY-TRANSPLANTATION; WORKING FORMULATION; INCREASED RISK AB The 13th Banff Conference on Allograft Pathology was held in Vancouver, British Columbia, Canada from October 5 to 10, 2015. The cardiac session was devoted to current diagnostic issues in heart transplantation with a focus on antibody-mediated rejection (AMR) and small vessel arteriopathy. Specific topics included the strengths and limitations of the current rejection grading system, the central role of microvascular injury in AMR and approaches to semiquantitative assessment of histopathologic and immunophenotypic indicators, the role of AMR in the development of cardiac allograft vasculopathy, the important role of serologic antibody detection in the management of transplant recipients, and the potential application of new molecular approaches to the elucidation of the pathophysiology of AMR and potential for improving the current diagnostic system. Herein we summarize the key points from the presentations, the comprehensive, open and wide-ranging multidisciplinary discussion that was generated, and considerations for future endeavors. This article summarizes the Banff conference on heart transplantation with a focus on antibody-mediated rejection, strengths and limitations of the current rejection grading system, the important role of serologic antibody detection and the potential application of new molecular approaches to the elucidation of the pathophysiology of antibody-mediated rejection, and the potential for improving the current diagnostic system. See the companion report on page 28. C1 [Bruneval, P.] Univ Paris Descartes Med, Paris Translat Res Ctr Organ Transplantat, Paris, France. [Bruneval, P.] Univ Paris Descartes Med, Hop Europeen Georges Pompidou, Dept Pathol, Paris, France. [Angelini, A.; Fedrigo, M.] Univ Padua, Sch Med, Dept Cardiac Thorac & Vasc Sci, Padua, Italy. [Miller, D.; Revelo, P.] Univ Utah, Intermt Med Ctr, Salt Lake City, UT USA. [Potena, L.] Univ Bologna, Acad Hosp S, Heart & Lung Transplant Program, Orsola Malpighi, Italy. [Loupy, A.; Huyen, J. P. Duong Van] Univ Paris 05, Necker Hosp, Paris Translat Res Ctr Organ Transplantat, INSERM,U970, Paris, France. [Zeevi, A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Reed, E. F.] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA USA. [Dragun, D.] Charite, Berlin Inst Hlth, Berlin, Germany. [Dragun, D.] Charite, Dept Nephrol & Crit Care Med, Berlin, Germany. [Reinsmoen, N.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Smith, R. N.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [West, L.] Alberta Transplant Inst, Edmonton, AB, Canada. [West, L.] Univ Alberta, Edmonton, AB, Canada. [Tebutt, S.] St Pauls Hosp, Ctr Heart Lung Innovat, Vancouver, BC, Canada. [Thum, T.] Hannover Med Sch, IFB, Mol & Translat Therapeut Strategies, Hannover, Germany. [Haas, M.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Mengel, M.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Berry, G. J.] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. EM alexandreloupy@gmail.com FU Roche Organ Transplantation Research Foundation (ROTRF) [608390948]; Astellas; Alexion; Novartis; One Lambda; Renal Pathology Society; American Society of Transplantation; Wiley; Qiagen; Canadian Institute for Health Research; Immucor; Bridge to Life; Organ Recovery Systems; Transplant Connect; Glycorex Transplantation; Transpath Inc.; University of Alberta FX We would like to acknowledge the instrumental support from the Roche Organ Transplantation Research Foundation (ROTRF) Grant 608390948 awarded to Dr. Kim Solez, which allowed establishment of the Banff Foundation for Allograft Pathology. The joint 2015 Banff and Canadian Transplant Society meeting acknowledges the receipt of sponsorship from Astellas, Alexion, Novartis, One Lambda, Renal Pathology Society, American Society of Transplantation, Wiley, Qiagen, Canadian Institute for Health Research, Immucor, Bridge to Life, Organ Recovery Systems, Transplant Connect, Glycorex Transplantation, Transpath Inc., and the University of Alberta. NR 49 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 IS 1 BP 42 EP 53 DI 10.1111/ajt.14112 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA EI5BK UT WOS:000392508200009 PM 27862968 ER PT J AU Gill, JS Wright, AJ Delmonico, FL Newell, KA AF Gill, J. S. Wright, A. J. Delmonico, F. L. Newell, K. A. TI Towards Improving the Transfer of Care of Kidney Transplant Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE editorial; personal viewpoint; kidney transplantation; nephrology; compliance; adherence; complication: infectious; complication: malignant; complication: medical; metabolic; complication: surgical; technical ID SINGLE-CENTER EXPERIENCE; UNITED-STATES; TOURISM AB Kidney transplant recipients require specialized medical care and may be at risk for adverse health outcomes when their care is transferred. This document provides opinion-based recommendations to facilitate safe and efficient transfers of care for kidney transplant recipients including minimizing the risk of rejection, avoidance of medication errors, ensuring patient access to immunosuppressant medications, avoidance of lapses in health insurance coverage, and communication of risks of donor disease transmission. The document summarizes information to be included in a medical transfer document and includes suggestions to help the patient establish an optimal therapeutic relationship with their new transplant care team. The document is intended as a starting point towards standardization of transfers of care involving kidney transplant recipients. The authors highlight potential risks when patient care transfers are fumbled and propose standardization of patient transfers to mitigate these risks. C1 [Gill, J. S.] Univ British Columbia, Div Nephrol, Vancouver, BC, Canada. [Gill, J. S.] Ctr Hlth Evaluat & Outcome Sci, Vancouver, BC, Canada. [Wright, A. J.] Univ British Columbia, Div Infect Dis, Vancouver, BC, Canada. [Delmonico, F. L.] Harvard Med Sch, Massachusetts Gen Hosp, Transplant Ctr, Dept Surg, Boston, MA USA. [Newell, K. A.] Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. EM jgill@providencehealth.bc.ca 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 IS 1 BP 54 EP 59 DI 10.1111/ajt.13997 PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA EI5BK UT WOS:000392508200010 PM 27495956 ER PT J AU Bababekov, Y Adler, J Hashimoto, D Stapleton, S Marks, I Chang, D Yeh, H AF Bababekov, Yanik Adler, Joel Hashimoto, Daniel Stapleton, Sahael Marks, Isobel Chang, David Yeh, Heidi TI Are There Inequalities in Access to the Liver Transplant Waiting List in New York State? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT ASTS 17th Annual State of the Art Water Symposiam CY JAN 26-29, 2017 CL Miami Beach, FL SP Amer Soc Transplant Surg, Novartis Pharmeceut Corp, Astellas, Sanofi Genzyme C1 [Bababekov, Yanik; Adler, Joel; Hashimoto, Daniel; Stapleton, Sahael; Marks, Isobel; Chang, David; Yeh, Heidi] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 SU 2 SI SI MA P-88 BP 62 EP 62 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA EI6QP UT WOS:000392621100116 ER PT J AU Bababekov, Y Fong, ZV Adler, J Yeh, H Chang, D Pomposelli, J AF Bababekov, Yanik Fong, Zhi Ven Adler, Joel Yeh, Heidi Chang, David Pomposelli, James TI Assessment of Transplant Health Literacy of Liver Transplant Candidates and Their Caregivers SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT ASTS 17th Annual State of the Art Water Symposiam CY JAN 26-29, 2017 CL Miami Beach, FL SP Amer Soc Transplant Surg, Novartis Pharmeceut Corp, Astellas, Sanofi Genzyme C1 [Bababekov, Yanik; Fong, Zhi Ven; Adler, Joel; Yeh, Heidi; Chang, David] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Pomposelli, James] Univ Colorado, Sch Med, Anschutz Med Campus, Aurora, CO 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 SU 2 SI SI MA P-89 BP 62 EP 63 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA EI6QP UT WOS:000392621100117 ER PT J AU Chow, E Choudhury, R Adler, J Segev, D Yeh, H Gentry, S AF Chow, Eric Choudhury, Rashikh Adler, Joel Segev, Dorry Yeh, Heidi Gentry, Sommer TI Redistricting, Disparities, and Shifts Towards Hispanic Recipients SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT ASTS 17th Annual State of the Art Water Symposiam CY JAN 26-29, 2017 CL Miami Beach, FL SP Amer Soc Transplant Surg, Novartis Pharmeceut Corp, Astellas, Sanofi Genzyme C1 [Chow, Eric; Choudhury, Rashikh; Segev, Dorry] Johns Hopkins Univ, Baltimore, MD USA. [Adler, Joel; Yeh, Heidi] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gentry, Sommer] US Naval Acad, Annapolis, MD 21402 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 SU 2 SI SI MA P-104 BP 69 EP 69 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA EI6QP UT WOS:000392621100132 ER PT J AU Chalphin, A Davis, R Khwaja, K AF Chalphin, Alexander Davis, Roger Khwaja, Khalid TI Pediatric Kidney and Liver Transplantation and the Affordable Care Act SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT ASTS 17th Annual State of the Art Water Symposiam CY JAN 26-29, 2017 CL Miami Beach, FL SP Amer Soc Transplant Surg, Novartis Pharmeceut Corp, Astellas, Sanofi Genzyme C1 [Chalphin, Alexander; Davis, Roger; Khwaja, Khalid] BIDMC, 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 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2017 VL 17 SU 2 SI SI MA P-149 BP 85 EP 85 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA EI6QP UT WOS:000392621100177 ER PT J AU Pathiraja, V Villani, V Tasaki, M Matar, AJ Duran-Struuck, R Yamada, R Moran, SG Clayman, ES Hanekamp, J Shimizu, A Sachs, DH Huang, CA Yamada, K AF Pathiraja, V. Villani, V. Tasaki, M. Matar, A. J. Duran-Struuck, R. Yamada, R. Moran, S. G. Clayman, E. S. Hanekamp, J. Shimizu, A. Sachs, D. H. Huang, C. A. Yamada, K. TI Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE translational research; science; islet transplantation; kidney transplantation; nephrology; tolerance: experimental; tolerance: chimerism; islet isolation ID HEMATOPOIETIC-CELL TRANSPLANTATION; LIVING DONOR PANCREAS; MINIATURE SWINE; THYMIC TRANSPLANTATION; COMPOSITE THYMOKIDNEYS; MISMATCHED BARRIERS; DIABETES-MELLITUS; CHIMERISM; INDUCTION; PANCREATECTOMY AB We previously reported that transplantation (Tx) of prevascularized donor islets as composite islet-kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cell (HSC) Tx in an attempt to induce tolerance in nonhuman primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IK Tx. HSC Tx was performed after mobilization and leukapheresis of the donors and conditioning of the recipients with total body irradiation, T cell depletion, and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IK Tx was performed either 20-22 (n = 3) or 208 (n = 1) days after HSC Tx. All animals accepted IKs without rejection. All recipients required >20 U/day insulin before IK Tx to maintain <200 mg/dL, whereas after IK Tx, three animals required minimal doses of insulin (1-3 U/day) and one animal was insulin free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression. The authors report the successful use of transient mixed hematopoietic chimerism to induce tolerance of composite islet-kidneys across a one-haplotype major histocompatibility complex barrier in rhesus monkeys. C1 [Pathiraja, V.; Villani, V.; Tasaki, M.; Matar, A. J.; Duran-Struuck, R.; Yamada, R.; Moran, S. G.; Clayman, E. S.; Hanekamp, J.; Shimizu, A.; Sachs, D. H.; Huang, C. A.; Yamada, K.] Harvard Med Sch, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM cahuang@mgh.harvard.edu; ky2323@cumc.columbia.edu FU National Institutes of Health [U01DK080653, U19AI102405] FX The authors would like to thank Drs. Kumaran Shanmugarajah and Hisashi Sahara for their helpful advice and review of the manuscript. We thank Amgen for providing GCSF and Genzyme for providing AMD3465. This research was supported by National Institutes of Health grants U01DK080653 and U19AI102405 (Project 2). Animals were cared for according to the guidelines of the MGH Institutional Animal Care and Use Committee. NR 28 TC 1 Z9 1 U1 1 U2 1 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 JAN PY 2017 VL 17 IS 1 BP 91 EP 102 DI 10.1111/ajt.13952 PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA EI5BK UT WOS:000392508200014 PM 27376692 ER PT J AU Monach, PA AF Monach, Paul A. TI Defining and Refining the Risk of Venous Thromboembolism in Giant Cell Arteritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Editorial Material ID PULMONARY-EMBOLISM; ISCHEMIC COMPLICATIONS; THROMBOSIS; GRANULOMATOSIS; METAANALYSIS; DISEASES; THERAPY; EVENTS C1 [Monach, Paul A.] Boston Univ, Sch Med, 72 East Concord St E-533, Boston, MA 02118 USA. [Monach, Paul A.] VA Boston Healthcare Syst, Boston, MA USA. EM pmonach@bu.edu NR 18 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 3 EP 5 DI 10.1002/art.39846 PG 3 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500002 PM 28029235 ER PT J AU Dalbeth, N Choi, HK Terkeltaub, R AF Dalbeth, Nicola Choi, Hyon K. Terkeltaub, Robert TI Gout A Roadmap to Approaches for Improving Global Outcomes SO ARTHRITIS & RHEUMATOLOGY LA English DT Review ID CRYSTAL-INDUCED INFLAMMATION; OF-RHEUMATOLOGY GUIDELINES; ACTIVATED PROTEIN-KINASE; GENOME-WIDE ASSOCIATION; URATE-LOWERING THERAPY; URIC-ACID; ASYMPTOMATIC HYPERURICEMIA; AMERICAN-COLLEGE; UNITED-STATES; DOUBLE-BLIND C1 [Dalbeth, Nicola] Univ Auckland, Auckland, New Zealand. [Choi, Hyon K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Choi, Hyon K.] Harvard Med Sch, Boston, MA USA. [Terkeltaub, Robert] VA San Diego Healthcare Syst, 111K 3350 Jolla Village Dr, San Diego, CA 92161 USA. [Terkeltaub, Robert] Univ Calif San Diego, San Diego, CA 92093 USA. RP Terkeltaub, R (reprint author), VA San Diego Healthcare Syst, 111K 3350 Jolla Village Dr, San Diego, CA 92161 USA. EM rterkeltaub@ucsd.edu FU Health Research Council of New Zealand [9101-3708025]; NIH [R01-AR-065944]; VA Research Service; AstraZeneca; Fonterra; Takeda; Pfizer; CymaBay; Crealta; Ardea/AstraZeneca; Menarini; Sobi; Revive; Selecta; Aequus; ProteoThera; Horizon; Relburn FX Supported by the Health Research Council of New Zealand (grant 9101-3708025 to Dr. Dalbeth), the NIH (grant R01-AR-065944 to Dr. Choi), and the VA Research Service (grant to Dr. Terkeltaub).r Dr. Dalbeth has received consulting fees, speaking fees, and/or honoraria from AstraZeneca, Fonterra, Takeda, Pfizer, CymaBay, Crealta, Ardea/AstraZeneca, and Menarini (less than $10,000 each) and has received research support from AstraZeneca. Dr. Choi has received consulting fees from Takeda and Ardea/AstraZeneca (less than $10,000 each). Dr. Terkeltaub has received consulting fees from Ardea/AstraZeneca (more than $10,000), and from Sobi, Revive, Selecta, Aequus, ProteoThera, Horizon, Relburn, and CymaBay (less than $10,000 each). NR 89 TC 2 Z9 2 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 22 EP 34 DI 10.1002/art.39799 PG 13 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500005 PM 27389665 ER PT J AU Shakoor, N Felson, DT Niu, JB Nguyen, US Segal, NA Singh, JA Nevitt, MC AF Shakoor, Najia Felson, David T. Niu, Jingbo Nguyen, Uyen-Sa Segal, Neil A. Singh, Jasvinder A. Nevitt, Michael C. TI The Association of Vibratory Perception and Muscle Strength With the Incidence and Worsening of Knee Instability: The Multicenter Osteoarthritis Study SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID PHYSICAL FUNCTION; CONTROLLED-TRIAL; PROPRIOCEPTION; PAIN; ADOLESCENTS; LIMITATIONS; PREVALENCE; CHILDREN; EXERCISE; THERAPY AB Objective. To examine neuromuscular factors that predict the incidence and progression of knee instability symptoms in older adults with or at high risk of knee osteoarthritis (OA). Methods. At the 60-month clinic visit, participants in the Multicenter Osteoarthritis Study underwent evaluation of quantitative vibratory sense at the knee and isokinetic quadriceps muscle strength. At this 60-month visit, participants were also asked about knee buckling and sensations of knee shifting or slipping without buckling in the past 3 months and then were asked the same questions at the 72- and 84-month follow-up visits. We performed a person-based analysis using Poisson regression analysis with robust error variance to estimate adjusted relative risks (RRs) for the association of vibratory sense and muscle strength with the incidence and worsening of knee slipping/shifting, buckling, and overall knee instability symptoms (either buckling or knee shifting/slipping), with adjustment for relevant confounders. Results. A total of 1,803 participants (61% women) were included. Approximately one-third of the participants reported incident or worsening of instability symptoms over the study period. After adjustment for relevant confounders, better vibratory acuity (adjusted RR 0.78, 95% confidence interval [95% CI] 0.56-1.09), P=0.020 for trend) and greater quadriceps strength (adjusted RR 0.53, 95% CI 0.38-0.75, P<0.001) protected against incident knee instability symptoms. Greater quadriceps strength (adjusted RR 0.73, 95% CI 0.58-0.92, P=0.008) also protected against worsening of knee instability symptoms. Conclusion. Vibratory acuity and quadriceps muscle strength are important predictors of the incidence and worsening of knee instability over 2 years. These neuromuscular factors are potentially modifiable and should be considered in interventional studies of instability in persons with or at risk of knee OA. C1 [Shakoor, Najia] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Felson, David T.; Niu, Jingbo] Boston Univ, Sch Med, Boston, MA 02215 USA. [Felson, David T.] Univ Manchester, Manchester, Lancs, England. [Nguyen, Uyen-Sa] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. [Segal, Neil A.] Univ Kansas, Kansas City, KS 66045 USA. [Singh, Jasvinder A.] Univ Alabama Birmingham, Birmingham, AL USA. [Singh, Jasvinder A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Nevitt, Michael C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. EM Najia_shakoor@rush.edu FU NIH (National Institute on Aging) [AG-18820, AG-18832, AG-18947, AG-19069] FX Supported by the NIH (National Institute on Aging grants AG-18820, AG-18832, AG-18947, and AG-19069). NR 29 TC 0 Z9 0 U1 1 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 JAN PY 2017 VL 69 IS 1 BP 94 EP 102 DI 10.1002/art.39821 PG 9 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500012 PM 27564789 ER PT J AU Cartin-Ceba, R Indrakanti, D Specks, U Stone, JH Hoffman, GS Kallenberg, CGM Langford, CA Merkel, PA Spiera, RF Monach, PA St Clair, EW Seo, P Tchao, NK Ytterberg, SR Brunetta, PG Song, HJ Birmingham, D Rovin, BH Grp, RITNR AF Cartin-Ceba, Rodrigo Indrakanti, Divya Specks, Ulrich Stone, John H. Hoffman, Gary S. Kallenberg, Cees G. M. Langford, Carol A. Merkel, Peter A. Spiera, Robert F. Monach, Paul A. St Clair, E. William Seo, Philip Tchao, Nadia K. Ytterberg, Steven R. Brunetta, Paul G. Song, Huijuan Birmingham, Dan Rovin, Brad H. Grp, RAVE-Immune Tolerance Network Res TI The Pharmacogenomic Association of Fc gamma Receptors and Cytochrome P450 Enzymes With Response to Rituximab or Cyclophosphamide Treatment in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID ANCA-ASSOCIATED VASCULITIS; WEGENERS-GRANULOMATOSIS; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; GENE POLYMORPHISMS; LUPUS NEPHRITIS; BREAST-CANCER; THERAPY; TOXICITY; IMPACT AB Objective The Rituximab in ANCA-Associated Vasculitis (RAVE) trial compared rituximab to cyclophosphamide as induction therapy for the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We undertook the current study to determine whether known single-nucleotide polymorphisms (SNPs) for Fc gamma receptors (Fc gamma R) or cytochrome P450 (CYP) enzymes were associated with the response to treatment with rituximab and cyclophosphamide, respectively. Methods Functional SNPs for Fc gamma R (Fc gamma RIIa 519G>A, Fc gamma RIIb 695T>C, Fc gamma RIIIa 559T>G) and CYP enzymes (CYP2B6 1459C>T, CYP2C19 681G>A) were analyzed by direct sequencing of polymerase chain reaction-amplified genomic DNA. Each SNP was tested as a predictor of complete remission at 6 months or remission with continued prednisone administration using logistic regression and including the covariates of baseline Birmingham Vasculitis Activity Score for Wegener's Granulomatosis, ANCA type, and new versus relapsing disease. The associations of these SNPs with the secondary outcomes of time to complete remission, time to relapse, or time to B cell reconstitution were analyzed by Cox proportional hazard tests. Results No significant associations were identified between complete remission and any Fc gamma R genotype in the rituximab group or any CYP genotype in the cyclophosphamide group. However, when the treatment groups were combined, an association was found between the 519AA genotype of Fc gamma RIIa and complete remission (P=0.01). The 519AA genotype predicted complete remission (P=0.006) and a shorter time to complete remission (P<0.001). Conclusion The finding that the homozygous Fc gamma RIIa 519AA variant was associated with complete response and a shorter time to complete response in the RAVE trial, independent of treatment type, implies that Fc gamma RIIa may be broadly involved in disease pathogenesis and response to therapy. C1 [Cartin-Ceba, Rodrigo; Specks, Ulrich; Ytterberg, Steven R.] Mayo Clin & Mayo Fdn, Rochester, MN USA. [Cartin-Ceba, Rodrigo; Specks, Ulrich; Ytterberg, Steven R.] Mayo Clin & Mayo Fdn, Scottsdale, AZ USA. [Indrakanti, Divya; Song, Huijuan; Birmingham, Dan; Rovin, Brad H.] Ohio State Univ, Columbus, OH USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9700 AB Groningen, Netherlands. [Merkel, Peter A.] Univ Penn, Philadelphia, PA 19104 USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY USA. [Monach, Paul A.] Boston Univ, Sch Med, Boston, MA USA. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Tchao, Nadia K.] Immune Tolerance Network, San Francisco, CA USA. [Brunetta, Paul G.] Genentech Inc, San Francisco, CA USA. RP Rovin, BH (reprint author), Ohio State Univ, Wexner Med Ctr, Div Nephrol, 395 West 12th Ave,Ground Floor, Columbus, OH 43210 USA. EM rovin.1@osu.edu FU Genentech; Roche; GiACTA FX Supported by a grant from Genentech.r Dr. Specks has received consulting fees from Genentech (less than $ 10,000). Dr. Stone has received consulting fees from Genentech and Roche (less than $ 10,000 each). Dr. Hoffman has received consulting fees from Roche and GiACTA (less than $ 10,000 each). Dr. Merkel has received consulting fees from Genentech (less than $ 10,000). Dr. Spiera has received consulting fees from Genentech (less than $ 10,000). Dr. Monach has received honoraria from Medscape (less than $ 10,000). NR 38 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 169 EP 175 DI 10.1002/art.39822 PG 7 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500021 PM 27482943 ER PT J AU Unizony, S Lu, N Tomasson, G Zhang, YQ Merkel, PA Stone, JH Avina-Zubieta, JA Choi, HK AF Unizony, Sebastian Lu, Na Tomasson, Gunnar Zhang, Yuqing Merkel, Peter A. Stone, John H. Avina-Zubieta, J. Antonio Choi, Hyon K. TI Temporal Trends of Venous Thromboembolism Risk Before and After Diagnosis of Giant Cell Arteritis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID IMPROVEMENT NETWORK THIN; PULMONARY-EMBOLISM; GENERAL-POPULATION; POLYMYALGIA-RHEUMATICA; ENDOTHELIAL FUNCTION; INNATE IMMUNITY; UNITED-KINGDOM; THROMBOSIS; INFLAMMATION; ARTHRITIS AB Objective Giant cell arteritis (GCA) and the use of glucocorticoids have both been associated with increased risk of venous thromboembolism (VTE). However, the possibility of confounding by indication has not been investigated. We undertook this study to examine the temporal risk of VTE in GCA patients before and after GCA diagnosis, accounting for confounders including glucocorticoid treatment. Methods We conducted a matched cohort study using an electronic medical record database representative of the UK population (1990-2013). We calculated age-, sex-, and entry time-matched and multivariate relative risks (RRs) of VTE, comparing 6,441 patients with new-onset GCA (defined by corresponding diagnosis codes and prescribed glucocorticoid treatment) to 63,985 controls before and after GCA diagnosis. Analysis before GCA diagnosis was stratified by oral glucocorticoid use to account for confounding. Results There were 27 incident VTE events during the 12 months preceding GCA diagnosis and 195 afterward. Compared to controls, during the 12, 9, 6, and 3 months preceding GCA diagnosis, the age-, sex-, and entry time-matched RRs for VTE among patients with imminent GCA not treated with glucocorticoids were 1.8, 2.2, 2.4, and 3.6, respectively. In the first 3, 6, 12, 24, 48, and 96 months after GCA diagnosis, the corresponding RRs were 9.9, 7.7, 5.9, 4.4, 3.3, and 2.4. Multivariate analyses including several common VTE risk factors showed similar trends. Conclusion The risk of VTE increases shortly before GCA diagnosis, peaks at the time of diagnosis, and then progressively declines thereafter. This risk is apparent in patients with imminent GCA unexposed to oral glucocorticoids, suggesting a role for inflammation-associated thrombosis that is independent of glucocorticoid use. C1 [Unizony, Sebastian; Lu, Na; Stone, John H.; Choi, Hyon K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Lu, Na; Tomasson, Gunnar; Zhang, Yuqing; Choi, Hyon K.] Boston Univ, Sch Med, Boston, MA USA. [Tomasson, Gunnar] Univ Iceland, Reykjavik, Iceland. [Merkel, Peter A.] Univ Penn, Philadelphia, PA USA. [Avina-Zubieta, J. Antonio] Univ British Columbia, Arthrit Res Canada, Richmond, BC, Canada. RP Unizony, S (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Rheumatol Allergy & Immunol Div, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM sunizony@mgh.harvard.edu OI Unizony, Sebastian/0000-0002-8935-7473 FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [P60-AR-047785] FX Supported in part by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant P60-AR-047785). NR 50 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 176 EP 184 DI 10.1002/art.39847 PG 9 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500022 PM 28029234 ER PT J AU Pepper, RJ Draibe, JB Caplin, B Fervenza, FC Hoffman, GS Kallenberg, CGM Langford, CA Monach, PA Seo, P Spiera, R St Clair, EW Tchao, NK Stone, JH Specks, U Merkel, PA Salama, AD AF Pepper, Ruth J. Draibe, Juliana B. Caplin, Ben Fervenza, Fernando C. Hoffman, Gary S. Kallenberg, Cees G. M. Langford, Carol A. Monach, Paul A. Seo, Philip Spiera, Robert St Clair, E. William Tchao, Nadia K. Stone, John H. Specks, Ulrich Merkel, Peter A. Salama, Alan D. CA RAVE-Immune Tolerance Network Res TI Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID ANCA-ASSOCIATED VASCULITIS; JUVENILE IDIOPATHIC ARTHRITIS; CALCIUM-BINDING PROTEINS; SMALL-VESSEL VASCULITIS; TERM-FOLLOW-UP; RHEUMATOID-ARTHRITIS; TREATMENT RESISTANCE; REMISSION; EXPRESSION; CYCLOPHOSPHAMIDE AB Objective S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. Methods Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. Results Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n=37), PR3-ANCA without relapse (n=56), myeloperoxidase (MPO)-ANCA with relapse (n=6), and MPO-ANCA without relapse (n=45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P=0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P=0.0043) and baseline and month 6 (P=0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P=0.028). Conclusion An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment. C1 [Pepper, Ruth J.; Draibe, Juliana B.; Caplin, Ben; Salama, Alan D.] UCL, Royal Free Hosp, Ctr Nephrol, Rowland Hill St, London NW3 2PF, England. [Fervenza, Fernando C.; Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Hoffman, Gary S.; Langford, Carol A.] Cleveland Clin Fdn, Cleveland, OH USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Monach, Paul A.] Boston Univ, Boston, MA 02215 USA. [Seo, Philip] Johns Hopkins Univ, Baltimore, MD USA. [Spiera, Robert] Hosp Special Surg, New York, NY USA. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Tchao, Nadia K.] Immune Tolerance Network, San Francisco, CA USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, Peter A.] Univ Penn, Philadelphia, PA USA. RP Salama, AD (reprint author), UCL, Royal Free Hosp, Ctr Nephrol, Rowland Hill St, London NW3 2PF, England. EM a.salama@ucl.ac.uk OI Caplin, Benjamin/0000-0001-9544-164X FU Kidney Research UK; project of the Immune Tolerance Network (NIH) [N01-AI-15416] FX Supported by Kidney Research UK. The RAVE trial was performed as a project of the Immune Tolerance Network (NIH contract N01-AI-15416; protocol ITN-21AI). NR 35 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 185 EP 193 DI 10.1002/art.39814 PG 9 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500023 PM 27428710 ER PT J AU Arvikar, SL Crowley, JT Sulka, KB Steere, AC AF Arvikar, Sheila L. Crowley, Jameson T. Sulka, Katherine B. Steere, Allen C. TI Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease SO ARTHRITIS & RHEUMATOLOGY LA English DT Article ID B-CELL RESPONSES; CLASSIFICATION CRITERIA; BORRELIA-BURGDORFERI; ANTIBODY-RESPONSES; GROWTH-FACTOR; ANNEXIN A2; TARGET; AUTOANTIBODIES; AUTOANTIGEN; PERSISTENCE AB Objective To describe systemic autoimmune joint diseases that develop following Lyme disease, and to compare their clinical features with those of Lyme arthritis (LA). Methods We reviewed records of all adult patients referred to our LA clinic over a 13-year period, in whom we had diagnosed a systemic autoimmune joint disease following Lyme disease. For comparison, records of patients enrolled in our LA cohort over the most recent 2-year period were analyzed. Levels of IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured. Results We identified 30 patients who had developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease (usually manifested by erythema migrans [EM]). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthritis (SpA). The 30 patients typically had polyarthritis, and those with PsA or SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 patients with LA, the usual clinical picture was monoarticular knee arthritis, without prior EM. Most of the patients with systemic autoimmune joint disorders were positive for B burgdorferi IgG antibodies, as detected by enzyme-linked immunosorbent assay, but had significantly lower titers and lower frequencies of Lyme disease-associated autoantibodies than patients with LA. Prior to our evaluation, these patients had often received additional antibiotics for presumed LA, without benefit. We prescribed antiinflammatory agents, most commonly disease-modifying antirheumatic drugs, resulting in improvement. Conclusion Systemic autoimmune joint diseases (i.e., RA, PsA, SpA) may follow Lyme disease. Development of polyarthritis after antibiotic-treated EM, previous psoriasis, or low-titer B burgdorferi antibodies may provide insight into the correct diagnosis. C1 [Arvikar, Sheila L.; Crowley, Jameson T.; Sulka, Katherine B.; Steere, Allen C.] Massachusetts Gen Hosp, Boston, MA USA. EM sarvikar@mgh.harvard.edu FU Rheumatology Research Foundation; NIH [R01-AI-110175]; English-Bonter-Mitchell Foundation; Ounsworth-Fitzgerald Foundation; Littauer Foundation; Lillian B. Davey Foundation; Eshe Fund FX Dr. Arvikar's work was supported by a postdoctoral fellowship from the Rheumatology Research Foundation. Dr. Steere's work was supported by the NIH (grant R01-AI-110175), the English-Bonter-Mitchell Foundation, the Ounsworth-Fitzgerald Foundation, the Littauer Foundation, the Lillian B. Davey Foundation, and the Eshe Fund. NR 49 TC 3 Z9 3 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 194 EP 202 DI 10.1002/art.39866 PG 9 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500024 PM 27636905 ER PT J AU Domsic, RT Lucas, M Nihtyanova, SI Denton, CP Wisniewski, SR Fine, MJ Kwoh, CK Medsger, TA AF Domsic, Robyn T. Lucas, Mary Nihtyanova, Svetlana I. Denton, Christopher P. Wisniewski, Stephen R. Fine, Michael J. Kwoh, C. Kent Medsger, Thomas A. TI Statistical considerations in the development of clinical predictive scores: comment on the article by Domsic et al Reply SO ARTHRITIS & RHEUMATOLOGY LA English DT Letter C1 [Domsic, Robyn T.; Lucas, Mary; Medsger, Thomas A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Nihtyanova, Svetlana I.; Denton, Christopher P.] UCL, Royal Free Hosp, Sch Med, London, England. [Wisniewski, Stephen R.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. [Fine, Michael J.] Vet Affairs Pittsburgh Healthcare, Vet Affairs Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Kwoh, C. Kent] Univ Arizona, Arthrit Ctr, Tucson, AZ USA. 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 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2326-5191 EI 2326-5205 J9 ARTHRITIS RHEUMATOL JI Arthritis Rheumatol. PD JAN PY 2017 VL 69 IS 1 BP 242 EP 242 DI 10.1002/art.39853 PG 1 WC Rheumatology SC Rheumatology GA EI5AJ UT WOS:000392505500031 PM 27589673 ER PT J AU Hamdi, Y Soucy, P Kuchenbaeker, KB Pastinen, T Droit, A Lemacon, A Adlard, J Aittomaki, K Andrulis, IL Arason, A Arnold, N Arun, BK Azzollini, J Bane, A Barjhoux, L Barrowdale, D Benitez, J Berthet, P Blok, MJ Bobolis, K Bonadona, V Bonanni, B Bradbury, AR Brewer, C Buecher, B Buys, SS Caligo, MA Chiquette, J Chung, WK Claes, KBM Daly, MB Damiola, F Davidson, R De la Hoya, M De Leeneer, K Diez, O Ding, YC Dolcetti, R Domchek, SM Dorfling, CM Eccles, D Eeles, R Einbeigi, Z Ejlertsen, B Engel, C Evans, DG Feliubadalo, L Foretova, L Fostira, F Foulkes, WD Fountzilas, G Friedman, E Frost, D Ganschow, P Ganz, PA Garber, J Gayther, SA Gerdes, AM Glendon, G Godwin, AK Goldgar, DE Greene, MH Gronwald, J Hahnen, E Hamann, U Hansen, TVO Hart, S Hays, JL Hogervorst, FBL Hulick, PJ Imyanitov, EN Isaacs, C Izatt, L Jakubowska, A James, P Janavicius, R Jensen, UB John, EM Joseph, V Just, W Kaczmarek, K Karlan, BY Kets, CM Kirk, J Kriege, M Laitman, Y Laurent, M Lazaro, C Leslie, G Lester, J Lesueur, F Liljegren, A Loman, N Loud, JT Manoukian, S Mariani, M Mazoyer, S McGuffog, L Meijers-Heijboer, HEJ Meindl, A Miller, A Montagna, M Mulligan, AM Nathanson, KL Neuhausen, SL Nevanlinna, H Nussbaum, RL Olah, E Olopade, OI Ong, KR Oosterwijk, JC Osorio, A Papi, L Park, SK Pedersen, IS Peissel, B Segura, PP Peterlongo, P Phelan, CM Radice, P Rantala, J Rappaport-Fuerhauser, C Rennert, G Richardson, A Robson, M Rodriguez, GC Rookus, MA Schmutzler, RK Sevenet, N Shah, PD Singer, CF Slavin, TP Snape, K Sokolowska, J Sonderstrup, IMH Southey, M Spurdle, AB Stadler, Z Stoppa-Lyonnet, D Sukiennicki, G Sutter, C Tan, Y Tea, MK Teixeira, MR Teule, A Teo, SH Terry, MB Thomassen, M Tihomirova, L Tischkowitz, M Tognazzo, S Toland, AE Tung, N van den Ouweland, AMW van der Luijt, RB van Engelen, K van Rensburg, EJ Varon-Mateeva, R Wappenschmidt, B Wijnen, JT Rebbeck, T Chenevix-Trench, G Offit, K Couch, FJ Nord, S Easton, DF Antoniou, AC Simard, J AF Hamdi, Yosr Soucy, Penny Kuchenbaeker, Karoline B. Pastinen, Tomi Droit, Arnaud Lemacon, Audrey Adlard, Julian Aittomaki, Kristiina Andrulis, Irene L. Arason, Adalgeir Arnold, Norbert Arun, Banu K. Azzollini, Jacopo Bane, Anita Barjhoux, Laure Barrowdale, Daniel Benitez, Javier Berthet, Pascaline Blok, Marinus J. Bobolis, Kristie Bonadona, Valerie Bonanni, Bernardo Bradbury, Angela R. Brewer, Carole Buecher, Bruno Buys, Saundra S. Caligo, Maria A. Chiquette, Jocelyne Chung, Wendy K. Claes, Kathleen B. M. Daly, Mary B. Damiola, Francesca Davidson, Rosemarie De la Hoya, Miguel De Leeneer, Kim Diez, Orland Ding, Yuan Chun Dolcetti, Riccardo Domchek, Susan M. Dorfling, Cecilia M. Eccles, Diana Eeles, Ros Einbeigi, Zakaria Ejlertsen, Bent Engel, Christoph Evans, D. Gareth Feliubadalo, Lidia Foretova, Lenka Fostira, Florentia Foulkes, William D. Fountzilas, George Friedman, Eitan Frost, Debra Ganschow, Pamela Ganz, Patricia A. Garber, Judy Gayther, Simon A. Gerdes, Anne-Marie Glendon, Gord Godwin, Andrew K. Goldgar, David E. Greene, Mark H. Gronwald, Jacek Hahnen, Eric Hamann, Ute Hansen, Thomas V. O. Hart, Steven Hays, John L. Hogervorst, Frans B. L. Hulick, Peter J. Imyanitov, Evgeny N. Isaacs, Claudine Izatt, Louise Jakubowska, Anna James, Paul Janavicius, Ramunas Jensen, Uffe Birk John, Esther M. Joseph, Vijai Just, Walter Kaczmarek, Katarzyna Karlan, Beth Y. Kets, Carolien M. Kirk, Judy Kriege, Mieke Laitman, Yael Laurent, Maite Lazaro, Conxi Leslie, Goska Lester, Jenny Lesueur, Fabienne Liljegren, Annelie Loman, Niklas Loud, Jennifer T. Manoukian, Siranoush Mariani, Milena Mazoyer, Sylvie McGuffog, Lesley Meijers-Heijboer, Hanne E. J. Meindl, Alfons Miller, Austin Montagna, Marco Mulligan, Anna Marie Nathanson, Katherine L. Neuhausen, Susan L. Nevanlinna, Heli Nussbaum, Robert L. Olah, Edith Olopade, Olufunmilayo I. Ong, Kai-ren Oosterwijk, Jan C. Osorio, Ana Papi, Laura Park, Sue Kyung Pedersen, Inge Sokilde Peissel, Bernard Segura, Pedro Perez Peterlongo, Paolo Phelan, Catherine M. Radice, Paolo Rantala, Johanna Rappaport-Fuerhauser, Christine Rennert, Gad Richardson, Andrea Robson, Mark Rodriguez, Gustavo C. Rookus, Matti A. Schmutzler, Rita Katharina Sevenet, Nicolas Shah, Payal D. Singer, Christian F. Slavin, Thomas P. Snape, Katie Sokolowska, Johanna Sonderstrup, Ida Marie Heeholm Southey, Melissa Spurdle, Amanda B. Stadler, Zsofia Stoppa-Lyonnet, Dominique Sukiennicki, Grzegorz Sutter, Christian Tan, Yen Tea, Muy-Kheng Teixeira, Manuel R. Teule, Alex Teo, Soo-Hwang Terry, Mary Beth Thomassen, Mads Tihomirova, Laima Tischkowitz, Marc Tognazzo, Silvia Toland, Amanda Ewart Tung, Nadine van den Ouweland, Ans M. W. van der Luijt, Rob B. van Engelen, Klaartje van Rensburg, Elizabeth J. Varon-Mateeva, Raymonda Wappenschmidt, Barbara Wijnen, Juul T. Rebbeck, Timothy Chenevix-Trench, Georgia Offit, Kenneth Couch, Fergus J. Nord, Silje Easton, Douglas F. Antoniou, Antonis C. Simard, Jacques CA EMBRACE GEMO Study Collaborators HEBON KConFab Investigators TI Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Genetic modifiers; Differential allelic expression; Genetic susceptibility; Cis-regulatory variants; BRCA1 and BRCA2 mutation carriers ID OVARIAN-CANCER; CYCLIN E-CDK2; HUMAN-CELLS; DISEASE; NPAT; INVESTIGATORS; CONSORTIUM; DNA AB Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of similar to 320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 x 10(-6)). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk. C1 [Hamdi, Yosr; Soucy, Penny; Droit, Arnaud; Lemacon, Audrey; Simard, Jacques] Ctr Hosp Univ Quebec, Res Ctr, Genom Ctr, 2705 Laurier Blvd, Quebec City, PQ G1V 4G2, Canada. [Kuchenbaeker, Karoline B.; Barrowdale, Daniel; Frost, Debra; Leslie, Goska; McGuffog, Lesley; Easton, Douglas F.; Antoniou, Antonis C.] Univ Cambridge, Dept Publ Hlth & Primary Care, Strangeways Res Lab, Ctr Canc Genet Epidemiol, Worts Causeway, Cambridge, England. [Kuchenbaeker, Karoline B.] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus Hinxton, Cambridge CB10 1HH, England. [Pastinen, Tomi] McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada. [Pastinen, Tomi] McGill Univ, Montreal, PQ H3A 0G1, Canada. [Adlard, Julian] Chapel Allerton Hosp, Yorkshire Reg Genet Serv, Leeds LS7 4SA, W Yorkshire, England. [Aittomaki, Kristiina] Helsinki Univ Hosp, Dept Clin Genet, Meilahdentie 2,POB 160, Helsinki 00029, Finland. [Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G IX5, Canada. [Andrulis, Irene L.; Mulligan, Anna Marie] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Arason, Adalgeir] Landspitali LSH V Hringbraut, Dept Pathol Hus 9, IS-101 Reykjavik, Iceland. [Arason, Adalgeir] Univ Iceland, Fac Med, BMC Biomed Ctr, Vatnsmyrarvegi 16, IS-101 Reykjavik, Iceland. [Arnold, Norbert; Meindl, Alfons] Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Dept Obstet & Gynaecol, Campus Kiel, D-24105 Kiel, Germany. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Pressler St CBP 5, Houston, TX 77030 USA. [Azzollini, Jacopo; Manoukian, Siranoush; Mariani, Milena; Peissel, Bernard] Fdn IRCCS Ist Ric Cura & Carattere Sci, Dept Prevent & Predict Med, Unit Med Genet, INT, Via Giacomo Venezian 1, I-20133 Milan, Italy. [Bane, Anita] McMaster Univ, Juravinski Hosp & Canc Ctr, Dept Pathol Mol Med, 711 Concess St, Hamilton, ON L8V 1C3, Canada. [Barjhoux, Laure; Damiola, Francesca] Ctr Leon Berard, Bat Cheney D,28 Rue Laennec, F-69373 Lyon, France. [Benitez, Javier; Osorio, Ana] Spanish Natl Canc Ctr CNIO, Human Genet Grp, Madrid, Spain. [Benitez, Javier; Osorio, Ana] Biomed Network Rare Dis CIBERER, Madrid 28029, Spain. [Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genotyping CEGEN Unit, Madrid, Spain. [Berthet, Pascaline] Ctr Francois Baclesse, 3 Ave Gen Harris, F-14076 Caen, France. [Blok, Marinus J.] Maastricht Univ, Dept Clin Genet, Med Ctr, POB 5800, NL-6202 AZ Maastricht, Netherlands. [Bobolis, Kristie] City Hope Natl Med Ctr, Clin Canc Genom Community Res Network, 1500 East Duarte Rd, Duarte, CA 91010 USA. [Bonadona, Valerie] Ctr Leon Berard, Unite Prevent & Epidemiol Genet, 28 Rue Laennec, F-69373 Lyon, France. [Bonanni, Bernardo] IEO, Div Canc Prevent & Genet, Via Ripamonti 435, I-20141 Milan, Italy. [Bradbury, Angela R.; Domchek, Susan M.; Nathanson, Katherine L.; Shah, Payal D.; Rebbeck, Timothy] Univ Penn, Dept Med, Abramson Canc Ctr, Perelman Sch Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Brewer, Carole] Royal Devon & Exeter Hosp, Dept Clin Genet, Exeter EX1 2ED, Devon, England. [Buecher, Bruno; Laurent, Maite; Stoppa-Lyonnet, Dominique] Inst Curie, Serv Genet Oncol, 26 Rue Ulm, F-75248 Paris 05, France. [Buys, Saundra S.] Huntsman Canc Inst, Dept Med, 2000 Circle Hope, Salt Lake City, UT 84112 USA. [Caligo, Maria A.] Univ & Univ Hosp Pisa, Sect Genet Oncol, Dept Lab Med, Pisa, Italy. [Chiquette, Jocelyne] Hop St Sacrement, Ctr Malad Sein Deschenes Fabia, Unite Rech Sante Populat, 1050 Chemin Sainte Foy, Quebec City, PQ G1S 4L8, Canada. [Chung, Wendy K.] Columbia Univ, Dept Pediat, 1150 St Nicholas Ave, New York, NY 10032 USA. [Claes, Kathleen B. M.; De Leeneer, Kim] Univ Ghent, Ctr Med Genet, De Pintelaan 185, Ghent, Belgium. [Daly, Mary B.] Fox Chase Canc Ctr, Div Populat Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. [Davidson, Rosemarie] South Glasgow Univ Hosp, Dept Clin Genet, Glasgow G51 4TF, Lanark, Scotland. [De la Hoya, Miguel] IdISSC Inst Invest Sanitaria Hosp Clin San Carlos, Hosp Clinico San Carlos, Mol Oncol Lab, Martin Lagos S-N, Madrid, Spain. [Diez, Orland] Vall dHebron Univ Hosp, Clin & Mol Genet Area, Oncogenet Grp, Vall dHebron Inst Oncol VHIO, Passeig Vall dHebron 119-129, Barcelona 08035, Spain. [Ding, Yuan Chun; Neuhausen, Susan L.] City Hope Natl Med Ctr, Dept Populat Sci, Beckman Res Inst, Duarte, CA USA. [Dolcetti, Riccardo] IRCCS Ist Ric & Cura Carattere Sci, Dept Med Oncol, Canc Bioimmunotherapy Unit, Ctr Riferimento Oncol,Natl Canc Inst, Via Franco Gallini 2, I-33081 Aviano, PN, Italy. [Dolcetti, Riccardo] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia. [Dorfling, Cecilia M.; van Rensburg, Elizabeth J.] Univ Pretoria, Dept Genet, Canc Genet Lab, Private Bag X323, ZA-0007 Arcadia, South Africa. [Eccles, Diana] Univ Southampton, Southampton Univ Hosp NHS Trust, Fac Med, Southampton, Hants, England. [Eeles, Ros] Inst Canc Res, Oncogenet Team, Sutton SM2 5NG, Surrey, England. [Einbeigi, Zakaria] Sahlgrens Univ Hosp, Dept Oncol, S-41345 Gothenburg, Sweden. [Ejlertsen, Bent] Copenhagen Univ Hosp, Dept Oncol, Rigshosp, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. [Engel, Christoph] Univ Leipzig, Inst Med Informat Stat & Epidemiol, D-04107 Leipzig, Germany. [Engel, Christoph] Univ Leipzig, Leipzig Res Ctr Civilizat Dis, LIFE, Leipzig, Germany. [Evans, D. Gareth] Univ Manchester, Manchester Acad Hlth Sci Ctr, Inst Human Dev, NHS Fdn Trust,Cent Manchester Univ Hosp,Genom Med, Manchester M13 9WL, Lancs, England. 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[Hays, John L.] Ctr Comprehens Canc, Arthur C James Canc Hosp & Richard J Solove Res I, Columbus, OH 43210 USA. Netherlands Canc Inst, Hereditary Breast & Ovarian Canc Res Grp Netherla, Coordinating Ctr, Amsterdam, Netherlands. [Hogervorst, Frans B. L.] Netherlands Canc Inst, Family Canc Clin, POB 90203, NL-1006 BE Amsterdam, Netherlands. [Hulick, Peter J.] Univ Chicago, Pritzker Sch Med, NorthShore Univ HealthSyst, Ctr Med Genet, 1000 Cent St,Suite 620, Evanston, IL 60201 USA. [Imyanitov, Evgeny N.] NN Petrov Inst Oncol, St Petersburg 197758, Russia. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, 3800 Reservoir Rd NW, Washington, DC 20007 USA. [Izatt, Louise] Guys & St Thomas NHS Fdn Trust, Clin Genet, London SE1 9RT, England. [James, Paul] Peter MacCallum Canc Ctr, Familial Canc Ctr, Melbourne, Vic 3000, Australia. [James, Paul] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic 3010, Australia. [Janavicius, Ramunas] Vilnius Univ Hosp, Santariskiu Clin, Dept Mol & Regenerat Med, Hematol Oncol & Transfus Med Ctr, Santariskiu St 2, LT-08661 Vilnius, Lithuania. [Janavicius, Ramunas] State Res Inst Ctr Innovat Med, Zygymantu St 9, Vilnius, Lithuania. [Jensen, Uffe Birk] Aarhus Univ Hosp, Dept Clin Genet, Brendstrupgaardsvej 21C, Aarhus N, Denmark. [John, Esther M.] Canc Prevent Inst Calif, Dept Epidemiol, 2201 Walnut Ave Suite 300, Fremont, CA 94538 USA. [John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA. [Joseph, Vijai; Offit, Kenneth] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Res Lab, 1275 York Ave, New York, NY 10044 USA. [Just, Walter] Univ Ulm, Inst Human Genet, D-89091 Ulm, Germany. [Karlan, Beth Y.; Lester, Jenny] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Womens Canc Program, 8700 Beverly Blvd,Suite 290W, Los Angeles, CA 90048 USA. Peter MacCallum Canc Ctr, Res Dept, Melbourne, Vic 8006, Australia. [Kets, Carolien M.] Radboud Univ Nijmegen, Dept Human Genet, Med Ctr, POB 9101, NL-6500 HB Nijmegen, Netherlands. [Kirk, Judy] Westmead Hosp, Familial Canc Serv, Hawkebury Rd,POB 533, Westmead, NSW 2145, Australia. [Kriege, Mieke] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Med Oncol, POB 5201, NL-3008 AE Rotterdam, Netherlands. [Lesueur, Fabienne] PSL Univ, Inst Curie Mines ParisTech, Genet Epidemiol Canc Team, INSERM,U900, 26 Rue Ulm, F-75248 Paris 05, France. [Liljegren, Annelie] Karolinska Univ Hosp, Dept Oncol, S-17176 Stockholm, Sweden. [Loman, Niklas] Univ Lund Hosp, Dept Oncol, S-22185 Lund, Sweden. [Mazoyer, Sylvie] Univ Lyon, Lyon Neurosci Res Ctr CRNL, INSERM, CNRS,UMR5292,U1028, Lyon, France. [Meijers-Heijboer, Hanne E. J.] Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet, POB 7057, NL-1007 MB Amsterdam, Netherlands. [Miller, Austin] Roswell Pk Canc Inst, NRG Oncol Stat & Data Management Ctr, Elm St & Carlton St, Buffalo, NY 14263 USA. [Montagna, Marco; Tognazzo, Silvia] Veneto Inst Oncol IOV IRCCS, Immunol & Mol Oncol Unit, Via Gattamelata 64, I-35128 Padua, Italy. [Mulligan, Anna Marie] St Michaels Hosp, Dept Lab Med, Toronto, ON, Canada. [Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Haartmaninkatu 8,POB 700, Helsinki 00029, Finland. [Nussbaum, Robert L.] Univ Calif San Francisco, Dept Med & Genet, 513 Parnassus Ave,HSE 901E, San Francisco, CA 94143 USA. [Olah, Edith] Natl Inst Oncol, Dept Mol Genet, Budapest, Hungary. [Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, 5841 South Maryland Ave,MC 2115, Chicago, IL 60637 USA. [Ong, Kai-ren] Birmingham Womens Hosp Healthcare NHS Trust, West Midlands Reg Genet Serv, Birmingham, W Midlands, England. [Oosterwijk, Jan C.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9700 RB Groningen, Netherlands. [Papi, Laura] Univ Florence, Dept Biomed Expt & Clin Sci, Unit Med Genet, Viale Morgagni 50, I-50134 Florence, Italy. [Park, Sue Kyung] Seoul Natl Univ, Dept Prevent Med, Coll Med, 103 Daehak Ro, Seoul 110799, South Korea. [Pedersen, Inge Sokilde] Aalborg Univ Hosp, Sect Mol Diagnost, Dept Biochem, Reberbansgade 15, Aalborg, Denmark. [Segura, Pedro Perez] IdISSC Inst Investigacin Sanitaria Hosp Clin, Hosp Clinico San Carlos, Dept Oncol, Martin Lagos S-N, Madrid, Spain. [Peterlongo, Paolo] IFOM, IFOM IEO Campus,Via Adamello 16, I-20139 Milan, Italy. [Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA. [Radice, Paolo] Fdn IRCCS Ist Ric & Cura Carattere Sci, Dept Prevent & Predicted Med, Unit Mol Bases Genet Risk & Genet Testing, Ist Nazl Tumori, Amaedeolab Via GA Amadeo 42, I-20133 Milan, Italy. [Rantala, Johanna] Karolinska Univ Hosp, Dept Clin Genet, Hosp L5 03, S-17176 Stockholm, Sweden. [Rappaport-Fuerhauser, Christine; Singer, Christian F.; Tan, Yen; Tea, Muy-Kheng] Med Univ Vienna, Dept OB GYN, Waehringer Guertel 18-20, A-1090 Vienna, Austria. [Rennert, Gad] Carmel Hosp, Clalit Natl Israeli Canc Control Ctr, 7 Michal St, IL-34362 Haifa, Israel. [Richardson, Andrea] Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD 21205 USA. [Robson, Mark] Mem Sloan Kettering Canc Ctr, Serv Dept Med, Clin Genet, 1275 York Ave, New York, NY USA. [Rodriguez, Gustavo C.] Univ Chicago, NorthShore Univ HealthSyst, Div Gynecol Oncol, 2650 Ridge Ave,Suite 1507, Evanston, IL 60201 USA. [Rookus, Matti A.] Netherlands Canc Inst, Dept Epidemiol, POB 90203, NL-1006 BE Amsterdam, Netherlands. [Schmutzler, Rita Katharina] Univ Hosp Cologne, Fac Med, Ctr Hereditary Breast & Ovarian Canc, D-50931 Cologne, Germany. [Schmutzler, Rita Katharina] Univ Hosp Cologne, Fac Med, Ctr Integrated Oncol CIO, Cologne, Germany. [Sevenet, Nicolas] Inst Bergonie, Oncogenet, 229 Cours Argonne, F-33076 Bordeaux, France. [Snape, Katie] St Georges Univ London, Med Genet Unit, London SW17 0RE, England. [Sokolowska, Johanna] Nancy Univ, Lab Genet Med, Ctr Hosp Reg & Univ, Rue Morvan, F-54511 Vandoeuvre Les Nancy 1, France. [Sonderstrup, Ida Marie Heeholm] Slagelse Hosp, Dept Pathol Reg Zealand Sect Slagelse, Ingemannsvej 18, Slagelse, Cpoenhagen, Denmark. [Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3010, Australia. [Spurdle, Amanda B.; Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Genet & Computat Biol Dept, Herston Rd, Herston, Qld 4006, Australia. [Stadler, Zsofia] Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, 1275 York Ave, New York, NY 10021 USA. [Sutter, Christian] Univ Heidelberg Hosp, Inst Human Genet, Dept Human Genet, Heidelberg, Germany. [Teixeira, Manuel R.] Portuguese Oncol Inst, Dept Genet, Rua Dr Antonio Bernardino Almeida, P-4200072 Oporto, Portugal. [Teixeira, Manuel R.] Univ Porto, Biomed Sci Inst ICBAS, Oporto, Portugal. [Teule, Alex] IDIBELL Bellvitge Biomed Res Inst, Catalan Inst Oncol, Hereditary Canc Program, Genet Counseling Unit, Gran Via Hosp 199-203, Barcelona 08908, Spain. [Teo, Soo-Hwang] Canc Res Initiat Fdn, Sime Darby Med Ctr, 1 Jalan SS12-1A, Subang Jaya 47500, Malaysia. [Teo, Soo-Hwang] Univ Malaya, Univ Malaya Canc Res Inst, 1 Jalan SS12-1A, Kuala Lumpur 50603, Malaysia. [Terry, Mary Beth] Columbia Univ, Dept Epidemiol, New York, NY USA. [Thomassen, Mads] Odense Univ Hosp, Dept Clin Genet, Sonder Blvd 29, Odense C, Denmark. [Tihomirova, Laima] Latvian Biomed Res & Study Ctr, Ratsupites Str 1, Riga, Latvia. [Tischkowitz, Marc] Addenbrookes Hosp, Dept Med Genet, Addenbrookes Treatment Ctr, Level 6,Hills Rd,Box 134, Cambridge CB2 0QQ, England. [Toland, Amanda Ewart] Ohio State Univ, Div Human Genet, Dept Internal Med, 998 Biomedical Res Tower, Columbus, OH 43210 USA. [Tung, Nadine] Beth Israel Deaconess Med Ctr, Dept Med Oncol, 330 Brookline Ave, Boston, MA 02215 USA. [van den Ouweland, Ans M. W.] Erasmus Univ, Med Ctr, Family Canc Clin, Dept Clin Genet, 330 Brookline Ave,POB 2040, NL-3000 CA Rotterdam, Netherlands. [van der Luijt, Rob B.] Univ Med Ctr Utrecht, Dept Med Genet, NL-3584 EA Utrecht, Netherlands. [van Engelen, Klaartje] Acad Med Ctr, Dept Clin Genet, POB 22700, NL-1100 DE Amsterdam, Netherlands. [Varon-Mateeva, Raymonda] Charite, Inst Human Genet, Campus Virchov Klinikum, D-13353 Berlin, Germany. [Wijnen, Juul T.] Leiden Univ, Med Ctr, Dept Human Genet, NL-2300 RC Leiden, Netherlands. [Rebbeck, Timothy] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, 200 First St SW, Rochester, MN 55905 USA. [Nord, Silje] Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Radiumhosp, N-0372 Oslo, Norway. [Hamdi, Yosr; Soucy, Penny; Droit, Arnaud; Lemacon, Audrey; Simard, Jacques] Univ Laval, 2705 Laurier Blvd, Quebec City, PQ G1V 4G2, Canada. [Pastinen, Tomi] Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada. [Andrulis, Irene L.; Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. [Arun, Banu K.] Univ Texas MD Anderson Canc Ctr, Clin Canc Genet Program, 1515 Pressler St CBP 5, Houston, TX 77030 USA. [Chung, Wendy K.] Columbia Univ, Dept Med, 1150 St Nicholas Ave, New York, NY 10032 USA. [Eeles, Ros] Royal Marsden NHS Fdn Trust, Sutton SM2 5NG, Surrey, England. [Foulkes, William D.; Tischkowitz, Marc] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada. [Ganz, Patricia A.] UCLA, Div Canc Prevent Control Res, Jonsson Comprehens Canc Ctr, Sch Publ Hlth, 650 Charles Young Dr South,Room A2-125 HS, Los Angeles, CA 90095 USA. [Hahnen, Eric; Schmutzler, Rita Katharina; Wappenschmidt, Barbara] Univ Hosp Cologne, Ctr Mol Med Cologne CMMC, Ctr Integrated Oncol CIO, D-50931 Cologne, Germany. [John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON, Canada. [Nevanlinna, Heli] Helsinki Univ Hosp, Biomedicum Helsinki, Haartmaninkatu 8,POB 700, Helsinki 00029, Finland. [Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, 7 Michal St, IL-34362 Haifa, Israel. [Rennert, Gad] B Rappaport Fac Med, 7 Michal St, IL-34362 Haifa, Israel. [Toland, Amanda Ewart] Ohio State Univ, Div Human Genet, Dept Canc Biol, 998 Biomedical Res Tower, Columbus, OH 43210 USA. [Toland, Amanda Ewart] Ohio State Univ, Genet Comprehens Canc Ctr, 998 Biomedical Res Tower, Columbus, OH 43210 USA. [Wijnen, Juul T.] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands. EM Jacques.Simard@crchudequebec.ulaval.ca RI Gronwald, Jacek/A-4576-2017; Arnold, Norbert/E-3012-2010; Jansen van Rensburg, Elizabeth (Lizette)/B-9104-2011; Osorio, Ana/I-4324-2014; Azzollini, Jacopo/E-7134-2017; manoukian, siranoush/E-7132-2017; Peissel, Bernard/E-8187-2017; montagna, marco/E-2225-2012; OI Gronwald, Jacek/0000-0002-3643-2871; Arnold, Norbert/0000-0003-4523-8808; Osorio, Ana/0000-0001-8124-3984; Azzollini, Jacopo/0000-0002-9364-9778; manoukian, siranoush/0000-0002-6034-7562; Peissel, Bernard/0000-0001-9233-3571; montagna, marco/0000-0002-4929-2150; Dunning, Alison Margaret/0000-0001-6651-7166 FU European Community's Seventh Framework Programme [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK [C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565, C1287/A11990, C5047/A8385]; National Institutes of Health [CA128978]; Post-cancer GWAS Initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112]; Department of Defence [W81XWH-10-1-0341]; Canadian Institutes of Health Research (CIHR); Komen Foundation for the Cure; Breast Cancer Research Foundation; Ovarian Cancer Research Fund; National Cancer Institute [UM1 CA164920, RC4CA153828]; Lithuania (BFBOCC-LT): Research Council of Lithuania [SEN-18/2015]; Cancer Association of South Africa (CANSA); Morris and Horowitz Families Endowed Professorship; Spanish Association Against Cancer [AECC08]; RTICC [06/0020/1060, FISPI08/1120]; Mutua Madrilena Foundation (FMMA); Office of the Director, National Institutes of Health; Fondazione IRCCS Istituto Nazionale Tumori; Cancer Research: UK [C12292/A11174, C12292/A20861]; Fondation ARC (FONDATION ARC) [SAE20131200623]; Canadian Institutes of Health Research [CRN-87521]; Ministry of Economic Development, Innovation and Export Trade [PSR-SIIRI-701]; Government of Canada through Genome Canada; Canadian Institutes of Health Research; Ministere de l'Economie, Innovation et Exportation du Quebec through Genome Quebec; Quebec Breast Cancer Foundation; Ministere de l'Economie, Innovation et Exportation du Quebec [PSR-SIIRI-701]; European Union (European Social Fund: ESF); Greek National Funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF): Research Funding Program of the General Secretariat for Research and Technology [SYN11_10_19 NBCA]; DKFZ; NIHR; University of Kansas Cancer Center [P30 CA168524]; Kansas Bioscience Authority Eminent Scholar Program; Chancellors Distinguished Chair in Biomedical Sciences Professorship; German Cancer Aid [110837]; European Regional Development Fund; Free State of Saxony, Germany (LIFE: Leipzig Research Centre for Civilization Diseases) [713-241202, 14505/2470]; Ligue Nationale Contre le Cancer; Association "Le cancer du sein, parlons-en!" Award; French National Institute of Cancer (INCa); Non-therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI) [P30-CA051008]; Fisher Center for Hereditary Cancer and Clinical GenomicsResearch; Swing Fore the Cure; IWT; ISCIII (Spain) [RD12/0036/0006, 15/00059]; European Regional Development FEDER Funds; Helsinki University Hospital Research Fund; Academy of Finland [266528]; Finnish Cancer Society; Sigrid Juselius Foundation; Dutch Cancer Society [NKI1998-1854, NKI2004-3088, NKI2007-3756]; Netherlands Organization of Scientific Research [NWO 91109024]; Pink Ribbon Grants [110005, 2014-187.WO76]; BBMRI [NWO 184.021.007/CP46]; Transcan Grant JTC Cancer [12-054]; Hong Kong Sanatorium and Hospital; Dr. Ellen Li Charitable Foundation; Kerry Group Kuok Foundation; National Institute of Health [1R 03CA130065]; North California Cancer Center; Hungarian Research Grants [KTIA-OTKA CK-80745, OTKA K-112228]; Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute; Autonomous Government of Catalonia [ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, PIE13/00022, 2009SGR290, 2014SGR364]; Icelandic Association; Landspitali University Hospital Research Fund; Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec; Ministero della Salute and "5x1000" Istituto Oncologico Veneto Grant; Liga Portuguesa Contra o Cancro; National Breast Cancer Foundation; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [1020350]; NIH [CA116167, CA192393, CA176785]; NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer [CA116201]; MH CZ: DRO (MMCI) [00209805]; State Budget of the Czech Republic (RECAMO) [CZ.1.05/2.1.00/03.0101]; Charles University in Prague [UNCE204024]; Robert and Kate Niehaus Clinical Cancer Genetics Initiative; Andrew Sabin Research Fund; Intramural Research Program of the US National Cancer Institute, NIH; Westat, Inc., Rockville, MD [NO2-CP-11019-50, N02-CP-65504]; Clalit Health Services in Israel; Israel Cancer Association; Breast Cancer Research Foundation (BCRF), NY; Russian Federation for Basic Research [15-04-01744, 16-54-00055]; NRG Oncology Operations Grant [U10 CA180868]; NRG SDMC Grant [U10 CA180822]; Gynecologic Oncology Group (GOG) Administrative Office; GOG Tissue Bank [CA 27469]; GOG Statistical and Data Center [CA 37517]; Intramural Research Program, NCI; Ohio State University Comprehensive Cancer Center; Italian Association of Cancer Research (AIRC) [IG 2013 N.14477]; Tuscany Institute for Tumors (ITT); Israeli Cancer Association; Swedish Cancer Society; NCI [CA125183, R01 CA142996, 1U01CA161032]; Ralph and Marion Falk Medical Research Trust; Entertainment Industry Fund National Women's Cancer Research Alliance; CRUK; [SAF2010-20493]; [5U01CA113916]; [R01CA140323]; [PBZ_KBN_122/P05/2004] FX Funding for the iCOGS infrastructure came from the European Community's Seventh Framework Programme under Grant Agreement No. 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), 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 Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. BCFR: this work was supported by Grant UM1 CA164920 from the National Cancer Institute. BFBOCC was supported by Lithuania (BFBOCC-LT): Research Council of Lithuania Grant SEN-18/2015. BIDMC was supported by the Breast Cancer Research Foundation. BRCA-gene mutations and breast cancer in South African women (BMBSA) was supported by Grants from the Cancer Association of South Africa (CANSA) to Elizabeth J. van Rensburg. BRICOH: SLN was partially supported by the Morris and Horowitz Families Endowed Professorship. CNIO: this work was partially supported by Spanish Association Against Cancer (AECC08), RTICC 06/0020/1060, FISPI08/1120, Mutua Madrilena Foundation (FMMA), and SAF2010-20493. COH-CCGCRN: patients were recruited for this study from the City of Hope Clinical Cancer Genomics Community Research Network, supported in part by Award Number RC4CA153828 (PI: J. Weitzel) from the National Cancer Institute and the Office of the Director, National Institutes of Health. CONSIT Team: Associazione Italiana Ricerca sul Cancro (AIRC) to P. Peterlongo (IG 2012 Id. 12821) and P. Radice (IG 2014 Id. 15547). Funds from Italian citizens who allocated the 5 9 1000 share of their tax payment in support of the Fondazione IRCCS Istituto Nazionale Tumori, according to Italian laws (INT-Institutional Strategic Projects '5x1000') to S. Manoukian. FiorGen Foundation for Pharmacogenomics to L. Papi. CORE: the CIMBA Data Management and Data Analysis were supported by Cancer Research: UK Grants C12292/A20861, C12292/A11174. ACA is a Cancer Research-UK Senior Cancer Research Fellow. GCT is an NHMRC Senior Principal Research Fellow. J. Lecarpentier has been financially supported by the Fondation ARC (FONDATION ARC, 9 rue Guy Moquet 94803 Villejuif: France), Grant Number SAE20131200623. This work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" Program: Grant No. CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade: Grant No. PSR-SIIRI-701. The PERSPECTIVE Project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministere de l'Economie, Innovation et Exportation du Quebec through Genome Quebec, and The Quebec Breast Cancer Foundation. This work was also supported by the Ministere de l'Economie, Innovation et Exportation du Quebec: Grant No. PSR-SIIRI-701. DEMOKRITOS: this research has been co-financed by the European Union (European Social Fund: ESF) and Greek National Funds through the Operational Program "Education and Lifelong Learning" of the National Strategic Reference Framework (NSRF): Research Funding Program of the General Secretariat for Research and Technology: SYN11_10_19 NBCA. Investing in Knowledge Society through the European Social Fund. The DKFZ Study was supported by the DKFZ.; EMBRACE was supported by Cancer Research UK Grants C1287/A10118 and C1287/A11990. D. Gareth Evans and Fiona Lalloo were supported by an NIHR Grant to the Biomedical Research Centre, Manchester. The Investigators at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust were supported by an NIHR Grant to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft were supported by Cancer Research UK Grant C5047/A8385. Ros Eeles was also supported by NIHR support to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. FCCC: the authors acknowledge the support from The University of Kansas Cancer Center (P30 CA168524) and the Kansas Bioscience Authority Eminent Scholar Program. A.K.G. was funded by 5U01CA113916, R01CA140323, and by the Chancellors Distinguished Chair in Biomedical Sciences Professorship. The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) was supported by the German Cancer Aid (Grant No. 110837, Rita K. Schmutzler). This work was supported by the European Regional Development Fund and Free State of Saxony, Germany (LIFE: Leipzig Research Centre for Civilization Diseases, Project Numbers 713-241202, 713-241202, 14505/2470, 14575/2470). GEMO: the study was supported by the Ligue Nationale Contre le Cancer; the Association "Le cancer du sein, parlons-en!" Award; the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" Program and the French National Institute of Cancer (INCa). GEORGETOWN: CI received support from the Non-therapeutic Subject Registry Shared Resource at Georgetown University (NIH/NCI Grant P30-CA051008), the Fisher Center for Hereditary Cancer and Clinical GenomicsResearch, and Swing Fore the Cure. G-FAST: Bruce Poppe is a Senior Clinical Investigator of FWO. Mattias Van Heetvelde obtained funding from IWT. HCSC was supported by a Grant RD12/0036/0006 and 15/00059 from ISCIII (Spain), partially supported by European Regional Development FEDER Funds. The HEBCS was financially supported by the Helsinki University Hospital Research Fund, Academy of Finland (266528), the Finnish Cancer Society and the Sigrid Juselius Foundation. HEBON Study was supported by the Dutch Cancer Society Grants NKI1998-1854, NKI2004-3088, and NKI2007-3756, the Netherlands Organization of Scientific Research Grant NWO 91109024, the Pink Ribbon Grants 110005 and 2014-187.WO76, the BBMRI Grant NWO 184.021.007/CP46, and the Transcan Grant JTC 2012 Cancer 12-054. HEBON thanks the Registration Teams of Dutch Cancer Registry (IKNL; S. Siesling, J. Verloop) and the Dutch Pathology database (PALGA; L. Overbeek) for their help in part of the data collection. HRBCP was supported by the Hong Kong Sanatorium and Hospital, Dr. Ellen Li Charitable Foundation, The Kerry Group Kuok Foundation, National Institute of Health 1R 03CA130065, and North California Cancer Center. Hungarian Breast and Ovarian Cancer Study (HUNBOCS) was supported by Hungarian Research Grants KTIA-OTKA CK-80745 and OTKA K-112228. ICO: Contract Grant Sponsor: Asociacion Espanola Contra el Cancer, Spanish Health Research Fund; Carlos III Health Institute; Catalan Health Institute and Autonomous Government of Catalonia. Contract Grant Numbers: ISCIIIRETIC RD06/0020/1051, RD12/0036/008, PI10/01422, PI10/00748, PI13/00285, PIE13/00022, 2009SGR290, and 2014SGR364. The IHCC was supported by Grant PBZ_KBN_122/P05/2004.; The ILUH Group was supported by the Icelandic Association "Walking for Breast Cancer Research" and by the Landspitali University Hospital Research Fund. INHERIT: this work was supported by the Canadian Institutes of Health Research for the "CIHR Team in Familial Risks of Breast Cancer" Program: Grant No. CRN-87521 and the Ministry of Economic Development, Innovation and Export Trade: Grant No. PSR-SIIRI-701. The PERSPECTIVE Project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (Grant GPH-129344), the Ministere de l'Economie, Science et Innovation du Quebec through Genome Quebec, and the Quebec Breast Cancer Foundation. IOVHBOCS was supported by Ministero della Salute and "5x1000" Istituto Oncologico Veneto Grant. IPOBCS: this study was in part supported by Liga Portuguesa Contra o Cancro. kConFab was supported by a Grant from the National Breast Cancer Foundation, and previously by the National Health and Medical Research Council (NHMRC), the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia, and the Cancer Foundation of Western Australia. KOHBRA was supported by a Grant from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea (1020350). MAYO was supported by NIH Grants CA116167, CA192393, and CA176785, an NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA116201), and a Grant from the Breast Cancer Research Foundation. MCGILL: Jewish General Hospital Weekend to End Breast Cancer, Quebec Ministry of Economic Development, Innovation and Export Trade. MODSQUAD was supported by MH CZ: DRO (MMCI, 00209805) and by the European Regional Development Fund and the State Budget of the Czech Republic (RECAMO, CZ.1.05/2.1.00/03.0101) to LF, and by Charles University in Prague Project UNCE204024 (MZ). MSKCC was supported by Grants from the Breast Cancer Research Foundation, the Robert and Kate Niehaus Clinical Cancer Genetics Initiative, and the Andrew Sabin Research Fund. NAROD: 1R01 CA149429-01. NCI: the research of Drs. MH Greene and PL Mai was supported by the Intramural Research Program of the US National Cancer Institute, NIH, and by Support Services Contracts NO2-CP-11019-50 and N02-CP-65504 with Westat, Inc., Rockville, MD. NICCC was supported by Clalit Health Services in Israel. Some of its activities were supported by the Israel Cancer Association and the Breast Cancer Research Foundation (BCRF), NY. NNPIO: this work has been supported by the Russian Federation for Basic Research (Grants 15-04-01744 and 16-54-00055). NRG Oncology: this study was supported by NRG Oncology Operations Grant Number U10 CA180868 as well as NRG SDMC Grant U10 CA180822, Gynecologic Oncology Group (GOG) Administrative Office and the GOG Tissue Bank (CA 27469), and the GOG Statistical and Data Center (CA 37517). Drs. Greene, Mai, and Savage were supported by Funding from the Intramural Research Program, NCI. OSUCCG was supported by the Ohio State University Comprehensive Cancer Center. PBCS: this work was supported by the Italian Association of Cancer Research (AIRC) [IG 2013 N.14477] and Tuscany Institute for Tumors (ITT) Grant 2014-2015-2016. SEABASS: Ministry of Science, Technology and Innovation, Ministry of Higher Education (UM.C/HlR/MOHE/06), and Cancer Research Initiatives Foundation. The SMC Team was in part sponsored by a Grant from the Israeli Cancer Association to the Israeli Consortium of Hereditary Breast Cancer.; SWE-BRCA Collaborators were supported by the Swedish Cancer Society. UCHICAGO was supported by NCI Specialized Program of Research Excellence (SPORE) in Breast Cancer (CA125183), R01 CA142996, 1U01CA161032, and by the Ralph and Marion Falk Medical Research Trust, the Entertainment Industry Fund National Women's Cancer Research Alliance, and the Breast Cancer Research Foundation. OIO is an ACS Clinical Research Professor. UCLA: Jonsson Comprehensive Cancer Center Foundation; Breast Cancer Research Foundation. UCSF: UCSF Cancer Risk Program and Helen Diller Family Comprehensive Cancer Center. UKFOCR was supported by a Project Grant from CRUK to Paul Pharoah. UPENN: National Institutes of Health (NIH) (R01-CA102776 and R01-CA083855; Breast Cancer Research Foundation; Susan G. Komen Foundation for the Cure, Basser Research Center for BRCA. VFCTG: Victorian Cancer Agency, Cancer Australia, National Breast Cancer Foundation. WCP: Dr. Karlan was funded by the American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN) and the National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124. NR 36 TC 0 Z9 0 U1 9 U2 9 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 JAN PY 2017 VL 161 IS 1 BP 117 EP 134 DI 10.1007/s10549-016-4018-2 PG 18 WC Oncology SC Oncology GA EI0TV UT WOS:000392188500012 PM 27796716 ER PT J AU Braunstein, LZ Taghian, AG Niemierko, A Salama, L Capuco, A Bellon, JR Wong, JS Punglia, RS MacDonald, SM Harris, JR AF Braunstein, Lior Z. Taghian, Alphonse G. Niemierko, Andrzej Salama, Laura Capuco, Alexander Bellon, Jennifer R. Wong, Julia S. Punglia, Rinaa S. MacDonald, Shannon M. Harris, Jay R. TI Breast-cancer subtype, age, and lymph node status as predictors of local recurrence following breast-conserving therapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Local recurrence; Breast-conserving therapy; Lumpectomy; Radiotherapy; Lymph node; Age; Subtype ID SURGICAL ADJUVANT BREAST; LOCOREGIONAL RECURRENCE; POSTOPERATIVE RADIOTHERAPY; RISK; MASTECTOMY; CHEMOTHERAPY; TRIALS; APPROXIMATION; TAMOXIFEN; PATTERNS AB Advances in breast-conserving therapy (BCT) have yielded local control rates comparable or superior to those of mastectomy. In this study, we sought to identify contemporary risk factors associated with local recurrence (LR) following BCT. We analyzed a multi-institutional cohort of 2233 consecutive breast-cancer patients who underwent BCT between 1998 and 2007. Patients were stratified by age, biologic subtype (as approximated by receptor status and tumor grade), and nodal status. Patients who received HER2/neu-directed therapy were excluded due to variations in practice over the study period. The association of clinicopathologic features with LR was evaluated using Cox proportional hazards regression models. With a median follow-up of 106 months, 69 LRs (3 %) were observed. On univariate analysis, LR was associated with non-luminal-A subtype (hazard ratio [HR] for luminal-B = 3.01, HER2 = 6.29, triple-negative [TNBC] = 4.72; p < 0.001 each), younger age (HR of oldest vs. youngest quartile = 0.43; p = 0.005), regional nodal involvement (HR for 4-9 involved nodes = 3.04; > 9 nodes = 5.82; p < 0.01 for each), positive margins (HR 2.43; p = 0.005), and high grade (HR 5.37; p < 0.001). Multivariate Cox regression demonstrated that non-luminal-A subtypes (HR for luminal-B = 2.64, HER2 = 5.42, TNBC = 4.32; p < 0.001 for each), younger age (HR for age > 50 = 0.56; p = 0.01), and nodal disease (HR 1.06 per involved node; p < 0.004) were associated with LR. The 8-year risk of LR was 2.8 % for node-negative patients and 5.2 % for node-positive patients. BCT yields favorable outcomes for the large majority of patients, although increased LR was observed among those with non-luminal-A subtypes, younger age, and increasing lymph node involvement. Risk factors for LR after BCT appear to be converging with those after mastectomy in the current era. C1 [Braunstein, Lior Z.] Harvard Radiat Oncol Program, Boston, MA USA. [Taghian, Alphonse G.; Niemierko, Andrzej; Salama, Laura; MacDonald, Shannon M.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Capuco, Alexander; Bellon, Jennifer R.; Wong, Julia S.; Punglia, Rinaa S.; Harris, Jay R.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. [Braunstein, Lior Z.] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. EM jharris@lroc.harvard.edu NR 17 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2017 VL 161 IS 1 BP 173 EP 179 DI 10.1007/s10549-016-4031-5 PG 7 WC Oncology SC Oncology GA EI0TV UT WOS:000392188500017 PM 27807809 ER PT J AU Eggers, S Barker, A Valentine, S Hess, T Duster, M Safdar, N AF Eggers, Shoshannah Barker, Anna Valentine, Susan Hess, Timothy Duster, Megan Safdar, Nasia TI Impact of Probiotics for Reducing Infections in Veterans (IMPROVE): Study protocol for a double-blind, randomized controlled trial to reduce carriage of Staphylococcus aureus SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Clinical trial; Staphylococcus aureus; MRSA; Lactobacilli; Probiotics; Veterans ID LACTOBACILLUS-RHAMNOSUS HN001; BIFIDOBACTERIUM-LACTIS HN019; VENTILATOR-ASSOCIATED PNEUMONIA; GRAM-NEGATIVE BACILLI; TERM-CARE FACILITY; METHICILLIN-RESISTANT; NASAL COLONIZATION; ACIDOPHILUS HN017; ANTIBIOTIC-THERAPY; ACID BACTERIA AB Background: Staphylococcus aureus (S. aureus) is an organism of great public health importance, causing 20,000 deaths annually. Decolonization of patients with S. aureus may prevent infections, yet current options are limited to antimicrobials that promote antibiotic resistance and can cause adverse side effects. Probiotics have potential to reduce colonization of pathogenic bacteria, representing a promising alternative for S. aureus decolonization, but thus far lack rigorous evaluation. Methods: Potential subjects were recruited from inpatient and outpatient settings within a VA medical center and screened for S. aureus gastrointestinal (GI) or extra-GI colonization using swabs at multiple body sites. Positive, eligible, consenting participants were stratified by colonization site and randomized in a 1:1 ratio to 4-Weeks of daily placebo or Lactobacillus rhamnosus (L. rhamnosus) HN001 probiotic treatment. Blood and stool samples, and treatment adherence reports were collected from each subject throughout the study, along with a final set of swabs at study completion to detect S. aureus carriage. The outcomes of this study are GI or extra-GI carriage by S. aureus at the end of 4 weeks of therapy, change in phagocytic activity of polymorphonticlear cells from pre-intervention to post-intervention, and symptomatic S. aureus infection at any site during the study period. Conclusion: 114 participants have been recruited for this study. Analysis of outcomes is underway. This is the first clinical trial to examine the efficacy of L. rhamnosus HN001 for decolonization of S. aureus, and investigates the mechanism by which L rhamnosus HN001 mediates its effect on S. aureus colonization. Published by Elsevier Inc. C1 [Eggers, Shoshannah; Valentine, Susan; Hess, Timothy; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. [Eggers, Shoshannah; Hess, Timothy; Duster, Megan] Univ Wisconsin Madison, Sch Med & Publ Hlth, Madison, WI USA. [Eggers, Shoshannah; Barker, Anna; Safdar, Nasia] Univ Wisconsin Madison, Sch Med & Publ Hlth, Dept Populat Hlth Sci, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. EM nasia.safdar@va.gov FU Biomedical Laboratory Research & Development Service of the VA Office of Research and Development [I01BX007080]; National Institute of Health [UL1TR000427, TL1TR000429] FX This work was supported by the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (Award Number I01BX007080). The views expressed in this article are those of the author(s) and do not necessarily represent the views of the Department of Veterans Affairs. AB is supported under National Institute of Health (awards UL1TR000427 and TL1TR000429, administered by the University of Wisconsin-Madison's Institute for Clinical and Translational Research). These funding sources had no role in the design or implementation of this study, and will have no role in data analysis, in of data, or the decision to submit results. NR 61 TC 1 Z9 1 U1 4 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 EI 1559-2030 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JAN PY 2017 VL 52 BP 39 EP 45 DI 10.1016/j.cct.2016.11.004 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA EI5VZ UT WOS:000392565700006 PM 27836508 ER PT J AU Dai, XQ Perez, PL Soria, G Scarinci, N Smoler, M Morsucci, DC Suzuki, K Cantero, MD Cantiello, HF AF Dai, Xiao Qing Perez, Paula L. Soria, Gonzalo Scarinci, Noelia Smoler, Mariano Morsucci, D. Cristian Suzuki, Kunimasa del Rocio Cantero, Maria Cantiello, Horacio F. TI External Ca2+ regulates polycystin-2 (TRPP2) cation currents in LLC-PK1 renal epithelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE TRP channels; Polycystin-2; TRPP2; Ca2+ sensing receptor ID CALCIUM-SENSING RECEPTOR; KIDNEY-DISEASE PROTEINS; APICAL K+ CHANNELS; EXTRACELLULAR CA2+; PRIMARY CILIUM; PKD2; LOCALIZATION; SECRETION; GENE AB Polycystin-2 (PC2, TRPP2) is a nonselective cation channel whose dysfunction is associated with the onset of autosomal dominant polycystic kidney disease (ADPKD). PC2 contributes to Ca2+ transport and cell signaling in renal epithelia and other tissues. Little is known however, as to the external Ca2+ regulation of PC2 channel function. In this study, we explored the effect of external Ca2+ on endogenous PC2 in wild type LLC-PK1 renal epithelial cells. We obtained whole cell currents at different external Ca2+ concentrations, and observed that the basal whole cell conductance in normal Ca2+(1.2 mM), decreased by 30.2% in zero (nominal) Ca2+ and conversely, increased by 38% in high external Ca2+(6.2 mM). The high Ca2+-increased whole cell currents were completely inhibited by either PC2 gene silencing, or intracellular dialysis with active, but not denatured by boiling, PC2 antibody. Exposure of cells to high Ca2+ was also associated with relocation of PC2 to the plasma membrane. To explore whether a Ca2+ sensing receptor (CaSR) was implicated in the external Ca2+ modulation of PC2 currents, we tested the effect of the CaSR agonists, spermine and the calcimimetic R-568, which largely mimicked the effect of high Ca2+ under Ca2+-free conditions. The CaSR agonist gentamicin also increased the PC2 currents in the presence of normal Ca2+. The presence of CaSR was confirmed by immunocytochemistry, which partially colocalized with the intracellular PC2 protein, in an external Ca2+-dependent manner. The data support a novel Ca2+ sensing mechanism for PC2 expression and functional regulation in renal epithelial cells. C1 [Dai, Xiao Qing] Univ Alberta, Dept Pharmacol, Alberta Diabet Inst, Edmonton, AB T6G 2M7, Canada. [Soria, Gonzalo; Morsucci, D. Cristian; Cantiello, Horacio F.] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Charlestown, MA USA. [Soria, Gonzalo; Morsucci, D. Cristian; Cantiello, Horacio F.] Harvard Med Sch, Charlestown, MA USA. [Perez, Paula L.; Scarinci, Noelia; Smoler, Mariano; del Rocio Cantero, Maria; Cantiello, Horacio F.] UBA, Lab Canales Ion, CONICET, Catedra Biofis & Bioestadist,Fac Odontol, Marcelo T de Alvear 2142 16B,CABA 1122, Buenos Aires, DF, Argentina. [Suzuki, Kunimasa] Univ Alberta, Alberta Diabet Inst, Mol Biol & Biochem Core Facil, Edmonton, AB, Canada. EM hcantiello@yahoo.com.ar OI Smoler, Mariano/0000-0001-6248-3851 FU NIDDK [1R01DK077079-01A2]; MinCyT, Argentina [1559] FX This work was partially supported by NIDDK grant 1R01DK077079-01A2 (HFC), and PICT 2012 #1559 MinCyT, Argentina, to HFC. MRC, PLP, MS and HFC are members of the National Research Council of Argentina (CONICET). DCM and GS were visiting graduate students from the School of Medicine, Mendoza, Argentina. We are grateful to Drs. Fernando Pieckenstain for the kind gift of spermine-tetrahydrochloride, and Ana Clara Casadoumecq and Dr. Cecilia Villa Etchegoyen for excellent technical support. XQD and KS would like to thank Dr. Patrick MacDonald for his support and generosity in allowing use of instrumentation and reagents in his laboratory. NR 44 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 EI 1090-2422 J9 EXP CELL RES JI Exp. Cell Res. PD JAN 1 PY 2017 VL 350 IS 1 BP 50 EP 61 DI 10.1016/j.yexcr.2016.11.004 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA EI3CH UT WOS:000392366800006 PM 27836810 ER PT J AU Antoni, MH Jacobs, JM Bouchard, LC Lechner, SC Jutagir, DR Gudenkauf, LM Blomberg, BB Gluck, S Carver, CS AF Antoni, Michael H. Jacobs, Jamie M. Bouchard, Laura C. Lechner, Suzanne C. Jutagir, Devika R. Gudenkauf, Lisa M. Blomberg, Bonnie B. Gluck, Stefan Carver, Charles S. TI Post-surgical depressive symptoms and long-term survival in non-metastatic breast cancer patients at 11-year follow-up SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article DE Breast neoplasms; Survival; Depressive symptoms; Recurrence; Follow-up study ID PSYCHOSOCIAL FACTORS; DISEASE PROGRESSION; PROGNOSTIC-FACTOR; RATING-SCALE; ANXIETY; MORTALITY; WOMEN; PREDICTOR; MODELS; COHORT AB Background: Mild to moderate depressive symptoms are common during treatment for non-metastatic breast cancer. The goal of this secondary analysis was to determine if depressive symptoms predict clinical outcomes at long-term follow-up. Methods: From 1998 to 2005, we interviewed 231 women with the Hamilton Rating Scale for Depression who were participating in a psychosocial study 2-10 weeks post-surgery for non-metastatic breast cancer (Stage 0-IIIb). We conducted Kaplan Meier (K-M) curves and Cox proportional hazards (PH) models to examine associations between depressive symptoms, overall survival, and disease-free survival at 8-15-year follow-up. Results: A total of 95 women (41.1%) scored in themild-moderately depressed range. Non-depressed women had longer overall survival (M = 13.56 years; SE = 0.26) than those in the mild/moderate depressed group (M = 11.45 years; SE = 0.40), Log-rank chi(2)(1) = 4.41, p = 0.036. Cox PH models, adjusting for covariates, showed comparable results: mild/moderate depressive symptoms hazard ratio = 2.56, [95% CI, 1.11 to 5.91], p = 0.027. Similar results were observed in a subsample with invasive disease (n = 191). Depression category did not predict disease-free survival in the overall or invasive sample. Conclusions: Screening and referrals for treatment of depressive symptoms, even at subclinical levels, is important early in treatment. A randomized trial is warranted to determine effects of depressive symptoms on clinical outcomes. (C) 2016 Elsevier Inc. All rights reserved. C1 [Antoni, Michael H.; Bouchard, Laura C.; Jutagir, Devika R.; Gudenkauf, Lisa M.; Carver, Charles S.] Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. [Antoni, Michael H.; Lechner, Suzanne C.] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. [Antoni, Michael H.; Lechner, Suzanne C.; Blomberg, Bonnie B.; Carver, Charles S.] Univ Miami, Miller Sch Med, Sylvester Canc Ctr, Miami, FL 33136 USA. [Jacobs, Jamie M.] Massachusetts Gen Hosp, Ctr Canc, Ctr Psychiat Oncol & Behav Sci, Boston, MA USA. [Jacobs, Jamie M.] Massachusetts Gen Hosp, Ctr Canc, Canc Outcomes Res Program, Boston, MA USA. [Blomberg, Bonnie B.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Gluck, Stefan] Celgene Corp, Summit, NJ USA. EM jjacobs@mgh.harvard.edu OI carver, charles/0000-0002-3688-8545 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NCI [R01-CA-064710]; U.S. Government [HHSN261200800001E] FX This project was funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, contract no. HHSN261200800001E and NCI grant R01-CA-064710. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Contract no. HHSN261200800001E provided statistical support and interpretation of data. NR 34 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 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2017 VL 44 BP 16 EP 21 DI 10.1016/j.genhosppsych.2016.10.002 PG 6 WC Psychiatry SC Psychiatry GA EI6TC UT WOS:000392628700004 PM 28041571 ER PT J AU Rundell, JR Huffman, JC AF Rundell, James R. Huffman, Jeff C. TI The COMPASS initiative: implementing a complex integrated care program SO GENERAL HOSPITAL PSYCHIATRY LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; IMPROVING PRIMARY-CARE; COLLABORATIVE CARE; CHRONIC ILLNESS; HEART-FAILURE; DEPRESSION; MANAGEMENT; INTERVENTION; OUTCOMES; HEALTH C1 [Rundell, James R.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Huffman, Jeff C.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jhuffman@partners.org NR 20 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD JAN-FEB PY 2017 VL 44 BP 67 EP 68 DI 10.1016/j.genhosppsych.2016.06.007 PG 2 WC Psychiatry SC Psychiatry GA EI6TC UT WOS:000392628700011 PM 27422084 ER PT J AU Trobaugh-Lotrario, AD Meyers, RL O'Neill, AF Feusner, JH AF Trobaugh-Lotrario, Angela D. Meyers, Rebecka L. O'Neill, Allison F. Feusner, James H. TI Unresectable hepatoblastoma: current perspectives SO Hepatic Medicine-Evidence and Research LA English DT Review DE hepatoblastoma; unresectable; pediatric ID INTENSITY FOCUSED ULTRASOUND; RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; LIVER-TRANSPLANTATION; SURGICAL RESECTION; TRANSARTERIAL CHEMOEMBOLIZATION; RISK HEPATOBLASTOMA; DRUG-RESISTANCE; ONCOLOGY-GROUP; CHILDREN AB Although rare, hepatoblastoma is the most common pediatric liver tumor. Complete resection is a critical component for cure; however, most patients will have tumors that are not resected at diagnosis. For these patients, administration of neoadjuvant chemotherapy renders tumors resectable in most patients. For patients whose tumors remain unresectable after chemotherapy, liver transplantation is indicated (in the absence of active unresectable metastatic disease). In patients whose tumors remain unresectable after conventional chemotherapy, interventional techniques may serve as a promising option to reduce tumor size, decrease systemic toxicity, decrease need for liver transplantation, and increase feasibility of tumor resection. C1 [Trobaugh-Lotrario, Angela D.] Providence Sacred Heart Childrens Hosp, Dept Pediat Hematol & Oncol, 101 West 8th Ave, Spokane, WA 99204 USA. [Meyers, Rebecka L.] Univ Utah, Primary Childrens Hosp, Salt Lake City, UT USA. [O'Neill, Allison F.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Neill, Allison F.] Harvard Univ, Boston, MA 02115 USA. [Feusner, James H.] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. RP Trobaugh-Lotrario, AD (reprint author), Providence Sacred Heart Childrens Hosp, Dept Pediat Hematol & Oncol, 101 West 8th Ave, Spokane, WA 99204 USA. EM angela.trobaugh@providence.org NR 49 TC 0 Z9 0 U1 1 U2 1 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1535 J9 HEPATIC MED-EVID RES JI HEPATIC MED.-EVID. RES. PY 2017 VL 9 BP 1 EP 6 DI 10.2147/HMER.S89997 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EJ5EF UT WOS:000393238600001 PM 28203111 ER PT J AU Nielsen, CS Gromov, K Jans, O Troelsen, A Husted, H AF Nielsen, Christian Skovgaard Gromov, Kirill Jans, Oivind Troelsen, Anders Husted, Henrik TI No Effect of a Bipolar Sealer on Total Blood Loss or Blood Transfusion in Nonseptic Revision Knee Arthroplasty-A Prospective Study With Matched Retrospective Controls SO JOURNAL OF ARTHROPLASTY LA English DT Article DE Aquamantys; bipolar sealer; revision knee arthroplasty; blood loss; blood transfusion ID INTRAVENOUS TRANEXAMIC ACID; CONTROLLED-TRIAL; TOURNIQUET USE; DOUBLE-BLIND; TOTAL HIP; METAANALYSIS; REPLACEMENT; MANAGEMENT; DRAINAGE; RECOVERY AB Background: Postoperative anemia is frequent after revision of total knee arthroplasty (TKA) with reported transfusion rates up to 83%. Despite increased efforts of reducing blood loss and enhancing fast recovery within the fast-track setup, a considerable transfusion rate is still evident. The aim of this study was therefore to evaluate the effect of a bipolar sealer on blood loss and transfusion in revision TKA. Methods: In this single-center prospective cohort study with retrospective controls, 51 patients were enrolled in a fast-track setup for revision TKA without the use of a tourniquet. Twenty-five prospectively enrolled patients received treatment with both a bipolar sealer and electrocautery, whereas 26 patients had received treatment with a conventional electrocautery only in the retrospective group. Results: No significant differences were found neither for calculated blood loss, with 1397 (standard deviation, +/- 452) mL in the bipolar sealer group vs 1452 (SD, +/- 530) mL in the control group (P = .66), nor for blood transfusion rates of 53% and 46% (P = .89), respectively. Four controls were readmitted within 90 days follow-up. Conclusion: The use of a bipolar sealer in a TKA revision setting without the use of a tourniquet did not reduce blood loss or blood transfusion rates. (C) 2016 Elsevier Inc. All rights reserved. C1 [Nielsen, Christian Skovgaard; Gromov, Kirill; Troelsen, Anders; Husted, Henrik] Copenhagen Univ Hosp, Dept Orthoped Surg, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark. [Nielsen, Christian Skovgaard] Massachusetts Gen Hosp, Harris Orthoped Lab, Dept Orthoped, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. [Jans, Oivind] Rigshosp, Copenhagen Univ Hosp, Sect Surg Pathophysiol, Copenhagen, Denmark. RP Nielsen, CS (reprint author), Copenhagen Univ Hosp, Dept Orthoped Surg, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.; Nielsen, CS (reprint author), Massachusetts Gen Hosp, Harris Orthoped Lab, Dept Orthoped, 55 Fruit St,GRJ 1126, Boston, MA 02114 USA. NR 41 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 JAN PY 2017 VL 32 IS 1 BP 177 EP 182 DI 10.1016/j.arth.2016.06.037 PG 6 WC Orthopedics SC Orthopedics GA EI6RG UT WOS:000392623000033 PM 27554781 ER PT J AU Laaksonen, I Donahue, GS Madanat, R Makela, KT Malchau, H AF Laaksonen, Inari Donahue, Gabrielle S. Madanat, Rami Makela, Keijo T. Malchau, Henrik TI Outcomes of the Recalled Articular Surface Replacement Metal-on-Metal Hip Implant System: A Systematic Review SO JOURNAL OF ARTHROPLASTY LA English DT Review DE articular surface replacement; total hip arthroplasty; hip resurfacing arthroplasty; systematic review; metal-on-metal ID FINNISH ARTHROPLASTY REGISTER; DIAMETER TOTAL HIP; ION LEVELS; RESURFACING ARTHROPLASTY; FOLLOW-UP; ACETABULAR INCLINATION; ADVERSE-REACTION; ASR; COMPONENT; REVISION AB Background: The aim of this review was to synthesize the main findings of clinical studies that have evaluated outcomes of the articular surface replacement (ASR) Hip System. Methods: We performed a systematic literature search to identify all articles published between January 2008 and June 2015 that included ASR hip resurfacing arthroplasty (ASR HRA) or ASR total hip arthroplasty (ASR XL THA) outcomes according to the PRISMA statement. Results: A total of 56 studies were assessed. The prevalence of adverse local tissue reactions (ALTRs) and revision rates were found to be high. ALTR prevalence varied from 12.5% to 69% (mean, 33.5%). Mean revision rate for any reason at 4-year to 7-year follow-up was 13.8% (range, 5.6%-31%) for ASR HRA and 14.5% (range, 0%-37%) for ASR XL THA. Femoral head size <53 mm was found to correlate with higher blood metal ion levels. Femoral head size >44 mm was not associated with higher ALTR prevalence or revision rates in ASR XL THA. High blood metal ion levels (>7 mu g/L Co, >7 mu g/L Cr) were associated with higher failure rates and bearing-related complications. The role of cup positioning was found to be controversial. Conclusion: ALTR prevalence and failure rates were high. High blood metal ion levels were a risk factor for ALTR and failure. Surprisingly, the role of cup positioning and large femoral head size in ASR XL THA were controversial. These findings should be considered in the clinical follow-up and risk stratification of patients with the ASR Hip System. (C) 2016 Elsevier Inc. All rights reserved. C1 [Laaksonen, Inari; Makela, Keijo T.] Turku Univ Hosp, Dept Orthoped & Traumatol, Luolavuorentie 2, Turku 20700, Finland. [Donahue, Gabrielle S.; Madanat, Rami; Malchau, Henrik] Massachusetts Gen Hosp, Harris Orthopaed Lab, Boston, MA 02114 USA. [Madanat, Rami; Malchau, Henrik] Harvard Med Sch, Dept Orthopaed Surg, Boston, MA USA. RP Laaksonen, I (reprint author), Turku Univ Hosp, Dept Orthoped & Traumatol, Luolavuorentie 2, Turku 20700, Finland. FU Orion-Farmos Research Foundation; Jane and Aatos Erkko Foundation FX RM received research support from the Orion-Farmos Research Foundation and the Jane and Aatos Erkko Foundation. NR 64 TC 0 Z9 0 U1 2 U2 2 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 JAN PY 2017 VL 32 IS 1 BP 341 EP 346 DI 10.1016/j.arth.2016.06.060 PG 6 WC Orthopedics SC Orthopedics GA EI6RG UT WOS:000392623000063 PM 27546469 ER PT J AU Beg, JM Anderson, TD Francis, K Meckley, LM Fitzhenry, D Foster, T Sukhtankar, S Kanes, SJ Moura, LMVR AF Beg, Jamil M. Anderson, Thomas D. Francis, Kevin Meckley, Lisa M. Fitzhenry, David Foster, Todd Sukhtankar, Susheel Kanes, Stephen J. Moura, Lidia M. V. R. TI Burden of illness for super-refractory status epilepticus patients SO JOURNAL OF MEDICAL ECONOMICS LA English DT Article DE Epilepsy; Super-refractory status epilepticus; Cost; Resource utilization; Burden of illness; Hospitalization ID CONVULSIVE STATUS EPILEPTICUS; INTENSIVE-CARE-UNIT; ADMINISTRATIVE DATA; SUBARACHNOID HEMORRHAGE; MEDICARE BENEFICIARIES; CASE-DEFINITION; HEALTH DATA; WEST CHINA; ICD CODES; EPILEPSY AB Objective: To provide an estimate of the annual number of super-refractory status epilepticus (SRSE) cases in the US and to evaluate utilization of hospital resources by these patients. Methods: The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure-related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.g. benzodiazepines, anti-epileptic drugs (AEDs), and ventilator use). Secondary analyses were conducted using more restrictive algorithms for SRSE. Results: A total of 6,325 hospital discharges were classified as SRSE cases from a total of 5,300,000 hospital discharges. Applying a weighting based on hospital characteristics and 2012US demographics, this projected to an estimated 41,156 cases of SRSE in the US during 2012, an estimated incidence rate of similar to 13/100,000 annually for SRSE in the US. Secondary analyses using stricter SRSE algorithms resulted in estimated incidence rates of similar to 11/100,000 and 8/100,000 annually. The mean LOS for SRSE hospitalizations was 16.5 days (median =11; interquartile range [IQR]=6-20), and the mean ICU LOS was 9.3 days (median =6; IQR =3-12). The mean cost of an SRSE hospitalization was $51,247 (median = $33,294; 95% CI = $49,634-$52,861). Limitations: The analysis uses ICD-9 diagnostic codes and claims information, and there are inherent limitations in any methodology based on treatment protocol, which created challenges in distinguishing with complete accuracy between SRSE, RSE, and SE on the basis of care patterns in the database. Conclusion: SRSE is associated with high mortality and morbidity, which place a high burden on healthcare resources. Projections based upon the findings of this study suggest an estimated 25,821-41,959 cases of SRSE may occur in the US each year, but more in-depth studies are required. C1 [Beg, Jamil M.; Anderson, Thomas D.; Kanes, Stephen J.] Sage Therapeut Inc, 215 First St, Cambridge, MA 02142 USA. [Francis, Kevin; Meckley, Lisa M.; Fitzhenry, David; Foster, Todd; Sukhtankar, Susheel] Trinity Partners, Waltham, MA USA. [Moura, Lidia M. V. R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM jamil@sagerx.com FU Sage Therapeutics, Inc. FX This study was supported by Sage Therapeutics, Inc. NR 52 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1369-6998 EI 1941-837X J9 J MED ECON JI J. Med. Econ. PY 2017 VL 20 IS 1 BP 45 EP 53 DI 10.1080/13696998.2016.1223680 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA EI6SW UT WOS:000392628100006 PM 27556834 ER PT J AU Lee, DJ Weathers, FW Sloan, DM Davis, MT Domino, JL AF Lee, Daniel J. Weathers, Frank W. Sloan, Denise M. Davis, Margaret T. Domino, Jessica L. TI Development and Initial Psychometric Evaluation of the Semi-Structured Emotion Regulation Interview SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID POSTTRAUMATIC STRESS SYMPTOMS; EXPERIENTIAL AVOIDANCE; REGULATION DIFFICULTIES; INDIVIDUAL-DIFFERENCES; THOUGHT SUPPRESSION; DISORDERS; QUESTIONNAIRE; DEPRESSION; STRATEGIES; INVENTORY AB Emotion regulation (ER) strategy use has been identified as a transdiagnostic predictor of the development, maintenance, and recovery from several forms of psychopathology. However, the ER strategy use literature relies primarily on self-report measures that have several important limitations. This article describes the development and initial psychometric evaluation of a novel clinician-administered measure of ER strategy use, the Semi-Structured Emotion Regulation Interview (SERI; Lee, Weathers, & Sloan, 2016). The SERI was developed in a construct validation framework with emphasis on a multistage content validity process. The SERI assesses frequency and efficacy (i.e., proximal change in the targeted emotion) of 9 strategies in regulation of a specified emotion type and intensity (e.g., severe anxiety) during the past 30 days. Undergraduates (N = 68) completed a battery of self-report measures and a subsequent interview. Frequency and efficacy of each strategy was assessed separately with respect to regulation of moderate and severe anxiety and anger. Each of the assessed strategies demonstrated excellent discriminant validity. Associations between SERI and self-report measures of ER strategy use varied by target emotion type and intensity for some strategies, but not others. Implications and suggestions for future research are described. C1 [Lee, Daniel J.; Weathers, Frank W.; Davis, Margaret T.; Domino, Jessica L.] Auburn Univ, Dept Psychol, Thach Hall, Auburn, AL 36849 USA. [Sloan, Denise M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Sloan, Denise M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. EM dannylee@auburn.edu NR 37 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0022-3891 EI 1532-7752 J9 J PERS ASSESS JI J. Pers. Assess. PY 2017 VL 99 IS 1 BP 56 EP 66 DI 10.1080/00223891.2016.1215992 PG 11 WC Psychology, Clinical; Psychology, Social SC Psychology GA EI6SU UT WOS:000392627900006 PM 27564399 ER PT J AU Chudnovsky, AA Koutrakis, P Kostinski, A Proctor, SP Garshick, E AF Chudnovsky, A. Alexandra Koutrakis, Petros Kostinski, Alex Proctor, Susan P. Garshick, Eric TI Spatial and temporal variability in desert dust and anthropogenic pollution in Iraq, 1997-2010 SO JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION LA English DT Article ID AEROSOL OPTICAL DEPTH; FINE PARTICULATE MATTER; OZONE MONITORING INSTRUMENT; DAILY EMERGENCY ADMISSIONS; STORM EVENTS; HOSPITAL ADMISSIONS; AIR-POLLUTION; RESPIRATORY SYMPTOMS; PM2.5 CONCENTRATIONS; EXPOSURE ASSESSMENT AB Satellite imaging has emerged as a method for monitoring regional air pollution and detecting areas of high dust concentrations. Unlike ground observations, continuous data monitoring is available with global coverage of terrestrial and atmospheric components. In this study we test the utility of different sources of satellite data to assess air pollution concentrations in Iraq. SeaWiFS and MODIS Deep Blue (DB) aerosol optical depth (AOD) products were evaluated and used to characterize the spatial and temporal pollution levels from the late 1990s through 2010. The AOD and Angstrom exponent (an indicator of particle size, since smaller Angstrom exponent values reflect a source that includes larger particles) were correlated on 50 x 50 km spatial resolution. Generally, AOD and Angstrom exponent were inversely correlated, suggesting a significant contribution of coarse particles from dust storms to AOD maxima. Although the majority of grid cells exhibited this trend, a weaker relationship in other locations suggested an additional contribution of fine particles from anthropogenic sources. Tropospheric NO2 densities from the OMI satellite were elevated over cities, also consistent with a contribution from anthropogenic sources. Our analysis demonstrates the use of satellite imaging data to estimate relative pollution levels and source contributions in areas of the world where direct measurements are not available. Implications: The authors demonstrated how satellite data can be used to characterize exposures to dust and to anthropogenic pollution for future health related studies. This approach is of a great potential to investigate the associations between subject-specific exposures to different pollution sources and their health effects in inaccessible regions and areas where ground monitoring is unavailable. C1 [Chudnovsky, A. Alexandra] Tel Aviv Univ, Dept Geog & Human Environm, Tel Aviv, Israel. [Chudnovsky, A. Alexandra; Koutrakis, Petros] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Kostinski, Alex] Michigan Technol Univ, Houghton, MI 49931 USA. [Proctor, Susan P.] US Army Res Inst Environm Med, Mil Performance Div, Natick, MA USA. [Proctor, Susan P.] Boston Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Proctor, Susan P.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm Allergy Sleep & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. EM achudnov@hsph.harvard.edu FU U.S. Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development, Cooperative Studies Program, U.S. Environmental Protection Agency (EPA) grant [RD 83479801]; National Science Foundation [AGS-111916] FX This work is supported by the U.S. Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development, Cooperative Studies Program, U.S. Environmental Protection Agency (EPA) grant RD 83479801, and National Science Foundation Grant AGS-111916. Its contents are solely the responsibility of the authors and do not represent the official views of the EPA, U.S. Department of Veterans Affairs, or the U.S. Department of Defense/Army. Further, EPA, U.S. Department of Veterans Affairs, and the U.S. Department of Defense/Army do not endorse the purchase of any commercial products or services mentioned in the publication. NR 69 TC 1 Z9 1 U1 5 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1096-2247 EI 2162-2906 J9 J AIR WASTE MANAGE JI J. Air Waste Manage. Assoc. PY 2017 VL 67 IS 1 BP 17 EP 26 DI 10.1080/10962247.2016.1153528 PG 10 WC Engineering, Environmental; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA EI7ED UT WOS:000392659700003 PM 28001122 ER PT J AU Masri, S Garshick, E Hart, J Bouhamra, W Koutrakis, P AF Masri, Shahir Garshick, Eric Hart, Jaime Bouhamra, Walid Koutrakis, Petros TI Use of visual range measurements to predict fine particulate matter exposures in Southwest Asia and Afghanistan SO JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION LA English DT Article ID AMBIENT AIR-POLLUTION; RESPIRATORY SYMPTOMS; LUNG-FUNCTION; MILITARY PERSONNEL; MASS CONCENTRATION; PARTICLE MASS; ADULT ASTHMA; VISIBILITY; DEPLOYMENT; AEROSOL AB Military personnel deployed to Southwest Asia and Afghanistan were exposed to high levels of ambient particulate matter (PM). However, quantitative ambient exposure data for conducting health studies are limited due to a lack of PM monitoring stations. Since visual range (VR) is proportional to particle light extinction, VR can serve as a surrogate for PM2.5 (particulate matter with an aerodynamic diameter <= 2.5 mu m) concentrations. We used data on VR, relative humidity (RH), and PM2.5 ground measurements collected in Kuwait from years 2004-2005 to establish the relationship between PM2.5 and VR. Model validation obtained by regressing trimester average PM2.5 predictions against PM2.5 measurements in Kuwait produced an r(2) value of 0.84. Cross validation of urban and rural sites in Kuwait also revealed good model fit. We applied this relationship to location-specific visibility data at 104 regional sites between years 2000-2012 to estimate monthly average PM2.5 concentrations. Monthly averages at sites in Iraq, Afghanistan, United Arab Emirates, Kuwait, Djibouti, and Qatar ranged from 10 to 365 mu g/m(3) during this period, while site averages ranged from 22 to 80 mu g/m(3), indicating considerable spatial and temporal heterogeneity in ambient PM2.5 across these regions. These data support the use of historical visibility data to estimate location-specific PM2.5 concentrations for application in epidemiological studies. Implications: This study demonstrates the ability to use airport visibility to estimate PM2.5 concentrations in Southwest Asian and Afghanistan. This supports the use of historical and ongoing visibility data to estimate PM2.5 exposure in this region of the world, where PM exposure information is otherwise scarce. This is of high utility to epidemiologists investigating the relationship between chronic exposure to PM2.5 and respiratory diseases among deployed military personnel stationed at various military bases throughout the region. Such information will enable the drafting of improved policies relating to military health. C1 [Masri, Shahir; Koutrakis, Petros] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr West,Room 412-E 401 Pk Dr, Boston, MA 02215 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm Allergy Sleep & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric; Hart, Jaime] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Dept Med, Boston, MA USA. [Bouhamra, Walid] Kuwait Univ, Coll Engn & Petr, Dept Chem Engn, Kuwait, Kuwait. EM shahirmasri@mail.harvard.edu FU United States (U.S.) Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development, Cooperative Studies Program [595]; U.S. Environmental Protection Agency (EPA) [RD-83479801] FX This work was supported by the VA Cooperative Studies Program #595: Respiratory Health and Deployment to Iraq and Afghanistan, from the United States (U.S.) Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development, Cooperative Studies Program. This publication was also made possible by U.S. Environmental Protection Agency (EPA) grant RD-83479801. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the EPA, U.S. Department of Veterans Affairs, or U.S. Government. NR 40 TC 2 Z9 2 U1 4 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1096-2247 EI 2162-2906 J9 J AIR WASTE MANAGE JI J. Air Waste Manage. Assoc. PY 2017 VL 67 IS 1 BP 75 EP 85 DI 10.1080/10962247.2016.1243169 PG 11 WC Engineering, Environmental; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA EI7ED UT WOS:000392659700009 PM 27700621 ER PT J AU Masri, S Garshick, E Coull, BA Koutrakis, P AF Masri, Shahir Garshick, Eric Coull, Brent A. Koutrakis, Petros TI A novel calibration approach using satellite and visibility observations to estimate fine particulate matter exposures in Southwest Asia and Afghanistan SO JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION LA English DT Article ID AEROSOL OPTICAL DEPTH; RESPIRATORY SYMPTOMS; PM2.5 CONCENTRATIONS; MILITARY PERSONNEL; MASS CONCENTRATION; NURSES HEALTH; DEPLOYMENT; IRAQ; AIR; SOLDIERS AB In order to study effects of ambient particulate matter (PM) it was previously necessary to have access to a comprehensive air monitoring network. However, there are locations in the world where PM levels are above generally accepted exposure standards but lack a monitoring infrastructure. This is true in Iraq and other locations in Southwest Asia and Afghanistan where U.S. and other coalition troops were deployed beginning in 2001. Since aerosol optical depth (AOD), determined by satellite, and visibility are both highly related to atmospheric PM2.5 (particulate matter with an aerodynamic diameter <= 2.5 mu m) concentrations, we employed a novel approach that took advantage of historic airport visibility measurements to calibrate the AOD-visibility relationship and determine visibility spatially and temporally (2006-2007) over an approximately 17,000 km(2) region of Iraq. We obtained daily visibility predictions that were highly associated with satellite-based 1x1 km AOD daily observations (R-2=0.87). Based on a previously derived calibration between PM2.5 and visibility, we were able to predict spatially and temporally resolved PM2.5 concentrations. Variability of PM2.5 among sites was high, with daily concentrations differing by as much as similar to 30 mu g/m3. This study demonstrates the feasibility of characterizing historic PM2.5 exposures in Iraq and other locations in Southwest Asia and Afghanistan with similar climate characteristics. This is of utility for epidemiologists seeking to assess the potential health effects related to PM2.5 exposures among previously deployed military personnel and of the population of the region. Implications: This study demonstrates the ability to utilize aerosol optical depth to successfully estimate visibility spatially and temporally in Southwest Asia and Afghanistan. This enables for the estimation of spatially resolved PM2.5 concentrations in the region. The ability to caracterize PM2.5 concentrations in Southwest Asia and Afghanistan is highly important for epidemiologists investigating the relationship between chronic exposure to PM2.5 and respiratory diseases among military personnel deployed to the region. This information will better position policy makers to draft meaningful legislation relating to military health. C1 [Masri, Shahir; Koutrakis, Petros] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm Allergy Sleep & Crit Care Med Sect, Boston, MA USA. [Garshick, Eric] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Masri, S (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Landmark Ctr West,Room 412-E 401 Pk Dr, Boston, MA 02215 USA. EM shahirmasri@mail.harvard.edu FU U.S. Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development, Cooperative Studies Program [595]; U.S. Environmental Protection Agency (EPA) [RD-83479801] FX This work was supported by the VA Cooperative Studies Program No. 595: Pulmonary Health and Deployment to Southwest Asia and Afghanistan, from the U.S. Department of Veterans Affairs, Office of Research and Development, Clinical Science Research and Development, Cooperative Studies Program. This publication was also made possible by U.S. Environmental Protection Agency (EPA) grant RD-83479801. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the EPA, U.S. Department of Veterans Affairs, or U.S. Government. NR 31 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1096-2247 EI 2162-2906 J9 J AIR WASTE MANAGE JI J. Air Waste Manage. Assoc. PY 2017 VL 67 IS 1 BP 86 EP 95 DI 10.1080/10962247.2016.1230079 PG 10 WC Engineering, Environmental; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA EI7ED UT WOS:000392659700010 PM 27649895 ER PT J AU Zanobetti, A Coull, BA Kloog, I Sparrow, D Vokonas, PS Gold, DR Schwartz, J AF Zanobetti, Antonella Coull, Brent A. Kloog, Itai Sparrow, David Vokonas, Pantel S. Gold, Diane R. Schwartz, Joel TI Fine-scale spatial and temporal variation in temperature and arrhythmia episodes in the VA Normative Aging Study SO JOURNAL OF THE AIR & WASTE MANAGEMENT ASSOCIATION LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; POTENTIALLY SUSCEPTIBLE INDIVIDUALS; CORONARY-ARTERY-DISEASE; AIR-TEMPERATURE; OUTDOOR TEMPERATURE; AMBIENT-TEMPERATURE; MORTALITY ASSOCIATION; PARTICULATE MATTER; BLOOD-PRESSURE; WEATHER AB Many studies have demonstrated that cold and hot temperatures are associated with increased deaths and hospitalization rates; new findings indicate also an association with more specific cardiac risk factors. Most of these existing studies have relied on few weather stations to characterize exposures; few have used residence-specific estimates of temperature, or examined the exposure-response function. We investigated the association of arrhythmia episodes with spatial and temporal variation in temperature. We also evaluated the association btween monitored ambient temperature (central) and the same outcome. This longitudinal analysis included 701 older men participating in the VA Normative Aging Study. Arrhythmia episodes were measured as ventricular ectopy (VE) (bigeminy, trigeminy, or couplets episodes) by 4-min electrocardiogram (ECG) monitoring in repeated visits during 2000-2010. The outcome was defined as having or not VE episodes during a study visit. We applied a mixed-effect logistic regression model with a random intercept for subject, controlling for seasonality, weekday, medication use, smoking, diabetes status, body mass index, and age. We also examined effect modification by personal characteristics, confounding by air pollution, and the exposure-response function. For 1 degrees C increase in the same day residence-specific temperature, the odds of having VE episodes was 1.10 (95% confidence interval [CI]: 1.04-1.17). The odds associated with 1 degrees C increase in central temperature was 1.05 (95% CI: 1.02-1.09). The exposure-response function was nonlinear for averages of temperature, presenting a J-shaped pattern, suggesting greater risk at lower and higher temperatures. Increased warm temperature and decreased cold temperature may increase the risk of ventricular arrhythmias. Implications: This is the first study to provide evidence that residence-specific temperature exposure is associated with increased risk of ventricular arrhythmias in cohort of elderly subjects without known chronic medical conditions; that the delayed effect of temperature has a nonlinear relationship; and therefore that both warm and cold temperature increase the risk of having ventricular arrhythmias. Moreover, we show that the use of residence-specific temperature data reduces downward bias due to exposure error, by comparing the estimated health effect based on our spatiotemporal exposure prediction model to those based on a single local weather monitor. C1 [Zanobetti, Antonella; Kloog, Itai; Gold, Diane R.; Schwartz, Joel] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Kloog, Itai] Ben Gurion Univ Negev, Dept Geog & Environm Dev, Beer Sheva, Israel. [Sparrow, David; Vokonas, Pantel S.] VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. [Sparrow, David; Vokonas, Pantel S.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Gold, Diane R.] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. EM azanobet@hsph.harvard.edu FU National Institute of Aging [R21 AG040027-01]; National Institute of Environmental Health Sciences [P01 ES009825, P30 ES000002, R21 ES020194-01, R21ES024012]; U.S. Environmental Protection Agency [RD-83241601, RD-83479801]; VA Research Career Scientist award; Cooperative Studies Program/Epidemiology Research and Information Centers of the U.S. Department of Veterans Affairs FX This work was supported by the National Institute of Aging, R21 AG040027-01, the National Institute of Environmental Health Sciences, P01 ES009825, P30 ES000002, R21 ES020194-01, and R21ES024012, and by the U.S. Environmental Protection Agency, RD-83241601 and RD-83479801. Its contents are solely the responsibility of the grantee and do not necessarily represent the official views of the EPA. Further, the EPA does not endorse the purchase of any commercial products or services mentioned in the publication. This study was also supported by a VA Research Career Scientist award to David Sparrow. The Veterans Administration's Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Centers of the U.S. Department of Veterans Affairs and is a component of the Massachusetts Veterans Epidemiology Research and Information Center, Boston, MA. NR 46 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1096-2247 EI 2162-2906 J9 J AIR WASTE MANAGE JI J. Air Waste Manage. Assoc. PY 2017 VL 67 IS 1 BP 96 EP 104 DI 10.1080/10962247.2016.1252808 PG 9 WC Engineering, Environmental; Environmental Sciences; Meteorology & Atmospheric Sciences SC Engineering; Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA EI7ED UT WOS:000392659700011 PM 28001123 ER PT J AU Towey, C Easton, C Simpson, R Pedlar, C AF Towey, Colin Easton, Chris Simpson, Robert Pedlar, Charles TI Conventional and novel body temperature measurement during rest and exercise induced hyperthermia SO JOURNAL OF THERMAL BIOLOGY LA English DT Article DE Core temperature; Moderate exercise; Hyperthermia ID CORE TEMPERATURE; HEAT-STRESS; INTESTINAL TEMPERATURE; RECTAL TEMPERATURES; ANAEROBIC THRESHOLD; TELEMETRY PILL; VALIDITY; RELIABILITY; DEVICES; SKIN AB Despite technological advances in thermal sensory equipment, few core temperature (T-CORE) measurement techniques have met the established validity criteria in exercise science. Additionally, there is debate as to what method serves as the most practically viable, yet upholds the proposed measurement accuracy. This study assessed the accuracy of current and novel T-CORE measurement techniques in comparison to rectal temperature (T-REC) as a reference standard. Fifteen well-trained subjects (11 male, 4 female) completed 60 min of exercise at an intensity equating to the lactate threshold; measured via a discontinuous exercise test. T-REC was significantly elevated from resting values (37.2 +/- 0.3 degrees C) at the end of moderate intensity exercise (39.6 +/- 0.04 degrees C; P=0.001). Intestinal telemetric pill (TNPILL) temperature and temporal artery temperature (T-TEM) did not differ significantly from T-REC at rest or during exercise (P > 0.05). However, aural canal temperature (T-AUR) and thermal imaging temperature (T-IMA) Were both significantly lower than Tanc (P < 0.05). Bland Altman analysis revealed only T-PILL was within acceptable limits of agreement (mean bias; 0.04 degrees C), while T-TEM, T-AUR and T-IMA demonstrated mean bias values outside of the acceptable range ( > 0.27 degrees C). Against T-REC, these results support the use of T-PILL over all other techniques as a valid measure of T-CORE at rest and during exercise induced hyperthermia. Novel findings illustrate that T-IMA (when measured at the inner eye canthus) shows poor agreement to T-REC during rest and exercise, which is similar to other 'surface' measures. C1 [Towey, Colin; Pedlar, Charles] St Marys Univ, Sch Sport Hlth & Appl Sci, Twickenham, England. [Pedlar, Charles] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Simpson, Robert] Natl Phys Lab, Teddington, Middx, England. [Easton, Chris] Univ West Scotland, Inst Clin Exercise & Hlth Sci, Hamilton, Scotland. RP Towey, C (reprint author), St Marys Univ, Sch Sport Hlth & Appl Sci, Twickenham, England. EM colin.towey@stmarys.ac.uk; Chris.Easton@uws.ac.uk; rob.simpson@npl.co.uk; charles.pedlar@stmarys.ac.uk NR 43 TC 0 Z9 0 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4565 J9 J THERM BIOL JI J. Therm. Biol. PD JAN PY 2017 VL 63 BP 124 EP 130 DI 10.1016/j.jtherbio.2016.11.010 PG 7 WC Biology; Zoology SC Life Sciences & Biomedicine - Other Topics; Zoology GA EI7NZ UT WOS:000392686200016 PM 28010810 ER PT J AU Kwak, PE Stasney, CR Hathway, JR Guffey, D Minard, CG Ongkasuwan, J AF Kwak, Paul E. Stasney, C. Richard Hathway, Jeremy R. Guffey, Danielle Minard, Charles G. Ongkasuwan, Julina TI Physiologic and Acoustic Effects of Opera Performance SO JOURNAL OF VOICE LA English DT Article; Proceedings Paper CT Annual Spring Meeting of the American-Laryngological-Association (ALA) at COSM CY MAY 15, 2014 CL Las Vegas, NV SP Amer Laryngol Assoc DE Professional voice; Stroboscopy; Acoustic measures of voice; Opera; Vocal performance ID VOCAL FOLD; SINGERS AB Introduction/Hypothesis. Opera performance is physiological and emotional, and singing performers utilize their larynges in often strenuous ways. Historically, the training of a classical voice has been considered the paragon of healthy singing. However, the natural history of a performing larynx has not been studied systematically. There is paucity of scientific studies to guide practice patterns, particularly with regard to the course and extent of post-performance physiologic and acoustic changes. Study Design. A prospective case series was carried out. Methods. Principal singers in the Houston Grand Opera's 2012-2013 repertory were enlisted, for a total of seven singers. Stroboscopy was performed prior to the start of rehearsals, and at the completion of the opera's run. Data points included erythema, edema, masses or lesions, mucosal waveform, supraglottic posture; acoustic measurements were also performed. Results. There were statistically significant differences (P < 0.05) in the mucosal wave on pre- and postperformance stroboscopic examinations. Acoustical measures did not achieve statistical significance, but there was a trend toward increased harmonic-to-noise ratio in postperformance measures, as well as decreased frequency range and reading F-0. Measures of intra- and inter-rater reliability indicated varying levels of intra- rater reliability, and generally poor inter-rater reliability. Conclusions. This pilot study describes physiologic and acoustic changes that may occur over the course of a series of rehearsals and performances in the operatic larynx. In so doing, it highlights a need for larger studies with increased frequency of serial examinations to study in a systematized way what may be natural reactive changes that occur during performance. C1 [Kwak, Paul E.] Harvard Med Sch, Massachusetts Gen Hosp, Div Laryngeal Surg, Boston, MA USA. [Stasney, C. Richard; Hathway, Jeremy R.] Houston Methodist Hosp, Texas Voice Ctr, Houston, TX USA. [Guffey, Danielle; Minard, Charles G.] Baylor Coll Med, Dan L Duncan Inst Clin & Translat Res, Houston, TX 77030 USA. [Ongkasuwan, Julina] Baylor Coll Med, Bobby R Alford Dept Otolaryngol Head & Neck Surg, Houston, TX 77030 USA. EM pkwak@partners.org OI Guffey, Danielle/0000-0003-3721-614X; Minard, Charles/0000-0003-4631-6943; Kwak, Paul/0000-0002-3864-9935 NR 10 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 0892-1997 EI 1873-4588 J9 J VOICE JI J. Voice PD JAN PY 2017 VL 31 IS 1 AR UNSP 117.e11 DI 10.1016/j.jvoice.2016.03.004 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA EI6QF UT WOS:000392619900038 PM 27208902 ER PT J AU Moole, H Bechtold, ML Forcione, D Puli, SR AF Moole, Harsha Bechtold, Matthew L. Forcione, David Puli, Srinivas R. TI A meta-analysis and systematic review: Success of endoscopic ultrasound guided biliary stenting in patients with inoperable malignant biliary strictures and a failed ERCP SO MEDICINE LA English DT Review DE endoscopic ultrasound guided biliary drainage; inoperable malignant biliary strictures; meta-analysis and systematic review; percutaneous transhepatic biliary drainage ID TRANS-HEPATIC CHOLANGIOGRAPHY; GROUP DOCUMENT EVALUATION; RANDOMIZED-TRIAL; METAL STENT; BILE-DUCT; OBSTRUCTIVE-JAUNDICE; CLINICAL-TRIALS; DRAINAGE; CHOLEDOCHODUODENOSTOMY; CHOLANGIOPANCREATOGRAPHY AB Background: In patients with inoperable malignant biliary strictures, endoscopic retrograde cholangiopancreatography (ERCP) guided biliary stenting fails in 5% to 10% patients due to difficult anatomy/inability to cannulate the papilla. Recently, endoscopic ultrasound guided biliary drainage (EUS-BD) has been described. Primary outcomes were to evaluate the biliary drainage success rates with EUS and compare it to percutaneous transhepatic biliary drainage (PTBD). Secondary outcomes were to evaluate overall procedure related complications. Methods: Study selection criteria: Studies evaluating the efficacy of EUS-BD and comparing EUS-BD versus PTBD in inoperable malignant biliary stricture patients with a failed ERCP were included in this analysis. Data collection and extraction: Articles were searched in Medline, PubMed, and Ovid journals. Two authors independently searched and extracted data. The study design was written in accordance to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Subgroup analyses of prospective studies and EUS-BD versus PTBD were performed. Statistical method: Pooled proportions were calculated using fixed and random effects model. I2 statistic was used to assess heterogeneity among studies. Results: Initial search identified 846 reference articles, of which 124 were selected and reviewed. Sixteen studies (N= 528) that met the inclusion criteria were included in this analysis. In the pooled patient population, the percentage of patients that had a successful biliary drainage with EUS was 90.91% (95% CI= 88.10-93.38). The proportion of patients that had overall procedure related complications with EUS-PD was 16.46% (95% CI= 13.20-20.01). The pooled odds ratio for successful biliary drainage in EUS-PD versus PTBD group was 3.06 (95% CI= 1.11-8.43). The risk difference for overall procedure related complications in EUS-PD versus PTBD group was -0.21 (95% CI= -0.35 to -0.06). Relative risk for infectious complications and bile leak in EUS-BD versus PTBD was 0.25 (95% CI= 0.07-0.94) and 0.33 (95% CI= 0.12-0.87), respectively. Conclusions: In patients with inoperable malignant biliary strictures who failed an ERCP guided biliary stenting, EUS-BD seems to be an excellent management option and superior to PTBD with higher successful biliary drainage rates and relatively fewer complications. C1 [Moole, Harsha] Univ Illinois, Coll Med Peoria, Div Gen Internal Med, Peoria, IL USA. [Bechtold, Matthew L.] Univ Missouri, Div Gastroenterol & Hepatol, Columbia, MO USA. [Forcione, David] Harvard Med Sch, Massachusetts Gen Hosp, Gastrointestinal Unit, Intervent Endoscopy Serv, Boston, MA USA. [Puli, Srinivas R.] Univ Illinois, Coll Med Peoria, Div Gastroenterol & Hepatol, Peoria, IL USA. EM harsha1778@yahoo.co.in NR 46 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7974 EI 1536-5964 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2017 VL 96 IS 3 AR e5154 DI 10.1097/MD.0000000000005154 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA EI4TR UT WOS:000392486800001 PM 28099327 ER PT J AU Beroukhim, R Zhang, XY Meyerson, M AF Beroukhim, Rameen Zhang, Xiaoyang Meyerson, Matthew TI Copy number alterations unmasked as enhancer hijackers SO NATURE GENETICS LA English DT Editorial Material ID PROSTATE-CANCER; GENE; NEIGHBORHOODS AB Our understanding of how DNA copy number changes contribute to disease, including cancer, has to a large degree been focused on the changes in gene dosage that they generate and has neglected the effects of the DNA rearrangements that lead to their formation. A new study reports an innovative analytical framework for copy number alterations that are oncogenic primarily owing to the genomic rearrangements that underlie them. C1 [Beroukhim, Rameen; Zhang, Xiaoyang; Meyerson, Matthew] Broad Inst Harvard & MIT, Dana Farber Canc Inst, Boston, MA USA. [Beroukhim, Rameen; Zhang, Xiaoyang; Meyerson, Matthew] Harvard Med Sch, Boston, MA USA. EM matthew_meyerson@dfci.harvard.edu NR 15 TC 0 Z9 0 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 JAN PY 2017 VL 49 IS 1 BP 5 EP 6 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA EG3WY UT WOS:000390976600003 ER PT J AU Dunford, A Weinstock, DM Savova, V Schumacher, SE Cleary, JP Yoda, A Sullivan, TJ Hess, JM Gimelbrant, AA Beroukhim, R Lawrence, MS Getz, G Lane, AA AF Dunford, Andrew Weinstock, David M. Savova, Virginia Schumacher, Steven E. Cleary, John P. Yoda, Akinori Sullivan, Timothy J. Hess, Julian M. Gimelbrant, Alexander A. Beroukhim, Rameen Lawrence, Michael S. Getz, Gad Lane, Andrew A. TI Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias SO NATURE GENETICS LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; H3K27ME3 DEMETHYLASE UTX; CHROMOSOME INACTIVATION; Y-CHROMOSOME; SOMATIC MUTATIONS; MOSAIC LOSS; EXPRESSION; DISPARITIES; DISORDERS; EVOLUTION AB There is a striking and unexplained male predominance across many cancer types. A subset of X-chromosome genes can escape X-inactivation, which would protect females from complete functional loss by a single mutation. To identify putative 'escape from X-inactivation tumor-suppressor' (EXITS) genes, we examined somatic alterations from >4,100 cancers across 21 tumor types for sex bias. Six of 783 non-pseudoautosomal region (PAR) X-chromosome genes (ATRX, CNKSR2, DDX3X, KDM5C, KDM6A, and MAGEC3) harbored loss-of-function mutations more frequently in males (based on a false discovery rate < 0.1), in comparison to zero of 18,055 autosomal and PAR genes (Fisher's exact P < 0.0001). Male-biased mutations in genes that escape X-inactivation were observed in combined analysis across many cancers and in several individual tumor types, suggesting a generalized phenomenon. We conclude that biallelic expression of EXITS genes in females explains a portion of the reduced cancer incidence in females as compared to males across a variety of tumor types. C1 [Dunford, Andrew; Weinstock, David M.; Schumacher, Steven E.; Sullivan, Timothy J.; Hess, Julian M.; Gimelbrant, Alexander A.; Beroukhim, Rameen; Getz, Gad; Lane, Andrew A.] Broad Inst Harvard & MIT, Cambridge, MA USA. [Weinstock, David M.; Cleary, John P.; Yoda, Akinori; Beroukhim, Rameen; Lane, Andrew A.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Savova, Virginia; Schumacher, Steven E.; Gimelbrant, Alexander A.; Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Savova, Virginia; Gimelbrant, Alexander A.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Lawrence, Michael S.; Getz, Gad] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Lawrence, Michael S.; Getz, Gad] Harvard Med Sch, Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. EM andrew_lane@dfci.harvard.edu FU National Cancer Institute [K08CA181340]; American Society of Hematology Scholar Award; V Foundation Scholar Award; Stand Up to Cancer Innovative Research Grant FX The authors thank C. Sievers and B. Bernstein for helpful discussions, Z. Herbert and the Molecular Biology Core Facilities at the Dana-Farber Cancer Institute for assistance with RNA-seq, and T. Golub for facilitating the project. This work was supported by National Cancer Institute grant K08CA181340 (A.A.L.), an American Society of Hematology Scholar Award (A.A.L.), and a V Foundation Scholar Award (A.A.L.). G.G. is the Paul C. Zamecnik, MD, Chair in Oncology at Massachusetts General Hospital. D.M.W. is a Leukemia and Lymphoma Society Scholar and is supported by a Stand Up to Cancer Innovative Research Grant. NR 49 TC 1 Z9 1 U1 5 U2 5 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 JAN PY 2017 VL 49 IS 1 BP 10 EP 16 DI 10.1038/ng.3726 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA EG3WY UT WOS:000390976600006 PM 27869828 ER PT J AU Marshall, CR Marshall, CR Howrigan, DP Merico, D Thiruvahindrapuram, B Wu, WT Greer, DS Antaki, D Shetty, A Holmans, PA Pinto, D Gujral, M Brandler, WM Malhotra, D Wang, ZZ Fajarado, KVF Maile, MS Ripke, S Agartz, I Albus, M Alexander, M Amin, F Atkins, J Bacanu, SA Belliveau, RA Bergen, SE Ertalan, M Bevilacqua, E Bigdeli, TB Black, DW Bruggeman, R Buccola, NG Buckner, RL Bulik-Sullivan, B Byerley, W Cahn, W Cai, GQ Cairns, MJ Campion, D Cantor, RM Carr, VJ Carrera, N Catts, SV Chambert, KD Cheng, W Cloninger, CR Cohen, D Cormican, P Craddock, N Crespo-Facorro, B Crowley, JJ Curtis, D Davidson, M Davis, KL Degenhardt, F Del Favero, J DeLisi, LE Dikeos, D Dinan, T Djurovic, S Donohoe, G Drapeau, E Duan, J Dudbridge, F Eichhammer, P Eriksson, J Escott-Price, V Essioux, L Fanous, AH Farh, KH Farrell, MS Frank, J Franke, L Freedman, R Freimer, NB Friedman, JI Forstner, AJ Fromer, M Genovese, G Georgieva, L Gershon, ES Giegling, I Giusti-Rodriguez, P Godard, S Goldstein, JI Gratten, J de Haan, L Hamshere, ML Hansen, M Hansen, T Haroutunian, V Hartmann, AM Henskens, FA Herms, S Hirschhorn, JN Hoffinann, P Hofman, A Huang, H Ikeda, M Joa, I Kahler, AK Kahn, RS Kalaydjieva, L Karjalainen, J Kavanagh, D Keller, MC Kelly, BJ Kennedy, JL Kim, Y Knowles, JA Konte, B Laurent, C Lee, P Lee, SH Legge, SE Lerer, B Levy, DL Liang, KY Lieberman, J Lonnqvist, J Loughland, CM Magnusson, PKE Maher, BS Maier, W Mallet, J Mattheisen, M Mattingsdal, M McCarley, RW McDonald, C McIntosh, AM Meier, S Meijer, CJ Melle, I Mesholam-Gately, RI Metspalu, A Michie, PT Milani, L Milanova, V Mokrab, Y Morris, DW Muller-Myhsok, B Murphy, KC Murray, RM Myin-Germeys, I Nenadic, I Nertney, DA Nestadt, G Nicodemus, KK Nisenbaum, L Nordin, A O'Callaghan, E O'Dushlaine, C Oh, SY Olincy, A Olsen, L O'Neill, FA Van Os, J Pantelis, C Papadimitriou, GN Parkhomenko, E Pato, MT Paunio, T Perkins, DO Pers, TH Pietilainen, O Pimm, J Pocklington, AJ Powell, J Price, A Pulver, AE Purcell, SM Quested, D Rasmussen, HB Reichenberg, A Reimers, MA Richards, AL Roffman, JL Roussos, P Ruderfer, DM Salomaa, V Sanders, AR Savitz, A Schall, U Schulze, TG Schwab, SG Scolnick, EM Scott, RJ Seidman, LJ Shi, JX Silverman, JM Smoller, JW Soderman, E Spencer, CCA Stahl, EA Strengman, E Strohmaier, J Stroup, TS Suvisaari, J Svrakic, DM Szatkiewicz, JP Thirumalai, S Tooney, PA Veijola, J Visscher, PM Waddington, J Walsh, D Webb, BT Weiser, M Wildenauer, DB Williams, NM Williams, S Witt, SH Wolen, AR Wormley, BK Wray, NR Wu, JQ Zai, CC Adolfsson, R Andreassen, OA Blackwood, DHR Bramon, E Buxbaum, JD Cichon, S Collier, DA Corvin, A Daly, MJ Darvasi, A Domenici, E Esko, T Gejman, PV Gill, M Gurling, H Hultman, CM Iwata, N Jablensky, AV Jonsson, EG Kendler, KS Kirov, G Knight, J Levinson, DF Li, QQS McCarroll, SA McQuillin, A Moran, JL Mowry, BJ Nothen, MM Ophoff, RA Owen, MJ Palotie, A Pato, CN Petryshen, TL Posthuma, D Rietschel, M Riley, BP Rujescu, D Sklar, P St Clair, D Walters, JTR Werge, T Siillivan, PF O'Donovan, MC Scherer, SW Neale, BM Sebat, J AF Marshall, Christian R. Marshall, Christian R. Howrigan, Daniel P. Merico, Daniele Thiruvahindrapuram, Bhooma Wu, Wenting Greer, Douglas S. Antaki, Danny Shetty, Aniket Holmans, Peter A. Pinto, Dalila Gujral, Madhusudan Brandler, William M. Malhotra, Dheeraj Wang, Zhouzhi Fajarado, Karin V. Fuentes Maile, Michelle S. Ripke, Stephan Agartz, Ingrid Albus, Margot Alexander, Madeline Amin, Farooq Atkins, Joshua Bacanu, Silviu A. Belliveau, Richard A., Jr. Bergen, Sarah E. Ertalan, Marcelo Bevilacqua, Elizabeth Bigdeli, Tim B. Black, Donald W. Bruggeman, Richard Buccola, Nancy G. Buckner, Randy L. Bulik-Sullivan, Brendan Byerley, William Cahn, Wiepke Cai, Guiqing Cairns, Murray J. Campion, Dominique Cantor, Rita M. Carr, Vaughan J. Carrera, Noa Catts, Stanley V. Chambert, Kimberley D. Cheng, Wei Cloninger, C. Robert Cohen, David Cormican, Paul Craddock, Nick Crespo-Facorro, Benedicto Crowley, James J. Curtis, David Davidson, Michael Davis, Kenneth L. Degenhardt, Franziska Del Favero, Jurgen DeLisi, Lynn E. Dikeos, Dimitris Dinan, Timothy Djurovic, Srdjan Donohoe, Gary Drapeau, Elodie Duan, Jubao Dudbridge, Frank Eichhammer, Peter Eriksson, Johan Escott-Price, Valentina Essioux, Laurent Fanous, Ayman H. Farh, Kai-How Farrell, Martilias S. Frank, Josef Franke, Lude Freedman, Robert Freimer, Nelson B. Friedman, Joseph I. Forstner, Andreas J. Fromer, Menachem Genovese, Giulio Georgieva, Lyudmila Gershon, Elliot S. Giegling, Ina Giusti-Rodriguez, Paola Godard, Stephanie Goldstein, Jacqueline I. Gratten, Jacob de Haan, Lieuwe Hamshere, Marian L. Hansen, Mark Hansen, Thomas Haroutunian, Vahram Hartmann, Annette M. Henskens, Frans A. Herms, Stefan Hirschhorn, Joel N. Hoffinann, Per Hofman, Andrea Huang, Hailiang Ikeda, Masashi Joa, Inge Kahler, Anna K. Kahn, Rene S. Kalaydjieva, Luba Karjalainen, Juha Kavanagh, David Keller, Matthew C. Kelly, Brian J. Kennedy, James L. Kim, Yunjung Knowles, James A. Konte, Bettina Laurent, Claudine Lee, Phil Lee, S. Hong Legge, Sophie E. Lerer, Bernard Levy, Deborah L. Liang, Kung-Yee Lieberman, Jeffrey Lonnqvist, Jouko Loughland, Carmel M. Magnusson, Patrik K. E. Maher, Brion S. Maier, Wolfgang Mallet, Jacques Mattheisen, Manuel Mattingsdal, Morten McCarley, Robert W. McDonald, Colm McIntosh, Andrew M. Meier, Sandra Meijer, Carin J. Melle, Ingrid Mesholam-Gately, Raquelle I. Metspalu, Andres Michie, Patricia T. Milani, Lili Milanova, Vihra Mokrab, Younes Morris, Derek W. Muller-Myhsok, Bertram Murphy, Kieran C. Murray, Robin M. Myin-Germeys, Inez Nenadic, Igor Nertney, Deborah A. Nestadt, Gerald Nicodemus, Kristin K. Nisenbaum, Laura Nordin, Annelie O'Callaghan, Eadbhard O'Dushlaine, Colm Oh, Sang-Yun Olincy, Ann Olsen, Line O'Neill, F. Anthony Van Os, Jim Pantelis, Christos Papadimitriou, George N. Parkhomenko, Elena Pato, Michele T. Paunio, Tiina Perkins, Diana O. Pers, Tune H. Pietilainen, Olli Pimm, Jonathan Pocklington, Andrew J. Powell, John Price, Alkes Pulver, Ann E. Purcell, Shaun M. Quested, Digby Rasmussen, Henrik B. Reichenberg, Abraham Reimers, Mark A. Richards, Alexander L. Roffman, Joshua L. Roussos, Panos Ruderfer, Douglas M. Salomaa, Veikko Sanders, Alan R. Savitz, Adam Schall, Ulrich Schulze, Thomas G. Schwab, Sibylle G. Scolnick, Edward M. Scott, Rodney J. Seidman, Larry J. Shi, Jianxin Silverman, Jeremy M. Smoller, Jordan W. Soderman, Erik Spencer, Chris C. A. Stahl, Eli A. Strengman, Eric Strohmaier, Jana Stroup, T. Scott Suvisaari, Jaana Svrakic, Dragan M. Szatkiewicz, Jin P. Thirumalai, Srinivas Tooney, Paul A. Veijola, Juha Visscher, Peter M. Waddington, John Walsh, Dermot Webb, Bradley T. Weiser, Mark Wildenauer, Dieter B. Williams, Nigel M. Williams, Stephanie Witt, Stephanie H. Wolen, Aaron R. Wormley, Brandon K. Wray, Naomi R. Wu, Jing Qin Zai, Clement C. Adolfsson, Rolf Andreassen, Ole A. Blackwood, Douglas H. R. Bramon, Elvira Buxbaum, Joseph D. Cichon, Sven Collier, David A. Corvin, Aiden Daly, Mark J. Darvasi, Ariel Domenici, Enrico Esko, Tonu Gejman, Pablo V. Gill, Michael Gurling, Hugh Hultman, Christina M. Iwata, Nakao Jablensky, Assen V. Jonsson, Erik G. Kendler, Kenneth S. Kirov, George Knight, Jo Levinson, Douglas F. Li, Qingqin S. McCarroll, Steven A. McQuillin, Andrew Moran, Jennifer L. Mowry, Bryan J. Nothen, Markus M. Ophoff, Roel A. Owen, Michael J. Palotie, Aarno Pato, Carlos N. Petryshen, Tracey L. Posthuma, Danielle Rietschel, Marcella Riley, Brien P. Rujescu, Dan Sklar, Pamela St Clair, David Walters, James T. R. Werge, Thomas Siillivan, Patrick F. O'Donovan, Michael C. Scherer, Stephen W. Neale, Benjamin M. Sebat, Jonathan CA CNV Schizophrenia Working Grp Psychosis Endophenotypes TI Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects SO NATURE GENETICS LA English DT Article ID GENE; 16P11.2; AUTISM; RISK; CNVS; REARRANGEMENTS; DUPLICATIONS; PHENOTYPES; DISORDERS; MUTATIONS AB Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination. C1 [Marshall, Christian R.; Merico, Daniele; Thiruvahindrapuram, Bhooma; Wang, Zhouzhi; Scherer, Stephen W.] Hosp Sick Children, Ctr Appl Genom, Toronto, ON, Canada. [Marshall, Christian R.; Merico, Daniele; Thiruvahindrapuram, Bhooma; Wang, Zhouzhi; Scherer, Stephen W.] Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON, Canada. [Howrigan, Daniel P.; Ripke, Stephan; Bulik-Sullivan, Brendan; Farh, Kai-How; Fromer, Menachem; Goldstein, Jacqueline I.; Huang, Hailiang; Lee, Phil; Daly, Mark J.; Palotie, Aarno; Neale, Benjamin M.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA. [Howrigan, Daniel P.; Ripke, Stephan; Belliveau, Richard A., Jr.; Bergen, Sarah E.; Bevilacqua, Elizabeth; Bulik-Sullivan, Brendan; Chambert, Kimberley D.; Fromer, Menachem; Genovese, Giulio; O'Dushlaine, Colm; Scolnick, Edward M.; Smoller, Jordan W.; Wolen, Aaron R.; Daly, Mark J.; McCarroll, Steven A.; Moran, Jennifer L.; Palotie, Aarno; Petryshen, Tracey L.; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Wu, Wenting; Greer, Douglas S.; Antaki, Danny; Shetty, Aniket; Gujral, Madhusudan; Brandler, William M.; Malhotra, Dheeraj; Fajarado, Karin V. Fuentes; Maile, Michelle S.; Palotie, Aarno; Sebat, Jonathan] Univ Calif San Diego, Beyster Ctr Psychiat Genom, La Jolla, CA 92093 USA. [Wu, Wenting; Greer, Douglas S.; Antaki, Danny; Shetty, Aniket; Gujral, Madhusudan; Brandler, William M.; Malhotra, Dheeraj; Fajarado, Karin V. Fuentes; Maile, Michelle S.; Palotie, Aarno; Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Holmans, Peter A.; Carrera, Noa; Craddock, Nick; Escott-Price, Valentina; Georgieva, Lyudmila; Hamshere, Marian L.; Kavanagh, David; Legge, Sophie E.; Pocklington, Andrew J.; Richards, Alexander L.; Ruderfer, Douglas M.; Williams, Nigel M.; Kirov, George; Owen, Michael J.; Palotie, Aarno; Walters, James T. R.; O'Donovan, Michael C.] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Sch Med, MRC Ctr Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales. [Holmans, Peter A.; Craddock, Nick; Richards, Alexander L.; Owen, Michael J.; O'Donovan, Michael C.] Cardiff Univ, Natl Ctr Mental Hlth, Cardiff, S Glam, Wales. [Pinto, Dalila; Cai, Guiqing; Davis, Kenneth L.; Drapeau, Elodie; Friedman, Joseph I.; Haroutunian, Vahram; Parkhomenko, Elena; Reichenberg, Abraham; Silverman, Jeremy M.; Buxbaum, Joseph D.; Palotie, Aarno] Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY USA. [Pinto, Dalila] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, Dept Genet & Genom Sci, Seaver Autism Ctr, New York, NY USA. [Malhotra, Dheeraj; Domenici, Enrico] F Hoffmann La Roche Ltd, Neurosci Discovery & Translat Area, Pharma Res & Early Dev, Basel, Switzerland. [Agartz, Ingrid; Djurovic, Srdjan; Mattingsdal, Morten; Melle, Ingrid; Andreassen, Ole A.; Jonsson, Erik G.] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Psychosis Res, NORMENT, Oslo, Norway. [Agartz, Ingrid] Diakonhjemmet Hosp, Dept Psychiat, Oslo, Norway. [Agartz, Ingrid; Soderman, Erik; Jonsson, Erik G.] Karolinska Inst, Psychiat Sect, Dept Clin Neurosci, Stockholm, Sweden. [Albus, Margot] State Mental Hosp, Haar, Germany. [Alexander, Madeline; Laurent, Claudine; Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Amin, Farooq] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Amin, Farooq] Atlanta Vet Affairs Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Atkins, Joshua; Cairns, Murray J.; Scott, Rodney J.; Tooney, Paul A.; Wu, Jing Qin] Univ Newcastle, Sch Biomed Sci & Pharm, Callaghan, NSW, Australia. [Atkins, Joshua] Hunter Med Res Inst, New Lambton, NSW, Australia. [Bacanu, Silviu A.; Bigdeli, Tim B.; Reimers, Mark A.; Webb, Bradley T.; Wolen, Aaron R.; Wormley, Brandon K.; Kendler, Kenneth S.; Palotie, Aarno; Riley, Brien P.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA USA. [Bergen, Sarah E.; Kahler, Anna K.; Magnusson, Patrik K. E.; Hultman, Christina M.; Siillivan, Patrick F.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Ertalan, Marcelo; Hansen, Thomas; Olsen, Line; Rasmussen, Henrik B.; Werge, Thomas] Mental Hlth Serv Copenhagen, Inst Biol Psychiat, Mental Hlth Ctr Set, Copenhagen, Denmark. [Ertalan, Marcelo; Hansen, Thomas; Mattheisen, Manuel; Olsen, Line; Rasmussen, Henrik B.; Palotie, Aarno; Werge, Thomas] iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Aaarhus, Denmark. [Black, Donald W.] Univ Iowa, Carver Coll Med, Dept Psychiat, Iowa City, IA USA. [Bruggeman, Richard] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands. [Buccola, Nancy G.] Louisiana State Univ, Hlth Sci Ctr, Sch Nursing, New Orleans, LA USA. [Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Buckner, Randy L.; Roffman, Joshua L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Buckner, Randy L.; Roffman, Joshua L.; Petryshen, Tracey L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Boston, MA 02114 USA. [Byerley, William] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Cahn, Wiepke; Kahn, Rene S.; Strengman, Eric; Ophoff, Roel A.] Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, Utrecht, Netherlands. [Cai, Guiqing; Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Human Genet, New York, NY 10029 USA. [Cairns, Murray J.; Carr, Vaughan J.; Catts, Stanley V.; Henskens, Frans A.; Lee, Phil; Loughland, Carmel M.; Michie, Patricia T.; Pantelis, Christos; Schall, Ulrich; Scott, Rodney J.; Tooney, Paul A.; Wu, Jing Qin; Jablensky, Assen V.; Palotie, Aarno] Schizophrenia Res Inst, Sydney, NSW, Australia. [Cairns, Murray J.; Henskens, Frans A.; Kelly, Brian J.; Loughland, Carmel M.; Schall, Ulrich; Tooney, Paul A.] Univ Newcastle, Prior Ctr Translat Neurosci & Mental Hlth, Newcastle, NSW, Australia. [Campion, Dominique; O'Neill, F. Anthony] Ctr Hosp Rouvray, Rouen, France. [Campion, Dominique; O'Neill, F. Anthony] INSERM U1079, Fac Med, Rouen, France. [Cantor, Rita M.; Ophoff, Roel A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA. [Carr, Vaughan J.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Catts, Stanley V.] Univ Queensland, Royal Brisbane & Womens Hosp, Dept Psychiat, Brisbane, Qld, Australia. [Cheng, Wei] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA. [Cloninger, C. Robert; Svrakic, Dragan M.; Palotie, Aarno] Washington Univ, Dept Psychiat, St Louis, MO USA. [Cohen, David] Pierre & Marie Curie Fac Med, AP HP, Dept Child & Adolescent Psychiat, Paris, France. [Cohen, David] Inst Intelligent Syst & Robot, Paris, France. [Cormican, Paul; Donohoe, Gary; Morris, Derek W.; Corvin, Aiden; Gill, Michael] Trinity Coll Dublin, Dept Psychiat, Neuropsychiat Genet Res Grp, Dublin, Ireland. 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[Degenhardt, Franziska; Forstner, Andreas J.; Herms, Stefan; Hoffinann, Per; Hofman, Andrea; Cichon, Sven; Nothen, Markus M.; Palotie, Aarno] Life & Brain Ctr, Dept Genom, Bonn, Germany. [Del Favero, Jurgen] Univ Antwerp, VIB Dept Mol Genet, Applied Mol Genom Unit, Antwerp, Belgium. [DeLisi, Lynn E.; McCarley, Robert W.] Virginia Boston Hlth Care Syst, Brockton, MA USA. [DeLisi, Lynn E.; Levy, Deborah L.; McCarley, Robert W.; Mesholam-Gately, Raquelle I.; Seidman, Larry J.; Palotie, Aarno; Petryshen, Tracey L.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Dikeos, Dimitris; Papadimitriou, George N.] Univ Athens, Sch Med, Dept Psychiat 1, Athens, Greece. [Dinan, Timothy] Univ Coll Cork, Dept Psychiat, Cork, Ireland. [Djurovic, Srdjan] Oslo Univ Hosp, Dept Med Genet, Oslo, Norway. [Donohoe, Gary; Morris, Derek W.] Natl Univ Ireland Galway, Sch Psychol, Cognit Genet & Therapy Grp, Galway, Ireland. 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[Melle, Ingrid; Andreassen, Ole A.] Oslo Univ Hosp, Div Mental Hlth & Addict, Oslo, Norway. [Mesholam-Gately, Raquelle I.; Seidman, Larry J.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth, Ctr Publ Psychiat Div, Boston, MA 02215 USA. [Metspalu, Andres; Milani, Lili; Esko, Tonu; Palotie, Aarno] Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. [Michie, Patricia T.] Univ Newcastle, Sch Psychol, Newcastle, NSW, Australia. [Milanova, Vihra] Med Univ, First Psychiat Clin, Sofia, Bulgaria. [Mokrab, Younes; Collier, David A.] Eli Lilly & Co Ltd, Windlesham, Surrey, England. [Muller-Myhsok, Bertram] Max Planck Inst Psychiat, Munich, Germany. [Muller-Myhsok, Bertram] Univ Liverpool, Inst Translat Med, Liverpool, Merseyside, England. [Muller-Myhsok, Bertram] Cluster Syst Neurol SyNergy, Munich, Germany. [Murphy, Kieran C.] Royal Coll Surgeons Ireland, Dept Psychiat, Dublin, Ireland. [Murray, Robin M.; Powell, John] Kings Coll London, Inst Psychiat, London, England. 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[Pantelis, Christos] Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia. [Pantelis, Christos] Melbourne Hlth, Melbourne, Vic, Australia. [Paunio, Tiina; Pietilainen, Olli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Perkins, Diana O.; Siillivan, Patrick F.] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. [Pers, Tune H.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, Kongens, Denmark. [Pietilainen, Olli] Univ Helsinki, Inst Mol Med Finland, FIMM, Helsinki, Finland. [Price, Alkes] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Quested, Digby] Univ Oxford, Dept Psychiat, Oxford, England. [Roussos, Panos; Sklar, Pamela] Icahn Sch Med Mt Sinai, Inst Multiscale Biol, New York, NY USA. [Savitz, Adam; Li, Qingqin S.] Janssen Res & Dev, Neurosci Therapeut Area, Raritan, NJ USA. [Schulze, Thomas G.] Univ Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany. [Schwab, Sibylle G.] Univ Erlangen Nurnberg, Psychiat & Psychotherapy Clin, Erlangen, Germany. [Scott, Rodney J.] Hunter New England Hlth Serv, Newcastle, NSW, Australia. [Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Silverman, Jeremy M.] Bronx Vet Affairs Med Ctr, Res & Dev, New York, NY USA. [Spencer, Chris C. A.] Wellcome Trust Ctr Human Genet, Oxford, England. [Strengman, Eric] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands. [Thirumalai, Srinivas] Berkshire Healthcare NHS Fdn Trust, Bracknell, Berks, England. [Veijola, Juha] Univ Oulu, Dept Psychiat, Oulu, Finland. [Veijola, Juha] Univ Hosp Oulu, Dept Psychiat, Oulu, Finland. [Waddington, John] Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland. [Walsh, Dermot] Hlth Res Board, Dublin, Ireland. [Wildenauer, Dieter B.; Jablensky, Assen V.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Perth, WA, Australia. [Bramon, Elvira] UCL, Div Psychiat, London, England. [Buxbaum, Joseph D.] Icahn Sch Med Mt Sinai, Dept Neurosci, New York, NY USA. [Cichon, Sven] Res Ctr Juelich, Inst Neurosci & Med INM 1, Julich, Germany. [Collier, David A.] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England. [Darvasi, Ariel] Hebrew Univ Jerusalem, Dept Genet, Jerusalem, Israel. [Domenici, Enrico] Univ Trento, Ctr Integrat Biol, Trento, Italy. [Jablensky, Assen V.] Univ Western Australia, Sch Psychiat & Clin Neurosci, Ctr Clin Res Neuropsychiat, Perth, WA, Australia. [Petryshen, Tracey L.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Posthuma, Danielle] Vrije Univ Amsterdam, Ctr Neurogen & Cognit Res, Dept Funct Genom, Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Posthuma, Danielle] Vrije Univ Amsterdam, Med Ctr Amsterdam, Dept Complex Trait Genet, Neurosci Campus Amsterdam, Amsterdam, Netherlands. [Posthuma, Danielle] Erasmus Univ, Dept Child & Adolescent Psychiat, Med Ctr, Rotterdam, Netherlands. [St Clair, David] Univ Aberdeen, Inst Med Sci, Aberdeen, Scotland. [Palotie, Aarno; Werge, Thomas] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark. [Scherer, Stephen W.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada. [Scherer, Stephen W.] Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada. [Sebat, Jonathan] Univ Calif San Diego, Dept Cellular & Mol Med, San Diego, CA 92103 USA. RI Scherer, Stephen /B-3785-2013; Pantelis, Christos/H-7722-2014; Powell, John/G-4412-2011; OI Scherer, Stephen /0000-0002-8326-1999; Visscher, Peter/0000-0002-2143-8760; Dinan, Timothy/0000-0002-2316-7220; McIntosh, Andrew/0000-0002-0198-4588; Knight, Joanne/0000-0002-7148-1660; Pantelis, Christos/0000-0002-9565-0238; Powell, John/0000-0001-6124-439X; Jonsson, Erik/0000-0001-8368-6332; Webb, Bradley/0000-0002-0576-5366; Domenici, Enrico/0000-0001-7436-6919; murray, robin/0000-0003-0829-0519; Adolfsson, Rolf/0000-0001-9785-8473 FU US National Institute of Mental Health (NIMH) [U01 MH094421] FX Core funding for the Psychiatric Genomics Consortium is from the US National Institute of Mental Health (NIMH, U01 MH094421). We thank T. Lehner, A. Addington and G. Senthil (NIMH). The work of the contributing groups was supported by numerous grants from governmental and charitable bodies as well as philanthropic donation. Details are provided in the Supplementary Note. NR 36 TC 0 Z9 0 U1 5 U2 5 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 JAN PY 2017 VL 49 IS 1 BP 27 EP 35 DI 10.1038/ng.3725 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA EG3WY UT WOS:000390976600008 ER PT J AU Redin, C Brand, H Collins, RL Kammin, T Mitchell, E Hodge, JC Hanscom, C Pillalamarri, V Seabra, CM Abbott, MA Abdul-Rahman, OA Aberg, E Adley, R Alcaraz-Estrada, SL Alkuraya, FS An, Y Anderson, MA Antolik, C Anyane-Yeboa, K Atkin, JF Bartell, T Bernstein, JA Beyer, E Blumenthal, I Bongers, EMHF Brilstra, EH Brown, CW Bruggenwirth, HT Callewaert, B Chiang, C Corning, K Cox, H Cuppen, E Currall, BB Cushing, T David, D Deardorff, MA Dheedene, A D'Hooghe, M de Vries, BBA Earl, DL Ferguson, HL Fisher, H FitzPatrick, DR Gerrol, P Giachino, D Glessner, JT Gliem, T Grady, M Graham, BH Griffis, C Gripp, KW Gropman, AL Hanson-Kahn, A Harris, DJ Hayden, MA Hill, R Hochstenbach, R Hoffman, JD Hopkin, RJ Hubshman, MW Innes, AM Irons, M Irving, M Jacobsen, JC Janssens, S Jewett, T Johnson, JP Jongmans, MC Kahler, SG Koolen, DA Korzelius, J Kroisel, PM Lacassie, Y Lawless, W Lemyre, E Leppig, K Levin, AV Li, HB Li, H Liao, EC Lim, C Lose, EJ Lucente, D Macera, MJ Manavalan, P Mandrile, G Marcelis, CL Margolin, L Mason, T Masser-Frye, D McClellan, MW Mendoza, CJZ Menten, B Middelkamp, S Mikami, LR Moe, E Mohammed, S Mononen, T Mortenson, ME Moya, G Nieuwint, AW Ordulu, Z Parkash, S Pauker, SP Pereira, S Perrin, D Phelan, K Aguilar, REP Poddighe, PJ Pregno, G Raskin, S Reis, L Rhead, W Rita, D Renkens, I Roelens, F Ruliera, J Rump, P Schilit, SLP Shaheen, R Sparkes, R Spiegel, E Stevens, B Stone, MR Tagoe, J Thakuria, JV van Bon, BW van de Kamp, J van Der Burgt, I van Essen, T van Ravenswaaij-Arts, CM van Roosmalen, MJ Vergult, S Volker-Touw, CML Warburton, DP Waterman, MJ Wiley, S Wilson, A Yerena-de Vega, MDA Zori, RT Levy, B Brunner, HG de Leeuw, N Kloosterman, WP Thorland, EC Morton, CC Gusella, JF Talkowski, ME AF Redin, Claire Brand, Harrison Collins, Ryan L. Kammin, Tammy Mitchell, Elyse Hodge, Jennelle C. Hanscom, Carrie Pillalamarri, Vamsee Seabra, Catarina M. Abbott, Mary-Alice Abdul-Rahman, Omar A. Aberg, Erika Adley, Rhett Alcaraz-Estrada, Sofia L. Alkuraya, Fowzan S. An, Yu Anderson, Mary-Anne Antolik, Caroline Anyane-Yeboa, Kwame Atkin, Joan F. Bartell, Tina Bernstein, Jonathan A. Beyer, Elizabeth Blumenthal, Ian Bongers, Ernie M. H. F. Brilstra, Eva H. Brown, Chester W. Bruggenwirth, Hennie T. Callewaert, Bert Chiang, Colby Corning, Ken Cox, Helen Cuppen, Edwin Currall, Benjamin B. Cushing, Tom David, Dezso Deardorff, Matthew A. Dheedene, Annelies D'Hooghe, Marc de Vries, Bert B. A. Earl, Dawn L. Ferguson, Heather L. Fisher, Heather FitzPatrick, David R. Gerrol, Pamela Giachino, Daniela Glessner, Joseph T. Gliem, Troy Grady, Margo Graham, Brett H. Griffis, Cristin Gripp, Karen W. Gropman, Andrea L. Hanson-Kahn, Andrea Harris, David J. Hayden, Mark A. Hill, Rosamund Hochstenbach, Ron Hoffman, Jodi D. Hopkin, Robert J. Hubshman, Monika W. Innes, A. Micheil Irons, Mira Irving, Melita Jacobsen, Jessie C. Janssens, Sandra Jewett, Tamison Johnson, John P. Jongmans, Marjolijn C. Kahler, Stephen G. Koolen, David A. Korzelius, Jerome Kroisel, Peter M. Lacassie, Yves Lawless, William Lemyre, Emmanuelle Leppig, Kathleen Levin, Alex V. Li, Haibo Li, Hong Liao, Eric C. Lim, Cynthia Lose, Edward J. Lucente, Diane Macera, Michael J. Manavalan, Poornima Mandrile, Giorgia Marcelis, Carlo L. Margolin, Lauren Mason, Tamara Masser-Frye, Diane McClellan, Michael W. Mendoza, Cinthya J. Zepeda Menten, Bjorn Middelkamp, Sjors Mikami, Liya R. Moe, Emily Mohammed, Shehla Mononen, Tarja Mortenson, Megan E. Moya, Graciela Nieuwint, Aggie W. Ordulu, Zehra Parkash, Sandhya Pauker, Susan P. Pereira, Shahrin Perrin, Danielle Phelan, Katy Pina Aguilar, Raul E. Poddighe, Pino J. Pregno, Giulia Raskin, Salmo Reis, Linda Rhead, William Rita, Debra Renkens, Ivo Roelens, Filip Ruliera, Jayla Rump, Patrick Schilit, Samantha L. P. Shaheen, Ranad Sparkes, Rebecca Spiegel, Erica Stevens, Blair Stone, Matthew R. Tagoe, Julia Thakuria, Joseph V. van Bon, Bregje W. van de Kamp, Jiddeke van Der Burgt, Ineke van Essen, Ton van Ravenswaaij-Arts, Conny M. van Roosmalen, Markus J. Vergult, Sarah Volker-Touw, Catharina M. L. Warburton, Dorothy P. Waterman, Matthew J. Wiley, Susan Wilson, Anna Yerena-de Vega, Maria de la Concepcion A. Zori, Roberto T. Levy, Brynn Brunner, Han G. de Leeuw, Nicole Kloosterman, Wigard P. Thorland, Erik C. Morton, Cynthia C. Gusella, James F. Talkowski, Michael E. TI The genomic landscape of balanced cytogenetic abnormalities associated with human congenital anomalies SO NATURE GENETICS LA English DT Article ID AUTISM SPECTRUM DISORDER; DE-NOVO MUTATIONS; SEVERE MENTAL-RETARDATION; OF-FUNCTION MUTATIONS; MICRODELETION SYNDROME; CHROMOSOME REARRANGEMENTS; INTELLECTUAL DISABILITY; STRUCTURAL VARIATION; DEVELOPMENTAL DELAY; CANCER GENOMES AB Despite the clinical significance of balanced chromosomal abnormalities (BCAs), their characterization has largely been restricted to cytogenetic resolution. We explored the landscape of BCAs at nucleotide resolution in 273 subjects with a spectrum of congenital anomalies. Whole-genome sequencing revised 93% of karyotypes and demonstrated complexity that was cryptic to karyotyping in 21 % of BCAs, highlighting the limitations of conventional cytogenetic approaches. At least 33.9% of BCAs resulted in gene disruption that likely contributed to the developmental phenotype, 5.2% were associated with pathogenic genomic imbalances, and 7.3% disrupted topologically associated domains (TADS) encompassing known syndromic loci. Remarkably, BCA breakpoints in eight subjects altered a single TAD encompassing MEF2C, a known driver of 5q14.3 microdeletion syndrome, resulting in decreased MEF2C expression. We propose that sequence-level resolution dramatically improves prediction of clinical outcomes for balanced rearrangements and provides insight into new pathogenic mechanisms, such as altered regulation due to changes in chromosome topology. C1 [Redin, Claire; Brand, Harrison; Collins, Ryan L.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Adley, Rhett; An, Yu; Antolik, Caroline; Blumenthal, Ian; Chiang, Colby; Currall, Benjamin B.; Glessner, Joseph T.; Lawless, William; Lucente, Diane; Manavalan, Poornima; Stone, Matthew R.; Waterman, Matthew J.; Wilson, Anna; Gusella, James F.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. [Redin, Claire; Brand, Harrison; Collins, Ryan L.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Antolik, Caroline; Glessner, Joseph T.; Stone, Matthew R.; Talkowski, Michael E.] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Psychiatr & Neurodev Genet Unit, Boston, MA 02114 USA. [Redin, Claire; Brand, Harrison; Collins, Ryan L.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Antolik, Caroline; Glessner, Joseph T.; Innes, A. Micheil; Stone, Matthew R.; Talkowski, Michael E.] Harvard Med Sch, Boston, MA 02115 USA. [Redin, Claire; Brand, Harrison; Collins, Ryan L.; Hanscom, Carrie; Pillalamarri, Vamsee; Seabra, Catarina M.; Antolik, Caroline; Glessner, Joseph T.; Stone, Matthew R.; Morton, Cynthia C.; Gusella, James F.; Talkowski, Michael E.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. [Collins, Ryan L.] Harvard Med Sch, Div Med Sci, Program Bioinformat & Integrat Gen, Boston, MA USA. [Kammin, Tammy; Currall, Benjamin B.; Ferguson, Heather L.; Gerrol, Pamela; Hayden, Mark A.; Mendoza, Cinthya J. Zepeda; Ordulu, Zehra; Pereira, Shahrin; Morton, Cynthia C.] Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. [Mitchell, Elyse; Hodge, Jennelle C.; Gliem, Troy; Thorland, Erik C.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Hodge, Jennelle C.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Hodge, Jennelle C.] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. [Seabra, Catarina M.] Univ Porto, GABBA Program, Oporto, Portugal. [Abbott, Mary-Alice] Baystate Med Ctr, Med Genet, Springfield, MA USA. [Abdul-Rahman, Omar A.] Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA. [Aberg, Erika; Parkash, Sandhya] IWK Hlth Ctr, Maritime Med Genet Serv, Halifax, NS, Canada. [Alcaraz-Estrada, Sofia L.; Pina Aguilar, Raul E.] ISSSTE, Ctr Med Nacl Noviembre 20, Med Genom Div, Mexico City, DF, Mexico. [Alkuraya, Fowzan S.; Shaheen, Ranad] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh, Saudi Arabia. [An, Yu] Fudan Univ, Shanghai Med Sch, IBS, Shanghai, Peoples R China. [An, Yu] Fudan Univ, MOE Key Lab Contemporary Anthropol, Shanghai, Peoples R China. [Anderson, Mary-Anne; Ruliera, Jayla] Ctr Human Genet Res DNA & Tissue Culture Res, Boston, MA USA. [Anyane-Yeboa, Kwame; Warburton, Dorothy P.] Columbia Univ, Med Ctr, Div Clin Genet, New York, NY USA. [Atkin, Joan F.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43210 USA. [Atkin, Joan F.] Nationwide Childrens Hosp, Div Mol & Human Genet, Columbus, OH USA. [Bartell, Tina] Kaiser Permanente, Dept Genet, Sacramento, CA USA. [Bernstein, Jonathan A.; Hanson-Kahn, Andrea] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Beyer, Elizabeth; Griffis, Cristin; Moe, Emily; Reis, Linda; Rhead, William] Med Coll Wisconsin, Dept Pediat, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. [Beyer, Elizabeth; Griffis, Cristin; Moe, Emily; Rhead, William] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. [Bongers, Ernie M. H. F.; de Vries, Bert B. A.; Jongmans, Marjolijn C.; Koolen, David A.; Marcelis, Carlo L.; van Bon, Bregje W.; van Der Burgt, Ineke; Brunner, Han G.; de Leeuw, Nicole] Radboud Univ Nijmegen, Radboud Inst Mol Life Sci, Dept Human Genet, Med Ctr, Nijmegen, Netherlands. [Bongers, Ernie M. H. F.; de Vries, Bert B. A.; Jongmans, Marjolijn C.; Koolen, David A.; Marcelis, Carlo L.; van Bon, Bregje W.; van Der Burgt, Ineke; Brunner, Han G.; de Leeuw, Nicole] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Med Ctr, Nijmegen, Netherlands. [Brilstra, Eva H.; Cuppen, Edwin; Hochstenbach, Ron; Korzelius, Jerome; Middelkamp, Sjors; Renkens, Ivo; van Roosmalen, Markus J.; Volker-Touw, Catharina M. L.; Kloosterman, Wigard P.] Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Div Biomed Genet, Utrecht, Netherlands. [Brown, Chester W.; Graham, Brett H.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Brown, Chester W.; Graham, Brett H.] Texas Childrens Hosp, Dept Genet, Houston, TX 77030 USA. [Bruggenwirth, Hennie T.] Erasmus Univ, Med Ctr, Dept Clin Genet, Rotterdam, Netherlands. [Callewaert, Bert; Dheedene, Annelies; Janssens, Sandra; Menten, Bjorn; Vergult, Sarah] Univ Ghent, Ctr Med Genet, Ghent, Belgium. [Corning, Ken] Greenwood Genet Ctr, Columbia, SC USA. [Cox, Helen] Birmingham Womens Hosp, West Midlands Reg Clin Genet Unit, Birmingham, W Midlands, England. [Currall, Benjamin B.; Schilit, Samantha L. P.; Gusella, James F.] Harvard Med Sch, Dept Genet, Boston, MA USA. [Cushing, Tom] Univ New Mexico, Sch Med, Dept Pediat, Div Pediat Genet, Albuquerque, NM 87131 USA. [David, Dezso] Natl Hlth Inst Doutor Ricardo Jorge, Dept Human Genet, Lisbon, Portugal. [Deardorff, Matthew A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. [Deardorff, Matthew A.] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. [D'Hooghe, Marc] Algemeen Ziekenhuis St Jan, Dept Neurol & Child Neurol, Brugge, Belgium. [Earl, Dawn L.] Seattle Childrens, Seattle, WA USA. [Fisher, Heather] Mt Sinai West Hosp, New York, NY USA. [FitzPatrick, David R.] Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland. [Giachino, Daniela; Mandrile, Giorgia; Pregno, Giulia] Univ Torino, Dept Clin & Biol Sci, Med Genet Unit, Turin, Italy. [Grady, Margo] UW Canc Ctr ProHlth Care, Waukesha, WI USA. [Gripp, Karen W.] Thomas Jefferson Univ, Sidney Kimmel Med Sch, Philadelphia, PA 19107 USA. [Gropman, Andrea L.] Childrens Natl Med Ctr, Div Neurogenet & Dev Pediat, Washington, DC 20010 USA. [Hanson-Kahn, Andrea] Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. [Harris, David J.] Boston Childrens Hosp, Div Genet, Boston, MA USA. [Harris, David J.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Hill, Rosamund] Auckland City Hosp, Dept Neurol, Auckland, New Zealand. [Hoffman, Jodi D.] Boston Med Ctr, Dept Pediat, Div Genet, Boston, MA USA. [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH 45229 USA. [Hopkin, Robert J.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. [Hubshman, Monika W.] Schneider Childrens Med Ctr Israel, Pediat Genet Unit, Petah Tiqwa, Israel. [Hubshman, Monika W.] Raphael Recanati Genet Inst, Rabin Med Ctr, Petah Tiqwa, Israel. [Hubshman, Monika W.] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel. [Innes, A. Micheil; Sparkes, Rebecca] Univ Calgary, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada. [Irons, Mira] Acad Affairs, Amer Board Med Specialties, Chicago, IL USA. [Irving, Melita; Mohammed, Shehla] Guys & St Thomas NHS Fdn Trust, Dept Clin Genet, London, England. [Jacobsen, Jessie C.] Kings Coll London, Div Med & Mol Genet, London, England. [Jacobsen, Jessie C.] Univ Auckland, Ctr Brain Res, Auckland, New Zealand. [Jacobsen, Jessie C.] Univ Auckland, Sch Biol Sci, Auckland, New Zealand. [Jewett, Tamison; Mortenson, Megan E.] Wake Forest Sch Med, Dept Pediat, Winston Salem, NC USA. [Johnson, John P.] Shodair Childrens Hosp, Dept Mol Genet, Helena, MT USA. [Kahler, Stephen G.; Lim, Cynthia] Arkansas Childrens Hosp, Div Genet & Metab, Little Rock, AR USA. [Kroisel, Peter M.] Med Univ Graz, Inst Human Genet, Graz, Austria. [Lacassie, Yves] LSUHSC, Dept Pediat, New Orleans, LA USA. [Lacassie, Yves] Childrens Hosp, New Orleans, LA USA. [Lemyre, Emmanuelle] Univ Montreal, CHU St Justine, Dept Pediat, Montreal, PQ, Canada. [Leppig, Kathleen] Univ Washington, Dept Med, Div Med Genet, Seattle, WA USA. [Leppig, Kathleen] Grp Hlth Cooperat Puget Sound, Clin Genet, Seattle, WA USA. [Levin, Alex V.] Thomas Jefferson Univ, Wills Eye Hosp, Philadelphia, PA 19107 USA. [Li, Haibo; Li, Hong] Nanjing Med Univ, Affiliated Suzhou Hosp, Ctr Reprod & Genet, Suzhou, Peoples R China. [Liao, Eric C.] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Liao, Eric C.; Mendoza, Cinthya J. Zepeda; Ordulu, Zehra; Pauker, Susan P.; Schilit, Samantha L. P.; Thakuria, Joseph V.; Morton, Cynthia C.] Harvard Med Sch, Boston, MA USA. [Liao, Eric C.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. [Liao, Eric C.] Harvard Stem Cell Inst, Cambridge, MA USA. [Lose, Edward J.] Virginia G Piper Canc Ctr HonorHlth, Scottsdale, AZ USA. [Lose, Edward J.] UAB, Dept Genet, Birmingham, AL USA. [Macera, Michael J.] Columbia Univ, Med Ctr, New York Presbyterian Hosp, Clin Cytogenet Lab, New York, NY USA. [Margolin, Lauren; Mason, Tamara; Perrin, Danielle] Broad Inst Harvard & MIT, Genom Platform, Cambridge, MA USA. [Masser-Frye, Diane] Rady Childrens Hosp, Dept Genet, San Diego, CA USA. [McClellan, Michael W.] Madigan Army Med Ctr, Dept Obstet & Gynecol, Tacoma, WA 98431 USA. [Mikami, Liya R.; Raskin, Salmo] Pontificia Univ Catolica Parana, Sch Med, Grad Program Hlth Sci, Grp Adv Mol Invest, Curitiba, Parana, Brazil. [Mikami, Liya R.] Ctr Univ Autonomo Brasil Unibrasil, Curitiba, Parana, Brazil. [Mononen, Tarja] Kuopio Univ Hosp, Dept Clin Genet, Kuopio, Finland. [Mortenson, Megan E.] Novant Hlth Derrick L Davis Canc Ctr, Winston Salem, NC USA. [Moya, Graciela] GENOS Lab, Buenos Aires, DF, Argentina. [Nieuwint, Aggie W.; Poddighe, Pino J.; van de Kamp, Jiddeke] Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Amsterdam, Netherlands. [Parkash, Sandhya] Dalhousie Univ, IWK Hlth Ctr, Maritime Med Genet Serv, Dept Pediat, Halifax, NS, Canada. [Pauker, Susan P.] Harvard Vanguard Med Associates, Med Genet, Watertown, MA USA. [Phelan, Katy] Tulane Univ, Sch Med, Dept Pediat, Hayward Genet Program, New Orleans, LA 70112 USA. [Pina Aguilar, Raul E.] Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen, Scotland. [Reis, Linda] Childrens Res Inst, Milwaukee, WI USA. [Rhead, William] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. [Rita, Debra] Aurora Clin Labs, Midwest Diagnost Pathol, Rosemont, IL USA. [Roelens, Filip] Algemeen Ziekenhuis Delta, Roeselare, Belgium. [Rump, Patrick; van Essen, Ton; van Ravenswaaij-Arts, Conny M.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands. [Spiegel, Erica] Columbia Univ, Med Ctr, Div Maternal Fetal Med, New York, NY USA. [Stevens, Blair] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Houston, TX 77030 USA. [Tagoe, Julia] Alberta Hlth Serv, Genet Serv, Lethbridge, AB, Canada. [Thakuria, Joseph V.] Massachusetts Gen Hosp, Div Med Genet, Boston, MA 02114 USA. [Waterman, Matthew J.] Eastern Nazarene Coll, Dept Biol, Quincy, MA USA. [Wiley, Susan] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Dev & Behav Pediat, Cincinnati, OH USA. [Yerena-de Vega, Maria de la Concepcion A.] ISSSTE, Ctr Med Nacl Noviembre 20, Lab Genet, Mexico City, DF, Mexico. [Zori, Roberto T.] Univ Florida, Div Pediat Genet & Metab, Gainesville, FL USA. [Levy, Brynn] Columbia Univ, Dept Pathol, New York, NY USA. [Brunner, Han G.] Maastricht Univ, Med Ctr, Dept Clin Genet, Maastricht, Netherlands. [Brunner, Han G.] Maastricht Univ, Med Ctr, Grow Sch Oncol & Dev Biol, Maastricht, Netherlands. [Morton, Cynthia C.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Morton, Cynthia C.] Univ Manchester, Manchester Acad Hlth Sci Ctr, Sch Biol Sci, Div Evolut & Genom Sci, Manchester, Lancs, England. [Brown, Chester W.] Univ Tennessee, Ctr Hlth Sci, Le Bonheur Childrens Hosp, Dept Pediat,Genet Div, Memphis, TN 38163 USA. EM talkowski@chgr.mgh.harvard.edu OI Graham, Brett/0000-0001-8451-8154; Collins, Ryan/0000-0003-1268-9995; Callewaert, Bert/0000-0002-9743-4205; FitzPatrick, David R./0000-0003-4861-969X; David, Dezso/0000-0003-2293-590X FU National Institutes of Health [GM061354, MH095867, HD081256]; March of Dimes [6-FY15-255]; European Commission [EMBO ALTF-183-2015]; Bettencourt-Schueller Foundation; Philippe Foundation; Harvard Medical School-Portugal Program in Translational and Clinical Research and Health Information (Fundacao para a Ciencia e a Tecnologia) [HMSP-ICT/0016/2013]; National Science Foundation [DGE1144152]; Fund for Scientific Research-Flanders; Clinical Medicine Science and Technology Projects of Jiangsu Province [BL2013019]; Suzhou Key Medical Center [Szzx201505]; Royal Society of New Zealand (Rutherford Discovery Fellowship); Desmond and Ann Heathwood MGH Research Scholars award FX We wish to thank all subjects and families who have been enrolled in this study, as well as the countless genetic counselors and clinical geneticists who contributed to the ascertainment of subjects. This study was supported by the National Institutes of Health (grant GM061354 to M.E.T., J.F.G., C.C.M., and E.L.; grants MH095867 and HD081256 to M.E.T.), the March of Dimes (6-FY15-255 to M.E.T.), the European Molecular Biology Organization and the Marie Curie Actions of the European Commission (fellowship EMBO ALTF-183-2015 to C.R.), the Bettencourt-Schueller Foundation (young investigator award to C.R.), the Philippe Foundation (award to C.R.), the Harvard Medical School-Portugal Program in Translational and Clinical Research and Health Information (Fundacao para a Ciencia e a Tecnologia, HMSP-ICT/0016/2013 to C.C.M. and D.D.), the National Science Foundation (NSF Graduate Research Fellowship DGE1144152 to S.L.P.S.), the Fund for Scientific Research-Flanders (B.C. and S.V. are an FWO senior clinical investigator and an FWO postdoctoral researcher, respectively), Clinical Medicine Science and Technology Projects of Jiangsu Province (grant BL2013019 to Haibo Li and Hong Li), the Suzhou Key Medical Center (grant Szzx201505 to Haibo Li and Hong Li), and the Royal Society of New Zealand (Rutherford Discovery Fellowship to J.C.J.). This study was also supported by the Desmond and Ann Heathwood MGH Research Scholars award to M.E.T. NR 79 TC 3 Z9 3 U1 6 U2 6 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 JAN PY 2017 VL 49 IS 1 BP 36 EP 45 DI 10.1038/ng.3720 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA EG3WY UT WOS:000390976600009 PM 27841880 ER PT J AU Okimoto, RA Breitenbuecher, F Olivas, VR Wu, W Gini, B Hofree, M Asthana, S Hrustanovic, G Flanagan, J Tulpule, A Blakely, CM Haringsma, HJ Simmons, AD Gowen, K Suh, J Miller, VA Ali, S Schuler, M Bivona, TG AF Okimoto, Ross A. Breitenbuecher, Frank Olivas, Victor R. Wu, Wei Gini, Beatrice Hofree, Matan Asthana, Saurabh Hrustanovic, Gorjan Flanagan, Jennifer Tulpule, Asmin Blakely, Collin M. Haringsma, Henry J. Simmons, Andrew D. Gowen, Kyle Suh, James Miller, Vincent A. Ali, Siraj Schuler, Martin Bivona, Trever G. TI Inactivation of Capicua drives cancer metastasis SO NATURE GENETICS LA English DT Article ID LUNG-CANCER; MATRIX METALLOPROTEINASES; DOWN-REGULATION; PROGRESSION; ACTIVATION; MUTATIONS; REPRESSOR; DISEASE; TORSO AB Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. Inactivation of CIC relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in people with lung and/or gastric cancer. Our findings reveal CIC as a conserved metastasis suppressor, highlighting new anti-metastatic strategies that could potentially improve patient outcomes. C1 [Okimoto, Ross A.; Olivas, Victor R.; Wu, Wei; Gini, Beatrice; Tulpule, Asmin; Blakely, Collin M.; Bivona, Trever G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Okimoto, Ross A.; Wu, Wei; Gini, Beatrice; Asthana, Saurabh; Hrustanovic, Gorjan; Flanagan, Jennifer; Tulpule, Asmin; Blakely, Collin M.; Bivona, Trever G.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Breitenbuecher, Frank; Schuler, Martin] Univ Hosp Essen, Dept Med Oncol, West German Canc Ctr, Essen, Germany. [Hofree, Matan] Broad Inst MIT & Harvard, Cambridge, MA USA. [Hofree, Matan] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Haringsma, Henry J.; Simmons, Andrew D.] Clovis Oncol Inc, San Francisco, CA USA. [Gowen, Kyle; Suh, James; Miller, Vincent A.; Ali, Siraj] Fdn Med, Cambridge, MA USA. [Schuler, Martin] German Canc Consortium DKTK, Heidelberg, Germany. EM trever.bivona@ucsf.edu FU A.P. Giannini Foundation; NIH Director's New Innovator Award [DP2 CA174497]; NIH/NCI [RO1 CA169338]; Pew-Stewart Foundation Trusts; [NIHT32CA177555-01] FX R.A.O. was supported by the A.P. Giannini Foundation and NIHT32CA177555-01. T.G.B. acknowledges support from NIH Director's New Innovator Award DP2 CA174497, NIH/NCI RO1 CA169338, and the Pew-Stewart Foundation Trusts. We thank B. Hann (UCSF Preclinical Therapeutics Core) for helpful discussions. The lentiviral GFP-Luc vector was a kind gift from M. Jensen (Seattle Children's Research Institute, Seattle, Washington, USA). NR 31 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 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JAN PY 2017 VL 49 IS 1 BP 87 EP 96 DI 10.1038/ng.3728 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA EG3WY UT WOS:000390976600014 PM 27869830 ER PT J AU Chu, AY Deng, X Fisher, VA Drong, A Zhang, Y Feitosa, MF Liu, CT Weeks, O Choh, AC Duan, Q Dyer, TD Eicher, JD Guo, XQ Heard-Costa, NL Kacprowski, T Kent, JW Lange, LA Liu, XG Lohman, K Lu, LY Mahajan, A O'Connell, JR Parihar, A Peralta, JM Smith, AV Zhang, Y Homuth, G Kissebah, AH Kullberg, J Laqua, R Launer, LJ Nauck, M Olivier, M Peyser, PA Terry, JG Wojczynski, MK Yao, J Bielak, LF Blangero, J Borecki, IB Bowden, DW Carr, JJ Czerwinski, SA Ding, JZ Friedrich, N Gudnason, V Harris, TB Ingelsson, E Johnson, AD Kardia, SLR Langefeld, CD Lind, L Liu, YM Mitchell, BD Morris, AP Mosley, TH Rotter, JI Shuldiner, AR Towne, B Volzke, H Wallaschofski, H Wilson, JG Allison, M Lindgren, CM Goessling, W Cupples, LA Steinhauser, ML Fox, CS AF Chu, Audrey Y. Deng, Xuan Fisher, Virginia A. Drong, Alexander Zhang, Yang Feitosa, Mary F. Liu, Ching-Ti Weeks, Olivia Choh, Audrey C. Duan, Qing Dyer, Thomas D. Eicher, John D. Guo, Xiuqing Heard-Costa, Nancy L. Kacprowski, Tim Kent, Jack W., Jr. Lange, Leslie A. Liu, Xinggang Lohman, Kurt Lu, Lingyi Mahajan, Anubha O'Connell, Jeffrey R. Parihar, Ankita Peralta, Juan M. Smith, Albert V. Zhang, Yi Homuth, Georg Kissebah, Ahmed H. Kullberg, Joel Laqua, Rene Launer, Lenore J. Nauck, Matthias Olivier, Michael Peyser, Patricia A. Terry, James G. Wojczynski, Mary K. Yao, Jie Bielak, Lawrence F. Blangero, John Borecki, Ingrid B. Bowden, Donald W. Carr, John Jeffrey Czerwinski, Stefan A. Ding, Jingzhong Friedrich, Nele Gudnason, Vilmunder Harris, Tamara B. Ingelsson, Erik Johnson, Andrew D. Kardia, Sharon L. R. Langefeld, Carl D. Lind, Lars Liu, Yongmei Mitchell, Braxton D. Morris, Andrew P. Mosley, Thomas H., Jr. Rotter, Jerome I. Shuldiner, Alan R. Towne, Bradford Voelzke, Henry Wallaschofski, Henri Wilson, James G. Allison, Matthew Lindgren, Cecilia M. Goessling, Wolfram Cupples, L. Adrienne Steinhauser, Matthew L. Fox, Caroline S. TI Multiethnic genome-wide meta-analysis of ectopic fat depots identifies loci associated with adipocyte development and differentiation SO NATURE GENETICS LA English DT Article ID INCIDENT CARDIOVASCULAR-DISEASE; METABOLIC RISK-FACTORS; ALL-CAUSE MORTALITY; CARDIOMETABOLIC RISK; VISCERAL ADIPOSITY; SUBCUTANEOUS FAT; SUSCEPTIBILITY; HYPERTENSION; QUALITY; BIOLOGY AB Variation in body fat distribution contributes to the metabolic sequelae of obesity. The genetic determinants of body fat distribution are poorly understood. The goal of this study was to gain new insights into the underlying genetics of body fat distribution by conducting sample-size-weighted fixed-effects genome-wide association meta-analyses in up to 9,594 women and 8,738 men of European, African, Hispanic and Chinese ancestry, with and without sex stratification, for six traits associated with ectopic fat (hereinafter referred to as ectopicfat traits). In total, we identified seven new loci associated with ectopic-fat traits (ATXN1, UBE2E2, EBF1, RREB1, GSDMB, GRAMD3 and ENSA; P < 5 x 10(-8); false discovery rate < 1 %). Functional analysis of these genes showed that loss of function of either Atxn1 or Ube2e2 in primary mouse adipose progenitor cells impaired adipocyte differentiation, suggesting physiological roles for ATXN1 and UBE2E2 in adipogenesis. Future studies are necessary to further explore the mechanisms by which these genes affect adipocyte biology and how their perturbations contribute to systemic metabolic disease. C1 [Chu, Audrey Y.; Eicher, John D.; Johnson, Andrew D.; Cupples, L. Adrienne; Fox, Caroline S.] NHLBIs Framingham Heart Study, Framingham, MA USA. [Chu, Audrey Y.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Chu, Audrey Y.; Zhang, Yang; Weeks, Olivia; Goessling, Wolfram; Steinhauser, Matthew L.; Fox, Caroline S.] Harvard Med Sch, Boston, MA 02115 USA. [Deng, Xuan; Fisher, Virginia A.; Liu, Ching-Ti; Heard-Costa, Nancy L.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Drong, Alexander; Mahajan, Anubha; Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Zhang, Yang; Steinhauser, Matthew L.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Zhang, Yang; Weeks, Olivia; Goessling, Wolfram; Steinhauser, Matthew L.] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA. [Feitosa, Mary F.; Wojczynski, Mary K.; Borecki, Ingrid B.] Washington Univ, Dept Genet, St Louis, MO 63110 USA. [Choh, Audrey C.; Towne, Bradford] Wright State Univ, Boonshoft Sch Med, Dept Populat & Publ Hlth Sci, Div Epidemiol & Biostat, Dayton, OH 45435 USA. [Duan, Qing; Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Dyer, Thomas D.; Peralta, Juan M.; Blangero, John] Univ Texas Hlth Sci Ctr San Antonio, South Texas Diabet & Obes Inst, Brownsville, TX USA. [Dyer, Thomas D.; Peralta, Juan M.; Blangero, John] Univ Texas Rio Grande Valley, Brownsville, TX USA. [Guo, Xiuqing; Yao, Jie; Rotter, Jerome I.] UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, LABioMed Harbor, Torrance, CA USA. [Kacprowski, Tim; Homuth, Georg] Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Kacprowski, Tim; Nauck, Matthias; Friedrich, Nele; Voelzke, Henry] German Ctr Cardiovasc Res DZHK, Greifswald, Germany. [Kent, Jack W., Jr.; Olivier, Michael] Texas Biomed Res Inst, Dept Genet, TOPS Nutr & Obes Res Ctr, San Antonio, TX USA. [Liu, Xinggang; O'Connell, Jeffrey R.; Parihar, Ankita; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Lohman, Kurt; Ding, Jingzhong; Liu, Yongmei] Wake Forest Sch Med, Winston Salem, NC USA. [Lohman, Kurt; Lu, Lingyi; Langefeld, Carl D.] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Smith, Albert V.; Gudnason, Vilmunder] Iceland Heart Assoc, Kopavogur, Iceland. [Smith, Albert V.; Gudnason, Vilmunder] Univ Iceland, Fac Med, Reykjavik, Iceland. [Zhang, Yi; Kissebah, Ahmed H.; Olivier, Michael] Med Coll Wisconsin, Biotechnol & Bioengn Ctr, TOPS Obes & Metab Res Ctr, Dept Psychol, Milwaukee, WI 53226 USA. [Kullberg, Joel; Lind, Lars] Uppsala Univ, Sect Radiol, Dept Surg Sci, Uppsala, Sweden. [Laqua, Rene] Univ Hosp Berne, Dept Neuroradiol, Bern, Switzerland. [Launer, Lenore J.; Harris, Tamara B.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Nauck, Matthias; Friedrich, Nele; Wallaschofski, Henri] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany. [Peyser, Patricia A.; Bielak, Lawrence F.; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Terry, James G.; Carr, John Jeffrey] Vanderbilt Univ, Med Ctr, Dept Cardiovasc Med, Dept Radiol & Radiol Sci, Nashville, TN USA. [Terry, James G.; Carr, John Jeffrey] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA. [Bowden, Donald W.] Wake Forest Univ Hlth Sci, Ctr Genom & Personalized Med Res, Winston Salem, NC USA. [Bowden, Donald W.] Wake Forest Univ, Sch Med, Ctr Diabet Res, Dept Biochem, Winston Salem, NC 27109 USA. [Bowden, Donald W.] Wake Forest Univ, Sch Med, Ctr Human Genom, Winston Salem, NC 27109 USA. [Czerwinski, Stefan A.] Univ Texas Hlth Sci Ctr UTHealth, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Brownsville Campus, Brownsville, TX USA. [Ding, Jingzhong] Wake Forest Sch Med, Gerontol & Geriatr Med, Winston Salem, NC USA. [Ingelsson, Erik] Uppsala Univ, Mol Epidemiol & Sci Life Lab, Dept Med Sci, Uppsala, Sweden. [Ingelsson, Erik] Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Mitchell, Braxton D.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA. [Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England. [Mosley, Thomas H., Jr.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. [Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany. [Voelzke, Henry] German Ctr Diabet Res DZD, Greifswald, Germany. [Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA. [Allison, Matthew] Univ Calif San Diego, Sch Med, Dept Family Med & Publ Hlth, Div Prevent Med, San Diego, CA 92103 USA. [Lindgren, Cecilia M.] Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England. [Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA USA. [Goessling, Wolfram] Harvard Med Sch, Brigham & Womens Hosp, Div Gastroenterol, Boston, MA USA. [Goessling, Wolfram] Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram; Steinhauser, Matthew L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. [Steinhauser, Matthew L.] Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, 75 Francis St, Boston, MA 02115 USA. [Chu, Audrey Y.; Fox, Caroline S.] Merck Res Labs, Boston, MA 02115 USA. EM audrey.chu@nih.gov; msteinhauser@partners.org; foxca@nhlbi.nih.gov RI Feitosa, Mary/K-8044-2012 OI Allison, Matthew/0000-0003-0777-8272; Carr, John/0000-0002-4398-8237; Mitchell, Braxton/0000-0003-4920-4744; Feitosa, Mary/0000-0002-0933-2410 FU NHLBI NIH HHS [R01 HL117078]; NIDDK NIH HHS [R01 DK106236] NR 27 TC 0 Z9 0 U1 3 U2 3 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 JAN PY 2017 VL 49 IS 1 BP 125 EP 130 DI 10.1038/ng.3738 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA EG3WY UT WOS:000390976600018 PM 27918534 ER PT J AU Markland, AD Jelovsek, JE Whitehead, WE Newman, DK Andy, UU Dyer, K Harm-Ernandes, I Cichowski, S McCormick, J Rardin, C Sutkin, G Shaffer, A Meikle, S AF Markland, A. D. Jelovsek, J. E. Whitehead, W. E. Newman, D. K. Andy, U. U. Dyer, K. Harm-Ernandes, I. Cichowski, S. McCormick, J. Rardin, C. Sutkin, G. Shaffer, A. Meikle, S. CA Pelvic Floor Disorders Network TI Improving biofeedback for the treatment of fecal incontinence in women: implementation of a standardized multi-site manometric biofeedback protocol SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE anal sphincter exercises; anorectal manometry; factorial design; fecal incontinence; manometry-assisted biofeedback; pelvic floor disorders; randomized placebo-controlled trial; treatment fidelity; urge resistance training ID OBJECTIVE STRUCTURED ASSESSMENT; RANDOMIZED CONTROLLED-TRIAL; ANAL INCONTINENCE; TECHNICAL SKILL; SURGICAL RESIDENTS; NATIONAL INSTITUTE; EXERCISES; TRAINEES; WORKSHOP; DESIGN AB BackgroundStandardized training and clinical protocols using biofeedback for the treatment of fecal incontinence (FI) are important for clinical care. Our primary aims were to develop, implement, and evaluate adherence to a standardized protocol for manometric biofeedback to treat FI. MethodsIn a Pelvic Floor Disorders Network (PFDN) trial, participants were enrolled from eight PFDN clinical centers across the United States. A team of clinical and equipment experts developed biofeedback software on a novel tablet computer platform for conducting standardized anorectal manometry with separate manometric biofeedback protocols for improving anorectal muscle strength, sensation, and urge resistance. The training protocol also included education on bowel function, anal sphincter exercises, and bowel diary monitoring. Study interventionists completed online training prior to attending a centralized, standardized certification course. For the certification, expert trainers assessed the ability of the interventionists to perform the protocol components for a paid volunteer who acted as a standardized patient. Postcertification, the trainers audited interventionists during trial implementation to improve protocol adherence. Key ResultsTwenty-four interventionists attended the in-person training and certification, including 46% advanced practice registered nurses (11/24), 50% (12/24) physical therapists, and 4% physician assistants (1/24). Trainers performed audio audits for 88% (21/24), representing 84 audited visits. All certified interventionists met or exceeded the prespecified 80% pass rate for the audit process, with an average passing rate of 93%. Conclusions & InferencesA biofeedback protocol can be successfully imparted to experienced pelvic floor health care providers from various disciplines. Our process promoted high adherence to a standard protocol and is applicable to many clinical settings. C1 [Markland, A. D.; McCormick, J.] Univ Alabama Birmingham, Dept Med, Div Gerontol Geriatr & Palliat Care, 700 19th St South, Birmingham, AL 35294 USA. [Markland, A. D.; McCormick, J.] Birmingham Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. [Jelovsek, J. E.] Cleveland Clin, Obstet Gynecol & Womens Hlth Inst, Cleveland, OH 44106 USA. [Whitehead, W. E.] Univ North Carolina Chapel Hill, Div Gastroenterol & Hepatol, Dept Med, Chapel Hill, NC USA. [Whitehead, W. E.] Univ North Carolina Chapel Hill, Div Urogynecol, Dept Obstet & Gynecol, Chapel Hill, NC USA. [Newman, D. K.] Univ Penn, Dept Surg, Perelman Sch Med, Div Urol, Philadelphia, PA 19104 USA. [Andy, U. U.] Univ Penn, Dept Obstet & Gynecol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Dyer, K.] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA. [Harm-Ernandes, I.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Cichowski, S.] Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. [Cichowski, S.] Univ New Mexico, Hlth Sci Ctr, Dept Surg, Albuquerque, NM 87131 USA. [Rardin, C.] Brown Univ, Alpert Med Sch, Dept Obstet & Gynecol, Providence, RI 02912 USA. [Sutkin, G.] Univ Pittsburgh, Med Ctr, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. [Shaffer, A.] RTI Int, Res Triangle Pk, NC USA. [Meikle, S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. EM amarkland@uabmc.edu OI Markland, Alayne/0000-0002-6567-6744 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10 HD054215, U10 HD041261, U10 HD069013, U10 HD054214, U10 HD041267, U10 HD069025, U10 HD069010, U10 HD069006, U01 HD069031]; National Institutes of Health Office of Research on Women's Health FX Supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (U10 HD054215, U10 HD041261, U10 HD069013, U10 HD054214, U10 HD041267, U10 HD069025, U10 HD069010, U10 HD069006, U01 HD069031) and the National Institutes of Health Office of Research on Women's Health. NR 19 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 EI 1365-2982 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JAN PY 2017 VL 29 IS 1 AR UNSP e12906 DI 10.1111/nmo.12906 PG 7 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA EI4YM UT WOS:000392500000009 ER PT J AU Chabner, BA Murphy, MJ AF Chabner, Bruce A. Murphy, Martin J. TI Let This Be Our New Year's Pledge SO ONCOLOGIST LA English DT Editorial Material ID MERKEL-CELL-CARCINOMA; CANCER C1 [Chabner, Bruce A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. EM bchabner@partners.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2017 VL 22 IS 1 BP 1 EP 2 DI 10.1634/theoncologist.2017-0001 PG 2 WC Oncology SC Oncology GA EI6IH UT WOS:000392598300001 PM 28126914 ER PT J AU Tolaney, SM Ziehr, DR Guo, H Ng, MR Barry, WT Higgins, MJ Isakoff, SJ Brock, JE Ivanova, EV Paweletz, CP Demeo, MK Ramaiya, NH Overmoyer, BA Jain, RK Winer, EP Duda, DG AF Tolaney, Sara M. Ziehr, David R. Guo, Hao Ng, Mei R. Barry, William T. Higgins, Michaela J. Isakoff, Steven J. Brock, Jane E. Ivanova, Elena V. Paweletz, Cloud P. Demeo, Michelle K. Ramaiya, Nikhil H. Overmoyer, Beth A. Jain, Rakesh K. Winer, Eric P. Duda, Dan G. TI Phase II and Biomarker Study of Cabozantinib in Metastatic Triple-Negative Breast Cancer Patients SO ONCOLOGIST LA English DT Article DE Triple-negative breast cancer; Cabozantinib; Soluble MET; Lymphocytes; Vascular endothelial growth factor receptor ID HEPATOCYTE GROWTH-FACTOR; C-MET; PROSTATE-CANCER; SURVIVAL; BEVACIZUMAB; EXPRESSION; CARCINOMA; RECEPTOR; TRIAL; ANGIOGENESIS AB Currently, no targeted therapies are available for metastatic triple-negative breast cancer (mTNBC). We evaluated the safety, efficacy, and biomarkers of response to cabozantinib, a multikinase inhibitor, in patients with mTNBC. We conducted a single arm phase II and biomarker study that enrolled patients with measurable mTNBC. Patients received cabozantinib (60mg daily) on a 3-week cycle and were restaged after 6 weeks and then every 9 weeks. The primary endpoint was objective response rate. Predefined secondary endpoints included progression-free survival (PFS), toxicity, and tissue and blood circulating cell and protein biomarkers. Of 35 patients who initiated protocol therapy, 3 (9% [95% confidence interval (CI): 2, 26]) achieved a partial response (PR). Nine patients achieved stable disease (SD) for at least 15 weeks, and thus the clinical benefit rate (PR1SD) was 34% [95% CI: 19, 52]. Median PFS was 2.0months [95% CI: 1.3, 3.3]. The most common toxicities were fatigue, diarrhea, mucositis, and palmar-plantar erythrodysesthesia. There were no grade 4 toxicities, but 12 patients (34%) required dose reduction. Two patients had TNBCs with MET amplification. During cabozantinib therapy, there were significant and durable increases in plasma placental growth factor, vascular endothelial growth factor (VEGF), VEGF-D, stromal cell-derived factor 1a, and carbonic anhydrase IX, and circulating CD31cells and CD8 + T lymphocytes, and decreases in plasma soluble VEGF receptor 2 and CD14+ monocytes (all p<.05). Higher baseline concentrations of soluble MET (sMET) associated with longer PFS (p = .03). In conclusion, cabozantinib showed encouraging safety and efficacy signals but did not meet the primary endpoint in pretreated mTNBC. Exploratory analyses of circulating biomarkers showed that cabozantinib induces systemic changes consistent with activation of the immune system and antiangiogenic activity, and that sMETshould be further evaluated a potential biomarker of response. C1 [Tolaney, Sara M.; Guo, Hao; Barry, William T.; Ivanova, Elena V.; Paweletz, Cloud P.; Demeo, Michelle K.; Ramaiya, Nikhil H.; Overmoyer, Beth A.; Winer, Eric P.] Dana Farber Canc Inst, 450 Brookline Ave,Y1257, Boston, MA 02215 USA. [Ziehr, David R.; Higgins, Michaela J.; Isakoff, Steven J.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Boston, MA 02114 USA. [Ng, Mei R.; Jain, Rakesh K.; Duda, Dan G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Labs, Res Inst, Boston, MA 02114 USA. [Brock, Jane E.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM stolaney@partners.org; gduda@partners.org FU Exelixis, Rosa's Pursuit of Hope; TripAdvisor Charitable Foundation; Department of Defense Breast Cancer Research Program Innovator Award [W81XWH-10-1-0016]; National Cancer Institute (NCI) [R01CA159258]; NCI Proton Beam/Federal Share Program; U.S. Department of Defense Breast Cancer Research Program Postdoctoral Fellowship [W81XWH-14-1-0034] FX We thank Anna Khachatryan and Cristina Koppel for technical assistance. The clinical trial was supported by funding from Exelixis, Rosa's Pursuit of Hope (Sara M. Tolaney); the TripAdvisor Charitable Foundation (Sara M. Tolaney); Department of Defense Breast Cancer Research Program Innovator Award W81XWH-10-1-0016 (to Rakesh K. Jain); and National Cancer Institute (NCI) Grant R01CA159258 (to Dan G. Duda) and NCI Proton Beam/Federal Share Program grants (to Rakesh K. Jain and Dan G. Duda). Mei R. Ng was supported by a U.S. Department of Defense Breast Cancer Research Program Postdoctoral Fellowship (W81XWH-14-1-0034). Clinical trial information: NCT02260531. NR 36 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2017 VL 22 IS 1 BP 25 EP 32 DI 10.1634/theoncologist.2016-0229 PG 8 WC Oncology SC Oncology GA EI6IH UT WOS:000392598300004 PM 27789775 ER PT J AU Herzberg, B Campo, MJ Gainor, JF AF Herzberg, Benjamin Campo, Meghan J. Gainor, Justin F. TI Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Lung cancer; Non-small cell lung cancer; Immune therapy; Programmed cell death protein-1 inhibitors; Checkpoint inhibition; Cytotoxic T-lymphocyte-associated antigen 4 ID METASTATIC MELANOMA; REGULATORY T; ANTI-PD-1 ANTIBODY; ANTITUMOR-ACTIVITY; PD-1 BLOCKADE; CTLA-4; NIVOLUMAB; ACTIVATION; IPILIMUMAB; RECEPTOR AB Historically, lung cancer was long considered a poorly immunogenic malignancy. In recent years, however, immune checkpoint inhibitors have emerged as promising therapeutic agents in non-small cell lung cancer (NSCLC). To date, the best characterized and most therapeutically relevant immune checkpoints have been cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death protein-1 (PD-1) pathway. In early studies, PD-1/programmed cell death ligand-1 (PD-L1) inhibitors demonstrated promising antitumor activity and durable clinical responses in a subset of patients. Based on these encouraging results, multiple different PD-1/PD-L1 inhibitors have entered clinical development, and two agents (nivolumab and pembrolizumab) have gained regulatory approval in the United States for the treatment of NSCLC. In several large, randomized studies, PD-1/PD-L1 inhibitors have produced significant improvements in overall survival compared with single-agent docetaxel delivered in the second-line setting, effectively establishing a new standard of care in NSCLC. In the present report, we provide an overview of the rationale for checkpoint inhibitors in lung cancer, recent clinical trial data, and the need for predictive biomarkers. C1 [Herzberg, Benjamin; Campo, Meghan J.; Gainor, Justin F.] Massachusetts Gen Hosp, Dept Med, 10 North Grove St,LRH-238, Boston, MA 02114 USA. EM jgainor@partners.org NR 62 TC 0 Z9 0 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2017 VL 22 IS 1 BP 81 EP 88 DI 10.1634/theoncologist.2016-0189 PG 8 WC Oncology SC Oncology GA EI6IH UT WOS:000392598300010 PM 27534574 ER PT J AU Niedzwiecki, D Hasson, RM Lenz, HJ Ye, C Redston, M Ogino, S Fuchs, CS Compton, CC Mayer, RJ Goldberg, RM Colacchio, TA Saltz, LB Warren, RS Bertagnolli, MM AF Niedzwiecki, Donna Hasson, Rian M. Lenz, Heinz-Josef Ye, Cynthia Redston, Mark Ogino, Shuji Fuchs, Charles S. Compton, Carolyn C. Mayer, Robert J. Goldberg, Richard M. Colacchio, Thomas A. Saltz, Leonard B. Warren, Robert S. Bertagnolli, Monica M. TI A Study of Thymidylate Synthase Expression as a Biomarker for Resectable Colon Cancer: Alliance (Cancer and Leukemia Group B) 9581 and 89803 SO ONCOLOGIST LA English DT Article DE Colon cancer; Biomarkers; Adjuvant therapy; Thymidylate synthase; Microsatellite instability; Mismatch repair deficiency ID MICROSATELLITE-INSTABILITY; ADJUVANT THERAPY; STAGE-II; COLORECTAL-CANCER; PREDICTIVE MARKER; FLUOROURACIL; CHEMOTHERAPY; PROGNOSIS; SURVIVAL; P53 AB Purpose. Tumor levels of thymidylate synthase (TS), a target of 5-fluorouracil (5-FU)-based chemotherapy for colorectal cancer, have been studied as a predictive or prognostic biomarker with mixed results. Patients and Methods. Tumor TS levels were prospectively evaluated in two adjuvant therapy trials for patients with resected stage II or III colon cancer. TS expression was determined by standard immunohistochemistry and by automated quantitative analysis. Tumor mismatch repair deficiency (MMR-D) and BRAF c.1799T>A (p.V600E) mutation status were also examined. Relationships between tumor TS, MMR-D, and BRAF mutation status, overall survival (OS), and disease-free survival (DFS) were investigated in the subset of stage III patients. Results. Patients whose tumors demonstrated high TS expression experienced better treatment outcomes, with DFS hazard ratio (HR) = 0.67, 95% confidence interval (CI) = 0.53, 0.84; and OS HR = 0.68, 95% CI = 0.53, 0.88, for high versus low TS expression, respectively. No significant interaction between TS expression and stage was observed (DFS: interaction HR = 0.94; OS: interaction HR = 0.94). Tumors with high TS expression were more likely to demonstrate MMR-D (22.2% vs. 12.8%; p = .0003). Patients whose tumors demonstrated both high TS and MMR-D had a 7-year DFS of 77%, compared with 58% for those whose tumors had low TS and were non-MMR-D (log-rank p = .0006). Tumor TS expression did not predict benefit of a particular therapeutic regimen. Conclusion. This large prospective analysis showed that high tumor TS levels were associated with improved DFS and OS following adjuvant therapy for colon cancer, although tumor TS expression did not predict benefit of 5-FU-based chemotherapy. Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility. Implications for Practice: This study finds that measurement of tumor levels of thymidylate synthase is not helpful in assigning specific adjuvant treatment for colorectal cancer. It also highlights the importance of using prospective analyses within treatment clinical trials as the optimal method of determining biomarker utility. C1 [Niedzwiecki, Donna; Ye, Cynthia] Duke Univ, Alliance Stat & Data Ctr, Durham, NC USA. [Niedzwiecki, Donna; Ye, Cynthia] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA. [Hasson, Rian M.; Bertagnolli, Monica M.] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Redston, Mark; Ogino, Shuji] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Lenz, Heinz-Josef] Univ Southern Calif, Norris Canc Ctr, Los Angeles, CA USA. [Ogino, Shuji; Fuchs, Charles S.; Mayer, Robert J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Compton, Carolyn C.] Arizona State Univ, Phoenix, AZ USA. [Goldberg, Richard M.] Ohio State Univ, Columbus, OH 43210 USA. [Colacchio, Thomas A.] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. [Saltz, Leonard B.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Warren, Robert S.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA. EM mbertagnolli@partners.org FU National Cancer Institute [CA31946, CA33601]; National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases [2T32DK007754-12] FX This work was supported in part by National Cancer Institute Grants CA31946 (to the Cancer and Leukemia Group B; Monica M. Bertagnolli, M.D., chair) and CA33601 (to the Cancer and Leukemia Group B Statistical Center; Daniel J. Sargent, Ph.D.) and the National Institute of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant 2T32DK007754-12 (to Rian M. Hasson). NR 26 TC 0 Z9 0 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 EI 1549-490X J9 ONCOLOGIST JI Oncologist PD JAN PY 2017 VL 22 IS 1 BP 107 EP 114 DI 10.1634/theoncologist.2016-0215 PG 8 WC Oncology SC Oncology GA EI6IH UT WOS:000392598300013 PM 27821793 ER PT J AU Brown, WJ Wilkerson, AK Milanak, ME Tuerk, PW Uhde, TW Cortese, BM Grubaugh, AL AF Brown, Wilson J. Wilkerson, Allison K. Milanak, Melissa E. Tuerk, Peter W. Uhde, Thomas W. Cortese, Bernadette M. Grubaugh, Anouk L. TI An examination of sleep quality in veterans with a dual diagnosis of PTSD and severe mental illness SO PSYCHIATRY RESEARCH LA English DT Article DE PTSD; Severe mental illness; Sleep; Veterans ID POSTTRAUMATIC-STRESS-DISORDER; BIPOLAR DISORDER; MILITARY VETERANS; OF-LIFE; DISTURBANCES; INSOMNIA; SYMPTOMS; INDEX; VALIDATION; DEPRESSION AB Poor sleep quality is one of the most frequently reported symptoms by veterans with Posttraumatic Stress Disorder (PTSD) and by veterans with severe mental illness (SMI; i.e., schizophrenia spectrum disorders, bipolar disorder, major depression with or without psychotic features). However, little is known about the compounding effects of co-occurring PTSD/SMI on sleep quality in this population. Given the high rates of comorbidity and poor functional outcomes associated with sleep dysfunction, there is a need to better understand patterns of poor sleep quality in this population. The present study provides a description of sleep quality in veterans with a dual diagnosis of PTSD/SMI relative to veterans with PTSD only. Results indicated that, despite similar reports of PTSD symptom severity between the groups, veterans with PTSD/SMI reported higher levels of poor sleep quality than veterans only diagnosed with PTSD. Specifically, veterans with PTSD/SMI reported significantly greater difficulties with sleep onset and overall more sleep disturbance than their non-SMI counterparts. Implications of the findings are discussed within the context of an existing model of insomnia and suggest that more comprehensive sleep assessment and the provision of targeted sleep interventions may be helpful for those with a dual diagnosis of PTSD/SMI. C1 [Brown, Wilson J.] Penn State Univ, Behrend Coll, Erie, PA 16563 USA. [Wilkerson, Allison K.; Milanak, Melissa E.; Tuerk, Peter W.; Uhde, Thomas W.; Cortese, Bernadette M.; Grubaugh, Anouk L.] Med Univ South Carolina, Charleston, SC USA. [Tuerk, Peter W.; Grubaugh, Anouk L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Brown, WJ (reprint author), Penn State Univ, Behrend Coll, Sch Humanities & Social Sci, 4701 Coll Dr, Erie, PA 16563 USA. EM wilsonbrown@psu.edu FU Veterans Affairs Health Services Research & Development grants [CD207015, IIR 11-306] FX This study was supported by Veterans Affairs Health Services Research & Development grants CD207015 and IIR 11-306 awarded to Anouk L. Grubaugh, Ph.D. NR 44 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD JAN PY 2017 VL 247 BP 15 EP 20 DI 10.1016/j.psychres.2016.07.062 PG 6 WC Psychiatry SC Psychiatry GA EI8QK UT WOS:000392772400004 PM 27863313 ER PT S AU Wang, YC Dai, TH Gu, Y AF Wang, Yucheng Dai, Tianhong Gu, Ying BE Luo, Q Li, X Gu, Y Tang, Y Zhu, D TI Antimicrobial blue light inactivation of Methicillin-resistant Staphylococcus aureus SO OPTICS IN HEALTH CARE AND BIOMEDICAL OPTICS VII SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optics in Health Care and Biomedical Optics VII CY OCT 12-14, 2016 CL Beijing, PEOPLES R CHINA SP SPIE, Chinese Opt Soc DE multidrug-resistant bacteria; Methicillin-resistant Staphylococcus aureus; antimicrobial blue light; burn infections ID MRSA IN-VITRO; CANDIDA; EPIDEMIOLOGY; MECHANISMS; PATHOGENS AB Background: With the increasing emergence of multidrug-resistant (MDR) bacterial strains, there is a pressing need for the development of alternative treatment for infections. Antimicrobial blue light (aBL) has provided a simple and effective approach. Methods: We first investigated the effectiveness of aBL (415 nm) inactivation of USA300 LAC:: lux (a community-acquired Methicillin-resistant Staphylococcus aureus strain) both in the planktonic and biofilm forms. The survival of the bacteria in suspensions was determined by serial dilution and that of the biofilm-embedded bacteria was determined by bioluminescence quantification. Using a mouse model of thermal burn infected with USA300 LAC:: lux, we further assessed the effectiveness of aBL for treating localized infections. Bioluminescence imaging was performed to monitor in real time bacterial viability in vivo. Results: In vitro study showed that, for the planktonic counterpart of the bacteria or the 24-h-old biofilms, an irradiance of 55 mW/cm(2) for 60 min resulted in a 4.61 log(10) or 2.56 log(10) inactivation, respectively. In vivo study using infected mouse burns demonstrated that a 2.56-log(10) inactivation was achieved after 100-mW/cm(2) irradiation for 62 min. Conclusions: aBL is a potential alternative approach for treating Methicillin-resistant Staphylococcus aureus infections. C1 [Wang, Yucheng; Gu, Ying] Chinese Peoples Liberat Army Gen Hosp, Dept Laser Med, Beijing, Peoples R China. [Wang, Yucheng] Aviat Gen Hosp, Dept Oncol, Beijing, Peoples R China. [Wang, Yucheng; Dai, Tianhong] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wang, Yucheng; Dai, Tianhong] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [Gu, Ying] Nankai Univ, Coll Med, Tianjin, Peoples R China. RP Gu, Y (reprint author), Chinese Peoples Liberat Army Gen Hosp, Dept Laser Med, Beijing, Peoples R China.; Dai, TH (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA.; Dai, TH (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Gu, Y (reprint author), Nankai Univ, Coll Med, Tianjin, Peoples R China. EM tdai@mgh.harvard.edu; guyinglaser301@163.com FU Center for Integration of Medicine and Innovative Technology (CIMIT) under U.S. Army Medical Research Acquisition Activity Cooperative Agreement [14-1894]; National Institutes of Health [1R21AI109172]; ASLMS Student Research Grant [BS. S02.15] FX This work was supported in part by the Center for Integration of Medicine and Innovative Technology (CIMIT) under U.S. Army Medical Research Acquisition Activity Cooperative Agreement (CIMIT No. 14-1894 to TD) and the National Institutes of Health (1R21AI109172 to TD). YW was supported by an ASLMS Student Research Grant (BS. S02.15). The information contained herein does not necessarily reflect the position or policy of the Government, and no official endorsement should be inferred. NR 29 TC 0 Z9 0 U1 2 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-1-5106-0467-4; 978-1-5106-0468-1 J9 PROC SPIE PY 2017 VL 0024 DI 10.1117/12.2246533 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BG8GP UT WOS:000392269600018 ER PT J AU LeBedis, CA Bates, DDB Soto, JA AF LeBedis, Christina A. Bates, David D. B. Soto, Jorge A. TI Iatrogenic, blunt, and penetrating trauma to the biliary tract SO ABDOMINAL RADIOLOGY LA English DT Article DE Biliary injury; Iatrogenic injury; Blunt trauma; Penetrating trauma ID BILE-DUCT INJURY; MULTIMODALITY IMAGING APPROACH; QUALITY-OF-LIFE; GD-EOB-DTPA; LAPAROSCOPIC CHOLECYSTECTOMY; NONOPERATIVE MANAGEMENT; ENDOSCOPIC MANAGEMENT; HEPATIC-TRAUMA; MR CHOLANGIOPANCREATOGRAPHY; LIVER-TRANSPLANTATION AB Iatrogenic and traumatic bile leaks are uncommon. However, given the overall increase in number of hepatobiliary surgeries and the paradigm shift toward nonoperative management of patients with liver trauma, they have become more prevalent in recent years. Imaging is essential to establishing early diagnosis and guiding treatment as the clinical signs and symptoms of bile leaks are nonspecific, and a delay in recognition of bile leaks portends a high morbidity and mortality rate. Findings suspicious for a bile leak at computed tomography or ultrasonography include free or contained peri- or intrahepatic low density fluid in the setting of recent trauma or hepatobiliary surgery. Hepatobiliary scintigraphy and magnetic resonance cholangiopancreatography (MRCP) with hepatobiliary contrast agents can be used to detect active or contained bile leak. MRCP with hepatobiliary contrast agents has the unique ability to reveal the exact location of bile leak, which often governs whether endoscopic management or surgical management is warranted. Percutaneous transhepatic cholangiography and fluoroscopy via an indwelling catheter that is placed either percutaneously or surgically are useful modalities to guide percutaneous transhepatic biliary drain placement which can provide biliary drainage and/or diversion in the setting of traumatic biliary injury. Surgical treatment of a bile duct injury with Roux-en-Y hepaticojejunostomy is warranted if definitive treatment cannot be accomplished through percutaneous or endoscopic means. C1 [LeBedis, Christina A.; Soto, Jorge A.] Boston Univ, Med Ctr, Dept Radiol, 820 Harrison Ave,3rd Floor, Boston, MA 02118 USA. [Bates, David D. B.] Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. RP LeBedis, CA (reprint author), Boston Univ, Med Ctr, Dept Radiol, 820 Harrison Ave,3rd Floor, Boston, MA 02118 USA. EM christina.lebedis@bmc.org OI Bates, David/0000-0002-3105-156X; LeBedis, Christina/0000-0002-8849-736X NR 97 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2017 VL 42 IS 1 BP 28 EP 45 DI 10.1007/s00261-016-0856-y PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI2BQ UT WOS:000392291700004 PM 27503381 ER PT J AU Richman, DM Tirumani, SH Hornick, JL Fuchs, CS Howard, S Krajewski, K Ramaiya, N Rosenthal, M AF Richman, Danielle M. Tirumani, Sree Harsha Hornick, Jason L. Fuchs, Charles S. Howard, Stephanie Krajewski, Katherine Ramaiya, Nikhil Rosenthal, Michael TI Beyond gastric adenocarcinoma: Multimodality assessment of common and uncommon gastric neoplasms SO ABDOMINAL RADIOLOGY LA English DT Article DE Gastric cancer; Benign gastric neoplasms; Malignant gastric neoplasms; Metastasis ID GASTROINTESTINAL STROMAL TUMORS; PATHOLOGICAL CORRELATION; CT FINDINGS; SUCCINATE-DEHYDROGENASE; HETEROTOPIC PANCREAS; RADIOLOGIC FEATURES; GERMLINE MUTATIONS; IMATINIB MESYLATE; IMAGING FINDINGS; GLOMUS TUMORS AB Despite advances in molecular biology, imaging, and treatment, gastric neoplasms remain a significant cause of morbidity and mortality; gastric adenocarcinoma is the fifth most common malignancy and third most common cause of death worldwide (Brenner et al., Methods Mol Biol 472:467-477, 2009; Howson et al. Epidemiol Rev 8:1-27, 1986; Roder, Gastric Cancer 5(Suppl 1):5-11, 2002; Ferlay et al., GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. International Agency for Research on Cancer, 2013). Because of both the frequency at which malignant gastric tumors occur as well as the worldwide impact, gastric neoplasms remain important lesions to identify and characterize on all imaging modalities. Despite the varied histologies and behaviors of these neoplasms, many have similar imaging features. Nonetheless, the treatment, management, and prognosis of gastric neoplasms vary by pathology, so it is essential for the radiologist to make every effort to differentiate between these lesions and raise the less common entities as differential diagnostic considerations when appropriate. C1 [Richman, Danielle M.; Tirumani, Sree Harsha] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. [Tirumani, Sree Harsha; Howard, Stephanie; Krajewski, Katherine; Ramaiya, Nikhil; Rosenthal, Michael] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Fuchs, Charles S.] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. RP Richman, DM (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM DMRichman@partners.org FU GI SPORE Grant [P50CA127003] FX Author C.S.F. is supported by GI SPORE Grant # P50CA127003. NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2017 VL 42 IS 1 BP 124 EP 140 DI 10.1007/s00261-016-0901-x PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI2BQ UT WOS:000392291700013 PM 27645897 ER PT J AU Besa, C Lewis, S Pandharipande, PV Chhatwal, J Kamath, A Cooper, N Knight-Greenfield, A Babb, JS Boffetta, P Padron, N Sirlin, CB Taouli, B AF Besa, Cecilia Lewis, Sara Pandharipande, Pari V. Chhatwal, Jagpreet Kamath, Amita Cooper, Nancy Knight-Greenfield, Ashley Babb, James S. Boffetta, Paolo Padron, Norma Sirlin, Claude B. Taouli, Bachir TI Hepatocellular carcinoma detection: diagnostic performance of a simulated abbreviated MRI protocol combining diffusion-weighted and T1-weighted imaging at the delayed phase post gadoxetic acid SO ABDOMINAL RADIOLOGY LA English DT Article DE Hepatocellular carcinoma; MRI; Diffusion-weighted imaging; Gadoxetic acid ID CHRONIC LIVER-DISEASE; ENHANCED MRI; CIRRHOTIC LIVER; DISODIUM; NODULES; HEPATOCARCINOGENESIS; SENSITIVITY; MORTALITY; EFFICACY; SEQUENCE AB Purpose: The purpose of this study was to evaluate the diagnostic performance of a "simulated'' abbreviated MRI (AMRI) protocol using diffusion-weighted imaging (DWI) and T1-weighted (T1w) imaging obtained at the hepatobiliary phase (HBP) post gadoxetic acid injection alone and in combination, compared to dynamic contrast-enhanced (CE)-T1w imaging for the detection of hepatocellular carcinoma (HCC). Methods: This was an IRB approved HIPAA compliant retrospective single institution study including patients with liver disease who underwent gadoxetic acid-enhanced MRI for HCC diagnosis. Three independent observers assessed 2 sets of images (full CE-set and AMRI including DWI+T1w-HBP). Diagnostic performance of T1w-HBP and DWI alone and in combination was compared to that of CE-set. All imaging sets included unenhanced T1w and T2w sequences. A preliminary analysis was performed to assess cost savings of AMRI protocol compared to a full MRI study. Results: 174 patients including 62 with 80 HCCs were assessed. Equivalent per-patient sensitivity and negative predictive value (NPV) were observed for DWI (85.5% and 92.2%, pooled data) and T1w-HBP (89.8% and 94.2%) (P = 0.1-0.7), while these were significantly lower for the full AMRI protocol (DWI+T1w-HBP, 80.6% and 80%, P = 0.02) when compared to CE-set (90.3% and 94.9%). Higher specificity and positive predictive value were observed for CE-set vs. AMRI (P = 0.02). The estimated cost reduction of AMRI versus full MRI ranged between 30.7 and 49.0%. Conclusion: AMRI using DWI and T1w-HBP has a clinically acceptable sensitivity and NPV for HCC detection. This could serve as the basis for a future study assessing AMRI for HCC screening and surveillance. C1 [Besa, Cecilia; Knight-Greenfield, Ashley; Taouli, Bachir] Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, 1470 Madison Ave, New York, NY 10029 USA. [Besa, Cecilia; Lewis, Sara; Kamath, Amita; Cooper, Nancy; Taouli, Bachir] Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY 10029 USA. [Pandharipande, Pari V.; Chhatwal, Jagpreet] Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA USA. [Babb, James S.] NYU, Dept Radiol, Langone Med Ctr, 560 1St Ave, New York, NY 10016 USA. [Boffetta, Paolo] Icahn Sch Med Mt Sinai, Dept Oncol Sci, Div Canc Prevent & Control, New York, NY 10029 USA. [Padron, Norma] Icahn Sch Med Mt Sinai, Dept Populat Hlth Sci & Policy, New York, NY 10029 USA. [Sirlin, Claude B.] Univ Calif San Diego, Dept Radiol, Liver Imaging Grp, San Diego, CA 92103 USA. RP Taouli, B (reprint author), Icahn Sch Med Mt Sinai, Translat & Mol Imaging Inst, 1470 Madison Ave, New York, NY 10029 USA.; Taouli, B (reprint author), Icahn Sch Med Mt Sinai, Dept Radiol, New York, NY 10029 USA. EM bachir.taouli@mountsinai.org NR 35 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2017 VL 42 IS 1 BP 179 EP 190 DI 10.1007/s00261-016-0841-5 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI2BQ UT WOS:000392291700018 PM 27448609 ER PT J AU Karaosmanoglu, AD Onur, MR Tabari, A Karcaaltincaba, M Arellano, RS AF Karaosmanoglu, Ali Devrim Onur, Mehmet Ruhi Tabari, Azadeh Karcaaltincaba, Musturay Arellano, Ronald S. TI Role of multimodality imaging in the diagnosis of lymphoproliferative malignancies and hematologic disorders of the kidneys SO ABDOMINAL RADIOLOGY LA English DT Article DE Kidney; Lymphoproliferative malignancies; Hematologic disorders; Ultrasonography; Computed tomography; Magnetic resonance imaging ID ERDHEIM-CHESTER-DISEASE; RETROPERITONEAL CYSTIC LYMPHANGIOMA; PRIMARY RENAL LYMPHOMA; NON-HODGKINS-LYMPHOMA; OF-THE-LITERATURE; CASTLEMANS-DISEASE; GRANULOCYTIC SARCOMA; EXTRAMEDULLARY HEMATOPOIESIS; PROLIFERATIVE DISORDERS; EXTRAOSSEOUS MYELOMA AB Lymphoproliferative and hematologic disorders of the kidney may present with focal or diffuse renal parenchymal involvement in clinical practice. Radiologic findings of lymphoproliferative and hematologic disorders of the kidney may mimick primary neoplastic and inflammatory disorders of the kidney. All cross-sectional imaging modalities including ultrasonography, computed tomography, and magnetic resonance imaging may be used in the diagnosis of these diseases. Percutaneous biopsy may be used in problematic cases for definitive diagnosis. C1 [Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Karcaaltincaba, Musturay] Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey. [Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Karcaaltincaba, Musturay] Hacettepe Univ, Tip Fak Hastanesi, TR-06100 Ankara, Turkey. [Tabari, Azadeh; Arellano, Ronald S.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. RP Onur, MR (reprint author), Hacettepe Univ, Sch Med, Dept Radiol, Ankara, Turkey.; Onur, MR (reprint author), Hacettepe Univ, Tip Fak Hastanesi, TR-06100 Ankara, Turkey. EM ruhionur@yahoo.com NR 71 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2017 VL 42 IS 1 BP 242 EP 253 DI 10.1007/s00261-016-0873-x PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI2BQ UT WOS:000392291700025 PM 27535385 ER PT J AU Hassanzadeh, E Glazer, DI Dunne, RM Fennessy, FM Harisinghani, MG Tempany, CM AF Hassanzadeh, Elmira Glazer, Daniel I. Dunne, Ruth M. Fennessy, Fiona M. Harisinghani, Mukesh G. Tempany, Clare M. TI Prostate imaging reporting and data system version 2 (PI-RADS v2): a pictorial review SO ABDOMINAL RADIOLOGY LA English DT Review ID CANCER; GUIDELINES; AGREEMENT; BIOPSY; MRI AB The most recent edition of the prostate imaging reporting and data system (PI-RADS version 2) was developed based on expert consensus of the international working group on prostate cancer. It provides the minimum acceptable technical standards for MR image acquisition and suggests a structured method for multiparametric prostate MRI (mpMRI) reporting. T1-weighted, T2-weighted (T2W), diffusion-weighted (DWI), and dynamic contrast-enhanced (DCE) imaging are the suggested sequences to include in mpMRI. The PI-RADS version 2 scoring system enables the reader to assess and rate all focal lesions detected at mpMRI to determine the likelihood of a clinically significant cancer. According to PI-RADS v2, a lesion with a Gleason score >= 7, volume >0.5 cc, or extraprostatic extension is considered clinically significant. PI-RADS v2 uses the concept of a dominant MR sequence based on zonal location of the lesion rather than summing each component score, as was the case in version 1. The dominant sequence in the peripheral zone is DWI and the corresponding apparent diffusion coefficient (ADC) map, with a secondary role for DCE in equivocal cases (PI-RADS score 3). For lesions in the transition zone, T2W images are the dominant sequence with DWI/ADC images playing a supporting role in the case of an equivocal lesion. C1 [Hassanzadeh, Elmira; Glazer, Daniel I.; Dunne, Ruth M.; Tempany, Clare M.] Brigham & Womens Hosp, Harvard Med Sch, Dept Radiol, Surg Planning Lab, 75 Francis St,ASB1-L1-Room 050, Boston, MA 02115 USA. [Fennessy, Fiona M.] Harvard Med Sch, Dana Farber Canc Inst, Dept Radiol, Boston, MA USA. [Harisinghani, Mukesh G.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. RP Hassanzadeh, E (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Dept Radiol, Surg Planning Lab, 75 Francis St,ASB1-L1-Room 050, Boston, MA 02115 USA. EM elmitt@gmail.com OI Hassanzadeh, Elmira/0000-0003-4460-698X FU [U01CA151261]; [R25CA89017]; [DPH403516]; [P41 EB015898] FX This study was funded by Grant numbers U01CA151261 (FMF), R25CA89017 (DIG), DPH403516 (EH), and P41 EB015898 (CT, FMF). NR 20 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 2366-004X EI 2366-0058 J9 ABDOM RADIOL JI Abdom. Radiol. PD JAN PY 2017 VL 42 IS 1 BP 278 EP 289 DI 10.1007/s00261-016-0871-z PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EI2BQ UT WOS:000392291700029 PM 27522352 ER PT J AU Wang, CN Schroeder, FA Hooker, JM AF Wang, Changning Schroeder, Frederick A. Hooker, Jacob M. TI Development of New Positron Emission Tomography Radiotracer for BET Imaging SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Bromodomain; PET; radiotracer; [C-11]MS417 ID BROMODOMAIN INHIBITION; DISCOVERY; FAMILY; BRD4; OPTIMIZATION; RECOGNITION; LEUKEMIA; I-BET151; LIGANDS; TARGET AB The bromodomain and extraterminal domain (BET) inhibitors have been extensively studied for tumor treatment in the past few years. Recently, BET containing proteins have been reported to play a key role in brain functions, such as learning and memory. BET proteins have also been shown to be a potential therapeutic target for substance abuse disorders. Development of a molecular probe for noninvasive imaging will elucidate the distribution and functional roles of BET in the living subject and accelerate medical research and drug discovery in this domain. Herein, we describe the synthesis and pilot imaging of a novel BET imaging agent, [C-11]MS417. Our imaging results demonstrate that this probe has moderate brain uptake, good specificity, good selectivity, and appropriate-kinetics and distribution. [C-11]MS417 is an ideal lead compound for further optimization of clinical BET PET radiotracer tools and MS417 could be used as a blood-brain-barrier-penetrant compound for preclinical research. C1 [Wang, Changning; Schroeder, Frederick A.; Hooker, Jacob M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Wang, CN (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, CNY 149,Room 5-022A,149 13th St, Charlestown, MA 02179 USA. EM cwang15@mgh.harvard.edu FU Harvard/MGH Nuclear Medicine Training Program from the Department of Energy [DE-SC0008430]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health [P41, P41EB015896]; NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program [S10RR017208, S10RR026666, S10RR022976, S10RR019933, S01RR029495] FX This research was supported by the Harvard/MGH Nuclear Medicine Training Program from the Department of Energy under Grant DE-SC0008430 (to C.W.). This research was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the Center for Functional Neuroimaging Technologies, P41EB015896, a P41 Regional Resource supported by the National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health. This work also involved the use of instrumentation supported by the NIH Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, Grant Numbers S10RR017208, S10RR026666, S10RR022976, S10RR019933, and S01RR029495. NR 24 TC 0 Z9 0 U1 3 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD JAN PY 2017 VL 8 IS 1 BP 17 EP 21 DI 10.1021/acschemneuro.6b00288 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA EI4JI UT WOS:000392459400005 PM 27806195 ER PT J AU Xiong, Y Lu, J Hunter, J Li, LB Scott, D Choi, HG Lim, SM Manandhar, A Gondi, S Sim, T Westover, KD Gray, NS AF Xiong, Yuan Lu, Jia Hunter, John Li, Lianbo Scott, David Choi, Hwan Geun Lim, Sang Min Manandhar, Anuj Gondi, Sudershan Sim, Taebo Westover, Kenneth D. Gray, Nathanael S. TI Covalent Guanosine Mimetic Inhibitors of G12C KRAS SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE KRAS G12C; drug design; covalent inhibitor; GDP mimetic; bisphosphonate; bioisostere; CPM; ActivX ID STRUCTURAL DIFFERENCES; GENOMIC INSTABILITY; SIGNAL-TRANSDUCTION; MURINE FIBROBLASTS; MOLECULAR SWITCH; ONCOGENIC RAS; K-RAS; EXPRESSION; PROTEINS; THERAPEUTICS AB Ras proteins are members of a large family of GTPase enzymes that are commonly mutated in cancer where they act as dominant oncogenes. We previously developed an irreversible guanosine-derived inhibitor, SML-8-73-1, of mutant G12C RAS that forms a covalent bond with cysteine 12. Here we report exploration of the structure activity relationships (SAR) of hydrolytically stable analogues of SML-8-73-1 as covalent G12C KRAS inhibitors. We report the discovery of difluoromethylene bisphosphonate analogues such as compound 11, which, despite exhibiting reduced efficiency as covalent G12C KRAS inhibitors, remove the liability of the hydrolytic instability of the diphosphate moiety present in SML-8-73-1 and provide the foundation for development of prodrugs to facilitate cellular uptake. The SAR and crystallographic results reaffirm the exquisite molecular recognition that exists in the diphosphate region of RAS for guanosine nucleotides which must be considered in the design of nucleotide-competitive inhibitors. C1 [Xiong, Yuan; Scott, David; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02115 USA. [Xiong, Yuan; Scott, David; Gray, Nathanael S.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA. [Lu, Jia; Hunter, John; Li, Lianbo; Scott, David; Manandhar, Anuj; Gondi, Sudershan; Westover, Kenneth D.] Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. [Lu, Jia; Hunter, John; Li, Lianbo; Manandhar, Anuj; Gondi, Sudershan; Westover, Kenneth D.] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. [Choi, Hwan Geun] Daegu Gyeongbuk Med Innovat Fdn, New Drug Dev Ctr, Daegu 41061, South Korea. [Lim, Sang Min] Korea Inst Sci & Technol, Ctr Neuromed, Seoul 02792, South Korea. [Sim, Taebo] Korea Inst Sci & Technol, Chem Kinom Res Ctr, Seoul 02792, South Korea. [Sim, Taebo] Korea Univ, KU KIST Grad Sch Converging Sci & Technol, Seoul 02841, South Korea. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 450 Brookline Ave, Boston, MA 02115 USA.; Gray, NS (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02215 USA.; Westover, KD (reprint author), Univ Texas Southwestern Med Ctr Dallas, Dept Biochem, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.; Westover, KD (reprint author), Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Kenneth.Westover@UTSouthwestern.edu; Nathanael_Gray@dfci.harvard.edu FU Astellas Pharma Inc.; Welch Foundation [11829]; V Foundation for Cancer Research; DOD [W81XWH-16-1-0106] FX Y.X., N.S.G., and K.D.W. were supported by Astellas Pharma Inc. K.D.W. was also supported by the Welch Foundation 11829, the V Foundation for Cancer Research, and DOD W81XWH-16-1-0106. NR 40 TC 0 Z9 0 U1 6 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD JAN PY 2017 VL 8 IS 1 BP 61 EP 66 DI 10.1021/acsmedchemlett.6b00373 PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA EH8UM UT WOS:000392047900010 PM 28105276 ER PT J AU Louis, DN Aldape, K Brat, DJ Capper, D Ellison, DW Hawkins, C Paulus, W Perry, A Reifenberger, G Figarella-Branger, D Wesseling, P Batchelor, TT Cairncross, JG Pfister, SM Rutkowski, S Weller, M Wick, W von Deimling, A AF Louis, David N. Aldape, Ken Brat, Daniel J. Capper, David Ellison, David W. Hawkins, Cynthia Paulus, Werner Perry, Arie Reifenberger, Guido Figarella-Branger, Dominique Wesseling, Pieter Batchelor, Tracy T. Cairncross, J. Gregory Pfister, Stefan M. Rutkowski, Stefan Weller, Michael Wick, Wolfgang von Deimling, Andreas TI Announcing cIMPACT-NOW: the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy SO ACTA NEUROPATHOLOGICA LA English DT Editorial Material C1 [Louis, David N.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Pathol Serv, WRN225,55 Fruit St, Boston, MA 02114 USA. [Aldape, Ken] Princess Margaret Hosp, Dept Pathol, Toronto, ON, Canada. [Brat, Daniel J.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Capper, David] Ruprecht Karls Univ Heidelberg, Inst Pathol, Dept Neuropathol, Heidelberg, Germany. [Capper, David] German Canc Res Ctr, Clin Cooperat Unit Neuropathol, Heidelberg, Germany. [Capper, David] German Canc Consortium DKTK, Heidelberg, Germany. [Ellison, David W.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Hawkins, Cynthia] Univ Toronto, Hosp Sick Children, Dept Paediat Lab Med, Toronto, ON, Canada. [Paulus, Werner] Univ Hosp Munster, Inst Neuropathol, Munster, Germany. [Perry, Arie] Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94140 USA. [Reifenberger, Guido] Heinrich Heine Univ, Dept Neuropathol, Dusseldorf, Germany. [Reifenberger, Guido] German Canc Consortium DKTK Partner Site Essen Du, Dusseldorf, Germany. [Figarella-Branger, Dominique] Aix Marseille Univ, La Timone Hosp, Dept Pathol & Neuropathol, Marseille, France. [Wesseling, Pieter] Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. [Wesseling, Pieter] Princess Maxima Ctr Pediat Oncol, Dept Pathol, Utrecht, Netherlands. [Wesseling, Pieter] Univ Med Ctr Utrecht, Utrecht, Netherlands. [Batchelor, Tracy T.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. [Cairncross, J. Gregory] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Pfister, Stefan M.] German Canc Res Ctr DKFZ Heidelberg, Div Pediat Neurooncol, Heidelberg, Germany. [Pfister, Stefan M.; Wick, Wolfgang] German Canc Consortium DKTK Core Ctr Heidelberg, Heidelberg, Germany. [Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany. [Rutkowski, Stefan] Univ Med Ctr Hamburg Eppendorf, Dept Pediat Haematol & Oncol, Hamburg, Germany. [Weller, Michael] Univ Hosp Zrich, Dept Neurol, Zurich, Switzerland. [Wick, Wolfgang] Univ Heidelberg Hosp, Neurol Clin, Heidelberg, Germany. [Wick, Wolfgang] Univ Heidelberg Hosp, Natl Ctr Tumor Dis NCT, Heidelberg, Germany. [Wick, Wolfgang] German Canc Res Ctr, Clin Cooperat Unit Neurooncol, Heidelberg, Germany. RP Louis, DN (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Pathol Serv, WRN225,55 Fruit St, Boston, MA 02114 USA. EM dlouis@mgh.harvard.edu RI von Deimling, Andreas/F-7774-2013 OI von Deimling, Andreas/0000-0002-5863-540X NR 3 TC 1 Z9 1 U1 2 U2 2 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 JAN PY 2017 VL 133 IS 1 BP 1 EP 3 DI 10.1007/s00401-016-1646-x PG 3 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA EI0AX UT WOS:000392134900001 PM 27909809 ER PT J AU Ruzek, JI Eftekhari, A Crowley, J Kuhn, E Karlin, BE Rosen, CS AF Ruzek, J. I. Eftekhari, A. Crowley, J. Kuhn, E. Karlin, B. E. Rosen, C. S. TI Post-training Beliefs, Intentions, and Use of Prolonged Exposure Therapy by Clinicians in the Veterans Health Administration SO ADMINISTRATION AND POLICY IN MENTAL HEALTH AND MENTAL HEALTH SERVICES RESEARCH LA English DT Article DE Post-training beliefs; Intentions; Use of prolonged exposure therapy by clinicians in the veterans health administration; Posttraumatic stress disorder; Training; Implementation ID POSTTRAUMATIC-STRESS-DISORDER; EVIDENCE-BASED-PSYCHOTHERAPIES; PSYCHOLOGICAL TREATMENTS; PTSD TREATMENT; IMPLEMENTATION; CARE; DISSEMINATION; ATTITUDES; BEHAVIORS; EFFICACY AB To examine how changes in beliefs during the training process predict adoption of prolonged exposure therapy (PE) by veterans health administration clinicians who received intensive training in this evidence-based treatment. Participants completed a 4-day PE workshop and received expert consultation as they used PE with two or more training cases. Participants were surveyed prior to the workshop, after the workshop, after case consultation (n = 1.034), and 6 months after training (n = 810). Hierarchical regression was used to assess how pre-training factors, and changes in beliefs during different stages of training incrementally predicted post-training intent to use PE and how many patients clinicians were treating with PE 6 months after training. Post-training intent to use PE was high (mean = 6.2, SD = 0.81 on a 1-7 scale), yet most participants treated only 1 or 2 patients at a time with PE. Pre-training factors predicted intent to use and actual use of PE. Changes in beliefs during the workshop had statistically significant yet modest effects on intent and use of PE. Changes in beliefs during case consultation had substantial effects on intent and actual use of PE. Pre-training factors and changes in beliefs during training (especially during case consultation) influence clinicians' adoption of PE. Use of PE was influenced not only by its perceived clinical advantages/disadvantages, but also by contextual factors (working in a PTSD specialty clinic, perceived control over one's schedule, and ability to promote PE to patients and colleagues). C1 [Ruzek, J. I.; Eftekhari, A.; Crowley, J.; Kuhn, E.; Rosen, C. S.] VA Palo Alto Hlth Care Syst, Disseminat & Training Div, Natl Ctr PTSD, 795 Willow Rd, Menlo Pk, CA 94025 USA. [Ruzek, J. I.] Palo Alto Univ, Palo Alto, CA USA. [Ruzek, J. I.; Kuhn, E.; Rosen, C. S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. [Karlin, B. E.] Educ Dev Ctr Inc, New York, NY USA. [Karlin, B. E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Karlin, B. E.] US Dept Vet Affairs, Cent Off, Mental Hlth Serv, Washington, DC USA. RP Ruzek, JI (reprint author), VA Palo Alto Hlth Care Syst, Disseminat & Training Div, Natl Ctr PTSD, 795 Willow Rd, Menlo Pk, CA 94025 USA.; Ruzek, JI (reprint author), Palo Alto Univ, Palo Alto, CA USA.; Ruzek, JI (reprint author), Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA. EM josef.ruzek@va.gov; afsoon.eftekhari@va.gov; jill.crowley@va.gov; eric.kuhn@va.gov; bradkarlin@gmail.com; craig.rosen@va.gov NR 42 TC 2 Z9 2 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-587X EI 1573-3289 J9 ADM POLICY MENT HLTH JI Adm. Policy. Ment. Health PD JAN PY 2017 VL 44 IS 1 BP 123 EP 132 DI 10.1007/s10488-015-0689-y PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA EI3IL UT WOS:000392383600012 PM 26487392 ER PT J AU Maleki-Yazdi, MR Singh, D Anzueto, A Tombs, L Fahy, WA Naya, I AF Maleki-Yazdi, M. Reza Singh, Dave Anzueto, Antonio Tombs, Lee Fahy, William A. Naya, Ian TI Assessing Short-term Deterioration in Maintenance naive Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials SO ADVANCES IN THERAPY LA English DT Article DE Chronic obstructive pulmonary disease; Clinically important deterioration; Respiratory; Umeclidinium; Vilanterol ID OBSTRUCTIVE PULMONARY-DISEASE; EFFICACY; SAFETY AB Introduction: Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy. The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD. Methods: This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naive (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747). Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis. The primary endpoint was trough forced expiratory volume in 1 s (FEV1). St George's Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; C >= 100 ml decrease in trough FEV1, >= 4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed. Results: UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001]. Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO. UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P <= 0.001]. Adverse events were similar across both populations and treatments. Conclusions: Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD. C1 [Maleki-Yazdi, M. Reza] Univ Toronto, Div Resp Med, Womens Coll Hosp, Toronto, ON, Canada. [Singh, Dave] Univ Manchester, Univ Hosp South Manchester Fdn Trust, Med Evaluat Unit, Manchester, Lancs, England. [Anzueto, Antonio] South Texas Vet Hlth Care Syst, Audie L Murphy Hosp, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Tombs, Lee] Precise Approach LTD, Birmingham, W Midlands, England. [Fahy, William A.; Naya, Ian] GSK, Resp Med Dev Ctr, Stockley Pk, Middx, England. RP Maleki-Yazdi, MR (reprint author), Univ Toronto, Div Resp Med, Womens Coll Hosp, Toronto, ON, Canada. EM maleki.pccrc@on.aibn.com FU GSK FX This study was funded by GSK. NR 19 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0741-238X EI 1865-8652 J9 ADV THER JI Adv. Ther. PD JAN PY 2017 VL 33 IS 12 BP 2188 EP 2199 DI 10.1007/s12325-016-0430-6 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA EI0CS UT WOS:000392140300008 PM 27796912 ER PT J AU Tsai, AC Hatcher, AM Bukusi, EA Weke, E Hufstedler, LL Dworkin, SL Kodish, S Cohen, CR Weiser, SD AF Tsai, Alexander C. Hatcher, Abigail M. Bukusi, Elizabeth A. Weke, Elly Hufstedler, Lee Lemus Dworkin, Shari L. Kodish, Stephen Cohen, Craig R. Weiser, Sheri D. TI A Livelihood Intervention to Reduce the Stigma of HIV in Rural Kenya: Longitudinal Qualitative Study SO AIDS AND BEHAVIOR LA English DT Article DE AIDS/HIV; Social stigma; Kenya; Qualitative research ID SUB-SAHARAN AFRICA; RANDOMIZED CONTROLLED-TRIAL; HOUSEHOLD FOOD INSECURITY; ANTIRETROVIRAL THERAPY; SOUTH-AFRICA; INTERNALIZED STIGMA; SOCIAL DETERMINANTS; MENTAL-DISORDERS; HEALTH OUTCOMES; RISK-FACTORS AB The scale-up of effective treatment has partially reduced the stigma attached to HIV, but HIV still remains highly stigmatized throughout sub-Saharan Africa. Most studies of anti-HIV stigma interventions have employed psycho-educational strategies such as information provision, counseling, and testimonials, but these have had varying degrees of success. Theory suggests that livelihood interventions could potentially reduce stigma by weakening the instrumental and symbolic associations between HIV and premature morbidity, economic incapacity, and death, but this hypothesis has not been directly examined. We conducted a longitudinal qualitative study among 54 persons with HIV participating in a 12-month randomized controlled trial of a livelihood intervention in rural Kenya. Our study design permitted assessment of changes over time in the perspectives of treatment-arm participants (N = 45), as well as an understanding of the experiences of control arm participants (N = 9, interviewed only at follow-up). Initially, participants felt ashamed of their seropositivity and were socially isolated (internalized stigma). They also described how others in the community discriminated against them, labeled them as being "already dead," and deemed them useless and unworthy of social investment (perceived and enacted stigma). At follow-up, participants in the treatment arm described less stigma and voiced positive changes in confidence and self-esteem. Concurrently, they observed that other community members perceived them as active, economically productive, and contributing citizens. None of these changes were noted by participants in the control arm, who described ongoing and continued stigma. In summary, our findings suggest a theory of stigma reduction: livelihood interventions may reduce internalized stigma among persons with HIV and also, by targeting core drivers of negative attitudes toward persons with HIV, positively change attitudes toward persons with HIV held by others. Further research is needed to formally test these hypotheses, assess the extent to which these changes endure over the long term, and determine whether this class of interventions can be implemented at scale. C1 [Tsai, Alexander C.] Massachusetts Gen Hosp, Ctr Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. [Tsai, Alexander C.] Mbarara Univ Sci & Technol, Mbarara, Uganda. [Hatcher, Abigail M.; Hufstedler, Lee Lemus; Weiser, Sheri D.] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA USA. [Hatcher, Abigail M.] Univ Witwatersrand, Wits Reprod Hlth & HIV Inst, Johannesburg, South Africa. [Bukusi, Elizabeth A.; Weke, Elly] Kenya Govt Med Res Ctr, Ctr Microbiol Res, Nairobi, Kenya. [Bukusi, Elizabeth A.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. [Dworkin, Shari L.; Cohen, Craig R.; Weiser, Sheri D.] Univ Calif San Francisco, Global Hlth Inst, Ctr Expertise Womens Hlth & Empowerment, San Francisco, CA 94143 USA. [Dworkin, Shari L.] Univ Calif San Francisco, Sch Nursing, Dept Social & Behav Sci, San Francisco, CA 94143 USA. [Kodish, Stephen] United Nations Childrens Fund, Abuja, Nigeria. [Cohen, Craig R.] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA. RP Tsai, AC (reprint author), Massachusetts Gen Hosp, Ctr Global Hlth, 125 Nashua St,Ste 722, Boston, MA 02114 USA.; Tsai, AC (reprint author), Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA.; Tsai, AC (reprint author), Mbarara Univ Sci & Technol, Mbarara, Uganda. EM actsai@partners.org OI Tsai, Alexander/0000-0001-6397-7917 FU U.S. National Institutes of Health (NIH) [R34MH094215]; United Nations World Food Programme; NIH [K23MH096620] FX This study was funded by U.S. National Institutes of Health (NIH) R34MH094215 and the United Nations World Food Programme The authors also acknowledge salary support through NIH K23MH096620. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 64 TC 5 Z9 5 U1 2 U2 2 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 JAN PY 2017 VL 21 IS 1 BP 248 EP 260 DI 10.1007/s10461-015-1285-6 PG 13 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA EI2HE UT WOS:000392306700022 PM 26767535 ER PT J AU Ng, CK Tsai, AC AF Ng, Courtney K. Tsai, Alexander C. TI Proximate Context of HIV-Related Stigma and Women's Use of Skilled Childbirth Services in Uganda SO AIDS AND BEHAVIOR LA English DT Article DE HIV stigma; Skilled childbirth services; Maternal health; PMTCT ID MATERNAL HEALTH-CARE; SUB-SAHARAN AFRICA; INTIMATE PARTNER VIOLENCE; ANTENATAL CARE; DEVELOPING-COUNTRIES; DELIVERY SERVICES; RURAL TANZANIA; PMTCT PROGRAMS; INDIA; BARRIERS AB HIV-related stigma compromises both HIV prevention and treatment and has recently been described as a barrier to utilization of skilled childbirth services in sub-Saharan Africa. This study uses the 2011 Uganda Demographic Health Survey to estimate the associations between HIV-related stigma, measured both at the individual and community level, and use of facility delivery among women. Consistent with theoretical predictions, higher levels of stigma are associated with reduced likelihood of facility delivery. The negative relationship between stigma and facility delivery is especially pronounced when stigma is measured at the community level, highlighting the importance of understanding the proximate context of HIV-related stigma and its potential effects on behavior. Reducing the stigma of HIV will be critical to achieving the twin goals of reducing overall maternal mortality and preventing mother-to-child HIV transmission. C1 [Ng, Courtney K.] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,11th Floor, Boston, MA 02115 USA. [Tsai, Alexander C.] Massachusetts Gen Hosp, MGH Global Hlth, Boston, MA 02114 USA. [Tsai, Alexander C.] Harvard Ctr Populat & Dev Studies, Cambridge, MA USA. RP Ng, CK (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, 665 Huntington Ave,11th Floor, Boston, MA 02115 USA. EM cng@mail.harvard.edu FU U.S. National Institutes of Health [K23MH096620] FX We would like to thank Measure DHS for access and authorization to the 2011 Uganda Demographic Health Survey data files for research purposes. The authors received no specific funding for this study and acknowledge salary support from U.S. National Institutes of Health K23MH096620. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 76 TC 1 Z9 1 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 JAN PY 2017 VL 21 IS 1 BP 307 EP 316 DI 10.1007/s10461-016-1401-2 PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA EI2HE UT WOS:000392306700028 PM 27106877 ER PT J AU Ho, ML Moonis, G Halpin, CF Curtin, HD AF Ho, M. -L. Moonis, G. Halpin, C. F. Curtin, H. D. TI Spectrum of Third Window Abnormalities: Semicircular Canal Dehiscence and Beyond SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Review ID LARGE VESTIBULAR AQUEDUCT; JUGULAR BULB ABNORMALITIES; AIR-BONE GAP; SENSORINEURAL HEARING-LOSS; MIDDLE-EAR CHOLESTEATOMA; SUPERIOR PETROSAL SINUS; LINKED MIXED DEAFNESS; TEMPORAL BONE; CAVITATING OTOSCLEROSIS; STAPES GUSHER AB Third window abnormalities are defects in the integrity of the bony structure of the inner ear, classically producing sound-/pressure -induced vertigo (Tullio and Hennebert signs) and/or a low-frequency air-bone gap by audiometry. Specific anatomic defects include semicircular canal dehiscence, perilabyrinthine fistula, enlarged vestibular aqueduct, dehiscence of the scala vestibuli side of the cochlea, X-linked stapes gusher, and bone dyscrasias. We discuss these various entities and provide key examples from our institutional teaching file with a discussion of symptomatology, temporal bone CT, audiometry, and vestibular-evoked myogenic potentials. C1 [Ho, M. -L.] Mayo Clin, Dept Radiol, 200 First St SW, Rochester, MN 55905 USA. [Moonis, G.] Columbia Univ, Dept Radiol, New York, NY USA. [Halpin, C. F.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. [Curtin, H. D.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Ho, ML (reprint author), Mayo Clin, Dept Radiol, 200 First St SW, Rochester, MN 55905 USA. EM ho.mai-lan@mayo.edu NR 54 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2017 VL 38 IS 1 BP 2 EP 9 DI 10.3174/ajnr.A4922 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA EI0KO UT WOS:000392163600002 PM 27561833 ER PT J AU Vajapeyam, S Stamoulis, C Ricci, K Kieran, M Poussaint, TY AF Vajapeyam, S. Stamoulis, C. Ricci, K. Kieran, M. Poussaint, T. Young TI Automated Processing of Dynamic Contrast-Enhanced MRI: Correlation of Advanced Pharmacokinetic Metrics with Tumor Grade in Pediatric Brain Tumors SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID BEVACIZUMAB PLUS IRINOTECAN; CEREBRAL BLOOD-VOLUME; PERFUSION MRI; MICROVASCULAR PERMEABILITY; GLIOMA; CONSORTIUM; EFFICACY; GLIOBLASTOMA; PARAMETERS; CHILDREN AB BACKGROUND AND PURPOSE: Pharmacokinetic parameters from dynamic contrast-enhanced MR imaging have proved useful for differentiating brain tumor grades in adults. In this study, we retrospectively reviewed dynamic contrast-enhanced perfusion data from children with newly diagnosed brain tumors and analyzed the pharmacokinetic parameters correlating with tumor grade. MATERIALS AND METHODS: Dynamic contrast-enhanced MR imaging data from 38 patients were analyzed by using commercially available software. Subjects were categorized into 2 groups based on pathologic analyses consisting of low-grade (World Health Organization I and II) and high-grade (World Health Organization III and IV) tumors. Pharmacokinetic parameters were compared between the 2 groups by using linear regression models. For parameters that were statistically distinct between the 2 groups, sensitivity and specificity were also estimated. RESULTS: Eighteen tumors were classified as low-grade, and 20, as high-grade. Transfer constant from the blood plasma into the extra cellular extravascular space (K-trans), rate constant from extracellular extravascular space back into blood plasma (K-ep), and extracellular extravascular volume fraction (V-e) were all significantly correlated with tumor grade; high-grade tumors showed higher K-trans, higher K-ep, and lower V-e. Although all 3 parameters had high specificity (range, 82%-100%), K-ep had the highest specificity for both grades. Optimal sensitivity was achieved for Ve, with a combined sensitivity of 76% (compared with 71% for K-trans and K-ep). CONCLUSIONS: Pharmacokinetic parameters derived from dynamic contrast-enhanced MR imaging can effectively discriminate low and high-grade pediatric brain tumors. C1 [Vajapeyam, S.; Stamoulis, C.; Poussaint, T. Young] Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. [Stamoulis, C.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. [Ricci, K.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Kieran, M.] Dana Farber Canc Ctr, Dept Pediat Oncol, Boston, MA USA. [Vajapeyam, S.; Stamoulis, C.; Kieran, M.; Poussaint, T. Young] Harvard Med Sch, Boston, MA USA. RP Vajapeyam, S (reprint author), Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM sridhar.vajapeyam@childrens.harvard.edu OI Vajapeyam, Sridhar/0000-0002-1782-1919 NR 35 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2017 VL 38 IS 1 BP 170 EP 175 DI 10.3174/ajnr.A4949 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA EI0KO UT WOS:000392163600027 PM 27633807 ER PT J AU Singh, JA Yu, SH AF Singh, Jasvinder A. Yu, Shaohua TI Allopurinol and the risk of atrial fibrillation in the elderly: a study using Medicare data SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID XANTHINE-OXIDASE INHIBITION; CONGESTIVE-HEART-FAILURE; LEFT-VENTRICULAR MASS; ALL-CAUSE MORTALITY; TERM-FOLLOW-UP; CARDIOVASCULAR EVENTS; MYOCARDIAL-INFARCTION; ENDOTHELIAL FUNCTION; BLOOD-PRESSURE; UNITED-STATES AB Objective To assess the effect of allopurinol use on the risk of incident atrial fibrillation (AF) in the elderly. Methods We used the 5% random Medicare Claims data from 2006 to 2012 to examine the association of allopurinol use and incident AF in a cohort of patients with an absence of AF at baseline (at least 365 days). Multivariable-adjusted Cox regression analyses compared allopurinol exposed and non-exposed periods for the risk of AF, controlling for age, sex, race, Charlson-Romano comorbidity index and use of statins, diuretics, ACE inhibitors and beta-blockers. HR with 95% CIs was calculated. Sensitivity analyses considered a longer baseline period (365 days vs 183 days) and individual comorbidities. Results There were 9244 episodes of incident allopurinol use in 8569 beneficiaries, of which 1366 episodes (14.8%) had incident AF. In multivariable-adjusted analyses, allopurinol use was associated with an HR of 0.83 (95% CI 0.74 to 0.93) for incident AF. In a separate multivariable-adjusted model, compared with no allopurinol use, longer allopurinol use durations were associated with a lower HR of AF: 180 days-2 years, 0.85 (95% CI 0.73 to 0.99) and >2 years, 0.65 (95% CI 0.52 to 0.82). Other factors significantly associated with a higher hazard of AF were: age 75-<85 years and >= 85 years, higher Charlson index score and current beta-blocker use. Sensitivity analyses confirmed these findings with minimal/no attenuation of HRs. Conclusions Allopurinol use was associated with a reduced risk of incident AF in the elderly, especially its use for >6 months duration. Future studies should assess the mechanisms underlying this beneficial effect of allopurinol. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Dept Med, Sch Med, Birmingham, AL USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Div Epidemiol, Sch Publ Hlth, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Dept Orthoped Surg, Coll Med, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU UAB Division of Rheumatology; Birmingham VA Medical Center; National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS) [P50 AR060772] FX This material is the result of work supported by research funds from the UAB Division of Rheumatology and the resources and use of facilities at the Birmingham VA Medical Center. JAS is also supported by a grant from the National Institute of Arthritis, Musculoskeletal, and Skin Diseases (NIAMS) P50 AR060772. NR 49 TC 2 Z9 2 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2017 VL 76 IS 1 BP 72 EP 78 DI 10.1136/annrheumdis-2015-209008 PG 7 WC Rheumatology SC Rheumatology GA EI3XG UT WOS:000392425200011 PM 27165177 ER PT J AU Singh, JA Yu, SH AF Singh, Jasvinder A. Yu, Shaohua TI Are allopurinol dose and duration of use nephroprotective in the elderly? A Medicare claims study of allopurinol use and incident renal failure SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CHRONIC KIDNEY-DISEASE; CLINICAL COMORBIDITY INDEX; RHEUMATIC CONDITIONS; UNITED-STATES; GOUT; HYPERURICEMIA; PROGRESSION; FEBUXOSTAT; ARTHRITIS; ISCHEMIA AB Objective To assess the effect of allopurinol dose/duration on the risk of renal failure in the elderly with allopurinol use. Methods We used the 5% random Medicare claims data from 2006 to 2012. Multivariable-adjusted Cox regression analyses assessed the association of allopurinol dose/duration with subsequent risk of developing incident renal failure or end-stage renal disease (ESRD) (no prior diagnosis in last 183 days) in allopurinol users, controlling for age, sex, race and Charlson-Romano comorbidity index. HRs with 95% CIs were calculated. Sensitivity analyses considered a longer baseline period (365 days), controlled for gout or used more specific codes. Results Among the 30 022 allopurinol treatment episodes, 8314 incident renal failure episodes occurred. Compared with 1-199 mg/day, allopurinol dose of 200299 mg/day (HR 0.81; 95% CI 0.75 to 0.87) and >= 300 mg/day, 0.71 (0.67 to 0.76), had significantly lower hazard of renal failure in multivariable-adjustment model, confirmed in multiple sensitivity analyses. Longer allopurinol use duration was significantly associated with lower hazards in sensitivity analyses (365-day look-back; reference, <0.5 year): 0.5-1 year, 1.00 (0.88, 1.15); >1-2 years, 0.85 (0.73 to 0.99); and >2 years, 0.81 (0.67 to 0.98). Allopurinol >= 300 mg/day was also associated with significantly lower risk of acute renal failure and ESRD with HR of 0.89 (0.83 to 0.94) and 0.57 (0.46 to 0.71), respectively. Conclusions Higher allopurinol dose is independently protective against incident renal failure in the elderly allopurinol users. A longer duration of allopurinol use may be associated with lower risk of incident renal failure. Potential mechanisms of these effects need to be examined. C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.; Yu, Shaohua] UAB, Div Epidemiol, Dept Med, Sch Med,Sch Publ Hlth, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Dept Orthoped Surg, Coll Med, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com FU UAB Division of Rheumatology; Birmingham VA Medical Center FX This material is the result of work supported by research funds from UAB Division of Rheumatology and the resources and use of facilities at the Birmingham VA Medical Center. NR 42 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2017 VL 76 IS 1 BP 133 EP 139 DI 10.1136/annrheumdis-2015-209046 PG 7 WC Rheumatology SC Rheumatology GA EI3XG UT WOS:000392425200019 PM 27296322 ER PT J AU Misra, D Lu, N Felson, D Choi, HK Seeger, J Einhorn, T Neogi, T Zhang, YQ AF Misra, Devyani Lu, Na Felson, David Choi, Hyon K. Seeger, John Einhorn, Thomas Neogi, Tuhina Zhang, Yuqing TI Does knee replacement surgery for osteoarthritis improve survival? The jury is still out SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID PATIENT SURVIVAL; FOLLOW-UP; TOTAL HIP; ARTHROPLASTY; MORTALITY; POPULATION; OUTCOMES; PAIN AB Background The relation of knee replacement (KR) surgery to all-cause mortality has not been well established owing to potential biases in previous studies. Thus, we aimed to examine the relation of KR to mortality risk among patients with knee osteoarthritis (OA) focusing on identifying biases that may threaten the validity of prior studies. Methods We included knee OA subjects (ages 50-89 years) from The Health Improvement Network, an electronic medical records database in the UK. Risk of mortality among KR subjects was compared with propensity score-matched non-KR subjects. To explore residual confounding bias, subgroup analyses stratified by age and propensity scores were performed. Results Subjects with KR had 28% lower risk of mortality than non-KR subjects (HR 0.72, 95% CI 0.66 to 0.78). However, when stratified by age, protective effect was noted only in older age groups (>63 years) but not in younger subjects (63 years). Further, the mortality rate among KR subjects decreased as candidacy (propensity score) for KR increased among subjects with KR, but no such consistent trend was noted among non-KR subjects. Conclusions While a protective effect of KR on mortality cannot be ruled out, findings of lower mortality among older KR subjects and those with higher propensity scores suggest that prognosis-based selection for KR may lead to intractable confounding by indication; hence, the protective effect of KR on all-cause mortality may be overestimated. C1 [Misra, Devyani; Lu, Na; Felson, David; Einhorn, Thomas; Neogi, Tuhina; Zhang, Yuqing] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Lu, Na; Choi, Hyon K.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Seeger, John] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Misra, D (reprint author), Boston Univ, Sch Med, Dept Med, Clin Epi Unit, 650 Albany St,Suite X200, Boston, MA 02118 USA. EM Demisra@bu.edu OI Neogi, Tuhina/0000-0002-9515-1711 FU Arthritis Foundation; NIAMS [P60AR47785]; ACR Rheumatology Research Foundation; Boston University CTSI KL2 scholarship [5KL2TR001411-02] FX This study was funded by Arthritis Foundation Postdoctoral Fellowship award and supported by NIAMS P60AR47785, ACR Rheumatology Research Foundation Investigator Award and Boston University CTSI KL2 scholarship (grant number 5KL2TR001411-02). NR 29 TC 0 Z9 0 U1 13 U2 13 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2017 VL 76 IS 1 BP 140 EP 146 DI 10.1136/annrheumdis-2016-209167 PG 7 WC Rheumatology SC Rheumatology GA EI3XG UT WOS:000392425200020 PM 27190096 ER PT J AU Neogi, T Dalbeth, N Stamp, L Castelar, G Fitzgerald, J Gaffo, A Mikuls, TR Singh, J Vazquez-Mellado, J Edwards, NL AF Neogi, Tuhina Dalbeth, Nicola Stamp, Lisa Castelar, Geraldo Fitzgerald, John Gaffo, Angelo Mikuls, Ted R. Singh, Jasvinder Vazquez-Mellado, Janitzia Edwards, N. Lawrence TI Renal dosing of allopurinol results in suboptimal gout care SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Letter ID ADVERSE EVENTS; HYPERURICEMIA; IMPAIRMENT; FEBUXOSTAT C1 [Neogi, Tuhina] Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Dalbeth, Nicola] Univ Auckland, Dept Immunol, Auckland, New Zealand. [Stamp, Lisa] Univ Otago, Dept Med, Canterbury, New Zealand. [Castelar, Geraldo] Pedro Ernesto Univ Hosp, Dept Rheumatol, Rio De Janeiro, Brazil. [Fitzgerald, John] Univ Calif Los Angeles, David Geffen Sch Med, Med Rheumatol, Los Angeles, CA 90095 USA. [Gaffo, Angelo] Birmingham VA Med Ctr, Dept Med, Birmingham, AL USA. [Gaffo, Angelo; Singh, Jasvinder] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA. [Vazquez-Mellado, Janitzia] Hosp Gen Mexico City, Serv Reumatol, Mexico City, DF, Mexico. [Edwards, N. Lawrence] Univ Florida, Coll Med, Dept Med, Gainesville, FL USA. RP Edwards, NL (reprint author), Univ Florida, Gainesville, FL 32610 USA. EM edwarni@medicine.ufl.edu OI Neogi, Tuhina/0000-0002-9515-1711 NR 12 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2017 VL 76 IS 1 BP E1 EP + DI 10.1136/annrheumdis-2016-210352 PG 2 WC Rheumatology SC Rheumatology GA EI3XG UT WOS:000392425200045 PM 27582422 ER PT J AU Gul, SS Hamilton, ARL Munoz, AR Phupitakphol, T Liu, W Hyoju, SK Economopoulos, KP Morrison, S Hu, D Zhang, WF Gharedaghi, MH Huo, H Hamarneh, SR Hodin, RA AF Gul, Sarah S. Hamilton, A. Rebecca L. Munoz, Alexander R. Phupitakphol, Tanit Liu, Wei Hyoju, Sanjiv K. Economopoulos, Konstantinos P. Morrison, Sara Hu, Dong Zhang, Weifeng Gharedaghi, Mohammad Hadi Huo, Haizhong Hamarneh, Sulaiman R. Hodin, Richard A. TI Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice SO APPLIED PHYSIOLOGY NUTRITION AND METABOLISM LA English DT Article DE non-nutritive sweeteners; noncaloric sweeteners; diet-induced insulin resistance; intestinal alkaline phosphatase; aspartame; obesity; insulin resistance ID SUGAR-SWEETENED BEVERAGES; HIGH-INTENSITY SWEETENERS; NECROSIS-FACTOR-ALPHA; NONNUTRITIVE SWEETENERS; ARTIFICIAL SWEETENERS; METABOLIC SYNDROME; INSULIN-RESISTANCE; ENERGY-INTAKE; BODY-WEIGHT; CONSUMPTION AB Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 +/- 0.03 vs 0.4 +/- 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 +/- 1.6 vs 42.4 +/- 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD +/- ASP groups (53 913 +/- 4000.58 (mg.min)/dL vs 42 003.75 +/- 5331.61 (mg.min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23-and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks. C1 [Gul, Sarah S.; Hamilton, A. Rebecca L.; Munoz, Alexander R.; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K.; Economopoulos, Konstantinos P.; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R.; Hodin, Richard A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, 15 Parkman St, Boston, MA 02114 USA. EM rhodin@mgh.harvard.edu NR 49 TC 0 Z9 0 U1 18 U2 18 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 1715-5312 EI 1715-5320 J9 APPL PHYSIOL NUTR ME JI Appl. Physiol. Nutr. Metab. PD JAN PY 2017 VL 42 IS 1 BP 77 EP 83 DI 10.1139/apnm-2016-0346 PG 7 WC Nutrition & Dietetics; Physiology; Sport Sciences SC Nutrition & Dietetics; Physiology; Sport Sciences GA EI1OC UT WOS:000392245900011 PM 27997218 ER PT J AU Lubberts, B Mellema, JJ Janssen, SJ Ring, D AF Lubberts, Bart Mellema, Jos J. Janssen, Stein J. Ring, David TI Fracture line distribution of olecranon fractures SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE Olecranon; Fractures; Mapping; Injury; Fracture lines; Computed tomography ID COMPUTED-TOMOGRAPHY; SURFACES AB The association between specific olecranon fracture characteristics (e.g., displacement, fragmentation, subluxation) and fracture line distribution might help surgeons predict intra-articular fracture location based on fracture characteristics that can be determined on radiographs. We hypothesized that fracture mapping techniques would reveal different fracture patterns for minimally displaced fractures, displaced fractures, and fracture-dislocations of the olecranon. A consecutive series of 78 patients with olecranon fractures were evaluated using initial radiographs and computed tomography scans and characterized according to the Mayo classification. Fracture lines were identified based on reduced three-dimensional computed tomography reconstructions and graphically superimposed onto a standard template to create two-dimensional fracture maps. The fracture maps were then converted into fracture heat maps. Based on fracture and heat maps, fracture line location and patterns were determined. Six (7.7%) patients had a non- or minimally displaced fracture, 22 (28%) a displaced fracture, and 50 (64%) a fracture-dislocation of the olecranon. There were 27 (54%) anterior and 23 (46%) posterior olecranon fracture-dislocations. Fracture lines of non- or minimally displaced fractures and posterior fracture-dislocations enter and exit the trochlear notch at the base of the coronoid, while fracture lines of displaced fractures and anterior fracture-dislocations were spread more broadly over the depths of the trochlear notch. Based on fracture characteristics depicted on radiographs, one can anticipate the amount of the olecranon involved (how close is the fracture line to the coronoid) and the orientation of the fracture line. Computer tomography could be reserved for when more specific knowledge of the fracture line might affect treatment. Level of evidence: III. C1 [Lubberts, Bart; Mellema, Jos J.; Janssen, Stein J.] Harvard Med Sch, Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Boston, MA USA. [Ring, David] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ring, David] Univ Texas Austin, Dell Med Sch, Austin, TX 78712 USA. RP Ring, D (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02115 USA.; Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, Austin, TX 78712 USA. EM David.Ring@austin.utexas.edu NR 18 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0936-8051 EI 1434-3916 J9 ARCH ORTHOP TRAUM SU JI Arch. Orthop. Trauma Surg. PD JAN PY 2017 VL 137 IS 1 BP 37 EP 42 DI 10.1007/s00402-016-2593-7 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA EH9WM UT WOS:000392122400005 PM 27832347 ER PT J AU Rundell, SD Goode, AP Suri, P Heagerty, PJ Comstock, BA Friedly, JL Gold, LS Bauer, Z Avins, AL Nedeljkovic, SS Nerenz, DR Kessler, L Jarvik, JG AF Rundell, Sean D. Goode, Adam P. Suri, Pradeep Heagerty, Patrick J. Comstock, Bryan A. Friedly, Janna L. Gold, Laura S. Bauer, Zoya Avins, Andrew L. Nedeljkovic, Srdjan S. Nerenz, David R. Kessler, Larry Jarvik, Jeffrey G. TI Effect of Comorbid Knee and Hip Osteoarthritis on Longitudinal Clinical and Health Care Use Outcomes in Older Adults With New Visits for Back Pain SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Back pain; Comorbidity; Osteoarthritis; Patient outcome assessment; Rehabilitation ID PATIENT-REPORTED OUTCOMES; LUMBAR SPINE; RHEUMATIC CONDITIONS; RESEARCH PRIORITIES; AFRICAN-AMERICANS; UNITED-STATES; PREVALENCE; IMPACT; REPLACEMENT; DISORDERS AB Objective: To examine if a comorbid diagnosis of knee or hip osteoarthritis (OA) in older adults with new back pain visits is associated with long-term patient-reported outcomes and back-related health care use. Design: Prospective cohort study. Setting: Three integrated health systems forming the Back pain Outcomes using Longitudinal Data cohort. Participants: Participants (N=5155) were older adults (>= 65y) with a new visit for back pain and a complete electronic health record data. Interventions: Not applicable; we obtained OA diagnoses using diagnostic codes in the electronic health record 12 months prior to the new back pain visit. Main Outcome Measures: The Roland-Morris Disability Questionnaire (RDQ) and the EuroQol-5D (EQ-5D) were key patient-reported outcomes. Health care use, measured by relative-value units (RVUs), was summed for the 12 months after the initial visit. We used linear mixed-effects models to model patient-reported outcomes. We also used generalized linear models to test the association between comorbid knee or hip OA and total back-related RVUs. Results: Of the 5155 participants, 368 (7.1%) had a comorbid knee OA diagnosis, and 94 (1.8%) had a hip OA diagnosis. Of the participants, 4711 (91.4%) had neither knee nor hip OA. In adjusted models, the 12-month RDQ score was 1.23 points higher (95% confidence interval [CI], 0.72-1.74) for patients with knee OA and 1.26 points higher (95% CI, 0.24-2.27) for those with hip OA than those without knee or hip OA, respectively. A lower EQ-5D score was found among participants with knee OA (.02 lower; 95% CI, -.04 to -.01) and hip OA diagnoses (.03 lower; 95% CI,-.05 to -.01) compared with those without knee or hip OA, respectively. Comorbid knee or hip OA was not significantly associated with total 12-month back-related resource use. Conclusions: Comorbid knee or hip OA in older adults with a new back pain visit was associated with modestly worse long-term disability and health-related quality of life. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Rundell, Sean D.; Suri, Pradeep; Friedly, Janna L.] Univ Washington, Dept Rehabil Med, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. [Rundell, Sean D.; Suri, Pradeep; Friedly, Janna L.; Gold, Laura S.; Bauer, Zoya; Jarvik, Jeffrey G.] Univ Washington, Comparat Effectiveness Cost & Outcomes Res Ctr, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. [Goode, Adam P.] Duke Univ, Dept Orthopaed, Durham, NC USA. [Suri, Pradeep] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Heagerty, Patrick J.; Comstock, Bryan A.] Univ Washington, Ctr Biomed Stat, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. [Gold, Laura S.; Bauer, Zoya; Jarvik, Jeffrey G.] Univ Washington, Dept Radiol, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. [Avins, Andrew L.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Nedeljkovic, Srdjan S.] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. [Nedeljkovic, Srdjan S.] Harvard Vanguard Med Associates, Spine Unit, Boston, MA USA. [Nerenz, David R.] Henry Ford Hosp, Inst Neurosci, Detroit, MI 48202 USA. [Kessler, Larry; Jarvik, Jeffrey G.] Univ Washington, Dept Hlth Serv, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. [Jarvik, Jeffrey G.] Univ Washington, Dept Neurol Surg, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. RP Rundell, SD (reprint author), Univ Washington, Box 359455,4333 Brooklyn Ave NE, Seattle, WA 98105 USA. EM srundell@uw.edu FU Agency for Healthcare Research and Quality [1R01HS01922201, 1R01HS022972-01]; K12 grant from Agency for Healthcare Research and Quality [1K12HS022982-01] FX Supported by the Agency for Healthcare Research and Quality (grant nos. 1R01HS01922201 and 1R01HS022972-01), and a K12 grant from the Agency for Healthcare Research and Quality (grant no. 1K12HS022982-01). NR 49 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 0003-9993 EI 1532-821X J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2017 VL 98 IS 1 BP 43 EP 50 DI 10.1016/j.apmr.2016.06.022 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA EI4JN UT WOS:000392460000005 PM 27519927 ER PT J AU Kernkamp, WA Van de Velde, SK Hosseini, A Tsai, TY Li, JS van Arkel, ERA Li, GA AF Kernkamp, Willem A. Van de Velde, Samuel K. Hosseini, Ali Tsai, Tsung-Yuan Li, Jing-Sheng van Arkel, Ewoud R. A. Li, Guoan TI In Vivo Anterolateral Ligament Length Change in the Healthy Knee During Functional Activities-A Combined Magnetic Resonance and Dual Fluoroscopic Imaging Analysis SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article ID ANTERIOR CRUCIATE LIGAMENT; ACL RECONSTRUCTION; ILIOTIBIAL TRACT; PIVOT SHIFT; DEFICIENCY; MOTION; ELONGATION; KINEMATICS; ANATOMY AB Purpose: To measure the in vivo anterolateral ligament (ALL) length change in healthy knees during step-up and sit-to-stand motions. Methods: Eighteen healthy knees were imaged using magnetic resonance and dual fluoroscopic imaging techniques during a step-up and sit-to-stand motion. The ALL length change was measured using the shortest three-dimensional wrapping path, with its femoral attachment located slightly anterior-distal (ALL-Claes) or posteriorproximal (ALL-Kennedy) to the fibular collateral ligament attachment. The ALL length measured from the extended knee position of the non-weight-bearing magnetic resonance scan was used as a reference to normalize the length change. Results: During the step-up motion (approximately 55 degrees flexion to full extension), both the ALL-Claes and ALL-Kennedy showed a significant decrease in length of 21.2% (95% confidence interval 18.0-24.4, P<.001) and 24.3% (20.6-28.1, P<.001), respectively. During the sit-to-stand motion (approximately 90 degrees flexion to full extension), both the ALL-Claes and ALL-Kennedy showed a consistent, significant decrease in length of 35.2% (28.8-42.2, P<.001) and 39.2% (32.4-46.0, P<.001), respectively. From approximately 90 degrees to 70 degrees of flexion, a decrease in length of approximately 6% was seen; 70 degrees of flexion to full extension resulted in an approximately 30% decrease in length. Conclusions: The ALL was found to be a nonisometric structure during the step-up and sit-to-stand motion. The length of the ALL was approximately 35% longer at approximately 90 degrees of knee flexion when compared with full extension and showed decreasing length at lower flexion angles. Similar ALL length change patterns were found with its femoral attachment located slightly anterior-distal or posterior-proximal to the fibular collateral ligament attachment. C1 [Kernkamp, Willem A.; Hosseini, Ali; Tsai, Tsung-Yuan; Li, Jing-Sheng; Li, Guoan] Harvard Med Sch, Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. [Van de Velde, Samuel K.; van Arkel, Ewoud R. A.] Med Ctr Haaglanden, Focus Clin Orthoped Surg, The Hague, Netherlands. [Van de Velde, Samuel K.; van Arkel, Ewoud R. A.] Bronovo Nebo, The Hague, Netherlands. RP Li, GA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Bioengn Lab, Boston, MA 02114 USA. EM Gli1@mgh.harvard.edu FU National Institutes of Health (NIH) [R-01 AR055612] FX The authors report that they have no conflicts of interest in the authorship and publication of this article. This investigation was made possible through the support of the National Institutes of Health (NIH) grant R-01 AR055612. NR 32 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 EI 1526-3231 J9 ARTHROSCOPY JI Arthroscopy PD JAN PY 2017 VL 33 IS 1 BP 133 EP 139 DI 10.1016/j.arthro.2016.07.008 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA EI1FI UT WOS:000392221600023 PM 27663034 ER PT J AU Wang, J Hosoda, M Tshikudi, DM Hajjarian, Z Nadkarni, SK AF Wang, Jing Hosoda, Masaki Tshikudi, Diane M. Hajjarian, Zeinab Nadkarni, Seemantini K. TI Intraluminal laser speckle rheology using an omni-directional viewing catheter SO BIOMEDICAL OPTICS EXPRESS LA English DT Article ID DIFFUSING-WAVE-SPECTROSCOPY; OPTICAL COHERENCE TOMOGRAPHY; DYNAMIC LIGHT-SCATTERING; COMPLEX FLUIDS; HYDRODYNAMIC INTERACTIONS; ATHEROSCLEROTIC PLAQUES; VISCOELASTIC MODULI; BLOOD-COAGULATION; BROWNIAN-MOTION; GLUCOSE-LEVELS AB A number of disease conditions in luminal organs are associated with alterations in tissue mechanical properties. Here, we report a new omni-directional viewing Laser Speckle Rheology (LSR) catheter for mapping the mechanical properties of luminal organs without the need for rotational motion. The LSR catheter incorporates multiple illumination fibers, an optical fiber bundle and a multi-faceted mirror to permit omni-directional viewing of the luminal wall. By retracting the catheter using a motor-drive assembly, cylindrical maps of tissue mechanical properties are reconstructed. Evaluation conducted in a test phantom with circumferentially-varying mechanical properties demonstrates the capability of the LSR catheter for the accurate mechanical assessment of luminal organs. (C) 2016 Optical Society of America C1 [Wang, Jing; Hosoda, Masaki; Tshikudi, Diane M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.] Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02114 USA. [Wang, Jing; Hosoda, Masaki; Tshikudi, Diane M.; Hajjarian, Zeinab; Nadkarni, Seemantini K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hosoda, Masaki] Canon USA Inc, Healthcare Opt Res Lab, Cambridge, MA 02139 USA. RP Nadkarni, SK (reprint author), Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02114 USA.; Nadkarni, SK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM snadkarni@mgh.harvard.edu FU Canon U.S.A. Inc. FX This research was supported by a sponsored research grant from Canon U.S.A. Inc. NR 56 TC 0 Z9 0 U1 4 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD JAN 1 PY 2017 VL 8 IS 1 BP 137 EP 150 DI 10.1364/BOE.8.000137 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA EI0ZO UT WOS:000392204700011 PM 28101407 ER PT J AU Nakagawa, A Von Alt, K Lillemoe, KD Fernandez-del Castillo, C Warshaw, AL Liss, AS AF Nakagawa, Akifumi Von Alt, Kate Lillemoe, Keith D. Fernandez-del Castillo, Carlos Warshaw, Andrew L. Liss, Andrew S. TI A method for fixing and paraffin embedding tissue to retain the natural fluorescence of reporter proteins SO BIOTECHNIQUES LA English DT Editorial Material C1 [Nakagawa, Akifumi] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02215 USA. Massachusetts Gen Hosp, Andrew L Warshaw MD Inst Pancreat Canc Res, Boston, MA 02215 USA. Harvard Med Sch, Boston, MA 02215 USA. RP Nakagawa, A (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 EI 1940-9818 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 2017 VL 62 IS 1 DI 10.2144/000114505 PG 1 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EI4XR UT WOS:000392497700012 ER PT J AU Yala, A Barzilay, R Salama, L Griffin, M Sollender, G Bardia, A Lehman, C Buckley, JM Coopey, SB Polubriaginof, F Garber, JE Smith, BL Gadd, MA Specht, MC Gudewicz, TM Guidi, AJ Taghian, A Hughes, KS AF Yala, Adam Barzilay, Regina Salama, Laura Griffin, Molly Sollender, Grace Bardia, Aditya Lehman, Constance Buckley, Julliette M. Coopey, Suzanne B. Polubriaginof, Fernanda Garber, Judy E. Smith, Barbara L. Gadd, Michele A. Specht, Michelle C. Gudewicz, Thomas M. Guidi, Anthony J. Taghian, Alphonse Hughes, Kevin S. TI Using machine learning to parse breast pathology reports SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Machine learning; Pathology reports; Natural language processing; Breast pathology; Atypia; Hyperplasia; Carcinoma in situ ID CANCER STAGES; CLASSIFICATION AB Extracting information from electronic medical record is a time-consuming and expensive process when done manually. Rule-based and machine learning techniques are two approaches to solving this problem. In this study, we trained a machine learning model on pathology reports to extract pertinent tumor characteristics, which enabled us to create a large database of attribute searchable pathology reports. This database can be used to identify cohorts of patients with characteristics of interest. We collected a total of 91,505 breast pathology reports from three Partners hospitals: Massachusetts General Hospital, Brigham and Women's Hospital, and Newton-Wellesley Hospital, covering the period from 1978 to 2016. We trained our system with annotations from two datasets, consisting of 6295 and 10,841 manually annotated reports. The system extracts 20 separate categories of information, including atypia types and various tumor characteristics such as receptors. We also report a learning curve analysis to show how much annotation our model needs to perform reasonably. The model accuracy was tested on 500 reports that did not overlap with the training set. The model achieved accuracy of 90% for correctly parsing all carcinoma and atypia categories for a given patient. The average accuracy for individual categories was 97%. Using this classifier, we created a database of 91,505 parsed pathology reports. Our learning curve analysis shows that the model can achieve reasonable results even when trained on a few annotations. We developed a user-friendly interface to the database that allows physicians to easily identify patients with target characteristics and export the matching cohort. This model has the potential to reduce the effort required for analyzing large amounts of data from medical records, and to minimize the cost and time required to glean scientific insight from these data. C1 [Yala, Adam; Barzilay, Regina] MIT, CSAIL, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Griffin, Molly; Buckley, Julliette M.; Coopey, Suzanne B.; Smith, Barbara L.; Gadd, Michele A.; Specht, Michelle C.; Hughes, Kevin S.] MGH, Div Surg Oncol, Boston, MA 02114 USA. [Salama, Laura; Taghian, Alphonse] MGH, Dept Radiat Oncol, Boston, MA USA. [Gudewicz, Thomas M.] MGH, Dept Pathol, Boston, MA USA. [Lehman, Constance] MGH, Dept Radiol, Boston, MA USA. [Garber, Judy E.] DFCI, Dept Med Oncol, Boston, MA USA. [Guidi, Anthony J.] NWH, Dept Pathol, Newton, MA USA. [Sollender, Grace] Geisel Sch Med Dartmouth, Hanover, NH USA. [Polubriaginof, Fernanda] Columbia Univ, Dept Biomed Informat, New York, NY USA. [Bardia, Aditya] MGH, Dept Med Oncol, Boston, MA USA. RP Griffin, M (reprint author), MGH, Div Surg Oncol, Boston, MA 02114 USA. EM megriff@post.harvard.edu OI Griffin, Molly/0000-0002-1615-2645 NR 12 TC 0 Z9 0 U1 13 U2 13 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 JAN PY 2017 VL 161 IS 2 BP 203 EP 211 DI 10.1007/s10549-016-4035-1 PG 9 WC Oncology SC Oncology GA EI3IZ UT WOS:000392385100003 PM 27826755 ER PT J AU Freedman, RA Seisler, DK Foster, JC Sloan, JA Lafky, JM Kimmick, GG Hurria, A Cohen, HJ Winer, EP Hudis, CA Partridge, AH Carey, LA Jatoi, A Klepin, HD Citron, M Berry, DA Shulman, LN Buzdar, AU Suman, VJ Muss, HB AF Freedman, Rachel A. Seisler, D. K. Foster, J. C. Sloan, J. A. Lafky, J. M. Kimmick, G. G. Hurria, A. Cohen, H. J. Winer, E. P. Hudis, C. A. Partridge, A. H. Carey, L. A. Jatoi, A. Klepin, H. D. Citron, M. Berry, D. A. Shulman, L. N. Buzdar, A. U. Suman, V. J. Muss, H. B. TI Risk of acute myeloid leukemia and myelodysplastic syndrome among older women receiving anthracycline-based adjuvant chemotherapy for breast cancer on Modern Cooperative Group Trials (Alliance A151511) SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Older patients; Leukemia; Myelodysplastic syndrome; Chemotherapy ID EXPERIENCE; TOXICITY; THERAPY; CYCLOPHOSPHAMIDE; COHORT AB We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with > 90 months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines. We used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age (>= 65 vs. < 65 years; separately for >= 70 vs. < 70 years), race/ethnicity, insurance, performance status, and anthracycline receipt. We also examined the effect of cyclophosphamide, the interaction of anthracycline and age, and outcomes for those developing AML/MDS. On Cancer and Leukemia Group B (CALGB) 40101, 49907, 9344, and 9741, 7290 received anthracyclines; 15% were in the age >= 65 and 7% were >= 70. Overall, 47 patients developed AML/MDS (30 AML [0.3%], 17 MDS [0.2%]); 83% of events occurred within 5 years of study registration. Among those age >= 65 and >= 70, 0.8 and 1.0% developed AML/MDS (vs. 0.4% for age < 65), respectively. In adjusted analyses, older age and anthracycline receipt were significantly associated with AML/MDS (adjusted hazard ratio [HR] for age >= 65 [vs. < 65] = 3.13, 95% confidence interval [CI] 1.18-8.33; HR for anthracycline receipt [vs. no anthracycline] = 5.16, 95% CI 1.47-18.19). There was no interaction between age and anthracycline use. Deaths occurred in 70% of those developing AML/MDS. We observed an increased risk for AML/MDS for older patients and those receiving anthracyclines, though these events were rare. Our results help inform discussions surrounding anticipated toxicities of adjuvant chemotherapy in older patients. C1 [Freedman, Rachel A.; Winer, E. P.; Partridge, A. H.] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Seisler, D. K.; Foster, J. C.; Sloan, J. A.; Suman, V. J.] Mayo Clin, Alliance Stat & Data Ctr, Rochester, MN USA. [Seisler, D. K.; Foster, J. C.; Sloan, J. A.; Suman, V. J.] Mayo Canc Ctr, Rochester, MN USA. [Lafky, J. M.; Jatoi, A.] Mayo Clin, Coll Med, Rochester, MN USA. [Kimmick, G. G.; Cohen, H. J.] Duke Univ, Sch Med, Durham, NC USA. [Hurria, A.] City Hope Natl Med Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA USA. [Hurria, A.] City Hope Natl Med Ctr, Dept Populat Sci, Duarte, CA USA. [Hudis, C. A.] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10021 USA. [Carey, L. A.; Muss, H. B.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Klepin, H. D.] Wake Forest Univ, Dept Hematol & Oncol, Winston Salem, NC 27109 USA. [Citron, M.] ProHLTH Care Associates, Lake Success, NY USA. [Berry, D. A.; Buzdar, A. U.] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Shulman, L. N.] Univ Penn, Div Hematol & Oncol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. RP Freedman, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM rafreedman@partners.org FU National Cancer Institute of the National Institutes of Health [UG1CA189823, U10CA032291, U10CA047559, U10CA047577, U10CA077597, U10CA077651, U10CA180790, U10CA180791, U10CA180838, U10CA180857, U10CA180867]; Susan G. Komen [CCR14298143]; American Cancer Society [125912-MRSG-14-240-01-CPPB] FX This study was supported by the National Cancer Institute of the National Institutes of Health under the Award Number UG1CA189823 (Alliance for Clinical Trials in Oncology NCORP Grant), U10CA032291, U10CA047559, U10CA047577, U10CA077597, U10CA077651, U10CA180790, U10CA180791, U10CA180838, U10CA180857, U10CA180867. RAF also receives funding Susan G. Komen (Grant No. CCR14298143) and American Cancer Society (Grant No. 125912-MRSG-14-240-01-CPPB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. NR 21 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 EI 1573-7217 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2017 VL 161 IS 2 BP 363 EP 373 DI 10.1007/s10549-016-4051-1 PG 11 WC Oncology SC Oncology GA EI3IZ UT WOS:000392385100017 PM 27866278 ER PT J AU Dizon, M Linos, E Arron, ST Abuabara, K de Luzuriaga, AMR Jin, C Boscardin, WJ Chren, MM AF Dizon, M. Linos, E. Arron, S. T. Abuabara, K. de Luzuriaga, A. M. Ruiz Jin, C. Boscardin, W. J. Chren, M. -M. TI Comparisons of patients' satisfaction should take expectations into account SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID CARE C1 [Dizon, M.] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Linos, E.; Arron, S. T.; Abuabara, K.; Chren, M. -M.] Univ Calif San Francisco, Dept Dermatol, Program Clin Res, San Francisco, CA 94143 USA. [Jin, C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Boscardin, W. J.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Arron, S. T.; Chren, M. -M.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [de Luzuriaga, A. M. Ruiz] Univ Chicago, Dept Med, Dermatol Sect, 5841 S Maryland Ave, Chicago, IL 60637 USA. RP Chren, MM (reprint author), Univ Calif San Francisco, Dept Dermatol, Program Clin Res, San Francisco, CA 94143 USA.; Chren, MM (reprint author), San Francisco VA Med Ctr, San Francisco, CA 94121 USA. EM chrenm@ucsf.edu FU University of California; San Francisco Resource Allocation Program for Trainees (RAPtr); San Francisco Resource Allocation Program (RAP); National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [R01 AR 054983, K24 AR052667] FX This study was supported, in part, by the University of California, San Francisco Resource Allocation Program for Trainees (RAPtr), University of California, San Francisco Resource Allocation Program (RAP) and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health (R01 AR 054983 and K24 AR052667). NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2017 VL 176 IS 1 BP 252 EP 254 PG 3 WC Dermatology SC Dermatology GA EI4OV UT WOS:000392474100062 PM 27203511 ER PT J AU George, MD Shah, R Kreider, M Miller, WT Merkel, PA Werth, VP AF George, M. D. Shah, R. Kreider, M. Miller, W. T., Jr. Merkel, P. A. Werth, V. P. TI Pulmonary function tests, interstitial lung disease and lung function decline in outpatients with classic and clinically amyopathic dermatomyositis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID GENE 5; MANIFESTATIONS; POLYMYOSITIS C1 [George, M. D.; Merkel, P. A.] Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. [Miller, W. T., Jr.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Shah, R.; Kreider, M.] Univ Penn, Div Pulm & Crit Care Med, Philadelphia, PA 19104 USA. [Shah, R.] Univ Calif San Francisco, Div Pulm Allergy & Crit Care Med, San Francisco, CA 94143 USA. [Merkel, P. A.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Werth, V. P.] Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. [Werth, V. P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP George, MD (reprint author), Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. EM michael.george@uphs.upenn.edu OI George, Michael/0000-0002-0398-2308 FU National Institutes of Health [NIH 5T32AR007442-28, NIH R21 AR066286]; Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) FX M.D.G. is supported by the National Institutes of Health (NIH 5T32AR007442-28). V.P.W. is supported by the Department of Veterans Affairs (Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development) and by the National Institutes of Health (NIH R21 AR066286). The funders had no involvement in the study design, data collection, data analysis, manuscript preparation and/or publication decisions. NR 11 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD JAN PY 2017 VL 176 IS 1 BP 262 EP 264 DI 10.1111/bjd.14771 PG 3 WC Dermatology SC Dermatology GA EI4OV UT WOS:000392474100065 PM 27229750 ER PT J AU Wu, XQ Giobbie-Hurder, A Liao, XY Connelly, C Connolly, EM Li, JJ Manos, MP Lawrence, D McDermott, D Severgnini, M Zhou, J Gjini, E Lako, A Lipschitz, M Pak, CJ Abdelrahman, S Rodig, S Hodi, FS AF Wu, Xinqi Giobbie-Hurder, Anita Liao, Xiaoyun Connelly, Courtney Connolly, Erin M. Li, Jingjing Manos, Michael P. Lawrence, Donald McDermott, David Severgnini, Mariano Zhou, Jun Gjini, Evisa Lako, Ana Lipschitz, Mikel Pak, Christine J. Abdelrahman, Sara Rodig, Scott Hodi, F. Stephen TI Angiopoietin-2 as a Biomarker and Target for Immune Checkpoint Therapy SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID ADVANCED MELANOMA; LYMPHOCYTE INFILTRATION; METASTATIC MELANOMA; DISEASE PROGRESSION; UNTREATED MELANOMA; TUMOR ANGIOGENESIS; PLUS IPILIMUMAB; MYELOID CELLS; CANCER; VEGF AB Immune checkpoint therapies targeting CTLA-4 and PD-1 have proven effective in cancer treatment. However, the identification of biomarkers for predicting clinical outcomes and mechanisms to overcome resistance remain as critical needs. Angiogenesis is increasingly appreciated as an immune modulator with potential for combinatorial use with checkpoint blockade. Angiopoietin-2 (ANGPT2) is an immune target in patients and is involved in resistance to anti-VEGF treatment with the monoclonal antibody bevacizumab. We investigated the predictive and prognostic value of circulating ANGPT2 in metastatic melanoma patients receiving immune checkpoint therapy. High pretreatment serum ANGPT2 was associated with reduced overall survival in CTLA-4 and PD-1 blockade-treated patients. These treatments also increased serum ANGPT2 in many patients early after treatment initiation, whereas ipilimumab plus bevacizumab treatment decreased serum concentrations. ANGPT2 increases were associated with reduced response and/or overall survival. Ipilimumab increased, and ipilimumab plus bevacizumab decreased, tumor vascular ANGPT2 expression in a subset of patients, which was associated with increased and decreased tumor infiltration by CD68(+) and CD163(+) macrophages, respectively. In vitro, bevacizumab blocked VEGF-induced ANGPT2 expression in tumor-associated endothelial cells, whereas ANGPT2 increased PD-L1 expression on M2-polarizedmacrophages. Treatments elicited long-lasting and functional antibody responses to ANGPT2 in a subset of patients receiving clinical benefit. Our findings suggest that serum ANGPT2 may be considered as a predictive and prognostic biomarker for immune checkpoint therapy and may contribute to treatment resistance via increasing proangiogenic and immunosuppressive activities in the tumor microenvironment. Targeting ANGPT2 provides a rational combinatorial approach to improve the efficacy of immune therapy. (C) 2016 AACR. C1 [Wu, Xinqi; Li, Jingjing; Zhou, Jun; Hodi, F. Stephen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wu, Xinqi; Giobbie-Hurder, Anita; Liao, Xiaoyun; Connelly, Courtney; Connolly, Erin M.; Li, Jingjing; Manos, Michael P.; Severgnini, Mariano; Zhou, Jun; Gjini, Evisa; Lako, Ana; Lipschitz, Mikel; Pak, Christine J.; Abdelrahman, Sara; Rodig, Scott; Hodi, F. Stephen] Harvard Med Sch, Boston, MA USA. [Giobbie-Hurder, Anita; Liao, Xiaoyun; Connelly, Courtney; Connolly, Erin M.; Manos, Michael P.; Severgnini, Mariano; Gjini, Evisa; Lako, Ana; Lipschitz, Mikel; Pak, Christine J.; Abdelrahman, Sara; Rodig, Scott; Hodi, F. Stephen] Dana Farber Canc Inst, Ctr Immunooncol, Boston, MA 02115 USA. [Giobbie-Hurder, Anita] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liao, Xiaoyun; Connelly, Courtney; Rodig, Scott] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Connolly, Erin M.; Hodi, F. Stephen] Dana Farber Canc Inst, Melanoma Dis Ctr, Boston, MA 02115 USA. [Lawrence, Donald] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [McDermott, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM stephen_hodi@dfci.harvard.edu FU Melanoma Research Alliance; Sharon Crowley Martin Memorial Fund for Melanoma Research; Malcolm and Emily Mac Naught Fund for Melanoma Research; Stand Up To Cancer - Cancer Research Institute Cancer Immunology Dream Team Translational Research [SU2C-AACR-DT1012] FX This study was supported by NIHCA143832 (F.S. Hodi), the Melanoma Research Alliance (F.S. Hodi), the Sharon Crowley Martin Memorial Fund for Melanoma Research (F.S. Hodi) and the Malcolm and Emily Mac Naught Fund for Melanoma Research (F.S. Hodi) at Dana-Farber Cancer Institute, Genentech/Roche, and Bristol-Myers Squibb. This study was also supported by a Stand Up To Cancer - Cancer Research Institute Cancer Immunology Dream Team Translational Research Grant (SU2C-AACR-DT1012). Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. NR 57 TC 0 Z9 0 U1 4 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2017 VL 5 IS 1 BP 17 EP 28 DI 10.1158/2326-6066.CIR-16-0206 PG 12 WC Oncology; Immunology SC Oncology; Immunology GA EI1MD UT WOS:000392240600003 PM 28003187 ER PT J AU Nathanson, T Ahuja, A Rubinsteyn, A Aksoy, BA Hellmann, MD Miao, D Van Allen, E Merghoub, T Wolchok, JD Snyder, A Hammerbacher, J AF Nathanson, Tavi Ahuja, Arun Rubinsteyn, Alexander Aksoy, Bulent Arman Hellmann, Matthew D. Miao, Diana Van Allen, Eliezer Merghoub, Taha Wolchok, Jedd D. Snyder, Alexandra Hammerbacher, Jeff TI Somatic Mutations and Neoepitope Homology in Melanomas Treated with CTLA-4 Blockade SO CANCER IMMUNOLOGY RESEARCH LA English DT Article ID CELL LUNG-CANCER; EXPRESSION PROFILES; METASTATIC MELANOMA; CLINICAL ACTIVITY; PD-1 BLOCKADE; INTERFERON; IMMUNOTHERAPY; ASSOCIATION; IPILIMUMAB; SIGNATURE AB Immune checkpoint inhibitors are promising treatments for patients with a variety of malignancies. Toward understanding the determinants of response to immune checkpoint inhibitors, it was previously demonstrated that the presence of somatic mutations is associated with benefit from checkpoint inhibition. A hypothesis was posited that neoantigen homology to pathogens may in part explain the link between somatic mutations and response. To further examine this hypothesis, we reanalyzed cancer exome data obtained from our previously published study of 64 melanoma patients treated with CTLA-4 blockade and a new dataset of RNA-Seq data from 24 of these patients. We found that the ability to accurately predict patient benefit did not increase as the analysis narrowed from somatic mutation burden, to inclusion of only those mutations predicted to be MHC class I neoantigens, to only including those neoantigens that were expressed or that had homology to pathogens. The only association between somatic mutation burden and response was found when examining samples obtained prior to treatment. Neoantigen and expressed neoantigen burden were also associated with response, but neither was more predictive than somatic mutation burden. Neither the previously described tetrapeptide signature nor an updated method to evaluate neoepitope homology to pathogens was more predictive than mutation burden. (C) 2016 AACR. C1 [Nathanson, Tavi; Ahuja, Arun; Rubinsteyn, Alexander; Aksoy, Bulent Arman; Hammerbacher, Jeff] Icahn Sch Med Mt Sinai, Genet & Genom Sci, New York, NY 10029 USA. [Hellmann, Matthew D.; Merghoub, Taha; Wolchok, Jedd D.; Snyder, Alexandra] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA. [Hellmann, Matthew D.; Merghoub, Taha; Wolchok, Jedd D.; Snyder, Alexandra] Weill Cornell Med Coll, Dept Med, New York, NY USA. [Miao, Diana; Van Allen, Eliezer] Broad Inst MIT & Harvard, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Miao, Diana; Van Allen, Eliezer] Dana Farber Canc Inst, Ctr Canc Precis Med, Boston, MA 02115 USA. [Merghoub, Taha; Wolchok, Jedd D.] Ludwig Ctr Canc Immunotherapy, Program Immunol, Swim Amer Ludwig Collaborat Res Lab, New York, NY USA. RP Snyder, A (reprint author), Mem Sloan Kettering Canc Ctr, 300 East 66th St, New York, NY 10065 USA. EM snyderca@mskcc.org FU [NCIK08 CA201544 01] FX This work was supported by NCIK08 CA201544 01 (to A. Snyder). NR 38 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 2326-6066 EI 2326-6074 J9 CANCER IMMUNOL RES JI Cancer Immunol. Res. PD JAN PY 2017 VL 5 IS 1 BP 84 EP 91 DI 10.1158/2326-6066.CIR-16-0019 PG 8 WC Oncology; Immunology SC Oncology; Immunology GA EI1MD UT WOS:000392240600009 PM 27956380 ER PT J AU Xu, XS Ryan, CJ Stuyckens, K Smith, MR Saad, F Griffin, TW Park, YC Yu, MK De Porre, P Vermeulen, A Poggesi, I Nandy, P AF Xu, Xu Steven Ryan, Charles J. Stuyckens, Kim Smith, Matthew R. Saad, Fred Griffin, Thomas W. Park, Youn C. Yu, Margaret K. De Porre, Peter Vermeulen, An Poggesi, Italo Nandy, Partha TI Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with Metastatic Castration-Resistant Prostate Cancer SO CLINICAL PHARMACOKINETICS LA English DT Article ID PLACEBO-CONTROLLED PHASE-3; CLINICAL DRUG DEVELOPMENT; ACETATE PLUS PREDNISONE; TUMOR-SIZE; SURVIVAL ANALYSIS; DOUBLE-BLIND; CYP17; INHIBITOR; DOCETAXEL; PREDICT AB Background and Objectives Recent analysis revealed strong associations between prostate-specific antigen (PSA) dynamics and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) and supported PSA dynamics as bridging surrogacy endpoints for clinical benefit from treatment with abiraterone acetate plus prednisone. This analysis aimed to investigate the abiraterone exposure-PSA dynamics relationship in mCRPC. Methods Abiraterone pharmacokinetics-PSA models were constructed using data from the COU-AA-301 (chemotherapy-pretreated) and COU-AA-302 (chemotherapy-na < ve) trials comparing abiraterone acetate 1000 mg/day plus prednisone 5 mg twice daily with prednisone alone in mCRPC. The drug effect-PSA dynamics relationship was modeled as a function of selected pharmacokinetic measures. The influences of baseline demographic variables, laboratory values, and disease status on PSA dynamics were assessed. Results A tumor growth inhibition model best described PSA dynamics post-treatment with abiraterone acetate. Abiraterone acetate treatment in chemotherapy-pretreated and chemotherapy-na < ve patients increased the PSA decay rate (k(dec)) to the same extent (1.28-fold, 95 % confidence interval [CI] 0.58-1.98; and 0.93-fold, 95 % CI 0.6-1.27, respectively). Lower baseline lactate dehydrogenase and higher baseline testosterone significantly increased k (dec). Findings from our analysis suggest a maximum-effect relationship between abiraterone trough concentration and PSA dynamics in both patient populations. The majority of patients had a steady-state trough concentration greater than the estimated half maximal effective concentration. Conclusion The model appropriately described the exposure-response relationship between abiraterone and PSA dynamics in chemotherapy-pretreated and chemotherapy-na < ve patients following oral administration of abiraterone acetate. C1 [Xu, Xu Steven; Park, Youn C.; Nandy, Partha] Janssen Res & Dev, 920 Route 202, Raritan, NJ 08869 USA. [Ryan, Charles J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Stuyckens, Kim; De Porre, Peter; Vermeulen, An; Poggesi, Italo] Janssen Res & Dev, Beerse, Belgium. [Smith, Matthew R.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Saad, Fred] Univ Montreal, Montreal, PQ, Canada. [Griffin, Thomas W.; Yu, Margaret K.] Janssen Res & Dev, Los Angeles, CA USA. RP Xu, XS (reprint author), Janssen Res & Dev, 920 Route 202, Raritan, NJ 08869 USA. EM sxu26@its.jnj.com FU Janssen Research & Development, Raritan, NJ, USA; Janssen Global Services, LLC FX This study was sponsored by Janssen Research & Development, Raritan, NJ, USA. Writing assistance was provided by S. Thomas, PhD, of PAREXEL, and was funded by Janssen Global Services, LLC. NR 33 TC 1 Z9 1 U1 0 U2 0 PU ADIS INT LTD PI NORTHCOTE PA 5 THE WAREHOUSE WAY, NORTHCOTE 0627, AUCKLAND, NEW ZEALAND SN 0312-5963 EI 1179-1926 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PD JAN PY 2017 VL 56 IS 1 BP 55 EP 63 DI 10.1007/s40262-016-0425-0 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EI0UH UT WOS:000392189700005 PM 27324190 ER PT J AU O'Callaghan, C Kveraga, K Shine, JM Adams, RB Bar, M AF O'Callaghan, Claire Kveraga, Kestutis Shine, James M. Adams, Reginald B., Jr. Bar, Moshe TI Predictions penetrate perception: Converging insights from brain, behaviour and disorder SO CONSCIOUSNESS AND COGNITION LA English DT Article DE Cognitive penetration; Prediction; Visual perception; Object recognition; Context; Top-down; Orbitofrontal cortex; Parahippocampal cortex; Visual hallucinations ID PRIMARY VISUAL-CORTEX; PARAHIPPOCAMPAL PLACE AREA; TOP-DOWN FACILITATION; DEFAULT MODE NETWORK; ORBITOFRONTAL CORTEX; OBJECT RECOGNITION; PARKINSONS-DISEASE; PREFRONTAL CORTEX; CAPGRAS DELUSION; MOTIVATIONAL INFLUENCES AB It is argued that during ongoing visual perception, the brain is generating top-down predictions to facilitate, guide and constrain the processing of incoming sensory input. Here we demonstrate that these predictions are drawn from a diverse range of cognitive processes, in order to generate the richest and most informative prediction signals. This is consistent with a central role for cognitive penetrability in visual perception. We review behavioural and mechanistic evidence that indicate a wide spectrum of domains including object recognition, contextual associations, cognitive biases and affective state that can directly influence visual perception. We combine these insights from the healthy brain with novel observations from neuropsychiatric disorders involving visual hallucinations, which highlight the consequences of imbalance between top-down signals and incoming sensory information. Together, these lines of evidence converge to indicate that predictive penetration, be it cognitive, social or emotional, should be considered a fundamental framework that supports visual perception. (C) 2016 Elsevier Inc. All rights reserved. C1 [O'Callaghan, Claire] Univ Cambridge, Behav & Clin Neurosci Inst, Downing St, Cambridge CB2 3EB, England. [O'Callaghan, Claire] Univ Cambridge, Dept Psychol, Cambridge, England. [O'Callaghan, Claire] Univ Sydney, Brain & Mind Ctr, Sydney, NSW, Australia. [Kveraga, Kestutis] Harvard Med Sch, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. [Shine, James M.] Stanford Univ, Sch Psychol, Stanford, CA 94305 USA. [Shine, James M.] Neurosci Res Australia, Sydney, NSW, Australia. [Adams, Reginald B., Jr.] Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. [Bar, Moshe] Bar Ilan Univ, Gonda Ctr Brain Res, Ramat Gan, Israel. RP O'Callaghan, C (reprint author), Univ Cambridge, Behav & Clin Neurosci Inst, Downing St, Cambridge CB2 3EB, England. EM claire.ocallaghan@sydney.edu.au OI O'Callaghan, Claire/0000-0001-5698-6364 FU National Health and Medical Research Council Neil Hamilton Fairley Fellowship [GNT1091310]; National Health and Medical Research Council CJ Martin Fellowship [GNT1072403]; Israeli Center of Research Excellence in Cognition [51/11]; [R01 MH101194]; [BRAINS R01 MH107797] FX We would like to thank Ishan Walpola for his helpful comments on the manuscript. CO is supported by a National Health and Medical Research Council Neil Hamilton Fairley Fellowship GNT1091310; KK is supported by grants R01 MH101194, BRAINS R01 MH107797; JMS is supported by a National Health and Medical Research Council CJ Martin Fellowship GNT1072403; RBA is supported by grant R01 MH101194; and MB supported by The Israeli Center of Research Excellence in Cognition, grant 51/11. NR 151 TC 2 Z9 2 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8100 EI 1090-2376 J9 CONSCIOUS COGN JI Conscious. Cogn. PD JAN PY 2017 VL 47 SI SI BP 63 EP 74 DI 10.1016/j.concog.2016.05.003 PG 12 WC Psychology, Experimental SC Psychology GA EI4IQ UT WOS:000392457400007 PM 27222169 ER PT J AU DiPasquale, DM AF DiPasquale, Dana M. TI Sex Difference in Diving: Fact or Folklore (vol 15, pg 389, 2016) SO CURRENT SPORTS MEDICINE REPORTS LA English DT Correction C1 [DiPasquale, Dana M.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP DiPasquale, DM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. NR 1 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 1537-890X EI 1537-8918 J9 CURR SPORT MED REP JI Curr. Sport. Med. Rep. PD JAN-FEB PY 2017 VL 16 IS 1 BP 56 EP 56 PG 1 WC Sport Sciences SC Sport Sciences GA EI4DM UT WOS:000392443300014 ER PT J AU Walling, AM Ahluwalia, SC Wenger, NS Booth, M Roth, CP Lorenz, K Kanwal, F Dy, S Asch, SM AF Walling, A. M. Ahluwalia, S. C. Wenger, N. S. Booth, M. Roth, C. P. Lorenz, K. Kanwal, F. Dy, S. Asch, S. M. CA Palliative Care Cirrhosis Quality TI Palliative Care Quality Indicators for Patients with End-Stage Liver Disease Due to Cirrhosis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Palliative care; End-stage liver disease; Quality ID OF-LIFE CARE; RANDOMIZED CONTROLLED-TRIAL; APPROPRIATENESS METHOD; HOSPITALIZED-PATIENTS; ADVANCED CANCER; HEALTH-CARE; MANAGEMENT; OUTCOMES; DEATH AB There are guidelines for the medical management of cirrhosis and associated quality indicators (QIs), but QIs focusing on standards for palliative aspects of care are needed. We convened a 9-member, multidisciplinary expert panel and used RAND/UCLA modified Delphi methods to develop palliative care quality indicators for patients with cirrhosis. Experts were provided with a report based on a systematic review of the literature that contained evidence concerning the proposed candidate QIs. Panelists rated QIs prior to a planned meeting using a standard 9-point RAND appropriateness scale. These ratings guided discussion during a day-long phone conference meeting, and final ratings were then provided by panel members. Final QI scores were computed and QIs with a final median score of greater than or equal to 7, and no disagreement was included in the final set. Among 28 candidate QIs, the panel rated 19 as valid measures of quality care. These 19 quality indicators cover care related to information and care planning (13) and supportive care (6). These QIs are evidence-based process measures of care that may be useful to improve the quality of palliative care. Research is needed to better understand the quality of palliative care provided to patients with cirrhosis. C1 [Walling, A. M.] Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. [Walling, A. M.; Wenger, N. S.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. [Walling, A. M.; Ahluwalia, S. C.; Wenger, N. S.; Booth, M.; Roth, C. P.] RAND Hlth, Santa Monica, CA 90401 USA. [Kanwal, F.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Kanwal, F.] Baylor Coll Med, Div Gastroenterol, Houston, TX 77030 USA. [Dy, S.] Johns Hopkins Kimmel Canc Ctr, Baltimore, MD USA. [Lorenz, K.; Asch, S. M.] Palo Alto VA Hlth Syst, Palo Alto, CA USA. [Lorenz, K.; Asch, S. M.] Div Gen Med Disciplines, Stanford, CA USA. [Ahluwalia, S. C.] UCLA Fielding Sch Publ Hlth, Los Angeles, CA USA. RP Walling, AM (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA.; Walling, AM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.; Walling, AM (reprint author), RAND Hlth, Santa Monica, CA 90401 USA. EM awalling@mednet.ucla.edu FU HIV/Hepatitis QUERI; Veterans Administration; VA HSRD [PPO 14-372]; NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant [UL1TR000124]; NIH loan repayment program FX This project was supported by the HIV/Hepatitis QUERI, Veterans Administration and VA HSR&D (PPO 14-372). Dr. Walling was also supported by NIH/National Center for Advancing Translational Science (NCATS) UCLA CTSI Grant Number (UL1TR000124) and the NIH loan repayment program. NR 34 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2017 VL 62 IS 1 BP 84 EP 92 DI 10.1007/s10620-016-4339-3 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EI2JE UT WOS:000392312200015 PM 27804005 ER PT J AU Stevens, BW Borren, NZ Velonias, G Conway, G Cleland, T Andrews, E Khalili, H Garber, JG Xavier, RJ Yajnik, V Ananthakrishnan, AN AF Stevens, Betsy W. Borren, Nynke Z. Velonias, Gabriella Conway, Grace Cleland, Thom Andrews, Elizabeth Khalili, Hamed Garber, John G. Xavier, Ramnik J. Yajnik, Vijay Ananthakrishnan, Ashwin N. TI Vedolizumab Therapy Is Associated with an Improvement in Sleep Quality and Mood in Inflammatory Bowel Diseases SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Vedolizumab; Sleep; Biologics; Depression; Anxiety ID C-REACTIVE PROTEIN; CROHNS-DISEASE; ULCERATIVE-COLITIS; DEPRESSIVE SYMPTOMS; OF-LIFE; ANKYLOSING-SPONDYLITIS; MAINTENANCE THERAPY; OPIOID USE; RISK; POPULATION AB Poor sleep, depression, and anxiety are common in patients with inflammatory bowel diseases (IBD) and associated with increased risk of relapse and poor outcomes. The effectiveness of therapies in improving such psychosocial outcomes is unclear but is an important question to examine with increasing selectivity of therapeutic agents. This prospective cohort enrolled patients with moderate-to-severe CD or UC starting biologic therapy with vedolizumab or anti-tumor necrosis factor alpha agents (anti-TNF). Sleep quality, depression, and anxiety were measured using validated short-form NIH PROMIS questionnaires assessing sleep and mood quality over the past 7 days. Disease activity was assessed using validated indices. Improvement in sleep and mood scores from baseline was assessed, and regression models were used to identify determinants of sleep quality. Our study included 160 patients with IBD (49 anti-TNF, 111 Vedolizumab) among whom half were women and the mean age was 40.2 years. In the combined cohort, we observed a statistically significant and meaningful decrease in mean scores from baseline (52.8) by week 6 (49.8, p = 0.002). Among vedolizumab users, sleep T-score improved from baseline (53.6) by week 6 (50.7) and persisted through week 54 (46.5, p = 0.009). Parallel reductions in depression and anxiety were also noted (p < 0.05 by week 6). We observed no difference in improvement in sleep, depression, and anxiety between vedolizumab and anti-TNF use at week 6. Both vedolizumab and anti-TNF biologic therapies were associated with improvement in sleep and mood quality in IBD. C1 [Stevens, Betsy W.; Borren, Nynke Z.; Velonias, Gabriella; Conway, Grace; Cleland, Thom; Andrews, Elizabeth; Khalili, Hamed; Garber, John G.; Xavier, Ramnik J.; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. [Borren, Nynke Z.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. [Khalili, Hamed; Garber, John G.; Xavier, Ramnik J.; Yajnik, Vijay; Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Div Gastroenterol, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA.; Ananthakrishnan, AN (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM aananthakrishnan@mgh.harvard.edu FU National Institutes of Health (NIH) [P30 DK043351]; National Institutes of Health [K23 DK097142] FX This work is supported by the National Institutes of Health (NIH) (P30 DK043351) to the Center for Study of Inflammatory Bowel Diseases. Ananthakrishnan is supported in part by a Grant from the National Institutes of Health (K23 DK097142). NR 63 TC 1 Z9 1 U1 4 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2017 VL 62 IS 1 BP 197 EP 206 DI 10.1007/s10620-016-4356-2 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EI2JE UT WOS:000392312200027 PM 27796768 ER PT J AU Greenstein, RJ Cameron, DW Brown, ST AF Greenstein, Robert J. Cameron, D. William Brown, Sheldon T. TI A Data-Based Hypothesis Explicating Thiopurine Therapeutic Failure in Biologic-Naive UC SO DIGESTIVE DISEASES AND SCIENCES LA English DT Letter ID AVIUM SUBSPECIES PARATUBERCULOSIS; PULMONARY TUBERCULOSIS; MYCOBACTERIUM; 6-MERCAPTOPURINE; DISEASE; DRUGS C1 [Greenstein, Robert J.; Brown, Sheldon T.] James J Peters VA Med Ctr, Bronx, NY 10468 USA. [Cameron, D. William] Ottawa Hosp, Res Inst, Ottawa, ON, Canada. RP Greenstein, RJ (reprint author), James J Peters VA Med Ctr, Bronx, NY 10468 USA. EM bgaxis@aol.com NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 EI 1573-2568 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD JAN PY 2017 VL 62 IS 1 BP 282 EP 283 DI 10.1007/s10620-016-4360-6 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EI2JE UT WOS:000392312200037 PM 27812848 ER PT J AU Alday, PH Doggett, JS AF Alday, P. Holland Doggett, Joseph Stone TI Drugs in development for toxoplasmosis: advances, challenges, and current status SO DRUG DESIGN DEVELOPMENT AND THERAPY LA English DT Review DE Toxoplasma gondii; therapeutics; preclinical medicine; experimental medicine; mechanism of action; Apicomplexa ID PROTEIN-KINASE 1; CENTRAL-NERVOUS-SYSTEM; IN-VIVO ACTIVITIES; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CELL TRANSPLANT RECIPIENTS; HIGH-AFFINITY INHIBITOR; HIV-INFECTED PATIENTS; FATTY-ACID SYNTHESIS; PLASMODIUM-FALCIPARUM; UNITED-STATES AB Toxoplasma gondii causes fatal and debilitating brain and eye diseases. Medicines that are currently used to treat toxoplasmosis commonly have toxic side effects and require prolonged courses that range from weeks to more than a year. The need for long treatment durations and the risk of relapsing disease are in part due to the lack of efficacy against T. gondii tissue cysts. The challenges for developing a more effective treatment for toxoplasmosis include decreasing toxicity, achieving therapeutic concentrations in the brain and eye, shortening duration, eliminating tissue cysts from the host, safety in pregnancy, and creating a formulation that is inexpensive and practical for use in resource-poor areas of the world. Over the last decade, significant progress has been made in identifying and developing new compounds for the treatment of toxoplasmosis. Unlike clinically used medicines that were repurposed for toxoplasmosis, these compounds have been optimized for efficacy against toxoplasmosis during preclinical development. Medicines with enhanced efficacy as well as features that address the unique aspects of toxoplasmosis have the potential to greatly improve toxoplasmosis therapy. This review discusses the facets of toxoplasmosis that are pertinent to drug design and the advances, challenges, and current status of preclinical drug research for toxoplasmosis. C1 [Alday, P. Holland; Doggett, Joseph Stone] Oregon Hlth & Sci Univ, Div Infect Dis, Portland, OR 97201 USA. [Doggett, Joseph Stone] Portland VA Med Ctr, Portland, OR USA. RP Doggett, JS (reprint author), Vet Affairs Med Ctr, 3710 Southwest US Vet Hosp Rd, Portland, OR 97239 USA. EM doggettj@ohsu.edu FU United States Department of Veterans Affairs Biomedical Laboratory Research and Development [BX002440] FX This work was supported by Career Development Award #BX002440 from the United States Department of Veterans Affairs Biomedical Laboratory Research and Development. NR 172 TC 0 Z9 0 U1 3 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1177-8881 J9 DRUG DES DEV THER JI Drug Des. Dev. Ther. PY 2017 VL 11 BP 273 EP 293 DI 10.2147/DDDT.S60973 PG 21 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EI7CV UT WOS:000392656000001 PM 28182168 ER PT J AU Wylie, BJ Matechi, E Kishashu, Y Fawzi, W Premji, Z Coull, BA Hauser, R Ezzati, M Roberts, DJ AF Wylie, Blair J. Matechi, Emmanuel Kishashu, Yahya Fawzi, Wafaie Premji, Zul Coull, Brent A. Hauser, Russ Ezzati, Majid Roberts, Drucilla J. TI Placental Pathology Associated with Household Air Pollution in a Cohort of Pregnant Women from Dar es Salaam, Tanzania SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID FETAL THROMBOTIC VASCULOPATHY; PARTICULATE MATTER; REACTION PATTERNS; CARBON-MONOXIDE; BIOMASS FUELS; REPRODUCIBILITY; CHORANGIOSIS; PARTICLES; NOSOLOGY; CHILDREN AB BACKGROUND: Smoke from the burning of biomass fuels has been linked with adverse pregnancy outcomes such as low birth weight, stillbirth, and prematurity. OBJECTIVE: To identify potential underlying mechanisms of adverse perinatal outcomes, we explored the association of placental pathology with household air pollution in pregnant women from urban/periurban Tanzania who cook predominantly with charcoal. METHODS: Between 2011 and 2013, we measured personal exposures to fine particulate matter (PM2.5) and carbon monoxide (CO) over 72 hr among a cohort of Tanzanian pregnant women. Placentas were collected after delivery for examination. Placental pathologies of inflammatory, hypoxic, ischemic/hypertensive, infectious and thrombotic etiologies were diagnosed, blinded to exposure levels. Using multiple logistic regression, we explored the association of PM2.5 and CO exposure with placental pathology. RESULTS: One hundred sixteen women had personal air exposure measurements and placental histopathology available for analysis. PM2.5 and CO exposures were moderate [geometric means (GSD) were 40.5 mu g/m(3) (17.3) and 2.21 ppm (1.47) respectively]; 88.6% of PM2.5 measurements exceeded World Health Organization air quality guidelines. We observed an increase in the odds (per 1-unit increase in exposure on the ln-scale) of fetal thrombotic vasculopathy (FTV) both with increasing PM2.5 [adjusted odds ratio (aOR) = 5.5; 95% CI: 1.1, 26.8] and CO measurements (aOR = 2.5; 95% CI: 1.0, 6.4) in adjusted models only. FTV also was more common among pregnancies complicated by stillbirth or low birth weight. CONCLUSIONS: Fetal thrombosis may contribute to the adverse outcomes associated with household air pollution from cook stoves during pregnancy. Larger studies are necessary for confirmation. C1 [Wylie, Blair J.; Hauser, Russ] Massachusetts Gen Hosp, Dept Obstet Gynecol, Boston, MA 02114 USA. [Wylie, Blair J.; Coull, Brent A.; Hauser, Russ] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Wylie, Blair J.; Hauser, Russ; Roberts, Drucilla J.] Harvard Med Sch, Boston, MA USA. [Matechi, Emmanuel] African Acad Publ Hlth, Dar Es Salaam, Tanzania. [Kishashu, Yahya; Premji, Zul] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Fawzi, Wafaie] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Coull, Brent A.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Hauser, Russ] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Ezzati, Majid] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Wylie, BJ (reprint author), Founders 4,55 Fruit St, Boston, MA 02114 USA. EM bwylie@partners.org FU Harvard Center for the Environment, Harvard Catalyst/The Harvard Clinical and Translational Science Center [National Institutes of Health (NIH)] [UL1 RR 025758]; NIH [U01HD061232, R01HD057941, K23 ES021471, ES 000002]; Department of Obstetrics and Gynecology at MGH; UK Medical Research Council FX Work was conducted with support from the Harvard Center for the Environment, Harvard Catalyst/The Harvard Clinical and Translational Science Center [National Institutes of Health (NIH) grant UL1 RR 025758], the NIH (grants U01HD061232 and R01HD057941), and the Department of Obstetrics and Gynecology at MGH. B.J.W. was supported by the NIH (grant K23 ES021471). B.A.C. was supported by the NIH (grant ES 000002). M.E. is supported by the UK Medical Research Council. NR 34 TC 0 Z9 0 U1 1 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2017 VL 125 IS 1 BP 134 EP 140 DI 10.1289/EHP256 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA EI0WD UT WOS:000392195000018 PM 27286442 ER PT J AU Ren, HX Luo, CM Feng, YQ Yao, XL Shi, Z Liang, FY Kang, JX Wan, JB Pei, Z Su, HX AF Ren, Huixia Luo, Chuanming Feng, Yanqing Yao, Xiaoli Shi, Zhe Liang, Fengyin Kang, Jing X. Wan, Jian-Bo Pei, Zhong Su, Huanxing TI Omega-3 polyunsaturated fatty acids promote amyloid-beta clearance from the brain through mediating the function of the glymphatic system SO FASEB JOURNAL LA English DT Article DE extracellular solutes clearance; DHA; perivascular pathways; fish oil; AQP4 polarization ID RECEPTOR-RELATED PROTEIN-1; MILD COGNITIVE IMPAIRMENT; DOCOSAHEXAENOIC ACID; ALZHEIMERS-DISEASE; TRANSGENIC MICE; RAT-BRAIN; FISH CONSUMPTION; TAU PATHOLOGY; DOUBLE-BLIND; MOUSE MODEL AB Impairment of amyloid-beta (A beta) clearance leads to A beta accumulation in the brain during the development of Alzheimer's disease (AD). Strategies that can restore or improve the clearance function hold great promise in delaying or preventing the onset of AD. Here, we show that n-3 polyunsaturated fatty acids (PUFAs), by use of fat-1 transgenic mice and oral administration of fish oil, significantly promote interstitial A beta clearance from the brain and resist A beta injury. Such beneficial effects were abolished in Aqp4-knockout mice, suggesting that the AQP4-dependent glymphatic system is actively involved in the promoting the effects of n-3 PUFAs on the clearance of extracellular A beta. Imaging on clarified brain tissues clearly displayed that n-3 PUFAs markedly inhibit the activation of astrocytes and protect the AQP4 polarization in the affected brain region after A beta injection. The results of the present study prove a novel mechanism by which n-3 PUFAs exert protective roles in reducing A beta accumulation via mediating the glymphatic system function.-Ren, H., Luo, C., Feng, Y., Yao, X., Shi, Z., Liang, F., Kang, J. X., Wan, J.-B., Pei, Z., Su, H. Omega-3 polyunsaturated fatty acids promote amyloid-b clearance from the brain through mediating the function of the glymphatic system. C1 [Ren, Huixia; Shi, Zhe; Wan, Jian-Bo; Su, Huanxing] Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China. [Luo, Chuanming; Liang, Fengyin] Guangdong Med Univ, Dept Neurol, Clin Med Coll 2, Dongguan, Peoples R China. [Feng, Yanqing; Yao, Xiaoli; Pei, Zhong] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou, Guangdong, Peoples R China. [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing X.] Harvard Med Sch, Boston, MA USA. RP Su, HX (reprint author), Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China. EM huanxingsu@umac.mo FU Macau Science and Technology Development Fund [018/2013/A1, 063/2015/A2]; University of Macau [MYRG122 (Y1-L3)-ICMS12-SHX, MYRG110 (Y1-L2)-ICMS13-SHX] FX This study was supported by Macau Science and Technology Development Fund (Grants 018/2013/A1 and 063/2015/A2) and by multiyear research Grants MYRG122 (Y1-L3)-ICMS12-SHX and MYRG110 (Y1-L2)-ICMS13-SHX (University of Macau). NR 51 TC 1 Z9 1 U1 8 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JAN PY 2017 VL 31 IS 1 BP 282 EP 293 DI 10.1096/fj.201600896 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA EI0PW UT WOS:000392177600027 PM 27789520 ER PT J AU Mosli, MH Feagan, BG Zou, G Sandborn, WJ D'Haens, G Khanna, R Shackelton, LM Walker, CW Nelson, S Vandervoort, MK Frisbie, V Samaan, MA Jairath, V Driman, DK Geboes, K Valasek, MA Pai, RK Lauwers, GY Riddell, R Stitt, LW Levesque, BG AF Mosli, Mahmoud H. Feagan, Brian G. Zou, Guangyong Sandborn, William J. D'Haens, Geert Khanna, Reena Shackelton, Lisa M. Walker, Christopher W. Nelson, Sigrid Vandervoort, Margaret K. Frisbie, Valerie Samaan, Mark A. Jairath, Vipul Driman, David K. Geboes, Karel Valasek, Mark A. Pai, Rish K. Lauwers, Gregory Y. Riddell, Robert Stitt, Larry W. Levesque, Barrett G. TI Development and validation of a histological index for UC SO GUT LA English DT Article ID ULCERATIVE-COLITIS; DISEASE-ACTIVITY; RELAPSE; REPRODUCIBILITY; THERAPY AB Objective Although the Geboes score (GS) and modified Riley score (MRS) are commonly used to evaluate histological disease activity in UC, their operating properties are unknown. Accordingly, we developed an alternative instrument. Design Four pathologists scored 48 UC colon biopsies using the GS, MRS and a visual analogue scale global rating. Intra-rater and inter-rater reliability for each index and individual index items were measured using intraclass correlation coefficients (ICCs). Items with high reliability were used to develop the Robarts histopathology index (RHI). The responsiveness/validity of the RHI and multiple histological, endoscopic and clinical outcome measures were evaluated by analyses of change scores, standardised effect size (SES) and Guyatt's responsiveness statistic (GRS) using data from a clinical trial of an effective therapy. Results Inter-rater ICCs (95% CIs) for the total GS and MRS scores were 0.79 (0.63 to 0.87) and 0.80 (0.69 to 0.87). The correlation estimates between change scores in RHI and change score in GS and MRS were 0.75 (0.67 to 0.82) and 0.84 (0.79 to 0.88), respectively. The SES and GRS estimates for GS, MRS and RHI were: 1.87 (1.54 to 2.20) and 1.23 (0.97 to 1.50), 1.29 (1.02 to 1.56) and 0.88 (0.65 to 1.12), and 1.05 (0.79 to 1.30) and 0.88 (0.64 to 1.12), respectively. Conclusions The RHI is a new histopathological index with favourable operating properties. C1 [Mosli, Mahmoud H.; Feagan, Brian G.; Zou, Guangyong; Sandborn, William J.; D'Haens, Geert; Khanna, Reena; Shackelton, Lisa M.; Walker, Christopher W.; Nelson, Sigrid; Vandervoort, Margaret K.; Frisbie, Valerie; Samaan, Mark A.; Jairath, Vipul; Stitt, Larry W.; Levesque, Barrett G.] Univ Western Ontario, Robarts Res Inst, Robarts Clin Trials, London, ON, Canada. [Mosli, Mahmoud H.; Feagan, Brian G.; Khanna, Reena] Univ Western Ontario, Dept Med, London, ON, Canada. [Mosli, Mahmoud H.] King Abdulaziz Univ, Dept Med, Jeddah, Saudi Arabia. [Feagan, Brian G.; Zou, Guangyong; Stitt, Larry W.] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Sandborn, William J.; Levesque, Barrett G.] Univ Calif San Diego, Div Gastroenterol, 9500 Gilman Dr, La Jolla, CA 92093 USA. [D'Haens, Geert] Acad Med Ctr, Dept Gastroenterol, Amsterdam, Netherlands. [Jairath, Vipul] Univ Oxford, Nuffield Dept Med, Oxford, England. [Jairath, Vipul] Univ Oxford, Oxford Clin Trials Res Unit, Oxford, England. [Driman, David K.] Univ Western Ontario, Dept Pathol, London, ON, Canada. [Geboes, Karel] Katholieke Univ Leuven, Univ Hosp, Dept Pathol, Leuven, Belgium. [Geboes, Karel] UZ Gent, Ghent, Belgium. [Valasek, Mark A.] Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. [Pai, Rish K.] Mayo Clin Arizona, Dept Lab Med & Pathol, Scottsdale, AZ USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Med Sch, Dept Pathol, Boston, MA USA. [Riddell, Robert] Univ Toronto, Mt Sinai Hosp, Dept Pathol, Toronto, ON, Canada. RP Levesque, BG (reprint author), Univ Calif San Diego, Div Gastroenterol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM bglevesque@ucsd.edu RI Zou, Guangyong/K-6408-2013; OI Mosli, Mahmoud/0000-0002-6975-1297 FU Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada (Central Reading, Database Management) FX Robarts Clinical Trials, University of Western Ontario, London, Ontario, Canada (Central Reading, Database Management). NR 27 TC 7 Z9 7 U1 3 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 EI 1468-3288 J9 GUT JI Gut PD JAN PY 2017 VL 66 IS 1 BP 50 EP 58 DI 10.1136/gutjnl-2015-310393 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EI1YN UT WOS:000392282900007 PM 26475633 ER PT J AU McCourt, CK Deng, W Dizon, DS Lankes, HA Birrer, MJ Lomme, MM Powell, MA Kendrick, JE Saltzman, JN Warshal, D Tenney, ME Kushner, DM Aghajanian, C AF McCourt, Carolyn K. Deng, Wei Dizon, Don S. Lankes, Heather. A. Birrer, Michael J. Lomme, Michele M. Powell, Matthew A. Kendrick, James E. Saltzman, Joel N. Warshal, David Tenney, Meaghan E. Kushner, David M. Aghajanian, Carol TI A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ixabepilone; Carcinosarcoma ID MICROTUBULE-STABILIZING AGENTS; MIXED MESODERMAL TUMORS; UTERINE CARCINOSARCOMA; BETA-TUBULIN; 2ND-LINE TREATMENT; EPOTHILONE ANALOG; CLINICAL-TRIALS; OVARIAN-CANCER; SOLID TUMORS; STAGE-I AB Background. The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (LICS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. Methods. Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40 mg/m(2) as a 3 hour IV infusion on day 1 of a 21 day cycle. Treatment was continued until disease progression or unacceptable toxicity occurred. Results. Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68 years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8 weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7 mo and 7.7 mo, respectively, with a median follow-up of 37 mo. Six month PFS was 20.6%. Major grade >= 3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. Conclusion. In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. (C) 2016 Published by Elsevier Inc. C1 [McCourt, Carolyn K.] Washington Univ, Sch Med, Dept Gynecol Oncol, St Louis, MO 63110 USA. [Deng, Wei; Lankes, Heather. A.] Roswell Pk Canc Inst, NRG Oncol Stat & Data Management Ctr, Buffalo, NY 14263 USA. [Dizon, Don S.; Birrer, Michael J.] Massachusetts Gen Hosp, Ctr Canc, Dept Gynecol Oncol, Boston, MA 02114 USA. [Lomme, Michele M.] Women & Infants Hosp Rhode Isl, Dept Pathol, Providence, RI 02905 USA. [Powell, Matthew A.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA. [Kendrick, James E.] Florida Hosp, Inst Canc, CCOP, Dept Gynecol Oncol, Orlando, FL 32804 USA. [Saltzman, Joel N.] Lake Univ, Ireland Canc Ctr, Dept Hematol & Oncol, Mentor, OH 44060 USA. [Warshal, David] Cooper Hlth, Dept Gynecol Oncol, Camden, NJ 08103 USA. [Tenney, Meaghan E.] Univ Chicago, Gynecol Oncol Sect, Chicago, IL 60637 USA. [Kushner, David M.] Univ Wisconsin, Dept Gynecol Oncol, Madison, WI 53792 USA. [Aghajanian, Carol] Mem Sloan Kettering Canc Ctr, Dept Med Oncol, 1275 York Ave, New York, NY 10021 USA. RP McCourt, CK (reprint author), Washington Univ, Sch Med, 4911 Barnes Jewish Hosp Plaza, St Louis, MO 63110 USA. EM mccourtc@wudosis.wustl.edu; wdeng@gogstats.org; ddizon@mgh.harvard.edtr; hlankes@gogstats.org; mbirrer@partners.org; mlomme@wihri.org; mpowell@wustl.edu; tkendrick2@gmail.com; Joel.Saltzman@uhhospitals.org; warshal-david@cooperhealth.edu; meaghan.tenney@northside.com; dmkushner@wisc.edu; aghajanc@mskcc.org FU Gynecologic Oncology Group FX Dr. David Warshal receives grant monies from the Gynecologic Oncology Group. He also received payment for lectures including service on speakers bureaus from AstraZeneca's Speakers Bureau. NR 41 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 144 IS 1 BP 101 EP 106 DI 10.1016/j.ygyno.2016.10.026 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA EI3CJ UT WOS:000392367000019 PM 28029447 ER PT J AU Dorney, KM Growdon, WB Clemmer, J Rauh-Hain, JA Hall, TR Diver, E Boruta, D del Carmen, MG Goodman, A Schorge, JO Horowitz, N Clark, RM AF Dorney, K. M. Growdon, W. B. Clemmer, J. Rauh-Hain, J. A. Hall, T. R. Diver, E. Boruta, D. del Carmen, M. G. Goodman, A. Schorge, J. O. Horowitz, N. Clark, R. M. TI Patient, treatment and discharge factors associated with hospital readmission within 30 days after surgery for vulvar cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Vulvectomy; Vulvar cancer; Readmission; Rehabilitation facility; Squamous cell carcinoma ID GYNECOLOGIC ONCOLOGY PATIENTS; CARCINOMA; QUALITY AB Objectives. The majority of hospital readmissions are unexpected and considered adverse events. The goal of this study was to examine the factors associated with unplanned readmission after surgery for vulvar cancer. Methods. Patient demographic, treatment, and discharge factors were collected on 363 patients with squamous cell carcinoma in situ or invasive cancer who underwent vulvectomy at our institution between January 2001 and June 2014. Clinical variables were correlated using chi(2) test and Student's t-test as appropriate for univariate analysis. Multivariate analysis was then performed. Results. Of 363 eligible patients, 35.6% had in situ disease and 64.5% had invasive disease. Radical vulvectomy was performed in 39.1% and 23.4% underwent lymph node assessment. Seventeen patients (4.7%) were readmitted within 30 days, with length of stay ranging 2 to 37 days and 35% of these patients required a re-operation. On univariate analyses comorbidities, radical vulvectomy, nodal assessment, initial length of stay, and discharge to a post acute care facility (PACF) were associated with hospital readmission. On multivariate analysis, only discharge to a PACF was significantly associated with readmission (OR 6.30, CI 1.12-35.53, P = 0.04). Of those who were readmitted within 30 days, 29.4% had been at a PACF whereas only 6.6% of the no readmission group had been discharged to PACF (P = 0.003). Conclusions. Readmission affected 4.7% of our population, and was associated with lengthy hospitalization and reoperation. After controlling for patient comorbidities and surgical radicality, multivariate analysis suggested that discharge to a PACF was significantly associated with risk of readmission. (C) 2016 Elsevier Inc. All rights reserved. C1 [Dorney, K. M.; Growdon, W. B.; Clemmer, J.; Rauh-Hain, J. A.; Hall, T. R.; Diver, E.; Boruta, D.; del Carmen, M. G.; Goodman, A.; Schorge, J. O.; Horowitz, N.; Clark, R. M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Boston, MA USA. RP Dorney, KM (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM kmdorney@partners.org NR 9 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 144 IS 1 BP 136 EP 139 DI 10.1016/j.ygyno.2016.11.009 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA EI3CJ UT WOS:000392367000025 PM 27836203 ER PT J AU Horowitz, NS Goldstein, DP Berkowitz, RS AF Horowitz, Neil S. Goldstein, Donald P. Berkowitz, Ross S. TI Placental site trophoblastic tumors and epithelioid trophoblastic tumors: Biology, natural history, and treatment modalities SO GYNECOLOGIC ONCOLOGY LA English DT Review DE Gestational trophoblastic neoplasia; Placental site trophoblastic tumor; Epithelioid trophoblastic tumor ID FREE BETA-SUBUNIT; OF-THE-LITERATURE; INTERMEDIATE TROPHOBLAST; CLINICAL-EXPERIENCE; DISEASE-CENTER; NEOPLASIA; MANAGEMENT; CHEMOTHERAPY; PSEUDOTUMOR; LESIONS AB Placental site (PSTT) and epithelioid trophoblastic tumor (ETT) are rare types of gestational trophoblastic neoplasia (GTN) that arise from intermediate trophoblast. Given that this cell of origin is different from other forms of GTN, it is not surprising that the clinical presentation, tumor marker profile, and treatment paradigm for PSTT and ETT are quite different as well. The mainstay for therapy for stage I PSTT and ETT is hysterectomy with adjuvant chemotherapy reserved for those presenting greater than four years from the antecedent pregnancy. Surgery is also important for metastatic disease. There is no standardized chemotherapy regimen for advanced stage disease but often consists of a platinum-containing combination therapy, usually EMA-EP or TE/TP. Despite its rarity, PSTT and ETT account for a disproportionate percentage of mortality from GTN likely resulting from their relative chemotherapy resistance. Novel therapeutic modalities therefore are needed to improve the outcomes of women with advanced stage or resistant PSTT and ETT. (C) 2016 Elsevier Inc. All rights reserved. C1 [Horowitz, Neil S.; Goldstein, Donald P.; Berkowitz, Ross S.] Harvard Med Sch, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Obstet Gynecol & Repro, New England Trophoblast Dis Ctr,Div Gynecol Oncol, Boston, MA 02115 USA. RP Berkowitz, RS (reprint author), Brigham & Womens Hosp, Div Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org FU Dyett Family Trophoblastic Disease Research and Registry Endowment FX We wish to acknowledge the support of the Donald P. Goldstein, MD Trophoblastic Tumor Registry Endowment and the Dyett Family Trophoblastic Disease Research and Registry Endowment. NR 57 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JAN PY 2017 VL 144 IS 1 BP 208 EP 214 DI 10.1016/j.ygyno.2016.10.024 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA EI3CJ UT WOS:000392367000036 PM 27789086 ER PT J AU Minnema, MC Kimby, E D'Sa, S Fornecker, LM Poulain, S Snijders, TJ Kastritis, E Kremer, S Fitsiori, A Simon, L Davi, F Lunn, M Castillo, JJ Patterson, CJ Le Garff-Tavernier, M Costopoulos, M Leblond, V Kersten, MJ Dimopoulos, MA Treon, SP AF Minnema, Monique C. Kimby, Eva D'Sa, Shirley Fornecker, Luc-Matthieu Poulain, Stephanie Snijders, Tom J. Kastritis, Efstathios Kremer, Stephane Fitsiori, Aikaterini Simon, Laurence Davi, Frederic Lunn, Michael Castillo, Jorge J. Patterson, Christopher J. Le Garff-Tavernier, Magali Costopoulos, Myrto Leblond, Veronique Kersten, Marie-Jose Dimopoulos, Meletios A. Treon, Steven P. TI Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome SO HAEMATOLOGICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PRIMARY CNS LYMPHOMA; OF-THE-LITERATURE; B-CELL LYMPHOMAS; WALDENSTROMS MACROGLOBULINEMIA; MONOCLONAL GAMMOPATHY; CEREBROSPINAL-FLUID; MYD88 L265P; UNDETERMINED SIGNIFICANCE; ORBITAL INVOLVEMENT AB Bing Neel syndrome is a rare disease manifestation of Waldenstrom's macroglobulinemia that results from infiltration of the central nervous system by malignant lymphoplasmacytic cells. In this guideline we describe the clinical symptoms, as well as the appropriate laboratory and radiological studies, that can aid in the diagnosis. The presentation of Bing Neel syndrome may be very diverse, and includes headaches, cognitive deficits, paresis, and psychiatric symptoms. The syndrome can present in patients with known Waldenstrom's macroglobulinemia, even in the absence of systemic progression, but also in previously undiagnosed patients. Diagnostic work-up should include cerebral spinal fluid analysis with multiparameter flow cytometry to establish B-cell clonality, protein electrophoresis and immunofixation for the detection and classification of a monoclonal protein as well as molecular diagnostic testing for immunoglobulin gene rearrangement and mutated MYD88. MRI of the brain and spinal cord is also essential. The second challenge is to expand our knowledge of prognosis and treatment outcome. Prospective clinical trials on Bing Neel syndrome patients that employ uniform treatment along with appropriate laboratory cerebral spinal fluid assessments and standardized MRI protocols will be invaluable, constituting a significant step forward in delineating treatment outcome for this intriguing disease manifestation. C1 [Minnema, Monique C.] UMC Utrecht, Ctr Canc, Dept Hematol, Utrecht, Netherlands. [Kimby, Eva] Karolinska Inst, Dept Med, Hematol Ctr, Stockholm, Sweden. [D'Sa, Shirley] Univ Coll London Hosp NHS Fdn Trust, Canc Div, London, England. [Fornecker, Luc-Matthieu; Simon, Laurence] Hop Univ Strasbourg, Dept Oncol & Hematol, Strasbourg, France. [Fornecker, Luc-Matthieu; Simon, Laurence] Univ Strasbourg, Strasbourg, France. [Poulain, Stephanie] CHRU Lille, Serv Hematol Immunol Cytogenet, Ctr Hosp Valenciennes, Lab Hematol,Ctr Biol & Pathol,INSERM, Lille, France. [Snijders, Tom J.] UMC Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands. [Kastritis, Efstathios; Dimopoulos, Meletios A.] Univ Athens, Dept Clin Therapeut, Athens, Greece. [Kremer, Stephane; Fitsiori, Aikaterini] CHU Strasbourg, Hop Hautepierre, Pole Imagerie Neuroradiol, Strasbourg, France. [Davi, Frederic; Le Garff-Tavernier, Magali; Costopoulos, Myrto] Hop La Pitie Salpetriere, Hematol Lab, Paris, France. [Lunn, Michael] Natl Hosp Neurol & Neurosurg, Ctr Neuromuscular Dis, Queen Sq, London, England. [Castillo, Jorge J.; Patterson, Christopher J.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. [Castillo, Jorge J.; Patterson, Christopher J.; Treon, Steven P.] Harvard Med Sch, Boston, MA USA. [Leblond, Veronique] UPMC Univ Paris, Hop Pitie Salpetriere, AP HP, Paris, France. [Kersten, Marie-Jose] Acad Med Ctr, Dept Hematol, Amsterdam, Netherlands. RP Minnema, MC (reprint author), UMC Utrecht, Ctr Canc, Dept Hematol, Utrecht, Netherlands. EM m.c.minnema@umcutrecht.nl OI Castillo, Jorge/0000-0001-9490-7532 NR 69 TC 1 Z9 1 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JAN PY 2017 VL 102 IS 1 BP 43 EP 51 DI 10.3324/haematol.2016.147728 PG 9 WC Hematology SC Hematology GA EJ0SW UT WOS:000392921800016 PM 27758817 ER PT J AU Castro, MM Kim, B Hill, E Fialho, MCQ Puga, LCHP Freitas, MB Breton, S Machado-Neves, M AF Castro, Mariana M. Kim, Bongki Hill, Eric Fialho, Maria C. Q. Puga, Luciano C. H. P. Freitas, Mariella B. Breton, Sylvie Machado-Neves, Mariana TI The expression patterns of aquaporin 9, vacuolar H+-ATPase, and cytokeratin 5 in the epididymis of the common vampire bat SO HISTOCHEMISTRY AND CELL BIOLOGY LA English DT Article DE Desmodus rotundus; Epithelium cells; Histology; V-ATPase-rich cells; KRT5 ID MALE REPRODUCTIVE-TRACT; MOLOSSUS-MOLOSSUS CHIROPTERA; FRUIT-EATING BAT; RAT EPIDIDYMIS; LUMINAL ACIDIFICATION; SEASONAL-VARIATION; BASAL-CELLS; V-ATPASE; TESTIS; IMMUNOLOCALIZATION AB Desmodus rotundus is a vampire bat species that inhabits Latin America. Some basic aspects of this species' biology are still unknown, as the histophysiological characteristics of the male reproductive tract. Our study has focused on its epididymis, which is an important organ for performing a variety of functions, especially the sperm maturation and storage. The aim of this study was to identify principal, narrow, clear, and basal cells using cell-specific markers such as aquaporin 9 (AQP9), vacuolar H+-ATPase (V-ATPase), and cytokeratin 5 (KRT5). Principal cells were labeled by AQP9 from initial segment to cauda region in their stereocilia. They were shown with a columnar shape, whereas V-ATPase-rich cells were identified with a goblet-shaped body along the entire epididymis, including the initial segment, which were named as clear cells. Pencil-shaped V-ATPase-rich cells (narrow cells) were not detected in the initial segment of the bat epididymis, unlike in the rodent. Basal cells were labeled by KRT5 and were located at the basal portion of the epithelium forming a dense network. However, no basal cells with a luminal-reaching body extension were observed in the bat epididymis. In summary, epithelial cells were identified by their specific markers in the vampire bat epididymis. Principal and basal cells were labeled by AQP9 and KRT5, respectively. Narrow cells were not observed in the vampire bat epididymis, whereas clear cells were identified by V-ATPase labeling along the entire duct in a goblet-shaped body. In addition, no luminal-reaching basal cells were observed in the vampire bat epididymis. C1 [Castro, Mariana M.; Machado-Neves, Mariana] Univ Fed Vicosa, Dept Gen Biol, BR-36570000 Vicosa, MG, Brazil. [Kim, Bongki; Hill, Eric; Breton, Sylvie] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Boston, MA 02114 USA. [Kim, Bongki; Hill, Eric; Breton, Sylvie] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Kim, Bongki; Hill, Eric; Breton, Sylvie] Harvard Med Sch, Boston, MA 02114 USA. [Fialho, Maria C. Q.] Univ Fed Amazonas, Dept Morphol, BR-69077000 Manaus, AM, Brazil. [Puga, Luciano C. H. P.] Inst Mineiro Agr, BR-36016011 Juiz De Fora, MG, Brazil. [Freitas, Mariella B.] Univ Fed Vicosa, Dept Anim Biol, BR-36570000 Vicosa, MG, Brazil. RP Machado-Neves, M (reprint author), Univ Fed Vicosa, Dept Gen Biol, BR-36570000 Vicosa, MG, Brazil. EM mariana.mneves@ufv.br RI NEVES, MARIANA/B-8833-2015; OI Neves, Mariana/0000-0002-7416-3529 FU National Institutes of Health (NIH) [HD040793, DK097124]; Brazilian Federal Agency for Support and Evaluation of Graduate School (CAPES); CAPES [99999.011031/2013-01] FX The authors thank Jerusa M. Oliveira, Bruno E.S. Melo, and Susana P. Ribeiro for their support during the collection of the bats. The study was carried out in the Program in Membrane Biology (PMB) Laboratory at Massachusetts General Hospital and supported by National Institutes of Health (NIH) grants HD040793 and DK097124 (to Sylvie Breton.); Mariana M. Castro has been granted a fellowship of Brazilian Federal Agency for Support and Evaluation of Graduate School (CAPES) and participated as a visiting graduate student in the PMB with scholarship from CAPES (Process Number-99999.011031/2013-01). NR 55 TC 2 Z9 2 U1 3 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0948-6143 EI 1432-119X J9 HISTOCHEM CELL BIOL JI Histochem. Cell Biol. PD JAN PY 2017 VL 147 IS 1 BP 39 EP 48 DI 10.1007/s00418-016-1477-9 PG 10 WC Cell Biology; Microscopy SC Cell Biology; Microscopy GA EH9AC UT WOS:000392063000005 PM 27549752 ER PT J AU Sacks, CA AF Sacks, Chana A. TI The Role of Physicians in Preventing Firearm Suicides SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Sacks, Chana A.] Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. [Sacks, Chana A.] Massachusetts Gen Hosp, Div Gen Internal Med, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. RP Sacks, CA (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA.; Sacks, CA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 1620 Tremont St,Ste 3030, Boston, MA 02120 USA. EM CSACKS@partners.org NR 10 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2017 VL 177 IS 1 BP 7 EP 8 DI 10.1001/jamainternmed.2016.6715 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA EI0WN UT WOS:000392196200002 PM 27842167 ER PT J AU Simonetti, JA Rowhani-Rahbar, A Rivara, FP AF Simonetti, Joseph A. Rowhani-Rahbar, Ali Rivara, Frederick P. TI The Road Ahead for Personalized Firearms SO JAMA INTERNAL MEDICINE LA English DT Editorial Material C1 [Simonetti, Joseph A.] Univ Colorado, Sch Med, Div Gen Internal Med, Denver, CO USA. [Simonetti, Joseph A.] Vet Affairs Eastern Colorado Healthcare Syst, Hosp Med Program, Denver, CO USA. [Rowhani-Rahbar, Ali; Rivara, Frederick P.] Univ Washington, Harborview Injury Prevent & Res Ctr, Seattle, WA 98195 USA. [Rowhani-Rahbar, Ali] Univ Washington, Dept Epidemiol, Sch Publ Hlth, Seattle, WA 98195 USA. [Rivara, Frederick P.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Simonetti, JA (reprint author), Denver VA Med Ctr, 4E-129,1055 Clermont St, Denver, CO 80220 USA. EM joseph.simonetti@ucdenver.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2017 VL 177 IS 1 BP 9 EP 10 DI 10.1001/jamainternmed.2016.6718 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA EI0WN UT WOS:000392196200003 PM 27893047 ER PT J AU Bagenski, AL Sink, J Rusiecki, J AF Bagenski, Amy L. Sink, Jacquelyn Rusiecki, Jennifer TI Thinking Beyond the Ostomy A Teachable Moment SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID HUNTINGTONS-DISEASE C1 [Bagenski, Amy L.] Univ Pittsburgh, Med Ctr, Presbyterian Montefiore Hosp, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sink, Jacquelyn] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. [Sink, Jacquelyn] Metropolitan Hosp Ctr, New York Med Ctr, New York, NY 10029 USA. [Rusiecki, Jennifer] Univ Chicago, Gen Internal Med, Chicago, IL 60637 USA. RP Bagenski, AL (reprint author), UPMC Presbyterian Montefiore Hosp, 200 Lothrop St, Pittsburgh, PA 15213 USA.; Bagenski, AL (reprint author), VA Pittsburgh Healthcare Syst, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM bagenskial@upmc.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2017 VL 177 IS 1 BP 13 EP 14 DI 10.1001/jamainternmed.2016.6868 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA EI0WN UT WOS:000392196200005 PM 27820609 ER PT J AU Okonkwo, OC Asthana, S AF Okonkwo, Ozioma C. Asthana, Sanjay TI Dementia Trends in the United States Read Up and Weigh Inle SO JAMA INTERNAL MEDICINE LA English DT Editorial Material ID ALZHEIMERS-DISEASE C1 [Okonkwo, Ozioma C.; Asthana, Sanjay] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Okonkwo, Ozioma C.; Asthana, Sanjay] Univ Wisconsin, Wisconsin Alzheimers Dis Res Ctr, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Okonkwo, Ozioma C.] Univ Wisconsin, Wisconsin Alzheimers Inst, Sch Med & Publ Hlth, Madison, WI 53706 USA. [Okonkwo, Ozioma C.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Asthana, S (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Geriatr Res Educ & Clin Ctr, 2870 Univ Ave,Ste 106, Madison, WI 53705 USA. EM sa@medicine.wisc.edu FU National Institute on Aging (NIA) [K23 AG045957, P50 AG033514] FX This work was supported by National Institute on Aging (NIA) grants K23 AG045957 and P50 AG033514. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JAN PY 2017 VL 177 IS 1 BP 58 EP 60 DI 10.1001/jamainternmed.2016.7073 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA EI0WN UT WOS:000392196200016 PM 27893015 ER PT J AU Sheehan, WJ Permaul, P Petty, CR Coull, BA Baxi, SN Gaffin, JM Lai, PS Gold, DR Phipatanakul, W AF Sheehan, William J. Permaul, Perdita Petty, Carter R. Coull, Brent A. Baxi, Sachin N. Gaffin, Jonathan M. Lai, Peggy S. Gold, Diane R. Phipatanakul, Wanda TI Association Between Allergen Exposure in Inner-City Schools and Asthma Morbidity Among Students SO JAMA PEDIATRICS LA English DT Article ID FEL D 1; ENVIRONMENTAL INTERVENTION; MOUSE ALLERGEN; UNITED-STATES; CHILDREN; CAT; SENSITIZATION; SYMPTOMS; DUST; HOME AB IMPORTANCE Home aeroallergen exposure is associated with increased asthma morbidity in children, yet little is known about the contribution of school aeroallergen exposures to such morbidity. OBJECTIVE To evaluate the effect of school-specific aeroallergen exposures on asthma morbidity among students, adjusting for home exposures. DESIGN, SETTING, AND PARTICIPANTS The School Inner-City Asthma Study was a prospective cohort study evaluating 284 students aged 4 to 13 years with asthma who were enrolled from 37 inner-city elementary schools in the northeastern United States between March 1, 2008, and August 31, 2013. Enrolled students underwent baseline clinical evaluations before the school year started and were then observed clinically for 1 year. During that same school year, classroom and home dust samples linked to the students were collected and analyzed for common indoor aeroallergens. Associations between school aeroallergen exposure and asthma outcomes during the school year were assessed, adjusting for home exposures. EXPOSURES Indoor aeroallergens, including rat, mouse, cockroach, cat, dog, and dust mites, measured in dust samples collected from inner-city schools. MAIN OUTCOMES AND MEASURES The primary outcome was maximum days in the past 2 weeks with asthma symptoms. Secondary outcomes included well-established markers of asthma morbidity, including asthma-associated health care use and lung function, measured by forced expiratory volume in 1 second. RESULTS Among 284 students (median age, 8 years [interquartile range, 6-9 years]; 148 boys and 136 girls), exposure to mouse allergen was detected in 441 (99.5%) of 443 school dust samples, cat allergen in 420 samples (94.8%), and dog allergen in 366 samples (82.6%). Levels of mouse allergen in schools were significantly higher than in students' homes (median settled dust level, 0.90 vs 0.14 mu g/g; P < .001). Exposure to higher levels of mouse allergen in school (comparing 75th with 25th percentile) was associated with increased odds of having an asthma symptom day (odds ratio, 1.27; 95% CI, 1.05-1.54; P = .02) and 4.0 percentage points lower predicted forced expiratory volume in 1 second (95% CI, -6.6 to -1.5; P = .002). This effect was independent of allergic sensitization. None of the other indoor aeroallergens were associated with worsening asthma outcomes. CONCLUSIONS AND RELEVANCE In this study of inner-city students with asthma, exposure to mouse allergen in schools was associated with increased asthma symptoms and decreased lung function. These findings demonstrate that the school environment is an important contributor to childhood asthma morbidity. Future school-based environmental interventions may be beneficial for this important public health problem. C1 [Sheehan, William J.; Baxi, Sachin N.; Phipatanakul, Wanda] Boston Childrens Hosp, Div Allergy & Immunol, 300 Longwood Ave, Boston, MA 02115 USA. [Sheehan, William J.; Permaul, Perdita; Baxi, Sachin N.; Gaffin, Jonathan M.; Lai, Peggy S.; Gold, Diane R.; Phipatanakul, Wanda] Harvard Med Sch, Boston, MA USA. [Permaul, Perdita] Massachusetts Gen Hosp, Div Pediat Allergy & Immunol, Boston, MA 02114 USA. [Petty, Carter R.] Boston Childrens Hosp, Clin Res Ctr, Boston, MA USA. [Coull, Brent A.; Lai, Peggy S.; Gold, Diane R.] Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Gaffin, Jonathan M.] Boston Childrens Hosp, Div Resp Dis, Boston, MA USA. [Lai, Peggy S.] Massachusetts Gen Hosp, Div Pulm & Crit Care, Boston, MA 02114 USA. [Gold, Diane R.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Phipatanakul, W (reprint author), Boston Childrens Hosp, Div Allergy & Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM wanda.phipatanakul@childrens.harvard.edu FU National Institutes of Health [R01AI073964, R01AI073964-02S1, K24AI106822, K23AI106945, K23ES023700, K23AI104780, U10HL098102, U01AI110397, ES-000002]; Harvard Catalyst and The Harvard Clinical and Translational Science Center from National Institutes of Health [8UL1TR000170]; Harvard University; American College of Allergy, Asthma, and Immunology Young Faculty Award; Boston Children's Hospital, Division of Immunology Clinical Research Advisory Group Research Grant; American Lung Association; American Academy of Allergy, Asthma, and Immunology Respiratory Diseases Faculty Award; Deborah Munroe Noonan Memorial Award FX This study was supported by grants R01AI073964, R01AI073964-02S1, K24AI106822, K23AI106945, K23ES023700, K23AI104780, U10HL098102, U01AI110397, and ES-000002 from the National Institutes of Health. This work was conducted with support from Harvard Catalyst and The Harvard Clinical and Translational Science Center, which received award 8UL1TR000170 from the National Institutes of Health, and financial contributions from Harvard University and its affiliated academic health care centers. This work was also supported in part by: the American College of Allergy, Asthma, and Immunology Young Faculty Award; Boston Children's Hospital, Division of Immunology Clinical Research Advisory Group Research Grant; the American Lung Association and American Academy of Allergy, Asthma, and Immunology Respiratory Diseases Faculty Award; and the Deborah Munroe Noonan Memorial Award. NR 36 TC 2 Z9 2 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6203 EI 2168-6211 J9 JAMA PEDIATR JI JAMA Pediatr. PD JAN PY 2017 VL 171 IS 1 BP 31 EP 38 DI 10.1001/jamapediatrics.2016.2543 PG 8 WC Pediatrics SC Pediatrics GA EI0XL UT WOS:000392198800012 PM 27893060 ER PT J AU Luther, SL Thomason, SS Sabharwal, S Finch, DK McCart, J Toyinbo, P Bouayad, L Matheny, ME Gobbel, GT Powell-Cope, G AF Luther, Stephen L. Thomason, Susan S. Sabharwal, Sunil Finch, Dezon K. McCart, James Toyinbo, Peter Bouayad, Lina Matheny, Michael E. Gobbel, Glenn T. Powell-Cope, Gail TI Leveraging Electronic Health Care Record Information to Measure Pressure Ulcer Risk in Veterans With Spinal Cord Injury: A Longitudinal Study Protocol SO JMIR RESEARCH PROTOCOLS LA English DT Article DE natural language processing; pressure ulcer; risk assessment; spinal cord injury; text mining ID PROGNOSTIC MODEL; AUTOMATED MODEL; HEART-FAILURE; BRADEN SCALE; INDIVIDUALS; READMISSION; SCORE AB Background: Pressure ulcers (PrUs) are a frequent, serious, and costly complication for veterans with spinal cord injury (SCI). The health care team should periodically identify PrU risk, although there is no tool in the literature that has been found to be reliable, valid, and sensitive enough to assess risk in this vulnerable population. Objective: The immediate goal is to develop a risk assessment model that validly estimates the probability of developing a PrU. The long-term goal is to assist veterans with SCI and their providers in preventing PrUs through an automated system of risk assessment integrated into the veteran's electronic health record (EHR). Methods: This 5-year longitudinal, retrospective, cohort study targets 12,344 veterans with SCI who were cared for in the Veterans Health Administration (VHA) in fiscal year (FY) 2009 and had no record of a PrU in the prior 12 months. Potential risk factors identified in the literature were reviewed by an expert panel that prioritized factors and determined if these were found in structured data or unstructured form in narrative clinical notes for FY 2009-2013. These data are from the VHA enterprise Corporate Data Warehouse that is derived from the EHR structured (ie, coded in database/table) or narrative (ie, text in clinical notes) data for FY 2009-2013. Results: This study is ongoing and final results are expected in 2017. Thus far, the expert panel reviewed the initial list of risk factors extracted from the literature; the panel recommended additions and omissions and provided insights about the format in which the documentation of the risk factors might exist in the EHR. This list was then iteratively refined through review and discussed with individual experts in the field. The cohort for the study was then identified, and all structured, unstructured, and semistructured data were extracted. Annotation schemas were developed, samples of documents were extracted, and annotations are ongoing. Operational definitions of structured data elements have been created and steps to create an analytic dataset are underway. Conclusions: To our knowledge, this is the largest cohort employed to identify PrU risk factors in the United States. It also represents the first time natural language processing and statistical text mining will be used to expand the number of variables available for analysis. A major strength of this quantitative study is that all VHA SCI centers were included in the analysis, reducing potential for selection bias and providing increased power for complex statistical analyses. This longitudinal study will eventually result in a risk prediction tool to assess PrU risk that is reliable and valid, and that is sensitive to this vulnerable population. C1 [Luther, Stephen L.; Thomason, Susan S.; Finch, Dezon K.; McCart, James; Toyinbo, Peter; Bouayad, Lina; Powell-Cope, Gail] Ctr Innovat Disabil & Rehabil Res, Hlth Serv Res & Dev, Dept Vet Affairs, Tampa, FL USA. [Luther, Stephen L.; Powell-Cope, Gail] Univ S Florida, Coll Publ Hlth, Tampa, FL USA. [Thomason, Susan S.] Tampa VA Res & Educ Fdn Inc, Tampa, FL USA. [Sabharwal, Sunil] VA New England Healthcare Syst, VA Boston Healthcare Syst, Dept Vet Affairs, West Roxbury, MA USA. [McCart, James] Univ S Florida, Muma Coll Business, Tampa, FL USA. [Matheny, Michael E.] Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Care, Dept Vet Affairs, Nashville, TN USA. [Matheny, Michael E.; Gobbel, Glenn T.] Vanderbilt Univ, Med Ctr, Dept Biomed Informat, Nashville, TN USA. [Matheny, Michael E.] Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN USA. [Matheny, Michael E.] Vanderbilt Univ, Med Ctr, Div Gen Internal Med, Nashville, TN USA. [Gobbel, Glenn T.] Tennessee Valley Healthcare Syst, Dept Vet Affairs, Res & Dev Serv, Nashville, TN USA. [Powell-Cope, Gail] Univ S Florida, Coll Nursing, Tampa, FL USA. RP Luther, SL (reprint author), James A Haley Vet Hosp 151R, Ctr Innovat Disabil & Rehabil Res, Hlth Serv Res & Dev, Dept Vet Affairs, 8900 Grand Oak Circle, Tampa, FL 33636 USA. EM steve.luther@va.gov OI Matheny, Michael/0000-0003-3217-4147; Toyinbo, Peter/0000-0003-3387-3943; Powell-Cope, Gail/0000-0002-4608-0128 FU Health Services Research and Development Service of the Veterans Health Administration FX This work was supported by the Health Services Research and Development Service of the Veterans Health Administration. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. This research is the result of work supported with resources and the use of facilities at the James A Haley Veterans Hospital and our Health Services Research and Development Center of Innovation on Disability and Rehabilitation Research. We would like to thank our project staff: Bridget Hahn, William Lapcevic, Kevin White, Keith White, and Lisa Goff. NR 30 TC 0 Z9 0 U1 3 U2 3 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1929-0748 J9 JMIR RES PROTOC JI JMIR RES. Protoc. PD JAN PY 2017 VL 6 IS 1 BP 40 EP 51 AR e3 DI 10.2196/resprot.5948 PG 12 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EI3NP UT WOS:000392398000005 PM 28104580 ER PT J AU Danielson, CK Cohen, JR Adams, ZW Youngstrom, EA Soltis, K Amstadter, AB Ruggiero, KJ AF Danielson, Carla Kmett Cohen, Joseph R. Adams, Zachary W. Youngstrom, Eric A. Soltis, Kathryn Amstadter, Ananda B. Ruggiero, Kenneth J. TI Clinical Decision-Making Following Disasters: Efficient Identification of PTSD Risk in Adolescents SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Stress disorders; Evidence-based assessment; Traumatic stress; Adolescents; PTSD risk assessment ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH PROBLEMS; DEPRESSIVE REACTIONS; NATIONAL SAMPLE; INTERNALIZING SYMPTOMS; HURRICANE-ANDREW; BIPOLAR DISORDER; SUBSTANCE-ABUSE; TASK BART; CHILDREN AB The present study aimed to utilize a Receiver Operating Characteristic (ROC) approach in order to improve clinical decision-making for adolescents at risk for the development of psychopathology in the aftermath of a natural disaster. Specifically we assessed theoretically-driven individual, interpersonal, and event-related vulnerability factors to determine which indices were most accurate in forecasting PTSD. Furthermore, we aimed to translate these etiological findings by identifying clinical cut-off recommendations for relevant vulnerability factors. Our study consisted of structured phone-based clinical interviews with 2000 adolescent-parent dyads living within a 5-mile radius of tornados that devastated Joplin, MO, and northern Alabama in Spring 2011. Demographics, tornado incident characteristics, prior trauma, mental health, and family support and conflict were assessed. A subset of youth completed two behavioral assessment tasks online to assess distress tolerance and risk-taking behavior. ROC analyses indicated four variables that significantly improved PTSD diagnostic efficiency: Lifetime depression (AUC = .90), trauma history (AUC = .76), social support (AUC = .70), and family conflict (AUC = .72). Youth were 2-3 times more likely to have PTSD if they had elevated scores on any of these variables. Of note, event-related characteristics (e.g., property damage) were not related to PTSD diagnostic status. The present study adds to the literature by making specific recommendations for empirically-based, efficient disaster-related PTSD assessment for adolescents following a natural disaster. Implications for practice and future trauma-related developmental psychopathology research are discussed. C1 [Danielson, Carla Kmett; Adams, Zachary W.] Med Univ South Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, 67 President St, Charleston, SC 29425 USA. [Cohen, Joseph R.] Univ Illinois, Dept Psychol, Champaign, IL USA. [Youngstrom, Eric A.] Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. [Soltis, Kathryn] Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. [Amstadter, Ananda B.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. [Ruggiero, Kenneth J.] Med Univ South Carolina, Coll Nursing, Technol Applicat Ctr Healthful Lifestyles, Charleston, SC USA. [Ruggiero, Kenneth J.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Danielson, CK (reprint author), Med Univ South Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, 67 President St, Charleston, SC 29425 USA. EM danielso@musc.edu FU National Institute of Mental Health (NIMH) [1R21MH086313, 1R01MH081056]; National Institute on Drug Abuse (NIDA) [R01DA031285]; National Institute on Alcohol Abuse and Alcoholism (NIAAA) [P50AA010761]; NIMH [T32MH018869] FX This work was supported by 1R21MH086313 (PI: Danielson) and 1R01MH081056 (PI: Ruggiero) from the National Institute of Mental Health (NIMH). The preparation of this manuscript was supported by R01DA031285 (PI: Danielson) from the National Institute on Drug Abuse (NIDA), P50AA010761 (PI: Becker) from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and T32MH018869 (PIs: Danielson & Kilpatrick) from the NIMH. Views expressed herein are those of the authors and do not necessarily represent the official views of NIMH, NIDA, or NIAAA. NR 78 TC 0 Z9 0 U1 10 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 EI 1573-2835 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD JAN PY 2017 VL 45 IS 1 BP 117 EP 129 DI 10.1007/s10802-016-0159-3 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA EH9DM UT WOS:000392071900010 PM 27103002 ER PT J AU Guo, J Khatri, A Maeda, A Potts, JT Juppner, H Gardella, TJ AF Guo, Jun Khatri, Ashok Maeda, Akira Potts, John T., Jr. Jueppner, Harald Gardella, Thomas J. TI Prolonged Pharmacokinetic and Pharmacodynamic Actions of a Pegylated Parathyroid Hormone (1-34) Peptide Fragment SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID POLYETHYLENE-GLYCOL; PHOSPHATE-TRANSPORT; PTH/PTHRP RECEPTOR; I COTRANSPORTER; PTH; HYPOPARATHYROIDISM; MICE; RATS; PATHWAY; IIA AB Polyethylene glycol (PEG) addition can prolong the pharmacokinetic and pharmacodynamic actions of a bioactive peptide in vivo, in part by impeding rates of glomerular filtration. For parathyroid hormone (PTH) peptides, pegylation could help in exploring the actions of the hormone in the kidney; e.g., in dissecting the relative roles that filtered versus blood-borne PTH play in regulating phosphate transport. It could also lead to potential alternate forms of treatment for hypoparathyroidism. We thus synthesized the fluorescent pegylated PTH derivative [Lys(13)(tetramethylrhodamine {TMR}), Cys(35)(PEG-20,000 Da)]PTH(1-35) (PEG-PTHTMR) and its non-pegylated counterpart [Lys(13)(TMR), Cys(35)]PTH(1-35) (PTHTMR) and assessed their properties in cells and in mice. In PTHR1-expressing HEK-293 cells, PEG-PTHTMR and PTHTMR exhibited similar potencies for inducing cAMP signaling, whereas when injected into mice, the pegylated analog persisted much longer in the circulation (>24 hours versus approximate to 1 hour) and induced markedly more prolonged calcemic and phosphaturic responses than did the non-pegylated control. Fluorescence microscopy analysis of kidney sections obtained from the injected mice revealed much less PEG-PTHTMR than PTHTMR on the luminal brush-border surfaces of renal proximal tubule cells (PTCs), on which PTH regulates phosphate transporter function, whereas immunostained phosphorylated PKA substrate, a marker of cAMP signaling, was increased to similar extents for the two ligands and for each, was localized to the basolateral portion of the PTCs. Pegylation of a bioactive PTH peptide thus led to prolonged pharmacokinetic/pharmacodynamic properties in vivo, as well as to new in vivo data that support a prominent role for PTH action at basolateral surfaces of renal proximal tubule cells. (c) 2016 American Society for Bone and Mineral Research. C1 [Gardella, Thomas J.] Massachusetts Gen Hosp, Endocrine Unit, Thier 1025,50 Blossom St, Boston, MA 02474 USA. Harvard Med Sch, Boston, MA USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1025,50 Blossom St, Boston, MA 02474 USA. EM Gardella@Helix.mgh.harvard.edu FU NIH [DK11794, AR066261] FX Authors' roles: J.G. performed experiments, A.K. prepared peptides, all authors contributed to experimental planning, data analysis and writing of the manuscript. The authors thank Braden Corbin, Monica Reyes and Tom Dean of the M.G.H. Endocrine Unit for technical assistance. This work was supported by NIH grants DK11794 and AR066261. NR 44 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0884-0431 EI 1523-4681 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 2017 VL 32 IS 1 BP 86 EP 98 DI 10.1002/jbmr.2917 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EH7YU UT WOS:000391989400011 PM 27428040 ER PT J AU Steinhilber, S Estrada, CA AF Steinhilber, Starr Estrada, Carlos A. TI Exercises in Clinical Reasoning: A Retrospective SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID ABDOMINAL-PAIN; WOMAN C1 [Steinhilber, Starr; Estrada, Carlos A.] Univ Alabama Birmingham, Birmingham, AL 35294 USA. [Steinhilber, Starr; Estrada, Carlos A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Steinhilber, S (reprint author), Univ Alabama Birmingham, Birmingham, AL 35294 USA. EM ssteinhilber@uabmc.edu NR 4 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 JAN PY 2017 VL 32 IS 1 BP 1 EP 2 DI 10.1007/s11606-016-3906-9 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA EI0ZB UT WOS:000392203200001 PM 27798776 ER PT J AU Wakeman, SE Rich, JD AF Wakeman, Sarah E. Rich, Josiah D. TI Barriers to Post-Acute Care for Patients on Opioid Agonist Therapy; An Example of Systematic Stigmatization of Addiction SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article C1 [Wakeman, Sarah E.] Massachusetts Gen Hosp, 55 Fruit St,Founders 880, Boston, MA 02114 USA. [Wakeman, Sarah E.] Harvard Med Sch, Boston, MA USA. [Wakeman, Sarah E.; Rich, Josiah D.] Ctr Prisoner Hlth & Human Rights, Providence, RI USA. [Rich, Josiah D.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Rich, Josiah D.] Miriam Hosp, Div Infect Dis, Providence, RI 02906 USA. RP Wakeman, SE (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Founders 880, Boston, MA 02114 USA. EM swakeman@partners.org FU National Institute On Drug Abuse [K24DA022112]; NIH; National Institutes of Health, Center for AIDS Research (NIH/CFAR) [P30-AI-42853] FX Dr. Rich is supported by Award No. K24DA022112 from the National Institute On Drug Abuse. The content of this piece is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute On Drug Abuse or the National Institutes of Health. Dr. Rich's research has also been facilitated in part by the infrastructure and resources provided by the Lifespan/Tufts/Brown Center for AIDS Research, an NIH-funded program, grant no. P30-AI-42853, from the National Institutes of Health, Center for AIDS Research (NIH/CFAR). 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 JAN PY 2017 VL 32 IS 1 BP 17 EP 19 DI 10.1007/s11606-016-3799-7 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA EI0ZB UT WOS:000392203200007 PM 27393486 ER PT J AU Schiavoni, KH Lehmann, LS Guan, W Rosenthal, M Sequist, TD Chien, AT AF Schiavoni, Katherine H. Lehmann, Lisa Soleymani Guan, Wendy Rosenthal, Meredith Sequist, Thomas D. Chien, Alyna T. TI How Primary Care Physicians Integrate Price Information into Clinical Decision-Making SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE primary care; technology assessment; health services research ID TEST-ORDERING BEHAVIOR; OF-POCKET COSTS; DIAGNOSTIC-TESTS; HEALTH-CARE; CHARGES; COMMUNICATION; AVAILABILITY; IMPACT; TRIAL; INTERVENTIONS AB Little is known about how primary care physicians (PCPs) in routine outpatient practice use paid price information (i.e., the amount that insurers finally pay providers) in daily clinical practice. To describe the experiences of PCPs who have had paid price information on tests and procedures for at least 1 year. Cross-sectional study using semi-structured interviews and the constant comparative method of qualitative analysis. Forty-six PCPs within an accountable care organization. Via the ordering screen of their electronic health record, PCPs were presented with the median paid price for commonly ordered tests and procedures (e.g., blood tests, x-rays, CTs, MRIs). We asked PCPs for (a) their "gut reaction" to having paid price information, (b) the situations in which they used price information in clinical decision-making separate from or jointly with patients, (c) their thoughts on who bore the chief responsibility for discussing price information with patients, and (d) suggestions for improving physician-targeted price information interventions. Among "gut reactions" that ranged from positive to negative, all PCPs were more interested in having patient-specific price information than paid prices from the practice perspective. PCPs described that when patients' out-of-pocket spending concerns were revealed, price information helped them engage patients in conversations about how to alter treatment plans to make them more affordable. PCPs stated that having price information only slightly altered their test-ordering patterns and that they avoided mentioning prices when advising patients against unnecessary testing. Most PCPs asserted that physicians bear the chief responsibility for discussing prices with patients because of their clinical knowledge and relationships with patients. They wished for help from patients, practices, health plans, and society in order to support price transparency in healthcare. Physician-targeted price transparency efforts may provide PCPs with the information they need to respond to patients' concerns regarding out-of-pocket affordability rather than that needed to change test-ordering habits. C1 [Schiavoni, Katherine H.; Lehmann, Lisa Soleymani; Sequist, Thomas D.; Chien, Alyna T.] Harvard Med Sch, Boston, MA USA. [Schiavoni, Katherine H.] Massachusetts Gen Hosp, Dept Med & Pediat, Boston, MA 02114 USA. [Lehmann, Lisa Soleymani; Sequist, Thomas D.] Brigham & Womens Hosp, Div Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. [Lehmann, Lisa Soleymani; Rosenthal, Meredith] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Lehmann, Lisa Soleymani] Vet Hlth Adm, Natl Ctr Eth Hlth Care, Washington, DC USA. [Guan, Wendy; Chien, Alyna T.] Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA 02115 USA. [Sequist, Thomas D.] Partners Healthcare Syst, Boston, MA USA. RP Chien, AT (reprint author), Boston Childrens Hosp, Dept Med, Div Gen Pediat, Boston, MA 02115 USA. EM alyna.chien@childrens.harvard.edu FU Robert Wood Johnson Foundation Health Care Financing Organization FX This work was financially supported by the Robert Wood Johnson Foundation Health Care Financing Organization. The sponsor had no role in the design or conduct of the study; the collection, analysis, or interpretation of the data; or the preparation, review, or approval of the manuscript or the decision to submit. NR 47 TC 2 Z9 2 U1 2 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 JAN PY 2017 VL 32 IS 1 BP 81 EP 87 DI 10.1007/s11606-016-3805-0 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA EI0ZB UT WOS:000392203200017 PM 27561735 ER PT J AU Gupta, N Feingold, K Dhaliwal, G AF Gupta, Neha Feingold, Kenneth Dhaliwal, Gurpreet TI Stressing Signal Versus Noise: An Exercise in Clinical Reasoning SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical reasoning; problem representation; signal detection theory ID PARANEOPLASTIC CUSHINGS-SYNDROME; CELL LUNG-CANCER C1 [Gupta, Neha; Feingold, Kenneth; Dhaliwal, Gurpreet] Univ Calif San Francisco, Dept Med, 505 Parnasus Ave, San Francisco, CA 94143 USA. [Feingold, Kenneth; Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Med Serv, San Francisco, CA USA. RP Gupta, N (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnasus Ave, San Francisco, CA 94143 USA. EM neha616@gmail.com NR 12 TC 0 Z9 0 U1 1 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 JAN PY 2017 VL 32 IS 1 BP 122 EP 126 DI 10.1007/s11606-016-3887-8 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA EI0ZB UT WOS:000392203200026 PM 27798784 ER PT J AU Judson, T Mihara, K AF Judson, Timothy Mihara, Kip TI Minocycline-induced Hyperpigmentation SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material DE clinical image; dermatology; pharmaceutical care C1 [Mihara, Kip] San Francisco VA Med Ctr, Emergency Dept, 4150 Clement St,Mail Code 111A3, San Francisco, CA 94121 USA. [Judson, Timothy; Mihara, Kip] Univ Calif San Francisco, Dept Internal Med, San Francisco, CA 94143 USA. RP Mihara, K (reprint author), San Francisco VA Med Ctr, Emergency Dept, 4150 Clement St,Mail Code 111A3, San Francisco, CA 94121 USA. EM Kip.mihara@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 JAN PY 2017 VL 32 IS 1 BP 133 EP 133 DI 10.1007/s11606-016-3735-x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA EI0ZB UT WOS:000392203200029 PM 27173498 ER PT J AU Storzbach, D Twamley, EW Roost, MS Golshan, S Williams, RM O'Neil, M Jak, AJ Turner, AP Kowalski, HM Pagulayan, KF Huckans, M AF Storzbach, Daniel Twamley, Elizabeth W. Roost, Mai S. Golshan, Shahrokh Williams, Rhonda M. O'Neil, Maya Jak, Amy J. Turner, Aaron P. Kowalski, Halina M. Pagulayan, Kathleen F. Huckans, Marilyn TI Compensatory Cognitive Training for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans With Mild Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE cognitive training; mild traumatic brain injury; OEF/OIF/OND Veterans ID POSTTRAUMATIC-STRESS-DISORDER; RANDOMIZED CONTROLLED-TRIAL; MEMORY QUESTIONNAIRE PRMQ; OF-THE-LITERATURE; NEUROPSYCHOLOGICAL OUTCOMES; RETROSPECTIVE MEMORY; MILITARY PERSONNEL; OIF/OEF VETERANS; LATENT STRUCTURE; NORMATIVE DATA AB Objective: The purpose of the study was to evaluate the efficacy of group-based compensatory cognitive training (CCT) for Operation Enduring Freedom (OEF)/Operation Iraqi Freedom(OIF)/Operation New Dawn (OND) Veterans with a history of mild traumatic brain injury. Method: One hundred nineteen OEF/OIF/OND Veterans with history of mild traumatic brain injury participated at 3 sites, and 50 of the Veterans were randomized to CCT group, while 69 Veterans were randomized to the usual care control group. The CCT group participated in 10 weeks of CCT. Both CCT and usual care groups were assessed at baseline, 5 weeks (midway through CCT), 10 weeks (immediately following CCT), and 15 weeks (5-week follow-up) on measures of subjective cognitive complaints, use of cognitive strategies, psychological functioning, and objective cognitive performance. Results: Veterans who participated in CCT reported significantly fewer cognitive and memory difficulties and greater use of cognitive strategies. They also demonstrated significant improvements on neurocognitive tests of attention, learning, and executive functioning, which were 3 of the cognitive domains targeted in CCT. Conclusions: Findings indicate that training in compensatory cognitive strategies facilitates behavioral change (ie, use of cognitive strategies) as well as both subjective and objective improvements in targeted cognitive domains. C1 [Storzbach, Daniel; Roost, Mai S.; O'Neil, Maya; Kowalski, Halina M.; Huckans, Marilyn] VA Portland Healthcare Syst, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. [Storzbach, Daniel; O'Neil, Maya; Huckans, Marilyn] Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. [Storzbach, Daniel] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Twamley, Elizabeth W.; Jak, Amy J.] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth, San Diego, CA USA. [Twamley, Elizabeth W.; Golshan, Shahrokh; Jak, Amy J.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. [Williams, Rhonda M.; Turner, Aaron P.; Pagulayan, Kathleen F.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Williams, Rhonda M.; Turner, Aaron P.] Univ Washington, Sch Med, Dept Rehabil Med, Seattle, WA 98195 USA. [Pagulayan, Kathleen F.] Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Storzbach, D (reprint author), VA Portland Healthcare Syst, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM daniel.storzbach@va.gov FU VA Merit Review Award [D7217-R]; Veterans Affairs Health Services Research and Development Center of Innovation grant; Center to Improve Veteran Involvement in Care [CIN 13-404]; Agency for Healthcare Research and Quality [1 K12 HS019456 01] FX This work was supported by VA Merit Review Award #D7217-R to Daniel Storzbach and Elizabeth Twamley from the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development. Author Maya O'Neil is currently receiving funding from a Veterans Affairs Health Services Research and Development Center of Innovation grant, Center to Improve Veteran Involvement in Care, Award #CIN 13-404, and an Agency for Healthcare Research and Quality-funded PCOR K12 award to MEO (#1 K12 HS019456 01). For the remaining authors, none were declared. This material is the result of work supported with resources and the use of facilities at the Veterans Affairs Medical Centers in Portland, Oregon, San Diego, California, and Seattle, Washington. NR 49 TC 2 Z9 2 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2017 VL 32 IS 1 BP 16 EP 24 DI 10.1097/HTR.0000000000000228 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA EI2GH UT WOS:000392304400002 PM 27022961 ER PT J AU Peltz, CB Gardner, RC Kenney, K Diaz-Arrastia, R Kramer, JH Yaffe, K AF Peltz, Carrie B. Gardner, Raquel C. Kenney, Kimbra Diaz-Arrastia, Ramon Kramer, Joel H. Yaffe, Kristine TI Neurobehavioral Characteristics of Older Veterans With Remote Traumatic Brain Injury SO JOURNAL OF HEAD TRAUMA REHABILITATION LA English DT Article DE cognitive impairment; psychiatric disorders; traumatic brain injury; veterans ID LONG-TERM OUTCOMES; ALZHEIMERS-DISEASE; HEAD-INJURY; NEUROPSYCHOLOGICAL OUTCOMES; RISK; DEPRESSION; PREVALENCE; SOLDIERS; HISTORY; SCALE AB Objective: While traumatic brain injury (TBI) is common across the life span, the detailed neurobehavioral characteristics of older adults with prior TBI remain unclear. Our goal was to compare the clinical profile of older independently living veterans with and without prior TBI. Setting: Two veterans' retirement communities. Participants: Seventy-five participants with TBI and 71 without (mean age = 78 years). Design: Cross-sectional. Main Measures: TBI history was determined by the Ohio State University TBI Questionnaire. We assessed psychiatric and medical history via interviews and chart review and conducted measures assessing functional/lifestyle, psychiatric, and cognitive outcomes. Regression analyses (adjusted for demographics, diabetes, prior depression, substance abuse, and site) were performed to compare between TBI and non-TBI participants. Results: Compared with veterans without TBI, those with TBI had greater functional impairment (adjusted P = .05), endorsed more current depressive (adjusted P = .04) and posttraumatic stress disorder symptoms (adjusted P = .01), and had higher rates of prior depression and substance abuse (both adjusted Ps < .01). While composite memory and language scores did not differ between groups, participants with TBI performed worse on tests of executive functioning/processing speed (adjusted P = .01). Conclusions: Our results suggest that TBI may have adverse long-term neurobehavioral consequences and that TBI-exposed adults may require careful screening and follow-up. C1 [Peltz, Carrie B.; Gardner, Raquel C.; Yaffe, Kristine] San Francisco VA Med Ctr, 4150 Clement St,116H, San Francisco, CA 94121 USA. [Peltz, Carrie B.; Yaffe, Kristine] NCIRE, San Francisco, CA USA. [Gardner, Raquel C.; Kramer, Joel H.; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kenney, Kimbra; Diaz-Arrastia, Ramon] Uniformed Serv Univ Hlth Sci, Rockville, MD USA. RP Peltz, CB (reprint author), San Francisco VA Med Ctr, 4150 Clement St,116H, San Francisco, CA 94121 USA. EM carrie.peltz2@va.gov FU Department of Defense [W81XWH-12-1-0581]; National Institute of Neurological Disorders and Stroke [K23 NS095755]; American Federation for Aging Research; UCSF Pepper Center; Center for Neuroscience and Regenerative Medicine; Military Clinical Neurosciences Center of Excellence; Department of Defense; VA [W81XWH-12-PHTBI-CENC, W81XHW-14-2-0137]; NIA [K24 AG031155] FX This project was supported by the Department of Defense (W81XWH-12-1-0581). R.C.G. receives support from the National Institute of Neurological Disorders and Stroke (K23 NS095755), the American Federation for Aging Research, and the UCSF Pepper Center. K.K. and R.D.-A. receive support from the Center for Neuroscience and Regenerative Medicine and the Military Clinical Neurosciences Center of Excellence. K. Y. receives support from the Department of Defense and VA (W81XWH-12-PHTBI-CENC, W81XHW-14-2-0137) and NIA (K24 AG031155). The authors thank their research participants, the Armed Forces Retirement Home in Washington, District of Columbia, the Veterans Home of California in Yountville, California, and their dedicated study staff including Kim Kelley, Ross Passo, and Leah Harburg. NR 44 TC 2 Z9 2 U1 8 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-9701 EI 1550-509X J9 J HEAD TRAUMA REHAB JI J. Head Trauma Rehabil. PD JAN-FEB PY 2017 VL 32 IS 1 BP E8 EP E15 DI 10.1097/HTR.0000000000000245 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA EI2GH UT WOS:000392304400015 PM 27323220 ER PT J AU Ge, LS Vujanovic, NL AF Ge, Lisheng Vujanovic, Nikola L. TI Soluble TNF Regulates TACE via AP-2 alpha Transcription Factor in Mouse Dendritic Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALPHA-CONVERTING-ENZYME; NECROSIS-FACTOR-ALPHA; NATURAL-KILLER-CELLS; FACTOR-RECEPTOR; HUMAN-MELANOMA; EGFR LIGANDS; CANCER CELLS; EXPRESSION; GROWTH; INFLAMMATION AB Dendritic cells (DCs), the essential immunoregulatory and APCs, are major producers of the central mediator of inflammation, soluble TNF-alpha (sTNF). sTNF is generated by TNF-alpha converting enzyme (TACE) proteolytic release of the transmembrane TNF (tmTNF) ectodomain. The mechanisms of TACE and sTNF regulation in DCs remain elusive. This study newly defines that sTNF regulates TACE in mouse DCs by engaging the AP-2 alpha transcription factor. We found that the expression of AP-2 alpha was higher, whereas the expression and activity of TACE were lower, in wild-type DCs (wtDCs) than in TNF knockout (TNFko) DCs. Exogenous sTNF rapidly and simultaneously induced increases of AP-2 alpha expression and decreases of TACE expression and activity in wtDCs and TNFko DCs, indicating that AP-2 alpha and TACE are inversely dependent on sTNF and are functionally associated. To define this functional association, we identified an AP-2 alpha binding site in TACE promoter and demonstrated, using EMSAs and chromatin immunoprecipitation assays, that AP-2 alpha could bind to TACE promoter in a TNF-dependent manner. Additionally, sTNF simultaneously enhanced AP-2 alpha expression and decreased TACE promoter luciferase activity in DCs. Similarly, transfection of AP-2 alpha cDNA decreased TACE promoter luciferase activity, TACE expression, and TACE enzymatic activity in wtDCs or TNFko DCs. In contrast, transfection of AP-2 alpha small interfering RNA increased TACE promoter luciferase activity, TACE expression, and TACE enzymatic activity in wtDCs. These results show that TACE is a target of, and is downregulated by, sTNF-induced AP-2 alpha transcription factor in DCs. C1 [Ge, Lisheng; Vujanovic, Nikola L.] Univ Pittsburgh, Inst Canc, Dept Pathol, Pittsburgh, PA 15232 USA. [Vujanovic, Nikola L.] Univ Pittsburgh, Inst Canc, Dept Immunol, Pittsburgh, PA 15232 USA. [Vujanovic, Nikola L.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. RP Vujanovic, NL (reprint author), Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, G 17d,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM vujanovicnl@upmc.edu FU National Institutes of Health [R01 DE14775, R01 DE17150]; U.S. Department of Veterans Affairs Merit Award [1-I01-BX000993-01/VUJ-ONCA-053-12S] FX This work was supported by National Institutes of Health Grants R01 DE14775 and R01 DE17150 and by U.S. Department of Veterans Affairs Merit Award Grant 1-I01-BX000993-01/VUJ-ONCA-053-12S (to N.L.V.). NR 44 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2017 VL 198 IS 1 BP 417 EP 427 DI 10.4049/jimmunol.1600524 PG 11 WC Immunology SC Immunology GA EI3ON UT WOS:000392400800042 PM 27852742 ER PT J AU Israelite, JC AF Israelite, Jill C. TI Pediatric Parenteral Nutrition-Associated Liver Disease SO JOURNAL OF INFUSION NURSING LA English DT Article DE intravenous fat emulsion; parenteral nutrition support; pediatric liver disease; short bowel syndrome ID INTESTINAL FAILURE AB Pediatric parenteral nutrition-associated liver disease (PNALD) is typically defined as a decrease in bile flow that is independent of a mechanical obstruction and of any other underlying liver disease. It is most often seen in pediatric patients receiving parenteral nutrition support. Up to 50% to 66% of children receiving long-term parenteral nutrition are reported to be diagnosed with PNALD. The goal of treatment for PNALD is advancement to full enteral nutrition and elimination of dependence on parenteral nutrition support. Achieving this goal is not always possible, especially in patients with short bowel syndrome. The following review article highlights some of the current treatment strategies focused on prevention or correction of PNALD as noted in current American Society for Parenteral and Enteral Nutrition guidelines. C1 [Israelite, Jill C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Israelite, JC (reprint author), 55 Fruit St BLK002, Boston, MA 02114 USA. EM jisraelite@partners.org 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 1533-1458 EI 1539-0667 J9 J INFUS MURS JI J. Infus.Nurs. PD JAN-FEB PY 2017 VL 40 IS 1 BP 51 EP 54 DI 10.1097/NAN.0000000000000206 PG 4 WC Nursing SC Nursing GA EI1ZI UT WOS:000392285100006 PM 28030482 ER PT J AU Mitsuki, YY Tuen, M Hioe, CE AF Mitsuki, Yu-Ya Tuen, Michael Hioe, Catarina E. TI Differential effects of HIV transmission from monocyte-derived dendritic cells vs. monocytes to IL-17(+)CD4(+) T cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Th17; Th1; HIV envelope ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVATED-RECEPTOR-GAMMA; HUMAN TH17 CELLS; IMMUNE ACTIVATION; INFECTED PATIENTS; TYPE-1 INFECTION; TRANS-INFECTION; CCR5 LIGANDS; HELPER-CELLS; TH2 CELLS AB HIV infection leads to CD4 helper T cell (Th) loss, but not all Th cells are equally depleted. The contribution of other immune cells in the Th depletion also remains unclear. This study investigates HIV transmission from monocyte-derived dendritic cells (MDDCs) vs. monocytes to Th17 and Th1 cells using an allogeneic coculture model. The addition of HIV to MDDCs increased the expression of the negative regulatory molecule PD-L1 and decreased the expression of the activation markers HLA-DR and CD86, whereas the virus up-regulated HLA-DR and CD86, but not PD-L1, on monocytes. Coculturing of CD4(+) T cells with MDDCs pretreated with HIV led to the decline of Th17, but not Th1, responses. In contrast, pretreatment of monocytes with HIV increased Th17 without affecting Th1 responses. The enhanced Th17 responses in the cocultures with HIV-treated monocytes were also accompanied by high numbers of virus-infected CD4(+) T cells. The Th17 expansion arose from memory CD4(+) T cells with minimal contribution from naive CD4(+) T cells. The Th17-enhancing activity was mediated by the HIV envelope and did not require productive virus infection. Comparison of MDDCs and monocytes further showed that, although HIV-treated MDDCs reduced Th proliferation and increased the activation of the apoptosis mediator caspase-3, HIV-treated monocytes enhanced Th proliferation without increasing the active caspase-3 levels. This study indicates the potential role of distinct myeloid cell populations in shaping Th17 responses during HIV infection. C1 [Mitsuki, Yu-Ya; Hioe, Catarina E.] Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, One Gustave L Levy Pl, New York, NY 10029 USA. [Tuen, Michael] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. [Tuen, Michael] NYU, Dept Pathol, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA. [Hioe, Catarina E.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Hioe, CE (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Infect Dis, One Gustave L Levy Pl, New York, NY 10029 USA. EM catarina.hioe@mssm.edu FU U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Department of Veterans Affairs Merit Review Award; U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases [AI093210, AI102740, AI114520] FX This study was supported in part by the U.S. Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, the Department of Veterans Affairs Merit Review Award (C.E.H.) and by U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases Grants AI093210, AI102740, and AI114520 (to C.E.H.). We thank Dr. Paul D. Bieniasz (Aaron Diamond AIDS Research Center) for providing the MT-4TMZR5 cell line, Dr. Susan Zolla-Pazner (Icahn School of Medicine at Mount Sinai) for providing monoclonal anti-HIV envelope Abs, and Ms. Radhika Wikramanayake for editing the manuscript. NR 65 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 EI 1938-3673 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD JAN PY 2017 VL 101 IS 1 BP 339 EP 350 DI 10.1189/jlb.4A0516-216R PG 12 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA EI0FN UT WOS:000392148500031 PM 27531931 ER PT J AU Chai, PR Carreiro, S Innes, BJ Rosen, RK O'Cleirigh, C Mayer, KH Boyer, EW AF Chai, Peter R. Carreiro, Stephanie Innes, Brendan J. Rosen, Rochelle K. O'Cleirigh, Conall Mayer, Kenneth H. Boyer, Edward W. TI Digital Pills to Measure Opioid Ingestion Patterns in Emergency Department Patients With Acute Fracture Pain: A Pilot Study SO JOURNAL OF MEDICAL INTERNET RESEARCH LA English DT Article DE medication adherence; opioid; digital pills; digital health; emergency medicine; pain management ID MEDICATION; ADHERENCE AB Background: Nonadherence to prescribed regimens for opioid analgesic agents contributes to increasing opioid abuse and overdose death. Opioids are frequently prescribed on an as-needed basis, placing the responsibility to determine opioid dose and frequency with the patient. There is wide variability in physician prescribing patterns because of the lack of data describing how patients actually use as-needed opioid analgesics. Digital pill systems have a radiofrequency emitter that directly measures medication ingestion events, and they provide an opportunity to discover the dose, timing, and duration of opioid therapy. Objective: The purpose of this study was to determine the feasibility of a novel digital pill system to measure as-needed opioid ingestion patterns in patients discharged from the emergency department (ED) after an acute bony fracture. Methods: We used a digital pill with individuals who presented to a teaching hospital ED with an acute extremity fracture. The digital pill consisted of a digital radiofrequency emitter within a standard gelatin capsule that encapsulated an oxycodone tablet. When ingested, the gastric chloride ion gradient activated the digital pill, transmitting a radiofrequency signal that was received by a hip-worn receiver, which then transmitted the ingestion data to a cloud-based server. After a brief, hands-on training session in the ED, study participants were discharged home and used the digital pill system to ingest oxycodone prescribed as needed for pain for one week. We conducted pill counts to verify digital pill data and open-ended interviews with participants at their follow-up appointment with orthopedics or at one week after enrollment in the study to determine the knowledge, attitudes, beliefs, and practices regarding digital pills. We analyzed open-ended interviews using applied thematic analysis. Results: We recruited 10 study participants and recorded 96 ingestion events (87.3%, 96/110 accuracy). Study participants reported being able to operate all aspects of the digital pill system after their training. Two participants stopped using the digital pill, reporting they were in too much pain to focus on the novel technology. The digital pill system detected multiple simultaneous ingestion events by the digital pill system. Participants ingested a mean 8 (SD 5) digital pills during the study period and four participants continued on opioids at the end of the study period. After interacting with the digital pill system in the real world, participants found the system highly acceptable (80%, 8/10) and reported a willingness to continue to use a digital pill to improve medication adherence monitoring (90%, 9/10). Conclusions: The digital pill is a feasible method to measure real-time opioid ingestion patterns in individuals with acute pain and to develop real-time interventions if opioid abuse is detected. Deploying digital pills is possible through the ED with a short instructional course. Patients who used the digital pill accepted the technology. C1 [Chai, Peter R.; Boyer, Edward W.] Brigham & Womens Hosp, Dept Emergency Med, Div Med Toxicol, 75 Francis St, Boston, MA 02215 USA. [Carreiro, Stephanie] Univ Massachusetts, Sch Med, Div Med Toxicol, Dept Emergency Med, Worcester, MA USA. [Innes, Brendan J.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Rosen, Rochelle K.] Miriam Hosp, Brown Sch Publ Hlth, Behav & Preventat Med, Providence, RI 02906 USA. [O'Cleirigh, Conall] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mayer, Kenneth H.] Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Chai, PR (reprint author), Brigham & Womens Hosp, Dept Emergency Med, Div Med Toxicol, 75 Francis St, Boston, MA 02215 USA. EM peterchai@gmail.com OI Innes, Brendan/0000-0003-2107-1767; Rosen, Rochelle/0000-0003-1598-667X; Carreiro, Stephanie/0000-0003-1798-9006 FU [5K24DA037109-03]; [5U01 HD068040-05]; [5R01 MH095624-05]; [1KL2 TR001455-01] FX Dr Boyer is funded by 5K24DA037109-03; Dr Mayer is funded by 5U01 HD068040-05; Dr O'Cleirigh is funded by 5R01 MH095624-05; and Dr Carreiro is funded by 1KL2 TR001455-01. EtectRx was not involved in the review or approval of this manuscript for publication. All study materials were purchased through 5K24DA037109-03 (PI: Boyer). NR 16 TC 0 Z9 0 U1 0 U2 0 PU JMIR PUBLICATIONS, INC PI TORONTO PA 59 WINNERS CIRCLE, TORONTO, ON M4L 3Y7, CANADA SN 1438-8871 J9 J MED INTERNET RES JI J. Med. Internet Res. PD JAN PY 2017 VL 19 IS 1 AR e19 DI 10.2196/jmir.7050 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA EI2PW UT WOS:000392330900023 PM 28087496 ER PT J AU Chakrabarti, S Hinczewski, M Thirumalai, D AF Chakrabarti, Shaon Hinczewski, Michael Thirumalai, D. TI Phenomenological and microscopic theories for catch bonds SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE Catch-bond; Force; Energy landscape; Cell adhesion ID CELL-ADHESION MOLECULES; BACTERIAL ADHESION; INTEGRIN ACTIVATION; ENDOTHELIAL-CELLS; SLIP BONDS; P-SELECTIN; FORCE; TRANSITION; DYNAMICS; PSGL-1 AB Lifetimes of bound states of protein complexes or biomolecule folded states typically decrease when subject to mechanical force. However, a plethora of biological systems exhibit the counter-intuitive phenomenon of catch bonding, where non-covalent bonds become stronger under externally applied forces. The quest to understand the origin of catch-bond behavior has led to the development of phenomenological and microscopic theories that can quantitatively recapitulate experimental data. Here, we assess the successes and limitations of such theories in explaining experimental data. The most widely applied approach is a phenomenological two-state model, which fits all of the available data on a variety of complexes: actomyosin, kinetochore-microtubule, selectin-ligand, and cadherin-catenin binding to filamentous actin. With a primary focus on the selectin family of cell-adhesion complexes, we discuss the positives and negatives of phenomenological models and the importance of evaluating the physical relevance of fitting parameters. We describe a microscopic theory for selectins, which provides a structural basis for catch bonds and predicts a crucial allosteric role for residues Asn82-Glu88. We emphasize the need for new theories and simulations that can mimic experimental conditions, given the complex response of cell adhesion complexes to force and their potential role in a variety of biological contexts. (C) 2016 Elsevier Inc. All rights reserved. C1 [Chakrabarti, Shaon] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Chakrabarti, Shaon] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Hinczewski, Michael] Case Western Reserve Univ, Dept Phys, Cleveland, OH 44106 USA. [Thirumalai, D.] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA. RP Chakrabarti, S (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM shaon@jimmy.harvard.edu FU National Science Foundation [CHE 13-61946]; National Institutes of Health [GM 089685] FX This work was supported in part by grants from the National Science Foundation (Grant No. CHE 13-61946) and the National Institutes of Health (GM 089685). NR 60 TC 1 Z9 1 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 EI 1095-8657 J9 J STRUCT BIOL JI J. Struct. Biol. PD JAN PY 2017 VL 197 IS 1 SI SI BP 50 EP 56 DI 10.1016/j.jsb.2016.03.022 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA EI0LV UT WOS:000392166900007 PM 27046010 ER PT J AU Goldman, RH Tuomala, RE Bengtson, JM Stagg, AR AF Goldman, Randi H. Tuomala, Ruth E. Bengtson, Joan M. Stagg, Amy R. TI How Effective are New Milestones Assessments at Demonstrating Resident Growth? 1 Year of Data SO JOURNAL OF SURGICAL EDUCATION LA English DT Article DE ACGME milestones; obstetrics and gynecology; evaluation tool; resident assessment; competency ID EMERGENCY-MEDICINE MILESTONES; PERFORMANCE AB OBJECTIVE: Assessment tools that accrue data for the Accreditation Council for Graduate Medical Education Milestones must evaluate residents across multiple dimensions, including medical knowledge, procedural skills, teaching, and professionalism. Our objectives were to: (1) develop an assessment tool to evaluate resident performance in accordance with the Milestones and (2) review trends in resident achievements during the inaugural year of Milestone implementation. DESIGN: A novel venue and postgraduate year (PGY) specific assessment tool was built, tested, and implemented for both operating room and labor and delivery "venues." Resident development of competence and independence was captured over time. To account for variable rotation schedules, the year was divided into thirds and compared using two-tailed Fisher's exact test. SETTING: Brigham and Women's and Massachusetts General Hospitals, Boston MA. PARTICIPANTS: Faculty evaluators and obstetrics and gynecology residents. RESULTS: A total of 822 assessments of 44 residents were completed between 9/2014 and 6/2015. The percentage of labor and delivery tasks completed "independently" increased monotonically across the start of all years: 8.4% for PGY-1, 60.3% for PGY-2, 73.7% for PGY-3, and 87.5% for PGY-4. Assessments of PGY-1 residents demonstrated a significant shift toward "with minimal supervision" and "independent" for the management of normal labor (p = 0.03). PGY-3 residents demonstrated an increase in "able to be primary surgeon" in the operating room, from 36% of the time in the first 2/3 of the year, to 62.3% in the last 1/3 (p < 0.01). CONCLUSION: Assessment tools developed to assist with Milestone assignments capture the growth of residents over time and demonstrate quantifiable differences in achievements between PGY classes. These tools will allow for targeted teaching opportunities for both individual residents and residency programs. (C) 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved. C1 [Goldman, Randi H.; Tuomala, Ruth E.; Bengtson, Joan M.] Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Tuomala, Ruth E.; Stagg, Amy R.] Harvard Med Sch, Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Boston, MA USA. RP Goldman, RH (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. EM rhgoldman@partners.org NR 17 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1931-7204 EI 1878-7452 J9 J SURG EDUC JI J. Surg. Educ. PD JAN-FEB PY 2017 VL 74 IS 1 BP 68 EP 73 DI 10.1016/j.jsurg.2016.06.009 PG 6 WC Education, Scientific Disciplines; Surgery SC Education & Educational Research; Surgery GA EI1SW UT WOS:000392259200011 PM 27395399 ER PT J AU Siegert, CJ Fisichella, PM Moseley, JM Shoni, M Lebenthal, A AF Siegert, Charles Jeff Fisichella, Piero Marco Moseley, Jennifer M. Shoni, Melina Lebenthal, Abraham TI Open access phone triage for veterans with suspected malignant pleural mesothelioma SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE Asbestos; Centralized care model; Evidence-based treatment; Guidelines based practice; Malignant pleural mesothelioma; Phone triage; Single-payer system; Veterans; Veterans Administration Healthcare System ID ASBESTOS; PNEUMONECTOMY; FEASIBILITY; MANAGEMENT; CISPLATIN; SURVIVAL; EXPOSURE; RISK AB Background: Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service. Methods: A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care. Results: Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines. Conclusions: Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timelymanner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service. Published by Elsevier Inc. C1 [Siegert, Charles Jeff; Moseley, Jennifer M.; Shoni, Melina; Lebenthal, Abraham] VA Boston Healthcare Syst, Sect Gen Thorac Surg, West Roxbury, MA USA. [Siegert, Charles Jeff; Fisichella, Piero Marco; Moseley, Jennifer M.] VA Boston Healthcare Syst, Dept Surg, West Roxbury, MA USA. [Shoni, Melina; Lebenthal, Abraham] Brigham & Womens Hosp, Div Gen Thorac Surg, 75 Francis St, Boston, MA 02115 USA. [Lebenthal, Abraham] Brigham & Womens Hosp, Int Mesothelioma Program, 75 Francis St, Boston, MA 02115 USA. RP Lebenthal, A (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Boston VA Hlth Care Syst, 75 Francis St,PBB5,Rm 549, Boston, MA 02115 USA. EM alebenthal@partners.org OI Fisichella, P. Marco/0000-0002-7697-7884 NR 20 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 207 BP 108 EP 114 DI 10.1016/j.jss.2016.08.031 PG 7 WC Surgery SC Surgery GA EI1CH UT WOS:000392212800015 PM 27979465 ER PT J AU Parikh, A Atreya, C Korn, WM Venook, AP AF Parikh, Aparna Atreya, Chloe Korn, W. Michael Venook, Alan P. TI Prolonged Response to HER2-Directed Therapy in a Patient With HER2-Amplified, Rapidly Progressive Metastatic Colorectal Cancer SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID TRASTUZUMAB EMTANSINE; BREAST-CANCER; OVEREXPRESSION; RESISTANCE AB HER2 gene amplifications and activating mutations in the HER2 receptor tyrosine kinase are present in 4% of metastatic colorectal cancers (mCRCs). HER2-targeted therapy is not standard of care, although preclinical and clinical data suggest that patients with HER2 amplifications and/or HER2-activating mutations may benefit from HER2-directed therapy. HER2 amplifications and activating mutations have also been implicated in resistance to anti-epidermal growth factor receptor based therapy. This report describes a patient with KRAS, NRAS, and BRAF wild-type mCRC who experienced disease progression on first-line treatment with FOLFIRI and cetuximab after only 5 months, and subsequently experienced progression on second-line treatment with capecitabine and oxaliplatin plus bevacizumab after 2 months with significant functional decline. Next-generation sequencing of the primary tumor identified HER2 amplification, and we were able to obtain trastuzumab-DM1 for off-label use. The patient had symptomatic clinical benefit from trastuzumab-DM1 and had radiographic disease control for 7 months. On progression, therapy was changed to trastuzumab and pertuzumab, but the patient's disease progressed 3 months later. Treatment with the trastuzumab-DM1 resulted in a sustained response that was longer than his prior responses in the first and second lines of treatment, with a dramatic improvement in the patient's functional status. This case represents the first report, to our knowledge, of successful single-agent treatment of HER2-amplifed CRC with trastuzumab-DM1. Clinical trials targeting patients with HER2-mutated and -amplified metastatic colon cancer are currently underway. Molecular insights from investigating HER2 activation and the impact of HER2-directed therapies in a wide variety of solid tumors will create the needed evidence base to more broadly inform patient care. C1 [Parikh, Aparna; Atreya, Chloe; Korn, W. Michael; Venook, Alan P.] Univ Calif San Francisco, Hellen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. RP Parikh, A (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM aparna.parikh@mgh.harvard.edu FU Genentech; GlaskoSmithKline; Novartis; Merck; Genentech/Roche; Bayer; Bristol-Myers Squibb; Lily; Onyx FX Dr. Parikh has disclosed receiving salary from Genentech. Dr. Atreya has disclosed receiving research support from GlaskoSmithKline, Novartis, and Merck, and has disclosed serving in a consulting/advisory role for Genentech, and Bayer Diagnostics. Dr. Korn has disclosed serving in a consulting/advisory role for Merrimack and Foundation Medicine; having a patent from Exelexis; and receiving travel expenses from Merrimack. Dr. Venook has disclosed serving in a consulting/advisory role for Genentech/Roche, and receiving research support from Genentech/Roche, Bayer, Bristol-Myers Squibb, GlaskoSmithKline, Lily, and Onyx. NR 26 TC 0 Z9 0 U1 1 U2 1 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2017 VL 15 IS 1 BP 3 EP 8 PG 6 WC Oncology SC Oncology GA EH8TT UT WOS:000392045900002 PM 28040715 ER PT J AU Daly, MB Pilarski, R Berry, M Buys, SS Farmer, M Friedman, S Garber, JE Kauff, ND Khan, S Klein, C Kohlmann, W Kurian, A Litton, JK Madlensky, L Merajver, SD Offit, K Pal, T Reiser, G Shannon, KM Swisher, E Vinayak, S Voian, NC Weitzel, JN Wick, MJ Wiesner, GL Dwyer, M Darlow, S AF Daly, Mary B. Pilarski, Robert Berry, Michael Buys, Saundra S. Farmer, Meagan Friedman, Susan Garber, Judy E. Kauff, Noah D. Khan, Seema Klein, Catherine Kohlmann, Wendy Kurian, Allison Litton, Jennifer K. Madlensky, Lisa Merajver, Sofia D. Offit, Kenneth Pal, Tuya Reiser, Gwen Shannon, Kristen Mahoney Swisher, Elizabeth Vinayak, Shaveta Voian, Nicoleta C. Weitzel, Jeffrey N. Wick, Myra J. Wiesner, Georgia L. Dwyer, Mary Darlow, Susan TI NCCN Guidelines (R) Insights Genetic/Familial High-Risk Assessment: Breast and Ovarian, Version 2.2017 Featured Updates to the NCCN Guidelines SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; DIFFUSE GASTRIC-CANCER; GERMLINE MUTATIONS; LYNCH-SYNDROME; NEUROFIBROMATOSIS TYPE-1; FAMILY-HISTORY; CONFER SUSCEPTIBILITY; ENDOMETRIAL CANCER; CDH1 MUTATIONS; ATM GENE AB The NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian provide recommendations for genetic testing and counseling for hereditary cancer syndromes and risk management recommendations for patients who are diagnosed with a syndrome. Guidelines focus on syndromes associated with an increased risk of breast and/or ovarian cancer. The NCCN Genetic/Familial High-Risk Assessment: Breast and Ovarian panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. The NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding risk management for carriers of moderately penetrant genetic mutations associated with breast and/or ovarian cancer. C1 [Daly, Mary B.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Pilarski, Robert] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Pilarski, Robert] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Berry, Michael] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Buys, Saundra S.; Kohlmann, Wendy] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Farmer, Meagan] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Friedman, Susan] FORCE Facing Our Risk Canc Empowered, Tampa, FL USA. [Garber, Judy E.] Dana Farber Brigham & Womens Canc Ctr, Milford, MA USA. [Kauff, Noah D.] Duke Canc Inst, Durham, NC USA. [Khan, Seema] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Klein, Catherine] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Kurian, Allison] Stanford Canc Inst, Stanford, CA USA. [Litton, Jennifer K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Madlensky, Lisa] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Merajver, Sofia D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Offit, Kenneth] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Pal, Tuya] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Reiser, Gwen] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Shannon, Kristen Mahoney] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Swisher, Elizabeth] Univ Washington, Med Ctr, Seattle Canc Care Alliance, Seattle, WA 98195 USA. [Vinayak, Shaveta] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, Qld, Australia. [Vinayak, Shaveta] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Voian, Nicoleta C.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Weitzel, Jeffrey N.] City Hope Comprehens Canc Ctr, Los Angeles, CA USA. [Wick, Myra J.] Mayo Clin, Ctr Canc, Rochester, MN USA. [Wiesner, Georgia L.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dwyer, Mary; Darlow, Susan] Natl Comprehens Canc Network, Ft Washington, MD USA. RP Daly, MB (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU Astellas; AstraZeneca; Celldex Therapeutics; Clovis Oncology; Genomic Health, Inc.; Kyowa Hakko Kirin; Jazz Pharmaceuticals; Novartis Pharmaceuticals Corporation; NOVOCURE; independent educational grant from Merck Co., Inc. FX This activity is supported by educational grants from Astellas, AstraZeneca, Celldex Therapeutics, Clovis Oncology, Genomic Health, Inc., Kyowa Hakko Kirin, Jazz Pharmaceuticals, Novartis Pharmaceuticals Corporation, and NOVOCURE. This activity is supported by an independent educational grant from Merck Co., Inc. NR 70 TC 1 Z9 1 U1 5 U2 5 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2017 VL 15 IS 1 BP 9 EP 19 PG 11 WC Oncology SC Oncology GA EH8TT UT WOS:000392045900003 PM 28040716 ER PT J AU Greenberg, PL Stone, RM Al-Kali, A Barta, SK Bejar, R Bennett, JM Carraway, H De Castro, CM Deeg, HJ DeZern, AE Fathi, AT Frankfurt, O Gaensler, K Garcia-Manero, G Griffiths, EA Head, D Horsfall, R Johnson, RA Juckett, M Klimek, VM Komrokji, R Kujawski, LA Maness, LJ O'Donnell, MR Pollyea, DA Shami, PJ Stein, BL Walker, AR Westervelt, P Zeidan, A Shead, DA Smith, C AF Greenberg, Peter L. Stone, Richard M. Al-Kali, Aref Barta, Stefan K. Bejar, Rafael Bennett, John M. Carraway, Hetty De Castro, Carlos M. Deeg, H. Joachim DeZern, Amy E. Fathi, Amir T. Frankfurt, Olga Gaensler, Karin Garcia-Manero, Guillermo Griffiths, Elizabeth A. Head, David Horsfall, Ruth Johnson, Robert A. Juckett, Mark Klimek, Virginia M. Komrokji, Rami Kujawski, Lisa A. Maness, Lori J. O'Donnell, Margaret R. Pollyea, Daniel A. Shami, Paul J. Stein, Brady L. Walker, Alison R. Westervelt, Peter Zeidan, Amer Shead, Dorothy A. Smith, Courtney TI Myelodysplastic Syndromes, Version 2.2017 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; QUALITY-OF-LIFE; BONE-MARROW-TRANSPLANTATION; WORLD-HEALTH-ORGANIZATION; TRANSFUSION-DEPENDENT PATIENTS; CHRONIC MYELOMONOCYTIC LEUKEMIA; CONVENTIONAL CARE REGIMENS; RANDOMIZED PHASE-III AB The myelodysplastic syndromes (MDS) comprise a heterogenous group of myeloid disorders with a highly variable disease course. Diagnostic criteria to better stratify patients with MDS continue to evolve, based on morphology, cytogenetics, and the presence of cytopenias. More accurate classification of patients will allow for better treatment guidance. Treatment encompasses supportive care, treatment of anemia, low intensity therapy, and high-intensity therapy. This portion of the guidelines focuses on diagnostic classification, molecular abnormalities, therapeutic options, and recommended treatment approaches. C1 [Greenberg, Peter L.] Stanford Canc Inst, Palo Alto, CA 94305 USA. [Stone, Richard M.; Fathi, Amir T.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. [Al-Kali, Aref] Mayo Clin, Ctr Canc, Cleveland, OH USA. [Barta, Stefan K.] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Bejar, Rafael] UC San Diego Moores Canc Ctr, San Diego, CA USA. [Carraway, Hetty] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Carraway, Hetty] Cleveland Clin, Taussig Canc Inst, Cleveland, OH USA. [De Castro, Carlos M.] Duke Canc Inst, Durham, NC USA. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA USA. [DeZern, Amy E.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Frankfurt, Olga] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Gaensler, Karin] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Garcia-Manero, Guillermo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Griffiths, Elizabeth A.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Head, David] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Johnson, Robert A.] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Juckett, Mark] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Klimek, Virginia M.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Komrokji, Rami] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Kujawski, Lisa A.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Maness, Lori J.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [O'Donnell, Margaret R.] City Hope Comprehens Canc Ctr, Los Angeles, CA USA. [Pollyea, Daniel A.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Shami, Paul J.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Stein, Brady L.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Walker, Alison R.] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Walker, Alison R.] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Westervelt, Peter] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Westervelt, Peter] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Zeidan, Amer] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. RP Greenberg, PL (reprint author), Stanford Canc Inst, Palo Alto, CA 94305 USA. NR 158 TC 0 Z9 0 U1 3 U2 3 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2017 VL 15 IS 1 BP 60 EP 87 PG 28 WC Oncology SC Oncology GA EH8TT UT WOS:000392045900007 PM 28040720 ER PT J AU Koh, WJ Greer, BE Abu-Rustum, NR Campos, SM Cho, KR Chon, HS Chu, C Cohn, D Crispens, MA Dizon, DS Dorigo, O Eifel, PJ Fisher, CM Frederick, P Gaffney, DK Han, E Higgins, S Huh, WK Lurain, JR Mariani, A Mutch, D Nagel, C Nekhlyudov, L Fader, AN Remmenga, SW Reynolds, RK Tillmanns, T Ueda, S Valea, FA Wyse, E Yashar, CM McMillian, N Scavone, J AF Koh, Wui-Jin Greer, Benjamin E. Abu-Rustum, Nadeem R. Campos, Susana M. Cho, Kathleen R. Chon, Hye Sook Chu, Christina Cohn, David Crispens, Marta Ann Dizon, Don S. Dorigo, Oliver Eifel, Patricia J. Fisher, Christine M. Frederick, Peter Gaffney, David K. Han, Ernest Higgins, Susan Huh, Warner K. Lurain, John R., III Mariani, Andrea Mutch, David Nagel, Christa Nekhlyudov, Larissa Fader, Amanda Nickles Remmenga, Steven W. Reynolds, R. Kevin Tillmanns, Todd Ueda, Stefanie Valea, Fidel A. Wyse, Emily Yashar, Catheryn M. McMillian, Nicole Scavone, Jillian TI Vulvar Cancer, Version 1.2017 Clinical Practice Guidelines in Oncology SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Review ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED-CARCINOMA; LYMPH-NODE METASTASES; SUPERFICIAL INGUINAL LYMPHADENECTOMY; POSITRON-EMISSION-TOMOGRAPHY; PHASE-II TRIAL; PROGNOSTIC-FACTORS; RADIATION-THERAPY; UNITED-STATES; INGUINOFEMORAL LYMPHADENECTOMY AB Vulvar cancer is a rare gynecologic malignancy.Ninety percent of vulvar cancers are predominantly squamous cell carcinomas (SCCs), which can arise through human papilloma virus (HPV)-dependent and HPV-independent pathways. The NCCN Vulvar Cancer panel is an interdisciplinary group of representatives from NCCN Member Institutions consisting of specialists in gynecological oncology, medical oncology, radiation oncology, and pathology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Vulvar Cancer provide an evidence- and consensus-based approach for the management of patients with vulvar SCC. This manuscript discusses the recommendations outlined in the NCCN Guidelines for diagnosis, staging, treatment, and follow-up. C1 [Koh, Wui-Jin; Greer, Benjamin E.] Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Abu-Rustum, Nadeem R.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Campos, Susana M.; Nekhlyudov, Larissa] Dana Farber Brigham & Womens Canc Ctr, Milford, MA USA. [Cho, Kathleen R.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chon, Hye Sook] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Chu, Christina] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Cohn, David] Ohio State Univ, Ctr Comprehens Canc, James Canc Hosp, Columbus, OH 43210 USA. [Cohn, David] Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. [Crispens, Marta Ann] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Dizon, Don S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Dorigo, Oliver] Stanford Canc Inst, Palo Alto, CA USA. [Eifel, Patricia J.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fisher, Christine M.] Univ Colorado, Ctr Canc, Boulder, CO 80309 USA. [Frederick, Peter] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gaffney, David K.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Han, Ernest] City Hope Comprehens Canc Ctr, Los Angeles, CA USA. [Higgins, Susan] Smilow Canc Hosp, Yale Canc Ctr, New Haven, CT USA. [Huh, Warner K.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL USA. [Lurain, John R., III] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA. [Mariani, Andrea] Mayo Clin, Ctr Canc, Cleveland, OH USA. [Mutch, David] Barnes Jewish Hosp, Siteman Canc Ctr, St Louis, MO 63110 USA. [Mutch, David] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Nagel, Christa] Univ Hosp Seidman Canc Ctr, Case Comprehens Canc Ctr, Cleveland, OH USA. [Nagel, Christa] Cleveland Clin, Taussig Canc Inst, Cleveland, OH 44106 USA. [Fader, Amanda Nickles] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Remmenga, Steven W.] Fred & Pamela Buffett Canc Ctr, Omaha, NE USA. [Reynolds, R. Kevin] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Tillmanns, Todd] Univ Tennessee, Hlth Sci Ctr, St Jude Childrens Res Hosp, Knoxville, TN 37996 USA. [Ueda, Stefanie] UCSF Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA. [Valea, Fidel A.] Duke Canc Inst, Durham, NC USA. [Yashar, Catheryn M.] UC San Diego Moores Canc Ctr, La Jolla, CA USA. RP Koh, WJ (reprint author), Fred Hutchinson Canc Res Ctr, Seattle Canc Care Alliance, Seattle, WA 98109 USA. NR 131 TC 0 Z9 0 U1 4 U2 4 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 EI 1540-1413 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD JAN PY 2017 VL 15 IS 1 BP 92 EP 120 PG 29 WC Oncology SC Oncology GA EH8TT UT WOS:000392045900008 PM 28040721 ER PT J AU Padia, SA Lewandowski, RJ Johnson, GE Sze, DY Ward, TJ Gaba, RC Baerlocher, MO Gates, VL Riaz, A Brown, DB Siddiqi, NH Walker, TG Silberzweig, JE Mitchell, JW Nikolic, B Salem, R AF Padia, Siddharth A. Lewandowski, Robert J. Johnson, Guy E. Sze, Daniel Y. Ward, Thomas J. Gaba, Ron C. Baerlocher, Mark O. Gates, Vanessa L. Riaz, Ahsun Brown, Daniel B. Siddiqi, Nasir H. Walker, T. Gregory Silberzweig, James E. Mitchell, Jason W. Nikolic, Boris Salem, Riad CA Soc Interventional Radiology Stand Practice Comm TI Radioembolization of Hepatic Malignancies: Background, Quality Improvement Guidelines, and Future Directions SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID UNRESECTABLE HEPATOCELLULAR-CARCINOMA; Y-90 RESIN MICROSPHERES; SINGLE-CENTER EXPERIENCE; CANCER LIVER METASTASES; CONE-BEAM CT; POSITRON-EMISSION-TOMOGRAPHY; RESPONSE EVALUATION CRITERIA; ART BRACHYTHERAPY TREATMENT; INTERNAL RADIATION-THERAPY; PORTAL-VEIN THROMBOSIS C1 [Padia, Siddharth A.] Univ Calif Los Angeles, David Geffen Sch Med, Div Intervent Radiol, Dept Radiol, Los Angeles, CA 90095 USA. [Sze, Daniel Y.] Stanford Univ, Sch Med, Div Intervent Radiol, Stanford, CA 94305 USA. [Lewandowski, Robert J.; Gates, Vanessa L.; Riaz, Ahsun; Salem, Riad] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Sect Intervent Radiol, Chicago, IL 60611 USA. [Gaba, Ron C.] Univ Illinois Hosp & Hlth Sci Syst, Dept Radiol, Div Intervent Radiol, Chicago, IL USA. [Johnson, Guy E.] Univ Washington, Dept Radiol, Sect Intervent Radiol, Seattle, WA 98195 USA. [Ward, Thomas J.] Florida Hosp, Dept Radiol, Sect Intervent Radiol, Orlando, FL USA. [Brown, Daniel B.] Vanderbilt Univ, Sch Med, Dept Radiol, Nashville, TN 37212 USA. [Ward, Thomas J.] Massachusetts Gen Hosp, Div Intervent Radiol, Boston, MA 02114 USA. [Silberzweig, James E.] Intervent Radiol PC, New York, NY USA. [Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA. [Mitchell, Jason W.] Univ Maryland, Sch Med, Div Vasc & Intervent Radiol, Dept Diagnost Radiol & Nucl Med, Baltimore, MD 21201 USA. [Baerlocher, Mark O.] Royal Victoria Hosp, Dept Med Imaging, Barrie, ON, Canada. [Siddiqi, Nasir H.] King Faisal Specialist Hosp & Res Ctr, Dept Radiol, Riyadh, Saudi Arabia. RP Padia, SA (reprint author), Care of Katsarelis D, SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM spadia@gmail.com FU BTG International (Ottawa, Ontario, Canada); Guerbet (Roissy, France); Cook (Bloomington, Indiana); BTG International; Sirtex (North Sydney, Australia); Boston Scientific; EmboIX (Los Altos, California); Cook; Covidien (Dublin, Ireland); Amgen (Thousand Oaks, California); Codman (Raynham, Massachusetts); Vascular Solutions (Minneapolis, Minnesota); Onyx Pharmaceuticals (South San Francisco, California); Merit Medical (South Jordan, Utah); Terumo (Tokyo, Japan); Siemens (Munich, Germany); Bayer (Leverkusen, Germany) FX S.A.P. is a paid consultant for and serves on the advisory board of BTG International (Ottawa, Ontario, Canada) and Guerbet (Roissy, France). R.J.L. serves on the advisory boards for BTG International and Boston Scientific (Marlborough, Massachusetts) and is a paid consultant for Cook (Bloomington, Indiana). D.Y.S. receives personal fees from BTG International, Sirtex (North Sydney, Australia), Boston Scientific, EmboIX (Los Altos, California), Cook, Covidien (Dublin, Ireland), Amgen (Thousand Oaks, California), and Codman (Raynham, Massachusetts). M.O.B. is a paid consultant for Boston Scientific. D.B.B. is a paid consultant for Cook, Vascular Solutions (Minneapolis, Minnesota), and Onyx Pharmaceuticals (South San Francisco, California). R.S. receives grants and personal fees from BTG International and personal fees from Boston Scientific, Merit Medical (South Jordan, Utah), Terumo (Tokyo, Japan), Siemens (Munich, Germany), and Bayer (Leverkusen, Germany). None of the other authors have identified a conflict of interest. NR 137 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JAN PY 2017 VL 28 IS 1 BP 1 EP 15 DI 10.1016/j.jvir.2016.09.024 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA EI4LM UT WOS:000392465200001 PM 27836405 ER PT J AU Shapero, BG McClung, G Bangasser, DA Abramson, LY Alloy, LB AF Shapero, Benjamin G. McClung, George Bangasser, Debra A. Abramson, Lyn Y. Alloy, Lauren B. TI Interaction of Biological Stress Recovery and Cognitive Vulnerability for Depression in Adolescence SO JOURNAL OF YOUTH AND ADOLESCENCE LA English DT Article DE Adolescence; Depression; Cortisol; Heart rate; Recovery; Cognitive vulnerability ID ACUTE PSYCHOLOGICAL STRESS; CORTISOL RESPONSES; MAJOR DEPRESSION; AUTONOMIC CONTROL; SOCIAL STRESS; LIFE STRESS; REACTIVITY; SYMPTOMS; RUMINATION; CHILDREN AB Major Depressive Disorder is a common mental illness with rates increasing during adolescence. This has led researchers to examine developmental antecedents of depression. This study examined the association between depressive symptoms and the interaction between two empirically supported risk factors for depression: poor recovery of the biological stress system as measured through heart rate and cortisol, and cognitive vulnerabilities as indexed by rumination and a negative cognitive style. Adolescents (n = 127; 49 % female) completed questionnaires and a social stress task to elicit a stress response measured with neuroendocrine (cortisol) and autonomic nervous system (heart rate) endpoints. The findings indicated that higher depressive symptoms were associated with the combination of higher cognitive vulnerabilities and lower cortisol and heart rate recovery. These findings can enhance our understanding of stress responses, lead to personalized treatment, and provide a nuanced understanding of depression in adolescence. C1 [Shapero, Benjamin G.; McClung, George; Bangasser, Debra A.; Alloy, Lauren B.] Temple Univ, Dept Psychol, 1701 N 13th St, Philadelphia, PA 19122 USA. [Shapero, Benjamin G.] Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Shapero, Benjamin G.] Harvard Med Sch, Boston, MA 02115 USA. [McClung, George; Bangasser, Debra A.] Temple Univ, Neurosci Program, 1701 N 13th St, Philadelphia, PA 19122 USA. [Abramson, Lyn Y.] Univ Wisconsin Madison, Dept Psychol, 1201 W Johnson St, Madison, WI 53706 USA. RP Shapero, BG (reprint author), Temple Univ, Dept Psychol, 1701 N 13th St, Philadelphia, PA 19122 USA.; Shapero, BG (reprint author), Massachusetts Gen Hosp, Dept Psychiat, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA.; Shapero, BG (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM bshapero@mgh.harvard.edu FU National Institute of Mental Health [MH79369, MH101168, MH099764] FX This research was supported by National Institute of Mental Health Grants MH79369 and MH101168 to Lauren B. Alloy and MH099764 to Benjamin G. Shapero. NR 61 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 0047-2891 EI 1573-6601 J9 J YOUTH ADOLESCENCE JI J. Youth Adolesc. PD JAN PY 2017 VL 46 IS 1 SI SI BP 91 EP 103 DI 10.1007/s10964-016-0451-0 PG 13 WC Psychology, Developmental SC Psychology GA EH9GM UT WOS:000392079700007 PM 26923989 ER PT J AU Lee, HH Choi, MG Hasan, T AF Lee, Han Hee Choi, Myung-Gyu Hasan, Tayyaba TI Application of photodynamic therapy in gastrointestinal disorders: an outdated or re-emerging technique? SO KOREAN JOURNAL OF INTERNAL MEDICINE LA English DT Review DE Photochemotherapy; Gastrointestinal diseases; Gastrointestinal neoplasms; Palliative care; Photosensitizing agents ID SUPERFICIAL ESOPHAGEAL CANCER; ADVANCED GASTRIC-CANCER; SQUAMOUS-CELL CARCINOMA; ND-YAG LASER; HILAR CHOLANGIOCARCINOMA; 5-AMINOLEVULINIC ACID; BARRETTS-ESOPHAGUS; LOCAL FAILURE; PORFIMER SODIUM; LIGHT-SOURCES AB Photodynamic therapy (PDT) is a promising therapeutic modality that involves the administration of a photosensitizer followed by local illumination with a specific wavelength of light in the presence of oxygen. PDT is minimally invasive, has high selectivity for cancer, and has good patient compliance due to the simplicity of the procedure; therefore, PDT is widely used as a palliative and salvage treatment in patients with various gastrointestinal malignancies. When used as a salvage treatment for locoregional failures after definitive chemoradiotherapy for esophageal cancer, favorable results have been reported. PDT in conjunction with biliary stenting is a promising palliative treatment for unresectable cholangio-carcinoma, and can be used as an advanced diagnostic and therapeutic strategy in peritoneal dissemination of gastric cancer. Recent clinical reports of PDT for treating non-resectable pancreatic cancer also show promising results. To widen the application of PDT, the integration of PDT with molecular imaging and nanotechnology is being extensively studied. Based on these new developments, PDT is likely to re-emerge as a valuable technique in the treatment of diverse gastrointestinal diseases. C1 [Lee, Han Hee; Choi, Myung-Gyu] Catholic Univ Korea, Dept Internal Med, Div Gastroenterol, Coll Med, Seoul, South Korea. [Hasan, Tayyaba] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Choi, MG (reprint author), Catholic Univ Korea, Div Gastroenterol, Dept Internal Med, Coll Med,Seoul St Marys Hosp, 222 Banpo Daero, Seoul 06591, South Korea. EM choim@catholic.ac.kr FU National Research Foundation of Korea (NRF) - Korea government (Ministry of Science, ICT & Future Planning) [NRF-2016R1C1B2015185]; program in the Global Research and Development Center through the NRF - Ministry of Science, ICT and Future Planning [NRF-2011-0031644]; Basic Science Research Program through the NRF - Ministry of Education, Science and Technology [NRF-2013R1A1A2007985]; Catholic Medical Center Research Foundation; National Institutes of Health/National Cancer Institute (NIH/NCI) of the United States of America [P01CA084203] FX This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science, ICT & Future Planning) (NRF-2016R1C1B2015185), by a program in the Global Research and Development Center through the NRF funded by the Ministry of Science, ICT and Future Planning (NRF-2011-0031644), by a Basic Science Research Program through the NRF funded by the Ministry of Education, Science and Technology (NRF-2013R1A1A2007985), by the Catholic Medical Center Research Foundation established in 2014, and by the National Institutes of Health/National Cancer Institute (NIH/NCI) of the United States of America (grant P01CA084203 awarded to T. Hasan). NR 55 TC 0 Z9 0 U1 7 U2 7 PU KOREAN ASSOC INTERNAL MEDICINE PI SEOUL PA 101-2501 LOTTE CASTLE PRESIDENT, 109 MAPO-DAERO, MAPO-GU, SEOUL, 121-916, SOUTH KOREA SN 1226-3303 EI 2005-6648 J9 KOREAN J INTERN MED JI Korean J. Intern. Med. PD JAN PY 2017 VL 32 IS 1 BP 1 EP 10 DI 10.3904/kjim.2016.200 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA EI1GA UT WOS:000392223500001 PM 28049283 ER PT J AU Sharma, P Verma, Y Sahu, K Kumar, S Varma, AV Kumawat, J Gupta, PK AF Sharma, Priyanka Verma, Yogesh Sahu, Khageswar Kumar, Sudhir Varma, Amit V. Kumawat, Jyoti Gupta, Pradeep Kumar TI Human ex-vivo oral tissue imaging using spectral domain polarization sensitive optical coherence tomography SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Optical coherence tomography; Spectral domain polarization sensitive optical coherence tomography; Oral cancer; Collagen; Submucosal fibrosis; Trichrome staining ID QUANTITATIVE-ANALYSIS; INVASION AB We report the use of spectral domain polarization sensitive optical coherence tomography for ex-vivo imaging of human oral mandibular tissue samples. Our results show that compared to the changes observed in the epithelium thickness and the decay constant of A-scan intensity profile, a much larger degree of change was observed in the phase retardation for tissue sites progressing from normal to the malignant state. These results suggest that monitoring of tissue retardance can help in better differentiation of normal and cancerous oral tissue sites. C1 [Sharma, Priyanka; Verma, Yogesh; Sahu, Khageswar; Kumar, Sudhir; Kumawat, Jyoti] Raja Ramanna Ctr Adv Technol, Laser Biomed Applicat Sect, Indore 452013, India. [Sharma, Priyanka; Gupta, Pradeep Kumar] Homi Bhabha Natl Inst, Bombay 400094, Maharashtra, India. [Verma, Yogesh] Harvard Med Sch, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. [Verma, Yogesh] Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Varma, Amit V.] Sri Aurobindo Med Coll & PG Inst, Indore 452013, India. RP Sharma, P (reprint author), Raja Ramanna Ctr Adv Technol, Laser Biomed Applicat Sect, Indore 452013, India.; Sharma, P (reprint author), Homi Bhabha Natl Inst, Bombay 400094, Maharashtra, India. EM priyanka@rrcat.gov.in FU Department of Atomic Energy, Government of India (PIC) [12-R&D-CAT-5.10-01 00] FX The study was funded by Department of Atomic Energy, Government of India (PIC no. 12-R&D-CAT-5.10-01 00). No other source of funding was involved. NR 29 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0268-8921 EI 1435-604X J9 LASER MED SCI JI Lasers Med. Sci. PD JAN PY 2017 VL 32 IS 1 BP 143 EP 150 DI 10.1007/s10103-016-2096-3 PG 8 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA EH9HH UT WOS:000392081900018 PM 27807650 ER PT J AU Counts, SE Ikonomovic, MD Mercado, N Vega, IE Mufson, EJ AF Counts, Scott E. Ikonomovic, Milos D. Mercado, Natosha Vega, Irving E. Mufson, Elliott J. TI Biomarkers for the Early Detection and Progression of Alzheimer's Disease SO NEUROTHERAPEUTICS LA English DT Review DE Alzheimer's disease; Mild cognitive impairment; Biomarker; Cerebrospinal fluid; Positron emission tomography; Amyloid ID MILD COGNITIVE IMPAIRMENT; POSITRON-EMISSION-TOMOGRAPHY; PITTSBURGH COMPOUND-B; CEREBROSPINAL-FLUID BIOMARKERS; CEREBRAL AMYLOID ANGIOPATHY; NEUROIMAGING INITIATIVE SUBJECTS; LINKED-IMMUNOSORBENT-ASSAY; BETA-PROTEIN PRECURSOR; MEMORY CLINIC COHORT; PHF-TAU RADIOLIGAND AB The recent failures of potential disease-modifying drugs for Alzheimer's disease (AD) may reflect the fact that the enrolled participants in clinical trials are already too advanced to derive a clinical benefit. Thus, well-validated biomarkers for the early detection and accurate diagnosis of the preclinical stages of AD will be crucial for therapeutic advancement. The combinatorial use of biomarkers derived from biological fluids, such as cerebrospinal fluid (CSF), with advanced molecular imaging and neuropsychological testing may eventually achieve the diagnostic sensitivity and specificity necessary to identify people in the earliest stages of the disease when drug modification is most likely possible. In this regard, positive amyloid or tau tracer retention on positron emission tomography imaging, low CSF concentrations of the amyloid-beta 1-42 peptide, high CSF concentrations in total tau and phospho-tau, mesial temporal lobe atrophy on magnetic resonance imaging, and temporoparietal/precuneus hypometabolism or hypoperfusion on 18F-fluorodeoxyglucose positron emission tomography have all emerged as biomarkers for the progression to AD. However, the ultimate AD biomarker panel will likely involve the inclusion of novel CSF and blood biomarkers more precisely associated with confirmed pathophysiologic mechanisms to improve its reliability for detecting preclinical AD. This review highlights advancements in biological fluid and imaging biomarkers that are moving the field towards achieving the goal of a preclinical detection of AD. C1 [Counts, Scott E.; Mercado, Natosha; Vega, Irving E.] Michigan State Univ, Dept Translat Sci & Mol Med, Grand Rapids, MI USA. [Counts, Scott E.] Michigan State Univ, Dept Family Med, Grand Rapids, MI USA. [Counts, Scott E.] Mercy Hlth St Marys Hosp, Hauenstein Neurosci Ctr, Grand Rapids, MI USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Ikonomovic, Milos D.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Mufson, Elliott J.] Barrow Neurol Inst, Dept Neurobiol & Neurol, Phoenix, AZ 85013 USA. RP Mufson, EJ (reprint author), Barrow Neurol Inst, Dept Neurobiol & Neurol, Phoenix, AZ 85013 USA. EM elliott.mufson@dignityhealth.org FU National Institutes of Health [PO1AG14449, RO1AG043375, AG025204, AG052528, R21AG026032, R21AG042146]; Saint Mary's Foundation, Miles for Memories of Battle Creek, MI; Barrow Neurological Institute Barrow and Beyond FX This study was supported by National Institutes of Health grants PO1AG14449, RO1AG043375, AG025204, AG052528, R21AG026032, and R21AG042146; the Saint Mary's Foundation, Miles for Memories of Battle Creek, MI; and Barrow Neurological Institute Barrow and Beyond. NR 289 TC 0 Z9 0 U1 19 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2017 VL 14 IS 1 BP 35 EP 53 DI 10.1007/s13311-016-0481-z PG 19 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA EI2NW UT WOS:000392325200005 PM 27738903 ER PT J AU Paganoni, S Schwarzschild, MA AF Paganoni, Sabrina Schwarzschild, Michael A. TI Urate as a Marker of Risk and Progression of Neurodegenerative Disease SO NEUROTHERAPEUTICS LA English DT Review DE Biomarker; Risk; Prognosis; Inosine; Oxidative stress ID AMYOTROPHIC-LATERAL-SCLEROSIS; URIC-ACID LEVELS; PARKINSONS-DISEASE; OXIDATIVE STRESS; PLASMA URATE; SERUM URATE; ANTIOXIDANT CAPACITY; CLINICAL-TRIAL; PC12 CELLS; RAT MODEL AB Urate is a naturally occurring antioxidant whose levels are associated with reduced risk of developing Parkinson's disease (PD) and Alzheimer's disease. Urate levels are also associated with favorable progression in PD, amyotrophic lateral sclerosis, Huntington's disease, and multisystem atrophy. These epidemiological data are consistent with laboratory studies showing that urate exhibits neuroprotective effects by virtue of its antioxidant properties in several preclinical models. This body of evidence supports the hypothesis that urate may represent a shared pathophysiologic mechanism across neurodegenerative diseases. Most importantly, beyond its role as a molecular predictor of disease risk and progression, urate may constitute a novel therapeutic target. Indeed, clinical trials of urate elevation in PD and amyotrophic lateral sclerosis are testing the impact of raising peripheral urate levels on disease outcomes. These studies will contribute to unraveling the neuroprotective potential of urate in human pathology. In parallel, preclinical experiments are deepening our understanding of the molecular pathways that underpin urate's activities. Altogether, these efforts will bring about new insights into the translational potential of urate, its determinants, and its targets and their relevance to neurodegeneration. C1 [Paganoni, Sabrina; Schwarzschild, Michael A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. [Paganoni, Sabrina] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. [Paganoni, Sabrina] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Schwarzschild, Michael A.] MIND, Boston, MA USA. RP Paganoni, S (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA.; Paganoni, S (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA.; Paganoni, S (reprint author), VA Boston Healthcare Syst, Boston, MA 02130 USA. EM spaganoni@partners.org FU National Institutes of Health (NIH) [2K12HD001097-16]; Target ALS; Salah Foundation; Spastic Paraplegia Foundation; ALS Association; ALS Finding a Cure; GHALS Therapy Fund; NIH; Michael J. Fox Foundation; Parkinson's Disease Foundation; Department of Defense; Hoffman Foundation; Biotie Therapeutics FX S.P. has received funding from the National Institutes of Health (NIH; Career Development Award 2K12HD001097-16), Target ALS, the Salah Foundation, the Spastic Paraplegia Foundation, the ALS Association, ALS Finding a Cure, and the MGHALS Therapy Fund. M.S. has received grants from the NIH, the Michael J. Fox Foundation, the Parkinson's Disease Foundation, the Department of Defense, the Hoffman Foundation, and Target ALS; M.S. has received personal fees from Biotie Therapeutics. NR 57 TC 0 Z9 0 U1 4 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2017 VL 14 IS 1 BP 148 EP 153 DI 10.1007/s13311-016-0497-4 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA EI2NW UT WOS:000392325200014 PM 27995438 ER PT J AU Costigan, M Seiger, A Ecklund, D Raulerson, S Thornell, B Cudkowicz, M Pierce, M Bosch, M Coffey, C Long, J Anderson, K Simon, N Hersch, S Brownstein, M AF Costigan, Michele Seiger, Ashley Ecklund, Dixie Raulerson, Sabrina Thornell, Brenda Cudkowicz, Merit Pierce, Mareena Bosch, Michael Coffey, Christopher Long, Jeffery Anderson, Karen Simon, Neal Hersch, Steven Brownstein, Michael TI Safety and Tolerability of SRX246 in Irritable Patients with HD (STAIR) SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Costigan, Michele; Ecklund, Dixie; Pierce, Mareena; Bosch, Michael; Coffey, Christopher; Long, Jeffery] Univ Iowa, Iowa City, IA USA. [Seiger, Ashley; Raulerson, Sabrina; Thornell, Brenda; Cudkowicz, Merit; Hersch, Steven] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Anderson, Karen] Georgetown Univ, Washington, DC USA. [Simon, Neal; Brownstein, Michael] Azevan Pharmaceut, Bethlehem, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2017 VL 14 IS 1 MA 7 BP 236 EP 236 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA EI2NW UT WOS:000392325200029 ER PT J AU Vijayvargia, R Jung, TY Hebert, H Seong, IS Song, JJ AF Vijayvargia, Ravi Jung, Tae-Yang Hebert, Hans Seong, Ihn Sik Song, Ji-Joon TI Structural and Biochemical Analysis of Full-length Huntingtin and the Effect of the Polyglutamine Expansion SO NEUROTHERAPEUTICS LA English DT Meeting Abstract C1 [Vijayvargia, Ravi; Seong, Ihn Sik] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jung, Tae-Yang; Song, Ji-Joon] Korea Adv Inst Sci & Technol, Daejeon, South Korea. [Hebert, Hans] Karolinska Inst, Huddinge, Sweden. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1933-7213 EI 1878-7479 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JAN PY 2017 VL 14 IS 1 MA 33 BP 247 EP 247 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA EI2NW UT WOS:000392325200055 ER PT J AU Jakobiec, FA Grob, SR Stagner, AM Curtin, H Massoud, V Fay, A AF Jakobiec, Frederick A. Grob, Seanna R. Stagner, Anna M. Curtin, Hugh Massoud, Vicky Fay, Aaron TI Orbital Conjunctival Cyst Associated With the Superior Rectus-Levator Muscles: A Clinicopathologic Study SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID COMMON SHEATH; LESIONS; MANAGEMENT; DACRYOPS; FEATURES; TUMORS AB A 55-year-old woman had a right orbital cyst detected incidentally on radiographic imaging. The patient's symptoms were mild and included intermittent pain and vertical diplopia; the patient was not aware of any visual decline. There was a palpable mass beneath the superior orbital rim. Radiographic imaging revealed a well-demarcated cystic lesion in the right superior orbit between the levator palpebrae superioris and superior rectus muscles. The mass was completely excised via a transconjunctival approach. Histopathologic evaluation disclosed a conjunctival cyst lined by nonkeratinized squamous epithelium with scattered, rare goblet cells. This case combined with 5 other similar reported cases suggests that an intermuscular cyst located in the superior rectus-levator complex is most likely of congenital embryonic conjunctival origin. C1 [Jakobiec, Frederick A.; Stagner, Anna M.] Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 328,243 Charles St, Boston, MA 02114 USA. [Jakobiec, Frederick A.; Grob, Seanna R.; Stagner, Anna M.; Massoud, Vicky; Fay, Aaron] Harvard Med Sch, Dept Ophthalmol, Boston, MA USA. [Grob, Seanna R.; Massoud, Vicky; Fay, Aaron] Massachusetts Eye & Ear Infirm, Ophthalm Plast Surg, Boston, MA 02114 USA. [Curtin, Hugh] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. RP Jakobiec, FA (reprint author), Massachusetts Eye & Ear Infirm, David G Cogan Lab Ophthalm Pathol, Suite 328,243 Charles St, Boston, MA 02114 USA. EM Fred_Jakobiec@meei.harvard.edu NR 26 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 0740-9303 EI 1537-2677 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD JAN-FEB PY 2017 VL 33 IS 1 BP E1 EP E4 DI 10.1097/IOP.0000000000000358 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA EI1PQ UT WOS:000392250400021 PM 25564256 ER PT J AU Gullbrand, SE Malhotra, NR Schaer, TP Zawacki, Z Martin, JT Bendigo, JR Milby, AH Dodge, GR Vresilovic, EJ Elliott, DM Mauck, RL Smith, LJ AF Gullbrand, S. E. Malhotra, N. R. Schaer, T. P. Zawacki, Z. Martin, J. T. Bendigo, J. R. Milby, A. H. Dodge, G. R. Vresilovic, E. J. Elliott, D. M. Mauck, R. L. Smith, L. J. TI A large animal model that recapitulates the spectrum of human intervertebral disc degeneration SO OSTEOARTHRITIS AND CARTILAGE LA English DT Article DE Goat; Caprine; Preclinical animal model; Disc degeneration; Chondroitinase ABC; Nucleotomy ID HUMAN LUMBAR DISC; NUCLEUS PULPOSUS; IN-VIVO; CHONDROITINASE-ABC; NEEDLE PUNCTURE; INJURY; GOAT; INJECTION; MOTION; CANINE AB Objective: The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design: Degeneration was induced in the lumbar intervertebral discs of large frame goats by either inti-adiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, microcomputed tomography (mu CT), and measurement of disc biomechanical properties. Results: Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1 rho, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical honey endplate adjacent to ChABC-injected discs also occurred. Spine segment range of motion (ROM) was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions: A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration. (C) 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. C1 [Gullbrand, S. E.; Martin, J. T.; Bendigo, J. R.; Dodge, G. R.; Mauck, R. L.; Smith, L. J.] Philadelphia VA Med Ctr, Translat Musculoskeletal Res Ctr, Philadelphia, PA USA. [Gullbrand, S. E.; Martin, J. T.; Bendigo, J. R.; Milby, A. H.; Dodge, G. R.; Mauck, R. L.; Smith, L. J.] Univ Penn, Dept Orthopaed Surg, McKay Orthopaed Res Lab, Philadelphia, PA USA. [Malhotra, N. R.; Bendigo, J. R.; Smith, L. J.] Univ Penn, Dept Neurosurg, 424 Stemmler Hall,3450 Hamilton Walk, Philadelphia, PA 19104 USA. [Schaer, T. P.; Zawacki, Z.] Univ Penn, Sch Vet Med, Comparat Orthopaed Res Lab, Kennett Sq, PA 19348 USA. [Vresilovic, E. J.] Penn State Univ, Penn State Hershey Bone & Joint Inst, Hershey, PA USA. [Elliott, D. M.] Univ Delaware, Dept Biomed Engn, Newark, DE USA. RP Smith, LJ (reprint author), Univ Penn, Dept Neurosurg, 424 Stemmler Hall,3450 Hamilton Walk, Philadelphia, PA 19104 USA. EM lachlans@mail.med.upenn.edu FU Department of Veterans Affairs (RRD) [I01RX00132]; Orthopaedic Research and Education Foundation; Sharpe Foundation; Departments of Neurosurgery and Orthopaedic Surgery at the University of Pennsylvania FX This work was supported by the Department of Veterans Affairs (RR&D I01RX00132). The authors would also like to acknowledge the Orthopaedic Research and Education Foundation (resident grant), the Sharpe Foundation, and the Departments of Neurosurgery and Orthopaedic Surgery at the University of Pennsylvania for financial support. Core equipment used in this study was provided by the Penn Center for Musculoskeletal Disorders (NIH P30AR050950) and the Center for Magnetic Resonance Imaging & Spectroscopy (CAMRIS). The authors would also like to acknowledge the veterinary staff at the New Bolton Center for their assistance with animal care and management throughout the study. NR 53 TC 0 Z9 0 U1 11 U2 11 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 JAN PY 2017 VL 25 IS 1 BP 146 EP 156 DI 10.1016/j.joca.2016.08.006 PG 11 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA EI2XN UT WOS:000392353100019 PM 27568573 ER PT J AU Manchikanti, L Helm, S Calodney, AK Hirsch, JA AF Manchikanti, Laxmaiah Helm, Standiford, II Calodney, Aaron K. Hirsch, Joshua A. TI Merit-Based Incentive Payment System: Meaningful Changes in the Final Rule Brings Cautious Optimism SO PAIN PHYSICIAN LA English DT Review DE Medicare Access and CHIP Reauthorization Act of 2015; merit-based incentive payment system; quality performance measures; resource use; improvement activities; advancing care information performance category ID QUALITY REPORTING SYSTEM; AFFORDABLE CARE ACT; HEALTH-CARE; STICK POLICY; REFORM; FUTURE; GROWTH; CARROT; PQRS AB The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) eliminated the flawed Sustainable Growth Rate (SGR) act formula-a longstanding crucial issue of concern for health care providers and Medicare beneficiaries. MACRA also included a quality improvement program entitled, "The Merit-Based Incentive Payment System, or MIPS." The proposed rule of MIPS sought to streamline existing federal quality efforts and therefore linked 4 distinct programs into one. Three existing programs, meaningful use (MU), Physician Quality Reporting System (PQRS), valuebased payment (VBP) system were merged with the addition of Clinical Improvement Activity category. The proposed rule also changed the name of MU to Advancing Care Information, or ACI. ACI contributes to 25% of composite score of the four programs, PQRS contributes 50% of the composite score, while VBP system, which deals with resource use or cost, contributes to 10% of the composite score. The newest category, Improvement Activities or IA, contributes 15% to the composite score. The proposed rule also created what it called a design incentive that drives movement to delivery system reform principles with the inclusion of Advanced Alternative Payment Models (APMs). Following the release of the proposed rule, the medical community, as well as Congress, provided substantial input to Centers for Medicare and Medicaid Services (CMS), expressing their concern. American Society of Interventional Pain Physicians (ASIPP) focused on 3 important aspects: delay the implementation, provide a 3-month performance period, and provide ability to submit meaningful quality measures in a timely and economic manner. The final rule accepted many of the comments from various organizations, including several of those specifically emphasized by ASIPP, with acceptance of 3-month reporting period, as well as the ability to submit non-MIPS measures to improve real quality and make the system meaningful. CMS also provided a mechanism for physicians to avoid penalties for non-reporting with reporting of just a single patient. In summary, CMS has provided substantial flexibility with mechanisms to avoid penalties, reporting for 90 continuous days, increasing the low volume threshold, changing the reporting burden and data thresholds and, finally, coordination between performance categories. The final rule has made MIPS more meaningful with bonuses for exceptional performance, the ability to report for 90 days, and to report on 50% of the patients in 2017 and 60% of the patients in 2018. The final rule also reduced the quality measures to 6, including only one outcome or high priority measure with elimination of cross cutting measure requirement. In addition, the final rule reduced the burden of ACI, improved the coordination of performance, reduced improvement activities burden from 60 points to 40 points, and finally improved coordination between performance categories. Multiple concerns remain regarding the reduction in scoring for quality improvement in future years, increase in proportion of MIPS scoring for resource use utilizing flawed, claims based methodology and the continuation of the disproportionate importance of ACI, an expensive program that can be onerous for providers which in many ways has not lived up to its promise. C1 [Manchikanti, Laxmaiah] Pain Management Ctr Paducah, Paducah, KY USA. [Manchikanti, Laxmaiah] Univ Louisville, Anesthesiol & Perioperat Med, Louisville, KY 40292 USA. [Helm, Standiford, II] Helm Ctr Pain Management, Laguna Woods, CA USA. [Calodney, Aaron K.] Texas Spine & Joint Hosp, Clin Res, Precis Spine Care, Tyler, TX USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Care, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, NeuroIntervent Spine, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent Radiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Massachusetts Gen Hosp, Intervent & Endovasc Neuroradiol, Boston, MA 02114 USA. [Hirsch, Joshua A.] Harvard Med Sch, Boston, MA USA. RP Manchikanti, L (reprint author), 2831 Lone Oak Rd, Paducah, KY 42003 USA. EM drlm@thepainmd.com FU Cephalon/Teva; AstraZeneca; Purdue Pharma, LP FX Dr. Manchikanti has provided limited consulting services to Semnur Pharmaceuticals, Incorporated, which is developing nonparticulate steroids. Dr. Helm is a clinical investigator with Epimed and receives research support from Cephalon/Teva, AstraZeneca, and Purdue Pharma, LP. He has attended an advisory group meeting for Activas. Dr. Calodney is a consultant for Stryker, Inc., Medtronic, Inc., and Nimbus Concepts. Dr. Hirsch is a consultant for Medtronic. NR 39 TC 0 Z9 0 U1 3 U2 3 PU AM SOC INTERVENTIONAL PAIN PHYSICIANS PI PADUCAH PA 81 LAKEVIEW DR, PADUCAH, KY 42001 USA SN 1533-3159 J9 PAIN PHYSICIAN JI Pain Physician PD JAN PY 2017 VL 20 IS 1 BP E1 EP E12 PG 12 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA EI1VA UT WOS:000392272900001 PM 28072793 ER PT J AU Wiens, MO Kissoon, N Moschovis, P Kabakyenga, J AF Wiens, Matthew O. Kissoon, Niranjan Moschovis, Peter Kabakyenga, Jerome TI Proposal of a New Pediatric Sequential Organ Failure Assessment Score for Possible Validation Reply SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Letter ID DEFINITIONS; SEPSIS C1 [Wiens, Matthew O.; Kissoon, Niranjan] Univ British Columbia, Vancouver, BC, Canada. [Moschovis, Peter] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kabakyenga, Jerome] Mbarara Univ Sci & Technol, Maternal Newborn & Child Hlth Inst, Mbarara, Uganda. RP Wiens, MO (reprint author), Univ British Columbia, Vancouver, BC, Canada. FU NHLBI NIH HHS [F32 HL124951] 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 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2017 VL 18 IS 1 BP 99 EP 100 DI 10.1097/PCC.0000000000001022 PG 3 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA EI1PJ UT WOS:000392249300024 PM 28060167 ER PT J AU Ward, SL Turpin, A Spicer, AC Treadwell, MJ Church, GD Flori, HR AF Ward, Shan L. Turpin, Autumn Spicer, Aaron C. Treadwell, Marsha J. Church, Gwynne D. Flori, Heidi R. TI Long-Term Pulmonary Function and Quality of Life in Children After Acute Respiratory Distress Syndrome: A Feasibility Investigation SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; long-term outcomes; pediatrics; pulmonary function testing; quality of life ID PEDIATRIC INTENSIVE-CARE; ACUTE LUNG INJURY; CRITICAL ILLNESS; RISK-FACTORS; OUTCOMES; UNIT; MULTICENTER; DISABILITY; ARDS; PHYSIOLOGY AB Objectives: To determine the feasibility of pulmonary function and quality of life evaluations in children after acute respiratory distress syndrome. Design: A prospective follow-up feasibility study. Setting: A tertiary PICU. Patients: Children less than 18 years old with acute respiratory distress syndrome admitted between 2000 and 2005. Intervention: Pulmonary function testing and patient and parental quality of life surveys approximately 12-month after acute respiratory distress syndrome. Measurements and Main Results: One hundred eighty patients met acute respiratory distress syndrome criteria; 37 (20%) died, 90 (51%) declined participation, 28 (16%) consented but did not return, and 24 (13%) returned for follow-up visit. Twenty-three patients completed quality of life testing and 17 completed pulmonary functions. Clinical characteristics of those who returned were no different from those who did not except for age (median age, 4.9 vs 1.8 yr). One-third had mild to moderate pulmonary function deficits. Quality of life scores were marginal with general health perception, physical functioning, and behavior being areas of concern. These scores were lower than scores in children with chronic asthma. Parental quality of life assessments report lower scores in single-parent homes but no differences were noted by race or parental employment status. Conclusions: Valuable information may be discerned from acute respiratory distress syndrome patients who return for follow-up evaluation. In this pilot study, up to one-third of children with acute respiratory distress syndrome exhibit pulmonary function deficits and 12-month postillness quality of life scores are lower than in children with chronic asthma. Parental perceptions of postillness quality of life may be negatively impacted by socioeconomic constraints. Long-term follow of children with acute respiratory distress syndrome is feasible and bears further investigation. C1 [Ward, Shan L.; Turpin, Autumn] UCSF, Benioff Childrens Hosp, Dept Pediat, Div Pediat Crit Care, San Francisco, CA 94143 USA. [Ward, Shan L.; Turpin, Autumn] UCSF, Benioff Childrens Hosp, Dept Pediat, Div Pediat Crit Care, Oakland, CA 94609 USA. [Spicer, Aaron C.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Treadwell, Marsha J.] UCSF, Benioff Childrens Hosp, Dept Hematol Oncol, Oakland, CA USA. [Church, Gwynne D.] UCSF, Benioff Childrens Hosp, Dept Pediat, Div Pediat Pulmonol, San Francisco, CA USA. [Flori, Heidi R.] Univ Michigan, CS Mott Childrens Hosp, Div Pediat Crit Care, Ann Arbor, MI 48109 USA. RP Ward, SL (reprint author), UCSF, Benioff Childrens Hosp, Dept Pediat, Div Pediat Crit Care, San Francisco, CA 94143 USA.; Ward, SL (reprint author), UCSF, Benioff Childrens Hosp, Dept Pediat, Div Pediat Crit Care, Oakland, CA 94609 USA. EM shan.ward@ucsf.edu FU National Institutes of Health (NIH) [5T32HD049303-08]; NCRR [RR15543]; CTSI NIH [RR 01271]; National Institutes of Health (NIH); NIH [5T32HD049303-08]; NIH T32 training grant; Vannucci Law Group FX Supported, in part, by National Institutes of Health (NIH) grants 5T32HD049303-08 (to Dr. Ward and Dr. Spicer), NCRR RR15543 (to Dr. Flori), and CTSI NIH RR 01271 (to Dr. Flori).; Dr. Ward received support for article research from the National Institutes of Health (NIH); his institution received funding from NIH grant 5T32HD049303-08. Dr. Spicer received support for article research from the NIH and received support for article research from the NIH; his institution received funding from NIH T32 training grant. Dr. Flori received support for article research from the NIH and received funding from Vannucci Law Group and hospital-based lectureship; her institution received funding from the NIH. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 42 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 1529-7535 EI 1947-3893 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD JAN PY 2017 VL 18 IS 1 BP E48 EP E55 DI 10.1097/PCC.0000000000001014 PG 8 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA EI1PJ UT WOS:000392249300031 PM 28060170 ER PT J AU Christensen, HL Paunescu, TG Matchkov, V Barbuskaite, D Brown, D Damkier, HH Praetorius, J AF Christensen, Henriette L. Paunescu, Teodor G. Matchkov, Vladimir Barbuskaite, Dagne Brown, Dennis Damkier, Helle H. Praetorius, Jeppe TI The V-ATPase is expressed in the choroid plexus and mediates cAMP-induced intracellular pH alterations SO PHYSIOLOGICAL REPORTS LA English DT Article DE BCECF fluorometry; cerebrospinal fluid; fluorescence-activated cell sorting; pH regulation ID VACUOLAR H+-ATPASE; MALE REPRODUCTIVE-TRACT; B2 SUBUNIT ISOFORM; CEREBROSPINAL-FLUID; INTERCALATED CELLS; ADENOSINE-TRIPHOSPHATASES; RESPIRATORY-ACIDOSIS; BUFFERING CAPACITY; PROTON PUMPS; RAT AB The cerebrospinal fluid (CSF) pH influences brain interstitial pH and, therefore, brain function. We hypothesized that the choroid plexus epithelium (CPE) expresses the vacuolar H+-ATPase (V-ATPase) as an acid extrusion mechanism in the luminal membrane to counteract detrimental elevations in CSF pH. The expression of mRNA corresponding to several V-ATPase sub-units was demonstrated by RT-PCR analysis of CPE cells (CPECs) isolated by fluorescence-activated cell sorting. Immunofluorescence and electron microscopy localized the V-ATPase primarily in intracellular vesicles with only a minor fraction in the luminal microvillus area. The vesicles did not translocate to the luminal membrane in two in vivo models of hypocapnia-induced alkalosis. The Na+-independent intracellular pH (pH(i)) recovery from acidification was studied in freshly isolated clusters of CPECs. At extracellular pH (pH(o)) 7.4, the cells failed to display significant concanamycin A-sensitive pH(i) recovery (i.e., V-ATPase activity). The recovery rate in the absence of Na+ amounted to <10% of the pH(i) recovery rate observed in the presence of Na+. Recovery of pH(i) was faster at pH(o) 7.8 and was abolished at pH(o) 7.0. The concanamycin A-sensitive pH(i) recovery was stimulated by cAMP at pH 7.4 in vitro, but intraventricular infusion of the membrane-permeant cAMP analog 8-CPT-cAMP did not result in trafficking of the V-ATPase. In conclusion, we find evidence for the expression of a minor fraction of V-ATPase in the luminal membrane of CPECs. This fraction does not contribute to enhanced acid extrusion at high extracellular pH, but seems to be activated by cAMP in a trafficking-independent manner. C1 [Christensen, Henriette L.; Matchkov, Vladimir; Praetorius, Jeppe] Aarhus Univ, Dept Biomed, Hlth, Wilhelm Meyers Alle 3,Bldg 1233-1234, DK-8000 Aarhus C, Denmark. [Paunescu, Teodor G.; Brown, Dennis] Massachusetts Gen Hosp, Ctr Syst Biol, Program Membrane Biol, Div Nephrol, Boston, MA 02114 USA. [Paunescu, Teodor G.; Brown, Dennis] Harvard Med Sch, Boston, MA USA. [Barbuskaite, Dagne; Damkier, Helle H.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Cellular & Mol Med, Copenhagen, Denmark. RP Praetorius, J (reprint author), Aarhus Univ, Dept Biomed, Hlth, Wilhelm Meyers Alle 3,Bldg 1233-1234, DK-8000 Aarhus C, Denmark. EM jp@ana.au.dk OI Matchkov, Vladimir/0000-0002-3303-1095 FU Graduate School of Health Sciences (Aarhus University); Aarhus University Research Foundation (AU Ideas programme); Lundbeck Foundation; Danish Council for Independent Research - Medical Sciences; Faculty of Health and Medical Sciences; Department of Cellular and Molecular Medicine (University of Copenhagen); Aase og Ejnar Danielsens Fond; Vera and Carl Johan Michaelsens Legat; Laege Sofus Carl Emil Friis og hustru Olga Doris Friis Legat; NIH [DK-42956]; Boston Area Diabetes and Endocrinology Research Center [DK -57521]; Center for the Study of Inflammatory Bowel Disease [DK-43351] FX The Graduate School of Health Sciences (Aarhus University) supported HLC with a PhD stipend. Aarhus University Research Foundation (AU Ideas programme), the Lundbeck Foundation, and the Danish Council for Independent Research - Medical Sciences are thanked for financial support to JP. The Faculty of Health and Medical Sciences and the Department of Cellular and Molecular Medicine (University of Copenhagen) supported DaB with a PhD stipend. Aase og Ejnar Danielsens Fond, Vera and Carl Johan Michaelsens Legat and Laege Sofus Carl Emil Friis og hustru Olga Doris Friis Legat are thanked for financial support to HHD. DeB and TP were supported by NIH grant DK-42956. The Microscopy Core facility of the MGH Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (DK -57521) and the Center for the Study of Inflammatory Bowel Disease (DK-43351). NR 42 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2051-817X J9 PHYSIOL REP JI PHYSIOL. REP. PD JAN PY 2017 VL 5 IS 1 AR e13072 DI 10.14814/phy2.13072 PG 15 WC Physiology SC Physiology GA EI1ND UT WOS:000392243200008 ER PT J AU Bajorek, AJ Slocum, C Goldstein, R Mix, J Niewczyk, P Ryan, CM Hendricks, CT Zafonte, R Schneider, JC AF Bajorek, Alexander J. Slocum, Chloe Goldstein, Richard Mix, Jacqueline Niewczyk, Paulette Ryan, Colleen M. Hendricks, Carla Tierney Zafonte, Ross Schneider, Jeffrey C. TI Impact of Cognition on Burn Inpatient Rehabilitation Outcomes SO PM&R LA English DT Article ID FUNCTIONAL INDEPENDENCE MEASURE; ELDERLY-PATIENTS; FIM INSTRUMENT; INJURY; STROKE; POPULATION; PREDICTORS; ADMISSION AB Background: A significant proportion of burn injury patients are admitted to inpatient rehabilitation facilities (IRFs). There is increasing interest in the use of functional variables, such as cognition, in predicting IRF outcomes. Cognitive impairment is an important cause of disability in the burn injury population, yet its relationship to IRF outcomes has not been studied. Objective: To assess how cognitive function affects rehabilitation outcomes in the burn injury population. Design: Retrospective study. Setting: Inpatient rehabilitation facilities in the United States. Participants: A total of 5347 adults admitted to an IRF with burn injury between 2002 and 2011. Methods or Interventions: Multivariable regression was used to model rehabilitation outcome measures, using the cognitive domain of the Functional Independence Measure (FIM) instrument as the independent variable and controlling for demographic, medical, and facility covariates. Main Outcome Measurements: FIM total gain, readmission to an acute care setting at any time during inpatient rehabilitation, readmission to an acute care setting in the first 3 days of IRF admission, rate of discharge to the community setting, and length of stay efficiency. Results: Cognitive FIM total at admission was a significant predictor of FIM total gain, length of stay efficiency, and acute readmission at 3 days (P < .05). Cognitive FIM total scores did not have an impact on acute care readmission rate or discharge to the community setting. Conclusions: Cognitive status may be an important predictor of rehabilitation outcomes in the burn injury population. Future work is needed to further examine the impact of specific cognitive interventions on rehabilitation outcomes in this population. C1 [Bajorek, Alexander J.; Slocum, Chloe; Goldstein, Richard; Zafonte, Ross; Schneider, Jeffrey C.] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 USA. [Mix, Jacqueline; Niewczyk, Paulette] Uniform Data Syst Med Rehabil, Amherst, NY USA. [Ryan, Colleen M.] Harvard Med Sch, Massachusetts Gen Hosp, Surg Serv, Sumner Redstone Burn Ctr, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children Boston, Boston, MA USA. [Hendricks, Carla Tierney] Spaulding Rehabil Hosp, Dept Speech Language Pathol, Boston, MA USA. [Schneider, Jeffrey C.] Spaulding Rehabil Hosp, 300 First Ave, Charlestown, MA 02129 USA. RP Schneider, JC (reprint author), Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02115 USA.; Schneider, JC (reprint author), Spaulding Rehabil Hosp, 300 First Ave, Charlestown, MA 02129 USA. EM jcschneider@partners.org FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0035] FX The contents of this journal article were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this journal article do not necessarily represent the policy of NIDILRR, ACL, NHS, and you should not assume endorsement by the Federal Government. NR 36 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 EI 1934-1563 J9 PM&R JI PM&R PD JAN PY 2017 VL 9 IS 1 BP 1 EP 7 DI 10.1016/j.pmrj.2016.06.023 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA EI4LC UT WOS:000392464200001 PM 27404335 ER PT J AU He, XM Toth, TL AF He, Xiaoming Toth, Thomas L. TI In vitro culture of ovarian follicles from Peromyscus SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Hanging drop; Microfluidics; Microcapsule; Ovulation; Mechanobiology; Alginate ID LONG-TERM CULTURE; OUTBRED DEER MICE; FERTILITY PRESERVATION; PREANTRAL FOLLICLES; SECONDARY FOLLICLES; LABORATORY MOUSE; GRANULOSA-CELLS; GROWTH; TISSUE; OOCYTES AB The ovarian follicle is the fundamental functional tissue unit of mammalian ovary. Each ovarian follicle contains one single oocyte. Isolation and in vitro culture of ovarian follicles to obtain fertilizable oocytes have been regarded as a promising strategy for women to combat infertility. The follicles from Peromyscus are considered as a better model than that from inbred mice for studying follicle culture. This is because Peromyscus mice are outbred (as with humans) with an increased life span. In this article, we reviewed studies on this subject conducted using Peromyscus follicles. These studies show that the conventional 2D micro-drop and 3D hanging-drop approaches established for in vitro culture of early preantral follicles from inbred mice are not directly applicable for cultivating the follicles from Peromyscus. However, the efficiency could be significantly improved by culturing multiple early preantral follicles in one hanging drop of Peromyscus ovarian cell-conditioned medium. It is further revealed that the mechanical heterogeneity in the extracellular matrix of ovary is crucial for developing early preantral follicles to the antral stage and for the subsequent ovulation to release cumulus-oocyte complex. These findings may provide valuable guidance for furthering the technology of in vitro follicle culture to restore fertility in the clinic. (C) 2016 Elsevier Ltd. All rights reserved. C1 [He, Xiaoming] Ohio State Univ, Dept Biomed Engn, 1080 Carmack Rd, Columbus, OH 43210 USA. [He, Xiaoming] Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. [He, Xiaoming] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Toth, Thomas L.] Massachusetts Gen Hosp, Vincent Dept Obstet & Gynecol, Vincent Reprod Med & IVF, Boston, MA 02114 USA. [Toth, Thomas L.] Harvard Med Sch, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP He, XM (reprint author), Ohio State Univ, Dept Biomed Engn, 1080 Carmack Rd, Columbus, OH 43210 USA. EM he.429@osu.edu FU NIH [R01EB012108] FX This work was partially supported by a grant from NIH (R01EB012108). The authors would like to thank Mr. Pranay Agarwal for preparing the sketches of ovarian follicles at various stages shown in Fig. 1. NR 68 TC 1 Z9 1 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD JAN PY 2017 VL 61 BP 140 EP 149 DI 10.1016/j.semcdb.2016.07.006 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA EH5UG UT WOS:000391837800018 PM 27397871 ER PT J AU Dardis, CM Gidycz, CA AF Dardis, Christina M. Gidycz, Christine A. TI The Frequency and Perceived Impact of Engaging in In-Person and Cyber Unwanted Pursuit after Relationship Break-Up among College Men and Women SO SEX ROLES LA English DT Article DE Relationship termination; Stalking; Unwanted pursuit behaviors; Pursuers; Partner abuse; Technology ID STALKING; CYBERSTALKING; PERSISTENCE; ATTACHMENT; INTRUSION; PARTNERS; BEHAVIOR; VIOLENCE; GENDER AB The present study examined the extent of cyber and in-person unwanted pursuit behaviors (UPBs) reported by undergraduate men and women who pursued former partners and the pursuer's perceptions of the impact of their pursuit on their targets. Among a sample of 1167 undergraduates (66.8 % women; 95.4 % heterosexual) approximately 80 % of men and women reported engaging in UPBs toward former partners, with cyber pursuit endorsed by a subset of those who engaged in in-person UPBs. Despite few gender differences in overall pursuit, men endorsed engaging in a number of specific behaviors more than did women. Most UPBs did receive responses from targets, and pursuers generally did not perceive their behaviors as annoying, threatening, or frightening. Women perceived that targets had more negative responses to UPBs, particularly to threatening or violent pursuit, and men perceived more positive or neutral responses overall. Minor UPBs were associated with relationship reconciliation among women and men, whereas severe UPBs were associated with reconciliation among men only. Results suggest that pursuers likely underestimate the impact of their behaviors on targets and that pursuers' efforts, even severe and threatening, are often reinforced, particularly for men who pursue. Universities must be aware of UPBs and provide prevention programs specific to healthy relationship dissolution and pursuit. Provision of corrective information regarding the impact of severe and threatening pursuit may assist in reducing these behaviors. C1 [Dardis, Christina M.] VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA. [Dardis, Christina M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. [Gidycz, Christine A.] Ohio Univ, Dept Psychol, Athens, OH 45701 USA. RP Dardis, CM (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave 116B-3, Boston, MA 02130 USA.; Dardis, CM (reprint author), Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02130 USA. EM Christina.Dardis@va.gov; gidycz@ohio.edu NR 41 TC 0 Z9 0 U1 12 U2 12 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-0025 EI 1573-2762 J9 SEX ROLES JI Sex Roles PD JAN PY 2017 VL 76 IS 1-2 BP 56 EP 72 DI 10.1007/s11199-016-0667-1 PG 17 WC Psychology, Developmental; Psychology, Social; Women's Studies SC Psychology; Women's Studies GA EH9SP UT WOS:000392111700005 ER PT J AU Rizzo, S Petrella, F Politi, LS Wang, P AF Rizzo, Stefania Petrella, Francesco Politi, Letterio S. Wang, Ping TI Molecular Imaging of Stems Cells: In Vivo Tracking and Clinical Translation SO STEM CELLS INTERNATIONAL LA English DT Editorial Material ID INFUSION; FISTULA C1 [Rizzo, Stefania] European Inst Oncol, Dept Radiol, Milan, Italy. [Petrella, Francesco] European Inst Oncol, Dept Thorac Surg, Milan, Italy. [Politi, Letterio S.] Boston Childrens Hosp, Dept Hematol Oncol, Boston, MA USA. [Politi, Letterio S.] Boston Childrens Hosp, Dept Radiol, Boston, MA USA. [Politi, Letterio S.] Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. [Politi, Letterio S.] Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. [Wang, Ping] Harvard Med Sch, Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Mol Imaging Lab,Dept Radiol, Boston, MA USA. RP Rizzo, S (reprint author), European Inst Oncol, Dept Radiol, Milan, Italy. EM stefania.rizzo@ieo.it OI Wang, Ping/0000-0001-6712-8939; Politi, Letterio Salvatore/0000-0002-6190-6688 NR 11 TC 0 Z9 0 U1 3 U2 3 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 1687-966X EI 1687-9678 J9 STEM CELLS INT JI Stem Cells Int. PY 2017 AR 1783841 DI 10.1155/2017/1783841 PG 2 WC Cell & Tissue Engineering SC Cell Biology GA EI5GL UT WOS:000392522200001 ER PT J AU Khor, B AF Khor, Bernard TI Regulatory T Cells: Central Concepts from Ontogeny to Therapy SO TRANSFUSION MEDICINE REVIEWS LA English DT Review DE Regulatory T cell; Immunotherapy; Cell processing; T-cell differentiation; Antigen specificity; Lineage stability ID LOW-DOSE INTERLEUKIN-2; TRANSCRIPTION FACTOR FOXP3; PLACEBO-CONTROLLED TRIAL; VERSUS-HOST-DISEASE; IN-VIVO; RECEPTOR DIVERSITY; TYPE-1; INFLAMMATION; GENERATION; EXPRESSION AB The balanced differentiation of naive CD4(+) T cells into either pro- or anti-inflammatory fates is a central regulator of immune homeostasis, dysregulation of which can lead to inflammatory disease or cancer. Accordingly, the development of diagnostics and therapeutics to measure and modulate this balance is of great interest. In this review, we focus on the predominant anti-inflammatory subset, regulatory T cells, discussing key concepts including development, function, antigen specificity, and lineage stability. In particular, we highlight how these notions are shaping the evolution of therapeutics, especially in the context of the transfusion medicine specialist, and identify several key areas that urgently need to be addressed. (C) 2016 Elsevier Inc. All rights reserved. C1 [Khor, Bernard] Massachusetts Gen Hosp, Dept Pathol, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Khor, B (reprint author), Massachusetts Gen Hosp, Dept Pathol, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. EM bkhor@partners.org FU National Institutes of Health [K08 DK104021A] FX This work was supported by the National Institutes of Health (grant K08 DK104021A). NR 120 TC 0 Z9 0 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 EI 1532-9496 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2017 VL 31 IS 1 BP 36 EP 44 DI 10.1016/j.tmrv.2016.07.003 PG 9 WC Hematology SC Hematology GA EI4JS UT WOS:000392460500004 PM 27523957 ER PT J AU Fitzgerald, JE Bui, ETH Simon, NM Fenniri, H AF Fitzgerald, Jessica E. Bui, Eric T. H. Simon, Naomi M. Fenniri, Hicham TI Artificial Nose Technology; Status and Prospects in Diagnostics SO TRENDS IN BIOTECHNOLOGY LA English DT Review ID VOLATILE ORGANIC-COMPOUNDS; SPECTROSCOPICALLY ENCODED RESINS; INFLAMMATORY-BOWEL-DISEASE; EXHALED BREATH; OXIDATIVE STRESS; COLORECTAL-CANCER; PERSONALIZED MEDICINE; ELECTRONIC NOSE; SENSOR ARRAY; LUNG-CANCER AB Biomimetic crossreactive sensor arrays have been used to detect and analyze a wide variety of vapor and liquid components in applications such as food science, public health and safety, and diagnostics. As technology has advanced over the past three decades, these systems have become selective, sensitive, and affordable. Currently, the need for noninvasive and accurate devices for early disease diagnosis remains a challenge. This Opinion article provides an overview of the various types of biomimetic crossreactive sensor arrays (also referred to as electronic noses or tongues in the literature), their current use and future directions, and an outlook for future technological development. C1 [Fitzgerald, Jessica E.; Fenniri, Hicham] Northeastern Univ, Dept Bioengn, 360 Huntington Ave, Boston, MA 02115 USA. [Fitzgerald, Jessica E.; Fenniri, Hicham] Northeastern Univ, Dept Chem Engn, 360 Huntington Ave, Boston, MA 02115 USA. [Bui, Eric T. H.; Simon, Naomi M.] Harvard Med Sch, Ctr Anxiety & Traumat Stress Disorders, Massachusetts Gen Hosp, 1 Bowdoin Sq, Boston, MA 02114 USA. [Bui, Eric T. H.; Simon, Naomi M.] Harvard Med Sch, 1 Bowdoin Sq, Boston, MA 02114 USA. RP Fenniri, H (reprint author), Northeastern Univ, Dept Bioengn, 360 Huntington Ave, Boston, MA 02115 USA.; Fenniri, H (reprint author), Northeastern Univ, Dept Chem Engn, 360 Huntington Ave, Boston, MA 02115 USA. EM h.fenniri@neu.edu NR 71 TC 1 Z9 1 U1 13 U2 13 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0167-7799 J9 TRENDS BIOTECHNOL JI Trends Biotechnol. PD JAN PY 2017 VL 35 IS 1 BP 33 EP 42 DI 10.1016/j.tibtech.2016.08.005 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA EI2XY UT WOS:000392354400007 PM 27612567 ER PT J AU Kryvenko, ON Williamson, SR Trpkov, K Gupta, NS Athanazio, D Selig, MK Smith, PT Magi-Galluzzi, C Jorda, M AF Kryvenko, Oleksandr N. Williamson, Sean R. Trpkov, Kiril Gupta, Nilesh S. Athanazio, Daniel Selig, Martin K. Smith, Paul Taylor Magi-Galluzzi, Cristina Jorda, Merce TI Small cell-like glandular proliferation of prostate: a rare lesion not related to small cell prostate cancer SO VIRCHOWS ARCHIV LA English DT Article DE Prostate; Cancer; Intraductal; Small cell-like ID INTRADUCTAL CARCINOMA; INTRAEPITHELIAL NEOPLASIA; INTERNATIONAL-SOCIETY; CONSENSUS-CONFERENCE; GRADING SYSTEM; NEEDLE-BIOPSY; FEATURES AB Small cell-like change (SCLC) is a rare prostate lesion which has been described in only two previous studies (total of eight cases). Its relation to possible neuroendocrine differentiation remained unclear. We evaluated 11 SCLC cases with immunohistochemistry and electron microscopy. SCLC was characterized by crowded hyperchromatic small nuclei with scant cytoplasm, rosette-like structures, finely granular chromatin with indistinct nucleoli, and lack of mitoses, apoptoses, and necroses. In nine cases, SCLC was admixed with high-grade cancer, and in two cases, it represented a separate intraductal process, spatially remote from a low-volume Gleason score 6 (grade group 1) cancer. Only 2/11 SCLC labeled for synaptophysin, chromogranin, and serotonin, although 6/11 were at least focally positive for TTF1. Staining for NKX3.1 and pancytokeratin was typically weak, focal, and markedly reduced compared to the adjacent cancer. SCLC was positive for ERG in 1/8 and for racemase in 6/10 cases, again typically in a focal and weak fashion. There was no immunoreactivity with CD56, p63, or HMWCK. Ki-67 highlighted only rare nuclei (< 1 %). No neuroendocrine granules were demonstrated by electron microscopy in four cases that showed no immunoreactivity for neuroendocrine markers. In summary, SCLC is more frequently found in high-grade prostate cancer, but it may also be encountered as a noninvasive lesion in Gleason score 6 (grade group 1) cancer. Importantly, it does not appear to indicate neuroendocrine differentiation. The low-grade cytology, the lack of mitoses and apoptoses, and the minimal Ki-67 reactivity are findings to support its discrimination from a small cell carcinoma. C1 [Kryvenko, Oleksandr N.; Smith, Paul Taylor; Jorda, Merce] Univ Miami, Dept Pathol & Lab Med, Miller Sch Med, 1400 NW 12th Ave,Room 4076, Miami, FL 33136 USA. [Kryvenko, Oleksandr N.; Jorda, Merce] Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33136 USA. [Kryvenko, Oleksandr N.; Jorda, Merce] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. [Williamson, Sean R.; Gupta, Nilesh S.] Henry Ford Hlth Syst, Dept Pathol & Lab Med, Detroit, MI USA. [Williamson, Sean R.] Henry Ford Hlth Syst, Josephine Ford Canc Inst, Detroit, MI USA. [Trpkov, Kiril; Athanazio, Daniel] Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB, Canada. [Trpkov, Kiril; Athanazio, Daniel] Univ Calgary, Calgary, AB, Canada. [Selig, Martin K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Selig, Martin K.] Harvard Med Sch, Boston, MA USA. [Magi-Galluzzi, Cristina] Cleveland Clin, RT Pathol & Lab Med Inst, Cleveland, OH 44106 USA. [Magi-Galluzzi, Cristina] Case Western Reserve Univ, Lerner Coll Med, Cleveland, OH 44106 USA. RP Kryvenko, ON (reprint author), Univ Miami, Dept Pathol & Lab Med, Miller Sch Med, 1400 NW 12th Ave,Room 4076, Miami, FL 33136 USA.; Kryvenko, ON (reprint author), Univ Miami, Miller Sch Med, Dept Urol, Miami, FL 33136 USA.; Kryvenko, ON (reprint author), Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA. EM o.kryvenko@med.miami.edu NR 24 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0945-6317 EI 1432-2307 J9 VIRCHOWS ARCH JI Virchows Arch. PD JAN PY 2017 VL 470 IS 1 BP 47 EP 54 DI 10.1007/s00428-016-2033-7 PG 8 WC Pathology SC Pathology GA EI2OB UT WOS:000392325900006 PM 27743032 ER PT J AU Cone, EB Pareek, G Ursiny, M Eisner, B AF Cone, Eugene B. Pareek, Gyan Ursiny, Michal Eisner, Brian TI Cost-effectiveness comparison of ureteral calculi treated with ureteroscopic laser lithotripsy versus shockwave lithotripsy SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Ureteral calculi; Shockwave lithotripsy; Ureteroscopy; Cost-effective; Decision analysis ID WAVE LITHOTRIPSY; BUNDLED PAYMENTS; MANAGEMENT; STONES AB To evaluate the cost-effectiveness of shockwave lithotripsy (SWL) versus ureteroscopic lithotripsy (URS) for patients with ureteral stones less than 1.5 cm in diameter. Patient age, stone diameter, stone location, and stone-free status were recorded for patients treated with SWL or URS for ureteral stones under 1.5 cm over a 1 year period. Institutional charges were obtained from in-house billing. A decision analysis model was constructed to compare the cost-effectiveness of SWL and URS using our results and success rates for modeling. Three separate models were created to reflect differing practice patterns. A total of 113 patients were included-51 underwent SWL and 62 underwent URS as primary treatment. Single procedure stone-free rates for SWL and URS were 47.1 and 88.7 %, respectively (p < 0.002). Decision analysis modeling demonstrated cost-effectiveness of SWL when SWL single procedure stone-free rates (SFR) were greater than or equal to 60-64 % or when URS single procedure SFRs were less than or equal to 57-76 %, depending on practice patterns. This retrospective study revealed superior SFR for ureteral stones less than 1.5 cm treated with URS compared to SWL. Our decision analysis model demonstrated that when SFR for SWL is less than 60-64 % or is greater than 57-76 % for URS, SWL is not a cost-effective treatment option. Based on these findings, careful stratification and selection of stone patients may enable surgeons to increase the cost-effectiveness of SWL. C1 [Cone, Eugene B.] Duke Univ, Sch Med, Div Urol, Durham, NC 27708 USA. [Pareek, Gyan] Brown Univ, Warren Alpert Sch Med, Div Urol, Providence, RI 02912 USA. [Ursiny, Michal; Eisner, Brian] Harvard Med Sch, Massachusetts Gen Hosp, Dept Urol, Boston, MA USA. RP Cone, EB (reprint author), Duke Univ, Sch Med, Div Urol, Durham, NC 27708 USA. EM eugene.cone@duke.edu OI Cone, Eugene/0000-0002-0292-7534 NR 16 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 EI 1433-8726 J9 WORLD J UROL JI World J. Urol. PD JAN PY 2017 VL 35 IS 1 BP 161 EP 166 DI 10.1007/s00345-016-1842-2 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA EI2KX UT WOS:000392317200021 PM 27145788 ER PT J AU Yeh, DD AF Yeh, Daniel Dante TI Transhepatic Feeding: Safe and Effective SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Yeh, Daniel Dante] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Yeh, DD (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. EM Dyeh2@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP E23 EP E23 DI 10.1097/SLA.0000000000001812 PG 1 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500002 ER PT J AU Hashimoto, DA Von Hofe, JB McDougall, MA AF Hashimoto, Daniel A. Von Hofe, Johanna B. McDougall, Matthew A. TI The Trainee Perspective: What Can Residency Programs Do to Promote Learner Well-Being? SO ACADEMIC MEDICINE LA English DT Letter C1 [Hashimoto, Daniel A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Von Hofe, Johanna B.] Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. [McDougall, Matthew A.] Univ South Dakota, Sanford Sch Med, Dept Psychiat, Vermillion, SD USA. RP Hashimoto, DA (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM dahashimoto@partners.org NR 1 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 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JAN PY 2017 VL 92 IS 1 BP 12 EP 12 DI 10.1097/ACM.0000000000001504 PG 1 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EH7OF UT WOS:000391961600008 PM 28027097 ER PT J AU Kenison, TC Madu, A Krupat, E Ticona, L Vargas, IM Green, AR AF Kenison, Tiffany C. Madu, Andrea Krupat, Edward Ticona, Luis Vargas, Iris M. Green, Alexander R. TI Through the Veil of Language: Exploring the Hidden Curriculum for the Care of Patients With Limited English Proficiency SO ACADEMIC MEDICINE LA English DT Article ID UNDERGRADUATE MEDICAL-EDUCATION; IMPLICIT BIAS; BARRIERS; INTERPRETERS; SATISFACTION; PHYSICIANS; EMERGENCY; SCHOOLS; EVENTS; IMPACT AB Purpose Patients with limited English proficiency (LEP) experience lower-quality health care and are at higher risk of experiencing adverse events than fluent English speakers. Despite some formal training for health professions students on caring for patients with LEP, the hidden curriculum may have a greater influence on learning. The authors designed this study to characterize the hidden curriculum that medical and nursing students experience regarding the care of patients with LEP. Method In 2014, the authors invited students from one medical school and one nursing school, who had completed an interprofessional pilot curriculum on caring for patients with LEP 6 to 10 months earlier, to participate in semistructured interviews about their clinical training experiences with LEP patients. The authors independently coded the interview transcripts, compared them for agreement, and performed content analysis to identify major themes. Results Thirteen students (7 medical and 6 nursing students) participated. Four major themes emerged: role modeling, systems factors, learning environment, and organizational culture. All 13 students described negative role modeling experiences, and most described role modeling that the authors coded as "indifferent." Students felt that the current system and learning environment did not support or emphasize high-quality care for patients with LEP. Conclusions The hidden curriculum that health professional students experience regarding the care of patients with LEP is influenced by systems limitations and a learning environment and organizational culture that value efficiency over effective communication. Role modeling seems strongly linked to these factors as supervisors struggle with these same challenges. C1 [Madu, Andrea; Green, Alexander R.] Massachusetts Gen Hosp, Dispar Solut Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. [Kenison, Tiffany C.] Mt Sinai Hosp, Dept Med, New York, NY 10029 USA. [Krupat, Edward] Harvard Med Sch, Ctr Evaluat, Boston, MA USA. [Ticona, Luis] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. [Vargas, Iris M.] MIT, MOSTEC MIT Online Sci Technol & Engn Community Pr, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Green, Alexander R.] Harvard Med Sch, Med, Boston, MA USA. RP Green, AR (reprint author), Massachusetts Gen Hosp, Dispar Solut Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM argreen@mgh.harvard.edu FU Arnold P. Gold Foundation FX This project was funded by the Arnold P. Gold Foundation. NR 34 TC 0 Z9 0 U1 8 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-2446 EI 1938-808X J9 ACAD MED JI Acad. Med. PD JAN PY 2017 VL 92 IS 1 BP 92 EP 100 DI 10.1097/ACM.0000000000001211 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA EH7OF UT WOS:000391961600028 PM 27166864 ER PT J AU Zash, RM Souda, S Leidner, J Binda, K Hick, C Powis, K Makhema, J Mmalane, M Essex, M Lockman, S Shapiro, RL AF Zash, Rebecca Marie Souda, Sajini Leidner, Jean Binda, Kelebogile Hick, Chazha Powis, Kathleen Makhema, Joseph Mmalane, Mompati Essex, Max Lockman, Shahin Shapiro, Roger L. TI High Proportion of Deaths Attributable to HIV Among Postpartum Women in Botswana Despite Widespread Uptake of Antiretroviral Therapy SO AIDS PATIENT CARE AND STDS LA English DT Article DE HIV; prenatal; antiretroviral ID SUB-SAHARAN AFRICA; INFECTED WOMEN; PREGNANT-WOMEN; LOW-INCOME; FOLLOW-UP; MORTALITY; CARE AB Mortality in the postpartum period may be impacted by antiretroviral therapy (ART) received in pregnancy, and whether ART is continued in the postpartum period. HIV-infected and HIV-uninfected mothers were enrolled within 48 h of delivery at five public hospital maternity wards throughout Botswana and followed for 24 months. Maternal deaths were reported by one of the approved contacts given by the mother at enrollment. Detailed information on the cause of death was not available. Risk factors for 24-month mortality were assessed using Cox proportional hazard models. From February 2012 to March 2013, 3000 mothers (1499 HIV infected and 1501 HIV uninfected) were enrolled, and 2985 (99.5%) were followed to 24 months or death, or until the death of their child. There were 26 total maternal deaths through 24 months postpartum [ 439 per 100,000 person-years (p-y)], 22 among HIV-infected women (758 per 100,000 p-y) and 4 among HIV-uninfected women (132 per 100,000 p-y). Maternal HIV-infection (aHR 5.0, 95% CI 1.6-15.2) and infant birth injury (aHR 3.8, 95% CI 1.3-11.4) were independent risk factors for maternal death. Universal ART in pregnancy became the standard-of-care after June 2012, and 978 (65%) women received ART in pregnancy; by 24 months postpartum or end of follow-up, 1148 (79%) had started ART overall. There was no significant difference in 24-month mortality among HIV-infected women who took ART in pregnancy and continued throughout the follow-up period compared with HIV-infected women who took ART or zidovudine in pregnancy and stopped postpartum (aHR 0.6, 95% CI 0.2-1.7). Despite high uptake of ART in pregnancy and postpartum, women with HIV infection in Botswana are five times more likely to die than HIV-uninfected women in the 24 months postpartum. C1 [Zash, Rebecca Marie; Shapiro, Roger L.] Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA. [Zash, Rebecca Marie; Powis, Kathleen; Essex, Max; Lockman, Shahin; Shapiro, Roger L.] TH Chan Harvard Sch Publ Hlth, Immunol & Infect Dis, Boston, MA USA. [Zash, Rebecca Marie; Binda, Kelebogile; Powis, Kathleen; Makhema, Joseph; Mmalane, Mompati; Essex, Max; Lockman, Shahin; Shapiro, Roger L.] Botswana Harvard AIDS Inst Partnership, Gaborone, Botswana. [Souda, Sajini] Univ Botswana, Fac Med, Dept Pathol, Gaborone, Botswana. [Leidner, Jean] Goodtables Data Consulting, Norman, OK USA. [Hick, Chazha] Care Qual Commiss, London, England. [Powis, Kathleen] Massachusetts Gen Hosp, Dept Med & Pediat, Boston, MA 02114 USA. [Lockman, Shahin] Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. RP Zash, RM (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, 110 Francis St,Suite GB, Boston, MA 02215 USA. EM rzash@bidmc.harvard.edu FU Center for Disease Control and Prevention [U2GPS000941]; NIH/NIAID [T32 5T32AI007433-21]; NIH/NICHD [K23 HD070774-01A1] FX Funding for this project came from the Center for Disease Control and Prevention (Grant No. U2GPS000941). In addition, R.M.Z. received support from NIH/NIAID T32 5T32AI007433-21 and K.P. received support from NIH/NICHD K23 HD070774-01A1. NR 22 TC 0 Z9 0 U1 2 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 EI 1557-7449 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD JAN PY 2017 VL 31 IS 1 BP 14 EP 19 DI 10.1089/apc.2016.0154 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA EH0ZV UT WOS:000391494000002 PM 28051898 ER PT J AU Feinstein, MJ Kim, JH Bibangambah, P Sentongo, R Martin, JN Tsai, AC Bangsberg, DR Hemphill, L Triant, VA Boum, Y Hunt, PW Okello, S Siedner, MJ AF Feinstein, Matthew J. Kim, June-Ho Bibangambah, Prossy Sentongo, Ruth Martin, Jeffrey N. Tsai, Alexander C. Bangsberg, David R. Hemphill, Linda Triant, Virginia A. Boum, Yap, II Hunt, Peter W. Okello, Samson Siedner, Mark J. TI Ideal Cardiovascular Health and Carotid Atherosclerosis in a Mixed Cohort of HIV-Infected and Uninfected Ugandans SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article DE human immunodeficiency virus; cardiovascular disease; ideal cardiovascular health; epidemiology; primary prevention; risk factors ID INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; ACTIVE ANTIRETROVIRAL THERAPY; ACUTE MYOCARDIAL-INFARCTION; RURAL UGANDA; RISK-FACTORS; LIFE EXPECTANCY; UNITED-STATES; ALL-CAUSE; MORTALITY AB Preventable cardiovascular disease (CVD) risk factors are responsible for the majority of CVD-related deaths, and are increasingly recognized as a cause of morbidity and mortality for HIV-infected persons taking antiretroviral therapy (ART). Simplified tools such as the American Heart Association's ideal cardiovascular health (iCVH) construct may identify and prognosticate CVD risk in resource-limited settings. No studies have evaluated iCVH metrics in sub-Saharan Africa or among HIV-infected adults. Thus, the central aim of this study was to compare levels of iCVH metrics and their correlations with carotid atherosclerosis for HIV-infected adults versus uninfected controls in a well-phenotyped Ugandan cohort. We analyzed the prevalence of iCVH metrics in a mixed cohort of HIV-infected persons on stable ART and uninfected, population-based comparators in Mbarara, Uganda. We also assessed the validity of iCVH by correlating iCVH values with common carotid intima media thickness (CCIMT). HIV-infected persons had a mean of 4.9 (SD 1.1) iCVH metrics at ideal levels versus 4.3 (SD 1.2) for uninfected controls (p=.002). This difference was largely driven by differences in blood pressure, blood glucose, and diet. In multivariable-adjusted linear regression models, each additional iCVH metric at an ideal level was associated with a significant 0.024 mm decrease in CCIMT (p<.001). HIV-infected persons on ART in rural Uganda had more iCVH metrics at ideal levels than uninfected persons. The difference appeared driven by factors that are putatively influenced by access to routine medical care. Composite scores of iCVH metrics were associated with subclinical atherosclerosis and more predictive of atherosclerosis for uninfected persons. C1 [Feinstein, Matthew J.] Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, 680 North Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. [Kim, June-Ho] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Bibangambah, Prossy; Sentongo, Ruth; Bangsberg, David R.; Okello, Samson] Mbarara Univ Sci & Technol, Fac Med, Mbarara, Uganda. [Martin, Jeffrey N.; Hunt, Peter W.] Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA USA. [Tsai, Alexander C.; Bangsberg, David R.; Siedner, Mark J.] Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02114 USA. [Bangsberg, David R.; Triant, Virginia A.; Siedner, Mark J.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Bangsberg, David R.; Hemphill, Linda; Triant, Virginia A.; Siedner, Mark J.] Harvard Med Sch, Boston, MA USA. [Hemphill, Linda] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Boum, Yap, II] Epictr Res Base, Mbarara, Uganda. RP Feinstein, MJ (reprint author), Northwestern Univ, Dept Med, Div Cardiol, Feinberg Sch Med, 680 North Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA. EM matthewjfeinstein@northwestern.edu FU National Institutes of Health [P30 AI027763, R01 MH054907, R21 HL 124712] FX The authors wish to thank all study participants and personnel from the UGANDAC study. This work was supported by several grants from the National Institutes of Health (P30 AI027763, R01 MH054907, and R21 HL 124712). NR 54 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 EI 1931-8405 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2017 VL 33 IS 1 BP 49 EP 56 DI 10.1089/aid.2016.0104 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA EH0QB UT WOS:000391467700009 PM 27476547 ER PT J AU Lanctot, KL Aguera-Ortiz, L Brodaty, H Francis, PT Geda, YE Ismail, Z Marshall, GA Mortby, ME Onyike, CU Padala, PR Politis, AM Rosenberg, PB Siegel, E Sultzer, DL Abraham, EH AF Lanctot, Krista L. Aguera-Ortiz, Luis Brodaty, Henry Francis, Paul T. Geda, Yonas E. Ismail, Zahinoor Marshall, Gad A. Mortby, Moyra E. Onyike, Chiadi U. Padala, Prasad R. Politis, Antonios M. Rosenberg, Paul B. Siegel, Emma Sultzer, David L. Abraham, Eleenor H. TI Apathy associated with neurocognitive disorders: Recent progress and future directions SO ALZHEIMERS & DEMENTIA LA English DT Review DE Apathy; Alzheimer's disease (AD); Mild behavioral impairment (MBI); neuropsychiatric symptoms (NPS); Neurocognitive disorders (NCD) ID MILD COGNITIVE IMPAIRMENT; MODERATE ALZHEIMERS-DISEASE; TRANSCRANIAL MAGNETIC STIMULATION; NURSING-HOME RESIDENTS; PROVISIONAL DIAGNOSTIC-CRITERIA; APOLIPOPROTEIN-E GENOTYPE; PLACEBO-CONTROLLED TRIAL; MALE 5XFAD MICE; NEUROPSYCHIATRIC-SYMPTOMS; PARKINSONS-DISEASE AB Introduction: Apathy is common in neurocognitive disorders (NCDs) such as Alzheimer's disease and mild cognitive impairment. Although the definition of apathy is inconsistent in the literature, apathy is primarily defined as a loss of motivation and decreased interest in daily activities. Methods: The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Neuropsychiatric Syndromes Professional Interest Area (NPS-PIA) Apathy workgroup reviewed the latest research regarding apathy in NCDs. Results: Progress has recently been made in three areas relevant to apathy: (I) phenomenology, including the use of diagnostic criteria and novel instruments for measurement, (2) neurobiology, including neuroimaging, neuropathological and biomarker correlates, and (3) interventions, including pharmacologic, nonpharmacologic, and noninvasive neuromodulatory approaches. Discussion: Recent progress confirms that apathy has a significant impact on those with major NCD and those with mild NCDs. As such, it is an important target for research and intervention. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved. C1 [Lanctot, Krista L.; Abraham, Eleenor H.] Sunnybrook Res Inst, Hurvitz Brain Sci Program, Toronto, ON, Canada. [Lanctot, Krista L.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada. [Lanctot, Krista L.] Univ Toronto, Dept Pharmacol Toxicol, Toronto, ON, Canada. [Aguera-Ortiz, Luis] CIBERSAM, Ctr Invest Biomed Red Salud Mental, Madrid, Spain. [Aguera-Ortiz, Luis] Univ Hosp 12 Octubre, Dept Psychiat, Madrid, Spain. [Aguera-Ortiz, Luis] Univ Hosp 12 Octubre, Res Inst Hosp, Madrid, Spain. [Brodaty, Henry; Siegel, Emma] Univ New South Wales, Ctr Hlth Brain Ageing, Sydney, NSW, Australia. [Brodaty, Henry; Siegel, Emma] Univ New South Wales, Dementia Collaborat Res, Sydney, NSW, Australia. [Francis, Paul T.] Kings Coll London, Wolfson Ctr Age Related Dis, London, England. [Geda, Yonas E.] Mayo Clin, Dept Psychiat, Scottsdale, AZ USA. [Geda, Yonas E.] Mayo Clin, Dept Neurol, Scottsdale, AZ USA. [Geda, Yonas E.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA. [Ismail, Zahinoor] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Dept Psychiat, Ron & Rene Ward Ctr Hlth Brain Aging Res,Hotchkis, Calgary, AB, Canada. [Ismail, Zahinoor] Univ Calgary, Mathison Ctr Mental Hlth Res & Educ, Dept Clin Neumsci, Ron & Rene Ward Ctr Hlth Brain Aging Res,Hotchkis, Calgary, AB, Canada. [Marshall, Gad A.] Harvard Med Sch, Massachusetts Gen Hosp, Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment,Dept Neurol, Boston, MA USA. [Mortby, Moyra E.] Australian Natl Univ, Res Sch Populat Hlth, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia. [Mortby, Moyra E.] Australian Natl Univ, NHMRC Natl Inst Dementia Res, Ctr Res Ageing Hlth & Wellbeing, Canberra, ACT, Australia. [Onyike, Chiadi U.] Johns Hopkins Univ, Sch Med, Johns Hopkins Sch Med, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD USA. [Padala, Prasad R.] Cent Arkansas Vet Healthcare Syst, Geriatr Res Educ & Clin Ctr, Little Rock, AR USA. [Padala, Prasad R.] Univ Arkansas Med Sci, Dept Psychiat, North Little Rock, AR USA. [Politis, Antonios M.] Natl & Kapodistrian Univ, Athens Med Sch, Eginit Hosp, Dept Psychiat 1, Athens, Greece. [Rosenberg, Paul B.] Johns Hopkins Sch Med, Johns Hopkins Bayview Med Ctr, Div Geriatr Psychiat & Neuropsychiat, Baltimore, MD USA. [Sultzer, David L.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Sultzer, David L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Lanctot, KL (reprint author), Sunnybrook Res Inst, Hurvitz Brain Sci Program, Toronto, ON, Canada. EM krista.lanctot@sunnybrook.ca OI Lanctot, Krista L./0000-0001-7024-6637; Mortby, Moyra/0000-0002-9568-6628 FU National Institute of Aging for "Apathy in Alzheimer's Disease Methylphenidate Trial II (ADMET II)" [R01AG046543]; Alzheimer Society Calgary, via the Hotch-kiss Brain Institute; Australian National Health and Medical Research Council (NHMRC) Australian Research Council (ARC) Dementia Research Development Fellowship [1102028]; Alzheimer's Australia Dementia Research Foundation (AADRF) grant [13F00029]; NIH/NIA [P50AG05146, U19AG033655]; NIH/NINDS [1U54NS092089-01]; Tau Therapeutics [TRx 237-007]; Jane Tanger Black Fund for Young Onset Dementia Research; Robert and Nancy Hall family; Department of Veterans Affairs (Merit Review Award); South Central VA Health Care Network Research Grant Program from the National Institute of Aging, Department of Veterans Affairs FX K.L.L. and P.B.R. are funded by the National Institute of Aging for "Apathy in Alzheimer's Disease Methylphenidate Trial II (ADMET II)" (award number R01AG046543). Z.I. is funded by the Alzheimer Society Calgary, via the Hotch-kiss Brain Institute. M.E.M. is funded by the Australian National Health and Medical Research Council (NHMRC) Australian Research Council (ARC) Dementia Research Development Fellowship (grant #1102028) and by an Alzheimer's Australia Dementia Research Foundation (AADRF) grant (#13F00029). C.U.O. is supported by NIH/NIA grants P50AG05146 and U19AG033655, NIH/NINDS grant 1U54NS092089-01, TRx 237-007 from Tau Therapeutics, the Jane Tanger Black Fund for Young Onset Dementia Research, and the Robert and Nancy Hall family. This work was supported in part by the Department of Veterans Affairs (Merit Review Award, Dr. Sultzer). P.R.P. is funded by South Central VA Health Care Network Research Grant Program from the National Institute of Aging, Department of Veterans Affairs. NR 162 TC 0 Z9 0 U1 8 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 EI 1552-5279 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD JAN PY 2017 VL 13 IS 1 BP 84 EP 100 DI 10.1016/j.jalz.2016.05.008 PG 17 WC Clinical Neurology SC Neurosciences & Neurology GA EH6VP UT WOS:000391912300009 PM 27362291 ER PT J AU Halbert, CH Gattoni-Celli, S Savage, S Prasad, SM Kittles, R Briggs, V Delmoor, E Rice, LJ Jefferson, M Johnson, JC AF Halbert, Chanita Hughes Gattoni-Celli, Sebastiano Savage, Stephen Prasad, Sandip M. Kittles, Rick Briggs, Vanessa Delmoor, Ernestine Rice, LaShanta J. Jefferson, Melanie Johnson, Jerry C. TI Ever and Annual Use of Prostate Cancer Screening in African American Men SO AMERICAN JOURNAL OF MENS HEALTH LA English DT Article DE PSA testing; health care utilization; health education ID HEALTH-CARE; DECISION-MAKING; COLLECTIVE EFFICACY; SOCIETY GUIDELINES; RACIAL-DIFFERENCES; TRIAL; KNOWLEDGE; WOMEN; RATES; COMPREHENSION AB Since prostate cancer continues to disproportionately affect African American men in terms of incidence, morbidity, and mortality, prostate-specific antigen (PSA) screening plays an important role in early detection, especially when men engage in informed decision making to accept or decline this test. The authors evaluated utilization of PSA testing among African American men based on factors that are important components of making informed decisions. Utilization of PSA testing was evaluated based on whether men had ever had PSA testing and PSA testing during the past year in a community-based sample of African American men ages 50 to 75 (n = 132). Overall, 64% of men (n = 85) reported that they had ever had a PSA test; the mean (SD) age for first use of PSA testing was 47.7 (SD = 7.4). The likelihood of ever having a PSA test increased significantly with physician communication (odds ratio [OR] = 14.2; 95% confidence interval [CI] = 4.20, 48.10; p = .0001) and with having an annual household income that was greater than $20,000 (OR = 9.80; 95% CI = 3.15, 30.51; p = 0001). The odds of ever having a PSA test were also decreased with each unit increase in future temporal orientation (OR = 0.66; 95% CI = 0.47, 0.93; p = .02). Of the men who had ever had PSA testing, 57% were screened during the past year. Only health insurance status had a significant independent association with having annual PSA testing (OR = 5.10; 95% CI = 1.67, 15.60; p = .004). Different factors were associated significantly with ever having PSA testing and annual testing among African American men. African American men may not be making an informed decision about prostate cancer screening. C1 [Halbert, Chanita Hughes; Gattoni-Celli, Sebastiano; Savage, Stephen; Prasad, Sandip M.; Rice, LaShanta J.; Jefferson, Melanie] Med Univ South Carolina, 68 President St,Suite BE103, Charleston, SC 29425 USA. [Halbert, Chanita Hughes; Gattoni-Celli, Sebastiano; Savage, Stephen; Prasad, Sandip M.] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. [Kittles, Rick] Univ Arizona, Tucson, AZ USA. [Briggs, Vanessa] Hlth Promot Council Southeastern Penn, Philadelphia, PA USA. [Delmoor, Ernestine] Natl Black Leadership Initiat Canc, Philadelphia Chapter, Philadelphia, PA USA. [Johnson, Jerry C.] Univ Penn, Philadelphia, PA 19104 USA. RP Halbert, CH (reprint author), Med Univ South Carolina, 68 President St,Suite BE103, Charleston, SC 29425 USA. EM hughesha@musc.edu FU National Cancer Institute [R01CA100254]; National Institute on Minority Health and Health Disparities [R24MD001594]; Veterans Health Administration; Charleston Health Equity and Rural Outreach Innovation Center; [CIN 13-410] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by Grant No. R01CA100254 from the National Cancer Institute and Grant No. R24MD001594 from the National Institute on Minority Health and Health Disparities, and CIN 13-410, Veterans Health Administration, Charleston Health Equity and Rural Outreach Innovation Center. NR 44 TC 1 Z9 1 U1 4 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1557-9883 EI 1557-9891 J9 AM J MENS HEALTH JI Am. J. Mens Health PD JAN PY 2017 VL 11 IS 1 SI SI BP 99 EP 107 DI 10.1177/1557988315596225 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EH1QO UT WOS:000391542300011 ER PT J AU Raju, SV Lin, VY Liu, L McNicholas, CM Karki, S Sloane, PA Tang, LP Jackson, PL Wang, W Wilson, L Macon, KJ Mazur, M Kappes, JC DeLucas, LJ Barnes, S Kirk, K Tearney, GJ Rowe, SM AF Raju, S. Vamsee Lin, Vivian Y. Liu, Limbo McNicholas, Carmel M. Karki, Suman Sloane, Peter A. Tang, Liping Jackson, Patricia L. Wang, Wei Wilson, Landon Macon, Kevin J. Mazur, Marina Kappes, John C. DeLucas, Lawrence J. Barnes, Stephen Kirk, Kevin Tearney, Guillermo J. Rowe, Steven M. TI The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE cystic fibrosis transmembrane conductance regulator potentiator; ivacaftor; cigarette smoke; mucociliary transport; optical coherence tomography ID BRONCHIAL EPITHELIAL-CELLS; FUNCTION IN-VITRO; CFTR; AIRWAY; EXPRESSION; SECRETION; DYSFUNCTION; ACTIVATION; MUTATIONS; RESIDUES AB Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-mu m resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis. C1 [Raju, S. Vamsee; Lin, Vivian Y.; Karki, Suman; Sloane, Peter A.; Tang, Liping; Jackson, Patricia L.; Kappes, John C.; Rowe, Steven M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [Raju, S. Vamsee; McNicholas, Carmel M.; Tang, Liping; Jackson, Patricia L.; Wang, Wei; Mazur, Marina; Kappes, John C.; DeLucas, Lawrence J.; Kirk, Kevin; Rowe, Steven M.] Univ Alabama Birmingham, Cyst Fibrosis Res Ctr, Birmingham, AL USA. [McNicholas, Carmel M.; Wang, Wei; Kirk, Kevin; Rowe, Steven M.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA. [Wilson, Landon; Barnes, Stephen] Univ Alabama Birmingham, Targeted Metabol & Prote Lab, Birmingham, AL USA. [Macon, Kevin J.; DeLucas, Lawrence J.] Univ Alabama Birmingham, Dept Optometry, Birmingham, AL USA. [Barnes, Stephen] Univ Alabama Birmingham, Dept Pharmacol, Birmingham, AL 35294 USA. [Rowe, Steven M.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA. [Liu, Limbo; Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Rowe, SM (reprint author), 1918 Univ Blvd,MCLM 706, Birmingham, AL 35294 USA. EM smrowe@uab.edu FU National Institutes of Health (NIH) [1R01 HL105487, P30 DK072482]; Cystic Fibrosis Foundation [R464-CF, CLANCY09Y0]; American Lung Association [RG-305752]; Flight Attendants Medical Research Association [YFA130008]; NIH Shared Instrumentation grant [S10 RR027822] FX This work was supported by National Institutes of Health (NIH) grants 1R01 HL105487 and P30 DK072482 (S.M.R.), and Cystic Fibrosis Foundation grants R464-CF and CLANCY09Y0 (S.M.R.). S.V.R. is supported by American Lung Association grant RG-305752 and Flight Attendants Medical Research Association grant YFA130008. The mass spectrometer was purchased with funds from NIH Shared Instrumentation grant S10 RR027822 (S.B.). NR 38 TC 0 Z9 0 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1044-1549 EI 1535-4989 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 2017 VL 56 IS 1 BP 99 EP 108 DI 10.1165/rcmb.2016-0226OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA EI0AG UT WOS:000392133000011 PM 27585394 ER PT J AU O'Neill, AC Tirumani, H Do, WS Keraliya, AR Hornick, JL Shinagare, AB Ramaiya, NH AF O'Neill, Ailbhe C. Tirumani, Harsha Do, Woo S. Keraliya, Abhishek R. Hornick, Jason L. Shinagare, Atul B. Ramaiya, Nikhil H. TI Metastatic Patterns of Solitary Fibrous Tumors: A Single-Institution Experience SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE extrathoracic; metastases; solitary fibrous tumor; thoracic ID SOFT-TISSUE; FEATURES; HEMANGIOPERICYTOMA; CLASSIFICATION; RECURRENCE; RESECTION; PLEURA; BONE; CT AB OBJECTIVE. The objective of our study was to evaluate the metastatic patterns and imaging features of solitary fibrous tumors (SFTs). MATERIALS AND METHODS. This retrospective study included 139 patients with pathologically proven SFT, 49 of whom developed metastases. Electronic medical records and all available images were reviewed to record the pattern and imaging appearances of metastatic disease, and comparisons of thoracic SFTs and extrathoracic SFTs were also performed. Associations of metastatic spread were studied using univariate and multivariate Cox regression analyses. RESULTS. A total of 49 (35%) patients developed metastases at a median of 124 months (interquartile range [IQR], 66-195 months) after SFT diagnosis; 11 patients (8%) had metastases at presentation. Of these 49 patients, 40 patients died at a mean of 183 months after diagnosis. The associations with metastatic disease on univariate analysis were tumor size >= 10 cm (p = 0.01) and malignant pathology or mitotic count >= 4 per 10 high-power fields (HPF) (p < 0.001). Malignant pathology and a mitotic count of = 4 per 10 HPF were also associated with metastatic disease on multivariate analysis (p = 0.01; hazard ratio, 0.22; 95% CI, 0.05-0.73). The most common sites of metastasis were the lungs (30/49, 61%) followed by the pleura (24/49, 49%) and then the liver (20/49, 41%), bones (20/49, 41%), and peritoneum (20/49, 41%). A significantly higher proportion of patients with extrathoracic SFT had metastatic disease (37/139, 27%) compared with those with thoracic SFT (12/139, 9%) (p = 0.003). The overall metastasis-free survival was a median of 117 months (IQR, 33-169 months) in patients with extrathoracic SFT and a median of 120 months (IQR, 82-169 months) in patients with thoracic SFT (p = 0.01). CONCLUSION. A mitotic count of >= 4 per 10 HPF or malignant pathology was significantly associated with metastatic disease on both univariate and multivariate analyses. The sites of metastatic disease differed depending on the site of the primary SFT but were most commonly the lung and pleura. Patients with extrathoracic SFT were statistically more likely to develop metastatic disease than those with thoracic SFT. C1 [O'Neill, Ailbhe C.; Tirumani, Harsha; Do, Woo S.; Keraliya, Abhishek R.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. [Hornick, Jason L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP O'Neill, AC (reprint author), Dana Farber Canc Inst, Dept Imaging, 450 Brookline Ave, Boston, MA 02115 USA. EM ailbheconeill@yahoo.co.uk FU Radiological Society of North America FX A.B. Shinagare received a research grant from the Radiological Society of North America. NR 23 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 208 IS 1 BP 2 EP 9 DI 10.2214/AJR.16.16662 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH6CP UT WOS:000391860500011 PM 27762594 ER PT J AU Kulkarni, NM Pinho, DF Narayanan, S Kambadakone, AR Abramson, JS Sahani, DV AF Kulkarni, Naveen M. Pinho, Daniella F. Narayanan, Srikala Kambadakone, Avinash R. Abramson, Jeremy S. Sahani, Dushyant V. TI Imaging for Oncologic Response Assessment in Lymphoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE DWI; International Working Group criteria; Lugano criteria; lymphoma; PET ID POSITRON-EMISSION-TOMOGRAPHY; DIFFUSION-WEIGHTED MRI; B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; CONTRAST-ENHANCED CT; FDG-PET; INTERNATIONAL WORKSHOP; COMPUTED-TOMOGRAPHY; MONITORING RESPONSE AB OBJECTIVE. The purpose of this article is to examine the role of different imaging bio-markers, focusing in particular on the use of updated CT and PET response criteria for the assessment of oncologic treatment effectiveness in patients with lymphoma but also discussing other potential functional imaging methods and their limitations. CONCLUSION. Lymph nodes are commonly involved by metastatic solid tumors as well as by lymphoma. Evolving changes in cancer therapy for lymphoma and metastases have led to improved clinical outcomes. Imaging is a recognized surrogate endpoint that uses established criteria based on changes in tumor bulk to monitor the effects of treatment. With the introduction of targeted therapies and novel antiangiogenic drugs, the oncologic expectations from imaging assessment are changing to move beyond simple morphologic methods. Molecular and functional imaging methods (e.g., PET, perfusion, DWI, and dual-energy CT) are therefore being investigated as imaging biomarkers of response and prognosis. The role of these advanced imaging biomarkers extends beyond measuring tumor burden and therefore might offer insight into early predictors of therapeutic response. Despite the potential benefits of these exciting imaging biomarkers, several challenges currently exist. C1 [Kulkarni, Naveen M.] Med Coll Wisconsin, Div Abdominal Imaging, Milwaukee, WI 53226 USA. [Pinho, Daniella F.] Univ Texas Southwestern Med Ctr Dallas, Dallas, TX 75390 USA. [Narayanan, Srikala] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Kambadakone, Avinash R.; Sahani, Dushyant V.] Massachusetts Gen Hosp, Harvard Med Sch, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. [Abramson, Jeremy S.] Massachusetts Gen Hosp, Harvard Med Sch, Ctr Canc, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org FU GE Healthcare FX D.V. Sahani has received research grant support from GE Healthcare, but none of the support is related to this study. NR 72 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2017 VL 208 IS 1 BP 18 EP 31 DI 10.2214/AJR.16.16180 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH6CP UT WOS:000391860500013 PM 27786547 ER PT J AU Chapman, MN Fujita, A Sung, EK Siegel, C Nadgir, RN Saito, N Sakai, O AF Chapman, Margaret N. Fujita, Akifumi Sung, Edward K. Siegel, Cory Nadgir, Rohini N. Saito, Naoko Sakai, Osamu TI Sarcoidosis in the Head and Neck: An Illustrative Review of Clinical Presentations and Imaging Findings SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE CT; head and neck; MRI; sarcoidosis ID OF-THE-LITERATURE; ORAL SARCOIDOSIS; SINONASAL SARCOIDOSIS; SJOGRENS-SYNDROME; GRAVES-DISEASE; THYROID-CANCER; FDG-PET; NEUROSARCOIDOSIS; MANIFESTATIONS; MR AB OBJECTIVE. Sarcoidosis is referred to as a great imitator because of its propensity to radiologically mimic a variety of pathologic entities. Symptomatic neurosarcoidosis is present in approximately 5% of patients with sarcoidosis, and it is found histopathologically in approximately 25% of asymptomatic patients. CONCLUSION. An understanding of the multifaceted imaging manifestations of head and neck sarcoidosis will aid early recognition of the diagnosis, with a goal for earlier initiation of therapy and prevention of irreversible sequelae of the disease. C1 [Chapman, Margaret N.; Fujita, Akifumi; Sung, Edward K.; Siegel, Cory; Nadgir, Rohini N.; Sakai, Osamu] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiol, 820 Harrison Ave,FGH Bldg,3rd Fl, Boston, MA 02118 USA. [Chapman, Margaret N.; Siegel, Cory] Boston VA Healthcare Syst, Dept Radiol, West Roxbury, MA USA. [Fujita, Akifumi] Jichi Med Univ, Sch Med, Dept Radiol, Shimotsuke, Tochigi, Japan. [Sung, Edward K.; Siegel, Cory] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. [Nadgir, Rohini N.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [Saito, Naoko] Saitama Med Univ, Saitama Int Med Ctr, Dept Radiol, Moroyama, Saitama, Japan. [Sakai, Osamu] Boston Univ, Sch Med, Boston Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA. [Sakai, Osamu] Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Sakai, O (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Radiol, 820 Harrison Ave,FGH Bldg,3rd Fl, Boston, MA 02118 USA.; Sakai, O (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Otolaryngol Head & Neck Surg, Boston, MA 02215 USA.; Sakai, O (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. EM osamu.sakai@bmc.org NR 68 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 208 IS 1 BP 66 EP 75 DI 10.2214/AJR.16.16058 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH6CP UT WOS:000391860500018 PM 27657552 ER PT J AU Chen, Y Gilman, MD Humphrey, KL Salazar, GM Sharma, A Muniappan, A Shepard, JAO Wu, CC AF Chen, Ying Gilman, Matthew D. Humphrey, Kathryn L. Salazar, Gloria M. Sharma, Amita Muniappan, Ashok Shepard, Jo-Anne O. Wu, Carol C. TI Pulmonary Artery Pseudoaneurysms: Clinical Features and CT FindingsE SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE hemoptysis; pulmonary artery; pulmonary artery pseudoaneurysm ID MASSIVE HEMOPTYSIS; LUNG; ANEURYSMS; MANAGEMENT; EMBOLIZATION; ANGIOGRAPHY; CARCINOMA; SECONDARY; RUPTURE AB OBJECTIVE. The purpose of this study was to analyze the clinical and CT features of pulmonary artery pseudoaneurysms (PAPs). MATERIALS AND METHODS. A database search of chest CT examinations performed from January 1, 2000 to December 31, 2014 identified 24 patients with findings consistent with PAPs. A CT finding consistent with a PAP was defined as a focal saccular outpouching of a pulmonary artery. Medical records were reviewed to determine clinical presentations, treatments, and outcomes. CT scans were reviewed by two board-certified fellowship-trained chest radiologists. RESULTS. A total of 35 PAPs were identified in 24 patients. Hemoptysis and shortness of breath were the most common presenting symptoms. The most commonly identified causes of PAPs were infection (33%), neoplasms (13%), and trauma (17%). Of the 35 PAPs, 29 (83%) were located in segmental or subsegmental pulmonary arteries. A solitary PAP was identified in 20 (83%) patients, and multiple PAPs were identified in three patients with endocarditis and one patient with pulmonary metastases. Only three of 35 (9%) PAPs were associated with a ground-glass halo. Endovascular treatment was successfully performed in 12 patients, and only one patient had immediate recurrent hemoptysis after treatment. PAP was clinically suspected by the referring clinicians in only three patients. Sixteen of the 35 (46%) PAPs were not reported on the initial CT studies. CONCLUSION. PAPs showed a strong predilection for the peripheral pulmonary arteries. Multiplicity of PAPs can be seen in the settings of endocarditis and pulmonary metastatic disease. Most PAPs were not associated with a ground-glass halo. PAPs can be lethal but were often not suspected clinically and were underreported by radiologists. C1 [Chen, Ying; Gilman, Matthew D.; Salazar, Gloria M.; Sharma, Amita; Shepard, Jo-Anne O.; Wu, Carol C.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Humphrey, Kathryn L.] Dept Breast Imaging & Intervent Spectrum Hlth, Grand Rapids, MI USA. [Muniappan, Ashok] Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. [Wu, Carol C.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, 1515 Holcombe Blvd,Unit 1478, Houston, TX 77030 USA. RP Wu, CC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.; Wu, CC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, 1515 Holcombe Blvd,Unit 1478, Houston, TX 77030 USA. EM carolcwu@gmail.com NR 33 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 208 IS 1 BP 84 EP 91 DI 10.2214/AJR.16.16312 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH6CP UT WOS:000391860500020 PM 27656954 ER PT J AU Kilcoyne, A Shenoy-Bhangle, AS Roberts, DJ Sisodia, RC Gervais, DA Lee, SI AF Kilcoyne, Aoife Shenoy-Bhangle, Anuradha S. Roberts, Drucilla J. Sisodia, Rachel Clark Gervais, Debra A. Lee, Susanna I. TI MRI of Placenta Accreta, Placenta Increta, and Placenta Percreta: Pearls and Pitfalls SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE abnormal placentation; MRI; placenta accreta; placenta increta; placenta percreta ID EMERGENCY PERIPARTUM HYSTERECTOMY; ABNORMAL PLACENTATION; CESAREAN DELIVERIES; PRENATAL-DIAGNOSIS; GESTATIONAL-AGE; RISK-FACTORS; PREVIA; ULTRASOUND; PREGNANCY; MANAGEMENT AB OBJECTIVE. The purpose of this article is to provide a primer for radiologists performing MRI for suspected placenta accreta, illustrating normal and abnormal findings and diagnostic pitfalls. Appropriate examination indications and recommendations for optimizing image acquisition and interpretation are summarized. CONCLUSION. MRI increases the accuracy of the workup of high-risk patients and aids in multidisciplinary delivery planning to improve maternal outcome. Reader accuracy and confidence require adherence to examination performance, image interpretation criteria, and awareness of common pitfalls. C1 [Kilcoyne, Aoife; Gervais, Debra A.; Lee, Susanna I.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. [Shenoy-Bhangle, Anuradha S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. [Roberts, Drucilla J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Sisodia, Rachel Clark] Harvard Med Sch, Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Boston, MA USA. RP Kilcoyne, A (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM akilcoyne1@mgh.harvard.edu FU Mac Erlaine Scholarship from the Academic Radiology Research Trust, St. Vincent's Radiology Group, Dublin, Ireland FX A. Kilcoyne is supported by the Mac Erlaine Scholarship from the Academic Radiology Research Trust, St. Vincent's Radiology Group, Dublin, Ireland. NR 42 TC 0 Z9 0 U1 3 U2 3 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 JAN PY 2017 VL 208 IS 1 BP 214 EP 221 DI 10.2214/AJR.16.16281 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH6CP UT WOS:000391860500037 PM 27762597 ER PT J AU Provencher, MT Kirby, H McDonald, LS Golijanin, P Gross, D Campbell, KJ LeClere, L Sanchez, G Anthony, S Romeo, AA AF Provencher, Matthew T. Kirby, Hannah McDonald, Lucas S. Golijanin, Petar Gross, Daniel Campbell, Kevin J. LeClere, Lance Sanchez, George Anthony, Shawn Romeo, Anthony A. TI Surgical Release of the Pectoralis Minor Tendon for Scapular Dyskinesia and Shoulder Pain SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article DE shoulder instability; weight lifting; pectoralis minor; scapular dyskinesia; shoulder impingement ID MUSCLE; KINEMATICS; POSTURE; LENGTH; LONG AB Background: Pectoralis minor (PM) tightness has been linked to pain and dysfunction of the shoulder joint secondary to anterior tilt and internal rotation of the scapula, thus causing secondary impingement of the subacromial space. Purpose: To describe outcomes pertaining to nonoperative and operative treatment via surgical release of the PM tendon for pathologic PM tightness in an active population. Study Design: Case series; Level of evidence, 4. Methods: Over a 3-year period, a total of 46 patients were enrolled (mean age, 25.5 years; range, 18-33 years). Inclusion criteria consisted of symptomatic shoulder pain, limited range of overhead motion, inability to participate in overhead lifting activities, and examination findings consistent with scapular dysfunction secondary to a tight PM with tenderness to palpation of the PM tendon. All patients underwent a lengthy physical therapy and stretching program (mean, 11.4 months; range, 3-23 months), which was followed by serial examinations for resolution of symptoms and scapular tilt. Of the 46 patients, 6 (13%) were unable to adequately stretch the PM and underwent isolated mini-open PM release. Outcomes were assessed with scapula protraction measurements and pain scales as well as American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric Evaluation (SANE), and visual analog scale (VAS) scores. Results: Forty of the 46 patients (87%) resolved the tight PM and scapular-mediated symptoms with a dedicated therapy program (pre- and posttreatment mean outcome scores: 58 and 91 [ASES], 50 and 90 [SANE], 4.9 and 0.8 [VAS]; P < .01 for all), but 6 patients were considered nonresponders (mean score, 48 [ASES], 40 [SANE], 5.9 [VAS]) and elected to have surgical PM release, with improved scores in all domains (mean score, 89 [ASES], 90.4 [SANE], 0.9 [VAS]; P < .01) at final follow-up of 26 months (range, 25-30 months). Additionally, protraction of the scapula improved from 1.2 to 0.3 cm in a mean midline measurement from the chest wall preoperatively to postoperatively (P < .01), similar to results in nonoperative responders. No surgical complications were reported, and all patients returned to full activities. Conclusion: In most patients, PM tightness can be successfully treated with a nonoperative focused PM stretching program. However, in refractory and pathologically tight PM cases, this series demonstrates predictable return to function with notable improvement in shoulder symptoms after surgical release of the PM. Additional research is necessary to evaluate the long-term efficacy of isolated PM treatment. C1 [Provencher, Matthew T.; Kirby, Hannah; McDonald, Lucas S.; Golijanin, Petar; Gross, Daniel; Campbell, Kevin J.; LeClere, Lance; Sanchez, George; Anthony, Shawn; Romeo, Anthony A.] Naval Med Ctr San Diego, San Diego, CA USA. [Provencher, Matthew T.] Steadman Clin, 181 W Meadow Dr,Suite 400, Vail, CO 81657 USA. [Golijanin, Petar] Geisel Sch Med Dartmouth, Hanover, NH USA. [Gross, Daniel] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Campbell, Kevin J.; Romeo, Anthony A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [LeClere, Lance] US Naval Acad, Annapolis, MD 21402 USA. [Sanchez, George] Steadman Philippon Res Inst, Dept Biomed Engn, Vail, CO USA. [Anthony, Shawn] Hosp Special Surg, 535 E 70th St, New York, NY 10021 USA. RP Provencher, MT (reprint author), Steadman Clin, 181 W Meadow Dr,Suite 400, Vail, CO 81657 USA. EM mprovencher@thesteadmanclinic.com FU Arthrex Inc; Joint Restoration Foundation; DJO Surgical; Ossur; Smith Nephew FX M.T.P. is a paid consultant for Arthrex Inc and Joint Restoration Foundation, and received IP royalties from Arthrex Inc. A.A.R. receives IP royalties and other financial or material support from and is a paid consultant and paid presenter or speaker for Arthrex Inc, and receives research support from DJO Surgical, Ossur, and Smith & Nephew. NR 22 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 EI 1552-3365 J9 AM J SPORT MED JI Am. J. Sports Med. PD JAN PY 2017 VL 45 IS 1 BP 173 EP 178 DI 10.1177/0363546516664720 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA EH5CF UT WOS:000391789500021 PM 27613762 ER PT J AU Klingensmith, ME Lillemoe, KD AF Klingensmith, Mary E. Lillemoe, Keith D. TI Annals of Surgery to offer self-assessment CME SO ANNALS OF SURGERY LA English DT Editorial Material C1 [Klingensmith, Mary E.; Lillemoe, Keith D.] Washington Univ, Dept Surg, St Louis, MO 63130 USA. RP Klingensmith, ME (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM klillemoe@partners.org NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP 1 EP 1 DI 10.1097/SLA.0000000000002057 PG 1 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500007 PM 28009727 ER PT J AU Masiakos, PT Warshaw, AL AF Masiakos, Peter T. Warshaw, Andrew L. TI Stopping the Bleeding Is Not Enough SO ANNALS OF SURGERY LA English DT Editorial Material ID UNITED-STATES; INJURIES C1 [Masiakos, Peter T.; Warshaw, Andrew L.] Harvard Med Sch, Dept Surg MGH, Boston, MA USA. RP Masiakos, PT (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM pmasiakos@partners.org NR 5 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP 37 EP 38 DI 10.1097/SLA.0000000000001969 PG 2 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500015 PM 27611613 ER PT J AU Sidhwa, F Moore, A Alligood, E Fisichella, PM AF Sidhwa, Feroze Moore, Alessandra Alligood, Elaine Fisichella, Piero Marco TI Diagnosis and Treatment of the Extraesophageal Manifestations of Gastroesophageal Reflux Disease SO ANNALS OF SURGERY LA English DT Article DE asthma; cough; gastroesophageal reflux disease; laryngopharyngeal reflux ID LAPAROSCOPIC ANTIREFLUX SURGERY; PLACEBO-CONTROLLED TRIAL; PROTON PUMP INHIBITOR; MULTICHANNEL INTRALUMINAL IMPEDANCE; CHRONIC UNEXPLAINED COUGH; LONG-TERM OUTCOMES; LARYNGOPHARYNGEAL REFLUX; DOUBLE-BLIND; ASTHMATIC-PATIENTS; SURGICAL FUNDOPLICATION AB Objective: To review the clinical presentation, diagnosis, and treatment options available for management of extraesophageal manifestations of gastroesophageal reflux disease (GERD) and to compare the most recent technological advances to the existing guidelines. Summary Background Data: Extraesophageal manifestations of GERD include cough, laryngopharyngeal reflux (LPR), and asthma. Recent advances in diagnostic modalities may have outpaced the existing diagnostic and therapeutic clinical guidelines. Methods: We searched the MEDLINE, Cochrane, and Embase databases for articles pertaining to the presentation, diagnosis, and treatment of extraesophageal manifestations of reflux, specifically cough due to reflux, LPR, and asthma due to reflux. Search terms applied to 3 thematic topics: diagnosis, medical treatment, and surgical treatment. We had searched the bibliographies of included studies, yielding a total of 271 articles for full review. We graded the level of evidence and classified recommendations by size of treatment effect, according to the guidelines from the American Heart Association Task Force on Practice Guidelines. Results: One hundred twenty-eight articles met criteria for analysis. Our findings show that the diagnosis of cough, LPR, or asthma due to gastroesophageal reflux is difficult, as no criterion standard test exits. Also, patients often present without heartburn or regurgitation typical of GERD. Combined multichannel intraluminal impedance, the pH (MII-pH) monitoring system, and the symptom association probability (SAP) test might distinguish extraesophageal manifestations of reflux from idiopathic chronic cough, laryngitis due to other causes, and atopic asthma. In addition, extraesophageal manifestations of reflux are most effectively diagnosed with a stepwise approach incorporating empiric treatment and antisecretory therapy, combined MII-pH monitoring, and surgical intervention in few selected cases. Conclusions: Recent studies demonstrate the potential diagnostic role of MII-pH monitoring. Surgical intervention provides resolution of extraesophageal symptoms less reliably than typical symptoms when the patient has GERD. C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Med Sch, Brigham & Womens Hosp, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA USA. RP Fisichella, PM (reprint author), Harvard Med Sch, Brigham & Womens Hosp, VA Boston Healthcare Syst, 1400 Vet ForeignWars Pkwy, West Roxbury, MA 02132 USA. EM piero.fisichella@va.gov NR 60 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP 63 EP 67 DI 10.1097/SLA.0000000000001907 PG 5 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500018 PM 27455157 ER PT J AU Nabozny, MJ Kruser, JM Steffens, NM Pecanac, KE Brasel, KJ Chittenden, EH Cooper, Z McKneally, MF Schwarze, ML AF Nabozny, Michael J. Kruser, Jacqueline M. Steffens, Nicole M. Pecanac, Kristen E. Brasel, Karen J. Chittenden, Eva H. Cooper, Zara McKneally, Martin F. Schwarze, Margaret L. TI Patient-reported Limitations to Surgical Buy-in A Qualitative Study of Patients Facing High-risk Surgery SO ANNALS OF SURGERY LA English DT Article DE advance directives; high-risk surgery; intensive care conflict; medical ethics; palliative care; patient communication; surgical buy-in ID POSTOPERATIVE LIFE-SUPPORT; ADVANCE DIRECTIVES; DECISION-MAKING; NATIONAL-SURVEY; CARE; END; INTENSIVISTS; OPERATIONS; BURNOUT; MODELS AB Objective: To characterize how patients buy-in to treatments beyond the operating room and what limits they would place on additional life-supporting treatments. Background: During a high-risk operation, surgeons generally assume that patients buy-in to life-supporting interventions that might be necessary postoperatively. How patients understand this agreement and their willingness to participate in additional treatment is unknown. Methods: We purposively sampled surgeons in Toronto, Ontario, Boston, Massachusetts, and Madison, Wisconsin, who are good communicators and routinely perform high-risk operations. We audio-recorded their conversations with patients considering high-risk surgery. For patients who were then scheduled for surgery, we performed open-ended preoperative and postoperative interviews. We used directed qualitative content analysis to analyze the interviews and surgeon visits, specifically evaluating the content about the use of postoperative life support. Results: We recorded 43 patients' conversations with surgeons, 34 preoperative, and 27 postoperative interviews. Patients expressed trust in their surgeon to make decisions about additional treatments if a serious complication occurred, yet expressed a preference for significant treatment limitations that were not discussed with their surgeon preoperatively. Patients valued the existence or creation of an advance directive preoperatively, but they did not discuss this directive with their surgeon. Instead they assumed it would be effective if needed and that family members knew their wishes. Conclusions: Patients implicitly trust their surgeons to treat postoperative complications as they arise. Although patients may buy-in to some additional postoperative interventions, they hold a broad range of preferences for treatment limitations that were not discussed with the surgeon preoperatively. C1 [Nabozny, Michael J.; Steffens, Nicole M.; Schwarze, Margaret L.] Univ Wisconsin, Dept Surg, Madison, WI USA. [Kruser, Jacqueline M.] Northwestern Univ, Dept Med, Chicago, IL 60611 USA. [Pecanac, Kristen E.] Univ Wisconsin, Sch Nursing, Madison, WI USA. [Brasel, Karen J.] Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97201 USA. [Chittenden, Eva H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Cooper, Zara] Brigham & Womens Hosp, Dept Surg, Ctr Surg & Publ Hlth, 75 Francis St, Boston, MA 02115 USA. [McKneally, Martin F.] Univ Toronto, Dept Surg, Toronto, ON, Canada. [McKneally, Martin F.] Univ Toronto, Joint Ctr Bioeth, Toronto, ON, Canada. [Schwarze, Margaret L.] Univ Wisconsin, Dept Med Hist & Bioeth, Madison, WI USA. RP Schwarze, ML (reprint author), G5-315 CSC,600 Highland Ave, Madison, WI 53792 USA. EM schwarze@surgery.wisc.edu FU Clinical and Translational Science Award (CTSA) program [KL2TR000428]; NIH National Center for Advancing Translational Sciences (NCATS) [UL1 TR000427]; Greenwall Foundation (Greenwall Faculty Scholars Program) FX Dr Schwarze is supported by a training award (KL2TR000428) from the Clinical and Translational Science Award (CTSA) program, through the NIH National Center for Advancing Translational Sciences (NCATS), grant (UL1 TR000427), and the Greenwall Foundation (Greenwall Faculty Scholars Program). These funding sources had no role in the design and conduct of the study; collection, management, analysis, or interpretation of the data; and preparation, review, or approval of the manuscript for publication. No other financial support was declared for the remaining authors. NR 29 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP 97 EP 102 DI 10.1097/SLA.0000000000001645 PG 6 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500022 PM 28009732 ER PT J AU Allen, PJ Kuk, D Fernandez-del Castillo, C Basturk, O Wolfgang, CL Cameron, JL Lillemoe, KD Ferrone, CR Morales-Oyarvide, V He, J Weiss, MJ Hruban, RH Gonen, M Klimstra, DS Mino-Kenudson, M AF Allen, Peter J. Kuk, Deborah Fernandez-del Castillo, Carlos Basturk, Olca Wolfgang, Christopher L. Cameron, John L. Lillemoe, Keith D. Ferrone, Cristina R. Morales-Oyarvide, Vicente He, Jin Weiss, Matthew J. Hruban, Ralph H. Gonen, Mithat Klimstra, David S. Mino-Kenudson, Mari TI Multi-institutional Validation Study of the American Joint Commission on Cancer (8th Edition) Changes for Tand N Staging in Patients With Pancreatic Adenocarcinoma SO ANNALS OF SURGERY LA English DT Article DE pancreatic adenocarcinoma; AJCC; staging; T stage; N stage; 8th ID DUCTAL ADENOCARCINOMA; RESECTION; SURVIVAL AB Objective: The aim of this study was to evaluate and validate the proposed 8th edition American Joint Committee on Cancer (AJCC) system for T and N staging of pancreatic adenocarcinoma. Summary of Background Data: Investigators have questioned the clinical relevance and reproducibility of previous AJCC staging for pancreatic adenocarcinoma. Methods: Prospective databases at Memorial Sloan Kettering (MSK), Massachusetts General Hospital (MGH), and Johns Hopkins Hospital (JHH) were queried for patients who had undergone resection for pancreatic adenocarcinoma. Patients who underwent a margin-negative (R0) resection, and who had previously undergone pathologic review, were included. Patients were staged according to 7th edition AJCC criteria, as well as the proposed 8th edition system that includes different definitions of tumor size (T) and nodal status (N). The dataset was randomly split into training and test sets. Results: Two thousand three hundred eighteen patients were identified who met inclusion criteria. Recursive partitioning on the training set (n = 1551) identified statistically appropriate cutoffs for tumor size (<2.2 cm, >= 4.8 cm,) and nodal status (no positive nodes, 1 to 3 positive nodes, >= 4 positive nodes) that supported the proposed 8th edition changes. Median survival in patients staged as T3, N0 by the 7th edition definitions was different between institutions (median Center 1, 24 mo; Center 2, 37 mo; Center 3, 29 mo; P = 0.054). This difference was not observed when patients were staged as T3, N0 by 8th edition criteria. Stage, and stage-specific outcome (7th edition), on the test set revealed a predominance of patients (68%) within the IIB subgroup, and a concordance probability estimate (CPE) of 0.57 for stage-specific survival. When assessed with 8th edition criteria, no stage subgroup had a majority of patients, and the CPE was 0.58. Conclusions: The proposed 8th edition changes for T and N classification were statistically valid and may allow a more reproducible system of T staging. This system also stratifies patients more evenly across stages without sacrificing prognostic accuracy. C1 [Allen, Peter J.] Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10065 USA. [Kuk, Deborah; Gonen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Fernandez-del Castillo, Carlos; Lillemoe, Keith D.; Ferrone, Cristina R.; Morales-Oyarvide, Vicente] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Basturk, Olca; Klimstra, David S.] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Wolfgang, Christopher L.; Cameron, John L.; He, Jin; Weiss, Matthew J.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Hruban, Ralph H.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. [Mino-Kenudson, Mari] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Allen, PJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10065 USA. EM allenp@mskcc.org FU NIH/NCI [P30 CA008748] FX This study was supported in part by NIH/NCI P30 CA008748 (Cancer Center Support Grant). NR 18 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP 185 EP 191 DI 10.1097/SLA.0000000000001763 PG 7 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500035 PM 27163957 ER PT J AU Markmann, JF Yeh, H AF Markmann, James F. Yeh, Heidi TI The Beginnings of a Transplant Revolution SO ANNALS OF SURGERY LA English DT Editorial Material ID NORMOTHERMIC PERFUSION; LIVER-TRANSPLANTATION; ORGAN-PRESERVATION; DONORS C1 [Markmann, James F.; Yeh, Heidi] Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Transplant Surg, Boston, MA 02114 USA. EM Jmarkmann@Partners.ORG NR 11 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-4932 EI 1528-1140 J9 ANN SURG JI Ann. Surg. PD JAN PY 2017 VL 265 IS 1 BP E3 EP E3 DI 10.1097/SLA.0000000000001947 PG 1 WC Surgery SC Surgery GA EH9QS UT WOS:000392106500003 PM 27464619 ER PT J AU Mullen, JT AF Mullen, John T. TI Identifying Candidates for Early Discharge After Gastrectomy: "It's Tough to Make Predictions, Especially About the Future" SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID C-REACTIVE PROTEIN; INFECTIOUS COMPLICATIONS; COLORECTAL SURGERY; GASTRIC-CANCER; READMISSION; RESECTION C1 [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. [Mullen, John T.] Harvard Med Sch, Boston, MA 02115 USA. RP Mullen, JT (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA.; Mullen, JT (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM jmullen@partners.org NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2017 VL 24 IS 1 BP 8 EP 10 DI 10.1245/s10434-016-5452-4 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA EH1FZ UT WOS:000391510400004 PM 27444108 ER PT J AU Yao, K Belkora, J Bedrosian, I Rosenberg, S Sisco, M Barrera, E Kyrillios, A Tilburt, J Wang, CS Rabbitt, S Pesce, C Simovic, S Winchester, DJ Sepucha, K AF Yao, Katharine Belkora, Jeff Bedrosian, Isabelle Rosenberg, Shoshana Sisco, Mark Barrera, Ermilo Kyrillios, Alexandra Tilburt, Jon Wang, Chihsiung Rabbitt, Sarah Pesce, Catherine Simovic, Sandra Winchester, David J. Sepucha, Karen TI Impact of an In-visit Decision Aid on Patient Knowledge about Contralateral Prophylactic Mastectomy: A Pilot Study SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID LONG-TERM SATISFACTION; BREAST-CANCER PATIENTS; SURGICAL-TREATMENT; INFORMED DECISION; RANDOMIZED-TRIAL; PERCEPTIONS; WOMEN; SURGERY; CHOICE; TRENDS AB Studies have reported that breast cancer patients have limited understanding about the oncologic outcomes following contralateral prophylactic mastectomy (CPM). We hypothesized that an in-visit decision aid (DA) would be associated with higher patient knowledge about the anticipated short and long term outcomes of CPM. We piloted a DA which used the SCOPED: (Situation, Choices, Objectives, People, Evaluation and Decision) framework. Knowledge, dichotomized as "low" (<= 3 correct) versus "high" (>= 4 correct), was assessed immediately after the visit by a 5 item survey. There were 97 DA patients (response rate 62.2 %) and 114 usual care (UC) patients (response rate 71.3 %). Patient demographic factors were similar between the two groups. Twenty-one (21.7 %) patients in the DA group underwent CPM compared with 18 (15.8 %) in the UC group (p = 0.22). Mean and median knowledge levels were significantly higher in the DA group compared with the UC group for patients of all ages, tumor stage, race, family history, anxiety levels, worry about CBC, and surgery type. Eighty-six (78.9 %) of UC versus 35 (37.9 %) DA patients had low knowledge. Of patients who underwent CPM, 15 (83.3 %) in the UC cohort versus 5 (25.0 %) of DA patients had "low" knowledge. Knowledge was higher in the DA group. The UC group had approximately three times the number of patients of the DA group who were at risk for making a poorly informed decision to have CPM. Future studies should assess the impact of increased knowledge on overall CPM rates. C1 [Yao, Katharine; Sisco, Mark; Barrera, Ermilo; Kyrillios, Alexandra; Rabbitt, Sarah; Pesce, Catherine; Simovic, Sandra; Winchester, David J.] NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA. [Belkora, Jeff] Univ Calif San Francisco, Sch Med, San Francisco, CA USA. [Bedrosian, Isabelle] Univ Texas MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. [Rosenberg, Shoshana] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tilburt, Jon] Mayo Clin, Rochester, MN USA. [Wang, Chihsiung] NorthShore Univ HealthSyst, Ctr Biomed Res Informat, Evanston, IL USA. [Sepucha, Karen] Massachusetts Gen Hosp, Hlth Decis Sci Ctr, Boston, MA 02114 USA. RP Yao, K (reprint author), NorthShore Univ HealthSyst, Dept Surg, Evanston, IL USA. EM kyao@northshore.org NR 26 TC 1 Z9 1 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 EI 1534-4681 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2017 VL 24 IS 1 BP 91 EP 99 DI 10.1245/s10434-016-5556-x PG 9 WC Oncology; Surgery SC Oncology; Surgery GA EH1FZ UT WOS:000391510400017 PM 27654108 ER PT J AU Cassano, P Bui, E Rogers, AH Walton, ZE Ross, R Zeng, M Nadal-Vicens, M Mischoulon, D Baker, AW Keshaviah, A Worthington, J Hoge, EA Alpert, J Fava, M Wong, KK Simon, NM AF Cassano, Paolo Bui, Eric Rogers, Andrew H. Walton, Zandra E. Ross, Rachel Zeng, Mary Nadal-Vicens, Mireya Mischoulon, David Baker, Amanda W. Keshaviah, Aparna Worthington, John Hoge, Elizabeth A. Alpert, Jonathan Fava, Maurizio Wong, Kwok K. Simon, Naomi M. TI Inflammatory cytokines in major depressive disorder: A case-control study SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Review DE Major depressive disorder; inflammation; cytokines; interleukin-1; interleukin-6; tumor necrosis factor- ID CEREBROSPINAL-FLUID; SYMPTOMS; PLASMA; SCALE; PATHOPHYSIOLOGY; ABNORMALITIES; METAANALYSIS; INVENTORY; ILLNESS; STRESS AB Introduction: There is mixed evidence in the literature on the role of inflammation in major depressive disorder. Contradictory findings are attributed to lack of rigorous characterization of study subjects, to the presence of concomitant medical illnesses, to the small sample sizes, and to the limited number of cytokines tested. Methods: Subjects aged 18-70years, diagnosed with major depressive disorder and presenting with chronic course of illness, as well as matched controls (n=236), were evaluated by trained raters and provided blood for cytokine measurements. Cytokine levels in EDTA plasma were measured with the MILLIPLEX Multi-Analyte Profiling Human Cytokine/Chemokine Assay employing Luminex technology. The Wilcoxon rank-sum test was used to compare cytokine levels between major depressive disorder subjects and healthy volunteers, before (interleukin [IL]-1, IL-6, and tumor necrosis factor-) and after Bonferroni correction for multiple comparisons (IL-1, IL-2, IL-3, IL-4, IL-5, IL-7, IL-8, IL-10, IL-12(p40), IL-12(p70), IL-13, IL-15, IFN--inducible protein 10, Eotaxin, interferon-, monotype chemoattractant protein-1, macrophage inflammatory protein-1, granulocyte-macrophage colony-stimulating factor and vascular endothelial growth factor). Results: There were no significant differences in cytokine levels between major depressive disorder subjects and controls, both prior to and after correction for multiple analyses (significance set at p0.05 and p0.002, respectively). Conclusion: Our well-characterized examination of cytokine plasma levels did not support the association of major depressive disorder with systemic inflammation. The heterogeneity of major depressive disorder, as well as a potential sampling bias selecting for non-inflammatory depression, might have determined our findings discordant with the literature. C1 [Cassano, Paolo; Bui, Eric; Rogers, Andrew H.; Ross, Rachel; Zeng, Mary; Nadal-Vicens, Mireya; Mischoulon, David; Baker, Amanda W.; Keshaviah, Aparna; Worthington, John; Hoge, Elizabeth A.; Alpert, Jonathan; Fava, Maurizio; Simon, Naomi M.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, One Bowdoin Sq,6th Floor,Suite 648, Boston, MA 02114 USA. [Walton, Zandra E.; Wong, Kwok K.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cassano, P (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Ctr Anxiety & Traumat Stress Disorders, One Bowdoin Sq,6th Floor,Suite 648, Boston, MA 02114 USA. EM pcassano@mgh.harvard.edu FU National Institute of Mental Health (NIMH) [NIMH R01MH077700-05] FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Institute of Mental Health (NIMH) (Grant Number NIMH R01MH077700-05). NR 39 TC 0 Z9 0 U1 2 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD JAN PY 2017 VL 51 IS 1 BP 23 EP 31 DI 10.1177/0004867416652736 PG 9 WC Psychiatry SC Psychiatry GA EH5BZ UT WOS:000391788900007 PM 27313138 ER PT J AU Cusin, C Ionescu, DF Pavone, KJ Akeju, O Cassano, P Taylor, N Eikermann, M Durham, K Swee, MB Chang, T Dording, C Soskin, D Kelley, J Mischoulon, D Brown, EN Fava, M AF Cusin, Cristina Ionescu, Dawn Flosnik Pavone, Kara Jean Akeju, Oluwaseun Cassano, Paolo Taylor, Norman Eikermann, Matthias Durham, Kelley Swee, Michaela Ballentyne Chang, Trina Dording, Christina Soskin, David Kelley, John Mischoulon, David Brown, Emery Neal Fava, Maurizio TI Ketamine augmentation for outpatients with treatment-resistant depression: Preliminary evidence for two-step intravenous dose escalation SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY LA English DT Article DE Major depressive disorder; depression; antidepressant; treatment-resistant; ketamine ID D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; MAJOR DEPRESSION; ANTIDEPRESSANT EFFICACY; BIPOLAR DEPRESSION; RATING-SCALE; QUESTIONNAIRE; INFUSIONS; REPLICATION; DISORDERS AB Objective: Preliminary evidence supports the safety and efficacy of subanesthetic ketamine as an experimental antidepressant, although its effects are often not sustained beyond one week. Studies are lacking that have examined the sustained effects of escalating ketamine doses as augmentation in outpatients with treatment-resistant depression. Therefore, the aims of this study were twofold: (1) to assess the safety and antidepressant efficacy of two-step, repeated-dose ketamine augmentation and (2) to assess the duration of ketamine's antidepressant efficacy as augmentation to ongoing antidepressant pharmacotherapy for 3months after the final infusion. Methods: Fourteen patients with treatment-resistant depression were eligible to receive augmentation with six open-label intravenous ketamine infusions over 3weeks. For the first three infusions, ketamine was administered at a dose of 0.5mg/kg over 45minutes; the dose was increased to 0.75mg/kg over 45minutes for the subsequent three infusions. The primary outcome measure was response (as measured on Hamilton Depression Rating Scale-28 items). Results: After the completion of three ketamine infusions, 7.1% (1/14) responded; after all six ketamine infusions, 41.7% (5/12) completers responded and 16.7% (2/12) remitted. Intent-to-treat response and remission rates at the end of the final infusion were 35.7% (5/14) and 14.3% (2/14), respectively. However, all but one responder relapsed within 2weeks after the final infusion. Conclusion: Repeated, escalating doses of intravenous ketamine augmentation were preliminarily found to be feasible, efficacious and well tolerated. Interaction with concomitant medications and elevated level of treatment resistance are possible factors for non-response. C1 [Cusin, Cristina; Ionescu, Dawn Flosnik; Pavone, Kara Jean; Cassano, Paolo; Durham, Kelley; Swee, Michaela Ballentyne; Chang, Trina; Dording, Christina; Kelley, John; Mischoulon, David; Fava, Maurizio] Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Pavone, Kara Jean; Akeju, Oluwaseun; Taylor, Norman; Eikermann, Matthias; Brown, Emery Neal] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Soskin, David] Natividad Med Ctr, Salinas, CA USA. [Kelley, John] Endicott Coll, Dept Psychol, Beverly, MA USA. RP Cusin, C (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 1 Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ccusin@partners.org FU Department of Psychiatry, Massachusetts General Hospital, Boston, MA; Harvard Clinical and Translational Science Center [8UL1TR000170-05]; National Center for Advancing Translational Science FX This work was supported by funds from the Department of Psychiatry, Massachusetts General Hospital, Boston, MA; from Harvard Clinical and Translational Science Center (Grant Number: 8UL1TR000170-05) and from the National Center for Advancing Translational Science. The funding source had no involvement in study design, collection, analysis or interpretation of data; in writing the report; or in the decision to submit the article for publication. NR 33 TC 3 Z9 3 U1 8 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0004-8674 EI 1440-1614 J9 AUST NZ J PSYCHIAT JI Aust. N. Z. J. Psych. PD JAN PY 2017 VL 51 IS 1 BP 55 EP 64 DI 10.1177/0004867416631828 PG 10 WC Psychiatry SC Psychiatry GA EH5BZ UT WOS:000391788900010 PM 26893373 ER PT J AU Politikos, I Kim, HT Karantanos, T Brown, J McDonough, S Li, LQ Cutler, C Antin, JH Ballen, KK Ritz, J Boussiotis, VA AF Politikos, Ioannis Kim, Haesook T. Karantanos, Theodoros Brown, Julia McDonough, Sean Li, Lequn Cutler, Corey Antin, Joseph H. Ballen, Karen K. Ritz, Jerome Boussiotis, Vassiliki A. TI Angiogenic Factors Correlate with T Cell Immune Reconstitution and Clinical Outcomes after Double-Unit Umbilical Cord Blood Transplantation in Adults SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Umbilical cord blood; transplantation; Immune reconstitution; Angiogenic factors; ANG-1; ANG-2; VEGF; TM ID ENDOTHELIAL-GROWTH-FACTOR; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; VON-WILLEBRAND-FACTOR; A SERUM-LEVELS; THROMBOTIC MICROANGIOPATHY; IN-VIVO; SOLUBLE THROMBOMODULIN; NONRELAPSE MORTALITY AB Umbilical cord blood (UCB) is a valuable graft source for allogeneic hematopoietic stem cell transplantation (HSCT) in patients who lack adult donors. UCB transplantation (UCBT) in adults results in delayed immune reconstitution, leading to high infection-related morbidity and mortality. Angiogenic factors and markers of endothelial dysfunction have biologic and prognostic significance in conventional HSCT, but their role in UCBT has not been investigated. Furthermore, the interplay between angiogenesis and immune reconstitution has not been studied. Here we examined whether angiogenic cytokines, angiopoietin-1 (ANG-1) and vascular endothelial growth factor (VEGF), or markers of endothelial injury, thrombomodulin (TM) and angiopoietin-2 (ANG-2), associate with thymic regeneration as determined by T cell receptor excision circle (TREC) values and recovery of T cell subsets, as well as clinical outcomes in adult recipients of UCBT. We found that plasma levels of ANG-1 significantly correlated with the reconstitution of naive CD4(+)CD45RA and CD8(+)CD45RA(+) T cell subsets, whereas plasma levels of VEGF displayed a positive correlation with CD4(+)CD45RO(+) T cells and regulatory T cells and a weak correlation with TRECs. Assessment of TM and ANG-2 revealed a strong inverse correlation of both factors with naive T cells and TRECs. The angiogenic capacity of each patient's plasma, as determined by an in vitro angiogenesis assay, positively correlated with VEGF levels and with reconstitution of CD4(+)T cell subsets. Higher VEGF levels were associated with worse progression-free survival and higher risk of relapse, whereas higher levels of TM were associated with chronic graft-versus-host disease and nonrelapse mortality. Thus, angiogenic factors may serve as valuable markers associated with T cell reconstitution and clinical outcomes after UCBT. (C) 2017 American Society for Blood and Marrow Transplantation. C1 [Politikos, Ioannis; Karantanos, Theodoros; Brown, Julia; Li, Lequn; Boussiotis, Vassiliki A.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Hematol Oncol & Canc Biol, Boston, MA USA. [Kim, Haesook T.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [McDonough, Sean; Cutler, Corey; Antin, Joseph H.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02114 USA. [Politikos, Ioannis] Mem Sloan Kettering Canc Ctr, Adult Bone Marrow Transplant Serv, Dept Med, 1275 York Ave,Box 298, New York, NY 10065 USA. [Li, Lequn] Huazhong Univ Sci & Technol, Tongji Med Sch, Tongji Hosp, Div Thorac Surg, Wuhan, Peoples R China. RP Boussiotis, VA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave,Dana 513, Boston, MA 02215 USA. EM vboussio@bidmc.harvard.edu OI Ritz, Jerome/0000-0001-5526-4669 FU National Institutes of Health [A1098129, CA183605, CA183605S1, CA142106, CA183559, CA183560]; HHV6 Foundation Pilot Grant FX Financial disclosure: This work was supported by the National Institutes of Health grants A1098129, CA183605, CA183605S1, CA142106, CA183559, and CA183560; and the HHV6 Foundation Pilot Grant. NR 65 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2017 VL 23 IS 1 BP 103 EP 112 DI 10.1016/j.bbmt.2016.10.013 PG 10 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA EH8ST UT WOS:000392043300016 PM 27777141 ER PT J AU Crombie, J Spring, L Li, SL Soiffer, RJ Antin, JH Alyea, EP Glotzbecker, B AF Crombie, Jennifer Spring, Laura Li, Shuli Soiffer, Robert J. Antin, Joseph H. Alyea, Edwin P., III Glotzbecker, Brett TI Readmissions after Umbilical Cord Blood Transplantation and Impact on Overall Survival SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Umbilical cord blood transplant; Readmissions ID HEMATOPOIETIC-CELL TRANSPLANTATION; 30-DAY READMISSION; MEDICARE BENEFICIARIES; REDUCTION PROGRAM; HEART-FAILURE; RISK-FACTORS; CARE; RATES AB Patients treated with allogeneic hematopoietic stem cell transplantation (SCT) have high rates of readmission, but the incidence after umbilical cord blood transplantation (UCBT) is poorly described. The goal of this study was to identify the incidence and risk factors for readmission after UCBT and the impact of readmission on overall survival (OS). A retrospective review of patients receiving a UCBT at Dana-Farber/Brigham and Women's Hospital between January 1, 2004 and December 31, 2013 was performed. The readmission rates 30 days after discharge from the UCBT admission and at day +100 after the UCBT were examined. Reasons for readmission, as well as sociodemographic, disease-, and SCT-related variables were evaluated. Predictors of readmission and the impact of readmission on OS were identified using multivariate regression analysis. Of patients who received a UCBT, 42 of 126 patients (33.3%) were readmitted within 30 days of discharge and 57 of 123 patients (46.3%) were readmitted by day +100 after transplantation. The most common causes for readmission were infection (38.3%), fever without a source (14.8%), and graft-versus-host disease (8.6%). Infection during the index admission was the only significant risk factor for readmission at both time points in a univariate and multivariate regression analysis (OR, 11.66; 95% CI, 2.77 to 49.13; P<.01 and OR, 5.4; 96% CI, 1.87 to 15.58; P<.01). Prior radiation therapy was also associated with an increased risk of readmission at both time points in the multivariate regression model (OR, 20.6; 95% CI, 3.53 to 120.04; P <=.01 and OR, 5; 95% CI, 1.21 to 20.71; P=.03). The multivariate regression model also showed that black race and a median income of <60,000 in the patient's home zip code increased the risk of readmission by day +100 (OR, 30.17; 95% CI, 1.33 to 684.48; P=.03 and OR, 2.88; 95% CI, 1.04 to 7.8; P=.04, respectively). After adjusting for age, disease type, and the disease status at transplant, OS was reduced for the patients who were readmitted by day +100 (HR, 2.44; 95% CI, 1.46 to 4.06; P <.01). There was also a trend toward decreased survival in patients readmitted 30 days after discharge (HR, 1.58; 95% CI,.96 to 2.6; P=.07). Readmissions are common after UCBT. Infections and fever without a source are the most common causes of readmission. Being readmitted by day +100 resulted in a lower 5-year OS rate as compared with patients who were not readmitted. Prior radiation and infection during the transplant admission resulted in increased risk of readmission by 30 days and day +100. Similarly, race and socioeconomic status predicted readmission by day +100. Further understanding of the mechanisms leading to readmissions in these groups may allow for identification of interventions that could reduce readmissions and thus improve mortality. 2017 American Society for Blood and Marrow Transplantation. C1 [Crombie, Jennifer; Spring, Laura; Li, Shuli; Soiffer, Robert J.; Antin, Joseph H.; Alyea, Edwin P., III; Glotzbecker, Brett] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. RP Crombie, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA. EM jlcrombie@partners.org OI Spring, Laura/0000-0001-8904-3514 NR 20 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2017 VL 23 IS 1 BP 113 EP 118 DI 10.1016/j.bbmt.2016.10.012 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA EH8ST UT WOS:000392043300017 PM 27789360 ER PT J AU Brunstein, CG Cutler, CS DeFor, TE Kim, H Bejanyan, N Garfall, A Verneris, MR Chen, YB Warlick, ED Spitzer, T Miller, JS Antin, JH Weisdorf, DJ Soiffer, R Wagner, JE Ballen, KK AF Brunstein, Claudio G. Cutler, Corey S. DeFor, Todd E. Kim, Haesook Bejanyan, Nelli Garfall, Alfred Verneris, Michael R. Chen, Yi-Bin Warlick, Erica D. Spitzer, Thomas Miller, Jeffrey S. Antin, Joseph H. Weisdorf, Daniel J. Soiffer, Robert Wagner, John E. Ballen, Karen K. TI Matching at Human Leukocyte Antigen-C Improved the Outcomes after Double Umbilical Cord Blood Transplantation for Recipients of Two to Four of Six Human Leukocyte Antigen-Matched Grafts SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Alternative donor; transplantation; Human leukocyte antigen; Double umbilical cord blood ID HLA ANTIBODIES; HEMATOLOGIC MALIGNANCY; IMPACT; INTENSITY; ADULTS; LEUKEMIA; MODELS AB We studied the effect of HLA-C matching in 515 patients after double umbilical cord blood (UCB) transplantation. After HLA matching HLA-A,-B, and-DRB1 at the allele level, we scored patients according to number of donor-recipient HLA-C matches at 4 possible loci: 2 from each donor unit, at the allele level. Given a direct interaction between HLA-A,-B, and-DRB1 matching and HLA-C score, we analyzed HLA-C matching in those receiving at least 1 2/6 to 4/6 HLA-matched unit (n = 389) versus those receiving only 5/6 or 6/6-matched units (n = 126). In those with at least 1 2/6 to 4/6 HLA-matched unit, a better HLA-C matching score was associated with significantly lower risk of death of any cause and nonrelapse mortality and better disease-free survival. There was no association with the risk of relapse, acute and chronic graft-versus-host disease, and hematopoietic recovery. In contrast, among patients receiving only allele-level 5/6 or 6/6 HLA-matched UCB units, HLA-C match had no demonstrable effect on any outcome. For patients receiving at least 1 allele-level 2/6 to 4/6 HLA-matched UCB unit, matching at HLA-C reduces nonrelapse mortality and improves survival. (C) 2017 Published by Elsevier Inc. on behalf of the American Society for Blood and Marrow Transplantation. C1 [Brunstein, Claudio G.; DeFor, Todd E.; Bejanyan, Nelli; Verneris, Michael R.; Warlick, Erica D.; Miller, Jeffrey S.; Weisdorf, Daniel J.; Wagner, John E.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA. [Cutler, Corey S.; Kim, Haesook; Antin, Joseph H.; Soiffer, Robert] Dana Farber Canc Inst, Boston, MA 02115 USA. [Garfall, Alfred] Univ Penn, Philadelphia, PA 19104 USA. [Chen, Yi-Bin; Spitzer, Thomas; Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brunstein, CG (reprint author), Univ Minnesota, Dept Med, Mayo Mail Code 480,420 Delaware St, Minneapolis, MN 55455 USA. EM bruns072@umn.edu FU National Cancer Institute [P01 CA65493]; Leukemia and Lymphoma Society Scholar in Clinical Research Award [CDP-2417-11]; National Heart, Lung, and Blood Institute [U54 HL081030-32] FX Financial disclosure: This work was supported in part by grants from the National Cancer Institute P01 CA65493 (C.G.B, T.E.D., M.R.V., J.E.W.), Leukemia and Lymphoma Society Scholar in Clinical Research Award, grant CDP-2417-11 (C.G.B.), and National Heart, Lung, and Blood Institute U54 HL081030-32 (CC and KKB). NR 21 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2017 VL 23 IS 1 BP 126 EP 133 DI 10.1016/j.bbmt.2016.10.018 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA EH8ST UT WOS:000392043300019 PM 27989929 ER PT J AU Switzer, GE Bruce, J Kiefer, DM Kobusingye, H Drexler, R Besser, RM Confer, DL Horowitz, MM King, RJ Shaw, BE Riches, M Hayes-Lattin, B Linenberger, M Bolwell, B Rowley, SD Litzow, MR Pulsipher, MA AF Switzer, Galen E. Bruce, Jessica Kiefer, Deidre M. Kobusingye, Hati Drexler, Rebecca Besser, RaeAnne M. Confer, Dennis L. Horowitz, Mary M. King, Roberta J. Shaw, Bronwen E. Riches, Marcie Hayes-Lattin, Brandon Linenberger, Michael Bolwell, Brian Rowley, Scott D. Litzow, Mark R. Pulsipher, Michael A. TI Health-Related Quality of Life among Older Related Hematopoietic Stem Cell Donors (> 60 Years) Is Equivalent to That of Younger Related Donors (18 to 60 Years): A Related Donor Safety Study SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic stem cell (HSC) donation; Related donation; HSC donor health-related quality of life (HRQoL) ID BONE-MARROW DONATION; UNRELATED DONORS; TRANSPLANTATION; AGE; RECOMMENDATIONS; ATTRITION; IMPACT AB The increasing number of older adults with blood-related disorders and the introduction of reduced intensity conditioning regimens has led to increases in hematopoietic stem cell (HSC) transplantation among older adults and a corresponding increase in the age of siblings who donate HSCs to these patients. Data regarding the donation-related experiences of older donors are lacking. The Related Donor Safety Study aimed to examine/compare health-related quality of life (HRQoL) of older versus younger HSC donors. Sixty peripheral blood stem cell (PBSC) donors ages 18 to 60 years and 104 PBSC donors age >60 years completed validated questionnaires before donation and 4 weeks and 1 year after donation. Before donation, older donors had poorer general physical health (t = 3.27; P=.001) but better mental health (t = 2.11; P<.05). There were no age differences in multiple other donation-related factors. At 4 weeks after donation, there were no group differences in general physical/mental health, but older donors were less likely to report donation-related pain (t=-2.26; P<.05) and concerns (t=-3.38; P=.001). At both 4 weeks and 1 year after donation, there were no significant differences in the percentage of each age group feeling physically back to normal or in the number of days it took donors to feel completely well. There was no evidence that increasing age within the older donor group was associated with poorer donation-related HRQoL. Taken together, these data support the current practice of HSC donation by sibling donors above age 60, providing no evidence of worsening HRQoL up to 1 year after donation in individuals up to age 76. (C) 2017 American Society for Blood and Marrow Transplantation. C1 [Switzer, Galen E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Switzer, Galen E.; Bruce, Jessica] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Switzer, Galen E.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA. [Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Kiefer, Deidre M.; Kobusingye, Hati; Drexler, Rebecca; Besser, RaeAnne M.; Confer, Dennis L.; King, Roberta J.] Be The Match, Natl Marrow Donor Program, Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA. [Horowitz, Mary M.; Shaw, Bronwen E.] Med Coll Wisconsin, Dept Med, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Riches, Marcie] Univ North Carolina Chapel Hill, Div Hematol Oncol, Chapel Hill, NC USA. [Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Knight Canc Inst, Div Hematol & Med Oncol, Portland, OR 97201 USA. [Linenberger, Michael] Univ Washington, Div Hematol, Seattle, WA 98195 USA. [Bolwell, Brian] Cleveland Clin, Lerner Sch Med, Cleveland, OH 44106 USA. [Rowley, Scott D.] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA. [Rowley, Scott D.] Georgetown Univ, Sch Med, Dept Med, Washington, DC USA. [Litzow, Mark R.] Mayo Clin, Rochester, NY USA. [Pulsipher, Michael A.] Univ Calif Los Angeles, Div Hematol Oncol & BMT, Los Angeles, CA USA. RP Switzer, GE (reprint author), Univ Pittsburgh, 3501 Forbes Ave,Oxford Bld Suite 410, Pittsburgh, PA 15213 USA. EM SwitzerGE@upmc.edu FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL085707] FX Supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI R01 HL085707). NR 23 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2017 VL 23 IS 1 BP 165 EP 171 DI 10.1016/j.bbmt.2016.10.008 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA EH8ST UT WOS:000392043300025 PM 27751935 ER PT J AU Greysen, SR Harrison, JD Kripalani, S Vasilevskis, E Robinson, E Metlay, J Schnipper, JL Meltzer, D Sehgal, N Ruhnke, GW Williams, MV Auerbach, AD AF Greysen, S. Ryan Harrison, James D. Kripalani, Sunil Vasilevskis, Eduard Robinson, Edmondo Metlay, Joshua Schnipper, Jeffery L. Meltzer, David Sehgal, Neil Ruhnke, Gregory W. Williams, Mark V. Auerbach, Andrew D. TI Understanding patient-centred readmission factors: a multi-site, mixed-methods study SO BMJ QUALITY & SAFETY LA English DT Article ID 30-DAY HOSPITAL READMISSIONS; RANDOMIZED CONTROLLED-TRIAL; HEALTH-SERVICES RESEARCH; TRANSITIONAL CARE; DISCHARGE READINESS; CLINICAL-TRIAL; RISK; HOME; REHOSPITALIZATION; INTERVENTIONS AB Importance Patient concerns at or before discharge inform many transitional care interventions; few studies examine patients' perceptions of self-care and other factors related to readmission. Objectives To characterise patient-reported or caregiver-reported factors contributing to readmission. Design, setting and participants Cross-sectional, national study of general medicine patients readmitted within 30 days at 12 US hospitals. Interviews included multiple-choice survey and open-ended survey questions of patients or their caregivers. Measurements Multiple-choice survey quantified post-discharge difficulty in seven domains of self-care: medication use, contacting providers, transportation, basic needs (eg, food and shelter), diet, social support and substance abuse. Open-ended responses were coded into themes that added depth to the domains above or captured additional patient-centred concerns. Results We interviewed 1066 readmitted patients. 91% reported understanding their discharge plan; however, only 37% reported that providers asked about barriers to carrying out the plan. 52% reported experiencing difficulty in >= 1 self-care domains ranging in frequency from 22% (diet) to 7% (substance use); 26% experienced difficulty in two or more domains. Among 508 patients (48% overall) who reported no difficulties in these domains, two-thirds either could not attribute their readmission to any specific difficulty (34%) or attributed their readmission to progression or persistence of their disease despite following their discharge plan (31%). Only 20% attributed their readmission to early discharge (8%), poor-quality hospital care (6%) or issues such as inadequate discharge instructions or follow-up care (6%). Limitations The study population included only patients readmitted at academic medical centres and may not be representative of community-based care. Conclusion Patients readmitted within 30 days reported understanding their discharge plans, but frequent difficulties in self-care and low anticipatory guidance for resolving these issues after discharge. C1 [Greysen, S. Ryan; Harrison, James D.; Auerbach, Andrew D.] Univ Calif San Francisco, Div Hosp Med, 533 Parnassus Ave,UC Hall,Suite 127A, San Francisco, CA 94143 USA. [Kripalani, Sunil; Vasilevskis, Eduard] Vanderbilt Univ, Sect Hosp Med, 221 Kirkland Hall, Nashville, TN 37235 USA. [Robinson, Edmondo] Christiana Heath Care Syst, Wilmington, DE USA. [Metlay, Joshua] Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. [Schnipper, Jeffery L.] Brigham & Womens Hosp, Div Gen Internal Med, 75 Francis St, Boston, MA 02115 USA. [Meltzer, David; Ruhnke, Gregory W.] Univ Chicago, Sect Hosp Med, Chicago, IL 60637 USA. [Sehgal, Neil] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Williams, Mark V.] Univ Kentucky, Div Hosp Med, Louisville, KY USA. RP Greysen, SR (reprint author), Univ Calif San Francisco, Div Hosp Med, 533 Parnassus Ave,UC Hall,Suite 127A, San Francisco, CA 94143 USA. EM ryan.greysen@ucsf.edu FU NIH, National Institute of Aging (NIA) through Claude D. Pepper Older Americans Independence Center (NIH/NIA) [P30AG021342]; NIH-NIA Loan Repayment Program; National Heart Lung and Blood Institute; Association of American Medical Colleges; [1K23AG045338-01] FX SRG is supported by the NIH, National Institute of Aging (NIA) through the Claude D. Pepper Older Americans Independence Center (P30AG021342 NIH/NIA), a Career Development Award (1K23AG045338-01) and the NIH-NIA Loan Repayment Program. ADA is supported by the National Heart Lung and Blood Institute through a K-24 Career Mentoring Award. The Association of American Medical Colleges provided start-up matching funds for the establishment of the Hospital Medicine Re-engineering Network (HOMERuN). NR 41 TC 2 Z9 2 U1 2 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-5415 EI 2044-5423 J9 BMJ QUAL SAF JI BMJ Qual. Saf. PD JAN PY 2017 VL 26 IS 1 BP 33 EP 41 DI 10.1136/bmjqs-2015-004570 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA EH0KW UT WOS:000391453900010 PM 26769841 ER PT J AU Hainline, B Drezner, J Baggish, A Harmon, KG Emery, MS Myerburg, RJ Sanchez, E Molossi, S Parsons, JT Thompson, PD AF Hainline, Brian Drezner, Jonathan Baggish, Aaron Harmon, Kimberly G. Emery, Michael S. Myerburg, Robert J. Sanchez, Eduardo Molossi, Silvana Parsons, John T. Thompson, Paul D. TI Interassociation consensus statement on cardiovascular care of college student-athletes SO BRITISH JOURNAL OF SPORTS MEDICINE LA English DT Article ID AMERICAN-HEART-ASSOCIATION; SUDDEN CARDIAC-ARREST; AUTOMATED EXTERNAL DEFIBRILLATORS; OF-CARDIOLOGY-FOUNDATION; SCIENTIFIC STATEMENT; DISQUALIFICATION RECOMMENDATIONS; HIGH-SCHOOL; CARDIOPULMONARY-RESUSCITATION; CLINICAL CARDIOLOGY; SEATTLE CRITERIA AB Cardiovascular evaluation and care of college student-athletes is gaining increasing attention from both the public and medical communities. Emerging strategies include screening of the general athlete population, recommendations of permissible levels of participation by athletes with identified cardiovascular conditions and preparation for responding to unanticipated cardiac events in athletic venues. The primary focus has been sudden cardiac death and the usefulness of screening with or without advanced cardiac screening. The National Collegiate Athletic Association convened a multidisciplinary task force to address cardiovascular concerns in collegiate student-athletes, and to develop consensus for an interassociation statement. This document summarises the task force deliberations and follow-up discussions, and includes available evidence on cardiovascular risk, preparticipation evaluation and the recognition of and response to cardiac arrest. Future recommendations for cardiac research initiatives, education and collaboration are also provided. C1 [Hainline, Brian; Parsons, John T.] Natl Collegiate Athlet Assoc, Sport Sci Inst, POB 6222, Indianapolis, IN 46206 USA. [Drezner, Jonathan; Harmon, Kimberly G.] Univ Washington, Dept Family Med, Seattle, WA 98195 USA. [Baggish, Aaron] Massachusetts Gen Hosp, Cardiovasc Performance Program, Boston, MA 02114 USA. [Emery, Michael S.] Indiana Univ Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. [Myerburg, Robert J.] Univ Miami, Miller Sch Med, Div Cardiol, Miami, FL 33136 USA. [Sanchez, Eduardo] Amer Heart Assoc, Dallas, TX USA. [Molossi, Silvana] Baylor Coll Med, Dept Pediat, Div Pediat Cardiol, Houston, TX 77030 USA. [Thompson, Paul D.] Hartford Hosp, Div Cardiol, Hartford, CT 06115 USA. RP Hainline, B (reprint author), Natl Collegiate Athlet Assoc, Sport Sci Inst, POB 6222, Indianapolis, IN 46206 USA. EM bhainline@ncaa.org FU Genomas; Roche; Sanofi; Regeneron; Esperion; Amarin; Pfizer; NCAA Sport Science Institute FX Funding for the multidisciplinary task force, held at the National Collegiate Athletic Association (NCAA) headquarters in September 2014, was provided by the NCAA Sport Science Institute. The task force included representatives from the following affiliations: American Academy of Pediatrics' Council on Sports Medicine and Physical Fitness; National Athletic Trainers' Association; College Athletic Trainers' Society; American Medical Society for Sports Medicine; American College of Cardiology Sports and Exercise Cardiology Leadership Council; National Federation of State High School Associations; American Orthopaedic Society for Sports Medicine; NCAA Student-Athlete Advisory Council; American Osteopathic Academy of Sports Medicine, National Strength and Conditioning Association; Collegiate Strength and Conditioning Coaches Association; American Heart Association; NCAA Committee on Competitive Safeguards and Medical Aspects of Sports; and the American College of Sports Medicine. PDT has received research support from Genomas, Roche, Sanofi, Regeneron, Esperion, Amarin and Pfizer; has served as a consultant for Amgen, Regeneron, Merck, Esperion and Sanofi; has received speaker honoraria from Merck, AstraZeneca, Regeneron, Sanofi and Amgen; owns stock in AbbVie, Abbott Labs, CVS, General Electric, Johnson & Johnson, Medtronic and JA Willey; and has provided expert legal testimony on exercise-related cardiac events and statin myopathy. NR 76 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-3674 EI 1473-0480 J9 BRIT J SPORT MED JI Br. J. Sports Med. PD JAN PY 2017 VL 51 IS 2 BP 74 EP 85 DI 10.1136/bjsports-2016-096323 PG 12 WC Sport Sciences SC Sport Sciences GA EH0GY UT WOS:000391443300003 PM 27247099 ER PT J AU Gunn, AJ Sheth, RA Luber, B Huynh, MH Rachamreddy, NR Kalva, SP AF Gunn, Andrew J. Sheth, Rahul A. Luber, Brandon Huynh, Minh-Huy Rachamreddy, Niranjan R. Kalva, Sanjeeva P. TI Predicting Outcomes After Chemo-Embolization in Patients with Advanced-Stage Hepatocellular Carcinoma: An Evaluation of Different Radiologic Response Criteria SO CARDIOVASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE Hepatocellular carcinoma; Loco-regional therapy; Trans-arterial chemoembolization; Radiologic response criteria ID SOLID TUMORS; SURVIVAL; EFFICACY; SAFETY AB The purpse of this study was to evaluate the ability of various radiologic response criteria to predict patient outcomes after trans-arterial chemo-embolization with drug-eluting beads (DEB-TACE) in patients with advanced-stage (BCLC C) hepatocellular carcinoma (HCC). Hospital records from 2005 to 2011 were retrospectively reviewed. Non-infiltrative lesions were measured at baseline and on follow-up scans after DEB-TACE according to various common radiologic response criteria, including guidelines of the World Health Organization (WHO), Response Evaluation Criteria in Solid Tumors (RECIST), the European Association for the Study of the Liver (EASL), and modified RECIST (mRECIST). Statistical analysis was performed to see which, if any, of the response criteria could be used as a predictor of overall survival (OS) or time-to-progression (TTP). 75 patients met inclusion criteria. Median OS and TTP were 22.6 months (95 % CI 11.6-24.8) and 9.8 months (95 % CI 7.1-21.6), respectively. Univariate and multivariate Cox analyses revealed that none of the evaluated criteria had the ability to be used as a predictor for OS or TTP. Analysis of the C index in both univariate and multivariate models showed that the evaluated criteria were not accurate predictors of either OS (C-statistic range: 0.51-0.58 in the univariate model; range: 0.54-0.58 in the multivariate model) or TTP (C-statistic range: 0.55-0.59 in the univariate model; range: 0.57-0.61 in the multivariate model). Current response criteria are not accurate predictors of OS or TTP in patients with advanced-stage HCC after DEB-TACE. C1 [Gunn, Andrew J.] Univ Alabama Birmingham, Div Vasc & Intervent Radiol, 619 19th St S, Birmingham, AL 35249 USA. [Sheth, Rahul A.] MD Anderson Canc Ctr, Div Intervent Radiol, Houston, TX USA. [Luber, Brandon] Johns Hopkins Univ, Div Biostat & Bioinformat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Huynh, Minh-Huy] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Rachamreddy, Niranjan R.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Kalva, Sanjeeva P.] Univ Texas Southwestern Med Ctr Dallas, Dept Radiol, Div Intervent Radiol, Dallas, TX USA. RP Gunn, AJ (reprint author), Univ Alabama Birmingham, Div Vasc & Intervent Radiol, 619 19th St S, Birmingham, AL 35249 USA. EM agunn@uabmc.edu NR 19 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0174-1551 EI 1432-086X J9 CARDIOVASC INTER RAD JI Cardiovasc. Interv. Radiol. PD JAN PY 2017 VL 40 IS 1 BP 61 EP 68 DI 10.1007/s00270-016-1451-x PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA EH0CT UT WOS:000391430800009 PM 27834009 ER PT J AU Yuan, GY Wang, F Stephenson, NA Wang, L Rotstein, BH Vasdev, N Tang, PP Liang, SH AF Yuan, Gengyang Wang, Feng Stephenson, Nickeisha A. Wang, Lu Rotstein, Benjamin H. Vasdev, Neil Tang, Pingping Liang, Steven H. TI Metal-free F-18-labeling of aryl-CF2H via nucleophilic radiofluorination and oxidative C-H activation SO CHEMICAL COMMUNICATIONS LA English DT Article ID DECARBOXYLATIVE FLUORINATION; MEDICINAL CHEMISTRY; UT-B; ARENES; INHIBITORS; ANALOGS AB A metal-free and selective method to form [F-18] aryl-CF2H through nucleophilic radiofluorination of benzyl (pseudo) halides and oxidative C-H activation of benzylic C-H bonds has been developed. The method is operationally simple and tolerates a variety of electronneutral/ deficient arenes and heteroarenes. C1 [Yuan, Gengyang; Stephenson, Nickeisha A.; Wang, Lu; Rotstein, Benjamin H.; Vasdev, Neil; Liang, Steven H.] Harvard Med Sch, Gordon Ctr Med Imaging, 55 Fruit St, Boston, MA 02114 USA. [Yuan, Gengyang; Stephenson, Nickeisha A.; Wang, Lu; Rotstein, Benjamin H.; Vasdev, Neil; Liang, Steven H.] Harvard Med Sch, Div Nucl Med & Mol Imaging, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. [Yuan, Gengyang; Stephenson, Nickeisha A.; Wang, Lu; Rotstein, Benjamin H.; Vasdev, Neil; Liang, Steven H.] Harvard Med Sch, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. [Yuan, Gengyang] Northeastern Univ, Dept Chem & Chem Biol, 360 Huntington Ave, Boston, MA 02115 USA. [Wang, Feng; Tang, Pingping] Nankai Univ, State Key Lab, Tianjin 300071, Peoples R China. [Wang, Feng; Tang, Pingping] Nankai Univ, Inst Elementoorgan Chem, Collaborat Innovat Ctr Chem Sci & Engn, Tianjin 300071, Peoples R China. [Stephenson, Nickeisha A.] Univ West Indies, Dept Chem, Kingston 7, Jamaica. [Rotstein, Benjamin H.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada. [Rotstein, Benjamin H.] Univ Ottawa, Inst Heart, 40 Ruskin St, Ottawa, ON, Canada. RP Liang, SH (reprint author), Harvard Med Sch, Gordon Ctr Med Imaging, 55 Fruit St, Boston, MA 02114 USA.; Liang, SH (reprint author), Harvard Med Sch, Div Nucl Med & Mol Imaging, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA.; Liang, SH (reprint author), Harvard Med Sch, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM liang.steven@mgh.harvard.edu FU National Institute on Drug Abuse [DA038000] FX We would like to thank the staff at the radiochemistry program, Gordon Center for Medical Imaging, Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, MA, and Department of Chemistry & Chemical Biology, Northeastern University for their generous support. We also thank Drs Lee Collier and Hema Krishnan for helpful discussion. S.H.L is a recipient of NIH career development award from the National Institute on Drug Abuse (DA038000). NR 32 TC 0 Z9 0 U1 6 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 EI 1364-548X J9 CHEM COMMUN JI Chem. Commun. PY 2017 VL 53 IS 1 BP 126 EP 129 DI 10.1039/c6cc07913j PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA EH2OM UT WOS:000391607100015 ER PT J AU Tishelman, AC Fontes, LA AF Tishelman, Amy C. Fontes, Lisa A. TI Religion in child sexual abuse forensic interviews SO CHILD ABUSE & NEGLECT LA English DT Article DE Child sexual abuse; Child advocacy centers; Religion; Investigative interviews; Catholic; Christian; Jewish ID ISSUES; TRAUMA; SPIRITUALITY; SURVIVORS AB Religion is an under-studied factor affecting children's sexual victimization and their willingness to discuss such experiences. In this qualitative study, 39 child forensic interviewers and child advocacy center (CAC) directors in the United States discussed religious influences on children's sexual abuse experiences, their relationships to CACs, and their disclosures in the forensic setting. Participants reported both harmonious and dissonant interactions between religiously observant children and families on one hand and child advocacy centers on the other. Themes emerged related to abuse in religious contexts and religious justifications for abuse; clergy and religious supports for disclosures as well as suppression of disclosures; and the ways CACS accommodate religious diversity and forge collaborations with clergy. Participants discussed a wide range of religions. Recommendations for practice and research are included. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Tishelman, Amy C.] Boston Childrens Hosp, Massachusetts Gen Hosp, Boston, MA USA. [Tishelman, Amy C.] Harvard Med Sch, Boston, MA USA. [Fontes, Lisa A.] Univ Massachusetts Amherst, Univ Walls, 100 Venture Way, Hadley, MA 01035 USA. RP Tishelman, AC (reprint author), Boston Childrens Hosp, 333 Longwood Ave, Boston, MA 02115 USA. EM amy.tishelman@childrens.harvard.edu; LFontes@uww.umass.edu FU Child Protection Program at Massachusetts General Hospital, Boston, MA, USA FX This research was supported in part by the Child Protection Program at Massachusetts General Hospital, Boston, MA, USA. NR 23 TC 0 Z9 0 U1 6 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 EI 1873-7757 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 2017 VL 63 BP 120 EP 130 DI 10.1016/j.chiabu.2016.11.025 PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA EH6VC UT WOS:000391911000012 PM 27914237 ER PT J AU Wood, JN Griffis, HM Taylor, CM Strane, D Harb, GC Mi, LY Song, LH Lynch, KG Rubin, DM AF Wood, Joanne N. Griffis, Heather M. Taylor, Christine M. Strane, Douglas Harb, Gerlinde C. Mi, Lanyu Song, Lihai Lynch, Kevin G. Rubin, David M. TI Under-ascertainment from healthcare settings of child abuse events among children of soldiers by the US Army Family Advocacy Program SO CHILD ABUSE & NEGLECT LA English DT Article DE Child maltreatment; Child abuse; Family Advocacy Program (FAP); Military ID EMERGENCY-DEPARTMENT VISITS; PHYSICAL ABUSE; UNITED-STATES; HEAD TRAUMA; MALTREATMENT; FRACTURES; HOSPITALS; MILITARY; IDENTIFICATION; DEPLOYMENT AB In cases of maltreatment involving children of U.S. Army service members, the U.S. Army Family Advocacy Program (FAP) is responsible for providing services to families and ensuring child safety. The percentage of cases of maltreatment that are known to FAP, however, is uncertain. Thus, the objective of this retrospective study was to estimate the percentage of U.S. Army dependent children with child maltreatment as diagnosed by a military or civilian medical provider who had a substantiated report with FAP from 2004 to 2007. Medical claims data were used to identify 0-17 year old child dependents of soldiers who received a medical diagnosis of child maltreatment. Linkage rates of maltreatment medical diagnoses with corresponding substantiated FAP reports were calculated. Bivariate and multivariable analyses examined the association of child, maltreatment episode, and soldier characteristics with linkage to substantiated FAP reports. Across 5945 medically diagnosed maltreatment episodes, 20.3% had a substantiated FAP report. Adjusting for covariates, the predicted probability of linkage to a substantiated FAP report was higher for physical abuse than for sexual abuse, 25.8%, 95% CI (23.4, 28.3) versus 14.5%, 95% CI (11.2, 17.9). Episodes in which early care was provided at civilian treatment facilities were less likely to have a FAP report than those treated at military facilities, 9.8%, 95% CI (7.3, 12.2) versus 23.6%, 95% CI (20.8, 26.4). The observed low rates of linkage of medically diagnosed child maltreatment to substantiated FAP reports may signal the need for further regulation of FAP reporting requirements, particularly for children treated at civilian facilities. (C) 2016 Elsevier Ltd. All rights reserved. C1 [Wood, Joanne N.; Griffis, Heather M.; Taylor, Christine M.; Strane, Douglas; Rubin, David M.] Childrens Hosp Philadelphia, PolicyLab, CHOP North,Room 1544,3535 Market St,15th Floor, Philadelphia, PA 19104 USA. [Wood, Joanne N.; Rubin, David M.] Childrens Hosp Philadelphia, Div Gen Pediat, 3401 Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Wood, Joanne N.; Rubin, David M.] Univ Penn, Dept Pediat, Perelman Sch Med, 3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. [Harb, Gerlinde C.; Lynch, Kevin G.] Philadelphia Vet Affairs Med Ctr, 3900 Woodland Ave, Philadelphia, PA 19104 USA. [Mi, Lanyu; Song, Lihai] Childrens Hosp Philadelphia, HAU, 3535 Market St,15th Floor, Philadelphia, PA 19104 USA. [Lynch, Kevin G.] Univ Penn, Dept Psychiat, Perelman Sch Med, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. RP Rubin, DM (reprint author), Childrens Hosp Philadelphia, PolicyLab, CHOP North,Room 1544,3535 Market St,15th Floor, Philadelphia, PA 19104 USA. EM woodjo@email.chop.edu; griffish@email.chop.edu; taylorc2@email.chop.edu; straned@email.chop.edu; gharb@upenn.edu; mil@email.chop.edu; songl@email.chop.edu; lynch3@mail.med.upenn.edu; rubin@email.chop.edu FU Department of the Army [W81XWH-11-2-0100]; U.S. Army Medical Research Acquisition Activity, Fort Detrick MD [21702-5014] FX This work was sponsored by the Department of the Army (award number: W81XWH-11-2-0100). The U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 was the awarding and administering acquisition office. The information in this manuscript does not necessarily reflect the position or the policy of the Government, and no official endorsement should be inferred. NR 34 TC 0 Z9 0 U1 8 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 EI 1873-7757 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD JAN PY 2017 VL 63 BP 202 EP 210 DI 10.1016/j.chiabu.2016.11.007 PG 9 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA EH6VC UT WOS:000391911000020 PM 27955871 ER PT J AU Handelsman, DJ Matsumoto, AM Gerrard, DF AF Handelsman, David J. Matsumoto, Alvin M. Gerrard, David F. TI Doping Status of DHEA Treatment for Female Athletes with Adrenal Insufficiency SO CLINICAL JOURNAL OF SPORT MEDICINE LA English DT Review DE DHEA; doping; adrenal disease; adrenal insufficiency; female athlete; therapeutic ID ANABOLIC-ANDROGENIC STEROIDS; CLINICAL-PRACTICE GUIDELINE; QUALITY-OF-LIFE; DEHYDROEPIANDROSTERONE DHEA; ORAL DEHYDROEPIANDROSTERONE; POSTMENOPAUSAL WOMEN; FREE TESTOSTERONE; MASS-SPECTROMETRY; HYPOADRENAL WOMEN; BODY-COMPOSITION AB Objective: To review the doping status of dehydroepiandrosterone (DHEA) for female athletes with adrenal insufficiency within the framework of Therapeutic Use Exemption (TUE) applications for this proandrogen, which is included on the World Anti-Doping Agency (WADA)'s Prohibited List. Data Sources and Main Results: Current knowledge of adrenal pathophysiology with a focus on the physiological role and pharmacological effects of DHEA in female athletes including placebo-controlled clinical trials of DHEA and consensus clinical practice and prescribing guidelines. Conclusions: Because there is no convincing clinical evidence to support the use of DHEA replacement therapy in women with adrenal failure, a TUE for DHEA is not justified by definite health benefit for either secondary or primary adrenal failure. This is consistent with the 2014 update of the US Endocrine Society guidelines, meta-analyses of DHEA treatment in women with or without adrenal failure, current WADA TUE guidance document for adrenal insufficiency and recent case law of WADA's Court of Arbitration for Sport. C1 [Handelsman, David J.] Univ Sydney, Concord Hosp, ANZAC Res Inst, Sydney, NSW 2139, Australia. [Matsumoto, Alvin M.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. [Matsumoto, Alvin M.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. [Gerrard, David F.] Univ Otago, Dunedin Sch Med, WADA TUE Expert Grp, New Zealand Chair, Dunedin, New Zealand. RP Handelsman, DJ (reprint author), Univ Sydney, Concord Hosp, ANZAC Res Inst, Sydney, NSW 2139, Australia. EM djh@anzac.edu.au NR 91 TC 0 Z9 0 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1050-642X EI 1536-3724 J9 CLIN J SPORT MED JI Clin. J. Sport Med. PD JAN PY 2017 VL 27 IS 1 BP 78 EP 85 PG 8 WC Orthopedics; Physiology; Sport Sciences SC Orthopedics; Physiology; Sport Sciences GA EH9OP UT WOS:000392101000014 PM 26844622 ER PT J AU Mohamadi, A Chan, JJ Claessen, FMAP Ring, D Chen, NC AF Mohamadi, Amin Chan, Jimmy J. Claessen, Femke M. A. P. Ring, David Chen, Neal C. TI Corticosteroid Injections Give Small and Transient Pain Relief in Rotator Cuff Tendinosis: A Meta-analysis SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; SUBACROMIAL IMPINGEMENT SYNDROME; DOUBLE-BLIND; CLINICAL-TRIALS; SHOULDER PAIN; MUSCULOSKELETAL DISORDERS; CONTINUOUS OUTCOMES; STEROID INJECTIONS; TREATMENT RESPONSE AB The ability of injection of corticosteroids into the subacromial space to relieve pain ascribed to rotator cuff tendinosis is debated. The number of patients who have an injection before one gets relief beyond what a placebo provides is uncertain. We asked: (1) Do corticosteroid injections reduce pain in patients with rotator cuff tendinosis 3 months after injection, and if so, what is the number needed to treat (NNT)? (2) Are multiple injections better than one single injection with respect to pain reduction at 3 months? We systematically searched seven electronic databases for randomized controlled trials of corticosteroid injection for rotator cuff tendinosis compared with a placebo injection. Eligible studies had at least 10 adults and used pain intensity as an outcome measure. The Hedges's g as adjusted pooled standardized mean difference (SMD) (which expresses the size of the intervention effect in each study relative to the total variability observed among pooled studies) and NNT were calculated at assessment points less than 1 month, 1-2 months, and 2-3 months. The protocol of this study was registered at the international prospective register of systematic reviews. Eleven studies of 726 patients satisfied our criteria for data pooling. Three studies containing 292 patients used repeat injections. A random effects model was used owing to substantial heterogeneity among studies. The funnel plot indicated the possibility of some missing studies, but Orwin's fail-safe N and Duval and Tweedie's trim and fill suggested that missing studies would not significantly affect the results. Corticosteroid injection did not reduce pain intensity in adult patients with rotator cuff tendinosis more than a placebo injection at the 3-month assessment. A small transient pain relief occurred at the assessment between 4 and 8 weeks with a SMD of 0.52 (range, 0.27-0.78) (p < 0.001). At least five patients must be treated for one patient's pain to be transiently reduced to no more than mild. Multiple injections were not found to be more effective than a single injection at any time. Corticosteroid injections provide-at best-minimal transient pain relief in a small number of patients with rotator cuff tendinosis and cannot modify the natural course of the disease. Given the discomfort, cost, and potential to accelerate tendon degeneration associated with corticosteroids, they have limited appeal. Their wide use may be attributable to habit, underappreciation of the placebo effect, incentive to satisfy rather than discuss a patient's drive toward physical intervention, or for remuneration, rather than their utility. Level I, therapeutic study. C1 [Mohamadi, Amin; Chan, Jimmy J.; Claessen, Femke M. A. P.; Chen, Neal C.] Massachusetts Gen Hosp, Dept Orthopaed, Hand & Upper Extrem Serv, Boston, MA 02114 USA. [Ring, David] Univ Texas Austin, Dell Med Sch, Comprehens Care, Austin, TX 78701 USA. RP Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, Comprehens Care, Austin, TX 78701 USA. EM david.ring@austin.utexas.edu OI Mohamadi, Amin/0000-0003-0958-0091 NR 54 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD JAN PY 2017 VL 475 IS 1 BP 232 EP 243 DI 10.1007/s11999-016-5002-1 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA EG9NW UT WOS:000391386700041 PM 27469590 ER PT J AU Laubach, JP Prada, CEP Richardson, PG Longo, DL AF Laubach, J. P. Prada, C. E. Paba Richardson, P. G. Longo, D. L. TI Daratumumab, Elotuzumab, and the Development of Therapeutic Monoclonal Antibodies in Multiple Myeloma SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG AB There has been substantial progress in clinical outcomes for patients withmultiple myeloma (MM). This encouraging trend derives in large part from the increasing number of effective therapeutic options and the ability because of this to achieve higher quality responses to treatment. The approval of both daratumumab and of elotuzumab in combination with lenalidomide and dexamethasone, in late 2015, was a notable achievement in the field, as daratumumab and elotuzumab represent the first monoclonal antibodies available for use in MM. Given their unique mechanisms of action and favorable side effect profiles, daratumumab and elotuzumab have considerable potential as therapeutic partners with agents in other drug classes and in different clinical settings ranging from newly diagnosed to relapsed disease. This review discusses the development of daratumumab and elotuzumab as well as other monoclonal antibodies currently being evaluated for use in MM. C1 [Laubach, J. P.; Prada, C. E. Paba; Richardson, P. G.; Longo, D. L.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Laubach, JP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM JacobP_Laubach@DFCI.harvard.edu NR 5 TC 2 Z9 2 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2017 VL 101 IS 1 BP 81 EP 88 DI 10.1002/cpt.550 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EH7BI UT WOS:000391927400020 PM 27806428 ER PT J AU Blum, K Febo, M Badgaiyan, RD Demetrovics, Z Simpatico, T Fahlke, C Oscar-Berman, M Li, M Dushaj, K Gold, MS AF Blum, Kenneth Febo, Marcelo Badgaiyan, Rajendra D. Demetrovics, Zsolt Simpatico, Thomas Fahlke, Claudia Oscar-Berman, M. Li, Mona Dushaj, Kristina Gold, Mark S. TI Common Neurogenetic Diagnosis and Meso-Limbic Manipulation of Hypodopaminergic Function in Reward Deficiency Syndrome (RDS): Changing the Recovery Landscape SO CURRENT NEUROPHARMACOLOGY LA English DT Review DE Dopamine homeostasis; genetics; reward deficiency solution system; Reward Deficiency Syndrome (RDS) ID ALCOHOL-DEPENDENT INDIVIDUALS; REDUCED STRIATAL RESPONSE; DOPAMINE-RECEPTOR GENE; DRUG-ADDICTION; INDUCED REINSTATEMENT; ETHANOL WITHDRAWAL; COCAINE REWARD; D2; MICRORNAS; BRAIN AB Background: In 1990, Blum and associates provided the first confirmed genetic link between the DRD2 polymorphisms and alcoholism. This finding was based on an earlier conceptual framework, which served as a blueprint for their seminal genetic association discovery they termed "Brain Reward Cascade." These findings were followed by a new way of understanding all addictive behaviors (substance and non-substance) termed "Reward Deficiency Syndrome" (RDS). RDS incorporates a complex multifaceted array of inheritable behaviors that are polygenic. Objective: In this review article, we attempt to clarify these terms and provide a working model to accurately diagnose and treat these unwanted behaviors. Method: We are hereby proposing the development of a translational model we term "Reward Deficiency Solution System (TM)" that incorporates neurogenetic testing and meso-limbic manipulation of a "hypodopaminergic" trait/state, which provides dopamine agonistic therapy (DAT) as well as reduced "dopamine resistance," while embracing "dopamine homeostasis." Result: The result is better recovery and relapse prevention, despite DNA antecedents, which could impact the recovery process and relapse. Understanding the commonality of mental illness will transform erroneous labeling based on symptomatology, into a genetic and anatomical etiology. WC: 184. C1 [Blum, Kenneth; Febo, Marcelo] Univ Florida, Coll Med, Dept Psychiat, Box 100183, Gainesville, FL 32610 USA. [Blum, Kenneth; Febo, Marcelo] McKnight Brain Inst, Gainesville, FL USA. [Blum, Kenneth; Simpatico, Thomas] Univ Vermont, Dept Psychiat, Burlington, VT USA. [Blum, Kenneth] Summit Estates Recovery Ctr, Div Neurosci Based Therapy, Las Gatos, CA USA. [Blum, Kenneth] Domin Diagnost LLC, North Kingstown, RI USA. [Blum, Kenneth] IGENE LLC, Austin, TX USA. [Blum, Kenneth] RDSolut Inc, Dept Nutrigen, Salt Lake City, UT USA. [Badgaiyan, Rajendra D.] Univ Minnesota, Dept Psychiat, Coll Med, Div Neuroimaging, Minneapolis, MN 55455 USA. [Blum, Kenneth] Eotvos Lorand Univ, Dept Psychol, Budapest, Hungary. [Fahlke, Claudia] Univ Gothenburg, Dept Psychol, Gothenburg, Sweden. [Oscar-Berman, M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Oscar-Berman, M.] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Oscar-Berman, M.] Boston Univ, Boston VA Healthcare Syst, Boston, MA 02215 USA. [Blum, Kenneth; Li, Mona; Dushaj, Kristina] PATH Fdn NY, New York, NY USA. [Blum, Kenneth; Gold, Mark S.] Keck Sch Med USC, Dept Psychiat & Behav Sci, Los Angeles, CA USA. [Gold, Mark S.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. [Blum, Kenneth] Shores Treatment & Recovery, Div Neurosci Res & Addict Therapy, Port St Lucie, FL USA. RP Blum, K (reprint author), Univ Florida, Coll Med, Dept Psychiat, Box 100183, Gainesville, FL 32610 USA.; Blum, K (reprint author), Univ Florida, McKnight Brain Inst, Coll Med, Box 100183, Gainesville, FL 32610 USA. EM drd2gene@ufl.edu FU National Institutes of Health [1R01NS073884]; [R01DA019946]; [R21 DA038009] FX The authors appreciate the expert edits by Margaret A. Madigan and assistance of Jia A. Blum. We acknowledge the grants of Marcelo Febo, recipient of R01DA019946 and R21 DA038009, and Rajendra D. Badgaiyan supported by the National Institutes of Health grants www.ncbi.nlm.nih.gov/ 1R01NS073884. NR 94 TC 0 Z9 0 U1 3 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X EI 1875-6190 J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PY 2017 VL 15 IS 1 BP 184 EP 194 DI 10.2174/1570159X13666160512150918 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA EH6AX UT WOS:000391855800019 PM 27174576 ER PT J AU Brady, MT Patts, GJ Rosen, A Kasotakis, G Siracuse, JJ Sachs, T Kuhnen, A Kunitake, H AF Brady, Matthew T. Patts, Gregory J. Rosen, Amy Kasotakis, George Siracuse, Jeffrey J. Sachs, Teviah Kuhnen, Angela Kunitake, Hiroko TI Postoperative Venous Thromboembolism in Patients Undergoing Abdominal Surgery for IBD: A Common but Rarely Addressed Problem SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY APR 30-MAY 04, 2016 CL Los Angeles, CA SP Amer Soc Colon & Rectal Surg DE Colon and rectal surgery; Crohn's disease; Deep venous thrombosis; Inflammatory bowel disease; Prophylaxis; Ulcerative colitis ID INFLAMMATORY-BOWEL-DISEASE; DEEP-VEIN THROMBOSIS; RISK-FACTORS; PULMONARY-EMBOLISM; PROPHYLAXIS; PROGRAM; CANCER; COMPLICATIONS AB BACKGROUND: Venous thromboembolism after abdominal surgery occurs in 2% to 3% of patients with Crohn's disease and ulcerative colitis. However, no evidence-based guidelines currently exist to guide postdischarge prophylactic anticoagulation. OBJECTIVE: We sought to determine the use of postoperative postdischarge venous thromboembolism chemical prophylaxis, 90-day venous thromboembolism rates, and factors associated with 90-day thromboembolic events in IBD patients following abdominal surgery. DESIGN: This was a retrospective evaluation of an administrative database. DATA SOURCE: Data were obtained from Optum Labs Data Warehouse, a large administrative database containing claims on privately insured and Medicare Advantage enrollees. PATIENTS: Seven thousand seventy-eight patients undergoing surgery for Crohn's disease or ulcerative colitis were included in the study. MAIN OUTCOME MEASURES: Primary outcomes were rates of postdischarge venous thromboembolism prophylaxis and 90-day rates of postdischarge thromboembolic events. In addition, patient clinical characteristics were identified to determine predictors of postdischarge venous thromboembolism. RESULTS: Postdischarge chemical prophylaxis was given to only 0.6% of patients in the study. Two hundred thirty-five patients (3.3%) developed a postdischarge thromboembolic complication. Postdischarge thromboembolism was more common in patients with ulcerative colitis than with Crohn's disease (5.8% vs 2.3%; p < 0.001). Increased rates of venous thromboembolism were seen in patients undergoing colectomy or proctectomy with simultaneous stoma creation compared with colectomy or proctectomy alone (5.8% vs 2.1%; p < 0.001). The strongest predictors of thromboembolic complications were stoma creation (adjusted OR, 1.95; 95% CI, 1.34-2.84), J-pouch reconstruction (adjusted OR, 2.66; 95% CI, 1.65-4.29), preoperative prednisone use (adjusted OR, 1.57; 95% CI, 1.19-2.08), and longer length of stay (adjusted OR, 1.89; 95% CI, 1.41-2.52). LIMITATIONS: This study is limited by its retrospective design. CONCLUSIONS: The use of postdischarge venous thromboembolism prophylaxis in this patient sample was infrequent. Development of evidence-based guidelines, particularly for high-risk patients, should be considered to improve the outcomes of IBD patients undergoing abdominal surgery. C1 [Brady, Matthew T.; Patts, Gregory J.; Rosen, Amy; Kasotakis, George; Siracuse, Jeffrey J.; Sachs, Teviah; Kuhnen, Angela] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Kunitake, Hiroko] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Sachs, Teviah] Boston Univ, Sch Med, Boston, MA 02118 USA. RP Brady, MT (reprint author), 88 East Newton St,C515, Boston, MA 02118 USA. EM matthew.t.brady.md@gmail.com FU Department of Surgery, Boston University School of Medicine FX Internal funding, Department of Surgery, Boston University School of Medicine. NR 25 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 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JAN PY 2017 VL 60 IS 1 BP 61 EP 67 DI 10.1097/DCR.0000000000000721 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA EH6GV UT WOS:000391871900013 PM 27926558 ER PT J AU Bordeianou, L Cauley, CE Antonelli, D Bird, S Rattner, D Hutter, M Mahmood, S Schnipper, D Rubin, M Bleday, R Kenney, P Berger, D AF Bordeianou, Liliana Cauley, Christy E. Antonelli, Donna Bird, Sarah Rattner, David Hutter, Matthew Mahmood, Sadiqa Schnipper, Deborah Rubin, Marc Bleday, Ronald Kenney, Pardon Berger, David TI Truth in Reporting: How Data Capture Methods Obfuscate Actual Surgical Site Infection Rates within a Health Care Network System SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT Annual Scientific Meeting of the American-Society-of-Colon-and-Rectal-Surgeons CY APR 30-MAY 04, 2016 CL Los Angeles, CA SP Amer Soc Colon & Rectal Surg DE Centers for Medicare & Medicaid Services; Colon surgery; Infection rate; Surgical quality; Surgical site infection ID QUALITY IMPROVEMENT PROGRAM; YORK-STATE 2009-2010; RISK-FACTORS; ADMINISTRATIVE DATA; COLORECTAL SURGERY; SURVEILLANCE; ADJUSTMENT AB BACKGROUND: Two systems measure surgical site infection rates following colorectal surgeries: the American College of Surgeons National Surgical Quality Improvement Program and the Centers for Disease Control and Prevention National Healthcare Safety Network. The Centers for Medicare & Medicaid Services pay-for-performance initiatives use National Healthcare Safety Network data for hospital comparisons. OBJECTIVE: This study aimed to compare database concordance. DESIGN: This is a multi-institution cohort study of systemwide Colorectal Surgery Collaborative. The National Surgical Quality Improvement Program requires rigorous, standardized data capture techniques; National Healthcare Safety Network allows 5 data capture techniques. Standardized surgical site infection rates were compared between databases. The Cohen.-coefficient was calculated. SETTING: This study was conducted at Boston-area hospitals. PATIENTS: National Healthcare Safety Network or National Surgical Quality Improvement Program patients undergoing colorectal surgery were included. MAIN OUTCOME MEASURES: Standardized surgical site infection rates were the primary outcomes of interest. RESULTS: Thirty-day surgical site infection rates of 3547 (National Surgical Quality Improvement Program) vs 5179 (National Healthcare Safety Network) colorectal procedures (2012-2014). Discrepancies appeared: National Surgical Quality Improvement Program database of hospital 1 (N = 1480 patients) routinely found surgical site infection rates of approximately 10%, routinely deemed rate "exemplary" or "as expected" (100%). National Healthcare Safety Network data from the same hospital and time period (N = 1881) revealed a similar overall surgical site infection rate (10%), but standardized rates were deemed "worse than national average" 80% of the time. Overall, hospitals using less rigorous capture methods had improved surgical site infection rates for National Healthcare Safety Network compared with standardized National Surgical Quality Improvement Program reports. The correlation coefficient between standardized infection rates was 0.03 (p = 0.88). During 25 site-time period observations, National Surgical Quality Improvement Program and National Healthcare Safety Network data matched for 52% of observations (13/25). kappa = 0.10 (95% CI, -0.1366 to 0.3402; p = 0.403), indicating poor agreement. LIMITATIONS: This study investigated hospitals located in the Northeastern United States only. CONCLUSIONS: Variation in Centers for Medicare & Medicaid Services-mandated National Healthcare Safety Network infection surveillance methodology leads to unreliable results, which is apparent when these results are compared with standardized data. High-quality data would improve care quality and compare outcomes among institutions. C1 [Bordeianou, Liliana; Cauley, Christy E.; Antonelli, Donna; Bird, Sarah; Rattner, David; Hutter, Matthew; Berger, David] Massachusetts Gen Hosp, Div Gen & GI Surg, Boston, MA 02114 USA. [Antonelli, Donna; Bird, Sarah; Hutter, Matthew] Massachusetts Gen Hosp, Codman Ctr, Boston, MA 02114 USA. [Mahmood, Sadiqa] Partners Healthcare, Dept Qual Safety & Value, Boston, MA USA. [Schnipper, Deborah] Newton Wellesley Hosp, Dept Surg, Newton, MA USA. [Rubin, Marc] North Shore Med Ctr, Dept Surg, Salem, MA USA. [Bleday, Ronald] Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. [Kenney, Pardon] Faulkner Hosp, Dept Surg, Boston, MA USA. RP Cauley, CE (reprint author), 15 Parkman St, Boston, MA 02114 USA. EM ccauley@partners.org FU National Cancer Institute at the NIH [R25CA092203] FX This work was supported by the National Cancer Institute at the NIH grant R25CA092203 to Dr Cauley. NR 24 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0012-3706 EI 1530-0358 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD JAN PY 2017 VL 60 IS 1 BP 96 EP 106 DI 10.1097/DCR.0000000000000715 PG 11 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA EH6GV UT WOS:000391871900018 PM 27926563 ER PT J AU Lin, BM Curhan, SG Wang, ML Jacobson, BC Eavey, R Stankovic, KM Curhan, GC AF Lin, Brian M. Curhan, Sharon G. Wang, Molin Jacobson, Brian C. Eavey, Roland Stankovic, Konstantina M. Curhan, Gary C. TI Prospective Study of Gastroesophageal Reflux, Use of Proton Pump Inhibitors and H2-Receptor Antagonists, and Risk of Hearing Loss SO EAR AND HEARING LA English DT Article DE H2-receptor antagonists; Hearing loss; Gastroesophageal reflux disease; Prospective study; Proton pump inhibitors ID ROUND WINDOW MEMBRANE; FOOD FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; OTITIS-MEDIA; NATIONAL-HEALTH; OLDER-ADULTS; DISEASE; WOMEN; REPRODUCIBILITY; PERMEABILITY AB Objectives: Gastroesophageal reflux disease (GERD) is common and often treated with proton pump inhibitors (PPIs) or H2-receptor antagonists (H2-RAs). GERD has been associated with exposure of the middle ear to gastric contents, which could cause hearing loss. Treatment of GERD with PPIs and H2-RAs may decrease exposure of the middle ear to gastric acid and decrease the risk of hearing loss. We prospectively investigated the relation between GERD, use of PPIs and H2-RAs, and the risk of hearing loss in 54,883 women in Nurses' Health Study II. Design: Eligible participants, aged 41 to 58 years in 2005, provided information on medication use and GERD symptoms in 2005, answered the question on hearing loss in 2009 or in 2013, and did not report hearing loss starting before the date of onset of GERD symptoms or medication use. The primary outcome was self-reported hearing loss. Cox proportional hazards regression was used to adjust for potential confounders. Results: During 361,872 person-years of follow-up, 9842 new cases of hearing loss were reported. Compared with no GERD symptoms, higher frequency of GERD symptoms was associated with higher risk of hearing loss (multivariable adjusted relative risks: <1 time/month 1.04 [0.97, 1.11], several times/week 1.17 [1.09, 1.25], daily 1.33 [1.19, 1.49]; p value for trend <0.001). After accounting for GERD symptoms, neither PPI nor H2-RA use was associated with the risk of hearing loss. Conclusions: GERD symptoms are associated with higher risk of hearing loss in women, but use of PPIs and H2-RAs are not independently associated with the risk. C1 [Lin, Brian M.; Stankovic, Konstantina M.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, 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. [Wang, Molin; Curhan, Gary C.] Dept Epidemiol, Boston, MA USA. [Wang, Molin] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Curhan, Gary C.] Brigham & Womens Hosp, Dept Med, Div Renal, 75 Francis St, Boston, MA 02115 USA. [Lin, Brian M.; Curhan, Sharon G.; Stankovic, Konstantina M.; Curhan, Gary C.] Harvard Med Sch, Boston, MA USA. [Jacobson, Brian C.] Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA. [Eavey, Roland] Vanderbilt Univ, Sch Med, Vanderbilt Bill Wilkerson Ctr Otolaryngol & Commu, Nashville, TN 37212 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 funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. NR 48 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD JAN-FEB PY 2017 VL 38 IS 1 BP 21 EP 27 DI 10.1097/AUD.0000000000000347 PG 7 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA EH2WV UT WOS:000391630200010 PM 27556519 ER PT J AU Jakien, KM Kampel, SD Gordon, SY Gallun, FJ AF Jakien, Kasey M. Kampel, Sean D. Gordon, Samuel Y. Gallun, Frederick J. TI The Benefits of Increased Sensation Level and Bandwidth for Spatial Release From Masking SO EAR AND HEARING LA English DT Article DE Aging; Bandwidth; Binaural hearing; Head-related-transfer-functions; Hearing aids; Hearing loss; Sensation level; Spatial release from masking ID INTERAURAL TIME DIFFERENCES; HEARING-LOSS; SPEECH; SEPARATION; RECEPTION; INTELLIGIBILITY; NOISE; MODEL; TASK AB Objective: Spatial release from masking (SRM) can increase speech intelligibility in complex listening environments. The goal of the present study was to document how speech-in-speech stimuli could be best processed to encourage optimum SRM for listeners who represent a range of ages and amounts of hearing loss. We examined the effects of equating stimulus audibility among listeners, presenting stimuli at uniform sensation levels (SLs), and filtering stimuli at two separate bandwidths. Design: Seventy-one participants completed two speech intelligibility experiments (36 listeners in experiment 1; all 71 in experiment 2) in which a target phrase from the coordinate response measure (CRM) and two masking phrases from the CRM were presented simultaneously via earphones using a virtual spatial array, such that the target sentence was always at 0 degree azimuth angle and the maskers were either colocated or positioned at +/-45 degrees. Experiments 1 and 2 examined the impacts of SL, age, and hearing loss on SRM. Experiment 2 also assessed the effects of stimulus bandwidth on SRM. Results: Overall, listeners' ability to achieve SRM improved with increased SL. Younger listeners with less hearing loss achieved more SRM than older or hearing-impaired listeners. It was hypothesized that SL and bandwidth would result in dissociable effects on SRM. However, acoustical analysis revealed that effective audible bandwidth, defined as the highest frequency at which the stimulus was audible at both ears, was the best predictor of performance. Thus, increasing SL seemed to improve SRM by increasing the effective bandwidth rather than increasing the level of already audible components. Conclusions: Performance for all listeners, regardless of age or hearing loss, improved with an increase in overall SL and/or bandwidth, but the improvement was small relative to the benefits of spatial separation. C1 [Jakien, Kasey M.; Gallun, Frederick J.] Oregon Hlth & Sci Univ, Otolaryngol Head & Neck Surg, Portland, OR 97201 USA. [Jakien, Kasey M.; Kampel, Sean D.; Gordon, Samuel Y.; Gallun, Frederick J.] Portland VA Med Ctr, Dept Vet Affairs, Natl Ctr Rehabil Auditory Res, Portland, OR USA. RP Jakien, KM (reprint author), VA Portland Hlth Care Syst, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Kasey.Jakien@va.gov FU National Institutes of Health's National Institute for Deafness and Communication Disorders [R01 DC011828]; VA RR&D National Center for Rehabilitative Auditory Research at the VA Portland Health Care System Medical Center FX Supported by the National Institutes of Health's National Institute for Deafness and Communication Disorders (R01 DC011828) and by the VA RR&D National Center for Rehabilitative Auditory Research, which is located at the VA Portland Health Care System Medical Center. The contents of this article are the private views of the authors and should not be assumed to represent the views of the Department of Veterans Affairs or the United States Government. NR 26 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0196-0202 EI 1538-4667 J9 EAR HEARING JI Ear Hear. PD JAN-FEB PY 2017 VL 38 IS 1 BP E13 EP E21 DI 10.1097/AUD.0000000000000352 PG 9 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA EH2WV UT WOS:000391630200002 PM 27556520 ER PT J AU Ghorbanhoseini, M Kwon, JY AF Ghorbanhoseini, Mohammad Kwon, John Y. TI Percutaneous Method to Determine Optimal Surgical Approach for Delayed Treatment of Calcaneus Fracture SO FOOT & ANKLE INTERNATIONAL LA English DT Editorial Material DE calcaneus fracture; sinus tarsi approach; extensile lateral approach; posterior facet reduction; percutaneous fracture reducibility ID DISPLACED INTRAARTICULAR FRACTURES; EXTENSILE LATERAL APPROACH; INTERNAL-FIXATION; OPEN REDUCTION; BOHLERS ANGLE; ARTERY; RADIOGRAPHS C1 [Ghorbanhoseini, Mohammad] Harvard Med Sch, Boston, MA USA. [Kwon, John Y.] Harvard Med Sch, BIDMC, Carl J Shapiro Dept Orthopaed, 330 Brookline Ave, Boston, MA 02215 USA. RP Ghorbanhoseini, M (reprint author), Harvard Med Sch, BIDMC, Carl J Shapiro Dept Orthopaed, 330 Brookline Ave, Boston, MA 02215 USA. EM mghorban@bidmc.harvard.edu NR 27 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 1071-1007 EI 1944-7876 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JAN PY 2017 VL 38 IS 1 BP 76 EP 79 DI 10.1177/1071100716667318 PG 4 WC Orthopedics SC Orthopedics GA EH5JB UT WOS:000391808100011 PM 27654044 ER PT J AU Cheuk, ML Anderson, AJ Han, JC Lippok, N Vanholsbeeck, F Ruddy, BP Loiselle, DS Nielsen, PMF Taberner, AJ AF Cheuk, Ming L. Anderson, Alexander J. Han, June-Chiew Lippok, Norman Vanholsbeeck, Frederique Ruddy, Bryan P. Loiselle, Denis S. Nielsen, Poul M. F. Taberner, Andrew J. TI Four-Dimensional Imaging of Cardiac Trabeculae Contracting In Vitro Using Gated OCT SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Biomedical imaging; electromechanical sensors; isolated cardiac muscle; microscopy; optical coherence tomography; optical imaging ID OPTICAL COHERENCE TOMOGRAPHY; BODY-TEMPERATURE; SARCOMERE-LENGTH; MUSCLE; ENERGETICS; CARNEAE AB Cardiac trabeculae are widely used as experimental muscle preparations for studying heartmuscle. However, their geometry (diameter, length, and shape) can vary not only among samples, but also within a sample, leading to inaccuracies in estimating their stress production, volumetric energy output, and/or oxygen consumption. Hence, it is desirable to have a system that can accurately image each trabecula in vitro during an experiment. To this end, we constructed an optical coherence tomography system and implemented a gated imaging procedure to image actively contracting trabeculae and reconstruct their time-varying geometry. By imaging a single cross section while monitoring the developed force, we found that gated stimulation of the muscle was sufficiently repeatable to allow us to reconstruct multiple contractions to form a four-dimensional representation of a single muscle contraction cycle. The complete muscle was imaged at various lengths and the cross-sectional area along the muscle was quantified during the contraction cycle. The variation of cross-sectional area along the length during a contraction tended to increase as the muscle was contracting, and this increase was greater at longer muscle lengths. To our knowledge, this is the first system that is able to measure the geometric change of cardiac trabeculae in vitro during a contraction, allowing cross-sectional stress and other volume-dependent parameters to be estimated with greater accuracy. C1 [Cheuk, Ming L.; Anderson, Alexander J.; Han, June-Chiew; Ruddy, Bryan P.; Loiselle, Denis S.; Nielsen, Poul M. F.; Taberner, Andrew J.] Univ Auckland, Auckland Bioengn Inst, Auckland 1010, New Zealand. [Lippok, Norman] Harvard Med Sch, Boston, MA USA. [Lippok, Norman] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Vanholsbeeck, Frederique] Univ Auckland, Dept Phys, Auckland 1, New Zealand. [Ruddy, Bryan P.; Nielsen, Poul M. F.; Taberner, Andrew J.] Univ Auckland, Dept Engn Sci, Auckland 1, New Zealand. [Loiselle, Denis S.] Univ Auckland, Dept Physiol, Auckland 1, New Zealand. RP Cheuk, ML (reprint author), Univ Auckland, Auckland Bioengn Inst, Auckland 1010, New Zealand. EM ming.cheuk@auckland.ac.nz FU Marsden Fund Council [UOA1108]; Heart Foundation of New Zealand [1601, 1611] FX This work was supported in part by the Marsden Fund Council, administered by the Royal Society of New Zealand under Grant #UOA1108 and in part by the Heart Foundation of New Zealand under Grant #1601 and Grant #1611. NR 25 TC 0 Z9 0 U1 1 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 EI 1558-2531 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JAN PY 2017 VL 64 IS 1 BP 218 EP 224 DI 10.1109/TBME.2016.2553154 PG 7 WC Engineering, Biomedical SC Engineering GA EH4IZ UT WOS:000391736200022 PM 27093310 ER PT J AU Di Marco, A Anguera, I Schmitt, M Klem, I Neilan, T White, JA Sramko, M Masci, PG Barison, A Mckenna, P Mordi, I Haugaa, KH Leyva, F Capitan, JR Satoh, H Nabeta, T Dallaglio, PD Campbell, NG Sabate, X Cequier, A AF Di Marco, Andrea Anguera, Ignasi Schmitt, Matthias Klem, Igor Neilan, Thomas White, James A. Sramko, Marek Masci, Pier Giorgio Barison, Andrea Mckenna, Peter Mordi, Ify Haugaa, Kristina H. Leyva, Francisco Rodriguez Capitan, Jorge Satoh, Hiroshi Nabeta, Takeru Domenico Dallaglio, Paolo Campbell, Niall G. Sabate, Xavier Cequier, Angel TI Late Gadolinium Enhancement and the Risk for Ventricular Arrhythmias or Sudden Death in Dilated Cardiomyopathy Systematic Review and Meta-Analysis SO JACC-HEART FAILURE LA English DT Review DE cardiac magnetic resonance; dilated cardiomyopathy; late gadolinium enhancement; sudden death; ventricular arrhythmias ID CARDIAC MAGNETIC-RESONANCE; IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; NONISCHEMIC CARDIOMYOPATHY; MYOCARDIAL FIBROSIS; RESYNCHRONIZATION THERAPY; HEART-FAILURE; PROGNOSTIC VALUE; PRIMARY PREVENTION; EJECTION FRACTION; TACHYCARDIA AB OBJECTIVES The aim of this study was to evaluate the association between late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging and ventricular arrhythmias or sudden cardiac death (SCD) in patients with dilated cardiomyopathy (DCM). BACKGROUND Risk stratification for SCD in DCM needs to be improved. METHODS A systematic review and meta-analysis were conducted. A systematic search of PubMed and Ovid was performed, and observational studies that analyzed the arrhythmic endpoint (sustained ventricular arrhythmia, appropriate implantable cardioverter-defibrillator [ICD] therapy, or SCD) in patients with DCM, stratified by the presence or absence of LGE, were included. RESULTS Twenty-nine studies were included, accounting for 2,948 patients. The studies covered a wide spectrum of DCM, with a mean left ventricular ejection fraction between 20% and 43%. LGE was significantly associated with the arrhythmic endpoint both in the overall population (odds ratio: 4.3; p < 0.001) and when including only those studies that performed multivariate analysis (hazard ratio: 6.7; p < 0.001). The association between LGE and the arrhythmic endpoint remained significant among studies with mean left ventricular ejection fractions >35% (odds ratio: 5.2; p < 0.001) and was maximal in studies that included only patients with primary prevention ICDs (odds ratio: 7.8; p = 0.008). CONCLUSIONS Across a wide spectrum of patients with DCM, LGE is strongly and independently associated with ventricular arrhythmia or SCD. LGE could be a powerful tool to improve risk stratification for SCD in patients with DCM. These results raise 2 major questions to be addressed in future studies: whether patients with LGE could benefit from primary prevention ICDs irrespective of their left ventricular ejection fractions, while patients without LGE might not need preventive ICDs despite having severe left ventricular dysfunction. (C) 2017 by the American College of Cardiology Foundation. C1 [Di Marco, Andrea; Anguera, Ignasi; Domenico Dallaglio, Paolo; Sabate, Xavier; Cequier, Angel] Bellvitge Univ Hosp, Heart Dis Inst, Arrhythmia Unit, Calle Feixa Llarga S-N, Barcelona 08907, Spain. [Schmitt, Matthias; Campbell, Niall G.] Univ South Manchester Hosp, Manchester, Lancs, England. [Klem, Igor] Duke Univ, Med Ctr, Duke Cardiovasc Magnet Resonance Ctr, Durham, NC USA. [Neilan, Thomas] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Neilan, Thomas] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [White, James A.] Libin Cardiovasc Inst Alberta, Stephenson CMR Ctr, Calgary, AB, Canada. [Sramko, Marek] Inst Clin & Expt Med, Dept Cardiol, Prague, Czech Republic. [Masci, Pier Giorgio] Univ Lausanne Hosp, Ctr Cardiovasc Magnet Resonance, Lausanne, Switzerland. [Barison, Andrea] CNR Reg Toscana, Fdn G Monasterio, Pisa, Italy. [Mckenna, Peter] FIDMAG Germanes Hosp Res Fdn, Barcelona, Spain. [Mordi, Ify] Univ Glasgow, Inst Cardiovasc & Med Sci, BHF Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Haugaa, Kristina H.] Oslo Univ Hosp, Dept Cardiol, Oslo, Norway. [Leyva, Francisco] Queen Elizabeth Hosp, Dept Cardiol, Birmingham, W Midlands, England. [Rodriguez Capitan, Jorge] Antequera Hosp, Malaga, Spain. [Satoh, Hiroshi] Hamamatsu Univ Hosp, Internal Med 3, Div Cardiol, Hamamatsu, Shizuoka, Japan. [Nabeta, Takeru] Kitasato Univ, Sch Med, Dept Cardiovasc Med, Tokyo, Japan. RP Di Marco, A (reprint author), Bellvitge Univ Hosp, Heart Dis Inst, Arrhythmia Unit, Calle Feixa Llarga S-N, Barcelona 08907, Spain. EM ayfanciu@hotmail.com OI Rodriguez Capitan, Jorge/0000-0001-6650-6264 FU Biotronik FX Dr. Di Marco is an Advanced European Heart Rhythm Association Fellow with a grant funded by Biotronik. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. NR 50 TC 1 Z9 1 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 JAN PY 2017 VL 5 IS 1 BP 28 EP 38 DI 10.1016/j.jchf.2016.09.017 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EH1JD UT WOS:000391520500005 ER PT J AU Singh, JP Thomas, SS AF Singh, Jagmeet P. Thomas, Sunu S. TI Atrial Fibrillation and Heart Failure Prevention Do We Need a Risk Score? SO JACC-HEART FAILURE LA English DT Editorial Material DE atrial fibrillation; heart failure; heart failure with preserved ejection fraction; outcomes C1 [Singh, Jagmeet P.; Thomas, Sunu S.] Harvard Med Sch, Div Cardiol, Massachusetts Gen Hosp, Boston, MA USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Ctr Heart, Div Cardiol, 55 Fruit St,GRB 842, Boston, MA 02114 USA. EM jsingh@mgh.harvard.edu NR 5 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 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JAN PY 2017 VL 5 IS 1 BP 53 EP 55 DI 10.1016/j.jchf.2016.11.005 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EH1JD UT WOS:000391520500008 PM 28034377 ER PT J AU Conway, CR George, MS Sackeim, HA AF Conway, Charles R. George, Mark S. Sackeim, Harold A. TI Toward an Evidence-Based, Operational Definition of Treatment-Resistant Depression When Enough Is Enough SO JAMA PSYCHIATRY LA English DT Editorial Material ID OUTCOMES; TERM C1 [Conway, Charles R.] Washington Univ, Sch Med, 660 S Euclid Ave,Campus Box 8134, St Louis, MO 63110 USA. [Conway, Charles R.] John Cochran Vet Affairs Med Ctr, St Louis, MO USA. [George, Mark S.] Med Univ South Carolina, Charleston, SC USA. [George, Mark S.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Sackeim, Harold A.] Columbia Univ, New York, NY USA. RP Conway, CR (reprint author), Washington Univ, Sch Med, 660 S Euclid Ave,Campus Box 8134, St Louis, MO 63110 USA. EM conwayc@psychiatry.wustl.edu FU Bristol-Myers Squibb; Stanley Medical Research Institute; National Institute of Mental Health; NeoSync; Cyberonics; Taylor Family Institute for Innovative Psychiatric Research; August Busch IV Foundation; Barnes-Jewish Hospital Foundation; Brainsway; Cervel/NeoStim; MECTA; Neuronetics FX Dr Conway has received research support from Bristol-Myers Squibb, the Stanley Medical Research Institute, the National Institute of Mental Health, NeoSync, Cyberonics, Taylor Family Institute for Innovative Psychiatric Research, August Busch IV Foundation, and Barnes-Jewish Hospital Foundation. He previously served as a speaker for Bristol-Myers Squibb and Otsuka Pharmaceuticals. He has served as an unpaid consultant to Cyberonics. Dr George has no equity ownership in any device or pharmaceutical company. He does occasionally consult with industry, although he has not accepted consulting fees from anyone who manufactures a transcranial magnetic stimulation device, because of his role in National Institutes of Health and US Department of Veterans Affairs studies evaluating this technology. His total industry-related compensation per year is less than 10% of his total university salary. He has consulted (unpaid) to BrainSonix, Brainsway, Cervel/NeoStim, MECTA, Neuronetics, NeoSync, and Nervive. He has consulted to PureTech Ventures and is a data and safety monitoring board member of MicroTransponder. He has received research grant funding or equipment from Brainsway, Cervel/NeoStim, MECTA, Neuronetics, and NeoSync. He is a journal editor for Elsevier Press. Dr Sackeim has consulted to Brainsway, Cyberonics, Eli Lilly, Magstim, MECTA, Neosync, Neuronetics, NeuroPace, Novartis, and Pfizer. NR 7 TC 2 Z9 2 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JAN PY 2017 VL 74 IS 1 BP 9 EP 10 DI 10.1001/jamapsychiatry.2016.2586 PG 2 WC Psychiatry SC Psychiatry GA EH9UQ UT WOS:000392117300003 PM 27784055 ER PT J AU Resick, PA Wachen, JS Dondanville, KA Pruiksma, KE Yarvis, JS Peterson, AL Mintz, J AF Resick, Patricia A. Wachen, Jennifer Schuster Dondanville, Katherine A. Pruiksma, Kristi E. Yarvis, Jeffrey S. Peterson, Alan L. Mintz, Jim CA STRONG STAR Consortium TI Effect of Group vs Individual Cognitive Processing Therapy in Active-Duty Military Seeking Treatment for Posttraumatic Stress Disorder A Randomized Clinical Trial SO JAMA PSYCHIATRY LA English DT Article ID PSYCHOTHERAPY; PTSD; VETERANS; HEALTH; METAANALYSIS; AFGHANISTAN; SURVIVORS; EFFICACY; VIOLENCE; VICTIMS AB IMPORTANCE Cognitive processing therapy (CPT), an evidence-based treatment for posttraumatic stress disorder (PTSD), has not been tested as an individual treatment among active-duty military. Group CPT may be an efficient way to deliver treatment. OBJECTIVE To determine the effects of CPT on PTSD and co-occurring symptoms and whether they differ when administered in an individual or a group format. DESIGN, SETTING, AND PARTICIPANTS In this randomized clinical trial, 268 active-duty servicemembers consented to assessment at an army medical center from March 8, 2012, to September 23, 2014, and were randomized to group or individual CPT. Inclusion criteria were PTSD after military deployment and stable medication therapy. Exclusion criteria consisted of suicidal or homicidal intent or psychosis. Data collection was completed on June 15, 2015. Analysis was based on intention to treat. INTERVENTIONS Participants received CPT (the version excluding written accounts) in 90-minute group sessions of 8 to 10 participants (15 cohorts total; 133 participants) or 60-minute individual sessions (135 participants) twice weekly for 6 weeks. The 12 group and individual sessions were conducted concurrently. MAIN OUTCOMES AND MEASURES Primary measures were scores on the Posttraumatic Symptom Scale-Interview Version (PSS-I) and the stressor-specific Posttraumatic Stress Disorder Checklist (PCL-S); secondary measures were scores on the Beck Depression Inventory-II (BDI-II) and the Beck Scale for Suicidal Ideation (BSSI). Assessments were completed by independent evaluators masked to treatment condition at baseline and 2 weeks and 6 months after treatment. RESULTS Among the 268 participants (244 men [91.0%]; 24women [9.0%]; mean [SD] age, 33.2 [7.4] years), improvement in PTSD severity at posttreatment was greater when CPT was administered individually compared with the group format (mean [SE] difference on the PSS-I, -3.7 [1.4]; Cohen d = 0.6; P=.006). Significant improvements were maintained with the individual (mean [SE] PSS-I, -7.8 [1.0]; Cohen d = 1.3; mean [SE] PCL-S, -12.6 [1.4]; Cohen d = 1.2) and group (mean [SE] PSS-I, -4.0 [0.97]; Cohen d = 0.7; mean [SE] PCL-S, -6.3 [1.4]; Cohen d = 0.6) formats, with no differences in remission or severity of PTSD at the 6-month follow-up. Symptoms of depression and suicidal ideation did not differ significantly between formats. CONCLUSIONS AND RELEVANCE Individual treatment resulted in greater improvement in PTSD severity than group treatment. Depression and suicidal ideation improved equally with both formats. However, even among those receiving individual CPT, approximately 50% still had PTSD and clinically significant symptoms. In the military population, improving existing treatments such as CPT or developing new treatments is needed. C1 [Resick, Patricia A.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 1121 W Chapel Hill St,Ste 201, Durham, NC 27701 USA. [Wachen, Jennifer Schuster] Vet Affairs Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder, Boston, MA USA. [Wachen, Jennifer Schuster] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Dondanville, Katherine A.; Pruiksma, Kristi E.; Peterson, Alan L.; Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Dondanville, Katherine A.; Pruiksma, Kristi E.; Peterson, Alan L.; Mintz, Jim] South Texas Vet Hlth Care Syst, Off Res & Dev, San Antonio, TX USA. [Yarvis, Jeffrey S.] Carl R Darnall Army Med Ctr, Dept Behav Hlth, Ft Hood, TX USA. [Peterson, Alan L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychol, San Antonio, TX 78229 USA. [Mintz, Jim] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA. RP Resick, PA (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, 1121 W Chapel Hill St,Ste 201, Durham, NC 27701 USA. EM patricia.resick@duke.edu FU US Department of Defense through the US Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs; Psychological Health and Traumatic Brain Injury Research Program [W81XWH-08-02-0116, W81XWH-08-02-109, W81XWH-08-02-0114] FX This study was supported by the US Department of Defense through the US Army Medical Research and Materiel Command, Congressionally Directed Medical Research Programs, and awards W81XWH-08-02-0116 (Dr Resick), W81XWH-08-02-109 (Dr Peterson), and W81XWH-08-02-0114 (Brett Litz, PhD) from the Psychological Health and Traumatic Brain Injury Research Program. NR 40 TC 1 Z9 1 U1 10 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JAN PY 2017 VL 74 IS 1 BP 28 EP 36 DI 10.1001/jamapsychiatry.2016.2729 PG 9 WC Psychiatry SC Psychiatry GA EH9UQ UT WOS:000392117300009 PM 27893032 ER PT J AU Thomas, ML Green, MF Hellemann, G Sugar, CA Tarasenko, M Calkins, ME Greenwood, TA Gur, RE Gur, RC Lazzeroni, LC Nuechterlein, KH Radant, AD Seidman, LJ Shiluk, AL Siever, LJ Silverman, J Sprock, J Stone, WS Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Braff, DL Light, GA AF Thomas, Michael L. Green, Michael F. Hellemann, Gerhard Sugar, Catherine A. Tarasenko, Melissa Calkins, Monica E. Greenwood, Tiffany A. Gur, Raquel E. Gur, Ruben C. Lazzeroni, Laura C. Nuechterlein, Keith H. Radant, Allen D. Seidman, Larry J. Shiluk, Alexandra L. Siever, Larry J. Silverman, JeremyM. Sprock, Joyce Stone, William S. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Braff, David L. Light, Gregory A. TI Modeling Deficits From Early Auditory Information Processing to Psychosocial Functioning in Schizophrenia SO JAMA PSYCHIATRY LA English DT Article ID MISMATCH NEGATIVITY DEFICITS; RANDOMIZED CONTROLLED-TRIAL; SOCIAL COGNITION; NEUROCOGNITIVE DEFICITS; WORKING-MEMORY; VERBAL MEMORY; PERFORMANCE; SYMPTOMS; BIOMARKERS; MMN AB IMPORTANCE Neurophysiologic measures of early auditory information processing (EAP) are used as endophenotypes in genomic studies and biomarkers in clinical intervention studies. Research in schizophrenia has established correlations among measures of EAP, cognition, clinical symptoms, and functional outcome. Clarifying these associations by determining the pathways through which deficits in EAP affect functioning would suggest when and where to therapeutically intervene. OBJECTIVES To characterize the pathways from EAP to outcome and to estimate the extent to which enhancement of basic information processing might improve cognition and psychosocial functioning in schizophrenia. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional data were analyzed using structural equation modeling to examine the associations among EAP, cognition, negative symptoms, and functional outcome. Participants were recruited from the community at 5 geographically distributed laboratories as part of the Consortium on the Genetics of Schizophrenia 2 from July 1, 2010, through January 31, 2014. This well-characterized cohort of 1415 patients with schizophrenia underwent EAP, cognitive, and thorough clinical and functional assessment. MAIN OUTCOME AND MEASURES Mismatch negativity, P3a, and reorienting negativity were used to measure EAP. Cognition was measured by the Letter Number Span test and scales from the California Verbal Learning Test-Second Edition, the Wechsler Memory Scale-Third Edition, and the Penn Computerized Neurocognitive Battery. Negative symptoms were measured by the Scale for the Assessment of Negative Symptoms. Functional outcome was measured by the Role Functioning Scale. RESULTS Participants included 1415 unrelated outpatients diagnosed with schizophrenia or schizoaffective disorder (mean [SD] age, 46 [11] years; 979 males [69.2%] and 619 white [43.7%]). Early auditory information processing had a direct effect on cognition (beta = 0.37, P<.001), cognition had a direct effect on negative symptoms (beta = -0.16, P<.001), and both cognition (beta = 0.26, P <.001) and experiential negative symptoms (beta = -0.75, P <.001) had direct effects on functional outcome. The indirect effect of EAP on functional outcome was significant as well (beta = 0.14, P <.001). Overall, EAP had a fully mediated effect on functional outcome, engaging general rather than modality-specific cognition, with separate pathways that involved or bypassed negative symptoms. CONCLUSIONS AND RELEVANCE The data support a model in which EAP deficits lead to poor functional outcome via impaired cognition and increased negative symptoms. Results can be used to help guide mechanistically informed, personalized treatments and support the strategy of using EAP measures as surrogate end points in early-stage procognitive intervention studies. C1 [Thomas, Michael L.; Tarasenko, Melissa; Greenwood, Tiffany A.; Shiluk, Alexandra L.; Sprock, Joyce; Swerdlow, Neal R.; Tsuang, Debby W.; Braff, David L.; Light, Gregory A.] Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. [Thomas, Michael L.; Tarasenko, Melissa; Light, Gregory A.] Vet Affairs VA San Diego Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 22, San Diego, CA USA. [Green, Michael F.; Hellemann, Gerhard; Nuechterlein, Keith H.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Green, Michael F.; Hellemann, Gerhard] VA Greater Los Angeles Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr 22, Los Angeles, CA USA. [Sugar, Catherine A.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. [Calkins, Monica E.; Gur, Raquel E.; Gur, Ruben C.; Turetsky, Bruce I.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Lazzeroni, Laura C.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. [Radant, Allen D.; Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Radant, Allen D.; Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, VISN Mental Illness Res Educ & Clin Ctr 20, Seattle, WA USA. [Seidman, Larry J.; Stone, William S.] Harvard Med Sch, Dept Psychiat, Boston, MA USA. [Seidman, Larry J.; Stone, William S.] Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02215 USA. [Siever, Larry J.; Silverman, JeremyM.] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Siever, Larry J.; Silverman, JeremyM.] James J Peters VA Med Ctr, VISN Mental Illness Res Educ & Clin Ctr 3, New York, NY USA. [Tsuang, Ming T.] Univ Calif San Diego, Ctr Behav Genom, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA. [Tsuang, Ming T.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. [Tsuang, Ming T.] VA Puget Sound Hlth Care Syst, VISN Geriatr Res Educ & Clin Ctr 20, Seattle, WA USA. RP Thomas, ML (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,MC 0738, La Jolla, CA 92093 USA. EM mlthomas@ucsd.edu FU University of California, San Diego [R01-MH065571, R01-MH042228, R01-MH079777, K01-MH087889, K23-MH102420]; Mount Sinai School of Medicine [R01-MH065554]; University of California, Los Angeles [R01-MH65707]; University of Pennsylvania [R01-MH65578]; University of Washington [R01-MH65558] FX This work was supported in part by grants R01-MH065571 (Dr Braff), R01-MH042228 (Dr Braff), R01-MH079777 (Dr Light), K01-MH087889 (Dr Greenwood), and K23-MH102420 (Dr Thomas) from the University of California, San Diego; grant R01-MH065554 (Dr Siever) from Mount Sinai School of Medicine; grant R01-MH65707 (Dr Green) from University of California, Los Angeles; grant R01-MH65578 (Dr R. C. Gur) from the University of Pennsylvania; and grant R01-MH65558 (Dr Tsuang) from the University of Washington. NR 83 TC 1 Z9 1 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JAN PY 2017 VL 74 IS 1 BP 37 EP 46 DI 10.1001/jamapsychiatry.2016.2980 PG 10 WC Psychiatry SC Psychiatry GA EH9UQ UT WOS:000392117300010 PM 27926742 ER PT J AU Mehta, D AF Mehta, Darshan TI Breast Cancer Survivorship: What Are We Waiting For? SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Editorial Material C1 [Mehta, Darshan] Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA. [Mehta, Darshan] Harvard Med Sch, Osher Ctr Integrat Med, Educ, Boston, MA 02115 USA. [Mehta, Darshan] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mehta, D (reprint author), Massachusetts Gen Hosp, Benson Henry Inst Mind Body Med, Boston, MA 02114 USA.; Mehta, D (reprint author), Harvard Med Sch, Osher Ctr Integrat Med, Educ, Boston, MA 02115 USA.; Mehta, D (reprint author), Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 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 1075-5535 EI 1557-7708 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD JAN PY 2017 VL 23 IS 1 BP 6 EP 6 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA EH5ZE UT WOS:000391851000004 ER PT J AU Quarmley, M Moberg, PJ Mechanic-Hamilton, D Kabadi, S Arnold, SE Wolk, DA Roalf, DR AF Quarmley, Megan Moberg, Paul J. Mechanic-Hamilton, Dawn Kabadi, Sushila Arnold, Steven E. Wolk, David A. Roalf, David R. TI Odor Identification Screening Improves Diagnostic Classification in Incipient Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; mild cognitive impairment; Montreal Cognitive Assessment; odor identification; smell; Sniffin' Sticks Olfactory Identification Test ID MILD COGNITIVE IMPAIRMENT; OLFACTORY IDENTIFICATION; PARKINSONS-DISEASE; DEMENTIA; COMMUNITY; SUBTYPES; DEFICIT; DISCRIMINATION; HIPPOCAMPAL; THRESHOLDS AB Background: Measurements of olfaction may serve as useful biomarkers of incipient dementia. Here we examine the improvement in diagnostic accuracy of Alzheimer's disease (AD) and mild cognitive impairment (MCI) when assessing both cognitive functioning and odor identification. Objective: To determine the utility of odor identification as a supplementary screening test in incipient AD. Methods: Sniffin' Sticks Odor Identification Test (SS-OIT) and the Montreal Cognitive Assessment (MoCA) were administered in 262 AD, 174 MCI [150 amnestic (aMCI), and 24 non-amnestic (naMCI)], and 292 healthy older adults (HOA). Results: Odor identification scores were higher in HOA relative to MCI or AD groups, and MCI outperformed AD. Odor identification scores were higher in aMCI single domain than aMCI multiple domain. Complementing MoCA scores with the SS-OIT significantly improved diagnostic accuracy of individuals with AD and MCI, including within MCI subgroups. Discussion: Odor identification is a useful supplementary screening tool that provides additional information relevant for clinical categorization of AD and MCI, including those who are at highest risk to convert to AD. C1 [Quarmley, Megan; Moberg, Paul J.; Kabadi, Sushila; Roalf, David R.] Dept Psychiat, Philadelphia, PA USA. [Moberg, Paul J.; Mechanic-Hamilton, Dawn; Wolk, David A.] Dept Neurol, Philadelphia, PA USA. [Moberg, Paul J.; Mechanic-Hamilton, Dawn; Wolk, David A.] Univ Penn, Alzheimers Dis Ctr, Perelman Sch Med, Philadelphia, PA 19104 USA. [Arnold, Steven E.] Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. RP Roalf, DR (reprint author), Univ Penn, Dept Psychiat, Neuropsychiat, 3400 Spruce St,Gates Bldg 10th Floor, Philadelphia, PA 19104 USA. EM roalf@upenn.edu FU NIMH [K01 MH102609]; NIA [P30 AG10124]; University of Pennsylvania Center of Excellence for Research on Neurodegenerative Diseases (CERND) FX This work was supported by NIMH [K01 MH102609 (DRR)]; NIA [P30 AG10124]; and the University of Pennsylvania Center of Excellence for Research on Neurodegenerative Diseases (CERND). NR 42 TC 0 Z9 0 U1 7 U2 7 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2017 VL 55 IS 4 BP 1497 EP 1507 DI 10.3233/JAD-160842 PG 11 WC Neurosciences SC Neurosciences & Neurology GA EH1JQ UT WOS:000391523200021 PM 27886011 ER PT J AU Hammerness, P Petty, C Faraone, SV Biederman, J AF Hammerness, Paul Petty, Carter Faraone, Stephen V. Biederman, Joseph TI Do Stimulants Reduce the Risk for Alcohol and Substance Use in Youth With ADHD? A Secondary Analysis of a Prospective, 24-Month Open-Label Study of Osmotic-Release Methylphenidate SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE stimulant; ADHD; substance use ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; USE SCREENING INVENTORY; FOLLOW-UP; DRUG-USE; ABUSE; ADOLESCENTS; OUTCOMES; THERAPY; ADULTS AB Objective: The purpose of this study was to examine the impact of stimulant treatment on risk for alcohol and illicit drug use in adolescents with ADHD. Method: Analysis of data derived from a prospective open-label treatment study of adolescent ADHD (n = 115, 76% male), and a historical, naturalistic sample of ADHD (n = 44, 68% male) and non-ADHD youth (n = 52, 73% male) of similar age and sex. Treatment consisted of extended-release methylphenidate in the clinical trial or naturalistic stimulant treatment. Self-report of alcohol and drug use was derived from a modified version of the Drug Use Screening Inventory. Results: Rates of alcohol and drug use in the past year were significantly lower in the clinical trial compared with untreated and treated naturalistic ADHD comparators, and similar to rates in non-ADHD comparators. Conclusion: Well-monitored stimulant treatment may reduce the risk for alcohol and substance use in adolescent ADHD. C1 [Hammerness, Paul; Petty, Carter; Biederman, Joseph] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hammerness, Paul; Petty, Carter; Biederman, Joseph] Harvard Med Sch, Boston, MA USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Syracuse, NY 13210 USA. RP Hammerness, P (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA.; Hammerness, P (reprint author), Harvard Med Sch, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM phammerness@partners.org FU Janssen Scientific Affairs FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Data derived from an Investigator Initiated Trial funded by Janssen Scientific Affairs (Clinical Trial Registration Number: NCT00181714). NR 23 TC 0 Z9 0 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 EI 1557-1246 J9 J ATTEN DISORD JI J. Atten. Disord. PD JAN PY 2017 VL 21 IS 1 BP 71 EP 77 DI 10.1177/1087054712468051 PG 7 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA EH5AA UT WOS:000391783800008 PM 23264367 ER PT J AU Wilens, TE McBurnett, K Turnbow, J Rugino, T White, C Youcha, S AF Wilens, Timothy E. McBurnett, Keith Turnbow, John Rugino, Thomas White, Carla Youcha, Sharon TI Morning and Evening Effects of Guanfacine Extended Release Adjunctive to Psychostimulants in Pediatric ADHD: Results From a Phase III Multicenter Trial SO JOURNAL OF ATTENTION DISORDERS LA English DT Article DE Intuniv; guanfacine XR; functioning; before school; after school ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DOUBLE-BLIND; ADDERALL-XR; CHILDREN; ADOLESCENTS; COMORBIDITY; PREVALENCE AB Objective: To examine efficacy and safety of adjunctive guanfacine extended release (GXR) on morning and evening ADHD symptoms using the Conners' Global Index-Parent (CGI-P) and Before-School Functioning Questionnaire (BSFQ). Method: Participants 6 to 17 years with ADHD (N = 461) and suboptimal psychostimulant response were maintained on current psychostimulants and randomized to dose-optimized GXR (4 mg/d) in the morning (GXR AM) or evening (GXR PM), or placebo. Results: CGI-P scores improved with GXR (morning assessment, GXR AM, placebo-adjusted least squares [LS] mean = -1.7, GXR PM = -2.6; evening assessment, GXR AM = -2.4, GXR PM = -3.0; all ps < .01). Parent-rated BSFQ scores reflected improved morning functioning with GXR (GXR AM, placebo-adjusted LS mean = -5.1; GXR PM = -4.7; both ps < .01). Most adverse events were mild or moderate. Conclusion: Adjunctive GXR AM or GXR PM was associated with improvements in morning and evening ADHD symptoms in children and adolescents. C1 [Wilens, Timothy E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Med Sch, YAW 6900,55 Fruit St, Boston, MA 02114 USA. [McBurnett, Keith] Univ Calif San Francisco, Langley Porter Psychiat Inst, Psychiat, San Francisco, CA USA. [Turnbow, John] Westex Clin Invest, Lubbock, TX USA. [Rugino, Thomas] Childrens Specialized Hosp, Toms River, NJ USA. [White, Carla] Shire Pharmaceut Dev Ltd, Basingstoke, Hants, England. [Youcha, Sharon] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Youcha, Sharon] Shire Dev LLC, Wayne, PA USA. RP Wilens, TE (reprint author), Harvard Med Sch, YAW 6900,55 Fruit St, Boston, MA 02114 USA.; Wilens, TE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org FU Shire Development LLC FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Clinical research was funded by the sponsor, Shire Development LLC. Shire Development LLC provided funding to SCI and MedErgy for support in writing and editing this manuscript. NR 24 TC 0 Z9 0 U1 7 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0547 EI 1557-1246 J9 J ATTEN DISORD JI J. Atten. Disord. PD JAN PY 2017 VL 21 IS 2 BP 110 EP 119 DI 10.1177/1087054713500144 PG 10 WC Psychology, Developmental; Psychiatry SC Psychology; Psychiatry GA EH5AB UT WOS:000391783900003 PM 24071772 ER PT J AU Cancio, LC Sheridan, RL Dent, R Hjalmarson, SG Gardner, E Matherly, AF Bebarta, VS Palmieri, T AF Cancio, Leopoldo C. Sheridan, Robert L. Dent, Rob Hjalmarson, Sarah Gene Gardner, Emmie Matherly, Annette F. Bebarta, Vikhyat S. Palmieri, Tina TI Guidelines for Burn Care Under Austere Conditions: Special Etiologies: Blast, Radiation, and Chemical Injuries SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID INDUCED LUNG INJURY; COLONY-STIMULATING FACTOR; TRAUMATIC BRAIN-INJURY; CHLORINE GAS; HYDROGEN-SULFIDE; SULFUR MUSTARD; INHALATION INJURY; EMERGENCY-DEPARTMENT; COMBAT EXPLOSIONS; ENDURING FREEDOM C1 [Cancio, Leopoldo C.; Bebarta, Vikhyat S.] US Army Inst Surg Res, Ft Sam Houston, TX USA. [Sheridan, Robert L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Dent, Rob; Matherly, Annette F.] Univ Utah, Burn Ctr, Salt Lake City, UT USA. [Hjalmarson, Sarah Gene] Primary Childrens Med Ctr, Salt Lake City, UT USA. [Gardner, Emmie] Intermt Hlth Care, Salt Lake City, UT USA. [Palmieri, Tina] Univ Calif Davis, Reg Burn Ctr, Sacramento, CA 95817 USA. [Palmieri, Tina] Shriners Hosp Children, Sacramento, CA 95817 USA. RP Palmieri, T (reprint author), Univ Calif Davis, Reg Burn Ctr, Sacramento, CA 95817 USA.; Palmieri, T (reprint author), Shriners Hosp Children, Sacramento, CA 95817 USA. EM tina.palmieri@ucdmc.ucdavis.edu RI Siry, Bonnie/D-7189-2017 FU U.S. Department of Energy [DE-AC05-06OR23100] FX Special thanks to Doran M. Christensen, Senior Medical Advisor, at the Radiation Emergency Assistance Center/Training Site (REAC/TS) for his assistance with this article. Work provided by Dr. Christensen and REAC/TS were provided under contract with the U.S. Department of Energy, Contract # DE-AC05-06OR23100. NR 98 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 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E482 EP E496 DI 10.1097/BCR.0000000000000367 PG 15 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500061 PM 27355658 ER PT J AU Goverman, J Mathews, K Goldstein, R Holavanahalli, R Kowalske, K Esselman, P Gibran, N Suman, O Herndon, D Ryan, CM Schneider, JC AF Goverman, Jeremy Mathews, Katie Goldstein, Richard Holavanahalli, Radha Kowalske, Karen Esselman, Peter Gibran, Nicole Suman, Oscar Herndon, David Ryan, Colleen M. Schneider, Jeffrey C. TI Adult Contractures in Burn Injury: A Burn Model System National Database Study SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID JOINT CONTRACTURE; SCAR CONTRACTURE; PRINCIPLES; MANAGEMENT; THERAPY AB As the overall survival rate for burn injury has improved, increased emphasis is placed on postburn morbidity and the optimization of functional and cosmetic outcomes. One major cause of morbidity and functional deficits is that of joint contractures. The true incidence of postburn contractures and their associated risk factors remains unknown. This study examines the incidence and severity of contractures in a large, multicenter, burn population. The associated risk factors for the development of contractures are determined. Data from the National Institute on Disability and Rehabilitation Research Burn Model System database, for adult burn survivors from 1994 to 2003, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures included the presence of contractures, number of contractures per patient, and severity of contractures at each of nine locations (shoulder, elbow, hip, knee, ankle, wrist, neck, lumbar spine, and thoracic spine) at time of hospital discharge. Regression analysis was performed to determine predictors of the presence, severity, and numbers of contractures, with P<.05 used for statistical significance. Of the 1865 study patients, 620 (33%) developed at least 1 contracture at hospital discharge. Among those with at least one contracture, the mean is three (3.38) contractures per person. The shoulder was the most frequently contracted joint (23.0%), followed by the elbow (19.9%), wrist (17.3%), ankle (13.6%), and knee (13.4%). Most contractures were mild (47.2%) or moderate (32.9%) in severity. Statistically significant predictors of contracture development were male sex, black race, Hispanic ethnicity, medical problems, neuropathy, TBSA grafted, and TBSA burned. Predictors of the severity of contracture included male sex, black race, medical problems, neuropathy, TBSA grafted, and TBSA burned. Predictors of the number of contractures included male sex, medical problems, flash burn, neuropathy, TBSA burned, and TBSA grafted. Similar to a previous single-center study on postburn contractures, approximately one third of the patients with an eligible burn injury requiring autografting developed a contracture at hospital discharge. It is likely that these contractures develop despite early therapeutic interventions such as positioning and splinting; therefore, the challenge to the burn community remains, to identify new and better prevention strategies. C1 [Goverman, Jeremy; Ryan, Colleen M.; Schneider, Jeffrey C.] Massachusetts Gen Hosp, Surg Serv, Sumner Redstone Burn Ctr, Boston, MA 02114 USA. [Goverman, Jeremy; Mathews, Katie; Goldstein, Richard; Ryan, Colleen M.; Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02129 USA. [Goverman, Jeremy; Ryan, Colleen M.; Schneider, Jeffrey C.] Harvard Med Sch, Boston, MA 02115 USA. [Goverman, Jeremy; Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA 02114 USA. [Holavanahalli, Radha; Kowalske, Karen] Univ Texas Southwestern Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. [Esselman, Peter; Gibran, Nicole] Univ Washington, Dept Surg, Med Reg Burn Ctr, Seattle, WA 98195 USA. [Suman, Oscar; Herndon, David] Univ Texas Med Branch, Shriners Hosp Children, Galveston, TX 77555 USA. RP Schneider, JC (reprint author), Massachusetts Gen Hosp, Surg Serv, Sumner Redstone Burn Ctr, Boston, MA 02114 USA.; Schneider, JC (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02129 USA.; Schneider, JC (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Schneider, JC (reprint author), Shriners Hosp Children, Boston, MA 02114 USA. EM jcschneider@partners.org FU National Institute on Disability and Rehabilitation Research [H133A120034] FX Supported by the National Institute on Disability and Rehabilitation Research grant H133A120034. NR 29 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 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E328 EP E336 DI 10.1097/BCR.0000000000000380 PG 9 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500041 PM 27380122 ER PT J AU Goverman, J Mathews, K Goldstein, R Holavanahalli, R Kowalske, K Esselman, P Gibran, N Suman, O Herndon, D Ryan, CM Schneider, JC AF Goverman, Jeremy Mathews, Katie Goldstein, Richard Holavanahalli, Radha Kowalske, Karen Esselman, Peter Gibran, Nicole Suman, Oscar Herndon, David Ryan, Colleen M. Schneider, Jeffrey C. TI Pediatric Contractures in Burn Injury: A Burn Model System National Database Study SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID JOINT CONTRACTURE; SCAR CONTRACTURE; MANAGEMENT; EXPERIENCE; SPLINT; PREVENTION; PRINCIPLES; CHILDREN; THERAPY; HAND AB Joint contractures are a major cause of morbidity and functional deficit. The incidence of postburn contractures and their associated risk factors in the pediatric population has not yet been reported. This study examines the incidence and severity of contractures in a large, multicenter, pediatric burn population. Associated risk factors for the development of contractures are determined. Data from the National Institute on Disability and Rehabilitation Research Burn Model System database, for pediatric (younger than 18 years) burn survivors from 1994 to 2003, were analyzed. Demographic and medical data were collected on each subject. The primary outcome measures included the presence of contractures, number of contractures per patient, and severity of contractures at each of nine locations (shoulder, elbow, hip, knee, ankle, wrist, neck, lumbar, and thoracic) at time of hospital discharge. Regression analysis was performed to determine predictors of the presence, severity, and numbers of contractures, with P < .05 used for statistical significance. Of the 1031 study patients, 237 (23%) developed at least 1 contracture at hospital discharge. Among those with at least one contracture, the mean was three (3.3) contractures per person. The shoulder was the most frequently contracted joint (27.9%), followed by the elbow (17.6%), wrist (14.2%), knee (13.3%), and ankle (11.9%). Most contractures were mild (38.5%) or moderate (36.3%) in severity. The statistically significant predictors of contracture development were age and intensive care unit (ICU) length of stay. The statistically significant predictors of severity of contracture were age, ICU length of stay, presence of amputation, and black race. Predictors of the number of contractures included total age, length of stay, length of ICU stay, presence of amputation, TBSA burned, and TBSA grafted. This is the first study to report the epidemiology of postburn contractures in the pediatric population. Approximately one quarter of children with a major burn injury developed a contracture at hospital discharge, and this could potentially increase as the child grows. Contractures develop despite early therapeutic interventions such as positioning and splinting; therefore, it is essential that we identify novel and more effective prevention strategies. C1 [Goverman, Jeremy; Ryan, Colleen M.; Schneider, Jeffrey C.] Massachusetts Gen Hosp, Dept Surg, Div Burns, Sumner Redstone Burn Ctr,Surg Serv, Boston, MA 02114 USA. [Goverman, Jeremy; Mathews, Katie; Goldstein, Richard; Ryan, Colleen M.; Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Goverman, Jeremy; Ryan, Colleen M.; Schneider, Jeffrey C.] Harvard Med Sch, Boston, MA 02115 USA. [Goverman, Jeremy; Ryan, Colleen M.; Schneider, Jeffrey C.] Shriners Hosp Children, Boston, MA 02114 USA. [Holavanahalli, Radha; Kowalske, Karen] Univ Texas Southwestern Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. [Esselman, Peter; Gibran, Nicole] Univ Washington, Dept Surg, Med Reg Burn Ctr, Seattle, WA 98195 USA. [Suman, Oscar; Herndon, David] Univ Texas Med Branch, Shriners Hosp Children, Galveston, TX 77555 USA. RP Schneider, JC (reprint author), Harvard Med Sch, Boston, MA 02115 USA.; Schneider, JC (reprint author), Shriners Hosp Children, Boston, MA 02114 USA.; Schneider, JC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Schneider, JC (reprint author), Spaulding Rehabil Hosp, Boston, MA 02129 USA. EM jcschneider@partners.org FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0035] FX Supported by a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grant number 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this manuscript do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 54 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 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E192 EP E199 DI 10.1097/BCR.0000000000000341 PG 8 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500024 PM 27355656 ER PT J AU Goverman, J Mathews, K Holavanahalli, RK Vardanian, A Herndon, DN Meyer, WJ Kowalske, K Fauerbach, J Gibran, NS Carrougher, GJ Amtmann, D Schneider, JC Ryan, CM AF Goverman, Jeremy Mathews, Katie Holavanahalli, Radha K. Vardanian, Andrew Herndon, David N. Meyer, Walter J. Kowalske, Karen Fauerbach, Jim Gibran, Nicole S. Carrougher, Gretchen J. Amtmann, Dagmar Schneider, Jeffrey C. Ryan, Colleen M. TI The National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System: Twenty Years of Contributions to Clinical Service and Research SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID COMMUNITY INTEGRATION; VIRTUAL-REALITY; RISK-FACTORS; INJURY; PAIN; DISTRESS; SCALE; SATISFACTION; SURVIVORS; PRURITUS AB The National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) established the Burn Model System (BMS) in 1993 to improve the lives of burn survivors. The BMS program includes 1) a multicenter longitudinal database describing the functional and psychosocial recovery of burn survivors; 2) site-specific burn-related research; and 3) a knowledge dissemination component directed toward patients and providers. Output from each BMS component was analyzed. Database structure, content, and access procedures are described. Publications using the database were identified and categorized to illustrate the content area of the work. Unused areas of the database were identified for future study. Publications related to site-specific projects were cataloged. The most frequently cited articles are summarized to illustrate the scope of these projects. The effectiveness of dissemination activities was measured by quantifying website hits and information downloads. There were 25 NIDILRR-supported publications that utilized the database. These articles covered topics related to psychological outcomes, functional outcomes, community reintegration, and burn demographics. There were 172 site-specific publications; highly cited articles demonstrate a wide scope of study. For information dissemination, visits to the BMS website quadrupled between 2013 and 2014, with 124,063 downloads of educational material in 2014. The NIDILRR BMS program has played a major role in defining the course of burn recovery, and making that information accessible to the general public. The accumulating information in the database serves as a rich resource to the burn community for future study. The BMS is a model for collaborative research that is multidisciplinary and outcome focused. C1 [Goverman, Jeremy; Mathews, Katie; Vardanian, Andrew; Schneider, Jeffrey C.; Ryan, Colleen M.] Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Boston, MA 02114 USA. [Goverman, Jeremy; Vardanian, Andrew; Schneider, Jeffrey C.; Ryan, Colleen M.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Goverman, Jeremy; Vardanian, Andrew; Schneider, Jeffrey C.; Ryan, Colleen M.] Harvard Med Sch, Boston, MA USA. [Goverman, Jeremy; Vardanian, Andrew; Schneider, Jeffrey C.; Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. [Herndon, David N.; Meyer, Walter J.] Univ Texas Med Branch, Shriners Hosp Children, Galveston, TX 77555 USA. [Holavanahalli, Radha K.; Kowalske, Karen] Univ Texas Southwestern Med Ctr Dallas, Dept Phys Med & Rehabil, Dallas, TX 75390 USA. [Gibran, Nicole S.; Carrougher, Gretchen J.; Amtmann, Dagmar] Univ Washington, Dept Surg, Med Reg Burn Ctr, Seattle, WA 98195 USA. [Fauerbach, Jim] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Ryan, CM (reprint author), Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Surg Serv, Boston, MA 02114 USA. EM cryan@partners.org FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0035] FX The contents of this article were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR Grant Number 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this manuscript do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 53 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E240 EP E253 DI 10.1097/BCR.0000000000000361 PG 14 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500030 PM 27294859 ER PT J AU Hendricks, CT Camara, K Boole, KV Napoli, MF Goldstein, R Ryan, CM Schneider, JC AF Hendricks, Carla Tierney Camara, Kristin Boole, Kathryn Violick Napoli, Maureen F. Goldstein, Richard Ryan, Colleen M. Schneider, Jeffrey C. TI Burn Injuries and Their Impact on Cognitive-Communication Skills in the Inpatient Rehabilitation Setting SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID STROKE; POPULATION; IMPAIRMENT; OUTCOMES; ADMISSION AB The prevalence and extent of cognitive-communication disorders and factors that have impact on outcomes are examined in the burn population within an inpatient rehabilitation facility. A retrospective data analysis was conducted on adults diagnosed with burn injury (n = 144). Descriptive statistics were used to identify the prevalence of cognitive-communication deficits on admission and discharge. The main outcomes were cognitive-communication ratings on discharge from inpatient rehabilitation as measured by the memory and problem-solving domains of the Functional Independence Measure (FIM (R)) and composite score of the Functional Communication Measure (FCM). Medical, demographic and rehabilitation predictors of the main outcomes were assessed using regression analyses. On admission to inpatient rehabilitation, 79% of the total population presented with cognitive-communication impairments, and of them, 27% presented with persistent deficits on discharge. Admission FIM memory score, marital status, and age were significant predictors of discharge FIM memory score. Admission FIM problem-solving score, age, marital status, and prehospital living-with were significant predictors of discharge FIM problem-solving score. Admission FCM score and age were significant predictors of discharge FCM cognitive score. Persons with burn injuries are at risk for cognitive-communication impairments, which may persist after inpatient rehabilitation. FIM data obtained on admission can be used as a screening tool to identify these at-risk patients. Future work is needed to assess the efficacy of speech-language pathologist intervention for cognitive-communication deficits within the burn injury population. C1 [Hendricks, Carla Tierney; Camara, Kristin; Boole, Kathryn Violick; Napoli, Maureen F.] Spaulding Rehabil Hosp, Dept Speech Language Pathol, Boston, MA 02129 USA. [Napoli, Maureen F.] Massachusetts Gen Hosp, Dept Speech Language & Swallowing Disorders, Boston, MA 02114 USA. [Goldstein, Richard; Schneider, Jeffrey C.] Harvard Med Sch, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Ryan, Colleen M.] Harvard Med Sch, Massachusetts Gen Hosp, Sumner Redstone Burn Ctr, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children, Boston, MA USA. RP Hendricks, CT (reprint author), Spaulding Rehabil Hosp, Dept Speech Language Pathol, Boston, MA 02129 USA. EM ctierney@partners.org FU Department of Education, NIDRR [H133A120034] FX The contents of this study were developed under a grant from the Department of Education, NIDRR grant number H133A120034. However, these contents do not necessarily represent the policy of the Department of Education, and the reader should not assume endorsement by the Federal Government. NR 24 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 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E359 EP E369 DI 10.1097/BCR.0000000000000388 PG 11 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500045 PM 27404164 ER PT J AU Holzer, PW Leonard, DA Shanmugarajah, K Moulton, KN Ng, ZY Cetrulo, CL Sachs, DH AF Holzer, Paul W. Leonard, David A. Shanmugarajah, Kumaran Moulton, Krysta N. Ng, Zhi Yang Cetrulo, Curtis L., Jr. Sachs, David H. TI A Comparative Examination of the Clinical Outcome and Histological Appearance of Cryopreserved and Fresh Split-Thickness Skin Grafts SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID MINIATURE SWINE; TRANSPLANTATION; DRESSINGS; SURVIVAL; PORCINE; PIG AB The clinical use of frozen, human allogeneic skin grafts is considered a suitable alternative to freshly harvested allogeneic skin grafts when the latter are not available. However, limited functional and histological information exists regarding the effects of cryopreservation on allogeneic skin grafts, especially those across mismatched histocompatibility barriers. Thus, we performed a side-by-side comparative study of fresh vs frozen skin grafts, across both minor and major histocompatibility barriers, in a miniature swine model. Since porcine skin shares many physical and immunological properties with human skin, our findings have relevance to current clinical practices involving allogeneic grafting and may support future, temporary wound therapies involving frozen xenografts, comprised genetically modified porcine skin. Four miniature swine underwent harvest and grafting of split-thickness skin, with and without cryopreservation, in order to observe autologous grafts and grafts across minor and major histocompatibility barriers. A biopsy of the grafts was done at regular intervals for study of architecture, vascularization, and outcomes. All grafts vascularized without technical complications. Differences were noted in the early appearance of some fresh vs frozen grafts, but no significant difference was observed in overall survival times in any of the experimental groups. These results demonstrate that despite early observable differences in the healing process, cryopreservation and thawing does not significantly affect long-term graft survival or time to rejection, thus supporting the clinical and experimental use of fresh and frozen split-thickness skin grafts as comparable and interchangeable. C1 [Holzer, Paul W.; Leonard, David A.; Shanmugarajah, Kumaran; Moulton, Krysta N.; Ng, Zhi Yang; Cetrulo, Curtis L., Jr.; Sachs, David H.] Harvard Med Sch, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. RP Holzer, PW (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East Bldg,149-9019,13th St, Boston, MA 02129 USA. EM paul.holzer.med@dartmouth.edu FU Steward Health Care; Department of Defense [W81XWH-09-1-0419 DOD (DR080729)]; National Institute of Health [1C 06 RR 20135-01] FX The authors wish to acknowledge funding and research support from Steward Health Care, the Department of Defense Grant W81XWH-09-1-0419 DOD (DR080729), and the National Institute of Health Grant No. 1C 06 RR 20135-01. NR 25 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 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E55 EP E61 DI 10.1097/BCR.0000000000000431 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500009 PM 27606556 ER PT J AU Liu, YM Mathews, K Vardanian, A Bozkurt, T Schneider, JC Hefner, J Schulz, JT Fagan, SP Goverman, J AF Liu, Yuk Ming Mathews, Katie Vardanian, Andrew Bozkurt, Taylan Schneider, Jeffrey C. Hefner, Jaye Schulz, John T. Fagan, Shawn P. Goverman, Jeremy TI Urban Telemedicine: The Applicability of Teleburns in the Rehabilitative Phase SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID CARE; BURNS; IMPACT AB Telemedicine has been successfully used in many areas of medicine, including triage and evaluation of the acute burn patient. The utility of telemedicine during the rehabilitative phase of burn care has yet to be evaluated; therefore, we expanded our telemedicine program to link our burn center with a rehabilitation facility. The goal of this project was to demonstrate cost-effective improvements in the transition and quality of care. A retrospective review was performed on all patients enrolled in our telemedicine/rehabilitation program between March 2013 and March 2014. Data collected included total number of encounters, visits, type of visit, physician time, and readmissions. Transportation costs were based on local ambulance rates between the two facilities. The impact of telemedicine was evaluated with respect to the time saved for the physician, burn center, and burn clinic, as well as rehabilitative days saved. A patient satisfaction survey was also administered. A total of 29 patients participated in 73 virtual visits through the telemedicine project. Virtual visits included new consults, preoperative evaluations, and postoperative follow-ups. A total of 146 ambulance transports were averted during the study period, totaling $101,110. Virtual visits saved 6.8 outpatient burn clinic days, or 73 clinic appointments of 30-min duration. The ability to perform more outpatient surgery resulted in 80 inpatient bed days saved at the burn hospital. The rehabilitation hospital saved an average of 2 to 3 patient days secondary to unnecessary travel. Satisfaction surveys demonstrated patient satisfaction with the encounters, primarily related to time saved. The decrease in travel time for the patient from the rehabilitation hospital to outpatient burn clinic improved adherence to the rehabilitation care plan and resulted in increased throughput at the rehabilitation facility. Videoconferencing between a burn center and rehabilitation hospital streamlined patient care and reduced health care costs, while maintaining quality of care and patient satisfaction. This program has improved inpatient burn rehabilitation by maximizing time spent in therapy and avoiding unnecessary patient travel to offsite appointments. C1 [Liu, Yuk Ming; Mathews, Katie; Vardanian, Andrew; Bozkurt, Taylan; Schulz, John T.; Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Sumner Redstone Burn Ctr, Boston, MA 02114 USA. [Mathews, Katie; Schneider, Jeffrey C.; Hefner, Jaye] Spaulding Rehabil Hosp, Charlestown, MA USA. [Fagan, Shawn P.] Still Burn Ctr, Augusta, GA USA. RP Goverman, J (reprint author), Massachusetts Gen Hosp, Dept Surg, Sumner Redstone Burn Ctr, Boston, MA 02114 USA. EM jgoverman@partners.org FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0035] FX The contents of this manuscript were developed under a grant from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR Grant Number 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this manuscript do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E235 EP E239 DI 10.1097/BCR.0000000000000360 PG 5 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500029 PM 27294853 ER PT J AU Marino, M Soley-Bori, M Jette, AM Slavin, MD Ryan, CM Schneider, JC Acton, A Amaya, F Rossi, M Soria-Saucedo, R Resnik, L Kazis, LE AF Marino, Molly Soley-Bori, Marina Jette, Alan M. Slavin, Mary D. Ryan, Colleen M. Schneider, Jeffrey C. Acton, Amy Amaya, Flor Rossi, Melinda Soria-Saucedo, Rene Resnik, Linda Kazis, Lewis E. TI Measuring the Social Impact of Burns on Survivors SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID PERCEIVED STIGMATIZATION; COMMUNITY INTEGRATION; QUALITATIVE RESEARCH; BODY-IMAGE; LIFE; QUESTIONNAIRE; ADULTS; SCALE; VALIDATION; INSTRUMENT AB Many burn survivors experience social challenges throughout their recovery. Measuring the social impact of a burn injury is important to identify opportunities for interventions. The aim of this study is to develop a pool of items addressing the social impact of burn injuries in adults to create a self-reported computerized adaptive test based on item response theory. The authors conducted a comprehensive literature review to identify preexisting items in other self-reported measures and used data from focus groups to create new items. The authors classified items using a guiding conceptual framework on social participation. The authors conducted cognitive interviews with burn survivors to assess clarity and interpretation of each item. The authors evaluated an initial pool of 276 items with burn survivors and reduced this to 192 items after cognitive evaluation by experts and burn survivors. The items represent seven domains from the guiding conceptual model: work, recreation and leisure, relating to strangers, romantic, sexual, family, and informal relationships. Additional item content that crossed domains included using self-comfort and others' comfort with clothing, telling one's story, and sense of purpose. This study was designed to develop a large item pool based on a strong conceptual framework using grounded theory analysis with focus groups of burn survivors and their caregivers. The 192 items represent 7 domains and reflect the unique experience of burn survivors within these important areas of social participation. This work will lead to developing the Life Impact Burn Recovery Evaluation profile, a self-reported outcome measure. C1 [Marino, Molly; Jette, Alan M.; Slavin, Mary D.] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02215 USA. [Marino, Molly; Soley-Bori, Marina; Jette, Alan M.; Slavin, Mary D.; Amaya, Flor; Rossi, Melinda; Soria-Saucedo, Rene; Kazis, Lewis E.] Boston Univ, Sch Publ Hlth, Ctr Assessment Pharmaceut Practices, Dept Hlth Law Policy & Management, Boston, MA 02215 USA. [Ryan, Colleen M.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Ryan, Colleen M.; Schneider, Jeffrey C.] Harvard Med Sch, Boston, MA USA. [Ryan, Colleen M.] Shriners Hosp Children Boston, Boston, MA USA. [Schneider, Jeffrey C.] Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA USA. [Acton, Amy] Phoenix Soc Burn Survivors, Grand Rapids, MI USA. [Resnik, Linda] Providence VA Med Ctr, Providence, RI USA. [Resnik, Linda] Brown Univ, Providence, RI 02912 USA. RP Kazis, LE (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Law Policy & Management, 715 Albany St,Talbot Bldg,119W, Boston, MA 02116 USA. EM lek@bu.edu FU National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR) [90DP0055, 90DP0035] FX Supported by grants from the National Institute on Disability, Independent Living, and Rehabilitation Research (NIDILRR grants 90DP0055 and 90DP0035). NIDILRR is a Center within the Administration for Community Living (ACL), Department of Health and Human Services (HHS). The contents of this article do not necessarily represent the policy of NIDILRR, ACL, HHS, and you should not assume endorsement by the Federal Government. NR 40 TC 0 Z9 0 U1 9 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E377 EP E383 DI 10.1097/BCR.0000000000000398 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500047 PM 27380121 ER PT J AU Stoddard, FJ Sorrentino, E Drake, JE Murphy, JM Kim, AJ Romo, S Kagan, J Snidman, N Saxe, G Sheridan, RL AF Stoddard, Frederick J., Jr. Sorrentino, Erica Drake, Jennifer E. Murphy, J. Michael Kim, Abigail J. Romo, Stephanie Kagan, Jerome Snidman, Nancy Saxe, Glenn Sheridan, Robert L. TI Posttraumatic Stress Disorder Diagnosis in Young Children With Burns SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID PRESCHOOL-CHILDREN; BRAIN-DEVELOPMENT; ADOLESCENTS; TRAUMA; PTSD; ABUSE; PERFORMANCE; PREVALENCE; CHILDHOOD; INTERVIEW AB The primary aim of this study was to assess the prevalence of posttraumatic stress disorder (PTSD) in young children hospitalized for burns. A secondary aim was to assess partial PTSD in this population. PTSD diagnosis and symptoms were evaluated utilizing both the diagnostic interview for children and adolescents (DICA-P) module and the PTSD semistructured interview and observational report (PTSDSSI). PTSD symptomatology was assessed from parent interviews at 1 month after discharge from a major pediatric burn center. Four of the 42 participants who completed the DICA-P met full criteria for a diagnosis of PTSD (10%). Of the 39 who also completed the PTSDSSI, 1 (3%) met full criteria for PTSD diagnosis on that measure. Twenty-seven percentage of subjects met partial criteria on the DICA-P vs 16% on the PTSDSSI, without impairment. Furthermore, 67% of subjects met DICA-P criteria for the re-experiencing cluster and 54% met the PTSDSSI re-experiencing criteria. Although only a small percentage met full PTSD diagnostic criteria by either measure, a high percentage of young children with burns manifested some posttraumatic symptoms 1 month after discharge. Because PTSDSSI diagnosis is strongly linked to the diagnostic and statistical manual-5 (DSM-5) criteria for "PTSD in children 6 years and younger," these results may offer clues to current diagnoses of PTSD in young children. Future research is needed to improve care by determining the risk factors and course of PTSD to further refine the diagnostic criteria for identifying children most in need of intervention, such as those hospitalized for burn injuries. C1 [Stoddard, Frederick J., Jr.; Sorrentino, Erica; Drake, Jennifer E.; Murphy, J. Michael; Romo, Stephanie; Sheridan, Robert L.] Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. [Stoddard, Frederick J., Jr.; Murphy, J. Michael; Kim, Abigail J.; Sheridan, Robert L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stoddard, Frederick J., Jr.; Murphy, J. Michael; Kagan, Jerome; Snidman, Nancy; Sheridan, Robert L.] Harvard Med Sch, Boston, MA USA. [Saxe, Glenn] NYU, Langone Med Ctr, New York, NY USA. RP Stoddard, FJ (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM fstoddard@mgh.harvard.edu OI Saxe, Glenn/0000-0002-4756-1169 FU Shriners Hospitals for Children [8760] FX The study is supported by Grant # 8760 from the Shriners Hospitals for Children. NR 46 TC 0 Z9 0 U1 10 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1559-047X EI 1559-0488 J9 J BURN CARE RES JI J. Burn Care Res. PD JAN-FEB PY 2017 VL 38 IS 1 BP E343 EP E351 DI 10.1097/BCR.0000000000000386 PG 9 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA EH6FF UT WOS:000391867500043 PM 27359192 ER PT J AU Gandhi, PU Chow, SL Rector, TS Krum, H Gaggin, HK McMurray, JJ Zile, MR Komajda, M McKelvie, RS Carson, PE Januzzi, JL Anand, IS AF Gandhi, Parul U. Chow, Sheryl L. Rector, Thomas S. Krum, Henry Gaggin, Hanna K. McMurray, John J. Zile, Michael R. Komajda, Michel McKelvie, Robert S. Carson, Peter E. Januzzi, James L., Jr. Anand, Inder S. TI Prognostic Value of Insulin-Like Growth Factor-Binding Protein 7 in Patients with Heart Failure and Preserved Ejection Fraction SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Heart failure; biomarkers; preserved left ventricular function; prognosis; insulin-like growth factor-binding protein 7 ID DIASTOLIC DYSFUNCTION; PREVALENCE; BIOMARKERS; OUTCOMES; TRENDS AB Background: The prognostic merit of insulin-like growth factor-binding protein 7 (IGFBP7) is unknown in heart failure and preserved ejection fraction (HFpEF). Methods and Results: Baseline IGFBP7 (BL-IGFBP7; n = 302) and 6-month change (Delta; n = 293) were evaluated in the Irbesartan in Heart Failure and Preserved Ejection Fraction (I-PRESERVE) trial. Primary outcome was all-cause mortality or cardiovascular hospitalization with median follow-up of 3.6 years; secondary outcomes included HF events. Median BL-IGFBP7 concentration was 218 ng/mL. BL-IGFBP7 was significantly correlated with age (R-2 = 0.13; P <.0001), amino-terminal pro-B-type NP (R-2= 0.22; P <.0001), and estimated glomerular filtration rate (eGFR; R-2 = 0.14; P <.0001), but not with signs/symptoms of HFpEF. BL-IGFBP7 was significantly associated with the primary outcome (hazard ratio ERR] = 1.007 per ng/ mL; P <.001), all-cause mortality (HR = 1.008 per ng/mL; P <.001), and HF events (HR = 1.007 per ng/ mL; P <.001). IGFBP7 remained significant for each outcome after adjustment for ln amino-terminal pro B-type NP and eGFR but not all variables in the I-PRESERVE prediction model. After 6 months, IGFBP7 did not change significantly in either treatment group. Delta IGFBP7 was significantly associated with decrease in eGFR in patients randomized to irbesartan (R-2 = 0.09; P =.002). Delta GFBP7 was not independently associated with outcome. Conclusions: Higher concentrations of IGFBP7 were associated with increased risk of cardiovascular events, but after multivariable adjustment this association was no longer present. Further studies of IGFBP7 are needed to elucidate its mechanism. C1 [Gandhi, Parul U.] VA Connecticut, Sect Cardiovasc Med, West Haven, CT USA. [Gandhi, Parul U.] Yale Univ, Sch Med, Sect Cardiovasc Med, New Haven, CT USA. [Chow, Sheryl L.] Western Univ Hlth Sci, Pomona, CA USA. [Rector, Thomas S.; Anand, Inder S.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Rector, Thomas S.; Anand, Inder S.] Univ Minnesota, Minneapolis, MN USA. [Krum, Henry] Monash Univ, CCRE Therapeut, Melbourne, Vic 3004, Australia. [Gaggin, Hanna K.; Januzzi, James L., Jr.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [McMurray, John J.] British Heart Fdn, Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland. [Zile, Michael R.] RHJ Dept Vet Affairs Med Ctr, Charleston, SC USA. [Zile, Michael R.] Med Univ South Carolina, Charleston, SC USA. [Komajda, Michel] Univ Paris 06, Pitie Salpetriere Hosp, Paris, France. [McKelvie, Robert S.] Populat Hlth Res Inst, Hamilton, ON, Canada. [McKelvie, Robert S.] McMaster Univ, Hamilton, ON, Canada. [Carson, Peter E.] Washington VAMC, Washington, DC USA. [Carson, Peter E.] Georgetown Univ, Washington, DC USA. RP Januzzi, JL (reprint author), Massachusetts Gen Hosp, 32 Fruit St,Yawkey 5984, Boston, MA 02114 USA. EM jjanuzzi@partners.org OI mcmurray, john/0000-0002-6317-3975 FU Dennis and Marilyn Barry Fellowship in Cardiology; Clark Fund for Cardiac Research Innovation; Roman W. DeSanctis Clinical Scholar Endowment; Hutter Family Professorship FX Dr. Gandhi was supported by the Dennis and Marilyn Barry Fellowship in Cardiology. Dr. Gaggin is supported in part by the Clark Fund for Cardiac Research Innovation. Dr. Januzzi is supported in part by the Roman W. DeSanctis Clinical Scholar Endowment and the Hutter Family Professorship. NR 27 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2017 VL 23 IS 1 BP 20 EP 28 DI 10.1016/j.cardfail.2016.06.006 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EH8SE UT WOS:000392041800005 PM 27317843 ER PT J AU Sato, N Lam, CSP Teerlink, JR Greenberg, BH Tsutsui, H Oh, BH Zhang, J Lefkowitz, M Hua, TA Holbro, T Marshood, M Wang, XL Ge, JB AF Sato, Naoki Lam, Carolyn S. P. Teerlink, John R. Greenberg, Barry H. Tsutsui, Hiroyuki Oh, Byung-Hee Zhang, Jian Lefkowitz, Martin Hua, Tsushung A. Holbro, Thomas Marshood, Miriam Wang, Xing Li Ge, Junbo TI Evaluating the Efficacy, Safety, and Tolerability of Serelaxin When Added to Standard Therapy in Asian Patients With Acute Heart Failure: Design and Rationale of RELAX-AHF-ASIA Trial SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE Serelaxin; efficacy; Asian; acute heart failur ID RECOMBINANT HUMAN RELAXIN-2; GLOMERULAR-FILTRATION-RATE; EUROPEAN-SOCIETY; EJECTION FRACTION; RENAL-FUNCTION; TASK-FORCE; ASSOCIATION; CONGESTION; CARDIOLOGY; DISEASE AB Background: Acute heart failure (AHF), a common and growing health concern worldwide, is associated with high risk of post-discharge rehospitalization and mortality. Existing evidence indicates potential therapeutic benefits of serelaxin in Caucasian AHF patients, but corresponding data in Asians remain scarce. RELAX-AHF-ASIA, a multinational, randomized, double-blind, placebo-controlled, phase III trial, will evaluate the effects of serelaxin on symptom relief and clinical outcomes in Asian AHF patients, with the use of novel assessments. Methods and Results: Patients with AHF, systolic blood pressure >= 125 mm Hg, and mild to moderate renal dysfunction will be randomized within 16 hours of presentation to receive 48-hour intravenous infusion of 30 mu g . kg(-1) . d(-1) serelaxin or placebo in addition to standard therapy. The composite primary end point includes: (1) treatment success (moderate/marked improvement in patient-reported dyspnea and physician-assessed signs of congestion on day 2); (2) treatment failure (in-hospital worsening of signs and/ or symptoms of heart failure [HF] requiring intensification of intravenous HF therapy or mechanical ventilation, renal/circulatory support, rehospitalization due to HF/renal-failure, or death through day 5); and (3) unchanged status. Secondary end points include time to in-hospital worsening HF through day 5 and all cause and cardiovascular deaths through day 180. Conclusions: RELAX-AHF-ASIA, the largest randomized clinical trial in Asian AHF patients to date, has a novel composite primary end point and the potential to become a hallmark of AHF trials. C1 [Sato, Naoki] Musashi Kosugi Hosp, Nippon Med Sch, Cardiol & Intens Care Unit, Kawasaki, Kanagawa, Japan. [Lam, Carolyn S. P.] Natl Heart Ctr Singapore, Singapore, Singapore. [Lam, Carolyn S. P.] Duke NUS, Singapore, Singapore. [Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Teerlink, John R.] San Francisco VA Med Ctr, Los Angeles, CA USA. [Greenberg, Barry H.] Univ Calif San Diego, Div Cardiol, La Jolla, CA 92093 USA. [Tsutsui, Hiroyuki] Kyushu Univ, Fac Med Sci, Dept Cardiovasc Med, Fukuoka, Japan. [Oh, Byung-Hee] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Zhang, Jian] Chinese Acad Med Sci, Natl Ctr Cardiovasc Dis, Fuwai Hosp, Beijing, Peoples R China. [Zhang, Jian] Peking Union Med Coll, Beijing, Peoples R China. [Lefkowitz, Martin; Hua, Tsushung A.; Marshood, Miriam; Wang, Xing Li] Novartis Pharmaceut, E Hanover, NJ USA. [Holbro, Thomas] Novartis Pharmaceut, Basel, Switzerland. [Ge, Junbo] Fudan Univ, Zhongshan Hosp, Dept Cardiol, Shanghai, Peoples R China. RP Sato, N (reprint author), Musashi Kosugi Hosp, Nippon Med Sch, Cardiol & Intens Care Unit, Nakahara Ku, 1-396 Kosugi Cho, Kawasaki, Kanagawa 2118533, Japan. EM nms-ns@nms.ac.jp FU Novartis Pharma FX This study is sponsored by Novartis Pharma. NR 43 TC 0 Z9 0 U1 2 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 EI 1532-8414 J9 J CARD FAIL JI J. Card. Fail. PD JAN PY 2017 VL 23 IS 1 BP 63 EP 71 DI 10.1016/j.cardfail.2016.10.016 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EH8SE UT WOS:000392041800010 PM 27825893 ER PT J AU Richards, MR Plummer, L Chan, YM Lippincott, MF Quinton, R Kumanov, P Seminara, SB AF Richards, Mary R. Plummer, Lacey Chan, Yee-Ming Lippincott, Margaret F. Quinton, Richard Kumanov, Philip Seminara, Stephanie B. TI Phenotypic spectrum of POLR3B mutations: isolated hypogonadotropic hypogonadism without neurological or dental anomalies SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID RNA-POLYMERASE-III; HYPOMYELINATING LEUKODYSTROPHY; RECESSIVE MUTATIONS; MISSENSE MUTATIONS; HORMONE-SECRETION; ATAXIA; TRANSCRIPTION; RECEPTOR; LEUKOENCEPHALOPATHY; ANNOTATION AB Background A constellation of neurodegenerative disorders exists (Gordon Holmes syndrome, 4H leucodystrophy, Boucher-Neuhauser syndrome) in which patients suffer from both neurological disease (typically manifested by ataxia) and reproductive failure (idiopathic hypogonadotropic hypogonadism (IHH)). POLR3B, which encodes the second largest subunit of RNA polymerase III (pol III), and POLR3A, which forms the pol III catalytic centre, are associated with 4H leucodystrophy. Methods Whole exome sequencing was performed on a large cohort of subjects with IHH (n=565). Detailed neuroendocrine studies were performed in some individuals within this cohort. Results Four individuals (two of them siblings) were identified with two rare nucleotide variants in POLR3B. On initial evaluation, all subjects were free of neurological disease. One patient underwent treatment with exogenous pulsatile gonadotropin-releasing hormone for 8 weeks which failed to result in normalisation of his sex steroid milieu due to pituitary resistance. Conclusions These findings suggest that the spectrum of phenotypes resulting from POLR3B mutations is wider than previously believed and that POLR3B can be associated exclusively with disorders characterised by abnormal gonadotropin secretion. C1 [Richards, Mary R.; Plummer, Lacey; Chan, Yee-Ming; Lippincott, Margaret F.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, 55 Fruit St,BHX 5, Boston, MA 02114 USA. [Richards, Mary R.; Plummer, Lacey; Chan, Yee-Ming; Lippincott, Margaret F.; Seminara, Stephanie B.] Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, 55 Fruit St,BHX 5, Boston, MA 02114 USA. [Chan, Yee-Ming] Boston Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA USA. [Quinton, Richard] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England. [Kumanov, Philip] Med Univ Sofia, Clin Ctr Endocrinol & Gerontol, Sofia, Bulgaria. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Harvard Reprod Sci Ctr, 55 Fruit St,BHX 5, Boston, MA 02114 USA.; Seminara, SB (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, 55 Fruit St,BHX 5, Boston, MA 02114 USA. EM sseminara@mgh.harvard.edu FU National Institutes of Health Eunice Kennecy Shriver National Institute of Child Health and Human Development [P50HD028138] FX The research was supported by the National Institutes of Health Eunice Kennecy Shriver National Institute of Child Health and Human Development (P50HD028138). NR 46 TC 0 Z9 0 U1 1 U2 1 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 EI 1468-6244 J9 J MED GENET JI J. Med. Genet. PD JAN PY 2017 VL 54 IS 1 BP 19 EP 25 DI 10.1136/jmedgenet-2016-104064 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA EH0MR UT WOS:000391458700003 PM 27512013 ER PT J AU Friend, TH Jennings, SJ Copenhaver, MS Levine, WC AF Friend, Tynan H. Jennings, Samantha J. Copenhaver, Martin S. Levine, Wilton C. TI Implementation of the Vocera Communication System in a Quaternary Perioperative Environment SO JOURNAL OF MEDICAL SYSTEMS LA English DT Article DE Hands-free communication; Vocera; Healthcare communication; Surgical team communication; Communication system implementation; Perioperative environment; OR communication AB In the hospital, fast and efficient communication among clinicians and other employees is paramount to ensure optimal patient care, workflow efficiency, patient safety and patient comfort. The implementation of the wireless Vocera (R) Badge, a hands-free wearable device distributed to perioperative team members, has increased communication efficiency across the perioperative environment at Massachusetts General Hospital (MGH). This quality improvement project, based upon identical pre- and post-implementation surveys, used qualitative and quantitative analysis to determine if and how the Vocera system affected the timeliness of information flow, ease of communication, and operating room noise levels throughout the perioperative environment. Overall, the system increased the speed of information flow and eased communication between coworkers yet was perceived to have raised the overall noise level in and around the operating rooms (ORs). The perceived increase in noise was outweighed by the closed-loop communication between clinicians. Further education of the system's features in regard to speech recognition and privacy along with expected conversation protocol are necessary to ensure hassle-free communication for all staff. C1 [Friend, Tynan H.; Jennings, Samantha J.; Copenhaver, Martin S.; Levine, Wilton C.] Massachusetts Gen Hosp, 55 Fruit St,WHT 400, Boston, MA 02114 USA. RP Levine, WC (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT 400, Boston, MA 02114 USA. EM tfriend@partners.org; wlevine@partners.org NR 6 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0148-5598 EI 1573-689X J9 J MED SYST JI J. Med. Syst. PD JAN PY 2017 VL 41 IS 1 AR 6 DI 10.1007/s10916-016-0652-9 PG 6 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA EH7CK UT WOS:000391930300009 PM 27826766 ER PT J AU Moussaoui, N Jacobs, JP Larauche, M Biraud, M Million, M Mayer, E Tache, Y AF Moussaoui, Nabila Jacobs, Jonathan P. Larauche, Muriel Biraud, Mandy Million, Mulugeta Mayer, Emeran Tache, Yvette TI Chronic Early-life Stress in Rat Pups Alters Basal Corticosterone, Intestinal Permeability, and Fecal Microbiota at Weaning: Influence of Sex SO JOURNAL OF NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE Corticosterone; Microbiota; Permeability; Stress; psychological; Weaning ID IRRITABLE-BOWEL-SYNDROME; PITUITARY-ADRENAL AXIS; MATERNAL SEPARATION; CHILDHOOD TRAUMA; NEONATAL STRESS; RODENT MODELS; GUT; DEPRESSION; INSIGHTS; BEHAVIOR AB Background/Aims Wistar rat dams exposed to limited nesting stress (LNS) from post-natal days (PND) 2 to 10 display erratic maternal behavior, and their pups show delayed maturation of the hypothalamic-pituitary-adrenal axis and impaired epithelial barrier at PND10 and a visceral hypersensitivity at adulthood. little is known about the impact of early life stress on the offspring before adulthood and the influence of sex. We investigated whether male and female rats previously exposed to LNS displays at weaning altered corticosterone, intestinal permeability, and microbiota. Methods Wistar rat dams and litters were maintained from PND2 to 10 with limited nesting/bedding materials and thereafter reverted to normal housing up to weaning (PND21). Control litters had normal housing. At weaning, we monitored body weight, corticosterone plasma levels (enzyme immunoassay), in vivo intestinal to colon permeability (fluorescein isothiocyanate-dextran 4 kDa) and fecal microbiota (DNA extraction and amplification of the V4 region of the 16S ribosomal RNA gene). Results At weaning, LNS pups had hypercorticosteronemia and enhanced intestinal permeability with females > males while body weights were similar. LNS decreased fecal microbial diversity and induced a distinct composition characterized by increased abundance of Gram positive cocci and reduction of fiber-degrading, butyrate-producing, and mucus-resident microbes. Conclusions These data indicate that chronic exposure to LNS during the first week post-natally has sustained effects monitored at weanirig including hypercorticosteronemia, a leaky gut, and dysbiosis. These alterations may impact on the susceptibility to develop visceral hypersensitivity in adult rats and have relevance to the development of irritable bowel syndrome in childhood. C1 Univ Calif Los Angeles, G Oppenheimer Ctr Neurobiol Stress & Resilience, CURE Digest Dis Res Ctr, Vatche & Tamar Manoukian Div Digest Dis,Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Moussaoui, N (reprint author), CURE VA GLAHS, Bldg 115,Rm 111,1301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM NMoussaoui@mednet.ucla.edu FU National Institute of Health [P50 DK-64539, DK-41301, R01 DK-57238, K01 DK088937]; VA Career Scientist Award FX This work was supported by National Institute of Health grants P50 DK-64539 and Center grant DK-41301 (Animal Model Core), R01 DK-57238, K01 DK088937, and VA Career Scientist Award. NR 52 TC 2 Z9 2 U1 7 U2 7 PU KOREAN SOC NEUROGASTROENTEROLOGY & MOTILITY PI GANGNAM-GU PA RM 305, LOTTE GOLD ROSE VILL II, 31 SEOLLEUNG-RO 86-GIL, GANGNAM-GU, SEOUL 135-839, SOUTH KOREA SN 2093-0879 EI 2093-0887 J9 J NEUROGASTROENTEROL JI J. Neurogastroenterol. Motil. PD JAN PY 2017 VL 23 IS 1 BP 135 EP 143 DI 10.5056/jnm16105 PG 9 WC Gastroenterology & Hepatology; Clinical Neurology SC Gastroenterology & Hepatology; Neurosciences & Neurology GA EH4XH UT WOS:000391776700019 PM 27829577 ER PT J AU Kobashi, H Kamiya, K Shimizu, K AF Kobashi, Hidenaga Kamiya, Kazutaka Shimizu, Kimiya TI Randomized Comparison Between Rebamipide Ophthalmic Suspension and Diquafosol Ophthalmic Solution for Dry Eye After Penetrating Keratoplasty SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE dry eye; penetrating keratoplasty; rebamipide; diquafosol; RCT ID CORNEAL EPITHELIAL-CELLS; SODIUM HYALURONATE; BARRIER FUNCTION; INCREASES; TETRASODIUM; 0.1-PERCENT; MULTICENTER; OPC-12759; RECOVERY; EFFICACY AB Purpose: To compare the ocular surfaces of patients treated with rebamipide (REB) ophthalmic suspension or diquafosol (DQS) ophthalmic solution for dry eye syndrome after penetrating keratoplasty (PK). Methods: A total of 40 eyes of 40 patients who had dry eyes after undergoing PK were enrolled and randomly divided into an REB group and a DQS group. Both REB and DQS groups used each eye drop four times. The tear breakup time (TBUT), corneal fluorescein staining scores, and dry eye-related quality-of-life score (DEQS) were evaluated before treatment, 2 weeks after start of treatment and 4 weeks after start of treatment. Results: We found a significant improvement in TBUT (P < 0.001, Dunnett's test) and fluorescein scores (P < 0.001) 4 weeks after treatment in the REB group. Similar results were obtained in the DQS group (P < 0.001 and P = 0.01, respectively). No significant improvements in DEQS were found 4 weeks after treatment in each group (P = 0.15 and P = 0.63, analysis of variance, respectively). No significant differences were seen in these variables and in the changes between the groups after treatment. Conclusions: REB and DQS may be effective for the management of dry eye syndrome after PK in terms of ocular surface findings. In our study, effects of REB appear to be equivalent to those of DQS in the patients. C1 [Kobashi, Hidenaga; Kamiya, Kazutaka; Shimizu, Kimiya] Kitasato Univ, Sch Med, Dept Ophthalmol, 1-15-1 Kitasato, Sagamihara, Kanagawa 2288555, Japan. [Kobashi, Hidenaga] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA USA. RP Kobashi, H (reprint author), Kitasato Univ, Sch Med, Dept Ophthalmol, 1-15-1 Kitasato, Sagamihara, Kanagawa 2288555, Japan. EM himon@hotmail.co.jp NR 25 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 1080-7683 EI 1557-7732 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD JAN-FEB PY 2017 VL 33 IS 1 BP 13 EP 18 DI 10.1089/jop.2016.0096 PG 6 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA EH4PB UT WOS:000391752000004 PM 27937084 ER PT J AU Gitajn, IL Heng, M Weaver, MJ Casemyr, N May, C Vrahas, MS Harris, MB AF Gitajn, Ida Leah Heng, Marilyn Weaver, Michael J. Casemyr, Natalie May, Collin Vrahas, Mark S. Harris, Mitchel B. TI Mortality Following Surgical Management of Vancouver B Periprosthetic Fractures SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE periprosthetic; periprosthetic fracture; fracture; femur fracture; total hip arthroplasty; THA; Vancouver classification ID HIP-ARTHROPLASTY REGISTER; FEMORAL FRACTURES; RISK-FACTORS; FEMUR; CLASSIFICATION; FAILURE; RELIABILITY; REPLACEMENT; VALIDATION; DATABASES AB Objectives: The goals of this study are to evaluate mortality after Vancouver B periprosthetic fractures and determine predictors of mortality; compare mortality among patients with loose femoral stems treated with revision arthroplasty versus fixation alone; compare mortality among patients with radiographically "indeterminate" fractures treated with revision or fixation; and evaluate the rate of return to surgery for patients who underwent revision compared with fixation. Design: Retrospective study. Setting: Three academic level 1 trauma centers. Patients/Participants: Two hundred three patients treated for Vancouver B periprosthetic fractures. Intervention: N/A. Main Outcome Measurements: The primary outcome measure was mortality. The secondary outcome measure was reoperation because of infection, failure of fixation, dislocation, or other mechanical failure. Results: Overall 1-year survival was 87% and 5-year survival was 54%. Among patients with loose femoral stems, there was no significant difference with regard to survival between patients treated with fracture fixation or revision arthroplasty (1-year survival 83% vs. 85%, 5-year survival 41% vs. 58%). Among patients whose radiographs were classified as indeterminate, there was no significant difference between patients treated with fracture fixation alone or revision arthroplasty. There was no significant difference between total reoperation rates between the two groups (11% vs. 16%). Conclusion: This study suggests that there is no discernible survival benefit to treating patients with periprosthetic fractures with either revision arthroplasty or fixation alone. Therefore, from a mortality perspective, when faced with Vancouver B periprosthetic fractures, the orthopaedic surgeon should feel comfortable performing the type of intervention he/she is most proficient to perform. C1 [Gitajn, Ida Leah; Casemyr, Natalie; May, Collin] Harvard Combined Orthopaed Residency Program, Boston, MA USA. [Heng, Marilyn; Vrahas, Mark S.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthoped Trauma Initiat, Boston, MA USA. [Weaver, Michael J.; Harris, Mitchel B.] Harvard Med Sch, Brigham & Womens Hosp, Dept Orthopaed Surg, Orthoped Trauma Initiat, Boston, MA USA. RP Weaver, MJ (reprint author), Brigham & Womens Hosp, Dept Orthoped Surg, 75 Francis St, Boston, MA 02115 USA. EM mjweaver@partners.org NR 27 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 0890-5339 EI 1531-2291 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD JAN PY 2017 VL 31 IS 1 BP 9 EP 14 DI 10.1097/BOT.0000000000000711 PG 6 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA EH4EM UT WOS:000391724100009 PM 27763959 ER PT J AU Brooks, GA Stuver, SO Zhang, YC Gottsch, S Fraile, B McNiff, K Dodek, A Jacobson, JO AF Brooks, Gabriel A. Stuver, Sherri O. Zhang, Yichen Gottsch, Stephanie Fraile, Belen McNiff, Kristen Dodek, Anton Jacobson, Joseph O. TI Characteristics Associated with In-Hospital Death among Commercially Insured Decedents with Cancer SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; MEDICARE BENEFICIARIES; PALLIATIVE CARE; PLACE; END; HEALTH; PREDICTORS; PREFERENCE; COSTS; SITE AB Background: A majority of patients with poor-prognosis cancer express a preference for in-home death; however, in-hospital deaths are common. Objective: We sought to identify characteristics associated with in-hospital death. Design: Case series. Setting/Subjects: Commercially insured patients with cancer who died between July 2010 and December 2013 and who had at least two outpatient visits at a tertiary cancer center during the last six months of life. Measurements: Patient characteristics, healthcare utilization, and in-hospital death (primary outcome) were ascertained from institutional records and healthcare claims. Bivariate and multivariable analyses were used to evaluate the association of in-hospital death with patient characteristics and end-of-life outcome measures. Results: We identified 904 decedents, with a median age of 59 years at death. In-hospital death was observed in 254 patients (28%), including 110 (12%) who died in an intensive care unit. Hematologic malignancy was associated with a 2.57 times increased risk of in-hospital death (95% confidence interval [CI] 1.91-3.45, p < 0.001), and nonenrollment in hospice was associated with a 14.5 times increased risk of in-hospital death (95% CI 9.81-21.4, p < 0.001). Time from cancer diagnosis to death was also associated with in-hospital death (p = 0.003), with the greatest risk among patients dying within six months of cancer diagnosis. All significant associations persisted in multivariable analyses that were adjusted for baseline characteristics. Conclusions: In-hospital deaths are common among commercially insured cancer patients. Patients with hematologic malignancy and patients who die without receiving hospice services have a substantially higher incidence of in-hospital death. C1 [Brooks, Gabriel A.] Dartmouth Hitchcock Med Ctr, One Med Ctr Dr, Lebanon, NH 03756 USA. [Stuver, Sherri O.; Zhang, Yichen; Gottsch, Stephanie; Fraile, Belen; McNiff, Kristen; Jacobson, Joseph O.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dodek, Anton] Blue Cross & Blue Shield Massachusetts, Boston, MA USA. RP Brooks, GA (reprint author), Dartmouth Hitchcock Med Ctr, One Med Ctr Dr, Lebanon, NH 03756 USA. EM gabriel.a.brooks@hitchcock.org NR 25 TC 0 Z9 0 U1 4 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JAN PY 2017 VL 20 IS 1 BP 42 EP 47 DI 10.1089/jpm.2016.0231 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EH4OF UT WOS:000391749800011 PM 27626711 ER PT J AU Ouchi, K Block, SD Schonberg, MA Jamieson, ES Aaronson, EL Pallin, DJ Tulsky, JA Schuur, JD AF Ouchi, Kei Block, Susan D. Schonberg, Mara A. Jamieson, Emily S. Aaronson, Emily L. Pallin, Daniel J. Tulsky, James A. Schuur, Jeremiah D. TI Feasibility Testing of an Emergency Department Screening Tool To Identify Older Adults Appropriate for Palliative Care Consultation SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID CANCER-PATIENTS; SURPRISE QUESTION; LUNG-CANCER; OUTCOMES; NEEDS; LIFE AB Background: Seriously ill older adults in the emergency department (ED) may benefit from palliative care referral, yet little is known about how to identify these patients. Objectives: To assess the performance and determine the acceptability of a content-validated palliative care screening tool. Design: We surveyed Emergency Medicine (EM) attending physicians at the end of their shifts using the screening tool and asked them to retrospectively apply it to all patients >= 65 years whom they had cared for. We conducted the survey for three consecutive weeks in October 2015. Setting/Subjects: EM attending physicians at an urban, university-affiliated ED. Measurement: Patient characteristics, acceptability rating, and time per patient screened. Results: We approached 38 attending physicians to apply the screening tool for 69 eligible shifts. Physicians agreed to participate during 55 shifts (80%) and screened 207 patients. On 14 shifts (20%), physicians declined to participate. Mean age of the screened patients was 75 years, 51% were male, and 45% had at least one life-limiting illness. Overall, 67 patients (32%) screened positive for palliative care needs. Seventy percent of physicians (n = 33) found the screening tool acceptable to use and the average time of completion was 1.8 minutes per patient screened. Conclusion: A rapid screen of older adults for palliative care needs was acceptable to a majority of EM physicians and identified a significant number of patients who may benefit from palliative care referral. Further research is needed to improve acceptability and determine the appropriate care pathway for patients with palliative care needs. C1 [Ouchi, Kei; Jamieson, Emily S.; Pallin, Daniel J.; Schuur, Jeremiah D.] Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville 200, Boston, MA 02125 USA. [Ouchi, Kei; Aaronson, Emily L.; Pallin, Daniel J.; Schuur, Jeremiah D.] Harvard Med Sch, Dept Emergency Med, Boston, MA USA. [Block, Susan D.; Tulsky, James A.] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. [Block, Susan D.; Tulsky, James A.] Brigham & Womens Hosp, Dept Med, Div Palliat Med, 75 Francis St, Boston, MA 02115 USA. [Block, Susan D.] Brigham & Womens Hosp, Dept Psychiat, 75 Francis St, Boston, MA 02115 USA. [Schonberg, Mara A.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Aaronson, Emily L.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Ouchi, K (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St,Neville 200, Boston, MA 02125 USA. EM kouchi@partners.org NR 23 TC 0 Z9 0 U1 3 U2 3 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 JAN PY 2017 VL 20 IS 1 BP 69 EP 73 DI 10.1089/jpm.2016.0213 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EH4OF UT WOS:000391749800016 PM 27632230 ER PT J AU Platts-Mills, TF Richmond, NL LeFebvre, EM Mangipudi, SA Hollowell, AG Travers, D Biese, K Hanson, LC Volandes, AE AF Platts-Mills, Timothy F. Richmond, Natalie L. LeFebvre, Eric M. Mangipudi, Sowmya A. Hollowell, Allison G. Travers, Debbie Biese, Kevin Hanson, Laura C. Volandes, Angelo E. TI Availability of Advance Care Planning Documentation for Older Emergency Department Patients: A Cross-Sectional Study SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Article ID OF-LIFE CARE; HEALTH-CARE; SUBSTITUTED JUDGMENT; PROGNOSTIC-FACTORS; 1-YEAR MORTALITY; COMMUNITY STROKE; 1ST-EVER STROKE; SURVIVAL; DIRECTIVES; PREFERENCES AB Introduction: Increasing advance care planning (ACP) among older adults is a national priority. Documentation of ACP in the electronic health record (EHR) is particularly important during emergency care. Objective: We sought to characterize completion and availability of ACP among a subset of older patients at an academic emergency department (ED) with an integrated EHR. Methods: In this cross-sectional study, patients were eligible if aged >= 80 years or aged 65-79 with >= 1 indicator of high risk for short-term mortality. Patient-reported completion of ACP and availability of ACP documentation in the EHR were assessed. Results: Among study patients (n = 104), 59% reported completing some form of ACP: living will 52%, heathcare power of attorney 54%, do not resuscitate 38%, and medical orders for scope of treatment or physician orders for life-sustaining treatment 6%. Whites were more likely to report having some form of ACP than minorities (66% vs. 37%, p < 0.01), as were patients aged >= 80 years than those aged 65-79 (79% vs. 44%, p < 0.01). Only 13% of all patients had either a current code status or any other current ACP documentation in the EHR. Among patients whose primary care provider uses the same EHR system as the study ED, only 19% had a current code status or any other ACP documentation in the EHR. Conclusion: In a sample of older ED patients likely to benefit from ACP, few patients had documented end-of-life care preferences in the EHR. C1 [Platts-Mills, Timothy F.; Richmond, Natalie L.; LeFebvre, Eric M.; Mangipudi, Sowmya A.; Hollowell, Allison G.; Biese, Kevin] Univ N Carolina, Dept Emergency Med, 170 Manning Dr, Chapel Hill, NC 27515 USA. [Platts-Mills, Timothy F.; Biese, Kevin; Hanson, Laura C.] Univ N Carolina, Div Geriatr Med, Chapel Hill, NC USA. [Travers, Debbie] Univ N Carolina, Sch Nursing, Chapel Hill, NC USA. [Volandes, Angelo E.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Platts-Mills, TF (reprint author), Univ N Carolina, Dept Emergency Med, 170 Manning Dr, Chapel Hill, NC 27515 USA. EM tplattsm@med.unc.edu NR 35 TC 0 Z9 0 U1 4 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JAN PY 2017 VL 20 IS 1 BP 74 EP 78 DI 10.1089/jpm.2016.0243 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EH4OF UT WOS:000391749800017 PM 27622294 ER PT J AU Diop, MS Rudolph, JL Zimmerman, KM Richter, MA Skarf, LM AF Diop, Michelle S. Rudolph, James L. Zimmerman, Kristin M. Richter, Mary A. Skarf, L. Michal TI Palliative Care Interventions for Patients with Heart Failure: A Systematic Review and Meta-Analysis SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Review DE cultural care; heart failure; palliative care; quality of life; symptoms; utilization ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; MEDICINE CONSULTATION; CANCER-PATIENTS; HEALTH-CARE; OUTCOMES; HOSPICE; DISEASE; IMPACT; SATISFACTION AB Objective: To systematically characterize interventions and effectiveness of palliative care for advanced heart failure (HF) patients. Background: Patients with advanced heart failure experience a high burden of distressing symptoms and diminished quality of life. Palliative care expertise with symptom management and healthcare decision-making benefits HF patients. Methods: A systematic PubMed search was conducted from inception to June 2016 for studies of palliative care interventions for HF patients. Studies of humans with a HF diagnosis who underwent a palliative care intervention were included. Data were extracted on study design, participant characteristics, intervention components, and in three groups of outcomes: patient-centered outcomes, quality-of-death outcomes, and resource utilization. Study characteristics were examined to determine if meta-analysis was possible. Results: The fifteen identified studies varied in design (prospective, n = 10; retrospective, n = 5). Studies enrolled older patients, but greater variability was found for race, sex, and marital status. A majority of studies measuring patient-centered outcomes demonstrated improvements including quality of life and satisfaction. Quality-of-death outcomes were mixed with a majority of studies reporting clarification of care preferences, but less improvement in death at home and hospice enrollment. A meta-analysis in three studies found that home-based palliative care consults in HF patients lower the risk of rehospitalization by 42% (RR = 0.58; 95% Confidence Interval 0.44, 0.77). Discussion: Available evidence suggests that home and team-based palliative interventions for HF patients improve patient-centered outcomes, documentation of preferences, and utilization. Increased high quality studies will aid the determination of the most effective palliative care approaches for the HF population. C1 [Diop, Michelle S.] Brown Univ, Warren Alpert Med Sch, Primary Care & Populat Med Program, Providence, RI 02912 USA. [Diop, Michelle S.; Rudolph, James L.] Providence VAMC, Ctr Innovat Long Term Serv & Supports, Providence, RI USA. [Rudolph, James L.] Brown Univ, Dept Med, Warren Alpert Med Sch Brown, Providence, RI 02912 USA. [Rudolph, James L.] Brown Univ, Sch Publ Hlth, Ctr Gerontol, Providence, RI 02912 USA. [Zimmerman, Kristin M.] Virginia Commonwealth Univ, Dept Pharmacotherapy & Outcomes, Richmond, VA USA. [Richter, Mary A.] Tulane Univ, Sch Med, Dept Obstet & Gynecol, 1430 Tulane Ave, New Orleans, LA 70112 USA. [Skarf, L. Michal] VA Boston Healthcare Syst, Div Geriatr & Palliat Care, Boston, MA USA. [Skarf, L. Michal] Harvard Med Sch, Boston, MA USA. RP Rudolph, JL (reprint author), VA Providence Healthcare Syst, 830 Chalkstone Ave, Providence, RI 02908 USA. EM james_rudolph@brown.edu FU Primary Care-Population Medicine program at Warren Alpert Medical School at Brown University; NIH [T35-AG038027-02]; VA Health Services Research and Development Center of Innovation in Long Term Services and Supports [CIN 13-419]; VA QUERI-Geriatrics and Extended Care Partnered Evaluation Center for Community Nursing Homes [PEC 15-465] FX The authors are grateful for the support of Paul Bain, PhD, Countway Library of Medicine, and Erika Sevetson, MS, Alpert Medical School, in assisting with the literature search. This work was funded by the Primary Care-Population Medicine program at Warren Alpert Medical School at Brown University (MD). Additional support was provided by NIH T35-AG038027-02 (M.A.R., J.L.R.). Dr. Rudolph is supported by the VA Health Services Research and Development Center of Innovation in Long Term Services and Supports (CIN 13-419) and the VA QUERI-Geriatrics and Extended Care Partnered Evaluation Center for Community Nursing Homes (PEC 15-465). Drs. Skarf and Rudolph are employees of the Veterans Health Administration. The views expressed are those of the authors and do not reflect the official policies of the Veterans Health Administration or U.S. Government. NR 52 TC 0 Z9 0 U1 12 U2 12 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 JAN PY 2017 VL 20 IS 1 BP 84 EP 92 DI 10.1089/jpm.2016.0330 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA EH4OF UT WOS:000391749800019 PM 27912043 ER PT J AU Wang, Q Drouin, EE Yao, CX Zhang, JY Huang, Y Leon, DR Steere, AC Costello, CE AF Wang, Qi Drouin, Elise E. Yao, Chunxiang Zhang, Jiyang Huang, Yu Leon, Deborah R. Steere, Allen C. Costello, Catherine E. TI Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Synovial Tissue, Synovial Fluid, or Peripheral Blood in Patients with Rheumatoid Arthritis or Lyme Arthritis SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE HLA-DR; synovial tissue; synovial fluid mononuclear cells; peripheral blood mononuclear cells; Lyme arthritis; rheumatoid arthritis; autoantigens ID B-CELL RESPONSES; HLA-DRB1 SHARED EPITOPE; MASS-SPECTROMETRY; BOUND PEPTIDES; T-CELLS; GROWTH-FACTOR; CUTTING EDGE; IN-VIVO; ANTIGEN; ANTIBODIES AB Human leukocyte antigen antigen D related (HLA-DR) molecules are highly expressed in synovial tissue (ST), the target of the immune response in chronic inflammatory forms of arthritis. Here, we used LC-MS/MS to identify HLA-DR-presented self-peptides in cells taken directly from clinical samples: ST, synovial fluid mononuclear cells (SFMC), or peripheral blood mononuclear cells (PBMC) from five patients with rheumatoid arthritis (RA) and eight with Lyme arthritis (LA). We identified 1593 non-redundant HLA-DR-presented peptides, derived from 870 source proteins. A total of 67% of the peptides identified in SFMC and 55% of those found in PBMC were found in ST, but analysis of SFMC/PBMC also revealed new antigen-presented peptides. Peptides were synthesized and examined for reactivity with the patients' PBMC. To date, three autoantigens in RA and four novel autoantigens in LA, presented in ST and/or PBMC, were shown to be targets of T- and B-cell responses in these diseases; ongoing analyses may add to this list. Thus, immunoprecipitation and LC-MS/MS can now identify hundreds of HLA-DR-presented self-peptides from individual patients' tissues or fluids with mixed cell populations. Importantly, identification of HLA-DR-presented peptides from SFMC or PBMC allows testing of more patients, including those early in the disease. Direct analysis of clinical samples facilitates identification of novel immunogenic T-cell epitopes. C1 [Wang, Qi; Yao, Chunxiang; Zhang, Jiyang; Huang, Yu; Leon, Deborah R.; Costello, Catherine E.] Boston Univ, Sch Med, Dept Biochem, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA. [Drouin, Elise E.; Steere, Allen C.] Harvard Med Sch, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Zhang, Jiyang] Natl Univ Def Technol, Changsha 410000, Hunan, Peoples R China. RP Costello, CE (reprint author), Boston Univ, Sch Med, Dept Biochem, Ctr Biomed Mass Spectrometry, Boston, MA 02118 USA. EM cecmsms@bu.edu FU NIH [P41 GM104603, S10 RR020946, S10 OD010724, R01 AI110175]; NIH-NHLBI [HHSN268201000031C]; Ounsworth-Fitzgerald Foundation; American College of Rheumatology, Mathers Foundation; English, Bonter, Mitchell Foundation; Littauer Foundation; Eshe Fund; Lillian B. Davey Foundation FX This research is supported by NIH grants P41 GM104603, S10 RR020946, and S10 OD010724, NIH-NHLBI contract HHSN268201000031C (to C.E.C.), and NIH grant R01 AI110175 (to A.C.S.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This research is also supported by grants from the following: the Ounsworth-Fitzgerald Foundation; American College of Rheumatology, Mathers Foundation; English, Bonter, Mitchell Foundation; Littauer Foundation; Eshe Fund; and the Lillian B. Davey Foundation (to A.C.S.). We are grateful to the participating patients and controls and to the clinicians who obtained the samples for our analyses: Drs. John M. Aversa and Dennis Burke, who helped by obtaining synovial tissue at the time of the patients' arthroscopic synovectomies, Dr. Sheila L. Arvikar for help with patient care, and Gail McHugh for laboratory support. We thank Thermo Fisher for loan of the Q-Exactive plus mass spectrometer. NR 74 TC 0 Z9 0 U1 3 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD JAN PY 2017 VL 16 IS 1 BP 122 EP 136 DI 10.1021/acs.jproteome.6b00386 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA EH4ZJ UT WOS:000391782100012 PM 27726376 ER PT J AU Brink, JA AF Brink, James A. TI Scenario Planning for an Uncertain Future SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material C1 [Brink, James A.] Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA. RP Brink, JA (reprint author), Massachusetts Gen Hosp, 55 Fruit St,FND-216, Boston, MA 02114 USA. EM jabrink@partners.org 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 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2017 VL 14 IS 1 BP 2 EP 3 DI 10.1016/j.jacr.2016.11.009 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH8TS UT WOS:000392045800001 PM 28061961 ER PT J AU Boland, GW Glenn, L Goldberg-Stein, S Jha, S Mangano, M Patel, S Schoppe, KA Seidenwurm, D Lohnes, J Silva, E Abramson, R Durand, DJ Pattie, L Kassing, P Heller, RE AF Boland, Giles W. Glenn, Lucille Goldberg-Stein, Shlomit Jha, Saurabh Mangano, Mark Patel, Samir Schoppe, Kurt A. Seidenwurm, David Lohnes, John Silva, Ezequiel, III Abramson, Richard Durand, Daniel J. Pattie, Laura Kassing, Pamela Heller, Richard E., III TI Report of the ACR's Economics Committee on Value-Based Payment Models SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Health care reform; Imaging 3.0; value; outcomes; payments; metrics; MACRA; MIPS; APM ID HEALTH-CARE; RADIOLOGISTS; DELIVERY; QUALITY; SUPPORT AB A major outcome of the current health care reform process is the move away from unrestricted fee-for-service payment models toward those that are based on the delivery of better patient value and outcomes. The authors' purpose, therefore, is to critically evaluate and define those components of the overall imaging enterprise that deliver meaningful value to both patients and referrers and to determine how these components might be measured and quantified. These metrics might then be used to lobby providers and payers for sustainable payment solutions for radiologists and radiology services. The authors evaluated radiology operations and services using the framework of the imaging value chain, which divides radiology service into a number of discrete value-added activities, which ultimately deliver the primary product, most often the actionable report for diagnostic imaging or an effective outcome for interventional radiology. These value activities include scheduling and imaging appropriateness and stewardship, patient preparation, protocol design, modality operations, reporting, report communication, and clinical follow-up (eg, mammography reminder letters). Two further categories are hospital or health care organization citizenship and examination outcome. Each is discussed in turn, with specific activities highlighted. C1 [Boland, Giles W.] Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. [Glenn, Lucille] Virginia Mason Med Ctr, Dept Radiol, Seattle, WA 98101 USA. [Goldberg-Stein, Shlomit] Mt Sinai Hosp, Dept Radiol, Icahn Sch Med, New York, NY 10029 USA. [Jha, Saurabh] Univ Penn, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Mangano, Mark] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Patel, Samir] Elkhart Gen Hosp, Dept Radiol, Elkhart, IN USA. [Schoppe, Kurt A.] Radiol Associates North Texas, Ft Worth, TX USA. [Seidenwurm, David] Sutter Hlth, Dept Radiol, Sacramento, CA USA. [Lohnes, John] Univ Kansas, Sch Med, Dept Radiol, Wichita, KS 67214 USA. [Silva, Ezequiel, III] South Texas Radiol Grp, San Antonio, TX USA. [Abramson, Richard] Vanderbilt Univ, Med Ctr, Dept Radiol, Nashville, TN 37232 USA. [Durand, Daniel J.] Lifebridge Hlth, Dept Radiol, Baltimore, MD USA. [Pattie, Laura; Kassing, Pamela] Amer Coll Radiol, Reston, VA USA. [Heller, Richard E., III] Radiol Partners, El Secundo, CA USA. RP Boland, GW (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM gboland@partners.org OI Patel, Samir/0000-0002-5143-2642 FU Toshiba Medical Systems FX Dr Durand has received support from the National Decision Support Company and Evolent Health, outside the submitted work. Dr Jha has received speaking fees from Toshiba Medical Systems. All other authors have no conflicts of interest related to the material discussed in this article. NR 18 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2017 VL 14 IS 1 BP 6 EP 14 DI 10.1016/j.jacr.2016.08.031 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH8TS UT WOS:000392045800005 PM 28061965 ER PT J AU Fleishon, HB Itri, JN Boland, GW Duszak, R AF Fleishon, Howard B. Itri, Jason N. Boland, Giles W. Duszak, Richard, Jr. TI Academic Medical Centers and Community Hospitals Integration: Trends and Strategies SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Article DE Academic medical centers; community hospitals; consolidation; mergers ID RADIOLOGY; SERVICES; PROGRAM AB Academic medical centers are widely recognized as vital components of the American health care system, generally differentiated from their community hospital peers by their tripartite mission of clinical care, education, and research. Community hospitals fill a critical and complementary role, serving as the primary sites for health care in most communities. Health care reform initiatives and economic pressures have created incentives for hospitals and health systems to integrate, resulting in a nationwide trend toward consolidation with academic medical centers leveraging their substantial assets to merge, acquire, or establish partnerships with their community peers. As these alliances accelerate, they have and will continue to affect the radiology groups providing services at these institutions. A deeper understanding of these new marketplace dynamics, changing relationships and potential strategies will help both academic and private practice radiologists adapt to this ongoing change. C1 [Fleishon, Howard B.] Emory Univ, Dept Radiol & Med Imaging, Atlanta, GA 30322 USA. [Itri, Jason N.] Univ Virginia, Charlottesville, VA USA. [Boland, Giles W.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Duszak, Richard, Jr.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. RP Fleishon, HB (reprint author), Emory Univ, Dept Radiol & Med Imaging, Emory St Josephs Hosp, Dept Radiol, 5665 Peachtree Dunwoody Rd, Atlanta, GA 30342 USA. EM hbf@cox.net NR 24 TC 0 Z9 0 U1 3 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2017 VL 14 IS 1 BP 45 EP 51 DI 10.1016/j.jacr.2016.07.006 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH8TS UT WOS:000392045800010 PM 27815052 ER PT J AU Rehani, B Gao, KT Lau, L Rehani, MM Zhang, YC Dillon, WP AF Rehani, Bhavya Gao, Kenneth T. Lau, Lawrence Rehani, Madan M. Zhang, Yi C. Dillon, William P. TI Radiology Education in Asia: Differences, Similarities, and Opportunities SO JOURNAL OF THE AMERICAN COLLEGE OF RADIOLOGY LA English DT Editorial Material ID CHINA C1 [Rehani, Bhavya; Gao, Kenneth T.; Zhang, Yi C.; Dillon, William P.] Univ Calif San Francisco, 505 Parnassus Ave, San Francisco, CA 94143 USA. [Rehani, Madan M.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Rehani, B (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM bhavya.rehani@ucsf.edu NR 9 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1546-1440 J9 J AM COLL RADIOL JI J. Am. Coll. Radiol. PD JAN PY 2017 VL 14 IS 1 BP 111 EP 118 DI 10.1016/j.jacr.2016.08.013 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EH8TS UT WOS:000392045800023 PM 28061957 ER PT J AU de Boer, IH Kahn, SE AF de Boer, Ian H. Kahn, Steven E. TI SGLT2 Inhibitors-Sweet Success for Diabetic Kidney Disease? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 [de Boer, Ian H.] Univ Washington, Div Nephrol, Seattle, WA 98195 USA. [de Boer, Ian H.] Univ Washington, Kidney Res Inst, Seattle, WA 98195 USA. [Kahn, Steven E.] Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. [de Boer, Ian H.; Kahn, Steven E.] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP de Boer, IH (reprint author), Univ Washington, Med Nephrol, Box 359606,325 9th Ave, Seattle, WA 98104 USA. EM deboer@u.washington.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK088762, R01DK099199]; American Diabetes Association [4-15-CKD-20]; Department of Veterans Affairs [I01BX001060]; NIDDK [P30DK017047]; VA Puget Sound Health Care System FX I.H.d.B. receives support from grants R01DK088762 and R01DK099199 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), grant 4-15-CKD-20 from the American Diabetes Association, an unrestricted gift from the Northwest Kidney Centers to the Kidney Research Institute, and the Veterans Affairs (VA) Puget Sound Health Care System. S.E.K. receives support from grant I01BX001060 from the Department of Veterans Affairs, grant P30DK017047 from the NIDDK, and the VA Puget Sound Health Care System. NR 15 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 EI 1533-3450 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 2017 VL 28 IS 1 BP 7 EP 10 DI 10.1681/ASN.2016060650 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA EH3CW UT WOS:000391647700004 PM 27539605 ER PT J AU Brasel, KJ Moore, EE Albrecht, RA deMoya, M Schreiber, M Karmy-Jones, R Rowell, S Namias, N Cohen, M Shatz, DV Biffl, WL AF Brasel, Karen J. Moore, Ernest E. Albrecht, Roxie A. deMoya, Marc Schreiber, Martin Karmy-Jones, Riyad Rowell, Susan Namias, Nicholas Cohen, Mitchell Shatz, David V. Biffl, Walter L. TI Western Trauma Association Critical Decisions in Trauma: Management of rib fractures SO JOURNAL OF TRAUMA AND ACUTE CARE SURGERY LA English DT Article DE Algorithm; rib fracture; elderly; pain control ID RANDOMIZED CONTROLLED-TRIAL; FLAIL CHEST; MECHANICAL VENTILATION; SURGICAL STABILIZATION; ELDERLY-PATIENTS; PAIN MANAGEMENT; FIXATION; OUTCOMES; SCORE; RISK AB This is a recommended management algorithm from the Western Trauma Association addressing the management of adult patients with rib fractures. Because there is a paucity of published prospective randomized clinical trials that have generated Class I data, these recommendations are based primarily on published observational studies and expert opinion of Western Trauma Association members. The algorithm and accompanying comments represent a safe and sensible approach that can be followed at most trauma centers. We recognize that there will be patient, personnel, institutional, and situational factors that may warrant or require deviation from the recommended algorithm. We encourage institutions to use this as a guideline to develop their own local protocols. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.) C1 [Brasel, Karen J.; Schreiber, Martin; Rowell, Susan] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Moore, Ernest E.] Denver Hlth Med Ctr, Denver, CO USA. [Albrecht, Roxie A.] Univ Oklahoma, Oklahoma City, OK USA. [deMoya, Marc] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karmy-Jones, Riyad] Legacy Emmanuel Med Ctr, Portland, OR USA. [Namias, Nicholas] Univ Miami, Miami, FL USA. [Cohen, Mitchell] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Shatz, David V.] Univ Calif Davis, Sacramento, CA 95817 USA. [Biffl, Walter L.] Queens Med Ctr, Honolulu, HI USA. RP Brasel, KJ (reprint author), Oregon Hlth & Sci Univ, Dept Surg, 3181 Sam Jackson Pk Rd, Portland, OR 97239 USA. EM brasel@ohsu.edu NR 30 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 2163-0755 EI 2163-0763 J9 J TRAUMA ACUTE CARE JI J. Trauma Acute Care Surg. PD JAN PY 2017 VL 82 IS 1 BP 200 EP 203 DI 10.1097/TA.0000000000001301 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA EH5ZT UT WOS:000391852600036 PM 27779590 ER PT J AU Clark, AM Wheeler, SE Young, CL Stockdale, L Neiman, JS Zhao, W Stolz, DB Venkataramanan, R Lauffenburger, D Griffith, L Wells, A AF Clark, A. M. Wheeler, S. E. Young, C. L. Stockdale, L. Neiman, J. Shepard Zhao, W. Stolz, D. B. Venkataramanan, R. Lauffenburger, D. Griffith, L. Wells, A. TI A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties SO LAB ON A CHIP LA English DT Article ID HUMAN BREAST-CANCER; EXTRACELLULAR-MATRIX; MALIGNANT PHENOTYPE; CARCINOMA; STIFFNESS; CULTURE; GROWTH; TISSUE; PROGRESSION; MICROENVIRONMENTS AB Distant metastasis is the major cause of breast cancer-related mortality, commonly emerging clinically after 5 or more years of seeming 'cure' of the primary tumor, indicating a quiescent dormancy. The lack of relevant accessible model systems for metastasis that recreate this latent stage has hindered our understanding of the molecular basis and the development of therapies against these lethal outgrowths. We previously reported on the development of an all-human 3D ex vivo hepatic microphysiological system that reproduces several features of liver physiology and enables spontaneous dormancy in a subpopulation of breast cancer cells. However, we observed that the dormant cells were localized primarily within the 3D tissue, while the proliferative cells were in contact with the polystyrene scaffold. As matrix stiffness is known to drive inflammatory and malignant behaviors, we explored the occurrence of spontaneous tumor dormancy and inflammatory phenotype. The microphysiological system was retrofitted with PEGDa-SynKRGD hydrogel scaffolding, which is softer and differs in the interface with the tissue. The microphysiological system incorporated donor-matched primary human hepatocytes and non-parenchymal cells (NPCs), with MDA-MB-231 breast cancer cells. Hepatic tissue in hydrogel scaffolds secreted lower levels of pro-inflammatory analytes, and was more responsive to inflammatory stimuli. The proportion of tumor cells entering dormancy was markedly increased in the hydrogel-supported tissue compared to polystyrene. Interestingly, an unexpected differential response of dormant cells to varying chemotherapeutic doses was identified, which if reflective of patient pathophysiology, has important implications for patient dosing regimens. These findings highlight the metastatic microphysiological system fitted with hydrogel scaffolds as a critical tool in the assessment and development of therapeutic strategies to target dormant metastatic breast cancer. C1 [Clark, A. M.; Wheeler, S. E.; Stolz, D. B.; Venkataramanan, R.; Wells, A.] Univ Pittsburgh, Dept Pathol, S711 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. [Wells, A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. [Young, C. L.; Stockdale, L.; Neiman, J. Shepard; Lauffenburger, D.; Griffith, L.] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Zhao, W.; Venkataramanan, R.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA USA. [Stolz, D. B.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA USA. [Wells, A.] VA Pittsburgh Healthcare Syst, Pittsburgh VA Med Ctr, Pittsburgh, PA 15240 USA. [Stolz, D. B.; Wells, A.] Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA. [Stolz, D. B.] Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. [Young, C. L.] Appl BioMath LLC, Lincoln, MA USA. RP Wells, A (reprint author), Univ Pittsburgh, Dept Pathol, S711 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA.; Wells, A (reprint author), Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA.; Wells, A (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh VA Med Ctr, Pittsburgh, PA 15240 USA.; Wells, A (reprint author), Univ Pittsburgh, McGowan Inst Regenerat Med, Pittsburgh, PA 15260 USA. EM wellsa@upmc.edu RI Zhao, Wenchen/D-1867-2017 OI Zhao, Wenchen/0000-0002-0501-8459 FU NIH [1UH3TR000496]; VA Merit Award; DARPA [BAA-11-73, W911NF-12-2-0039] FX The authors thank other members of their laboratories for thoughtful discussions as well as Dr. Jonathan Coppeta (The Charles Stark Draper Laboratory, LLC) for his helpful suggestions with respect to the hydrogel scaffolds. The work described within is funded by grants from the NIH (1UH3TR000496), a VA Merit Award, and DARPA (BAA-11-73 Microphysiological Systems: W911NF-12-2-0039). NR 59 TC 0 Z9 0 U1 9 U2 9 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 EI 1473-0189 J9 LAB CHIP JI Lab Chip PY 2017 VL 17 IS 1 BP 156 EP 168 DI 10.1039/c6lc01171c PG 13 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA EH2NH UT WOS:000391604000013 ER PT S AU Razavi, P Cheng, JT Furlong, C Rosowski, JJ AF Razavi, Payam Cheng, Jeffrey Tao Furlong, Cosme Rosowski, John J. BE Korach, CS Tekalur, SA Zavattieri, P TI High-Speed Holography for In-Vivo Measurement of Acoustically Induced Motions of Mammalian Tympanic Membrane SO MECHANICS OF BIOLOGICAL SYSTEMS AND MATERIALS, VOL 6 SE Conference Proceedings of the Society for Experimental Mechanics Series LA English DT Proceedings Paper CT SEM Annual Conference and Exposition on Experimental and Applied Mechanics CY JUN 06-09, 2016 CL Orlando, FL SP Soc Expt Mech DE High-speed digital holography; In-vivo measurements; Middle ear mechanics; Transient acoustic excitation; Tympanic membrane AB Measurements of human Tympanic Membrane (TM, eardrum) motions require nanometer and microsecond spatio-temporal resolutions while maintaining a field-of-view of about one centimeter. Previously, we have developed holographic methods to successfully measuring continuous and transient responses of post-mortem TM's. To expand our capabilities to in-vivo measurements, it is necessary to overcome such challenges as the influence of submillimeter physiological motions as well as the confined location of the TM. We are developing novel High-speed Digital Holographic Methods (HDHM) in combination with recently developed image and data processing algorithms to overcome such challenges. Our developments have unique capabilities that utilize the full spatio-temporal resolution of high-speed cameras (i.e., > 147,000 points at > 42,000 fps) to measure nanometer-scale TM motions in the audible range (0.02-20 kHz). We present preliminary holographic measurements made on an anesthetized chinchilla in a controlled anechoic chamber in-vivo and in-vitro. To the best of our knowledge, these data are reported for the first time and establish the potential of HDHM as a hearing research and clinical tool to further expand our understanding of the human hearing processes. C1 [Razavi, Payam; Furlong, Cosme] Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechTron CHSLT, Worcester, MA 01609 USA. [Razavi, Payam; Furlong, Cosme] Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. [Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Cheng, Jeffrey Tao; Furlong, Cosme; Rosowski, John J.] Harvard Med Sch, Dept Otol & Laryngol, Boston, MA USA. RP Razavi, P (reprint author), Worcester Polytech Inst, Ctr Holog Studies & Laser MicromechTron CHSLT, Worcester, MA 01609 USA.; Razavi, P (reprint author), Worcester Polytech Inst, Dept Mech Engn, Worcester, MA 01609 USA. EM prazavi@wpi.edu FU National Institute on Deafness and Other Communication Disorders (NIDCD); National Institute of Health (NIH); Massachusetts Eye and Ear Infirmary (MEEI); NSF MRI [CMMI-1428921]; Mittal Fund FX This work has been funded by the National Institute on Deafness and Other Communication Disorders (NIDCD), the National Institute of Health (NIH), the Massachusetts Eye and Ear Infirmary (MEEI), NSF MRI program award: CMMI-1428921, and the Mittal Fund. The authors would like to acknowledge contributions of Nima Maftoon, Melissa McKinnon, and Michael E. Ravicz from the MEEI and Ivo Dobrev and Koohyar Pooladvand from the CHSLT at the Worcester Polytechnic Institute. NR 13 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2191-5644 BN 978-3-319-41351-8; 978-3-319-41350-1 J9 C PROC SOC EXP MECH PY 2017 BP 75 EP 81 DI 10.1007/978-3-319-41351-8_11 PG 7 WC Mechanics; Materials Science, Biomaterials SC Mechanics; Materials Science GA BG8BO UT WOS:000392181400011 ER PT J AU Haridas, V Ranjbar, S Vorobjev, IA Goldfeld, AE Barteneva, NS AF Haridas, Viraga Ranjbar, Shahin Vorobjev, Ivan A. Goldfeld, Anne E. Barteneva, Natasha S. TI Imaging flow cytometry analysis of intracellular pathogens SO METHODS LA English DT Article DE Imaging flow cytometry; Fluorescent protein; Intracellular pathogen; Mycobacteria tuberculosis; Toxoplasma gondii; Feature Finder; Cellular heterogeneity; Colocalization; Phagosome maturation; Rab5; Rab7 ID GREEN FLUORESCENT PROTEIN; ENTERICA SEROVAR TYPHIMURIUM; INNATE IMMUNE-RESPONSE; MYCOBACTERIUM-TUBERCULOSIS; TOXOPLASMA-GONDII; IN-VITRO; HIGH-THROUGHPUT; ENTAMOEBA-HISTOLYTICA; PHAGOSOME MATURATION; MONOMERIC RED AB Imaging flow cytometry has been applied to address questions in infection biology, in particular, infections induced by intracellular pathogens. This methodology, which utilizes specialized analytic software makes it possible to analyze hundreds of quantified features for hundreds of thousands of individual cellular or subcellular events in a single experiment. Imaging flow cytometry analysis of host cell-pathogen interaction can thus quantitatively addresses a variety of biological questions related to intracellular infection, including cell counting, internalization score, and subcellular patterns of co-localization. Here, we provide an overview of recent achievements in the use of fluorescently labeled prokaryotic or eukaryotic pathogens in human cellular infections in analysis of host-pathogen interactions. Specifically, we give examples of Imagestream-based analysis of cell lines infected with Toxoplasma gondii or Mycobacterium tuberculosis. Furthermore, we illustrate the capabilities of imaging flow cytometry using a combination of standard IDEAS' software and the more recently developed Feature Finder algorithm, which is capable of identifying statistically significant differences between researcher-defined image galleries. We argue that the combination of imaging flow cytometry with these software platforms provides a powerful new approach to understanding host control of intracellular pathogens. (C) 2016 Elsevier Inc. All rights reserved. C1 [Haridas, Viraga; Ranjbar, Shahin; Goldfeld, Anne E.; Barteneva, Natasha S.] Harvard Med Sch, Boston Childrens Hosp, Program Cellular & Mol Med, Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. [Haridas, Viraga; Ranjbar, Shahin; Goldfeld, Anne E.; Barteneva, Natasha S.] Harvard Med Sch, Dept Pediat, Boston, MA USA. [Vorobjev, Ivan A.; Barteneva, Natasha S.] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 117234, Russia. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Dept Cell Biol & Histol, Moscow, Russia. RP Goldfeld, AE (reprint author), Harvard Med Sch, Boston Childrens Hosp, Program Cellular & Mol Med, Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA.; Barteneva, NS (reprint author), Harvard Med Sch, D-239 Armenise Bldg,200 Longwood Ave, Boston, MA 02115 USA. EM Anne.Goldfeld@childrens.harvard.edu; natasha.barteneva@childrens.harvard.edu FU MES of Republic of Kazakhstan PI NURIS 055 project [100/14]; NIH [1R01AI117929-01A1]; Annenberg Foundation; RFBR [13-04-40189-H] FX This work was supported by grants from MES of Republic of Kazakhstan PI NURIS 055 project #100/14 to N.S.B., from the NIH (1R01AI117929-01A1) and the Annenberg Foundation to A.E.G., and by RFBR # 13-04-40189-H to I.A.V. We thank Sabrina Hawthorn and Rich De Marco of Amnis-Millipore-Sigma and Kenneth Ketman from PCMM for their generous help and advice with Imagestream instrumentation. NR 127 TC 0 Z9 0 U1 5 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 1 PY 2017 VL 112 BP 91 EP 104 DI 10.1016/j.ymeth.2016.09.007 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EH6RK UT WOS:000391901400012 PM 27642004 ER PT J AU Vorobjev, IA Barteneva, NS AF Vorobjev, Ivan A. Barteneva, Natasha S. TI Multi-parametric imaging of cell heterogeneity in apoptosis analysis SO METHODS LA English DT Article DE Apoptosis; Fluorescent microscopy; Imaging flow cytometry; Flow cytometry; Programmed cell death; Multicolor imaging ID LASER-SCANNING CYTOMETRY; RESONANCE ENERGY-TRANSFER; ALPHA-INDUCED APOPTOSIS; FLOW-CYTOMETRY; CYTOCHROME-C; CASPASE ACTIVATION; TUMOR-CELLS; PHOSPHATIDYLSERINE EXPRESSION; OXIDIZED PHOSPHATIDYLSERINE; MITOCHONDRIAL-MEMBRANE AB Apoptosis is a multistep process of programmed cell death where different morphological and molecular events occur simultaneously and/or consequently. Recent progress in programmed cell death analysis uncovered large heterogeneity in response of individual cells to the apoptotic stimuli. Analysis of the complex and dynamic process of apoptosis requires a capacity to quantitate multiparametric data obtained from multicolor labeling and/or fluorescent reporters of live cells in conjunction with morphological analysis. Modern methods of multiparametric apoptosis study include but are not limited to fluorescent microscopy, flow cytometry and imaging flow cytometry. In the current review we discuss the image-based evaluation of apoptosis on the single-cell and population level by imaging flow cytometry in parallel with other techniques. The advantage of imaging flow cytometry is its ability to interrogate multiparametric morphometric and fluorescence quantitative data in statistically robust manner. Here we describe the current status and future perspectives of this emerging field, as well as some challenges and limitations. We also highlight a number of assays and multicolor labeling probes, utilizing both microscopy and different variants of imaging cytometry, including commonly based assays and novel developments in the field. (C) 2016 Published by Elsevier Inc. C1 [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, AN Belozersky Inst PhysicoChem Biol, Moscow, Russia. [Vorobjev, Ivan A.] Moscow MV Lomonosov State Univ, Dept Cell Biol & Histol, Moscow, Russia. [Vorobjev, Ivan A.] Nazarbayev Univ, Sch Sci & Technol, Astana, Kazakhstan. [Barteneva, Natasha S.] Harvard Med Sch, Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA USA. [Barteneva, Natasha S.] Harvard Med Sch, Dept Pediat, Boston, MA USA. RP Vorobjev, IA (reprint author), Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys & Chem Biol, Lab Cell Motil, Leninskie Gory 1,Bldg 40, Moscow 117234, Russia. EM vorob@libro.genebee.msu.ru FU RFBR (Russian Federation) [13-04-40189-H]; project TFP [0212/PCF-14-OT(3)]; Republic of Kazakhstan [0472/GF4]; Harvard Pilot Grant; MES of Republic of Kazakhstan [100/14] FX We apologize to numerous authors whose significant works are not cited due to the space limitations. The financial support was provided in part by RFBR #13-04-40189-H (Russian Federation), project TFP # 0212/PCF-14-OT(3) and State Grant # 0472/GF4 (Republic of Kazakhstan) to I.A.V. and Harvard Pilot Grant and by MES of Republic of Kazakhstan NLA 055 project 100/14 to N.S.B. NR 174 TC 0 Z9 0 U1 8 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 EI 1095-9130 J9 METHODS JI Methods PD JAN 1 PY 2017 VL 112 BP 105 EP 123 DI 10.1016/j.ymeth.2016.07.003 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA EH6RK UT WOS:000391901400013 PM 27392934 ER PT J AU Liyanage, SU Coyaud, E Laurent, EMN Hurren, R Maclean, N Wood, SR Kazak, L Shamas-Din, A Holt, I Raught, B Schimmer, A AF Liyanage, Sanduni U. Coyaud, Etienne Laurent, Estelle M. N. Hurren, Rose Maclean, Neil Wood, Stuart R. Kazak, Lawrence Shamas-Din, Aisha Holt, Ian Raught, Brian Schimmer, Aaron TI Characterizing the mitochondrial DNA polymerase gamma interactome by BioID identifies Ruvbl2 localizes to the mitochondria SO MITOCHONDRION LA English DT Article DE POLG; Ruvbl2; mtDNA; Nucleoid; BioID; Co-localization ID PROTEINS; CELLS AB Human mitochondrial DNA (mtDNA) is replicated by the mitochondrial DNA polymerase gamma (POLG). Using proximity dependent biotin labelling (BioID), we characterized the POLG interactome and identified new interaction partners involved in mtDNA maintenance, transcription, translation and protein quality control. We also identified interaction with the nuclear AAA+ ATPase Ruvbl2, suggesting mitochondria( localization for this protein. Ruvbl2 was detected in mitochondria-enriched fractions in leukemic cells. Additionally, transgenic overexpression of Ruvbl2 from an alternative translation initiation site resulted in mitochondrial co-localization. Overall, POLG interactome mapping identifies novel proteins which support mitochondrial biogenesis and a potential novel mitochondrial isoform of Ruvbl2. (C) 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 [Liyanage, Sanduni U.; Coyaud, Etienne; Laurent, Estelle M. N.; Hurren, Rose; Maclean, Neil; Shamas-Din, Aisha; Raught, Brian; Schimmer, Aaron] Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada. [Liyanage, Sanduni U.; Schimmer, Aaron] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. [Wood, Stuart R.; Kazak, Lawrence; Holt, Ian] MRC, Mitochondria Biol Unit, Cambridge, England. [Wood, Stuart R.] Discuva Ltd, Merrifield Ctr, 12 Rosemary Lane, Cambridge, England. [Kazak, Lawrence] Harvard Univ, Dana Farber Canc Inst, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. RP Schimmer, A (reprint author), Princess Margaret Canc Ctr, Room 7-417,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM aaron.schimmer@utoronto.ca FU Canadian Stem Cell Network; Leukemia and Lymphoma Society [6456-15]; Canadian Institutes of Health Research [MOP-125868]; Princess Margaret Cancer Centre Foundation; Ministry of Long Term Health and Planning in the Province of Ontario; UK Medical Research Council FX This work was supported by the Canadian Stem Cell Network, the Leukemia and Lymphoma Society (6456-15), Canadian Institutes of Health Research (MOP-125868), the Princess Margaret Cancer Centre Foundation, and the Ministry of Long Term Health and Planning in the Province of Ontario. SRW, LK and IJH were supported by the UK Medical Research Council. 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 1567-7249 EI 1872-8278 J9 MITOCHONDRION JI Mitochondrion PD JAN PY 2017 VL 32 BP 31 EP 35 DI 10.1016/j.mito.2016.11.001 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA EI0LG UT WOS:000392165400006 PM 27845271 ER PT J AU Ahmed, R Yetisen, AK El Khoury, A Butt, H AF Ahmed, Rajib Yetisen, Ali K. El Khoury, Anthony Butt, Haider TI Printable ink lenses, diffusers, and 2D gratings SO NANOSCALE LA English DT Article ID BEAM LITHOGRAPHY; LASER-ABLATION; FLAT LENSES; BROAD-BAND; HOLOGRAMS; NANOSTRUCTURES; ARCHITECTURES; FABRICATION AB Advances in holography have led to applications including data storage, displays, security labels, and colorimetric sensors. However, existing top-down approaches for the fabrication of holographic devices are complex, expensive, and expertise dependent, limiting their use in practical applications. Here, ink-based holographic devices have been created for a wide range of applications in diffraction optics. A single pulse of a 3.5 ns Nd:YAG laser allowed selective ablation of ink to nanofabricate planar optical devices. The practicality of this method is demonstrated by fabricating ink-based diffraction gratings, 2D holographic patterns, optical diffusers, and Fresnel zone plate (FZP) lenses by using the ink. The fabrication processes were rationally designed using predictive computational modeling and the devices were fabricated within a few minutes demonstrating amenability for large scale printable optics through industrial manufacturing. It is anticipated that ink will be a promising diffraction optical material for the rapid printing of low-cost planar nanophotonic devices. C1 [Ahmed, Rajib; El Khoury, Anthony; Butt, Haider] Univ Birmingham, Sch Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. [Yetisen, Ali K.] Harvard Med Sch, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.] Massachusetts Gen Hosp, Wellman Ctr Photomed, 65 Landsdowne St, Cambridge, MA 02139 USA. [Yetisen, Ali K.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Butt, H (reprint author), Univ Birmingham, Sch Engn, Nanotechnol Lab, Birmingham B15 2TT, W Midlands, England. EM h.butt@bham.ac.uk OI Butt, Haider/0000-0003-2434-9525 FU Leverhulme Trust; Wellcome Trust; Royal Society FX H. B. thanks the Leverhulme Trust, Wellcome Trust and Royal Society for the research funding. The authors thank Jeff Blyth and Aydin Sabouri for help and discussions. R. A. designed the project, fabricated devices, carried out the experiments, simulations, analysis results and wrote the article. A. K. Y. contributed to the lens fabrication and edited the article. A. K. helped R. A. during diffraction grating experiments. H. B. supervised the simulations and experiments, provided the MATLAB code, and led the project. NR 39 TC 3 Z9 3 U1 8 U2 8 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 2040-3364 EI 2040-3372 J9 NANOSCALE JI Nanoscale PY 2017 VL 9 IS 1 BP 266 EP 276 DI 10.1039/c6nr07841a PG 11 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA EH4KE UT WOS:000391739300034 PM 27906403 ER PT J AU Sperling, AS Gibson, CJ Ebert, BL AF Sperling, Adam S. Gibson, Christopher J. Ebert, Benjamin L. TI The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia SO NATURE REVIEWS CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; PROGNOSTIC SCORING SYSTEM; GAIN-OF-FUNCTION; CHRONIC MYELOMONOCYTIC LEUKEMIA; STEM-CELL TRANSPLANTATION; AGE-RELATED MUTATIONS; SOMATIC MUTATIONS; RING SIDEROBLASTS; APLASTIC-ANEMIA; BONE-MARROW AB Myelodysplastic syndrome (MDS) is a clonal disease that arises from the expansion of mutated haematopoietic stem cells. In a spectrum of myeloid disorders ranging from clonal haematopoiesis of indeterminate potential (CHIP) to secondary acute myeloid leukaemia (sAML), MDS is distinguished by the presence of peripheral blood cytopenias, dysplastic haematopoietic differentiation and the absence of features that define acute leukaemia. More than 50 recurrently mutated genes are involved in the pathogenesis of MDS, including genes that encode proteins involved in pre-mRNA splicing, epigenetic regulation and transcription. In this Review we discuss the molecular processes that lead to CHIP and further clonal evolution to MDS and sAML. We also highlight the ways in which these insights are shaping the clinical management of MDS, including classification schemata, prognostic scoring systems and therapeutic approaches. C1 [Sperling, Adam S.; Gibson, Christopher J.; Ebert, Benjamin L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sperling, Adam S.; Gibson, Christopher J.; Ebert, Benjamin L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sperling, Adam S.; Gibson, Christopher J.; Ebert, Benjamin L.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. RP Ebert, BL (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Ebert, BL (reprint author), Brigham & Womens Hosp, Boston, MA 02115 USA.; Ebert, BL (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. EM bebert@partners.org FU US National Institutes of Health (NIH) [R01 HL082945, R24 DK099808]; Department of Defense; Edward P. Evans Foundation; Leukemia and Lymphoma Society; STARR Cancer Consortium FX This work was supported by grants from the US National Institutes of Health (NIH) (R01 HL082945 and R24 DK099808), the Department of Defense, the Edward P. Evans Foundation, the Leukemia and Lymphoma Society and the STARR Cancer Consortium to B.L.E. NR 200 TC 3 Z9 3 U1 9 U2 9 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 JAN PY 2017 VL 17 IS 1 BP 5 EP 19 DI 10.1038/nrc.2016.112 PG 15 WC Oncology SC Oncology GA EH1IT UT WOS:000391518900004 PM 27834397 ER PT J AU Bateman, BT Patorno, E Desai, RJ Seely, EW Mogun, H Dejene, SZ Fischer, MA Friedman, AM Hernandez-Diaz, S Huybrechts, KF AF Bateman, Brian T. Patorno, Elisabetta Desai, Rishi J. Seely, Ellen W. Mogun, Helen Dejene, Sara Z. Fischer, Michael A. Friedman, Alexander M. Hernandez-Diaz, Sonia Huybrechts, Krista F. TI Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 31st International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 22-26, 2015 CL Boston, MA SP Int Soc Pharmacoepidemiol ID 1ST-TRIMESTER EXPOSURE; ANTIDEPRESSANT USE; PREGNANCY; POPULATION; DEFECTS; COHORT; METAANALYSIS; HYPERTENSION; FETOPATHY; BLOCKERS AB OBJECTIVE: To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. METHODS: We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. RESULTS: The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. CONCLUSIONS: After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations. C1 Harvard Med Sch, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Boston, MA USA. Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesiol Crit Care & Pain Med, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Columbia Univ, Dept Obstet & Gynecol, Coll Phys & Surg, New York, NY USA. RP Bateman, BT (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA.; Bateman, BT (reprint author), Harvard Med Sch, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM bbateman@partners.org FU Lilly; Pfizer; Baxalta; Takeda; Bayer; Asisa FX Drs. Huybrechts, Brian T. Bateman, and Sonia Hernandez-Diaz are investigators on grants to the Brigham and Women's Hospital from Lilly and Pfizer and Dr. Bateman on grants from Baxalta unrelated to the topic of this article. Dr. Bateman consults for Optum for unrelated projects. Dr. Hernandez-Diaz has consulted for Boehringer-Ingelheim and UCB for unrelated projects. The Pharmacoepidemiology Program at the Harvard School of Public Health is supported by Pfizer, Takeda, Bayer, and Asisa. The other authors did not report any potential conflicts of interest. NR 30 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2017 VL 129 IS 1 BP 174 EP 184 DI 10.1097/AOG.0000000000001775 PG 11 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA EH7KO UT WOS:000391951900023 PM 27926639 ER PT J AU Khan, AA Hanley, DA Rizzoli, R Bollerslev, J Young, JEM Rejnmark, L Thakker, R D'Amour, P Paul, T Van Uum, S Shrayyef, MZ Goltzman, D Kaiser, S Cusano, NE Bouillon, R Mosekilde, L Kung, AW Rao, SD Bhadada, SK Clarke, BL Liu, J Duh, Q Lewiecki, EM Bandeira, F Eastell, R Marcocci, C Silverberg, SJ Udelsman, R Davison, KS Potts, JT Brandi, ML Bilezikian, JP AF Khan, A. A. Hanley, D. A. Rizzoli, R. Bollerslev, J. Young, J. E. M. Rejnmark, L. Thakker, R. D'Amour, P. Paul, T. Van Uum, S. Shrayyef, M. Zakaria Goltzman, D. Kaiser, S. Cusano, N. E. Bouillon, R. Mosekilde, L. Kung, A. W. Rao, S. D. Bhadada, S. K. Clarke, B. L. Liu, J. Duh, Q. Lewiecki, E. Michael Bandeira, F. Eastell, R. Marcocci, C. Silverberg, S. J. Udelsman, R. Davison, K. Shawn Potts, J. T., Jr. Brandi, M. L. Bilezikian, J. P. TI Primary hyperparathyroidism: review and recommendations on evaluation, diagnosis, and management. A Canadian and international consensus SO OSTEOPOROSIS INTERNATIONAL LA English DT Review DE Diagnosis; Management; Osteoporosis; Primary hyperparathyroidism; Surgery; Treatment ID MILD PRIMARY HYPERPARATHYROIDISM; ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM; NORMOCALCEMIC PRIMARY HYPERPARATHYROIDISM; TRABECULAR BONE SCORE; VITAMIN-D DEFICIENCY; POSTMENOPAUSAL WOMEN; KIDNEY-STONES; VERTEBRAL FRACTURES; MEDICAL-MANAGEMENT; MINERAL DENSITY AB The purpose of this review is to assess the most recent evidence in the management of primary hyperparathyroidism (PHPT) and provide updated recommendations for its evaluation, diagnosis and treatment. A Medline search of "Hyperparathyroidism. Primary" was conducted and the literature with the highest levels of evidence were reviewed and used to formulate recommendations. PHPT is a common endocrine disorder usually discovered by routine biochemical screening. PHPT is defined as hypercalcemia with increased or inappropriately normal plasma parathyroid hormone (PTH). It is most commonly seen after the age of 50 years, with women predominating by three to fourfold. In countries with routine multichannel screening, PHPT is identified earlier and may be asymptomatic. Where biochemical testing is not routine, PHPT is more likely to present with skeletal complications, or nephrolithiasis. Parathyroidectomy (PTx) is indicated for those with symptomatic disease. For asymptomatic patients, recent guidelines have recommended criteria for surgery, however PTx can also be considered in those who do not meet criteria, and prefer surgery. Non-surgical therapies are available when surgery is not appropriate. This review presents the current state of the art in the diagnosis and management of PHPT and updates the Canadian Position paper on PHPT. An overview of the impact of PHPT on the skeleton and other target organs is presented with international consensus. Differences in the international presentation of this condition are also summarized. C1 [Khan, A. A.; Young, J. E. M.] McMaster Univ, Hamilton, ON, Canada. [Khan, A. A.] Bone Res & Educ Ctr, 223-3075 Hosp Gate, Oakville, ON, Canada. [Hanley, D. A.] Univ Calgary, Calgary, AB, Canada. [Rizzoli, R.] Univ Hosp Geneva, Div Bone Dis, Geneva, Switzerland. [Rizzoli, R.] Fac Med, Geneva, Switzerland. [Bollerslev, J.] Univ Oslo, Oslo, Norway. [Rejnmark, L.] Aarhus Univ Hosp, Dept Endocrinol & Internal Med, Aarhus, Denmark. [Thakker, R.] Univ Oxford, Oxford, England. [D'Amour, P.] CHUM, Montreal, PQ, Canada. [Paul, T.; Van Uum, S.] Western Univ, London, ON, Canada. [Shrayyef, M. Zakaria] Univ Toronto, Div Endocrinol, Mississauga, ON, Canada. [Goltzman, D.] McGill Univ, Montreal, PQ, Canada. [Kaiser, S.] Dalhousie Univ, Halifax, NS, Canada. [Cusano, N. E.] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Bouillon, R.] KU, Leuven, Belgium. [Mosekilde, L.] Univ Aarhus, Aarhus, Denmark. [Kung, A. W.] Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. [Rao, S. D.] Henry Ford Hosp, Detroit, MI 48202 USA. [Bhadada, S. K.] Postgrad Inst Med Educ & Res, Chandigarth, India. [Clarke, B. L.] Mayo Clin, Rochester, MN USA. [Liu, J.] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, Shanghai, Peoples R China. [Duh, Q.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lewiecki, E. Michael] Univ New Mexico, Sch Med, New Mexico Clin Res & Osteoporosis Ctr, Albuquerque, NM 87131 USA. [Bandeira, F.] Univ Pernambuco, Sch Med, Div Endocrinol Diabet & Metab Bone Dis, Agamenon Magalhaes Hosp,Brazilian Minist Hlth, Recife, PE, Brazil. [Eastell, R.] Univ Sheffield, Dept Human Metab, Sheffield, S Yorkshire, England. [Marcocci, C.] Univ Hosp Pisa, Dept Clin & Expt Med, Endocrine Unit 2, Pisa, Italy. [Silverberg, S. J.; Bilezikian, J. P.] Columbia Univ, Coll Phys & Surg, Div Endocrinol, New York, NY USA. [Udelsman, R.] Yale Univ, Sch Med, Dept Surg, New Haven, CT 06510 USA. [Davison, K. Shawn] Univ Victoria, Victoria, BC, Canada. [Potts, J. T., Jr.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. [Brandi, M. L.] Univ Florence, Florence, Italy. RP Khan, AA (reprint author), McMaster Univ, Hamilton, ON, Canada.; Khan, AA (reprint author), Bone Res & Educ Ctr, 223-3075 Hosp Gate, Oakville, ON, Canada. EM Aliya@mcmaster.ca FU Calcium Disorders Clinic, McMaster University Hamilton, Ontario, Canada FX This work was supported by the Calcium Disorders Clinic, McMaster University Hamilton, Ontario, Canada. NR 132 TC 0 Z9 0 U1 6 U2 6 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-941X EI 1433-2965 J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JAN PY 2017 VL 28 IS 1 BP 1 EP 19 DI 10.1007/s00198-016-3716-2 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG9PB UT WOS:000391390100001 PM 27613721 ER PT J AU McGraw, SA Garber, J Janne, PA Lindeman, N Oliver, N Sholl, LM Van Allen, EM Wagle, N Garraway, LA Joffe, S Gray, SW AF McGraw, Sarah A. Garber, Judy Janne, Pasi A. Lindeman, Neal Oliver, Nelly Sholl, Lynette M. Van Allen, Eliezer M. Wagle, Nikhil Garraway, Levi A. Joffe, Steven Gray, Stacy W. TI The fuzzy world of precision medicine: deliberations of a precision medicine tumor board SO PERSONALIZED MEDICINE LA English DT Article DE cancer; decision-making; genomics; precision medicine; sequencing; tumor board; US ID CELL LUNG-CANCER; GENOMIC MEDICINE; OPPORTUNITIES; CHALLENGES; MUTATIONS; DIAGNOSIS; LESSONS; IMPACT; RETURN; CARE AB Aim: To understand how a cancer precision medicine tumor board (CPM-TB) made choices about return of results. Materials & methods: Observed CPM-TB deliberations and completed in-depth interviews with committee members. Results: Responding to complex evidence of ambiguous significance, deliberations of the CPM-TB were predicated on analytic validity and clinical utility. Members had concerns both about potential harms due to returning results based on weak evidence and about withholding potentially meaningful results. Group dynamics and the clinical experiences of individual committee members shaped their work. Conclusion: Both scientific evidence and the social context surrounding deliberations of a CPM-TB influenced decisions about return of results. Subjective elements, while present in any scientific endeavor, may carry more weight in the face of ambiguous findings. C1 [McGraw, Sarah A.] Hastings Ctr, Garrison, NY 10524 USA. [Garber, Judy; Janne, Pasi A.; Oliver, Nelly; Van Allen, Eliezer M.; Wagle, Nikhil; Garraway, Levi A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Garber, Judy; Janne, Pasi A.; Lindeman, Neal; Sholl, Lynette M.; Van Allen, Eliezer M.; Wagle, Nikhil; Garraway, Levi A.] Harvard Med Sch, Boston, MA USA. [Garber, Judy; Janne, Pasi A.; Van Allen, Eliezer M.; Wagle, Nikhil; Garraway, Levi A.] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Lindeman, Neal; Sholl, Lynette M.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Van Allen, Eliezer M.; Wagle, Nikhil; Garraway, Levi A.] Broad Inst, Cambridge, MA USA. [Joffe, Steven] Univ Penn, Dept Med Eth & Hlth Policy, Perelman Sch Med, Philadelphia, PA 19104 USA. [Joffe, Steven] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Gray, Stacy W.] City Hope Natl Med Ctr, Ctr Comprehens Canc, Dept Populat Sci, Duarte, CA USA. RP McGraw, SA (reprint author), Hastings Ctr, Garrison, NY 10524 USA. EM mcgraws@thehastingscenter.org FU National Human Genome Research Institute [U01HG006492, U01 HG007303]; American Cancer Society [120529-MRSG-11-006-01-CPPB]; Dana-Farber Cancer Institute under NHGRI grant [U01HG006492, U01 HG007303]; Myriad Genetics; Ambry Genetics; Novartis Oncology; Bristol-Myers Squibb; Novartis; Pfizer; Astellas; BMS; Merck FX The research reported in this publication was supported by National Human Genome Research Institute U01HG006492 and U01 HG007303. SW Gray was also supported by the American Cancer Society (120529-MRSG-11-006-01-CPPB). SA McGraw was supported through a subcontract with The Dana-Farber Cancer Institute under NHGRI grant numbers U01HG006492 and U01 HG007303. J Garber has consulting or advisory roles for Helix and Biogen and receives research funding from Myriad Genetics and Ambry Genetics. A family member has a consulting role for Novartis Oncology, SV Life Sciences and Pfizer and receives research support from Novartis Oncology. PA Janne receives post-marketing royalties from DFCI-owned intellectual property on EGFR mutation testing licensed to Lab Corp. EM Van Allen is a stockholder in Syapse, a consultant/advisor for Roche, Third Rock Ventures, and Takeda, and receives sponsored research support from Bristol-Myers Squibb. N Wagle is a stockholder in Foundation Medicine, a consultant/advisor for Novartis, and receives sponsored research support from Novartis and Pfizer. LA Garraway is a consultant for Foundation Medicine, Novartis, Boehringer Ingelheim, Third Rock and Eli Lilly, an equity holder in Foundation Medicine, and a member of the Scientific Advisory Board at Warp Drive. LA Garraway receives sponsored research support from Novartis, Astellas, BMS and Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 35 TC 0 Z9 0 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 EI 1744-828X J9 PERS MED JI Pers. Med. PD JAN PY 2017 VL 14 IS 1 BP 37 EP 50 DI 10.2217/pme-2016-0074 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA EH6FC UT WOS:000391867200007 ER PT J AU Zhang, CS Pirrone, M Imber, DAE Ackman, JB Fumagalli, J Kacmarek, RM Berra, L AF Zhang, Changsheng Pirrone, Massimiliano Imber, David A. E. Ackman, Jeanne B. Fumagalli, Jacopo Kacmarek, Robert M. Berra, Lorenzo TI Optimization of Mechanical Ventilation in a 31-Year-Old Morbidly Obese Man With Refractory Hypoxemia SO A & A CASE REPORTS LA English DT Article ID END-EXPIRATORY PRESSURE; ICU; RECRUITMENT; ATELECTASIS; ANESTHESIA AB Morbidly obese, critically ill patients are prone to develop hypoxemic respiratory failure and ventilator dependency. The best method for recruiting the lungs of these patients and keeping alveoli open without causing injury remains unclear. We present the case of a 31-year-old patient with severe refractory hypoxemia reversed by lung recruitment maneuvers and subsequent application of positive end-expiratory pressure (PEEP) at a level determined by a decremental PEEP trial. The patient was extubated at a high PEEP level of 22 cm H2O followed by noninvasive ventilatory support after extubation. This case suggests that a recruitment maneuver followed by PEEP titration is necessary in obese patients for optimizing mechanical ventilation. Extubation to noninvasive ventilatory support with the identified optimal PEEP may decrease an inappropriate increased work of breathing and the risk of reintubation. C1 [Zhang, Changsheng; Pirrone, Massimiliano; Imber, David A. E.; Fumagalli, Jacopo; Berra, Lorenzo] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, White 434B,55 Fruit St, Boston, MA 02114 USA. [Zhang, Changsheng] Chinese Peoples Liberat Army Gen Hosp, Anesthesia & Operat Ctr, Beijing, Peoples R China. [Ackman, Jeanne B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Berra, L (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, White 434B,55 Fruit St, Boston, MA 02114 USA. EM lberra@mgh.harvard.edu NR 13 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 JAN 1 PY 2017 VL 8 IS 1 BP 7 EP 10 DI 10.1213/XAA.0000000000000408 PG 4 WC Anesthesiology SC Anesthesiology GA EH0BE UT WOS:000391426500003 PM 27782908 ER PT J AU Thadhani, R Zella, JB Knutson, DC Blaser, WJ Plum, LA Clagett-Dame, M Buck, RD DeLuca, HF AF Thadhani, Ravi Zella, Julia B. Knutson, Danielle C. Blaser, William J. Plum, Lori A. Clagett-Dame, Margaret Buck, Raymond D. DeLuca, Hector F. TI 2MD (DP001), a Single Agent in the Management of Hemodialysis Patients: A Randomized Trial SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Vitamin D analog; Parathyroid hormone; Secondary hyperparathyroidism ID CHRONIC KIDNEY-DISEASE; VITAMIN-D ANALOGS; SECONDARY HYPERPARATHYROIDISM; DIALYSIS PATIENTS; PERITONEAL-DIALYSIS; PARATHYROID-HORMONE; ORAL PARICALCITOL; CALCITRIOL; EFFICACY; TOLERABILITY AB Background: Vitamin D analogs and calcimimetics are used to manage secondary hyperparathyroidism (SHPT) in dialysis patients. DP001 is an oral vitamin D analog that suppresses parathyroid hormone (PTH) in uremic rats, osteopenic women, and hemodialysis patients. The safety and effectiveness of DP001 suppressing PTH in dialysis patients previously managed with active vitamin D with or without a calcimimetic are presented. Methods: A multicenter, randomized, double-blind study compared DP001 to placebo in hemodialysis patients with serum-intact PTH (iPTH) >= 300 pg/ml. The primary efficacy endpoint was the proportion of patients achieving 2 consecutive >= 30% decreases in iPTH levels during the 12 weeks of treatment. Calcium, phosphorus, calcium x phosphorus product and safety were also evaluated. The responses to DP001 were compared in patients previously treated with both active vitamin D and a calcimimetic to those previously on active vitamin D alone. Results: Sixty-two patients were randomized (n = 34 DP001; n = 28 placebo). At week 12, 78% of all DP001-treated patients and 7% of all placebo-treated patients achieved the primary endpoint (p < 0.0001); iPTH fell 45% in the DP001 group and increased 37% in the placebo group. No patient exceeded the safety threshold of 2 consecutively corrected serum calcium levels >= 11.0 mg/dl. Patients previously on cinacalcet plus active vitamin D also responded to DP001 (n = 10) resulting in a 55% decrease in iPTH, while those on placebo (n = 9) increased by 70%. Conclusion: DP001 safely and effectively suppressed iPTH in hemodialysis patients with SHPT that were previously managed with active vitamin D alone or with a calcimimetic. (C) 2016 S. Karger AG, Basel C1 [Thadhani, Ravi] Harvard Med Sch, Massachusetts Gen Hosp, Div Nephrol, Boston, MA USA. [Zella, Julia B.; Knutson, Danielle C.; Blaser, William J.; Plum, Lori A.; Clagett-Dame, Margaret; DeLuca, Hector F.] Univ Wisconsin, Dept Biochem, 420 Henry Mall, Madison, WI 53705 USA. [Zella, Julia B.; Knutson, Danielle C.; Blaser, William J.; Plum, Lori A.; Clagett-Dame, Margaret; DeLuca, Hector F.] Deltanoid Pharmaceut Inc, Madison, WI USA. [Clagett-Dame, Margaret] Univ Wisconsin, Sch Pharm, 425 N Charter St, Madison, WI 53706 USA. [Buck, Raymond D.] Raymond Buck Consulting, Chapel Hill, NC USA. RP Thadhani, R (reprint author), Harvard Med Sch, Med, 55 Fruit St,Bigelow 1008G, Boston, MA 02018 USA.; Thadhani, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, 55 Fruit St,Bigelow 1008G, Boston, MA 02018 USA. EM rthadhani@mgh.harvard.edu FU Deltanoid FX R.T. and R.D.B. have been paid as advisors by Deltanoid. R.T. is a consultant to Fresenius Medical Care North America. J.B.Z., D.C.K., W.J.B., L.A.P., M.C.-D., and H.F.D. have financial interest in Deltanoid Pharmaceuticals, Inc. that is developing DP001 as a pharmaceutical. NR 34 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2017 VL 45 IS 1 BP 40 EP 48 DI 10.1159/000452680 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA EH0CB UT WOS:000391428900006 PM 27880946 ER PT J AU Taber, DJ Fleming, JN Fominaya, CE Gebregziabher, M Hunt, KJ Srinivas, TR Baliga, PK McGillicuddy, JW Egede, LE AF Taber, David J. Fleming, James N. Fominaya, Cory E. Gebregziabher, Mulugeta Hunt, Kelly J. Srinivas, Titte R. Baliga, Prabhakar K. McGillicuddy, John W. Egede, Leonard E. TI The Impact of Health Care Appointment Non-Adherence on Graft Outcomes in Kidney Transplantation SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Kidney transplant; Non-adherence; Acute rejection; Graft survival ID SOLID-ORGAN TRANSPLANTATION; ASSESSING MEDICATION ADHERENCE; RENAL-TRANSPLANTATION; CLAIMS DATA; RECIPIENTS; FAILURE; REGIMEN; IMMUNOSUPPRESSANTS; NONCOMPLIANCE; THERAPY AB Background: Non-adherence to medication is a well-studied and known cause of late allograft loss, but it is difficult to measure and prospectively monitor. The aim of this study was to assess if appointment non-adherence was correlated with medication non-adherence and a predictor of graft outcomes. Methods: This was a longitudinal cohort study that used the National United States Renal Data System and veterans affairs health records data with time-to-event analyses conducted to assess the impact on graft and patient survival. Results: The number of transplants that were included in the analysis was 4,646 (3,656 with complete records); 14.6% of patients had an appointment no show rate of = 12% (non-adherence). Appointment and medication non-adherence were highly correlated and both were significant independent predictors of outcomes. Those with appointment non-adherence had 1.5 times the risk of acute rejection (22.0 vs. 14.7%, p < 0.0001) and a 65% higher risk of graft loss (adjusted hazards ratio (aHR) 1.65, 95% CI 1.38-1.97, p < 0.0001). There was a significant interaction between appointment and medication non-adherence; those with appointment and medication non-adherence were at very high risk of graft loss (aHR 4.18, 95% CI 3.39-5.15, p < 0.0001), compared to those with only appointment non-adherence (aHR 1.39, 95% CI 0.97-2.01, p = 0.0766) or only medication non-adherence (aHR 2.44, 95% CI 2.11-2.81, p < 0.0001). Conclusion: These results demonstrate that non-adherence to health care appointments is a significant and independent risk factor for graft loss. (C) 2016 S. Karger AG, Basel C1 [Taber, David J.; Baliga, Prabhakar K.; McGillicuddy, John W.] Med Univ South Carolina, Coll Med, Div Transplant Surg, Charleston, SC USA. [Gebregziabher, Mulugeta; Hunt, Kelly J.] Med Univ South Carolina, Coll Med, Dept Publ Hlth Sci, Charleston, SC USA. [Srinivas, Titte R.] Med Univ South Carolina, Coll Med, Div Transplant Nephrol, Charleston, SC USA. [Fleming, James N.] Med Univ South Carolina, Dept Pharm Serv, Charleston, SC USA. [Taber, David J.; Fominaya, Cory E.] Ralph H Johnson VAMC, Dept Pharm Serv, Charleston, SC USA. [Egede, Leonard E.] Ralph H Johnson VAMC, Vet Affairs HSR&D Hlth Equ & Rural Outreach Innov, Charleston, SC USA. RP Taber, DJ (reprint author), Med Univ South Carolina, Div Transplant Surg, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. EM taberd@musc.edu OI Gebregziabher, Mulugeta/0000-0002-4826-481X FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [K23DK099440] FX Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award number K23DK099440. NR 30 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 EI 1421-9670 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2017 VL 45 IS 1 BP 91 EP 98 DI 10.1159/000453554 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA EH0CB UT WOS:000391428900014 PM 27907919 ER PT J AU Ahn, S Lee, SJ Kim, Y Kim, A Shin, N Choi, KU Lee, CH Huh, GY Kim, KM Setia, N Lauwers, GY Park, DY AF Ahn, Sangjeong Lee, So-Jeong Kim, Yonugkeum Kim, Ahrong Shin, Nari Choi, Kyung Un Lee, Chang-Hun Huh, Gi Yeong Kim, Kyong-Mee Setia, Namrata Lauwers, Gregory Y. Park, Do Youn TI High-throughput Protein and mRNA Expression-based Classification of Gastric Cancers Can Identify Clinically Distinct Subtypes, Concordant With Recent Molecular Classifications SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE diagnosis; gastric cancer; immunohistochemical analysis; in situ hybridization; molecular classification ID HELICOBACTER-PYLORI INFECTION; LABEL PHASE-3 TRIAL; MICROSATELLITE INSTABILITY; E-CADHERIN; GASTROESOPHAGEAL JUNCTION; COLORECTAL ADENOCARCINOMAS; PATIENT SURVIVAL; CARCINOMA; CHEMOTHERAPY; FEATURES AB Gastric cancers have recently been classified into several types on the basis of molecular characterization, and the new taxonomy has shown to have clinical relevance. However, the technology required for thorough molecular classification is complicated and expensive, currently preventing widespread use. We aimed to reproduce the results of molecular classification using only simple techniques, that is, immunohistochemical analysis and in situ hybridization. We classified a cohort of 349 successive gastric adenocarcinomas into 5 subtypes, on the basis of protein or mRNA expression of MLH1, E-cadherin, p53, and Epstein-Barr virus. We observed that the subtypes presented distinct clinicopathologic characteristics and corresponded to the molecular classifications previously reported. Epstein-Barr virus-positive tumors were more common in male individuals and in the body of the stomach. Microsatellite-unstable (MSI) tumors, which showed aberrant MLH1 expression, were correlated with increased age and intestinal histology. Both types showed better overall survival than the other types. Gastric cancers with reduced expression of E-cadherin, corresponding to the epithelial to mesenchymal transition or genome stable subtypes, showed the poorest overall survival, with a high prevalence of poorly cohesive carcinoma (ie, diffuse type, of the Lauren classification system). In conclusion, we were able to reproduce a previously reported molecular classification of gastric cancers using immunohistochemical analysis and in situ hybridization. We verified the effectiveness and applicability of this method, which shows promise for use in a clinical setting in the foreseeable future. C1 [Ahn, Sangjeong; Lee, So-Jeong; Kim, Yonugkeum; Kim, Ahrong; Choi, Kyung Un; Lee, Chang-Hun; Park, Do Youn] Pusan Natl Univ Hosp, Dept Pathol, 1-10 Ami Dong, Busan 602739, South Korea. [Ahn, Sangjeong; Lee, So-Jeong; Kim, Yonugkeum; Kim, Ahrong; Choi, Kyung Un; Lee, Chang-Hun; Park, Do Youn] Pusan Natl Univ, Sch Med, 1-10 Ami Dong, Busan 602739, South Korea. [Ahn, Sangjeong; Lee, So-Jeong; Kim, Yonugkeum; Kim, Ahrong; Choi, Kyung Un; Lee, Chang-Hun; Park, Do Youn] Pusan Natl Univ, Biomed Res Inst, Busan, South Korea. [Ahn, Sangjeong] Sungkyunkwan Univ, Sch Med, Kangbuk Samsung Hosp, Dept Pathol, Seoul, South Korea. [Shin, Nari] Pusan Natl Univ, Yangsan Hosp, Dept Pathol, Busan, South Korea. [Huh, Gi Yeong] Pusan Natl Univ, Sch Med, Dept Forens Med, Busan, South Korea. [Huh, Gi Yeong] Pusan Natl Univ, Med Res Inst, Busan, South Korea. [Kim, Kyong-Mee] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pathol & Translat Genom, Seoul, South Korea. [Setia, Namrata] Univ Chicago, Dept Anat Pathol, Chicago, IL 60637 USA. [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Park, DY (reprint author), Pusan Natl Univ Hosp, Dept Pathol, 1-10 Ami Dong, Busan 602739, South Korea.; Park, DY (reprint author), Pusan Natl Univ, Sch Med, 1-10 Ami Dong, Busan 602739, South Korea. EM pdy220@pusan.ac.kr FU Ministry of Health, Welfare, and Family Affairs; National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea [0920050] FX The biospecimens for this study were provided by the Pusan National University Hospital or by members of the National Biobank of Korea, which is supported by the Ministry of Health, Welfare, and Family Affairs. This study was supported by a grant (0920050) from the National R&D Program for Cancer Control, Ministry for Health, Welfare and Family Affairs, Republic of Korea. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 62 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2017 VL 41 IS 1 BP 106 EP 115 DI 10.1097/PAS.0000000000000756 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA EH0BL UT WOS:000391427300013 PM 27819872 ER PT J AU Everett, J Srivastava, A Misdraji, J AF Everett, Jamie Srivastava, Amitabh Misdraji, Joseph TI Fibrin Ring Granulomas in Checkpoint Inhibitor-induced Hepatitis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ipilimumab; nivolumab; immune checkpoint inhibitor; fibrin ring granuloma; hepatitis; liver biopsy ID Q-FEVER; IPILIMUMAB; LIVER; INFECTION; PATHOLOGY AB Fibrin ring granulomas are an uncommon finding in liver biopsies although they have been described in liver injury secondary to several infectious and noninfectious entities, most notably Q fever. Immune checkpoint inhibitors are recent advances in cancer therapy, and stimulate the immune system to cause antitumoral effects but may also lead to adverse immune events such as hepatitis and colitis. We report 2 patients on combination ipilimumab/nivolumab who developed hepatitis and had fibrin ring granulomas in their liver biopsies. C1 [Everett, Jamie; Misdraji, Joseph] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. [Srivastava, Amitabh] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Misdraji, J (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 105, Boston, MA 02118 USA. EM jmisdraji@partners.org NR 25 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 0147-5185 EI 1532-0979 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2017 VL 41 IS 1 BP 134 EP 137 DI 10.1097/PAS.0000000000000759 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA EH0BL UT WOS:000391427300017 PM 27792061 ER PT J AU Moura, LMVR Westover, MB Kwasnik, D Cole, AJ Hsu, J AF Moura, Lidia M. V. R. Westover, M. Brandon Kwasnik, David Cole, Andrew J. Hsu, John TI Causal inference as an emerging statistical approach in neurology: an example for epilepsy in the elderly SO CLINICAL EPIDEMIOLOGY LA English DT Review DE epilepsy; epidemiology; neurostatistics; causal inference ID NURSING-HOME RESIDENTS; ANTIEPILEPTIC DRUG-USE; GENERIC SUBSTITUTION; RANDOMIZED-TRIALS; CASE-DEFINITION; OLDER-PEOPLE; 1ST SEIZURE; HEALTH DATA; CARE; VALIDATION AB The elderly population faces an increasing number of cases of chronic neurological conditions, such as epilepsy and Alzheimer's disease. Because the elderly with epilepsy are commonly excluded from randomized controlled clinical trials, there are few rigorous studies to guide clinical practice. When the elderly are eligible for trials, they either rarely participate or frequently have poor adherence to therapy, thus limiting both generalizability and validity. In contrast, large observational data sets are increasingly available, but are susceptible to bias when using common analytic approaches. Recent developments in causal inference-analytic approaches also introduce the possibility of emulating randomized controlled trials to yield valid estimates. We provide a practical example of the application of the principles of causal inference to a large observational data set of patients with epilepsy. This review also provides a framework for comparative-effectiveness research in chronic neurological conditions. C1 [Moura, Lidia M. V. R.; Westover, M. Brandon; Kwasnik, David; Cole, Andrew J.] Massachusetts Gen Hosp, Dept Neurol, Epilepsy Serv, Boston, MA 02114 USA. [Moura, Lidia M. V. R.; Westover, M. Brandon; Cole, Andrew J.] Harvard Med Sch, Boston, MA USA. [Hsu, John] Massachusetts Gen Hosp, Mongan Inst, Boston, MA 02114 USA. [Hsu, John] Harvard Med Sch, Dept Med, Boston, MA USA. [Hsu, John] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. RP Moura, LMVR (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM lidia.moura@mgh.harvard.edu FU Clinical Research Fellowship by American Brain Foundation; NIH (NIH-NINDS) [1K23NS090900]; NIH [1R01 CA164023-04, 2P01AG032952-06A1, R01 HD075121-04, R01 MH104560-02] FX The authors acknowledge Miguel Hernan, MD, PhD, MPH, MSc of the Harvard T Chan School of Public Health, Departments of Epidemiology and Biostatistics for statistical consultation. LMVRM is the recipient of a 2015-2016 Clinical Research Fellowship sponsored by the American Brain Foundation. MBW receives grant funding from NIH (NIH-NINDS 1K23NS090900). JH receives grant funding from NIH (1R01 CA164023-04, 2P01AG032952-06A1, R01 HD075121-04, R01 MH104560-02). NR 59 TC 0 Z9 0 U1 3 U2 3 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1179-1349 J9 CLIN EPIDEMIOL JI Clin. Epidemiol. PY 2017 VL 9 BP 9 EP 18 DI 10.2147/CLEP.S121023 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA EG9EI UT WOS:000391360700001 PM 28115873 ER PT J AU Dubin, RF Deo, R Bansal, N Anderson, AH Yang, P Go, AS Keane, M Townsend, R Porter, A Budoff, M Malik, S He, J Rahman, M Wright, J Cappola, T Kallem, R Roy, J Sha, DH Shlipak, MG AF Dubin, Ruth F. Deo, Rajat Bansal, Nisha Anderson, Amanda H. Yang, Peter Go, Alan S. Keane, Martin Townsend, Ray Porter, Anna Budoff, Matthew Malik, Shaista He, Jiang Rahman, Mahboob Wright, Jackson Cappola, Thomas Kallem, Radhakrishna Roy, Jason Sha, Daohang Shlipak, Michael G. CA CRIC Study Investigators TI Associations of Conventional Echocardiographic Measures with Incident Heart Failure and Mortality: The Chronic Renal Insufficiency Cohort SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CHRONIC KIDNEY-DISEASE; CARDIOVASCULAR EVENTS; DIASTOLIC FUNCTION; DIALYSIS PATIENTS; ESRD PATIENTS; RISK; MASS; RECOMMENDATIONS; METAANALYSIS AB Background and objectives Heart failure is the most frequent cardiac complication of CKD. Left ventricular hypertrophy is common and develops early in CKD, but studies have not adequately evaluated the association of left ventricular mass index with heart failure incidence among men and women with CKD. Design, setting, participants, & measurements We evaluated echocardiograms of 2567 participants without self reported heart failure enrolled in the Chronic Renal Insufficiency Cohort Study. Two-dimensional echocardiograms were performed at the year 1 study visit and interpreted at a central core laboratory. Left ventricular mass index was calculated using the linear method, indexed to height(2.7), and analyzed using sex-specific quartiles. The primary outcomes of incident heart failure and all-cause mortality were adjudicated over a median of 6.6 (interquartile range, 5.7-7.6) years. Results Among 2567 participants, 45% were women, and 54% were nonwhite race; mean (SD) age was 59 +/- 11 years old, and mean eGFR was 44 +/- 17 ml/min per 1.73 m(2). During a median follow-up period of 6.6 years, 262 participants developed heart failure, and 470 participants died. Compared with participants in the first quartile of left ventricular mass index, those in the highest quartile had higher rates of incident heart failure (hazard ratio, 3.96; 95% confidence interval, 1.96 to 8.02) and mortality (hazard ratio, 1.86; 95% confidence interval, 1.22 to 2.85), even after adjustment for B type natriuretic peptide, troponin T, mineral metabolism markers, and other cardiovascular disease risk factors. Those in the lowest quartile of ejection fraction had higher rates of incident heart failure (hazard ratio, 3.01; 95% confidence interval, 1.94 to 4.67) but similar mortality rates (hazard ratio, 1.18; 95% confidence interval, 0.89 to 1.57) compared with those in the highest quartile. Diastolic dysfunction was not significantly associated with heart failure or death. Conclusions Among persons with CKD and without history of cardiovascular disease, left ventricular mass index is strongly associated with incident heart failure, even after adjustment for major cardiovascular risk factors and biomarkers. C1 [Dubin, Ruth F.; Shlipak, Michael G.] Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Deo, Rajat; Anderson, Amanda H.; Yang, Peter; Townsend, Ray; Cappola, Thomas; Kallem, Radhakrishna; Roy, Jason; Sha, Daohang] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Bansal, Nisha] Univ Washington, Seattle, WA 98195 USA. [Go, Alan S.] Kaiser Permanente, Div Clin Res, Oakland, CA USA. [Keane, Martin; Malik, Shaista] Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. [Porter, Anna] Univ Calif Irvine, Irvine, CA USA. [Budoff, Matthew] Univ Calif Los Angeles, Los Angeles, CA USA. [He, Jiang] Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA USA. [Rahman, Mahboob; Wright, Jackson] Univ Hosp Case Med Ctr, Cleveland, OH USA. RP Dubin, RF (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 111A1, San Francisco, CA 94121 USA. EM ruth.dubin@ucsf.edu FU National Institutes of Health (NIH) [K23 DK092354, R03DK104013, 5R01DK066488, 1R01DK098234]; National Institute of Diabetes and Digestive and Kidney Diseases [U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, U01DK060902]; Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) grant [UL1TR000003]; Johns Hopkins University [UL1 TR-000424]; University of Maryland General Clinical Research Center [M01 RR-16500]; Clinical and Translational Science Collaborative of Cleveland; NCATS component of the NIH [UL1TR000439]; NIH Roadmap for Medical Research; Michigan Institute for Clinical and Health Research [UL1TR000433]; University of Illinois at Chicago Clinical and Translational Science Award [UL1RR029879]; Tulane University Translational Research in Hypertension and Renal Biology grant [P30GM103337]; Kaiser Permanente NIH/National Center for Research Resources University California San Francisco-Clinical and Translational Science Institute [L1 RR-024131] FX This work was supported by National Institutes of Health (NIH) research grants K23 DK092354 (to R.F.D.), R03DK104013 (to R.F.D.), 5R01DK066488 (to M.G.S.), and 1R01DK098234 (to M.G.S.). Funding for the Chronic Renal Insufficiency Cohort Study was obtained under a cooperative agreement from the National Institute of Diabetes and Digestive and Kidney Diseases (grants U01DK060990, U01DK060984, U01DK061022, U01DK061021, U01DK061028, U01DK060980, U01DK060963, and U01DK060902). In addition, this work was supported, in part, by the Perelman School of Medicine at the University of Pennsylvania Clinical and Translational Science Award NIH/National Center for Advancing Translational Sciences (NCATS) grant UL1TR000003, Johns Hopkins University grant UL1 TR-000424, University of Maryland General Clinical Research Center grant M01 RR-16500, the Clinical and Translational Science Collaborative of Cleveland, grant UL1TR000439 from the NCATS component of the NIH and NIH Roadmap for Medical Research, Michigan Institute for Clinical and Health Research grant UL1TR000433, University of Illinois at Chicago Clinical and Translational Science Award grant UL1RR029879, Tulane University Translational Research in Hypertension and Renal Biology grant P30GM103337, and Kaiser Permanente NIH/National Center for Research Resources University California San Francisco-Clinical and Translational Science Institute grant L1 RR-024131. NR 33 TC 0 Z9 0 U1 4 U2 4 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 JAN PY 2017 VL 12 IS 1 BP 60 EP 68 DI 10.2215/CJN.02700316 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA EG9YD UT WOS:000391416700010 PM 28062676 ER PT J AU Taber, DJ Hunt, KJ Gebregziabher, M Srinivas, T Chavin, KD Baliga, PK Egede, LE AF Taber, David J. Hunt, Kelly J. Gebregziabher, Mulugeta Srinivas, Titte Chavin, Kenneth D. Baliga, Prabhakar K. Egede, Leonard E. TI A Comparative Effectiveness Analysis of Early Steroid Withdrawal in Black Kidney Transplant Recipients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID AFRICAN-AMERICAN RECIPIENTS; RENAL-ALLOGRAFT SURVIVAL; LONG-TERM; ACUTE REJECTION; RECEIVING SIROLIMUS; SURVEILLANCE BIOPSY; GRAFT OUTCOMES; FLOW-CYTOMETRY; DOUBLE-BLIND; TACROLIMUS AB Background and objectives There is continued debate whether early steroid withdrawal is safe to use in high immunologic risk patients, such as blacks. The goal of this study was to use comparative effectiveness methodology to elucidate the safety of early steroid withdrawal in blacks with kidney transplants. Design, setting, participants, & measurements Our cohort study used United Network of Organ Sharing data including all adult black kidney transplant recipients from 2000 to 2009 followed through 2014. Propensity score matching was used to equalize baseline risk between continued steroid and early steroid withdrawal groups. Interaction terms were used to assess if the effect of early steroid withdrawal on outcomes varied by baseline and post-transplant factors. Of 26,582 eligible black patients with kidney transplants (5825 [21.9%] with early steroid withdrawal), 5565 patients with early steroid withdrawal were matched to 5565 blacks on continued steroid use. Results Black patients with early steroid withdrawal had similar risk of graft loss (hazard ratio, 0.98; 95% confidence interval, 0.92 to 1.04; P=0.42) and lower risk of death (hazard ratio, 0.91; 95% confidence interval, 0.84 to 0.99; P=0.02), primarily driven by a late mortality advantage (>4 years post-transplant). Delayed graft function, cytolytic induction, tacrolimus, and mycophenolate significantly modified the effect of early steroid withdrawal on outcomes (P<0.05). Acute rejection rates were slightly higher in the continued steroid group (13.0% versus 11.3%, respectively; P<0.01), but this was not associated with graft or patient survival. Conclusions Overall, early steroid withdrawal in black kidney transplant recipients was not associated with graft loss but seemed to be associated with better long term patient survival. Early steroid withdrawal in blacks not receiving cytolytic induction, tacrolimus, and mycophenolate or those with delayed graft function was associated with higher risk of graft loss and death. C1 [Taber, David J.; Chavin, Kenneth D.; Baliga, Prabhakar K.] Med Univ South Carolina, Div Transplant Surg, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Srinivas, Titte] Med Univ South Carolina, Div Transplant Nephrol, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Hunt, Kelly J.; Gebregziabher, Mulugeta] Med Univ South Carolina, Coll Med, Dept Publ Hlth Sci, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Taber, David J.] Ralph H Johnson Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Vet Affairs Hlth Serv Res & Dev, Dept Pharm Serv, Charleston, SC USA. [Egede, Leonard E.] Ralph H Johnson Vet Affairs Med Ctr, Hlth Equ & Rural Outreach Innovat Ctr, Vet Affairs Hlth Serv Res & Dev, Dept Med, Charleston, SC USA. RP Taber, DJ (reprint author), Med Univ South Carolina, Div Transplant Surg, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. EM taberd@musc.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [K23DK099440] FX Research reported in this publication was supported by National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health award K23DK099440. NR 38 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 EI 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2017 VL 12 IS 1 BP 131 EP 139 DI 10.2215/CJN.04880516 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA EG9YD UT WOS:000391416700018 PM 27979979 ER PT J AU Yurgelun, MB Boland, CR AF Yurgelun, Matthew B. Boland, C. Richard TI "New" Cancer Genes and Inherited Colorectal Cancer Risk: Caveat Emptor SO GASTROENTEROLOGY LA English DT Editorial Material ID MISMATCH REPAIR DEFICIENCY; GERMLINE MUTATIONS; ADENOMATOUS POLYPOSIS; COLON-CANCER; IDENTIFICATION; PREDISPOSE; HOMOLOG C1 [Yurgelun, Matthew B.] Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. [Yurgelun, Matthew B.] Harvard Med Sch, Boston, MA USA. [Boland, C. Richard] Baylor Univ, Med Ctr, GI Canc Res Lab, Dallas, TX 75226 USA. RP Boland, CR (reprint author), Baylor Univ, Med Ctr, GI Canc Res Lab, Dallas, TX 75226 USA. EM crichardboland@gmail.com NR 18 TC 1 Z9 1 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2017 VL 152 IS 1 BP 12 EP 13 DI 10.1053/j.gastro.2016.11.027 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EG3PC UT WOS:000390956200016 PM 27889571 ER PT J AU Shelton, E Ananthakrishnan, AN AF Shelton, Edward Ananthakrishnan, Ashwin N. TI No Excess Cancer Recurrence After Immunosuppressive Drugs in a Meta-analysis of Cohorts of Patients With Immune-mediated Diseases: A Mirage Related to Propensity Bias? Reply SO GASTROENTEROLOGY LA English DT Letter ID NONMELANOMA SKIN-CANCER; RISK C1 [Shelton, Edward; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Med Sch, Boston, MA USA. RP Shelton, E (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 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 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 2017 VL 152 IS 1 BP 306 EP 306 DI 10.1053/j.gastro.2016.11.037 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EG3PC UT WOS:000390956200054 PM 27893976 ER PT J AU Safdar, N Sengupta, S Musuuza, JS Juthani-Mehta, M Drees, M Abbo, LM Milstone, AM Furuno, JP Varman, M Anderson, DJ Morgan, DJ Miller, LG Snyder, GM AF Safdar, Nasia Sengupta, Sharmila Musuuza, Jackson S. Juthani-Mehta, Manisha Drees, Marci Abbo, Lilian M. Milstone, Aaron M. Furuno, Jon P. Varman, Meera Anderson, Deverick J. Morgan, Daniel J. Miller, Loren G. Snyder, Graham M. CA SHEA Res Comm TI Status of the Prevention of Multidrug-Resistant Organisms in International Settings: A Survey of the Society for Healthcare Epidemiology of America Research Network SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID STAPHYLOCOCCUS-AUREUS; INFECTIONS; PREVALENCE; HOSPITALS; BACTERIA AB OBJECTIVE. To examine self-reported practices and policies to reduce infection and transmission of multidrug-resistant organisms (MDRO) in healthcare settings outside the United States. DESIGN. Cross-sectional survey. PARTICIPANTS. International members of the Society for Healthcare Epidemiology of America (SHEA) Research Network. METHODS. Electronic survey of infection control and prevention practices, capabilities, and barriers outside the United States and Canada. Participants were stratified according to their country's economic development status as defined by the World Bank as low-income, lower-middle-income, upper-middle-income, and high-income. RESULTS. A total of 76 respondents (33%) of 229 SHEA members outside the United States and Canada completed the survey questionnaire, representing 30 countries. Forty (53%) were high-, 33 (43%) were middle-, and 1 (1%) was a low-income country. Country data were missing for 2 respondents (3%). Of the 76 respondents, 64 (84%) reported having a formal or informal antibiotic stewardship program at their institution. High-income countries were more likely than middle-income countries to have existing MDRO policies (39/64 [61%] vs 25/64 [39%], P=.003) and to place patients with MDRO in contact precautions (40/72 [56%] vs 31/72 [44%], P=.05). Major barriers to preventing MDRO transmission included constrained resources (infrastructure, supplies, and trained staff) and challenges in changing provider behavior. CONCLUSIONS. In this survey, a substantial proportion of institutions reported encountering barriers to implementing key MDRO prevention strategies. Interventions to address capacity building internationally are urgently needed. Data on the infection prevention practices of low income countries are needed. C1 [Safdar, Nasia] Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin Hosp & Clin, Dept Infect Dis, Madison, WI 53792 USA. [Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Sengupta, Sharmila] Medanta Medicity, Sect 38, Gurgaon, Haryana, India. [Musuuza, Jackson S.] Univ Wisconsin, Inst Clin & Translat Res, Madison, WI USA. [Juthani-Mehta, Manisha] Yale Univ, Sch Med, Dept Internal Med, Infect Dis Sect, New Haven, CT 06510 USA. [Drees, Marci] Christiana Care Hlth Syst, Dept Med, Newark, DE USA. [Drees, Marci] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA. [Abbo, Lilian M.] Univ Miami, Miller Sch Med, Dept Med, Div Infect Dis, Miami, FL 33136 USA. [Milstone, Aaron M.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Infect Dis, Baltimore, MD 21205 USA. [Furuno, Jon P.] Oregon Hlth & Sci Univ, Oregon State Univ, Coll Pharm, Dept Pharm Practice, Portland, OR 97201 USA. [Varman, Meera] Creighton Univ, Med Ctr, Dept Pediat, Div Infect Dis, Omaha, NE USA. [Anderson, Deverick J.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA. [Morgan, Daniel J.] Univ Maryland, Sch Med, Vet Affairs Maryland Healthcare Syst, Baltimore, MD 21201 USA. [Morgan, Daniel J.] Ctr Dis Dynam Econ & Policy, Washington, DC USA. [Miller, Loren G.] Harbor UCLA Med Ctr, Div Infect Dis, Torrance, CA 90509 USA. [Snyder, Graham M.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Safdar, N (reprint author), UWMF Centennial Bldg,1685 Highland Ave, Madison, WI 53705 USA. EM ns2@medicine.wisc.edu NR 18 TC 0 Z9 0 U1 0 U2 0 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 JAN PY 2017 VL 38 IS 1 BP 53 EP 60 DI 10.1017/ice.2016.242 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA EG7QD UT WOS:000391243000009 PM 27817759 ER PT J AU Bernstein, D Sood, A Mellema, J Li, Y Ring, D AF Bernstein, David N. Sood, Ankit Mellema, Jos J. Li, Yue Ring, David TI Lifetime prevalence of and factors associated with non-traumatic musculoskeletal pains amongst surgeons and patients SO INTERNATIONAL ORTHOPAEDICS LA English DT Article DE Non-traumatic pain; Coping strategy; Biopsychosocial; Pain management ID QUALITY-OF-LIFE; HEALTH; DEPRESSION; DISABILITY; PERFORMANCE; ILLNESS; ANXIETY AB Purpose There is evidence that surgeons make different recommendations for people seeking their care than they make for themselves. There may also be differences in pain episodes and management strategies between surgeons and people seeking care, knowledge of which might improve care. We aimed to assess whether the prevalence of non-traumatic pains, treatments and other factors differed between patients and surgeons. Materials and methods Two-hundred and twenty surgeons, members of the Science of Variation Group (SOVG), and 248 patients seeking care at the Hand Service at a large academic hospital completed a survey regarding the lifetime incidence of non-traumatic pains lasting > one month using short versions of the Pain Catastrophising Scale (PCS-4); Patient Health Questionnaire (PHQ-2); and Short Health Anxiety Inventory (SHAI-5). Results Surgeons had a higher prevalence of at least one non-traumatic pain than patients and were more likely to report pain at more than one anatomical site. Patients were more likely to receive any treatment: surgery; injection; non-opioid medication; opioid medication; physical or occupational therapy. Patients missed work more often than surgeons. Age was the only factor independently associated with patient pain. Practicing in the United States was the only factor independently associated with surgeon pain. Conclusions Non-traumatic pains are extremely common. Surgeons have particularly effective coping strategies, allowing them to maintain their life roles with limited medical care when in pain. Increasing the appeal and availability of methods for optimising coping strategies might help to narrow the gap between surgeon and patient health. C1 [Bernstein, David N.] Univ Rochester, Sch Med & Dent, 601 Elmwood Ave,Box 54, Rochester, NY 14642 USA. [Sood, Ankit] Harvard Med Sch, Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv,Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. [Mellema, Jos J.] Rode Kruis Ziekenhuis, Dept Surg, Vondellaan 13, NL-1942 LE Beverwijk, Netherlands. [Li, Yue] Univ Rochester, Div Hlth Policy & Outcomes Res, Dept Publ Hlth Sci, Med Ctr, Box CU 420644,265 Crittenden Blvd, Rochester, NY 14642 USA. [Ring, David] Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, 1400 Barbara Jordan Blvd Suite 2-834 MC R1800, Austin, TX 78723 USA. RP Ring, D (reprint author), Univ Texas Austin, Dell Med Sch, Dept Surg & Perioperat Care, 1400 Barbara Jordan Blvd Suite 2-834 MC R1800, Austin, TX 78723 USA. EM david_bernstein@urmc.rochester.edu; isoodu@gmail.com; josjmellema@gmail.com; yue_li@urmc.rochester.edu; david.ring@austin.utexas.edu OI Bernstein, David/0000-0002-1784-3288 NR 30 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0341-2695 EI 1432-5195 J9 INT ORTHOP JI Int. Orthop. PD JAN PY 2017 VL 41 IS 1 BP 31 EP 38 DI 10.1007/s00264-016-3338-5 PG 8 WC Orthopedics SC Orthopedics GA EG9IL UT WOS:000391372100005 PM 27864586 ER PT J AU Kulke, MH Horsch, D Caplin, ME Anthony, LB Bergsland, E Oberg, K Welin, S Warner, RRP Lombard-Bohas, C Kunz, PL Grande, E Valle, JW Fleming, D Lapuerta, P Banks, P Jackson, S Zambrowicz, B Sands, AT Pavel, M AF Kulke, Matthew H. Hoersch, Dieter Caplin, Martyn E. Anthony, Lowell B. Bergsland, Emily Oberg, Kjell Welin, Staffan Warner, Richard R. P. Lombard-Bohas, Catherine Kunz, Pamela L. Grande, Enrique Valle, Juan W. Fleming, Douglas Lapuerta, Pablo Banks, Phillip Jackson, Shanna Zambrowicz, Brian Sands, Arthur T. Pavel, Marianne TI Telotristat Ethyl, a Tryptophan Hydroxylase Inhibitor for the Treatment of Carcinoid Syndrome SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; NEUROENDOCRINE-TUMORS; SEROTONIN SYNTHESIS; POPULATION; OCTREOTIDE; MANAGEMENT; DIAGNOSIS; ETIPRATE; DISEASE AB Purpose Preliminary studies suggested that telotristat ethyl, a tryptophan hydroxylase inhibitor, reduces bowel movement (BM) frequency in patients with carcinoid syndrome. This placebo-controlled phase III study evaluated telotristat ethyl in this setting. Patients and Methods Patients (N = 135) experiencing four or more BMs per day despite stable-dose somatostatin analog therapy received (1: 1: 1) placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg three times per day orally during a 12-week double-blind treatment period. The primary end point was change from baseline in BM frequency. In an open-label extension, 115 patients subsequently received telotristat ethyl 500 mg. Results Estimated differences in BM frequency per day versus placebo averaged over 12 weeks were -0.81 for telotristat ethyl 250 mg (P < .001) and -0.69 for telotristat ethyl 500 mg (P,.001). At week 12, mean BM frequency reductions per day for placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg were -0.9, -1.7, and -2.1, respectively. Responses, predefined as a BM frequency reduction >= 30% from baseline for >= 50% of the double-blind treatment period, were observed in 20%, 44%, and 42% of patients given placebo, telotristat ethyl 250 mg, and telotristat ethyl 500 mg, respectively. Both telotristat ethyl dosages significantly reduced mean urinary 5-hydroxyindole acetic acid versus placebo at week 12 (P < .001). Mild nausea and asymptomatic increases in gamma-glutamyl transferase were observed in some patients receiving telotristat ethyl. Follow-up of patients during the open-label extension revealed no new safety signals and suggested sustained BM responses to treatment. Conclusion Among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in BM frequency and urinary 5-hydroxyindole acetic acid. (C) 2016 by American Society of Clinical Oncology C1 [Kulke, Matthew H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fleming, Douglas] Ipsen Biosci, Cambridge, MA USA. [Hoersch, Dieter] Zentralklinik Bad Berka, Bad Berka, Germany. [Pavel, Marianne] Charite, Berlin, Germany. [Caplin, Martyn E.] Royal Free Hosp, London, England. [Valle, Juan W.] Univ Manchester, Christie Natl Hlth Serv Fdn Trust, Manchester, Lancs, England. [Anthony, Lowell B.] Univ Kentucky, Lexington, KY USA. [Bergsland, Emily] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Kunz, Pamela L.] Stanford Univ, Palo Alto, CA 94304 USA. [Oberg, Kjell; Welin, Staffan] Uppsala Univ, Uppsala, Sweden. [Warner, Richard R. P.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Lombard-Bohas, Catherine] Hosp Civils Lyon, Hop Edouard Herriot, Lyon, France. [Lapuerta, Pablo; Banks, Phillip; Jackson, Shanna; Zambrowicz, Brian; Sands, Arthur T.] Lexicon Pharmaceut, The Woodlands, TX USA. [Grande, Enrique] Hosp Univ Ramon y Cajal, Madrid, Spain. RP Kulke, MH (reprint author), Harvard Med Sch, Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM Matthew_Kulke@dfci.harvard.edu FU Lexicon Pharmaceuticals FX Supported by Lexicon Pharmaceuticals. NR 24 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2017 VL 35 IS 1 BP 14 EP + DI 10.1200/JCO.2016.69.2780 PG 15 WC Oncology SC Oncology GA EG9LV UT WOS:000391381300005 PM 27918724 ER PT J AU Herrera, AF Mei, M Low, L Kim, HT Griffin, GK Song, JY Merryman, RW Bedell, V Pak, C Sun, H Paris, T Stiller, T Brown, JR Budde, LE Chan, WC Chen, R Davids, MS Freedman, AS Fisher, DC Jacobsen, ED Jacobson, CA LaCasce, AS Murata-Collins, J Nademanee, AP Palmer, JM Pihan, GA Pillai, R Popplewell, L Siddiqi, T Sohani, AR Zain, J Rosen, ST Kwak, LW Weinstock, DM Forman, SJ Weisenburger, DD Kim, Y Rodig, SJ Krishnan, A Armand, P AF Herrera, Alex F. Mei, Matthew Low, Lawrence Kim, Haesook T. Griffin, Gabriel K. Song, Joo Y. Merryman, Reid W. Bedell, Victoria Pak, Christine Sun, Heather Paris, Tanya Stiller, Tracey Brown, Jennifer R. Budde, Lihua E. Chan, Wing C. Chen, Robert Davids, Matthew S. Freedman, Arnold S. Fisher, David C. Jacobsen, Eric D. Jacobson, Caron A. LaCasce, Ann S. Murata-Collins, Joyce Nademanee, Auayporn P. Palmer, Joycelynne M. Pihan, German A. Pillai, Raju Popplewell, Leslie Siddiqi, Tanya Sohani, Aliyah R. Zain, Jasmine Rosen, Steven T. Kwak, Larry W. Weinstock, David M. Forman, Stephen J. Weisenburger, Dennis D. Kim, Young Rodig, Scott J. Krishnan, Amrita Armand, Philippe TI Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; CHOP CONSORTIUM PROGRAM; NON-HODGKIN-LYMPHOMA; SALVAGE CHEMOTHERAPY; PROTEIN EXPRESSION; MYC REARRANGEMENTS; BCL2; TRANSLOCATIONS; VINCRISTINE AB Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% (P = .049), and the 4-year OS was 56% versus 67% (P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% (P = .013), and 4-year OS was 25% versus 61% (P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response (v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT. (C) 2016 by American Society of Clinical Oncology C1 [Herrera, Alex F.; Mei, Matthew; Low, Lawrence; Song, Joo Y.; Bedell, Victoria; Paris, Tanya; Stiller, Tracey; Budde, Lihua E.; Chan, Wing C.; Chen, Robert; Murata-Collins, Joyce; Nademanee, Auayporn P.; Palmer, Joycelynne M.; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Zain, Jasmine; Rosen, Steven T.; Kwak, Larry W.; Forman, Stephen J.; Weisenburger, Dennis D.; Kim, Young; Krishnan, Amrita] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Kim, Haesook T.; Brown, Jennifer R.; Davids, Matthew S.; Freedman, Arnold S.; Fisher, David C.; Jacobsen, Eric D.; Jacobson, Caron A.; LaCasce, Ann S.; Weinstock, David M.; Rodig, Scott J.; Armand, Philippe] Dana Farber Canc Inst, Boston, MA 02115 USA. [Griffin, Gabriel K.; Merryman, Reid W.; Pak, Christine; Sun, Heather] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Pihan, German A.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Sohani, Aliyah R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Armand, P (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02215 USA. EM parmand@partners.org FU Conquer Cancer Foundation/ASCO Young Investigator Award; National Cancer Institute (NCI) [NIH 2K12CA001727-21, P50 CA107399, P30CA033572]; Dana-Farber Cancer Institute Award Fund for Collaborative Research Initiatives in Hematologic Oncology; Harold and Virginia Lash/David Lash Fund for Lymphoma Research FX Supported by a Conquer Cancer Foundation/ASCO Young Investigator Award (A.F.H.) and National Cancer Institute (NCI) Grants No. NIH 2K12CA001727-21 and P50 CA107399 (A.F.H.); the Dana-Farber Cancer Institute Award Fund for Collaborative Research Initiatives in Hematologic Oncology (A.F.H., D.M.W., S.J.R., P.A.); the Harold and Virginia Lash/David Lash Fund for Lymphoma Research; and NCI Grant No. P30CA033572 for work performed in the COH Pathology Core. NR 37 TC 2 Z9 2 U1 5 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2017 VL 35 IS 1 BP 24 EP + DI 10.1200/JCO.2016.68.2740 PG 12 WC Oncology SC Oncology GA EG9LV UT WOS:000391381300006 PM 28034071 ER PT J AU Ferrell, BR Temel, JS Temin, S Alesi, ER Balboni, TA Basch, EM Firn, JI Paice, JA Peppercorn, JM Phillips, T Stovall, EL Zimmermann, C Smith, TJ AF Ferrell, Betty R. Temel, Jennifer S. Temin, Sarah Alesi, Erin R. Balboni, Tracy A. Basch, Ethan M. Firn, Janice I. Paice, Judith A. Peppercorn, Jeffrey M. Phillips, Tanyanika Stovall, Ellen L. Zimmermann, Camilla Smith, Thomas J. TI Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; OF-LIFE CARE; FAMILY CAREGIVERS; 30-DAY READMISSIONS; HOSPICE ENROLLMENT; TERMINALLY-ILL; UNITED-STATES; HEALTH-CARE; CONSULTATION AB Purpose To provide evidence-based recommendations to oncology clinicians, patients, family and friend caregivers, and palliative care specialists to update the 2012 American Society of Clinical Oncology (ASCO) provisional clinical opinion (PCO) on the integration of palliative care into standard oncology care for all patients diagnosed with cancer. Methods ASCO convened an Expert Panel of members of the ASCO Ad Hoc Palliative Care Expert Panel to develop an update. The 2012 PCO was based on a review of a randomized controlled trial (RCT) by the National Cancer Institute Physicians Data Query and additional trials. The panel conducted an updated systematic review seeking randomized clinical trials, systematic reviews, and meta-analyses, as well as secondary analyses of RCTs in the 2012 PCO, published from March 2010 to January 2016. Results The guideline update reflects changes in evidence since the previous guideline. Nine RCTs, one quasiexperimental trial, and five secondary analyses from RCTs in the 2012 PCO on providing palliative care services to patients with cancer and/or their caregivers, including family caregivers, were found to inform the update. Recommendations Inpatients and outpatients with advanced cancer should receive dedicated palliative care services, early in the disease course, concurrent with active treatment. Referral of patients to interdisciplinary palliative care teams is optimal, and services may complement existing programs. Providers may refer family and friend caregivers of patients with early or advanced cancer to palliative care services. (C) 2016 by American Society of Clinical Oncology C1 [Temin, Sarah] Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. [Ferrell, Betty R.] City Hope Med Ctr, Duarte, CA USA. [Temel, Jennifer S.; Peppercorn, Jeffrey M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Alesi, Erin R.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Basch, Ethan M.] Univ North Carolina Chapel Hill, Chapel Hill, NC USA. [Firn, Janice I.] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Paice, Judith A.] Northwestern Univ, Evanston, IL USA. [Phillips, Tanyanika] CHRISTUS St Frances Cabrini Hosp, Alexandria, LA USA. [Stovall, Ellen L.] Natl Coalit Canc Survivorship, Silver Spring, MD USA. [Smith, Thomas J.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Zimmermann, Camilla] Princess Margaret Canc Ctr, Toronto, ON, Canada. RP Ferrell, BR (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM guidelines@asco.org FU Helsinn Therapeutics; Pfizer FX Helsinn Therapeutics (Inst), Pfizer (Inst); Pfizer NR 72 TC 5 Z9 5 U1 7 U2 7 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 1 PY 2017 VL 35 IS 1 BP 96 EP + DI 10.1200/JCO.2016.70.1474 PG 19 WC Oncology SC Oncology GA EG9LV UT WOS:000391381300015 PM 28029308 ER PT J AU Birnbaum, FA Hamrah, P Jacobs, DS Song, BJ AF Birnbaum, Faith A. Hamrah, Pedram Jacobs, Deborah S. Song, Brian J. TI Acquired Corneal Neuropathy and Photoallodynia Associated With Malposition of an Ex-PRESS Shunt SO JOURNAL OF GLAUCOMA LA English DT Article DE corneal neuropathy; neuropathic pain; photoallodynia; Ex-PRESS shunt; trabeculectomy ID DRY EYE; PAIN AB Purpose: Corneal neuropathy is a recently described disease process that is not well understood and is likely underdiagnosed as a result. This is the first reported case of an acquired corneal neuropathy associated with malposition of an Ex-PRESS shunt. Methods: A single case report. Results: We report the case of a 50-year-old man with a history of multiple procedures for glaucoma who subsequently developed photoallodynia and corneal neuropathy in association with malposition of an Ex-PRESS shunt in the peripheral cornea. Laser confocal microscopy (HRT3/RCM) of the cornea showed the presence of neuromas, decreased nerve density, and a significant increase of dendritiform immune cells consistent with our diagnosis. Initial treatment with steroid pulse therapy did not result in decreased inflammation or symptomatic improvement leading to surgical explantation of the shunt. One month after surgery, there was noticeable improvement in the patient's pain and photoallodynia (approximately 40%) as well as the abnormalities seen on confocal microscopy. Conclusions: We hypothesize that poor Ex-PRESS shunt positioning can act as a nidus for corneal inflammation, resulting in corneal neuropathy and lowering of the nociception threshold. C1 [Birnbaum, Faith A.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Hamrah, Pedram] Tufts Univ, Sch Med, Dept Ophthalmol, New England Eye Ctr,Tufts Med Ctr, Boston, MA 02111 USA. [Jacobs, Deborah S.; Song, Brian J.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Song, BJ (reprint author), 243 Charles St, Boston, MA 02114 USA. EM brian_song@meei.harvard.edu NR 12 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1057-0829 EI 1536-481X J9 J GLAUCOMA JI J. Glaucoma PD JAN PY 2017 VL 26 IS 1 BP E19 EP E21 DI 10.1097/IJG.0000000000000502 PG 3 WC Ophthalmology SC Ophthalmology GA EG5XY UT WOS:000391119300006 PM 27513904 ER PT J AU Hope, TA Truillet, C Ehman, EC Afshar-Oromieh, A Aggarwal, R Ryan, CJ Carroll, PR Small, EJ Evans, MJ AF Hope, Thomas A. Truillet, Charles Ehman, Eric C. Afshar-Oromieh, Ali Aggarwal, Rahul Ryan, Charles J. Carroll, Peter R. Small, Eric J. Evans, Michael J. TI Ga-68-PSMA-11 PET Imaging of Response to Androgen Receptor Inhibition: First Human Experience SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE oncology: GU; PET; androgen receptor; PSMA PET; prostate cancer ID RESISTANT PROSTATE-CANCER; MEMBRANE ANTIGEN; DEPRIVATION THERAPY; PSMA; EXPRESSION; SURVIVAL; MARKER; CELLS AB The purpose of this work was to evaluate the effect of androgen receptor (AR) inhibition on prostate-specific membrane antigen (PSMA) uptake imaged using 68Ga-PSMA-11 PET in a mouse xenograft model and in a patient with castration-sensitive prostate cancer. Methods: We imaged 3 groups of 4 mice bearing LNCaPAR xenografts before and 7 d after treatment with ARN-509, orchiectomy, or control vehicle. Additionally, we imaged one patient with castration-sensitive prostate cancer before and 4 wk after treatment with androgen deprivation therapy (ADT). Uptake on pre-and posttreatment imaging was measured and compared. Results: PSMA uptake increased 1.5-to 2.0-fold in the xenograft mouse model after treatment with both orchiectomy and ARN-509 but not with vehicle. Patient imaging demonstrated a 7-fold increase in PSMA uptake after the initiation of ADT. Thirteen of 22 lesions in the imaged patient were visualized on PSMA PET only after treatment with ADT. Conclusion: Inhibition of the AR can increase PSMA expression in prostate cancer metastases and increase the number of lesions visualized using PSMA PET. The effect seen in cell and animal models can be recapitulated in humans. A better understanding of the temporal changes in PSMA expression is needed to leverage this effect for both improved diagnosis and improved therapy. C1 [Hope, Thomas A.; Truillet, Charles; Evans, Michael J.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St,Lobby 6,Ste 350, San Francisco, CA 94107 USA. [Hope, Thomas A.] San Francisco VA Med Ctr, Dept Radiol, San Francisco, CA USA. [Hope, Thomas A.; Aggarwal, Rahul; Ryan, Charles J.; Carroll, Peter R.; Small, Eric J.] Univ Calif San Francisco, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA 94143 USA. [Ehman, Eric C.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Afshar-Oromieh, Ali] Univ Heidelberg Hosp, Dept Nucl Med, Heidelberg, Germany. [Aggarwal, Rahul; Ryan, Charles J.; Small, Eric J.] Univ Calif San Francisco, Dept Med, Div Hematol Oncol, San Francisco, CA USA. [Carroll, Peter R.] Univ Calif San Francisco, Dept Urol, San Francisco, CA USA. RP Evans, MJ (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 185 Berry St,Lobby 6,Ste 350, San Francisco, CA 94107 USA. EM michael.evans@ucsf.edu FU Radiological Society of North America; Department of Radiology and Biomedical Imaging, UCSF; GE Healthcare; Prostate Cancer Foundation; National Institutes of Health [R00CA172695, 1R01CA17661]; Department of Defense Idea Development Award [PC140107]; UCSF Academic Senate; Department of Defense Prostate Cancer Research Program [PC151060]; National Cancer Institute of the National Institutes of Health [P30CA082103]; ORIC Pharmaceuticals, Inc. FX Dr. Hope receives grant support, is on the speaker's bureau for GE Healthcare, and was supported by the Radiological Society of North America and the Department of Radiology and Biomedical Imaging, UCSF. Dr. Evans receives consulting fees, owns shares in ORIC Pharmaceuticals, Inc., and was supported by the 2013 David H. Koch Young Investigator Award from the Prostate Cancer Foundation, the National Institutes of Health (R00CA172695, 1R01CA17661), a Department of Defense Idea Development Award (PC140107), the UCSF Academic Senate, and GE Healthcare. Dr. Truillet was supported by a postdoctoral fellowship from the Department of Defense Prostate Cancer Research Program (PC151060). Research from UCSF reported in this publication was supported in part by the National Cancer Institute of the National Institutes of Health under award P30CA082103. No other potential conflict of interest relevant to this article was reported. NR 25 TC 1 Z9 1 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 EI 1535-5667 J9 J NUCL MED JI J. Nucl. Med. PD JAN PY 2017 VL 58 IS 1 BP 81 EP 84 DI 10.2967/jnumed.116.181800 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EG8YM UT WOS:000391343400022 PM 27660139 ER PT J AU Schreuder, WH Peacock, ZS Ebb, D Chuang, SK Kaban, LB AF Schreuder, Willem H. Peacock, Zachary S. Ebb, David Chuang, Sung-Kiang Kaban, Leonard B. TI Adjuvant Antiangiogenic Treatment for Aggressive Giant Cell Lesions of the Jaw: A 20-Year Experience at Massachusetts General Hospital SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; RECOMBINANT INTERFERON ALPHA-2A; LIFE-THREATENING HEMANGIOMAS; IN-VITRO; CALCITONIN THERAPY; TUMOR; ANGIOGENESIS; BONE; GRANULOMA; EXPRESSION AB Purpose: To document long-term outcomes using a standardized treatment protocol of enucleation with preservation of vital structures and adjuvant subcutaneous interferon for aggressive giant cell lesions (GCLs) of the jaws. Materials and Methods: A retrospective cohort study was designed. We evaluated all patients treated at Massachusetts General Hospital from April 1995 through September 2015 by enucleation with preservation of vital structures and adjuvant daily subcutaneous interferon for aggressive GCLs. The sample included patients with complete medical records consisting of clinical, radiographic, histopathologic, and follow-up data. The exclusion criteria included patients with incomplete records, contraindications to interferon therapy, non-aggressive GCLs, and GCLs associated with syndromes or with hyperparathyroidism. The primary outcome variable was long-term progression-free survival (PFS). The secondary outcome variables were adverse effects and laboratory abnormalities classified by type, frequency, and severity. Predictor variables for recurrence or failure included age, gender, location and features of lesion, type of procedure, duration of interferon treatment, amount of bone fill at end of treatment, and adverse effects. Descriptive statistics, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis were computed. Results: Of a total of 77 patients, 45 (mean age, 18.8 +/- 12.5 years; 29 female patients; 36 in whom the mandible was affected) met the inclusion criteria. The mean duration of interferon therapy was 7.9 +/- 2.3 months. After follow-up of 4.8 +/- 3.9 years, 6 patients showed progression of the lesion, considered recurrence (13.3% failure rate, 82.6% PFS rate). Most patients had mild (n = 42; 93.3%) and/or moderate (n = 31; 68.8%) side effects, which were readily managed. Adverse effects required stoppage of interferon in 7 patients, whereas no patients had long-termtoxicity. No variable was significantly associated with PFS. Conclusions: The results of this study indicate that enucleation with preservation of vital structures in combination with adjuvant interferon alfa is a reliable treatment for aggressive GCLs of the jaws associated with a low recurrence rate. (C) 2016 American Association of Oral and Maxillofacial Surgeons C1 [Schreuder, Willem H.; Peacock, Zachary S.; Chuang, Sung-Kiang; Kaban, Leonard B.] Harvard Sch Dent Med, Massachusetts Gen Hosp Children, Dept Oral & Maxillofacial Surg, Boston, MA USA. [Ebb, David] Harvard Sch Dent Med, Massachusetts Gen Hosp Children, Div Pediat Hematol Oncol, Boston, MA USA. [Schreuder, Willem H.; Peacock, Zachary S.; Chuang, Sung-Kiang; Kaban, Leonard B.] Harvard Med Sch, Dept Oral & Maxillofacial Surg, Boston, MA USA. [Ebb, David] Harvard Med Sch, Div Pediat Hematol Oncol, Boston, MA USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM kaban.leonard@mgh.harvard.edu FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; Dutch Government ZonMW Priority Medicines and Rare Disease Program FX This research project was supported by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund and by the Dutch Government ZonMW Priority Medicines and Rare Disease Program. NR 67 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 2017 VL 75 IS 1 BP 105 EP 118 DI 10.1016/j.joms.2016.06.007 PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA EG6HF UT WOS:000391144700015 PM 27393579 ER PT J AU Leventhal, JS Wyatt, CM Ross, MJ AF Leventhal, Jeremy S. Wyatt, Christina M. Ross, Michael J. TI Recycling to discover something new: the role of autophagy in kidney disease SO KIDNEY INTERNATIONAL LA English DT Editorial Material ID FIBROSIS; MUTANTS AB This year, the Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi for his groundbreaking work in dissecting the mechanisms of autophagy, a cellular process resulting in the organized degradation of cytoplasmic components. Ohsumi's work paved the way for subsequent studies that demonstrated critical roles for autophagy in modulating both acute and chronic kidney injury. This work may lead to future therapeutic approaches that target the autophagy system to prevent or treat kidney diseases. C1 [Leventhal, Jeremy S.; Wyatt, Christina M.; Ross, Michael J.] Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. [Leventhal, Jeremy S.; Ross, Michael J.] James J Peters Bronx VA Med Ctr, Renal Div, Bronx, NY USA. RP Leventhal, JS (reprint author), Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, One Gustave L Levy Pl,Box 1243, New York, NY 10029 USA. EM Jeremy.leventhal@mssm.edu FU NIDDK NIH HHS [K08 DK090217] NR 8 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2017 VL 91 IS 1 BP 4 EP 6 DI 10.1016/j.kint.2016.11.004 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA EG6NH UT WOS:000391162700001 PM 28003091 ER PT J AU Kalim, S Rhee, EP AF Kalim, Sahir Rhee, Eugene P. TI An overview of renal metabolomics SO KIDNEY INTERNATIONAL LA English DT Review DE acute kidney injury; chronic kidney disease; uremia; uremic toxins ID TRIMETHYLAMINE-N-OXIDE; CHRONIC KIDNEY-DISEASE; GENERAL-POPULATION; UREMIC SOLUTES; METABOLISM; PLASMA; CKD; SERUM; ACID; RISK AB The high-throughput, high-resolution phenotyping enabled by metabolomics has been applied increasingly to a variety of questions in nephrology research. This article provides an overview of current metabolomics methodologies and nomenclature, citing specific considerations in sample preparation, metabolite measurement, and data analysis that investigators should understand when examining the literature or designing a study. Furthermore, we review several notable findings that have emerged in the literature that both highlight some of the limitations of current profiling approaches, as well as outline specific strengths unique to metabolomics. More specifically, we review data on the following: (i) tryptophan metabolites and chronic kidney disease onset, illustrating the interpretation of metabolite data in the context of established biochemical pathways; (ii) trimethylamine-N-oxide and cardiovascular disease in chronic kidney disease, illustrating the integration of exogenous and endogenous inputs to the blood metabolome; and (iii) renal mitochondrial function in diabetic kidney disease and acute kidney injury, illustrating the potential for rapid translation of metabolite data for diagnostic or therapeutic aims. Finally, we review future directions, including the need to better characterize interperson and intraperson variation in the metabolome, pool existing data sets to identify the most robust signals, and capitalize on the discovery potential of emerging nontargeted methods. C1 [Kalim, Sahir; Rhee, Eugene P.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA USA. [Rhee, Eugene P.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. RP Rhee, EP (reprint author), Massachusetts Gen Hosp, Thier Bldg,50 Blossom St,Their 1051, Boston, MA 02114 USA. EM eprhee@partners.org FU National Institutes of Health [K23 DK106479, U01 DK060990, K08-DK-090142]; Extramural Grant Program of Satellite Healthcare FX Supported by National Institutes of Health grants K23 DK106479 (SK), U01 DK060990 (EPR), and K08-DK-090142 (EPR), and the Extramural Grant Program of Satellite Healthcare, a not-for-profit renal care provider (EPR). NR 67 TC 1 Z9 1 U1 13 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD JAN PY 2017 VL 91 IS 1 BP 61 EP 69 DI 10.1016/j.kint.2016.08.021 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA EG6NH UT WOS:000391162700012 PM 27692817 ER PT J AU Vinding, MS Guerin, B Vosegaard, T Nielsen, NC AF Vinding, Mads S. Guerin, Bastien Vosegaard, Thomas Nielsen, Niels Chr. TI Local SAR, global SAR, and power-constrained large-flip-angle pulses with optimal control and virtual observation points SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE virtual observation points; local SAR; optimal control; multidimensional spatial-selective excitation; hard constraints ID LEAST-SQUARES OPTIMIZATION; MULTIPLE-QUANTUM FILTER; PARALLEL TRANSMISSION; SELECTIVE EXCITATION; RF PULSES; ABSORPTION RATE; SIMULTANEOUS MULTISLICE; WAVE-FORMS; 8 CHANNELS; DESIGN AB PurposeTo present a constrained optimal-control (OC) framework for designing large-flip-angle parallel-transmit (pTx) pulses satisfying hardware peak-power as well as regulatory local and global specific-absorption-rate (SAR) limits. The application is 2D and 3D spatial-selective 90 degrees and 180 degrees pulses. Theory and MethodsThe OC gradient-ascent-pulse-engineering method with exact gradients and the limited-memory Broyden-Fletcher-Goldfarb-Shanno method is proposed. Local SAR is constrained by the virtual-observation-points method. Two numerical models facilitated the optimizations, a torso at 3 T and a head at 7 T, both in eight-channel pTx coils and acceleration-factors up to 4. ResultsThe proposed approach yielded excellent flip-angle distributions. Enforcing the local-SAR constraint, as opposed to peak power alone, reduced the local SAR 7 and 5-fold with the 2D torso excitation and inversion pulse, respectively. The root-mean-square errors of the magnetization profiles increased less than 5% with the acceleration factor of 4. ConclusionA local and global SAR, and peak-power constrained OC large-flip-angle pTx pulse design was presented, and numerically validated for 2D and 3D spatial-selective 90 degrees and 180 degrees pulses at 3 T and 7 T. Magn Reson Med 77:374-384, 2017. (c) 2015 Wiley Periodicals, Inc. C1 [Vinding, Mads S.; Vosegaard, Thomas; Nielsen, Niels Chr.] Aarhus Univ, Ctr Insoluble Prot Struct inSPIN, Interdisciplinary Nanosci Ctr iNANO, Aarhus C, Denmark. [Vinding, Mads S.; Vosegaard, Thomas; Nielsen, Niels Chr.] Aarhus Univ, Dept Chem, Aarhus C, Denmark. [Guerin, Bastien] Massachusetts Gen Hosp, Dept Radiol, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Guerin, Bastien] Harvard Med Sch, Boston, MA USA. RP Vinding, MS (reprint author), Aarhus Univ, Interdisciplinary Nanosci Ctr iNANO, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark. EM msv@inano.au.dk FU Danish National Research Foundation [DNRF59]; Ministry of Higher Education and Science [AU-2010-612-181]; Innovation Fund Denmark [0603-00439B] FX Grant sponsor: the Danish National Research Foundation; Grant number: DNRF59; Grant sponsor: the Ministry of Higher Education and Science; Grant number: AU-2010-612-181; Grant sponsor: Innovation Fund Denmark; Grant number: 0603-00439B. NR 59 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD JAN PY 2017 VL 77 IS 1 BP 374 EP 384 DI 10.1002/mrm.26086 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EG4UI UT WOS:000391038800038 PM 26715084 ER PT J AU Henninger, J Santoso, B Hans, S Durand, E Moore, J Mosimann, C Brand, M Traver, D Zon, L AF Henninger, Jonathan Santoso, Buyung Hans, Stefan Durand, Ellen Moore, Jessica Mosimann, Christian Brand, Michael Traver, David Zon, Leonard TI Clonal fate mapping quantifies the number of haematopoietic stem cells that arise during development SO NATURE CELL BIOLOGY LA English DT Article ID AORTIC ENDOTHELIUM; IN-VIVO; ZEBRAFISH; IDENTIFICATION; TRACKING; MOUSE; COLONIZATION; TRANSITION; EXPRESSION; DYNAMICS AB Haematopoietic stem cells (HSCs) arise in the developing aorta during embryogenesis. The number of HSC clones born has been estimated through transplantation, but experimental approaches to assess the absolute number of forming HSCs in a native setting have remained challenging. Here, we applied single-cell and clonal analysis of HSCs in zebrafish to quantify developing HSCs. Targeting creER(T2) in developing cd41:eGFP(+) HSCs enabled long-term assessment of their blood contribution. We also applied the Brainbow-based multicolour Zebrabow system with drhcreER(T2) that is active in early haematopoiesis to induce heritable colour barcoding unique to each HSC and its progeny. Our findings reveal that approximately 21 HSC clones exist prior to HSC emergence and 30 clones are present during peak production from aortic endothelium. Our methods further reveal that stress haematopoiesis, including sublethal irradiation and transplantation, reduces clonal diversity. Our findings provide quantitative insights into the early clonal events that regulate haematopoietic development. C1 [Henninger, Jonathan; Durand, Ellen; Moore, Jessica; Zon, Leonard] Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Henninger, Jonathan; Durand, Ellen; Moore, Jessica; Zon, Leonard] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Henninger, Jonathan; Durand, Ellen; Moore, Jessica; Zon, Leonard] Harvard Med Sch, Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. [Henninger, Jonathan; Durand, Ellen; Zon, Leonard] Harvard Univ, Biol & Biomed Sci, Cambridge, MA 02138 USA. [Santoso, Buyung; Traver, David] Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. [Hans, Stefan; Brand, Michael] Tech Univ Dresden, Biotechnol Ctr, Tatzberg 47-49, D-01307 Dresden, Germany. [Hans, Stefan; Brand, Michael] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, Tatzberg 47-49, D-01307 Dresden, Germany. [Mosimann, Christian] Univ Zurich, Inst Mol Life Sci, CH-8057 Zurich, Switzerland. [Traver, David] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. RP Zon, L (reprint author), Boston Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA.; Zon, L (reprint author), Boston Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA.; Zon, L (reprint author), Harvard Med Sch, Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA.; Zon, L (reprint author), Harvard Univ, Biol & Biomed Sci, Cambridge, MA 02138 USA.; Traver, D (reprint author), Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.; Traver, D (reprint author), Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. EM dtraver@ucsd.edu; zon@enders.tch.harvard.edu RI Brand, Michael/A-5509-2010 OI Brand, Michael/0000-0001-5711-6512 FU HHMI; NIH [F31HL126338, R01-DK074482, F32DK752433, R01-HL04880, P01-HL032262, 5P30-DK49216, 5R01-DK53298, 5U01-HL10001, R24-DK09276]; Deutsche Forschungsgemeinschaft [SFB655]; TU Dresden; European Union (Zf Health); MPN Research Foundation Grant; EMBO long-term fellowship; HSFP long-term fellowship; SNF advanced fellowship; SNF professorship FX We thank the following for their support and contributions: M. Distel, E. Butko, J. Bertrand and D. Stachura for critical reading of the manuscript; K. Richter for laboratory management; J. Abkowitz for comments and suggestions; A. Schier and A. Pan for the Zebrabow-M line and guidance; L. Ding and D. Tom at the HMS Enhanced Neuroimaging Core for help with confocal microscopy. This work was supported by HHMI and NIH F31HL126338 (J.H.), NIH R01-DK074482 (D.T.), NIH F32DK752433 (B.S.), the Deutsche Forschungsgemeinschaft (SFB655), the TU Dresden and the European Union (Zf Health), NIH R01-HL04880, NIH P01-HL032262, NIH 5P30-DK49216, NIH 5R01-DK53298, NIH 5U01-HL10001, NIH R24-DK09276 and an MPN Research Foundation Grant. C.M. received funding from an EMBO long-term fellowship, an HSFP long-term fellowship, an SNF advanced fellowship and an SNF professorship. NR 33 TC 2 Z9 2 U1 2 U2 2 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 JAN PY 2017 VL 19 IS 1 BP 17 EP 27 DI 10.1038/ncb3444 PG 11 WC Cell Biology SC Cell Biology GA EG9AI UT WOS:000391349000005 PM 27870830 ER PT J AU Tsanov, KM Pearson, DS Wu, Z Han, A Triboulet, R Seligson, MT Powers, JT Osborne, JK Kane, S Gygi, SP Gregory, RI Daley, GQ AF Tsanov, Kaloyan M. Pearson, Daniel S. Wu, Zhaoting Han, Areum Triboulet, Robinson Seligson, Marc T. Powers, John T. Osborne, Jihan K. Kane, Susan Gygi, Steven P. Gregory, Richard I. Daley, George Q. TI LIN28 phosphorylation by MAPK/ERK couples signalling to the post-transcriptional control of pluripotency SO NATURE CELL BIOLOGY LA English DT Article ID EMBRYONIC STEM-CELLS; SELF-RENEWAL; MAP KINASE; LET-7; MICRORNA; LIN-28; RNA; DIFFERENTIATION; METABOLISM; TRANSLATION AB Signalling and post-transcriptional gene control are both critical for the regulation of pluripotency(1,2), yet how they are integrated to influence cell identity remains poorly understood. LIN28 (also known as LIN28A), a highly conserved RNA-binding protein, has emerged as a central post-transcriptional regulator of cell fate through blockade of let-7 microRNA biogenesis and direct modulation of mRNA translation(3). Here we show that LIN28 is phosphorylated by MAPK/ERK in pluripotent stem cells, which increases its levels via post-translational stabilization. LIN28 phosphorylation had little impact on let-7 but enhanced the effect of LIN28 on its direct mRNA targets, revealing a mechanism that uncouples LIN28's let-7-dependent and -independent activities. We have linked this mechanism to the induction of pluripotency by somatic cell reprogramming and the transition from naive to primed pluripotency. Collectively, our findings indicate that MAPK/ERK directly impacts LIN28, defining an axis that connects signalling, post-transcriptional gene control, and cell fate regulation. C1 [Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Daley, George Q.] Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA. [Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Daley, George Q.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Triboulet, Robinson; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Gregory, Richard I.; Daley, George Q.] Harvard Med Sch, Harvard Stem Cell Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Tsanov, Kaloyan M.; Pearson, Daniel S.; Wu, Zhaoting; Han, Areum; Seligson, Marc T.; Powers, John T.; Osborne, Jihan K.; Daley, George Q.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Triboulet, Robinson; Gregory, Richard I.] Boston Childrens Hosp, Stem Cell Program, Div Hematol Oncol, Boston, MA 02115 USA. [Kane, Susan] Cell Signaling Technol Inc, Danvers, MA 01923 USA. [Gygi, Steven P.] Harvard Med Sch, Dept Cell Biol, Boston, MA 02115 USA. RP Daley, GQ (reprint author), Boston Childrens Hosp, Manton Ctr Orphan Dis Res, Div Hematol Oncol, Stem Cell Transplantat Program, Boston, MA 02115 USA.; Daley, GQ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA.; Daley, GQ (reprint author), Harvard Med Sch, Harvard Stem Cell Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Daley, GQ (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. EM george.daley@childrens.harvard.edu FU NIH [NIH-P30-HD 18655]; NIGMS [T32GM007753, R01GM086386, R01GM107536] FX We thank P. Sharp, L. Cantley, G. Ruvkun, and members of the Daley laboratory for invaluable discussions, A. D. L. Angeles for critical feedback on the manuscript, X. Wu/Yi Zhang's laboratory and R. Rubio/DFCI CCCB for assistance with RNA-seq, and R. Tomaino at the Taplin Biological Mass Spectrometry Core for assistance with mass spectrometry. Bioanalyser analysis was performed in the BCH IDDRC Molecular Genetics Core, which is supported by NIH (NIH-P30-HD 18655). Sequencing analysis was conducted on the Orchestra High Performance Computing Cluster at Harvard Medical School. K.M.T. was an HHMI International Student Research Fellow and a Herchel Smith Graduate Fellow. D.S.P. was supported by a grant from NIGMS (T32GM007753). R.I.G. was supported by a grant from NIGMS (R01GM086386). G.Q.D. is an investigator of the Howard Hughes Medical Institute and the Manton Center for Orphan Disease Research, and was supported by a grant from NIGMS (R01GM107536). NR 29 TC 2 Z9 2 U1 9 U2 9 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 JAN PY 2017 VL 19 IS 1 BP 60 EP 67 DI 10.1038/ncb3453 PG 8 WC Cell Biology SC Cell Biology GA EG9AI UT WOS:000391349000009 PM 27992407 ER PT J AU Kim, JJ Bong, KW Reategui, E Irimia, D Doyle, PS AF Kim, Jae Jung Bong, Ki Wan Reategui, Eduardo Irimia, Daniel Doyle, Patrick S. TI Porous microwells for geometry-selective, large-scale microparticle arrays SO NATURE MATERIALS LA English DT Article ID SOFT LITHOGRAPHY; OPTICAL TWEEZERS; CELL; NEUTROPHIL; MIGRATION; PARTICLES; MICROCOMPONENTS; INFLAMMATION; CHEMOTAXIS; GRADIENTS AB Large-scale microparticle arrays (LSMAs) are key for material science and bioengineering applications. However, previous approaches suffer from trade-offs between scalability, precision, specificity and versatility. Here, we present a porous microwell-based approach to create large-scale microparticle arrays with complex motifs. Microparticles are guided to and pushed into microwells by fluid flow through small open pores at the bottom of the porous well arrays. A scaling theory allows for the rational design of LSMAs to sort and array particles on the basis of their size, shape, or modulus. Sequential particle assembly allows for proximal and nested particle arrangements, as well as particle recollection and pattern transfer. We demonstrate the capabilities of the approach by means of three applications: high-throughput single-cell arrays; microenvironment fabrication for neutrophil chemotaxis; and complex, covert tags by the transfer of an upconversion nanocrystal-laden LSMA. C1 [Kim, Jae Jung; Doyle, Patrick S.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Bong, Ki Wan; Reategui, Eduardo; Irimia, Daniel] Harvard Med Sch, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02129 USA. [Bong, Ki Wan; Reategui, Eduardo; Irimia, Daniel] Shriners Hosp Children, Boston, MA 02129 USA. [Bong, Ki Wan] Korea Univ, Dept Chem & Biol Engn, Seoul 02841, South Korea. [Reategui, Eduardo] Harvard Med Sch, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Doyle, PS (reprint author), MIT, Dept Chem Engn, Cambridge, MA 02139 USA.; Irimia, D (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, BioMEMS Resource Ctr, Boston, MA 02129 USA.; Irimia, D (reprint author), Shriners Hosp Children, Boston, MA 02129 USA. EM dirimia@mgh.harvard.edu; pdoyle@mit.edu FU National Science Foundation [CMMI-1120724]; Samsung Scholarship; National Institutes of Health [GM092804]; MRSEC Program of the National Science Foundation [DMR-1419807] FX We gratefully acknowledge funding from the National Science Foundation grants CMMI-1120724, a Samsung Scholarship to J.J.K., and National Institutes of Health (GM092804). This work was supported in part by the MRSEC Program of the National Science Foundation under award number DMR-1419807. Microfabrication was performed at BioMEMS Resource Center (EB002503) and MTL, MIT. The modulus measurement was performed in G. McKinley's and A. S. Myerson's laboratories at MIT. We thank B. Hamza and E. J. Lim of the BioMEMS Resource Center for fabrication of Si wafer and insightful discussion, and L. C. Hsiao and H. Burak Eral for the modulus measurement. NR 49 TC 1 Z9 1 U1 32 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1476-1122 EI 1476-4660 J9 NAT MATER JI Nat. Mater. PD JAN PY 2017 VL 16 IS 1 BP 139 EP 146 DI 10.1038/NMAT4747 PG 8 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Materials Science; Physics GA EG8YL UT WOS:000391343300025 PM 27595351 ER PT J AU Cheng, CW Yilmaz, OH AF Cheng, Chia-Wei Yilmaz, Omer H. TI Starving leukemia to induce differentiation SO NATURE MEDICINE LA English DT Editorial Material ID STEM-CELLS; CANCER; DIETARY AB A new study shows that fasting induces the differentiation and elimination of some types of leukemia in mice, which implicates fasting or its mimetics as a novel strategy for the treatment of this disease. C1 [Cheng, Chia-Wei; Yilmaz, Omer H.] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Cheng, Chia-Wei; Yilmaz, Omer H.] MIT, Dept Biol, Cambridge, MA 02139 USA. [Yilmaz, Omer H.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Yilmaz, Omer H.] Harvard Med Sch, Boston, MA 02114 USA. RP Yilmaz, OH (reprint author), MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Yilmaz, OH (reprint author), MIT, Dept Biol, Cambridge, MA 02139 USA.; Yilmaz, OH (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA.; Yilmaz, OH (reprint author), Harvard Med Sch, Boston, MA 02114 USA. EM ohyilmaz@mit.edu FU NCI NIH HHS [R01 CA211184]; NIA NIH HHS [R00 AG045144] NR 10 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2017 VL 23 IS 1 BP 14 EP 15 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA EH3CN UT WOS:000391646800008 PM 28060803 ER PT J AU Hahm, E Wei, CL Fernandez, I Li, J Tardi, NJ Tracy, M Wadhwani, S Cao, YX Peev, V Zloza, A Lusciks, J Hayek, SS O'Connor, C Bitzer, M Gupta, V Sever, S Sykes, DB Scadden, DT Reiser, J AF Hahm, Eunsil Wei, Changli Fernandez, Isabel Li, Jing Tardi, Nicholas J. Tracy, Melissa Wadhwani, Shikha Cao, Yanxia Peev, Vasil Zloza, Andrew Lusciks, Jevgenijs Hayek, Salim S. O'Connor, Christopher Bitzer, Markus Gupta, Vineet Sever, Sanja Sykes, David B. Scadden, David T. Reiser, Jochen TI Bone marrow-derived immature myeloid cells are a main source of circulating suPAR contributing to proteinuric kidney disease SO NATURE MEDICINE LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; SOLUBLE UROKINASE RECEPTOR; PLASMINOGEN-ACTIVATOR RECEPTOR; IDIOPATHIC NEPHROTIC SYNDROME; HEMATOPOIETIC STEM-CELLS; HUMANIZED MOUSE MODELS; GLOMERULAR-DISEASE; MICE; PODOCYTES; PERMEABILITY AB Excess levels of protein in urine (proteinuria) is a hallmark of kidney disease that typically occurs in conjunction with diabetes, hypertension, gene mutations, toxins or infections but may also be of unknown cause (idiopathic)(1). Systemic soluble urokinase plasminogen activator receptor (suPAR) is a circulating factor implicated in the onset and progression of chronic kidney disease (CKD)(2), such as focal segmental glomeruloscierosis (FSGS)(3,4). The cellular source(s) of elevated suPAR associated with future and progressing kidney disease is unclear, but is likely extra-renal, as the pathological uPAR is circulating and FSGS can recur even after a damaged kidney is replaced with a healthy donor organ. Here we report that bone marrow (BM) Gr-1(lo) immature myeloid cells are responsible for the elevated, pathological levels of suPAR, as evidenced by BM chimera and BM ablation and cell transfer studies. A marked increase of Gr-1(lo) myeloid cells was commonly found in the BM of proteinuric animals having high suPAR, and these cells efficiently transmit proteinuria when transferred to healthy mice. In accordance with the results seen in suPAR-associated proteinuric animal models, in which kidney damage is caused not by local podocyte-selective injury but more likely by systemic insults, a humanized xenograft model of FSGS resulted in an expansion of Gr-1(lo) cells in the BM, leading to high plasma suPAR and proteinuric kidney disease. Together, these results identify suPAR as a functional connection between the BM and the kidney, and they implicate BM immature myeloid cells as a key contributor to glomerular dysfunction. C1 [Hahm, Eunsil; Wei, Changli; Fernandez, Isabel; Li, Jing; Tardi, Nicholas J.; Tracy, Melissa; Wadhwani, Shikha; Cao, Yanxia; Peev, Vasil; Zloza, Andrew; Lusciks, Jevgenijs; Gupta, Vineet; Reiser, Jochen] Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. [Zloza, Andrew; Lusciks, Jevgenijs] Rush Univ, Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. [Zloza, Andrew] Rutgers Canc Inst New Jersey, Div Surg Oncol Res Sect, Sect Surg Oncol, New Brunswick, NJ USA. [Zloza, Andrew] Rutgers Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ USA. [Hayek, Salim S.] Emory Univ, Sch Med, Emory Clin Cardiovasc Res Inst, Div Cardiol, Atlanta, GA 30322 USA. [O'Connor, Christopher; Bitzer, Markus] Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Sever, Sanja] Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA USA. [Sykes, David B.; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Ct Regenerat Med, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Sykes, David B.; Scadden, David T.] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. RP Reiser, J (reprint author), Rush Univ, Med Ctr, Dept Internal Med, Chicago, IL 60612 USA. EM Jochen_Reiser@rush.edu FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [R01DK101350, R01DK106051, R01DK107984, R01DK084195] FX We thank A.S. Shaw (Washington University School of Medicine) for the Racl transgenic mice; S. Shankland (University of Washington) for providing the nephrotoxic serum (NTS); A. Finnegan (Rush University Medical Center) for reagents and advice; B. Samelko (ne Tryniszewska) (Rush University Medical Center) for technical assistance; and S. Mangos (Rush University Medical Center) for help with manuscript revisions. This research was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) R01DK101350 (J.R.), R01DK106051(J.R.), R01DK107984(V.G.) and R01DK084195(V.G.). NR 40 TC 1 Z9 1 U1 4 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JAN PY 2017 VL 23 IS 1 BP 100 EP 106 DI 10.1038/nm.4242 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA EH3CN UT WOS:000391646800018 PM 27941791 ER PT S AU Karczewski, KJ Tatonetti, NP Manrai, AK Patel, CJ Brown, CT Ioannidis, JPA AF Karczewski, Konrad J. Tatonetti, Nicholas P. Manrai, Arjun K. Patel, Chirag J. Brown, C. Titus Ioannidis, John P. A. BE Altman, RB Dunker, AK Hunter, L Ritchie, MD Murray, T Klein, TE TI METHODS TO ENSURE THE REPRODUCIBILITY OF BIOMEDICAL RESEARCH SO PACIFIC SYMPOSIUM ON BIOCOMPUTING 2017 SE Biocomputing Series LA English DT Proceedings Paper CT 22nd Pacific Symposium on Biocomputing (PSB) CY JAN 04-08, 2017 CL HI AB Science is not done in a vacuum - across fields of biomedicine, scientists have built on previous research and used data published in previous papers. A mainstay of scientific inquiry is the publication of one's research and recognition for this work is given in the form of citations and notoriety -ideally given in proportion to the quality of the work. Academic incentives, however, may encourage individual researchers to prioritize career ambitions over scientific truth. Recently, the New England Journal of Medicine published a commentary calling scientists who repurpose data "research parasites" who misuse data generated by others to demonstrate alternative hypotheses(1). In our opinion, the concept of data hoarding not only runs contrary to the spirit of, but also hinders scientific progress. Scientific research is meant to seek objective truth, rather than promote a personal agenda, and the only way to do so is through maximum transparency and reproducibility, no matter who is using the data. C1 [Karczewski, Konrad J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karczewski, Konrad J.] Broad Inst, Cambridge, MA 02142 USA. [Tatonetti, Nicholas P.] Columbia Univ, New York, NY USA. [Manrai, Arjun K.; Patel, Chirag J.] Harvard Med Sch, Boston, MA USA. [Brown, C. Titus] Univ Calif Davis, Davis, CA 95616 USA. [Ioannidis, John P. A.] Stanford Univ, Stanford, CA 94305 USA. RP Karczewski, KJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA.; Karczewski, KJ (reprint author), Broad Inst, Cambridge, MA 02142 USA. EM konradjkarczewski@gmail.com; nick.tatonetti@columbia.edu; manrai@post.harvard.edu; chirag_patel@hms.harvard.edu; ctbrown@ucdavis.edu; jioannid@stanford.edu NR 14 TC 0 Z9 0 U1 1 U2 1 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE SN 2335-6936 BN 978-981-3207-81-3; 978-981-3207-80-6 J9 BIOCOMPUTING PY 2017 BP 117 EP 119 PG 3 WC Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA BG7FY UT WOS:000391254200012 ER PT J AU Kohler, RE Gopal, S Miller, AR Lee, CN Reeve, BB Weiner, BJ Wheeler, SB AF Kohler, Racquel E. Gopal, Satish Miller, Anna R. Lee, Clara N. Reeve, Bryce B. Weiner, Bryan J. Wheeler, Stephanie B. TI A framework for improving early detection of breast cancer in sub-Saharan Africa: A qualitative study of help-seeking behaviors among Malawian women SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Breast cancer; Breast symptoms; Help-seeking behavior; Early detection; Delay; Malawi; Sub-Saharan Africa ID DELAYED PRESENTATION; RESOURCE COUNTRIES; HEALTH; MODEL; INTERVENTIONS; DIAGNOSIS; SYMPTOMS; CARE AB Objective: Many women in Africa are diagnosed with advanced breast cancer. We explored Malawian breast cancer patients' perspectives about their diagnosis and ability to access care to identify help-seeking behaviors and to describe factors influencing delay. Methods: We purposively sampled 20 Malawian breast cancer patients to conduct in-depth interviews. Transcripts were double coded to identify major themes of breast cancer help-seeking behaviors and what delayed or facilitated access to care. Results: We outlined a breast cancer help-seeking pathway describing decisions, behaviors, and interactions from symptom presentation to receipt of cancer care. Patients were largely unaware of breast cancer and did not immediately notice or interpret symptoms. As symptoms progressed, women inferred illness and sought help from social networks, traditional remedies, and medical care. Economic hardship, distance to the facility, provider knowledge, health system factors, and social norms often delayed reaching the facility, referrals, diagnosis, and receipt of care. Conclusions: Social-contextual factors at the individual, interpersonal, health system, and societal levels delay decisions, behaviors, and access to breast cancer detection and appropriate care. Practice implications: A comprehensive approach to improving breast cancer early detection must address public awareness and misconceptions, provider knowledge and communication, and cancer care delivery. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Kohler, Racquel E.; Reeve, Bryce B.; Weiner, Bryan J.; Wheeler, Stephanie B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Policy & Management, Chapel Hill, NC 27514 USA. [Kohler, Racquel E.; Gopal, Satish] UNC Project Malawi, Lilongwe, Malawi. [Gopal, Satish; Lee, Clara N.; Reeve, Bryce B.; Weiner, Bryan J.; Wheeler, Stephanie B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. [Miller, Anna R.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav, Chapel Hill, NC USA. [Kohler, Racquel E.] Dana Farber Canc Inst, 450 Brookline Ave,LW 601, Boston, MA 02215 USA. RP Kohler, RE (reprint author), Univ N Carolina, 1101 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM rkohler@email.unc.edu FU UNC Cancer Care Quality Training Program [R25 CA116339]; UNC Hopkins Morehouse Tulane Fogarty Global Health Fellows Program [R25 TW009340] FX Dr. Kohler was supported by UNC Cancer Care Quality Training Program (R25 CA116339) and the UNC Hopkins Morehouse Tulane Fogarty Global Health Fellows Program (R25 TW009340). NR 35 TC 2 Z9 2 U1 3 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JAN PY 2017 VL 100 IS 1 BP 167 EP 173 DI 10.1016/j.pec.2016.08.012 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA EG7JU UT WOS:000391224200024 PM 27528411 ER PT J AU Koenen, KC Sumner, JA Gilsanz, P Glymour, MM Ratanatharathorn, A Rimm, EB Roberts, AL Winning, A Kubzansky, LD AF Koenen, K. C. Sumner, J. A. Gilsanz, P. Glymour, M. M. Ratanatharathorn, A. Rimm, E. B. Roberts, A. L. Winning, A. Kubzansky, L. D. TI Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice SO PSYCHOLOGICAL MEDICINE LA English DT Review DE Cardiovascular disease; causality; diabetes; post-traumatic stress disorder ID ADVERSE CHILDHOOD EXPERIENCES; CORONARY-HEART-DISEASE; MAJOR DEPRESSIVE DISORDER; COMORBIDITY SURVEY-REPLICATION; RANDOMIZED CONTROLLED-TRIAL; MILITARY SERVICE MEMBERS; TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; VIETNAM VETERANS; BIDIRECTIONAL ASSOCIATION AB Post-traumatic stress disorder (PTSD) has been declared ` a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D. C1 [Koenen, K. C.; Sumner, J. A.; Ratanatharathorn, A.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge 505, Boston, MA 02115 USA. [Koenen, K. C.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. [Koenen, K. C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sumner, J. A.] Columbia Univ, Med Ctr, Ctr Behav Cardiovasc Hlth, New York, NY 10025 USA. [Gilsanz, P.; Glymour, M. M.; Roberts, A. L.; Winning, A.; Kubzansky, L. D.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Glymour, M. M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Ratanatharathorn, A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. [Rimm, E. B.] Harvard Med Sch, Brigham & Womens Hosp, Channing Div Network Med, Boston, MA USA. [Rimm, E. B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rimm, E. B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Koenen, KC (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave,Kresge 505, Boston, MA 02115 USA. EM kkoenen@hsph.harvard.edu FU National Institutes of Health [R01MH078928, R01MH101269, UM1CA176726, K01HL130650, T32MH017119]; Yerby Postdoctoral Fellowship Program FX This work was supported by the National Institutes of Health (to K.C.K., R01MH078928; to K.C.K., L.D. K. and A.W., R01MH101269; NHS II infrastructure, UM1CA176726; to J.A.S., K01HL130650; and to P.G., T32MH017119) and by the Yerby Postdoctoral Fellowship Program (to P.G.). NR 124 TC 0 Z9 0 U1 5 U2 5 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 EI 1469-8978 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 2017 VL 47 IS 2 BP 209 EP 225 DI 10.1017/S0033291716002294 PG 17 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA EG8PU UT WOS:000391320100003 PM 27697083 ER PT J AU Sebro, R DeLaney, TF Hornicek, F Schwab, J Choy, E Nielsen, GP Rosenthal, DI AF Sebro, Ronnie DeLaney, Thomas F. Hornicek, Francis Schwab, Joseph Choy, Edwin Nielsen, G. Petur Rosenthal, Daniel I. TI Frequency and Risk Factors for Additional Lesions in the Axial Spine in Subjects With Chordoma Indications for Screening SO SPINE LA English DT Article DE benign notochordal tumor; chondroid chordoma; chordoma; chordoma metastases; dedifferentiated chordoma; metachronous chordoma; pediatric; screening; spine; synchronous chordoma ID EXTRAAXIAL CHORDOMA; METASTATIC-DISEASE; BRACHYURY; BONES AB Study Design. Retrospective cohort study. Objective. We aim to evaluate the frequency and clinical significance of additional lesions in the axial spine in subjects with chordoma and to assess the need for screening. Summary of Background Data. Chordomas are rare tumors that may be multicentric or metastasize and affect several bones in the axial spine. The incidence of multiple lesions in the axial spine is unknown. Understanding the incidence rate of multiple lesions in the spine in subjects with chordomas will help guide utilization of total spine screening imaging. Methods. We performed a retrospective review of medical records of 42 subjects with histologically confirmed chordomas who had complete imaging of the axial spine. Lesions with imaging characteristics suggestive of chordomas/notochordal remnants were identified. Data on age at diagnosis, sex, size (in maximal dimension), type of chordoma (conventional, chondroid, or dedifferentiated), and whether pulmonary metastases were present were recorded. Binomial two-sample tests of proportions were used to compare proportions. Logistic regression was used to assess predictors of additional lesions. Results. Forty-two subjects (57.1% male) were identified. The proportion of subjects with additional lesions in the axial spine was 16.7% (7/42). Age, sex, size, and subtype of chordoma were not significant predictors of having additional lesions (P > 0.05 for each variable). However, having pulmonary metastases was a significant predictor of having additional lesions (P < 0.05). Conclusion. Approximately 17% of subjects with chordomas had additional lesions in the axial spine. It is unclear whether these represent metastases, synchronous primary chordomas or notochordal remnant tissue. Screening imaging of the axial spine may reveal additional lesions in particular in subjects with pulmonary metastases. C1 [Sebro, Ronnie] Univ Penn, Perelman Sch Med, Dept Radiol, Musculoskeletal Radiol, Philadelphia, PA 19104 USA. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [DeLaney, Thomas F.; Hornicek, Francis; Schwab, Joseph; Choy, Edwin; Nielsen, G. Petur] Harvard Med Sch, Boston, MA USA. [DeLaney, Thomas F.; Hornicek, Francis; Schwab, Joseph; Choy, Edwin; Nielsen, G. Petur; Rosenthal, Daniel I.] Massachusetts Gen Hosp, Harris Ctr Chordoma Care, Boston, MA USA. [Hornicek, Francis; Schwab, Joseph] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. [Choy, Edwin] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Nielsen, G. Petur] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Rosenthal, Daniel I.] Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, Dept Radiol, Yawkey 6E,55 Fruit St, Boston, MA 02114 USA. EM dirosenthal@mgh.harvard.edu NR 21 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0362-2436 EI 1528-1159 J9 SPINE JI SPINE PD JAN 1 PY 2017 VL 42 IS 1 BP E37 EP E40 DI 10.1097/BRS.0000000000001723 PG 4 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA EG5YX UT WOS:000391121800006 PM 27254658 ER PT J AU Gavrila, A Hasselgren, PO Glasgow, A Doyle, AN Lee, AJ Fox, P Gautam, S Hennessey, JV Kolodny, GM Cypess, AM AF Gavrila, Alina Hasselgren, Per-Olof Glasgow, Allison Doyle, Ashley N. Lee, Alice J. Fox, Peter Gautam, Shiva Hennessey, James V. Kolodny, Gerald M. Cypess, Aaron M. TI Variable Cold-Induced Brown Adipose Tissue Response to Thyroid Hormone Status SO THYROID LA English DT Article DE brown adipose tissue; thyroid hormone; hypothyroidism; thyrotoxicosis; thermogenesis ID NONSHIVERING THERMOGENESIS; METABOLISM; HUMANS; ACTIVATION; MECHANISMS; OBESITY; MUSCLE; ADULTS; MICE; FAT AB Background: In addition to its role in adaptive thermogenesis, brown adipose tissue (BAT) may protect from weight gain, insulin resistance/diabetes, and metabolic syndrome. Prior studies have shown contradictory results regarding the influence of thyroid hormone (TH) levels on BAT volume and activity. The aim of this pilot study was to gain further insights regarding the effect of TH treatment on BAT function in adult humans by evaluating the BAT mass and activity prospectively in six patients, first in the hypothyroid and then in the thyrotoxic phase. Methods: The study subjects underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) scanning after cold exposure to measure BAT mass and activity while undergoing treatment for differentiated thyroid cancer, first while hypothyroid following TH withdrawal at the time of the radioactive iodine treatment and then three to six months after starting TH suppressive treatment when they were iatrogenically thyrotoxic. Thermogenic and metabolic parameters were measured in both phases. Results: All study subjects had detectable BAT under cold stimulation in both the hypothyroid and thyrotoxic state. The majority but not all (4/6) subjects showed an increase in detectable BAT volume and activity under cold stimulation between the hypothyroid and thyrotoxic phase (total BAT volume: 72.0+/-21.0 vs. 87.7+/-16.5mL, p = 0.25; total BAT activity 158.1+/-72.8 vs. 189.0+/-55.5 SUV*g/mL, p = 0.34). Importantly, circulating triiodothyronine was a stronger predictor of energy expenditure changes compared with cold-induced BAT activity. Conclusions: Iatrogenic hypothyroidism lasting two to four weeks does not prevent cold-induced BAT activation, while the use of TH to induce thyrotoxicosis does not consistently increase cold-induced BAT activity. It remains to be determined which physiological factors besides TH play a role in regulating BAT function. Keywords: brown adipose tissue, thyroid hormone, hypothyroidism, thyrotoxicosis, thermogenesis C1 [Gavrila, Alina; Gautam, Shiva; Hennessey, James V.; Cypess, Aaron M.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Hasselgren, Per-Olof] Beth Israel Deaconess Med Ctr, Dept Surg, 330 Brookline Ave, Boston, MA 02215 USA. [Glasgow, Allison; Doyle, Ashley N.; Lee, Alice J.] Beth Israel Deaconess Med Ctr, Harvard Catalyst Clin Res Ctr, Boston, MA 02215 USA. [Kolodny, Gerald M.] Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. [Fox, Peter; Cypess, Aaron M.] Harvard Med Sch, Joslin Diabet Ctr, Div Res, Sect Integrat Physiol & Metab, Boston, MA USA. [Cypess, Aaron M.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RP Cypess, AM (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.; Gavrila, A (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, 330 Brookline Ave GZ6, Boston, MA 02215 USA. EM agavrila@bidmc.harvard.edu; aaron.cypess@nih.gov FU Harvard Catalyst Clinical Research Center (HCCRC); National Institutes of Health (NIH) [K23 DK081604]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Center for Research Resources (NCRR) [UL1RR025758, UL1TR000170, UL1TR001102]; National Center for Advancing Translational Science; Harvard University and its affiliated academic healthcare centers FX This work was supported by the 2012 Harvard Catalyst Clinical Research Center (HCCRC) Resources and Services Funding Award; the 2013 Harvard Catalyst Clinical Research Center (HCCRC) Laboratory Support and Genotyping Award; National Institutes of Health (NIH) grants K23 DK081604, the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); and the Clinical Translational Science Awards UL1RR025758, UL1TR000170 and UL1TR001102 to Harvard University and its affiliated academic healthcare centers from the National Center for Research Resources (NCRR) and the National Center for Advancing Translational Science and financial contributions from Harvard University and its affiliated academic healthcare 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 healthcare centers, or the National Institutes of Health. NR 32 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN PY 2017 VL 27 IS 1 BP 1 EP 10 DI 10.1089/thy.2015.0646 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG9RV UT WOS:000391398100001 PM 27750020 ER PT J AU Rabinowits, G Barletta, J Sholl, LM Reche, E Lorch, J Goguen, L AF Rabinowits, Guilherme Barletta, Justine Sholl, Lynette M. Reche, Encarnacion Lorch, Jochen Goguen, Laura TI Successful Management of a Patient with Malignant Thyroid Teratoma SO THYROID LA English DT Article DE PNET; thyroid cancer; teratoma; tumor sequencing; treatment ID SOMATIC DICER1 MUTATIONS; NEUROFIBROMATOSIS; TUMORS AB Background: Malignant thyroid teratomas are rare tumors with a poor prognosis. Little is known about their pathogenesis or treatment. Here, the case is reported of an adult woman with an aggressive thyroid teratoma with primitive neuroectodermal tumor (PNET) malignant transformation, successfully managed with neoadjuvant chemotherapy and surgery. Patient Findings: Sequencing of paired tumor and normal tissues revealed a DICER1 c.5438A>G (p.E1813G) somatic mutation in 56% of sequencing reads consistent with a driver event. Summary and Conclusions: To the authors' knowledge, DICER1 mutations have not been previously reported in teratomas but have been described in PNETs, suggesting a role in the malignant transformation of this case. C1 [Rabinowits, Guilherme; Lorch, Jochen] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Barletta, Justine; Sholl, Lynette M.] Brigham & Womens Hosp, Dept Anat Pathol, 75 Francis St, Boston, MA 02115 USA. [Goguen, Laura] Brigham & Womens Hosp, Dept Otolaryngol, 75 Francis St, Boston, MA 02115 USA. [Reche, Encarnacion] Hosp Marina Salud Denia, Med Oncol, Alicante, Spain. RP Rabinowits, G (reprint author), Dana Farber Canc Inst, Ctr Head & Neck Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM grabinowits@partners.org NR 18 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 1050-7256 EI 1557-9077 J9 THYROID JI Thyroid PD JAN PY 2017 VL 27 IS 1 BP 125 EP 128 DI 10.1089/thy.2016.0201 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG9RV UT WOS:000391398100016 PM 27784193 ER PT J AU Calabrese, JR Gao, K Sachs, G AF Calabrese, Joseph R. Gao, Keming Sachs, Gary TI Diagnosing Mania in the Age of DSM-5 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 [Calabrese, Joseph R.] Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Cleveland Med Ctr, Cleveland, OH 44106 USA. Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA USA. RP Calabrese, JR (reprint author), Case Western Reserve Univ, Sch Med, Dept Psychiat, Univ Hosp Cleveland Med Ctr, Cleveland, OH 44106 USA. EM joseph.calabrese@uhhospitals.org FU Department of Defense; Health Resources Services Administration; NIMH; Abbott Laboratories; AstraZeneca; Bristol-Myers Squibb; Teva; Dainippon Sumitomo; GlaxoSmithkline; Janssen; Eli Lilly; Intra-Cellular Therapies; Pfizer; Lundbeck; Sunovion; Takeda; Brain and Behavior Foundation; Cleveland Foundation FX Dr. Calabrese has received federal funding from the Department of Defense, the Health Resources Services Administration, and NIMH and grant support from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon (now Teva), Dainippon Sumitomo, GlaxoSmithkline, Janssen, Eli Lilly, Intra-Cellular Therapies, Pfizer, Lundbeck, Sunovion, and Takeda; he has also served as a consultant advisory board member, or speaker for Abbott, Allergan, AstraZeneca, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo, GlaxoSmithKline, Janssen, Lundbeck, Otsuka, Pfizer, Repligen, Servier, Sunovion, Solvay, and Takeda. Dr. Gao has received grant support from AstraZeneca, the Brain and Behavior Foundation, and the Cleveland Foundation, and he has served on an advisory board and speakers bureau for Sunovion. Dr. Sachs is a full-time employee of Bracket and a part-time employee of Massachusetts General Hospital; he has served on advisory boards for Allergan, Janssen, Intracellular Therapies, Lundbeck, Neuralstem, Otsuka, Pfizer, Sunovion, Supernus, and Takeda, and he is a shareholder in Amyris, ExpressScripts, and Oracle. NR 5 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2017 VL 174 IS 1 BP 8 EP 10 DI 10.1176/appi.ajp.2016.16091084 PG 3 WC Psychiatry SC Psychiatry GA EG4BB UT WOS:000390987300004 PM 28040998 ER PT J AU Boedhoe, PSW Schmaal, L Abe, Y Ameis, SH Arnold, PD Batistuzzo, MC Benedetti, F Beucke, JC Bollettini, I Bose, A Brem, S Calvo, A Cheng, YQ Cho, KIK Dallaspezia, S Denys, D Fitzgerald, KD Fouche, JP Gimenez, M Gruner, P Hanna, GL Hibar, DP Hoexter, MQ Hu, H Huyser, C Ikari, K Jahanshad, N Kathmann, N Kaufmann, C Koch, K Kwon, JS Lazaro, L Liu, Y Lochner, C Marsh, R Martinez-Zalacain, I Mataix-Cols, D Menchon, JM Minuzzi, L Nakamae, T Nakao, T Narayanaswamy, JC Piras, F Piras, F Pittenger, C Reddy, YCJ Sato, JR Simpson, HB Soreni, N Soriano-Mas, C Spalletta, G Stevens, MC Szeszko, PR Tolin, DF Venkatasubramanian, G Walitza, S Wang, Z van Wingen, GA Xu, J Xu, XF Yun, JY Zhao, Q Thompson, PM Stein, DJ van den Heuvel, OA AF Boedhoe, Premika S. W. Schmaal, Lianne Abe, Yoshinari Ameis, Stephanie H. Arnold, Paul D. Batistuzzo, Marcelo C. Benedetti, Francesco Beucke, Jan C. Bollettini, Irene Bose, Anushree Brem, Silvia Calvo, Anna Cheng, Yuqi Cho, Kang Ik K. Dallaspezia, Sara Denys, Damiaan Fitzgerald, Kate D. Fouche, Jean-Paul Gimenez, Monica Gruner, Patricia Hanna, Gregory L. Hibar, Derrek P. Hoexter, Marcelo Q. Hu, Hao Huyser, Chaim Ikari, Keisuke Jahanshad, Neda Kathmann, Norbert Kaufmann, Christian Koch, Kathrin Kwon, Jun Soo Lazaro, Luisa Liu, Yanni Lochner, Christine Marsh, Rachel Martinez-Zalacain, Ignacio Mataix-Cols, David Menchon, Jose M. Minuzzi, Luciano Nakamae, Takashi Nakao, Tomohiro Narayanaswamy, Janardhanan C. Piras, Fabrizio Piras, Federica Pittenger, Christopher Reddy, Y. C. Janardhan Sato, Joao R. Simpson, H. Blair Soreni, Noam Soriano-Mas, Caries Spalletta, Gianfranco Stevens, Michael C. Szeszko, Philip R. Tolin, David F. Venkatasubramanian, Ganesan Walitza, Susanne Wang, Zhen van Wingen, Guido A. Xu, Jian Xu, Xiufeng Yun, Je-Yeon Zhao, Qing Thompson, Paut M. Stein, Dan J. van den Heuvel, Odile A. CA ENIGMA OCD Working Grp TI Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; VOXEL-BASED MORPHOMETRY; MANUAL SEGMENTATION; AMYGDALA VOLUMES; BRAIN-REGIONS; METAANALYSIS; MRI; HIPPOCAMPAL; RELIABILITY; FREESURFER AB Objective: Structural brain imaging studies in obsessive compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta and mega-analyses of data from OCD sites worldwide. Method: T-1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. Results: The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohen's d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. Conclusions: The results indicate different patterns of sub cortical abnormalities in pediatric and adult OCD patients. The patlidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful. C1 [Boedhoe, Premika S. W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Anat & Neurosci, Amsterdam, Netherlands. Free Univ Amsterdam, VU Univ, Med Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands. Kyoto Prefectural Univ Med, Dept Psychiat, Grad Sch Med Sci, Kyoto, Japan. Ctr Addict & Mental Hlth, Toronto, ON, Canada. Hosp Sick Children, Toronto, ON, Canada. Univ Calgary, Cumming Sch Med, Mathison Ctr Mental Hlth Res & Educ, Calgary, AB, Canada. Univ Sao Paulo, Sch Med, Dept Psychiat, Inst Psychiat, Sao Paulo, Brazil. Osped San Raffaele, Inst Sci, Clin Res Grp Psychiat & Clin Psychobiol, Div Neurosci, Milan, Italy. Humboldt Univ, Dept Psychol, Berlin, Germany. Natl Inst Mental Hlth & Neurosci, Dept Psychiat, Obsess Compuls Disorder Clin, Bangalore, Karnataka, India. Univ Zurich, Hosp Psychiat, Dept Child & Adolescent Psychiat & Psychotherapy, Zurich, Switzerland. Inst Invest Biomed August Pi I Sunyer IDIBAPS, Magnet Resonance Image Core Facil, Barcelona, Spain. Kunming Med Univ, Affiliated Hosp 1, Dept Psychiat, Kunming, Peoples R China. Seoul Natl Univ, Coll Nat Sci, Dept Brain & Cognit Sci, Seoul, South Korea. Univ Amsterdam, Acad Med Ctr, Dept Psychiat, Amsterdam, Netherlands. Royal Netherlands Acad Arts & Sci, Netherlands Inst Neurosci, Amsterdam, Netherlands. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. Univ Cape Town, Dept Psychiat, Cape Town, South Africa. Univ Stellenbosch, Dept Psychiat, Cape Town, South Africa. Bellvitge Biomed Res Inst IDIBELL, Bellvitge Univ Hosp, Dept Psychiat, Barcelona, Spain. Ctr Invest Biomed Red Salud Mental CIBERSAM, Barcelona, Spain. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Univ Southern Calif, Keck Sch Med, Mark & Mary Stevens Inst Neuroimaging & Informat, Imaging Genet Ctr, Marina Del Rey, CA USA. De Bascule, Acad Ctr Child & Adolescent Psychiat, Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, Dept Child & Adolescent Psychiat, Amsterdam, Netherlands. Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka, Japan. Tech Univ Munich, Dept Neuroradiol, Klinikum Rechts Isar, Munich, Germany. Tech Univ Munich, TUM Neuroimaging Ctr TUM NIC, Klinikum Rechts Isar, Munich, Germany. Seoul Natl Univ, Dept Psychiat, Coll Med, Seoul, South Korea. Hosp Clin Univ, Inst Neurosci, Dept Child & Adolescent Psychiat & Psychol, Barcelona, Spain. Inst Invest Biomed August Pi I Sunyer IDIBAPS, Barcelona, Spain. Univ Barcelona, Dept Psychiat & Clin Psychobiol, Barcelona, Spain. Univ Stellenbosch, Dept Psychiat, SU UCT MRC Unit Anxiety & Stress Disorders, Cape Town, South Africa. Columbia Univ, Med Ctr, New York, NY USA. New York State Psychiat Inst & Hosp, Div Child & Adolescent Psychiat, New York, NY USA. Columbia Univ, New York, NY USA. Karolinska Inst, Ctr Psychiat Res & Educ, Dept Clin Neurosci, Stockholm, Sweden. Univ Barcelona, Dept Clin Sci, Barcelona, Spain. St Josephs HealthCare, Mood Disorders Clin, Hamilton, ON, Canada. St Josephs HealthCare, Anxiety Treatment & Res Ctr, Hamilton, ON, Canada. ATR Brain Informat Commun Res Lab Grp, Dept Neural Computat Decis Making, Kyoto, Japan. IRCCS Santa Lucia Fdn, Dept Clin & Behav Neurol, Lab Neuropsychiat, Rome, Italy. Univ Fed ABC, Ctr Math Computat & Cognit, Santo Andre, Brazil. New York State Psychiat Inst & Hosp, Ctr OCD & Related Disorders, New York, NY 10032 USA. Univ Autonoma Barcelona, Dept Psychobiol & Methodol Hlth Sci, Barcelona, Spain. Baylor Coll Med, Beth K & Stuart C Yudofsky Div Neuropsychiat, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Olin Neuropsychiat Res Ctr, Clin Neurosci & Dev Lab, Hartford, CT USA. Icahn Sch Med Mt Sinai, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, Bronx, NY USA. Hartford Hosp, Inst Living, Hartford, CT USA. Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Sch Med, Shanghai, Peoples R China. Shanghai Key Lab Psychot Disorders, Shanghai, Peoples R China. Kunming Med Univ, Affiliated Hosp 1, Dept Internal Med, Kunming, Peoples R China. RP Boedhoe, PSW (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Amsterdam, Netherlands. EM p.boedhoe@vumc.nl RI Batistuzzo, Marcelo/H-7790-2015; OI Benedetti, Francesco/0000-0003-4949-856X FU NIH BD2K [U54 EB020403-02]; Neuroscience Campus Amsterdam; IPB-grant; Hartmann Muller Foundation [1460]; International Obsessive-Compulsive Disorder Foundation Research Award; Deutsche Forschungsgemeinschaft [KO 3744/2-1]; Marato TV3 Foundation [01/2010, 091710]; Wellcome Trust; South London and Maudsley Trust, London [064846]; Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT KAKENHI) [26461753]; Government of India of the Department of Science and Technology [SR/S0/HS/0016/2011, IFA12-LSBM-26]; Government of India of the Department of Biotechnology [BT/PR13334/Med/30/259/2009, BT/06/IYBA/2012]; Wellcome-DBT India Alliance grant [500236/Z/11/Z]; Carlos III Health Institute [CP10/00604, PI13/00918, PI13/01958, PI14/00413/PI040829]; FEDER funds/European Regional Development Fund, AGAUR [2014 SGR 1672, 2014 SGR 489]; "Miguel Server" contract from the Carlos III Health Institute [CP10/00604]; Italian Ministry of Health [RC10-11-12-13-14-15A]; Swiss National Science Foundation [320030_130237]; Netherlands Organization for Scientific Research [NWO VIDI 917-15-318]; AB-Biotics; Ferrer; GlaxoSmithKline; Janssen; Lundbeck; Medtronic; Otsuka; Spanish Ministry of Science and Innovation (CIBERSAM); Alternative Funding Plan Innovation Fund; Brain and Behavioral Foundation; Canadian Institutes of Health Research; Hamilton Health Sciences Foundation; Ontario Brain Institute; Ontario Mental Health Foundation; Swiss National Science Foundation; German Research Foundation; Hochspezialisierte Medizin of the Canton of Zurich; German Federal Ministry of Education and Research; AMBRF; Biocodex; Cipla; National Responsible Gambling Foundation; Novartis; Servier; Sun; PhotoPharmics FX The ENIGMA OCD Working Group gratefully acknowledges support from the NIH BD2K award U54 EB020403-02 (principal investigator, Dr. Thompson). Supported by the Neuroscience Campus Amsterdam, IPB-grant to Dr. Schmaal and Dr. van den Heuvel; the Hartmann Muller Foundation (No. 1460 to Dr. Brem); the International Obsessive-Compulsive Disorder Foundation Research Award to Dr. Gruner; the Deutsche Forschungsgemeinschaft (KO 3744/2-1 to Dr. Koch); the Marato TV3 Foundation grants 01/2010 and 091710 to Dr. Lazaro; the Wellcome Trust and a pump priming grant from the South London and Maudsley Trust, London (project grant no. 064846) to Dr. Mataix-Cols; the Japanese Ministry of Education, Culture, Sports, Science, and Technology (MEXT KAKENHI No. 26461753 to Dr. Nakamae); Government of India grants to Prof. Reddy (SR/S0/HS/0016/2011) and Dr. Narayanaswamy (DST INSPIRE faculty grant -IFA12-LSBM-26) of the Department of Science and Technology; the Government of India grants to Prof. Reddy (No.BT/PR13334/Med/30/259/2009) and Dr. Narayanaswamy (BT/06/IYBA/2012) of the Department of Biotechnology; the Wellcome-DBT India Alliance grant to Dr. Venkatasubramanian (500236/Z/11/Z); the Carlos III Health Institute (CP10/00604, PI13/00918, PI13/01958, PI14/00413/PI040829); FEDER funds/European Regional Development Fund, AGAUR (2014 SGR 1672 and 2014 SGR 489); a "Miguel Server" contract (CP10/00604) from the Carlos III Health Institute to Dr. Soriano-Mas; the Italian Ministry of Health (RC10-11-12-13-14-15A to Dr. Spalletta); the Swiss National Science Foundation (No. 320030_130237 to Dr. Walitza); and the Netherlands Organization for Scientific Research (NWO VIDI 917-15-318 to Dr. van Wingen).; Dr. Menchon has received grants and served as consultant, adviser, or speaker for AB-Biotics, Ferrer, GlaxoSmithKline, Janssen, Lundbeck, Medtronic, Otsuka, and the Spanish Ministry of Science and Innovation (CIBERSAM). Dr. Minuzzi has received grant or research support from the Alternative Funding Plan Innovation Fund, the Brain and Behavioral Foundation, the Canadian Institutes of Health Research, the Hamilton Health Sciences Foundation, the Ontario Brain Institute, and the Ontario Mental Health Foundation; he has served as a consultant or speaker for Bristol-Myers Squibb, the Canadian Psychiatric Association, the Canadian Network for Mood and Anxiety Treatments, and Lundbeck. Dr. Simpson receives royalties from Cambridge University Press and UpToDate. Prof. Dr. Walitza has received lecture honoraria from Opopharma and Eli Lilly; her work and research have been partially supported by the Swiss National Science Foundation, the German Research Foundation, Hochspezialisierte Medizin of the Canton of Zurich, and the German Federal Ministry of Education and Research. Dr. Stein has received research grants or consultancy honoraria from AMBRF, Biocodex, Cipla, Lundbeck, the National Responsible Gambling Foundation, Novartis, Servier, and Sun. Dr. van den Heuvel has received research funding (sponsor-initiated clinical trial) from PhotoPharmics and has served as a speaker for Lundbeck. The other authors report no financial relationships with commercial interests. NR 38 TC 0 Z9 0 U1 7 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X EI 1535-7228 J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2017 VL 174 IS 1 BP 60 EP 69 DI 10.1176/appi.ajp.2016.16020201 PG 10 WC Psychiatry SC Psychiatry GA EG4BB UT WOS:000390987300012 PM 27609241 ER PT J AU de Andrade, JA Luckhardt, T AF de Andrade, Joao A. Luckhardt, Tracy TI What Is in a Pattern? That Which We Call Idiopathic Pulmonary Fibrosis by Any Other Pattern Would Behave Alike! SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID USUAL INTERSTITIAL PNEUMONIA; DIAGNOSIS; SURVIVAL C1 [de Andrade, Joao A.; Luckhardt, Tracy] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA. [de Andrade, Joao A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. RP de Andrade, JA (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.; de Andrade, JA (reprint author), Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. NR 12 TC 0 Z9 0 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2017 VL 195 IS 1 BP 10 EP 12 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG3ZB UT WOS:000390982100007 PM 28035849 ER PT J AU Bellani, G Laffey, JG Pham, T Madotto, F Fan, E Brochard, L Esteban, A Gattinoni, L Bunnbasirevic, V Piquilloud, L van Haren, F Larsson, A McAuley, DF Bauer, PR Arabi, YM Ranieri, M Antonelli, M Rubenfeld, GD Thompson, BT Wrigge, H Slutsky, AS Pesenti, A AF Bellani, Giacomo Laffey, John G. Tai Pham Madotto, Fabiana Fan, Eddy Brochard, Laurent Esteban, Andres Gattinoni, Luciano Bunnbasirevic, Vesna Piquilloud, Lise van Haren, Frank Larsson, Anders McAuley, Daniel F. Bauer, Philippe R. Arabi, Yaseen M. Ranieri, Marco Antonelli, Massimo Rubenfeld, Gordon D. Thompson, B. Taylor Wrigge, Hermann Slutsky, Arthur S. Pesenti, Antonio CA LUNG SAFE Investigators ESICM Trials Grp TI Noninvasive Ventilation of Patients with Acute Respiratory Distress Syndrome Insights from the LUNG SAFE Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE noninvasive ventilation; acute respiratory distress syndrome ID POSITIVE-PRESSURE VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; REANIMATION ONCO-HEMATOLOGIQUE; CRITICALLY-ILL PATIENTS; BERLIN DEFINITION; AIRWAY PRESSURE; FAILURE; METAANALYSIS; MALIGNANCIES; EXACERBATIONS AB Rationale: Noninvasive ventilation (NIV) is increasingly used in patients with acute respiratory distress syndrome (ARDS). The evidence supporting NIV use in patients with ARDS remains relatively sparse. Objectives: To determine whether, during NIV, the categorization of ARDS severity based on the Pa-O2/FIO2 Berlin criteria is useful. Methods: The LUNG SAFE (Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure) study described the management of patients with ARDS. This substudy examines the current practice of NIV use in ARDS, the utility of thePa(O2)/FIO2 ratio in classifying patients receiving NIV, and the impact of NIV on outcome. Measurements and Main Results: Of 2,813 patients with ARDS, 436 (15.5%) were managed with NIV on Days 1 and 2 following fulfillment of diagnostic criteria. Classification of ARDS severitybased on PaolFio, ratio was associated with an increase in intensity of ventilatory support, NIV failure, and intensive care unit (ICU) mortality. NIV failure occurred in 22.2% of mild, 42.3% of moderate, and 47.1% of patients with severe ARDS. Hospital mortality in patients with NIV success and failure was 16.1% and 45.4%, respectively. NIV use was independently associated with increased ICU (hazard ratio, 1.446 [95% confidence interval, 1.159-1.805D, but not hospital, mortality. In a propensity matched analysis, ICU mortality was higher in NIV than invasively ventilated patients with a Pa-O2/FIO2 lower than 150 mm Hg. Conclusions: NIV was used in 15% of patients with ARDS, irrespective of severity category. NIV seems to be associated with higher ICU mortality in patients with a Pa-O2/FIO2 lower than 150 mm Hg. C1 [Bellani, Giacomo] Univ Milano Bicocca, Dept Med & Surg, Monza, Italy. [Bellani, Giacomo] San Gerardo Hosp, Dept Emergency & Intens Care, Monza, Italy. [Laffey, John G.] St Michaels Hosp, Dept Anesthesia, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Laffey, John G.; Brochard, Laurent] St Michaels Hosp, Dept Crit Care Med, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Laffey, John G.; Brochard, Laurent; Slutsky, Arthur S.] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Li Ka Shing Knowledge Inst, Toronto, ON, Canada. [Laffey, John G.] Univ Toronto, Dept Anesthesia, Toronto, ON, Canada. [Laffey, John G.] Univ Toronto, Dept Physiol, Toronto, ON, Canada. [Laffey, John G.; Brochard, Laurent; Rubenfeld, Gordon D.; Slutsky, Arthur S.] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada. [Fan, Eddy] Univ Toronto, Inst Hlth Policy Management & Evaluat, Toronto, ON, Canada. [Fan, Eddy; Brochard, Laurent; Rubenfeld, Gordon D.; Slutsky, Arthur S.] Univ Toronto, Dept Med, Toronto, ON, Canada. [Tai Pham] Hop Tenon, AP HP, Grp Hosp Hop Univ Est Parisien, Unite Reanimat Medicochirurg,Pole Thorax Voies Ae, Paris, France. [Tai Pham] Univ Paris Diderot, Unite Mixte Rech 1153, INSERM, Sorbonne Paris Cite,Epidemiol Clin & Stat,Rech Sa, Paris, France. [Tai Pham] Univ Paris 06, Sorbonne Univ, Paris 06, France. [Madotto, Fabiana] Univ Milano Bicocca, Res Ctr Publ Hlth, Dept Med & Surg, Milan, Italy. [Fan, Eddy] Univ Hlth Network, Dept Med, Toronto, ON, Canada. [Esteban, Andres] Hosp Univ Getafe, Ctr Invest Biorned Red Enfermedades Resp, Madrid, Spain. [Gattinoni, Luciano] Univ Med Ctr Gottingen, Dept Anesthesiol Emergency & Intens Care Med, Gottingen, Germany. [Bunnbasirevic, Vesna] Univ Belgrade, Sch Med, Belgrade, Serbia. [Bunnbasirevic, Vesna] Clin Ctr Serbia, Emergency Ctr, Dept Anesthesia & Intens Care, Belgrade, Serbia. [Piquilloud, Lise] Univ Lausanne Hosp, Adult Intens Care & Bum Unit, Lausanne, Switzerland. [Piquilloud, Lise] Univ Hosp Angers, Dept Med Intens Care, Angers, France. [van Haren, Frank] Canberra Hosp, Intens Care Unit, Canberra, ACT, Australia. [van Haren, Frank] Australian Natl Univ, Canberra, ACT, Australia. [Larsson, Anders] Uppsala Univ, Dept Surg Sci, Sect Anesthesiol & Intens Care, Uppsala, Sweden. [McAuley, Daniel F.] Queens Univ Belfast, Ctr Expt Med, Wellcome Wolfson Inst Expt Med, Belfast, Antrim, North Ireland. [McAuley, Daniel F.] Royal Victoria Hosp, Reg Intens Care Unit, Belfast, Antrim, North Ireland. [Bauer, Philippe R.] Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN USA. [Arabi, Yaseen M.] King Saud Bin Abdulaziz Univ Hlth Sci, Riyadh, Saudi Arabia. [Arabi, Yaseen M.] King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia. [Ranieri, Marco] Sapienza Univ Roma, Policlin Umberto I, Dipartimento Anestesia & Rianimaz, Rome, Italy. [Antonelli, Massimo] Univ Cattolica Sacro Cuore, Ist Anestesiol & Rianimaz, Fdn Policlin Univ A Gemelli, Rome, Italy. [Rubenfeld, Gordon D.] Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Thompson, B. Taylor] Harvard Med Sch, Div Pulm & Crit Care, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. [Wrigge, Hermann] Univ Leipzig, Dept Anesthesiol & Intens Care Med, Leipzig, Germany. [Pesenti, Antonio] Osped Maggiore Policlin, Dipartimento Anestesia Rianimaz & Emergenza Urgen, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Milan, Italy. [Pesenti, Antonio] Univ Milan, Dipartimento Fisiopatol Med Chirurg & Traplanti, Milan, Italy. RP Laffey, JG (reprint author), Univ Toronto, St Michaels Hosp, Keenan Res Ctr Biomed Sci, Dept Anesthesia, Toronto, ON, Canada.; Laffey, JG (reprint author), Univ Toronto, St Michaels Hosp, Keenan Res Ctr Biomed Sci, Dept Crit Care Med, Toronto, ON, Canada. EM laffeyj@smh.ca OI Van Haren, Frank/0000-0001-8037-4229 FU European Society of Intensive Care Medicine (ESICM), Brussels, Belgium; St. Michael's Hospital, Toronto, Canada; University of Milan-Bicocca, Monza, Italy FX Supported by the European Society of Intensive Care Medicine (ESICM), Brussels, Belgium; by St. Michael's Hospital, Toronto, Canada; and by the University of Milan-Bicocca, Monza, Italy. The ESICM provided support in data collection and study coordination. ESICM, St. Michael's Hospital, and University of Milan-Bicocca had no role in the design and conduct of the study; management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. NR 33 TC 1 Z9 1 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2017 VL 195 IS 1 BP 67 EP 77 DI 10.1164/rccm.201606-1306OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA EG3ZB UT WOS:000390982100016 PM 27753501 ER PT J AU Nandan, AR Bohnen, JD Chang, DC Yeh, DD Lee, J Velmahos, GC Kaafarani, HMA AF Nandan, Anirudh R. Bohnen, Jordan D. Chang, David C. Yeh, D. Dante Lee, Jarone Velmahos, George C. Kaafarani, Haytham M. A. TI The impact of major intraoperative adverse events on hospital readmissions SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Patient safety; Intraoperative adverse events; Major intraoperative adverse events; iAEs; Readmissions; AHRQ ID QUALITY IMPROVEMENT PROGRAM; PATIENT SAFETY; RISK-FACTORS; AMERICAN-COLLEGE; MULTIVARIABLE PREDICTORS; SURGICAL-PATIENTS; VASCULAR-SURGERY; CARE; RATES; SITE AB BACKGROUND: Hospital-wide readmission rates recently became a recognized benchmarking quality metric. We sought to study the independent impact of major intraoperative adverse events (iAEs) on 30-day readmission in abdominal surgery. METHODS: The 2007 to 2012 institutional American College of Surgeons National Surgical Quality Improvement Program and administrative databases for abdominal operations were matched then screened for iAEs using the International Classification of Diseases, 9th Revision, Clinical Modification based Patient Safety Indicator "Accidental Puncture/Laceration". Flagged charts were reviewed to confirm the presence of iAEs. Major iAEs were defined as class 3 or above, as per our recently validated iAE Classification System. The inpatient database was queried for readmission within 30 days from discharge. Univariate and multivariable models were constructed to analyze the independent impact of major iAEs on readmission, controlling for demographics, comorbidities, American Society of Anesthesiology class, and procedure type/approach/complexity (using relative value units as proxy). Reasons for readmission were investigated using the Agency for Healthcare Research and Quality's International Classification of Diseases, 9th Revision, Clinical Modification based Clinical Classification Software. RESULTS: Of 9,274 surgical procedures; 921 resulted in readmission (9.9%), 183 had confirmed iAEs, 73 of which were major iAEs. Procedures with major iAEs had a higher readmission rate compared with procedures with no iAEs [24.7% vs 9.8%, P < .001]. In multivariable analyses, major iAEs were independently associated with a 2-fold increase in readmission rates [OR = 2.17 (95% CI = 1.22 to 3.86); P = .008]; 67% of readmissions after major iAEs were caused by "complications of surgical procedures or medical care" as defined by Agency for Healthcare Research and Quality. CONCLUSIONS: Major iAEs are independently associated with increased rates of 30-day readmission. Preventing iAEs or mitigating their effects can serve as a quality improvement target to decrease surgical readmissions. (C) 2016 Elsevier Inc. All rights reserved. C1 [Nandan, Anirudh R.; Bohnen, Jordan D.; Chang, David C.; Yeh, D. Dante; Lee, Jarone; Velmahos, George C.; Kaafarani, Haytham M. A.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. [Chang, David C.] Massachusetts Gen Hosp, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu OI Lee, Jarone/0000-0002-4532-8523 NR 33 TC 0 Z9 0 U1 2 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JAN PY 2017 VL 213 IS 1 BP 10 EP 17 DI 10.1016/j.amjsurg.2016.03.018 PG 8 WC Surgery SC Surgery GA EG4AZ UT WOS:000390987100002 PM 27435433 ER PT J AU Oriel, BS Chen, Q Itani, KMF AF Oriel, Brad S. Chen, Qi Itani, Kamal M. F. TI The impact of surgical hand antisepsis technique on surgical site infection SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Surgical site infection; Surgical hand antisepsis; Surgical scrub; Surgical rub; Hand hygiene ID CARE-ASSOCIATED INFECTIONS; RISK-FACTORS; RUB; BEHAVIOR; SURGERY; DISINFECTION; EQUIVALENCE; PREVENTION; GUIDELINE; ADHERENCE AB Background: Limited evidence exists regarding the effect on superficial and deep incisional surgical site infections (SDSSIs) of alcohol-based hand rubs (ABR) versus traditional aqueous surgical scrubs (TSS). User preferences and practice are unknown. Methods: A retrospective cohort study examining SDSSIs using VA Surgical Quality Improvement Program cases before ABR implementation (2007-2009, TSS group) and after (2013-2014, ABR group). A descriptive survey. Results: SDSSI rates were 1.8% and 1.5% for TSS (n=4051) and ABR (n=2293), respectively (p=0.31). The adjusted odds of SDSSI using ABR was not significant (OR 0.82; 95% CI, 0.51-1.32). Greatest SDSSI risk was from preoperative radiotherapy (OR, 2.78; 95% CI,1.14-6.78), general surgery (OR, 2.39; 95% CI, 1.30-4.39) and preoperative smoking (OR, 1.58: 95% CI, 1.02-2.44). Of 95 surveys included, 52% favored ABR. Although 95% self-reported correct product application, improper duration was revealed in both groups (TSS 18% and ABR 10%). Conclusions: Implementation of an ABR for use in surgical hand antisepsis did not alter SDSSI rates. Improving product knowledge and compliance may improve SSI rates. Published by Elsevier Inc. C1 [Oriel, Brad S.; Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. [Oriel, Brad S.] Tufts Univ, Sch Med, Dept Surg, 136 Harrison Ave, Boston, MA 02110 USA. [Chen, Qi] VA Boston Healthcare Syst, CHOIR, 150 South Huntington Ave,Bldg 9, Boston, MA 02130 USA. [Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, 72 East Concord St, Boston, MA 02118 USA. [Itani, Kamal M. F.] Harvard Med Sch, Dept Surg, 25 Shattuck St, Boston, MA 02115 USA. RP Itani, KMF (reprint author), VA Boston Healthcare Syst, Dept Surg, 1400 VFW Pkwy, West Roxbury, MA 02132 USA. EM brad.oriel@va.gov; qi.chen2@va.gov; kamal.itani@va.gov FU Merck; Sanofi; Dr. Reddy's laboratories FX Drs. Brad S. Oriel and Qi Chen have no conflicts of interest. Dr. Kamal M.P. Itani has received research funds to his institution from Merck, Sanofi, and Dr. Reddy's laboratories. He was a research consultant for Irrimax. NR 35 TC 0 Z9 0 U1 5 U2 5 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 JAN PY 2017 VL 213 IS 1 BP 24 EP 29 DI 10.1016/j.amjsurg.2016.09.058 PG 6 WC Surgery SC Surgery GA EG4AZ UT WOS:000390987100004 PM 27817826 ER PT J AU Sjoding, MW Schoenfeld, DA Brown, SM Hough, CL Yealy, DM Moss, M Angus, DC Iwashyna, TJ AF Sjoding, Michael W. Schoenfeld, David A. Brown, Samuel M. Hough, Catherine L. Yealy, Donald M. Moss, Marc Angus, Derek C. Iwashyna, Theodore J. CA NHLBI Prevention Early Treatment TI Power Calculations to Select Instruments for Clinical Trial Secondary Endpoints A Case Study of Instrument Selection for Post-Traumatic Stress Symptoms in Subjects with Acute Respiratory Distress Syndrome SO ANNALS OF THE AMERICAN THORACIC SOCIETY LA English DT Article AB Rationale: After the sample size of a randomized clinical trial (RCT) is set by the power requirement of its primary endpoint, investigators select secondary endpoints while unable to further adjust sample size. How the sensitivity and specificity of an instrument used to measure these outcomes, together with their expected underlying event rates, affect an RCT's power to measure significant differences in these outcomes is poorly understood. Objectives: Motivated by the design of an RCT of neuromuscular blockade in acute respiratory distress syndrome, we examined how power to detect a difference in secondary endpoints varies with the sensitivity and specificity of the instrument used to measure such outcomes. Methods: We derived a general formula and Stata code for calculating an RCT's power to detect differences in binary outcomes when such outcomes are measured with imperfect sensitivity and specificity. The formula informed the choice of instrument for measuring post-traumatic stress-like symptoms in the Reevaluation of Systemic Early Neuromuscular Blockade RCT (www.clinicaltrials.gov identifier NCT02509078). Measurements and Main Results: On the basis of published sensitivities and specificities, the Impact of Events Scale-Revised was predicted to measure a 36% symptom rate, whereas the Post-Traumatic Stress Symptoms instrument was predicted to measure a 23% rate, if the true underlying rate of post-traumatic stress symptoms were 25%. Despite its lower sensitivity, the briefer Post-Traumatic Stress Symptoms instrument provided superior power to detect a difference in rates between trial arms, owing to its higher specificity. Conclusions: Examining instruments' power to detect differences in outcomes may guide their selection when multiple instruments exist, each with different sensitivities and specificities. C1 [Sjoding, Michael W.; Iwashyna, Theodore J.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Sjoding, Michael W.] Univ Michigan, Inst Healthcare Policy & Innovat, Ann Arbor, MI 48109 USA. [Schoenfeld, David A.] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. [Schoenfeld, David A.] Harvard Univ, Boston, MA 02115 USA. [Brown, Samuel M.] Intermt Med Ctr, Dept Pulm & Crit Care Med, Salt Lake City, UT USA. [Brown, Samuel M.] Univ Utah, Sch Med, Salt Lake City, UT USA. [Hough, Catherine L.] Univ Washington, Div Pulm & Crit Care Med, Harborview Med Ctr, Seattle, WA 98195 USA. [Yealy, Donald M.] Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA USA. [Angus, Derek C.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. [Moss, Marc] Univ Colorado, Dept Med, Denver, CO USA. [Iwashyna, Theodore J.] Vet Affairs Ctr Clin Management Res, Ann Arbor, MI USA. RP Sjoding, MW (reprint author), Univ Michigan, Dept Internal Med, Taubman Ctr 3916, 1500 East Med Ctr Dr,SPC 5360, Ann Arbor, MI 48109 USA. EM msjoding@med.umich.edu FU National Institutes of Health under U.S. National Heart, Lung, and Blood Institute (NHLBI) [HL123009-01, HL123010-01, HL123004-01, HL123022-01, HL122989-01, HL123008-01, HL123027-01, HL123020-01, HL123018-01, HL123031-01, HL123033-01, HL122998-01, HL123023-01]; NHLBI [T32HL007749] FX Supported by the National Institutes of Health under U.S. National Heart, Lung, and Blood Institute (NHLBI) U01 grants HL123009-01, HL123010-01, HL123004-01, HL123022-01, HL122989-01, HL123008-01, HL123027-01, HL123020-01, HL123018-01, HL123031-01, HL123033-01, HL122998-01, and HL123023-01, and by a grant to M.W.S. from the NHLBI (T32HL007749). NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1546-3222 EI 2325-6621 J9 ANN AM THORAC SOC JI Ann. Am. Thoracic Society PD JAN PY 2017 VL 14 IS 1 BP 110 EP 117 DI 10.1513/AnnalsATS.201608-585OC PG 8 WC Respiratory System SC Respiratory System GA EG2OV UT WOS:000390884100018 PM 27788018 ER PT J AU Jorge, A Lertratanakul, A Lee, J Pearce, W McPherson, D Thompson, T Barinas-Mitchell, E Ramsey-Goldman, R AF Jorge, April Lertratanakul, Apinya Lee, Jungwha Pearce, William McPherson, David Thompson, Trina Barinas-Mitchell, Emma Ramsey-Goldman, Rosalind TI Depression and Progression of Subclinical Cardiovascular Disease in Systemic Lupus Erythematosus SO ARTHRITIS CARE & RESEARCH LA English DT Article ID INTIMA-MEDIA THICKNESS; RISK-FACTORS; HEART-DISEASE; WOMEN; ATHEROSCLEROSIS; CORONARY; PLAQUE; INDEX; CALCIFICATION; ASSOCIATION AB ObjectiveWomen with systemic lupus erythematosus (SLE) have an increased incidence of premature cardiovascular disease (CVD). A relationship between depression and increased inflammation leading to CVD has been proposed. The aim of this study was to evaluate the relationship between depression and the progression of subclinical atherosclerosis in women with SLE. MethodsIn this prospective case-control study, 149 participants with SLE and 126 controls were followed over 5 years. Evaluation included laboratory studies, assessment of CVD risk factors, depression screening, ultrasound evaluations of carotid intima-media thickness (CIMT) and carotid plaque, and assessment of SLE disease activity for the SLE cases. ResultsThe SLE group had a higher rate of depression: 29% compared with 11% in the control group (P=0.003). When controlling for traditional CVD risk factors, the presence of baseline depression correlated with increased progression of CIMT in the SLE group, but not in the control group. The mean increase in CIMT was 0.026 mm in the SLE group without depression versus 0.064 mm in the depressed SLE group (P=0.0096). There was no association between depression and carotid plaque in either group, with a calculated odds ratio for plaque progression in the depressed SLE group of 1.118 (95% confidence interval 0.476, 2.623) in the adjusted model. ConclusionWomen with SLE and concomitant depression have an increased risk of developing subclinical atherosclerosis, as measured by CIMT, but not by carotid plaque. The data suggest that depression, a potentially modifiable risk factor, may contribute to the increased risk of subclinical atherosclerosis in women with SLE. C1 [Jorge, April] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Jorge, April; Lertratanakul, Apinya; Lee, Jungwha; Pearce, William; Ramsey-Goldman, Rosalind] Northwestern Univ, Chicago, IL 60611 USA. [Lertratanakul, Apinya] AbbVie, N Chicago, IL USA. [McPherson, David] Univ Texas Houston, Houston, TX USA. [Thompson, Trina; Barinas-Mitchell, Emma] Univ Pittsburgh, Pittsburgh, PA USA. RP Ramsey-Goldman, R (reprint author), Northwestern Univ, Feinberg Sch Med, Div Rheumatol, 240 East Huron St, Chicago, IL 60611 USA. EM rgramsey@northwestern.edu FU NIH [K24-AR-02318, P60-AR-066464, T32-AR-0761, 1U54TR-001353]; Mary Kirkland Center for Lupus Research; Rheuminations, Inc.; Driskill Foundation FX Supported by the NIH (grants K24-AR-02318, P60-AR-066464, T32-AR-0761, and 1U54TR-001353), the Mary Kirkland Center for Lupus Research, Rheuminations, Inc., and the Driskill Foundation. NR 28 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2151-464X EI 2151-4658 J9 ARTHRIT CARE RES JI Arthritis Care Res. PD JAN PY 2017 VL 69 IS 1 BP 5 EP 11 DI 10.1002/acr.22992 PG 7 WC Rheumatology SC Rheumatology GA EG4VO UT WOS:000391042000002 PM 27390248 ER PT J AU Fu, ZL Liu, M Zhang, J Li, Z Li, Q AF Fu, Zhanli Liu, Meng Zhang, Jin Li, Ziao Li, Qian TI IgG4-Related Renal Lesions Detected by Delayed F-18-FDG PET/CT Scan SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE F-18-FDG; IgG4-related disease; kidney; PET/CT ID KIDNEY-DISEASE; FDG-PET/CT AB Multiple renal lesions, which showed clearly demarcated low densities on contrast-enhanced CT, were revealed in a 56-year-old woman. The F-18-FDG avidity of the renal lesions was equal to or mildly higher than that of the renal cortex on the routine PET/CT scan, but significantly higher on the delayed scan. IgG4-related disease with renal involvement was confirmed subsequently by the measurement of serous IgG4 and the pathology of renal lesion. C1 [Fu, Zhanli; Liu, Meng; Li, Ziao] Peking Univ, Hosp 1, Dept Nucl Med, 8 Xishiku St, Beijing 100034, Peoples R China. [Zhang, Jin] Beijing Univ Chinese Med, Dongzhimen Hosp, Dept Nucl Med, Beijing, Peoples R China. [Li, Qian] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Fu, ZL (reprint author), Peking Univ, Hosp 1, Dept Nucl Med, 8 Xishiku St, Beijing 100034, Peoples R China. EM fuzhanli2002@163.com NR 12 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0363-9762 EI 1536-0229 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD JAN PY 2017 VL 42 IS 1 BP 66 EP 67 DI 10.1097/RLU.0000000000001427 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA EG2ED UT WOS:000390855000035 PM 27764042 ER PT J AU Widge, AS Ellard, KK Paulk, AC Basu, I Yousefi, A Zorowitz, S Gilmour, A Afzal, A Deckersbach, T Cash, SS Kramer, MA Eden, UT Dougherty, DD Eskandar, EN AF Widge, Alik S. Ellard, Kristen K. Paulk, Angelique C. Basu, Ishita Yousefi, Ali Zorowitz, Samuel Gilmour, Anna Afzal, Afsana Deckersbach, Thilo Cash, Sydney S. Kramer, Mark A. Eden, Uri T. Dougherty, Darin D. Eskandar, Emad N. TI Treating refractory mental illness with closed-loop brain stimulation: Progress towards a patient-specific transdiagnostic approach SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Deep brain stimulation; Psychiatric illness; Psychiatric diagnosis; Functional imaging; Mood disorders; Anxiety disorders; Electrophysiology; Modeling; Local field potential ID TREATMENT-RESISTANT DEPRESSION; POSTTRAUMATIC-STRESS-DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; VENTRAL CAPSULE/VENTRAL STRIATUM; OBSESSIVE-COMPULSIVE DISORDER; VAGUS NERVE-STIMULATION; PREFRONTAL CORTEX; PROLONGED EXPOSURE; EMOTION REGULATION; GRANGER CAUSALITY AB Mental disorders are a leading cause of disability, morbidity, and mortality among civilian and military populations. Most available treatments have limited efficacy, particularly in disorders where symptoms vary over relatively short time scales. Targeted modulation of neural circuits, particularly through open-loop deep brain stimulation (DBS), showed initial promise but has failed in blinded clinical trials. We propose a new approach, based on targeting neural circuits linked to functional domains that cut across diagnoses. Through that framework, which includes measurement of patients using six psychophysical tasks, we seek to develop a closed loop DBS system that corrects dysfunctional activity in brain circuits underlying those domains. We present convergent preliminary evidence from functional neuroimaging, invasive human electrophysiology, and human brain stimulation experiments suggesting that this approach is feasible. Using the Emotional Conflict Resolution (ECR) task as an example, we show that emotion-related networks can be identified and modulated in individual patients. Invasive and non-invasive methodologies both identify a network between prefrontal cortex, cingulate cortex, insula, and amygdala. Further, stimulation in cingulate and amygdala changes patients' performance in ways that are linked to the task's emotional content. We present preliminary statistical models that predict this change and allow us to track it at a single-trial level. As these diagnostic and modeling strategies are refined and embodied in an implantable device, they offer the prospect of a new approach to psychiatric treatment and its accompanying neuroscience. (C) 2016 Elsevier Inc. All rights reserved. C1 [Widge, Alik S.; Ellard, Kristen K.; Zorowitz, Samuel; Gilmour, Anna; Afzal, Afsana; Deckersbach, Thilo; Dougherty, Darin D.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Widge, Alik S.; Ellard, Kristen K.; Zorowitz, Samuel; Gilmour, Anna; Afzal, Afsana; Deckersbach, Thilo; Dougherty, Darin D.] Harvard Med Sch, Charlestown, MA USA. [Widge, Alik S.] MIT, Picower Inst Learning & Memory, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Paulk, Angelique C.; Basu, Ishita; Yousefi, Ali; Eskandar, Emad N.] Massachusetts Gen Hosp, Dept Neurol Surg, Boston, MA 02114 USA. [Paulk, Angelique C.; Basu, Ishita; Yousefi, Ali; Cash, Sydney S.; Eskandar, Emad N.] Harvard Med Sch, Boston, MA USA. [Cash, Sydney S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kramer, Mark A.; Eden, Uri T.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Widge, AS (reprint author), 149 13th St,Room 2625, Charlestown, MA 02129 USA. EM awidge@partners.org FU Medtronic; Cyberonics; U.S. Army Research Office; Defense Advanced Research Projects Agency [W911NF-14-2-0045] FX We thank Mr. David Clifford and Dr. Geoffrey Ling for their helpful comments on an earlier draft of the manuscript. ACP, ASW, AY, DDD, ENE, KKE, TD, and UTE are named inventors on patent applications related to transdiagnostic tasks and their use in calibrating brain stimulation. DDD and ENE have served as paid consultants to Medtronic and Cyberonics, which manufacture clinical brain stimulators. This research was sponsored by the U.S. Army Research Office and the Defense Advanced Research Projects Agency and was accomplished under cooperative agreement number W911NF-14-2-0045. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the Army Research Office, DARPA, or the U.S. Government. The U.S. Government is authorized to reproduce and distribute reprints for Government purposes notwithstanding any copyright notation hereon. NR 83 TC 0 Z9 0 U1 11 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2017 VL 287 SI SI BP 461 EP 472 DI 10.1016/j.expneurol.2016.07.021 PN 4 PG 12 WC Neurosciences SC Neurosciences & Neurology GA EG6LU UT WOS:000391158800004 PM 27485972 ER PT J AU Eapen, BC Murphy, DP Cifu, DX AF Eapen, Blessen C. Murphy, Douglas P. Cifu, David X. TI Neuroprosthetics in amputee and brain injury rehabilitation SO EXPERIMENTAL NEUROLOGY LA English DT Review DE Neuroprosthetics; Rehabilitation; Brain injury; Amputee ID TRANSCRANIAL MAGNETIC STIMULATION; CONTROLLED-TRIAL; EARLY HISTORY; LIMB; DISORDERS; ATTENTION; CONSCIOUSNESS; PROSTHESES; NEUROPLASTICITY; EPIDEMIOLOGY AB The goals of rehabilitation medicine programs are to promote health, restore functional impairments and improve quality of life. The field of neuroprosthetics has evolved over the last decade given an improved understanding of neuroscience and the incorporation of advanced biotechnology and neuroengineering in the rehabilitation setting to develop adaptable applications to help facilitate recovery for individuals with amputations and brain injury. These applications may include a simple cognitive prosthetics aid for impaired memory in brain-injured individuals to myoelectric prosthetics arms with artificial proprioceptive feedback for those with upper extremity amputations. The integration of neuroprosthetics into the existing framework of current rehabilitation approaches not only improves quality-of-care and outcomes but help broadens current rehabilitation treatment paradigms. Although, we are in the infancy of the understanding the true benefit of neuroprosthetics and its clinical applications in the rehabilitation setting there is tremendous amount of promise for future research and development of tools to help facilitate recovery and improve quality of life in individuals with disabilities. Published by Elsevier Inc. C1 [Eapen, Blessen C.] South Texas Vet Hlth Care Syst, Phys Med & Rehabil Serv, Polytrauma Rehabil Ctr, San Antonio, TX USA. [Eapen, Blessen C.; Cifu, David X.] VA DoD Chron Effects Neurotrauma Consortium, Richmond, VA USA. [Murphy, Douglas P.; Cifu, David X.] Virginia Commonwealth Univ, Dept Phys Med & Rehabil, Richmond, VA USA. [Murphy, Douglas P.; Cifu, David X.] Hunter Holmes McGuire VA Med Ctr, Phys Med & Rehabil Serv, Richmond, VA USA. RP Eapen, BC (reprint author), South Texas Vet Hlth Care Syst, Phys Med & Rehabil Serv, Polytrauma Rehabil Ctr, San Antonio, TX USA.; Eapen, BC (reprint author), VA DoD Chron Effects Neurotrauma Consortium, Richmond, VA USA. EM blessen.eapen2@va.gov; Douglas.Murphy3@va.gov; david.cifu@vcuhealth.org NR 69 TC 0 Z9 0 U1 22 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2017 VL 287 SI SI BP 479 EP 485 DI 10.1016/j.expneurol.2016.08.004 PN 4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA EG6LU UT WOS:000391158800006 PM 27519275 ER PT J AU Wylie, BJ Kishashu, Y Matechi, E Zhou, Z Coull, B Abioye, AI Dionisio, KL Mugusi, F Premji, Z Fawzi, W Hauser, R Ezzati, M AF Wylie, B. J. Kishashu, Y. Matechi, E. Zhou, Z. Coull, B. Abioye, A. I. Dionisio, K. L. Mugusi, F. Premji, Z. Fawzi, W. Hauser, R. Ezzati, M. TI Maternal exposure to carbon monoxide and fine particulate matter during pregnancy in an urban Tanzanian cohort SO INDOOR AIR LA English DT Article DE Household air pollution; Personal exposure; Birth outcome; Carbon monoxide; Particulate matter ID INDOOR AIR-POLLUTION; BIOMASS FUELS; PERSONAL EXPOSURE; HOUSEHOLD; CHILDREN; COOKING; INFANTS; GAMBIA; CHINA; WOMEN AB Low birthweight contributes to as many as 60% of all neonatal deaths; exposure during pregnancy to household air pollution has been implicated as a risk factor. Between 2011 and 2013, we measured personal exposures to carbon monoxide (CO) and fine particulate matter (PM2.5) in 239 pregnant women in Dar es Salaam, Tanzania. CO and PM2.5 exposures during pregnancy were moderately high (geometric means 2.0ppm and 40.5g/m(3)); 87% of PM2.5 measurements exceeded WHO air quality guidelines. Median and high (75th centile) CO exposures were increased for those cooking with charcoal and kerosene versus kerosene alone in quantile regression. High PM2.5 exposures were increased with charcoal use. Outdoor cooking reduced median PM2.5 exposures. For PM2.5, we observed a 0.15kg reduction in birthweight per interquartile increase in exposure (23.0g/m(3)) in multivariable linear regression; this finding was of borderline statistical significance (95% confidence interval 0.30, 0.00kg; P=0.05). PM2.5 was not significantly associated with birth length or head circumference nor were CO exposures associated with newborn anthropometrics. Our findings contribute to the evidence that exposure to household air pollution, and specifically fine particulate matter, may adversely affect birthweight. C1 [Wylie, B. J.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. [Wylie, B. J.; Zhou, Z.; Coull, B.; Dionisio, K. L.; Hauser, R.] Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. [Kishashu, Y.; Mugusi, F.; Premji, Z.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Matechi, E.] Africa Acad Publ Hlth, Dar Es Salaam, Tanzania. [Coull, B.] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Abioye, A. I.; Dionisio, K. L.; Fawzi, W.] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Ezzati, M.] Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Norfolk Pl, London, England. RP Wylie, BJ (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, 55 Fruit St, Boston, MA 02114 USA. EM bwylie@partners.org FU Harvard Center for the Environment (HUCE); Harvard Catalyst \ The Harvard Clinical and Translational Science Center (NIH) [UL1 RR 025758]; NIH [U01HD061232, R01HD057941]; Vincent Department of Obstetrics and Gynecology at MGH; National Institute of Environmental Health Sciences [NIH K23 ES021471]; National Institutes of Health [NIH ES 000002]; UK Medical Research Council FX We would like to thank the study staff, Anne Marie Darling, Laura Meloney, and Jeremy Kane for their efforts on behalf of the study. We gratefully acknowledge the time of the women who participated in our study. Work was conducted with support from the Harvard Center for the Environment (HUCE), Harvard Catalyst vertical bar The Harvard Clinical and Translational Science Center (NIH Award #UL1 RR 025758), NIH Award #U01HD061232, NIH Award #R01HD057941, and the Vincent Department of Obstetrics and Gynecology at MGH. BJW was supported by the National Institute of Environmental Health Sciences (NIH K23 ES021471). BC was supported by the National Institutes of Health (NIH ES 000002). ME is supported by the UK Medical Research Council. NR 29 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-6947 EI 1600-0668 J9 INDOOR AIR JI Indoor Air PD JAN PY 2017 VL 27 IS 1 BP 136 EP 146 DI 10.1111/ina.12289 PG 11 WC Construction & Building Technology; Engineering, Environmental; Public, Environmental & Occupational Health SC Construction & Building Technology; Engineering; Public, Environmental & Occupational Health GA EG4RY UT WOS:000391032600013 PM 26880607 ER PT J AU Young, RH Clement, PB AF Young, Robert H. Clement, Philip B. TI History of Gynecological Pathology XXX. Robert E. Scully, MD SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Biographical-Item C1 [Young, Robert H.] Harvard Med Sch, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. [Clement, Philip B.] Univ British Columbia, Dept Pathol, Vancouver Gen Hosp, Vancouver, BC, Canada. RP Young, RH (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. EM rhyoung@partners.org NR 10 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 0277-1691 EI 1538-7151 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD JAN PY 2017 VL 36 IS 1 BP 2 EP 23 DI 10.1097/PGP.0000000000000371 PG 22 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA EG3WN UT WOS:000390975500002 ER PT J AU Peng, YB Song, CL Yang, CF Guo, QG Yao, M AF Peng, Yinbo Song, Chenlu Yang, Chuanfeng Guo, Qige Yao, Min TI Low molecular weight chitosan-coated silver nanoparticles are effective for the treatment of MRSA-infected wounds SO INTERNATIONAL JOURNAL OF NANOMEDICINE LA English DT Article DE silver nanoparticles; LMWC-AgNPs; MRSA; PVP-AgNPs; PVP; biocompatibility ID TISSUE DISTRIBUTION; PARTICLE-SIZE; IN-VITRO; TOXICITY; CYTOTOXICITY; DELIVERY; GENOTOXICITY; PARAMETERS; KINETICS; COMPLEX AB Silver nanoparticles (AgNPs) are being widely applied as topical wound materials; however, accumulated deposition of silver in the liver, spleen, and other main organs may lead to organ damage and dysfunction. We report here that low molecular weight chitosan-coated silver nanoparticles (LMWC-AgNPs) are effective against methicillin-resistant Staphylococcus aureus (MRSA), have better biocompatibility, and have lower body absorption characteristics when compared with polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) and silver nanoparticles without surface stabilizer (uncoated-AgNPs) in a dorsal MRSA wound infection mouse model. LMWC-AgNPs were synthesized by reducing silver nitrate with low molecular weight chitosan as a stabilizer and reducing agent, while PVP-AgNPs were synthesized using polyvinylpyrrolidone as a stabilizer and ethanol as a reducing agent. AgNPs with different surface stabilizers were identified by UV-visible absorption spectrometry, and particle size was determined by transmission electron microscopy. UV-visible absorption spectra of LMWC-AgNPs, PVP-AgNPs and uncoated-AgNPs were similar and their sizes were in the range of 10-30 nm. In vitro experiments showed that the three types of AgNPs had similar MRSA-killing effects, with obvious effect at 4 mu g/mL and 100% effect at 8 mu g/mL. Bacteriostatic annulus experiments also showed that all the three types of AgNPs had similar antibacterial inhibitory effect at 10 mu g/mL. Cell counting kit-8 assay and Hoechst/propidium iodide (PI) staining showed that LMWC-AgNPs were significantly less toxic to human fibroblasts than PVP-AgNPs and uncoated-AgNPs. Treatment of mice with MRSA wound infection demonstrated that the three types of AgNPs effectively controlled MRSA wound infection and promoted wound healing. After continuous application for 14 days, LMWC-AgNPs-treated mice showed significantly reduced liver dysfunction as demonstrated by the reduced alanine aminotransferase and aspartate aminotransferase levels and liver deposition of silver, in comparison to mice treated with uncoated-AgNPs or PVP-AgNPs. Our results demonstrated that LMWC-AgNPs had good anti-MRSA effects, while harboring a better biocompatibility and lowering the body's absorption characteristics. C1 [Peng, Yinbo; Song, Chenlu; Yang, Chuanfeng; Guo, Qige; Yao, Min] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Burns & Plast Surg,Inst Traumat Med, 280 Mohe Rd, Shanghai 201900, Peoples R China. [Yao, Min] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Dept Dermatol, Boston, MA USA. RP Yao, M (reprint author), Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Burns & Plast Surg,Inst Traumat Med, 280 Mohe Rd, Shanghai 201900, Peoples R China. EM my058@vip.sina.com FU Youth Program of National Natural Science Fund Projects [81501656] FX This research was supported by the Youth Program of National Natural Science Fund Projects (81501656). NR 34 TC 0 Z9 0 U1 9 U2 9 PU DOVE MEDICAL PRESS LTD PI ALBANY PA PO BOX 300-008, ALBANY, AUCKLAND 0752, NEW ZEALAND SN 1178-2013 J9 INT J NANOMED JI Int. J. Nanomed. PY 2017 VL 12 BP 295 EP 304 DI 10.2147/IJN.S122357 PG 10 WC Nanoscience & Nanotechnology; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Pharmacology & Pharmacy GA EG7CM UT WOS:000391202900002 PM 28115847 ER PT J AU De Rienzo, A Cook, RW Wilkinson, J Gustafson, CE Amin, W Johnson, CE Oelschlager, KM MaetzoLd, DJ Stone, JF Feldman, MD Becich, MJ Yeap, BY Richards, WG Bueno, R AF De Rienzo, Assunta Cook, Robert W. Wilkinson, Jeff Gustafson, Corinne E. Amin, Waqas Johnson, Clare E. Oelschlager, Kristen M. MaetzoLd, Derek J. Stone, John F. Feldman, Michael D. Becich, Michael J. Yeap, Beow Y. Richards, William G. Bueno, Raphael TI Validation of a Gene Expression Test for Mesothelioma Prognosis in Formalin-Fixed Paraffin-Embedded Tissues SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MALIGNANT PLEURAL MESOTHELIOMA; EXTRAPLEURAL PNEUMONECTOMY; CUTANEOUS MELANOMA; LUNG-CANCER; RATIO TEST; SURVIVAL; PREDICT; RECURRENCE; DIAGNOSIS; RESECTION AB A molecular test performed using fresh-frozen tissue was proposed for use in the prognosis of patients with pleural mesothelioma. The accuracy of the test and its properties was assessed under Clinical Laboratory Improvement Amendments approved guidelines using FFPE tissue from an independent multicenter patient cohort. Concordance studies were performed using matched frozen and FFPE mesothelioma samples. The prognostic value of the test was evaluated in an independent validation cohort of 73 mesothelioma patients who underwent surgical resection. FFPE-based classification demonstrated overall high concordance (83%) with the matched frozen specimens, on removal of cases with low confidence scores, showing sensitivity and specificity in predicting type B classification (poor outcome) of 43% and 98%, respectively. Concordance between research and clinical methods increased to 87% on removal of low confidence cases. Median survival times in the validation cohort were 18 and 7 months in type A and type B cases, respectively (P = 0.002). Multivariate classification adding pathologic staging information to the gene expression score resulted in significant stratification of risk groups. The median survival times were 52 and 14 months in the low-risk (class 1) and intermediate-risk (class 2) groups, respectively. The prognostic molecular test for mesothelioma can be performed on FFPE tissues to predict survival, and can provide an orthogonal tool, in combination with established pathologic parameters, for risk evaluation. C1 [De Rienzo, Assunta; Gustafson, Corinne E.; Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Div Thorac Surg, Thorac Surg Oncol Lab, 75 Francis St, Boston, MA 02115 USA. [De Rienzo, Assunta; Gustafson, Corinne E.; Richards, William G.; Bueno, Raphael] Brigham & Womens Hosp, Div Thorac Surg, Int Mesothelioma Program, 75 Francis St, Boston, MA 02115 USA. [De Rienzo, Assunta; Gustafson, Corinne E.; Yeap, Beow Y.; Richards, William G.; Bueno, Raphael] Harvard Med Sch, Boston, MA USA. [Cook, Robert W.; Johnson, Clare E.; Oelschlager, Kristen M.; MaetzoLd, Derek J.] Castle Biosci Inc, Friendswood, TX USA. [Wilkinson, Jeff; Stone, John F.] St Josephs Hosp, DNA Diagnost Lab, Phoenix, AZ USA. [Amin, Waqas; Feldman, Michael D.; Becich, Michael J.] Natl Mesothelioma Virtual Bank, Pittsburgh, PA USA. [Amin, Waqas] Univ Pittsburgh, Dept Biomed Informat, Pittsburgh, PA USA. [Feldman, Michael D.; Becich, Michael J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Yeap, Beow Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Bueno, R (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. EM rbueno@partners.org FU National Cancer Institute [2 R01 CA120528]; International Mesothelioma Program; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health [U24 OH009077-06]; Brigham and Women's Hospital (BWH) FX Supported by National Cancer Institute grant 2 R01 CA120528 (R.B.), by the International Mesothelioma Program, and by the Centers for Disease Control and Prevention and the National Institute for Occupational Safety and Health for funding National Mesothelioma Virtual Bank grant U24 OH009077-06. Castle Biosciences, which has licensed the prognostic test described herein from Brigham and Women's Hospital (BWH), supported some of the work through a grant to BWH and the laboratory of R.B. (Thoracic Surgery Oncology Laboratory). NR 27 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 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2017 VL 19 IS 1 BP 65 EP 71 DI 10.1016/j.jmoldx.2016.07.011 PG 7 WC Pathology SC Pathology GA EG3ZL UT WOS:000390983100007 PM 27863259 ER PT J AU Nowak, JA Yurgelun, MB Bruce, JL Rojas-Rudilla, V Hall, DL Shivdasani, P Garcia, EP Agoston, AT Srivastava, A Ogino, S Kuo, FC Lindeman, NI Dong, F AF Nowak, Jonathan A. Yurgelun, Matthew B. Bruce, Jacqueline L. Rojas-Rudilla, Vanesa Hall, Dimity L. Shivdasani, Priyanka Garcia, Elizabeth P. Agoston, Agoston T. Srivastava, Amitabh Ogino, Shuji Kuo, Frank C. Lindeman, Neal. I. Dong, Fei TI Detection of Mismatch Repair Deficiency and Microsatellite Instability in Colorectal Adenocarcinoma by Targeted Next-Generation Sequencing SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID LYNCH-SYNDROME; DNA-POLYMERASE; BRAF MUTATION; COLON-CANCER; PHENOTYPE; CETUXIMAB AB Mismatch repair protein deficiency (MMR-D) and high microsatellite instability (MSI-H) are features of Lynch syndrome associated colorectal carcinomas and have implications in clinical management. We evaluate the ability of a targeted next-generation sequencing panel to detect MMR-D and MSI-H based on mutational phenotype. Using a criterion of >40 total mutations per megabase or >5 single-base insertion or deletion mutations in repeats per megabase, sequencing achieves 92% sensitivity and 100% specificity for MMR-D by immunohistochemistry in a training cohort of 149 colorectal carcinomas and 91% sensitivity and 98% specificity for MMR-D in a validation cohort of 94 additional colorectal carcinomas. False-negative samples are attributable to tumor heterogeneity, and next-generation sequencing results are concordant with analysis of microsatellite loci by PCR. In a subset of 95 carcinomas with microsatellite analysis, sequencing achieves 100% sensitivity and 99% specificity for MSI-H in the combined training and validation set. False-positive results for MMR-D and MSI-H are attributable to ultramutated cancers with POLE mutations, which are confirmed by direct sequencing of the POLE gene and are detected by mutational signature analysis. These findings provide a framework for a targeted tumor sequencing panel to accurately detect MMR-D and MSI-H in colorectal carcinomas. C1 [Nowak, Jonathan A.; Bruce, Jacqueline L.; Rojas-Rudilla, Vanesa; Hall, Dimity L.; Shivdasani, Priyanka; Garcia, Elizabeth P.; Agoston, Agoston T.; Srivastava, Amitabh; Ogino, Shuji; Kuo, Frank C.; Lindeman, Neal. I.; Dong, Fei] Harvard Med Sch, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Yurgelun, Matthew B.] Harvard Med Sch, Dana Farber Canc Inst, Ctr Med Genet & Prevent, Boston, MA USA. [Yurgelun, Matthew B.; Ogino, Shuji] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Ogino, Shuji] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Dong, F (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3, Boston, MA 02114 USA. EM fdong1@partners.org FU Department of Pathology; Dana Farber Cancer Institute; NIH [R35 CA197735]; Brigham and Women's Hospital FX Supported by the Department of Pathology, Brigham and Women's Hospital, Dana Farber Cancer Institute, and NIH grant R35 CA197735 (S.O.). NR 20 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-1578 EI 1943-7811 J9 J MOL DIAGN JI J. Mol. Diagn. PD JAN PY 2017 VL 19 IS 1 BP 84 EP 91 DI 10.1016/j.jmoldx.2016.07.010 PG 8 WC Pathology SC Pathology GA EG3ZL UT WOS:000390983100009 PM 27863258 ER PT J AU Hennessy, M Hamblin, MR AF Hennessy, Madison Hamblin, Michael R. TI Photobiomodulation and the brain: a new paradigm SO JOURNAL OF OPTICS LA English DT Review DE transcranial photobiomodulation; low level laser therapy; brain disorders; traumatic brain injury; stroke; Alzheimer's disease; psychiatric diseases ID NEAR-INFRARED LIGHT; CYTOCHROME-C-OXIDASE; PRIMARY CORTICAL-NEURONS; POWER LASER IRRADIATION; DOPAMINERGIC CELL-SURVIVAL; TRANSGENIC MOUSE MODELS; BIPHASIC DOSE-RESPONSE; ALZHEIMERS-DISEASE; TRANSCRANIAL LASER; THERAPY LLLT AB Transcranial photobiomodulation (PBM), also known as low level laser therapy (LLLT), relies on the use of red/NIR light to stimulate, preserve and regenerate cells and tissues. The mechanism of action involves photon absorption in the mitochondria (cytochrome c oxidase), and ion channels in cells leading to activation of signaling pathways, up-regulation of transcription factors and increased expression of protective genes. We have studied PBM for treating traumatic brain injury in mice using a NIR laser spot delivered to the head. Mice had improved memory and learning, increased neuroprogenitor cells in the dentate gyrus and subventricular zone, increased BDNF and more synaptogenesis in the cortex. These highly beneficial effects on the brain suggest that the applications of LLLT are much broader than first conceived. Other groups have studied stroke (animal models and clinical trials), Alzheimer's disease, Parkinson's disease, depression and cognitive enhancement in healthy subjects. C1 [Hennessy, Madison] Briarcliff High Sch, Briarcliff Manor, NY USA. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA. [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.; Hamblin, MR (reprint author), Harvard Med Sch, Dept Dermatol, Boston, MA 02115 USA.; Hamblin, MR (reprint author), Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU US NIH [R01AI050875, R21AI121700]; Air Force Office of Scientific Research [FA9550-13-1-0068]; US Army Medical Research Acquisition Activity [W81XWH-09-1-0514]; US Army Medical Research and Materiel Command grant [W81XWH-13-2-0067] FX MRH was supported by US NIH grants R01AI050875 and R21AI121700, Air Force Office of Scientific Research grant FA9550-13-1-0068, by US Army Medical Research Acquisition Activity grant W81XWH-09-1-0514, and by US Army Medical Research and Materiel Command grant W81XWH-13-2-0067. NR 107 TC 0 Z9 0 U1 11 U2 11 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 2040-8978 EI 2040-8986 J9 J OPTICS-UK JI J. Opt. PD JAN PY 2017 VL 19 IS 1 AR 013003 DI 10.1088/2040-8986/19/1/013003 PG 14 WC Optics SC Optics GA EG8IL UT WOS:000391300000001 ER PT J AU Mellema, JJ Kuntz, MT Guitton, TG Ring, D AF Mellema, Jos J. Kuntz, Michael T. Guitton, Thierry G. Ring, David TI The Effect of Two Factors on Interobserver Reliability for Proximal Humeral Fractures SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID CLASSIFICATION-SYSTEM; NEER-CLASSIFICATION; 3-DIMENSIONAL CT; REPRODUCIBILITY; AGREEMENT; INTRAOBSERVER; DOCTORS AB Introduction: The purpose of this study was to assess whether training observers and simplifying proximal humeral fracture classifications improve interobserver reliability among a large number of orthopaedic surgeons. Methods: One hundred eighty-five observers were randomized to receive training or no training in a simple classification for proximal humeral fractures before evaluating preoperative radiographs of a consecutive series of 30 patients who were treated with open reduction and internal fixation. Results: The overall interobserver reliability of the simple proximal humeral fracture classification system was low and not significantly different between the training and the no training group (kappa = 0.20 and kappa = 0.18, respectively; P = 0.10). Subgroup analyses showed that training improved the agreement among surgeons who have been in independent practice <= 5 years (kappa = 0.23 versus kappa = 0.14; P < 0.001), surgeons from the United States (kappa = 0.23 versus kappa = 0.16; P = 0.002), and general orthopaedic surgeons (kappa = 0.42 versus kappa = 0.15; P = 0.021). Discussion: Simplifying classifications and training observers did not improve the interobserver reliability for the diagnosis of proximal humeral fractures. However, training observers improved interobserver reliability of a simple proximal humeral fracture classification system among surgeons from the United States and, in particular, younger and less specialized surgeons. This finding may suggest that our interpretations of radiographic information might become more fixed and immutable with experience. C1 [Mellema, Jos J.; Kuntz, Michael T.] Harvard Med Sch, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Guitton, Thierry G.] Univ Amsterdam, Dept Orthoped Surg, Acad Med Ctr, Amsterdam, Netherlands. [Ring, David] Univ Texas Austin, Dept Surg & Perioperat Care, Dell Med Sch, Austin, TX 78712 USA. RP Mellema, JJ (reprint author), Harvard Med Sch, Hand & Upper Extrem Serv, Dept Orthopaed Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. FU Acumed; Zimmer Biomet FX Dr. Ring or an immediate family member has received royalties from Zimmer Biomet, Medartis, Skeletal Dynamics, and Wright Medical Technology; serves as a paid consultant to Acumed and Zimmer Biomet; has stock or stock options held in IlluminOss; serves as a board member, owner, officer, or committee member of the American Shoulder and Elbow Surgeons and the American Society for Surgery of the Hand. None of the following authors or any immediate family member has received anything of value from or has stock or stock options held in a commercial company or institution related directly or indirectly to the subject of this article: Dr. Mellema, Dr. Kuntz, and Dr. Guitton. NR 23 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JAN PY 2017 VL 25 IS 1 BP 69 EP 76 DI 10.5435/JAAOS-D-16-00223 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA EG4AP UT WOS:000390986100010 PM 27906770 ER PT J AU Polyzos, SA Bugianesi, E Kountouras, J Mantzoros, CS AF Polyzos, Stergios A. Bugianesi, Elisabetta Kountouras, Janus Mantzoros, Christos S. TI Nonalcoholic fatty liver disease: Updates on associations with the metabolic syndrome and lipid profile and effects of treatment with PPAR-gamma agonists SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Editorial Material ID NATURAL-HISTORY; PIOGLITAZONE; STEATOHEPATITIS; SIMVASTATIN; ADIPONECTIN; MANAGEMENT; THERAPY; RISK C1 [Polyzos, Stergios A.; Kountouras, Janus] Aristotle Univ Thessaloniki, Sch Med, Med Clin 2, Thessaloniki, Greece. [Bugianesi, Elisabetta] Univ Torino, Dept Med Sci, Div Gastroenterol, Turin, Italy. [Mantzoros, Christos S.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Internal Med, Div Endocrinol Diabet & Metab, Boston, MA USA. [Mantzoros, Christos S.] Harvard Med Sch, Boston VA Healthcare Syst, Endocrinol Sect, Boston, MA USA. RP Polyzos, SA (reprint author), 13 Simou Lianidi, Thessaloniki 55134, Macedonia, Greece. EM stergios@endo.gr NR 47 TC 0 Z9 0 U1 3 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2017 VL 66 BP 64 EP 68 DI 10.1016/j.metabol.2016.08.001 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG6KX UT WOS:000391156200007 PM 27594084 ER PT J AU Li, TB Wernersson, R Hansen, RB Horn, H Mercer, J Slodkowicz, G Workman, CT Rigina, O Rapacki, K Staerfeldt, HH Brunak, S Jensen, TS Lage, K AF Li, Taibo Wernersson, Rasmus Hansen, Rasmus B. Horn, Heiko Mercer, Johnathan Slodkowicz, Greg Workman, Christopher T. Rigina, Olga Rapacki, Kristoffer Staerfeldt, Hans H. Brunak, Soren Jensen, Thomas S. Lage, Kasper TI A scored human protein-protein interaction network to catalyze genomic interpretation SO NATURE METHODS LA English DT Article ID INTERACTION DATABASE; GENETIC ARCHITECTURE; WIDE ASSOCIATION; DISEASE; DISORDERS; PATTERNS; INSIGHTS; LOCI AB Genome-scale human protein-protein interaction networks are critical to understanding cell biology and interpreting genomic data, but challenging to produce experimentally. Through data integration and quality control, we provide a scored human protein-protein interaction network (InWeb_InBioMap, or InWeb_IM) with severalfold more interactions (>500,000) and better functional biological relevance than comparable resources. We illustrate that InWeb_InBioMap enables functional interpretation of >4,700 cancer genomes and genes involved in autism. C1 [Li, Taibo; Horn, Heiko; Mercer, Johnathan; Lage, Kasper] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Li, Taibo; Horn, Heiko; Mercer, Johnathan; Lage, Kasper] Broad Inst & MIT Harvard, Cambridge, MA 02138 USA. [Li, Taibo] MIT, Cambridge, MA 02138 USA. [Wernersson, Rasmus; Hansen, Rasmus B.; Jensen, Thomas S.] Int A S, Lyngby, Denmark. [Wernersson, Rasmus; Slodkowicz, Greg; Workman, Christopher T.; Rigina, Olga; Rapacki, Kristoffer; Staerfeldt, Hans H.] Tech Univ Denmark, Ctr Biol Sequence Anal, Lyngby, Denmark. [Horn, Heiko; Lage, Kasper] Harvard Med Sch, Boston, MA USA. [Brunak, Soren] Univ Copenhagen, Novo Nordisk Fdn Ctr Prot Res, Copenhagen, Denmark. [Lage, Kasper] Univ Copenhagen, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Roskilde, Denmark. [Slodkowicz, Greg] EMBL, European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge, England. RP Lage, K (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA.; Lage, K (reprint author), Broad Inst & MIT Harvard, Cambridge, MA 02138 USA.; Jensen, TS (reprint author), Int A S, Lyngby, Denmark.; Lage, K (reprint author), Harvard Med Sch, Boston, MA USA.; Lage, K (reprint author), Univ Copenhagen, Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Roskilde, Denmark. EM tsj@intomics.com; lage.kasper@mgh.harvard.edu RI Workman, Christopher/K-1066-2015 OI Workman, Christopher/0000-0002-2210-3743 FU Fund for Medical Discovery Award from the Executive Committee on Research of Massachusetts General Hospital; Stanley Center at the Broad Institute of MIT and Harvard; Broadnext10 Grant from the Broad Institute of MIT and Harvard; NIMH [1R01MH109903]; Lundbeck Foundation; Novo Nordisk Foundation [NNF14CC0001]; [1P01HD068250] FX The authors would like to thank L. Wich for developing the graphical user interface for InWeb_IM at https://www.intomics.com/inbio/map. K.L. and H.H. are supported by grant 1P01HD068250, and H.H. is supported by a Fund for Medical Discovery Award from the Executive Committee on Research of Massachusetts General Hospital (project period 02/01/2015-01/31/2016). T.L., H.H., J.M. and K.L. are supported by a grant from the Stanley Center at the Broad Institute of MIT and Harvard (PI: K.L.), a Broadnext10 Grant from the Broad Institute of MIT and Harvard (PI: K.L.), grant 1R01MH109903 from the NIMH (PI: K.L.) and a grant from the Lundbeck Foundation (PI: K.L.). S.B. acknowledges funding from the Novo Nordisk Foundation (grant agreement NNF14CC0001). NR 27 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 EI 1548-7105 J9 NAT METHODS JI Nat. Methods PD JAN PY 2017 VL 14 IS 1 BP 61 EP 64 DI 10.1038/NM.4083 PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA EG6ND UT WOS:000391162300026 PM 27892958 ER PT J AU Dagley, A LaPoint, M Huijbers, W Hedden, T McLaren, DG Chatwal, JP Papp, KV Amariglio, RE Blacker, D Rentz, DM Johnson, KA Sperling, RA Schultz, AP AF Dagley, Alexander LaPoint, Molly Huijbers, Willem Hedden, Trey McLaren, Donald G. Chatwal, Jasmeer P. Papp, Kathryn V. Amariglio, Rebecca E. Blacker, Deborah Rentz, Dorene M. Johnson, Keith A. Sperling, Reisa A. Schultz, Aaron P. TI Harvard Aging Brain Study: Dataset and accessibility SO NEUROIMAGE LA English DT Article ID DEMENTIA; DISEASE AB The Harvard Aging Brain Study is sharing its data with the global research community. The longitudinal dataset consists of a 284-subject cohort with the following modalities acquired: demographics, clinical assessment, comprehensive neuropsychological testing, clinical biomarkers, and neuroimaging. To promote more extensive analyses, imaging data was designed to be compatible with other publicly available datasets. A cloud-based system enables access to interested researchers with blinded data available contingent upon completion of a data usage agreement and administrative approval. Data collection is ongoing and currently in its fifth year. (C) 2015 Elsevier Inc. All rights reserved. C1 [Dagley, Alexander; LaPoint, Molly; Huijbers, Willem; Hedden, Trey; McLaren, Donald G.; Chatwal, Jasmeer P.; Papp, Kathryn V.; Amariglio, Rebecca E.; Blacker, Deborah; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.; Schultz, Aaron P.] Massachusetts Gen Hosp, Harvard Aging Brain Study, Dept Neurol, Boston, MA 02114 USA. [Huijbers, Willem; Chatwal, Jasmeer P.; Papp, Kathryn V.; Amariglio, Rebecca E.; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Brigham & Womens Hosp, Ctr Alzheimer Res & Treatment, Dept Neurol, Boston, MA 02115 USA. [Hedden, Trey; McLaren, Donald G.; Papp, Kathryn V.; Amariglio, Rebecca E.; Blacker, Deborah; Rentz, Dorene M.; Johnson, Keith A.; Sperling, Reisa A.] Harvard Med Sch, Boston, MA 02115 USA. [Dagley, Alexander; LaPoint, Molly; Hedden, Trey; McLaren, Donald G.; Chatwal, Jasmeer P.; Schultz, Aaron P.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Hedden, Trey] Harvard Univ, Ctr Brain Sci, Dept Psychol, Cambridge, MA 02138 USA. [Johnson, Keith A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Huijbers, Willem] German Ctr Neurodegenerat Dis DZNE, Populat Hlth Sci, Bonn, Germany. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Blacker, Deborah] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Cambridge, MA USA. RP Dagley, A (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. EM adagley@partners.org FU National Institute on Aging of the National Institutes of Health; National Institutes of Health/National Institute on Aging [R01 AG046396, P01 AG036694, P50 AG00513421]; Eli Lilly; Janssen; National Institutes on Aging; Alzheimer's Association; Fidelity Biosciences; Harvard Neurodiscovery Center FX Research reported in this publication was supported by the National Institute on Aging of the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. To disclose all conflicts of interest, Reisa Sperling has provided consulting services for Janssen, Roche, Isis Pharmaceuticals, Genentech, and receives research funding from Eli Lilly, Janssen, National Institutes on Aging and Alzheimer's Association. Keith Johnson has provided consulting services for Lilly, Novartis, Janssen, Roche, Piramal, GE Healthcare, Siemens, Lundbeck, AZTherapy, Biogen and receives research funding from National Institutes of Health/National Institute on Aging (R01 AG046396, P01 AG036694, P50 AG00513421), Fidelity Biosciences, Harvard Neurodiscovery Center, and the Alzheimer's Association. NR 19 TC 4 Z9 4 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2017 VL 144 SI SI BP 255 EP 258 DI 10.1016/j.neuroimage.2015.03.069 PN B PG 4 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA EG4AY UT WOS:000390987000001 PM 25843019 ER PT J AU Lugea, A Waldron, RT AF Lugea, Aurelia Waldron, Richard T. TI Exosome-Mediated Intercellular Communication Between Stellate Cells and Cancer Cells in Pancreatic Ductal Adenocarcinoma SO PANCREAS LA English DT Editorial Material ID MESSENGER-RNAS; MICRORNAS; MICROENVIRONMENT; PROGRESSION; CARCINOMA C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Dept Med, Div Gastroenterol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Gastroenterol & Hepatol, VA Greater Los Angeles Hlth Syst, Los Angeles, CA 90095 USA. RP Lugea, A (reprint author), Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. EM lugeaa@cshs.org FU NCI NIH HHS [P01 CA163200]; NIAAA NIH HHS [R01 AA019954]; NIDDK NIH HHS [P01 DK098108, U01 DK108314] NR 22 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD JAN PY 2017 VL 46 IS 1 BP 1 EP 4 DI 10.1097/MPA.0000000000000686 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EG3JU UT WOS:000390940700001 PM 27977625 ER PT J AU Baek, JH Kim, JH Kim, BN Park, SJ Fava, M Mischoulon, D Lee, D Jeon, HJ AF Baek, Ji Hyun Kim, Ji-Hae Kim, Bin-Na Park, Seung Jin Fava, Maurizio Mischoulon, David Lee, Dongsoo Jeon, Hong Jin TI Comparisons of Subthreshold Versus Full Posttraumatic Stress Disorder Distinguished by Subjective Functional Impairment Among Train Drivers: A Population-Based Nationwide Study in South Korea SO PSYCHIATRY INVESTIGATION LA English DT Article DE PTSD; Subthreshold; Human error; Train driver ID CLINICAL-SIGNIFICANCE CRITERION; IV DIAGNOSTIC CRITERION; DSM-IV; NICOTINE DEPENDENCE; IMPULSIVITY; PREVALENCE; HEALTH; IMPACT; PTSD; COMORBIDITY AB Objective Subthreshold posttraumatic stress disorder (SPTSD), a condition that meets the full symptomatic criteria of posttraumatic stress disorder (PTSD) without subjective functional impairment, has yet to be fully investigated. In this study, we aimed to determine the prevalence and characteristics of SPTSD. Methods The web-based survey including psychiatric diagnosis and experience of human error was conducted in actively working train drivers in South Korea. Results Of the 4,634 subjects, 103 (2.23%) were categorized as full PTSD and 322 (6.96%) were categorized as having SPTSD. Individuals with full PTSD showed higher impulsivity and anxiety compared to those with SPTSD and those without PTSD, while those with SPTSD had more frequent clinically meaningful depression, posttraumatic stress, and alcohol and nicotine dependence and significant human error. Conclusion Despite not qualifying as a subjective functional disability, SPTSD still had significant psychiatric symptoms. More clinical attentions need to be given to the diagnosis and-treatment of SPTSD. C1 [Baek, Ji Hyun; Kim, Ji-Hae; Lee, Dongsoo; Jeon, Hong Jin] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Depress Ctr,Dept Psychiat, 81 Irwon Ro, Seoul 06351, South Korea. [Fava, Maurizio; Mischoulon, David; Jeon, Hong Jin] Massachusetts Gen Hosp, Harvard Med Sch, Depress Clin & Res Program, Boston, MA USA. [Kim, Bin-Na; Park, Seung Jin] Seoul Natl Univ, Dept Psychol, Seoul, South Korea. RP Jeon, HJ (reprint author), Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Depress Ctr,Dept Psychiat, 81 Irwon Ro, Seoul 06351, South Korea. EM jeonhj@skku.edu FU Korean National Railroad Corporation (KORAIL); Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education, Science and Technology [2011-0013064]; Samsung Medical Center Clinical Research Development Program (CRDP) [SMO1131461] FX This study was supported by the Korean National Railroad Corporation (KORAIL). This study was also supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2011-0013064), and the Samsung Medical Center Clinical Research Development Program (CRDP) Grant SMO1131461. NR 43 TC 0 Z9 0 U1 5 U2 5 PU KOREAN NEUROPSYCHIATRIC ASSOC PI SEOUL PA RN 522, G-FIVE CENTRAL PLAZA 1685-8 SEOCHO 4-DONG, SEOCHO-GU, SEOUL, 137-882, SOUTH KOREA SN 1738-3684 EI 1976-3026 J9 PSYCHIAT INVEST JI Psychiatry Investig. PD JAN PY 2017 VL 14 IS 1 BP 1 EP 7 DI 10.4306/pi.2017.14.1.1 PG 7 WC Psychiatry SC Psychiatry GA EG6NV UT WOS:000391164100001 PM 28096868 ER PT S AU Composto, AM Reisner, LA Pandya, AK Edelman, DA Jacobs, KL Bagian, TM AF Composto, Anthony M. Reisner, Luke A. Pandya, Abhilash K. Edelman, David A. Jacobs, Katrina L. Bagian, Tandi M. BE Duffy, VG Lightner, N TI Methods to Characterize Operating Room Variables in Robotic Surgery to Enhance Patient Safety SO ADVANCES IN HUMAN FACTORS AND ERGONOMICS IN HEALTHCARE SE Advances in Intelligent Systems and Computing LA English DT Proceedings Paper CT 7th International Conference on Applied Human Factors and Ergonomics / International Conference on Human Factors and Ergonomics in Healthcare CY JUL 27-31, 2016 CL Bay Lake, FL DE Task analysis; Robotic surgery; Patient safety; Clinical teams; Veterans health administration; Best practices ID OUTCOMES; MANAGEMENT; ERROR AB Surgical team experience is an important determinant of operative outcome. However, even the most experienced team will not be familiar with all potential variability that could be encountered during a surgical procedure. Robotic surgery adds further complexity through advanced technology, additional equipment, intricate process steps, etc. One method that is crucial to understanding a robotic procedure is surgical observation, which can be used to identify the process flow and involved objects. Another method is task excursion analysis, a proactive approach to understanding system variability and key factors that may affect system performance and patient safety. Finally, a method must be used to efficiently present the gathered information to surgical teams. As rapidly evolving technology is introduced into health care systems, the adoption of these types of methods is necessary to ensure patient safety. This paper describes the proposed methodology for analyzing robotic surgery variability and provides some example data. C1 [Composto, Anthony M.; Reisner, Luke A.; Pandya, Abhilash K.] Wayne State Univ, Dept Elect & Comp Engn, Wayne, NJ 48202 USA. [Edelman, David A.] Wayne State Univ, Dept Surg, Wayne, NJ 48202 USA. [Jacobs, Katrina L.; Bagian, Tandi M.] US Dept Vet Affairs, Natl Ctr Patient Safety, Ann Arbor, MI 48107 USA. RP Bagian, TM (reprint author), US Dept Vet Affairs, Natl Ctr Patient Safety, Ann Arbor, MI 48107 USA. EM aj6568@wayne.edu; lreisner@wayne.edu; apandya@ece.eng.wayne.edu; dedelman@med.wayne.edu; Katrina.Jacobs@va.gov; Tandi.Bagian@va.gov NR 12 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INT PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2194-5357 BN 978-3-319-41652-6; 978-3-319-41651-9 J9 ADV INTELL SYST PY 2017 VL 482 BP 215 EP 223 DI 10.1007/978-3-319-41652-6_21 PG 9 WC Computer Science, Artificial Intelligence; Public, Environmental & Occupational Health; Medical Informatics SC Computer Science; Public, Environmental & Occupational Health; Medical Informatics GA BG6SE UT WOS:000390838700021 ER PT J AU Eneanya, ND Hailpern, SM O'Hare, AM Tamura, MK Katz, R Kreuter, W Montez-Rath, ME Hebert, PL Hall, YN AF Eneanya, Nwamaka D. Hailpern, Susan M. O'Hare, Ann M. Tamura, Manjula Kurella Katz, Ronit Kreuter, William Montez-Rath, Maria E. Hebert, Paul L. Hall, Yoshio N. TI Trends in Receipt of Intensive Procedures at the End of Life Among Patients Treated With Maintenance Dialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE End-of-life; dialysis; intensive procedures; end-stage renal disease (ESRD); Hispanic; elderly; age differences; ethnic disparities; Medicare spending; health care costs; hospitalization; mortality follow-back ID HOSPITAL CARDIOPULMONARY-RESUSCITATION; RESURRECTING TREATMENT HISTORIES; LAST 6 MONTHS; MEDICARE BENEFICIARIES; REGIONAL-VARIATIONS; CARE PREFERENCES; OLDER LATINOS; DEAD PATIENTS; EXPENDITURES; OUTCOMES AB Background: Many dialysis patients receive intensive procedures intended to prolong life at the very end of life. However, little is known about trends over time in the use of these procedures. We describe temporal trends in receipt of inpatient intensive procedures during the last 6 months of life among patients treated with maintenance dialysis. Study Design: Mortality follow-back study. Setting & Participants: 649,607 adult Medicare beneficiaries on maintenance dialysis therapy who died in 2000 to 2012. Predictors: Period of death (2000-2003, 2004-2008, or 2009-2012), age at time of death (18-59, 60-64, 65-69, 70-74, 75-79, 80-84, and >= 85 years), and race/ethnicity (Hispanic, non-Hispanic black, or non-Hispanic white). Outcome: Receipt of an inpatient intensive procedure (defined as invasive mechanical ventilation/intubation, tracheostomy, gastrostomy/jejunostomy tube insertion, enteral or parenteral nutrition, or cardiopulmonary resuscitation) during the last 6 months of life. Results: Overall, 34% of cohort patients received an intensive procedure in the last 6 months of life, increasing from 29% in 2000 to 36% in 2012 (with 2000-2003 as the referent category; adjusted risk ratios [RRs] were 1.06 [95% CI, 1.05-1.07] and 1.10 [95% CI, 1.09-1.12] for 2004-2008 and 2009-2012, respectively). Use of intensive procedures increased more markedly over time in younger versus older patients (comparing 2009-2012 to 2000-2003, adjusted RR was 1.18 [95% CI, 1.15-1.20] for the youngest age group as opposed to 1.00 [95% CI, 0.96-1.04] for the oldest group). Comparing 2009 to 2012 to 2000 to 2003, the use of intensive procedures increased more dramatically for Hispanic patients than for non-Hispanic black or non-Hispanic white patients (adjusted RRs of 1.18 [95% CI, 1.14-1.22], 1.09 [95% CI, 1.07-1.11], and 1.10 [95% CI, 1.08-1.12], respectively). Limitations: Data sources do not provide insight into reasons for observed trends in the use of intensive procedures. Conclusions: Among patients treated with maintenance dialysis, there is a trend toward more frequent use of intensive procedures at the end of life, especially in younger patients and those of Hispanic ethnicity. (C) 2016 by the National Kidney Foundation, Inc. C1 [Eneanya, Nwamaka D.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Internal Med, Div Nephrol, 165 Cambridge St,Ste 302, Boston, MA 02114 USA. [Hailpern, Susan M.; O'Hare, Ann M.; Katz, Ronit; Kreuter, William; Hall, Yoshio N.] Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. [Hailpern, Susan M.; O'Hare, Ann M.; Katz, Ronit; Kreuter, William; Hall, Yoshio N.] Univ Washington, Kidney Res Inst, Dept Med, Seattle, WA 98195 USA. [O'Hare, Ann M.] Vet Affairs Puget Sound Hlth Care Syst, Hosp & Specialty Med, Seattle, WA USA. [O'Hare, Ann M.] Grp Hlth Res Inst, Seattle, WA USA. [Tamura, Manjula Kurella] Vet Affairs Palo Alto Hlth Care Syst, Geriatr Res & Educ Clin Ctr, Palo Alto, CA USA. [Montez-Rath, Maria E.] Stanford Univ, Sch Med, Div Nephrol, Palo Alto, CA 94304 USA. [Hebert, Paul L.] Vet Affairs Puget Sound Healthcare Syst, Seattle Denver Ctr Innovat, Seattle, WA USA. RP Eneanya, ND (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Internal Med, Div Nephrol, 165 Cambridge St,Ste 302, Boston, MA 02114 USA. EM aeneanya@partners.org FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) program at the National Institutes of Health [1U01DK102150-01]; NIDDK [K24-DK094872]; American Society of Nephrology's Foundation for Kidney Research Fellowship Program FX The data reported here have been supplied by the USRDS. The interpretation and reporting of these data are the responsibility of the authors and in no way should be seen as official policy or interpretation of the US government. This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) program at the National Institutes of Health (1U01DK102150-01 to Drs O'Hare and Kurella Tamura). Dr Eneanya was supported in part by a mentorship grant from the NIDDK (K24-DK094872: Principal Investigator, Ravi Thadhani) and a grant from the American Society of Nephrology's Foundation for Kidney Research Fellowship Program (Principal Investigator, Dr Eneanya). The funding sources for this study did not have a role in study design, collection, analysis, and interpretation of data; writing the report; or decision to submit the report for publication. NR 43 TC 1 Z9 1 U1 6 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 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2017 VL 69 IS 1 BP 60 EP 68 DI 10.1053/j.ajkd.2016.07.028 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA EF7RG UT WOS:000390526300014 PM 27693262 ER PT J AU Tsuang, DW Bird, TD AF Tsuang, Debby W. Bird, Thomas D. TI Genetic factors in neurodegenerative diseases SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Editorial Material C1 [Tsuang, Debby W.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Tsuang, Debby W.] Univ Washington, Dept Med Genet, Seattle, WA 98195 USA. [Tsuang, Debby W.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Tsuang, Debby W.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. [Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. RP Tsuang, DW (reprint author), Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA.; Tsuang, DW (reprint author), Univ Washington, Dept Med Genet, Seattle, WA 98195 USA.; Tsuang, DW (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.; Tsuang, DW (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. EM dwt1@uw.edu NR 1 TC 0 Z9 0 U1 1 U2 1 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 JAN PY 2017 VL 174 IS 1 BP 3 EP 4 DI 10.1002/ajmg.b.32504 PG 2 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA EF9PB UT WOS:000390661000001 PM 27770499 ER PT J AU Shah, C DeMichele-Sweet, MAA Sweet, RA AF Shah, Chintan DeMichele-Sweet, Mary Ann A. Sweet, Robert A. TI Genetics of psychosis of Alzheimer disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE Alzheimer disease; psychosis; genome-wide association; heritability ID COPY-NUMBER VARIATION; INCREASED FAMILIAL RISK; GENOME-WIDE SCAN; NEUROPSYCHIATRIC SYMPTOMS; PSYCHOLOGICAL SYMPTOMS; RECEPTOR POLYMORPHISM; SEROTONIN TRANSPORTER; VARIATION ASSOCIATION; AGGRESSIVE-BEHAVIOR; APOLIPOPROTEIN-E AB Psychotic symptoms, comprised of delusions and hallucinations, occur in about half of individuals with Alzheimer disease (AD with psychosis, AD+P). These individuals have greater agitation, aggression, depression, functional impairment, and mortality than individuals without psychosis (AD-P). Although the exact etiopathogenesis of AD+P is unclear, the rapidly developing field of genomics continues to expand our understanding of this disease. Several independent studies have demonstrated familial aggregation and heritability of AD+P. Linkage studies have been suggestive of loci on several chromosomes associated with AD+P. Association studies examining apolipoprotein E gene, the best established genetic risk factor for late-onset AD, did not find any significant association of this gene with AD+P. Other candidate gene studies focusing on monoamine neurotransmitter systems have yielded equivocal results. A genome-wide association study and studies examining copy number variations recently have detected suggestive associations, but have been underpowered. Approaches to increase sizes of AD+P samples for genome wide association studies are discussed. (c) 2016 Wiley Periodicals, Inc. C1 [Shah, Chintan; DeMichele-Sweet, Mary Ann A.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Sweet, Robert A.] Univ Pittsburgh, Dept Psychiat & Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Hlth Illness Res Educ & Clin Ctr MIRE, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Univ Pittsburgh, Dept Psychiat & Neurol, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU NIA NIH HHS [P50 AG005133, R01 AG027224] NR 86 TC 1 Z9 1 U1 5 U2 5 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 JAN PY 2017 VL 174 IS 1 BP 27 EP 35 DI 10.1002/ajmg.b.32413 PG 9 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA EF9PB UT WOS:000390661000003 PM 26756273 ER PT J AU Domoto-Reilly, K Davis, MY Keene, CD Bird, TD AF Domoto-Reilly, Kimiko Davis, Marie Y. Keene, C. Dirk Bird, Thomas D. TI Unusually long duration and delayed penetrance in a family with FTD and mutation in MAPT (V337M) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dementia; frontotemporal dementia; MAPT; tau; penetrance ID FRONTOTEMPORAL DEMENTIA; PRESENILE-DEMENTIA; ALZHEIMER-DISEASE; TAU GENE; APOE; CHROMOSOME-17; DEGENERATION; CARRIERS; ONSET AB Mutations in the MAPT gene coding for the tau protein are one of the most common causes of familial frontotemporal dementia (FTD). In a previously described family with the V337M mutation in MAPT, we now report an affected woman who died at age 92 with a >40 year duration of symptoms, more than three times the mean disease duration in her family (13.8 years). Neuropathology showed the typical findings of a diffuse tauopathy. Conversely, her 67-year-old son with the same mutation remains asymptomatic more than 15 years beyond the mean age of onset in the family (51.5 years). These two cases demonstrate the marked variability in onset and duration of familial FTD and underscore the difficulties of discussing these issues with patients and families. The presumed genetic and environmental factors influencing these parameters remain largely unknown. (c) 2016 Wiley Periodicals, Inc. C1 [Domoto-Reilly, Kimiko; Davis, Marie Y.; Bird, Thomas D.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Keene, C. Dirk] Univ Washington, Dept Pathol, Seattle, WA 98195 USA. [Bird, Thomas D.] Univ Washington, Dept Med, Seattle, WA USA. [Bird, Thomas D.] VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. RP Bird, TD (reprint author), 1660 SColumbian Way,S-182 GRECC, Seattle, WA 98108 USA. EM tomnroz@uw.edu FU NIH/NIA ADRC [P50-AG005136]; VA Research Funds FX Grant sponsor: NIH/NIA ADRC; Grant number: P50-AG005136; Grant sponsor: VA Research Funds. NR 19 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN PY 2017 VL 174 IS 1 BP 70 EP 74 DI 10.1002/ajmg.b.32443 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA EF9PB UT WOS:000390661000005 PM 26990251 ER PT J AU Mata, IF Davis, MY Lopez, AN Dorschner, MO Martinez, E Yearout, D Cholerton, BA Hu, SC Edwards, KL Bird, TD Zabetian, CP AF Mata, Ignacio F. Davis, Marie Y. Lopez, Alexis N. Dorschner, Michael O. Martinez, Erica Yearout, Dora Cholerton, Brenna A. Hu, Shu-Ching Edwards, Karen L. Bird, Thomas D. Zabetian, Cyrus P. TI The discovery of LRRK2 p.R1441S, a novel mutation for Parkinson's disease, adds to the complexity of a mutational hotspot (vol 171, pg 925, 2016) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Correction C1 [Zabetian, Cyrus P.] VA Puget Sound Hlth Care Syst, GRECC S-182,1660 South Columbian Way, Seattle, WA 98108 USA. RP Zabetian, CP (reprint author), VA Puget Sound Hlth Care Syst, GRECC S-182,1660 South Columbian Way, Seattle, WA 98108 USA. EM zabetian@u.washington.edu NR 2 TC 1 Z9 1 U1 6 U2 6 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 JAN PY 2017 VL 174 IS 1 BP 113 EP 113 DI 10.1002/ajmg.b.32510 PG 1 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA EF9PB UT WOS:000390661000008 PM 27943640 ER PT J AU Birtolo, C Pham, H Morvaridi, S Chheda, C Go, VLW Ptasznik, A Edderkaoui, M Weisman, MH Noss, E Brenner, MB Larsonr, B Guindi, M Wang, Q Pandol, SJ AF Birtolo, Chiara Pham, Hung Morvaridi, Susan Chheda, Chintan Go, Vay Liang W. Ptasznik, Andrzej Edderkaoui, Mouad Weisman, Michael H. Noss, Erika Brenner, Michael B. Larsonr, Brent Guindi, Maha Wang, Qiang Pandol, Stephen J. TI Cadherin-11 Is a Cell Surface Marker Up-Regulated in Activated Pancreatic Stellate Cells and Is Involved in Pancreatic Cancer Cell Migration SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID DUCTAL ADENOCARCINOMA; POTENTIAL ROLE; IN-VIVO; ADHESION; EXPRESSION; CARCINOMA; FIBROSIS; GENE; METASTASIS; INVASION AB Chronic pancreatitis is a prominent risk factor for the development of pancreatic ductal adenocarcinoma. In both conditions, the activation of myofibroblast-like pancreatic stellate cells (PSCs) plays a predominant role in the formation of desmoplastic reaction through the synthesis of connective tissue and extracellular matrix, inducing local pancreatic fibrosis and an inflammatory response. Yet the signaling events involved in chronic pancreatitis and pancreatic cancer progression and metastasis remain poorly defined. Cadherin-11 (Cad-11, also known as OB cadherin or CDH11) is a cell-to-cell adhesion molecule implicated in many biological functions, including tissue morphogenesis and architecture, extracellular matrix-mediated tissue remodeling, cytoskeletal organization, epithelial-to-mesenchymal transition, and cellular migration. In this study, we show that, in human chronic pancreatitis and pancreatic cancer tissues, Cad-11 expression was significantly increased in PSCs and pancreatic cancer cells. In particular, an increased expression of Cad-11 can be detected on the plasma membrane of activated PSCs isolated from chronic pancreatitis tissues and in pancreatic cancer cells Metastasized to the Liver. Moreover, knockdown of Cad-11 in cancer cells reduced pancreatic Cancer cell migration. Taken together, our data underline the potential role of Cad-11 in PSC activation and pancreatic cancer metastasis. C1 [Birtolo, Chiara; Pham, Hung; Morvaridi, Susan; Chheda, Chintan; Ptasznik, Andrzej; Edderkaoui, Mouad; Weisman, Michael H.; Wang, Qiang; Pandol, Stephen J.] Cedars Sinai Med Ctr, Dept Med, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. [Larsonr, Brent; Guindi, Maha] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Birtolo, Chiara] Univ Bologna, S Orsola Malpighi Hosp, Dept Internal Med, Bologna, Italy. [Go, Vay Liang W.; Pandol, Stephen J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Noss, Erika; Brenner, Michael B.] Harvard Med Sch, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA USA. [Pandol, Stephen J.] VA Greater Los Angeles Hlth Care Syst, Dept Vet Affairs, Los Angeles, CA USA. RP Wang, Q; Pandol, SJ (reprint author), Cedars Sinai Med Ctr, Dept Med, 8700 Beverly Blvd, Los Angeles, CA 90048 USA. EM qiang.wang@cshs.org; stephen.pandol@cshs.org OI Wang, Qiang/0000-0001-9409-0251 FU Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute Developmental Funds for Liver Metastasis Team Grant Research Award "Colon, pancreas, and prostate cancer engraftment in the liver metastatic niche"; National Center for Advancing Translational Sciences UCLA CTSI grant [UL1TR000124]; Department of Veterans Affairs [I01BX001484, P01CA163200, P50 AA11999, P01DK098108] FX Supported by the Cedars-Sinai Medical Center Samuel Oschin Comprehensive Cancer Institute Developmental Funds for Liver Metastasis Team Grant Research Award "Colon, pancreas, and prostate cancer engraftment in the liver metastatic niche"; the National Center for Advancing Translational Sciences UCLA CTSI grant UL1TR000124 (Q.W.); the Department of Veterans Affairs grant I01BX001484 (S.J.P.); and NM grants P01CA163200, P50 AA11999, and P01DK098108 (S.J.P.). NR 63 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 EI 1525-2191 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2017 VL 187 IS 1 BP 146 EP 155 DI 10.1016/j.ajpath.2016.09.012 PG 10 WC Pathology SC Pathology GA EG1YC UT WOS:000390829300015 PM 27855278 ER PT J AU Al Hazzouri, AZ Elfassy, T Sidney, S Jacobs, D Stable, EJP Yaffe, K AF Al Hazzouri, Adina Zeki Elfassy, Tali Sidney, Stephen Jacobs, David Stable, Eliseo J. Perez Yaffe, Kristine TI Sustained Economic Hardship and Cognitive Function: The Coronary Artery Risk Development in Young Adults Study SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SOCIOECONOMIC POSITION; EDUCATIONAL-ATTAINMENT; MIDDLE-AGE; HEALTH; LIFE; INCOME; INEQUALITY; TRAJECTORIES; POPULATION; LIFECOURSE AB Introduction: The relationship between low income and worse health outcomes is evident, yet its association with cognitive outcomes is less explored. Most studies have measured income at one time and none have examined how sustained exposure to low income influences cognition in a relatively young cohort. This study examined the effect of sustained poverty and perceived financial difficulty on cognitive function in midlife. Methods: Income data were collected six times between 1985 and 2010 for 3,383 adults from the Coronary Artery Risk Development in Young Adults prospective cohort study. Sustained poverty was defined by the percentage of time participants' household income was <200% of the federal poverty level-"never" in poverty, "0< to <1/3," " >= 1/3 to <100%" or " all-time." In 2010, at a mean age of 50 years, participants underwent a cognitive battery. Data were analyzed in 2015. Results: In demographic-adjusted linear regression models, individuals with all-time poverty performed significantly worse than individuals never in poverty: 0.92 points worse on verbal memory (z-score, -0.28; 95% CI=-0.43, -0.13), 11.60 points worse on processing speed (z-score, -0.72; 95% CI=- 0.85, -0.58), and 3.50 points worse on executive function (z-score, -0.32; 95% CI=-0.47, -0.17). Similar results were observed with perceived financial difficulty. Findings were robust when restricted to highly educated participants, suggesting little evidence for reverse causation. Conclusions: Cumulative exposure to low income over 2 decades was strongly associated with worse cognitive function of a relatively young cohort. Poverty and perceived hardship may be important contributors to premature aging among disadvantaged populations. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Al Hazzouri, Adina Zeki; Elfassy, Tali] Univ Miami, Dept Publ Hlth Sci, Div Epidemiol & Populat Hlth Sci, Miami, FL 33136 USA. [Sidney, Stephen] Kaiser Permanente, Div Res, Oakland, CA USA. [Jacobs, David] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Stable, Eliseo J. Perez] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA. [Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA. RP Al Hazzouri, AZ (reprint author), Univ Miami, Dept Publ Hlth Sci, Div Epidemiol & Populat Hlth Sci, Miami, FL 33136 USA. EM axz122@miami.edu FU NIH, National Institute on Aging (NIA) [K01AG047273]; NIH/NIA [k24AG031155]; T32 training grant from NIH, National Heart, Lung, and Blood Institute (NHLBI), "Behavioral Medicine Approaches to Cardiovascular Disease" [HL 007426]; University of California at San Francisco Center for Aging in Diverse Communities under "Resource Centers for Minority Aging Research program of the National Institute on Aging" [P30-AG15272]; NHLBI [HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268-201300028C, HHSN268201300029C, HHSN26820-0900041C, AG0005]; Intramural Research Program of NIA; NIA [AG0005] FX Dr. Zeki Al Hazzouri was supported by a grant from NIH, National Institute on Aging (NIA) (K01AG047273). Dr. Yaffe was supported by a grant from the NIH/NIA (k24AG031155). Tali Elfassy was supported by a T32 training grant from NIH, National Heart, Lung, and Blood Institute (NHLBI), "Behavioral Medicine Approaches to Cardiovascular Disease," (HL 007426). Funding for this study was supported in part by the University of California at San Francisco Center for Aging in Diverse Communities (P30-AG15272) under the "Resource Centers for Minority Aging Research program of the National Institute on Aging." The Coronary Artery Risk Development in Young Adults Study is supported by contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C, HHSN268-201300028C, HHSN268201300029C, and HHSN26820-0900041C from NHLBI, the Intramural Research Program of NIA, and an intra-agency agreement between NIA and NHLBI (AG0005). NR 41 TC 0 Z9 0 U1 7 U2 7 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 JAN PY 2017 VL 52 IS 1 BP 1 EP 9 DI 10.1016/j.amepre.2016.08.009 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA EF9RM UT WOS:000390667400005 ER PT J AU Weininger, S Jaffe, MB Rausch, T Goldman, JM AF Weininger, Sandy Jaffe, Michael B. Rausch, Tracy Goldman, Julian M. TI Capturing Essential Information to Achieve Safe Interoperability SO ANESTHESIA AND ANALGESIA LA English DT Article AB In this article, we describe the role of "clinical scenario" information to assure the safety of interoperable systems, as well as the system's ability to deliver the requisite clinical functionality to improve clinical care. Described are methods and rationale for capturing the clinical needs, workflow, hazards, and device interactions in the clinical environment. Key user (clinician and clinical engineer) needs and system requirements can be derived from this information, therefore, improving the communication from clinicians to medical device and information technology system developers. This methodology is intended to assist the health care community, including researchers, standards developers, regulators, and manufacturers, by providing clinical definition to support requirements in the systems engineering process, particularly those focusing on development of Integrated Clinical Environments described in standard ASTM F2761. Our focus is on identifying and documenting relevant interactions and medical device capabilities within the system using a documentation tool called medical device interface data sheets and mitigating hazardous situations related to workflow, product usability, data integration, and the lack of effective medical device-health information technology system integration to achieve safe interoperability. Portions of the analysis of a clinical scenario for a "patient-controlled analgesia safety interlock" are provided to illustrate the method. Collecting better clinical adverse event information and proposed solutions can help identify opportunities to improve current device capabilities and interoperability and support a learning health system to improve health care delivery. Developing and analyzing clinical scenarios are the first steps in creating solutions to address vexing patient safety problems and enable clinical innovation. A Web-based research tool for implementing a means of acquiring and managing this information, the Clinical Scenario Repository (TM) (MD PnP Program), is described. C1 [Weininger, Sandy] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. [Jaffe, Michael B.] Massachusetts Gen Hosp, MD PnP Program, Boston, MA 02114 USA. [Rausch, Tracy] DocBox, Newton, MA USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Goldman, Julian M.] Partners HealthCare Syst, Boston, MA USA. RP Weininger, S (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sandy.weininger@fda.hhs.gov FU Intramural FDA HHS [FD999999]; NIBIB NIH HHS [U01 EB012470] NR 18 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2017 VL 124 IS 1 BP 83 EP 94 DI 10.1213/ANE.0000000000001351 PG 12 WC Anesthesiology SC Anesthesiology GA EF8WW UT WOS:000390613500013 PM 27387840 ER PT J AU Weininger, S Jaffe, MB Goldman, JM AF Weininger, Sandy Jaffe, Michael B. Goldman, Julian M. TI The Need to Apply Medical Device Informatics in Developing Standards for Safe Interoperable Medical Systems SO ANESTHESIA AND ANALGESIA LA English DT Article ID APNEA AB Medical device and health information technology systems are increasingly interdependent with users demanding increased interoperability. Related safety standards must be developed taking into account these systems' perspective. In this article, we describe the current development of medical device standards and the need for these standards to address medical device informatics. Medical device information should be gathered from a broad range of clinical scenarios to lay the foundation for safe medical device interoperability. Five clinical examples show how medical device informatics principles, if applied in the development of medical device standards, could help facilitate the development of safe interoperable medical device systems. These examples illustrate the clinical implications of the failure to capture important signals and device attributes. We provide recommendations relating to the coordination between historically separate Standards development groups, some of which focus on safety and effectiveness and others focus on health informatics. We identify the need for a shared understanding among stakeholders and describe organizational structures to promote cooperation such that device-to-device interactions and related safety information are considered during standards development. C1 [Weininger, Sandy] US FDA, Off Sci & Engn Labs, CDRH, Silver Spring, MD USA. [Jaffe, Michael B.; Goldman, Julian M.] Massachusetts Gen Hosp, MDPnP Program, Boston, MA 02114 USA. [Goldman, Julian M.] ISO, Geneva, Switzerland. [Goldman, Julian M.] AAMI, Arlington, VA USA. [Goldman, Julian M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Goldman, Julian M.] Partners HealthCare Syst, Boston, MA USA. RP Weininger, S (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sandy.weininger@fda.hhs.gov FU Intramural FDA HHS [FD999999]; NIBIB NIH HHS [U01 EB012470] NR 38 TC 0 Z9 0 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2017 VL 124 IS 1 BP 127 EP 135 DI 10.1213/ANE.0000000000001386 PG 9 WC Anesthesiology SC Anesthesiology GA EF8WW UT WOS:000390613500017 PM 27584685 ER PT J AU Luedi, MM Doll, D Boggs, SD Stueber, F AF Luedi, Markus M. Doll, Dietrich Boggs, Steven D. Stueber, Frank TI Successful Personalities in Anesthesiology and Acute Care Medicine: Are We Selecting, Training, and Supporting the Best? SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material ID EMOTIONAL INTELLIGENCE; RESIDENT PERFORMANCE; PHYSICIAN RESILIENCE; BURNOUT; PROMOTE; TRAITS C1 [Luedi, Markus M.; Stueber, Frank] Univ Bern, Univ Hosp Bern, Inselspital, Dept Anesthesiol & Pain Med, Bern, Switzerland. [Doll, Dietrich] Hannover Med Sch, Acad Teaching Hosp, St Marienhosp Vechta, Dept Gen Surg, Vechta, Germany. [Boggs, Steven D.] James J Peters VA Med Ctr, Dept Anesthesiol, New York, NY USA. [Boggs, Steven D.] Icahn Sch Med Mt Sinai, Dept Anesthesiol, New York, NY 10029 USA. RP Luedi, MM (reprint author), Univ Bern, Univ Hosp Bern, Inselspital, Dept Anesthesiol, Freiburgstr, CH-3010 Bern, Switzerland. EM markus.luedi2@insel.ch NR 33 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2017 VL 124 IS 1 BP 359 EP 361 DI 10.1213/ANE.0000000000001714 PG 3 WC Anesthesiology SC Anesthesiology GA EF8WW UT WOS:000390613500039 PM 27861434 ER PT J AU Milan, DJ Saul, JP Somberg, JC Molnar, J AF Milan, David J. Saul, J. Philip Somberg, John C. Molnar, Janos TI Efficacy of Intravenous and Oral Sotalol in Pharmacologic Conversion of Atrial Fibrillation: A Systematic Review and Meta-Analysis SO CARDIOLOGY LA English DT Review DE Atrial fibrillation; Pharmacologic conversion; Sotalol; Injection; Meta-analysis ID CONTROLLED-TRIAL; IBUTILIDE; DIGOXIN; CARDIOVERSION; AMIODARONE; QUINIDINE; FLUTTER; SAFETY; MANAGEMENT; FLECAINIDE AB Objectives: The role of sotalol is well established for the maintenance of sinus rhythm after successful conversion of atrial fibrillation (AF). However, its role in pharmacologic conversion of AF is poorly defined. The purpose of this study is to compare the efficacy of sotalol to that of other antiarrhythmic agents for AF conversion. Methods: Standard methods of meta-analysis were employed. Full-text publications of clinical trials in English that compared the efficacy of sotalol to that of other antiarrhythmics or placebo/no treatment were eligible for inclusion. Results: A systematic review revealed 10 eligible publications. Sotalol was superior to placebo and/or no antiarrhythmic therapy in AF conversion, with a relative success of 24 (95% CI 4.7-119, p < 0.001). Sotalol was not significantly different from class IA antiarrhythmic drugs. Similarly, sotalol was not different from class IC antiarrhythmic drugs or amiodarone in terms of conversion efficacy. In one study, sotalol was less effective than high-dose ibutilide (2 mg), with a relative success of 0.248 (95% CI 0.128-0.481, p < 0.001). Ibutilide caused more proarrhythmia. Conclusions: Sotalol is as effective as class IA and class IC antiarrhythmic agents, and it is also as effective as amiodarone for pharmacologic conversion of AF. Only ibutilide at a high dose showed a greater conversion rate of AF. (C) 2016 S. Karger AG, Basel C1 [Milan, David J.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Saul, J. Philip] West Virginia Univ, Dept Pediat, Sch Med, Morgantown, WV USA. [Somberg, John C.] Rush Univ, Dept Med & Pharmacol, Chicago, IL 60612 USA. [Molnar, Janos] Amer Inst Therapeut, 21 N Skokie Hwy,G-3, Lake Bluff, IL 60044 USA. [Molnar, Janos] Rosalind Franklin Univ Med & Sci, Dept Med, Chicago Med Sch, N Chicago, IL USA. RP Molnar, J (reprint author), Amer Inst Therapeut, 21 N Skokie Hwy,G-3, Lake Bluff, IL 60044 USA. EM Janos.Molnar@rosalindfranklin.edu NR 22 TC 0 Z9 0 U1 3 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 EI 1421-9751 J9 CARDIOLOGY JI Cardiology PY 2017 VL 136 IS 1 BP 52 EP 60 DI 10.1159/000447237 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EF7WN UT WOS:000390540200009 PM 27554842 ER PT J AU Ng, CY Heist, EK AF Ng, Chee Yuan Heist, E. Kevin TI Cardiac Resynchronization Therapy Maximizing the Response to Biventricular Pacing SO CARDIOLOGY IN REVIEW LA English DT Review DE cardiac resynchronization therapy; biventricular pacing; left bundle branch block ID VENTRICULAR LEAD PLACEMENT; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; HEART-FAILURE PATIENTS; INTERVENTRICULAR DELAY; QRS MORPHOLOGY; NARROW QRS; FOLLOW-UP; ATRIOVENTRICULAR DELAY; RANDOMIZED-TRIAL; CRT TRIAL AB Cardiac resynchronization therapy (CRT) has become a mainstay therapy to improve clinical outcomes of patients with left ventricular systolic dysfunction and a wide QRS complex, in addition to guideline-directed medical therapy. As clinical experience with CRT continues to expand, the device and lead design, along with implantation techniques, have evolved as well. However, there is a significant proportion of patients with heart failure who do not have a favorable response to CRT. In this review article, we will discuss how to maximize the response to CRT, which includes patient characteristics, device features, positioning of the lead, and device programming. We will also discuss the ongoing efforts to improve CRT. C1 [Ng, Chee Yuan; Heist, E. Kevin] Harvard Med Sch, Cardiac Arrhythmia Serv, Corrigan Minehan Heart Ctr, Massachusetts Gen Hosp, Boston, MA USA. RP Heist, EK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM kheist@partners.org NR 65 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 1061-5377 EI 1538-4683 J9 CARDIOL REV JI Cardiol. Rev. PD JAN-FEB PY 2017 VL 25 IS 1 BP 6 EP 11 DI 10.1097/CRD.0000000000000127 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA EF9ZV UT WOS:000390691100004 PM 27861420 ER PT J AU Palioura, S Colby, K AF Palioura, Sotiria Colby, Kathryn TI Outcomes of Descemet Stripping Endothelial Keratoplasty Using Eye Bank-Prepared Preloaded Grafts SO CORNEA LA English DT Article DE DSEK; EndoGlide; endothelial cell count; penetrating keratoplasty; Fuchs dystrophy; eye banking ID POSTERIOR LAMELLAR KERATOPLASTY; DONOR INSERTION DEVICE; PENETRATING KERATOPLASTY; CELL LOSS; VISUAL-ACUITY; FORCEPS; COMPLICATIONS; ENDOGLIDE; SURVIVAL; TISSUE AB Purpose: To evaluate the feasibility of Descemet stripping endothelial keratoplasty using grafts preloaded by an eye bank in a commercially available insertion device. Methods: In this retrospective case series, a series of 35 eyes in 34 consecutive patients who underwent Descemet stripping endothelial keratoplasty for Fuchs endothelial dystrophy or previously failed full-thickness grafts at a single tertiary care center from March 2013 to March 2014 was included. The donor tissue had undergone pre-lamellar dissection, trephination, and loading into EndoGlide Ultrathin inserters at the Lions Eye Institute for Transplant and Research (Tampa, FL) and was shipped overnight in Optisol GS to the surgeon (K.C.). Surgery was performed within 24 hours from tissue preparation and loading by the eye bank. Donor and recipient characteristics, endothelial cell density (ECD), best-corrected visual acuity, and central corneal thickness were recorded. The main outcome measures were intraoperative and postoperative complications and ECD loss at 3, 6, and 12 months. Results: One primary graft failure (2.8%), 2 rebubblings (5.7%), and 1 graft rejection (2.8%) occurred. Mean preoperative donor ECD was 2821 +/- 199 cells/mm(2). Six months postoperatively, the mean endothelial cell loss was 25.3% +/- 17.2% (n = 32), which remained stable at 1 year (31.5% +/- 17.9%, n = 32). Mean best-corrected visual acuity improved from 20/100 preoperatively to 20/25 at a mean follow-up of 1 year (n = 32). Mean central corneal thickness was reduced from 711 +/- 110 mm to 638 +/- 66 mu m at the last follow-up visit. Conclusions: Donor graft tissue preloaded by an eye bank can be used successfully for endothelial keratoplasty. Preloading reduces intraoperative tissue manipulation. C1 [Palioura, Sotiria; Colby, Kathryn] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. [Palioura, Sotiria] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Cornea Serv, Miami, FL 33136 USA. [Colby, Kathryn] Univ Chicago, Dept Ophthalmol & Visual Sci, Chicago, IL 60637 USA. RP Colby, K (reprint author), Univ Chicago Med & Biol Sci, Dept Ophthalmol & Visual Sci, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM kcolby@bsd.uchicago.edu FU Hellenic Society of Intraocular Implant and Refractive Surgery FX S. Palioura holds the 2015 "Spyros Georgaras" scholarship from the Hellenic Society of Intraocular Implant and Refractive Surgery. NR 33 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 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JAN PY 2017 VL 36 IS 1 BP 21 EP 25 DI 10.1097/ICO.0000000000001039 PG 5 WC Ophthalmology SC Ophthalmology GA EF9YR UT WOS:000390687900010 PM 27741016 ER PT J AU Kobashi, H Kamiya, K Shimizu, K AF Kobashi, Hidenaga Kamiya, Kazutaka Shimizu, Kimiya TI Dry Eye After Small Incision Lenticule Extraction and Femtosecond Laser-Assisted LASIK: Meta-Analysis SO CORNEA LA English DT Article DE small incision lenticule extraction; femtosecond laser-assisted laser in situ keratomileusis; ocular surface; dry eye; corneal sensitivity; corneal subbasal nerve ID CORNEAL REFRACTIVE SURGERY; MYOPIC ASTIGMATISM; OCULAR SURFACE; FS-LASIK; SMILE; OUTCOMES; SENSATION; DISEASE AB Purpose: To compare postoperative ocular surface integrity and innervation between small incision lenticule extraction (SMILE) and femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK). Methods: The Cochrane Central Register of Controlled Trials, PubMED, and EMBASE were searched for prospective comparative studies. Trials meeting the selection criteria were quality appraised, and the data were extracted by 2 independent authors. The weighted mean differences (WMDs) and 95% confidence intervals (CIs) were used to compare dry eye examinations and corneal subbasal nerve density (SMILE-FS-LASIK). Results: The study covered 5 trials. No significant difference was found in the Schirmer test score between both groups (WMD = -1.91 and 0.27; 95% CI, -5.02 to 1.20 and -0.99 to 1.54; P = 0.23 and 0.67 at 1- and 6-month follow-ups, respectively). Tear breakup time in the SMILE group significantly exceeded that in the FS-LASIK group (WMD = 0.65 and 1.14; 95% CI, 0.20-1.10 and 0.18-2.10; P = 0.004 and 0.02, at 1- and 6-month follow-ups, respectively). Ocular surface disease index scores were significantly better in the SMILE group 6 months postoperatively (WMD = -10.12, 95% CI, -16.07 to -4.18, P = 0.0008). No significant difference was found in tear osmolarity between both groups (WMD = -5.19 and -6.37; 95% CI, -17.15 to 6.76 and -22.74 to 10.00; P = 0.39 and 0.45 at 1- and 6-month follow-ups, respectively). Higher corneal sensitivity was observed in the SMILE group 1 and 6 months postoperatively (WMD = 11.35 and 3.49; 95% CI, 7.29-15.40 and 1.76-5.21; P < 0.00001 and <0.0001, at 1- and 6-month follow-ups, respectively). Corneal subbasal nerve density was also significantly higher in SMILE-treated eyes than it was in FS-LASIK-treated eyes 1 month postoperatively (WMD = 4.72, 95% CI, 1.10-8.34, P = 0.01). Conclusions: According to this meta-analysis, the SMILE procedure has fewer negative impacts on the ocular surface and corneal innervation than does FS-LASIK. Furthermore, SMILE shows superiority over FS-LASIK by a exhibiting a lower risk of postoperative dry eye. C1 [Kobashi, Hidenaga; Kamiya, Kazutaka; Shimizu, Kimiya] Kitasato Univ, Sch Med, Dept Ophthalmol, 1-15-1 Kitasato, Sagamihara, Kanagawa 2288555, Japan. [Kobashi, Hidenaga] Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02115 USA. RP Kobashi, H (reprint author), Kitasato Univ, Sch Med, Dept Ophthalmol, 1-15-1 Kitasato, Sagamihara, Kanagawa 2288555, Japan.; Kobashi, H (reprint author), Harvard Med Sch, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02115 USA. EM himon@hotmail.co.jp NR 24 TC 0 Z9 0 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JAN PY 2017 VL 36 IS 1 BP 85 EP 91 DI 10.1097/ICO.0000000000000999 PG 7 WC Ophthalmology SC Ophthalmology GA EF9YR UT WOS:000390687900023 PM 27560032 ER PT J AU Singh, AD Dupps, WJ Biscotti, CV Suh, JH Lathrop, KL Nairn, JP Shih, H AF Singh, Arun D. Dupps, William J., Jr. Biscotti, Charles V. Suh, John H. Lathrop, Kira L. Nairn, John P. Shih, Helen TI Limbal Stem Cell Preservation During Proton Beam Irradiation for Diffuse Iris Melanoma SO CORNEA LA English DT Article DE limbal stem cells; proton beam irradiation; iris melanoma; palisades of Vogt ID PLAQUE RADIOTHERAPY AB Purpose: To report the outcome after limbal stem cell preservation during proton beam irradiation for diffuse iris melanoma. Methods: This is a single-case report of diffuse iris melanoma that was managed with proton beam radiation (53 Gy), wherein pre-emptively harvested superior and inferior limbal stem cells before radiation were replaced after irradiation. Regeneration of the palisades of Vogt and the limbal stem cells was documented by an optical coherence tomography-based imaging protocol. Results: At 24 months after radiation therapy, best-corrected visual acuity was 20/25. The cornea was clear without evidence of limbal stem cell dysfunction. Clinical examination (including gonioscopy and ultrasound biomicroscopy [UBM]) was indicative of local control, and systemic surveillance was negative for metastatic disease. At posttransplant (21 months), there were more palisade structures visible in both anterior and posterior regions of the superior and inferior limbus, and the linear presentation of the inferior palisades appears to have regenerated. Conclusions: Diffuse iris melanoma can be managed successfully with proton beam radiation while preserving corneal limbal stem cells by harvesting them before radiation and then replacing them after irradiation. Regeneration of the palisades of Vogt could be documented by an optical coherence tomography-based imaging protocol. C1 [Singh, Arun D.; Dupps, William J., Jr.] Cleveland Clin, Cole Eye Inst, Dept Ophthalm Oncol, 9500 Euclid Ave,Desk i32, Cleveland, OH 44195 USA. [Dupps, William J., Jr.] Cleveland Clin, Dept Biomed Engn, Cleveland, OH 44106 USA. [Biscotti, Charles V.] Cleveland Clin, Dept Anat Pathol, Cleveland, OH 44106 USA. [Suh, John H.] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Suh, John H.] Univ Pittsburgh, Sch Med Ophthalmol, Pittsburgh, PA USA. [Lathrop, Kira L.] Swanson Sch Engn Bioengn, Pittsburgh, PA USA. [Nairn, John P.] Associates Ophthalmol, Pittsburgh, PA USA. [Shih, Helen] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Singh, AD (reprint author), Cleveland Clin, Cole Eye Inst, Dept Ophthalm Oncol, 9500 Euclid Ave,Desk i32, Cleveland, OH 44195 USA. EM singha@ccf.org NR 10 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-3740 EI 1536-4798 J9 CORNEA JI Cornea PD JAN PY 2017 VL 36 IS 1 BP 119 EP 122 DI 10.1097/ICO.0000000000001063 PG 4 WC Ophthalmology SC Ophthalmology GA EF9YR UT WOS:000390687900031 PM 27755196 ER PT J AU Cefalu, WT Boulton, AJM Tamborlane, WV Moses, RG LeRoith, D Greene, EL Hu, FB Bakris, G Wylie-Rosett, J Rosenstock, J Kahn, SE Weinger, K Blonde, L de Groot, M Rich, S D'Alessio, D Reynolds, L Riddle, MC AF Cefalu, William T. Boulton, Andrew J. M. Tamborlane, William V. Moses, Robert G. LeRoith, Derek Greene, Eddie L. Hu, Frank B. Bakris, George Wylie-Rosett, Judith Rosenstock, Julio Kahn, Steven E. Weinger, Katie Blonde, Lawrence de Groot, Mary Rich, Stephen D'Alessio, David Reynolds, Lyn Riddle, Matthew C. TI Diabetes Care: "Taking It to the Limit One More Time" SO DIABETES CARE LA English DT Editorial Material ID CHRONIC KIDNEY-DISEASE; POSITION STATEMENT; METABOLIC SURGERY; METFORMIN USE; TYPE-2; RESTRICTIONS; ASSOCIATION; HYPOTHESIS; MANAGEMENT; YOUTH C1 [Cefalu, William T.] Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. [Boulton, Andrew J. M.] Univ Manchester, Manchester Diabet Ctr, Manchester, Lancs, England. [Tamborlane, William V.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Moses, Robert G.] ISLHD, Wollongong, NSW, Australia. [LeRoith, Derek] Icahn Sch Med Mt Sinai, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. [Greene, Eddie L.] Mayo Clin, Div Nephrol & Hypertens, Rochester, MN USA. [Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Hu, Frank B.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Bakris, George] Univ Chicago Med, Div Endocrinol Diabet & Metab, Dept Med, ASH Comprehens Hypertens Ctr, Chicago, IL USA. [Wylie-Rosett, Judith] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Rosenstock, Julio] Dallas Diabet Res Ctr Med City, Dallas, TX USA. [Kahn, Steven E.] VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. [Kahn, Steven E.] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Weinger, Katie] Harvard Med Sch, Joslin Diabet Ctr, Boston, MA USA. [Blonde, Lawrence] Ochsner Med Ctr, Dept Endocrinol, Frank Riddick Diabet Inst, Ochsner Diabet Clin Res Unit, New Orleans, LA USA. [de Groot, Mary] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Rich, Stephen] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [D'Alessio, David] Duke Univ, Div Endocrinol Diabet & Metab, Durham, NC USA. [Reynolds, Lyn] Amer Diabet Assoc, Indianapolis, IN USA. [Riddle, Matthew C.] Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. RP Cefalu, WT (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. EM cefaluwt@pbrc.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCCIH NIH HHS [P50 AT002776]; NIGMS NIH HHS [U54 GM104940] NR 39 TC 0 Z9 0 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2017 VL 40 IS 1 BP 3 EP 6 DI 10.2337/dc16-2326 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG2BA UT WOS:000390846100004 PM 27999000 ER PT J AU Katz, ML Kollman, CR Dougher, CE Mubasher, M Laffel, LMB AF Katz, Michelle L. Kollman, Craig R. Dougher, Carly E. Mubasher, Mohamed Laffel, Lori M. B. TI Influence of HbA(1c) and BMI on Lipid Trajectories in Youths and Young Adults With Type 1 Diabetes SO DIABETES CARE LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; GLYCEMIC CONTROL; GENERAL-POPULATION; GLUCOSE CONTROL; DISEASE; CHILDHOOD; MORTALITY; ONSET; INTERVENTION; ADOLESCENTS AB OBJECTIVE To assess the influence of HbA(1c) and BMI (measured as BMI z score [zBMI]) on LDL, HDL, and non-HDL trajectories as youths with type 1 diabetes age into early adulthood. RESEARCH DESIGN AND METHODS Dynamic, retrospective cohort study examining changes in lipid values in 572 youths with type 1 diabetes followed longitudinally for a median of 9.3 years. Through longitudinal modeling, we describe the relationship of HbA(1c) and zBMI on lipid values as subjects age after adjusting for other relevant factors, including lipid-lowering medication use. RESULTS The median number of lipid assessments was 7 (range 2-39). Every 1% increase in HbA(1c) was associated with an similar to 2-6 mg/dL increase in LDL levels, with a greater increase in LDL levels as subjects progressed from prepubertal to postpubertal age ranges. A 1-SD increase in BMI was associated with a mean LDL increase of 2.1 mg/dL when subjects were 10 years old and increased to a mean of 8.2 mg/dL when subjects were 19 years old. The association between changes in HbA(1c) level and zBMI and changes in non-HDL levels as youths aged were similar to the associations found with LDL. The influence of HbA(1c) and zBMI on HDL levels was small and not dependent on age. CONCLUSIONS Changes in HbA(1c) level and zBMI modestly impact LDL and non-HDL cholesterol and have greater impacts as children age. Addressing elevations in HbA(1c) and zBMI as children enter into adolescence and beyond may lead to improvements in lipid levels. C1 [Katz, Michelle L.; Dougher, Carly E.; Laffel, Lori M. B.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Kollman, Craig R.; Mubasher, Mohamed] Jaeb Ctr Hlth Res, Tampa, FL USA. RP Katz, ML (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. EM michelle.katz@joslin.harvard.edu FU National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health [K12DK094721, P30DK036836]; National Heart, Lung, and Blood Institute of the National Institutes of Health [K23HL125976]; Katherine Adler Astrove Youth Education Fund; Maria Griffin Drury Pediatric Fund; Eleanor Chesterman Beatson Fund FX This work was supported in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award numbers K12DK094721 and P30DK036836, the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number K23HL125976, the Katherine Adler Astrove Youth Education Fund, the Maria Griffin Drury Pediatric Fund, and the Eleanor Chesterman Beatson Fund. NR 35 TC 0 Z9 0 U1 3 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2017 VL 40 IS 1 BP 30 EP 37 DI 10.2337/dc16-0430 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG2BA UT WOS:000390846100008 PM 27797924 ER PT J AU Mosenzon, O Leibowitz, G Bhatt, DL Cahn, A Hirshberg, B Wei, C Im, K Rozenberg, A Yanuv, I Stahre, C Ray, KK Iqbal, N Braunwald, E Scirica, BM Raz, I AF Mosenzon, Ofri Leibowitz, Gil Bhatt, Deepak L. Cahn, Avivit Hirshberg, Boaz Wei, Cheryl Im, KyungAh Rozenberg, Aliza Yanuv, Ilan Stahre, Christina Ray, Kausik K. Iqbal, Nayyar Braunwald, Eugene Scirica, Benjamin M. Raz, Itamar TI Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial SO DIABETES CARE LA English DT Article ID CHRONIC KIDNEY-DISEASE; INDUCED DIABETIC-RATS; POST-HOC ANALYSIS; CARDIOVASCULAR RISK; ALBUMINURIA; NEPHROPATHY; MICROALBUMINURIA; PROTEINURIA; INHIBITION; REDUCTION AB OBJECTIVE Dipeptidyl peptidase 4 inhibitors may have a protective effect in diabetic nephropathy. RESEARCH DESIGN AND METHODS We studied renal outcomes of 16,492 patients with type 2 diabetes, randomized to saxagliptin versus placebo and followed for a median of 2.1 years in the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR-TIMI 53) trial. RESULTS At baseline, 9,696 (58.8%) subjects had normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g), 4,426 (26.8%) had microalbuminuria (ACR 30-300 mg/g), and 1,638 (9.9%) had macroalbuminuria (ACR >300 mg/g). Treatment with saxagliptin was associated with improvement in and/or less deterioration in ACR categories from baseline to end of trial (EOT) (P = 0.021, P < 0.001, and P = 0.049 for individuals with baseline normoalbuminuria, microalbuminuria, and macroalbuminuria, respectively). At 2 years, the difference in mean ACR change between saxagliptin and placebo arms was 219.3 mg/g (P = 0.033) for estimated glomerular filtration rate (eGFR) >50 mL/min/body surface area per 1.73 m(2) (BSA), 2105 mg/g (P = 0.011) for 50 >= eGFR >= 30 mL/min/BSA, and 2245.2 mg/g (P = 0.086) for eGFR <30 mL/min/BSA. Analyzing ACR as a continuous variable showed reduction in ACR with saxagliptin (1 year, P < 0.0001; 2 years, P = 0.0143; and EOT, P = 0.0158). The change in ACR did not correlate with that in HbA(1c) (r = 0.041, 0.052, and 0.036; 1 year, 2 years, and EOT, respectively). The change in eGFR was similar in the saxagliptin and placebo groups. Safety renal outcomes, including doubling of serum creatinine, initiation of chronic dialysis, renal transplantation, or serum creatinine >6.0 mg/dL, were similar as well. CONCLUSIONS Treatment with saxagliptin improved ACR, even in the normoalbuminuric range, without affecting eGFR. The beneficial effect of saxagliptin on albuminuria could not be explained by its effect on glycemic control. C1 [Mosenzon, Ofri; Rozenberg, Aliza; Yanuv, Ilan; Raz, Itamar] Hadassah Hebrew Univ Hosp, Div Internal Med, Diabet Unit, Jerusalem, Israel. [Leibowitz, Gil; Cahn, Avivit] Hadassah Hebrew Univ Hosp, Serv Endocrinol, Diabet Unit, Jerusalem, Israel. [Bhatt, Deepak L.; Im, KyungAh; Braunwald, Eugene; Scirica, Benjamin M.] Harvard Med Sch, Brigham & Womens Hosp, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA USA. [Hirshberg, Boaz] MedImmune, Gaithersburg, MD USA. [Wei, Cheryl; Iqbal, Nayyar] AstraZeneca, Res & Dev, Gaithersburg, MD USA. [Stahre, Christina] AstraZeneca, Res & Dev, Molndal, Sweden. [Ray, Kausik K.] Imperial Coll, Dept Primary Care & Publ Hlth, London, England. RP Raz, I (reprint author), Hadassah Hebrew Univ Hosp, Div Internal Med, Diabet Unit, Jerusalem, Israel. EM ntv502@netvision.net.il FU AstraZeneca; Bristol-Myers Squibb FX The SAVOR-TIMI 53 trial was sponsored by AstraZeneca and Bristol-Myers Squibb. NR 37 TC 0 Z9 0 U1 2 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 2017 VL 40 IS 1 BP 69 EP 76 DI 10.2337/dc16-0621 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA EG2BA UT WOS:000390846100013 PM 27797925 ER PT J AU Steinestel, J Bernemann, C Schrader, AJ Lennerz, JK AF Steinestel, Julie Bernemann, Christof Schrader, Andres J. Lennerz, Jochen K. TI Reply from Authors re: Emmanuel S. Antonarakis, Howard I. Scher. Do Patients With AR-V7-Positive Prostate Cancer Benefit from Novel Hormonal Therapies? It All Depends on Definitions. Eur Urol 2017;71:4-6 SO EUROPEAN UROLOGY LA English DT Editorial Material ID INCREASED SURVIVAL C1 [Steinestel, Julie; Bernemann, Christof; Schrader, Andres J.] Univ Hosp Munster, Urol Clin, Albert Schweitzer Campus 1, D-48149 Munster, Germany. [Lennerz, Jochen K.] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. RP Steinestel, J (reprint author), Univ Hosp Munster, Urol Clin, Albert Schweitzer Campus 1, D-48149 Munster, Germany. EM julie.steinestel@ukmuenster.de NR 10 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0302-2838 EI 1873-7560 J9 EUR UROL JI Eur. Urol. PD JAN PY 2017 VL 71 IS 1 BP 6 EP 7 DI 10.1016/j.eururo.2016.08.071 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA EF8FM UT WOS:000390564400018 PM 27641787 ER PT J AU Volta, U Caio, G Karunaratne, TB Alaedini, A De Giorgio, R AF Volta, Umberto Caio, Giacomo Karunaratne, Tennekoon B. Alaedini, Armin De Giorgio, Roberto TI Non-coeliac gluten/wheat sensitivity: advances in knowledge and relevant questions SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Review DE Biomarkers; gut microbiome; innate immunity; adaptive immunity; intestinal epithelial barrier; non-coeliac gluten sensitivity; wheat sensitivity ID IRRITABLE-BOWEL-SYNDROME; COMMON AUSTRALIAN VEGETABLES; BRAIN AXIS DYSFUNCTION; FREE DIET; WHEAT-SENSITIVITY; CONTROLLED-TRIAL; GASTROINTESTINAL SYMPTOMS; INDUCED INFLAMMATION; CLINICAL ENTITY; GUT MICROBIOTA AB Introduction: Non-coeliac gluten/wheat sensitivity (NCG/WS) is a syndrome characterized by intestinal and extra-intestinal symptoms occurring a few hours or days after the ingestion of gluten and wheat proteins in patients testing negative for coeliac disease and wheat allergy.Areas covered: The present review deals with recent scientific acquisitions of this gluten-related syndrome, including pathogenetic mechanisms, clinical picture, symptom score, biomarkers and double-blind placebo-controlled trial for diagnosis, and treatment. The methodology used was a literature search on NCG/WS using Medline and Premedline from 1970 to August 2016.Expert commentary: We discussed the pathogenesis of symptom generation and altered gut physiology in NCG/WS. Possible mechanisms include innate and adaptive immune activation, impaired intestinal epithelial barrier and changes in gut microbiome. These interlinked factors may be exploited for their clinical relevance as possible biomarkers. A systemic immune response to microbial and wheat antigens, together with intestinal cell damage, occurs in patients with NCG/WS. Due to the lack of established biomarkers, it is mandatory to validate the diagnosis of the syndrome by means of a well-defined work-up involving dietary challenge. Finally, dietary and other therapeutic indications have been thoroughly reviewed. C1 [Volta, Umberto; Caio, Giacomo; Karunaratne, Tennekoon B.; De Giorgio, Roberto] Univ Bologna, St Orsola Malpighi Hosp, Dept Med & Surg Sci & Digest Syst, CRBA, Bologna, Italy. [Caio, Giacomo] Harvard Med Sch, Massachusetts Gen Hosp, Mucosal Immunol & Biol Res Ctr, Boston, MA USA. [Alaedini, Armin] Columbia Univ, Dept Med, Med Ctr, New York, NY USA. [Alaedini, Armin] Columbia Univ, Celiac Dis Ctr, Med Ctr, New York, NY USA. [Alaedini, Armin] Columbia Univ, Inst Human Nutr, Med Ctr, New York, NY 10032 USA. RP Volta, U (reprint author), Univ Bologna, Dept Med & Surg Sci, St Orsola Malpighi Hosp, Via Massarenti 9, I-40138 Bologna, Italy. EM umberto.volta@aosp.bo.it NR 76 TC 1 Z9 1 U1 18 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD JAN PY 2017 VL 11 IS 1 BP 9 EP 18 DI 10.1080/17474124.2017.1260003 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA EG2BF UT WOS:000390846700003 PM 27852116 ER PT J AU Pastore, LM Young, SL Manichaikul, A Baker, VL Wang, XQ Finkelstein, JS AF Pastore, Lisa M. Young, Steven L. Manichaikul, Ani Baker, Valerie L. Wang, Xin Q. Finkelstein, Joel S. TI Distribution of the FMR1 gene in females by race/ethnicity: women with diminished ovarian reserve versus women with normal fertility (SWAN study) SO FERTILITY AND STERILITY LA English DT Article DE Diminished ovarian reserve; FMR1; race/ethnicity; European Continental Ancestry Group; Asian Continental Ancestry Group; ovarian reserve; infertility; female ID TRIPLE CGG REPEATS; FRAGILE-X; MENTAL-RETARDATION; INFERTILE WOMEN; PREVALENCE; CARRIER; INSUFFICIENCY; ALLELES; PREMUTATION; RANGE AB Objective: To study whether reported, but inconsistent, associations between the FMR1 CGG repeat lengths in the intermediate, high normal, or low normal range differentiate women diagnosed with diminished ovarian reserve (DOR) from population controls and whether associations vary by race/ethnic group. Design: Case-control study. Setting: Academic and private fertility clinics. Patient(s): DOR cases (n = 129; 95 Whites, 22 Asian, 12 other) from five U. S. fertility clinics were clinically diagnosed, with regular menses and no fragile X syndrome family history. Normal fertility controls (n = 803; 386 Whites, 219 African-Americans, 102 Japanese, 96 Chinese) from the United States-based SWAN Study had one or more menstrual period in the 3 months preenrollment, one or more pregnancy, no history of infertility or hormone therapy, and menopause R46 years. Previously, the SWAN Chinese and Japanese groups had similar FMR1 CGG repeat lengths, thus they were combined. Intervention(s): None. Main Outcome Measure(s): FMR1 CGG repeat lengths. Result(s): Median CGG repeats were nearly identical by case/control group. DOR cases had fewer CGG repeats in the shorter FMR1 allele than controls among Whites, but this was not significant among Asians. White cases had fewer CGG repeats in the shorter allele than Asian cases. No significant differences were found in the high normal/intermediate range between cases and controls or by race/ethnic group within cases in the longer allele. Conclusion(s): This study refutes prior reports of an association between DOR and high normal/intermediate repeats and confirms an association between DOR and low normal repeats in Whites. (C) 2016 by American Society for Reproductive Medicine. C1 [Pastore, Lisa M.] Stony Brook Med, OB GYN & Reprod Med Dept, Stony Brook, NY USA. [Young, Steven L.] Univ N Carolina, UNC Fertil, Chapel Hill, NC USA. [Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Manichaikul, Ani; Wang, Xin Q.] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA. [Baker, Valerie L.] Stanford Univ, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Stanford, CA 94305 USA. [Finkelstein, Joel S.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Pastore, LM (reprint author), SUNY Stony Brook, OB GYN & Reprod Med Dept, Stony Brook, NY 11794 USA. EM pastorestudies@gmail.com FU National Center for Child Health and Human Development at the National Institutes of Health (NIH) [R01HD068440]; NIH, Department of Health and Human Services, through the National Institute on Aging (NIA); National Institute of Nursing Research (NINR); NIH Office of Research on Women's Health (ORWH) [U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495]; NIH [U01AG017719]; National Center for Research Resources; National Center for Advancing Translational Sciences, NIH, through University of California at San Francisco's Clinical & Translational Science Institute [UL1 RR024131] FX Supported by the National Center for Child Health and Human Development at the National Institutes of Health (NIH; grant no. R01HD068440 to L.M.P.). The Study of Women's Health Across the Nation (SWAN) has grant support from the NIH, Department of Health and Human Services, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR), and the NIH Office of Research on Women's Health (ORWH; grant nos. U01NR004061, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The SWAN Repository is funded by NIH grant no. U01AG017719. This publication was also supported in part by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through University of California at San Francisco's Clinical & Translational Science Institute grant no. UL1 RR024131. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, or NIH. NR 32 TC 0 Z9 0 U1 5 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2017 VL 107 IS 1 BP 205 EP + DI 10.1016/j.fertnstert.2016.09.032 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA EF9SD UT WOS:000390669600036 PM 27816231 ER PT J AU Reinke, LF Feemster, LC McDowell, J Gunnink, E Tartaglione, EV Udris, E Curtis, JR Au, DH AF Reinke, Lynn F. Feemster, Laura C. McDowell, Jennifer Gunnink, Eric Tartaglione, Erica V. Udris, Edmunds Curtis, J. Randall Au, David H. TI The long term impact of an end-of-life communication intervention among veterans with COPD SO HEART & LUNG LA English DT Article DE End of life communication; Advance care planning; Chronic obstructive pulmonary disease (COPD); Clinician communication skills; Intervention ID INTENSIVE-CARE-UNIT; ADVANCE CARE; RANDOMIZED-TRIAL; DECISION-MAKING; ELDERLY-PATIENTS; PALLIATIVE CARE; OUTCOMES; HEALTH; FACILITATORS; PREFERENCES AB Objective: To assess if an end-of-life communication intervention with patients with COPD led to higher long-term documentation of advance care planning discussions at the end-of-life. Background: We previously demonstrated that providing clinicians a patient-specific feedback form about patients' communication preferences improved the occurrence and quality of clinician communication about end-of-life care. Methods: Among those individuals enrolled in the intervention study (2004-2007) who had died during the follow-up period (up to 2013), we assessed if patients in the intervention arm had more goals of care discussions and formal advance directives completed as compared to controls. We conducted logistic models accounting for provider level clustering, adjusting for age, FEVi, and race. Results: Among the 376 patients in the study, 157 died (76 in the intervention arm, 81 in the control arm). Over an average duration of 3.6 years (from the time of the first study appointment to death), 115 (73%) patients engaged in 451 unique end-of-life care discussions. The intervention was not associated with a higher percentage of patients with documented end-of-life conversations (I:C 75% vs 72%, p = 0.63) or completion of advance care directives (26% vs 29%, p = 0.55). Conclusions: Despite initially improving the occurrence of end-of-life conversations, the intervention did not increase the documentation of subsequent conversations about end-of-life care, nor did it improve documentation of advance directives. Future research should focus on testing multi-faceted, longitudinal, system-level interventions to enhance conversations about goals of care that promote goal-concurrent care. Published by Elsevier Inc. C1 [Reinke, Lynn F.; Feemster, Laura C.; McDowell, Jennifer; Gunnink, Eric; Tartaglione, Erica V.; Udris, Edmunds; Au, David H.] Puget Sound Hlth Care Syst, Hlth Serv R&D, Dept Vet Affairs, Seattle, WA USA. [Reinke, Lynn F.] Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. [Feemster, Laura C.; Curtis, J. Randall; Au, David H.] Univ Washington, Sch Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. RP Reinke, LF (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbia Way, Seattle, WA 98108 USA. EM reinkl@uw.edu FU Office of Nursing Services [10-004] FX This work was supported by a pilot project award from the Office of Nursing Services, #10-004, Reinke, LF (PI), from the United States (U.S.) Department of Veterans Affairs. NR 35 TC 0 Z9 0 U1 7 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0147-9563 EI 1527-3288 J9 HEART LUNG JI Heart Lung PD JAN-FEB PY 2017 VL 46 IS 1 BP 30 EP 34 DI 10.1016/j.hrtlng.2016.10.003 PG 5 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA EG2AG UT WOS:000390834900007 PM 27989399 ER PT J AU Topaz, M Goss, F Blumenthal, K Lai, K Seger, DL Slight, SP Wickner, PG Robinson, GA Fung, KW McClure, RC Spiro, S Acker, WW Bates, DW Zhou, L AF Topaz, Maxim Goss, Foster Blumenthal, Kimberly Lai, Kenneth Seger, Diane L. Slight, Sarah P. Wickner, Paige G. Robinson, George A. Fung, Kin Wah McClure, Robert C. Spiro, Shelly Acker, Warren W. Bates, David W. Zhou, Li TI Towards improved drug allergy alerts: Multidisciplinary expert recommendations SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Letter ID ORDER-ENTRY SYSTEM C1 [Topaz, Maxim; Lai, Kenneth; Seger, Diane L.; Slight, Sarah P.; Wickner, Paige G.; Acker, Warren W.; Bates, David W.; Zhou, Li] Brigham & Womens Hosp, Gen Internal Med & Primary Care, 75 Francis St, Boston, MA 02115 USA. [Topaz, Maxim; Blumenthal, Kimberly; Bates, David W.; Zhou, Li] Harvard Med Sch, Boston, MA USA. [Goss, Foster; Zhou, Li] Univ Colorado, Dept Emergency Med, Aurora, CO USA. [Blumenthal, Kimberly] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. [Blumenthal, Kimberly] Massachusetts Gen Hosp, Dept Med, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Seger, Diane L.; Acker, Warren W.] Partners Healthcare Syst, Clin & Qual Anal, Wellesley, MA USA. [Slight, Sarah P.] Univ Durham, Sch Med Pharm & Hlth, Div Pharm, Durham, England. [Robinson, George A.] First Databank Inc, San Francisco, CA USA. [Fung, Kin Wah] NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. [McClure, Robert C.] MD Partners Inc, Lafayette, CO USA. [Spiro, Shelly] Pharm HIT Collaborat, Alexandria, VA USA. RP Topaz, M (reprint author), 93 Worcester St,Wellesley Gateway,Suite 20301, Wellesley, MA 02481 USA. EM mtopaz80@gmail.com OI Acker, Warren/0000-0002-9338-8782 NR 9 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD JAN PY 2017 VL 97 BP 353 EP 355 DI 10.1016/j.ijmedinf.2016.10.006 PG 3 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA EF7BQ UT WOS:000390485500034 PM 27729200 ER PT J AU Lusardi, TA Phillips, JI Wiedrick, JT Harrington, CA Lind, B Lapidus, JA Quinn, JF Saugstad, JA AF Lusardi, Theresa A. Phillips, Jay I. Wiedrick, Jack T. Harrington, Christina A. Lind, Babett Lapidus, Jodi A. Quinn, Joseph F. Saugstad, Julie A. TI MicroRNAs in Human Cerebrospinal Fluid as Biomarkers for Alzheimer's Disease SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article DE Alzheimer's disease; ApoE; biomarker; cerebrospinal fluid; microRNA; PCR ID EXPRESSION; TECHNOLOGIES; DIAGNOSIS; DEMENTIA; MARKERS; ALLELE; ADULTS AB Background: Currently available biomarkers of Alzheimer's disease (AD) include cerebrospinal fluid (CSF) protein analysis and amyloid PET imaging, each of which has limitations. The discovery of extracellular microRNAs (miRNAs) in CSF raises the possibility that miRNA may serve as novel biomarkers of AD. Objective: Investigate miRNAs in CSF obtained from living donors as biomarkers for AD. Methods: We profiled miRNAs in CSF from 50 AD patients and 49 controls using TaqMan (R) arrays. Replicate studies performed on a subset of 32 of the original CSF samples verified 20 high confidence miRNAs. Stringent data analysis using a four-step statistical selection process including log-rank and receiver operating characteristic (ROC) tests, followed by random forest tests, identified 16 additional miRNAs that discriminate AD from controls. Multimarker modeling evaluated linear combinations of these miRNAs via best-subsets logistic regression, and computed area under the ROC (AUC) curve ascertained classification performance. The influence of ApoE genotype on miRNA biomarker performance was also evaluated. Results: We discovered 36 miRNAs that discriminate AD from control CSF. 20 of these retested in replicate studies verified differential expression between AD and controls. Stringent statistical analysis also identified these 20 miRNAs, and 16 additional miRNA candidates. Top-performing linear combinations of 3 and 4 miRNAs have AUC of 0.80-0.82. Addition of ApoE genotype to the model improved performance, i.e., AUC of 3 miRNA plus ApoE4 improves to 0.84. Conclusions: CSF miRNAs can discriminate AD from controls. Combining miRNAs improves sensitivity and specificity of biomarker performance, and adding ApoE genotype improves classification. C1 [Lusardi, Theresa A.] Oregon Hlth & Sci Univ, Computat Biol Program, Portland, OR 97201 USA. [Phillips, Jay I.; Saugstad, Julie A.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, 3181 SW Sam Jackson Pk Rd,L459, Portland, OR 97239 USA. [Wiedrick, Jack T.; Lapidus, Jodi A.] Oregon Hlth & Sci Univ, Sch Publ Hlth, Biostat, Portland, OR 97201 USA. [Harrington, Christina A.] Oregon Hlth & Sci Univ, Integrated Genom Lab, Portland, OR 97201 USA. [Lind, Babett; Quinn, Joseph F.] Oregon Hlth & Sci Univ, Dept Neurol, Layton Aging & Alzheimers Ctr, Portland, OR 97201 USA. [Quinn, Joseph F.] Portland VA Med Ctr, Dept Neurol, Portland, OR USA. RP Saugstad, JA (reprint author), Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, 3181 SW Sam Jackson Pk Rd,L459, Portland, OR 97239 USA. EM saugstad@ohsu.edu FU NIH [NCATS UH2TR000903, NIA AG08017, NCATS UL1TR000128] FX These studies were supported by NIH grants NCATS UH2TR000903 (JAS, JFQ), NIA AG08017 (JFQ), and NCATS UL1TR000128 (Oregon Clinical and Translational Research Institute). We thank Dr. Steven Rekow for assistance in interpreting the Expression Suite data, and Dr. Shawn Westaway for the ApoE genotyping data. We also thank the OHSU Gene Profiling Shared Resource for technical advice and access to core instrumentation. NR 35 TC 0 Z9 0 U1 3 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 EI 1875-8908 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PY 2017 VL 55 IS 3 BP 1223 EP 1233 DI 10.3233/JAD-160835 PG 11 WC Neurosciences SC Neurosciences & Neurology GA EG1BN UT WOS:000390766600031 PM 27814298 ER PT J AU Carter, BS Chang, DC AF Carter, Bob S. Chang, David C. TI Health care reform and the uninsured: lessons from Massachusetts SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 [Carter, Bob S.] Univ Calif San Diego, Dept Neurosurg, La Jolla, CA 92093 USA. [Chang, David C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Carter, BS (reprint author), Univ Calif San Diego, Dept Neurosurg, La Jolla, CA 92093 USA. NR 3 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 0022-3085 EI 1933-0693 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 2017 VL 126 IS 1 BP 165 EP 166 DI 10.3171/2015.11.JNS151576 PG 2 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA EG0LY UT WOS:000390725500023 PM 26967778 ER EF