FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chang, MS Barton, K Crockett, M Tuomala, RE Rutherford, AE Mutinga, ML Andersson, KL Brown, RS Oken, E Ukomadu, C AF Chang, Matthew S. Barton, Kerri Crockett, Molly Tuomala, Ruth E. Rutherford, Anna E. Mutinga, Muthoka L. Andersson, Karin L. Brown, Robert S., Jr. Oken, Emily Ukomadu, Chinweike TI Postpartum Laboratory Follow-up in Women With Hepatitis B in Massachusetts From 2007 to 2012 SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract (SSAT) / Digestive Disease Week (DDW) CY MAY 02-06, 2014 CL Chicago, IL SP Soc Surg Alimentary Tract DE access; adherence; guidelines; surveillance ID VIRUS INFECTION; HEPATOCELLULAR-CARCINOMA; COST-EFFECTIVENESS; UNITED-STATES AB Background: Screening for HBV infection in pregnant women is standard of care. Guidelines recommend that patients with chronic HBV have ongoing care and laboratory testing, but little is known about postpartum maternal HBV care outcomes. Study: We conducted a retrospective cohort study using Massachusetts Virtual Epidemiologic Network, an electronic public health surveillance system maintained by the Massachusetts Department of Public Health. We identified women who tested hepatitis B surface antigen positive during their first reported (index) pregnancy in Massachusetts from 2007 to 2012 and measured HBV-related laboratory tests reported to Massachusetts Department of Public Health during and after pregnancy. Results: We identified 983 hepatitis B surface antigen positive pregnant women. Half (492/983) did not have evidence of additional postpartum HBV laboratory testing following their index pregnancy. Women who had postpartum laboratory tests reported were younger [mean age (SD): 29 (5.3) vs. 31 (5.5) y, P = 0.0001] and more likely to have >1 pregnancy during the study period (41% vs. 1%, P < 0.0001). There were no differences in race, ethnicity, and US born status. On multivariable logistic regression, older age predicted a lower likelihood of having postpartum laboratory testing (odds ratio, 0.77; 95% confidence interval, 0.70-0.90). Conclusions: Postpartum maternal HBV follow-up laboratory testing occurred in only half of Massachusetts women and did not vary by race, ethnicity, or US born status. Our results were limited to a single state surveillance database, which likely underestimates the number of tests ordered. C1 [Chang, Matthew S.; Rutherford, Anna E.; Mutinga, Muthoka L.; Ukomadu, Chinweike] Brigham & Womens Hosp, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA. [Tuomala, Ruth E.] Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. [Barton, Kerri; Crockett, Molly] Massachusetts Dept Publ Hlth, Bureau Infect Dis, Boston, MA USA. [Andersson, Karin L.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Oken, Emily] Harvard Med Sch, Dept Populat Med, Boston, MA USA. [Oken, Emily] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Brown, Robert S., Jr.] Columbia Univ Coll Phys & Surg, Ctr Liver Dis & Transplantat, 630 W 168th St, New York, NY 10032 USA. [Ukomadu, Chinweike] Novartis Inst Biomed Res, Cambridge, MA USA. RP Chang, MS (reprint author), Stanford Univ, Sch Med, Div Gastroenterol & Hepatol, 300 Pasteur Dr,Rm M211, Palo Alto, CA 94304 USA. EM matthew.chang@stanford.edu FU NICHD NIH HHS [K24 HD069408] 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 0192-0790 EI 1539-2031 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD JUL PY 2016 VL 50 IS 6 BP E60 EP E64 DI 10.1097/MCG.0000000000000530 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DR1MH UT WOS:000379669100002 PM 27092430 ER PT J AU Vasconcelos, RM Sanfilippo, N Paster, BJ Kerr, AR Li, Y Ramalho, L Queiroz, EL Smith, B Sonis, ST Corby, PM AF Vasconcelos, R. M. Sanfilippo, N. Paster, B. J. Kerr, A. R. Li, Y. Ramalho, L. Queiroz, E. L. Smith, B. Sonis, S. T. Corby, P. M. TI Host-Microbiome Cross-talk in Oral Mucositis SO JOURNAL OF DENTAL RESEARCH LA English DT Review DE cancer; oral microbiome; Toll-like receptor; pathogen-associated molecular pattern; damage-associated molecular pattern; cancer complications ID STEM-CELL TRANSPLANTATION; NECK-CANCER PATIENTS; RECEIVING STOMATOTOXIC CHEMOTHERAPY; BONE-MARROW-TRANSPLANTATION; DOUBLE-BLIND; SELECTIVE ELIMINATION; INDUCTION CHEMOTHERAPY; CLINICAL-TRIAL; PHASE-III; HEAD AB Oral mucositis (OM) is among the most common, painful, and debilitating toxicities of cancer regimen-related treatment, resulting in the formation of ulcers, which are susceptible to increased colonization of microorganisms. Novel discoveries in OM have focused on understanding the host-microbial interactions, because current pathways have shown that major virulence factors from microorganisms have the potential to contribute to the development of OM and may even prolong the existence of already established ulcerations, affecting tissue healing. Additional comprehensive and disciplined clinical investigation is needed to carefully characterize the relationship between the clinical trajectory of OM, the local levels of inflammatory changes (both clinical and molecular), and the ebb and flow of the oral microbiota. Answering such questions will increase our knowledge of the mechanisms engaged by the oral immune system in response to mucositis, facilitating their translation into novel therapeutic approaches. In doing so, directed clinical strategies can be developed that specifically target those times and tissues that are most susceptible to intervention. C1 [Vasconcelos, R. M.; Sanfilippo, N.; Smith, B.; Corby, P. M.] NYU, Sch Med, One Pk Ave, New York, NY 10010 USA. [Vasconcelos, R. M.; Kerr, A. R.; Li, Y.; Queiroz, E. L.; Corby, P. M.] NYU, Coll Dent, One Pk Ave, New York, NY 10010 USA. [Vasconcelos, R. M.; Ramalho, L.] Univ Fed Bahia, Fac Odontol, Salvador, BA, Brazil. [Sanfilippo, N.; Smith, B.] NYU, Perlmutter Canc Ctr, One Pk Ave, New York, NY 10010 USA. [Paster, B. J.] Forsyth Inst, Cambridge, MA USA. [Paster, B. J.] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. [Sonis, S. T.] Biomodels LLC, Watertown, MA USA. [Sonis, S. T.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Sonis, S. T.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Corby, PM (reprint author), NYU, Sch Med, One Pk Ave, New York, NY 10010 USA.; Sonis, ST (reprint author), Brigham & Womens Hosp, Div Oral Med & Dent, 75 Francis St, Boston, MA 02115 USA. EM ssonis@Biomodels.com; Patricia.Corby@nyumc.org FU New York University (NYU) Provost's Mega-Grants Initiative; National Institutes of Health National Center for Advancing Translational Sciences (CTSA) [1UL1 TR001445]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior [CAPES - 9162-13-5] FX This study was supported by the New York University (NYU) Provost's Mega-Grants Initiative, a Philanthropic Gift from Marty and Connie Silver (to study effects of radiation therapy in patients with head and neck cancer), the National Institutes of Health National Center for Advancing Translational Sciences (CTSA grant 1UL1 TR001445 to NYU), and the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES - 9162-13-5). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 52 TC 3 Z9 3 U1 7 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD JUL PY 2016 VL 95 IS 7 BP 725 EP 733 DI 10.1177/0022034516641890 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DQ9UQ UT WOS:000379555200001 PM 27053118 ER PT J AU Kaye, EK Chen, N Cabral, HJ Vokonas, P Garcia, RI AF Kaye, E. K. Chen, N. Cabral, H. J. Vokonas, P. Garcia, R. I. TI Metabolic Syndrome and Periodontal Disease Progression in Men SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE periodontitis; bone loss; epidemiology; risk factors; systemic health/disease; Metabolic Syndrome X ID SCIENTIFIC STATEMENT; JAPANESE ADULTS; OLDER-ADULTS; ORAL-HEALTH; US ADULTS; ASSOCIATION; ADIPOSITY AB Metabolic syndrome, a cluster of 3 or more risk factors for cardiovascular disease, is associated with periodontal disease, but few studies have been prospective in design. This study's aim was to determine whether metabolic syndrome predicts tooth loss and worsening of periodontal disease in a cohort of 760 men in the Department of Veterans Affairs Dental Longitudinal Study and Normative Aging Study who were followed up to 33 y from 1981 to 2013. Systolic and diastolic blood pressures were measured with a standard mercury sphygmomanometer. Waist circumference was measured in units of 0.1 cm following a normal expiration. Fasting blood samples were measured in duplicate for glucose, triglyceride, and high-density lipoprotein. Calibrated periodontists served as dental examiners. Periodontal outcome events on each tooth were defined as progression to predefined threshold levels of probing pocket depth (>= 5 mm), clinical attachment loss (>= 5 mm), mobility (>= 0.5 mm), and alveolar bone loss (>= 40% of the distance from the cementoenamel junction to the root apex, on radiographs). Hazards ratios (95% confidence intervals) of tooth loss or a periodontitis event were estimated from tooth-level extended Cox proportional hazards regression models that accounted for clustering of teeth within individuals and used time-dependent status of metabolic syndrome. Covariates included age, education, smoking status, plaque level, and initial level of the appropriate periodontal disease measure. Metabolic syndrome as defined by the International Diabetes Federation increased the hazards of tooth loss (1.39; 1.08 to 1.79), pocket depth >= 5 mm (1.37; 1.14 to 1.65), clinical attachment loss >= 5 mm (1.19; 1.00 to 1.41), alveolar bone loss >= 40% (1.25; 1.00 to 1.56), and tooth mobility >= 0.5 mm (1.43; 1.07 to 1.89). The number of positive metabolic syndrome conditions was also associated with each of these outcomes. These findings suggest that the metabolic disturbances that comprise the metabolic syndrome may play a role in the development or worsening of periodontitis. C1 [Kaye, E. K.; Garcia, R. I.] Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, 560 Harrison Ave, Boston, MA 02118 USA. [Kaye, E. K.; Vokonas, P.; Garcia, R. I.] VA Boston Healthcare Syst, Dept Vet Affairs, Boston, MA USA. [Chen, N.] Boston Univ, Sch Med, Dept Pediat, 560 Harrison Ave, Boston, MA 02118 USA. [Cabral, H. J.] Boston Univ, Sch Publ Hlth, Dept Biostat, 560 Harrison Ave, Boston, MA 02118 USA. [Vokonas, P.] Boston Univ, Sch Med, Dept Med, Div Prevent Med & Epidemiol, 560 Harrison Ave, Boston, MA 02118 USA. [Vokonas, P.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, 560 Harrison Ave, Boston, MA 02118 USA. RP Kaye, EK (reprint author), Boston Univ, Henry M Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, 560 Harrison Ave, Boston, MA 02118 USA. EM kralle@bu.edu FU National Institute of Dental and Craniofacial Research [R03 DE021730]; US Department of Veterans Affairs Cooperative Studies Program FX This study was supported by the National Institute of Dental and Craniofacial Research (R03 DE021730). The Dental Longitudinal Study and the Normative Aging Study are components of the Massachusetts Veterans Epidemiology Research and Information Center, which is supported by the US Department of Veterans Affairs Cooperative Studies Program. Views expressed in this paper are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 29 TC 1 Z9 1 U1 5 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD JUL PY 2016 VL 95 IS 7 BP 822 EP 828 DI 10.1177/0022034516641053 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DQ9UQ UT WOS:000379555200013 PM 27025874 ER PT J AU Fine, N Hassanpour, S Borenstein, A Sima, C Oveisi, M Scholey, J Cherney, D Glogauer, M AF Fine, N. Hassanpour, S. Borenstein, A. Sima, C. Oveisi, M. Scholey, J. Cherney, D. Glogauer, M. TI Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE inflammation; chronic periodontitis; immunologic surface markers; cell degranulation; neutrophil extracellular traps; reactive oxygen species ID LOW-DENSITY GRANULOCYTES; HUMAN PERIPHERAL-BLOOD; EXTRACELLULAR TRAPS; DIAGNOSTIC MARKER; FLOW-CYTOMETRY; INFLAMMATION; EXPRESSION; QUANTIFICATION; IDENTIFICATION; PATHOGENESIS AB Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD ( cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state. C1 [Fine, N.; Hassanpour, S.; Borenstein, A.; Oveisi, M.; Glogauer, M.] Univ Toronto, Matrix Dynam Grp, Dept Dent, Toronto, ON, Canada. [Sima, C.] Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA USA. [Sima, C.] Harvard Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA USA. [Scholey, J.; Cherney, D.] Univ Hlth Network, Dept Med, Div Nephrol, Toronto, ON, Canada. RP Glogauer, M (reprint author), Univ Toronto, Fac Dent, Matrix Dynam Grp, Fitzgerald Bldg,150 Coll St, Toronto, ON M5S 3E2, Canada. EM michael.glogauer@utoronto.ca FU Canadian Institutes of Health Research [TBO-122068] FX Cell sorting was performed by Dionne White at the flow cytometry facility at the University of Toronto, Department of Immunology. This research was funded by a Bone Team grant from the Canadian Institutes of Health Research to M.G. (TBO-122068). The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article. NR 41 TC 1 Z9 1 U1 2 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-0345 EI 1544-0591 J9 J DENT RES JI J. Dent. Res. PD JUL PY 2016 VL 95 IS 8 BP 931 EP 938 DI 10.1177/0022034516645564 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DQ9US UT WOS:000379555400013 PM 27270666 ER PT J AU Dawson, AZ Walker, RJ Campbell, JA Egede, LE AF Dawson, Aprill Z. Walker, Rebekah J. Campbell, Jennifer A. Egede, Leonard E. TI Validation of theoretical pathway between discrimination, diabetes self-care and glycemic control SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE Discrimination; Glycemic control; Self-care; Pathways; Stress ID PERCEIVED RACIAL-DISCRIMINATION; AFRICAN-AMERICANS; RATED HEALTH; STRESS; ADULTS; RESILIENCY; BEHAVIORS; SERVICES; MELLITUS; VALIDITY AB Aims: This study examined the mechanisms through which discrimination influences diabetes self-care and glycemic control in patients with diabetes by using structured equation modeling. Methods: 615 patients were recruited from two adult primary care clinics in the southeastern United States. Measures were based on a theoretical model and included perceived discrimination, social support, social cohesion, and perceived stress. Structured equation modeling examined the relationship with diabetes self-care and glycemic control. Results: The final model (chi2(211) = 328.82, p < 0.0001, R-2 = 0.99, RMSEA = 0.03 and CFI = 0.98) shows that higher stress is directly significantly related to a decreased self-care (r = -0.59, p <0.001) and increased HbA1c (r = 0.27, p < 0.05). There was no significant direct association between discrimination, social support or social cohesion, and glycemic control or self-care. There was, however, a direct significant association between increased discrimination (r = 0.46, p < 0.001), decreased social support (r = -0.34, p < 0.001), increased social cohesion (r = 0.14, p < 0.05) and increased stress. Conclusions: These results support the hypothesized pathway of discrimination on health outcomes, showing both a direct and indirect influence through stress on HbA1c in adults with diabetes. Understanding the pathways through which discrimination influences diabetes outcomes is important for providing more comprehensive and effective care. These results suggest future interventions targeting patients with diabetes should take discrimination-induced stress into account. (C) 2016 Elsevier Inc. All rights reserved. C1 [Dawson, Aprill Z.; Walker, Rebekah J.; Campbell, Jennifer A.; Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280, Charleston, SC 29425 USA. [Walker, Rebekah J.; Egede, Leonard E.] Ralph H Johnson VAMC, Charleston VA HSR&D COIN, HEROIC, 109 Bee St, Charleston, SC USA. [Egede, Leonard E.] Med Univ S Carolina, Div Gen Internal Med & Geriatr, Dept Med, 135 Rutledge Ave, Charleston, SC 29425 USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280, Charleston, SC 29425 USA. EM dawson@musc.edu; walkerrj@musc.edu; campbja@musc.edu; egedel@musc.edu FU National Institute of Diabetes and Digestive and Kidney Disease [K24DK093699-01] FX This study was supported by Grant K24DK093699-01 from The National Institute of Diabetes and Digestive and Kidney Disease (PI: Leonard Egede). NR 38 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 1056-8727 EI 1873-460X J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD JUL PY 2016 VL 30 IS 5 BP 858 EP 863 DI 10.1016/j.jdiacomp.2016.03.014 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP8PI UT WOS:000378759700018 PM 27068266 ER PT J AU Jones, CN Hoang, AN Martel, JM Dimisko, L Mikkola, A Inoue, Y Kuriyama, N Yamada, M Hamza, B Kaneki, M Warren, HS Brown, DE Irimia, D AF Jones, Caroline N. Hoang, Anh N. Martel, Joseph M. Dimisko, Laurie Mikkola, Amy Inoue, Yoshitaka Kuriyama, Naohide Yamada, Marina Hamza, Bashar Kaneki, Masao Warren, H. Shaw Brown, Diane E. Irimia, Daniel TI Technical Advance: Microfluidic assay for precise measurements of mouse, rat, and human neutrophil chemotaxis in whole-blood droplets SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE neutrophil; migration; inbred lines ID MICE; RECEPTOR; ACTIVATION; GENERATION; C57BL/6J; PLATFORM; DISEASES; STRAINS; MODELS AB Animal models of human disease differ in innate immune responses to stress, pathogens, or injury. Precise neutrophil phenotype measurements could facilitate interspecies comparisons. However, such phenotype comparisons could not be performed accurately with the use of current assays, as they require the separation of neutrophils from blood using species-specific protocols, and they introduce distinct artifacts. Here, we report a microfluidic technology that enables robust characterization of neutrophil migratory phenotypes in a manner independent of the donor species and performed directly in a droplet of whole blood. The assay relies on the particular ability of neutrophils to deform actively during chemotaxis through microscale channels that block the advance of other blood cells. Neutrophil migration is measured directly in blood, in the presence of other blood cells and serum factors. Our measurements reveal important differences among migration counts, velocity, and directionality among neutrophils from 2 common mouse strains, rats, and humans. C1 [Jones, Caroline N.; Hoang, Anh N.; Martel, Joseph M.; Dimisko, Laurie; Inoue, Yoshitaka; Hamza, Bashar; Irimia, Daniel] Harvard Med Sch, Dept Surg, BioMEMS Resource Ctr, Massachusetts Gen Hosp, Boston, MA USA. [Kuriyama, Naohide; Yamada, Marina; Kaneki, Masao] Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Massachusetts Gen Hosp, Boston, MA USA. [Warren, H. Shaw] Harvard Med Sch, Dept Pediat & Med, Infect Dis Unit, Massachusetts Gen Hosp, Boston, MA USA. [Brown, Diane E.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. [Mikkola, Amy; Brown, Diane E.] Massachusetts Gen Hosp, Ctr Comparat Med, Boston, MA 02114 USA. [Jones, Caroline N.] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. RP Irimia, D (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, BioMEMS Resource Ctr, MGH CNY 114 16th St,1404, Boston, MA 02129 USA.; Irimia, D (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Dept Surg, MGH CNY 114 16th St,1404, Boston, MA 02129 USA. EM dirimia@hms.harvard.edu FU U.S. National Institutes of Health [GM092804]; Shriners Burns Institute [8700]; Defense Advanced Research Projects Agency (DARPA) [W911NF-13-1] FX Microfabrication work was performed at the BioMEMS Research Center (EB002503). This work was supported by grants from the U.S. National Institutes of Health (GM092804; to D.I.), Shriners Burns Institute (8700; to H.S.W.), and Defense Advanced Research Projects Agency (DARPA; W911NF-13-1; to H.S.W.). NR 42 TC 0 Z9 0 U1 5 U2 9 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 JUL PY 2016 VL 100 IS 1 BP 241 EP 247 DI 10.1189/jlb.5TA0715-310RR PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA DR2MI UT WOS:000379738200025 PM 26819316 ER PT J AU Kluk, MJ Lindsley, RC Aster, JC Lindeman, NI Szeto, D Hall, D Kuo, FC AF Kluk, Michael. J. Lindsley, R. Coleman Aster, Jon C. Lindeman, Neal. I. Szeto, David Hall, Dimity Kuo, Frank C. TI Validation and Implementation of a Custom Next-Generation Sequencing Clinical Assay for Hematologic Malignancies SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; MYELOPROLIFERATIVE NEOPLASMS; SOMATIC MUTATIONS; MYELODYSPLASTIC SYNDROMES; COHESIN COMPLEX; DIAGNOSTICS; INHIBITION; GENOME; CELL AB Targeted next-generation sequencing panels to identify genetic alterations in cancers are increasingly becoming an integral part of clinical practice. We report here the design, validation, and implementation of a comprehensive 95-gene next-generation sequencing panel targeted for hematologic malignancies that we named rapid heme panel. Rapid heme panel is amplicon based and covers hotspot regions of oncogenes and most of the coding regions of tumor suppressor genes. It is composed of 1330 amplicons and covers 175 kb of genomic sequence in total. Rapid heme panel's average coverage is 1500x with <5% of the amplicons with <50x coverage, and it reproducibly detects single nucleotide variants and small insertions/deletions at allele frequencies of >= 5%. Comparison with a capture-based next-generation sequencing assay showed that there is >95% concordance among a wide array of variants across a range of allele frequencies. Read count analyses that used rapid heme panel showed high concordance with karyotypic results when tumor content was >30%. The average turnaround time was 7 days over a 6-month span with an average volume of >= 40 specimens per week and a low sample fail rate (<= 1%), demonstrating its suitability for clinical application. C1 [Kluk, Michael. J.; Aster, Jon C.; Lindeman, Neal. I.; Szeto, David; Hall, Dimity; Kuo, Frank C.] Brigham & Womens Hosp, Ctr Adv Mol Diagnost, 75 Francis St, Boston, MA 02115 USA. [Lindsley, R. Coleman] Dana Farber Canc Inst, Dept Med Oncol, Div Hematol Malignancies, Boston, MA 02115 USA. RP Kuo, FC (reprint author), Brigham & Womens Hosp, Dept Pathol, Ctr Adv Mol Diagnost, 75 Francis St, Boston, MA 02115 USA. EM fkuo@partners.org FU Department of Pathology at Brigham and Women's Hospital FX Supported by internal funds dedicated for test validation in the laboratory through the Department of Pathology at Brigham and Women's Hospital for assay development. NR 32 TC 3 Z9 3 U1 1 U2 1 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 JUL PY 2016 VL 18 IS 4 BP 507 EP 515 DI 10.1016/j.jmoldx.2016.02.003 PG 9 WC Pathology SC Pathology GA DR0ZM UT WOS:000379635600005 PM 27339098 ER PT J AU Corey, VR Pisano, VD Halpern, JH AF Corey, Vicka Rael Pisano, Vincent D. Halpern, John H. TI Effects of 3,4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE PTSD; MDMA; talk therapy; patient utterances ID POSTTRAUMATIC-STRESS-DISORDER; PTSD; MDMA; EPIDEMIOLOGY; VETERANS; EFFICACY AB 3,4-Methylenedioxymethamphetamine (MDMA) administered as an adjunct to talk therapy influences patient speech content and increases improvement in treatment-resistant posttraumatic stress disorder (PTSD). Data came from the recordings of Mithoefer et al. (2011). In the third therapeutic session studied, patientswere assigned, double blind, to anMDMAor a placebo group. Condition-blind scorers listened to therapy recordings and scored utterances where patients initiated topics that were empathic (regarding others' emotions), entactic (requesting or appreciating physical touch), or ensuic (describing a change in their sense of themselves). Patients who received MDMA produced high levels of ensuic, empathic, and entactic utterances compared with those who received the placebo. Interrater discourse scoring was reliable. The relationship between the number of scored utterances and the Clinician Administered PTSD Scale scores measuring PTSD severity after the treatment was significant, and reanalysis grouped bimodally into "many" or "few" such utterances remained significant. MDMA assisted these patients in having meaningful and disorder-resolving thoughts and discourse in talk therapy. C1 [Corey, Vicka Rael; Halpern, John H.] Harvard Med Sch, Boston, MA USA. [Corey, Vicka Rael; Halpern, John H.] McLean Hosp, Div Alcohol & Drug Abuse, Lab Integrat Psychiat, 115 Mill St, Belmont, MA 02178 USA. [Pisano, Vincent D.] Massachusetts Gen Hosp, Clin Trials Network Inst, Boston, MA 02114 USA. RP Corey, VR (reprint author), 35 Kidder Ave, Somerville, MA 02144 USA. EM vcorey@mclean.harvard.edu NR 21 TC 0 Z9 0 U1 12 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0022-3018 EI 1539-736X J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD JUL PY 2016 VL 204 IS 7 BP 519 EP 523 DI 10.1097/NMD.0000000000000499 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DQ8GS UT WOS:000379447700006 PM 26998697 ER PT J AU Pronk, NP McLellan, DL McGrail, MP Olson, SM McKinney, ZJ Katz, JN Wagner, GR Sorensen, G AF Pronk, Nicolaas P. McLellan, Deborah L. McGrail, Michael P. Olson, Shawn M. McKinney, Zeke J. Katz, Jeffrey N. Wagner, Gregory R. Sorensen, Glorian TI Measurement Tools for Integrated Worker Health Protection and Promotion: Lessons Learned From the SafeWell Project SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID WORKPLACE HEALTH; BEHAVIOR-CHANGE; UNITED-STATES; CARE COSTS; SAFETY; ASSOCIATION; PROGRAMS; ORGANIZATIONS; INTERVENTIONS; PRODUCTIVITY AB Objectives: To describe (a) a conceptual approach, (b) measurement tools and data collection processes, (c) characteristics of an integrated feedback report and action plan, and (d) experiences of three companies with an integrated measurement approach to worker safety and health. Methods: Three companies implemented measurement tools designed to create an integrated view of health protection and promotion based on organizational-and individual-level assessments. Feedback and recommended actions were presented following assessments at baseline and 1-year follow-up. Measurement processes included group dialogue sessions, walk-through, online surveys, and focus groups. Results: The approach and measurement tools generated actionable recommendations and documented changes in the physical (eg, safety hazards) and psychosocial (eg, health and safety culture) work environment between baseline and 1-year follow-up. Conclusions: The measurement tools studied were feasible, acceptable, and meaningful to companies in the SafeWell study. C1 [Pronk, Nicolaas P.; Olson, Shawn M.; McKinney, Zeke J.] HealthPartners, Minneapolis, MN USA. [Pronk, Nicolaas P.; Olson, Shawn M.; McKinney, Zeke J.] HealthPartners Inst Educ & Res, Minneapolis, MN USA. [Pronk, Nicolaas P.; McLellan, Deborah L.; Katz, Jeffrey N.; Wagner, Gregory R.; Sorensen, Glorian] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [McGrail, Michael P.] Aspirus, Wausau, WI USA. [McLellan, Deborah L.; Sorensen, Glorian] Dana Farber Canc Inst, Boston, MA 02115 USA. [Katz, Jeffrey N.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Wagner, Gregory R.] NIOSH, Washington, DC USA. RP Pronk, NP (reprint author), HealthPartners, 8170 33rd Ave South, Bloomington, MN 55425 USA. EM nico.p.pronk@healthpartners.com FU National Institute for Occupational Safety and Health [U19 OH008861] FX This work was supported by a grant from the National Institute for Occupational Safety and Health (U19 OH008861) for the Harvard T.H. Chan School of Public Health Center for Work, Health and Well-being. NR 29 TC 1 Z9 1 U1 8 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1076-2752 EI 1536-5948 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD JUL PY 2016 VL 58 IS 7 BP 651 EP 658 DI 10.1097/JOM.0000000000000752 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DR0RB UT WOS:000379613500007 PM 27206128 ER PT J AU van de Vondervoort, I Poelmans, G Aschrafi, A Pauls, DL Buitelaar, JK Glennon, JC Franke, B AF van de Vondervoort, Ilse Poelmans, Geert Aschrafi, Armaz Pauls, David L. Buitelaar, Jan K. Glennon, Jeffrey C. Franke, Barbara TI An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive-compulsive disorder SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID GENOME-WIDE ASSOCIATION; DIABETES-MELLITUS; GENE; BEHAVIOR; EPIDEMIOLOGY; PROTEIN; MICE; PATHOPHYSIOLOGY; SYMPTOMATOLOGY; COMORBIDITY AB Background: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder with onset in childhood and is characterized by obsessions (recurrent, intrusive, persistent thoughts, impulses and/or ideas that often cause anxiety or distress) and compulsions (ritualized and stereotypic behaviours or mental acts that are often performed to relieve anxiety or distress associated with obsessions). Although OCD is a heritable disorder, its complex molecular etiology is poorly understood. Methods: We combined enrichment analyses and an elaborate literature review of the top-ranked genes emerging from the 2 published genome-wide association studies of OCD and candidate genes implicated through other evidence in order to identify biological processes that, when dysregulated, increase the risk for OCD. Results: The resulting molecular protein landscape was enriched for proteins involved in regulating postsynaptic dendritic spine formation - and hence synaptic plasticity -through insulin-dependent molecular signalling cascades. Limitations: This study is a first attempt to integrate molecuar information from different sources in order to identify biological mechanisms underlying OCD etiology. Our findings are constrained by the limited information from hypothesis-free studies and the incompleteness and existing limitations of the OCD literature and the gene function annotations of gene enrichment tools. As this study was solely based on in silico analyses, experimental validation of the provided hypotheses is warranted. Conclusion: Our work suggests a key role for insulin and insulin-related signalling in OCD etiology and - if confirmed by independent studies - could eventually pave the way for the development of novel OCD treatments. C1 [van de Vondervoort, Ilse; Poelmans, Geert; Buitelaar, Jan K.; Glennon, Jeffrey C.] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Cognit Neurosci, Nijmegen, Netherlands. [Poelmans, Geert; Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, POB 9101 HP 855, NL-6500 HB Nijmegen, Netherlands. [Poelmans, Geert] Radboud Univ Nijmegen, RIMLS, Donders Inst Brain Cognit & Behav, Dept Mol Anim Physiol, Nijmegen, Netherlands. [Aschrafi, Armaz] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neuroinformat, Nijmegen, Netherlands. [Pauls, David L.] Harvard Med Sch, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA USA. [Franke, Barbara] Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Psychiat, Nijmegen, Netherlands. [Buitelaar, Jan K.] Karakter Child & Adolescent Psychiat Univ Ctr, Nijmegen, Netherlands. RP Franke, B (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, POB 9101 HP 855, NL-6500 HB Nijmegen, Netherlands. EM Barbara.Franke@radboudumc.nl RI Franke, Barbara/D-4836-2009; Glennon, Jeffrey/D-2379-2013 OI Franke, Barbara/0000-0003-4375-6572; FU European Community [278948] FX The authors thank the families who made all the genetic studies of OCD possible and the many investigators whose work drives the OCD genetics field forward. The authors also thank the anonymous reviewers for their useful comments and suggestions regarding text revision. The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no278948 (TACTICS). This funding organization has had no involvement with the conception, design, data analysis and interpretation, review and/or any other aspects relating to this paper. NR 50 TC 2 Z9 2 U1 2 U2 4 PU CMA-CANADIAN MEDICAL ASSOC PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 5W8, CANADA SN 1180-4882 EI 1488-2434 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD JUL PY 2016 VL 41 IS 4 BP 280 EP 285 DI 10.1503/jpn.140327 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DR2RK UT WOS:000379751400010 PM 26854754 ER PT J AU Pedrelli, P Borsari, B Lipson, SK Heinze, JE Eisenberg, D AF Pedrelli, Paola Borsari, Brian Lipson, Sarah Ketchen Heinze, Justin E. Eisenberg, Daniel TI Gender Differences in the Relationships Among Major Depressive Disorder, Heavy Alcohol Use, and Mental Health Treatment Engagement Among College Students SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; SUBSTANCE USE BEHAVIORS; BINGE-DRINKING; QUESTIONNAIRE PHQ-9; SUICIDE PRONENESS; LATE ADOLESCENCE; UNITED-STATES; YOUNG-ADULTS; RISK-FACTORS; INJURY RISK AB Objective: Although major depressive disorder (MDD) and heavy episodic drinking (HED, 4+/5+ drinks in a single sitting for women/men) are common among young adults in college, the relationship between the two remains unclear. This study examined the association between MDD and HED in this population, the effect of gender on this association, and whether comorbid MDD and heavy alcohol use are associated with higher rates of mental health treatment engagement. Method: The study comprised 61,561 (65.3% female) undergraduate students who answered an online survey on depression, alcohol use, and treatment engagement in the past year. Hierarchical linear regressions examined the association between MDD and alcohol use (RED and peak blood alcohol concentration [pBAC]) and whether gender moderated these associations. Logistic regressions were then conducted to examine the influence of MDD, heavy alcohol use, and gender on treatment engagement. Results: Students with MDD reported more frequent HED and higher pBAC than did students without MDD; this was especially true for female students. Rates of treatment engagement were higher among women than men, among students with MDD than students without MDD, and among female students with HED than women without HED. Conclusions: The presence of an association between MDD and heavy alcohol use suggests the need for systematic screenings of both conditions. Low rates of treatment engagement in college students with MDD and heavy alcohol use calls for the development of strategies to engage this high-risk group in treatment. C1 [Pedrelli, Paola] Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. [Borsari, Brian] San Francisco Veteran Affairs Med Ctr, San Francisco, CA USA. [Borsari, Brian] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Lipson, Sarah Ketchen] Univ Michigan, Sch Educ, Ctr Study Higher & Postsecondary Educ, Ann Arbor, MI 48109 USA. [Lipson, Sarah Ketchen; Eisenberg, Daniel] Univ Michigan, Sch Publ Hlth, Dept Hlth Management & Policy, Ann Arbor, MI 48109 USA. [Heinze, Justin E.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. [Eisenberg, Daniel] Univ Michigan, Inst Social Res, Ctr Populat Studies, Ann Arbor, MI 48109 USA. RP Pedrelli, P (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Depress Clin Res Program, One Bowdoin Sq,6th Floor, Boston, MA 02114 USA. EM ppedrelli@mgh.harvard.edu FU National Institute on Alcohol Abuse and Alcoholism [K23AA020064, R01AA017427]; VISN1 Career Development Award [V1CDA2012-18] FX This study was supported by National Institute on Alcohol Abuse and Alcoholism Grants K23AA020064 (to Paola Pedrelli) and R01AA017427 (to Brian Borsari), and VISN1 Career Development Award V1CDA2012-18 (to Brian Borsari). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Alcohol Abuse and Alcoholism, the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 64 TC 0 Z9 0 U1 17 U2 25 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 1937-1888 EI 1938-4114 J9 J STUD ALCOHOL DRUGS JI J. Stud. Alcohol Drugs PD JUL PY 2016 VL 77 IS 4 BP 620 EP 628 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA DQ7HG UT WOS:000379376900017 PM 27340967 ER PT J AU Meyer, AND Murphy, DR Singh, H AF Meyer, Ashley N. D. Murphy, Daniel R. Singh, Hardeep TI Communicating Findings of Delayed Diagnostic Evaluation to Primary Care Providers SO JOURNAL OF THE AMERICAN BOARD OF FAMILY MEDICINE LA English DT Article DE Algorithms; Ambulatory Care Facilities; Communication; Control Groups; Electronic Health Records; Electronic Mail; Follow-Up Studies; Humans; Neoplasms; Primary Care Providers; Telephone ID ELECTRONIC HEALTH RECORDS; INFORMATION OVERLOAD; PATIENT; COMMON AB Background: We previously found that an intervention involving electronic algorithms to detect delays in follow-up of cancer-related abnormal or "red-flag" findings and communicating this information to primary care providers (PCPs) led to more timely diagnostic evaluation. In this study, we examined the effectiveness of various communication strategies to inform PCPs about the delayed follow-up. Methods: After identifying follow-up delays through electronic health record-based algorithms and record reviews, we communicated this information to PCPs using 3 escalating steps. First, we sent secure E-mails. If no evidence of follow-up was found in a medical record review after 1 week, we made up to 3 attempts to reach the PCPs or their nurses via telephone. If they could not be reached, we informed clinic directors as the third and final step. In this analysis, we evaluate PCPs' follow-up in response to these methods of communication. Results: A total of 733 patients with follow-up delays were identified (369 patients in the intervention group and 364 patients in the control group). Communicating information to PCPs about possible follow-up delays led to decreased times to diagnostic evaluation, but communication related to delays did not always lead to follow-up for the patients in the intervention group. Specifically, secure E-mails led to follow-up in 11.1% of cases (41 of 369), telephone calls led to follow-up in 68.6% of cases (225 of 328), and contacting clinic directors led to follow-up in 5 of 11 cases in which communication escalated to this level. Conclusion: Strategies to communicate to PCPs information on delayed follow-up of findings suspicious for cancer were useful, but not fail-safe. Additional back-up strategies, such as using case coordinators, might be needed. C1 Michael E De Bakey Vet Affairs Med Ctr, Houston Vet Affairs Ctr Innovat Qual Effectivenes, Houston, TX USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX USA. RP Meyer, AND (reprint author), Ctr Innovat Qual Effectiveness & Safety 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM ameyer@bcm.edu FU Agency for Health Care Research and Quality [R18HS017820, K08-HS022901, R01HS022087]; Houston Veterans Affairs Health Services Research & Development Center for Innovations in Quality, Effectiveness and Safety [CIN 13-413]; VA Health Services Research and Development Service [CRE 12-033, USA 14274]; VA National Center for Patient Safety FX This work was supported by the Agency for Health Care Research and Quality (grant no. R18HS017820) and the Houston Veterans Affairs Health Services Research & Development Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413). DRM is supported by a Mentored Career Development Award (grant K08-HS022901) from the Agency for Healthcare Research and Quality. HS is also supported by the VA Health Services Research and Development Service (CRE 12-033; Presidential Early Career Award for Scientists and Engineers USA 14274), the VA National Center for Patient Safety, and the Agency for Health Care Research and Quality (grant R01HS022087). NR 14 TC 1 Z9 1 U1 3 U2 3 PU AMER BOARD FAMILY MEDICINE PI LEXINGTON PA 2228 YOUNG DR, LEXINGTON, KY 40505 USA SN 1557-2625 EI 1558-7118 J9 J AM BOARD FAM MED JI J. Am. Board Fam. Med. PD JUL-AUG PY 2016 VL 29 IS 4 BP 469 EP 473 DI 10.3122/jabfm.2016.04.150363 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA DR0MC UT WOS:000379600600008 PM 27390378 ER PT J AU Taudorf, EH Lerche, CM Erlendsson, AM Philipsen, PA Hansen, SH Janfelt, C Paasch, U Anderson, RR Haedersdal, M AF Taudorf, E. H. Lerche, C. M. Erlendsson, A. M. Philipsen, P. A. Hansen, S. H. Janfelt, C. Paasch, U. Anderson, R. R. Haedersdal, M. TI Fractional laser-assisted drug delivery: Laser channel depth influences biodistribution and skin deposition of methotrexate SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE Er:Yag laser; fluorescence microscopy; Franz skin permeability Cells; high performance liquid chromatography; laser-assisted drug delivery ID ERBIUM-YAG LASER; TRANSDERMAL DELIVERY; INTRALESIONAL METHOTREXATE; TOPICAL METHOTREXATE; PHOTODYNAMIC THERAPY; PSORIASIS-VULGARIS; PHARMACOKINETICS; KERATOACANTHOMA; ABLATION; GEL AB Background and ObjectiveAblative fractional laser (AFXL) facilitates delivery of topical methotrexate (MTX). This study investigates impact of laser-channel depth on topical MTX-delivery. Materials and MethodsMTX (1% [w/v]) diffused for 21 hours through AFXL-exposed porcine skin in in vitro Franz Cells (n=120). A 2,940nm AFXL generated microscopic ablation zones (MAZs) into epidermis (11mJ/channel, MAZ-E), superficial-dermis (26mJ/channel, MAZ-DS), and mid-dermis (256mJ/channel, MAZ-DM). High performance liquid chromatography (HPLC) was used to quantify MTX deposition in full-thickness skin, biodistribution profiles at specific skin levels, and transdermal permeation. Fluorescence microscopy was used to visualize UVC-activated MTX-fluorescence (254nm) and semi-quantify MTX distribution in skin. ResultsAFXL increased topical MTX-delivery (P<0.001). Without laser exposure, MTX-concentration in full-thickness skin was 0.07mg/cm(2), increasing sixfold (MAZ-E), ninefold (MAZ-DS), and 11-fold (MAZ-DM) after AFXL (P<0.001). Deeper MAZs increased MTX-concentrations in all skin layers (P<0.038) and favored maximum accumulation in deeper skin layers (MAZ-E: 1.85mg/cm(3) at 500m skin-level vs. MAZ-DM: 3.75mg/cm(3) at 800m, P=0.002). Ratio of skin deposition versus transdermal permeation remained constant, regardless of MAZ depth (P=0.172). Fluorescence intensities confirmed MTX biodistribution through coagulation zones and into surrounding skin, regardless of thickness of coagulation zones (6-47m, P0.438). ConclusionAFXL greatly increases topical MTX-delivery. Deeper MAZs deliver higher MTX-concentrations than superficial MAZs, which indicates that laser channel depth may be important for topical delivery of hydrophilic molecules. Lasers Surg. Med. 48:519-529, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Taudorf, E. H.; Lerche, C. M.; Erlendsson, A. M.; Philipsen, P. A.; Haedersdal, M.] Univ Copenhagen, Bispebjerg Univ Hosp, Dept Dermatol, D-92,Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. [Hansen, S. H.; Janfelt, C.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2400 Copenhagen NV, Denmark. [Paasch, U.] Univ Leipzig, Dept Dermatol, Div Dermatopathol Aesthet & Laserdermatol, D-04109 Leipzig, Germany. [Anderson, R. R.; Haedersdal, M.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. RP Taudorf, EH (reprint author), Univ Copenhagen, Bispebjerg Univ Hosp, Dept Dermatol, D-92,Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. EM ehtaudorf@dadlnet.dk FU Pantec Biosolutions AG FX Merete Haedersdal received a research grant from Pantec Biosolutions AG. The company has had no influence on study design, study conduction or manuscript preparation. All other authors state no conflicts of interest. NR 45 TC 1 Z9 1 U1 9 U2 9 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 JUL PY 2016 VL 48 IS 5 BP 519 EP 529 DI 10.1002/lsm.22484 PG 11 WC Dermatology; Surgery SC Dermatology; Surgery GA DQ9GQ UT WOS:000379518800009 PM 26846733 ER PT J AU Senthil-Kumar, P Ni, T Randolph, MA Velmahos, GC Kochevar, IE Redmond, RW AF Senthil-Kumar, Prabhu Ni, Tao Randolph, Mark A. Velmahos, George C. Kochevar, Irene E. Redmond, Robert W. TI A light-activated amnion wrap strengthens colonic anastomosis and reduces peri-anastomotic adhesions SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE rose bengal; photochemistry; anastomosis; colon; crosslinking; amnion; anastomotic leak ID PHOTOCHEMICAL KERATODESMOS; CORNEAL INCISIONS; FIBRIN SEALANT; REPAIR; MODEL; SKIN; RAT; OMENTOPLASTY; MEMBRANE; DEFECTS AB Background and ObjectiveColonic anastomotic failure is a dreaded complication, and multiple surgical techniques have failed to eliminate it. Photochemical tissue bonding (PTB) is a method of sealing tissue surfaces by light-activated crosslinking. We evaluated if a human amniotic membrane (HAM), sealed over the anastomotic line by PTB, increases the anastomotic strength. Study DesignSprague-Dawley rats underwent midline laparotomy followed by surgical transection of the left colon. Animals were randomized to colonic anastomosis by one of the following methods (20 per group): single-layer continuous circumferential suture repair (SR); SR with a HAM wrap attached by suture (SR+HAM-S); SR with HAM bonded photochemically over the anastomotic site using 532nm light (SR+HAM-PTB); approximation of the bowel ends with only three sutures and sealing with HAM-PTB (3+ HAM-PTB). A control group underwent laparotomy alone with no colon resection (NR). Sub-groups (n=10) were sacrificed at days 3 and 7 post-operatively and adhesions were evaluated. A 6cm section of colon was then removed and strength of anastomosis evaluated by burst pressure (BP) measurement. ResultsA fourfold increase in BP was observed in the SR+HAM-PTB group compared to suture repair alone (943 vs. 25 +/- 8mmHg, P<0.0001) at day 3. At day 7 the burst pressures were 165 +/- 40 and 145 +/- 31mmHg (P=1), respectively. A significant decrease in peri-anastomotic adhesions was observed in the SR+HAM-PTB group compared to the SR group at both time points (P<0.001). ConclusionSealing sutured colonic anastomotic lines with HAM-PTB increases the early strength of the repair and reduces peri-anastomotic adhesions. Lasers Surg. Med. 48:530-537, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Senthil-Kumar, Prabhu; Ni, Tao; Kochevar, Irene E.; Redmond, Robert W.] Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Their 218, Boston, MA 02114 USA. [Senthil-Kumar, Prabhu; Randolph, Mark A.] Massachusetts Gen Hosp, Dept Surg, Plast Surg Res Lab, Boston, MA 02114 USA. [Ni, Tao] Shanghai Jiao Tong Univ, Dept Burns & Plast Surg, Peoples Hosp 3, Shanghai 201900, Peoples R China. [Ni, Tao] Shanghai Jiao Tong Univ, Inst Traumat Med, Sch Med, Shanghai 201900, Peoples R China. [Velmahos, George C.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. RP Redmond, RW (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Wellman Ctr Photomed, Their 218, Boston, MA 02114 USA. EM redmond@helix.mgh.harvard.edu FU CIMIT [W81XWH-09-2-0001] FX Contract grant sponsor: CIMIT; Contract grant number: W81XWH-09-2-0001. NR 35 TC 0 Z9 0 U1 3 U2 5 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 JUL PY 2016 VL 48 IS 5 BP 530 EP 537 DI 10.1002/lsm.22507 PG 8 WC Dermatology; Surgery SC Dermatology; Surgery GA DQ9GQ UT WOS:000379518800010 PM 26996284 ER PT J AU Kositratna, G Hibert, ML Jaspan, M Welford, D Manstein, D AF Kositratna, Garuna Hibert, Matthew Louis Jaspan, Martin Welford, David Manstein, Dieter TI Effects of deviation from focal plane on lesion geometry for ablative fractional photothermolysis SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE focal plane; deviation; ablative fractional resurfacing; ablative fractional photothermolysis; complications; Rayleigh range; fill factor; thermal injury; lesion geometry ID ASSISTED DRUG-DELIVERY; RESURFACING DEVICE; TECHNOLOGY; ASIANS AB Background and ObjectiveFractional Photothermolysis (FP) is a method of skin treatment that generates a thermal damage pattern consisting of multiple columns of thermal damage, also known as microscopic treatment zones (MTZs). They are very small in diameter and are generated by application of highly focused laser beams. In order to obtain the smallest spot size, the treatment should be performed in the focal plane. Any deviation from the focal plane (DFP) results in an increase of spot size. FP devices typically utilize distance holders in order to facilitate exposures at this specific location. In spite of the use of distance holders, DFP can occur. In particular, variations of contact pressure to the skin surface and anatomical treatment areas of high surface curvature may be prone to DFP during FP treatments. The impact of such distance variation on lesion geometry, such as depth and diameter of the thermal injury, has not previously been evaluated. The objective of this study was to investigate the relation between DFP and the resulting lesion geometry for a selected ablative fractional device. Material and MethodsA handpiece of an ablative fractional laser (DeepFX, UltraPulse Encore, Lumenis, Yokneam, Israel) was mounted to a rigid stand. Full thickness human skin obtained from abdominoplasty was mounted to a separate stand perpendicular to the handpiece. The tissue stand allowed the distance between the handpiece and the tissue to be adjusted to produce a variation up to3mm from the focal plane. A 1x1cm(2) scanning area of 169 MTZs, 50mJ energy per MTZ, 120m nominal spot size, was applied at -3, -2, -1, 0, +1, +2, and +3mm deviated from the focal plane. Minus (-) and plus (+) signs indicate decreasing and increasing distance between the handpiece and the tissue, respectively. Depth and diameter of the laser induced tissue lesions were assessed and quantified. ResultsDFPs produced a significant alteration of the lesion geometry. DFPs of -3, -2, -1, 0, +1, +2, +3mm resulted in average lesion depths of 1,020 (-40%), 1,180 (-31%), 1,400 (-18%), styled-content style="text-decoration:underline"1,700 (0%)styled-content, 1,620 (-5%), 780 (-55%), 680 (-60%) mu m, and average lesion diameters of 314 (+26%), 311 (+25%), 273 (+10%), styled-content style="text-decoration:underline"248 (0%)styled-content, 256 (+3%), 316 (+27%), 359 (+44%) mu m, respectively. The underlined values represent the focal plane. The percentage changes relative to values at focal plane are in parentheses. ConclusionsA relatively minor DFP has a marked impact on the thermal injury profile, including lesion depth and diameter, of the laser-exposed tissue. Such marked changes of the thermal injury profile might affect the wound healing, safety, and efficacy of ablative fractional resurfacing procedures. Clinicians should carefully maintain the focal plane during ablative fractional treatment for reproducible results. The presented data are device specific and the clinical impact of such alteration of thermal injury profile warrants further investigation. Lasers Surg. Med. 48:555-561, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Kositratna, Garuna; Hibert, Matthew Louis; Manstein, Dieter] Massachusetts Gen Hosp, Res Inst, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA 02129 USA. [Kositratna, Garuna; Manstein, Dieter] Harvard Med Sch, Boston, MA 02115 USA. [Jaspan, Martin; Welford, David] Endeavour Laser Technol Inc, Hathorne, MA 01937 USA. RP Kositratna, G (reprint author), Massachusetts Gen Hosp, Res Inst, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA 02129 USA. EM gkositratna@mgh.harvard.edu NR 20 TC 0 Z9 0 U1 1 U2 1 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 JUL PY 2016 VL 48 IS 5 BP 555 EP 561 DI 10.1002/lsm.22481 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA DQ9GQ UT WOS:000379518800013 PM 26842919 ER PT J AU Amin, RM Bhayana, B Hamblin, MR Dai, TH AF Amin, Rehab M. Bhayana, Brijesh Hamblin, Michael R. Dai, Tianhong TI Antimicrobial blue light inactivation of Pseudomonas aeruginosa by photo-excitation of endogenous porphyrins: In vitro and in vivo studies SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE Pseudomonas aeruginosa; blue light; endogenous porphyrins; drug resistance; mouse ID RESISTANT ACINETOBACTER-BAUMANNII; PHOTODYNAMIC THERAPY; ANTIBIOTIC-RESISTANCE; WOUND INFECTIONS; MICE; MODEL; 21ST-CENTURY; PROPHYLAXIS; BACTERIA AB Pseudomonas aeruginosa is among the most common pathogens that cause nosocomial infections and is responsible for about 10% of all hospital-acquired infections. In the present study, we investigated the potential development of tolerance of P. aeruginosa to antimicrobial blue light by carrying 10 successive cycles of sublethal blue light inactivation. The high-performance liquid chromatographic (HPLC) analysis was performed to identify endogenous porphyrins in P. aeruginosa cells. In addition, we tested the effectiveness of antimicrobial blue light in a mouse model of nonlethal skin abrasion infection by using a bioluminescent strain of P. aeruginosa. The results demonstrated that no tolerance was developed to antimicrobial blue light in P. aeruginosa after 10 cycles of sub-lethal inactivation. HPLC analysis showed that P. aeruginosa is capable of producing endogenous porphyrins in particularly, coproporphyrin III, which are assumed to be responsible for the photodynamic effects of blue light alone. P. aeruginosa infection was eradicated by antimicrobial blue light alone (48J/cm(2)) without any added photosensitizer molecules in the mouse model. In conclusion, endogenous photosensitization using blue light should gain considerable attention as an effective and safe alternative antimicrobial therapy for skin infections. Lasers Surg. Med. 48:562-568, 2016. (c) 2016 Wiley Periodicals, Inc. C1 [Amin, Rehab M.; Bhayana, Brijesh; Hamblin, Michael R.; Dai, Tianhong] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Amin, Rehab M.; Bhayana, Brijesh; Hamblin, Michael R.; Dai, Tianhong] Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. [Amin, Rehab M.] Cairo Univ, Natl Inst Laser Enhanced Sci, Giza 12613, Egypt. RP Amin, RM (reprint author), Cairo Univ, Natl Inst Laser Enhanced Sci, Giza 12613, Egypt.; Dai, TH (reprint author), Harvard Med Sch, Boston, MA 02114 USA. EM rehabamin@niles.edu.eg; rehabamin@niles.edu.eg FU ASLMS [BS.F04.14]; NIH [R21AI109172]; Binational Fulbright Commission in Egypt [AY2013-2014]; US NIH [R01AI050875] FX Contract grant sponsor: ASLMS; Contract grant number: BS.F04.14; Contract grant sponsor: NIH; Contract grant number: R21AI109172; Contract grant sponsor: Binational Fulbright Commission in Egypt; Contract grant number: AY2013-2014; Contract grant sponsor: US NIH grant; Contract grant number: R01AI050875. NR 28 TC 2 Z9 2 U1 7 U2 12 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 JUL PY 2016 VL 48 IS 5 BP 562 EP 568 DI 10.1002/lsm.22474 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA DQ9GQ UT WOS:000379518800014 PM 26891084 ER PT J AU Bhatnagar, B Blachly, JS Kohlschmidt, J Eisfeld, AK Volinia, S Nicolet, D Carroll, AJ Block, AW Kolitz, JE Stone, RM Mrozek, K Byrd, JC Bloomfield, CD AF Bhatnagar, B. Blachly, J. S. Kohlschmidt, J. Eisfeld, A-K Volinia, S. Nicolet, D. Carroll, A. J. Block, A. W. Kolitz, J. E. Stone, R. M. Mrozek, K. Byrd, J. C. Bloomfield, C. D. TI Clinical features and gene- and microRNA-expression patterns in adult acute leukemia patients with t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3) SO LEUKEMIA LA English DT Letter ID ACUTE MYELOID-LEUKEMIA; PROFILES C1 [Bhatnagar, B.; Blachly, J. S.; Byrd, J. C.; Bloomfield, C. D.] Dept Internal Med, Div Hematol, Columbus, OH 43210 USA. [Bhatnagar, B.; Blachly, J. S.; Kohlschmidt, J.; Eisfeld, A-K; Nicolet, D.; Mrozek, K.; Byrd, J. C.; Bloomfield, C. D.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Kohlschmidt, J.; Nicolet, D.] Mayo Clin, Alliance Clin Trials Oncol Stat, Rochester, MN USA. [Kohlschmidt, J.; Nicolet, D.] Mayo Clin, Ctr Data, Rochester, MN USA. [Volinia, S.] Univ Ferrara, Dept Morphol Surg & Expt Med, Ferrara, Italy. [Carroll, A. J.] Univ Alabama Birmingham, Birmingham, AL USA. [Block, A. W.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Kolitz, J. E.] Hofstra North Shore Long Isl Jewish Sch Med, Monter Canc Ctr, Lake Success, NY USA. [Stone, R. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bhatnagar, B (reprint author), Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.; Bhatnagar, B (reprint author), Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. EM bhavana.bhatnagar@osumc.edu; clara.bloomfield@osumc.edu FU NCI NIH HHS [P30 CA016058, P50 CA140158, U10 CA180821, U10 CA180850, U10 CA180855, U10 CA180861, U10 CA180867, U10 CA180882, U24 CA114725] NR 15 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 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD JUL PY 2016 VL 30 IS 7 BP 1586 EP 1589 DI 10.1038/leu.2015.345 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA DQ9BC UT WOS:000379504400017 PM 26669971 ER PT J AU Forman, DE Fix, GM McDannold, S McIntosh, N Schopfer, DW Whooley, MA Charns, MP AF Forman, Daniel E. Fix, Gemmae M. McDannold, Sarah McIntosh, Nathalie Schopfer, David W. Whooley, Mary A. Charns, Martin P. TI Decisive Bearing of Organizational Dynamics on the Application and Success of Hospital-Based Cardiac Rehabilitation SO MAYO CLINIC PROCEEDINGS LA English DT Letter ID HEART-ASSOCIATION; DISEASE C1 [Forman, Daniel E.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15238 USA. [Forman, Daniel E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. [Forman, Daniel E.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Fix, Gemmae M.; McDannold, Sarah] Edith Nourse Rogers Mem Vet Hosp, Bedford, MA USA. [Fix, Gemmae M.; McDannold, Sarah] Boston Univ, Sch Publ Hlth, Boston, MA USA. [McIntosh, Nathalie] VA Boston Healthcare Syst, Boston, MA USA. [Schopfer, David W.; Whooley, Mary A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Schopfer, David W.; Whooley, Mary A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Charns, Martin P.] Boston Univ, Sch Publ Hlth, VA Boston Healthcare Syst, Boston, MA USA. RP Forman, DE (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15238 USA.; Forman, DE (reprint author), Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA.; Forman, DE (reprint author), Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 6 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 JUL PY 2016 VL 91 IS 7 BP 975 EP + DI 10.1016/j.mayocp.2016.04.019 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DR0BE UT WOS:000379572200026 PM 27378045 ER PT J AU Steensma, DP Kyle, RA Shampo, MA AF Steensma, David P. Kyle, Robert A. Shampo, Marc A. TI Elizabeth Blackburn and Maintenance of Telomeres SO MAYO CLINIC PROCEEDINGS LA English DT Biographical-Item C1 [Steensma, David P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kyle, Robert A.; Shampo, Marc A.] Mayo Clin, Rochester, MN USA. RP Steensma, DP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 1 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 JUL PY 2016 VL 91 IS 7 BP E105 EP E105 DI 10.1016/j.mayocp.2016.01.026 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DR0BE UT WOS:000379572200004 PM 27378050 ER PT J AU Sweet, RA MacDonald, ML Kirkwood, CM Ding, Y Schempf, T Jones-Laughner, J Kofler, J Ikonomovic, MD Lopez, OL Garver, ME Fitz, NF Koldamova, R Yates, NA AF Sweet, Robert A. MacDonald, Matthew L. Kirkwood, Caitlin M. Ding, Ying Schempf, Tadhg Jones-Laughner, Jackie Kofler, Julia Ikonomovic, Milos D. Lopez, Oscar L. Garver, Megan E. Fitz, Nicholas F. Koldamova, Radosveta Yates, Nathan A. TI Apolipoprotein E*4 (APOE*4) Genotype Is Associated with Altered Levels of Glutamate Signaling Proteins and Synaptic Coexpression Networks in the Prefrontal Cortex in Mild to Moderate Alzheimer Disease SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID AMYLOID-BETA; COGNITIVE IMPAIRMENT; ELDERLY SUBJECTS; TRANSGENIC MICE; FRONTAL-CORTEX; EXPRESSION; PATHOLOGY; DEFICITS; ISOFORM; BRAIN AB It has been hypothesized that Alzheimer disease (AD) is primarily a disorder of the synapse. However, assessment of the synaptic proteome in AD subjects has been limited to a small number of proteins and often included subjects with end-stage pathology. Protein from prefrontal cortex gray matter of 59 AD subjects with mild to moderate dementia and 12 normal elderly subjects was assayed using targeted mass spectrometry to quantify 191 synaptically expressed proteins. The profile of synaptic protein expression clustered AD subjects into two groups. One of these was characterized by reduced expression of glutamate receptor proteins, significantly increased synaptic protein network coexpression, and associated with Apolipoprotein E*4 (APOE*4) carrier status. The second group, by contrast, showed few differences from control subjects. A subset of AD subjects had altered prefrontal cortex synaptic proteostasis for glutamate receptors and their signaling partners. Efforts to therapeutically target glutamate receptors in AD may have outcomes dependent on APOE*4 genotype. C1 [Sweet, Robert A.; MacDonald, Matthew L.; Kirkwood, Caitlin M.; Schempf, Tadhg; Lopez, Oscar L.; Garver, Megan E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Ding, Ying] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. [Jones-Laughner, Jackie; Yates, Nathan A.] Univ Pittsburgh, Dept Cell Biol, Pittsburgh, PA USA. [Kofler, Julia] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Sweet, Robert A.; Ikonomovic, Milos D.; Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. [Fitz, Nicholas F.; Koldamova, Radosveta] Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA USA. [Sweet, Robert A.] VISN 4 Mental Illness Res Educ & Clin Ctr MIRECC, Pittsburgh, PA USA. [Ikonomovic, Milos D.] VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. RP Sweet, RA (reprint author), Biomedical Sci Tower,Rm W-1645,3811 OHara St, Pittsburgh, PA 15213 USA.; Sweet, RA (reprint author), Biomed Sci Tower,Rm W-1645,Lothrop & Terrace St, Pittsburgh, PA 15213 USA. EM sweetra@upmc.edu FU VAPHS [BX000452]; [MH16804]; [AG05133]; [AG014449]; [AG027224]; [AG037481]; [AG044490]; [P30CA047904] FX This work was supported by grants MH16804 (MLM), AG05133 (OLL), AG014449 (MDI), AG027224 (RAS), AG037481 (RK), AG044490 (NFF), and VAPHS grant BX000452 (RAS). The Biomedical Mass Spectrometry Center and UPCI Cancer Proteomics Facility are supported in part by award P30CA047904. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, the Department of Veterans Affairs, or the United States Government. NR 53 TC 0 Z9 0 U1 3 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUL PY 2016 VL 15 IS 7 BP 2252 EP 2262 DI 10.1074/mcp.M115.056580 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA DQ9SS UT WOS:000379550200005 PM 27103636 ER PT J AU Gwathmey, KG Conaway, MR Sadjadi, R Joshi, A Barnett, C Bril, V Ng, E David, W Gable, K Guptill, JT Hobson-Webb, LD Dineen, J Hehir, M Brannagan, TH Byun, E Adler, M Burns, TM AF Gwathmey, Kelly G. Conaway, Mark R. Sadjadi, Reza Joshi, Amruta Barnett, Carolina Bril, Vera Ng, Eduardo David, William Gable, Karissa Guptill, Jeffrey T. Hobson-Webb, Lisa D. Dineen, Jennifer Hehir, Michael Brannagan, Thomas H. Byun, Esther Adler, Margaret Burns, Ted M. TI Construction and validation of the chronic acquired polyneuropathy patient-reported index (CAP-PRI): A disease-specific, health-related quality-of-life instrument SO MUSCLE & NERVE LA English DT Article DE CAP-PRI; chronic inflammatory demyelinating polyneuropathy; immune-mediated polyneuropathy; patient-reported outcome; quality of life ID INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; TRIAL; ICE AB Introduction: Generic health-related quality-of-life (HRQOL) patient-reported outcome measures have been used in patients with chronic immune-mediated polyneuropathies. We have created a disease-specific HRQOL instrument. Methods: The chronic acquired polyneuropathy patient-reported index (CAP-PRI) was developed and validated in multiple steps. Items were initially generated through patient and specialist input. The performance of the preliminary 20 items was analyzed via a prospective, 5-center study involving chronic immune-mediated polyneuropathy patients. Results: Data analysis suggested modification to a 15-item scale with 3 response categories rather than 5. The final CAP-PRI was validated in another prospective, 5-center study. The CAP-PRI appeared to be a unidimensional outcome measure that fit the Rasch model in our multicenter cohort. It correlated appropriately with outcome measures commonly used in this patient population. Conclusions: The CAP-PRI is a simple disease-specific HRQOL measure that appears to be useful for clinical care and possibly also for clinical trials. Muscle Nerve54: 9-17, 2016 C1 [Gwathmey, Kelly G.; Sadjadi, Reza; Joshi, Amruta; Burns, Ted M.] Univ Virginia, Dept Neurol, POB 800394, Charlottesville, VA 22908 USA. [Conaway, Mark R.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA. [Barnett, Carolina; Bril, Vera; Ng, Eduardo] Univ Toronto, Div Neurol, Dept Med, Ellen & Martin Prosserman Ctr Neuromuscular Dis, Toronto, ON, Canada. [Barnett, Carolina; Bril, Vera; Ng, Eduardo] Univ Hlth Network, Toronto, ON, Canada. [David, William] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA USA. [Gable, Karissa; Guptill, Jeffrey T.; Hobson-Webb, Lisa D.] Duke Univ, Med Ctr, Dept Neurol, Durham, NC USA. [Dineen, Jennifer] Harvard Med Sch, Dept Neurol, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Hehir, Michael] Univ Vermont, Dept Neurol, Burlington, VT USA. [Brannagan, Thomas H.] Columbia Univ, Dept Neurol, New York, NY USA. [Byun, Esther] Jerry L Pettis VA Med Ctr, Dept Neurol, Loma Linda, CA USA. [Adler, Margaret] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. RP Burns, TM (reprint author), Univ Virginia, Dept Neurol, POB 800394, Charlottesville, VA 22908 USA. EM tmb8r@virginia.edu FU NINDS NIH HHS [K23 NS085049] NR 18 TC 1 Z9 1 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0148-639X EI 1097-4598 J9 MUSCLE NERVE JI Muscle Nerve PD JUL PY 2016 VL 54 IS 1 BP 9 EP 17 DI 10.1002/mus.24985 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DQ2HP UT WOS:000379023700002 PM 26600438 ER PT J AU Liang, F Zhang, YY Hong, WY Dong, YL Xie, ZC Quan, QM AF Liang, Feng Zhang, Yiying Hong, Wooyoung Dong, Yuanlin Xie, Zhongcong Quan, Qimin TI Direct Tracking of Amyloid and Tau Dynamics in Neuroblastoma Cells Using Nanoplasmonic Fiber Tip Probes SO NANO LETTERS LA English DT Article DE nanoplasmonic fiber tip probe (nFTP); protein dynamics; A beta; tau; Alzheimer's disease; photonic crystal nanosensor ID CRYSTAL NANOBEAM CAVITIES; ALZHEIMERS-DISEASE; SINGLE-CELL; LIVING CELLS; HYPOTHESIS; HYPERPHOSPHORYLATION; PHOSPHOPROTEOMICS; MECHANISMS; STRATEGIES; BIOPROBES AB Amyloid plaques and neurofibrillary tangles are the pathological hallmarks of Alzheimer's disease. However, there has been a long-standing discussion on the dynamic relations between A beta and tau proteins, partially due to the lack of a tool to track protein dynamics in individual live neurons' at the early stage of A beta generation and tau phosphorylation. Here, we developed nanoplasmonic fiber tip probe (nFTP) technology to simultaneously monitor A beta 42 generation and 0 tau phosphorylation (at serine 262) in living, single neuroblastoma cells over 12 h. We observed that A beta 42 generation, under clinically relevant anesthetic treatment, preceded tau phosphorylation, which then facilitated A beta(4)2 generation. This observation is also supported by measuring proteins in cell lysates using the ultrasensitive label-free photonic crystal nanosensors. nFTP therefore provides an advanced method to investigate protein expression and post-translational modification in live cells and determine outcomes of intervention of Alzheimer's disease and other neurodegenerative disorders. C1 [Liang, Feng; Hong, Wooyoung; Quan, Qimin] Harvard Univ, Rowland Inst, Cambridge, MA 02142 USA. [Zhang, Yiying; Dong, Yuanlin; Xie, Zhongcong] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA. [Zhang, Yiying; Dong, Yuanlin; Xie, Zhongcong] Harvard Med Sch, Charlestown, MA 02129 USA. [Hong, Wooyoung] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RP Quan, QM (reprint author), Harvard Univ, Rowland Inst, Cambridge, MA 02142 USA.; Xie, ZC (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Geriatr Anesthesia Res Unit, Charlestown, MA 02129 USA.; Xie, ZC (reprint author), Harvard Med Sch, Charlestown, MA 02129 USA. EM zxie@mgh.harvard.edu; quan@rowland.harvard.edu RI liang, feng/S-4539-2016 FU Rowland Junior Fellowship Award at Rowland Institute at Harvard University, Cambridge, Massachusetts; National Institutes of Health, Bethesda, Maryland [R01 GM088801, R01 AG041274, R01 HD086977] FX The authors are thankful for helpful discussions with Diane Schaak at Rowland Institute at Harvard University. The authors thank Fang Fang and Lining Huang from Massachusetts General Hospital and Harvard Medical School for their help in harvesting cortex neurons of mice. The cost of isoflurane was generously provided by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School. The research was supported in part by the Rowland Junior Fellowship Award at Rowland Institute at Harvard University, Cambridge, Massachusetts (to Q.Q.), and in part by R01 GM088801, R01 AG041274, and R01 HD086977 from the National Institutes of Health, Bethesda, Maryland (to Z.X.). NR 36 TC 1 Z9 1 U1 11 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 EI 1530-6992 J9 NANO LETT JI Nano Lett. PD JUL PY 2016 VL 16 IS 7 BP 3989 EP 3994 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DR3HL UT WOS:000379794200004 PM 27266855 ER PT J AU Richards, DJ Tan, Y Coyle, R Li, Y Xu, RY Yeung, N Parker, A Menick, DR Tian, BZ Mei, Y AF Richards, Dylan J. Tan, Yu Coyle, Robert Li, Yang Xu, Ruoyu Yeung, Nelson Parker, Arran Menick, Donald R. Tian, Bozhi Mei, Ying TI Nanowires and Electrical Stimulation Synergistically Improve Functions of hiPSC Cardiac Spheroids SO NANO LETTERS LA English DT Article DE Silicon nanowires; electrical stimulation; cardiac spheroids; human induced pluripotent stem cell-derived cardiomyocytes ID CELL-DERIVED CARDIOMYOCYTES; PLURIPOTENT STEM-CELLS; MYOCARDIAL-INFARCTION; HEART-FAILURE; IN-VITRO; GAP-JUNCTIONS; RAT HEARTS; MATURATION; TISSUE; EXPRESSION AB The advancement of human induced pluripotent stem-cell-derived cardiomyocyte (hiPSC-CM) technology has shown promising potential to provide a patient-specific, regenerative cell therapy strategy to treat cardiovascular disease. Despite the progress, the unspecific, underdeveloped phenotype of hiPSC-CMs has shown arrhythmogenic risk and limited functional improvements after transplantation. To address this, tissue engineering strategies have utilized both exogenous and endogenous stimuli to accelerate the development of hiPSC-CMs. Exogenous electrical stimulation provides a biomimetic pacemaker-like stimuli that has been shown to advance the electrical properties of tissue engineered cardiac constructs. Recently, we demonstrated that the incorporation of electrically conductive silicon nanowires to hiPSC cardiac spheroids led to advanced structural and functional development of hiPSC-CMs by improving the endogenous electrical microenvironment. Here, we reasoned that the enhanced endogenous electrical microenvironment of nanowired hiPSC cardiac spheroids would synergize with exogenous electrical stimulation to further advance the functional development of nanowired hiPSC cardiac spheroids. For the first time, we report that the combination of nanowires and electrical stimulation enhanced cell cell junction formation, improved development of contractile machinery, and led to a significant decrease in the spontaneous beat rate of hiPSC cardiac spheroids. The advancements made here address critical challenges for the use of hiPSC-CMs in cardiac developmental and translational research and provide an advanced cell delivery vehicle for the next generation of cardiac repair. C1 [Richards, Dylan J.; Tan, Yu; Coyle, Robert; Li, Yang; Yeung, Nelson; Parker, Arran; Mei, Ying] Clemson Univ, Bioengn Dept, Clemson, SC 29634 USA. [Xu, Ruoyu; Tian, Bozhi] Univ Chicago, James Franck Inst, Dept Chem, Chicago, IL 60637 USA. [Xu, Ruoyu; Tian, Bozhi] Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. [Menick, Donald R.] Med Univ South Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, Charleston, SC 29425 USA. [Mei, Ying] Med Univ South Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. [Menick, Donald R.] Med Univ South Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Mei, Y (reprint author), Clemson Univ, Bioengn Dept, Clemson, SC 29634 USA.; Mei, Y (reprint author), Med Univ South Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA. EM mei@clemson.edu FU National Institutes of Health [8P20 GM103444, U54 GM104941]; Clemson University; National Science Foundation [NSF - EPS-0903795]; NIH Cardiovascular Training Grant [T32 HL007260]; US Department of Veterans Affairs Merit Review [I01 BX002327]; NIH-NIGMS [P30 GM103342] FX The work is supported by the National Institutes of Health (8P20 GM103444, U54 GM104941), the startup funds from Clemson University, the National Science Foundation (NSF - EPS-0903795), the NIH Cardiovascular Training Grant (T32 HL007260), and US Department of Veterans Affairs Merit Review (I01 BX002327). This study used the services of the Morphology, Imaging, and Instrumentation Core, which is supported by NIH-NIGMS P30 GM103342 to the South Carolina COBRE for Developmentally Based Cardiovascular Diseases. NR 56 TC 1 Z9 1 U1 17 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 EI 1530-6992 J9 NANO LETT JI Nano Lett. PD JUL PY 2016 VL 16 IS 7 BP 4670 EP 4678 DI 10.1021/acs.nanolett.6b02093 PG 9 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA DR3HL UT WOS:000379794200101 PM 27328393 ER PT J AU Ben-David, U Ha, G Khadka, P Jin, X Wong, B Franke, L Golub, TR AF Ben-David, Uri Ha, Gavin Khadka, Prasidda Jin, Xin Wong, Bang Franke, Lude Golub, Todd R. TI The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis SO NATURE COMMUNICATIONS LA English DT Article ID COPY-NUMBER ALTERATION; COMPREHENSIVE MOLECULAR PORTRAITS; GENE-EXPRESSION PROFILES; PLURIPOTENT STEM-CELLS; GROWTH-FACTOR-BETA; TUMOR-SUPPRESSOR; MAMMARY-TUMORS; 14-3-3 SIGMA; SENSITIVITY; IDENTIFICATION AB Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45 mouse models, providing the first comprehensive catalogue of chromosomal aberrations in cancer GEMMs. Mining this resource, we find that most chromosomal aberrations accumulate late during breast tumorigenesis, and observe marked differences in CNA prevalence between mouse mammary tumours initiated with distinct drivers. Some aberrations are recurrent and unique to specific GEMMs, suggesting distinct driver-dependent routes to tumorigenesis. Synteny-based comparison of mouse and human tumours narrows critical regions in CNAs, thereby identifying candidate driver genes. We experimentally validate that loss of Stratifin (SFN) promotes HER2-induced tumorigenesis in human cells. These results demonstrate the power of GEMM CNA analysis to inform the pathogenesis of human cancer. C1 [Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Golub, Todd R.] Harvard & MIT, Broad Inst, Canc Program, Cambridge, MA 02142 USA. [Ha, Gavin; Golub, Todd R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Franke, Lude] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, NL-9711 Groningen, Netherlands. [Golub, Todd R.] Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD 20811 USA. RP Golub, TR (reprint author), Harvard & MIT, Broad Inst, Canc Program, Cambridge, MA 02142 USA.; Golub, TR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Golub, TR (reprint author), Harvard Univ, Harvard Med Sch, Boston, MA 02115 USA.; Golub, TR (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20811 USA. EM golub@broadinstitute.org RI Franke, Lude/P-7036-2016 OI Franke, Lude/0000-0002-5159-8802 FU Human Frontiers Science Program postdoctoral fellowship FX We thank Pablo Tamayo, Steven Schumacher, Craig Bielski and John Mercer for assistance with the data assembly; Dihua Yu for the MCF10A cells; and Gad Getz, Rameen Beroukhim and Zuzana Tothova for the helpful discussions. U.B.-D. is supported by a Human Frontiers Science Program postdoctoral fellowship. NR 51 TC 3 Z9 3 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2041-1723 J9 NAT COMMUN JI Nat. Commun. PD JUL PY 2016 VL 7 AR 12160 DI 10.1038/ncomms12160 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DR4ZJ UT WOS:000379912200001 PM 27374210 ER PT J AU Rambout, X Detiffe, C Bruyr, J Mariavelle, E Cherkaoui, M Brohee, S Demoitie, P Lebrun, M Soin, R Lesage, B Guedri, K Beullens, M Bollen, M Farazi, TA Kettmann, R Struman, I Hill, DE Vidal, M Kruys, V Simonis, N Twizere, JC Dequiedt, F AF Rambout, Xavier Detiffe, Cecile Bruyr, Jonathan Mariavelle, Emeline Cherkaoui, Majid Brohee, Sylvain Demoitie, Pauline Lebrun, Marielle Soin, Romuald Lesage, Bart Guedri, Katia Beullens, Monique Bollen, Mathieu Farazi, Thalia A. Kettmann, Richard Struman, Ingrid Hill, David E. Vidal, Marc Kruys, Veronique Simonis, Nicolas Twizere, Jean-Claude Dequiedt, Franck TI The transcription factor ERG recruits CCR4-NOT to control mRNA decay and mitotic progression SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID BINDING PROTEINS; MAMMALIAN-CELLS; STRESS GRANULES; GENE-EXPRESSION; FISSION YEAST; P-BODIES; DEGRADATION; COMPLEX; FAMILY; STABILITY AB Control of mRNA levels, a fundamental aspect in the regulation of gene expression, is achieved through a balance between mRNA synthesis and decay. E26-related gene (Erg) proteins are canonical transcription factors whose previously described functions are confined to the control of mRNA synthesis. Here, we report that ERG also regulates gene expression by affecting mRNA stability and identify the molecular mechanisms underlying this function in human cells. ERG is recruited to mRNAs via interaction with the RNA-binding protein RBPMS, and it promotes mRNA decay by binding CNOT2, a component of the CCR4-NOT deadenylation complex. Transcriptome-wide mRNA stability analysis revealed that ERG controls the degradation of a subset of mRNAs highly connected to Aurora signaling, whose decay during S phase is necessary for mitotic progression. Our data indicate that control of gene expression by mammalian transcription factors may follow a more complex scheme than previously anticipated, integrating mRNA synthesis and degradation. C1 [Rambout, Xavier; Detiffe, Cecile; Bruyr, Jonathan; Mariavelle, Emeline; Cherkaoui, Majid; Demoitie, Pauline; Lebrun, Marielle; Guedri, Katia; Kettmann, Richard; Struman, Ingrid; Twizere, Jean-Claude; Dequiedt, Franck] Univ Liege ULg, Interdisciplinary Cluster Appl Genoprote GIGA R, Liege, Belgium. [Rambout, Xavier; Detiffe, Cecile; Bruyr, Jonathan; Mariavelle, Emeline; Cherkaoui, Majid; Demoitie, Pauline; Guedri, Katia; Kettmann, Richard; Twizere, Jean-Claude; Dequiedt, Franck] ULg, GIGA Mol Biol Dis, Liege, Belgium. [Brohee, Sylvain; Simonis, Nicolas] ULB, BiGRe, Brussels, Belgium. [Brohee, Sylvain] ULB, Comp Sci Dept, Brussels, Belgium. [Lebrun, Marielle] ULg, GIGA Inflammat Infect & Immun, Liege, Belgium. [Soin, Romuald; Kruys, Veronique] ULB, Fac Sci, Gosselies, Belgium. [Lesage, Bart; Beullens, Monique; Bollen, Mathieu] Univ Leuven KUL, Dept Cellular & Mol Med, Leuven, Belgium. [Farazi, Thalia A.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. [Struman, Ingrid] ULg, GIGA Canc, Liege, Belgium. [Hill, David E.; Vidal, Marc] DFCI, Dept Canc Biol, CCSB, Boston, MA USA. [Hill, David E.; Vidal, Marc] Harvard Med Sch, Dept Genet, Boston, MA USA. RP Dequiedt, F (reprint author), Univ Liege ULg, Interdisciplinary Cluster Appl Genoprote GIGA R, Liege, Belgium.; Dequiedt, F (reprint author), ULg, GIGA Mol Biol Dis, Liege, Belgium. EM fdequiedt@ulg.ac.be FU University of Liege; Fonds Leon Fredericq; Belgian Foundation against Cancer (Special Equipment Fund); Belgian National Fund for Scientific Research (FNRS), Televie; Interuniversity Attraction Poles Program-Belgian Science Policy (IUAP-BELSPO) [PVI/28, PVII/13]; National Human Genome research Institute [R01HG001715] FX We thank the Vidal laboratory at the Center for Cancer Systems Biology at the Dana-Farber Cancer Institute (CCSB, DFCI) for supplying reagents, advice and technical support for the HT-Y2H screen. We thank the Tuschl laboratory (Howard Hughes Medical Institute, Rockefeller University) for sharing reagents. We are grateful to E. Izaurralde (European Molecular Biology Laboratory) for kindly providing HA-tagged CNOT2, CNOT3, CNOT6 and CNOT. We would like to thank the laboratories of the Molecular Biology in Diseases Unit (GIGA-R, ULg) for helpful discussions and C. Vindry from the Kruys laboratory for technical assistance. We thank the GIGA interactomics, imaging and flow cytometry and genotranscriptomics platforms for their technical support. This work was supported by grants from the University of Liege, the Fonds Leon Fredericq, the Belgian Foundation against Cancer (Special Equipment Fund), the Belgian National Fund for Scientific Research (FNRS), Televie, the Interuniversity Attraction Poles Program-Belgian Science Policy IUAP-BELSPO PVI/28 and PVII/13 to F.D. and M. Bollen) and the National Human Genome research Institute (grant R01HG001715 to M.V. and D.E.H.). X.R., J-C.T. and N.S. are supported as an FNRS Research Fellow, Research Associate and Postdoctoral Fellow, respectively. C.D. and K.G. are supported as Televie-FNRS PhD students. NR 52 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 1545-9993 EI 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD JUL PY 2016 VL 23 IS 7 BP 663 EP 672 DI 10.1038/nsmb.3243 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA DQ7DX UT WOS:000379368200008 PM 27273514 ER PT J AU Sivaraman, KR Jivrajka, RV Soin, K Bouchard, CS Movahedan, A Shorter, E Jain, S Jacobs, DS Djalilian, AR AF Sivaraman, Kavitha R. Jivrajka, Renu V. Soin, Ketki Bouchard, Charles S. Movahedan, Asadolah Shorter, Ellen Jain, Sandeep Jacobs, Deborah S. Djalilian, Ali R. TI Superior Limbic Keratoconjunctivitis-like Inflammation in Patients with Chronic Graft-Versus-Host Disease SO OCULAR SURFACE LA English DT Article DE Limbal stem cell dysfunction; ocular chronic graft-versus-host disease; prosthetic replacement of the ocular surface (PROSE); superior limbic keratoconjunctivitis ID STEM-CELL TRANSPLANTATION; EYE DISEASE; DRY EYE; MANAGEMENT; PATHOGENESIS; DIAGNOSIS; BLINK; LENS AB Purpose: Describe the presentation and management of superior limbic keratoconjunctivitis (SLK)-like inflammation and secondary limbal stem cell dysfunction in the setting of ocular chronic graft-versus-host disease (cGVHD). Methods: Retrospective observational case series in a multicenter clinical practice. Participants were 13 patients (26 eyes) with ocular cGVHD and SLK-like inflammation presenting to the University of Illinois at Chicago and BostonSight (R) between January 1, 2009 and July 1, 2013. Main outcome measures: 1) Reversal or worsening of SLK, and 2) development of limbal stem cell dysfunction. Results: All eyes showed evidence of SLK-like inflammation and superior limbal stem cell dysfunction manifested by conjunctival injection and superior conjunctival and corneal staining. In addition to aggressive lubrication, management strategies for SLK included topical steroids (20/26), punctal occlusion (18/26), topical cyclosporine (24/26), autologous serum tears (12/26), therapeutic soft contact lens (13/26 eyes) and scleral lenses (4/26 eyes). SLK and limbal stem cell dysfunction were reversed in 23/26 eyes. Three eyes of two patients with long-standing disease demonstrated frank limbal stem cell deficiency (LSCD) and corneal pannus, with one patient requiring multiple reconstructive surgical procedures. Conclusions: SLK-like inflammation is an under-recognized condition in patients with severe dry eyes secondary to ocular cGVHD. Untreated SLK can potentially lead to permanent LSCD over time. Early recognition and management of SLK in ocular cGVHD can improve vision, reverse signs, and may prevent these long-term consequences. C1 [Sivaraman, Kavitha R.; Jivrajka, Renu V.; Soin, Ketki; Movahedan, Asadolah; Shorter, Ellen; Jain, Sandeep; Djalilian, Ali R.] Univ Illinois, Illinois Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL USA. [Bouchard, Charles S.] Loyola Univ, Dept Ophthalmol, Maywood, IL USA. [Jacobs, Deborah S.] BostonSight, Needham Hts, MA USA. [Jacobs, Deborah S.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Djalilian, AR (reprint author), 1855 W Taylor St M-C 648, Chicago, IL 60612 USA. EM adjalili@uic.edu FU National Institutes of Health (Bethesda, Maryland) [EY01792]; Research to Prevent Blindness FX Core grant EY01792 from the National Institutes of Health (Bethesda, Maryland), Career development grant (Ali R. Djalilian) and unrestricted grant from Research to Prevent Blindness. The sponsors or funding organizations had no role in the design or conduct of this research. NR 23 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1542-0124 EI 1937-5913 J9 OCUL SURF JI Ocul. Surf. PD JUL PY 2016 VL 14 IS 3 BP 393 EP 400 PG 8 WC Ophthalmology SC Ophthalmology GA DQ9CI UT WOS:000379507600009 PM 27179980 ER PT J AU Grunmuller, L Thierauf, J Weissinger, SE Bergmann, C Bankfalvi, A Veit, J Hoffmann, TK Moller, P Lennerz, JK AF Gruenmueller, Lisa Thierauf, Julia Weissinger, Stephanie E. Bergmann, Christoph Bankfalvi, Agnes Veit, Johannes Hoffmann, Thomas K. Moeller, Peter Lennerz, Jochen K. TI Biopanel identifies expression status of targetable proteins in sinonasal melanoma SO PERSONALIZED MEDICINE LA English DT Article DE biopanel; biomarker; prognostic; trial design ID MUCOSAL MALIGNANT-MELANOMA; GROWTH-FACTOR RECEPTOR; METASTATIC MELANOMA; BRAF MUTATIONS; THERAPEUTIC TARGET; CLINICAL-PRACTICE; PHASE-II; C-MET; HEAD; NECK AB Background: Advanced stage at presentation, lack of BRAF mutations and overall rarity pose unique challenges to the therapy and trial design in sinonasal melanoma. Methods: Here, we assessed the expression status of 12 proteins in two independent cohorts of sinonasal melanoma (n = 20). Results: Each case showed expression of at least one protein (KIT, TP53, MYC, HER2, EGFR, MET, VEGFR, BRAF V600E and/or MDM2), whereas lack of ALK, FLI1 and PDGFR alpha expression underscores differences to cutaneous melanoma. Comparison of marker frequencies to a metareview of the literature indicates that MYC, HER2, EGFR and MET had not been previously assessed. Conclusion: Expression of at least one potentially targetable protein per case illustrates proteome pathway profiling as one starting point for marker stratified trial design. C1 [Gruenmueller, Lisa; Weissinger, Stephanie E.; Moeller, Peter; Lennerz, Jochen K.] Univ Ulm, Inst Pathol, Ulm, Germany. [Thierauf, Julia; Veit, Johannes; Hoffmann, Thomas K.] Univ Med Ctr Ulm, Dept Otorhinolaryngol Head & Neck Surg, Ulm, Germany. [Bergmann, Christoph] Univ Hosp Essen, Dept Otorhinolaryngol, Essen, Germany. [Bankfalvi, Agnes] Univ Hosp Essen, Dept Pathol, Essen, Germany. [Lennerz, Jochen K.] Harvard Med Sch, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Lennerz, JK (reprint author), Univ Ulm, Inst Pathol, Ulm, Germany.; Lennerz, JK (reprint author), Harvard Med Sch, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. EM jlennerz@partners.org FU Else-Kroner Fresenius Foundation; Dres. Bayer foundation (Ravensburg, Germany); Hertha Nathorff Program (University Ulm, Ulm Germany) FX The Else-Kroner Fresenius Foundation supported JK Lennerz; SE Weissinger is supported by the Dres. Bayer foundation (Ravensburg, Germany) and the Hertha Nathorff Program (University Ulm, Ulm Germany). All authors contributed to conception and design, manuscript preparation, read and approved the final manuscript. 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 71 TC 0 Z9 0 U1 2 U2 2 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 JUL PY 2016 VL 13 IS 4 BP 291 EP 301 DI 10.2217/pme-2016-0023 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DQ6ZA UT WOS:000379354800003 ER PT J AU Hardiman, G Savage, SJ Hazard, ES Wilson, RC Courtney, SM Smith, MT Hollis, BW Halbert, CH Gattoni-Celli, S AF Hardiman, Gary Savage, Stephen J. Hazard, E. Starr Wilson, Robert C. Courtney, Sean M. Smith, Michael T. Hollis, Bruce W. Halbert, Chanita Hughes Gattoni-Celli, Sebastiano TI Systems analysis of the prostate transcriptome in African-American men compared with European-American men SO PHARMACOGENOMICS LA English DT Article DE African-American; health disparities; prostate; RNA-seq; transcription; vitamin D ID VITAMIN-D-RECEPTOR; DIFFERENTIAL EXPRESSION ANALYSIS; CANCER PREVENTION TRIAL; 1,25-DIHYDROXYVITAMIN D-3; 25-HYDROXYVITAMIN D; WHITE MEN; SUPPLEMENTATION; CELLS; RISK; GENE AB Aim: African-Americans (AA) have increased prostate cancer risk and a greater mortality rate than European-Americans (EA). AA exhibit a high prevalence of vitamin D deficiency. We examined the global prostate transcriptome in AA and EA, and the effect of vitamin D-3 supplementation. Patients & methods: Twenty-seven male subjects (ten AA and 17 EA), slated to undergo prostatectomy were enrolled in the study. Fourteen subjects received vitamin D-3 (4000 IU daily) and 13 subjects received placebo for 2 months prior to surgery. Results: AA show higher expression of genes associated with immune response and inflammation. Conclusion: Systems level analyses support the concept that Inflammatory processes may contribute to disease progression in AA. These transcripts can be modulated by a short course of vitamin D-3 supplementation. C1 [Hardiman, Gary] Med Univ South Carolina, Dept Med & Publ Hlth, Charleston, SC 29425 USA. [Hardiman, Gary; Hazard, E. Starr; Wilson, Robert C.; Courtney, Sean M.] Med Univ South Carolina, Ctr Genom Med, Charleston, SC 29425 USA. [Hazard, E. Starr] Med Univ South Carolina, Lib Sci & Informat, Charleston, SC USA. [Savage, Stephen J.] Ralph H Johnson VA Med Ctr, Dept Urol, Charleston, SC USA. [Savage, Stephen J.; Halbert, Chanita Hughes; Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC USA. [Wilson, Robert C.; Smith, Michael T.] Med Univ South Carolina, Dept Pathol & Lab Med, Charleston, SC USA. [Hollis, Bruce W.] Med Univ South Carolina, Dept Pediat, Charleston, SC USA. [Halbert, Chanita Hughes] Med Univ South Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. [Gattoni-Celli, Sebastiano] Med Univ South Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. RP Hardiman, G (reprint author), Med Univ South Carolina, Dept Med & Publ Hlth, Charleston, SC 29425 USA.; Hardiman, G (reprint author), Med Univ South Carolina, Ctr Genom Med, Charleston, SC 29425 USA.; Gattoni-Celli, S (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA.; Gattoni-Celli, S (reprint author), Med Univ South Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. EM hardiman@musc.edu; gattonis@musc.edu FU Veterans Administration (VA) CSRD Merit Award [CX000753]; MUSC Center for Genomic Medicine; MUSCCOM; Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina; Hollings Cancer Center, Medical University of South Carolina [P30 CA 138313] FX This research was funded by Veterans Administration (VA) CSR&D Merit Award CX000753 and a Pilot Project grant from the MUSC Center for Genomic Medicine to SG-C and MUSCCOM start-up funds to GTH. The authors also acknowledge support from the Genomics Shared Resource, Hollings Cancer Center, Medical University of South Carolina. This shared resource is supported in part by the Hollings Cancer Center, Medical University of South Carolina Support Grant (P30 CA 138313). 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 46 TC 2 Z9 2 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 EI 1744-8042 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUL PY 2016 VL 17 IS 10 BP 1129 EP 1143 DI 10.2217/pgs-2016-0025 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA DR3XC UT WOS:000379835000003 PM 27359067 ER PT J AU Mastroianni, M Lin, AM Smith, BL Austen, WG Colwell, AS AF Mastroianni, Melissa Lin, Alex M. Smith, Barbara L. Austen, William G., Jr. Colwell, Amy S. TI Nipple Loss following Nipple-Sparing Mastectomy SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID BREAST RECONSTRUCTION; OUTCOMES; CANCER; AREOLA; SKIN; COMPLICATIONS; INVOLVEMENT AB Background: Nipple preservation at the time of mastectomy is increasingly performed to enhance the overall result from the reconstruction. Unfortunately, some of these patients may lose their nipples for oncologic reasons or because of necrosis. Several studies have investigated risk factors associated with nipple loss, but few data exist on the incidence of cancer in the nipple specimen, nipple removal for cosmesis or symmetry, and whether these patients subsequently pursue nipple reconstruction. Methods: A retrospective review was performed on nipple-sparing mastectomies and immediate reconstruction from 2007 to 2013. Results: Of 443 patients (775 breasts), 51 nipples (6.6 percent) were removed. Of the 51 nipple losses, 76 percent had total nipple or nipple-areola complex loss and 24 percent had partial loss. Twenty-five of the nipples (49 percent) required excision for oncologic reasons, 18 nipples (35 percent) were either partially or totally lost because of necrosis, and one nipple (2 percent) was excised for cosmetic reasons. In cases of bilateral reconstruction and unilateral nipple loss, 65 percent of contralateral normal nipples were retained and 35 percent (n = 7) were removed for symmetry. Fourteen nipples had residual cancer or atypia, whereas 37 had normal pathologic findings. Twenty-one nipples (40 percent) were reconstructed and 30 were not. Conclusions: In this series, the incidence of nipple loss following nipple-sparing mastectomy was 6.6 percent and related primarily to positive oncologic margins. The rate of removal for cosmesis was low, suggesting that for most patients the nipple lies in an acceptable position. After removal, 40 percent of patients had nipple reconstruction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg Oncol, Boston, MA USA. RP Colwell, AS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WACC 435, Boston, MA 02114 USA. EM acolwell@partners.org NR 16 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 2016 VL 138 IS 1 BP 24E EP 30E DI 10.1097/PRS.0000000000002296 PG 7 WC Surgery SC Surgery GA DQ6RG UT WOS:000379332200004 PM 27348682 ER PT J AU Gassman, AA Lewis, MS Lee, JC AF Gassman, Andrew A. Lewis, Michael S. Lee, Justine C. TI Remote Ischemic Preconditioning Recipient Tissues Improves the Viability of Murine Fat Transfer SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID REPERFUSION INJURY; RAT MODEL; BREAST; RECONSTRUCTION; TRANSPLANTATION; SURVIVAL; HARVEST; CELLS; HEART; SIZE AB Background: Local ischemia before the development of recipient circulation may contribute to the highly variable long-term results of fat grafting. Remote ischemic preconditioning before adipose procurement augments the retention of fat grafts and limits subsequent liposclerosis. However, there is no literature examining what role remote ischemic preconditioning has on the fat graft recipient site. Methods: Subcutaneous adipose tissue from transgenic mice expressing green fluorescent protein/luciferase was injected into skin folds of wild-type mice. Donors and recipients experienced intermittent temporary hindlimb tourniquet application before harvest and transfer, respectively. The viability of the transferred tissue was examined over 28 days by luciferin bioluminescence and subsequent histologic analysis. Results: There was a difference in bioluminescence at days 0, 14, and 28. The remote ischemic preconditioning donor or recipient mouse-alone groups demonstrated an approximately 2- to 3-fold increase in bioluminescence. Donor and recipient remote ischemic preconditioning had a 9-fold increase in bioluminescence. Histologic analysis at 28 days confirmed the presence of donor adipocytes, and they were gradually replaced by recipient inflammation and scar tissue. However, the amount of interstitial fibrosis was substantially less in the remote ischemic preconditioning groups. These findings were more pronounced when remote ischemic preconditioning was used for both donor and recipient mice. Conclusions: Remote ischemic preconditioning has the ability to increase the viability of donor adipocytes and limit interstitial fibrosis. More specifically, remote ischemic preconditioning treatment of both donated adipose tissue and recipient wound beds demonstrates the greatest overall adipose cellular viability and native architecture. C1 [Gassman, Andrew A.] Univ Texas Southwestern Med Ctr, Dept Plast Surg, 1801 Inwood Rd, Dallas, TX 75390 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Plast & Reconstruct Surg, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Dept Pathol, Los Angeles, CA USA. RP Gassman, AA (reprint author), Univ Texas Southwestern Med Ctr, Dept Plast Surg, 1801 Inwood Rd, Dallas, TX 75390 USA. EM andrew.gassman@utsouthwestern.edu FU Plastic Surgery Foundation [274376]; Jean Perkins Foundation FX This work was supported by the Plastic Surgery Foundation (Pilot Research Grant number 274376) (to A.A.G.) and the Jean Perkins Foundation (to J.C.L.). NR 24 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 2016 VL 138 IS 1 BP 55E EP 63E DI 10.1097/PRS.0000000000002295 PG 9 WC Surgery SC Surgery GA DQ6RG UT WOS:000379332200008 PM 27348686 ER PT J AU Liao, EC AF Liao, Eric C. TI Different Acellular Dermal Matrix Preparations, Different Surgeons, Different Outcomes: What Factors Matter? SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter ID POSTMASTECTOMY BREAST RECONSTRUCTION C1 [Liao, Eric C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast & Reconstruct Surg, Boston, MA USA. RP Liao, EC (reprint author), Harvard Univ, Sch Med, WACC Suite 435,15 Parkman St, Boston, MA 02114 USA. EM cliao@partners.org NR 6 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 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 2016 VL 138 IS 1 BP 145E EP 146E DI 10.1097/PRS.0000000000002273 PG 2 WC Surgery SC Surgery GA DQ6RG UT WOS:000379332200020 PM 27351472 ER PT J AU Mattos, D Liao, EC AF Mattos, David Liao, Eric C. TI Reply: Lifetime Costs of Prophylactic Mastectomies and Reconstruction versus Surveillance SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Letter C1 [Mattos, David; Liao, Eric C.] Massachusetts Gen Hosp, Div Plast & Reconstruct Surg, Boston, MA 02114 USA. RP Liao, EC (reprint author), 15 Parkman St,WACC 435, Boston, MA 02114 USA. EM cliao@partners.org NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0032-1052 EI 1529-4242 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD JUL PY 2016 VL 138 IS 1 BP 152E EP 153E DI 10.1097/PRS.0000000000002279 PG 3 WC Surgery SC Surgery GA DQ6RG UT WOS:000379332200027 PM 27351478 ER PT J AU Siddiqui, IJ Luz, J Borg-Stein, J O'Connor, K Bockbrader, M Rainey, H Way, D Colachis, S Bahner, DP Kohler, MJ AF Siddiqui, Imran J. Luz, Jennifer Borg-Stein, Joanne O'Connor, Kevin Bockbrader, Marcia Rainey, Heather Way, David Colachis, Sam Bahner, David P. Kohler, Minna J. TI The Current State of Musculoskeletal Ultrasound Education in Physical Medicine and Rehabilitation Residency Programs SO PM&R LA English DT Article ID COMPETENCE ASSESSMENT; UNITED-STATES; RHEUMATOLOGY; ULTRASONOGRAPHY; SONOGRAPHY; CURRICULUM; KNOWLEDGE; FELLOWS AB Background: Exposure to musculoskeletal ultrasound (MSUS) is now a mandatory component of physical medicine and rehabilitation (PM&R) residency training. However, reports on the extent of the implementation and efficacy of MSUS education are lacking in the literature. Objective: To determine the extent to which PM&R residencies are implementing MSUS education. Design: Cross-sectional. Setting: Institutional. Participants: Thirty-six of the 78 United States PM&R residency programs accredited by the Accreditation Council for Graduate Medical Education. Methods: All 78 programs were solicited with an online survey via the residency program director and coordinator in July 2014. The 25 questions on the survey were aimed at determining program MSUS educational characteristics and their effectiveness. Main Outcome Measures: Description of teaching methods used for MSUS, residency demographics, characteristics of MSUS faculty expertise, and faculty-perceived competency in MSUS examinations and procedures among residents. Data were analyzed using both descriptive statistics and tests for independence to identify correlations between program characteristics and resident MSUS competency. Results: A response was received from 36 of the 78 residency programs (46.2%). Of the 36 residency programs that responded, 97.2% provide exposure to MSUS (a figure that drops to 44.9% when nonrespondents are included); 61% had mandatory MSUS training (28.2% when including nonrespondents); and 44.4% had a formal curriculum (20.5% when including nonrespondents). The most common MSUS educational tools used were lecture (88.9%), outpatient clinic (86.1%), and hands-on workshops (86.1%). Sixty-one percent of responding programs evaluate residents with formal assessment tools. Overall, faculty at 38.8% and 44.4% of programs believed that at least 50% of residents who graduate are competent in diagnostic and interventional MSUS, respectively. These rates were significantly associated with the use of formal assessment. Conclusion: MSUS education is growing in PM&R, but many programs still have not adopted a formal educational curriculum. Formal assessment to evaluate resident MSUS skills significantly improves faculty-perceived MSUS competency. C1 [Siddiqui, Imran J.; Luz, Jennifer; Borg-Stein, Joanne; O'Connor, Kevin] Harvard Med Sch, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, Boston, MA USA. [Siddiqui, Imran J.] Regenerat Orthoped & Sports Med, Washington, DC USA. [Bockbrader, Marcia; Rainey, Heather; Way, David; Colachis, Sam] Ohio State Univ, Wexner Med Ctr, Dept Phys Med & Rehabil, Columbus, OH 43210 USA. [Bahner, David P.] Ohio State Univ, Dept Emergency Med, Wexner Med Ctr, Columbus, OH 43210 USA. [Kohler, Minna J.] Harvard Med Sch, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. RP Kohler, MJ (reprint author), Harvard Med Sch, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, 55 Fruit St,Yawkey 2C, Boston, MA 02114 USA. EM mkohler@mgh.harvard.edu RI Bockbrader, Marcia/J-6203-2013; OI Bockbrader, Marcia/0000-0001-6419-0630; Way, David/0000-0002-1896-3425 FU Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources, National Institute of Health); Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institute of Health) [UL138 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 UL138 TR001102) and financial contributions from Harvard University and its affiliated academic health care centers. The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, or the National Institutes of Health. NR 30 TC 0 Z9 0 U1 3 U2 7 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 JUL PY 2016 VL 8 IS 7 BP 660 EP 666 DI 10.1016/j.pmrj.2015.11.010 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DR1RB UT WOS:000379681500007 PM 26690020 ER PT J AU Nagpal, A Xu, R Pangarkar, S Dworkin, I Singh, JR AF Nagpal, Ameet Xu, Rachel Pangarkar, Sanjog Dworkin, Ian Singh, Jaspal R. TI Driving Under the Influence of Opioids SO PM&R LA English DT Editorial Material ID CHRONIC NONMALIGNANT PAIN; DRUG-ABUSING VOLUNTEERS; NEUROPSYCHOLOGICAL PERFORMANCE; PRESCRIPTION OPIOIDS; ORAL OXYCODONE; NONCANCER PAIN; UNITED-STATES; MORPHINE; PSYCHOMOTOR; THERAPY C1 [Nagpal, Ameet; Xu, Rachel] Univ Texas Hlth Sci Ctr San Antonio, Dept Anesthesiol, San Antonio, TX 78229 USA. [Pangarkar, Sanjog] Vet Hlth Serv, Inpatient Pain Serv, Dept Phys Med & Rehabil, Los Angeles, CA USA. [Dworkin, Ian] Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Dept Phys Med & Rehabil, Los Angeles, CA USA. [Singh, Jaspal R.] Weill Cornell Med Coll, Phys Med & Rehabil, 525 E 68th St,Baker 16, New York, NY 10065 USA. RP Singh, JR (reprint author), Weill Cornell Med Coll, Phys Med & Rehabil, 525 E 68th St,Baker 16, New York, NY 10065 USA. EM jrs9012@med.cornell.edu NR 43 TC 0 Z9 0 U1 1 U2 2 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 JUL PY 2016 VL 8 IS 7 BP 698 EP 705 DI 10.1016/j.pmrj.2016.05.010 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DR1RB UT WOS:000379681500011 PM 27406008 ER PT J AU Schapira, MM Imbert, D Oh, E Byhoff, E Shea, JA AF Schapira, Marilyn M. Imbert, Diana Oh, Eric Byhoff, Elena Shea, Judy A. TI Public engagement with scientific evidence in health: A qualitative study among primary-care patients in an urban population SO PUBLIC UNDERSTANDING OF SCIENCE LA English DT Article DE decision making in science; health communication; patients; public understanding of science ID STATISTICAL LITERACY; INFORMATION; NUMERACY; RISK; COMMUNICATION; MEDICINE; PERCEPTIONS; CONFIDENCE; EXPERIENCE; CHOICE AB The purpose of this study is to explore the experience and perspective of patients regarding scientific evidence in health and the degree that this information impacts health behavior and medical decision making. A focus group study was conducted. Participants were recruited from an urban primary-care practice. The focus group discussions were audio-recorded, transcribed verbatim, and coded by two independent investigators. Emergent themes were identified. Participants (n=30) ranged in age from 30 to 79years, 60% were female, 77% were black, and 50% had at least some college experience. Three thematic areas informed a wide range in level of interest regarding scientific study design and result information: (1) scientific literacy, (2) medical decision making style, and (3) impact of culture and community on decision making. Our findings indicate that communication strategies that incorporate key elements of scientific study design, methods, and results will most effectively translate findings from comparative effectiveness research to patient-informed decision making regarding evidence-based health interventions. C1 [Schapira, Marilyn M.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Schapira, Marilyn M.; Imbert, Diana; Byhoff, Elena; Shea, Judy A.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Oh, Eric] Swarthmore Coll, Swarthmore, PA 19081 USA. RP Schapira, MM (reprint author), Univ Penn, Perelman Sch Med, Dept Med, Div Gen Internal Med, 1110 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mschap@upenn.edu FU Robert Wood Johnson Foundation Health & Society Scholars program at the University of Pennsylvania FX The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a grant from the Robert Wood Johnson Foundation Health & Society Scholars program at the University of Pennsylvania. NR 40 TC 0 Z9 0 U1 6 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0963-6625 EI 1361-6609 J9 PUBLIC UNDERST SCI JI Public Underst. Sci. PD JUL PY 2016 VL 25 IS 5 BP 612 EP 626 DI 10.1177/0963662514560489 PG 15 WC Communication; History & Philosophy Of Science SC Communication; History & Philosophy of Science GA DR3EW UT WOS:000379786400008 PM 25491359 ER PT J AU Grandhige, AP Timmer, M O'Neill, MJ Binney, ZO Quest, TE AF Grandhige, Anjali P. Timmer, Marjorie O'Neill, Michael J. Binney, Zachary O. Quest, Tammie E. TI Respiratory Therapists' Experiences and Attitudes Regarding Terminal Extubations and End-of-Life Care SO RESPIRATORY CARE LA English DT Article DE palliative care; respiratory therapist; ventilator; end of life ID WITHDRAWAL; SUPPORT; OUTCOMES; UNIT AB BACKGROUND: Respiratory therapists (RTs) routinely care for patients with life- limiting illnesses and in some hospitals are responsible for terminal extubations. Data on how such experiences affect RTs are scarce. The objective of this work was to survey RTs at 2 academic medical centers about their experiences caring for patients with terminal extubations. METHODS: An online survey was distributed to the hospitals' RTs. Survey data included demographics and experiences with end-of-life care and terminal extubations. The survey was derived from previously published questionnaires plus input from hospital RT leaders. RESULTS: Sixty-five of 173 RTs (37.6%) responded. Of these, 42.4% were >= 50 y old, and 62.7% were female. 20.3% had <= 5 y experience; 52.5% had >= 16 y. 93.8% self-reported being involved in at least one terminal extubation; of those, 36.1% reported performing >= 20. Nearly half (47.5%) wanted to be involved in family meetings discussing terminal extubations, but just 6.6% were frequently involved. Only 32.3% felt that they received adequate education regarding terminal illness in RT school; 32.3% reported gathering this knowledge while working. 60.0% wanted more formal education around terminal patient care. 27.9% reported sometimes being uncomfortable with performing a terminal extubation; most of these rarely felt that they had the option not to perform the extubation. CONCLUSIONS: RTs are rarely involved in end-of-life discussions despite a desire to be, and they experience situations that generate discomfort. There is demand for more formal RT training around care for terminal patients. Clinical protocols that involve RTs in meetings before ventilator withdrawal should be considered. C1 [Grandhige, Anjali P.; O'Neill, Michael J.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Timmer, Marjorie] Emory Univ Hosp, Dept Resp Care, Atlanta, GA USA. [Grandhige, Anjali P.; O'Neill, Michael J.; Binney, Zachary O.; Quest, Tammie E.] Emory Univ, Emory Palliat Care Ctr, Atlanta, GA USA. [Binney, Zachary O.] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA USA. [Quest, Tammie E.] US Dept Vet Affairs, Med Ctr, Atlanta, GA USA. [Quest, Tammie E.] Emory Univ, Sch Med, Dept Emergency Med, Atlanta, GA USA. RP Grandhige, AP (reprint author), Emory Univ, Sch Med, Dept Med, Atlanta, GA USA.; Grandhige, AP (reprint author), Emory Univ, Emory Palliat Care Ctr, Atlanta, GA USA. EM anjali.grandhige@emory.edu NR 14 TC 1 Z9 1 U1 4 U2 4 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD JUL PY 2016 VL 61 IS 7 BP 891 EP 896 DI 10.4187/respcare.04168 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ5EU UT WOS:000379228600002 PM 27274094 ER PT J AU McConnell, RA Kerlin, MP Schweickert, WD Ahmad, F Patel, MS Fuchs, BD AF McConnell, Ryan A. Kerlin, Meeta Prasad Schweickert, William D. Ahmad, Faraz Patel, Mitesh S. Fuchs, Barry D. TI Using a Post-Intubation Checklist and Time Out to Expedite Mechanical Ventilation Monitoring: Observational Study of a Quality Improvement Intervention SO RESPIRATORY CARE LA English DT Article DE blood gas analysis; acidosis; artificial respiration; mechanical ventilators; checklist; quality improvement ID SURGICAL SAFETY CHECKLIST; CRITICALLY-ILL PATIENTS; INTENSIVE-CARE-UNIT; BLOOD-GAS-ANALYSIS; INTRAHOSPITAL TRANSPORT; HOSPITAL MORTALITY; MEDICAL TEAM; ARTERIAL; COMMUNICATION; OXYGEN AB BACKGROUND: Delayed mechanical ventilation monitoring may impede recognition of life-threatening acidemia. Coordination of multidisciplinary processes can be improved by using a checklist and time-out procedure. The study objective was to evaluate process-related outcomes after implementation of a post-intubation checklist and time out. METHODS: An observational study of a 24-bed medical ICU in Philadelphia, Pennsylvania, was conducted from January to December 2011. A random sample of mechanically ventilated adults was selected from the pre-intervention (n = 80) and post-intervention (n = 144) periods. The primary outcome was the proportion of subjects with an arterial blood gas (ABG) result within 60 min of mechanical ventilation initiation. Secondary outcomes included rates of respiratory acidosis, moderate-severe acidemia (pH < 7.25), checklist initiation, and project sustainability. Chi-square analysis was used to evaluate differences in outcomes between time periods. RESULTS: After the intervention, the proportion of subjects with an ABG result within 60 min increased (56% vs 37%, P = .01), and time to ABG result improved (58 min vs 79 min, P = .004). Adjusting for illness severity, the proportion with an ABG result within 60 min remained significantly higher in the post-intervention period (odds ratio 2.42, 95% CI 1.25-4.68, P = .009). Checklist adherence was higher with ICU intubations than for intubations performed outside the ICU (71% vs 27% checklist initiation rate, P < .001). Transfer from referring institutions (23% checklist initiation rate, P = .006) negatively impacted checklist use. Implementation challenges included frequent stakeholder turnover, undefined process ownership, and lack of real-time performance feedback. CONCLUSIONS: A post-intubation checklist and time out improved the timeliness of mechanical ventilation monitoring through more rapid assessment of arterial blood gases. Implementing this peri-intubation procedure may reduce the risks associated with transitioning to full mechanical ventilatory support. Optimal implementation necessitates strategies to surmount organizational and behavioral barriers to change. C1 [McConnell, Ryan A.] Univ Calif San Francisco, Dept Med, Div Gastroenterol, San Francisco, CA 94143 USA. [Kerlin, Meeta Prasad; Schweickert, William D.; Fuchs, Barry D.] Univ Penn, Dept Med, Div Pulm Allergy & Crit Care, Philadelphia, PA 19104 USA. [Ahmad, Faraz] Northwestern Univ, Dept Med, Div Cardiol, Chicago, IL 60611 USA. [Patel, Mitesh S.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Patel, Mitesh S.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP McConnell, RA (reprint author), Univ Calif San Francisco, Div Gastroenterol, 513 Parnassus Ave,S-357, San Francisco, CA 94143 USA. EM ryan.mcconnell@ucsf.edu NR 38 TC 1 Z9 1 U1 2 U2 2 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 EI 1943-3654 J9 RESP CARE JI Respir. Care PD JUL PY 2016 VL 61 IS 7 BP 902 EP 912 DI 10.4187/respcare.04191 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ5EU UT WOS:000379228600004 PM 26932381 ER PT J AU Saadi, A Patenaude, B Nirola, DK Deki, S Tshering, L Clark, S Shaull, L Sorets, T Fink, G Mateen, F AF Saadi, Altaf Patenaude, Bryan Nirola, Damber Kumar Deki, Sonam Tshering, Lhab Clark, Sarah Shaull, Lance Sorets, Tali Fink, Guenther Mateen, Farrah TI Quality of life in epilepsy in Bhutan SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE Quality of life; Epilepsy; Asia; Education; Global health ID INVENTORY QOLIE-31; PSYCHOMETRIC PROPERTIES; SEIZURE FREQUENCY; HEALTH; RELIABILITY; VALIDITY; VERSION; STIGMA; COUNTRIES; PEOPLE AB Purpose: To assess the quality of life in epilepsy (QOLIE) among adults in the lower middle-income country of Bhutan and assess the potential demographic and clinical associations with better QOLIE. Methods: People with clinically diagnosed epilepsy were prospectively enrolled at the Jigme Dorji Wangchuck National Referral Hospital in Thimphu (2014-2015). Regression models were constructed to assess the potential impact of age, sex, residence in the capital city, wealth quintile, educational attainment, seizure in the prior year, seizures with loss of consciousness, self-reported stigma score, and need for multiple antiepileptic drugs. Results: The mean Bhutanese QOLIE-31 score among 172 adults (mean age 31.1 years, 93 female) was 48.9/100 +/- 17.7. Younger age, lower educational attainment level, and increased self-perceived stigma were each observed to have an independent, negative association with QOLIE (p < 0.05), while a patient's wealth quintile, sex, seizure frequency, seizure type and number of antiepileptic drugs were not. Education appeared to be most strongly associated with QOL at the high school and college levels. Conclusions: There are potentially modifiable associations with low QOLIE. Addressing the educational level and self-perceived stigma of PWE may have an especial impact. The low QOLIE in Bhutan may reflect cultural approaches to epilepsy, health services, or other factors including those outside of the health sector. (C) 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. C1 [Saadi, Altaf] Massachusetts Gen Hosp, Partners Neurol Residency, Boston, MA 02114 USA. [Saadi, Altaf] Brigham & Womans Hosp, Boston, MA USA. [Patenaude, Bryan; Fink, Guenther] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Nirola, Damber Kumar; Deki, Sonam; Tshering, Lhab] Jigme Dorji Wangchuck Natl Referral Hosp, Thimphu, Bhutan. [Clark, Sarah; Shaull, Lance; Sorets, Tali; Mateen, Farrah] Massachusetts Gen Hosp, 165 Cambridge St 627, Boston, MA 02114 USA. [Mateen, Farrah] Harvard Med Sch, Boston, MA USA. RP Mateen, F (reprint author), Massachusetts Gen Hosp, 165 Cambridge St 627, Boston, MA 02114 USA. EM asaadi@partners.org; bryanpatenaude@gmail.com; drnirola@yahoo.com; somlcey90@gmail.com; tsheringlhab999@gmail.com; sclark0929@gmail.com; Irshaull@gmail.com; tsorets@bbns.org; gfink@hsph.harvard.edu; fmateen@mgh.harvard.edu OI Nirola, Damber/0000-0003-3941-6081 FU Government of Canada FX Grand Challenges Canada, funded by the Government of Canada. NR 39 TC 2 Z9 2 U1 7 U2 7 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1059-1311 EI 1532-2688 J9 SEIZURE-EUR J EPILEP JI Seizure PD JUL PY 2016 VL 39 BP 44 EP 48 DI 10.1016/j.seizure.2016.05.001 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DQ7FG UT WOS:000379371700009 PM 27257785 ER PT J AU Smock, KJ Plumhoff, EA Meijer, P Hsu, PH Zantek, ND Heikal, NM Van Cott, EM AF Smock, Kristi J. Plumhoff, Elizabeth A. Meijer, Piet Hsu, Peihong Zantek, Nicole D. Heikal, Nahla M. Van Cott, Elizabeth M. TI Protein S testing in patients with protein S deficiency, factor V Leiden, and rivaroxaban by North American Specialized Coagulation Laboratories SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Protein S; proficiency testing; NASCOLA; factor V Leiden; direct oral anticoagulants ID VENOUS THROMBOSIS; RISK-FACTOR; ASSAYS; ANTITHROMBIN; DABIGATRAN; DIAGNOSIS; FAMILIES; SEX; AGE AB In 2010-2012, the North American Specialized Coagulation Laboratory Association (NASCOLA) distributed 12 proficiency testing challenges to evaluate laboratory testing for protein S (PS). Results were analysed to assess the performance of PS activity, PS free antigen, and PS total antigen testing. Statistical analysis was performed on the numeric results and qualitative classification submitted for each method. There were 2,106 total results: 716 results from PS activity assays, 833 results from PS free antigen assays, and 557 results from PS total antigen assays. The three assay types performed well in the classification of five normal samples and nine abnormal samples, although certain PS activity methods were more likely to classify normal samples as abnormal and one PS total antigen assay was more likely to classify abnormal samples as normal. PS activity methods were affected by interfering substances such as heterozygous or homozygous factor V Leiden mutation (underestimation) and the anticoagulant drug rivaroxaban (overestimation). In conclusion, NASCOLA laboratories using a variety of PS assays performed well in the classification of clearly normal and abnormal samples. Laboratories performing PS activity assays should be aware of potential interferences in samples positive for FV Leiden or containing certain anticoagulant medications. C1 [Smock, Kristi J.; Heikal, Nahla M.] Univ Utah, Dept Pathol, ARUP Labs, 500 Chipeta Way,Mail Stop 115-G04, Salt Lake City, UT 84108 USA. [Plumhoff, Elizabeth A.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Meijer, Piet] ECAT Fdn, Voorschoten, Netherlands. [Hsu, Peihong] Northwell Hlth Syst, Dept Pathol & Lab Med, Lake Success, NY USA. [Hsu, Peihong] Hofstra Northwell Sch Med, Lake Success, NY USA. [Zantek, Nicole D.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA. [Van Cott, Elizabeth M.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Smock, KJ (reprint author), Univ Utah, Dept Pathol, ARUP Labs, 500 Chipeta Way,Mail Stop 115-G04, Salt Lake City, UT 84108 USA. EM Kristi.smock@hsc.utah.edu FU Sekisui Diagnostics, Inc. FX NDZ has received research funding from Sekisui Diagnostics, Inc. The other authors declare no conflicts of interest related to the content of the manuscript. NR 22 TC 2 Z9 2 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2016 VL 116 IS 1 BP 50 EP 57 DI 10.1160/TH15-12-0918 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DQ8XM UT WOS:000379495000006 PM 27075008 ER PT J AU Carreras, ET Hochholzer, W Frelinger, AL Nordio, F O'Donoghue, ML Wiviott, SD Angiolillo, DJ Michelson, AD Sabatine, MS Mega, JL AF Carreras, Edward T. Hochholzer, Willibald Frelinger, Andrew L., III Nordio, Francesco O'Donoghue, Michelle L. Wiviott, Stephen D. Angiolillo, Dominick J. Michelson, Alan D. Sabatine, Marc S. Mega, Jessica L. TI Diabetes mellitus, CYP2C19 genotype, and response to escalating doses of clopidogrel Insights from the ELEVATE-TIMI 56 Trial SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Diabetes mellitus; ischaemic heart disease; platelet pharmacology; polymorphisms ID CORONARY-ARTERY-DISEASE; OPTIMIZING ANTIPLATELET THERAPY; PLATELET REACTIVITY; CARDIOVASCULAR OUTCOMES; CLINICAL-OUTCOMES; COMBINED ASPIRIN; INTERVENTION; RESPONSIVENESS; IMPACT; POLYMORPHISM AB Both diabetes mellitus (DM) and carriage of the CYP2C19*2 allele are associated with a reduced response to clopidogrel. The relative contributions of these factors and whether higher clopidogrel doses can overcome both factors remain unknown. The objective of this study was to test the ability of clopidogrel doses up to 300 mg daily to decrease platelet reactivity in patients with DM and/or CYP2C19*2. ELEVATE-TIMI 56 randomised 333 patients with coronary artery disease to different maintenance doses of clopidogrel in four treatment periods, each lasting approximately 14 days. On-treatment platelet reactivity was compared between patients stratified by DM, CYP2C19*2 status and clopidogrel dose. Both DM and CYP2C19*2 were independently associated with elevated on-treatment platelet reactivity with clopidogrel 75 mg daily (p<0.0001 for each). With 75 mg, mean on-treatment PRU was progressively higher (p trend < 0.001) when evaluating patients: with neither DM nor CYP2C19*2 (150.7; 95 % CI 140.5-162.6), with only DM (187.2; 95 % CI, 171.3-206.9), with only CYP2C19*2 (227.9; 95 % CI, 205.1-250.8), and with both DM and CYP2C19*2 (239.9; 95 % CI, 209.7-270.1). Notably, with 75 mg, patients with only CYP2C19*2 had higher on-treatment platelet reactivity than those with only DM (p=0.0068). To achieve on-treatment platelet reactivity similar to that seen with clopidogrel 75 mg in patients with neither DM nor CYP2C19*2, the following doses were required: 150 mg with only DM, 225 mg with only CYP2C19*2, and 300 mg with both DM and CYP2C19*2. Patients with both DM and CYP2C19*2 required a four-fold increase in clopidogrel maintenance dose as compared to patients without these factors to achieve a similar antiplatelet response. C1 [Carreras, Edward T.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. [Hochholzer, Willibald] Univ Heart Ctr Freiburg, Dept Cardiol & Angiol 2, Bad Krozingen, Germany. [Frelinger, Andrew L., III; Michelson, Alan D.] Harvard Med Sch, Dana Farber Canc Inst, Boston Childrens Hosp, Div Hematol Oncol,Ctr Platelet Res Studies, Boston, MA USA. [Nordio, Francesco; O'Donoghue, Michelle L.; Wiviott, Stephen D.; Sabatine, Marc S.; Mega, Jessica L.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. [Nordio, Francesco; O'Donoghue, Michelle L.; Wiviott, Stephen D.; Sabatine, Marc S.; Mega, Jessica L.] Harvard Med Sch, Boston, MA USA. [Angiolillo, Dominick J.] Univ Florida, Coll Med, Jacksonville, FL USA. [Mega, Jessica L.] Verily Life Sci, Mountain View, CA USA. RP Carreras, ET; Sabatine, MS (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ecarreras@partners.org; msabatine@partners.org FU Bristol-Myers Squibb/sanofi-aventis; National Institutes of Health [K99/R00 HL098461]; German Heart Foundation FX The ELEVATE-TIMI 56 trial was funded by an investigator-initiated grant from Bristol-Myers Squibb/sanofi-aventis. Research supplies were provided by Accumetrics and Nanosphere. Dr. Mega was supported in part by grant K99/R00 HL098461 from the National Institutes of Health. Dr. Hochholzer is supported in part by the German Heart Foundation. NR 30 TC 0 Z9 1 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2016 VL 116 IS 1 BP 69 EP 77 DI 10.1160/TH15-12-0981 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA DQ8XM UT WOS:000379495000008 PM 27009617 ER PT J AU Hodak, S Tuttle, RM Maytal, G Nikiforov, YE Randolph, G AF Hodak, Steven Tuttle, R. Michael Maytal, Guy Nikiforov, Yuri E. Randolph, Gregory TI Changing the Cancer Diagnosis: The Case of Follicular Variant of Papillary Thyroid Cancer-Primum Non Nocere and NIFTP SO THYROID LA English DT Editorial Material ID BRAF V600E; CARCINOMA; RISK; OVERDIAGNOSIS; MANAGEMENT; TUMORS C1 [Hodak, Steven] NYU, Dept Endocrinol, New York, NY USA. [Tuttle, R. Michael] Mem Sloan Kettering Canc Ctr, Dept Endocrinol, 1275 York Ave, New York, NY 10021 USA. [Maytal, Guy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Nikiforov, Yuri E.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. [Randolph, Gregory] Massachusetts Gen Hosp, Dept Otolaryngol Head Neck Surg, Massachusetts Eye & Ear Infirm, Surg Oncol, Boston, MA 02114 USA. RP Randolph, G (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Thyroid & Parathyroid Surg, 243 Charles St, Boston, MA 02114 USA. EM Gregory_Randolph@meei.harvard.edu NR 21 TC 1 Z9 1 U1 1 U2 2 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 JUL PY 2016 VL 26 IS 7 BP 869 EP 871 DI 10.1089/thy.2016.0205 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DR0PU UT WOS:000379610200001 PM 27184034 ER PT J AU Daniels, GH AF Daniels, Gilbert H. TI Follicular Variant of Papillary Thyroid Carcinoma: Hybrid or Mixture? SO THYROID LA English DT Editorial Material ID GENERATION SEQUENCING ASSAY; DIAGNOSIS; IMPACT; CANCER; CYTOLOGY; NODULES; MALIGNANCY; MUTATIONS; INVASION; LESIONS C1 [Daniels, Gilbert H.] Massachusetts Gen Hosp, Ctr Canc, Thyroid Unit, Boston, MA 02114 USA. [Daniels, Gilbert H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Daniels, Gilbert H.] Harvard Med Sch, Boston, MA USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC 730, Boston, MA 02114 USA. EM gdaniels@partners.org NR 23 TC 2 Z9 2 U1 1 U2 2 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 JUL PY 2016 VL 26 IS 7 BP 872 EP 874 DI 10.1089/thy.2016.0244 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DR0PU UT WOS:000379610200002 PM 27214083 ER PT J AU Winter, CC Katiyar, KS Hernandez, NS Song, YJ Struzyna, LA Harris, JP Cullen, DK AF Winter, Carla C. Katiyar, Kritika S. Hernandez, Nicole S. Song, Yeri J. Struzyna, Laura A. Harris, James P. Cullen, D. Kacy TI Transplantable living scaffolds comprised of micro-tissue engineered aligned astrocyte networks to facilitate central nervous system regeneration SO ACTA BIOMATERIALIA LA English DT Article DE Tissue engineering; Living scaffold; Glial cell transplant; Biomaterials; Regeneration; Neurotrauma; Neurodegeneration; Traumatic brain injury; Cell migration; Axon pathfinding; Neural stem cells ID SPINAL-CORD-INJURY; ROSTRAL MIGRATORY STREAM; NEURAL STEM-CELLS; NEURITE OUTGROWTH; IN-VITRO; SUBSTRATE CURVATURE; SUBVENTRICULAR ZONE; NEURONAL MIGRATION; BRAIN-INJURY; TRACT AXONS AB Neurotrauma, stroke, and neurodegenerative disease may result in widespread loss of neural cells as well as the complex interconnectivity necessary for proper central nervous system function, generally resulting in permanent functional deficits. Potential regenerative strategies involve the recruitment of endogenous neural stem cells and/or directed axonal regeneration through the use of tissue engineered "living scaffolds" built to mimic features of three-dimensional (3-D) in vivo migratory or guidance pathways. Accordingly, we devised a novel biomaterial encasement scheme using tubular hydrogel-collagen micro-columns that facilitated the self-assembly of seeded astrocytes into 3-D living scaffolds consisting of long, cable-like aligned astrocytic networks. Here, robust astrocyte alignment was achieved within a micro-column inner diameter (ID) of 180 mu m or 300-350 mu m but not 1.0 mm, suggesting that radius of curvature dictated the extent of alignment. Moreover, within small ID micro-columns, >70% of the astrocytes assumed a bi-polar morphology, versus similar to 10% in larger micro-columns or planar surfaces. Cell-cell interactions also influenced the aligned architecture, as extensive astrocyte-collagen contraction was achieved at high (9-12 x 10(5) cells/mL) but not lower (2-6 x 10(5) cells/mL) seeding densities. This high density micro-column seeding led to the formation of ultra-dense 3-D "bundles" of aligned bi-polar astrocytes within collagen measuring up to 150 mu m in diameter yet extending to a remarkable length of over 2.5 cm. Importantly, co-seeded neurons extended neurites directly along the aligned astrocytic bundles, demonstrating permissive cues for neurite extension. These transplantable cable-like astrocytic networks structurally mimic the glial tube that guides neuronal progenitor migration in vivo along the rostral migratory stream, and therefore may be useful to guide progenitor cells to repopulate sites of widespread neurodegeneration. Statement of Significance This manuscript details our development of novel micro-tissue engineering techniques to generate robust networks of longitudinally aligned astrocytes within transplantable micro-column hydrogels. We report a novel biomaterial encasement scheme that facilitated the self-assembly of seeded astrocytes into long, aligned regenerative pathways. These miniature "living scaffold" constructs physically emulate the glial tube - a pathway in the brain consisting of aligned astrocytes that guide the migration of neuronal progenitor cells - and therefore may facilitate directed neuronal migration for central nervous system repair. The small size and self-contained design of these aligned astrocyte constructs will permit minimally invasive transplantation in models of central nervous system injury in future studies. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. C1 [Winter, Carla C.; Katiyar, Kritika S.; Hernandez, Nicole S.; Song, Yeri J.; Struzyna, Laura A.; Harris, James P.; Cullen, D. Kacy] Univ Penn, Perelman Sch Med, Ctr Brain Injury & Repair, Dept Neurosurg, Philadelphia, PA 19104 USA. [Winter, Carla C.; Struzyna, Laura A.] Univ Penn, Sch Engn & Appl Sci, Dept Bioengn, Philadelphia, PA 19104 USA. [Winter, Carla C.; Katiyar, Kritika S.; Struzyna, Laura A.; Harris, James P.; Cullen, D. Kacy] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Katiyar, Kritika S.] Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19104 USA. [Hernandez, Nicole S.; Song, Yeri J.; Cullen, D. Kacy] Univ Penn, Perelman Sch Med, Neurosci Grad Grp, Philadelphia, PA 19104 USA. RP Cullen, DK (reprint author), 105E Hayden Hall 3320 Smith Walk, Philadelphia, PA 19104 USA. EM dkacy@mail.med.upenn.edu FU Penn Medicine Neuroscience Center; National Science Foundation [DGE-1321851]; National Institutes of Health [T32-NS043126, F31-NS090746]; Michael J. Fox Foundation (Therapeutic Pipeline Program) [9998]; Department of Veterans Affairs (RRD Merit Review) [B1097-I]; U.S. Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program [W81XWH-13-207004]; Penn's Center for Undergraduate Research Fellowships FX Financial support was provided by the Penn Medicine Neuroscience Center, National Science Foundation (Graduate Research Fellowship DGE-1321851), National Institutes of Health (T32-NS043126; F31-NS090746), Michael J. Fox Foundation (Therapeutic Pipeline Program #9998), Department of Veterans Affairs (RR&D Merit Review #B1097-I), U.S. Army Medical Research and Materiel Command through the Joint Warfighter Medical Research Program (#W81XWH-13-207004), and Penn's Center for Undergraduate Research & Fellowships. We thank Patricia Murphy for technical assistance in these studies. NR 56 TC 1 Z9 1 U1 18 U2 31 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD JUL 1 PY 2016 VL 38 BP 44 EP 58 DI 10.1016/j.actbio.2016.04.021 PG 15 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA DQ1LZ UT WOS:000378963800005 PM 27090594 ER PT J AU Stoeckel, LE Chai, XQJ Zhang, JH Whitfield-Gabrieli, S Evins, AE AF Stoeckel, Luke E. Chai, Xiaoqian J. Zhang, Jiahe Whitfield-Gabrieli, Susan Evins, A. Eden TI Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers SO ADDICTION BIOLOGY LA English DT Article DE Executive function; functional connectivity; nicotine addiction; salience; voxel-based morphometry ID GLOBAL SIGNAL REGRESSION; PREFRONTAL CORTEX; WITHDRAWAL SYMPTOMS; BRAIN; NICOTINE; NETWORK; ADDICTION; ORGANIZATION; SMOKING; FMRI AB Although nicotine addiction is characterized by both structural and functional abnormalities in brain networks involved in salience and cognitive control, few studies have integrated these data to understand how these abnormalities may support addiction. This study aimed to (1) evaluate gray matter density and functional connectivity of the anterior insula in cigarette smokers and never smokers and (2) characterize how differences in these measures were related to smoking behavior. We compared structural magnetic resonance imaging (MRI) (gray matter density via voxel-based morphometry) and seed-based functional connectivity MRI data in 16 minimally deprived smokers and 16 matched never smokers. Compared with controls, smokers had lower gray matter density in left anterior insula extending into inferior frontal and temporal cortex. Gray matter density in this region was inversely correlated with cigarettes smoked per day. Smokers exhibited negative functional connectivity (anti-correlation) between the anterior insula and regions involved in cognitive control (left lPFC) and semantic processing/emotion regulation (lateral temporal cortex), whereas controls exhibited positive connectivity between these regions. There were differences in the anterior insula, a central region in the brain's salience network, when comparing both volumetric and functional connectivity data between cigarette smokers and never smokers. Volumetric data, but not the functional connectivity data, were also associated with an aspect of smoking behavior (daily cigarettes smoked). C1 [Stoeckel, Luke E.; Evins, A. Eden] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Stoeckel, Luke E.; Evins, A. Eden] Harvard Med Sch, Boston, MA USA. [Chai, Xiaoqian J.; Zhang, Jiahe; Whitfield-Gabrieli, Susan] MIT, Dept Brain & Cognit Sci, McGovern Inst Brain Res, E25-618, Cambridge, MA 02139 USA. RP Stoeckel, LE (reprint author), Massachusetts Gen Hosp, Ctr Addict Med, 60 Staniford St, Boston, MA 02114 USA. EM lstoeckel@mgh.harvard.edu FU Harvard Medical School Norman E. Zinberg Fellowship in Addiction Psychiatry Research; Brain and Behavior Research Foundation NARSAD; Charles A. King Trust; NIH [K23DA032612, K24 DA030443] FX We wish to acknowledge Ms. Vanessa Calderon, Alice Coakley, Caroline Chan, Janani Raveendran, Satrajit Ghosh, Carlo de los Angeles, Jodi Gilman, Gretchen Reynolds and Julia Stern for imaging study support, discussion of methods, assistance with manuscript preparation and critical review of the manuscript. This research was carried out at the Athinoula A. Martinos Imaging Center at the McGovern Institute for Brain Research at the Massachusetts Institute of Technology. Finally, the study was supported by the Harvard Medical School Norman E. Zinberg Fellowship in Addiction Psychiatry Research (L.E.S.), a Brain and Behavior Research Foundation NARSAD Young Investigator Award (L.E.S.), the Charles A. King Trust (L.E.S.), NIH K23DA032612 (L.E.S.) and NIH K24 DA030443 (A.E.E.). NR 53 TC 3 Z9 3 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1355-6215 EI 1369-1600 J9 ADDICT BIOL JI Addict. Biol. PD JUL PY 2016 VL 21 IS 4 BP 972 EP 981 DI 10.1111/adb.12262 PG 10 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA DQ4CP UT WOS:000379151100020 PM 25990865 ER PT J AU Elsesser, SA Oldenburg, CE Biello, KB Mimiaga, MJ Safren, SA Egan, JE Novak, DS Krakower, DS Stall, R Mayer, KH AF Elsesser, Steven A. Oldenburg, Catherine E. Biello, Katie B. Mimiaga, Matthew J. Safren, Steven A. Egan, James E. Novak, David S. Krakower, Douglas S. Stall, Ron Mayer, Kenneth H. TI Seasons of Risk: Anticipated Behavior on Vacation and Interest in Episodic Antiretroviral Pre-exposure Prophylaxis (PrEP) Among a Large National Sample of US Men Who have Sex with Men (MSM) SO AIDS AND BEHAVIOR LA English DT Article DE PrEP; MSM; Episodic PrEP; Epi-PrEP; HIV ID BISEXUAL MEN; TRANSGENDER WOMEN; LIMITED KNOWLEDGE; HIV PREVENTION; GAY; PERSPECTIVES; INTERMITTENT; INFECTION; EDUCATION; BARRIERS AB The current analysis evaluates interest in and acceptability of daily PrEP during short episodes of anticipated increased risk (i.e. Epi-PrEP). In 2013, U.S. members of an internet-based MSM sexual networking site were invited to complete a survey about HIV prevention practices in the context of vacationing. 7305 MSM responded to the survey. Of respondents who had vacationed in the past year, 25.6 % reported condomless anal sex (CAS) with new male sex partners while vacationing. Most (92.6 %) respondents agreed that having to use PrEP every day was a barrier to PrEP use and 74.3 % indicated they would take PrEP if they knew it would be helpful for short periods of anticipated increased risk. MSM who reported increased CAS while on vacation in the past year were more likely to indicate that they would take PrEP if it were helpful when used for short periods than respondents who did not (aOR = 2.02, 95 % CI 1.59-2.56, p < 0.001). Studies designed to evaluate uptake, adherence, and protective benefit of short PrEP courses are warranted. C1 [Elsesser, Steven A.; Oldenburg, Catherine E.; Biello, Katie B.; Mimiaga, Matthew J.; Safren, Steven A.; Krakower, Douglas S.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, 8th Floor,1340 Boylston St, Boston, MA 02115 USA. [Oldenburg, Catherine E.; Biello, Katie B.; Mimiaga, Matthew J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Mimiaga, Matthew J.; Safren, Steven A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Safren, Steven A.; Mayer, Kenneth H.] Harvard Med Sch, Dept Med, Boston, MA 02115 USA. [Egan, James E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Behav & Community Hlth Sci, Pittsburgh, PA USA. [Novak, David S.] Online Buddies Inc, OLB Res Inst, Cambridge, MA USA. [Krakower, Douglas S.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Stall, Ron] Univ Pittsburgh, Dept Behav & Social Sci, Pittsburgh, PA USA. [Mayer, Kenneth H.] Harvard Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. RP Mayer, KH (reprint author), Fenway Hlth, Fenway Inst, 8th Floor,1340 Boylston St, Boston, MA 02115 USA.; Mayer, KH (reprint author), Harvard Med Sch, Dept Med, Boston, MA 02115 USA.; Mayer, KH (reprint author), Harvard Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA 02115 USA. EM kmayer@fenwayhealth.org FU Gilead Sciences FX This work was funded by an unrestricted research grant from Gilead Sciences. NR 40 TC 2 Z9 2 U1 4 U2 7 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 JUL PY 2016 VL 20 IS 7 BP 1400 EP 1407 DI 10.1007/s10461-015-1238-0 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DQ1ZS UT WOS:000379000500003 PM 26538056 ER PT J AU Kuhns, LM Reisner, SL Mimiaga, MJ Gayles, T Shelendich, M Garofalo, R AF Kuhns, Lisa M. Reisner, Sari L. Mimiaga, Matthew J. Gayles, Travis Shelendich, Michael Garofalo, Robert TI Correlates of PrEP Indication in a Multi-Site Cohort of Young HIV-Uninfected Transgender Women SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Transgender; PrEP; Young adults ID PREEXPOSURE PROPHYLAXIS; RISK; MEN; SEX AB Transgender women are at high risk of HIV infection, with younger transgender women (YTW) particularly vulnerable. Pre-Exposure Prophylaxis (PrEP) has shown efficacy in reducing HIV acquisition, but little is known about PrEP indication or initiation among YTW. Baseline data from 180 YTW age 18-29 years enrolled in Project LifeSkills, an on-going HIV prevention intervention for YTW, were analyzed to examine factors associated with PrEP indication. The sample (mean age = 23.4, SD = 3.2) was comprised largely of women of color (69 %) and of low socioeconomic status (71 % unemployed). Overall, 62 % met criteria for PrEP indication, but only 5 % reported ever taking PrEP. Factors associated with increased odds of PrEP indication were: PrEP interest (aOR 3.24; 95 % CI 1.44, 7.33), number of recent anal sex partners (aOR 1.23; 95 % CI 1.04, 1.46), and lower collective self-esteem scores (aOR 0.67; 95 % CI 0.47, 0.94). Despite high levels of PrEP indication, there remain low levels of PrEP awareness and uptake among YTW. C1 [Kuhns, Lisa M.; Gayles, Travis; Garofalo, Robert] Ann & Robert H Lurie Childrens Hosp, Div Adolescent Med, 225 E Chicago Ave,Box 161, Chicago, IL 60611 USA. [Kuhns, Lisa M.; Gayles, Travis; Shelendich, Michael; Garofalo, Robert] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA. [Reisner, Sari L.; Mimiaga, Matthew J.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Reisner, Sari L.; Mimiaga, Matthew J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Kuhns, LM (reprint author), Ann & Robert H Lurie Childrens Hosp, Div Adolescent Med, 225 E Chicago Ave,Box 161, Chicago, IL 60611 USA.; Kuhns, LM (reprint author), Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA. EM lkuhns@luriechildrens.org FU National Institute of Mental Health of the National Institutes of Health [R01MH094323]; Northwestern University Clinical and Translational Science Institute from the National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (CTSA) [UL1TR000150] FX We thank members of the LifeSkills Study Team in Boston and Chicago for their contribution to sample accrual and data collection and Abigail Muldoon for preparation of data for analysis. Research reported in this publication was supported by the National Institute of Mental Health of the National Institutes of Health under Award Number R01MH094323. The project described was also supported, in part, by the Northwestern University Clinical and Translational Science Institute, Grant Number UL1TR000150 from the National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (CTSA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. The CTSA is a registered trademark of the U.S. Department of Health and Human Services (DHHS). ClinicalTrials.gov registration number NCT01575938. NR 24 TC 3 Z9 3 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JUL PY 2016 VL 20 IS 7 BP 1470 EP 1477 DI 10.1007/s10461-015-1182-z PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DQ1ZS UT WOS:000379000500011 PM 26336946 ER PT J AU Calabrese, SK Underhill, K Earnshaw, VA Hansen, NB Kershaw, TS Magnus, M Krakower, DS Mayer, KH Betancourt, JR Dovidio, JF AF Calabrese, Sarah K. Underhill, Kristen Earnshaw, Valerie A. Hansen, Nathan B. Kershaw, Trace S. Magnus, Manya Krakower, Douglas S. Mayer, Kenneth H. Betancourt, Joseph R. Dovidio, John F. TI Framing HIV Pre-Exposure Prophylaxis (PrEP) for the General Public: How Inclusive Messaging May Prevent Prejudice from Diminishing Public Support SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Pre-exposure prophylaxis (PrEP); Framing; Public opinion; Prejudice; Black/African American; Men who have sex with men (MSM) ID SOCIAL CONSTRUCTION; ANTIRETROVIRAL PROPHYLAXIS; TRANSGENDER WOMEN; UNITED-STATES; BLACK-MEN; HIGH-RISK; SEX; INFECTION; ATTITUDES; POLICY AB Strategic framing of public messages about HIV pre-exposure prophylaxis (PrEP) may influence public support for policies and programs affecting access. This survey study examined how public attitudes toward PrEP differed based on the social group PrEP was described as benefiting ("beneficiary'') and the moderating effect of prejudice. Members of the general public (n = 154) recruited online were randomly assigned to three beneficiary conditions: general population, gay men, or Black gay men. All participants received identical PrEP background information before completing measures of PrEP attitudes (specifying beneficiary), racism, and heterosexism. Despite anticipating greater PrEP adherence among gay men and Black gay men and perceiving PrEP as especially beneficial to the latter, participants expressed lower support for policies/programs making PrEP affordable for these groups vs. the general population. This disparity in support was stronger among participants reporting greater prejudice. Inclusive framing of PrEP in public discourse may prevent prejudice from undermining implementation efforts. C1 [Calabrese, Sarah K.; Kershaw, Trace S.] Yale Univ, Dept Chron Dis Epidemiol, Yale Sch Publ Hlth, 135 Coll St,Suite 358, New Haven, CT 06510 USA. [Calabrese, Sarah K.; Underhill, Kristen; Earnshaw, Valerie A.; Hansen, Nathan B.; Kershaw, Trace S.; Dovidio, John F.] Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. [Underhill, Kristen] Yale Univ, Yale Law Sch, New Haven, CT USA. [Earnshaw, Valerie A.] Harvard Med Sch, Boston Childrens Hosp, Boston, MA USA. [Hansen, Nathan B.] Univ Georgia, Coll Publ Hlth, Dept Hlth Promot & Behav, Athens, GA 30602 USA. [Magnus, Manya] George Washington Univ, Sch Publ Hlth, Milken Inst, Dept Epidemiol & Biostat, Washington, DC USA. [Krakower, Douglas S.; Mayer, Kenneth H.] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Krakower, Douglas S.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Betancourt, Joseph R.] Harvard Med Sch, Dispar Solut Ctr, Massachusetts Gen Hosp, Boston, MA USA. [Dovidio, John F.] Yale Univ, Dept Psychol, New Haven, CT USA. RP Calabrese, SK (reprint author), Yale Univ, Dept Chron Dis Epidemiol, Yale Sch Publ Hlth, 135 Coll St,Suite 358, New Haven, CT 06510 USA.; Calabrese, SK (reprint author), Yale Univ, Ctr Interdisciplinary Res AIDS, New Haven, CT 06520 USA. EM sarah.calabrese@yale.edu FU National Institute of Mental Health (NIMH) [K01-MH103080, P30-MH062294]; Yale University Fund for Lesbian and Gay Studies Award; NIMH [K01-MH093273, K23-MH098795]; Agency for Healthcare Research and Quality (AHRQ) [K12-HS022986] FX This research was supported by Award Numbers K01-MH103080 and P30-MH062294 from the National Institute of Mental Health (NIMH) and the Yale University Fund for Lesbian and Gay Studies Award. Kristen Underhill and Douglas S. Krakower were supported by NIMH Award Numbers K01-MH093273 and K23-MH098795, respectively. Valerie A. Earnshaw was supported by the Agency for Healthcare Research and Quality (AHRQ) Award Number K12-HS022986. Mentorship was received from the Social and Behavioral Sciences Research Network (SBSRN) of the National Institutes of Health Centers for AIDS Research (2013 SBSRN National Scientific Meeting Mentoring Day) and P30-AI060354. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIMH, the SBSRN, the National Institutes of Health, the AHRQ, or Yale Lesbian and Gay Studies. The authors wish to thank Valen Grandelski for programming the survey, Suzanne Horowitz for her technical assistance on the survey, and Adam Eldahan for his support with reference management software and proofreading. The authors are also grateful to the individuals who generously contributed their time and effort by participating in this study. NR 91 TC 0 Z9 0 U1 6 U2 7 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 JUL PY 2016 VL 20 IS 7 BP 1499 EP 1513 DI 10.1007/s10461-016-1318-9 PG 15 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DQ1ZS UT WOS:000379000500014 PM 26891840 ER PT J AU Jain, S Oldenburg, CE Mimiaga, MJ Mayer, KH AF Jain, Sachin Oldenburg, Catherine E. Mimiaga, Matthew J. Mayer, Kenneth H. TI High Levels of Concomitant Behavioral Health Disorders Among Patients Presenting for HIV Non-occupational Post-exposure Prophylaxis at a Boston Community Health Center Between 1997 and 2013 SO AIDS AND BEHAVIOR LA English DT Article DE HIV; PEP; nPEP; Syndemic; Mental illness ID CHILDHOOD SEXUAL-ABUSE; SEVERE MENTAL-ILLNESS; RISK BEHAVIOR; ANTIRETROVIRAL PROPHYLAXIS; TRANSMISSION RISK; SUBSTANCE USE; SOUTH-AFRICA; YOUNG MEN; FOLLOW-UP; INFECTION AB A paucity of information regarding mental health exists for patients presenting for HIV non-occupational post-exposure prophylaxis (nPEP). We reviewed electronicmedical records of 894 adult nPEP patients seen at a large Boston community health center between 1997 and 2013. Of 821 patients with consensual sexual exposures, 88.3 % were men who have sex with men, and 40.0 % had a mental health diagnosis. Diagnoses included: depression (24.4 %), anxiety (21.9 %), attention deficit disorder (7.8 %), post-traumatic stress disorder (3.3 %), and psychotic disorders (3.3 %). Of 129 patients with substance use disorders, alcohol dependence (65.9 %) and crystal methamphetamine (43.4 %) predominated. Unprotected receptive anal intercourse was associated with psychotic disorders (aOR = 4.86; 95 % CI: 1.76-13.5) and substance use disorders (aOR = 1.89; 95 % CI: 1.28-2.80). Substance use at the time of exposure was associated with: depression (aOR = 1.95; 95 % CI: 1.36-2.80), anxiety (aOR = 2.22; 95 % CI: 1.51-3.25), attention deficit disorder (aOR = 1.96; 95 % CI: 1.18-3.27), and substance use disorder (aOR = 4.78; 95 % CI: 3.30-6.93). Mental illness should be screened for and addressed at nPEP visits to optimize HIV risk-reduction. C1 [Jain, Sachin] Montefiore Med Ctr, Albert Einstein Coll Med, Div Infect Dis, Bronx, NY 10467 USA. [Oldenburg, Catherine E.; Mimiaga, Matthew J.; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Oldenburg, Catherine E.; Mimiaga, Matthew J.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Mimiaga, Matthew J.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. RP Jain, S (reprint author), Montefiore Med Ctr, Albert Einstein Coll Med, Div Infect Dis, Bronx, NY 10467 USA. EM sajain@montefiore.org FU Harvard University Center For AIDS Research (CFAR), an NIH [P30 AI060354]; National Institute of Allergy and Infectious Disease T32 NRSA Grant [T32AI007535]; National Institute of Drug Abuse T32 NRSA Grant [T32DA013911] FX The Fenway Institute Data Team, including Chris Grasso, Ken Levine, and Shayne Zaslow, screened eligible patients for this study, aided with construction of the data abstraction tool, and provided database support. The Harvard University Center For AIDS Research (CFAR), an NIH funded program (P30 AI060354; PI: Walker), provided statistical consultation and contributes to Mayer's funding. Oldenburg is supported by a National Institute of Allergy and Infectious Disease T32 NRSA Grant (T32AI007535; PI: Seage) and a National Institute of Drug Abuse T32 NRSA Grant (T32DA013911; PI: Flanigan). NR 53 TC 0 Z9 0 U1 3 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD JUL PY 2016 VL 20 IS 7 BP 1556 EP 1563 DI 10.1007/s10461-015-1021-2 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA DQ1ZS UT WOS:000379000500020 PM 25689892 ER PT J AU Duncan, DT Rienti, M Kulldorff, M Aldstadt, J Castro, MC Frounfelker, R Williams, JH Sorensen, G Johnson, RM Hemenway, D Williams, DR AF Duncan, Dustin T. Rienti, Michael, Jr. Kulldorff, Martin Aldstadt, Jared Castro, Marcia C. Frounfelker, Rochelle Williams, James H. Sorensen, Glorian Johnson, Renee M. Hemenway, David Williams, David R. TI Local spatial clustering in youths' use of tobacco, alcohol, and marijuana in Boston SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Spatial clustering; drug use; tobacco use; alcohol use; marijuana use; youth ID AFRICAN-AMERICAN ADOLESCENTS; SUBSTANCE USE DISORDERS; ILLICIT DRUG-USE; CIGARETTE-SMOKING; NATURAL-HISTORY; SOCIAL NETWORK; UNITED-STATES; HIGH-SCHOOL; URBAN; STRESS AB Background: Understanding geographic variation in youth drug use is important for both identifying etiologic factors and planning prevention interventions. However, little research has examined Spatial clustering of drug use among youths by using rigorous statistical methods. Objectives: The purpose of this study was to examine spatial clustering of youth use of tobacco, alcohol, and marijuana. Methods! Responses on, tobacco, alcohol, and Marijuana use from 1,292 high school students ages 13-19 who provided complete residential addresses were drawn from the 2008 Boston Youth Survey Geospatial Dataset. Response options on past month use included "none," "1-2," "3-9," and "10 or more." The response rate for each substance was approximately 94%. Spatial clustering Of youth drug use was assessed using the spatial Bernoulli model in. the SatScan (TM) Software package. Results Approximately 12%, 3:6%, and 18% of youth reported any past-month use of tobacco, alcohol, and/or Marijuana, respectively. Two clusters of elevated past tobacco use among: Boston youths were generated, one of which was statistically significant. This cluster, located in the South Boston neighborhood, had a relative risk of 5:37 with,a p-Value of 0.00014. There was no significant localized spatial clustering in youth past alcohol or marijuana use in either the unadjusted or adjusted. Models. Conclusion: Significant Spatial-clustering in youth tobacco use was-found.. Finding a significant cluster in the South Boston neighborhood provides reason for further investigation into neighborhood characteristics that may shape adolescents' substance use behaviors. This type of research can be used to evaluate the underlying reasons behind spatial clustering of youth substance and to target local drug abuse prevention interventions and use. C1 [Duncan, Dustin T.; Williams, James H.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA. [Duncan, Dustin T.] NYU, Coll Global Publ Hlth, New York, NY USA. [Duncan, Dustin T.] NYU, Coll Nursing, Ctr Drug Use & HIV Res, New York, NY USA. [Duncan, Dustin T.] NYU, Coll Arts & Sci, Populat Ctr, New York, NY USA. [Duncan, Dustin T.] NYU, Ctr Data Sci, New York, NY USA. [Rienti, Michael, Jr.; Aldstadt, Jared] SUNY Buffalo, Dept Geog, Buffalo, NY USA. [Rienti, Michael, Jr.] SUNY Buffalo, Ctr Hlth & Social Res, Buffalo, NY USA. [Kulldorff, Martin] Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. [Kulldorff, Martin] Harvard Med Sch, Boston, MA USA. [Castro, Marcia C.] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA USA. [Castro, Marcia C.] Harvard Univ, Harvard Ctr Populat & Dev Studies, Cambridge, MA 02138 USA. [Frounfelker, Rochelle; Williams, David R.] Harvard TH Chan Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Sorensen, Glorian; Williams, David R.] Harvard TH Chan Sch Publ Hlth, Lung Canc Dispar Ctr, Boston, MA USA. [Sorensen, Glorian; Johnson, Renee M.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Hemenway, David] Harvard TH Chan Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Williams, David R.] Harvard Univ, Dept African & African Amer Studies, Cambridge, MA 02138 USA. [Williams, David R.] Harvard Univ, Dept Sociol, Cambridge, MA 02138 USA. RP Duncan, DT (reprint author), New York Univ, Dept Populat Hlth, Spatial Epidemiol Lab, Sch Med, 227 East 30th St,Off 621, New York, NY 10016 USA. EM Dustin.Duncan@nyumc.org OI Johnson, Renee/0000-0001-5083-8686 FU New York University School of Medicine Start-Up Research Fund; National Institutes of Health [R01CA165057]; Centers for Disease Control and Prevention [U49CE00740]; Robert Wood Johnson Foundation's Active Living Research Program [67129]; Robert Wood Johnson Foundation Health; Society Scholars Seed Grant Program Harvard Center for Population and Development Studies, Harvard School of Public Health FX Dr. Dustin Duncan was supported by his New York University School of Medicine Start-Up Research Fund to work on this project. Dr. Martin Kulldorff was supported in part by a grant from the National Institutes of Health (grant # R01CA165057). The 2008 Boston Youth Survey was funded by a grant from the Centers for Disease Control and Prevention (grant U49CE00740) to the Harvard Youth Violence Prevention Center at Harvard School of Public Health (David Hemenway, PhD, Principal Investigator). A grant to Dustin Duncan from Robert Wood Johnson Foundation's Active Living Research Program (grant # 67129) supported the development of the Boston Youth Survey Geospatial Dataset. This study was supported by the Robert Wood Johnson Foundation Health and Society Scholars Seed Grant Program (grant to Dustin Duncan), Harvard Center for Population and Development Studies, Harvard School of Public Health. NR 58 TC 0 Z9 0 U1 4 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 0095-2990 EI 1097-9891 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD JUL PY 2016 VL 42 IS 4 BP 412 EP 421 DI 10.3109/00952990.2016.1151522 PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA DQ1MW UT WOS:000378966100007 PM 27096932 ER PT J AU Vijayan, A Faubel, S Askenazi, DJ Cerda, J Fissell, WH Heung, M Humphreys, BD Koyner, JL Liu, KD Mour, G Nolin, TD Bihorac, A AF Vijayan, Anitha Faubel, Sarah Askenazi, David J. Cerda, Jorge Fissell, William H. Heung, Michael Humphreys, Benjamin D. Koyner, Jay L. Liu, Kathleen D. Mour, Girish Nolin, Thomas D. Bihorac, Azra CA Amer Soc Nephrology Acute Kidney Injury Advisory Grp TI Clinical Use of the Urine Biomarker [TIMP-2] x [ IGFBP7] for Acute Kidney Injury Risk Assessment SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Acute kidney injury (AKI); biomarker; [TIMP-2] x [IGFBP7]; diagnosis; critically ill; tissue inhibitor of metalloproteinase 2; insulin-like growth factor binding protein 7; NephroCheck; early detection; risk assessment; renal dysfunction; decreased kidney function ID ACUTE-RENAL-FAILURE; CYCLE ARREST BIOMARKERS; CRITICALLY-ILL PATIENTS; FUROSEMIDE STRESS TEST; ACID-BINDING PROTEIN; CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; TISSUE INHIBITOR; NEPHROLOGY CONSULTATION; POOR OUTCOMES AB Acute kidney injury (AKI) is a serious complication, commonly occurring in the critically ill population, with devastating short- and long-term consequences. Despite standardization of the definition and staging of AKI, early recognition remains challenging given that serum creatinine level is a marker, albeit imperfect, of kidney function and not kidney injury. Furthermore, the delay in increase in serum creatinine level after loss of glomerular filtration also prevents timely detection of decreased kidney function in patients with AKI. During the past decade, numerous clinical investigations have evaluated the utility of several biomarkers in the early diagnosis and risk stratification of AKI. In 2014, the US Food and Drug Administration approved the marketing of a test based on the combination of urine concentrations of tissue inhibitor of metalloproteinase 2 and insulinlike growth factor binding protein 7 ([TIMP-2] 3 [ IGFBP7]) to determine whether certain critically ill patients are at risk for developing moderate to severe AKI. The optimal role of this biomarker in the diagnosis, management, and prognosis of AKI in different clinical settings requires further clarification. In this perspective, we summarize the biological actions of these 2 cell-cycle arrest biomarkers and present important considerations regarding the clinical application, interpretation, and limitations of this novel test for the early detection of AKI. Am J Kidney Dis. 68(1): 19-28. (C) 2016 by the National Kidney Foundation, Inc. C1 [Vijayan, Anitha; Humphreys, Benjamin D.] Washington Univ, Dept Med, Div Renal, St Louis, MO USA. [Faubel, Sarah] Univ Colorado, Div Renal, Denver, CO 80202 USA. [Faubel, Sarah] Denver VA Med Ctr, Denver, CO USA. [Askenazi, David J.] Univ Alabama Birmingham, Div Pediat Nephrol, Birmingham, AL USA. [Cerda, Jorge] Albany Med Coll, Albany, NY 12208 USA. [Fissell, William H.] Vanderbilt Univ, Dept Med, Div Nephrol, 221 Kirkland Hall, Nashville, TN 37235 USA. [Heung, Michael] Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI 48109 USA. [Koyner, Jay L.] Univ Chicago, Dept Med, Sect Nephrol, 5841 S Maryland Ave, Chicago, IL 60637 USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Liu, Kathleen D.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA USA. [Mour, Girish] Univ Pittsburgh, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. [Nolin, Thomas D.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Bihorac, Azra] Univ Florida, Dept Med, Gainesville, FL USA. [Bihorac, Azra] Univ Florida, Dept Anesthesiol, Gainesville, FL USA. [Bihorac, Azra] Univ Florida, Dept Surg, Gainesville, FL USA. RP Vijayan, A (reprint author), Washington Univ, Div Renal, Campus Box 8129,660 S Euclid Ave, St Louis, MO 63110 USA. EM avijayan@dom.wustl.edu FU Spectral Medical Inc and AM-Pharma; Astute Medical Inc; NIH [U01DK104308, U01DK085649]; Abbott; Achaogen Inc; Chemocentryx Inc; Durect Corporation; Center for Sepsis and Critical Illness Award from the National Institute of General Medical Sciences [P50 GM-111152]; Society of Critical Care Medicine FX Dr Vijayan was a clinical adjudicator for the Topaz trial and has research support from Spectral Medical Inc and AM-Pharma. Dr Askenazi is a speaker for the AKI Foundation. Dr Heung reports receiving grant funding from Astute Medical Inc, the manufacturer of NEPHROCHECK. Dr Humphreys is a Co-Principal Investigator on an NIH grant to develop novel biomarkers of chronic kidney disease (CKD) (U01DK104308). Dr Koyner reports receiving grant funding from Abbott and Astute Medical Inc for enrolling patients in observational AKI biomarker studies and consulting fees from Astute Medical Inc. Dr Liu was a clinical adjudicator for the Topaz trial and reports consultancy agreements with Achaogen Inc, Astute Medical Inc, Chemocentryx Inc, and Durect Corporation. She is a Co-Principal Investigator on an NIH grant to test novel biomarkers of CKD (U01DK085649). Dr Nolin is member of the Independent Data Monitoring Committee for Thrasos Innovation Inc. Dr Bihorac is supported by Center for Sepsis and Critical Illness Award P50 GM-111152 from the National Institute of General Medical Sciences and has received research grants from the Society of Critical Care Medicine, Astute Medical Inc, and the I. Heermann Anesthesia Foundation Inc. The remaining authors declare that they have no relevant financial interests. NR 74 TC 8 Z9 8 U1 4 U2 7 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 JUL PY 2016 VL 68 IS 1 BP 19 EP 28 DI 10.1053/j.ajkd.2015.12.033 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA DP6VB UT WOS:000378636100010 PM 26948834 ER PT J AU Kraut, JA AF Kraut, Jeffrey A. TI Approach to the Treatment of Methanol Intoxication SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Toxic alcohols; serum osmolal gap; serum anion gap; fomepizole; methanol; methanol intoxication; ethanol; hemodialysis ID ETHYLENE-GLYCOL; OSMOLAL GAP; FORMATE KINETICS; ANION-GAP; EXTRACORPOREAL TREATMENTS; METABOLIC-ACIDOSIS; SERUM OSMOLALITY; DIAGNOSIS; FOMEPIZOLE; HEMODIALYSIS AB Methanol intoxication is an uncommon but serious poisoning. Its adverse effects are due primarily to the impact of its major metabolite formic acid and lactic acid resulting from cellular hypoxia. Symptoms including abdominal pain and loss of vision can appear a few hours to a few days after exposure, reflecting the time necessary for accumulation of the toxic byproducts. In addition to a history of exposure, increases in serum osmolal and anion gaps can be clues to its presence. However, increments in both parameters can be absent depending on the nature of the toxic alcohol, time of exposure, and coingestion of ethanol. Definitive diagnosis requires measurement with gas or liquid chromatography, which are laborious and expensive procedures. Tests under study to detect methanol or its metabolite formate might facilitate the diagnosis of this poisoning. Treatment can include administration of ethanol or fomepizole, both inhibitors of the enzyme alcohol dehydrogenase to prevent formation of its metabolites, and hemodialysis to remove methanol and formate. In this Acid-Base and Electrolyte Teaching Case, a patient with methanol intoxication due to ingestion of model airplane fuel is described, and the value and limitations of current and new diagnostic and treatment measures are discussed. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. C1 [Kraut, Jeffrey A.] UCLA Membrane Biol Lab, Med & Res Serv Vet Adm Greater Los Angeles Health, Los Angeles, CA USA. [Kraut, Jeffrey A.] Vet Adm Greater Los Angeles Healthcare Syst, Div Nephrol, Los Angeles, CA USA. [Kraut, Jeffrey A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Kraut, JA (reprint author), VHAGLA Healthcare Syst, Div Nephrol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkraut@ucla.edu FU UCLA Academic Senate; Veterans Administration FX Support: The manuscript was supported by funds from the UCLA Academic Senate and Veterans Administration. NR 55 TC 1 Z9 1 U1 3 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2016 VL 68 IS 1 BP 161 EP 167 DI 10.1053/j.ajkd.2016.02.058 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA DP6VB UT WOS:000378636100026 PM 27180631 ER PT J AU Badhwar, V Rankin, JS Jacobs, JP Shahian, DM Habib, RH D'Agostino, RS Thourani, VH Suri, RM Prager, RL Edwards, FH AF Badhwar, Vinay Rankin, J. Scott Jacobs, Jeffrey P. Shahian, David M. Habib, Robert H. D'Agostino, Richard S. Thourani, Vinod H. Suri, Rakesh M. Prager, Richard L. Edwards, Fred H. TI The Society of Thoracic Surgeons Adult Cardiac Surgery Database: 2016 Update on Research SO ANNALS OF THORACIC SURGERY LA English DT Article ID AORTIC-VALVE-REPLACEMENT; NATIONAL DATABASE; OUTCOMES; QUALITY; RISK AB The Society of Thoracic Surgeons Adult Cardiac Database (ACSD) is an international voluntary effort that is the foundation of our specialty's efforts in clinical performance assessment and quality improvement. Containing nearly 6,000,000 patient records, the ACSD is a robust resource for clinical research. Seven major original publications and four review articles were generated from the ACSD in 2015. The risk-adjusted outcome analyses and quality measures reported in these studies have made substantial contributions to inform daily clinical practice. This report summarizes the ACSD-based research efforts published in 2015. (C) 2016 by The Society of Thoracic Surgeons C1 W Virginia Univ, Div Cardiothorac Surg, Morgantown, WV 26506 USA. Johns Hopkins All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, Dept Surg, Div Cardiovasc Surg, St Petersburg, FL USA. Johns Hopkins All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, Dept Surg, Div Cardiovasc Surg, Tampa, FL USA. Johns Hopkins All Childrens Hosp, Johns Hopkins All Childrens Heart Inst, Dept Surg, Div Cardiovasc Surg, Orlando, FL USA. Florida Hosp Children, St Petersburg, FL USA. Florida Hosp Children, Tampa, FL USA. Florida Hosp Children, Orlando, FL USA. Johns Hopkins Univ, Sch Med, Dept Surg, Div Cardiac Surg, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Qual & Safety, Massachusetts Gen Hosp, Boston, MA 02115 USA. Soc Thorac Surg Res Ctr, Chicago, IL USA. Lahey Hosp & Med Ctr, Dept Thorac & Cardiovasc Surg, Burlington, MA USA. Emory Univ, Div Cardiothorac Surg, Atlanta, GA 30322 USA. Cleveland Clin, Div Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA. Univ Michigan, Dept Cardiac Surg, Ann Arbor, MI 48109 USA. Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA. RP Badhwar, V (reprint author), W Virginia Univ, 1 Med Ctr Dr, Morgantown, WV 26506 USA. EM vinay.badhwar@wvumedicine.org FU BioStable Science and Engineering; Admedus Corp; AtriCure USA FX Dr Rankin discloses a financial relationship with BioStable Science and Engineering, Admedus Corp, and AtriCure USA. NR 14 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2016 VL 102 IS 1 BP 7 EP 13 DI 10.1016/j.athoracsur.2016.05.009 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DP6UL UT WOS:000378634400029 PM 27262913 ER PT J AU Stephens, EH Robich, MP Walters, DM DeNino, WF Aftab, M Tchantchaleishvili, V Eilers, AL Rice, RD Goldstone, AB Shlestad, RC Malas, T Cevasco, M Gillaspie, EA Fiedler, AG LaPar, DJ Shah, AA AF Stephens, Elizabeth H. Robich, Michael P. Walters, Dustin M. DeNino, Walter F. Aftab, Muhammad Tchantchaleishvili, Vakhtang Eilers, Amanda L. Rice, Robert D. Goldstone, Andrew B. Shlestad, Ryan C. Malas, Tarek Cevasco, Marisa Gillaspie, Erin A. Fiedler, Amy G. LaPar, Damien J. Shah, Asad A. TI Gender and Cardiothoracic Surgery Training: Specialty Interests, Satisfaction, and Career Pathways SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 23-27, 2016 CL Phoenix, AZ SP Soc Thorac Surg ID GENERAL-SURGERY; WOMEN; PERCEPTIONS; PERFORMANCE; RESIDENTS AB Background. The cardiothoracic surgical workforce is changing. Although 5% of practicing surgeons are women, 20% of current cardiothoracic surgery residents are women. The purpose of this study was to evaluate the influence of gender on specialty interest, satisfaction, and career pathways of current residents. Methods. Responses to the mandatory 2015 Thoracic Surgery Residents Association/Thoracic Surgery Directors Association in-training examination survey taken by 354 residents (100% response rate) were evaluated. The influence of gender was assessed with the use of standard univariate analyses. Results. Women accounted for 20% of residents, and the percentage did not vary with postgraduate year or program type (traditional versus integrated). Although no differences were found between the genders related to specialty interest, academic versus private practice career, or pursuit of additional training, women were more likely to pursue additional training in minimally invasive thoracic surgery (10% versus 2.5%, p = 0.001) and less likely to perform research in their careers (65% versus 88%, p = 0.043). Although women were equally satisfied with their career choice, had similar numbers of interviews and job offers, and felt equally prepared for their boards, graduating women felt less prepared technically (77% versus 90%, p = 0.01) and for practicing independently (71% versus 87%, p = 0.01). Women were less likely to be married (26% versus 62%, p < 0.001) and have children (19% versus 49%, p < 0.001). Conclusions. Although career satisfaction and specialty interest were similar between the genders, women were less likely to intend to perform research during their careers despite similar previous research experience. Women also demonstrated lower rates of marriage and childbearing compared with their male counterparts. (C) 2016 by The Society of Thoracic Surgeons C1 Columbia Univ, New York, NY USA. Maine Med Ctr, Cardiovasc Inst, Dept Cardiothorac Surg, Portland, ME 04102 USA. Univ Washington, Seattle, WA 98195 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Colorado, Denver, CO 80202 USA. Univ Rochester, Rochester, NY USA. Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. Mem Hermann Heart & Vasc Inst, Houston, TX USA. Univ Penn, Philadelphia, PA 19104 USA. Ottawa Heart Inst, Ottawa, ON, Canada. Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Virginia, Charlottesville, VA USA. Duke Univ, Med Ctr, Div Cardiovasc & Thorac Surg, Durham, NC USA. RP Shah, AA (reprint author), Duke Univ, Med Ctr, Div Cardiovasc & Thorac Surg, DUMC 3443, Durham, NC 27710 USA. EM asad.shah@duke.edu NR 24 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2016 VL 102 IS 1 BP 200 EP 206 DI 10.1016/j.athoracsur.2016.03.043 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DP6UL UT WOS:000378634400055 PM 27157051 ER PT J AU Raymond, DP Seder, CW Wright, CD Magee, MJ Kosinski, AS Cassivi, SD Grogan, EL Blackmon, SH Allen, MS Park, BJ Burfeind, WR Chang, AC DeCamp, MM Wormuth, DW Fernandez, FG Kozower, BD AF Raymond, Daniel P. Seder, Christopher W. Wright, Cameron D. Magee, Mitchell J. Kosinski, Andrzej S. Cassivi, Stephen D. Grogan, Eric L. Blackmon, Shanda H. Allen, Mark S. Park, Bernard J. Burfeind, William R. Chang, Andrew C. DeCamp, Malcolm M. Wormuth, David W. Fernandez, Felix G. Kozower, Benjamin D. TI Predictors of Major Morbidity or Mortality After Resection for Esophageal Cancer: A Society of Thoracic Surgeons General Thoracic Surgery Database Risk Adjustment Model SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 04-07, 2015 CL Orlando, FL SP So Thorac Surg Assoc ID OUTCOMES AB Background. The purpose of this analysis was to revise the model for perioperative risk for esophagectomy for cancer utilizing The Society of Thoracic Surgeons General Thoracic Surgery Database to provide enhanced risk stratification and quality improvement measures for contributing centers. Methods. The Society of Thoracic Surgeons General Thoracic Surgery Database was queried for all patients treated for esophageal cancer with esophagectomy between July 1, 2011, and June 30, 2014. Multivariable risk models for major morbidity, perioperative mortality, and combined morbidity and mortality were created with the inclusion of surgical approach as a risk factor. Results. In all, 4,321 esophagectomies were performed by 164 participating centers. The most common procedures included Ivor Lewis (32.5%), transhiatal (21.7%), minimally invasive esophagectomy, Ivor Lewis type (21.4%), and McKeown (10.0%). Sixty-nine percent of patients received induction therapy. Perioperative mortality (inpatient and 30day) was 135 of 4,321 (3.4%). Major morbidity occurred in 1,429 patients (33.1%). Major morbidities include unexpected return to operating (15.6%), anastomotic leak (12.9%), reintubation (12.2%), initial ventilation beyond 48 hours (3.5%), pneumonia (12.2%), renal failure (2.0%), and recurrent laryngeal nerve paresis (2.0%). Statistically significant predictors of combined major morbidity or mortality included age more than 65 years, body mass index 35 kg/m(2) or greater, preoperative congestive heart failure, Zubrod score greater than 1, McKeown esophagectomy, current or former smoker, and squamous cell histology. Conclusion. Thoracic surgeons participating in The Society of Thoracic Surgeons General Thoracic Surgery Database perform esophagectomy with low morbidity and mortality. McKeown esophagectomy is an independent predictor of combined postoperative morbidity or mortality. Revised predictors for perioperative outcome were identified to facilitate quality improvement processes and hospital comparisons. (C) 2016 by The Society of Thoracic Surgeons C1 [Raymond, Daniel P.] Cleveland Clin Fdn, Thorac & Cardiovasc Surg, 9500 Euclid Ave,J4-1, Cleveland, OH 44195 USA. [Seder, Christopher W.] Rush Med Univ, Univ Thorac Surg, Chicago, IL USA. [Wright, Cameron D.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Magee, Mitchell J.] HCA North Texas Div, Dallas, TX USA. [Kosinski, Andrzej S.] Duke Clin Res Inst, Durham, NC USA. [Cassivi, Stephen D.; Blackmon, Shanda H.; Allen, Mark S.] Mayo Clin, Dept Thorac Surg, Rochester, MN USA. [Grogan, Eric L.] Vanderbilt Univ, Med Ctr, Dept Thorac Surg, Nashville, TN USA. [Park, Bernard J.] Mem Sloan Kettering Canc Ctr, Thorac Serv, 1275 York Ave, New York, NY 10021 USA. [Burfeind, William R.] St Lukes Hlth Network, Cardiovasc & Thorac Surg Associates, Bethlehem, PA USA. [Chang, Andrew C.] Univ Michigan Hlth Syst, Thorac Surg Sect, Ann Arbor, MI USA. [DeCamp, Malcolm M.] NW Mem Hosp, Div Thorac Surg, Chicago, IL 60611 USA. [Wormuth, David W.] Upstate Surg Grp, Syracuse, NY USA. [Fernandez, Felix G.] Emory Univ, Div Cardiothorac Surg, Atlanta, GA 30322 USA. [Kozower, Benjamin D.] Univ Virginia Hlth Syst, Dept Gen Thorac Surg, Charlottesville, VA USA. RP Raymond, DP (reprint author), Cleveland Clin Fdn, Thorac & Cardiovasc Surg, 9500 Euclid Ave,J4-1, Cleveland, OH 44195 USA. EM raymond3@ccf.org FU NCI NIH HHS [P30 CA008748] NR 18 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2016 VL 102 IS 1 BP 207 EP 214 DI 10.1016/j.athoracsur.2016.04.055 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DP6UL UT WOS:000378634400056 PM 27240449 ER PT J AU Rodriguez, E Nifong, LW Bonatti, J Casula, R Falk, V Folliguet, TA Kiaii, BB Mack, MJ Mihaljevic, T Smith, JM Suri, RM Bavaria, JE MacGillivray, TE Chitwood, WR AF Rodriguez, Evelio Nifong, L. Wiley Bonatti, Johannes Casula, Roberto Falk, Volkmar Folliguet, Thierry A. Kiaii, Bob B. Mack, Michael J. Mihaljevic, Tomislav Smith, J. Michael Suri, Rakesh M. Bavaria, Joseph E. MacGillivray, Thomas E. Chitwood, W. Randolph, Jr. TI Pathway for Surgeons and Programs to Establish and Maintain a Successful Robot-Assisted Adult Cardiac Surgery Program SO ANNALS OF THORACIC SURGERY LA English DT Review ID MITRAL-VALVE REPAIRS; MULTICENTER TRIAL; BYPASS SURGERY; ARTERY; EXPERIENCE; SAFETY; GRAFT C1 [Rodriguez, Evelio] St Thomas Heart Hosp, 4230 Harding Rd,Ste 430, Nashville, TN 37205 USA. [Nifong, L. Wiley] East Carolina Heart Inst, Dept Cardiovasc Sci, Greenville, NC USA. [Bonatti, Johannes] Cleveland Clin, Abu Dhabi Heart & Vasc Inst, Abu Dhabi, U Arab Emirates. [Casula, Roberto] Imperial Coll Healthcare NHS Trust, London, England. [Casula, Roberto] St Marys Hosp, Dept Cardiothorac Surg, London, England. [Falk, Volkmar] Charite, Deutsch Herzzentrum Berlin, Berlin, Germany. [Folliguet, Thierry A.] Ctr Hosp Univ Brabois ILCV, Vandoeuvre Les Nancy, France. [Kiaii, Bob B.] London Hlth Sci Ctr, Dept Cardiovasc & Thorac Surg, London, ON, Canada. [Mack, Michael J.] Heart Hosp, Baylor Hlth Care Syst, Plano, TX USA. [Mihaljevic, Tomislav] Cleveland Clin Abu Dhabi, Abu Dhabi, U Arab Emirates. [Smith, J. Michael] Good Samaritan Hosp, Cincinnati, OH USA. [Suri, Rakesh M.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Bavaria, Joseph E.] Hosp Univ Penn, Div Cardiovasc Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chitwood, W. Randolph, Jr.] Vidant Med Ctr, Greenville, NC USA. [Chitwood, W. Randolph, Jr.] E Carolina Univ, Greenville, NC USA. RP Rodriguez, E (reprint author), St Thomas Heart Hosp, 4230 Harding Rd,Ste 430, Nashville, TN 37205 USA. EM evelio.rodriguez@sth.org NR 14 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 0003-4975 EI 1552-6259 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD JUL PY 2016 VL 102 IS 1 BP 340 EP 344 DI 10.1016/j.athoracsur.2016.02.085 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DP6UL UT WOS:000378634400076 PM 27343505 ER PT J AU Grajo, JR Patino, M Prochowski, A Sahani, DV AF Grajo, Joseph R. Patino, Manuel Prochowski, Andrea Sahani, Dushyant V. TI Dual energy CT in practice: Basic principles and applications SO APPLIED RADIOLOGY LA English DT Article ID IODINE OVERLAY TECHNIQUE; RENAL MASSES; COMPUTED-TOMOGRAPHY; MULTIDETECTOR CT; PHANTOM; IMAGES; CONTRAST C1 [Grajo, Joseph R.] Univ Florida, Coll Med, Gainesville, FL 32611 USA. [Patino, Manuel; Prochowski, Andrea; Sahani, Dushyant V.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA USA. RP Grajo, JR (reprint author), Univ Florida, Coll Med, Gainesville, FL 32611 USA. NR 27 TC 0 Z9 0 U1 0 U2 0 PU ANDERSON PUBLISHING, INC PI SCOTCH PLAINS PA 180 GLENSIDE AVE, SCOTCH PLAINS, NJ 07076 USA SN 0160-9963 EI 1879-2898 J9 APPL RADIOL JI Appl. Radiol. PD JUL PY 2016 VL 45 IS 7 BP 6 EP 12 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DQ5AH UT WOS:000379216300001 ER PT J AU Kamaraj, DC Dicianno, BE Mahajan, HP Buhari, AM Cooper, RA AF Kamaraj, Deepan C. Dicianno, Brad E. Mahajan, Harshal P. Buhari, Alhaji M. Cooper, Rory A. TI Interrater Reliability of the Power Mobility Road Test in the Virtual Reality-Based Simulator-2 SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Durable medical equipment; Neurological rehabilitation; Process assessment (health care); Rehabilitation; Reproducibility of results; Simulation training; Virtual reality exposure therapy; Wheelchairs ID WHEELCHAIR DRIVING PERFORMANCE; TRAUMATIC BRAIN-INJURY; SPINAL-CORD-INJURY; COMMUNITY; USERS; AGREEMENT; VALIDITY; JOYSTICK; PEOPLE; SKILLS AB Objective: To assess interrater reliability of the Power Mobility Road Test (PMRT) when administered through the Virtual Reality based SIMulator-version 2 (VRSIM-2). Design: Within-subjects repeated-measures design. Setting: Participants interacted with VRSIM-2 through 2 display options (desktop monitor vs immersive virtual reality screens) using 2 control interfaces (roller system vs conventional movement-sensing joystick), providing 4 different driving scenarios (driving conditions 1-4). Participants performed 3 virtual driving sessions for each of the 2 display screens and 1 session through a real-world driving course (driving condition 5). The virtual PMRT was conducted in a simulated indoor office space, and an equivalent course was charted in an open space for the real-world assessment. After every change in driving condition, participants completed a self-reported workload assessment questionnaire, the Task Load Index, developed by the National Aeronautics and Space Administration. Participants: A convenience sample of electric-powered wheelchair (EPW) athletes (N=21) recruited at the 31st National Veterans Wheelchair Games. Interventions: Not applicable. Main Outcome Measures: Total composite PMRT score. Results: The PMRT had high interrater reliability (intraclass correlation coefficient [ICC]>.75) between the 2 raters in all 5 driving conditions. Post hoc analyses revealed that the reliability analyses had >80% power to detect high ICCs in driving conditions 1 and 4. Conclusions: The PMRT has high interrater reliability in conditions 1 and 4 and could be used to assess EPW driving performance virtually in VRSIM-2. However, further psychometric assessment is necessary to assess the feasibility of administering the PMRT using the different interfaces of VRSIM-2. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Kamaraj, Deepan C.; Dicianno, Brad E.; Mahajan, Harshal P.; Buhari, Alhaji M.; Cooper, Rory A.] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. [Kamaraj, Deepan C.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Dicianno, Brad E.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Dicianno, BE (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. EM dicianno@pitt.edu OI Kamaraj, Dr.C/0000-0003-0639-8518; Kamaraj, Deepan C/0000-0003-1241-1723 FU Department of Veteran Affairs Research and Development Merit Review Award [A6035R] FX Supported by the Department of Veteran Affairs Research and Development Merit Review Award (grant no. A6035R) with resources and facilities at the Human Engineering Research Laboratories, VA Pittsburgh HealthCare System The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. NR 50 TC 0 Z9 0 U1 5 U2 9 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 JUL PY 2016 VL 97 IS 7 BP 1078 EP 1084 DI 10.1016/j.apmr.2016.02.005 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DQ1RZ UT WOS:000378979400005 PM 26921680 ER PT J AU Kamaraj, DC Dicianno, BE Mahajan, HP Buhari, AM Cooper, RA AF Kamaraj, Deepan C. Dicianno, Brad E. Mahajan, Harshal P. Buhari, Alhaji M. Cooper, Rory A. TI Stability and Workload of the Virtual Reality-Based Simulator-2 SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Durable medical equipment; Process assessment (health care); Rehabilitation; Reproducibility of results; Simulation training; Virtual reality exposure therapy; Wheelchairs ID SPINAL-CORD-INJURY; WHEELCHAIR SKILLS; ADVERSE CONSEQUENCES; MOBILITY DEVICES; PEOPLE; RELIABILITY; PERFORMANCE; VALIDITY; REPAIRS; PROGRAM AB Objective: To assess the stability of clinicians' and users' rating of electric-powered wheelchair (EPW) driving while using 4 different human machine interfaces (HMIs) within the Virtual Reality-based SIMulator-version 2 (VRSIM-2) and in the real world (accounting for a total of 5 unique driving conditions). Design: Within-subjects repeated-measures design. Setting: Simulation-based assessment in a research laboratory. Participants: A convenience sample of EPW athletes (N=21) recruited at the 31st National Veterans Wheelchair Games. Interventions: Not applicable. Main Outcome Measures: Composite PMRT scores from the Power Mobility Road Test (PMRT); Raw Task Load Index; and the 6 subscale scores from the Task Load Index developed by the National Aeronautics and Space Administration (NASA-TLX). Results: There was moderate stability (intraclass correlation coefficient between .50 and .75) in the total composite PMRT scores (P<001) and the users' self-reported performance scores (P<.001) among the 5 driving conditions. There was a significant difference in the workload among the 5 different driving conditions as reflected by the Raw Task Load Index (P=.009). Subanalyses revealed this difference was due to the difference in the mental demand (P=.007) and frustration (P=.007) subscales. Post hoc analyses revealed that these differences in the NASA-TLX subscale scores were due to the differences between real-world and virtual driving scores, particularly attributable to the conditions (1 and 3) that lacked the rollers as a part of the simulation. Conclusions: Further design improvements in the simulator to increase immersion experienced by the EPW user, along with a standardized training program for clinicians to deliver PMRT in VRSIM-2, could improve the stability between the different HMIs and real-world driving. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Kamaraj, Deepan C.; Dicianno, Brad E.; Mahajan, Harshal P.; Buhari, Alhaji M.; Cooper, Rory A.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Related Technol, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. [Kamaraj, Deepan C.; Dicianno, Brad E.; Mahajan, Harshal P.; Buhari, Alhaji M.; Cooper, Rory A.] Human Engn Res Labs, Pittsburgh, PA USA. [Kamaraj, Deepan C.; Cooper, Rory A.] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Dicianno, Brad E.; Cooper, Rory A.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Cooper, Rory A.] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Dicianno, BE (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Ctr Excellence Wheelchairs & Related Technol, 6425 Penn Ave,Ste 400, Pittsburgh, PA 15206 USA. EM dicianno@pitt.edu OI Kamaraj, Dr.C/0000-0003-0639-8518; Kamaraj, Deepan C/0000-0003-1241-1723 FU Department of Veteran Affairs Research and Development Merit Review Award [A6035R] FX Supported by the Department of Veteran Affairs Research and Development Merit Review Award (grant no. A6035R) with resources and facilities at the Human Engineering Research Laboratories, VA Pittsburgh HealthCare System The contents of this publication do not represent the views of the Department of Veterans Affairs or the United States Government. NR 31 TC 0 Z9 0 U1 5 U2 7 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 JUL PY 2016 VL 97 IS 7 BP 1085 EP 1092 DI 10.1016/j.apmr.2016.01.032 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DQ1RZ UT WOS:000378979400006 PM 26921682 ER PT J AU Hiremath, SV Intille, SS Kelleher, A Cooper, RA Ding, D AF Hiremath, Shivayogi V. Intille, Stephen S. Kelleher, Annmarie Cooper, Rory A. Ding, Dan TI Estimation of Energy Expenditure for Wheelchair Users Using a Physical Activity Monitoring System SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE Energy metabolism; Estimation; Exercise test; Motor activity; Rehabilitation; Smartphone; Spinal cord injuries; Wheelchairs ID SPINAL-CORD-INJURY; RANDOMIZED CONTROLLED-TRIAL; WEIGHT-LOSS; VALIDATION; ACCELEROMETER; INTERVENTION; DISABILITIES; PARAPLEGIA; PEOPLE AB Objective: To develop and evaluate energy expenditure (EE) estimation models for a physical activity monitoring system (PAMS) in manual wheelchair users with spinal cord injury (SCI). Design: Cross-sectional study. Setting: University-based laboratory environment, a semistructured environment at the National Veterans Wheelchair Games, and the participants' home environments. Participants: Volunteer sample of manual wheelchair users with SCI (N=45). Intervention: Participants were asked to perform 10 physical activities (PAs) of various intensities from a list. The PAMS consists of a gyroscope-based wheel rotation monitor (G-WRM) and an accelerometer device worn on the upper arm or on the wrist. Criterion EE using a portable metabolic cart and raw sensor data from PAMS were collected during each of these activities. Main Outcome Measures: Estimated EE using custom models for manual wheelchair users based on either the G-WRM and arm accelerometer (PAMS-Arm) or the G-WRM and wrist accelerometer (PAMS-Wrist). Results: EE estimation performance for the PAMS-Arm (average error +/- SD: -9.82%+/- 37.03%) and PAMS-Wrist (-5.65%+/- 32.61%) on the validation dataset indicated that both PAMS-Arm and PAMS-Wrist were able to estimate EE for a range of PAs with <10% error. Moderate to high intraclass correlation coefficients (ICCs) indicated that the EE estimated by PAMS-Arm (ICC3,1 = .82, P<.05) and PAMS-Wrist (ICC3,1 = .89, P<.05) are consistent with the criterion EE. Conclusions: Availability of PA monitors can assist wheelchair users to track PA levels, leading toward a healthier lifestyle. The new models we developed can estimate PA levels in manual wheelchair users with SCI in laboratory and community settings. (C) 2016 by the American Congress of Rehabilitation Medicine C1 [Hiremath, Shivayogi V.; Kelleher, Annmarie; Cooper, Rory A.; Ding, Dan] Vet Affairs Pittsburgh Healthcare Syst, Human Engn Res Labs, US Dept Vet Affairs, Pittsburgh, PA USA. [Hiremath, Shivayogi V.; Kelleher, Annmarie; Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. [Hiremath, Shivayogi V.] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Hiremath, Shivayogi V.] Temple Univ, Dept Phys Therapy, Philadelphia, PA 19140 USA. [Intille, Stephen S.] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA. [Intille, Stephen S.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Cooper, Rory A.; Ding, Dan] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. RP Hiremath, SV (reprint author), Temple Univ, Dept Phys Therapy, Coll Publ Hlth, 3307 N Broad St,Jones Hall,Ste 623, Philadelphia, PA 19140 USA. EM Shiv.Hiremath@temple.edu RI Emchi, Karma/Q-1952-2016 FU Department of Defense [W81XWH-10-1-0816]; Switzer Research Fellowship [H133F110032]; National Institute on Disability and Rehabilitation Research, Department of Education; Human Engineering Research Laboratories, Veterans Affairs Pittsburgh Healthcare System FX Supported by the Department of Defense (grant no. W81XWH-10-1-0816); the Switzer Research Fellowship (grant no. H133F110032), awarded by the National Institute on Disability and Rehabilitation Research, Department of Education; and the Human Engineering Research Laboratories, Veterans Affairs Pittsburgh Healthcare System. The contents do not represent the views of the Department of Veterans Affairs or the United States Government. NR 30 TC 0 Z9 0 U1 2 U2 5 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 JUL PY 2016 VL 97 IS 7 BP 1146 EP 1153 DI 10.1016/j.apmr.2016.02.016 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA DQ1RZ UT WOS:000378979400014 PM 26976800 ER PT J AU Elliott, DS Newman, KJH Forward, DP Hahn, DM Ollivere, B Kojima, K Handley, R Rossiter, ND Wixted, JJ Smith, RM Moran, CG AF Elliott, D. S. Newman, K. J. H. Forward, D. P. Hahn, D. M. Ollivere, B. Kojima, K. Handley, R. Rossiter, N. D. Wixted, J. J. Smith, R. M. Moran, C. G. TI A unified theory of bone healing and nonunion SO BONE & JOINT JOURNAL LA English DT Article ID INTERNAL-FIXATION; FRACTURE; MECHANOBIOLOGY; COMPLICATIONS; STABILITY; MODEL AB This article presents a unified clinical theory that links established facts about the physiology of bone and homeostasis, with those involved in the healing of fractures and the development of nonunion. The key to this theory is the concept that the tissue that forms in and around a fracture should be considered a specific functional entity. This 'bone-healing unit' produces a physiological response to its biological and mechanical environment, which leads to the normal healing of bone. This tissue responds to mechanical forces and functions according to Wolff's law, Perren's strain theory and Frost's concept of the "mechanostat". In response to the local mechanical environment, the bone-healing unit normally changes with time, producing different tissues that can tolerate various levels of strain. The normal result is the formation of bone that bridges the fracture-healing by callus. Nonunion occurs when the bone-healing unit fails either due to mechanical or biological problems or a combination of both. In clinical practice, the majority of nonunions are due to mechanical problems with instability, resulting in too much strain at the fracture site. In most nonunions, there is an intact bone-healing unit. We suggest that this maintains its biological potential to heal, but fails to function due to the mechanical conditions. The theory predicts the healing pattern of multifragmentary fractures and the observed morphological characteristics of different nonunions. It suggests that the majority of nonunions will heal if the correct mechanical environment is produced by surgery, without the need for biological adjuncts such as autologous bone graft. C1 [Elliott, D. S.; Newman, K. J. H.; Forward, D. P.; Hahn, D. M.; Ollivere, B.; Kojima, K.; Handley, R.; Rossiter, N. D.; Wixted, J. J.; Smith, R. M.; Moran, C. G.] Univ Nottingham Hosp, Dept Trauma & Orthopaed, Nottingham, England. [Elliott, D. S.; Newman, K. J. H.] Ashford & St Peters Hosp NHS Fdn Trust, Guildford Rd, Chertsey KT160PZ, Surrey, England. [Smith, R. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Forward, D. P.; Hahn, D. M.; Ollivere, B.] Nottingham Univ Hosp NHS Trust, Nottingham NG7 2UH, England. [Moran, C. G.] Nottingham Univ Hosp NHS Trust, Trauma, Nottingham NG7 2UH, England. [Moran, C. G.] Nottingham Univ Hosp NHS Trust, Orthopaed Trauma Surg, Nottingham NG7 2UH, England. [Kojima, K.] Univ Sao Paulo, Orthoped Trauma Grp, Rua Dr Ovidio Pires Campos 333, Sao Paulo, Brazil. [Handley, R.] John Radcliffe Hosp, Oxford OX3 9DU, England. [Rossiter, N. D.] Basingstoke & Northamptonshire Hosp, Basingstoke RG24 9NA, Hants, England. [Wixted, J. J.] Beth Israel Hosp, Boston, MA USA. RP Smith, RM (reprint author), Univ Nottingham Hosp, Dept Trauma & Orthopaed, Nottingham, England.; Smith, RM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM RMSMITH1@PARTNERS.ORG NR 39 TC 2 Z9 2 U1 5 U2 8 PU BRITISH EDITORIAL SOC BONE JOINT SURGERY PI LONDON PA 22 BUCKINGHAM STREET, LONDON WC2N 6ET, ENGLAND SN 2049-4394 J9 BONE JOINT J JI Bone Joint J. PD JUL PY 2016 VL 98B IS 7 BP 884 EP 891 DI 10.1302/0301-620X.98B7.36061 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DQ5JN UT WOS:000379241400004 PM 27365465 ER PT J AU Harshman, LC AF Harshman, Lauren C. TI Mind the gap: What is driving the survival disparity between the sexes in bladder cancer? SO CANCER LA English DT Editorial Material ID CELL CARCINOMA; UROTHELIAL CARCINOMA; CHEMOTHERAPY; EXPRESSION; RESPONSES; GENDER; NIVOLUMAB; IMMUNITY; MELANOMA; SUBTYPES AB Bladder cancer is well known to preferentially afflict men. However, women are significantly more likely to die of the disease even when corrected for stage, tumor characteristics, and age. In this issue of Cancer, Rose and colleagues highlight concerning disparities in bladder cancer treatment and outcomes between the sexes. See also pages 2012-20. C1 [Harshman, Lauren C.] Dana Farber Canc Inst, Lank Ctr Genitourinary Canc, Boston, MA 02115 USA. RP Harshman, LC (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Lank Ctr Genitourinary Canc, 450 Brookline Ave, Boston, MA 02215 USA. EM LaurenC_Harshman@dfci.harvard.edu NR 27 TC 1 Z9 1 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2016 VL 122 IS 13 BP 1966 EP 1970 DI 10.1002/cncr.30027 PG 5 WC Oncology SC Oncology GA DQ3XS UT WOS:000379137900004 PM 27224470 ER PT J AU Liao, ZW Rodrigues, MC Poynter, JN Amatruda, JF Rodriguez-Galindo, C Frazier, AL AF Liao, Zi Wei Rodrigues, Maria Clarissa Poynter, Jenny N. Amatruda, James F. Rodriguez-Galindo, Carlos Frazier, A. Lindsay TI Risk of second gonadal cancers in women and children with germ cell tumors SO CANCER LA English DT Article DE epidemiology; germ cell tumor; pediatrics; second cancer; Surveillance; Epidemiology; and End Results (SEER); testicular cancer ID LONG-TERM SURVIVORS; TESTICULAR-CANCER; MALIGNANT NEOPLASMS; UNITED-STATES; ASSOCIATIONS; PERSPECTIVE; CHILDHOOD; PROFILES; FEATURES; DISEASE AB BACKGROUNDMen with testicular cancer have an increased risk of developing cancer in the contralateral testis, but the risks of second gonadal cancers (SGCs) in women and children treated for germ cell tumors (GCTs) have not previously been quantified. METHODSThe incidence of SGCs was ascertained in patients who had survived for at least 1 year after GCT diagnosis using data from the Surveillance, Epidemiology, and End Results SEER 9 registries (1980-2012). Relative risks of SGCs were estimated separately for boys, women, and girls compared with men based on Poisson regression analysis. RESULTSThe cohort included 21,546 individuals (1116 boys, 827 women, 622 girls, and 18,981 men). A total of 25 SGCs were identified in boys, 1 in women, and 2 in girls compared with 254 in men. The risk of SGC in postpubertal boys (aged 10 years) was comparable to that of adult men (boys: standardized incidence ratio, 15.90; 95% confidence interval, 10.29-23.47; men: standardized incidence ratio, 10.88; 95% confidence interval, 9.58-12.30). However, no SGCs were observed in boys who were diagnosed with a testicular GCT before age 10 years (N = 179). An elevated risk of SGC was also not observed for women or girls. CONCLUSIONSThe apparent lack of an SGC in prepubertal boys suggests that susceptibility is either age-dependent and/or histology-dependent. The sex differences in the risk of SGC suggest differences in the etiology of ovarian versus testicular GCT. The finding that the risk of SGCs in postpubertal boys is similar to that observed in men indicates that long-term follow-up for SGC is warranted in postpubertal boys. Cancer 2016;122:2076-82. (c) 2016 American Cancer Society. Postpubertal boys and men with germ cell tumors share a similar risk of developing a second testicular cancer. However, neither prepubertal boys with testicular cancer nor females with ovarian germ cell tumors appear to have an increased risk of second gonadal cancer. C1 [Liao, Zi Wei; Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Dana Farber Canc Inst, 450 Brookline Ave,D-3127, Boston, MA 02216 USA. [Liao, Zi Wei; Rodriguez-Galindo, Carlos; Frazier, A. Lindsay] Boston Childrens Hosp, 450 Brookline Ave,D-3127, Boston, MA 02216 USA. [Liao, Zi Wei] Wellesley Coll, Interdept Program Biochem, Wellesley, MA 02181 USA. [Rodrigues, Maria Clarissa] Coll Med Sci Santa Casa Sao Paulo, Sao Paulo, Brazil. [Poynter, Jenny N.] Univ Minnesota, Dept Pediat, Div Epidemiol & Clin Res, Minneapolis, MN 55455 USA. [Poynter, Jenny N.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Amatruda, James F.] Univ Texas Southwestern Med Ctr, Dept Pediat, Dallas, TX USA. [Amatruda, James F.] Univ Texas Southwestern Med Ctr, Dept Mol Biol, Dallas, TX USA. [Amatruda, James F.] Childrens Med Ctr, Ctr Canc & Blood Disorders, Dallas, TX 75235 USA. RP Frazier, AL (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,D-3127, Boston, MA 02216 USA.; Frazier, AL (reprint author), Boston Childrens Hosp, 450 Brookline Ave,D-3127, Boston, MA 02216 USA. EM lindsay_frazier@dfci.harvard.edu FU Global Engagement Internship; Department of Biological Sciences at Wellesley College FX This study was supported by the Global Engagement Internship and by the Department of Biological Sciences at Wellesley College. NR 31 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2016 VL 122 IS 13 BP 2076 EP 2082 DI 10.1002/cncr.30014 PG 7 WC Oncology SC Oncology GA DQ3XS UT WOS:000379137900017 PM 27152727 ER PT J AU Halasz, LM Uno, H Hughes, M D'Amico, T Dexter, EU Edge, SB Hayman, JA Niland, JC Otterson, GA Pisters, KMW Theriault, R Weeks, JC Punglia, RS AF Halasz, Lia M. Uno, Hajime Hughes, Melissa D'Amico, Thomas Dexter, Elisabeth U. Edge, Stephen B. Hayman, James A. Niland, Joyce C. Otterson, Gregory A. Pisters, Katherine M. W. Theriault, Richard Weeks, Jane C. Punglia, Rinaa S. TI Comparative effectiveness of stereotactic radiosurgery versus whole-brain radiation therapy for patients with brain metastases from breast or non-small cell lung cancer SO CANCER LA English DT Article DE breast neoplasms; comparative effectiveness research; neoplasm metastasis; non-small cell lung carcinoma; radiosurgery ID ONCOLOGY-GROUP; TRIALS; NCCN AB BACKGROUNDThe optimal treatment for patients with brain metastases remains controversial as the use of stereotactic radiosurgery (SRS) alone, replacing whole-brain radiation therapy (WBRT), has increased. This study determined the patterns of care at multiple institutions before 2010 and examined whether or not survival was different between patients treated with SRS and patients treated with WBRT. METHODSThis study examined the overall survival of patients treated with radiation therapy for brain metastases from non-small cell lung cancer (NSCLC; initially diagnosed in 2007-2009) or breast cancer (initially diagnosed in 1997-2009) at 5 centers. Propensity score analyses were performed to adjust for confounding factors such as the number of metastases, the extent of extracranial metastases, and the treatment center. RESULTSOverall, 27.8% of 400 NSCLC patients and 13.4% of 387 breast cancer patients underwent SRS alone for the treatment of brain metastases. Few patients with more than 3 brain metastases or lesions 4 cm in size underwent SRS. Patients with fewer than 4 brain metastases less than 4 cm in size (n = 189 for NSCLC and n = 117 for breast cancer) who were treated with SRS had longer survival (adjusted hazard ratio [HR] for NSCLC, 0.58; 95% confidence Interval [CI], 0.38-0.87; P = .01; adjusted HR for breast cancer, 0.54; 95% CI, 0.33-0.91; P = .02) than those treated with WBRT. CONCLUSIONSPatients treated for fewer than 4 brain metastases from NSCLC or breast cancer with SRS alone had longer survival than those treated with WBRT in this multi-institutional, retrospective study, even after adjustments for the propensity to undergo SRS. Cancer 2016;122:2091-100. (c) 2016 American Cancer Society. With data from a multi-institutional, longitudinal database, propensity score analyses have been performed for patients treated for brain metastases from non-small cell lung cancer or breast cancer. Patients treated initially for fewer than 4 brain metastases with stereotactic radiosurgery alone have improved survival. C1 [Halasz, Lia M.] Univ Washington, Dept Radiat Oncol, 1959 NE Pacific St, Seattle, WA 98195 USA. [Uno, Hajime; Hughes, Melissa; Weeks, Jane C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [D'Amico, Thomas] Duke Canc Inst, Dept Surg, Durham, NC USA. [Dexter, Elisabeth U.; Edge, Stephen B.] Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14263 USA. [Dexter, Elisabeth U.; Edge, Stephen B.] Univ Buffalo, Buffalo, NY USA. [Hayman, James A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Niland, Joyce C.] City Hope Natl Med Ctr, Informat Sci, Duarte, CA USA. [Otterson, Gregory A.] Ohio State Univ, Ctr Comprehens Canc, Dept Med, Columbus, OH 43210 USA. [Pisters, Katherine M. W.; Theriault, Richard] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Punglia, Rinaa S.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Halasz, LM (reprint author), Univ Washington, Dept Radiat Oncol, 1959 NE Pacific St, Seattle, WA 98195 USA. EM lhalasz@uw.edu FU National Institutes of Health/National Cancer Institute [RC2CA148185]; Career Development Award from the National Institutes of Health [1K07CA118629]; National Comprehensive Cancer Network FX This study was supported by a grant from the National Institutes of Health/National Cancer Institute (Building CER Capacity: Aligning CRN, CMS, and State Resources to Map Cancer Care [RC2CA148185]) and by a Career Development Award from the National Institutes of Health (1K07CA118629 to Rinaa S. Punglia). The National Comprehensive Cancer Network provided funding for the data collection. NR 18 TC 6 Z9 6 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2016 VL 122 IS 13 BP 2091 EP 2100 DI 10.1002/cncr.30009 PG 10 WC Oncology SC Oncology GA DQ3XS UT WOS:000379137900019 PM 27088755 ER PT J AU Nipp, RD El-Jawahri, A Fishbein, JN Eusebio, J Stagl, JM Gallagher, ER Park, ER Jackson, VA Pirl, WF Greer, JA Temel, JS AF Nipp, Ryan D. El-Jawahri, Areej Fishbein, Joel N. Eusebio, Justin Stagl, Jamie M. Gallagher, Emily R. Park, Elyse R. Jackson, Vicki A. Pirl, William F. Greer, Joseph A. Temel, Jennifer S. TI The relationship between coping strategies, quality of life, and mood in patients with incurable cancer SO CANCER LA English DT Article DE anxiety; coping behavior; depression; incurable cancer; palliative care; quality of life ID CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; EARLY PALLIATIVE CARE; STAGE BREAST-CANCER; NEAR-DEATH; GYNECOLOGIC CANCER; SYMPTOM BURDEN; WOMEN; PREDICTORS; ADJUSTMENT AB BACKGROUNDPatients with incurable cancer face many physical and emotional stressors, yet little is known about their coping strategies or the relationship between their coping strategies, quality of life (QOL), and mood. METHODSAs part of a randomized trial of palliative care, this study assessed baseline QOL (Functional Assessment of Cancer Therapy-General), mood (Hospital Anxiety and Depression Scale), and coping (Brief COPE) in patients within 8 weeks of a diagnosis of incurable lung or gastrointestinal cancer and before randomization. To examine associations between coping strategies, QOL, and mood, we used linear regression, adjusting for patients' age, sex, marital status, and cancer type. RESULTSThere were 350 participants (mean age, 64.9 years), and the majority were male (54.0%), were married (70.0%), and had lung cancer (54.6%). Most reported high utilization of emotional support coping (77.0%), whereas fewer reported high utilization of acceptance (44.8%), self-blame (37.9%), and denial (28.2%). Emotional support (QOL: = 2.65, P < .01; depression: = -0.56, P = .02) and acceptance (QOL: = 1.55, P < .01; depression: = -0.37, P = .01; anxiety: = -0.34, P = .02) correlated with better QOL and mood. Denial (QOL: = -1.97, P < .01; depression: = 0.36, P = .01; anxiety: = 0.61, P < .01) and self-blame (QOL: = -2.31, P < .01; depression: = 0.58, P < .01; anxiety: = 0.66, P < .01) correlated with worse QOL and mood. CONCLUSIONSPatients with newly diagnosed, incurable cancer use a variety of coping strategies. The use of emotional support and acceptance coping strategies correlated with better QOL and mood, whereas the use of denial and self-blame negatively correlated with these outcomes. Interventions to improve patients' QOL and mood should seek to cultivate the use of adaptive coping strategies. Cancer 2016;122:2110-6. (c) 2016 American Cancer Society. Patients with a new diagnosis of incurable cancer cope in a variety of unique ways. Patients' use of certain coping strategies correlate with their quality of life and mood, and this suggests that evaluating and addressing patients' coping behaviors may affect other key patient-reported outcomes. C1 [Nipp, Ryan D.; El-Jawahri, Areej; Gallagher, Emily R.; Temel, Jennifer S.] Massachusetts Gen Hosp, Dept Med, Ctr Canc, Div Hematol & Oncol, Boston, MA 02114 USA. [Nipp, Ryan D.; El-Jawahri, Areej; Fishbein, Joel N.; Eusebio, Justin; Stagl, Jamie M.; Gallagher, Emily R.; Park, Elyse R.; Jackson, Vicki A.; Pirl, William F.; Greer, Joseph A.; Temel, Jennifer S.] Harvard Med Sch, Boston, MA USA. [Fishbein, Joel N.; Eusebio, Justin; Stagl, Jamie M.; Park, Elyse R.; Pirl, William F.; Greer, Joseph A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Jackson, Vicki A.] Massachusetts Gen Hosp, Dept Med, Div Palliat Care, Boston, MA 02114 USA. RP Nipp, RD (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM rnipp@mgh.harvard.edu OI Jacobs, Jamie M./0000-0001-9740-624X FU National Institute of Nursing Research [R01 NR012735]; National Cancer Institute [K24 CA181253] FX This study was funded by the National Institute of Nursing Research (R01 NR012735 to Jennifer S. Temel) and the National Cancer Institute (K24 CA181253 to Jennifer S. Temel). NR 45 TC 3 Z9 3 U1 8 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD JUL 1 PY 2016 VL 122 IS 13 BP 2110 EP 2116 DI 10.1002/cncr.30025 PG 7 WC Oncology SC Oncology GA DQ3XS UT WOS:000379137900021 PM 27089045 ER PT J AU Gaffney, AW Verhoef, PA Hall, JB AF Gaffney, Adam W. Verhoef, Philip A. Hall, Jesse B. TI POINT: Should Pulmonary/ICU Physicians Support Single-payer Health-care Reform? Yes SO CHEST LA English DT Editorial Material ID INHALED MEDICATIONS; UNITED-STATES; INSURANCE; DISPARITIES; DISEASE; COSTS; WILL C1 [Gaffney, Adam W.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Verhoef, Philip A.; Hall, Jesse B.] Univ Chicago, Sect Pulm & Crit Care Med, Chicago, IL 60637 USA. RP Verhoef, PA (reprint author), Univ Chicago, Dept Med, Sect Pulm & Crit Care, 5841 S Maryland Ave,MC 6076, Chicago, IL 60637 USA. EM philip.verhoef@uchospitals.edu NR 19 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2016 VL 150 IS 1 BP 9 EP 11 DI 10.1016/j.chest.2016.02.660 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ5BS UT WOS:000379220000011 PM 27396772 ER PT J AU Gaffney, AW Verhoef, PA Hall, JB AF Gaffney, Adam W. Verhoef, Philip A. Hall, Jesse B. TI Rebuttal From Drs Gaffney, Verhoef, and Hall SO CHEST LA English DT Editorial Material ID CARE; INSURANCE C1 [Gaffney, Adam W.] Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. [Verhoef, Philip A.; Hall, Jesse B.] Univ Chicago, Sect Pulm & Crit Care Med, Chicago, IL 60637 USA. RP Verhoef, PA (reprint author), Univ Chicago, Dept Med, Sect Pulm & Crit Care, 5841 S Maryland Ave,MC 6076, Chicago, IL 60637 USA. EM philip.verhoef@uchospitals.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2016 VL 150 IS 1 BP 14 EP 15 DI 10.1016/j.chest.2016.02.661 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ5BS UT WOS:000379220000013 PM 27396774 ER PT J AU Bourge, RC Waxman, AB Gomberg-Maitland, M Shapiro, SM Tarver, JH Zwicke, DL Feldman, JP Chakinala, MM Frantz, RP Torres, F Cerkvenik, J Morris, M Thalin, M Peterson, L Rubin, LJ AF Bourge, Robert C. Waxman, Aaron B. Gomberg-Maitland, Mardi Shapiro, Shelley M. Tarver, James H., III Zwicke, Dianne L. Feldman, Jeremy P. Chakinala, Murali M. Frantz, Robert P. Torres, Fernando Cerkvenik, Jeffrey Morris, Marty Thalin, Melissa Peterson, Leigh Rubin, Lewis J. TI Treprostinil Administered to Treat Pulmonary Arterial Hypertension Using a Fully Implantable Programmable Intravascular Delivery System Results of the DelIVery for PAH Trial SO CHEST LA English DT Article DE central venous catheters; drugs; health-related quality of life; pulmonary arterial hypertension; pulmonary hypertension; treprostinil ID QUALITY-OF-LIFE; CATHETERS; INFUSION; INFECTIONS; SAFETY AB BACKGROUND: The use of systemic prostanoids in severe pulmonary arterial hypertension (PAH) is often limited by patient/physician dissatisfaction with the delivery methods. Complications associated with external pump-delivered continuous therapy include IV catheter-related bloodstream infections and subcutaneous infusion site pain. We therefore investigated a fully implantable intravascular delivery system for treprostinil infusion. METHODS: A multicenter, prospective, single-arm, clinical trial (DelIVery for Pulmonary Arterial Hypertension) was conducted by using an implantable intravascular delivery system. The implanted pumps were refilled percutaneously at least every 12 weeks. The primary end point was the rate of catheter-related complications using the new model 10642 catheter compared with a predefined objective performance criterion of 2.5 per 1,000 patient-days based on the literature. RESULTS: Patients (n = 60) with severe PAH (World Health Organization group 1) receiving a stable dose of IV treprostinil for at least 4 weeks received an implant device and were followed up for 12.1 +/- 4.4 months. Six catheter-related complications occurred, corresponding to a complication rate of 0.27 per 1,000 patient-days. The 97.5% upper one-sided confidence bound of 0.59 was less than the predefined criterion of 2.5 per 1,000 patient-days (P < .0001). Plasma treprostinil levels at 1 week postimplantation were highly correlated with baseline levels (r = 0.91; P < .0001). The delivery system management time as reported by the patients was 2.5 +/- 1.7 hours per week preimplantation, and this time decreased to 0.6 +/- 0.8 hour per week at 6 months' postimplantation (P < .0001). All patients rated overall satisfaction with the implantable system as good, very good, or excellent at 6 weeks and 6 months. There were no catheter-related bloodstream infections or catheter occlusions. CONCLUSIONS: The implantable intravascular delivery system delivered treprostinil to patients with PAH with a low rate of catheter-related complications and a high rate of patient satisfaction. C1 [Bourge, Robert C.] Univ Alabama Birmingham, 321k Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. [Waxman, Aaron B.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Gomberg-Maitland, Mardi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Shapiro, Shelley M.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Shapiro, Shelley M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Tarver, James H., III] Orlando Reg Med Ctr Inc, Orlando, FL USA. [Zwicke, Dianne L.] Aurora St Lukes Med Ctr, Milwaukee, WI USA. [Feldman, Jeremy P.] Arizona Pulm Specialists Ltd, Scottsdale, AZ USA. [Chakinala, Murali M.] Washington Univ, Sch Med, St Louis, MO USA. [Frantz, Robert P.] Mayo Clin, Rochester, MN USA. [Torres, Fernando] Univ Texas Southwestern Med Ctr, Rochester, MN USA. [Cerkvenik, Jeffrey; Morris, Marty; Thalin, Melissa] Medtronic Inc, Minneapolis, MN USA. [Peterson, Leigh] United Therapeut Corp, Res Triangle Pk, NC USA. [Rubin, Lewis J.] Univ Calif San Diego, Div Pulm & Crit Care Med, La Jolla, CA USA. RP Bourge, RC (reprint author), Univ Alabama Birmingham, 321k Tinsley Harrison Tower,1900 Univ Blvd, Birmingham, AL 35294 USA. EM bbourge@uab.edu FU Medtronic, Inc; United Therapeutics Corporation FX The sponsor of this study was Medtronic, Inc, and the funding for this study came from United Therapeutics Corporation. NR 20 TC 4 Z9 5 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2016 VL 150 IS 1 BP 27 EP 34 DI 10.1016/j.chest.2015.11.005 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ5BS UT WOS:000379220000016 PM 27396777 ER PT J AU Hasegawa, K Tsugawa, Y Clark, S Eastin, CD Gabriel, S Herrera, V Bittner, JC Camargo, CA AF Hasegawa, Kohei Tsugawa, Yusuke Clark, Sunday Eastin, Carly D. Gabriel, Susan Herrera, Vivian Bittner, Jane C. Camargo, Carlos A., Jr. CA MARC-37 Investigators TI Improving Quality of Acute Asthma Care in US Hospitals Changes Between 1999-2000 and 2012-2013 SO CHEST LA English DT Article DE asthma; guideline; hospitalization; quality of care ID EMERGENCY-DEPARTMENT; UNITED-STATES; OF-CARE; HEALTH-CARE; CHILDREN; PERFORMANCE; GUIDELINES; MANAGEMENT; ADHERENCE; OUTCOMES AB BACKGROUND: Little is known about the longitudinal change in the quality of acute asthma care for hospitalized children and adults in the United States. We investigated whether the concordance of inpatient asthma care with the national guidelines improved over time, identified hospital characteristics predictive of guideline concordance, and determined whether guideline-concordant care is associated with a shorter hospital length of stay (LOS). METHODS: This study was an analysis of data from two multicenter chart review studies of hospitalized patients aged 2 to 54 years with acute asthma during two time periods: 19992000 and 2012-2013. Outcomes were guideline concordance at the patient and hospital levels, and association of patient composite concordance with hospital LOS. RESULTS: The analytic cohort for the comparison of guideline concordance comprised 1,634 patients: 834 patients from 1999-2000 vs 800 patients from 2012-2013. Over these 15 years, inpatient asthma care became more concordant at the hospital-level, with the mean composite score increasing from 74 to 82 (P < .001). However, during 2012-2013, wide variability in guideline concordance of acute asthma care remained across hospitals, with the greatest variation in provision of individualized written action plan at discharge (SD, 36). Guideline concordance was significantly lower in Midwestern and Southern hospitals compared with Northeastern hospitals. After adjusting for severity, patients who received care perfectly concordant with the guidelines had significantly shorter hospital LOS (-14% [95% CI, -23 to -4]; P = .009). CONCLUSIONS: Between 1999 and 2013, the guideline concordance of acute asthma care for hospitalized patients improved. However, interhospital variability remains substantial. Greater concordance with evidence-based guidelines was associated with a shorter hospital LOS. C1 [Hasegawa, Kohei; Bittner, Jane C.; Camargo, Carlos A., Jr.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA USA. [Tsugawa, Yusuke] Harvard Sch Publ Hlth, Boston, MA USA. [Clark, Sunday] Weill Cornell Med Coll, Dept Emergency Med, New York, NY USA. [Eastin, Carly D.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Gabriel, Susan; Herrera, Vivian] Novartis Pharmaceut, E Hanover, NJ USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Ste 920, Boston, MA 02114 USA. EM khasegawa1@partners.org FU University HealthSystem Consortium; Novartis Pharmaceuticals Corporation FX The 1999-2000 study was supported by the University HealthSystem Consortium; the 2012-2013 study was supported by Novartis Pharmaceuticals Corporation (Principal Investigator, Dr Camargo). NR 32 TC 1 Z9 1 U1 2 U2 2 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2016 VL 150 IS 1 BP 112 EP 122 DI 10.1016/j.chest.2016.03.037 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ5BS UT WOS:000379220000024 PM 27056585 ER PT J AU Gubatan, J Staller, K Barshop, K Kuo, B AF Gubatan, John Staller, Kyle Barshop, Kenneth Kuo, Braden TI Cannabis Abuse Is Increasing and Associated with Increased Emergency Department Utilization in Gastroenterology Patients SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Medical marijuana; Cannabis; Cannabinoids; Epidemiology; Healthcare utilization; Functional GI disorders ID IRRITABLE-BOWEL-SYNDROME; HEALTH-CARE UTILIZATION; QUALITY-OF-LIFE; MEDICAL MARIJUANA; CROHNS-DISEASE; SUBSTANCE USE; SOCIOECONOMIC-STATUS; RECEPTOR AGONIST; CB2 RECEPTORS; UNITED-STATES AB The role of cannabinoids in gastrointestinal diseases is controversial and of great interest, yet their use in patients has not been critically examined. To determine the prevalence and effects of cannabis abuse on healthcare utilization, as measured by emergency department (ED) visits, in a large, tertiary gastroenterology practice. All patients seen in the gastroenterology clinic at a tertiary care center during a 27-year period (1986-2013) were included in our study to determine the overall prevalence of cannabis abuse. We matched cannabis abusers 1:2 with non-abusing controls to determine the effect of cannabis on ED utilization, our primary outcome. We used multivariate linear regression to adjust for confounders and define the independent effect of cannabis abuse on ED utilization. Our prevalence study cohort included 190,303 GI clinic patients with an overall cannabis abuse prevalence of 0.80 % (1520 patients). From 1986 to 2012, the prevalence of cannabis abuse in this clinic increased by 0.73 % (0.03 %/year) (p < 0.0001). From the 1520 cannabis abusers identified, 467 patients were randomly selected as cases and were matched to 934 controls. From this retrospective cohort, the median ED visits/year for cannabis abusers was 1.88 versus 0.89 for non-abusers (p < 0.0001). After multivariate adjustment, cannabis abuse was associated with a 1.47-fold increase (95 % CI 1.23-1.76, p < 0.0001) in median ED visits/year. Reported cannabis abuse in GI clinic patients is less prevalent than in the adult US population, but is increasing. Cannabis abuse among gastroenterology patients is associated with increased ED visits. C1 [Gubatan, John] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. [Staller, Kyle; Kuo, Braden] Harvard Med Sch, Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA USA. [Staller, Kyle; Kuo, Braden] Massachusetts Gen Hosp, Ctr Neurointestinal Hlth, Boston, MA 02114 USA. [Barshop, Kenneth] Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Gubatan, J (reprint author), Harvard Med Sch, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM jgubatan@bidmc.harvard.edu OI Staller, Kyle/0000-0003-4925-4290; Gubatan, John Mark/0000-0001-6037-2883 FU Vibrant FX J. Gubatan, K. Staller, and K. Barshop declare no conflict of interest; B. Kuo receives clinical trial support from Vibrant. NR 47 TC 1 Z9 1 U1 4 U2 5 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 JUL PY 2016 VL 61 IS 7 BP 1844 EP 1852 DI 10.1007/s10620-016-4090-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DQ2EA UT WOS:000379013300013 PM 26935430 ER PT J AU Cadoni, S Falt, P Sanna, S Argiolas, M Fanari, V Gallittu, P Liggi, M Mura, D Porcedda, ML Smajstrla, V Erriu, M Leung, FW AF Cadoni, Sergio Falt, Premysl Sanna, Stefano Argiolas, Mariangela Fanari, Viviana Gallittu, Paolo Liggi, Mauro Mura, Donatella Porcedda, Maria L. Smajstrla, Vit Erriu, Matteo Leung, Felix W. TI Impact of Colonoscopy Insertion Techniques on Adenoma Detection SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Bowel cleanliness; Colon lesion detection; Interval cancer; Small adenomas; Water-aided colonoscopy ID INTERVAL COLORECTAL CANCERS; BOWEL PREPARATION QUALITY; WATER EXCHANGE; NEGATIVE COLONOSCOPY; MISS RATE; RISK; IMMERSION; POLYPS; RATES; METAANALYSIS AB Low adenoma detection rate (ADR) predicts development of interval cancers, found mainly in the right (cecum-ascending) colon, where poor bowel preparation is an associated factor. Single-site studies reported increased detection of adenomas in the proximal colon segments by water exchange (WE). Data about colon cleansing revealed that WE had the greatest impact in the right colon. To test the hypothesis that WE had the greatest impact on ADR in colon segments with the most favorable bowel cleanliness scores, namely the right colon. We pooled right colon and overall ADR data of three similarly designed colonoscopy trials that compared WE, water immersion (WI) and insufflation of air or carbon dioxide (AICD) in a mixed gender European population. In this study, 1200 (704 males) subjects and were included. 288 were screening cases. Demographic and procedural data were comparable. Water exchange achieved significantly higher right colon < 10 mm ADR (11.9 %, vs WI 6.9 %, p = 0.016; vs AICD 7.2 %, p = 0.025). Water exchange achieved the lowest proportions of poor bowel preparation and the highest right colon and overall Boston bowel preparation scale scores (p range 0.003, < 0.0005). In patients with right colon excellent bowel cleanliness, water exchange was the only method significantly associated with right colon adenoma detection. One of the limitations is unblinded colonoscopists. In a mixed gender European population, water exchange is confirmed to be a superior insertion technique showing a significant increase in < 10 mm right colon adenoma detection, achieving the cleanest colon and lowest proportions of poor bowel preparation requiring repeat procedures. NCT01781650, 01954862, 01780818. C1 [Cadoni, Sergio; Gallittu, Paolo; Liggi, Mauro; Mura, Donatella] St Barbara Hosp, Digest Endoscopy Unit, Via S Leonardo 1, I-09016 Iglesias, CI, Italy. [Falt, Premysl; Smajstrla, Vit] Vitkovice Hosp, Ctr Digest Dis, Zaluzanskeho 1192-15, Ostrava 70384, Czech Republic. [Sanna, Stefano; Argiolas, Mariangela; Fanari, Viviana; Porcedda, Maria L.] NS Bonaria Hosp, Digest Endoscopy Unit, I-09037 San Gavino Monreale, VS, Italy. [Erriu, Matteo] Univ Cagliari, Dept Surg Sci, I-09121 Cagliari, Italy. [Leung, Felix W.] Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, North Hills, CA 91343 USA. [Leung, Felix W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. RP Cadoni, S (reprint author), St Barbara Hosp, Digest Endoscopy Unit, Via S Leonardo 1, I-09016 Iglesias, CI, Italy. EM cadonisergio@gmail.com; faltprem@centrum.cz; endo.sangav@tiscali.it; Margiolas2003@tiscali.it; mavivi@tiscali.it; paologallittu@gmail.com; liggim@gmail.com; muradonatella@live.it; toniolaura@tiscali.it; bormed1@volny.cz; matteoerr@gmail.com; felixleung@socal.rr.com NR 44 TC 2 Z9 2 U1 1 U2 2 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 JUL PY 2016 VL 61 IS 7 BP 2068 EP 2075 DI 10.1007/s10620-016-4053-1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DQ2EA UT WOS:000379013300037 PM 26846118 ER PT J AU Corey, KE Klebanoff, MJ Tramontano, AC Chung, RT Hur, C AF Corey, Kathleen E. Klebanoff, Matthew J. Tramontano, Angela C. Chung, Raymond T. Hur, Chin TI Screening for Nonalcoholic Steatohepatitis in Individuals with Type 2 Diabetes: A Cost-Effectiveness Analysis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE Nonalcoholic steatohepatitis; Fibrosis; Cirrhosis; Screening ID FATTY LIVER-DISEASE; PLACEBO-CONTROLLED TRIAL; UNITED-STATES; HEPATOCELLULAR-CARCINOMA; VITAMIN-E; PIOGLITAZONE; PREVALENCE; MELLITUS; OUTCOMES; BIOPSY AB Individuals with type 2 diabetes are at heightened risk for nonalcoholic fatty liver disease, which gives rise to nonalcoholic steatohepatitis (NASH) and cirrhosis. Yet, current guidelines do not recommend screening for NASH among these high-risk patients. Using a simulation model, we assessed the effectiveness and cost-effectiveness of screening diabetic patients for NASH. A Markov model was constructed to compare two management strategies for 50-year-olds with diabetes. In the No Screening strategy, patients do not undergo screening, although NASH may be diagnosed incidentally over their lifetime. In the NASH Screening strategy, all patients receive a one-time screening ultrasound. Individuals with fatty infiltration on ultrasound then have a liver biopsy, and those found to have NASH receive medical therapy, which decreases progression to cirrhosis. Endpoints evaluated included quality-adjusted life years (QALYs) gained, costs, and incremental cost-effectiveness ratios (ICERs). Screening for NASH decreased the number of individuals who developed cirrhosis by 12.9 % and resulted in an 11.9 % decrease in liver-related deaths. However, screening resulted in 0.02 fewer QALYs, due to the disutility associated with treatment, and was therefore dominated by the No Screening strategy. When the model excluded this quality-of-life decrement, screening became cost-effective, at an ICER of $42,134 per QALY. Screening for NASH may improve liver-related outcomes, but is not cost-effective at present, due to side effects of therapy. As better tolerated treatments for NASH become available, even with modest efficacy, screening for NASH will become cost-effective. C1 [Corey, Kathleen E.; Klebanoff, Matthew J.; Chung, Raymond T.; Hur, Chin] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Corey, Kathleen E.; Chung, Raymond T.; Hur, Chin] Harvard Med Sch, Boston, MA 02115 USA. [Klebanoff, Matthew J.; Tramontano, Angela C.; Hur, Chin] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Corey, KE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA.; Corey, KE (reprint author), Harvard Med Sch, Boston, MA 02115 USA. EM kcorey@partners.org; mklebanoff@mgh.harvard.edu; angela@mgh-ita.org; rtchung@mgh.harvard.edu; chur@mgh.harvard.edu OI Hur, Chin/0000-0002-2819-7576 FU NIH [K23 DK099422, K24 DK078772] FX Kathleen E. Corey and Raymond T. Chung received grant support from NIH K23 DK099422 and K24 DK078772, respectively. NR 48 TC 1 Z9 1 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 JUL PY 2016 VL 61 IS 7 BP 2108 EP 2117 DI 10.1007/s10620-016-4044-2 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DQ2EA UT WOS:000379013300042 PM 26825843 ER PT J AU Braunwald, E AF Braunwald, Eugene TI Reduction of LDL-cholesterol: important at all ages SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID RISK-FACTORS; CAROTID PLAQUE; METAANALYSIS; INFARCTION; MORTALITY; SMOKING; DISEASE; SEX C1 [Braunwald, Eugene] Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. [Braunwald, Eugene] Harvard Med Sch, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 13 TC 1 Z9 1 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD JUL 1 PY 2016 VL 37 IS 25 BP 1982 EP 1984 DI 10.1093/eurheartj/ehw100 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DQ3TN UT WOS:000379126000012 PM 26984858 ER PT J AU Griffith, M Griffith, OL Krysiak, K Skidmore, ZL Christopher, MJ Klco, JM Ramu, A Lamprecht, TL Wagner, AH Campbell, KM Lesurf, R Hundal, J Zhang, J Spies, NC Ainscough, BJ Larson, DE Heath, SE Fronick, C O'Laughlin, S Fulton, RS Magrini, V McGrath, S Smith, SM Miller, CA Maher, CA Payton, JE Walker, JR Eldred, JM Walter, MJ Link, DC Graubert, TA Westervelt, P Kulkarni, S DiPersio, JF Mardis, ER Wilson, RK Ley, TJ AF Griffith, Malachi Griffith, Obi L. Krysiak, Kilannin Skidmore, Zachary L. Christopher, Matthew J. Klco, Jeffery M. Ramu, Avinash Lamprecht, Tamara L. Wagner, Alex H. Campbell, Katie M. Lesurf, Robert Hundal, Jasreet Zhang, Jin Spies, Nicholas C. Ainscough, Benjamin J. Larson, David E. Heath, Sharon E. Fronick, Catrina O'Laughlin, Shelly Fulton, Robert S. Magrini, Vincent McGrath, Sean Smith, Scott M. Miller, Christopher A. Maher, Christopher A. Payton, Jacqueline E. Walker, Jason R. Eldred, James M. Walter, Matthew J. Link, Daniel C. Graubert, Timothy A. Westervelt, Peter Kulkarni, Shashikant DiPersio, John F. Mardis, Elaine R. Wilson, Richard K. Ley, Timothy J. TI Comprehensive genomic analysis reveals FLT3 activation and a therapeutic strategy for a patient with relapsed adult B-lymphoblastic leukemia SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID GENE-EXPRESSION; YOUNG-ADULTS; RISK; MUTATIONS; PAX5; SUSCEPTIBILITY; ADOLESCENTS; INHIBITION; DIAGNOSIS; INFANT AB The genomic events responsible for the pathogenesis of relapsed adult B-lymphoblastic leukemia (B-ALL) are not yet clear. We performed integrative analysis of whole-genome, whole-exome, custom capture, whole-transcriptome (RNA-seq), and locus-specific genomic assays across nine time points from a patient with primary de novo B-ALL. Comprehensive genome and transcriptome characterization revealed a dramatic tumor evolution during progression, yielding a tumor with complex clonal architecture at second relapse. We observed and validated point mutations in EP300 and NF1, a highly expressed EP300-ZNF384 gene fusion, a microdeletion in IKZF1, a focal deletion affecting SETD2, and large deletions affecting RB1, PAX5, NF1, and ETV6. Although the genome analysis revealed events of potential biological relevance, no clinically actionable treatment options were evident at the time of the second relapse. However, transcriptome analysis identified aberrant overexpression of the targetable protein kinase encoded by the FLT3 gene. Although the patient had refractory disease after salvage therapy for the second relapse, treatment with the FLT3 inhibitor sunitinib rapidly induced a near complete molecular response, permitting the patient to proceed to a matched-unrelated donor stem cell transplantation. The patient remains in complete remission more than 4 years later. Analysis of this patient's relapse genome revealed an unexpected, actionable therapeutic target that led to a specific therapy associated with a rapid clinical response. For some patients with relapsed or refractory cancers, this approach may indicate a novel therapeutic intervention that could alter outcome. Copyright (C) 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. C1 [Griffith, Malachi; Griffith, Obi L.; Krysiak, Kilannin; Skidmore, Zachary L.; Ramu, Avinash; Wagner, Alex H.; Campbell, Katie M.; Lesurf, Robert; Hundal, Jasreet; Zhang, Jin; Spies, Nicholas C.; Ainscough, Benjamin J.; Larson, David E.; Fronick, Catrina; O'Laughlin, Shelly; Fulton, Robert S.; Magrini, Vincent; McGrath, Sean; Smith, Scott M.; Miller, Christopher A.; Maher, Christopher A.; Walker, Jason R.; Eldred, James M.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.] Washington Univ, McDonnell Genome Inst, St Louis, MO USA. [Griffith, Malachi; Griffith, Obi L.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Dept Genet, St Louis, MO 63108 USA. [Griffith, Malachi; Griffith, Obi L.; Ainscough, Benjamin J.; Maher, Christopher A.; Payton, Jacqueline E.; Walter, Matthew J.; Link, Daniel C.; Westervelt, Peter; DiPersio, John F.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Siteman Canc Ctr, St Louis, MO USA. [Griffith, Obi L.; Christopher, Matthew J.; Heath, Sharon E.; Miller, Christopher A.; Maher, Christopher A.; Payton, Jacqueline E.; Walter, Matthew J.; Link, Daniel C.; Westervelt, Peter; DiPersio, John F.; Mardis, Elaine R.; Wilson, Richard K.; Ley, Timothy J.] Washington Univ, Dept Med, St Louis, MO 63108 USA. [Klco, Jeffery M.; Lamprecht, Tamara L.] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA. [Maher, Christopher A.] Washington Univ, Dept Biomed Engn, St Louis, MO USA. [Payton, Jacqueline E.; Kulkarni, Shashikant] Washington Univ, Dept Pathol, St Louis, MO 63130 USA. [Graubert, Timothy A.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Griffith, M (reprint author), Washington Univ, Dept Genet, St Louis, MO 63108 USA.; Ley, TJ (reprint author), Washington Univ, Dept Med, St Louis, MO 63108 USA. EM mgriffit@wustl.edu OI Krysiak, Kilannin/0000-0002-6299-9230; Ainscough, Benjamin/0000-0001-8340-514X; Campbell, Katie/0000-0001-6491-4432; Klco, Jeffery/0000-0003-2961-6960 FU National Institutes of Health (NIH) National Cancer Institute (NCI) [P01 CA101937, P30 CA91842]; NIH National Human Genome Research Institute (NHGRI) [U54 HG003079]; NIH NHGRI [K99 HG007940]; NIH NCI [K22 CA188163, R21 CA185983, R00 CA149182] FX This work was supported by grants from the National Institutes of Health (NIH) National Cancer Institute (NCI) (P01 CA101937, P30 CA91842) with support for analysis from NIH National Human Genome Research Institute (NHGRI) (U54 HG003079). MG was supported by NIH NHGRI grant K99 HG007940. OLG was supported by NIH NCI grant K22 CA188163. CAM was supported by NIH NCI grants R21 CA185983 and R00 CA149182. NR 36 TC 0 Z9 0 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X EI 1873-2399 J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2016 VL 44 IS 7 BP 603 EP 613 DI 10.1016/j.exphem.2016.04.011 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA DP7DS UT WOS:000378660000011 PM 27181063 ER PT J AU Sung, YJ Winkler, TW Manning, AK Aschard, H Gudnason, V Harris, TB Smith, AV Boerwinkle, E Brown, MR Morrison, AC Fornage, M Lin, LA Richard, M Bartz, TM Psaty, BM Hayward, C Polasek, O Marten, J Rudan, I Feitosa, MF Kraja, AT Province, MA Deng, X Fisher, VA Zhou, Y Bielak, LF Smith, J Huffman, JE Padmanabhan, S Smith, BH Ding, J Liu, Y Lohman, K Bouchard, C Rankinen, T Rice, TK Arnett, D Schwander, K Guo, X Palmas, W Rotter, JI Alfred, T Bottinger, EP Loos, RJF Amin, N Franco, OH van Duijn, CM Vojinovic, D Chasman, DI Ridker, PM Rose, LM Kardia, S Zhu, X Rice, K Borecki, IB Rao, DC Gauderman, WJ Cupples, LA AF Sung, Yun Ju Winkler, Thomas W. Manning, Alisa K. Aschard, Hugues Gudnason, Vilmundur Harris, Tamara B. Smith, Albert V. Boerwinkle, Eric Brown, Michael R. Morrison, Alanna C. Fornage, Myriam Lin, Li-An Richard, Melissa Bartz, Traci M. Psaty, Bruce M. Hayward, Caroline Polasek, Ozren Marten, Jonathan Rudan, Igor Feitosa, Mary F. Kraja, Aldi T. Province, Michael A. Deng, Xuan Fisher, Virginia A. Zhou, Yanhua Bielak, Lawrence F. Smith, Jennifer Huffman, Jennifer E. Padmanabhan, Sandosh Smith, Blair H. Ding, Jingzhong Liu, Yongmei Lohman, Kurt Bouchard, Claude Rankinen, Tuomo Rice, Treva K. Arnett, Donna Schwander, Karen Guo, Xiuqing Palmas, Walter Rotter, Jerome I. Alfred, Tamuno Bottinger, Erwin P. Loos, Ruth J. F. Amin, Najaf Franco, Oscar H. van Duijn, Cornelia M. Vojinovic, Dina Chasman, Daniel I. Ridker, Paul M. Rose, Lynda M. Kardia, Sharon Zhu, Xiaofeng Rice, Kenneth Borecki, Ingrid B. Rao, Dabeeru C. Gauderman, W. James Cupples, L. Adrienne TI An Empirical Comparison of Joint and Stratified Frameworks for Studying G x E Interactions: Systolic Blood Pressure and Smoking in the CHARGE Gene-Lifestyle Interactions Working Group SO GENETIC EPIDEMIOLOGY LA English DT Article DE gene-environment interaction; meta-analysis; low-frequency variants ID GENOME-WIDE ASSOCIATION; GENERALIZED ESTIMATING EQUATIONS; ENVIRONMENT INTERACTION; GENOTYPE IMPUTATION; QUANTITATIVE TRAITS; METAANALYSIS; VARIANTS; DISEASES; PACKAGE AB Studying gene-environment (G x E) interactions is important, as they extend our knowledge of the genetic architecture of complex traits and may help to identify novel variants not detected via analysis of main effects alone. The main statistical framework for studying G x E interactions uses a single regression model that includes both the genetic main and G x E interaction effects (the joint framework). The alternative stratified framework combines results from genetic main-effect analyses carried out separately within the exposed and unexposed groups. Although there have been several investigations using theory and simulation, an empirical comparison of the two frameworks is lacking. Here, we compare the two frameworks using results from genome-wide association studies of systolic blood pressure for 3.2 million low frequency and 6.5 million common variants across 20 cohorts of European ancestry, comprising 79,731 individuals. Our cohorts have sample sizes ranging from 456 to 22,983 and include both family-based and population-based samples. In cohort-specific analyses, the two frameworks provided similar inference for population-based cohorts. The agreement was reduced for family-based cohorts. In meta-analyses, agreement between the two frameworks was less than that observed in cohort-specific analyses, despite the increased sample size. In meta-analyses, agreement depended on (1) the minor allele frequency, (2) inclusion of family-based cohorts in meta-analysis, and (3) filtering scheme. The stratified framework appears to approximate the joint framework well only for common variants in population-based cohorts. We conclude that the joint framework is the preferred approach and should be used to control false positives when dealing with low-frequency variants and/or family-based cohorts. C1 [Sung, Yun Ju; Rice, Treva K.; Schwander, Karen; Rao, Dabeeru C.] Washington Univ, Div Biostat, St Louis, MO USA. [Winkler, Thomas W.] Univ Regensburg, Dept Genet Epidemiol, Inst Epidemiol & Prevent Med, Regensburg, Germany. [Manning, Alisa K.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Manning, Alisa K.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Aschard, Hugues; Chasman, Daniel I.; Ridker, Paul M.] Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, Vilmundur; Smith, Albert V.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, NIH, Bethesda, MD 20892 USA. [Boerwinkle, Eric; Brown, Michael R.; Morrison, Alanna C.; Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Human Genet Ctr, Houston, TX 77030 USA. [Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. [Fornage, Myriam; Lin, Li-An; Richard, Melissa] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA. [Bartz, Traci M.; Psaty, Bruce M.; Rice, Kenneth] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Bartz, Traci M.; Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Hayward, Caroline; Marten, Jonathan; Huffman, Jennifer E.] Univ Edinburgh, MRC Human Genet Unit, IGMM, Edinburgh, Midlothian, Scotland. [Polasek, Ozren] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia. [Polasek, Ozren; Rudan, Igor] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Feitosa, Mary F.; Kraja, Aldi T.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA. [Deng, Xuan; Fisher, Virginia A.; Zhou, Yanhua; Cupples, L. Adrienne] Boston Univ, Sch Med, Dept Biostat, Boston, MA 02118 USA. [Bielak, Lawrence F.; Smith, Jennifer; Kardia, Sharon] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Padmanabhan, Sandosh] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland. [Padmanabhan, Sandosh; Smith, Blair H.] Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland. [Smith, Blair H.] Univ Dundee, Div Populat Hlth Sci, Dundee, Scotland. [Ding, Jingzhong] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA. [Liu, Yongmei] Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA. [Lohman, Kurt] Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA. [Bouchard, Claude; Rankinen, Tuomo] Pennington Biomed Res Ctr, Human Genom Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. [Arnett, Donna] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Guo, Xiuqing; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, LABioMed, Torrance, CA 90509 USA. [Palmas, Walter] Columbia Univ, Dept Med, Med Ctr, New York, NY USA. [Alfred, Tamuno; Bottinger, Erwin P.; Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA. [Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA. [Amin, Najaf; van Duijn, Cornelia M.; Vojinovic, Dina] Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands. [Franco, Oscar H.] Erasmus MC, Cardiovasc Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands. [Chasman, Daniel I.; Ridker, Paul M.; Rose, Lynda M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Zhu, Xiaofeng] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Gauderman, W. James] Univ Southern Calif, Dept Prevent Med, Los Angeles, CA USA. [Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Sung, YJ (reprint author), Washington Univ, Sch Med, Div Biostat, 660 South Euclid Ave,Campus Box 8067, St Louis, MO 63110 USA. EM yunju@wubios.wustl.edu RI Padmanabhan, Sandosh/S-3963-2016; Lin, LiAn/C-5819-2017; Bouchard, Claude/A-7637-2009; Polasek, Ozren/B-6002-2011; Feitosa, Mary/K-8044-2012 OI Lin, LiAn/0000-0003-2731-1346; Polasek, Ozren/0000-0002-5765-1862; Feitosa, Mary/0000-0002-0933-2410 FU Chief Scientist Office [CZD/16/6/4]; Medical Research Council [MC_PC_U127561128]; NCATS NIH HHS [UL1 TR000124]; NHLBI NIH HHS [K25 HL121091, R01 HL118305]; NIDDK NIH HHS [P30 DK063491] NR 38 TC 0 Z9 0 U1 3 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2016 VL 40 IS 5 BP 404 EP 415 DI 10.1002/gepi.21978 PG 12 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DQ2ZU UT WOS:000379073200005 PM 27230302 ER PT J AU Marabelli, M Cheng, SC Parmigiani, G AF Marabelli, Monica Cheng, Su-Chun Parmigiani, Giovanni TI Penetrance of ATM Gene Mutations in Breast Cancer: A Meta-Analysis of Different Measures of Risk SO GENETIC EPIDEMIOLOGY LA English DT Article DE ataxia-telangiectasia mutated (ATM) gene; hereditary breast cancer; penetrance; genetic predisposition ID ATAXIA-TELANGIECTASIA; EARLY-ONSET; SUSCEPTIBILITY; MISSENSE; PREDISPOSITION; VARIANTS; CARRIERS; FAMILY AB The gene responsible for ataxia-telangiectasia syndrome, ATM, is also an intermediate-risk breast cancer (BC) susceptibility gene. Numerous studies have been carried out to determine the contribution of ATM gene mutations to BC risk. Epidemiological cohorts, segregation analyses, and case-control studies reported BC risk in different forms, including penetrance, relative risk, standardized incidence ratio, and odds ratio. Because the reported estimates vary both qualitatively and quantitatively, we developed a general model allowing the integration of the different types of cancer risk available in the literature. We performed a comprehensive meta-analysis identifying 19 studies, and used our model to obtain a consensus estimate of BC penetrance. We estimated the cumulative risk of BC in heterozygous ATM mutation carriers to be 6.02% by 50 years of age (95% credible interval: 4.58-7.42%) and 32.83% by 80 years of age (95% credible interval: 24.55-40.43%). An accurate assessment of cancer penetrance is crucial to help mutation carriers make medical and lifestyle decisions that can reduce their chances of developing the disease. C1 [Marabelli, Monica] Univ Pavia, Dept Biol & Biotechnol, Via Ferrata 1, I-27100 Pavia, Italy. [Cheng, Su-Chun; Parmigiani, Giovanni] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Cheng, Su-Chun; Parmigiani, Giovanni] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Marabelli, M (reprint author), Univ Pavia, Dept Biol & Biotechnol, Via Ferrata 1, I-27100 Pavia, Italy. EM monica.marabelli01@ateneopv.it FU NCI NIH HHS [R21 CA177233] NR 29 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2016 VL 40 IS 5 BP 425 EP 431 DI 10.1002/gepi.21971 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA DQ2ZU UT WOS:000379073200007 PM 27112364 ER PT J AU Rauh-Hain, JA Gonzalez, R Bregar, AJ Clemmer, J Hernandez-Blanquisett, A Clark, RM Schorge, JO del Carmen, MG AF Rauh-Hain, J. Alejandro Gonzalez, Rafael Bregar, Amy J. Clemmer, Joel Hernandez-Blanquisett, Abraham Clark, Rachel M. Schorge, John O. del Carmen, Marcela G. TI Patterns of care, predictors and outcomes of chemotherapy for ovarian carcinosarcoma: A National Cancer Database analysis SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Ovarian cancer; Carcinosarcoma; Chemotherapy ID UTERINE; ADENOCARCINOMA; SURVIVAL; TRENDS; HER2 AB Objective. The aim of this study is to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from those of women with high-grade papillary serous ovarian carcinoma (HG-PSOC) when compared by stage and treatment modalities. Methods. The National Cancer Database was queried to identify patients with OCS and HG-PSOC diagnosed between 2003 and 2011. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan-Meier method. Factors predictive of outcome were compared using the Cox proportional hazards model. Results. The final study group consisted of 45,153 women. 2886 (6.39%) had OCS and 42,267 (93.61%) had HG-PSOC. The mean age at diagnosis was 65.43 (+/- 12.21) years for women with OCS and 61.52 (+/- 12.6) years for HG-PSOC (P < 0.001). African-American women had higher rate of OCS relative to white non-hispanic women (7.84% vs. 6.37%; P = 0.002). Overall, women with OCS had a worse five-year survival rate, 26.63% [95% Confidence Interval (CI) = 24.86%-28.53%] vs. 43.61% (95% CI = 43.07%-44.17%). This difference persisted for each FIGO disease stage I-IV, with five-year survival consistently worse for women with OCS compared to those with HG-PSOC. Over the entire study period and after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, and lymph node dissection, carcinosarcoma histology was associated with decreased survival. Conclusion. OCS is associated with a poor prognosis compared to HG-PSOC. This difference was noted across all FIGO stages. (C) 2016 Elsevier Inc. All rights reserved. C1 [Rauh-Hain, J. Alejandro; Gonzalez, Rafael; Bregar, Amy J.; Clemmer, Joel; Hernandez-Blanquisett, Abraham; Clark, Rachel M.; Schorge, John O.; del Carmen, Marcela G.] Harvard Med Sch, Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, Boston, MA USA. RP del Carmen, MG (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, 55 Fruit St,Yawkey 9 E, Boston, MA 02114 USA. EM mdelcarmen@partners.org FU Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital FX This work was supported by The Deborah Kelly Center for Outcomes Research, Massachusetts General Hospital. NR 26 TC 2 Z9 2 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 JUL PY 2016 VL 142 IS 1 BP 38 EP 43 DI 10.1016/j.ygyno.2016.04.025 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DQ3KB UT WOS:000379100100009 PM 27107722 ER PT J AU del Campo, JM Birrer, M Davis, C Fujiwara, K Gollerkeri, A Gore, M Houk, B Lau, S Poveda, A Gonzalez-Martin, A Muller, C Muro, K Pierce, K Suzuki, M Vermette, J Oza, A AF Maria del Campo, Josep Birrer, Michael Davis, Craig Fujiwara, Keiichi Gollerkeri, Ashwin Gore, Martin Houk, Brett Lau, Susie Poveda, Andres Gonzalez-Martin, Antonio Muller, Carolyn Muro, Kei Pierce, Kristen Suzuki, Mie Vermette, Jennifer Oza, Amit TI A randomized phase II non-comparative study of PF-04691502 and gedatolisib (PF-05212384) in patients with recurrent endometrial cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Endometrial cancer; Gedatolisib; mTOR; PI3K; Stathmin ID DUAL INHIBITOR; SMALL-MOLECULE; BREAST-CANCER; MTOR; CARCINOMA; PI3K; PNEUMONITIS; CISPLATIN; KINASES; PATHWAY AB Objective. PF-04691502 and gedatolisib (PF-05212384) are potent, dual PI3K/mTOR inhibitors. This phase II study (B1271004) was conducted in patients with recurrent endometrial cancer following platinum containing chemotherapy. The primary endpoint was to assess clinical benefit response (complete or partial response, or stable disease for 16 weeks) following treatment with PF-04691502 or gedatolisib. Methods. The main study consisted of four independent arms based on a Simon two-stage design. Patients were assigned to putative PI3K-basal (PF-04691502 or gedatolisib) or PI3K-activated (PF-04691502 or gedatolisib) arms based on stathmin-low or stathmin-high tumor expression, respectively. Japanese patients were also enrolled in a separate lead-in cohort. Results. In stage 1 (main study), eighteen patients were randomized to PF-04691502 and 40 to gedatolisib. The two PF-04691502 arms were discontinued early due to unacceptable toxicity, including pneumonia and pneumonitis. The most common treatment-related adverse events associated with gedatolisib were nausea (53%), mucosal inflammation (50%), decreased appetite (40%), diarrhea (38%), fatigue (35%), and dysgeusia and vomiting (each 30%). Clinical benefit response rate was 53% (10/19) in the gedatolisib/stathmin-low arm and 26% (5/19) in the gedatolisib/stathmin-high arm. Safety profile and pharmacokinetic characteristics of both drugs in the Japanese lead-in cohort were comparable to the Western population. Conclusions. Gedatolisib administered by weekly intravenous infusion demonstrated acceptable tolerability and moderate activity in patients with recurrent endometrial cancer. PF-04691502 daily oral dosing was not well tolerated. Clinical benefit response criteria for proceeding to stage 2 were only met in the gedatolisib/stathmin-low arm. Stathmin-high expression did not correlate with greater treatment efficacy. (C) 2016 Published by Elsevier Inc. C1 [Maria del Campo, Josep] VHIO, Pg Vall dHebron 119-129, Barcelona 08035, Spain. [Birrer, Michael] Massachusetts Gen Hosp, 55 Fruit St 410, Boston, MA 02114 USA. [Davis, Craig; Houk, Brett] Pfizer Oncol, 10646 Sci Ctr Dr, La Jolla, CA 92121 USA. [Fujiwara, Keiichi] Saitama Med Univ, Int Med Ctr, 1397-1 Yamane, Hidaka, Saitama 3501298, Japan. [Gollerkeri, Ashwin] Pfizer Worldwide Res & Dev, 35 Cambridge Pk Dr, Cambridge, MA 02140 USA. [Gore, Martin] Royal Marsden Hosp, 203 Fullham Rd, London SW3 6JJ, England. [Lau, Susie] McGill Univ, Jewish Gen Hosp, 3755 Chemin Cote Ste Catherine, Montreal, PQ H3R 1E2, Canada. [Poveda, Andres] Fdn Inst Valenciano Oncol, C Gregorio Gea 31, Valencia 46009, Spain. [Gonzalez-Martin, Antonio] MD Anderson Canc Ctr, Serv Oncol Med, C Arturo Soria 270, Madrid 28033, Spain. [Muller, Carolyn] Univ New Mexico, Hlth Sci Ctr, MSC07 4025 1201 Camino Salud NE, Albuquerque, NM 87131 USA. [Muro, Kei] Aichi Canc Ctr Hosp, Chikusa Ku, 1-1 Kanododen, Nagoya, Aichi 4648681, Japan. [Pierce, Kristen] Pfizer Oncol, 558 Eastern Point Rd, Groton, CT 06340 USA. [Suzuki, Mie] Pfizer Japan, Shibuya Ku, 3-22-7 Yoyogi, Tokyo 1518589, Japan. [Vermette, Jennifer] Pfizer Oncol, 300 Technol Sq,Suite 302, Cambridge, MA 02139 USA. [Oza, Amit] Princess Margaret Canc Ctr, 610 Univ Ave, Toronto, ON M5G 2M9, Canada. RP del Campo, JM (reprint author), Vall dHebron Univ Hosp, VHIO, Pg Vall dHebron 119-129, Barcelona 08035, Spain. EM jmcampof2@seom.org; mbirrer@mgh.harvard.edu; craig.davis@pfizer.com; fujiwara@saitama-med.ac.jp; ashwingollerkeri@gmail.com; Martin.Gore@rmh.nhs.uk; susie.lau@mcgill.ca; apoveda@fivo.org; agonzalezm@seom.org; cmuller@salud.unm.edu; kmuro@aichi-cc.jp; kristen.j.pierce@pfizer.com; mie.suzuki@pfizer.com; jennifer.vermette@pfizer.com; Amit.Oza@uhn.ca FU Pfizer FX This study was supported by Pfizer. NR 22 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2016 VL 142 IS 1 BP 62 EP 69 DI 10.1016/j.ygyno.2016.04.019 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA DQ3KB UT WOS:000379100100013 PM 27103175 ER PT J AU Brown, JR Harb, WA Hill, BT Gabrilove, J Sharman, JP Schreeder, MT Barr, PM Foran, JM Miller, TP Burger, JA Kelly, KR Mahadevan, D Ma, S Li, Y Pierce, DW Barnett, E Marine, J Miranda, M Azaryan, A Yu, XJ Nava-Parada, P Mei, J Kipps, TJ AF Brown, Jennifer R. Harb, Wael A. Hill, Brian T. Gabrilove, Janice Sharman, Jeff P. Schreeder, Marshall T. Barr, Paul M. Foran, James M. Miller, Thomas P. Burger, Jan A. Kelly, Kevin R. Mahadevan, Daruka Ma, Shuo Li, Yan Pierce, Daniel W. Barnett, Evelyn Marine, Jeffrey Miranda, Monika Azaryan, Ada Yu, Xujie Nava-Parada, Pilar Mei, Jay Kipps, Thomas J. TI Phase I study of single-agent CC-292, a highly selective Bruton's tyrosine kinase inhibitor, in relapsed/refractory chronic lymphocytic leukemia SO HAEMATOLOGICA LA English DT Letter DE CC-292; single-agent; chronic lymphocytic leukemia; small lymphocytic lymphoma; relapsed; refractory; BTK inhibitors ID B-CELL RECEPTOR; TARGETING BTK; IBRUTINIB; LYMPHOMA C1 [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA USA. [Harb, Wael A.] Horizon Oncol Ctr, Lafayette, IN USA. [Hill, Brian T.] Cleveland Clin, Taussig Canc Inst, Dept Hematol & Med Oncol, Cleveland, OH 44195 USA. [Gabrilove, Janice] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Sharman, Jeff P.] US Oncol Res, Willamette Valley Canc Inst & Res Ctr, Eugene, OR USA. [Schreeder, Marshall T.] Clearview Canc Inst, Huntsville, AL USA. [Barr, Paul M.] Univ Rochester, Med Ctr, Hematol Oncol, Rochester, NY 14642 USA. [Foran, James M.] Mayo Clin, Hematol & Oncol, Jacksonville, FL USA. [Miller, Thomas P.] Univ Arizona, Ctr Canc, Tucson, AZ USA. [Burger, Jan A.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Kelly, Kevin R.] Univ Texas Hlth Sci Ctr San Antonio, CTRC Inst Drug Dev, San Antonio, TX 78229 USA. [Mahadevan, Daruka] Univ Tennessee, Ctr Hlth Sci, ACORN Res LLC, West Clin, Memphis, TN 38163 USA. [Ma, Shuo] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Li, Yan; Pierce, Daniel W.] Celgene Corp, Dept Translat Med, San Francisco, CA USA. [Barnett, Evelyn; Marine, Jeffrey; Miranda, Monika; Nava-Parada, Pilar; Mei, Jay] Celgene Corp, Summit, NJ USA. [Azaryan, Ada; Yu, Xujie] Celgene Corp, Berkeley Hts, NJ USA. [Kipps, Thomas J.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. RP Brown, JR (reprint author), Dana Farber Canc Inst, Boston, MA USA. EM jennifer_brown@dfci.harvard.edu FU NCI NIH HHS [P30 CA016672] NR 13 TC 2 Z9 2 U1 2 U2 7 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD JUL PY 2016 VL 101 IS 7 BP 295 EP 298 DI 10.3324/haematol.2015.140806 PG 4 WC Hematology SC Hematology GA DQ8SN UT WOS:000379481500007 PM 27151992 ER PT J AU Simon, TG Bonilla, H Yan, P Chung, RT Butt, AA AF Simon, Tracey G. Bonilla, Hector Yan, Peng Chung, Raymond T. Butt, Adeel A. TI Atorvastatin and Fluvastatin Are Associated With Dose-Dependent Reductions in Cirrhosis and Hepatocellular Carcinoma, Among Patients With Hepatitis C Virus: Results From ERCHIVES SO HEPATOLOGY LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; LOVASTATIN-INDUCED APOPTOSIS; FIBROSIS PROGRESSION; METABOLIC SYNDROME; LIVER-CIRRHOSIS; STELLATE CELLS; UNITED-STATES; RISK-FACTOR; STATINS; CANCER AB Statins are associated with delayed fibrosis progression and a reduced risk of hepatocellular carcinoma (HCC) in chronic hepatitis C virus (HCV). Limited data exist regarding the most effective type and dose of statin in this population. We sought to determine the impact of statin type and dose upon fibrosis progression and HCC in patients with HCV. Using the Electronically Retrieved Cohort of HCV Infected Veterans (ERCHIVES) database, we identified all subjects initiated on HCV antibody (anti-HCV) therapy from 2001 to 2014, and all incident cases of cirrhosis and HCC. Statin use was measured using cumulative defined daily dose (cDDD). Multivariable Cox's proportional hazard regression models were used to examine the relationship between statin use and development of cirrhosis and HCC. Among 9,135 eligible subjects, 1,649 developed cirrhosis and 239 developed incident HCC. Statin use was associated with a 44% reduction in development of cirrhosis (adjusted hazard ratio [HR]: 0.6; 95% confidence interval [CI]: 0.53, 0.68). The adjusted HRs (95% CI) of fibrosis progression with statin cDDD 28-89, 89-180, and >180 were 0.74 (0.59, 0.93), 0.71 (0.59, 0.88), and 0.6 (0.53, 0.68), respectively. Mean change in FIB-4 score with atorvastatin (n = 944) and fluvastatin (n = 34) was -0.17 and -0.13, respectively (P = 0.04), after adjustment for baseline FIB-4 score and established predictors of cirrhosis. Statin use was also associated with a 49% reduction in incident HCC (adjusted HR: 0.51; 95% CI: 0.36, 0.72). A similar dose-response relationship was observed. Conclusion: In patients with chronic HCV, statin use was associated with a dose-dependent reduction in incident cirrhosis and HCC. Atorvastatin and fluvastatin were associated with the most significant antifibrotic effects, compared with other statins. C1 [Simon, Tracey G.; Chung, Raymond T.] Massachusetts Gen Hosp, Dept Med, Gastrointestinal Div, Ctr Liver, Boston, MA 02114 USA. [Simon, Tracey G.; Chung, Raymond T.] Harvard Med Sch, Boston, MA USA. [Bonilla, Hector] Diablo Infect Dis, Castro Valley, CA USA. [Yan, Peng; Butt, Adeel A.] Weill Cornell Med Coll, Doha, Qatar. [Yan, Peng; Butt, Adeel A.] Weill Cornell Med Coll, New York, NY USA. [Yan, Peng; Butt, Adeel A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Butt, Adeel A.] Hamad Healthcare Qual Inst, Doha, Qatar. [Butt, Adeel A.] Hamad Med Corp, Doha, Qatar. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Ctr Liver, 55 Fruit St Warren 1007, Boston, MA 02114 USA.; Chung, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St Warren 1007, Boston, MA 02114 USA. EM rtchung@partners.org FU NIH [K24 DK078772] FX Supported by NIH K24 DK078772 (to R.T.C.). NR 52 TC 7 Z9 7 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JUL PY 2016 VL 64 IS 1 BP 47 EP 57 DI 10.1002/hep.28506 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DQ5GP UT WOS:000379233400011 PM 26891205 ER PT J AU Swiderska-Syn, M Xie, GH Michelotti, GA Jewell, ML Premont, RT Syn, WK Diehl, AM AF Swiderska-Syn, Marzena Xie, Guanhua Michelotti, Gregory A. Jewell, Mark L. Premont, Richard T. Syn, Wing-Kin Diehl, Anna Mae TI Hedgehog Regulates Yes-Associated Protein 1 in Regenerating Mouse Liver SO HEPATOLOGY LA English DT Article ID HEPATIC-FIBROSIS; HEPATOCYTE DIFFERENTIATION; TRANSCRIPTION FACTOR; PARTIAL-HEPATECTOMY; ACTIVATION; PATHWAY; CELLS; YAP; TUMORIGENESIS; CANCER AB Adult liver regeneration requires induction and suppression of proliferative activity in multiple types of liver cells. The mechanisms that orchestrate the global changes in gene expression that are required for proliferative activity to change within individual liver cells, and that coordinate proliferative activity among different types of liver cells, are not well understood. Morphogenic signaling pathways that are active during fetal development, including Hedgehog and Hippo/Yes-associated protein 1 (Yap1), regulate liver regeneration in adulthood. Cirrhosis and liver cancer result when these pathways become dysregulated, but relatively little is known about the mechanisms that coordinate and control morphogenic signaling during effective liver regeneration. We evaluated the hypothesis that the Hedgehog pathway controls Yap1 activation during liver regeneration by studying intact mice and cultured liver cells. In cultured hepatic stellate cells (HSCs), disrupting Hedgehog signaling blocked activation of Yap1, and knocking down Yap1 inhibited induction of both Yap1- and Hedgehog-regulated genes that enable HSC to become myofibroblasts (MFs). In mice, disrupting Hedgehog signaling in MFs inhibited liver regeneration after partial hepactectomy (PH). Reduced proliferative activity in the liver epithelial compartment resulted from loss of stroma-derived paracrine signals that activate Yap1 and the Hedgehog pathway in hepatocytes. This prevented hepatocytes from up-regulating Yap1- and Hedgehog-regulated transcription factors that normally promote their proliferation. Conclusions: Morphogenic signaling in HSCs is necessary to reprogram hepatocytes to regenerate the liver epithelial compartment post-PH. This discovery identifies novel molecules that might be targeted to correct defective repair during cirrhosis and liver cancer. C1 [Swiderska-Syn, Marzena; Xie, Guanhua; Michelotti, Gregory A.; Jewell, Mark L.; Premont, Richard T.; Diehl, Anna Mae] Duke Univ, Med Ctr, Dept Med, Div Gastroenterol, Durham, NC USA. [Syn, Wing-Kin] Fdn Liver Res, Inst Hepatol, Regenerat & Repair, London, England. [Syn, Wing-Kin] Med Univ South Carolina, Dept Med, Div Gastroenterol & Hepatol, Charleston, SC USA. [Syn, Wing-Kin] Ralph H Johnson VAMC, Gastroenterol Sect, Charleston, SC USA. RP Diehl, AM (reprint author), Duke Univ, Med Ctr, Div Gastroenterol, 595 LaSalle St,Snyderman Bldg,Suite 1073, Durham, NC 27710 USA. EM diehl004@mc.duke.edu FU National Institute of Health (NIH) - NIDDK [R37 AA010154, R56 DK106633, R01 DK077794] FX This work was supported by the following grants: National Institute of Health (NIH) - NIDDK, R37 AA010154, R56 DK106633, and R01 DK077794 (to A.M.D.). NR 31 TC 3 Z9 3 U1 4 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JUL PY 2016 VL 64 IS 1 BP 232 EP 244 DI 10.1002/hep.28542 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DQ5GP UT WOS:000379233400027 PM 26970079 ER PT J AU Fitzpatrick, MA Suda, KJ Safdar, N Goldstein, B Jones, MM Poggensee, L Ramanathan, S LeWan, R Evans, CT AF Fitzpatrick, Margaret A. Suda, Katie J. Safdar, Nasia Goldstein, Barry Jones, Makoto M. Poggensee, Linda Ramanathan, Swetha LeWan, Ryan Evans, Charlesnika T. TI Unique Risks and Clinical Outcomes Associated With Extended-Spectrum beta-Lactamase Enterobacteriaceae in Veterans With Spinal Cord Injury or Disorder: A Case-Case-Control Study SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI BACTEREMIA; ACUTE REHABILITATION UNIT; NOSOCOMIAL INFECTIONS; URINARY-TRACT; ADMINISTRATIVE DATA; IMPACT; PREVALENCE; ORGANISMS; SUSCEPTIBILITY AB OBJECTIVES. To describe the burden of extended-spectrum beta-lactamase (ESBL) Enterobacteriaceae in veterans with spinal cord injury or disorder (SCI/D), to identify risk factors for ESBL acquisition, and to assess impact on clinical outcomes DESIGN. Retrospective case-case-control study PATIENTS AND SETTING. Veterans with SCI/D and utilization at a Veterans' Affairs medical center from January 1, 2012, to December 31, 2013. METHODS. Patients with a positive culture for ESBL Klebsiella pneumoniae, Escherichia coli, or Proteus mirabilis were matched with patients with non-ESBL organisms by organism, facility, and level of care and to uninfected controls by facility and level of care. Inpatients were also matched by time at risk. Univariate and multivariate matched models were assessed for differences in risk factors and outcomes. RESULTS. A total of 492 cases (62.6% outpatients) were matched 1:1 with each comparison group. Recent prior use of fluoroquinolones and prior use of third- and fourth-generation cephalosporins were independently associated with ESBL compared to the non-ESBL group (adjusted odds ratio [aOR], 2.61; 95% confidence interval [CI], 1.77-3.84; P < .001 for fluoroquinolones and aOR, 3.86; 95% CI, 2.06-7.25; P < .001 for third- and fourth-generation cephalosporins) and the control group (aOR, 2.10; 95% CI, 1.29-3.43; P = .003 for fluoroquinolones; and aOR, 3.31; 95% CI, 1.56-7.06; P = .002 for third- and fourth-generation cephalosporins). Although there were no differences in mortality rate, the ESBL group had a longer post-culture length of stay (LOS) than the non-ESBL group (incidence rate ratio, 1.36; 95% CI, 1.13-1.63; P = .001). CONCLUSIONS. All SCI/D patients with ESBL were more likely to have had recent exposure to fluoroquinolones or third- and fourth generation cephalosporins, and hospitalized patients were more likely to have increased post-culture LOS. Programs targeted toward reduced antibiotic use in SCI/D patients may prevent subsequent ESBL acquisition. C1 [Fitzpatrick, Margaret A.; Suda, Katie J.; Poggensee, Linda; Ramanathan, Swetha; LeWan, Ryan; Evans, Charlesnika T.] Dept Vet Affairs, Ctr Innovat Complex Chron Healthcare, Hines, IL USA. [Fitzpatrick, Margaret A.; Suda, Katie J.; Poggensee, Linda; Ramanathan, Swetha; LeWan, Ryan; Evans, Charlesnika T.] Edward Hines Jr VA Hosp, Spinal Cord Injury Qual Enhancement Res Initiat, Hines, IL USA. [Fitzpatrick, Margaret A.] Loyola Univ, Stritch Sch Med, Dept Med, Div Infect Dis, Maywood, IL 60153 USA. [Suda, Katie J.] Univ Illinois, Coll Pharm, Dept Pharm Syst Outcomes & Policy, Chicago, IL USA. [Safdar, Nasia] Dept Vet Affairs, William S Middleton VA Med Ctr, Madison, WI USA. [Safdar, Nasia] Univ Wisconsin, Dept Med, Div Infect Dis, Madison, WI USA. [Goldstein, Barry] VA Puget Sound Healthcare Syst, Dept Vet Affairs, Off Spinal Cord Injury & Disorders Serv, Seattle, WA USA. [Goldstein, Barry] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. [Jones, Makoto M.] VA Salt Lake City Healthcare Syst, Dept Vet Affairs, Salt Lake City, UT USA. [Jones, Makoto M.] Univ Utah, Dept Med, Div Epidemiol, Salt Lake City, UT 84112 USA. [Ramanathan, Swetha] Edward Hines Jr VA Hosp, Dept Vet Affairs, Dept Pharm, Hines, IL USA. [Evans, Charlesnika T.] Northwestern Univ, Ctr Healthcare Studies, Feinberg Sch Med, Chicago, IL 60611 USA. [Evans, Charlesnika T.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Inst Publ Hlth & Med, Chicago, IL 60611 USA. RP Fitzpatrick, MA (reprint author), 5000 S 5th Ave, Hines, IL 60141 USA. EM Margaret.fitzpatrick@va.gov FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service Merit Review Award [B-1583-P]; Health Services Research and Development Service Post-Doctoral Fellowship Award [TPR 42-005]; Spinal Cord Injury Quality Enhancement Research Initiative [SCI-98-001]; VA FX We would like to thank Scott Miskevics for his assistance with programming and data analysis. This work was supported by The Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development Service Merit Review Award (grant no. B-1583-P), Health Services Research and Development Service Post-Doctoral Fellowship Award (grant no. TPR 42-005), and the Spinal Cord Injury Quality Enhancement Research Initiative (grant no. SCI-98-001). Dr. Nasia Safdar is additionally supported by a VA-funded Patient Safety Center of Inquiry. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the U.S. government. NR 37 TC 0 Z9 0 U1 1 U2 1 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 JUL PY 2016 VL 37 IS 7 BP 768 EP 776 DI 10.1017/ice.2016.60 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DQ3KL UT WOS:000379101100004 PM 27025908 ER PT J AU Shenoy, ES Lee, H Hou, TG Ware, W Ryan, EE Hooper, DC Walensky, RP AF Shenoy, Erica S. Lee, Hang Hou, Taige Ware, Winston Ryan, Erin E. Hooper, David C. Walensky, Rochelle P. TI The Impact of Methicillin-Resistant Staphylococcus aureus (MRSA) and Vancomycin-Resistant Enterococcus (VRE) Flags on Hospital Operations SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID HEALTH-CARE SETTINGS; CONTACT PRECAUTIONS; PROLONGED CARRIAGE; NATURAL-HISTORY; RISK-FACTORS; COLONIZATION; DURATION; DELAYS; ROOMS; PREVALENCE AB OBJECTIVE. To determine the impact of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus (MRSA/VRE) designations, or flags, on selected hospital operational outcomes. DESIGN. Retrospective cohort study of inpatients admitted to the Massachusetts General Hospital during 2010-2011. METHODS. Operational outcomes were time to bed arrival, acuity-unrelated within-hospital transfers, and length of stay. Covariates considered included demographic and clinical characteristics: age, gender, severity of illness on admission, admit day of week, residence prior to admission, hospitalization within the prior 30 days, clinical service, and discharge destination. RESULTS. Overall, 81,288 admissions were included. After adjusting for covariates, patients with a MRSA/VRE flag at the time of admission experienced a mean delay in time to bed arrival of 1.03 hours (9.63 hours [95% CI, 9.39-9.88] vs 8.60 hours [95% CI, 8.47-8.73]). These patients had 1.19 times the odds of experiencing an acuity-unrelated within-hospital transfer [95% CI, 1.13-1.26] and a mean length of stay 1.76 days longer (7.03 days [95% CI, 6.82-7.24] vs 5.27 days [95% CI, 5.15-5.38]) than patients with no MRSA/VRE flag. CONCLUSIONS. MRSA/VRE designation was associated with delays in time to bed arrival, increased likelihood of acuity-unrelated within hospital transfers and extended length of stay. Efforts to identify patients who have cleared MRSA/VRE colonization are critically important to mitigate inefficient use of resources and to improve inpatient flow. C1 [Shenoy, Erica S.; Hooper, David C.] Massachusetts Gen Hosp, Infect Control Unit, 55 Fruit St,Bulfinch 334, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Shenoy, Erica S.; Hou, Taige; Ryan, Erin E.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Med Practice Evaluat Ctr, Boston, MA 02114 USA. [Shenoy, Erica S.; Hooper, David C.; Walensky, Rochelle P.] Harvard Med Sch, Boston, MA USA. [Lee, Hang] Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. [Ware, Winston] Massachusetts Gen Hosp, Clin Care Management Unit, Boston, MA 02114 USA. RP Shenoy, ES (reprint author), Massachusetts Gen Hosp, Infect Control Unit, 55 Fruit St,Bulfinch 334, Boston, MA 02114 USA. EM eshenoy@partners.org FU National Institute of Allergy and Infectious Diseases of the National Institutes of Health [K01AI110524]; Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Research Resources); Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award) [ULI TR001102]; Harvard University FX This work was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant no. K01AI110524 to E.S.S.). 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 ULI 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 33 TC 0 Z9 0 U1 3 U2 3 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 JUL PY 2016 VL 37 IS 7 BP 782 EP 790 DI 10.1017/ice.2016.54 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA DQ3KL UT WOS:000379101100006 PM 27019995 ER PT J AU Kim, J Saitou, K Matuszak, MM Balter, JM AF Kim, Jihun Saitou, Kazuhiro Matuszak, Martha M. Balter, James M. TI A finite element head and neck model as a supportive tool for deformable image registration SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY LA English DT Article DE Finite element method; Image registration; Head and neck; Deformation; Radiation therapy ID CONE-BEAM CT; RADIATION-THERAPY; CERVICAL-SPINE; ACCURACY; RADIOTHERAPY; CANCER; UNCERTAINTIES AB A finite element (FE) head and neck model was developed as a tool to aid investigations and development of deformable image registration and patient modeling in radiation oncology. Useful aspects of a FE model for these purposes include ability to produce realistic deformations (similar to those seen in patients over the course of treatment) and a rational means of generating new configurations, e.g., via the application of force and/or displacement boundary conditions. The model was constructed based on a cone-beam computed tomography image of a head and neck cancer patient. The three-node triangular surface meshes created for the bony elements (skull, mandible, and cervical spine) and joint elements were integrated into a skeletal system and combined with the exterior surface. Nodes were additionally created inside the surface structures which were composed of the three-node triangular surface meshes, so that four-node tetrahedral FE elements were created over the whole region of the model. The bony elements were modeled as a homogeneous linear elastic material connected by intervertebral disks. The surrounding tissues were modeled as a homogeneous linear elastic material. Under force or displacement boundary conditions, FE analysis on the model calculates approximate solutions of the displacement vector field. A FE head and neck model was constructed that skull, mandible, and cervical vertebrae were mechanically connected by disks. The developed FE model is capable of generating realistic deformations that are strain-free for the bony elements and of creating new configurations of the skeletal system with the surrounding tissues reasonably deformed. The FE model can generate realistic deformations for skeletal elements. In addition, the model provides a way of evaluating the accuracy of image alignment methods by producing a ground truth deformation and correspondingly simulated images. The ability to combine force and displacement conditions provides flexibility for simulating realistic anatomic configurations. C1 [Kim, Jihun] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Saitou, Kazuhiro] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. [Matuszak, Martha M.; Balter, James M.] Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. RP Kim, J (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jkim115@mgh.harvard.edu OI Kim, Jihun/0000-0003-4856-6305 FU [NIHP01CA59827] FX This work was supported by NIHP01CA59827. NR 18 TC 0 Z9 0 U1 5 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1861-6410 EI 1861-6429 J9 INT J COMPUT ASS RAD JI Int. J. Comput. Assist. Radiol. Surg. PD JUL PY 2016 VL 11 IS 7 BP 1311 EP 1317 DI 10.1007/s11548-015-1335-6 PG 7 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA DQ2KW UT WOS:000379032200007 PM 26704371 ER PT J AU Llerena, K Wynn, JK Hajcak, G Green, MF Horan, WP AF Llerena, Katiah Wynn, Jonathan K. Hajcak, Greg Green, Michael F. Horan, William P. TI Patterns and reliability of EEG during error monitoring for internal versus external feedback in schizophrenia SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE Event related potentials; Schizophrenia; Principal component analysis; Reward; Electroencephalography; Performance monitoring ID EVENT-RELATED POTENTIALS; TIME-ESTIMATION TASK; BRAIN ACTIVITY; HEALTHY-VOLUNTEERS; ANTISACCADE TASK; REWARD MAGNITUDE; NEURAL SYSTEM; NEGATIVITY; ERP; STATE AB Background: Accurately monitoring one's performance on daily life tasks, and integrating internal and external performance feedback are necessary for guiding productive behavior. Although internal feedback processing, as indexed by the error-related negativity (ERN), is consistently impaired in schizophrenia, initial findings suggest that external performance feedback processing, as indexed by the feedback negativity (FN), may actually be intact. The current study evaluated internal and external feedback processing task performance and test-retest reliability in schizophrenia. Methods: 92 schizophrenia outpatients and 63 healthy controls completed a flanker task (ERN) and a time estimation task (FN). Analyses examined the Delta ERN and Delta FN defined as difference waves between correct/positive versus error/negative feedback conditions. A temporal principal component analysis was conducted to distinguish the Delta ERN and Delta FN from overlapping neural responses. We also assessed test-retest reliability of Delta ERN and Delta FN in patients over a 4-week interval. Results: Patients showed reduced Delta ERN accompanied by intact Delta FN. In patients, test-retest reliability for both Delta ERN and Delta FN over a four-week period was fair to good. Conclusion: Individuals with schizophrenia show a pattern of impaired internal, but intact external, feedback processing. This pattern has implications for understanding the nature and neural correlates of impaired feedback processing in schizophrenia. Published by Elsevier B.V. C1 [Llerena, Katiah; Wynn, Jonathan K.; Green, Michael F.; Horan, William P.] VISN 22 Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, 11301 Wilshire Blvd,Bldg 210, Los Angeles, CA 90073 USA. [Llerena, Katiah; Wynn, Jonathan K.; Green, Michael F.; Horan, William P.] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Hajcak, Greg] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA. RP Llerena, K (reprint author), VA Greater Los Angeles, Healthcare Syst, MIRECC, Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM kllerena@ucla.edu FU AbbVie; DSP; Forum; Mnemosyne (scientific board); Takeda; Roche; Amgen FX Dr. Green reports having received consulting fees from AbbVie, DSP, Forum, Mnemosyne (scientific board), Takeda, Roche. He has received grant funding from Amgen and Forum. The rest of the authors report no biomedical financial interests or potential conflicts of interest. NR 59 TC 0 Z9 0 U1 7 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 EI 1872-7697 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD JUL PY 2016 VL 105 BP 39 EP 46 DI 10.1016/j.ijpsycho.2016.04.012 PG 8 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA DQ3MQ UT WOS:000379106800006 PM 27166742 ER PT J AU McCurry, SM Guthrie, KA Morin, C Woods, NF Landis, CA Ensrud, KE Larson, JC Joffe, H Cohen, LS Hunt, JR Newton, KM Otte, JL Reed, SD Sternfeld, B Tinker, LF LaCroix, AZ AF McCurry, Susan M. Guthrie, Katherine A. Morin, CharlesM. Woods, Nancy F. Landis, Carol A. Ensrud, Kristine E. Larson, Joseph C. Joffe, Hadine Cohen, Lee S. Hunt, Julie R. Newton, Katherine M. Otte, Julie L. Reed, Susan D. Sternfeld, Barbara Tinker, Lesley F. LaCroix, Andrea Z. TI Telephone-Based Cognitive Behavioral Therapy for Insomnia in Perimenopausal and Postmenopausal Women With Vasomotor Symptoms A MsFLASH Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID SLEEP DISTURBANCE; MENOPAUSAL SYMPTOMS; BREAST-CANCER; HOT FLASHES; METAANALYSIS; QUALITY; HEALTH; MEDICATION; TRANSITION; DISORDERS AB IMPORTANCE Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings. OBJECTIVE To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). DESIGN, SETTING, AND PARTICIPANTS A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, >= 12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. INTERVENTIONS Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health. MAIN OUTCOMES AND MEASURES Primary outcome was scores on the ISI (score range, 0-28; scores >= 15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. RESULTS At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, -3.9 to -1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (-15.7; 95% CI, -20.4 to -11.0) compared with the MEC group (-7.1; 95% CI, -14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (-22.8; 95% CI, -28.6 to -16.9) and MEC group (-11.6; 95% CI, -19.4 to -3.8) (P = .003). CONCLUSIONS AND RELEVANCE Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. C1 [McCurry, Susan M.] Univ Washington, Dept Psychosocial & Community Hlth, 6200 NE 74th St,Ste 42, Seattle, WA 98115 USA. [Guthrie, Katherine A.; Larson, Joseph C.; Hunt, Julie R.; Tinker, Lesley F.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Washington, DC USA. [Morin, CharlesM.] Univ Laval, Dept Psychol, Quebec City, PQ, Canada. [Woods, Nancy F.; Landis, Carol A.] Univ Washington, Biobehav Nursing & Hlth Syst, Seattle, WA 98115 USA. [Ensrud, Kristine E.] Univ Minnesota, Dept Med, Div Epidemiol & Community Hlth, Box 736 UMHC, Minneapolis, MN 55455 USA. [Ensrud, Kristine E.] Minneapolis VA Hlth Care Syst, Ctr Chron Dis Outcomes Res, Minneapolis, MN USA. [Joffe, Hadine] Harvard Med Sch, Brigham & Womens Hosp, Div Womens Mental Hlth, Dept Psychiat, Boston, MA USA. [Joffe, Hadine] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Cohen, Lee S.] Harvard Med Sch, Ctr Womens Mental Hlth, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Newton, Katherine M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA. [Otte, Julie L.] Indiana Univ, Dept Sci Nursing Care, Indianapolis, IN 46204 USA. [Reed, Susan D.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98115 USA. [Sternfeld, Barbara] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [LaCroix, Andrea Z.] Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA. RP McCurry, SM (reprint author), Univ Washington, Dept Psychosocial & Community Hlth, 6200 NE 74th St,Ste 42, Seattle, WA 98115 USA. EM smccurry@uw.edu FU National Institute on Aging; Eunice Kennedy Shriver National Institute of Child Health and Development; National Center for Complementary and Alternative Medicine; Office of Research on Women's Health; National Institute on Aging, National Institutes of Health [U01AG032699] FX The Menopause Strategies Finding Lasting Answers for Symptoms and Health research network was established under a National Institutes of Health cooperative agreement to conduct studies of the efficacy of treatments for the management of menopausal hot flashes. The studies were sponsored by the National Institute on Aging in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Development, the National Center for Complementary and Alternative Medicine, and the Office of Research on Women's Health. This study was supported by grant U01AG032699 from the National Institute on Aging, National Institutes of Health. NR 50 TC 1 Z9 1 U1 6 U2 7 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 JUL PY 2016 VL 176 IS 7 BP 913 EP 920 DI 10.1001/jamainternmed.2016.1795 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700012 PM 27213646 ER PT J AU Percac-Lima, S Ashburner, J Zai, AH Chang, YC Oo, SA Guimaraes, E Atlas, SJ AF Percac-Lima, Sanja Ashburner, JeffreyM. Zai, Adrian H. Chang, Yuchiao Oo, Sarah A. Guimaraes, Erica Atlas, Steven J. TI Patient Navigation for Comprehensive Cancer Screening in High-Risk Patients Using a Population-Based Health Information Technology System A Randomized Clinical Trial SO JAMA INTERNAL MEDICINE LA English DT Article ID FORCE RECOMMENDATION STATEMENT; PRIMARY-CARE; MANAGEMENT-SYSTEM; WOMEN; DISPARITIES; BARRIERS; QUALITY; EQUITY AB IMPORTANCE Patient navigation (PN) to improve cancer screening in low-income and racial/ethnic minority populations usually focuses on navigating for single cancers in community health center settings. OBJECTIVE We evaluated PN for breast, cervical, and colorectal cancer screening using a population-based information technology (IT) system within a primary care network. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted from April 2014 to December 2014 in 18 practices in an academic primary care network. All patients eligible and overdue for cancer screening were identified and managed using a population-based IT system. Those at high risk for nonadherence with completing screening were identified using an electronic algorithm (language spoken, number of overdue tests, no-show visit history), and randomized to a PN intervention (n = 792) or usual care (n = 820). Navigators used the IT system to track patients, contact them, and provide intense outreach to help them complete cancer screening. MAIN OUTCOMES AND MEASURES Mean cancer screening test completion rate over 8-month trial for each eligible patient, with all overdue cancer screening tests combined using linear regression models. Secondary outcomes included the proportion of patients completing any and each overdue cancer screening test. RESULTS Among 1612 patients (673 men and 975 women; median age, 57 years), baseline patient characteristics were similar among randomized groups. Of 792 intervention patients, patient navigators were unable to reach 151 (19%), deferred 246 (38%) (eg, patient declined, competing comorbidity), and navigated 202 (32%). The mean proportion of patients who were up to date with screening among all overdue screening examinations was higher in the intervention vs the control group for all cancers combined (10.2% vs 6.8%; 95% CI [for the difference], 1.5%-5.2%; P < .001), and for breast (14.7% vs 11.0%; 95% CI, 0.2%-7.3%; P = .04), cervical (11.1% vs 5.7%; 95% CI, 0.8%-5.2%; P = .002), and colon (7.6% vs 4.6%; 95% CI, 0.8%-5.2%; P = .01) cancer compared with control. The proportion of overdue patients who completed any cancer screening during follow-up was higher in the intervention group (25.5% vs 17.0%; 95% CI, 4.7%-12.7%; P < .001). The intervention group had more patients completing screening for breast (23.4% vs 16.6%; 95% CI, 1.8%-12.0%; P = .009), cervical (14.4% vs 8.6%; 95% CI, 1.6%-10.5%; P = .007), and colorectal (13.7% vs 7.0%; 95% CI, 3.2%-10.4%; P < .001) cancer. CONCLUSIONS AND RELEVANCE Patient navigation as part of a population-based IT system significantly increased screening rates for breast, cervical, and colorectal cancer in patients at high risk for nonadherence with testing. Integrating patient navigation into population health management activities for low-income and racial/ethnic minority patients might improve equity of cancer care. C1 [Percac-Lima, Sanja; Ashburner, JeffreyM.; Chang, Yuchiao; Atlas, Steven J.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Percac-Lima, Sanja; Oo, Sarah A.; Guimaraes, Erica] Massachusetts Gen Hosp, Chelsea HealthCare Ctr, Chelsea, MA USA. [Percac-Lima, Sanja; Ashburner, JeffreyM.; Zai, Adrian H.; Chang, Yuchiao; Atlas, Steven J.] Harvard Med Sch, Boston, MA USA. [Zai, Adrian H.] Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Percac-Lima, S (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,Ninth Floor, Boston, MA 02114 USA. EM spercaclima@mgh.harvard.edu FU American Cancer Society: Cancer Control Career Development Award for Primary Care Physicians [CCCDAA-14-012-01-CCCDA]; Lazarex Cancer Foundation; Harvard Medical School Center for Primary Care Innovation Fellowship FX This work was supported by American Cancer Society: Cancer Control Career Development Award for Primary Care Physicians, CCCDAA-14-012-01-CCCDA, Lazarex Cancer Foundation, and the Harvard Medical School Center for Primary Care Innovation Fellowship. NR 30 TC 5 Z9 5 U1 5 U2 8 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 JUL PY 2016 VL 176 IS 7 BP 930 EP 937 DI 10.1001/jamainternmed.2016.0841 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700015 PM 27273602 ER PT J AU Jena, AB Goldman, D Karaca-Mandic, P AF Jena, Anupam B. Goldman, Dana Karaca-Mandic, Pinar TI Hospital Prescribing of Opioids to Medicare Beneficiaries SO JAMA INTERNAL MEDICINE LA English DT Article ID PAIN MANAGEMENT; UNITED-STATES; OLDER-ADULTS; RISK-FACTORS; ANALGESICS; COHORT; CARE; FRACTURES; ARTHRITIS; OVERDOSE AB IMPORTANCE Use of opioids during and shortly after an acute hospitalization is warranted in some clinical settings. However, given the potential of opioids for short-term adverse events and long-term physiologic tolerance, it is important to understand the frequency of opioid prescribing at hospital discharge, hospital variation, and patient and hospital factors associated with opioid prescribing, which is currently unknown in the United States. OBJECTIVE To estimate the frequency of opioid prescribing at hospital discharge among Medicare beneficiaries without an opioid prescription claim 60 days prior to hospitalization; to document hospital variation in prescribing; and to analyze patient and hospital factors associated with prescribing, including hospital average performance on pain-related Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) measures. DESIGN, SETTING, AND PARTICIPANTS Analysis of pharmacy claims of a 20% random sample of Medicare beneficiaries hospitalized in 2011 without an opioid prescription claim in the 60 days before hospitalization. MAIN OUTCOMES AND MEASURES Our main outcome was a new opioid claim within 7 days of hospital discharge. We estimated a multivariable linear probability model of patient factors associated with new opioid use and described hospital variation in adjusted rates of new opioid use. In multivariable linear regression analysis, we also analyzed hospital factors associated with average adjusted new opioid use at the hospital level, including the percentage of each hospital's patients who reported that their pain during hospitalization was always well controlled in the 2011 HCAHPS surveys. RESULTS Among 623 957 hospitalizations, 92 882 (14.9%) were associated with a new opioid claim. Among those hospitalizations with an associated opioid claim within 7 days of hospital discharge, 32 731 (42.5%) of 77 092 were associated with an opioid claim after 90 days postdischarge. Across 2512 hospitals, the average adjusted rate of new opioid use within 7 days of hospitalization was 15.1% (interquartile range, 12.3%-17.4%; interdecile range, 10.5%-20.0%). A hospital's adjusted rate of new opioid use was modestly positively associated with the percentage of its inpatients reporting that their pain was always well managed (increase from 25th to the 75th percentile in the HCAHPS measure was associated with an absolute increase in new opioid use of 0.89 percentage points or a relative increase of 6.0%; P < .001). CONCLUSIONS AND RELEVANCE New opioid use after hospitalization is common among Medicare beneficiaries, with substantial variation across hospitals and a large proportion of patients using a prescription opioid 90 days after hospitalization. The degree to which observed hospital variation in short-and longer-term opioid use reflects variation in inappropriate prescribing at hospital discharge is unknown. C1 [Jena, Anupam B.] Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. [Jena, Anupam B.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Jena, Anupam B.] Natl Bur Econ Res, Cambridge, MA 02138 USA. [Goldman, Dana] Univ So Calif, Leonard D Schaeffer Ctr Hlth Policy & Econ, Los Angeles, CA USA. [Goldman, Dana] RAND Corp, Santa Monica, CA USA. [Karaca-Mandic, Pinar] Univ Minnesota, Sch Publ Hlth, Div Hlth Policy & Management, Minneapolis, MN USA. RP Jena, AB (reprint author), Harvard Med Sch, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. EM jena@hcp.med.harvard.edu FU Office of the Director, National Institutes of Health [1DP50D017897-01]; National Institute on Aging [5P01AG033559, 5K01AG036740]; University of Minnesota Academic Health Center Faculty Development Grant FX The authors report funding from the Office of the Director, National Institutes of Health (Early Independence Award, grant 1DP50D017897-01 [Dr Jena]), National Institute on Aging (grants 5P01AG033559 [Dr Goldman] and 5K01AG036740 [Dr Karaca-Mandic]), and a University of Minnesota Academic Health Center Faculty Development Grant (Dr Karaca-Mandic). NR 21 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2016 VL 176 IS 7 BP 990 EP 997 DI 10.1001/jamainternmed.2016.2737 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700025 PM 27294595 ER PT J AU Kirkpatrick, JN Hauptman, PJ Swetz, KM Blume, ED Gauvreau, K Maurer, M Goodlin, SJ AF Kirkpatrick, James N. Hauptman, Paul J. Swetz, Keith M. Blume, Elizabeth D. Gauvreau, Kimberlee Maurer, Mathew Goodlin, Sarah J. TI Palliative Care for Patients With End-Stage Cardiovascular Disease and Devices: A Report From the Palliative Care Working Group of the Geriatrics Section of the American College of Cardiology SO JAMA INTERNAL MEDICINE LA English DT Letter ID VENTRICULAR ASSIST DEVICES C1 [Kirkpatrick, James N.] Univ Washington, Div Cardiol, Eth Consultat Serv, 1959 NE Pacific St, Seattle, WA 98125 USA. [Hauptman, Paul J.] St Louis Univ, Div Cardiol, Dept Med, St Louis, MO 63103 USA. [Swetz, Keith M.] Univ Alabama Birmingham, Ctr Palliat & Support Care, Birmingham, AL USA. [Swetz, Keith M.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Blume, Elizabeth D.; Gauvreau, Kimberlee] Boston Childrens Hosp, Dept Cardiol, Boston, MA USA. [Maurer, Mathew] Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA. [Goodlin, Sarah J.] Portland VA Med Ctr, Portland, OR USA. [Goodlin, Sarah J.] Patient Ctr Educ & Res, Portland, OR USA. RP Kirkpatrick, JN (reprint author), Univ Washington, Div Cardiol, Eth Consultat Serv, 1959 NE Pacific St, Seattle, WA 98125 USA. EM kirkpatj@uw.edu NR 6 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 JUL PY 2016 VL 176 IS 7 BP 1017 EP 1019 DI 10.1001/jamainternmed.2016.2096 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700032 PM 27214624 ER PT J AU Munshi, MN Slyne, C Segal, AR Saul, N Lyons, C Weinger, K AF Munshi, Medha N. Slyne, Christine Segal, Alissa R. Saul, Nora Lyons, Courtney Weinger, Katie TI Simplification of Insulin Regimen in Older Adults and Risk of Hypoglycemia SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Munshi, Medha N.; Slyne, Christine; Segal, Alissa R.; Saul, Nora; Lyons, Courtney; Weinger, Katie] Joslin Diabet Ctr, Boston, MA 02215 USA. [Munshi, Medha N.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Munshi, Medha N.; Weinger, Katie] Harvard Med Sch, Dept Med, Boston, MA USA. [Segal, Alissa R.] MCPHS Univ, Sch Pharm, Boston, MA USA. RP Munshi, MN (reprint author), 110,Francis St,LMOB 1B, Boston, MA 02215 USA. EM mmunshi@bidmc.harvard.edu NR 7 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-6106 EI 2168-6114 J9 JAMA INTERN MED JI JAMA Intern. Med. PD JUL PY 2016 VL 176 IS 7 BP 1023 EP 1025 DI 10.1001/jamainternmed.2016.2288 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700035 PM 27273335 ER PT J AU Talebreza, S Widera, E AF Talebreza, Shaida Widera, Eric TI A Perspective on Hospice Reform and Additional Caregiver Support Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Talebreza, Shaida] Univ Utah, Div Geriatr, Sch Med, Salt Lake City, UT USA. [Talebreza, Shaida] Home Based Primary Care, Salt Lake City, UT USA. [Talebreza, Shaida] George E Wahlen Salt Lake City Vet Affairs Med Ct, Salt Lake City, UT USA. [Talebreza, Shaida] Inspirat Hosp, Salt Lake City, UT USA. [Widera, Eric] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Widera, Eric] San Francisco VA Med Ctr, Hosp & Palliat Care, 4150 Clement St, San Francisco, CA 94121 USA. RP Widera, E (reprint author), San Francisco VA Med Ctr, Hosp & Palliat Care, 4150 Clement St, San Francisco, CA 94121 USA.; Widera, E (reprint author), UCSF, Div Geriatr & Geriatr Med Fellowship, San Francisco, CA 94121 USA. EM eric.widera@ucsf.edu NR 1 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 JUL PY 2016 VL 176 IS 7 BP 1032 EP 1033 DI 10.1001/jamainternmed.2016.2742 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700041 PM 27379480 ER PT J AU Majmudar, MD Aungst, TD AF Majmudar, Maulik D. Aungst, Timothy Dy TI Telemedicine in Heart Failure-Ineffective or Just Ill Used? SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Majmudar, Maulik D.] Massachusetts Gen Hosp, Healthcare Transformat Lab, 60 Staniford St, Boston, MA 02114 USA. [Majmudar, Maulik D.] Harvard Med Sch, Boston, MA USA. [Aungst, Timothy Dy] Massachusetts Coll Pharm & Hlth Sci Univ, Worcester, MA USA. RP Majmudar, MD (reprint author), Massachusetts Gen Hosp, Healthcare Transformat Lab, 60 Staniford St, Boston, MA 02114 USA. EM mmajmudar@partners.org 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 JUL PY 2016 VL 176 IS 7 BP 1035 EP 1035 DI 10.1001/jamainternmed.2016.2857 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700045 PM 27379484 ER PT J AU Ong, MK Romano, PS Fonarow, GC AF Ong, Michael K. Romano, Patrick S. Fonarow, Gregg C. TI Telemedicine in Heart Failure-Ineffective or Just Ill Used? Reply SO JAMA INTERNAL MEDICINE LA English DT Letter C1 [Ong, Michael K.; Fonarow, Gregg C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 10940 Wilshire Blvd,Ste 700, Los Angeles, CA 90024 USA. [Ong, Michael K.] VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. [Romano, Patrick S.] Univ Calif Davis, Dept Internal Med, Davis, CA 95616 USA. [Romano, Patrick S.] Univ Calif Davis, Dept Pediat, Davis, CA 95616 USA. RP Ong, MK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 10940 Wilshire Blvd,Ste 700, Los Angeles, CA 90024 USA. EM michael.ong@ucla.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 JUL PY 2016 VL 176 IS 7 BP 1035 EP 1036 DI 10.1001/jamainternmed.2016.2860 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA DQ2NR UT WOS:000379039700046 PM 27379485 ER PT J AU Faraone, SV Biederman, J AF Faraone, Stephen V. Biederman, Joseph TI Can Attention-Deficit/Hyperactivity Disorder Onset Occur in Adulthood? SO JAMA PSYCHIATRY LA English DT Editorial Material ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; TWIN C1 [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. [Faraone, Stephen V.] Univ Bergen, Dept Biomed, KG Jebsen Ctr Neuropsychiat Disorders, Bergen, Norway. [Biederman, Joseph] Harvard Med Sch, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Biederman, Joseph] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM sfaraone@childpsychresearch.org FU Shire; Alcobra; Otsuka; McNeil; Janssen; Novartis; Pfizer; Eli Lilly; K. G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway; European Union's Seventh Framework Programme for research, technological development; National Institute of Mental Health; AACAP; APSARD; ElMindA; Forest Research Institute; Ironshore; Lundbeck; Magceutics Inc; Merck; National Institutes of Health; Neurocentria Inc; PamLab; Shire Pharmaceuticals Inc; SPRITES; Sunovion; US Department of Defense; US Food & Drug Administration; Vaya Pharma/Enzymotec; Ingenix; Prophase; Bracket Global; Theravance; Department of Psychiatry at MGH FX In the past year, Dr Faraone received income, potential income, travel expenses, and/or research support from Rhodes, Arbor, Pfizer, Ironshore, Shire, Akili Interactive Labs, CogCubed, Alcobra, VAYA Pharma, and NeuroLifeSciences. With his institution, he has US patent US20130217707 A1 for the use of sodium-hydrogen exchange inhibitors in the treatment of attention-deficit/hyperactivity disorder (ADHD). In previous years, he received income or research support from Shire, Alcobra, Otsuka, McNeil, Janssen, Novartis, Pfizer, and Eli Lilly. Dr Faraone receives royalties from books. Dr Faraone is also supported by the K. G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway, the European Union's Seventh Framework Programme for research, technological development, and the National Institute of Mental Health. Dr Biederman reported receiving research support from the AACAP, Alcobra, APSARD, ElMindA, Forest Research Institute, Ironshore, Lundbeck, Magceutics Inc, McNeil, Merck, the National Institutes of Health, Neurocentria Inc, PamLab, Pfizer, Shire Pharmaceuticals Inc, SPRITES, Sunovion, the US Department of Defense, the US Food & Drug Administration, and Vaya Pharma/Enzymotec; honoraria from the Massachusetts General Hospital (MGH) Psychiatry Academy for tuition-funded continuing medical education (CME) courses and Alcobra and American Academy of Child and Adolescent Psychiatry; and departmental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Ingenix, Prophase, Shire, Bracket Global, Sunovion, and Theravance; these royalties were paid to the Department of Psychiatry at MGH. Dr Biederman also has a US patent application pending (provisional No. 61/233,686) through MGH corporate licensing on a method to prevent stimulant abuse. No other disclosures were reported. NR 10 TC 7 Z9 7 U1 2 U2 3 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 JUL PY 2016 VL 73 IS 7 BP 655 EP 656 DI 10.1001/jamapsychiatry.2016.0400 PG 2 WC Psychiatry SC Psychiatry GA DQ2OT UT WOS:000379042700005 PM 27191055 ER PT J AU Shear, MK Reynolds, CF Simon, NM Zisook, S Wang, YJ Mauro, C Duan, NH Lebowitz, B Skritskaya, N AF Shear, M. Katherine Reynolds, Charles F., III Simon, Naomi M. Zisook, Sidney Wang, Yuanjia Mauro, Christine Duan, Naihua Lebowitz, Barry Skritskaya, Natalia TI Optimizing Treatment of Complicated Grief A Randomized Clinical Trial SO JAMA PSYCHIATRY LA English DT Article ID PROLONGED GRIEF; MISSING DATA; BEREAVEMENT; DEPRESSION; DISORDER; SCALE; INTERVENTION; SUICIDALITY; INVENTORY; VALIDITY AB IMPORTANCE To our knowledge, this is the first placebo-controlled randomized clinical trial to evaluate the efficacy of antidepressant pharmacotherapy, with and without complicated grief psychotherapy, in the treatment of complicated grief. OBJECTIVE To confirm the efficacy of a targeted complicated grief treatment (CGT), determine whether citalopram (CIT) enhances CGT outcome, and examine CIT efficacy without CGT. DESIGN, SETTING, AND PARTICIPANTS Included in the study were 395 bereaved adults who met criteria for CG recruited from March 2010 to September 2014 from academic medical centers in Boston, Massachusetts; New York, New York; Pittsburgh, Pennsylvania; and San Diego, California. Co-occurring substance abuse, psychosis, mania, and cognitive impairment were exclusionary. Study participants were randomized using site-specific permuted blocks stratified by major depression into groups prescribed CIT (n = 101), placebo (PLA; n = 99), CGT with CIT (n = 99), and CGT with PLA (n = 96). Independent evaluators conducted monthly assessments for 20 weeks. Response rates were compared under the intention-to-treat principle, including all randomized participants in a logistic regression with inverse probability weighting. INTERVENTIONS All participants received protocolized pharmacotherapy optimized by flexible dosing, psychoeducation, grief monitoring, and encouragement to engage in activities. Half were also randomized to receive manualized CGT in 16 concurrent weekly sessions. MAIN OUTCOMES AND MEASURES Complicated grief-anchored Clinical Global Impression scale measurments every 4 weeks. Response was measured as a rating of "much improved" or "very much improved." RESULTS Of the 395 study participants, 308 (78.0%) were female and 325 (82.3%) were white. Participants' response to CGT with PLA vs PLA (82.5% vs 54.8%; relative risk [RR], 1.51; 95% CI, 1.16-1.95; P = .002; number needed to treat [NNT], 3.6) suggested the efficacy of CGT, and the addition of CIT did not significantly improve CGT outcome (CGT with CIT vs CGT with PLA: 83.7% vs 82.5%; RR, 1.01; 95% CI, 0.88-1.17; P = .84; NNT, 84). However, depressive symptoms decreased significantly more when CIT was added to treatment (CGT with CIT vs CGT with PLA: model-based adjusted mean [standard error] difference, -2.06 [1.00]; 95% CI, -4.02 to -0.11; P = .04). By contrast, adding CGT improved CIT outcome (CIT vs CGT with CIT: 69.3% vs 83.7%; RR, 1.21; 95% CI, 1.00-1.46; P = .05; NNT, 6.9). Last, participant response to CIT was not significantly different from PLA at week 12 (45.9% vs 37.9%; RR, 1.21; 95% CI, 0.82-1.81; P = .35; NNT, 12.4) or at week 20 (69.3% vs 54.8%; RR, 1.26; 95% CI, 0.95-1.68; P = .11; NNT, 6.9). Rates of suicidal ideation diminished to a substantially greater extent among participants receiving CGT than among those who did not. CONCLUSIONS AND RELEVANCE Complicated grief treatment is the treatment of choice for CG, and the addition of CIT optimizes the treatment of co-occurring depressive symptoms. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01179568 C1 [Shear, M. Katherine; Skritskaya, Natalia] Columbia Univ Coll Phys & Surg, Columbia Sch Social Work, 1255 Amsterdam Ave, New York, NY 10027 USA. [Shear, M. Katherine] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Reynolds, Charles F., III] Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. [Simon, Naomi M.] Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. [Simon, Naomi M.] Harvard Med Sch, Boston, MA USA. [Zisook, Sidney; Lebowitz, Barry] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Zisook, Sidney] Vet Affairs San Diego Healthcare Syst, La Jolla, CA USA. [Zisook, Sidney] Vet Med & Res Fdn, La Jolla, CA USA. [Wang, Yuanjia; Mauro, Christine] Columbia Univ, Mailman Sch Publ Hlth, Dept Biostat, New York, NY USA. [Duan, Naihua] Columbia Univ Coll Phys & Surg, Dept Psychiat, Div Biostat, New York, NY 10027 USA. RP Shear, MK (reprint author), Columbia Univ Coll Phys & Surg, Columbia Sch Social Work, 1255 Amsterdam Ave, New York, NY 10027 USA. EM ks2394@columbia.edu FU National Institutes of Health [R01MH60783, R01MH085297, R01MH085288, R01MH085308, P30 MH90333]; American Foundation for Suicide Prevention [LSRG-S-172-12] FX This work was supported by grants R01MH60783, R01MH085297, R01MH085288, R01MH085308, and P30 MH90333 from the National Institutes of Health and by grant LSRG-S-172-12 from the American Foundation for Suicide Prevention. NR 37 TC 3 Z9 3 U1 10 U2 13 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 JUL PY 2016 VL 73 IS 7 BP 685 EP 694 DI 10.1001/jamapsychiatry.2016.0892 PG 10 WC Psychiatry SC Psychiatry GA DQ2OT UT WOS:000379042700009 PM 27276373 ER PT J AU Stein, MB Chen, CY Ursano, RJ Cai, TX Gelernter, J Heeringa, SG Jain, S Jensen, KP Maihofer, AX Mitchell, C Nievergelt, CM Nock, MK Neale, BM Polimanti, R Ripke, S Sun, XY Thomas, ML Wang, Q Ware, EB Borja, S Kessler, RC Smoller, J AF Stein, Murray B. Chen, Chia-Yen Ursano, Robert J. Cai, Tianxi Gelernter, Joel Heeringa, Steven G. Jain, Sonia Jensen, Kevin P. Maihofer, Adam X. Mitchell, Colter Nievergelt, Caroline M. Nock, Matthew K. Neale, Benjamin M. Polimanti, Renato Ripke, Stephan Sun, Xiaoying Thomas, Michael L. Wang, Qian Ware, Erin B. Borja, Susan Kessler, Ronald C. Smoller, JordanW. CA Army Study Assess Risk Resilience TI Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers SO JAMA PSYCHIATRY LA English DT Article ID COMBAT-RELATED PTSD; C-REACTIVE PROTEIN; OF-THE-LITERATURE; ASSESS RISK; RHEUMATOID-ARTHRITIS; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; SUSCEPTIBILITY LOCI; MENTAL-DISORDERS; TRAUMA EXPOSURE AB IMPORTANCE Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological foundation of vulnerability and comorbidity. OBJECTIVE To discover genetic loci associated with the lifetime risk for PTSD in 2 cohorts from the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS). DESIGN, SETTING, AND PARTICIPANTS Two coordinated genome-wide association studies of mental health in the US military contributed participants. The New Soldier Study (NSS) included 3167 unique participants with PTSD and 4607 trauma-exposed control individuals; the Pre/Post Deployment Study (PPDS) included 947 unique participants with PTSD and 4969 trauma-exposed controls. The NSS data were collected from February 1, 2011, to November 30, 2012; the PDDS data, from January 9 to April 30, 2012. The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015. MAIN OUTCOMES AND MEASURES Association analyses for PTSD used logistic regression models within each of 3 ancestral groups (European, African, and Latino American) by study, followed by meta-analysis. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated. RESULTS The NSS population was 80.7% male (6277 of 7774 participants; mean [SD] age, 20.9 [3.3] years); the PPDS population, 94.4% male (5583 of 5916 participants; mean [SD] age, 26.5 [6.0] years). A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 x 10(-8)) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 x 10(-8)) in the African American samples from the NSS. A genome-wide significant locus was also found in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 x 10(-8)) in the European American samples from the NSS. Similar results were not found for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses. Single-nucleotide polymorphism-based heritability was nonsignificant, and no significant genetic correlations were observed between PTSD and 6 mental disorders or 9 immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis. CONCLUSIONS AND RELEVANCE In the largest genome-wide association study of PTSD to date, involving a US military sample, limited evidence of association for specific loci was found. Further efforts are needed to replicate the genome-wide significant association with ANKRD55-associated in prior research with several autoimmune and inflammatory disorders-and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis. C1 [Stein, Murray B.; Maihofer, Adam X.; Nievergelt, Caroline M.; Thomas, Michael L.] Univ Calif San Diego, Dept Psychiat, Mail Code 0855,9500 Gilman Dr, La Jolla, CA 92093 USA. [Stein, Murray B.; Jain, Sonia; Sun, Xiaoying] UCSD, Dept Family Med & Publ Hlth, La Jolla, CA USA. [Stein, Murray B.] Vet Affairs San Diego Healthcare Syst, Psychiat Serv, San Diego, CA USA. [Chen, Chia-Yen; Smoller, JordanW.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Chen, Chia-Yen; Smoller, JordanW.] Harvard Med Sch, Boston, MA USA. [Chen, Chia-Yen; Neale, Benjamin M.; Ripke, Stephan; Smoller, JordanW.] Broad Inst Massachusetts Inst Technol & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA USA. [Ursano, Robert J.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Cai, Tianxi] Harvard TH Chan Sch Publ Hlth, Boston, MA USA. [Gelernter, Joel; Jensen, Kevin P.; Polimanti, Renato; Wang, Qian] Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. [Gelernter, Joel; Polimanti, Renato; Wang, Qian] Yale Univ, Dept Genet, New Haven, CT USA. [Gelernter, Joel; Polimanti, Renato; Wang, Qian] Yale Univ, Dept Neurobiol, New Haven, CT USA. [Heeringa, Steven G.; Mitchell, Colter; Ware, Erin B.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA. [Nock, Matthew K.] Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. [Wang, Qian] Yale Univ, Grad Sch Arts & Sci, Dept Computat Biol & Bioinformat, New Haven, CT USA. [Borja, Susan] NIMH, NIH, Bethesda, MD 20892 USA. [Kessler, Ronald C.] Harvard Med Sch, Dept Hlth Care Policy, Boston, MA USA. RP Stein, MB (reprint author), Univ Calif San Diego, Dept Psychiat, Mail Code 0855,9500 Gilman Dr, La Jolla, CA 92093 USA. EM mstein@ucsd.edu RI Wang, Qian/Q-4664-2016; OI Wang, Qian/0000-0002-5615-4506; Ware, Erin/0000-0003-4731-8158 FU Department of the Army; US Department of Health and Human Services [U01MH087981]; National Institute of Drug Abuse [R01 DA12690]; National Institutes of Health, National Institute of Mental Health (NIMH) FX This study was sponsored by the Department of the Army and supported by cooperative agreement U01MH087981 from the US Department of Health and Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) (Drs Stein and Ursano). The GPA analyses were supported by grant R01 DA12690 from the National Institute of Drug Abuse (Dr Gelemter). NR 89 TC 6 Z9 6 U1 5 U2 12 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 JUL PY 2016 VL 73 IS 7 BP 695 EP 704 DI 10.1001/jamapsychiatry.2016.0350 PG 10 WC Psychiatry SC Psychiatry GA DQ2OT UT WOS:000379042700010 PM 27167565 ER PT J AU Hoge, CW Yehuda, R Castro, CA McFarlane, AC Vermetten, E Jetly, R Koenen, KC Greenberg, N Shalev, AY Rauch, SAM Marmar, CR Rothbaum, BO AF Hoge, Charles W. Yehuda, Rachel Castro, Carl A. McFarlane, Alexander C. Vermetten, Eric Jetly, Rakesh Koenen, Karestan C. Greenberg, Neil Shalev, Arieh Y. Rauch, Sheila A. M. Marmar, Charles R. Rothbaum, Barbara O. TI Unintended Consequences of Changing the Definition of Posttraumatic Stress Disorder in DSM-5 Critique and Call for Action SO JAMA PSYCHIATRY LA English DT Article ID IV-TR; PTSD; CRITERIA; PREVALENCE; ICD-11; CHECKLIST; SYMPTOMS; VETERANS; IMPACT; TRIALS C1 [Hoge, Charles W.] US Army Med Res & Mat Command, Walter Reed Army Inst Res, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. [Castro, Carl A.] Univ So Calif, Sch Social Work, Los Angeles, CA 90089 USA. [McFarlane, Alexander C.] Univ Adelaide, Ctr Traumat Stress Studies, Adelaide, SA, Australia. [Vermetten, Eric] Minist Def, Mil Mental Hlth Res Ctr, Utrecht, Netherlands. [Vermetten, Eric] Leiden Univ, Med Ctr, Dept Psychiat, Leiden, Netherlands. [Vermetten, Eric] Arq Psychotrauma Expert Grp, Diemen, Netherlands. [Jetly, Rakesh] Directorate Mental Hlth, Canadian Forces Hlth Serv Grp Headquarters, Ottawa, ON, Canada. [Koenen, Karestan C.] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Koenen, Karestan C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenberg, Neil] Kings Coll London, Kings Ctr Military Hlth Res, London, England. [Shalev, Arieh Y.] NYU Langone Med Ctr, Dept Psychiat, New York, NY USA. [Shalev, Arieh Y.] Hadassah & Hebrew Univ, Sch Med, Jerusalem, Israel. [Rauch, Sheila A. M.; Rothbaum, Barbara O.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA USA. [Rauch, Sheila A. M.] Atlanta Vet Affairs Med Ctr, Mental Hlth Serv, Atlanta, GA USA. [Marmar, Charles R.] NYU Langone Med Ctr, Dept Psychiat, Steven & Alexandra Cohen Vet Ctr Posttraumat Stre, New York, NY USA. RP Hoge, CW (reprint author), US Army Med Res & Mat Command, Walter Reed Army Inst Res, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM charles.w.hoge.civ@mail.mil OI Shalev, Arieh/0000-0001-9425-050X NR 34 TC 12 Z9 12 U1 11 U2 12 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 JUL PY 2016 VL 73 IS 7 BP 750 EP 752 DI 10.1001/jamapsychiatry.2016.0647 PG 3 WC Psychiatry SC Psychiatry GA DQ2OT UT WOS:000379042700016 PM 27224895 ER PT J AU Kudler, H Day, K Schnurr, PP AF Kudler, Harold Day, Kristine Schnurr, Paula P. TI Treatment Options for Veterans With Posttraumatic Stress Disorder SO JAMA PSYCHIATRY LA English DT Letter C1 [Kudler, Harold] US Dept Vet Affairs, Mental Hlth Serv, Washington, DC 20420 USA. [Day, Kristine] US Dept Vet Affairs, Natl Evidence Based Psychotherapy Program, Washington, DC 20420 USA. [Schnurr, Paula P.] US Dept Vet Affairs, Natl Ctr PTSD, Washington, DC 20420 USA. RP Kudler, H (reprint author), US Dept Vet Affairs, 810 Vermont Ave NW, Washington, DC 20420 USA. EM harold.kudler@va.gov NR 4 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUL PY 2016 VL 73 IS 7 BP 756 EP 757 DI 10.1001/jamapsychiatry.2016.0746 PG 2 WC Psychiatry SC Psychiatry GA DQ2OT UT WOS:000379042700019 PM 27191547 ER PT J AU Yehuda, R Hoge, CW AF Yehuda, Rachel Hoge, Charles W. TI Treatment Options for Veterans With Posttraumatic Stress Disorder Reply SO JAMA PSYCHIATRY LA English DT Letter ID MENTAL-HEALTH-CARE; PSYCHOTHERAPY; SOLDIERS; DROPOUT; PTSD; IRAQ C1 [Yehuda, Rachel] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Yehuda, Rachel] Icahn Sch Med Mt Sinai, 1 Gustave L Levy Pl, New York, NY 10029 USA. [Hoge, Charles W.] Walter Reed Army Inst Res, Silver Spring, MD USA. RP Yehuda, R (reprint author), Icahn Sch Med Mt Sinai, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM rachel.yehuda@mssm.edu NR 6 TC 1 Z9 1 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 2168-622X EI 2168-6238 J9 JAMA PSYCHIAT JI JAMA Psychiatry PD JUL PY 2016 VL 73 IS 7 BP 758 EP 758 DI 10.1001/jamapsychiatry.2016.0572 PG 1 WC Psychiatry SC Psychiatry GA DQ2OT UT WOS:000379042700021 PM 27191824 ER PT J AU Nathan, DG Nathan, DM AF Nathan, David G. Nathan, David M. TI Eulogy for the clinical research center SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID HORMONE-RELEASING HORMONE; LONG-ACTING ANALOG; PRECOCIOUS PUBERTY; DIABETES-MELLITUS; TERM TREATMENT; COMPLICATIONS AB The extramural General Clinical Research Center (GCRC) program has been funded for more than 50 years, first by the National Center for Research Resources, NIH, and more recently as part of the Clinical Translational Science Award (CTSA) program through the newly formed National Center for Advancing Translation Sciences (NCATS). The GCRCs represent the federally funded laboratories that employ a highly trained cadre of research nurses, dietitians, and other support staff and in which generations of clinical investigators trained and performed groundbreaking human studies that advanced medical science and improved clinical care. Without the opportunity for adequate discussion, NCATS has now stopped funding these Research Centers. In this "eulogy," we review the origins and history of the GCRCs, their contributions to the advancement of medicine, and the recent events that have essentially defunded them. We mourn their loss. C1 [Nathan, David G.] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Nathan, David M.] Massachusetts Gen Hosp, Harvard Med Sch, Ctr Diabet, Boston, MA USA. [Nathan, David M.] Massachusetts Gen Hosp, Harvard Med Sch, Clin Res Ctr, Boston, MA USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, Dana 1644,450 Brookline Ave, Boston, MA 02215 USA. EM david_nathan@dfci.harvard.edu NR 19 TC 2 Z9 2 U1 2 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 2015 MANCHESTER RD, ANN ARBOR, MI 48104 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2016 VL 126 IS 7 BP 2388 EP 2391 DI 10.1172/JCI88381 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DQ3IA UT WOS:000379094800002 PM 27270173 ER PT J AU Souma, T Tompson, SW Thomson, BR Siggs, OM Kizhatil, K Yamaguchi, S Feng, L Limviphuvadh, V Whisenhunt, KN Maurer-Stroh, S Yanovitch, TL Kalaydjieva, L Azmanov, DN Finzi, S Mauri, L Javadiyan, S Souzeau, E Zhou, T Hewitt, AW Kloss, B Burdon, KP MacKey, DA Allen, KF Ruddle, JB Lim, SH Rozen, S Tran-Viet, KN Liu, XR John, S Wiggs, JL Pasutto, F Craig, JE Jin, J Quaggin, SE Young, TL AF Souma, Tomokazu Tompson, Stuart W. Thomson, Benjamin R. Siggs, Owen M. Kizhatil, Krishnakumar Yamaguchi, Shinji Feng, Liang Limviphuvadh, Vachiranee Whisenhunt, Kristina N. Maurer-Stroh, Sebastian Yanovitch, Tammy L. Kalaydjieva, Luba Azmanov, Dimitar N. Finzi, Simone Mauri, Lucia Javadiyan, Shahrbanou Souzeau, Emmanuelle Zhou, Tiger Hewitt, Alex W. Kloss, Bethany Burdon, Kathryn P. MacKey, David A. Allen, Keri F. Ruddle, Jonathan B. Lim, Sing-Hui Rozen, Steve Tran-Viet, Khanh-Nhat Liu, Xiaorong John, Simon Wiggs, Janey L. Pasutto, Francesca Craig, Jamie E. Jin, Jing Quaggin, Susan E. Young, Terri L. TI Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OPEN-ANGLE GLAUCOMA; AQUEOUS-HUMOR DYNAMICS; CELL-CELL CONTACTS; MOLECULAR-GENETICS; CYTOCHROME P4501B1; CRYSTAL-STRUCTURES; TYROSINE KINASES; WEB SERVER; TIE2; CYP1B1 AB Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures of the eye result in elevated intraocular pressure (IOP); however, the genes and molecular mechanisms involved in the etiology of these defects have not been fully characterized. Previously, we observed PCG-like phenotypes in transgenic mice that lack functional angiopoietin-TEK signaling. Herein, we identified rare TEK variants in 10 of 189 unrelated PCG families and demonstrated that each mutation results in haploinsufficiency due to protein loss of function. Multiple cellular mechanisms were responsible for the loss of protein function resulting from individual TEK variants, including an absence of normal protein production, protein aggregate formation, enhanced proteasomal degradation, altered subcellular localization, and reduced responsiveness to ligand stimulation. Further, in mice, hemizygosity for Tek led to the formation of severely hypomorphic Schlemm's canal and trabecular meshwork, as well as elevated IOP, demonstrating that anterior chamber vascular development is sensitive to Tek gene dosage and the resulting decrease in angiopoietin-TEK signaling. Collectively, these results identify TEK mutations in patients with PCG that likely underlie disease and are transmitted in an autosomal dominant pattern with variable expressivity. C1 [Souma, Tomokazu; Thomson, Benjamin R.; Yamaguchi, Shinji; Jin, Jing; Quaggin, Susan E.] Northwestern Univ, Feinberg Sch Med, Feinberg Cardiovasc Res Inst, Chicago, IL 60611 USA. [Souma, Tomokazu; Thomson, Benjamin R.; Yamaguchi, Shinji; Jin, Jing; Quaggin, Susan E.] Northwestern Univ, Feinberg Sch Med, Div Nephrol Hypertens, Chicago, IL 60611 USA. [Tompson, Stuart W.; Whisenhunt, Kristina N.; Kloss, Bethany; Young, Terri L.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, 2828 Marshall Ct,Ste 200, Madison, WI 53705 USA. [Siggs, Owen M.; Javadiyan, Shahrbanou; Souzeau, Emmanuelle; Zhou, Tiger; Burdon, Kathryn P.; Craig, Jamie E.] Flinders Univ S Australia, Dept Ophthalmol, Adelaide, SA 5001, Australia. [Kizhatil, Krishnakumar; John, Simon] Howard Hughes Med Inst, Jackson Lab, Bar Harbor, ME USA. [Feng, Liang; Liu, Xiaorong] Northwestern Univ, Feinberg Sch Med, Dept Ophthalmol, Chicago, IL 60611 USA. [Limviphuvadh, Vachiranee; Maurer-Stroh, Sebastian] Agcy Sci Technol & Res, Bioinformat Inst, Singapore, Singapore. [Maurer-Stroh, Sebastian] Nanyang Technol Univ, Sch Biol Sci, Singapore 639798, Singapore. [Yanovitch, Tammy L.] Univ Oklahoma, Dean McGee Eye Inst, Dept Ophthalmol, Oklahoma City, OK USA. [Kalaydjieva, Luba; Azmanov, Dimitar N.] Univ Western Australia, Harry Perkins Inst Med Res, Perth, WA 6009, Australia. [Kalaydjieva, Luba; Azmanov, Dimitar N.] Univ Western Australia, Med Res Ctr, Perth, WA 6009, Australia. [Azmanov, Dimitar N.] PathWest, QEII Med Ctr, Dept Diagnost Gen, Perth, WA, Australia. [Finzi, Simone] Univ Sao Paulo, Hosp Clin, Dept Ophthalmol, Sao Paulo, Brazil. [Mauri, Lucia] Osped Niguarda Ca Granda, Milan, Italy. [Hewitt, Alex W.; Ruddle, Jonathan B.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia. [Hewitt, Alex W.; MacKey, David A.] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia. [Hewitt, Alex W.; Burdon, Kathryn P.; MacKey, David A.] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia. [Allen, Keri F.; Wiggs, Janey L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Lim, Sing-Hui; Rozen, Steve; Young, Terri L.] Duke Nat Univ Singapore, Grad Sch Med, Singapore, Singapore. [Tran-Viet, Khanh-Nhat] Calif State Univ Sacramento, Med Ctr, Sacramento, CA 95819 USA. [John, Simon] Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. [John, Simon] Tufts Univ, Sch Med, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA. [Pasutto, Francesca] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany. RP Young, TL (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 2828 Marshall Ct,Ste 200, Madison, WI 53705 USA.; Quaggin, SE (reprint author), Northwestern Univ, Feinberg Cardiovasc Res Inst, 303 E Super St,Suite 10-105, Chicago, IL 60611 USA.; Quaggin, SE (reprint author), Northwestern Univ, Div Nephrol Hypertens, 303 E Super St,Suite 10-105, Chicago, IL 60611 USA. EM quaggin@northwestern.edu; tyoung6@wisc.edu RI Mackey, David/H-5340-2014 OI Mackey, David/0000-0001-7914-4709 FU NIH [R01 HL124120, R01 EY014685, 1K23EY020554]; Research to Prevent Blindness Inc.; Duke National University of Singapore; University of Wisconsin; March of Dimes Foundation; Howard Hughes Medical Center; Ophthalmic Research Institute of Australia; Channel Seven Children's Research Foundation; Department of Innovation, Industry, Science and Research; National Health and Medical Research Council of Australia (NHMRC); Japan Society for the Promotion of Science; Mallinckrodt Pharmaceuticals; Canadian Institute of Health Research; NHMRC; NCI CCSG [P30 CA060553]; University of Wisconsin-Madison Department of Ophthalmology and Visual Sciences [NEI P30EY016665]; [EY 11721] FX We thank the patient subjects for participating in this study. We also thank John Pater, Joanna Black, Jane Kelly, Sharon Freedman, Ivailo Tourney, and Sylvia Cherninkova for clinical input and Richard Smith for assessment of murine eye phenotypes; Daniel Berner for sequencing assistance; and Andrew Wei and Anna Woo for technical assistance. This study was funded by NIH R01 HL124120 (S.E. Quaggin); NIH R01 EY014685, the Research to Prevent Blindness Inc. Lew R. Wasserman Award, the Duke National University of Singapore Core Grant, and the University of Wisconsin Centennial Scholars Award (T.L. Young); and NIH Career Development Award K12, 1K23EY020554 (T.L. Yanovitch). This work was also supported by grants from the March of Dimes Foundation (J.L. Wiggs), Howard Hughes Medical Center and EY 11721 (S. John and K. Kizhatil), the Ophthalmic Research Institute of Australia, the Channel Seven Children's Research Foundation, Department of Innovation, Industry, Science and Research, and the National Health and Medical Research Council of Australia (NHMRC). T. Souma is supported by fellowship grants from the Japan Society for the Promotion of Science and Mallinckrodt Pharmaceuticals. B.R. Thomson is supported by the Canadian Institute of Health Research. K.P. Burdon, J.E. Craig, and D.N. Azmanov are supported by fellowships from the NHMRC. Imaging was performed at the Northwestern University Center for Advanced Microscopy supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. We also acknowledge support from Vision Core Grant NEI P30EY016665 of the University of Wisconsin-Madison Department of Ophthalmology and Visual Sciences. Proteomics analyses were supported by the Northwestern University Proteomics Core. We thank Dhaval Nanavati (Northwestern University, Proteomics Core) for technical support and helpful discussions. NR 65 TC 1 Z9 1 U1 2 U2 9 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2016 VL 126 IS 7 BP 2575 EP 2587 DI 10.1172/JCI85830 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DQ3IA UT WOS:000379094800021 PM 27270174 ER PT J AU Won, OJ Zhang, L Wang, JH Su, QT Feng, Q Zhang, XHF Mani, SA Paulter, R Creighton, CJ Ittmann, MM Xin, L AF Won, Oh-Joon Zhang, Li Wang, Jianghua Su, Qingtai Feng, Qin Zhang, Xiang H. F. Mani, Sendurai A. Paulter, Robia Creighton, Chad J. Ittmann, Michael M. Xin, Li TI Notch promotes tumor metastasis in a prostate-specific Pten-null mouse model SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TO-MESENCHYMAL TRANSITION; CELL-GROWTH INHIBITION; CANCER-CELLS; DOWN-REGULATION; ANDROGEN RECEPTOR; SEMINAL-VESICLE; BREAST-CANCER; SIGNALING PATHWAYS; ORGANOID CULTURES; EPITHELIAL-CELLS AB Although Notch signaling is deregulated in prostate cancer, the role of this pathway in disease development and progression is not fully understood. Here, we analyzed 2 human prostate cancer data sets and found that higher Notch signaling correlates with increased metastatic potential and worse disease survival rates. We used the Pten-null mouse prostate cancer model to investigate the function of Notch signaling in the initiation and progression of prostate cancer. Disruption of the transcription factor RBPJ in Pten-null mice revealed that endogenous canonical Notch signaling is not required for disease initiation and progression. However, augmentation of Notch activity in this model promoted both proliferation and apoptosis of prostate epithelial cells, which collectively reduced the primary tumor burden. The increase in cellular apoptosis was linked to DNA damage-induced p53 activation. Despite a reduced primary tumor burden, Notch activation in Pten-null mice promoted epithelial-mesenchymal transition and FOXC2-dependent tumor metastases but did not confer resistance to androgen deprivation. Notch activation also resulted in transformation of seminal vesicle epithelial cells in Pten-null mice. Our study highlights a multifaceted role for Notch signaling in distinct aspects of prostate cancer biology and supports Notch as a potential therapeutic target for metastatic prostate cancer. C1 [Won, Oh-Joon; Zhang, Li; Su, Qingtai; Feng, Qin; Zhang, Xiang H. F.; Xin, Li] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. [Wang, Jianghua; Ittmann, Michael M.; Xin, Li] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA. [Zhang, Xiang H. F.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA. [Zhang, Xiang H. F.; Creighton, Chad J.; Ittmann, Michael M.; Xin, Li] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA. [Mani, Sendurai A.] Univ Texas MD Anderson Canc Ctr, Div Pathol & Lab Med, Dept Translat Mol Pathol, Houston, TX 77030 USA. [Paulter, Robia] Baylor Coll Med, Dept Mol Physiol, Houston, TX 77030 USA. [Creighton, Chad J.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Ittmann, Michael M.] Baylor Coll Med, Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Xin, L (reprint author), Baylor Coll Med, M533 DeBakey Bldg,BCM MS130,One Baylor Plaza, Houston, TX 77030 USA. EM xin@bcm.edu RI Mani, Sendurai/A-7244-2009 OI Mani, Sendurai/0000-0002-5918-4276 FU NIH [P30-AI036211, P30-CA125123, S10-RR024574, R01-CA190378, R21-CA196570, U01-CA141497] FX We thank Joseph Valdez for initiating some early studies, Boyu Zhang for technical help, Yiqun Zhang for analyzing expression microarray analyses, the Small Animal Imaging Facilities at Baylor College of Medicine and Texas Children's Hospital, the Cytometry and Cell Sorting Core at Baylor College of Medicine for technical support with funding from the NIH (P30-AI036211, P30-CA125123, and S10-RR024574), and Joel M. Sederstrom for expert assistance. This work is supported by NIH R01-CA190378 and R21-CA196570 (to L. Xin), NIH U01-CA141497 (to M.M. Ittmann), and NIH P30-CA125123 (the Cancer Center Shared Resources Grant). NR 63 TC 0 Z9 0 U1 4 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2016 VL 126 IS 7 BP 2626 EP 2641 DI 10.1172/JCI84637 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DQ3IA UT WOS:000379094800026 ER PT J AU Saha, A O'Connor, RS Thangavelu, G Lovitch, SB Dandamudi, DB Wilson, CB Vincent, BG Tkachev, V Pawlicki, JM Furlan, SN Kean, LS Aoyama, K Taylor, PA Panoskaltsis-Mortari, A Foncea, R Ranganathan, P Devine, SM Burrill, JS Guo, LL Sacristan, C Snyder, NW Blair, IA Milone, MC Dustin, ML Riley, JL Bernlohr, DA Murphy, WJ Fife, BT Munn, DH Miller, JS Serody, JS Freeman, GJ Sharpe, AH Turka, LA Blazer, BR AF Saha, Asim O'Connor, Roddy S. Thangavelu, Govindarajan Lovitch, Scott B. Dandamudi, Durga Bhavani Wilson, Caleph B. Vincent, Benjamin G. Tkachev, Victor Pawlicki, Jan M. Furlan, Scott N. Kean, Leslie S. Aoyama, Kazutoshi Taylor, Patricia A. Panoskaltsis-Mortari, Angela Foncea, Rocio Ranganathan, Parvathi Devine, Steven M. Burrill, Joel S. Guo, Lili Sacristan, Catarina Snyder, Nathaniel W. Blair, Ian A. Milone, Michael C. Dustin, Michael L. Riley, James L. Bernlohr, David A. Murphy, William J. Fife, Brian T. Munn, David H. Miller, Jeffrey S. Serody, Jonathan S. Freeman, Gordon J. Sharpe, Arlene H. Turka, Laurence A. Blazer, Bruce R. TI Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; IMMUNE REGULATORY CELLS; FATTY-ACID-METABOLISM; FALSE DISCOVERY RATE; RNA-SEQ DATA; LYMPHOCYTE-ACTIVATION; DIFFERENTIAL EXPRESSION; SIGNALING PATHWAY; EFFECTOR FUNCTION; VIRAL-INFECTION AB Programmed death ligand-1 (PD-L1) interaction with PD-1 induces T cell exhaustion and is a therapeutic target to enhance immune responses against cancer and chronic infections. In murine bone marrow transplant models, PD-L1 expression on host target tissues reduces the incidence of graft-versus-host disease (GVHD). PD-L1 is also expressed on T cells; however, it is unclear whether PD-L1 on this population influences immune function. Here, we examined the effects of PD-L1 modulation of T cell function in GVHD. In patients with severe GVHD, PD-L1 expression was increased on donor T cells. Compared with mice that received WT T cells, GVHD was reduced in animals that received T cells from Pdl1(-/-) donors. PD-L1-deficient T cells had reduced expression of gut homing receptors, diminished production of inflammatory cytokines, and enhanced rates of apoptosis. Moreover, multiple bioenergetic pathways, including aerobic glycolysis, oxidative phosphorylation, and fatty acid metabolism, were also reduced in T cells lacking PD-L1. Finally, the reduction of acute GVHD lethality in mice that received Pdl1(-/-) donor cells did not affect graft-versus-leukemia responses. These data demonstrate that PD-L1 selectively enhances T cell-mediated immune responses, suggesting a context-dependent function of the PD-1/PD-L1 axis, and suggest selective inhibition of PD-L1 on donor T cells as a potential strategy to prevent or ameliorate GVHD. C1 [Saha, Asim; Thangavelu, Govindarajan; Aoyama, Kazutoshi; Taylor, Patricia A.; Panoskaltsis-Mortari, Angela; Blazer, Bruce R.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA. [Saha, Asim; Thangavelu, Govindarajan; Aoyama, Kazutoshi; Taylor, Patricia A.; Panoskaltsis-Mortari, Angela; Blazer, Bruce R.] Univ Minnesota, Dept Pediat, Div Blood & Marrow Transplantat, Minneapolis, MN 55455 USA. [O'Connor, Roddy S.; Milone, Michael C.] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Lovitch, Scott B.; Sharpe, Arlene H.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA. [Lovitch, Scott B.; Sharpe, Arlene H.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Dandamudi, Durga Bhavani] NYU, Sch Med, Sackler Grad Program, New York, NY USA. [Wilson, Caleph B.; Pawlicki, Jan M.; Riley, James L.] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. [Vincent, Benjamin G.; Serody, Jonathan S.] Univ N Carolina, Dept Med, Chapel Hill, NC USA. [Tkachev, Victor; Furlan, Scott N.; Kean, Leslie S.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Foncea, Rocio; Bernlohr, David A.] Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN USA. [Ranganathan, Parvathi; Devine, Steven M.] Ohio State Univ, Ctr Comprehens Canc, Dept Med, Columbus, OH 43210 USA. [Guo, Lili; Snyder, Nathaniel W.; Blair, Ian A.] Univ Penn, Penn SRP Ctr, Dept Syst Pharmacol Translat Therapeut, Perelman Sch Med, Philadelphia, PA 19104 USA. [Sacristan, Catarina; Dustin, Michael L.] NYU, Sch Med, Dept Pathol, New York, NY USA. [Snyder, Nathaniel W.] Drexel Univ, AJ Drexel Autism Inst, Philadelphia, PA 19104 USA. [Dustin, Michael L.] Univ Oxford, Nuffield Dept Orthoped Rheumatol & Musculoskeleta, S Parks Rd, Oxford, England. [Murphy, William J.] UCD, Dept Dermatol & Internal Med, Sacramento, CA USA. [Fife, Brian T.] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA. [Fife, Brian T.] Univ Minnesota, Ctr Immunol, Minneapolis, MN USA. [Munn, David H.] Georgia Regents Univ, Dept Pediat, Augusta, GA USA. [Miller, Jeffrey S.] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Box 736 UMHC, Minneapolis, MN 55455 USA. [Serody, Jonathan S.] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. [Turka, Laurence A.] Massachusetts Gen Hosp, Dept Surg, Ctr Transplantat Sci, Boston, MA 02114 USA. [Turka, Laurence A.] Harvard Univ, Sch Med, Boston, MA USA. [Blazer, Bruce R.] Univ Minnesota, Dept Pediat, MMC 109,420 Delaware St SE, Minneapolis, MN 55455 USA. RP Blazer, BR (reprint author), Univ Minnesota, Dept Pediat, MMC 109,420 Delaware St SE, Minneapolis, MN 55455 USA. EM blaza001@umn.edu OI Lovitch, Scott/0000-0001-9013-0105; Fife, Brian/0000-0001-9826-5637; Dustin, Michael/0000-0003-4983-6389 FU NIH [HL056067, AI034495, AI056299, AI043542]; Wellcome Trust FX We thank Christopher Lees and colleagues of B.R. Blazar's laboratory for technical assistance, S. Davis (University of Oxford, Oxford, UK) for human PD-L1, and S. Garrett and S. Almo (Einstein School of Medicine, New York, NY) for data on interspecies interactions. This study was supported in part by NIH grants HL056067 (to B.R. Blazar), AI034495 (to B.R. Blazar), AI056299 (to B.R. Blazar), and AI043542 (to M.L. Dustin), and the Wellcome Trust (to M.L. Dustin). NR 92 TC 4 Z9 5 U1 1 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2016 VL 126 IS 7 BP 2642 EP 2660 DI 10.1172/JCI85796 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DQ3IA UT WOS:000379094800027 PM 27294527 ER PT J AU Xie, Q Wu, QL Kim, L Miller, TE Liau, BB Mack, SC Yang, KL Factor, DC Fang, XG Huang, Z Zhou, WC Alazem, K Wang, XX Bernstein, BE Bao, SD Rich, JN AF Xie, Qi Wu, Qiulian Kim, Leo Miller, Tyler E. Liau, Brian B. Mack, Stephen C. Yang, Kailin Factor, Daniel C. Fang, Xiaoguang Huang, Zhi Zhou, Wenchao Alazem, Kareem Wang, Xiuxing Bernstein, Bradley E. Bao, Shideng Rich, Jeremy N. TI RBPJ maintains brain tumor-initiating cells through CDK9-mediated transcriptional elongation SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BET BROMODOMAIN INHIBITION; GLIOMA STEM-CELLS; FACTOR COMPLEX; PAUSE RELEASE; C-MYC; GLIOBLASTOMA; SURVIVAL; TEMOZOLOMIDE; ADDICTION; PROMOTES AB Glioblastomas co-opt stem cell regulatory pathways to maintain brain tumor-initiating cells (BTICs), also known as cancer stem cells. NOTCH signaling has been a molecular target in BTICs, but NOTCH antagonists have demonstrated limited efficacy in clinical trials. Recombining binding protein suppressor of hairless (RBPJ) is considered a central transcriptional mediator of NOTCH activity. Here, we report that pharmacologic NOTCH inhibitors were less effective than targeting RBPJ in suppressing tumor growth. While NOTCH inhibitors decreased canonical NOTCH gene expression, RBPJ regulated a distinct profile of genes critical to BTIC sternness and cell cycle progression. RBPJ was preferentially expressed by BTICs and required for BTIC self-renewal and tumor growth. MYC, a key BTIC regulator, bound the RBPJ promoter and treatment with a bromodomain and extraterminal domain (BET) family bromodomain inhibitor decreased MYC and RBPJ expression. Proteomic studies demonstrated that RBPJ binds CDK9, a component of positive transcription elongation factor b (P-TEFb), to target gene promoters, enhancing transcriptional elongation. Collectively, RBPJ links MYC and transcriptional control through CDK9, providing potential nodes of fragility for therapeutic intervention, potentially distinct from NOTCH. C1 [Xie, Qi; Wu, Qiulian; Kim, Leo; Mack, Stephen C.; Yang, Kailin; Fang, Xiaoguang; Huang, Zhi; Zhou, Wenchao; Alazem, Kareem; Wang, Xiuxing; Bao, Shideng; Rich, Jeremy N.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Stem Cell Biol & Regenerat Med,Lerner Res In, Cleveland, OH 44106 USA. [Kim, Leo; Miller, Tyler E.; Yang, Kailin; Bao, Shideng; Rich, Jeremy N.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Mol Med, Cleveland, OH 44106 USA. [Liau, Brian B.; Bernstein, Bradley E.] Broad Inst MIT & Harvard Univ, Cambridge, MA USA. [Liau, Brian B.; Bernstein, Bradley E.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Liau, Brian B.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Liau, Brian B.; Bernstein, Bradley E.] Harvard Med Sch, Boston, MA USA. [Liau, Brian B.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Liau, Brian B.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Factor, Daniel C.] Case Western Reserve Univ, Dept Genet & Genome Sci, Cleveland, OH 44106 USA. RP Rich, JN (reprint author), Cleveland Clin, Lerner Res Inst, Dept Stem Cell Biol & Regenerat Med, Cleveland, OH 44195 USA. EM drjeremyrich@gmail.com OI Yang, Kailin/0000-0001-5968-6738; Miller, Tyler E/0000-0002-1269-1895 FU NIH [CA197718, CA154130, CA171652, CA169117, CA198892, NS087913, NS089272, NS070315, HG006991]; Research Programs Committees of Cleveland Clinic; James S. McDonnell Foundation; Howard Hughes Medical Institute FX We appreciate the kind provision of the 4XRBPJ-Luc reporter plasmid from Takahiro Maeda (Harvard University) and the tk-renilla reporter plasmid from Zengqiang Yuan (Institute of Biophysics, Chinese Academy of Sciences). Mary McGraw and the Cleveland Clinic Foundation Tissue Procurement Service provided primary brain tumor tissues. We would like to thank the Cleveland Clinic Lerner Research Institute imaging core and proteomics core for technical assistance and the members of the Rich and Bao laboratories for critical reading of the manuscript and helpful discussions. Finally, we would like to thank our funding sources: The NIH (grants CA197718, CA154130, CA171652, CA169117, CA198892, NS087913, NS089272 [to J.N. Rich], NS070315 [to S. Bao], and HG006991 [to B.E. Bernstein]), Research Programs Committees of Cleveland Clinic (to J.N. Rich), James S. McDonnell Foundation (to J.N. Rich), and the Howard Hughes Medical Institute (to B.E. Bernstein). NR 35 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 EI 1558-8238 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2016 VL 126 IS 7 BP 2757 EP 2772 DI 10.1172/JCI86114 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA DQ3IA UT WOS:000379094800035 PM 27322055 ER PT J AU Silver, JK Binder, DS Zubcevik, N Zafonte, RD AF Silver, Julie K. Binder, David S. Zubcevik, Nevena Zafonte, Ross D. TI Healthcare Hackathons Provide Educational and Innovation Opportunities: A Case Study and Best Practice Recommendations SO JOURNAL OF MEDICAL SYSTEMS LA English DT Article DE Hackathon; Interdisciplinary; Healthcare training; Education; Rehabilitation; Innovation ID MEDICINE AB Physicians and other healthcare professionals are often the end users of medical innovation; however, they are rarely involved in the beginning design stages. This often results in ineffective healthcare solutions with poor adoption rates. At the early design stage, innovation would benefit from input from healthcare professionals. This report describes the first-ever rehabilitation hackathon-an interdisciplinary and competitive team event aimed at accelerating and improving healthcare solutions and providing an educational experience for participants. Hackathons are gaining traction as a way to accelerate innovation by bringing together a diverse group of interdisciplinary professionals from different industries who work collaboratively in teams and learn from each other, focus on a specific problem ("pain point"), develop a solution using design thinking techniques, pitch the solution to participants, gather fast feedback and quickly alter the prototype design ("pivoting"). 102 hackers including 19 (18.6 %) physicians and other professionals participated, and over the course of 2 days worked in teams, pitched ideas and developed design prototypes. Three awards were given for prototypes that may improve function in persons with disabilities. 43 hackers were women (42.2 %) and 59 men (57.8 %); they ranged in age from 16 to 79 years old; and, of the 75 hackers who reported their age, 63 (84 %) were less than 40 years old and 12 (16 %) were 40 years or older. This report contributes to the emerging literature on healthcare hackathons as a means of providing interdisciplinary education and training and supporting innovation. C1 [Silver, Julie K.; Binder, David S.; Zubcevik, Nevena; Zafonte, Ross D.] Harvard Med Sch, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, 300 1st Ave, Charlestown, MA 02139 USA. [Silver, Julie K.; Binder, David S.; Zubcevik, Nevena; Zafonte, Ross D.] Massachusetts Gen Hosp, Phys Med & Rehabil, Boston, MA 02114 USA. [Silver, Julie K.; Zafonte, Ross D.] Brigham & Womens Hosp, Phys Med & Rehabil, 75 Francis St, Boston, MA 02115 USA. RP Silver, JK (reprint author), Harvard Med Sch, Dept Phys Med & Rehabil, Spaulding Rehabil Hosp, 300 1st Ave, Charlestown, MA 02139 USA.; Silver, JK (reprint author), Massachusetts Gen Hosp, Phys Med & Rehabil, Boston, MA 02114 USA.; Silver, JK (reprint author), Brigham & Womens Hosp, Phys Med & Rehabil, 75 Francis St, Boston, MA 02115 USA. EM julie_silver@hms.harvard.edu FU Microsoft; HeartWare; Eastham Capital; RAWZ Foundation; Ekso Bionics; Goodwin Procter; MadPowAmy Cueva; Cambridge Innovation Center FX Massachusetts Institute of Technology (MIT) Hacking Medicine Team assisted with logistical support and planning as well as some recruitment of attendees. Financial support was provided by Microsoft, HeartWare, Eastham Capital, RAWZ Foundation, Ekso Bionics, Goodwin Procter, MadPowAmy Cueva, and an anonymous donor. Physical space was subsidized by the Cambridge Innovation Center. Promotional support was provided by the American Academy of Physical Medicine and Rehabilitation. NR 13 TC 0 Z9 0 U1 3 U2 5 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 JUL PY 2016 VL 40 IS 7 AR 177 DI 10.1007/s10916-016-0532-3 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA DQ0NH UT WOS:000378895600019 PM 27277278 ER PT J AU Rosenberg, L Thomas, JD AF Rosenberg, Leah Thomas, Jane deLima TI Pharmacologic Management of Depression in Advanced Illness #309 SO JOURNAL OF PALLIATIVE MEDICINE LA English DT Editorial Material ID CANCER-PATIENTS; TRIAL; PAIN C1 [Rosenberg, Leah] Massachusetts Gen Hosp, Palliat Care Dept, 55 Fruit St,Founders 602, Boston, MA 02114 USA. RP Rosenberg, L (reprint author), Massachusetts Gen Hosp, Palliat Care Dept, 55 Fruit St,Founders 602, Boston, MA 02114 USA. EM leah_rosenberg@dfci.harvard.edu NR 16 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 1096-6218 EI 1557-7740 J9 J PALLIAT MED JI J. Palliat. Med. PD JUL PY 2016 VL 19 IS 7 BP 783 EP 784 DI 10.1089/jpm.2016.0075 PG 2 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DP7CC UT WOS:000378655600019 PM 27286475 ER PT J AU Hill, ID Fasano, A Guandalini, S Hoffenberg, E Levy, J Reilly, N Verma, R AF Hill, Ivor D. Fasano, Alessio Guandalini, Stefano Hoffenberg, Edward Levy, Joseph Reilly, Norelle Verma, Ritu TI NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article DE celiac disease; celiac disease serological tests; gluten-free diet; IgE-specific antibodies; nonceliac gluten sensitivity; wheat allergy ID ANTITISSUE TRANSGLUTAMINASE ANTIBODIES; PEDIATRIC CELIAC-DISEASE; QUALITY-OF-LIFE; INFLAMMATORY-BOWEL-DISEASE; POPULATION-BASED COHORT; FREE DIET; FOLLOW-UP; FOOD ALLERGY; GASTROINTESTINAL SYMPTOMS; CHANGING PATTERN AB Dietary exclusion of gluten-containing products has become increasingly popular in the general population, and currently similar to 30% of people in the United States are limiting gluten ingestion. Although celiac disease (CD), wheat allergy (WA), and nonceliac gluten sensitivity (NCGS) constitute a spectrum of gluten-related disorders that require exclusion of gluten from the diet, together these account for a relatively small percentage of those following a gluten-free diet, and the vast majority has no medical necessity for doing so. Differentiating between CD, WA, and NCGS has important prognostic and therapeutic implications. Because of the protean manifestations of gluten-related disorders, it is not possible to differentiate between them on clinical grounds alone. This clinical report will compare and contrast the manifestations of gluten-related disorders, emphasize the importance of differentiating between these conditions, discuss initial and subsequent tests needed to confirm the diagnosis, and provide recommendations on treatment and follow-up for each condition. C1 [Hill, Ivor D.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Columbus, OH 43210 USA. [Fasano, Alessio] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Celiac Res,Children & Celiac Program, Boston, MA USA. [Guandalini, Stefano] Univ Chicago, Sect Pediat Gastroenterol Hepatol & Nutr, Celiac Dis Ctr, Chicago, IL 60637 USA. [Hoffenberg, Edward] Univ Colorado, Ctr Celiac Dis, Digest Hlth Inst, Childrens Hosp Colorado,Sch Med, Aurora, CO USA. [Levy, Joseph] NYU, Sch Med, Special Projects Div Pediat Gastroenterol, Langone Med Ctr, New York, NY USA. [Reilly, Norelle] Columbia Univ, Med Ctr, Div Pediat Gastroenterol, New York, NY USA. [Reilly, Norelle] Columbia Univ, Med Ctr, Celiac Dis Ctr, New York, NY USA. [Verma, Ritu] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Philadelphia, PA 19104 USA. RP Hill, ID (reprint author), Nationwide Childrens Hosp, Div Gastroenterol, 700 Childrens Dr, Columbus, OH 43205 USA. EM Ivor.Hill@nationwidechildrens.org NR 76 TC 1 Z9 1 U1 5 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 2016 VL 63 IS 1 BP 156 EP 165 DI 10.1097/MPG.0000000000001216 PG 10 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA DP7PX UT WOS:000378692400037 PM 27035374 ER PT J AU Raymond, SB Gee, MS Anupindi, SA Shailam, R Kaplan, JL Nimkin, K AF Raymond, Scott B. Gee, Michael S. Anupindi, Sudha A. Shailam, Randheer Kaplan, Jess L. Nimkin, Katherine TI CT and MRI of Rare Extraintestinal Manifestations of Inflammatory Bowel Disease in Children and Adolescents SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review DE Crohn disease; imaging; pediatric ID RECURRENT MULTIFOCAL OSTEOMYELITIS; PRIMARY SCLEROSING CHOLANGITIS; ANTI-TNF THERAPY; CROHNS-DISEASE; AUTOIMMUNE PANCREATITIS; PEDIATRIC-PATIENTS; LIVER-ABSCESS; PULMONARY MANIFESTATIONS; ULCERATIVE-COLITIS; VENOUS THROMBOSIS AB Inflammatory bowel disease (IBD) is associated with a spectrum of extraintestinal manifestations (EIMs) affecting many organ systems. EIMs can occur in more than 40% of patients with IBD and are associated with significant morbidity. They occur at any time point in the course of disease, often during an active phase of bowel inflammation, but sometimes preceding bowel disease. Prompt recognition of EIMs enables timely and more effective therapy. Physicians who image patients with IBD should be aware of the myriad extraintestinal conditions that may be detected on imaging studies, both within and outside of the abdomen, as they may predate the diagnosis of IBD. Cross-sectional imaging of unusual conditions associated with IBD will be presented, including pathology in the hepatobiliary, pancreatic, genitourinary, musculoskeletal, mucocutaneous, vascular, neurologic, and pulmonary systems. C1 [Raymond, Scott B.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Gee, Michael S.; Shailam, Randheer; Nimkin, Katherine] Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 55 Fruit St,Ellison 237, Boston, MA 02114 USA. [Anupindi, Sudha A.] Childrens Hosp Philadelphia, Dept Radiol, Philadelphia, PA 19104 USA. [Kaplan, Jess L.] MassGen Hosp Children, Dept Pediat, Div Pediat Gastroenterol, Boston, MA USA. RP Nimkin, K (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 55 Fruit St,Ellison 237, Boston, MA 02114 USA. EM knimkin@partners.org NR 78 TC 0 Z9 0 U1 3 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0277-2116 EI 1536-4801 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD JUL PY 2016 VL 63 IS 1 BP E1 EP E9 DI 10.1097/MPG.0000000000001225 PG 9 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA DP7PX UT WOS:000378692400001 PM 27050046 ER PT J AU Raciborska, A Bilska, K Rychlowska-Pruszynska, M Duczkowski, M Duczkowska, A Drabko, K Chaber, R Sobol, G Wyrobek, E Michalak, E Rodriguez-Galindo, C Wozniak, W AF Raciborska, Anna Bilska, Katarzyna Rychlowska-Pruszynska, Magdalena Duczkowski, Marek Duczkowska, Agnieszka Drabko, Katarzyna Chaber, Radoslaw Sobol, Grazyna Wyrobek, Elzbieta Michalak, Elzbieta Rodriguez-Galindo, Carlos Wozniak, Wojciech TI Management and follow-up of Ewing sarcoma patients with isolated lung metastases SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article DE Ewing sarcoma; Lung metastases; Thoracotomy; Radiation; Survival ID CHILDRENS ONCOLOGY GROUP; PULMONARY METASTASES; PROGNOSTIC-FACTORS; FAMILY TUMORS; IRRADIATION; RESECTION; SURVIVAL; THERAPY; CHEMOTHERAPY; BONE AB Background: Ewing sarcoma (ES) is the second most common pediatric malignant bone tumor with a wide spectrum of clinical presentations. Although metastatic disease to the lungs is often the cause of death, isolated lung metastases at diagnosis are not frequent. The specific role of chemotherapy, surgery, and lung radiation has not been clearly defined. We investigated prognostic factors and the impact of the different treatment modalities in a cohort of patients with ES with isolated lung metastases. Materials and methods: Thirty-eight patients with ES and isolated lung metastases were treated using modern multimodal therapy during the period 2000-2014. According to the imaging characteristics of lung nodules patients were allocated into one of four treatment groups: "0" without nodules, "1" one solitary nodule of <0.5 cm or several nodules of <0.3 cm, "2" solitary nodule of 0.5-1 cm or multiple nodules of 0.3-0.5 cm, "3" one pulmonary/pleural nodule of >1 cm, or more than one nodule of >0.5 cm. Factors predictive of outcome were analyzed. Overall survival was estimated by Kaplan-Meier methods and compared using long-rank test and Cox models. Results: Treatment of the lung metastases was performed in 23 cases (60.5%): twenty patients underwent lung surgery, 6 of them received additional postoperative whole lung radiation; three patients received lung radiation only. Malignant cells were found in all lung nodules of patients from group " 3", in 5 (62.5%) patients from group " 2", and none of the group "1". There was a correlation between histological response of the primary tumor and outcome. Three-year estimates of EFS and OS were 45.19% and 60.7%, respectively. Patients with good response measured by chest CT had significantly better EFS than patients with poor response (81% vs. 27.66%, respectively, p=0.006). Conclusions: Metastatectomy may have a role in the treatment of highly selected patients with ES and isolated lung metastases depending on the histologic response to therapy. Further studies are needed to better define the use of surgery and the response-adapted criteria in the upfront management of this population. (C) 2016 Elsevier Inc. All rights reserved. C1 [Raciborska, Anna; Bilska, Katarzyna; Rychlowska-Pruszynska, Magdalena; Wozniak, Wojciech] Inst Mother & Child Hlth, Dept Surg Oncol Children & Youth, Kasprzaka 17A Str, PL-01211 Warsaw, Poland. [Duczkowski, Marek; Duczkowska, Agnieszka] Inst Mother & Child Hlth, Dept Radiol, Kasprzaka 17A Str, PL-01211 Warsaw, Poland. [Drabko, Katarzyna] Med Univ Lublin, Dept Pediat Hematol Oncol & Bone Marrow Transplan, A Gebali 6 Str, PL-20093 Lublin, Poland. [Chaber, Radoslaw] Wroclaw Med Univ, Dept & Clin Pediat Oncol Hematol & Bone Marrow Tr, Bujwida 44 Str, PL-50368 Wroclaw, Poland. [Sobol, Grazyna] Med Univ Silesia, Unit Pediat Oncol Hematol & Chemotherapy, Medykow 16 Str, PL-40752 Katowice, Poland. [Wyrobek, Elzbieta] Univ Childrens Hosp Cracow, Dept Hematol & Oncol, Krakow, Poland. [Michalak, Elzbieta] Inst Mother & Child Hlth, Dept Pathol, Kasprzaka 17A Str, PL-01211 Warsaw, Poland. [Rodriguez-Galindo, Carlos] Harvard Med Sch, Dana Farber Canc Inst, Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. [Rodriguez-Galindo, Carlos] Harvard Med Sch, Childrens Hosp, 450 Brookline Ave, Boston, MA 02215 USA. RP Raciborska, A (reprint author), Inst Mother & Child Hlth, Dept Surg Oncol Children & Youth, Ul Kasprzaka 17A, PL-01211 Warsaw, Poland. EM anna.raciborska@hoga.pl NR 25 TC 2 Z9 2 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 0022-3468 EI 1531-5037 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JUL PY 2016 VL 51 IS 7 BP 1067 EP 1071 DI 10.1016/j.jpedsurg.2015.11.012 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA DQ0SR UT WOS:000378910700002 PM 26707423 ER PT J AU Jackson, PR AF Jackson, Peter R. TI The Neuroscience of Clinical Psychiatry: The Pathophysiology of Behavior and Mental Illness, 2nd edition SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Book Review C1 [Jackson, Peter R.] Massachusetts Gen Hosp, McLean Hosp, Boston, MA USA. [Jackson, Peter R.] Harvard Med Sch, Boston, MA USA. RP Jackson, PR (reprint author), Massachusetts Gen Hosp, McLean Hosp, Boston, MA USA.; Jackson, PR (reprint author), Harvard Med Sch, Boston, MA USA. EM prjackson@partners.org NR 3 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 0890-8567 EI 1527-5418 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2016 VL 55 IS 7 BP 632 EP 633 DI 10.1016/j.jaac.2016.06.001 PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA DQ1UF UT WOS:000378985200017 ER PT J AU Setia, N Agoston, AT Han, HS Mullen, JT Duda, DG Clark, JW Deshpande, V Mino-Kenudson, M Srivastava, A Lennerz, JK Hong, TS Kwak, EL Lauwers, GY AF Setia, Namrata Agoston, Agoston T. Han, Hye S. Mullen, John T. Duda, Dan G. Clark, Jeffrey W. Deshpande, Vikram Mino-Kenudson, Mari Srivastava, Amitabh Lennerz, Jochen K. Hong, Theodore S. Kwak, Eunice L. Lauwers, Gregory Y. TI A protein and mRNA expression-based classification of gastric cancer SO MODERN PATHOLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; E-CADHERIN EXPRESSION; LYMPHOEPITHELIOMA-LIKE CARCINOMA; MICROSATELLITE INSTABILITY; CLINICOPATHOLOGICAL FEATURES; P53 PROTEIN; MOLECULAR CHARACTERIZATION; PROMOTER HYPERMETHYLATION; SIGNALING PATHWAY; SURVIVAL AB The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques. C1 [Setia, Namrata; Han, Hye S.; Deshpande, Vikram; Mino-Kenudson, Mari; Lennerz, Jochen K.; Lauwers, Gregory Y.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Agoston, Agoston T.; Srivastava, Amitabh] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Han, Hye S.] Konkuk Univ, Sch Med, Seoul, South Korea. [Mullen, John T.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Duda, Dan G.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Clark, Jeffrey W.; Kwak, Eunice L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 2, Boston, MA 02114 USA. EM glauwers@partners.org NR 62 TC 3 Z9 3 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0893-3952 EI 1530-0285 J9 MODERN PATHOL JI Mod. Pathol. PD JUL PY 2016 VL 29 IS 7 BP 772 EP 784 DI 10.1038/modpathol.2016.55 PG 13 WC Pathology SC Pathology GA DQ1AR UT WOS:000378933500012 PM 27032689 ER PT J AU Parikh, S Karaa, A Goldstein, A Ng, YS Gorman, G Feigenbaum, A Christodoulou, J Haas, R Tarnopolsky, M Cohen, BK Dimmock, D Feyma, T Koenig, MK Mundy, H Niyazov, D Saneto, RP Wainwright, MS Wusthoff, C McFarland, R Scaglia, F AF Parikh, Sumit Karaa, Amel Goldstein, Amy Ng, Yi S. Gorman, Grainne Feigenbaum, Annette Christodoulou, John Haas, Richard Tarnopolsky, Mark Cohen, Bruce K. Dimmock, David Feyma, Tim Koenig, Mary K. Mundy, Helen Niyazov, David Saneto, Russell P. Wainwright, Mark S. Wusthoff, Courtney McFarland, Robert Scaglia, Fernando TI Solid organ transplantation in primary mitochondrial disease: Proceed with caution SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Mitochondrial disease; Solid organ transplant; Heart transplant; Kidney transplant; Liver transplant ID DEOXYGUANOSINE KINASE-DEFICIENCY; KEARNS-SAYRE SYNDROME; LIVER-TRANSPLANTATION; CARDIAC TRANSPLANTATION; PRIMARY-CARE; CARDIOMYOPATHY; EXPERIENCE; MUTATIONS; CHILDREN; OUTCOMES AB Solid organ transplants are rarely performed in both adult and pediatric patients with primary mitochondrial disease. Poor outcomes have been described in case reports and small case series. It is unclear whether the underlying genetic disease has a significant impact on post-transplant morbidity and mortality. Data were obtained for 35 patients from 17 Mitochondrial Disease Centers across North America, the United Kingdom and Australia. Patient outcomes were noted after liver, kidney or heart transplantation. Excluding patients with POLG-related disease, post-transplant survival approached or met outcomes seen in non-mitochondrial disease transplant patients. The majority of mitochondrial disease patients did not have worsening of their mitochondrial disease within 90-days post-transplant. Post-transplant complications, including organ rejection, were not a common occurrence and were generally treatable. Many patients did not have a mitochondrial disease considered or diagnosed prior to transplantation. In conclusion, patients with mitochondrial disease in this cohort generally tolerated solid-organ transplantation. Such patients may not need to be excluded from transplant solely for their mitochondrial diagnosis; additional caution may be needed for patients with POLG-related disease. Transplant teams should be aware of mitochondrial disease as an etiology for organ-failure and consider appropriate consultation in patients without a known cause of their symptoms. (C) 2016 Elsevier Inc. All rights reserved. C1 [Parikh, Sumit] Cleveland Clin, Ctr Pediat Neurol, Neurogenet & Mitochondrial Dis, Cleveland, OH 44106 USA. [Karaa, Amel] Massachusetts Gen Hosp, Dept Med Genet, Boston, MA 02114 USA. [Goldstein, Amy] Childrens Hosp Pittsburgh, Ctr Pediat Neurol, Pittsburgh, PA 15213 USA. [Ng, Yi S.; Gorman, Grainne; McFarland, Robert] Newcastle Univ, Wellcome Trust Ctr Mitochondrial Res, Newcastle Upon Tyne, Tyne & Wear, England. [Feigenbaum, Annette] Rady Childrens Hosp, Dept Med Genet, San Diego, CA USA. [Christodoulou, John] Childrens Hosp Westmead, Western Sydney Genet Program, Sydney, NSW, Australia. [Christodoulou, John] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW, Australia. [Christodoulou, John] Univ Sydney, Discipline Genet Med, Sydney, NSW, Australia. [Haas, Richard] Rady Childrens Hosp, Dept Pediat Neurol, San Diego, CA USA. [Tarnopolsky, Mark] McMaster Univ, Div Neuromuscular & Neurometab Dis, Dept Pediat, Hamilton, ON, Canada. [Cohen, Bruce K.] Akron Childrens Hosp, Dept Pediat Neurol, Akron, OH USA. [Dimmock, David] Med Coll Wisconsin, Dept Med Genet, Milwaukee, WI 53226 USA. [Feyma, Tim] Gillette Childrens Specialty Healthcare, Dept Pediat Neurol, St Paul, MN USA. [Koenig, Mary K.] Univ Texas Houston, Sch Med, Dept Pediat, Div Child & Adolescent Neurol, Houston, TX USA. [Mundy, Helen] Evelina London Childrens Healthcare, Pediat Metab, London, England. [Niyazov, David] Ochsner Clin Fdn, Dept Pediat, Div Med Genet, New Orleans, LA USA. [Saneto, Russell P.] Seattle Childrens Hosp, Dept Pediat Neurol, Seattle, WA USA. [Wainwright, Mark S.] Lurie Childrens Hosp, Dept Pediat, Div Neurol, Chicago, IL USA. [Wusthoff, Courtney] Lucile Packard Childrens Hosp, Dept Pediat Neurol, Palo Alto, CA USA. [Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Baylor, TX USA. RP Parikh, S (reprint author), 9500 Euclid Ave,S60, Cleveland, OH 44195 USA. EM parikhs@ccf.org OI Christodoulou, John/0000-0002-8431-0641 FU Genzyme/Sanofi; Shire; Biomarin; Alexion FX Dr Dimmock has consulting agreements with, BioMarin Pharmaceutical Inc. Audentes Therapeutics, Demeter Therapeutics LLC and Complete Genomics. He has had previous consulting agreements with Illumina. He has or currently receives support for clinical trials from Genzyme/Sanofi, Shire, Biomarin, Alexion. He is employed by the Medical College of Wisconsin which is a not for profit academic organization that offers fee for service testing and clinical evaluation and care of children and adults with mitochondrial disease. In the authors opinion none of these agreements constitute a conflict of interest with the data presented within this paper. NR 26 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 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUL PY 2016 VL 118 IS 3 BP 178 EP 184 DI 10.1016/j.ymgme.2016.04.009 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA DQ1SX UT WOS:000378981800008 PM 27312126 ER PT J AU Paiardini, M Lichterfeld, M AF Paiardini, Mirko Lichterfeld, Mathias TI Follicular T helper cells: hotspots for HIV-1 persistence SO NATURE MEDICINE LA English DT Editorial Material ID REPLICATION; RESERVOIR AB Reservoirs of virally infected cells that are resistant to standard antiretroviral therapy make HIV-1 infection an incurable disease. A new study shows that follicular T helper cells in lymph node germinal centers are prime niches for HIV-1 persistence during antiviral therapy. C1 [Paiardini, Mirko] Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. [Paiardini, Mirko] Yerkes Natl Primate Res Ctr, Atlanta, GA USA. [Lichterfeld, Mathias] Harvard Med Sch, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Lichterfeld, Mathias] MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Lichterfeld, Mathias] Harvard Univ, Cambridge, MA 02138 USA. RP Lichterfeld, M (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA.; Lichterfeld, M (reprint author), MIT, Massachusetts Gen Hosp, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.; Lichterfeld, M (reprint author), Harvard Univ, Cambridge, MA 02138 USA. EM mlichterfeld@partners.org FU NIAID NIH HHS [R21 AI106468] NR 9 TC 2 Z9 2 U1 2 U2 7 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 JUL PY 2016 VL 22 IS 7 BP 711 EP 712 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DQ7DK UT WOS:000379366900008 PM 27387885 ER PT J AU Ni, J Ramkissoon, SH Xie, SZ Goel, S Stover, DG Guo, HB Luu, V Marco, E Ramkissoon, LA Kang, YJ Hayashi, M Nguyen, QD Ligon, AH Du, R Claus, EB Alexander, BM Yuan, GC Wang, ZGC Iglehart, JD Krop, IE Roberts, TM Winer, EP Lin, NU Ligon, KL Zhao, JJ AF Ni, Jing Ramkissoon, Shakti H. Xie, Shaozhen Goel, Shom Stover, Daniel G. Guo, Hanbing Luu, Victor Marco, Eugenio Ramkissoon, Lori A. Kang, Yun Jee Hayashi, Marika Quang-De Nguyen Ligon, Azra H. Du, Rose Claus, Elizabeth B. Alexander, Brian M. Yuan, Guo-Cheng Wang, Zhigang C. Iglehart, J. Dirk Krop, Ian E. Roberts, Thomas M. Winer, Eric P. Lin, Nancy U. Ligon, Keith L. Zhao, Jean J. TI Combination inhibition of PI3K and mTORC1 yields durable remissions in mice bearing orthotopic patient-derived xenografts of HER2-positive breast cancer brain metastases SO NATURE MEDICINE LA English DT Article ID PTEN LOSS; EVEROLIMUS AB Brain metastases represent the greatest clinical challenge in treating HER2-positive breast cancer. We report the development of orthotopic patient-derived xenografts (PDXs) of HER2-expressing breast cancer brain metastases (BCBM), and their use for the identification of targeted combination therapies. Combined inhibition of PI3K and mTOR resulted in durable tumor regressions in three of five PDXs, and therapeutic response was correlated with a reduction in the phosphorylation of 4EBP1, an mTORC1 effector. The two nonresponding PDXs showed hypermutated genomes with enrichment of mutations in DNA-repair genes, which suggests an association of genomic instability with therapeutic resistance. These findings suggest that a biomarker-driven clinical trial of PI3K inhibitor in combination with an mTOR inhibitor should be conducted for patients with HER2-positive BCBM. C1 [Ni, Jing; Xie, Shaozhen; Goel, Shom; Guo, Hanbing; Luu, Victor; Wang, Zhigang C.; Iglehart, J. Dirk; Roberts, Thomas M.; Zhao, Jean J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Ni, Jing; Xie, Shaozhen; Guo, Hanbing; Luu, Victor; Roberts, Thomas M.; Zhao, Jean J.] Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Goel, Shom; Stover, Daniel G.; Ramkissoon, Lori A.; Kang, Yun Jee; Hayashi, Marika; Wang, Zhigang C.; Iglehart, J. Dirk; Krop, Ian E.; Winer, Eric P.; Lin, Nancy U.; Ligon, Keith L.] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Ramkissoon, Shakti H.; Ligon, Azra H.; Ligon, Keith L.] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Marco, Eugenio; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Quang-De Nguyen] Dana Farber Canc Inst, Lurie Family Imaging Ctr, Boston, MA 02115 USA. [Du, Rose; Claus, Elizabeth B.] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA. [Claus, Elizabeth B.] Yale Univ, Sch Publ Hlth, New Haven, CT USA. [Alexander, Brian M.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Alexander, Brian M.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. RP Zhao, JJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA.; Zhao, JJ (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA.; Lin, NU; Ligon, KL (reprint author), Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.; Ligon, KL (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. EM nancy_lin@dfci.harvard.edu; keith_ligon@dfci.harvard.edu; jean_zhao@dfci.harvard.edu OI Stover, Daniel/0000-0001-9003-8165; Du, Rose/0000-0003-2641-6496 FU Breast Cancer Research Foundation; Aid for Cancer Research; Breast Cancer Alliance; Komen scholar grant; US National Institutes of Health (NIH) [R01 CA187918, CA172461, 1K08NS087118, P50 CA165962, P01 CA142536, 1P50CA168504] FX We thank D. Livingston for reading the manuscript. We thank R. Modiste and G. Dai at the Dana-Farber Lurie Family Image Center for MRI imaging. We thank R. Bronson and the Dana-Farber/Harvard Cancer Center Rodent Histoplathology Core for histopathological analyses. We thank F. Pan, D. Light and R. Qi (Life Technologies, Thermo Fisher) for assistance with WES and transcriptome analyses with the Ion Torrent sequencing system. We thank J. Ruan and M. Ruan (VigeneTech) for quantification of pS6RP and p4EBP IHC data by the Cellvigene data-analysis program. This work was supported by the Breast Cancer Research Foundation (N.U.L., E.P.W., Z.W. and J.J.Z.); Aid for Cancer Research (E.P.W. and J.J.Z.); Breast Cancer Alliance (J.J.Z.); Komen scholar grant (E.P.W.); and US National Institutes of Health (NIH) grants R01 CA187918 (T.M.R. and J.J.Z.), CA172461 (J.J.Z.), 1K08NS087118 (S.H.R.), P50 CA165962 (T.M.R., K.L.L. and J.J.Z.), P01 CA142536 (J.J.Z.) and 1P50CA168504 (T.M.R., I.E.K., E.P.W., N.U.L., and J.J.Z.). NR 13 TC 6 Z9 6 U1 7 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JUL PY 2016 VL 22 IS 7 BP 723 EP 726 DI 10.1038/nm.4120 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DQ7DK UT WOS:000379366900010 PM 27270588 ER PT J AU Vaccari, M Gordon, SN Fourati, S Schifanella, L Liyanage, NPM Cameron, M Keele, BF Shen, XY Tomaras, GD Billings, E Rao, M Chung, AW Dowell, KG Bailey-Kellogg, C Brown, EP Ackerman, ME Vargas-Inchaustegui, DA Whitney, S Doster, MN Binello, N Pegu, P Montefiori, DC Foulds, K Quinn, DS Donaldson, M Liang, F Lore, K Roederer, M Koup, RA McDermott, A Ma, ZM Miller, CJ Phan, TB Forthal, DN Blackburn, M Caccuri, F Bissa, M Ferrari, G Kalyanaraman, V Ferrari, MG Thompson, D Robert-Guroff, M Ratto-Kim, S Kim, JH Michael, NL Phogat, S Barnett, SW Tartaglia, J Venzon, D Stablein, DM Alter, G Sekaly, RP Franchini, G AF Vaccari, Monica Gordon, Shari N. Fourati, Slim Schifanella, Luca Liyanage, Namal P. M. Cameron, Mark Keele, Brandon F. Shen, Xiaoying Tomaras, Georgia D. Billings, Erik Rao, Mangala Chung, Amy W. Dowell, Karen G. Bailey-Kellogg, Chris Brown, Eric P. Ackerman, Margaret E. Vargas-Inchaustegui, Diego A. Whitney, Stephen Doster, Melvin N. Binello, Nicolo Pegu, Poonam Montefiori, David C. Foulds, Kathryn Quinn, David S. Donaldson, Mitzi Liang, Frank Lore, Karin Roederer, Mario Koup, Richard A. McDermott, Adrian Ma, Zhong-Min Miller, Christopher J. Phan, Tran B. Forthal, Donald N. Blackburn, Matthew Caccuri, Francesca Bissa, Massinilliano Ferrari, Guido Kalyanaraman, Vaniambadi Ferrari, Maria G. Thompson, DeVon Robert-Guroff, Marjorie Ratto-Kim, Silvia Kim, Jerome H. Michael, Nelson L. Phogat, Sanjay Barnett, Susan W. Tartaglia, Jim Venzon, David Stablein, Donald M. Alter, Galit Sekaly, Rafick-Pierre Franchini, Genoveffa TI Adjuvant-dependent innate and adaptive immune signatures of risk of SIVmac251 acquisition SO NATURE MEDICINE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; HIV-1 VACCINE EFFICACY; NK CELLS; NITRIC-OXIDE; ACTIVATION; INFECTION; PROTECTION; ANTIBODIES; TRIAL; IMMUNOGENICITY AB A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum. decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution, of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies. C1 [Vaccari, Monica; Gordon, Shari N.; Schifanella, Luca; Liyanage, Namal P. M.; Doster, Melvin N.; Binello, Nicolo; Pegu, Poonam; Blackburn, Matthew; Caccuri, Francesca; Bissa, Massinilliano; Franchini, Genoveffa] NCI, Anim Models & Vaccine Sect, Bethesda, MD 20892 USA. [Fourati, Slim; Sekaly, Rafick-Pierre] Case Wetern Reserve, Dept Pathol, Cleveland, OH USA. [Schifanella, Luca] Univ Milan, L Sacco Hosp, Dept Biomed & Clin Sci, Milan, Italy. [Cameron, Mark] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH USA. [Keele, Brandon F.] Leidos Biomed Res Inc, Frederick Natl Lab, AIDS & Canc Virus Program, Frederick, MD USA. [Shen, Xiaoying; Tomaras, Georgia D.; Ferrari, Guido] Duke Human Vaccine Inst, Durham, NC USA. [Billings, Erik; Rao, Mangala; Ratto-Kim, Silvia; Kim, Jerome H.; Michael, Nelson L.] Walter Red Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA. [Chung, Amy W.; Alter, Galit] Massachusetts Inst Technol & Harvard, Massachusetts Gen Hosp, Ragon Inst, Boston, MA USA. [Dowell, Karen G.; Bailey-Kellogg, Chris] Darthmouth Coll, Dept Comp Sci, Hanover, NH USA. [Brown, Eric P.; Ackerman, Margaret E.] Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. [Vargas-Inchaustegui, Diego A.; Robert-Guroff, Marjorie] NCI, Immune Biol Retrovial Infect Sect, Bethesda, MD USA. [Whitney, Stephen; Kalyanaraman, Vaniambadi; Ferrari, Maria G.; Thompson, DeVon] Adv Biosci Labs, Rockville, MD USA. [Montefiori, David C.] Duke Univ, Med Ctr, Durham, NC USA. [Foulds, Kathryn; Quinn, David S.; Donaldson, Mitzi; Roederer, Mario; Koup, Richard A.; McDermott, Adrian] US Natl Inst Hlth, Vaccine Res Ctr, Bethesda, MD USA. [Liang, Frank; Lore, Karin] Karolinska Inst, Stockholm, Sweden. [Ma, Zhong-Min; Miller, Christopher J.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA USA. [Phan, Tran B.; Forthal, Donald N.] Univ Calif Irvine, Irvine Sch Med, Irvine, CA USA. [Phogat, Sanjay; Tartaglia, Jim] Sanofi Pasteur, Swiftwater, PA USA. [Barnett, Susan W.] Novartis Vaccines & Diagonst Inc, Cambridge, MA USA. [Venzon, David] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD USA. [Stablein, Donald M.] EMMES Corp, Rockville, MD USA. [Barnett, Susan W.] GSK Vaccines, Cambridge, MA USA. [Kim, Jerome H.] Int Vaccine Inst, Seoul, South Korea. RP Franchini, G (reprint author), NCI, Anim Models & Vaccine Sect, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Chung, Amy/0000-0003-0020-9704; Fourati, Slim/0000-0001-6609-7587 FU Simian Vaccine Evaluation Unit (SVEU) [HHSN266200600005C]; intramural US National Cancer Institute (NCI) program; extramural US National Institute of Allergy and Infectious Diseases (NIAID) program; US Army Medical Research and Material Command (USAMRMC) [W81XWH-07-2-0067]; Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; US Department of Defense; Collaboration for AIDS Vaccine Discovery (CAVD) grants from the Bill and Melinda Gates Foundation [OPP1032325, OPP1032817]; NCI; US National Institutes of Health (NIH) [HHSN261200800001E]; NIH [HHSN27201100016C]; Center for AIDS Research [AI064518]; Bill and Melinda Gates' Foundation [OPP111572]; NIH/NIAID [5R01AI102691]; Intramural Research Program of the Vaccine Research Center, NIAID, NIH; CAVD from the Bill and Melinda Gates Foundation [OPP1032325, R01 AI118581, R01 AI102715] FX We would like to thank T. Nolan and D. Abram for their editorial assistance, N. Miller and A. Shultz for their help in the study design, and J. Warren for support with systems biology and several antibody assays under Simian Vaccine Evaluation Unit (SVEU) contract number HHSN266200600005C, awarded to Advanced BioScience Laboratories, Inc. (ABL). This work was supported by the intramural US National Cancer Institute (NCI) program and the extramural US National Institute of Allergy and Infectious Diseases (NIAID) program, together with the US Army Medical Research and Material Command (USAMRMC) (W81XWH-07-2-0067), the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the US Department of Defense, the Collaboration for AIDS Vaccine Discovery (CAVD) grants OPP1032325 and OPP1032817 from the Bill and Melinda Gates Foundation, and in part, with federal funds from the NCI, US National Institutes of Health (NIH), under contract no. HHSN261200800001E (to the whole team). We would like to acknowledge the following institutions for the grants supporting the authors: NIH primate grant HHSN27201100016C (D.M.); Center for AIDS Research grant AI064518 (G.F.); Bill and Melinda Gates' Foundation grant OPP111572 (M.E.A., C.B.K., E.F.B., K.G.D.); NIH/NIAID grant 5R01AI102691 (M.E.A, E.F.B.); Intramural Research Program of the Vaccine Research Center, NIAID, NIH, and CAVD from the Bill and Melinda Gates Foundation grants OPP1032325 (R.A.K.), R01 AI118581 and R01 AI102715 (D.F.). The views expressed are those of the authors and should not be construed to represent the positions of the US Army, the Department of Defense or the Department of Health and Human Services. Mention of trade names, commercial products, or organizations do not imply endorsement by the US Government. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: CEM.NKR CCR5+ by P. Creswell. The anti-alpha 4 beta 7 in APC was kindly provided by A. A. Ansari (cat. #11718, 1:50 dilution) through the NIH AIDS Reagent Program, Division of AIDS, NIAID. NR 31 TC 16 Z9 16 U1 4 U2 7 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 JUL PY 2016 VL 22 IS 7 BP 762 EP 770 DI 10.1038/nm.4105 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DQ7DK UT WOS:000379366900015 PM 27239761 ER PT J AU Li, S Garrett-Bakelman, FE Chung, SS Sanders, MA Hricik, T Rapaport, F Patel, J Dillon, R Vijay, P Brown, AL Perl, AE Cannon, J Bullinger, L Luger, S Becker, M Lewis, ID To, LB Delwel, R Lowenberg, B Dohner, H Guzman, ML Hassane, DC Roboz, GJ Grimwade, D Valk, PJM D'Andrea, RJ Carroll, M Park, CY Neuberg, D Levine, R Melnick, AM Mason, CE AF Li, Sheng Garrett-Bakelman, Francine E. Chung, Stephen S. Sanders, Mathijs A. Hricik, Todd Rapaport, Franck Patel, Jay Dillon, Richard Vijay, Priyanka Brown, Anna L. Perl, Alexander E. Cannon, Joy Bullinger, Lars Luger, Selina Becker, Michael Lewis, Ian D. To, Luen Bik Delwel, Ruud Lowenberg, Bob Doehner, Hartmut Guzman, Monica L. Hassane, Duane C. Roboz, Gail J. Grimwade, David Valk, Peter J. M. D'Andrea, Richard J. Carroll, Martin Park, Christopher Y. Neuberg, Donna Levine, Ross Melnick, Ari M. Mason, Christopher E. TI Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia SO NATURE MEDICINE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CLONAL EVOLUTION; DNA METHYLATION; MUTATIONS RESULT; TET2 FUNCTION; CANCER; DIFFERENTIATION; CHEMOTHERAPY; MALIGNANCIES; PROGRESSION AB Genetic heterogeneity contributes to clinical outcome and progression of most tumors, but little is known about allelic diveisity for epigenetic compartments, and almost no data exist for acute myeloid leukemia (AML). We examined epigenetic heterogeneity as assessed by cytosine methylation within defined genomic loci with four CpGs (epialleles), somatic mutations, and transcriptomes of AML patient samples at serial time points. We observed that epigenetic allele burden is linked to inferior outcome and varies considerably during disease progression. Epigenetic and genetic allelic burden and patterning followed different patterns and kinetics during disease progression. We observed a subset of AMLs with high epiallele and low somatic mutation burden at diagnosis, a subset with high somatic mutation and lower epiallele burdens at diagnosis, and a subset with a mixed profile, suggesting distinct modes of tumor heterogeneity. Genes linked to promoter-associated epiallele shifts during tumor progression showed increased single-cell transcriptional variance and differential expression, suggesting functional impact on gene regulation. Thus, genetic and epigenetic heterogeneity can occur with distinct kinetics likely to affect the biological and clinical features of tumors. C1 [Li, Sheng; Mason, Christopher E.] Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA. [Li, Sheng; Mason, Christopher E.] Weill Cornell Med, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al Sa, New York, NY 10065 USA. [Garrett-Bakelman, Francine E.; Guzman, Monica L.; Hassane, Duane C.; Roboz, Gail J.; Melnick, Ari M.] Weill Cornell Med, Div Hematol Med Oncol, Dept Med, New York, NY 10065 USA. [Chung, Stephen S.; Hricik, Todd; Rapaport, Franck; Patel, Jay; Levine, Ross] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. [Sanders, Mathijs A.; Delwel, Ruud; Lowenberg, Bob; Valk, Peter J. M.] Erasmus Univ, Med Ctr, Dept Hematol, Rotterdam, Netherlands. [Dillon, Richard; Grimwade, David] Kings Coll London, Dept Med & Mol Genet, Fac Life Sci & Med, London, England. [Vijay, Priyanka] Weill Cornell Med, Triinst Training Program Computat Biol & Med, New York, NY USA. [Brown, Anna L.; Lewis, Ian D.; D'Andrea, Richard J.] SA Pathol, Ctr Canc Biol, Adelaide, SA, Australia. [Brown, Anna L.; Lewis, Ian D.; D'Andrea, Richard J.] Univ South Australia, Adelaide, SA, Australia. [Brown, Anna L.; D'Andrea, Richard J.] Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia. [Brown, Anna L.; Lewis, Ian D.; To, Luen Bik; D'Andrea, Richard J.] SA Pathol, Dept Hematol, Adelaide, SA, Australia. [Brown, Anna L.; Lewis, Ian D.; To, Luen Bik; D'Andrea, Richard J.] Royal Adelaide Hosp, Adelaide, SA, Australia. [Perl, Alexander E.; Cannon, Joy; Luger, Selina; Carroll, Martin] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA. [Bullinger, Lars; Doehner, Hartmut; Guzman, Monica L.] Univ Hosp Ulm, Dept Internal Med 3, Ulm, Germany. [Becker, Michael] Univ Rochester, Med Ctr, Rochester, NY 14642 USA. [Lewis, Ian D.; To, Luen Bik] Univ Adelaide, Sch Med, Adelaide, SA, Australia. [Park, Christopher Y.] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. [Park, Christopher Y.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Mason, Christopher E.] Feil Family Brain & Mind Res Inst, New York, NY USA. [Li, Sheng] Weill Cornell Med, Dept Neurosurg, New York, NY USA. RP Mason, CE (reprint author), Weill Cornell Med, Dept Physiol & Biophys, New York, NY 10065 USA.; Mason, CE (reprint author), Weill Cornell Med, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al Sa, New York, NY 10065 USA.; Melnick, AM (reprint author), Weill Cornell Med, Div Hematol Med Oncol, Dept Med, New York, NY 10065 USA.; Mason, CE (reprint author), Feil Family Brain & Mind Res Inst, New York, NY USA. EM amm2014@med.cornell.edu; chm2042@med.cornell.edu FU Starr Cancer Consortium [I4-A442, I7-A765, I9-A9-071]; Irma T. Hirschl Charitable Trust; Monique Weill-Caulier Charitable Trust; Bert L. and N. Kuggie Vallee Foundation; WorldQuant Foundation; Pershing Square Sohn Cancer Research Alliance; NASA [NNX14AH50G]; LLS SCOR [7006-13]; NCI [K08CA169055]; American Society of Hematology award under the ASH-AMFDP partnership [ASHAMFDP-20121]; Robert Wood Johnson Foundation; ASH/EHA TRTH; Doris Duke Medical Foundation; Leukemia and Lymphoma Society Translational Research Program; Geoffrey Beene Cancer Center; Leukaemia and Lymphoma Research award; German Research Foundation (DFG) [SFB 1074]; DFG Heisenberg-Stipendium [BU 1339/3-1]; Australian National Health and Medical Research Council; Royal Adelaide Hospital Contributing Haematologists Fund; US National Institutes of Health [R01CA102031, R01NS076465]; Leukemia Fighters funding FX We thank J. Phillips, J. Ishii, L. Wang, J. Busuttil, T. Lee, P. Zumbo, J. Gandara, and A. Zeilemaker for technical support; C. Sheridan for technical support, assistance with organization, and maintenance of sample database and banking; M. Perugini, D. Iarossi, and I.S. Tiong for assistance with clinical database management; and Y. Neelamraju, Z. Li, J. Glass, and M.R. De Massy for data annotation and management. Next-generation sequencing protocols and sequencing were performed by the Weill Cornell Medicine Epigenomics Core and the New York Genome Center. We thank A. Viale from the Integrated Genomics Operation and N. Socci from the bioinformatics core at Memorial Sloan Kettering Cancer Center for sequencing services. We thank the South Australian Cancer Research Biobank for access to clinical samples. We thank F. Michor for recommendations regarding data analyses. This work was supported by Starr Cancer Consortium grant I4-A442 (A.M.M., R.L., and C.E.M.), STARR Cancer Consortium grant I7-A765 and I9-A9-071 (C.E.M.), the Irma T. Hirschl and Monique Weill-Caulier Charitable Trusts, Bert L. and N. Kuggie Vallee Foundation and the WorldQuant Foundation, Pershing Square Sohn Cancer Research Alliance, and NASA (NNX14AH50G) (C.E.M.); LLS SCOR 7006-13 (A.M.M.); NCI K08CA169055 (F.E.G.-B.); an American Society of Hematology (ASHAMFDP-20121) award under the ASH-AMFDP partnership with the Robert Wood Johnson Foundation and ASH/EHA TRTH (F.E.G.-B.); a Doris Duke Medical Foundation, Leukemia and Lymphoma Society Translational Research Program, and Geoffrey Beene Cancer Center (C.Y.P.); a Leukaemia and Lymphoma Research award (D.G. and R. Dillon); German Research Foundation (DFG) grant SFB 1074 (project B3; K.D. and L.B.); DFG Heisenberg-Stipendium BU 1339/3-1 (L.B.); an Australian National Health and Medical Research Council and the Royal Adelaide Hospital Contributing Haematologists Fund financial support (R.J.D., A.L.B., and I.D.L.); US National Institutes of Health R01CA102031 (G.J.R. and M.L.G.) and R01NS076465 (C.E.M. and A.M.M.); and Leukemia Fighters funding (G.J.R., M.L.G., and D.C.H.). NR 48 TC 17 Z9 18 U1 11 U2 14 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 JUL PY 2016 VL 22 IS 7 BP 792 EP 799 DI 10.1038/nm.4125 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DQ7DK UT WOS:000379366900018 PM 27322744 ER PT J AU Li, PL Kaiser, P Lampiris, HW Kim, P Yukl, SA Havlir, DV Greene, WC Wong, JK AF Li, Peilin Kaiser, Philipp Lampiris, Harry W. Kim, Peggy Yukl, Steven A. Havlir, Diane V. Greene, Warner C. Wong, Joseph K. TI Stimulating the RIG-I pathway to kill cells in the latent HIV reservoir following viral reactivation SO NATURE MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; RETINOIC ACID; SIGNAL-ACTIVATION; T-CELL; RNA; RECOGNITION; ACITRETIN; INFECTION; REPLICATION; RECEPTORS AB The persistence of latent HIV proviruses in long-lived CD4(+) T cells despite antiretroviral therapy (ART)(1-3) is a major obstacle to viral eradication(4-6). Because current candidate latency reversing agents (LRAs) induce HIV transcription, but fail to clear these cellular reservoirs(7,8), new approaches for killing these reactivated latent HIV reservoir cells are urgently needed. HIV latency depends upon the transcriptional quiescence of the integrated provirus and the circumvention of immune defense mechanisms(4-6,9). These defenses include cell-intrinsic innate responses that use pattern-recognition receptors (PRRs) to detect viral pathogens, and that subsequently induce apoptosis of the infected cell(10). Retinoic acid (RA)-inducible gene I (RIG-I, encoded by DDX58) forms one class of PRRs that mediates apoptosis and the elimination of infected cells after recognition of viral RNA(11-14). Here we show that acitretin, an RA derivative approved by the US Food and Drug Administration (FDA), enhances RIG-I signaling ex vivo, increases HIV transcription, and induces preferential apoptosis of HIV-infected cells. These effects are abrogated by DDX58 knockdown. Acitretin also decreases proviral DNA levels in CD4(+) T cells from HIV-positive subjects on suppressive ART, an effect that is amplified when combined with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor. Pharmacological enhancement of an innate cellular-defense network could provide a means by which to eliminate reactivated cells in the latent HIV reservoir. C1 [Li, Peilin; Kaiser, Philipp; Lampiris, Harry W.; Kim, Peggy; Yukl, Steven A.; Wong, Joseph K.] San Francisco VA Med Ctr, Med Serv, Infect Dis Sect, San Francisco, CA 94121 USA. [Li, Peilin; Lampiris, Harry W.; Yukl, Steven A.; Havlir, Diane V.; Greene, Warner C.; Wong, Joseph K.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Havlir, Diane V.] San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94110 USA. [Greene, Warner C.] Univ Calif San Francisco, Dept Microbiol & Biol, San Francisco, CA 94143 USA. [Greene, Warner C.] Gladstone Inst Virol & Immunol, San Francisco, CA USA. RP Li, PL (reprint author), San Francisco VA Med Ctr, Med Serv, Infect Dis Sect, San Francisco, CA 94121 USA.; Li, PL (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. EM peilin.li@ucsf.edu FU NIH [1R21AI104445-01A1, R56 AI116342, R21 AI116218]; Department of Veterans Affairs Merit Review Award [5101 BX001048]; UCSF-Gladstone Center for AIDS Research Virology Core [P30AI027763, U19 AI096113]; amfAR Institute for HIV Cure Research [109301] FX We thank the study participants, without whom this research could not have been performed. We thank S. Deeks, H. Gunthard, C. Lopez, and H. Hatano for their helpful comments and support, and M. Vu for assistance with participant recruitment. We thank J.C.W. Carroll for graphics arts, S. Ordway for editorial assistance, and S. Wilcox for administrative assistance. We thank the US National Institutes of Health (NIH) AIDS Reagent Program, Division of AIDS, NIAID, NIH for cell lines, plasmid, and reagents. This work was supported by the NIH (grants 1R21AI104445-01A1 (P.L.), R56 AI116342 and R21 AI116218 (J.K.W.)), the Department of Veterans Affairs Merit Review Award 5101 BX001048 (J.K.W.), the UCSF-Gladstone Center for AIDS Research Virology Core P30AI027763 (W.C.G. and J.K.W.), U19 AI096113 (W.C.G.) and research supported as part of the amfAR Institute for HIV Cure Research with grant number 109301(W.G., J.K.W., and P.L.). NR 39 TC 4 Z9 4 U1 4 U2 7 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 JUL PY 2016 VL 22 IS 7 BP 807 EP 811 DI 10.1038/nm.4124 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA DQ7DK UT WOS:000379366900020 PM 27294875 ER PT J AU Vodopivec, I Cho, TA Rizzo, JF Frosch, MP Sims, KB AF Vodopivec, Ivana Cho, Tracey A. Rizzo, Joseph F., III Frosch, Matthew P. Sims, Katherine B. TI Mitochondrial Encephalopathy and Optic Neuropathy Due to m.10158 MT-ND3 Complex I Mutation Presenting in an Adult Patient Case Report and Review of the Literature SO NEUROLOGIST LA English DT Review DE mitochondrial disease; MT-ND3; optic neuropathy; headache; stroke-like episodes; epilepsy ID ND3 GENE; LEIGH-SYNDROME; DNA MUTATION; MISSENSE MUTATION; DEFICIENCY; DISEASE; PREVALENCE; DISORDERS; CHILDREN; LESIONS AB Introduction: Establishing a diagnosis of mitochondrial disease in adults remains a clinician's challenge. We report a case of syndrome reminiscent of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) in an adult patient who carries m.10158T>C mutation in complex I respiratory chain gene MT-ND3 (mitochondrially encoded NADH dehydrogenase 3). Case Report: This 26-year-old man from Thailand presented with new-onset headaches, seizures, stroke-like episodes, and poor vision due to optic neuropathy and cortical blindness. Instead of expected mutations in the mitochondrial tRNA gene that are frequently associated with MELAS, the mutation in MT-ND3 with variable tissue heteroplasmy (blood 5.3%, muscle 89.5%) was demonstrated. The patient's clinical features, blood biomarkers, neuroimaging findings, muscle biopsy with histochemical and functional in vitro analysis, and genetic studies were analyzed and compared with all previously reported ND3 disease cases. Conclusions: ND3 disease due to m.10158T>C mutation was previously described only in patients with Leigh or Leigh-like syndrome. Our findings thus indicate that ND3 disease can manifest with atypical phenotype in adults. The diagnosis of mitochondrial disease caused by other than typical MELAS-associated mutations in adults with stroke-like episodes, headaches, and seizures should be considered. An analysis of tissue other than blood, which is more likely to harbor a tissue-specific mitochondrial DNA mutation at a measurable level, may be necessary for diagnosis. C1 [Vodopivec, Ivana; Cho, Tracey A.; Rizzo, Joseph F., III; Frosch, Matthew P.; Sims, Katherine B.] Harvard Med Sch, Boston, MA USA. [Vodopivec, Ivana; Cho, Tracey A.; Sims, Katherine B.] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. [Vodopivec, Ivana; Rizzo, Joseph F., III] Massachusetts Eye & Ear Infirm, Neuroophthalmol Serv, Boston, MA 02114 USA. [Frosch, Matthew P.] Massachusetts Gen Hosp, Neuropathol Serv, Boston, MA 02114 USA. RP Vodopivec, I (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St, Boston, MA 02114 USA. EM ivodopivec@partners.org NR 26 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 1074-7931 J9 NEUROLOGIST JI Neurologist PD JUL PY 2016 VL 21 IS 4 BP 61 EP 65 DI 10.1097/NRL.0000000000000084 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA DQ2LE UT WOS:000379033000004 PM 27348141 ER PT J AU Cardenas, DP Muir, ER Duong, TQ AF Cardenas, Damon P. Muir, Eric R. Duong, Timothy Q. TI MRI of cerebral blood flow under hyperbaric conditions in rats SO NMR IN BIOMEDICINE LA English DT Article DE arterial spin labeling; CBF; oxygen therapy; BOLD; magnetic susceptibility ID LONGITUDINAL RELAXATION-TIME; OXYGEN-TENSION; MAGNETIC-FIELD; FUNCTIONAL MRI; TRANSIT-TIME; BOLD FMRI; BRAIN; HYPEROXIA; HYPOXIA; CBF AB Hyperbaric oxygen (HBO) therapy has a number of clinical applications. However, the effects of acute HBO on basal cerebral blood flow (CBF) and neurovascular coupling are not well understood. This study explored the use of arterial spin labeling MRI to evaluate changes in baseline and forepaw stimulus-evoked CBF responses in rats (n = 8) during normobaric air (NB), normobaric oxygen (NBO) (100% O-2), 3 atm absolute (ATA) hyperbaric air (HB) and 3 ATA HBO conditions. T-1 was also measured, and the effects of changes in T-1 caused by increasing oxygen on the CBF calculation were investigated. The major findings were as follows: (i) increased inhaled oxygen concentrations led to a reduced respiration rate; (ii) increased dissolved paramagnetic oxygen had significant effects on blood and tissue T-1, which affected the CBF calculation using the arterial spin labeling method; (iii) the differences in blood T-1 had a larger effect than the differences in tissue T-1 on CBF calculation; (iv) if oxygen-induced changes in blood and tissue T-1 were not taken into account, CBF was underestimated by 33% at 3 ATA HBO, 10% at NBO and <5% at HB; (v) with correction, CBF values under HBO, HB and NBO were similar (p > 0.05) and all were higher than CBF under NB by similar to 40% (p < 0.05), indicating that hypercapnia from the reduced respiration rate masks oxygen-induced vasoconstriction, although blood gas was not measured; and (vi) substantial stimulus-evoked CBF increases were detected under HBO, similar to NB, supporting the notion that activation-induced CBF regulation in the brain does not operate through an oxygen-sensing mechanism. CBF MRI provides valuable insights into the effects of oxygen on basal CBF and neurovascular coupling under hyperbaric conditions. Copyright (c) 2016 John Wiley & Sons, Ltd. C1 [Cardenas, Damon P.; Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. [Cardenas, Damon P.] Univ Texas San Antonio, Grad Sch Biomed Sci, San Antonio, TX USA. [Muir, Eric R.; Duong, Timothy Q.] Univ Texas Hlth Sci Ctr San Antonio, Dept Ophthalmol, San Antonio, TX 78229 USA. [Duong, Timothy Q.] South Texas Vet Hlth Care Syst, Dept Vet Affairs, San Antonio, TX USA. RP Muir, ER; Duong, TQ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Inst, 8403 Floyd Curl Dr, San Antonio, TX 78229 USA. EM muire@uthscsa.edu; duongt@uthscsa.edu FU National Institute of General Medical Sciences, Minority Biomedical Research Support, Research Initiative for Scientific Enhancement fellowship [GM060655] FX This work was supported in part by a National Institute of General Medical Sciences, Minority Biomedical Research Support, Research Initiative for Scientific Enhancement GM060655 fellowship to D.P.C. NR 37 TC 0 Z9 0 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD JUL PY 2016 VL 29 IS 7 BP 961 EP 968 DI 10.1002/nbm.3555 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA DQ2JM UT WOS:000379028600012 PM 27192391 ER PT J AU Panagia, M Chen, YCI Chen, HH Ernande, L Chen, C Chao, W Kwong, K Scherrer-Crosbie, M Sosnovik, DE AF Panagia, Marcello Chen, Yin-Ching Iris Chen, Howard H. Ernande, Laura Chen, Chan Chao, Wei Kwong, Kenneth Scherrer-Crosbie, Marielle Sosnovik, David E. TI Functional and anatomical characterization of brown adipose tissue in heart failure with blood oxygen level dependent magnetic resonance SO NMR IN BIOMEDICINE LA English DT Article DE brown adipose tissue; BOLD; heart failure; MRI ID IN-VIVO; NATRIURETIC PEPTIDES; CONTRAST ULTRASOUND; SKELETAL-MUSCLE; PERFUSION; MICE; MRI; BRAIN; FLOW; IDENTIFICATION AB Recent studies have suggested that brown adipose tissue (BAT) plays an important role in obesity, insulin resistance and heart failure. The characterization of BAT in vivo, however, has been challenging. No technique to comprehensively image BAT anatomy and function has been described. Moreover, the impact on BAT of the neuroendocrine activation seen in heart failure has only recently begun to be evaluated in vivo. The aim of this study was to use MRI to characterize the impact of heart failure on the morphology and function of BAT. Mice subjected to permanent ligation of the left coronary artery were imaged with MRI 6weeks later. T-2 weighted MRI of BAT volume and blood oxygen level dependent MRI of BAT function were performed. T-2* maps of BAT were obtained at multiple time points before and after administration of the (3) adrenergic agonist CL 316 243 (CL). Blood flow to BAT was studied after CL injection using the flow alternating inversion recovery (FAIR) approach. Excised BAT tissue was analyzed for lipid droplet content and for uncoupling protein 1 (UCP1) mRNA expression. BAT volume was significantly lower in heart failure (511mm(3) versus 65 +/- 3mm(3); p<0.05), and characterized by a reduction in lipid globules and a fourfold increase in UCP1 mRNA (p<0.05). CL injection increased BAT T-2* in healthy animals but not in mice with heart failure (24 +/- 4% versus 6 +/- 2%; p<0.01), consistent with an increase in flow in control BAT. This was confirmed by a significant difference in the FAIR response in BAT in control and heart failure mice. Heart failure results in the chronic activation of BAT, decreased BAT lipid stores and decreased BAT volume, and it is associated with a marked decrease in ability to respond to acute physiological stimuli. This may have important implications for substrate utilization and overall metabolic homeostasis in heart failure. Copyright (c) 2016 John Wiley & Sons, Ltd. C1 [Panagia, Marcello] Boston Med Ctr, Cardiol Sect, Boston, MA USA. [Panagia, Marcello; Ernande, Laura; Scherrer-Crosbie, Marielle; Sosnovik, David E.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Panagia, Marcello; Chen, Yin-Ching Iris; Chen, Howard H.; Kwong, Kenneth; Sosnovik, David E.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA USA. [Ernande, Laura] Hop Henri Mondor, AP HP, DHU Ageing Thorax Vessel Blood, Creteil, France. [Chen, Chan; Chao, Wei] Harvard Med Sch, Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA USA. RP Sosnovik, DE (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02115 USA. EM sosnovik@nmr.mgh.harvard.edu FU National Institutes of Health [K08 HL123744-03, R01 HL093038, R01HL112831, P41RR14075, R01 GM080906, R01 GM097259]; SPARK grant from MGH; [DK R21 092909] FX This research was supported by the following National Institutes of Health grants: K08 HL123744-03 (M.P.), R01 HL093038 (D.E.S.), R01HL112831 (D.E.S.), P41RR14075 to the Martinos Center for Biomedical Imaging, R01 GM080906 (W.C.), R01 GM097259 (W.C.), a SPARK grant from MGH (M.S.-C.) and DK R21 092909 (M.S.-C.). NR 46 TC 0 Z9 0 U1 8 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD JUL PY 2016 VL 29 IS 7 BP 978 EP 984 DI 10.1002/nbm.3557 PG 7 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA DQ2JM UT WOS:000379028600014 PM 27226402 ER PT J AU Ciris, PA Balasubramanian, M Seethamraju, RT Tokuda, J Scalera, J Penzkofer, T Fennessy, FM Tempany-Afdhal, CM Tuncali, K Mulkern, RV AF Ciris, Pelin Aksit Balasubramanian, Mukund Seethamraju, Ravi T. Tokuda, Junichi Scalera, Jonathan Penzkofer, Tobias Fennessy, Fiona M. Tempany-Afdhal, Clare M. Tuncali, Kemal Mulkern, Robert V. TI Characterization of gradient echo signal decays in healthy and cancerous prostate at 3T improves with a Gaussian augmentation of the mono-exponential (GAME) model SO NMR IN BIOMEDICINE LA English DT Article DE biophysical modeling; Lorentzian; Gaussian; transverse relaxation; prostate cancer; hypoxia ID MAGNETIC-FIELD INHOMOGENEITIES; TUMOR HYPOXIA; MRI; T-2; T-2-ASTERISK; OXYGENATION; CARCINOMA; ELECTRODE; PREDICTS; BEHAVIOR AB A biomarker of cancer aggressiveness, such as hypoxia, could substantially impact treatment decisions in the prostate, especially radiation therapy, by balancing treatment morbidity (urinary incontinence, erectile dysfunction, etc.) against mortality. R-2(*) mapping with Mono-Exponential (ME) decay modeling has shown potential for identifying areas of prostate cancer hypoxia at 1.5T. However, Gaussian deviations from ME decay have been observed in other tissues at 3T. The purpose of this study is to assess whether gradient-echo signal decays are better characterized by a standard ME decay model, or a Gaussian Augmentation of the Mono-Exponential (GAME) decay model, in the prostate at 3T. Multi-gradient-echo signals were acquired on 20 consecutive patients with a clinical suspicion of prostate cancer undergoing MR-guided prostate biopsies. Data were fitted with both ME and GAME models. The information contents of these models were compared using Akaike's information criterion (second order, AIC(C)), in skeletal muscle, the prostate central gland (CG), and peripheral zone (PZ) regions of interest (ROIs). The GAME model had higher information content in 30% of the prostate on average (across all patients and ROIs), covering up to 67% of cancerous PZ ROIs, and up to 100% of cancerous CG ROIs (in individual patients). The higher information content of GAME became more prominent in regions that would be assumed hypoxic using ME alone, reaching 50% of the PZ and 70% of the CG as ME R-2(*) approached 40 s(-1). R-2(*) mapping may have important applications in MRI; however, information lost due to modeling could mask differences in parameters due to underlying tissue anatomy or physiology. The GAME model improves characterization of signal behavior in the prostate at 3T, and may increase the potential for determining correlates of fit parameters with biomarkers, for example of oxygenation status. C1 [Ciris, Pelin Aksit] Akdeniz Univ, Dept Biomed Engn, Antalya, Turkey. [Ciris, Pelin Aksit; Balasubramanian, Mukund; Tokuda, Junichi; Scalera, Jonathan; Penzkofer, Tobias; Fennessy, Fiona M.; Tempany-Afdhal, Clare M.; Tuncali, Kemal; Mulkern, Robert V.] Harvard Med Sch, Boston, MA USA. [Ciris, Pelin Aksit; Tokuda, Junichi; Scalera, Jonathan; Penzkofer, Tobias; Fennessy, Fiona M.; Tempany-Afdhal, Clare M.; Tuncali, Kemal] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. [Balasubramanian, Mukund; Mulkern, Robert V.] Boston Childrens Hosp, Boston, MA USA. [Seethamraju, Ravi T.] Siemens Healthcare, Boston, MA USA. [Penzkofer, Tobias] Charite Univ Med Berlin, Berlin, Germany. [Fennessy, Fiona M.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ciris, PA (reprint author), Harvard Med Sch, Brigham & Womens Hosp, Dept Radiol, MR Phys, 75 Francis St,Thorn 328, Boston, MA 02115 USA. EM pelin.aksit@gmail.com OI Ciris, Pelin/0000-0002-6405-2462 FU NIH [5R25CA089017-10, 5-EB015898 10, CA 1112888] FX This research was partially supported by NIH 5R25CA089017-10, 5-EB015898 10, and CA 1112888. NR 39 TC 0 Z9 0 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0952-3480 EI 1099-1492 J9 NMR BIOMED JI NMR Biomed. PD JUL PY 2016 VL 29 IS 7 BP 999 EP 1009 DI 10.1002/nbm.3556 PG 11 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA DQ2JM UT WOS:000379028600016 PM 27241215 ER PT J AU Hivert, MF Rifas-Shiman, SL Gillman, MW Oken, E AF Hivert, Marie-France Rifas-Shiman, Sheryl L. Gillman, Matthew W. Oken, Emily TI Greater Early and Mid-Pregnancy Gestational Weight Gains are Associated with Excess Adiposity in Mid-Childhood SO OBESITY LA English DT Article ID HYPOTHALAMIC NEURONS; OFFSPRING OBESITY; OUTCOMES; WOMEN; RISK; LEPTIN; GROWTH; RATIO; WAIST; MASS AB Objective: It is unclear how specific periods of gestational weight gain (GWG) during pregnancy relate to childhood adiposity. The goal of this study was to assess the differential impact of GWG timing on childhood body composition. Methods: In 979 mother-child pairs from the pre-birth Project Viva cohort, trimester-specific GWG was calculated using clinically recorded weights. Outcomes included body mass index (BMI) z-score, dual X-ray absorptiometry fat mass index (kg/m(2)), and fat-free mass index (kg/m(2)) in mid-childhood. Linear regression models were used to assess associations of each trimester's GWG (per 0.2 kg/week) with childhood outcomes, adjusted for maternal prepregnancy BMI, sociodemographic variables, lifestyle, and GWG in prior trimester(s). Results: Mean (SD) first trimester GWG was 0.22 (0.22) kg/week, second trimester 0.49 (0.18) kg/week, and third trimester 0.47 (0.20) kg/week. Faster first trimester GWG was associated with higher BMI z-score (0.06 units [95% CI: 0.01-0.12] per 0.2 kg/week) and with higher adiposity according to all indices; associations were strongest in women with prepregnancy BMI >30 kg/m(2). Faster second trimester GWG was associated with higher BMI z-score (0.11 [0.04-0.18]), fat mass (fat mass index = 0.16 [0.02-0.31] kg/m(2)), and lean mass (fat-free mass index = 0.11 [0.01-0.22] kg/m(2)). Third trimester GWG was not associated with childhood adiposity. Conclusions: These results reinforce the importance of addressing appropriate GWG in early pregnancy. C1 [Hivert, Marie-France; Rifas-Shiman, Sheryl L.; Gillman, Matthew W.; Oken, Emily] Harvard Med Sch, Obes Prevent Program, Dept Populat Med, Boston, MA 02115 USA. [Hivert, Marie-France; Rifas-Shiman, Sheryl L.; Gillman, Matthew W.; Oken, Emily] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. [Hivert, Marie-France] Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada. RP Hivert, MF (reprint author), Harvard Med Sch, Obes Prevent Program, Dept Populat Med, Boston, MA 02115 USA.; Hivert, MF (reprint author), Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA.; Hivert, MF (reprint author), Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.; Hivert, MF (reprint author), Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada. EM mhivert@partners.org FU NIH [R37 HD34568]; [K24 HD069408]; [P30 DK092924] FX Project Viva is supported by NIH grant R37 HD34568. EO received funding from K24 HD069408 and P30 DK092924. NR 40 TC 1 Z9 1 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1930-7381 EI 1930-739X J9 OBESITY JI Obesity PD JUL PY 2016 VL 24 IS 7 BP 1546 EP 1553 DI 10.1002/oby.21511 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA DQ6GT UT WOS:000379303200020 PM 27345963 ER PT J AU Okello, S Nasasira, B Muiru, ANW Muyingo, A AF Okello, Samson Nasasira, Benson Muiru, Anthony Ndichu Wa Muyingo, Anthony TI Validity and Reliability of a Self-Reported Measure of Antihypertensive Medication Adherence in Uganda SO PLOS ONE LA English DT Article ID CARDIOVASCULAR RISK; PREDICTIVE-VALIDITY; HYPERTENSION; POPULATION; HEALTH; SCALE; CARE; SERVICES; VERSION; INCOME AB Background The Morisky Medication Adherence scale (MMAS-8) is a widely used self-reported measure of adherence to antihypertensive medications that has not been validated in hypertensive patients in sub-Saharan Africa. Methods We carried out a cross-sectional study to examine psychometric properties of a translated MMAS-8 (MMAS-U) in a tertiary care hypertension clinic in Uganda. We administered the MMAS-U to consecutively selected hypertensive adults and used principal factor analysis and Cronbach's alpha to determine its validity and internal consistency respectively. Then we randomly selected one-sixth of participants for a 2-week test-retest telephone interview. Lastly, we used ordinal logistic regression modeling to explore factors associated with levels of medication adherence. Results Of the 329 participants, 228 (69%) were females, median age of 55 years [Interquartile range (IQR) (46-66)], and median duration of hypertension of 4 years [IQR (2-8)]. The adherence levels were low (MMAS-U score <= 5) in 85%, moderate (MMAS-U score 6-7) in 12% and high (MMAS-U score >= 8) in 3%. The factor analysis of construct validity was good (overall Kaiser's measure of sampling adequacy for residuals of 0.72) and identified unidimensionality of MMAS-U. The internal consistency of MMAS-U was moderate (Cronbach alpha = 0.65), and test-retest reliability was low (weighted kappa = 0.36; 95% CI -0.01, 0.73). Age of 40 years or greater was associated with low medication adherence (p = 0.02) whereas a family member buying medication for participants (p = 0.02) and purchasing medication from a private clinic (p = 0.02) were associated with high adherence. Conclusion The Ugandan version of the MMAS-8 (MMAS-U) is a valid and reliable measure of adherence to antihypertensive medication among Ugandan outpatients receiving care at a public tertiary facility. Though the limited supply of medication affected adherence, this easy to use tool can be adapted to assess medication adherence among adults with hypertension in Uganda. C1 [Okello, Samson; Nasasira, Benson; Muyingo, Anthony] Mbarara Univ Sci & Technol, Dept Internal Med, Mbarara, Uganda. [Okello, Samson; Muiru, Anthony Ndichu Wa] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Muiru, Anthony Ndichu Wa] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Okello, S (reprint author), Mbarara Univ Sci & Technol, Dept Internal Med, Mbarara, Uganda.; Okello, S (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM okello.samson@must.ac.ug OI Okello, Samson/0000-0001-7377-6094 FU Bernard Lown Scholars in Cardiovascular Health Program at Harvard T.H. School of Public Health, Boston, MA, USA FX Author SO receives support from the Bernard Lown Scholars in Cardiovascular Health Program at Harvard T.H. School of Public Health, Boston, MA, USA. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 36 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 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 1 PY 2016 VL 11 IS 7 AR e0158499 DI 10.1371/journal.pone.0158499 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ0TX UT WOS:000378914900037 PM 27367542 ER PT J AU Wolf, EJ Bovin, MJ Green, JD Mitchell, KS Stoop, TB Barretto, KM Jackson, CE Lee, LO Fang, SC Trachtenberg, F Rosen, RC Keane, TM Marx, BP AF Wolf, E. J. Bovin, M. J. Green, J. D. Mitchell, K. S. Stoop, T. B. Barretto, K. M. Jackson, C. E. Lee, L. O. Fang, S. C. Trachtenberg, F. Rosen, R. C. Keane, T. M. Marx, B. P. TI Longitudinal associations between post-traumatic stress disorder and metabolic syndrome severity SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Accelerated aging; cross-lagged design; longitudinal; metabolic syndrome; PTSD; veterans ID TYPE-2 DIABETES-MELLITUS; EARLY-LIFE ADVERSITY; BODY-MASS INDEX; CARDIOVASCULAR-DISEASE; RISK-FACTORS; CARDIOMETABOLIC RISK; PHYSICAL-ACTIVITY; OXIDATIVE STRESS; UNITED-STATES; METAANALYSIS AB Background. Post-traumatic stress disorder (PTSD) is associated with elevated risk for metabolic syndrome (MetS). However, the direction of this association is not yet established, as most prior studies employed cross-sectional designs. The primary goal of this study was to evaluate bidirectional associations between PTSD and MetS using a longitudinal design. Method. A total of 1355 male and female veterans of the conflicts in Iraq and Afghanistan underwent PTSD diagnostic assessments and their biometric profiles pertaining to MetS were extracted from the electronic medical record at two time points (spanning similar to 2.5 years, n = 971 at time 2). Results. The prevalence of MetS among veterans with PTSD was just under 40% at both time points and was significantly greater than that for veterans without PTSD; the prevalence of MetS among those with PTSD was also elevated relative to age-matched population estimates. Cross-lagged panel models revealed that PTSD severity predicted subsequent increases in MetS severity (beta = 0.08, p = 0.002), after controlling for initial MetS severity, but MetS did not predict later PTSD symptoms. Logistic regression results suggested that for every 10 PTSD symptoms endorsed at time 1, the odds of a subsequent MetS diagnosis increased by 56%. Conclusions. Results highlight the substantial cardiometabolic concerns of young veterans with PTSD and raise the possibility that PTSD may predispose individuals to accelerated aging, in part, manifested clinically as MetS. This demonstrates the need to identify those with PTSD at greatest risk for MetS and to develop interventions that improve both conditions. C1 [Wolf, E. J.; Bovin, M. J.; Mitchell, K. S.; Keane, T. M.; Marx, B. P.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, E. J.; Bovin, M. J.; Green, J. D.; Mitchell, K. S.; Jackson, C. E.; Lee, L. O.; Keane, T. M.; Marx, B. P.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Green, J. D.; Barretto, K. M.; Lee, L. O.] VA Boston Healthcare Syst, Res Serv, Boston, MA USA. [Stoop, T. B.] Boston VA Res Inst, Boston, MA USA. [Jackson, C. E.] VA Boston Healthcare Syst, Educ & Clin Ctr, Geriatr Res, Boston, MA USA. [Jackson, C. E.] VA Boston Healthcare Syst, Translat Res Ctr TBI & Stress Disorders, Boston, MA USA. [Fang, S. C.; Trachtenberg, F.; Rosen, R. C.] New England Res Inst, Watertown, MA USA. RP Wolf, EJ; Marx, BP (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B 2, 150 South Huntington Ave, Boston, MA 02130 USA. EM erika.wolf@va.gov; brian.marx@va.gov FU United States Department of Veterans Affairs, Clinical Sciences Research and Development Program; Department of Defense [W81XWH-08-2-0100, W81XWH-12-2-0117, W81XWH-10-2-0181, W81XWH-12-1-0532, W81XWH-14-2-0139, W81XWH-08-2-0102, W81XWH-12-2-0121]; National Institute of Mental Health [1R01MH095737-01A1, 5T32MH019836-16, K01MH093750]; Defense Advanced Research Programs Agency [N66001-11-C-4006]; Department of Veterans Affairs [591]; Consortium to Alleviate PTSD; National Institute on Aging [K08AG048221]; National Center for Advancing Translational Sciences [1UL1TR001430] FX This work was supported by a Career Development Award to Erika J. Wolf from the United States Department of Veterans Affairs, Clinical Sciences Research and Development Program. Brian Marx and Terence Keane were supported by funding from the Department of Defense (W81XWH-08-2-0100, W81XWH-12-2-0117). Dr. Marx was additionally supported by funding from the National Institute of Mental Health (1R01MH095737-01A1), Defense Advanced Research Programs Agency (N66001-11-C-4006), and Department of Defense (W81XWH-10-2-0181), and the Department of Veterans Affairs (Cooperative Studies Program no. 591). Dr. Keane was additionally supported by funding from the Consortium to Alleviate PTSD and National Institute of Mental Health (5T32MH019836-16). Raymond Rosen was supported by funding from the Department of Defense, (W81XWH-12-1-0532; W81XWH-14-2-0139; W81XWH-08-2-0102, and W81XWH-12-2-0121). Karen Mitchell's contribution was partly supported by funding from the National Institute of Mental Health (K01MH093750). Lewina Lee was supported by funding from the National Institute on Aging (K08AG048221) and the National Center for Advancing Translational Sciences (BU-CTSI Grant Number 1UL1TR001430). The contents of this article do not represent the views of the U.S. Department of Veterans Affairs or the United States Government. NR 65 TC 2 Z9 2 U1 4 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 JUL PY 2016 VL 46 IS 10 BP 2215 EP 2226 DI 10.1017/S0033291716000817 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA DQ4GV UT WOS:000379163000017 PM 27087657 ER PT J AU Bai, XY Oberley-Deegan, RE Bai, A Ovrutsky, AR Kinney, WH Weaver, M Zhang, G Honda, JR Chan, ED AF Bai, Xiyuan Oberley-Deegan, Rebecca E. Bai, An Ovrutsky, Alida R. Kinney, William H. Weaver, Michael Zhang, Gong Honda, Jennifer R. Chan, Edward D. TI Curcumin enhances human macrophage control of Mycobacterium tuberculosis infection SO RESPIROLOGY LA English DT Article DE apoptosis; autophagy; curcumin; nuclear-factor kappa B; tuberculosis ID NF-KAPPA-B; MULTIDRUG-RESISTANT TUBERCULOSIS; NITRIC-OXIDE; IN-VIVO; APOPTOSIS; CANCER; ACTIVATION; PATHWAY; LIPOARABINOMANNAN; AUTOPHAGOSOME AB Background and objectiveWith the worldwide emergence of highly drug-resistant tuberculosis (TB), novel agents that have direct antimycobacterial effects or that enhance host immunity are urgently needed. Curcumin is a polyphenol responsible for the bright yellow-orange colour of turmeric, a spice derived from the root of the perennial herb Curcuma longa. Curcumin is a potent inducer of apoptosisan effector mechanism used by macrophages to kill intracellular Mycobacterium tuberculosis (MTB). MethodsAn in vitro human macrophage infection model was used to determine the effects of curcumin on MTB survival. ResultsWe found that curcumin enhanced the clearance of MTB in differentiated THP-1 human monocytes and in primary human alveolar macrophages. We also found that curcumin was an inducer of caspase-3-dependent apoptosis and autophagy. Curcumin mediated these anti-MTB cellular functions, in part, via inhibition of nuclear factor-kappa B (NFB) activation. ConclusionCurcumin protects against MTB infection in human macrophages. The host-protective role of curcumin against MTB in macrophages needs confirmation in an animal model; if validated, the immunomodulatory anti-TB effects of curcumin would be less prone to drug resistance development. The effects of curcumin (a polyphenol of tumeric) on Mycobacterium tuberculosis (MTB) infection using human macrophages were investigated in this study. Curcumin reduced the intracellular burden of MTB in infected macrophages through inhibition of NFB activation resulting in the induction of caspase-3-dependent apoptosis and autophagy. C1 [Bai, Xiyuan; Bai, An; Chan, Edward D.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Bai, Xiyuan; Oberley-Deegan, Rebecca E.; Bai, An; Ovrutsky, Alida R.; Kinney, William H.; Weaver, Michael; Honda, Jennifer R.; Chan, Edward D.] Natl Jewish Hlth, Dept Med & Acad Affairs, Denver, CO USA. [Bai, Xiyuan; Ovrutsky, Alida R.; Kinney, William H.; Honda, Jennifer R.; Chan, Edward D.] Univ Colorado, Sch Med, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA. [Oberley-Deegan, Rebecca E.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. [Zhang, Gong] Shaanxi Univ Chinese Med, Coll Pharm, Xianyang, Shaanxi, Peoples R China. RP Bai, XY (reprint author), Natl Jewish Hlth, D509 Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM baix@njhealth.org NR 45 TC 0 Z9 0 U1 6 U2 14 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1323-7799 EI 1440-1843 J9 RESPIROLOGY JI Respirology PD JUL PY 2016 VL 21 IS 5 BP 951 EP 957 DI 10.1111/resp.12762 PG 7 WC Respiratory System SC Respiratory System GA DQ2VQ UT WOS:000379061900024 PM 27012592 ER PT J AU Dionigi, G Kim, HY Randolph, GW Wu, CW Sun, H Liu, XL Barczynski, M Chiang, FY AF Dionigi, Gianlorenzo Kim, Hoon Yub Randolph, Gregory W. Wu, Che-Wei Sun, Hui Liu, Xiaoli Barczynski, Marcin Chiang, Feng-Yu TI Prospective validation study of Cernea classification for predicting EMG alterations of the external branch of the superior laryngeal nerve SO SURGERY TODAY LA English DT Article DE Cernea classification; External branch of the superior laryngeal nerve; EBSLN; Intraoperative nerve monitoring; IONM; Nerve injury; Neural monitoring study group; INMSG ID VIDEO-ASSISTED THYROIDECTOMY; SURGICAL ANATOMY; SURGERY; IDENTIFICATION; RECURRENT; INJURY; NECK AB Purposes Cernea classification is applied to describe the external branch of the superior laryngeal nerve (EBSLN). Using intraoperative neural monitoring we evaluated whether or not this classification is useful for predicting which EBSLN subtype has an increased risk of injury. Methods An analysis of 400 EBSLN. The identification of EBSLN was achieved with both cricothyroid muscle twitch and the glottis evoked electromyography response. We defined S1 initial EBSLN stimulation at identification and S2 final nerve stimulation achieved in the most cranial aspect of the nerve exposed above the area of surgical dissection after superior artery ligation. Results The mean S1 amplitude acquired was 259+/67 (180-421), 321 +/79 (192-391), 371 +/38 (200-551) mu V, respectively, for type 1, 2A, 2B (p = 0.08). The S1 and S2 amplitudes were similar in type 1 (p = 0.3). The S1 and S2 determinations changed significantly in type 2A and 2B (p = 0.04 and 0.03). EBSLN which demonstrated a >25 % decreased amplitude in S2 increased significantly from Type 1 (4.9 %) to Type 2A (11.2 %) and 2B (18 %) (p = 0.01). None of type 1, 2.8 % type 2A and 3 % type 2B showed a loss of EBSLN conductivity. The latency determinations did not vary significantly for any parameter compared. Conclusions The Cernea classification was, therefore, found to predict the risk of EBSLN stress. We identified amplitude differences between S1 and S2 determinations in type 2A and 2B, thus confirming that surgical dissection in these subtypes is, therefore, extremely difficult to perform. C1 [Dionigi, Gianlorenzo] Univ Insubria Como Varese, Div Surg 1, Dept Surg Sci & Human Morphol, Res Ctr Endocrine Surg, Via Guicciardini 9, I-21100 Varese, Italy. [Kim, Hoon Yub] Korea Univ, Minimally Invas Surg & Robot Surg Ctr, Div Breast & Endocrine Surg, Dept Surg,KUMC Thyroid Ctr,Anam Hosp,Coll Med, 73 Inchon Ro, Seoul 136705, South Korea. [Randolph, Gregory W.] Harvard Med Sch, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Div Thyroid & Parathyroid Endocrine Surg, Boston, MA USA. [Wu, Che-Wei; Chiang, Feng-Yu] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Otolaryngol Head & Neck Surg, Kaohsiung, Taiwan. [Sun, Hui; Liu, Xiaoli] Jilin Univ, China Japan Union Hosp, Jilin Prov Key Lab Surg Translat Med, Div Thyroid Surg, Changchun, Jilin Province, Peoples R China. [Barczynski, Marcin] Jagiellonian Univ, Chair & Dept Gen Surg 3, Coll Med, Krakow, Poland. RP Kim, HY (reprint author), Korea Univ, Minimally Invas Surg & Robot Surg Ctr, Div Breast & Endocrine Surg, Dept Surg,KUMC Thyroid Ctr,Anam Hosp,Coll Med, 73 Inchon Ro, Seoul 136705, South Korea. EM hoonyubkim@gmail.com OI dionigi, gianlorenzo/0000-0003-0864-6087; Wu, Che-Wei/0000-0003-1052-5348 NR 39 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-1291 EI 1436-2813 J9 SURG TODAY JI Surg. Today PD JUL PY 2016 VL 46 IS 7 BP 785 EP 791 DI 10.1007/s00595-015-1245-9 PG 7 WC Surgery SC Surgery GA DQ4QB UT WOS:000379187300005 PM 26362419 ER PT J AU Jones, JA AF Jones, Jeffrey A. TI Editorial Commentary: Understanding Marfan syndrome, or "how not to invent the light bulb" SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Editorial Material ID SMOOTH-MUSCLE-CELLS; II TYPE-1 RECEPTOR; AORTIC-ANEURYSM; BETA RECEPTOR; MOUSE MODEL; ACTIVATION; MUTATIONS; LOSARTAN; MICE; ALPHA-V-BETA-3 C1 [Jones, Jeffrey A.] Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg Res, Strom Thurmond Res Bldg, Charleston, SC 29425 USA. [Jones, Jeffrey A.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Strom Thurmond Res Bldg, Charleston, SC 29425 USA. RP Jones, JA (reprint author), Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg Res, Strom Thurmond Res Bldg, Charleston, SC 29425 USA.; Jones, JA (reprint author), Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Strom Thurmond Res Bldg, Charleston, SC 29425 USA. EM jonesja@musc.edu FU BLRD VA [I01 BX000904] NR 35 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JUL PY 2016 VL 26 IS 5 BP 429 EP 432 DI 10.1016/j.tcm.2016.02.005 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DP7FD UT WOS:000378663700006 PM 27013137 ER PT J AU Atkinson, W Catana, C Abramson, JS Arabasz, G McDermott, S Catalano, O Muse, V Blake, MA Barnes, J Shelly, M Hochberg, E Rosen, BR Guimaraes, AR AF Atkinson, Wendy Catana, Ciprian Abramson, Jeremy S. Arabasz, Grae McDermott, Shanaugh Catalano, Onofrio Muse, Victorine Blake, Michael A. Barnes, Jeffrey Shelly, Martin Hochberg, Ephraim Rosen, Bruce R. Guimaraes, Alexander R. TI Hybrid FDG-PET/MR compared to FDG-PET/CT in adult lymphoma patients SO ABDOMINAL RADIOLOGY LA English DT Article DE PET/MRI; FDG; Lymphoma; Diffusion weighted imaging; SUV ID APPARENT DIFFUSION-COEFFICIENT; POSITRON-EMISSION-TOMOGRAPHY; STANDARDIZED UPTAKE VALUES; NON-HODGKINS-LYMPHOMA; SQUAMOUS-CELL CARCINOMA; WHOLE-BODY PET/CT; WEIGHTED MRI; MALIGNANT-LYMPHOMA; ATTENUATION CORRECTION; CLINICAL-EXPERIENCE AB The goal of this study is to evaluate the diagnostic performance of simultaneous FDG-PET/MR including diffusion compared to FDG-PET/CT in patients with lymphoma. Eighteen patients with a confirmed diagnosis of non-Hodgkin's (NHL) or Hodgkin's lymphoma (HL) underwent an IRB-approved, single-injection/dual-imaging protocol consisting of a clinical FDG-PET/CT and subsequent FDG-PET/MR scan. PET images from both modalities were reconstructed iteratively. Attenuation correction was performed using low-dose CT data for PET/CT and Dixon-MR sequences for PET/MR. Diffusion-weighted imaging was performed. SUVmax was measured and compared between modalities and the apparent diffusion coefficient (ADC) using ROI analysis by an experienced radiologist using OsiriX. Strength of correlation between variables was measured using the Pearson correlation coefficient (r (p)). Of the 18 patients included in this study, 5 had HL and 13 had NHL. The median age was 51 +/- 14.8 years. Sixty-five FDG-avid lesions were identified. All FDG-avid lesions were visible with comparable contrast, and therefore initial and follow-up staging was identical between both examinations. SUVmax from FDG-PET/MR [(mean +/- sem) (21.3 +/- 2.07)] vs. FDG-PET/CT (mean 23.2 +/- 2.8) demonstrated a strongly positive correlation [r (s) = 0.95 (0.94, 0.99); p < 0.0001]. There was no correlation found between ADC(min) and SUVmax from FDG-PET/MR [r = 0.17(-0.07, 0.66); p = 0.09]. FDG-PET/MR offers an equivalent whole-body staging examination as compared with PET/CT with an improved radiation safety profile in lymphoma patients. Correlation of ADC to SUVmax was weak, understating their lack of equivalence, but not undermining their potential synergy and differing importance. C1 [Atkinson, Wendy; Catana, Ciprian; Arabasz, Grae; Catalano, Onofrio; Rosen, Bruce R.; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Abramson, Jeremy S.; Barnes, Jeffrey; Hochberg, Ephraim] Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. [Muse, Victorine] Massachusetts Gen Hosp, Dept Radiol, Div Thorac Radiol, Boston, MA 02114 USA. [McDermott, Shanaugh; Blake, Michael A.; Shelly, Martin; Guimaraes, Alexander R.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA. [Guimaraes, Alexander R.] Oregon Hlth & Sci Univ, Div Body Imaging, Dept Diagnost Radiol, 3181 SW Sam Jackson Pk Rd,Mail Code L340, Portland, OR 97239 USA. RP Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA.; Guimaraes, AR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA.; Guimaraes, AR (reprint author), Oregon Hlth & Sci Univ, Div Body Imaging, Dept Diagnost Radiol, 3181 SW Sam Jackson Pk Rd,Mail Code L340, Portland, OR 97239 USA. EM guimaraa@ohsu.edu NR 56 TC 2 Z9 2 U1 2 U2 4 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 JUL PY 2016 VL 41 IS 7 BP 1338 EP 1348 DI 10.1007/s00261-016-0638-6 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8XR UT WOS:000378781800016 PM 27315095 ER PT J AU Leibovici, V Keuthen, NJ AF Leibovici, Vera Keuthen, Nancy J. TI SENSE OF TENSION BEFORE PICKING AND RELIEF DURING OR AFTER PICKING IN ISRAELI ADULTS SCREENING POSITIVE FOR EXCORIATION (SKIN PICKING) DISORDER SO ACTA DERMATO-VENEREOLOGICA LA English DT Meeting Abstract C1 Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 EI 1651-2057 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PD JUL PY 2016 VL 96 SU 217 MA PL26 BP 124 EP 124 PG 1 WC Dermatology SC Dermatology GA DQ0FJ UT WOS:000378873700052 ER PT J AU Sher, L AF Sher, L. TI Buprenorphine and the treatment of depression, anxiety, non-suicidal self-injury, and suicidality SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Letter C1 [Sher, L.] James J Peters Vet Adm Med Ctr, New York, NY USA. [Sher, L.] Icahn Sch Med Mt Sinai, New York, NY 10029 USA. RP Sher, L (reprint author), James J Peters Vet Adm Med Ctr, New York, NY USA.; Sher, L (reprint author), Icahn Sch Med Mt Sinai, New York, NY 10029 USA. EM leo.sher@mssm.edu NR 5 TC 1 Z9 1 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0001-690X EI 1600-0447 J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JUL PY 2016 VL 134 IS 1 BP 84 EP 85 DI 10.1111/acps.12577 PG 2 WC Psychiatry SC Psychiatry GA DP7UZ UT WOS:000378706000011 PM 27009622 ER PT J AU Denburg, A Galindo, CR Joffe, S AF Denburg, Avram Galindo, Carlos Rodriguez Joffe, Steven TI Trials Infrastructure as Good Old-Fashioned Health System Strengthening SO AMERICAN JOURNAL OF BIOETHICS LA English DT Letter ID MIDDLE-INCOME COUNTRIES; CLINICAL-TRIALS; CARE C1 [Denburg, Avram] Hosp Sick Children, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. [Denburg, Avram] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Galindo, Carlos Rodriguez] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joffe, Steven] Univ Penn, Philadelphia, PA 19104 USA. RP Denburg, A (reprint author), Hosp Sick Children, Haematol Oncol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM avram.denburg@sickkids.ca OI Denburg, Avram/0000-0003-0039-0742 NR 8 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 1526-5161 EI 1536-0075 J9 AM J BIOETHICS JI Am. J. Bioeth. PD JUL PY 2016 VL 16 IS 7 BP W3 EP W5 DI 10.1080/15265161.2016.1180465 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA DP5VS UT WOS:000378566900002 PM 27292865 ER PT J AU Lewiss, RE Adhikari, S Carmody, K Fields, JM Hunt, P Liteplo, AS Nagdev, A Raio, C Gaspari, R AF Lewiss, Resa E. Adhikari, Srikar Carmody, Kristin Fields, J. Matthew Hunt, Patrick Liteplo, Andrew S. Nagdev, Arun Raio, Christopher Gaspari, Romolo TI The Society of Clinical Ultrasound Fellowships: An innovation in the point of care ultrasound fellowship application process SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Letter C1 [Lewiss, Resa E.] Univ Colorado, Sch Med, Dept Emergency Med, Aurora, CO USA. [Adhikari, Srikar] Univ Arizona, Dept Emergency Med, Tucson, AZ USA. [Carmody, Kristin] NYU, Sch Med, Dept Emergency Med, New York, NY USA. [Fields, J. Matthew] Thomas Jefferson Univ, Dept Emergency Med, Philadelphia, PA 19107 USA. [Hunt, Patrick] Univ S Carolina, Dept Emergency Med, Columbia, SC 29208 USA. [Liteplo, Andrew S.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Nagdev, Arun] Alameda Hlth Syst, Dept Emergency Med, Oakland, CA USA. [Raio, Christopher] Good Samaritan Hosp, Med Ctr, Dept Emergency Med, West Islip, NY USA. [Gaspari, Romolo] Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. RP Lewiss, RE (reprint author), Leprino Bldg,12401 East 17th Ave Box B215, Aurora, CO 80045 USA. EM Resa.Lewiss@ucdenver.edu OI Carmody, Kristin/0000-0003-1223-5280 NR 4 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 0735-6757 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JUL PY 2016 VL 34 IS 7 BP 1303 EP 1305 DI 10.1016/j.ajem.2016.03.070 PG 5 WC Emergency Medicine SC Emergency Medicine GA DP9HR UT WOS:000378807800023 PM 27131632 ER PT J AU Baltajian, K Bajracharya, S Salahuddin, S Berg, AH Geahchan, C Wenger, JB Thadhani, R Karumanchi, SA Rana, S AF Baltajian, Kedak Bajracharya, Surichhya Salahuddin, Saira Berg, Anders H. Geahchan, Carl Wenger, Julia B. Thadhani, Ravi Karumanchi, S. Ananth Rana, Sarosh TI Sequential plasma angiogenic factors levels in women with suspected preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE angiogenic factors; preeclampsia; sequential changes; adverse outcomes ID LATE-ONSET PREECLAMPSIA; HYPERTENSION; ENDOTHELIUM; ECLAMPSIA; OUTCOMES; REMOVAL AB BACKGROUND: Alterations in circulating angiogenic factors are associated with the diagnosis of preeclampsia and correlate with adverse perinatal outcomes during the third trimester. OBJECTIVE: Analysis of the sequential levels of plasma angiogenic factors among patients admitted for evaluation of preeclampsia. STUDY DESIGN: We performed an observational study among women with singleton pregnancies admitted to Beth Israel Deaconess Medical Center, Boston, Massachusetts, for evaluation of preeclampsia at less than 37 weeks of gestation. Plasma samples were collected on admission and daily for the first 3 days and then weekly until delivery. Doppler ultrasound was performed on admission (within 48 hours) and then weekly (within 24 hours of blood collection) to evaluate uteroplacental and umbilical blood flows. Maternal demographics, hospital course, mode of delivery, diagnosis of hypertensive disorder, adverse maternal outcomes (elevated liver function enzymes, low platelet count, pulmonary edema, cerebral hemorrhage, convulsion, acute renal insufficiency, or maternal death), and adverse fetal/neonatal outcomes (small for gestational age, abnormal umbilical artery Doppler, fetal death, and neonatal death) were recorded. Circulating angiogenic factors (soluble fms-like tyrosine kinase and placental growth factor were measured on automated platform in a single batch after delivery and in a blinded fashion. Data are presented as median (25th to 75th centile), mean, or proportions as appropriate. RESULTS: During the study period, data from 100 women were analyzed for the study, and 43 had adverse outcomes. Women with adverse outcomes had lower gestational age of delivery, higher systolic and diastolic blood pressures during hospitalization, and lower birthweight and placental weight (all P < .01). These patients had higher soluble fms-like tyrosine kinase and soluble fms-like tyrosine kinase/placental growth factor ratio on admission and continued to have an increase in levels throughout hospital course. The median (25th to 75th) soluble fms-like tyrosine kinase/placental growth factor ratio among patients with adverse outcomes was 205.9 (72.5, 453.1) versus 47.5 (9.7, 87.0) among women without adverse outcomes (P < .001). The median (25th to 75th) absolute change per day in soluble fms-like tyrosine kinase levels (pg/mL) was 491.0 pg/mL (120.3, 1587.2) among women with adverse outcomes versus 81.3 pg/mL (-177.9, 449.0) among women without adverse outcomes (P = .01). Similarly the absolute change per day for soluble fms-like tyrosine kinase/placental growth factor ratio was 15.1 (1.8, 58.1) versus 2.7 (-0.6, 8.3) between the two groups (P = .004). The mean (range) days from admission to delivery was 6 (0-35) among subjects with soluble fms-like tyrosine kinase/placental growth factor ratio >= 85 and 14 (0-39) below a ratio of 85 (P<.001). The positive predictive value for plasma soluble fms-like tyrosine kinase/placental growth factor ratio >= 85 at admission for indicated delivery within 2 weeks was 91% (83-99%). Admission plasma soluble fms-like tyrosine kinase/placental growth factor ratio positively correlated with pre-delivery uterine artery resistive index (r = 0.35; P = .004). CONCLUSION: Among women admitted for evaluation of preeclampsia, women at risk for adverse pregnancy outcomes have higher soluble fms-like tyrosine kinase/placental growth factor ratio on admission, which continued to rise until delivery. Women with high soluble fms-like tyrosine kinase/placental growth factor ratios delivered sooner than women with low soluble fms-like tyrosine kinase/placental growth factor levels. These data support the hypothesis that targeting angiogenic imbalance in preeclampsia may lead to prolongation of pregnancy. C1 [Baltajian, Kedak; Bajracharya, Surichhya; Salahuddin, Saira; Geahchan, Carl; Karumanchi, S. Ananth; Rana, Sarosh] Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA. [Baltajian, Kedak; Bajracharya, Surichhya; Salahuddin, Saira; Berg, Anders H.; Geahchan, Carl; Wenger, Julia B.; Thadhani, Ravi; Karumanchi, S. Ananth; Rana, Sarosh] Harvard Univ, Sch Med, Boston, MA USA. [Berg, Anders H.] Beth Israel Deaconess Med Ctr, Dept Pathol, 330 Brookline Ave, Boston, MA 02215 USA. [Wenger, Julia B.; Thadhani, Ravi] Massachusetts Gen Hosp, Dept Med, Div Nephrol, Boston, MA 02114 USA. [Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. [Rana, Sarosh] Univ Chicago, Dept Obstet & Gynecol, Maternal Fetal Med, Chicago, IL 60637 USA. RP Rana, S (reprint author), Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Div Maternal Fetal Med, Boston, MA 02215 USA.; Rana, S (reprint author), Harvard Univ, Sch Med, Boston, MA USA.; Rana, S (reprint author), Univ Chicago, Dept Obstet & Gynecol, Maternal Fetal Med, Chicago, IL 60637 USA. EM srana@bsd.uchicago.edu FU American Heart Association (AHA); K24 award from the NIH; Howard Hughes Medical Institute FX Supported by the American Heart Association (AHA) grant given to S.R. AHA had no 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 article for publication. R.T. is supported by K24 award from the NIH; S.A.K was supported by Howard Hughes Medical Institute. NR 26 TC 0 Z9 1 U1 7 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2016 VL 215 IS 1 AR 89.e1-e10 DI 10.1016/j.ajog.2016.01.168 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA DP6SV UT WOS:000378630000020 PM 26827880 ER PT J AU Strittmatter, K Pomeroy, H Marneros, AG AF Strittmatter, Karin Pomeroy, Hayley Marneros, Alexander G. TI Targeting Platelet-Derived Growth Factor Receptor beta(+) Scaffold Formation Inhibits Choroidal Neovascularization SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VEGF-A; MACULAR DEGENERATION; THERAPY; MICE AB Neovascular age-related macular degeneration is among the most common causes of irreversible blindness and manifests with choroidal neovascularization (CNV). Anti-vascular endothelial growth factor-A therapies are only partially effective and their chronic administration may impair functions of the choriocapillaris and retina. Thus, novel therapeutic targets are needed urgently. We have observed in a laser-induced model of CNV that a platelet-derived growth factor receptor beta positive (PDGFR beta(+)) scaffold is formed before infiltration of neovessels into this scaffold to form CNV lesions, and that this scaffold limits the extent of neovascularization. Based on these observations we hypothesized that ablation of proliferating PDGFR beta(+) cells to prevent the formation of this scaffold might inhibit CNV growth and present a novel therapeutic approach for neovascular age-related macular degeneration. To test this hypothesis we targeted proliferating PDGFR beta(+) cells through independent distinct approaches after laser injury: i) by using an inducible genetic model to inhibit specifically proliferating PDGFR beta cells, ii) by treating mice with a neutralizing anti-PDGFR beta antibody, iii) by administering an anti-PDGF-AB/BB aptamer, and iv) by using small chemical inhibitor approaches. The results show that therapeutic targeting of proliferating PDGFR beta(+) cells potently inhibits the formation of the pericyte-like scaffold, with concomitant attenuation of CNV. Moreover, we show that early inhibition of PDGFR beta cell proliferation before neovessel formation is sufficient to inhibit scaffold formation and neovascularization. C1 [Marneros, Alexander G.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, CNY 149,Rm 3-216,13th St, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Marneros, AG (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, CNY 149,Rm 3-216,13th St, Charlestown, MA 02129 USA. EM amarneros@mgh.harvard.edu FU Ophthotech Corporation FX Supported by a grant from Ophthotech Corporation. NR 15 TC 2 Z9 2 U1 3 U2 6 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 JUL PY 2016 VL 186 IS 7 BP 1890 EP 1899 DI 10.1016/j.ajpath.2016.02.018 PG 10 WC Pathology SC Pathology GA DP8OV UT WOS:000378758400016 PM 27338108 ER PT J AU Greenwald, SH Charette, JR Staniszewska, M Shi, LY Brown, SDM Stone, L Liu, Q Hicks, WL Collin, GB Bowl, MR Krebs, MP Nishina, PM Pierce, EA AF Greenwald, Scott H. Charette, Jeremy R. Staniszewska, Magdalena Shi, Lan Ying Brown, Steve D. M. Stone, Lisa Liu, Qin Hicks, Wanda L. Collin, Gayle B. Bowl, Michael R. Krebs, Mark P. Nishina, Patsy M. Pierce, Eric A. TI Mouse Models of NMNAT1-Leber Congenital Amaurosis (LCA9) Recapitulate Key Features of the Human Disease SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PUPILLARY LIGHT RESPONSES; APOPTOSIS-INDUCING FACTOR; GENE-THERAPY; WALLERIAN DEGENERATION; RETINAL DEGENERATION; MONONUCLEOTIDE ADENYLYLTRANSFERASE; CONE ELECTRORETINOGRAM; KNOCKOUT MICE; CELL-DEATH; MELANOPSIN AB The nicotinamide nucleotide adenylyltransferase 1 (NMNAT1) enzyme is essential for regenerating the nuclear pool of NAD(+) in all nucleated cells in the body, and mounting evidence also suggests that it has a separate role in neuroprotection. Recently, mutations in the NMNAT1 gene were associated with Leber congenital amaurosis, a severe retinal degenerative disease that causes blindness during infancy. Availability of a reliable mammalian model of NMNAT1-Leber congenital amaurosis would assist in determining the mechanisms through which disruptions in NMNAT1 lead to retinal cell degeneration and would provide a resource for testing treatment options. To this end, we identified two separate N-ethyl-N-nitrosourea-generated mouse lines that harbor either a p.V9M or a p.D243G mutation. Both mouse models recapitulate key aspects of the human disease and confirm the pathogenicity of mutant NMNAT1. Homozygous Nmnat1 mutant mice develop a rapidly progressing chorioretinal disease that begins with photoreceptor degeneration and includes attenuation of the retinal vasculature, optic atrophy, and retinal pigment epithelium Loss. Retinal function deteriorates in both mouse lines, and, in the more rapidly progressing homozygous Nmnat1(V9M) mutant mice, the electroretinogram becomes undetectable and the pupillary light response weakens. These mouse models offer an opportunity for investigating the cellular mechanisms underlying disease pathogenesis, evaluating potential therapies for NMNAT1-Leber congenital amaurosis, and conducting in situ studies on NMNAT1 function and NAD+ metabolism. C1 [Greenwald, Scott H.; Staniszewska, Magdalena; Liu, Qin; Pierce, Eric A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Sch Med,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. [Charette, Jeremy R.; Shi, Lan Ying; Stone, Lisa; Hicks, Wanda L.; Collin, Gayle B.; Krebs, Mark P.; Nishina, Patsy M.] Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. [Brown, Steve D. M.; Bowl, Michael R.] MRC, Mammalian Genet Unit, Harwell Campus, London W1N 4AL, Oxon, England. RP Pierce, EA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Ocular Genom Inst, Sch Med,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM eric_pierce@meei.harvard.edu OI Krebs, Mark/0000-0001-9017-6066; Pierce, Eric/0000-0002-2354-4102 FU NIH/National Eye Institute [EY012910, 5T32 EY-007145-16, EY016501, P30 EY003790, P30 EY014104]; Foundation for Retinal Research/Gavin R. Stevens Foundation; Fight for Sight [PD15001]; NIH/National Cancer Institute [CA34196] FX Supported by NIH/National Eye Institute grants EY012910 (E.A.P.), 5T32 EY-007145-16 (S.H.G.), EY016501 (P.M.N.), P30 EY003790 (Schepens Ophthalmology Core), P30 EY014104 (Massachusetts Eye and Ear Infirmary Ophthalmology Core); the Foundation for Retinal Research/Gavin R. Stevens Foundation (E.A.P.); Fight for Sight (PD15001; S.H.G.); and NIH/National Cancer Institute grant CA34196 (The Jackson Laboratory). NR 80 TC 0 Z9 0 U1 1 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 JUL PY 2016 VL 186 IS 7 BP 1925 EP 1938 DI 10.1016/j.ajpath.2016.03.013 PG 14 WC Pathology SC Pathology GA DP8OV UT WOS:000378758400019 PM 27207593 ER PT J AU Ho, JE Gao, W Levy, D Santhanakrishnan, R Araki, T Rosas, IO Hatabu, H Latourelle, JC Nishino, M Dupuis, J Washko, GR O'Connor, GT Hunninghake, GM AF Ho, Jennifer E. Gao, Wei Levy, Daniel Santhanakrishnan, Rajalakshmi Araki, Tetsuro Rosas, Ivan O. Hatabu, Hiroto Latourelle, Jeanne C. Nishino, Mizuki Dupuis, Josee Washko, George R. O'Connor, George T. Hunninghake, Gary M. TI Galectin-3 Is Associated with Restrictive Lung Disease and Interstitial Lung Abnormalities SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE biomarker; epidemiology; interstitial lung disease; pulmonary fibrosis ID IDIOPATHIC PULMONARY-FIBROSIS; HEART-FAILURE; PROGNOSTIC VALUE; INFLAMMATION; EXPRESSION; PNEUMONIA; MACROPHAGES; COMMUNITY; PROTEIN; MARKER AB Rationale: Galectin-3 (Gal-3) has been implicated in the development of pulmonary fibrosis in experimental studies, and Gal-3 levels have been found to be elevated in small studies of human pulmonary fibrosis. Objectives: We sought to study whether circulating Gal-3 concentrations are elevated early in the course of pulmonary fibrosis. Methods: We examined 2,596 Framingham Heart Study participants (mean age, 57 yr; 54% women; 14% current smokers) who underwent Gal-3 assessment using plasma samples and pulmonary function testing between 1995 and 1998. Of this sample, 1,148 underwent subsequent volumetric chest computed tomography. Measurements and Main Results: Higher Gal-3 concentrations were associated with lower lung volumes (1.4% decrease in percentage of predicted FEV1 per 1 SD increase in log Gal-3; 95% confidence interval [CI], 0.8-2.0%; P < 0.001; 1.2% decrease in percentage of predicted FVC; 95% CI, 0.6-1.8%; P < 0.001) and decreased diffusing capacity of the lung for carbon monoxide (2.1% decrease; 95% CI, 1.3-2.9%; P < 0.001). These associations remained significant after multivariable adjustment (P <= 0.008 for all). Compared with the lowest quartile, participants in the highest Gal-3 quartile were more than twice as likely to have interstitial lung abnormalities visualized by computed tomography (multivariable-adjusted odds ratio, 2.67; 95% CI, 1.49-4.76; P < 0.001). Conclusions: Elevated Gal-3 concentrations are associated with interstitial lung abnormalities coupled with a restrictive pattern, including decreased lung volumes and altered gas exchange. These findings suggest a potential role for Gal-3 in early stages of pulmonary fibrosis. C1 [Ho, Jennifer E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. [Ho, Jennifer E.; Levy, Daniel; Dupuis, Josee; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Gao, Wei; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Levy, Daniel] NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA. [Santhanakrishnan, Rajalakshmi] Boston Univ, Sch Med, Dept Med, Cardiovasc Med Sect, Boston, MA 02118 USA. [Latourelle, Jeanne C.; O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Latourelle, Jeanne C.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. [Araki, Tetsuro; Hatabu, Hiroto; Nishino, Mizuki; Washko, George R.; Hunninghake, Gary M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Pulm Funct Imaging, Boston, MA 02115 USA. [Araki, Tetsuro; Hatabu, Hiroto; Nishino, Mizuki] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Rosas, Ivan O.; Washko, George R.; Hunninghake, Gary M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Pulm & Crit Care Div, Boston, MA 02115 USA. RP Ho, JE (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, CPZN 185 Cambridge St 3224, Boston, MA 02114 USA. EM jho1@mgh.harvard.edu FU NHLBI's Framingham Heart Study [N01-HC-25195, HHSN268201500001I]; National Institutes of Health [NIH] [R01 HL111024, K23-HL116780, 5K23-CA157631, R01 HL107246, R01 HL116473, R01 HL122464, P01 HL114501]; Boston University School of Medicine, Department of Medicine Career Investment Award FX This work was partially supported by the NHLBI's Framingham Heart Study (contract numbers N01-HC-25195 and HHSN268201500001I, and National Institutes of Health [NIH] grant R01 HL111024); NIH grants K23-HL116780 (J.E.H.), 5K23-CA157631 (M.N.), R01 HL107246 (G.R.W.), R01 HL116473 (G.R.W.), R01 HL122464 (G.R.W.), P01 HL114501 (I.O.R. and G.M.H.), and R01 HL111024 (G.M.H.); and a Boston University School of Medicine, Department of Medicine Career Investment Award (J.E.H.). Galectin-3 assays were provided by BG Medicine (Waltham, MA). NR 40 TC 5 Z9 5 U1 1 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 1 PY 2016 VL 194 IS 1 BP 77 EP 83 DI 10.1164/rccm.201509-1753OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA DQ1RW UT WOS:000378979100015 PM 26771117 ER PT J AU Howard, SAH Krajewski, KM Jagannathan, JP Braschi-Amirfarzan, M Tirumani, SH Shinagare, AB Ramaiya, NH AF Howard, Stephanie A. Holler Krajewski, Katherine M. Jagannathan, Jyothi P. Braschi-Amirfarzan, Marta Tirumani, Sree H. Shinagare, Atul B. Ramaiya, Nikhil H. TI A New Look at Toxicity in the Era of Precision Oncology: Imaging Findings, Their Relationship With Tumor Response, and Effect on Metastasectomy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE adverse events; biomarker; metastasectomy; toxicity ID METASTATIC COLORECTAL-CANCER; RENAL-CELL CARCINOMA; LONG-TERM SURVIVAL; LIVER RESECTION; HEPATIC RESECTION; TARGETED THERAPY; ADVERSE EVENTS; RADIOLOGIC MANIFESTATIONS; HEPATOCELLULAR-CARCINOMA; BEVACIZUMAB TREATMENT AB OBJECTIVE. As cancer care becomes increasingly personalized and patients with metastatic disease live longer, oncologists' approach to drug toxicity is also evolving. CONCLUSION. This article aims to broaden the radiologist's understanding of imaging-evident toxicity by describing how oncologists grade toxicity, exploring toxicity as a biomarker of treatment response, discussing the effect of toxicity in patients who are candidates for metastasectomy, and illustrating how combining drugs of varying classes amplifies toxicity. C1 [Howard, Stephanie A. Holler; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Braschi-Amirfarzan, Marta; Tirumani, Sree H.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02115 USA. [Howard, Stephanie A. Holler; Krajewski, Katherine M.; Jagannathan, Jyothi P.; Braschi-Amirfarzan, Marta; Tirumani, Sree H.; Shinagare, Atul B.; Ramaiya, Nikhil H.] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. RP Howard, SAH (reprint author), Dana Farber Canc Inst, Dept Radiol, 450 Brookline Ave, Boston, MA 02115 USA.; Howard, SAH (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM sahoward@partners.org NR 66 TC 1 Z9 1 U1 0 U2 2 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 JUL PY 2016 VL 207 IS 1 BP 4 EP 14 DI 10.2214/AJR.15.15480 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP7DE UT WOS:000378658500009 PM 27065346 ER PT J AU Chesebro, AL Chikarmane, SA Gombos, EC Giardino, AA AF Chesebro, Allyson L. Chikarmane, Sona A. Gombos, Eva C. Giardino, Angela A. TI Radiation-Associated Angiosarcoma of the Breast: What the Radiologist Needs to Know SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Review DE angiosarcoma; breast; radiation ID CUTANEOUS ANGIOSARCOMA; IMAGING FINDINGS; SECONDARY ANGIOSARCOMA; LOCAL EXCISION; POOR SURVIVAL; CANCER; RADIOTHERAPY; THERAPY; RISK; CARCINOMA AB OBJECTIVE. The purpose of this article is to describe the diagnosis, treatment, and follow-up of radiation-associated angiosarcoma (RAS) of the breast. CONCLUSION. Radiologists play an important role in the diagnosis of RAS, which may initially present clinically as erythema, ecchymosis, or skin thickening. Conventional imaging with mammography and ultrasound is less sensitive than MRI for the diagnosis of RAS. Follow-up CT is important to monitor treatment response. C1 [Chesebro, Allyson L.; Chikarmane, Sona A.; Gombos, Eva C.; Giardino, Angela A.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Chesebro, Allyson L.; Chikarmane, Sona A.; Gombos, Eva C.; Giardino, Angela A.] Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. RP Chesebro, AL (reprint author), Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA.; Chesebro, AL (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM allyson.chesebro@gmail.com NR 42 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 JUL PY 2016 VL 207 IS 1 BP 217 EP 225 DI 10.2214/AJR.15.15888 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP7DE UT WOS:000378658500036 PM 27099969 ER PT J AU Johnson, SD Levingston, C Young, MRI AF Johnson, Sara D. Levingston, Corinne Young, M. Rita I. TI Premalignant Oral Lesion Cells Elicit Increased Cytokine Production and Activation of T-cells SO ANTICANCER RESEARCH LA English DT Article DE head and neck cancer; premalignant oral lesions; cytokines; T cell activation ID UPPER AERODIGESTIVE TRACT; NECK-CANCER; HEAD; CARCINOMA; MECHANISMS; IL-6; CARCINOGENESIS; PROGRESSION; DISEASE; CAVITY AB Background: Head and neck squamous cell carcinomas (HNSCC) are known to evade the host immune response. How premalignant oral lesions modulate the immune response, however, has yet to be elucidated. Materials and Methods: A mouse model of oral carcinogenesis was used to determine how mediators from premalignant oral lesion cells vs. HNSCC cells impact on immune cytokine production and activation. Results: Media conditioned by premalignant lesion cells elicited an increased production of T cell-associated cytokines and proinflammatory mediators from cervical lymph node cells compared to media conditioned by HNSCC cells or media alone. In the presence of premalignant lesion cell-conditioned media, CD4(+) T cell expression of the IL-2 receptor CD25 and CD8(+) T cell expression of the activation marker CD69 was greater, compared to what was induced in HNSCC cell-conditioned media or media alone. Conclusion: Premalignant lesion cells promote a proinflammatory environment and induce immune changes before HNSCC tumors are established. C1 [Johnson, Sara D.; Levingston, Corinne; Young, M. Rita I.] Res Serv 151 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. [Johnson, Sara D.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Johnson, Sara D.; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. [Young, M. Rita I.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Clinical Sciences Research and Development Program of the Department of Veterans Affairs [I01-CX000851]; National Institutes of Health [RO1-CA128837] FX This work was supported by the Clinical Sciences Research and Development Program (I01-CX000851) of the Department of Veterans Affairs and by grants from the National Institutes of Health (RO1-CA128837) (MRIY). NR 39 TC 1 Z9 1 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 EI 1791-7530 J9 ANTICANCER RES JI Anticancer Res. PD JUL PY 2016 VL 36 IS 7 BP 3261 EP 3270 PG 10 WC Oncology SC Oncology GA DQ0DC UT WOS:000378867600004 PM 27354582 ER PT J AU Battista, MC Boutin, M Venne, P Blais, L Berard, A Lacroix, M Patenaude, J Guillemette, L Cossette, B Hivert, MF Auray-Blais, C AF Battista, Marie-Claude Boutin, Michel Venne, Philippe Blais, Lucie Berard, Anick Lacroix, Marilyn Patenaude, Julie Guillemette, Laetitia Cossette, Benoit Hivert, Marie-France Auray-Blais, Christiane TI Maternal inhaled fluticasone propionate intake during pregnancy is detected in neonatal cord blood SO BIOANALYSIS LA English DT Article DE asthma; cord blood; fluticasone propionate; pregnancy; UPLC-MS/MS ID TANDEM MASS-SPECTROMETRY; BUDESONIDE FOLLOWING INHALATION; DRY-POWDER INHALERS; FABRY-DISEASE; LC-MS/MS; INTRANASAL CORTICOSTEROIDS; PLASMA-CONCENTRATIONS; MULTIPLEX ANALYSIS; ASTHMA; SALMETEROL AB Background: Despite recommendations to use inhaled corticosteroids as treatment to control asthma during pregnancy, it is unknown whether inhaled fluticasone propionate (FP) reaches the fetus. Results & methodology: We collected maternal blood on the morning following delivery. FP was detected by ultra-performance LC-MS/MS (UPLC-MS/MS) in 9/17 asthmatic women using FP. Delay between last FP inhalation and maternal blood sampling ranged between 3 and 33 h and FP was detected in a range of 1.572-46.440 pg/ml. Among the nine offspring of these FP users, FP was detected in five cord blood samples. Delay between last predelivery FP inhalation and cord blood sampling ranged from 4 to 20 h and FP was detected in a range of 0.423-4.510 pg/ml. Conclusion: Our findings demonstrate placental passage of inhaled FP. C1 [Battista, Marie-Claude; Lacroix, Marilyn; Patenaude, Julie; Guillemette, Laetitia; Hivert, Marie-France] Univ Sherbrooke, Div Endocrinol, Dept Med, Fac Med & Hlth Sci, Sherbrooke, PQ J1K 2R1, Canada. [Boutin, Michel; Venne, Philippe; Auray-Blais, Christiane] Univ Sherbrooke, Dept Pediat, Fac Med & Hlth Sci, Div Med Genet, Sherbrooke, PQ J1K 2R1, Canada. [Blais, Lucie; Cossette, Benoit; Hivert, Marie-France; Auray-Blais, Christiane] CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ J1H 5N4, Canada. [Blais, Lucie; Berard, Anick; Cossette, Benoit] Univ Montreal, Fac Pharm, Quebec City, PQ, Canada. [Blais, Lucie] Hop Sacre Coeur Montreal, Res Ctr, Quebec City, PQ, Canada. [Berard, Anick] CHU Ste Justine, Res Ctr, Montreal, PQ, Canada. [Cossette, Benoit] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Pharm, Sherbrooke, PQ J1K 2R1, Canada. [Hivert, Marie-France] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Hivert, Marie-France] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hivert, MF (reprint author), Univ Sherbrooke, Div Endocrinol, Dept Med, Fac Med & Hlth Sci, Sherbrooke, PQ J1K 2R1, Canada.; Auray-Blais, C (reprint author), Univ Sherbrooke, Dept Pediat, Fac Med & Hlth Sci, Div Med Genet, Sherbrooke, PQ J1K 2R1, Canada.; Hivert, MF; Auray-Blais, C (reprint author), CHU Sherbrooke, Ctr Rech, Sherbrooke, PQ J1H 5N4, Canada.; Hivert, MF (reprint author), Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.; Hivert, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM marie-france_hivert@harvardpilgrim.org; christiane.auray-blais@usherbrooke.ca FU 'Fonds de Recherche du Quebec - Sante' (FRQS); Le Reseau Quebecois de Recherche sur les Medicaments FX This study was conducted at the CR-CHUS which is a 'Fonds de Recherche du Quebec - Sante' (FRQS) supported research center. This study was supported by 'Le Reseau Quebecois de Recherche sur les Medicaments.' A Berard holds a "Chaire FRQ-S" on Medications and Pregnancy. 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 37 TC 0 Z9 0 U1 3 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD JUL PY 2016 VL 8 IS 14 BP 1441 EP 1450 DI 10.4155/bio-2016-0065 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA DP9EV UT WOS:000378800400003 ER PT J AU Flowers, CR Costa, LJ Pasquini, MC Le-Rademacher, J Lill, M Shore, TB Vaughan, W Craig, M Freytes, CO Shea, TC Horwitz, ME Fay, JW Mineishi, S Rondelli, D Mason, J Braunschweig, I Ai, WY Yeh, RF Rodriguez, TE Flinn, I Comeau, T Yeager, AM Pulsipher, MA Bence-Bruckler, I Laneuyille, P Bierman, P Chen, AI Kato, K Wang, YL Xu, C Smith, AJ Waller, EK AF Flowers, Christopher R. Costa, Luciano J. Pasquini, Marcelo C. Le-Rademacher, Jennifer Lill, Michael Shore, Tsiporah B. Vaughan, William Craig, Michael Freytes, Cesar O. Shea, Thomas C. Horwitz, Mitchell E. Fay, Joseph W. Mineishi, Shin Rondelli, Damiano Mason, James Braunschweig, Ira Ai, Weiyun Yeh, Rosa F. Rodriguez, Tulio E. Flinn, Ian Comeau, Terrance Yeager, Andrew M. Pulsipher, Michael A. Bence-Bruckler, Isabelle Laneuyille, Pierre Bierman, Philip Chen, Andy I. Kato, Kazunobu Wang, Yanlin Xu, Cong Smith, Angela J. Waller, Edmund K. TI Efficacy of Pharmacokinetics-Directed Busulfan, Cyclophosphamide, and Etoposide Conditioning and Autologous Stem Cell Transplantation for Lymphoma: Comparison of a Multicenter Phase II Study and CIBMTR Outcomes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Non-Hodgkin lymphoma; Hodgkin lymphoma; Busulfan; Autologous stem cell transplantation; Stem cell transplantation; Lymphoma; Chemotherapy ID HIGH-DOSE CHEMOTHERAPY; NON-HODGKINS-LYMPHOMA; BONE-MARROW-TRANSPLANTATION; DAILY INTRAVENOUS BUSULFAN; HIGH-RISK PATIENTS; DAILY IV BUSULFAN; PREPARATIVE REGIMENS; AGGRESSIVE LYMPHOMA; BEAM CHEMOTHERAPY; RANDOMIZED-TRIAL AB Busulfan, cyclophosphamide, and etoposide (BuCyE) is a commonly used conditioning regimen for autologous stem cell transplantation (ASCT). This multicenter, phase II study examined the safety and efficacy of BuCyE with individually adjusted busulfan based on preconditioning pharmacokinetics. The study initially enrolled Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) patients ages 18 to 80 years but was amended, due to high early treatment-related mortality (TRM) in patients > 65 years. BuCyE outcomes were compared with contemporaneous recipients of carmustine, etoposide, cytarabine, and melphalan (BEAM) from the Center for International Blood and Marrow Transplant Research. Two hundred seven subjects with HL (n = 66) or NHL (n = 141) were enrolled from 32 centers in North America, and 203 underwent ASCT. Day 100 TRM for all subjects (n = 203), patients > 65 years (n = 17), and patients <= 65 years (n = 186) were 4.5%, 23.5%, and 2.7%, respectively. The estimated rates of 2-year progression-free survival (PFS) were 33% for HL and 58%, 77%, and 43% for diffuse large B cell lymphoma (DLBCL; n = 63), mantle cell lymphoma (Ma; n = 29), and follicular lymphoma (FL; n = 23), respectively. The estimated rates of 2-year overall survival (OS) were 76% for HL and 65%, 89%, and 89% for DLBCL, MCL, and FL, respectively. In the matched analysis rates of 2-year TRM were 3.3% for BuCyE and 3.9% for BEAM, and there were no differences in outcomes for NHL. Patients with HL had lower rates of 2-year PFS with BuCyE, 33% (95% CI, 21% to 46%), than with BEAM, 59% (95% CI, 52% to 66%), with no differences in TRM or OS. BuCyE provided adequate disease control and safety in B cell NHL patients <= 65 years but produced worse PFS in HL patients when compared with BEAM. (C) 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license. C1 [Flowers, Christopher R.; Waller, Edmund K.] Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Div BMT, 1365B Clifton Rd,Suite B5119, Atlanta, GA 30322 USA. [Costa, Luciano J.] Med Univ S Carolina, Charleston, SC 29425 USA. [Pasquini, Marcelo C.; Le-Rademacher, Jennifer] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Lill, Michael] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Shore, Tsiporah B.] New York Hosp, Weill Cornell Med Ctr Hematol Oncol, New York, NY 10021 USA. [Vaughan, William] Univ Alabaman Birmingham, Bone Marrow Transplantat Program, Birmingham, AL USA. [Craig, Michael] W Virginia Univ, Hlth Sci Ctr, Morgantown, WV 26506 USA. [Freytes, Cesar O.] Univ Texas Hlth Sci Ctr San Antonio, South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Shea, Thomas C.] Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. [Horwitz, Mitchell E.] Duke Univ, Med Ctr, Dept Med, Adult Stem Cell Transplant Program,Div Cellular T, Durham, NC 27710 USA. [Fay, Joseph W.] Baylor Univ, Med Ctr, Dallas, TX USA. [Mineishi, Shin] Univ Michigan, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. [Rondelli, Damiano] Univ Illinois, Dept Med, Hematol Oncol Sect, Chicago, IL USA. [Mason, James] Scripps Clin, La Jolla, CA USA. [Braunschweig, Ira] Montefiore Med Ctr, Dept Oncol, 111 E 210Th St, Bronx, NY 10467 USA. [Ai, Weiyun] Univ Calif San Francisco, Med, San Francisco, CA 94143 USA. [Yeh, Rosa F.] Seattle Canc Care Alliance, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Rodriguez, Tulio E.] Loyola Univ Chicago, Cardinal Bernardin Canc Ctr, Maywood, IL USA. [Flinn, Ian] Sarah Cannon Res Inst, Nashville, TN USA. [Comeau, Terrance] New Brunswick Stem Cell Transplant Program, St John, NB, Canada. [Yeager, Andrew M.] Univ Arizona, Ctr Canc, Blood & Marrow Transplantat Program, Tucson, AZ USA. [Pulsipher, Michael A.] Childrens Hosp Los Angeles, Keck Sch Med, Div Hematol Oncol & Blood & Marrow Transplant, Los Angeles, CA 90027 USA. [Pulsipher, Michael A.] Univ So Calif, Los Angeles, CA USA. [Bence-Bruckler, Isabelle] Univ Ottawa, Ottawa Hosp, Ottawa, ON, Canada. [Laneuyille, Pierre] McGill Univ, Ctr Hlth, Royal Victoria Hosp, Montreal, PQ, Canada. [Bierman, Philip] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. [Chen, Andy I.] Oregon Hlth & Sci Univ, Ctr Hematol Malignancies, Portland, OR 97201 USA. [Kato, Kazunobu; Wang, Yanlin; Xu, Cong; Smith, Angela J.] Otsuka Pharmaceut Dev & Commercializat Inc, Princeton, NJ USA. [Costa, Luciano J.; Mineishi, Shin] Univ Alabama Birmingham, Bone Marrow Transplantat Program, Birmingham, AL USA. [Le-Rademacher, Jennifer] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Kato, Kazunobu] Bristol Myers Squibb, Princeton, NJ USA. RP Waller, EK (reprint author), Emory Univ, Dept Hematol & Med Oncol, Winship Canc Inst, Div BMT, 1365B Clifton Rd,Suite B5119, Atlanta, GA 30322 USA.; Waller, EK (reprint author), Emory Univ, Winship Canc Inst, 1365B Clifton Rd,Suite B5119, Atlanta, GA 30322 USA. EM ewaller@emory.edu RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 FU Otsuka Pharmaceutical Development & Commercialization, Inc. FX Otsuka Pharmaceutical Development & Commercialization, Inc. sponsored this study and provided the i.v. Bu for the analyses. NR 51 TC 3 Z9 3 U1 5 U2 8 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 JUL PY 2016 VL 22 IS 7 BP 1197 EP 1205 DI 10.1016/j.bbmt.2016.03.018 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DP4JR UT WOS:000378462700008 PM 27040394 ER PT J AU Rowe, RG Guo, DJ Lee, M Margossian, S London, WB Lehmann, L AF Rowe, R. Grant Guo, Dongjing Lee, Michelle Margossian, Steven London, Wendy B. Lehmann, Leslie TI Cytomegalovirus Infection in Pediatric Hematopoietic Stem Cell Transplantation: Risk Factors for Primary Infection and Cases of Recurrent and Late Infection at a Single Center SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Cytomegalovirus; Umbilical cord transplant; Graft-versus host disease ID BONE-MARROW-TRANSPLANTATION; CORD BLOOD TRANSPLANTATION; PREEMPTIVE THERAPY; HOST-DISEASE; CMV REACTIVATION; GANCICLOVIR PROPHYLAXIS; REDUCED-INTENSITY; ACUTE GRAFT; RECIPIENTS; DONOR AB Cytomegalovirus (CMV) infection is a significant source of morbidity and mortality in allogeneic stem cell transplantation (SCT). We identified a cohort of 91 pediatric SCT patients at risk (defined as either donor and/or recipient seropositivity) for CMV infection at our institution. We retrospectively categorized at-risk SCT recipients as those who (1) were at risk of CMV infection in the post-SCT period, (2) had documented CMV infection before SCT, (3) experienced recurrence of post-SCT CMV viremia, or (4) experienced late post-SCT CMV viremia; categories were not mutually exclusive. We analyzed the impact of SCT-related factors on incidence of CMV infection and outcome, and we described the outcome of each of these cohorts. In univariate analysis, recipient CMV seropositivity, use of umbilical cord blood graft, and acute graft-versus-host disease (GVHD) predicted post-SCT CMV viremia, and the effects of acute GVHD (odds ratio, 4.018; 95% confidence interval, 1.032 to 15.643) and CMV seropositivity (odds ratio, 16.525; 95% confidence interval, 2.041 to 133.803) were confirmed in multivariate analysis. Patients with recurrence of post-SCT CMV viremia had a 50% all-cause mortality rate, compared with 12% in all 91 patients. Patients with pre-SCT CMV infection had a high incidence of post-SCT CMV infection but could successfully undergo SCT with antiviral prophylaxis and pre-emptive CMV treatment. All patients with late CMV infection had prior GVHD. Theses findings identify risk factors for post-SCT CMV infection and provide novel descriptions of childhood SCT recipients with pre-SCT, recurrent, and late CMV infection, which may contribute to risk stratification strategies for CMV at-risk patients in pediatric allogeneic SCT. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Rowe, R. Grant; Lee, Michelle; Margossian, Steven; London, Wendy B.; Lehmann, Leslie] Dana Farber Canc Inst, Dana Farber Boston Childrens Canc & Blood Disorde, Stem Cell Transplantat Program, 450 Brookline Ave, Boston, MA 02215 USA. [Rowe, R. Grant; Guo, Dongjing; Lee, Michelle; Margossian, Steven; London, Wendy B.; Lehmann, Leslie] Boston Childrens Hosp, Boston, MA USA. [Lee, Michelle; Margossian, Steven; London, Wendy B.] Harvard Univ, Sch Med, Boston, MA USA. RP Lehmann, L (reprint author), Dana Farber Canc Inst, Dana Farber Boston Childrens Canc & Blood Disorde, Stem Cell Transplantat Program, 450 Brookline Ave, Boston, MA 02215 USA. EM leslie_lehmann@dfci.harvard.edu FU Natalia Fund at the Dana-Farber Cancer Institute FX This research was supported by the Natalia Fund at the Dana-Farber Cancer Institute. NR 34 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 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2016 VL 22 IS 7 BP 1275 EP 1283 DI 10.1016/j.bbmt.2016.04.004 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DP4JR UT WOS:000378462700019 PM 27090959 ER PT J AU Loggers, ET LeBlanc, TW El-Jawahri', A Fihn, J Bumpus, M David, J Horak, P Lee, SJ AF Loggers, Elizabeth T. LeBlanc, Thomas W. El-Jawahri', Areej Fihn, Judy Bumpus, Molly David, Jodie Horak, Petr Lee, Stephanie J. TI Pretransplantation Supportive and Palliative Care Consultation for High-Risk Hematopoietic Cell Transplantation Patients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Palliative care; Hematopoietic cell transplantation ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; HEMATOLOGIC MALIGNANCIES; FUNCTIONAL ASSESSMENT; SYMPTOM BURDEN; RETROSPECTIVE COHORT; CLINICAL ONCOLOGY; AMERICAN SOCIETY; CANCER-PATIENTS; CHRONIC ILLNESS AB Early palliative care (EPC) for patients with metastatic solid tumors is now standard of care, but the effect of EPC in hematopoietic cell transplantation (HCT) is less well understood. We studied the acceptability of pre-HCT EPC as measured by trial participation, changes in patient-reported outcomes, and follow-up with palliative care providers. English-speaking adults (age >17 years) with an HCT comorbidity index of >= 3, relapse risk > 25%, or planned HLA-mismatched allogeneic or myeloablative HCT received EPC before HCT admission with monthly or more frequent visits. Twenty-two (69%) of 32 subjects provided consent; 2 were later excluded (HCT cancelled, consent retracted) for a 63% participation rate. Comfort with EPC was high (82% very comfortable). Subjects reported stable or improved mood and sense of hope, without apparent negative effects with a median of 3 visits. Follow-up surveys were returned by 75% of participants at 60 days and by 65% at 90 days. Four (20%) were admitted to the intensive care unit before day 100 and 3 (15%) received life-support measures. Five (25%) died with median follow-up of 14 months. EPC is feasible, acceptable, and has the potential to improve the HCT experience, whether or not the patient survives. EPC for HCT patients should be tested in a randomized trial. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Loggers, Elizabeth T.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Loggers, Elizabeth T.; Lee, Stephanie J.] Univ Washington, Div Hematol & Oncol, Seattle, WA 98195 USA. [Loggers, Elizabeth T.; Fihn, Judy; Bumpus, Molly; David, Jodie; Horak, Petr] Seattle Canc Care Alliance, Palliat Care Serv, Seattle, WA USA. [LeBlanc, Thomas W.] Duke Univ, Sch Med, Dept Med, Div Hematol Malignancies & Cellular Therapy, Durham, NC 27706 USA. [LeBlanc, Thomas W.] Duke Canc Inst, Program Canc Control & Populat Sci, Durham, NC USA. [El-Jawahri', Areej] Massachusetts Gen Hosp, Ctr Canc, Bone Marrow Transplant Program, Boston, MA USA. [El-Jawahri', Areej] Harvard Univ, Sch Med, Boston, MA USA. RP Loggers, ET (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave,Mailstop D5-380, Seattle, WA 98109 USA. EM eloggers@seattlecca.org OI Loggers, Elizabeth/0000-0003-3432-0443 FU Cambia Foundation Sojourns Scholar Award FX T.W.L. is supported by a Cambia Foundation Sojourns Scholar Award. NR 43 TC 0 Z9 0 U1 1 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 JUL PY 2016 VL 22 IS 7 BP 1299 EP 1305 DI 10.1016/j.bbmt.2016.03.006 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DP4JR UT WOS:000378462700022 PM 26976242 ER PT J AU Strouse, C Richardson, P Prentice, G Korman, S Hume, R Nejadnik, B Horowitz, MM Saber, W AF Strouse, Christopher Richardson, Paul Prentice, Grant Korman, Sandra Hume, Robin Nejadnik, Bijan Horowitz, Mary M. Saber, Wael TI Defibrotide for Treatment of Severe Veno-Occlusive Disease in Pediatrics and Adults: An Exploratory Analysis Using Data from the Center for International Blood and Marrow Transplant Research SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Defibrotide; Veno-occlusive disease; Hematopoietic cell transplantation ID STEM-CELL TRANSPLANTATION; SINUSOIDAL OBSTRUCTION SYNDROME AB Veno-occlusive disease (VOD) is an early and serious complication of hematopoietic cell transplantation (HCT) that is associated with inferior survival, particularly when it is complicated by multiorgan failure (severe VOD). We evaluated the efficacy of defibrotide in the treatment of severe VOD using observational data from the Center for International Blood and Marrow Transplant Research (CIBMTR). Eight thousand three hundred forty-one patients treated by HCT between 2008 and 2011 were identified from the CIBMTR clinical database; 3.2% met criteria for VOD and 1.2% met criteria for severe VOD. Patients with a diagnosis of VOD as reported to the CIBMTR by their transplanting centers, who had no prior history of cirrhosis, and who had a maximum total bilirubin level > 2.0 mg/dL by day +100 post-HCT were selected for study. Severe VOD was defined as VOD occurring in the setting of renal impairment requiring dialysis or any noninfectious pulmonary abnormality. Patients with severe VOD were divided into 2 groups for analysis: those treated with defibrotide (n = 41) and those not treated with defibrotide (n = 55). Patients in the nondefibrotide group were older, were more likely to be male, were more likely to have a history of previous fungal infection, and had a higher proportion of clinically significant pre-existing disease or organ impairment. Survival rate at day +100 was 39% (95% CI, 24.8% to 54.3%) in patients receiving defibrotide and 30.9% (95% CI, 19.5% to 43.6%) in those not receiving defibrotide. Resolution rate of VOD at day +100 was 51% in the defibrotide group and 29% in the nondefibrotide group (difference, 22.1%; 95% CI, 2.6% to 42%). The results of our study are consistent with previously reported experiences with defibrotide, confirm the poor outcome of this syndrome, and suggest defibrotide is effective in the treatment of severe VOD. (C) 2016 American Society for Blood and Marrow Transplantation. C1 [Strouse, Christopher; Korman, Sandra; Horowitz, Mary M.; Saber, Wael] Med Coll Wisconsin, Dept Med, Div Hematol Oncol, Milwaukee, WI 53226 USA. [Richardson, Paul] Dana Farber Canc Inst, Dept Hematol Oncol, Boston, MA 02115 USA. [Prentice, Grant; Hume, Robin; Nejadnik, Bijan] Jazz Pharmaceut, Palo Alto, CA USA. RP Saber, W (reprint author), Med Coll Wisconsin, CIBMTR Milwaukee, Dept Med, Div Hematol Oncol, 9200 W Wisconsin Ave,Suite C5500, Milwaukee, WI 53226 USA. EM wsaber@mcw.edu FU Health Resources and Services Administration [HHSH250201200016C]; Office of Naval Research [N00014-13-1-0039, N00014-14-1-0028]; Alexion; Amgen, Inc.; Match Foundation; Bristol Myers Squibb Oncology; Celgene Corporation; Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; Jazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; Leukemia & Lymphoma Society; Medical College of Wisconsin; Merck Co, Inc.; Mesoblast; Takeda Oncology Co.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. Japan; Oxford Immunotec; Perkin Elmer, Inc.; Pharmacyclics; Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Telomere Diagnostics, Inc.; TerumoBCT; Therakos, Inc.; University of Minnesota; Wellpoint, Inc.; National Cancer Institute (NCI) [5U24-CA076518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases; NHLBI [5U10HL069294]; NCI FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases; Grant/Cooperative Agreement 5U10HL069294 from the NHLBI and NCI; contract HHSH250201200016C with Health Resources and Services Administration; 2 grants (N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research; and grants from Alexion; *Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Be the Match Foundation; *Bristol Myers Squibb Oncology; *Celgene Corporation; *Chimerix, Inc.; Fred Hutchinson Cancer Research Center; Gamida Cell Ltd.; Genentech, Inc.; Genzyme Corporation; *Gilead Sciences, Inc.; Health Research, Inc. Roswell Park Cancer Institute; HistoGenetics, Inc.; Incyte Corporation; *Jazz Pharmaceuticals, Inc.; Jeff Gordon Children's Foundation; The Leukemia & Lymphoma Society; The Medical College of Wisconsin; Merck & Co, Inc.; Mesoblast; The Takeda Oncology Co.; *Miltenyi Biotec, Inc.; National Marrow Donor Program; Neovii Biotech NA, Inc.; Novartis Pharmaceuticals Corporation; Onyx Pharmaceuticals; Optum Healthcare Solutions, Inc.; Otsuka America Pharmaceutical, Inc.; Otsuka Pharmaceutical Co, Ltd. Japan; Oxford Immunotec; Perkin Elmer, Inc.; Pharmacyclics; *Sanofi US; Seattle Genetics; Sigma-Tau Pharmaceuticals; *Spectrum Pharmaceuticals, Inc.; St. Baldrick's Foundation; *Sunesis Pharmaceuticals, Inc.; Swedish Orphan Biovitrum, Inc.; Telomere Diagnostics, Inc.; TerumoBCT; Therakos, Inc.; University of Minnesota; and *Wellpoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institutes of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration or any other agency of the U.S. Government. NR 21 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2016 VL 22 IS 7 BP 1306 EP 1312 DI 10.1016/j.bbmt.2016.04.011 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA DP4JR UT WOS:000378462700023 PM 27108694 ER PT J AU Yang, MZ Orgah, J Zhu, J Fan, GW Han, JH Wang, XY Zhang, BL Zhu, Y AF Yang, Mingzhu Orgah, John Zhu, Jie Fan, Guanwei Han, Jihong Wang, Xiaoying Zhang, Boli Zhu, Yan TI Danhong injection attenuates cardiac injury induced by ischemic and reperfused neuronal cells through regulating arginine vasopressin expression and secretion SO BRAIN RESEARCH LA English DT Article DE Arginine vasopressin; Ischemic; Reperfusion; Cerebrovascular; Cardiac function; Danhong injection ID CONGESTIVE-HEART-FAILURE; RECEPTOR ANTAGONIST; ATRIAL-FIBRILLATION; CRYPTOGENIC STROKE; RAT-HEART; SYSTEM; DEATH; LATERALIZATION; FIBROBLASTS; ACTIVATION AB Ischemic stroke is associated with cardiac myocyte vulnerability through some unknown mechanisms. Arginine vasopressin (AVP) may exert considerable function in the relationship of brain damage and heart failure. Danhong injection (DHI) can protect both stroke and heart failure patients with good efficacy in clinics. The aim of this study is to investigate the mechanism of DHI in heart and brain co-protection effects to determine whether AVP plays key role in this course. In the present study, we found that both the supernatant from oxygen-glucose deprivation (OGD) and reperfused primary rat neuronal cells (PRNCs) and AVP treatment caused significant reduction in cell viability and mitochondrial activity in primary rat cardiac myocytes (RCMs). Besides, DHI had the same protective effects with conivaptan, a dual vasopressin V-1A and V-2 receptor antagonist, in reducing the RCM damage induced by overdose AVP. DHI significantly decreased the injury of both PRNCs and RCMs. Meanwhile, the AVP level was elevated dramatically in OGD and reperfusion PRNCs, and DHI was able to decrease the AVP expression in the injured PRNCs. Therefore, our present results suggested that OGD and reperfusion PRNCs might induce myocyte injury by elevating the AVP expression in PRNCs. The ability of DHI to reinstate AVP level may be one of the mechanisms of its brain and heart co-protection effects. (C) 2016 Elsevier B.V. All rights reserved. C1 [Yang, Mingzhu; Orgah, John; Zhu, Jie; Fan, Guanwei; Wang, Xiaoying; Zhang, Boli; Zhu, Yan] Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, 312 Anshanxi Rd, Tianjin 300193, Peoples R China. [Yang, Mingzhu; Orgah, John; Zhu, Jie; Wang, Xiaoying; Zhu, Yan] Tianjin Int Joint Acad Biotechnol & Med, TEDA, Res & Dev Ctr TCM, 220 Dongting Rd, Tianjin 300457, Peoples R China. [Zhu, Yan] Tufts Med Ctr, Mol Cardiol Res Inst, 750 Washington St, Boston, MA 02111 USA. [Zhu, Yan] Tufts Univ, Sch Med, 750 Washington St, Boston, MA 02111 USA. [Han, Jihong] Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China. [Han, Jihong] Nankai Univ, Collaborat Innovat Ctr Biotherapy, Tianjin 300071, Peoples R China. [Wang, Xiaoying] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosci Program,Neuroprotect Res Lab,Dept Neurol, Boston, MA 02135 USA. RP Zhu, Y (reprint author), Tianjin Univ Tradit Chinese Med, Tianjin State Key Lab Modern Chinese Med, 312 Anshanxi Rd, Tianjin 300193, Peoples R China. EM yanzhu.harvard@iCloud.com FU National Major New Drug Discovery Grant [2013ZX 0920102]; National Natural Science Foundation of China (NSFC) [81274128]; Program for Tianjin Innovative Research Team in University [TD12-5031]; International Cooperation Project of MOST, China [2013DFA31620] FX This study was supported by the National Major New Drug Discovery Grant (2013ZX 0920102), the National Natural Science Foundation of China (NSFC) Grant (81274128); the Program for Tianjin Innovative Research Team in University (TD12-5031), and International Cooperation Project of MOST, China (2013DFA31620). NR 44 TC 2 Z9 2 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD JUL 1 PY 2016 VL 1642 BP 516 EP 523 DI 10.1016/j.brainres.2016.04.046 PG 8 WC Neurosciences SC Neurosciences & Neurology GA DP7EI UT WOS:000378661600058 PM 27107944 ER PT J AU Saleh, MH Wang, L Goldberg, MS AF Saleh, Mohammad H. Wang, Lei Goldberg, Michael S. TI Improving cancer immunotherapy with DNA methyltransferase inhibitors SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE CITIM 2015; Epigenetic modifier; DNA methyltransferase inhibitor; Decitabine; Immunotherapy; Ovarian cancer ID HISTONE DEACETYLASE INHIBITORS; RENAL-CELL CARCINOMA; CD8 T-CELLS; IFN-GAMMA; ANTIGENS EXPRESSION; SUPPRESSOR-CELLS; AGENT 5-AZACYTIDINE; CUTANEOUS MELANOMA; IMMUNE-RESPONSE; GENE-EXPRESSION AB Immunotherapy confers durable clinical benefit to melanoma, lung, and kidney cancer patients. Challengingly, most other solid tumors, including ovarian carcinoma, are not particularly responsive to immunotherapy, so combination with a complementary therapy may be beneficial. Recent findings suggest that epigenetic modifying drugs can prime antitumor immunity by increasing expression of tumor-associated antigens, chemokines, and activating ligands by cancer cells as well as cytokines by immune cells. This review, drawing from both preclinical and clinical data, describes some of the mechanisms of action that enable DNA methyltransferase inhibitors to facilitate the establishment of antitumor immunity. C1 [Saleh, Mohammad H.; Wang, Lei; Goldberg, Michael S.] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. RP Goldberg, MS (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & Virol, Boston, MA 02115 USA. EM michael_goldberg1@dfci.harvard.edu OI Saleh, Mohammad H./0000-0001-8828-4367 FU Ovarian Cancer Research Fund (Liz Tilberis Scholar award); Susan F. Smith Center for Women's Cancer FX We thank the Ovarian Cancer Research Fund (Liz Tilberis Scholar award) and the Susan F. Smith Center for Women's Cancer for supporting this work. NR 65 TC 5 Z9 5 U1 9 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 EI 1432-0851 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JUL PY 2016 VL 65 IS 7 BP 787 EP 796 DI 10.1007/s00262-015-1776-3 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA DQ0EU UT WOS:000378872000003 PM 26646852 ER PT J AU Khalil, HA Lei, NY Brinkley, G Scott, A Wang, JF Kar, UK Jabaji, ZB Lewis, M Martin, MG Dunn, JCY Stelzner, MG AF Khalil, Hassan A. Lei, Nan Ye Brinkley, Garrett Scott, Andrew Wang, Jiafang Kar, Upendra K. Jabaji, Ziyad B. Lewis, Michael Martin, Martin G. Dunn, James C. Y. Stelzner, Matthias G. TI A novel culture system for adult porcine intestinal crypts SO CELL AND TISSUE RESEARCH LA English DT Article DE Porcine intestinal culture; Enteroid; Intestinal spheroid; Intestinal subepithelial myofibroblast; Transduction of intestinal epithelium ID STEM-CELL; IN-VITRO; ANIMAL-MODELS; TRANSPLANTATION; EPITHELIUM; ORGANOIDS; COLON; DIFFERENTIATION; PROGENITORS; ENGRAFTMENT AB Porcine models are useful for investigating therapeutic approaches to short bowel syndrome and potentially to intestinal stem cell (ISC) transplantation. Whereas techniques for the culture and genetic manipulation of ISCs from mice and humans are well established, similar methods for porcine stem cells have not been reported. Jejunal crypts were isolated from murine, human, and juvenile and adult porcine small intestine, suspended in Matrigel, and co-cultured with syngeneic intestinal subepithelial myofibroblasts (ISEMFs) or cultured without feeder cells in various culture media. Media containing epidermal growth factor, noggin, and R-spondin 1 (ENR medium) were supplemented with various combinations of Wnt3a- or ISEMF-conditioned medium (CM) and with glycogen synthase kinase 3 inhibitor (GSK3i), and their effects were studied on cultured crypts. Cell lineage differentiation was assessed by immunohistochemistry and quantitative polymerase chain reaction. Cultured porcine cells were serially passaged and transduced with a lentiviral vector. Whereas ENR medium supported murine enteroid growth, it did not sustain porcine crypts beyond 5 days. Supplementation of Wnt3a-CM and GSK3i resulted in the formation of complex porcine enteroids with budding extensions. These enteroids contained a mixture of stem and differentiated cells and were successfully passaged in the presence of GSK3i. Crypts grown in media supplemented with porcine ISEMF-CM formed spheroids that were less well differentiated than enteroids. Enteroids and spheroids were transfected with a lentivirus with high efficiency. Thus, our method maintains juvenile and adult porcine crypt cells long-term in culture. Porcine enteroids and spheroids can be successfully passaged and transduced by using lentiviral vectors. C1 [Khalil, Hassan A.; Lei, Nan Ye; Scott, Andrew; Jabaji, Ziyad B.; Dunn, James C. Y.; Stelzner, Matthias G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Brinkley, Garrett; Wang, Jiafang; Kar, Upendra K.; Martin, Martin G.] Mattel Childrens Hosp, Dept Pediat, Div Gastroenterol & Nutr, Los Angeles, CA USA. [Brinkley, Garrett; Wang, Jiafang; Kar, Upendra K.; Martin, Martin G.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Lewis, Michael] VA Greater Los Angeles Hlth Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Stelzner, Matthias G.] VA Greater Los Angeles Hlth Syst, Dept Surg, Los Angeles, CA USA. RP Stelzner, MG (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA.; Stelzner, MG (reprint author), VA Greater Los Angeles Hlth Syst, Dept Surg, Los Angeles, CA USA. EM stelzner@ucla.edu OI Khalil, Hassan/0000-0002-3835-1290 FU National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infections Diseases [DK085535-01, DK085535-02S2]; California Institute of Regenerative Medicine [RT2-01985]; [CURE/P30 DK041301] FX The UCLA Vectorcore is supported by CURE/P30 DK041301. This research was performed as a project of the Intestinal Stem Cell Consortium, a collaborative research project funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Allergy and Infections Diseases (DK085535-01 and DK085535-02S2) and was supported in part by the California Institute of Regenerative Medicine (RT2-01985). NR 36 TC 2 Z9 2 U1 6 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-766X EI 1432-0878 J9 CELL TISSUE RES JI Cell Tissue Res. PD JUL PY 2016 VL 365 IS 1 BP 123 EP 134 DI 10.1007/s00441-016-2367-0 PG 12 WC Cell Biology SC Cell Biology GA DQ0GR UT WOS:000378877600011 PM 26928041 ER PT J AU Ananthakrishnan, AN Cagan, A Cai, TX Gainer, VS Shaw, SY Churchill, S Karlson, EW Murphy, SN Liao, KP Kohane, I AF Ananthakrishnan, Ashwin N. Cagan, Andrew Cai, Tianxi Gainer, Vivian S. Shaw, Stanley Y. Churchill, Susanne Karlson, Elizabeth W. Murphy, Shawn N. Liao, Katherine P. Kohane, Isaac TI Statin Use Is Associated With Reduced Risk of Colorectal Cancer in Patients With Inflammatory Bowel Diseases SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Colon Cancer; CD; UC; HMG-CoA Reductase Inhibitors; Lipid-Lowering Drug; Crohn's Disease; Ulcerative Colitis; Statin; Colon Cancer ID PRIMARY SCLEROSING CHOLANGITIS; ULCERATIVE-COLITIS; 5-AMINOSALICYLIC ACID; URSODEOXYCHOLIC ACID; METAANALYSIS; NEOPLASIA; CARCINOMA; CHEMOPREVENTION; SURVEILLANCE; PREVENTION AB BACKGROUND & AIMS: Inflammatory bowel diseases (IBDs) such as Crohn's disease and ulcerative colitis are associated with an increased risk of colorectal cancer (CRC). Chemopreventive strategies have produced weak or inconsistent results. Statins have been associated inversely with sporadic CRC. We examined their role as chemopreventive agents in patients with IBD. METHODS: We collected data from 11,001 patients with IBD receiving care at hospitals in the Greater Boston metropolitan area from 1998 through 2010. Diagnoses of CRC were determined using validated International Classification of Diseases, 9th revision, Clinical Modification codes. Statin use before diagnosis was assessed through analysis of electronic prescriptions. We performed multivariate logistic regression analyses, adjusting for potential confounders including primary sclerosing cholangitis, smoking, increased levels of inflammation markers, and CRC screening practices to identify an independent association between statin use and CRC. We performed sensitivity analyses using propensity score adjustment and variation in the definition of statin use. RESULTS: In our cohort, 1376 of the patients (12.5%) received 1 or more prescriptions for a statin. Patients using statins were more likely to be older, male, white, smokers, and have greater comorbidity than nonusers. Over a follow-up period of 9 years, 2% of statin users developed CRC compared with 3% of nonusers (age-adjusted odds ratio, 0.35; 95% confidence interval, 0.24-0.53). On multivariate analysis, statin use remained independently and inversely associated with CRC (odds ratio, 0.42; 95% confidence interval, 0.28-0.62). Our findings were robust on a variety of sensitivity and subgroup analyses. CONCLUSIONS: Statin use was associated inversely with the risk of CRC in a large IBD cohort. Prospective studies on the role of statins as chemopreventive agents are warranted. C1 [Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Murphy, Shawn N.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Churchill, Susanne; Kohane, Isaac] Harvard Univ, Sch Med, Dept Biomed Informat, Boston, MA USA. [Ananthakrishnan, Ashwin N.; Shaw, Stanley Y.; Karlson, Elizabeth W.; Murphy, Shawn N.; Liao, Katherine P.; Kohane, Isaac] Harvard Univ, Sch Med, Boston, MA USA. [Cagan, Andrew; Gainer, Vivian S.] Partners HealthCare, Res Informat Serv & Comp, Charlestown, MA USA. [Cai, Tianxi] Harvard Univ, Dept Biostat, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Karlson, Elizabeth W.; Liao, Katherine P.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, 75 Francis St, Boston, MA 02115 USA. [Kohane, Isaac] Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU National Institutes of Health [U54-LM008748, K08 AR060257, K24 AR052403, P60 AR047782, R01 AR049880]; US National Institutes of Health [K23 DK097142]; Harold and Duval Bowen Fund; American Gastroenterological Association FX Supported by National Institutes of Health (U54-LM008748 to I.K.); the American Gastroenterological Association and the US National Institutes of Health (K23 DK097142 to A.N.A.); National Institutes of Health grant K08 AR060257 and the Harold and Duval Bowen Fund (K.P.L.); and supported by grants from the National Institutes of Health (K24 AR052403, P60 AR047782, and R01 AR049880 to E.W.K.). NR 56 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 EI 1542-7714 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JUL PY 2016 VL 14 IS 7 BP 973 EP 979 DI 10.1016/j.cgh.2016.02.017 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DP3KS UT WOS:000378392900015 PM 26905907 ER PT J AU Chen, SP Ayata, C AF Chen, Shih-Pin Ayata, Cenk TI Spreading Depression in Primary and Secondary Headache Disorders SO CURRENT PAIN AND HEADACHE REPORTS LA English DT Review DE Intracranial hemorrhage; Ischemic stroke; Migraine aura; Spreading depression; Spreading depolarization; Traumatic brain injury ID TRAUMATIC BRAIN-INJURY; HUMAN CEREBRAL-CORTEX; FAMILIAL HEMIPLEGIC MIGRAINE; SUBARACHNOID HEMORRHAGE; ISCHEMIC-STROKE; CLUSTER HEADACHE; INTRACEREBRAL HEMATOMAS; ONLINE MICRODIALYSIS; POSTICTAL HEADACHE; MALIGNANT STROKE AB Purpose of Review Spreading depression (SD) is a wave of simultaneous and near-complete depolarization of virtually all cells in brain tissue associated with a transient "depression" of all spontaneous or evoked electrical activity in the brain. SD is widely accepted as the pathophysiological event underlying migraine aura and may play a role in headache pathogenesis in secondary headache disorders such as ischemic stroke, subarachnoid or intracerebral hemorrhage, traumatic brain injury, and epilepsy. Here, we provide an overview of the pathogenic mechanisms and propose plausible hypotheses on the involvement of SD in primary and secondary headache disorders. Recent Findings SD can activate downstream trigeminovascular nociceptive pathways to explain the cephalgia in migraine, and possibly in secondary headache disorders as well. In healthy, well-nourished tissue (such as migraine), the intense transmembrane ionic shifts, the cell swelling, and the metabolic and hemodynamic responses associated with SD do not cause tissue injury; however, when SD occurs in metabolically compromised tissue (e.g., in ischemic stroke, intracranial hemorrhage, or traumatic brain injury), it can lead to irreversible depolarization, injury, and neuronal death. Recent non-invasive technologies to detect SDs in human brain injury may aid in the investigation of SD in headache disorders in which invasive recordings are not possible. Summary SD explains migraine aura and progression of neurological deficits associated with other neurological disorders. Studying the nature of SD in headache disorders might provide pathophysiological insights for disease and lead to targeted therapies in the era of precision medicine. C1 [Chen, Shih-Pin] Taipei Vet Gen Hosp, Dept Neurol, Taipei, Taiwan. [Chen, Shih-Pin] Natl Yang Ming Univ, Sch Med, Dept Neurol, Taipei 112, Taiwan. [Ayata, Cenk] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Serv, Boston, MA 02115 USA. [Ayata, Cenk] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Neurosci Intens Care Unit, Boston, MA 02115 USA. RP Ayata, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurovasc Res Lab,Dept Radiol, Charlestown, MA 02129 USA.; Ayata, C (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Stroke Serv, Boston, MA 02115 USA.; Ayata, C (reprint author), Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp,Neurosci Intens Care Unit, Boston, MA 02115 USA. EM cayata@mgh.harvard.edu NR 99 TC 0 Z9 0 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1531-3433 EI 1534-3081 J9 CURR PAIN HEADACHE R JI Curr. Pain Headache Rep. PD JUL PY 2016 VL 20 IS 7 AR 44 DI 10.1007/s11916-016-0574-8 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA DP7UL UT WOS:000378704600001 PM 27215627 ER PT J AU Tanigaki, K Chambliss, KL Yuhanna, IS Sacharidou, A Ahmed, M Atochin, DN Huang, PL Shaul, PW Mineo, C AF Tanigaki, Keiji Chambliss, Ken L. Yuhanna, Ivan S. Sacharidou, Anastasia Ahmed, Mohamed Atochin, Dmitriy N. Huang, Paul L. Shaul, Philip W. Mineo, Chieko TI Endothelial Fc gamma Receptor IIB Activation Blunts Insulin Delivery to Skeletal Muscle to Cause Insulin Resistance in Mice SO DIABETES LA English DT Article ID C-REACTIVE PROTEIN; NITRIC-OXIDE SYNTHASE; PHENOTYPIC HETEROGENEITY; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; GLUCOSE DISPOSAL; IN-VIVO; CELLS; TRANSPORT; DYSFUNCTION AB Modest elevations in C-reactive protein (CRP) are associated with type 2 diabetes. We previously revealed in mice that increased CRP causes insulin resistance and mice globally deficient in the CRP receptor Fc gamma receptor IIB (Fc gamma RIIB) were protected from the disorder. Fc gamma RIIB is expressed in numerous cell types including endothelium and B lymphocytes. Here we investigated how endothelial Fc gamma RIIB influences glucose homeostasis, using mice with elevated CRP expressing or lacking endothelial Fc gamma RIIB. Whereas increased CRP caused insulin resistance in mice expressing endothelial Fc gamma RIIB, mice deficient in the endothelial receptor were protected. The insulin resistance with endothelial Fc gamma RIIB activation was due to impaired skeletal muscle glucose uptake caused by attenuated insulin delivery, and it was associated with blunted endothelial nitric oxide synthase (eNOS) activation in skeletal muscle. In culture, CRP suppressed endothelial cell insulin transcytosis via Fc gamma RIIB activation and eNOS antagonism. Furthermore, in knock-in mice harboring constitutively active eNOS, elevated CRP did not invoke insulin resistance. Collectively these findings reveal that by inhibiting eNOS, endothelial Fc gamma RIIB activation by CRP blunts insulin delivery to skeletal muscle to cause insulin resistance. Thus, a series of mechanisms in endothelium that impairs insulin movement has been identified that may contribute to type 2 diabetes pathogenesis. C1 [Tanigaki, Keiji; Chambliss, Ken L.; Yuhanna, Ivan S.; Sacharidou, Anastasia; Ahmed, Mohamed; Shaul, Philip W.; Mineo, Chieko] Univ Texas SW Med Ctr Dallas, Dept Pediat, Ctr Pulm & Vasc Biol, Dallas, TX 75390 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA USA. RP Shaul, PW; Mineo, C (reprint author), Univ Texas SW Med Ctr Dallas, Dept Pediat, Ctr Pulm & Vasc Biol, Dallas, TX 75390 USA. EM philip.shaul@utsouthwestern.edu; chieko.mineo@utsouthwestern.edu RI Atochin, Dmitriy/Q-3150-2016 FU National Institutes of Health, National Heart, Lung, and Blood Institute [R01-HL115122]; American Diabetes Association [1-10-BS-124]; American Heart Association [13GRNT16080003] FX This work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute, grant R01-HL115122 (to P.W.S.); American Diabetes Association grant 1-10-BS-124 (to C.M.); and American Heart Association grant 13GRNT16080003 (to C.M.). NR 42 TC 0 Z9 0 U1 2 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUL PY 2016 VL 65 IS 7 BP 1996 EP 2005 DI 10.2337/db15-1605 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP4JU UT WOS:000378463000026 PM 27207525 ER PT J AU Boffetta, P Hayes, RB Sartori, S Lee, YCA Muscat, J Olshan, A Winn, DM Castellsague, X Zhang, ZF Morgenstern, H Chen, C Schwartz, SM Vaughan, TL Wunsch, V Purdue, M Koifman, S Curado, MP Vilensky, M Gillison, M Fernandez, L Menezes, A Daudt, AW Schantz, S Yu, GP D'Souza, G Haddad, RI La Vecchia, C Hashibe, M AF Boffetta, Paolo Hayes, Richard B. Sartori, Samantha Lee, Yuan-Chin A. Muscat, Joshua Olshan, Andrew Winn, Deborah M. Castellsague, Xavier Zhang, Zuo-Feng Morgenstern, Hal Chen, Chu Schwartz, Stephen M. Vaughan, Thomas L. Wunsch-Filho, Victor Purdue, Mark Koifman, Sergio Curado, Maria P. Vilensky, Marta Gillison, Maura Fernandez, Leticia Menezes, Ana Daudt, Alexander W. Schantz, Stimson Yu, Guopei D'Souza, Gypsyamber Haddad, Robert I. La Vecchia, Carlo Hashibe, Mia TI Mouthwash use and cancer of the head and neck: a pooled analysis from the International Head and Neck Cancer Epidemiology Consortium SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE alcohol; head and neck cancer; laryngeal cancer; mouthwash; oral cancer; pharyngeal cancer ID UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMA; ORAL-CANCER; HUMAN-PAPILLOMAVIRUS; RISK-FACTORS; OROPHARYNX; ESOPHAGUS; HEALTH AB Most mouthwashes contain alcohol, a known cause of head and neck cancer (oral cavity, pharynx, larynx), likely through the carcinogenic activity of acetaldehyde, formed in the oral cavity from alcohol. We carried out a pooled analysis of 8981 cases of head and neck cancer and 10090 controls from 12 case-control studies with comparable information on mouthwash use in the International Head and Neck Cancer Epidemiology Consortium. Logistic regression was used to assess the association of mouthwash use with cancers of the oral cavity, oropharynx, hypopharynx, and larynx, adjusting for study, age, sex, pack-years of tobacco smoking, number of alcoholic drinks/day, and education. Compared with never users of mouthwash, the odds ratio (OR) of all head and neck cancers was 1.01 [95% confidence interval (CI): 0.94-1.08] for ever users, based on 12 studies. The corresponding ORs of cancer of the oral cavity and oropharynx were 1.11 (95% CI: 1.00-1.23) and 1.28 (95% CI: 1.06-1.56), respectively. OR for all head and neck cancer was 1.15 (95% CI: 1.01-1.30) for use for more than 35 years, based on seven studies (P for linear trend=0.01), and OR 1.31 (95% CI: 1.09-1.58) for use more than one per day, based on five studies (P for linear trend <0.001). Although limited by the retrospective nature of the study and the limited ability to assess risks of mouthwash use in nonusers of tobacco and alcohol, this large investigation shows potential risks for head and neck cancer subsites and in long-term and frequent users of mouthwash. This pooled analysis provides the most precise estimate of the association between mouthwash use and head and neck cancer. C1 [Boffetta, Paolo; Sartori, Samantha] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. [Boffetta, Paolo; Sartori, Samantha] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA. [Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, Dept Populat Hlth, New York, NY USA. [Schantz, Stimson] New York Eye & Ear Infirm, New York, NY USA. [Lee, Yuan-Chin A.; Hashibe, Mia] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Family & Prevent Med,Div Publ Hlth, Salt Lake City, UT USA. [Muscat, Joshua] Penn State Coll Med, Hershey, PA USA. [Olshan, Andrew] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [Winn, Deborah M.; Purdue, Mark] NCI, Bethesda, MD 20892 USA. [Gillison, Maura] Johns Hopkins Med Inst, Baltimore, MD USA. [D'Souza, Gypsyamber] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol & Environm Hlth Sci, Ann Arbor, MI 48109 USA. [Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Chen, Chu; Schwartz, Stephen M.; Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Seattle, WA USA. [Haddad, Robert I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. [Castellsague, Xavier] Hosp Llobregat, Catalan Inst Oncol ICO IDIBELL, Barcelona, Spain. [Castellsague, Xavier] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Barcelona, Spain. [Wunsch-Filho, Victor] Univ Sao Paulo, Sao Paulo, Brazil. [Koifman, Sergio] Fundacao Oswaldo Cruz, Natl Sch Publ Hlth, Rio De Janeiro, Brazil. [Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil. [Daudt, Alexander W.] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil. [Curado, Maria P.] Int Prevent Res Inst, Lyon, France. [Vilensky, Marta] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina. [Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba. [Yu, Guopei] Peking Univ, Med Informat Ctr, Beijing 100871, Peoples R China. [La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy. RP Boffetta, P (reprint author), Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA. EM paolo.boffetta@mssm.edu RI Castellsague Pique, Xavier/N-5795-2014; Kowalski, Luiz/D-1701-2012; Menezes, Ana/G-7266-2012; Curado, Maria Paula/M-6200-2013; OI Castellsague Pique, Xavier/0000-0002-0802-3595; Kowalski, Luiz/0000-0001-5865-9308; Curado, Maria Paula/0000-0001-8172-2483; La Vecchia, Carlo/0000-0003-1441-897X; Hayes, Richard/0000-0002-0918-661X FU NIH [NCI R03CA113157, NIDCR R03DE016611, P01CA068384 K07CA104231, R01CA048996, R01DE012609, R01CA061188, P50CA090388, R01DA011386, R03CA077954, T32CA 009142, U01CA096134, R21ES011667, R01CA051845, DE016631]; National Institute of Environmental Health Sciences [P30ES010126]; Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; National Institutes of Health (NCI) US; NIDCR; Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina; IMIM (Barcelona); Fundaco de Amparo a' Pesquisa no Estado de Sao Paulo (FAPESP) [01/01768-2]; European Commission [IC18-CT97-0222]; Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013]; International Union Against Cancer (UICC); Yamagiwa-Yoshida Memorial International Cancer Study Grant; NCI, NIH, United States; Johns Hopkins Richard Gelb Cancer Prevention Award FX The INHANCE Consortium was supported by NIH grants NCI R03CA113157 and NIDCR R03DE016611. Studies participating in the pooled analysis were supported by grants: New York multicenter: NIH [P01CA068384 K07CA104231]; Seattle (1985-1995): NIH [R01CA048996, R01DE012609]; North Carolina (1994-1997): NIH [R01CA061188], and in part by a grant from the National Institute of Environmental Health Sciences [P30ES010126]; Los Angeles: NIH [P50CA090388, R01DA011386, R03CA077954, T32CA 009142, U01CA096134, R21ES011667] and the Alper Research Program for Environmental Genomics of the UCLA Jonsson Comprehensive Cancer Center; Puerto Rico: jointly funded by National Institutes of Health (NCI) US and NIDCR intramural programs; Latin America: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a' Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768-2], and European Commission [IC18-CT97-0222]; IARC Multicenter: Fondo de Investigaciones Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013], International Union Against Cancer (UICC), and Yamagiwa-Yoshida Memorial International Cancer Study Grant; US multicenter: The Intramural Program of the NCI, NIH, United States; MSKCC: NIH [R01CA051845]; Baltimore: NIH [DE016631]; Hotspot: Johns Hopkins Richard Gelb Cancer Prevention Award. NR 21 TC 0 Z9 1 U1 6 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0959-8278 EI 1473-5709 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JUL PY 2016 VL 25 IS 4 BP 344 EP 348 DI 10.1097/CEJ.0000000000000179 PG 5 WC Oncology SC Oncology GA DP6RK UT WOS:000378625900013 PM 26275006 ER PT J AU Jimenez, MC Curhan, GC Choi, HK Forman, JP Rexrode, KM AF Jimenez, M. C. Curhan, G. C. Choi, H. K. Forman, J. P. Rexrode, K. M. TI Plasma uric acid concentrations and risk of ischaemic stroke in women SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE hyperuricemia; ischaemic stroke; uric acid; women ID INCIDENT HYPERTENSION; ALL-CAUSE; HYPERURICEMIA; METAANALYSIS; MORTALITY; COHORT; LEVEL; DEATH; GOUT AB Background and purposeElevated plasma uric acid has been inconsistently associated with an increased risk of total stroke; however, data are sparse amongst women. The association between plasma uric acid concentrations and ischaemic stroke amongst women was examined and the effect modification by key cardiovascular risk factors was evaluated. MethodsA nested case-control design with matching by age, race/ethnicity, smoking status, menopausal status, postmenopausal hormone therapy use, date of blood draw and fasting status was utilized amongst female participants of the Nurses' Health Study who provided blood samples between 1989 and 1990. Plasma uric acid was measured on stored blood samples. The National Survey of Stroke criteria were utilized to confirm 460 incident cases of ischaemic stroke by medical records from 1990 to 2006. Multivariable conditional logistic regression models were estimated. ResultsIn matched analysis, risk of ischaemic stroke increased by 15% for each 1 mg/dl increase in plasma uric acid [95% confidence interval (CI) 3%-28%], but was no longer significant after adjustment for cardiovascular risk factors, particularly history of hypertension. The highest quartile of uric acid was significantly associated with greater risk of ischaemic stroke (relative risk 1.56; 95% CI 1.06-2.29, extreme quartiles) in matched analysis, but estimates were no longer significant after adjustment for cardiovascular risk factors (relative risk 1.43; 95% CI 0.93-2.18). Significant effect modification by key cardiovascular risk factors was not observed. ConclusionsPlasma uric acid levels were not independently associated with increased risk of ischaemic stroke in this cohort of women. Whilst plasma uric acid was associated with stroke risk factors, it was not independently associated with stroke risk. C1 [Jimenez, M. C.; Rexrode, K. M.] Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. [Jimenez, M. C.; Curhan, G. C.; Choi, H. K.; Forman, J. P.; Rexrode, K. M.] Harvard Univ, Sch Med, Boston, MA USA. [Curhan, G. C.; Forman, J. P.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Choi, H. K.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Rexrode, KM (reprint author), 900 Commonwealth Ave,3rd Floor, Boston, MA 02215 USA. EM krexrode@partners.org FU National Heart, Lung and Blood Institute of the National Institutes of Health [HL088521, HL088521-S1, HL34594]; National Cancer Institute [CA186107, CA87969, CA49449]; National Heart, Lung, and Blood Institute [K01HL124391]; Brigham and Women's Hospital Faculty Career Development Award; Minority Faculty Career Development Award; National Institute of Diabetes and Digestive and Kidney Diseases [DK91417] FX We acknowledge HL088521, HL088521-S1 and HL34594 from the National Heart, Lung and Blood Institute of the National Institutes of Health and CA186107, CA87969 and CA49449 from the National Cancer Institute. Dr Jimenez is supported by K01HL124391 from the National Heart, Lung, and Blood Institute and the Brigham and Women's Hospital Faculty Career Development Award and Minority Faculty Career Development Award. Dr Curhan is supported by DK91417 from the National Institute of Diabetes and Digestive and Kidney Diseases. NR 24 TC 2 Z9 2 U1 4 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-5101 EI 1468-1331 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2016 VL 23 IS 7 BP 1158 EP 1164 DI 10.1111/ene.12998 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP3YC UT WOS:000378431100011 PM 27061733 ER PT J AU Khera, AV Natarajan, P Kathiresan, S AF Khera, Amit V. Natarajan, Pradeep Kathiresan, Sekar TI The future of low-density lipoprotein cholesterol lowering therapy: An end to statin exceptionalism? SO EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY LA English DT Editorial Material ID CARDIOVASCULAR EVENTS; REDUCING LIPIDS; EFFICACY; SAFETY C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Khera, AV (reprint author), 55 Fruit St,Yawkey 5B, Boston, MA 02114 USA. EM avkhera@mgh.harvard.edu OI Natarajan, Pradeep/0000-0001-8402-7435 FU NHLBI NIH HHS [T32 HL007208] NR 7 TC 1 Z9 1 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 2047-4873 EI 2047-4881 J9 EUR J PREV CARDIOL JI Eur. J. Prev. Cardiol. PD JUL PY 2016 VL 23 IS 10 BP 1062 EP 1064 DI 10.1177/2047487315600818 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DP8RD UT WOS:000378764500007 PM 26268264 ER PT J AU Jiang, L Chen, HD Pinello, L Yuan, GC AF Jiang, Lan Chen, Huidong Pinello, Luca Yuan, Guo-Cheng TI GiniClust: detecting rare cell types from single-cell gene expression data with Gini index SO GENOME BIOLOGY LA English DT Article DE Clustering; Single-cell analysis; RNA-seq; qPCR; Gini index; Rare cell type ID RNA-SEQ; CHARACTERIZING HETEROGENEITY; TRANSCRIPTOMICS AB High-throughput single-cell technologies have great potential to discover new cell types; however, it remains challenging to detect rare cell types that are distinct from a large population. We present a novel computational method, called GiniClust, to overcome this challenge. Validation against a benchmark dataset indicates that GiniClust achieves high sensitivity and specificity. Application of GiniClust to public single-cell RNA-seq datasets uncovers previously unrecognized rare cell types, including Zscan4-expressing cells within mouse embryonic stem cells and hemoglobin-expressing cells in the mouse cortex and hippocampus. GiniClust also correctly detects a small number of normal cells that are mixed in a cancer cell population. C1 [Jiang, Lan; Chen, Huidong; Pinello, Luca; Yuan, Guo-Cheng] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA. [Jiang, Lan; Chen, Huidong; Pinello, Luca; Yuan, Guo-Cheng] Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Jiang, Lan] Boston Childrens Hosp, Boston, MA 02115 USA. [Chen, Huidong] Tongji Univ, Dept Comp Sci & Technol, Shanghai, Peoples R China. [Yuan, Guo-Cheng] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Yuan, GC (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02215 USA.; Yuan, GC (reprint author), Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. EM gcyuan@jimmy.harvard.edu FU Claudia Barr Award; NIH [R01HL119099]; NHGRI Career Development Award [K99HG008399] FX This work was supported by a Claudia Barr Award and NIH grant R01HL119099 to GCY and by an NHGRI Career Development Award K99HG008399 to LP. NR 28 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1474-760X J9 GENOME BIOL JI Genome Biol. PD JUL 1 PY 2016 VL 17 AR 144 DI 10.1186/s13059-016-1010-4 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA DQ0PL UT WOS:000378902100001 PM 27368803 ER PT J AU Basler, G Nikoloski, Z Larhlimi, A Barabasi, AL Liu, YY AF Basler, Georg Nikoloski, Zoran Larhlimi, Abdelhalim Barabasi, Albert-Laszlo Liu, Yang-Yu TI Control of fluxes in metabolic networks SO GENOME RESEARCH LA English DT Article ID S-ADENOSYLHOMOCYSTEINE HYDROLASE; DIACYLGLYCEROL KINASE; ESCHERICHIA-COLI; IN-VITRO; DEOXYGUANOSINE KINASE; DNA HYPOMETHYLATION; IMP DEHYDROGENASE; COUPLING ANALYSIS; PLANT-METABOLISM; CANCER GENES AB Understanding the control of large-scale metabolic networks is central to biology and medicine. However, existing approaches either require specifying a cellular objective or can only be used for small networks. We introduce new coupling types describing the relations between reaction activities, and develop an efficient computational framework, which does not require any cellular objective for systematic studies of large-scale metabolism. We identify the driver reactions facilitating control of 23 metabolic networks from all kingdoms of life. We find that unicellular organisms require a smaller degree of control than multicellular organisms. Driver reactions are under complex cellular regulation in Escherichia coil, indicating their preeminent role in facilitating cellular control. In human cancer cells, driver reactions play pivotal roles in malignancy and represent potential therapeutic targets. The developed framework helps us gain insights into regulatory principles of diseases and facilitates design of engineering strategies at the interface of gene regulation, signaling, and metabolism. C1 [Basler, Georg] Univ Calif Berkeley, Dept Chem & Biomol Engn, Berkeley, CA 94720 USA. [Basler, Georg] CSIC, Estn Expt Zaidin, Dept Environm Protect, E-18008 Granada, Spain. [Nikoloski, Zoran] Max Planck Inst Mol Plant Physiol, Syst Biol & Math Modeling, D-14476 Potsdam, Germany. [Larhlimi, Abdelhalim] Univ Nantes, Lab Informat Nantes Atlantique, F-44322 Nantes, France. [Barabasi, Albert-Laszlo] Northeastern Univ, Ctr Complex Network Res, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo] Northeastern Univ, Dept Phys Comp Sci & Biol, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo; Liu, Yang-Yu] Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Dept Med,Med Sch, Boston, MA 02115 USA. [Barabasi, Albert-Laszlo; Liu, Yang-Yu] Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Sch Med, Boston, MA 02115 USA. RP Liu, YY (reprint author), Harvard Univ, Brigham & Womens Hosp, Channing Div Network Med, Dept Med,Med Sch, Boston, MA 02115 USA.; Liu, YY (reprint author), Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Sch Med, Boston, MA 02115 USA. EM yyl@channing.harvard.edu FU Marie Curie Intra European Fellowship within the European Union's Seventh Framework Programme (FP7); Max Kade Foundation; National Institutes of Health (NIH) Grants: Centers of Excellence of Genomic Science (CEGS) [1P50HG004233, 1R01HL118455-01A1]; John Templeton Foundation [PFI-777, 51977]; European Commission (ERC) grant [329682] FX We thank Alisdair Femie, Tino Krell, Jan Lisec, and Clemens A. Schmitt for critical comments on the manuscript, and Francesco Gatto and Jens Nielsen for kindly providing the cancer networks. This work was supported by a Marie Curie Intra European Fellowship within the European Union's Seventh Framework Programme (FP7/2007-2013), European Commission (ERC) grant agreement number 329682, the Max Kade Foundation, the National Institutes of Health (NIH) Grants: Centers of Excellence of Genomic Science (CEGS) 1P50HG004233 and 1R01HL118455-01A1, and the John Templeton Foundation Awards PFI-777 and 51977. NR 77 TC 2 Z9 2 U1 5 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD JUL PY 2016 VL 26 IS 7 BP 956 EP 968 DI 10.1101/gr.202648.115 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA DQ1UN UT WOS:000378986000009 PM 27197218 ER PT J AU Breithardt, G Baumgartner, H Berkowitz, SD Hellkamp, AS Piccini, JP Lokhnygina, Y Halperin, JL Singer, DE Hankey, GJ Hacke, W Becker, RC Nessel, CC Mahaffey, KW Califf, RM Fox, KAA Patel, MR AF Breithardt, Guenter Baumgartner, Helmut Berkowitz, Scott D. Hellkamp, Anne S. Piccini, Jonathan P. Lokhnygina, Yuliya Halperin, Jonathan L. Singer, Daniel E. Hankey, Graeme J. Hacke, Werner Becker, Richard C. Nessel, Christopher C. Mahaffey, Kenneth W. Califf, Robert M. Fox, Keith A. A. Patel, Manesh R. CA ROCKET AF Steering Comm TI Native valve disease in patients with non-valvular atrial fibrillation on warfarin or rivaroxaban SO HEART LA English DT Article ID VALVULAR HEART-DISEASE; VON-WILLEBRAND-FACTOR; BLEEDING GASTROINTESTINAL ANGIODYSPLASIA; AORTIC-STENOSIS; MITRAL REGURGITATION; THROMBOEMBOLIC EVENTS; HEYDES-SYNDROME; ROCKET AF; ASSOCIATION; STROKE AB Objective To compare the characteristics and outcomes of patients with atrial fibrillation (AF) and aortic stenosis (AS) with patients with AF with mitral regurgitation (MR) or aortic regurgitation (AR) and patients without significant valve disease (no SVD). Methods Using Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) data, we analysed efficacy and safety outcomes, adjusting hazard ratios (HRs) for potential confounders using Cox regression analysis. Results Among 14 119 intention-to-treat ROCKET AF trial patients, a trial that excluded patients with mitral stenosis or artificial valve prosthesis, 214 had AS with or without other valve abnormalities, 1726 had MR or AR and 12 179 had no SVD. After adjusting for prognostic factors, the composite of stroke, systemic embolism or vascular death increased approximately twofold in patients with AS (AS 10.84, MR or AR 4.54 and no SVD 4.31 events per 100 patient-years, p=0.0001). All-cause death also significantly increased (AS 11.22, MR or AR 4.90 and no SVD 4.39 events per 100 patient-years, p=0.0003). Major bleeding occurred more frequently in AS (adjusted HR 1.61, confidence intervals (CI) 1.03 to 2.49, p<0.05) and MR or AR (HR 1.30, 1.07 to 1.57, p<0.01) than in no SVD, but there was no difference between AS and MR or AR (HR 1.24, 0.78 to 1.97). The relative efficacy of rivaroxaban versus warfarin was consistent among patients with and without valvular disease. Rivaroxaban was associated with higher rates of major bleeding than warfarin in patients with MR or AR (HR 1.63, 1.15 to 2.31). Conclusions We found that patients with AF and AS on oral anticoagulants may have distinctly different efficacy and safety outcomes than patients with MR or AR or no SVD. C1 [Breithardt, Guenter] Univ Hosp Munster, Dept Cardiovasc Med, Div Electrophysiol, Munster, Germany. [Baumgartner, Helmut] Univ Hosp Munster, Dept Cardiovasc Med, Div Adult Congenital & Valvular Heart Dis, Munster, Germany. [Berkowitz, Scott D.] Bayer Healthcare Pharmaceut LP, Whippany, NJ USA. [Hellkamp, Anne S.; Piccini, Jonathan P.; Lokhnygina, Yuliya; Patel, Manesh R.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Halperin, Jonathan L.] Mt Sinai Med Ctr, Cardiovasc Inst, New York, NY 10029 USA. [Singer, Daniel E.] Massachusetts Gen Hosp, Div Gen Internal Med, Clin Epidemiol Unit, Boston, MA 02114 USA. [Singer, Daniel E.] Harvard Univ, Sch Med, Boston, MA USA. [Hankey, Graeme J.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [Hacke, Werner] Heidelberg Univ, Heidelberg, Germany. [Becker, Richard C.] Univ Cincinnati, Coll Med, Dept Med, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA. [Nessel, Christopher C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Mahaffey, Kenneth W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA. [Califf, Robert M.] Duke Univ, Med Ctr, Duke Translat Med Inst, Durham, NC USA. [Fox, Keith A. A.] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fox, Keith A. A.] Royal Infirm Edinburgh NHS Trust, Edinburgh, Midlothian, Scotland. RP Breithardt, G (reprint author), Univ Hosp Munster, Dept Cardiovasc Med, Div Electrophysiol, Munster, Germany. EM g.breithardt@uni-muenster.de RI Hankey, Graeme /H-4968-2014 OI Hankey, Graeme /0000-0002-6044-7328 FU Janssen Research & Development (Raritan, New Jersey, USA); Bayer HealthCare AG (Leverkusen, Germany) FX The ROCKET AF trial was supported by research grants from Janssen Research & Development (Raritan, New Jersey, USA) and Bayer HealthCare AG (Leverkusen, Germany). NR 46 TC 6 Z9 6 U1 2 U2 3 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 EI 1468-201X J9 HEART JI Heart PD JUL PY 2016 VL 102 IS 13 BP 1036 EP 1043 DI 10.1136/heartjnl-2015-308120 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DP7YZ UT WOS:000378716400012 PM 26888572 ER PT J AU Choi, AJ Thomas, SS Singh, JP AF Choi, Anthony J. Thomas, Sunu S. Singh, Jagmeet P. TI Cardiac Resynchronization Therapy and Implantable Cardioverter Defibrillator Therapy in Advanced Heart Failure SO HEART FAILURE CLINICS LA English DT Article DE Heart failure; CIED; Defibrillator; Cardiac resynchronization therapy; Arrhythmia ID VENTRICULAR ASSIST DEVICE; MECHANICAL CIRCULATORY SUPPORT; ANTIARRHYTHMIC-DRUG THERAPY; INTERMACS ANNUAL-REPORT; BUNDLE-BRANCH BLOCK; LONG-TERM SURVIVAL; CONTINUOUS-FLOW; PRIMARY PREVENTION; INTERNATIONAL SOCIETY; ELECTRICAL DELAY AB Patients with advanced heart failure are at high risk for progression of their disease and sudden cardiac death. The role of device therapy in this patient population continues to evolve and is directed toward improving cardiac pump function and/or reducing sudden arrhythmic death. C1 [Choi, Anthony J.; Singh, Jagmeet P.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Electrophysiol Lab,Cardiac Arrhythmia Se, 55 Fruit St, Boston, MA 02114 USA. [Thomas, Sunu S.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Heart Failure & Transplant Serv,Dept Med, 55 Fruit St, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Electrophysiol Lab,Cardiac Arrhythmia Se, 55 Fruit St, Boston, MA 02114 USA. EM JSINGH@mgh.harvard.edu NR 69 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 1551-7136 J9 HEART FAIL CLIN JI Heart Fail. Clin. PD JUL PY 2016 VL 12 IS 3 BP 423 EP + DI 10.1016/j.hfc.2016.03.010 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DQ0QM UT WOS:000378905000010 PM 27371518 ER PT J AU Kadokura, A Frydenlund, N Leone, DA Yang, S Hoang, MP Deng, A Hernandez-Perez, M Biswas, A Singh, R Yaar, R Mahalingam, M AF Kadokura, Alexander Frydenlund, Noah Leone, Dominick A. Yang, Shi Hoang, Mai P. Deng, April Hernandez-Perez, Mader Biswas, Asok Singh, Rajendra Yaar, Ron Mahalingam, Meera TI Neurofibromin protein loss in desmoplastic melanoma subtypes: implicating NF1 allelic loss as a distinct genetic driver? SO HUMAN PATHOLOGY LA English DT Article DE Desmoplastic melanoma subtypes; Pure variant; Mixed variant; Neurofibromin; RETp ID CUTANEOUS MALIGNANT-MELANOMA; OF-THE-LITERATURE; PERINEURAL INVASION; TYPE-1; MUTATIONS; TUMORS; ASSOCIATION; DISEASE; PATIENT; PURE AB Loss of the NF1 allele, coding for the protein neurofibromin, and polymorphism in the protooncogene RET (RETp) are purportedly common in desmoplastic melanoma (DM). DM is categorized into pure (PDM) and mixed (MDM) subtypes, which differ in prognosis. Most NF1 mutations result in a truncated/absent protein, making immunohistochemical screening for neurofibromin an ideal surrogate for NF1 allelic loss. Using antineurofibromin, our aims were to ascertain the incidence of neurofibromin loss in DM subtypes and to evaluate the relationship with RET, perineural invasion (PNI) and established histopathologic prognosticators. A total of 78 archival samples of DM met criteria for inclusion (54 cases of non-DM serving as controls). Immunohistochemistry was performed for neurofibromin, whereas direct DNA sequencing was used for RETp and BRAF mutation status. Statistical analyses included chi(2) test as well as Fisher exact test. Neurofibromin loss was more common in DM than non-DM (69% versus 54%; P = .02). In DM, significant differences in neurofibromin loss were noted in the following: non head and neck versus head and neck biopsy site (88% versus 55%) and PDM versus MDM variants (80% versus 56%). No significant associations were noted with sex, presence of a junctional component, Breslow depth, ulceration, mitoses, host response, RETp, BRAF status, or PNI. RETp was marginally associated with PNI-positive DM versus PNI-negative DM (36 versus 18%; P = .08). Our findings, the largest to date investigating neurofibromin in DM, validate the incidence of NF1 mutations/allelic loss in DM and suggest that the DM subtypes have distinct genetic drivers. Published by Elsevier Inc. C1 [Kadokura, Alexander] Boston Univ, Sch Med, Div Grad Med Sci, Boston, MA 02118 USA. [Frydenlund, Noah] Univ Iowa, Carver Coll Med, Iowa City, IA 52240 USA. [Leone, Dominick A.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. [Yang, Shi] Boston Univ Med, Dept Pathol, Boston, MA 02118 USA. [Hoang, Mai P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02118 USA. [Deng, April] Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01601 USA. [Hernandez-Perez, Mader] Miraca Life Sci, Newton Upper Falls, MA 02458 USA. [Biswas, Asok] Western Gen Hosp, Dept Pathol, Edinburgh EH13 9QW, Midlothian, Scotland. [Singh, Rajendra] Icahn Sch Med Mt Sinai, Dept Pathol & Dermatol, New York, NY 10001 USA. [Yaar, Ron] Aurora Diagnost GPA Labs, Greensboro, NC 27401 USA. [Mahalingam, Meera] VA Consolidated Labs, Dept Pathol & Lab Med, Dermatopathol Sect, 1400 VFW PKWY, West Roxbury, MA 02132 USA. RP Mahalingam, M (reprint author), VA Consolidated Labs, Dept Pathol & Lab Med 113, Dermatopathol Sect, 1400 VFW PKWY, West Roxbury, MA 02132 USA. EM me@meeramahalingam.com NR 45 TC 2 Z9 2 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 0046-8177 EI 1532-8392 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 2016 VL 53 BP 82 EP 90 DI 10.1016/j.humpath.2016.02.012 PG 9 WC Pathology SC Pathology GA DP7GW UT WOS:000378668200011 PM 26980030 ER PT J AU Mendes, RT Nguyen, D Stephens, D Pamuk, F Fernandes, D Van Dyke, TE Kantarci, A AF Mendes, Reila Taina Nguyen, Daniel Stephens, Danielle Pamuk, Ferda Fernandes, Daniel Van Dyke, Thomas E. Kantarci, Alpdogan TI Endothelial Cell Response to Fusobacterium nucleatum SO INFECTION AND IMMUNITY LA English DT Article ID PORPHYROMONAS-GINGIVALIS; GROWTH-FACTOR; IN-VITRO; DISEASE; ANGIOGENESIS; EXPRESSION; ADHESION; VEGF; CD31; PERIODONTITIS AB Vascular response is an essential aspect of an effective immune response to periodontal disease pathogens, as new blood vessel formation contributes to wound healing and inflammation. Gaining a greater understanding of the factors that affect vascular response may then contribute to future breakthroughs in dental medicine. In this study, we have characterized the endothelial cell response to the common bacterium Fusobacterium nucleatum, an important bridging species that facilitates the activity of late colonizers of the dental biofilm. Endothelial cells were infected with Fusobacterium nucleatum (strain 25586) for periods of 4, 12, 24, or 48 h. Cell proliferation and tube formation were analyzed, and expression of adhesion molecules (CD31 and CD34) and vascular endothelial growth factor (VEGF) receptors 1 and 2 was measured by fluorescence-activated cell sorter (FACS) analysis. Data indicate that F. nucleatum impaired endothelial cell proliferation and tube formation. The findings suggest that the modified endothelial cell response acts as a mechanism promoting the pathogenic progression of periodontal diseases and may potentially suggest the involvement of periodontopathogens in systemic diseases associated with periodontal inflammation. C1 [Mendes, Reila Taina; Nguyen, Daniel; Stephens, Danielle; Pamuk, Ferda; Van Dyke, Thomas E.; Kantarci, Alpdogan] Forsyth Inst, Cambridge, MA USA. [Mendes, Reila Taina; Fernandes, Daniel] Univ Estadual Ponta Grossa, Ponta Grossa, PR, Brazil. [Pamuk, Ferda] Istanbul Aydin Univ, Istanbul, Turkey. RP Kantarci, A (reprint author), Forsyth Inst, Cambridge, MA USA. EM akantarci@forsyth.org FU NIH/NIDCR [DE020906, DE15566]; Capes/Brazil [2100/13-4] FX This work, including the efforts of Alpdogan Kantarci, was funded by NIH/NIDCR (DE020906 and DE15566). This work, including the efforts of Reila Taina Mendes, was funded by Capes/Brazil - Science without borders (2100/13-4). NR 50 TC 1 Z9 1 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2016 VL 84 IS 7 BP 2141 EP 2148 DI 10.1128/IAI.01305-15 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA DP5IO UT WOS:000378529700022 PM 27185790 ER PT J AU O'Neill, AF Adil, EA Irace, AL Neff, L Davis, IJ Perez-Atayde, AR Voss, SD Weinberg, O Rahbar, R AF O'Neill, Allison F. Adil, Eelam A. Irace, Alexandria L. Neff, Laura Davis, Ian J. Perez-Atayde, Antonio R. Voss, Stephan D. Weinberg, Olga Rahbar, Reza TI Post-transplant lymphoproliferative disorder of the pediatric airway: Presentation and management SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Review DE Post-transplant lymphoproliferative disorder; Airway obstruction; Epstein-Barr virus; Rituximab ID EPSTEIN-BARR-VIRUS; ORGAN TRANSPLANT RECIPIENTS; LIVER-TRANSPLANTATION; DISEASE PTLD; IMMUNOSUPPRESSION; RITUXIMAB; CHEMOTHERAPY; LYMPHOCYTES; CHILDREN; LOADS AB Objective: Post-transplant lymphoproliferative disorder (PTLD) is a rare complication of immunosuppression with little consensus on its evaluation and management. The purpose of this contemporary review is to describe a pediatric patient with PTLD of the airway and review the literature to provide multidisciplinary recommendations regarding management. Data Sources: Retrospective chart and literature review. Review Methods: A pediatric patient with PTLD of the airway is described. An extensive literature search to review the existing data on pediatric PTLD of the upper airway was also performed. Results: A pediatric patient with mixed fetal/embryonal hepatoblastoma developed laryngo-tracheal PTLD following liver transplantation. Diagnostic positron emission tomography (PET) scan demonstrated multiple sites of abnormal fluorodeoxyglucose (FDG) uptake within the larynx, distal esophagus, cervical lymph nodes, and abdomen concerning for PTLD. Laryngeal biopsy demonstrated Epstein Barr virus (EBV) positive cells confirming the diagnosis. Rituximab therapy and reduction of immunosuppression resulted in resolution of his laryngeal disease in 3 months. An extensive literature search to review the existing data on pediatric PTLD of the larynx and trachea revealed 14 reported cases. Conclusions: PTLD of the pediatric airway is an EBV-associated disease that requires a high index of suspicion as patients can often present with non-specific signs and symptoms but progress to have significant airway compromise. Evaluation consists of peripheral blood polymerase chain reaction (PCR) assays, biopsy, and PET/CT imaging. Management options include reduction of immunosuppression and/or systemic therapies. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [O'Neill, Allison F.] Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol,Med Sch, 300 Longwood Ave, Boston, MA 02115 USA. [Adil, Eelam A.; Irace, Alexandria L.; Rahbar, Reza] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, 300 Longwood Ave, Boston, MA 02115 USA. [Adil, Eelam A.; Rahbar, Reza] Harvard Univ, Dept Otolaryngol, Sch Med, 25 Shattuck St, Boston, MA 02115 USA. [Neff, Laura] Childrens Mercy Hosp, Dept Otolaryngol, 2401 Gillham Rd, Kansas City, MO 64108 USA. [Davis, Ian J.] Univ N Carolina, Dept Pediat & Genet, Chapel Hill, NC 27599 USA. [Davis, Ian J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Perez-Atayde, Antonio R.; Weinberg, Olga] Boston Childrens Hosp, Dept Pathol, 300 Longwood Ave, Boston, MA 02115 USA. [Voss, Stephan D.] Boston Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. RP O'Neill, AF (reprint author), Harvard Univ, Boston Childrens Hosp, Dana Farber Canc Inst, Dept Pediat Oncol,Med Sch, 300 Longwood Ave, Boston, MA 02115 USA. EM allison_oneill@dfci.harvard.edu NR 39 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2016 VL 86 BP 218 EP 223 DI 10.1016/j.ijpor1.2016.04.035 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA DP4EM UT WOS:000378449000042 PM 27260610 ER PT J AU Strychowsky, JE Albert, D Chan, K Cheng, A Daniel, SJ De Alarcon, A Garabedian, N Hart, C Hartnick, C Inglis, A Jacobs, I Kleinman, ME Mehta, NM Nicollas, R Nuss, R Pransky, S Russell, J Rutter, M Schilder, A Thompson, D Triglia, JM Volk, M Ward, B Watters, K Wyatt, M Zalzal, G Zur, K Rahbar, R AF Strychowsky, Julie E. Albert, David Chan, Kenny Cheng, Alan Daniel, Sam J. De Alarcon, Alessandro Garabedian, Noel Hart, Catherine Hartnick, Christopher Inglis, Andy Jacobs, Ian Kleinman, Monica E. Mehta, Nilesh M. Nicollas, Richard Nuss, Roger Pransky, Seth Russell, John Rutter, Mike Schilder, Anne Thompson, Dana Triglia, Jean-Michel Volk, Mark Ward, Bob Watters, Karen Wyatt, Michelle Zalzal, George Zur, Karen Rahbar, Reza TI International Pediatric Otolaryngology Group (IPOG) consensus recommendations: Routine peri-operative pediatric tracheotomy care SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Tracheotomy; Tracheostomy; Pediatric AB Objectives: To develop consensus recommendations for pen-operative tracheotomy care in pediatric patients. Methods: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). The mission of the IPOG is to develop expertise-based consensus recommendations for the management of pediatric otolaryngologic disorders with the goal of improving patient care. The consensus recommendations herein represent the first publication by the group. Results: Consensus recommendations including pre-operative, intra-operative, and post-operative considerations, as well as sedation and nutrition management are described. These recommendations are based on the collective opinion of the IPOG members and are targeted to (i) otolaryngologists who perform tracheotomies on pediatric patients, (ii) intensivists who are involved in the shared-care of these patients, and (iii) allied health professionals. Conclusion: Pediatric pen-operative tracheotomy care consensus recommendations are aimed at improving patient-centered care in this patient population. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Strychowsky, Julie E.; Nuss, Roger; Volk, Mark; Watters, Karen; Rahbar, Reza] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Strychowsky, Julie E.] Univ Western Ontario, Childrens Hosp, London Hlth Sci Ctr, Dept Otolaryngol Head & Neck Surg, London, ON, Canada. [Albert, David; Wyatt, Michelle] Great Ormond St Hosp Sick Children, Great Ormond St, London WC1N 3JH, England. [Chan, Kenny] Childrens Hosp Colorado, Aurora, CO USA. [Cheng, Alan] Univ Sydney, Dept Pediat Otolaryngol, Sydney Childrens Hosp Network, Westmead Campus, Sydney, NSW 2006, Australia. [Daniel, Sam J.] McGill Univ, Montreal Childrens Hosp, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [De Alarcon, Alessandro; Hart, Catherine; Rutter, Mike] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Garabedian, Noel] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Pediat ENT Dept, Paris, France. [Hartnick, Christopher] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. [Inglis, Andy] Seattle Childrens Hosp, Seattle, WA USA. [Jacobs, Ian; Zur, Karen] Childrens Hosp Philadelphia, Div Otolaryngol, Philadelphia, PA 19104 USA. [Kleinman, Monica E.; Mehta, Nilesh M.] Boston Childrens Hosp, Dept Anesthesiol Perioperat & Pain Med, Div Crit Care Med, Boston, MA USA. [Nicollas, Richard; Triglia, Jean-Michel] Aix Marseille Univ, La Timone Childrens Hosp, Dept Pediat Otolaryngol, Marseille, France. [Nuss, Roger; Volk, Mark; Watters, Karen; Rahbar, Reza] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Pransky, Seth] Rady Childrens Hosp, San Diego, CA USA. [Russell, John] Our Ladys Childrens Hosp, Dublin, Ireland. [Schilder, Anne] Royal Natl Throat Nose & Ear Hosp, UCL Ear Inst, EvidENT, Grays Inn Rd, London WC1X 8DA, England. [Thompson, Dana] Ann & Robert H Lurie Childrens Hosp Chicago, Div Otolaryngol Head & Neck Surg, Chicago, IL 60611 USA. [Ward, Bob] NYU, Dept Otolaryngol Head & Neck Surg, Langone Med Ctr, New York, NY USA. [Zalzal, George] Natl Childrens Hosp, Dept Otolaryngol, Washington, DC USA. RP Strychowsky, JE (reprint author), Univ Western Ontario, Dept Otolaryngol Head & Neck Surg, VH B3-444 800 Commissioners Rd East, London, ON N6A 5W9, Canada. EM julie.strychowsky@lhsc.on.ca RI Mehta, Nilesh/G-7073-2016 FU Department of Health [NIHR-RP-011-045]; NCATS NIH HHS [UL1 TR001425] NR 1 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2016 VL 86 BP 250 EP 255 DI 10.1016/j.ijpor1.2016.03.029 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA DP4EM UT WOS:000378449000049 PM 27132195 ER PT J AU Carter, J Rahbar, R Brigger, M Chan, K Cheng, A Daniel, SJ De Alarcon, A Garabedian, N Hart, C Hartnick, C Jacobs, I Liming, B Nicollas, R Pransky, S Richter, G Russell, J Rutter, MJ Schilder, A Smith, RJH Strychowsky, J Ward, R Watters, K Wyatt, M Zalzal, G Zur, K Thompson, D AF Carter, John Rahbar, Reza Brigger, Matthew Chan, Kenny Cheng, Alan Daniel, Sam J. De Alarcon, Alessandro Garabedian, Noel Hart, Catherine Hartnick, Christopher Jacobs, Ian Liming, Bryan Nicollas, Richard Pransky, Seth Richter, Gresham Russell, John Rutter, Michael J. Schilder, Anne Smith, Richard J. H. Strychowsky, Julie Ward, Robert Watters, Karen Wyatt, Michelle Zalzal, George Zur, Karen Thompson, Dana TI International Pediatric ORL Group (IPOG) laryngomalacia consensus recommendations SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE Laryngomalacia; Infant; Stridor; Pediatric AB Objective: To provide recommendations for the comprehensive management of young infants who present with signs or symptoms concerning for laryngomalacia. Methods: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG). Results: Consensus recommendations include initial care and triage recommendations for health care providers who commonly evaluate young infants with noisy breathing. The consensus statement also provides comprehensive care recommendations for otolaryngologists who manage young infants with laryngomalacia including: evaluation and treatment considerations for commonly debated issues in laryngomalacia, initial work-up of infants presenting with inspiratory stridor, treatment recommendations based on disease severity, management of the infant with feeding difficulties, post-surgical treatment management recommendations, and suggestions for acid suppression therapy. Conclusion: Laryngomalacia care consensus recommendations are aimed at improving patient centered care in infants with laryngomalacia. (C) 2016 Elsevier Ireland Ltd. All rights reserved. C1 [Carter, John; Thompson, Dana] Ann & Robert H Lurie Childrens Hosp Chicago, Div Otolaryngol Head & Neck Surg, 225 Chicago Ave, Chicago, IL 60611 USA. [Rahbar, Reza; Watters, Karen] Boston Childrens Hosp, Dept Otolaryngol & Commun Enhancement, Boston, MA USA. [Brigger, Matthew; Pransky, Seth] Rady Childrens Hosp, San Diego, CA USA. [Chan, Kenny] Childrens Hosp Colorado, Aurora, CO USA. [Cheng, Alan] Univ Sydney, Sydney Childrens Hosp Network, Dept Pediat Otolaryngol, Westmead Campus, Sydney, NSW 2006, Australia. [Daniel, Sam J.] McGill Univ, Montreal Childrens Hosp, Dept Otolaryngol Head & Neck Surg, Ctr Hlth, Montreal, PQ H3H 1P3, Canada. [De Alarcon, Alessandro; Hart, Catherine; Rutter, Michael J.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Garabedian, Noel] Univ Paris 05, Hop Necker Enfants Malad, AP HP, Pediat ENT Dept, Paris, France. [Hartnick, Christopher] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. [Jacobs, Ian; Zur, Karen] Childrens Hosp Philadelphia, Div Otolaryngol, Philadelphia, PA 19104 USA. [Liming, Bryan; Smith, Richard J. H.] Univ Iowa Hosp & Clin, Dept Otolaryngol, Iowa City, IA 52242 USA. [Nicollas, Richard] Aix Marseille Univ, La Timone Childrens Hosp, Dept Pediat Otolaryngol, Marseille, France. [Richter, Gresham] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Russell, John] Our Ladys Childrens Hosp, Dublin, Ireland. [Schilder, Anne] Royal Natl Throat Nose & Ear Hosp, UCL Ear Inst, EvidENT, Grays Inn Rd, London WC1X 8DA, England. [Strychowsky, Julie] Univ Western Ontario, Dept Otolaryngol Head & Neck Surg, Childrens Hosp, London Hlth Sci Ctr, London, ON, Canada. [Ward, Robert] NYU, Dept Otolaryngol Head & Neck Surg, Langone Med Ctr, New York, NY USA. [Wyatt, Michelle] Great Ormond St Hosp Sick Children, Great Ormond St, London WC1N 3JH, England. [Zalzal, George] Natl Childrens Hosp, Dept Otolaryngol, Washington, DC USA. RP Carter, J (reprint author), Ann & Robert H Lurie Childrens Hosp Chicago, Div Otolaryngol Head & Neck Surg, 225 Chicago Ave, Chicago, IL 60611 USA. EM jmcarter@luriechildrens.org FU Department of Health [NIHR-RP-011-045]; NCATS NIH HHS [UL1 TR001425] NR 0 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 EI 1872-8464 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2016 VL 86 BP 256 EP 261 DI 10.1016/j.ijpor1.2016.04.007 PG 6 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA DP4EM UT WOS:000378449000050 PM 27107728 ER PT J AU Morrison, K Winter, L Gitlin, LN AF Morrison, Karen Winter, Laraine Gitlin, Laura N. TI Recruiting Community-Based Dementia Patients and Caregivers in a Nonpharmacologic Randomized Trial: What Works and How Much Does It Cost? SO JOURNAL OF APPLIED GERONTOLOGY LA English DT Article DE caregiving; dementia care; home care; clinical trials ID ALZHEIMER-DISEASE RESEARCH; OLDER-ADULTS; INTERVENTION RESEARCH; AFRICAN-AMERICAN; AGING RESEARCH; RETENTION; MANAGEMENT; PARTICIPATION; PREVENTION; ATTITUDES AB Objectives: The aim of this study was to evaluate the yield and cost of three recruitment strategiesdirect mail, newspaper advertisements, and community outreachfor identifying and enrolling dementia caregivers into a randomized trial testing a nonpharmacologic approach to enhancing quality of life of patients and caregivers (dyads). Method: Enrollment occurred between 2006 and 2008. The number of recruitment inquiries, number and race of enrollees, and costs for each recruitment strategy were recorded. Results: Of 284 inquiries, 237 (83%) dyads enrolled. Total cost for recruitment across methodologies was US$154 per dyad. Direct mailings resulted in the most enrollees (n = 135, 57%) and was the least costly method (US$63 per dyad) compared with newspaper ads (US$224 per dyad) and community outreach (US$350 per dyad). Although enrollees were predominately White, mailings yielded the highest number of non-Whites (n = 37). Discussion: Direct mailings was the most effective and least costly method for enrolling dyads in a nonpharmacologic dementia trial. C1 [Morrison, Karen] Bayada Home Hlth Care, 190 N Independence Mall West,Suite 700, Philadelphia, PA 19106 USA. [Winter, Laraine] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Gitlin, Laura N.] Johns Hopkins Univ, Ctr Innovat Care Aging, Baltimore, MD USA. RP Morrison, K (reprint author), Bayada Home Hlth Care, 190 N Independence Mall West,Suite 700, Philadelphia, PA 19106 USA. EM morrisonkk49@gmail.com FU National Institute on Aging; National Institute on Nursing Research [RO1 AG22254]; PA Department of Health, Tobacco Settlement [SAP 100027298] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Research reported in this article was supported by funds from the National Institute on Aging and the National Institute on Nursing Research (Grant RO1 AG22254) and the PA Department of Health, Tobacco Settlement (SAP 100027298). NR 40 TC 3 Z9 3 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0733-4648 EI 1552-4523 J9 J APPL GERONTOL JI J. Appl. Gerontol. PD JUL PY 2016 VL 35 IS 7 BP 788 EP 800 DI 10.1177/0733464814532012 PG 13 WC Gerontology SC Geriatrics & Gerontology GA DP7PM UT WOS:000378691300006 PM 24799354 ER PT J AU Dy, ME Chang, FCF De Jesus, S Anselm, I Mahant, N Zeilman, P Rodan, LH Foote, KD Tan, WH Eskandar, E Sharma, N Okun, MS Fung, VSC Waugh, JL AF Dy, Marisela E. Chang, Florence C. F. De Jesus, Sol Anselm, Irina Mahant, Neil Zeilman, Pamela Rodan, Lance H. Foote, Kelly D. Tan, Wen-Hann Eskandar, Emad Sharma, Nutan Okun, Michael S. Fung, Victor S. C. Waugh, Jeff L. TI Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series SO JOURNAL OF CHILD NEUROLOGY LA English DT Article DE chorea; ADCY5; deep brain stimulation; whole-exome sequencing; hyperkinetic movements ID FACIAL MYOKYMIA FDFM; FAMILIAL DYSKINESIA; ADCY5 MUTATIONS; EXPRESSION; GENE AB ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials. All had extensive imaging, metabolic, and genetic testing prior to confirmation of their ADCY5 mutation. Two of the patients had the c.1252C>T; p.R418W mutation, while the youngest and most severely affected had a de novo c.2080_2088del; p.K694_M696 mutation. All had variable and incomplete, but positive responses to deep brain stimulation. The authors conclude that deep brain stimulation may provide benefit in ADCY5-related movement disorders. Long-term efficacy remains to be confirmed by longitudinal observation. ADCY5 should be considered in the differential diagnosis of early onset hyperkinetic movement disorders, and may respond to deep brain stimulation. C1 [Dy, Marisela E.; Anselm, Irina; Sharma, Nutan; Waugh, Jeff L.] Boston Childrens Hosp, Dept Neurol, 333 Longwood Ave,Fegan 11, Boston, MA 02115 USA. [Dy, Marisela E.; Sharma, Nutan; Waugh, Jeff L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Dy, Marisela E.; Anselm, Irina; Rodan, Lance H.; Tan, Wen-Hann; Eskandar, Emad; Sharma, Nutan; Waugh, Jeff L.] Harvard Med Sch, Boston, MA USA. [Chang, Florence C. F.; Mahant, Neil; Fung, Victor S. C.] Westmead Hosp, Dept Neurol, Movement Disorders Unit, Westmead, NSW, Australia. [Chang, Florence C. F.; Mahant, Neil; Fung, Victor S. C.] Univ Sydney, Sydney Med Sch, Sydney, NSW, Australia. [De Jesus, Sol; Zeilman, Pamela; Okun, Michael S.] Univ Florida, Dept Neurol, Ctr Movement Disorders & Neurorestorat, Gainesville, FL USA. [Rodan, Lance H.; Tan, Wen-Hann] Boston Childrens Hosp, Div Genet & Genom, 333 Longwood Ave,Fegan 11, Boston, MA 02115 USA. [Foote, Kelly D.; Okun, Michael S.] Univ Florida, Dept Neurosurg, Ctr Movement Disorders & Neurorestorat, Gainesville, FL USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Dy, ME (reprint author), Boston Childrens Hosp, Dept Neurol, 333 Longwood Ave,Fegan 11, Boston, MA 02115 USA. EM marisela.dy@childrens.harvard.edu NR 18 TC 2 Z9 2 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0883-0738 EI 1708-8283 J9 J CHILD NEUROL JI J. Child Neurol. PD JUL PY 2016 VL 31 IS 8 BP 1027 EP 1035 DI 10.1177/0883073816635749 PG 9 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA DQ0GL UT WOS:000378876900011 PM 27052971 ER PT J AU Bevers, MB McGuone, D Jerath, NU Musolino, PL AF Bevers, Matthew B. McGuone, Declan Jerath, Nivedita U. Musolino, Patricia L. TI Leptomeningeal transthyretin-type amyloidosis presenting as acute hydrocephalus and subarachnoid hemorrhage SO JOURNAL OF CLINICAL NEUROSCIENCE LA English DT Article DE Amyloidosis; Subarachnoid hemorrhage; Transthyretin ID MENINGOCEREBROVASCULAR AMYLOIDOSIS; POLYNEUROPATHY; TAFAMIDIS AB We present a report of a 47-year-old woman with developmental delay who presented with subarachnoid hemorrhage and acute hydrocephalus. She did not have an aneurysm, but there was symmetric calcification and gadolinium-enhancement of the meninges within the Sylvian fissure. Biopsy and genetic testing confirmed transthyretin-type amyloidosis. It is important to consider such rare causes in atypical presentations of non-aneurysmal subarachnoid hemorrhage. (c) 2016 Elsevier Ltd. All rights reserved. C1 [Bevers, Matthew B.; Jerath, Nivedita U.; Musolino, Patricia L.] Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 835, Boston, MA 02118 USA. [McGuone, Declan] Massachusetts Gen Hosp, Dept Neuropathol, Boston, MA 02118 USA. [McGuone, Declan] Off Chief Med Examiner, New York, NY USA. [Jerath, Nivedita U.] Univ Iowa Hosp & Clin, Dept Neurol, Iowa City, IA 52242 USA. RP Bevers, MB (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,WACC 835, Boston, MA 02118 USA. EM mbevers@partners.org NR 9 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 0967-5868 EI 1532-2653 J9 J CLIN NEUROSCI JI J. Clin. Neurosci. PD JUL PY 2016 VL 29 BP 203 EP 205 DI 10.1016/j.jocn.2015.12.017 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP4EU UT WOS:000378449800047 PM 26896372 ER PT J AU Song, Y Chou, EL Baecker, A You, NCY Song, YQ Sun, Q Liu, SM AF Song, Yan Chou, Elizabeth L. Baecker, Aileen You, Nai-Chieh Y. Song, Yiqing Sun, Qi Liu, Simin TI Endocrine-disrupting chemicals, risk of type 2 diabetes, and diabetes-related metabolic traits: A systematic review and meta-analysis SO JOURNAL OF DIABETES LA English DT Article DE bisphenol A; diabetes; endocrine-disrupting chemical; phthalate; meta-analysis ID PERSISTENT ORGANIC POLLUTANTS; NUTRITION EXAMINATION SURVEY; BISPHENOL-A CONCENTRATION; POLYCHLORINATED BIPHENYL EXPOSURE; CAPACITOR MANUFACTURING PLANT; INSULIN-RESISTANCE; PHTHALATE METABOLITES; SERUM CONCENTRATIONS; NATIONAL-HEALTH; ORGANOCHLORINE PESTICIDES AB BackgroundElevated blood or urinary concentrations of endocrine-disrupting chemicals (EDCs) may be related to increased risk of type 2 diabetes (T2D). The aim of the present study was to assess the role of EDCs in affecting risk of T2D and related metabolic traits. MethodsMEDLINE was searched for cross-sectional and prospective studies published before 8 March 2014 into the association between EDCs (dioxin, polychlorinated biphenyl [PCB], chlorinated pesticide, bisphenol A [BPA], phthalate) and T2D and related metabolic traits. Three investigators independently extracted information on study design, participant characteristics, EDC types and concentrations, and association measures. ResultsForty-one cross-sectional and eight prospective studies from ethnically diverse populations were included in the analysis. Serum concentrations of dioxins, PCBs, and chlorinated pesticides were significantly associated with T2D risk; comparing the highest to lowest concentration category, the pooled relative risks (RR) were 1.91 (95% confidence interval [CI] 1.44-2.54) for dioxins, 2.39 (95% CI 1.86-3.08) for total PCBs, and 2.30 (95% CI 1.81-2.93) for chlorinated pesticides. Urinary concentrations of BPA and phthalates were also associated with T2D risk; comparing the highest to lowest concentration categories, the pooled RR were 1.45 (95% CI 1.13-1.87) for BPA and 1.48 (95% CI 0.98-2.25) for phthalates. Further, EDC concentrations were associated with indicators of impaired fasting glucose and insulin resistance. ConclusionsPersistent and non-persistent EDCs may affect the risk of T2D. There is an urgent need for further investigation of EDCs, especially non-persistent ones, and T2D risk in large prospective studies. C1 [Song, Yan; Baecker, Aileen; You, Nai-Chieh Y.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA. [Song, Yan; Liu, Simin] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA. [Liu, Simin] Brown Univ, Dept Med, Alpert Med Sch, Providence, RI 02912 USA. [Song, Yiqing] Indiana Univ, Dept Epidemiol, Richard M Fairbanks Sch Publ Hlth, Indianapolis, IN 46204 USA. [Sun, Qi] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA. [Sun, Qi] Harvard Med Sch, Boston, MA USA. [Sun, Qi] Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA. [Chou, Elizabeth L.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Liu, SM (reprint author), Brown Univ, Box G-S121-2,121 South Main St, Providence, RI 02912 USA. EM simin_liu@brown.edu FU Burroughs Wellcome Fund FX This research was funded by the Burroughs Wellcome Fund. NR 74 TC 9 Z9 10 U1 15 U2 27 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1753-0393 EI 1753-0407 J9 J DIABETES JI J. Diabetes PD JUL PY 2016 VL 8 IS 4 BP 516 EP 532 DI 10.1111/1753-0407.12325 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DP8DE UT WOS:000378727300009 PM 26119400 ER PT J AU Ziegler, A Walker, R Varvares, M AF Ziegler, Andrea Walker, Ronald Varvares, Mark TI Oncologic Outcomes of Invasive Squamous Cell Carcinoma of the Scalp Requiring Resection of Cranial Bone SO JOURNAL OF NEUROLOGICAL SURGERY PART A-CENTRAL EUROPEAN NEUROSURGERY LA English DT Article DE squamous cell carcinoma; scalp cancer; head and neck cancer; survival outcomes; periosteal invasion ID CLINICAL PERINEURAL INVASION; RISK-FACTORS; HEAD; NECK; METASTASIS; SKIN; RECURRENCE; CANCER AB ObjectivesTo identify the recurrence rates and survival outcomes of patients with invasive squamous cell carcinoma of the scalp. MethodsThis study was a retrospective chart review of eight patients that had squamous cell carcinoma of the scalp with either periosteal or skull invasion on clinical and/or radiographic evaluation. ResultsThe disease-free survival was 62.5% (5/8 patients) with a local control rate of 75% (6/8 patients) for the entire group. The two patients with full-thickness craniectomy had a local control rate of 100% (2/2 patients); the patients with outer cortex removal had a local control rate of 66.7% (4/6 patients). The disease-free survival of the full-thickness group was 50% (1/2 patients ), and the disease-free survival of the outer cortex removal patients was 66.7% (4/6 patients). ConclusionDespite the invasive nature of this disease, a high degree of local control can be achieved in this high-risk group with multiple comorbidities using outer cortex drilldown, and, in properly selected patients, full-thickness calvarial resection. We conclude that for patients without evidence of medullary involvement that outer table drilldown offers a well-tolerated approach with reasonable oncologic control. C1 [Ziegler, Andrea] Loyola Univ, Stritch Sch Med, Dept Otolaryngol, 2160 S 1st Ave, Maywood, IL 60153 USA. [Walker, Ronald] St Louis Univ, Sch Med, Dept Otolaryngol, St Louis, MO USA. [Varvares, Mark] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RP Varvares, M (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, 243 Charter St, Boston, MA 02114 USA. EM mark_varvares@meei.harvard.edu NR 14 TC 0 Z9 0 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 2193-6315 EI 2193-6323 J9 J NEUROL SURG PART A JI J. Neurol. Surg. Part A PD JUL PY 2016 VL 77 IS 4 BP 308 EP 311 DI 10.1055/s-0035-1567859 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA DP6MC UT WOS:000378610200005 PM 26807618 ER PT J AU Costine, B Smith, C Price, G McGuone, D Duhaime, AC AF Costine, Beth Smith, Colin Price, George McGuone, Declan Duhaime, Ann-Christine TI NEUROBLASTS DIFFERENTIATE AT THE WHITE MATTER LESION AFTER TBI IN THE GYRENCEPHALIC BRAIN SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE cortical impact; gyrencephalic; doublecortin; white matter C1 [Costine, Beth; Smith, Colin; Price, George; McGuone, Declan; Duhaime, Ann-Christine] Massachusetts Gen Hosp, Neurosurg, Boston, MA 02114 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSA-153 BP A66 EP A67 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200181 ER PT J AU Dixon, CE Carlson, SW AF Dixon, C. Edward Carlson, Shaun W. TI FUNCTIONAL DEFICITS ARE ATTENUATED IN HUMAN ALPHA SYNUCLEIN TRANSGENIC RATS AFTER TBI SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE alpha synuclein; transgenic; CCI; function C1 [Dixon, C. Edward; Carlson, Shaun W.] Univ Pittsburgh, Neurosurg, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Neurosurg, Pittsburgh, PA 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-190 BP A80 EP A81 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200219 ER PT J AU Duhaime, AC Murphy, S Rincon, S Young, J Adapa, P Caruso, P AF Duhaime, Ann-Christine Murphy, Sarah Rincon, Sandra Young, Joseph Adapa, Pavani Caruso, Paul TI MRI-CENTRIC ASSESSMENT AND MANAGEMENT IN ACUTE PEDIATRIC TBI: UTILITY AND RELIABILITY COMPARED TO CT SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE MRI; CT; neuroimaging; management; emergency department; intensive care unit C1 [Duhaime, Ann-Christine; Murphy, Sarah; Rincon, Sandra; Young, Joseph; Adapa, Pavani; Caruso, Paul] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Neurosurg, Boston, MA 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-271 BP A110 EP A110 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200300 ER PT J AU Edlow, B Chatelle, C Spencer, C Chu, C O'Connor, K Hirschberg, R Hochberg, L Giacino, J Rosenthal, E Wu, O AF Edlow, Brian Chatelle, Camille Spencer, Camille Chu, Catherine O'Connor, Kathryn Hirschberg, Ronald Hochberg, Leigh Giacino, Joseph Rosenthal, Eric Wu, Ona TI DETECTING CONSCIOUSNESS AND PREDICTING RECOVERY IN ACUTE SEVERE TRAUMATIC BRAIN INJURY SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE coma; consciousness C1 [Edlow, Brian; Chatelle, Camille; Spencer, Camille; Chu, Catherine; O'Connor, Kathryn; Hochberg, Leigh; Rosenthal, Eric] Harvard Univ, Massachusetts Gen Hosp, Neurol, Boston, MA 02115 USA. [Wu, Ona] Harvard Univ, Massachusetts Gen Hosp, Radiol, Boston, MA 02115 USA. [Hirschberg, Ronald; Giacino, Joseph] Spaulding Rehabil Hosp, PM&R, Charlestown, MA USA. NR 0 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSA-094 BP A46 EP A47 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200123 ER PT J AU Grovola, M Harris, JP Brown, DP Wolf, JA Cullen, DK AF Grovola, Michael Harris, James P. Brown, Daniel P. Wolf, John A. Cullen, D. Kacy TI NEUROPATHOLOGICAL ALTERATIONS IN THE HILUS AFTER DIFFUSE BRAIN INJURY SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE large animal models; mossy cell; diffuse brain injury; synaptic changes C1 [Grovola, Michael; Harris, James P.; Brown, Daniel P.; Wolf, John A.; Cullen, D. Kacy] Univ Penn, Neurosurg, Philadelphia, PA 19104 USA. [Grovola, Michael; Harris, James P.; Brown, Daniel P.; Wolf, John A.; Cullen, D. Kacy] Philadelphia VA Med Ctr, Neurosurg, Philadelphia, PA 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-247 BP A101 EP A101 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200276 ER PT J AU Gupta, R Ahmadi, E Namati, J Blair, P Padole, A Chico-Calero, I Lev, M Lee, J Hamblin, M Vakoc, B AF Gupta, Rajiv Ahmadi, Emad Namati, Jacqueline Blair, Parry Padole, Atul Chico-Calero, Isabel Lev, Michael Lee, Jarone Hamblin, Michael Vakoc, Benjamin TI LOW-LEVEL LIGHT THERAPY FOR TRAUMATIC BRAIN INJURY (TBI) SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE low-level light therapy; advanced MRI imaging; diffusion tensor imaging; resting-state fMRI; hypercapnia; cerbrovascular reserve C1 [Gupta, Rajiv; Ahmadi, Emad; Namati, Jacqueline; Blair, Parry; Padole, Atul; Chico-Calero, Isabel; Lev, Michael; Lee, Jarone; Hamblin, Michael; Vakoc, Benjamin] Massachusetts Gen Hosp, Neuroradiol, Boston, MA 02114 USA. [Gupta, Rajiv; Ahmadi, Emad; Namati, Jacqueline; Padole, Atul; Chico-Calero, Isabel; Lev, Michael; Lee, Jarone; Hamblin, Michael; Vakoc, Benjamin] Harvard Univ, Sch Med, Radiol, Boston, MA USA. NR 0 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA AANS02-03 BP A2 EP A3 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200004 ER PT J AU Haghighi, F Carr, W LoPresti, M Yarnell, A Karmakar, M Mendelev, N Umali, M McCarron, R Elder, G Ahlers, S AF Haghighi, Fatemeh Carr, Walter LoPresti, Matthew Yarnell, Angela Karmakar, Moumita Mendelev, Natalia Umali, Michelle McCarron, Richard Elder, Gregory Ahlers, Stephen TI EPIGENETIC AND TRANSCRIPTIONAL SIGNATURES OF BLAST EXPOSURE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE epigenetics; methylation; blast C1 [Haghighi, Fatemeh; Karmakar, Moumita; Mendelev, Natalia] Icahn Sch Med Mt Sinai, Neurosci, New York, NY 10029 USA. [Haghighi, Fatemeh; Umali, Michelle; Elder, Gregory] James J Peters VA Med Ctr, Med Epigen, New York, NY USA. [Carr, Walter; LoPresti, Matthew; Yarnell, Angela] Walter Reed Army Inst Res, Rockville, MD USA. [McCarron, Richard; Ahlers, Stephen] Naval Med Res Ctr, Silver Spring, MD 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-183 BP A78 EP A78 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200212 ER PT J AU Harel, N Yung, L Romero, A Santiago, T Guber, K Kastuar, S Nguyen, N Wu, YK Carmel, J Spungen, A Bauman, W AF Harel, Noam Yung, Lok Romero, Angelica Santiago, Tiffany Guber, Kenneth Kastuar, Shivani Nhuquynh Nguyen Wu, Yu-Kuang Carmel, Jason Spungen, Ann Bauman, William TI PAIRED MAGNETIC AND ELECTRICAL STIMULATION FOR CERVICAL SCI SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE non-invasive brain stimulation; TMS; cervical electrical stimulation; spike timing-dependent plasticity C1 [Harel, Noam; Yung, Lok; Romero, Angelica; Santiago, Tiffany; Guber, Kenneth; Nhuquynh Nguyen; Wu, Yu-Kuang; Spungen, Ann; Bauman, William] James J Peters VA Med Ctr, Neurol, Spinal Cord Injury, Bronx, NY USA. [Harel, Noam; Kastuar, Shivani; Spungen, Ann; Bauman, William] Icahn Sch Med Mt Sinai, Neurol, Rehabil Med, New York, NY 10029 USA. [Carmel, Jason] Cornell Univ, Coll Med, Burke Med Res Inst, Neurol, White Plains, NY 10605 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA AANS03-02 BP A3 EP A3 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200006 ER PT J AU Padole, A Ahmadi, E He, J Vablus, M Chan, P Namati, J Vakoc, B Tan, C Hayman, A Gupta, R AF Padole, Atul Ahmadi, Emad He, Julian Vablus, Mark Chan, Phoebe Namati, Jacqueline Vakoc, Benjamin Tan, Can Hayman, Anne Gupta, Rajiv TI ASSESSMENT OF WHITE MATTER TRACTS IN ACUTE HEAD TRAUMA USING ANATOM-E SOFTWARE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE acute head trauma; white matter tracts systems; software with deformable anatomic template C1 [Padole, Atul; Ahmadi, Emad; He, Julian; Chan, Phoebe; Namati, Jacqueline; Vakoc, Benjamin; Tan, Can; Hayman, Anne; Gupta, Rajiv] Massachusetts Gen Hosp, Neuroradiol, Boston, MA 02114 USA. [Vablus, Mark] Anatom E Syst, Houston, TX USA. NR 0 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSA-175 BP A75 EP A75 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200203 ER PT J AU Spencer, C Chatelle, C Chu, C Wu, O Giacino, J Rosenthal, E Edlow, B AF Spencer, Camille Chatelle, Camille Chu, Catherine Wu, Ona Giacino, Joseph Rosenthal, Eric Edlow, Brian TI LONGITUDINAL CHANGES IN CORTICAL NETWORK CONNECTIVITY AFTER RECOVERY FROM TRAUMATIC COMA SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE consciousness; coma; EEG; networks C1 [Spencer, Camille; Chatelle, Camille; Chu, Catherine; Rosenthal, Eric; Edlow, Brian] Massachusetts Gen Hosp, Neurol, Boston, MA 02114 USA. [Wu, Ona] Massachusetts Gen Hosp, Radiol, Boston, MA 02114 USA. [Giacino, Joseph] Spaulding Rehabil Hosp, PM&R, Charlestown, MA 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-255 BP A104 EP A104 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200284 ER PT J AU Tan, CO Hu, RL Padole, A Besheli, LD Lev, M Forghani, R Young, J Romero, J Gupta, R AF Tan, Can Ozan Hu, Ranliang Padole, Atul Besheli, Laleh Daftari Lev, Michael Forghani, Reza Young, Joseph Romero, Javier Gupta, Rajiv TI DUAL ENERGY CT SPOT SIGN FOR ASSESSMENT OF ACUTE INTRACRANIAL HEMORRHAGE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE intracranial hemorrhage; dual energy computed tomography; hematoma expansion; spot sign C1 [Hu, Ranliang; Padole, Atul; Besheli, Laleh Daftari; Lev, Michael; Young, Joseph; Romero, Javier; Gupta, Rajiv] Massachusetts Gen Hosp, Neuroradiol, Boston, MA 02114 USA. [Tan, Can Ozan] Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA USA. [Forghani, Reza] McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. [Tan, Can Ozan; Hu, Ranliang; Padole, Atul; Besheli, Laleh Daftari; Lev, Michael; Young, Joseph; Romero, Javier; Gupta, Rajiv] Harvard Univ, Sch Med, Boston, MA USA. [Forghani, Reza] McGill Univ, Montreal, PQ, Canada. NR 0 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-265 BP A108 EP A108 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200294 ER PT J AU Wofford, KL Browne, K Harris, JP Mietus, C Brown, DP Grovola, M Kuo, E Wolf, JA Duda, JE Spiller, KL Cullen, DK AF Wofford, Kathryn L. Browne, Kevin Harris, James P. Mietus, Constance Brown, Daniel P. Grovola, Michael Kuo, Emory Wolf, John A. Duda, John E. Spiller, Kara L. Cullen, D. Kacy TI RAPID MICROGLIAL ACTIVATION NEAR INJURED NEURONS FOLLOWING DIFFUSE BRAIN INJURY IN SWINE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 34th Annual National Neurotrauma Symposium CY JUN 26-29, 2016 CL Lexington, KY DE diffuse brain injury; plasmalemmal disruption; glial reactivity C1 [Wofford, Kathryn L.; Browne, Kevin; Harris, James P.; Brown, Daniel P.; Grovola, Michael; Kuo, Emory; Wolf, John A.; Duda, John E.; Cullen, D. Kacy] Vet Affairs Med Ctr, Philadelphia, PA USA. [Wofford, Kathryn L.; Browne, Kevin; Harris, James P.; Mietus, Constance; Brown, Daniel P.; Grovola, Michael; Kuo, Emory; Wolf, John A.; Cullen, D. Kacy] Univ Penn, Neurosurg, Ctr Brain Injury & Repair, Philadelphia, PA 19104 USA. [Wofford, Kathryn L.; Spiller, Kara L.] Drexel Univ, Biomed Engn, Philadelphia, PA 19104 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 0897-7151 EI 1557-9042 J9 J NEUROTRAUM JI J. Neurotrauma PD JUL 1 PY 2016 VL 33 IS 13 MA PSB-295 BP A118 EP A119 PG 2 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA DP2QY UT WOS:000378336200324 ER PT J AU Renapurkar, S Pasternack, MS Nielsen, GP Kaban, LB AF Renapurkar, Shravan Pasternack, Mark S. Nielsen, G. Petur Kaban, Leonard B. TI Juvenile Mandibular Chronic Osteomyelitis: Role of Surgical Debridement and Antibiotics SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID DIFFUSE SCLEROSING OSTEOMYELITIS; RECURRENT MULTIFOCAL OSTEOMYELITIS; OSTEITIS SAPHO SYNDROME; OF-THE-LITERATURE; RETROSPECTIVE ANALYSIS; HYPEROSTOSIS; PUSTULOSIS; SYNOVITIS; ACNE; CLASSIFICATION AB Purpose: To document outcomes of management of juvenile mandibular chronic osteomyelitis (JMCO) using a standardized treatment protocol including open biopsy, decortication, microbial culture, and long-term antibiotic therapy. Materials and Methods: This was a retrospective case study of pediatric patients with JMCO treated at Massachusetts General Hospital for Children from 1996 through 2014. Inclusion criteria included age younger than 18 years, diagnosis of JMCO, management by the protocol, adequate clinical and radiographic data in the record, and follow-up of at least 1 year after initial treatment. Inpatient and outpatient records were reviewed for demographics, clinical and radiographic findings, and histologic and laboratory evaluations. The predictor variable was the standardized treatment protocol and the primary outcome variables were disease status at end of treatment and complications of treatment. Results: Twenty patients (mean age at onset, 10.7 yr; range, 3 to 14 yr) were treated, 12 (11 girls) of whom met the inclusion criteria. Management of all patients consisted of biopsy (extraoral when feasible, n = 9; intraoral, n = 3), decortication, cultures, and long-term antibiotic therapy. Nonsteroidal antiinflammatory drugs (NSAIDs) were administered only as needed for pain control. There was complete resolution of osteomyelitis with no recurrence in 7 of 12 patients (mean follow-up, 4.3 yr; range, 1 to 11 yr). Five patients had partial responses, with decreased frequency and severity of disease recurrence. These were well controlled with short courses of antibiotics (4 to 12 weeks) with NSAIDs only as needed for pain control (mean follow-up, 1.4 yr; range, 1 to 3 yr). There were no major complications related to antibiotic therapy. Minor complications included rash (n = 2), nausea and vomiting (n = 1), and vaginal candidiasis (n = 1). Conclusion: The results of this study indicate that 58.3% of patients were cured and had no recurrent symptoms (mean follow-up, 4.3 yr). The remaining patients continue on intermittent treatment with antibiotics for recurrent episodes of swelling and pain. Favorable responses to antibiotic therapy support the hypothesis that JMCO is an infectious disease and that negative cultures might represent a failure of standard culture techniques to isolate the responsible organisms. (C) 2016 American Association of Oral and Maxillofacial Surgeons. C1 [Renapurkar, Shravan] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, 188 Longwood Ave, Boston, MA 02115 USA. [Pasternack, Mark S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Infect Dis, Boston, MA USA. [Nielsen, G. Petur] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Kaban, Leonard B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp,Massachusetts Gen Hosp Chi, 188 Longwood Ave, Boston, MA 02115 USA. RP Kaban, LB (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM Kaban.leonard@mgh.harvard.edu FU Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund; MGH/AO Pediatric CMF fellowship FX This study was funded by the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund and MGH/AO Pediatric CMF fellowship. NR 31 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2016 VL 74 IS 7 BP 1368 EP 1382 DI 10.1016/j.joms.2016.01.027 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DP5ZH UT WOS:000378576200015 PM 26921614 ER PT J AU Partridge, JC Cipriani, N Faquin, WC Chuang, SK Keith, DA Lahey, ET AF Partridge, Justin C. Cipriani, Nicole Faquin, William C. Chuang, Sung K. Keith, David A. Lahey, Edward Thomas TI Periarticular Cysts of the Temporomandibular Joint Are More Frequently Synovial Than Ganglion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article AB Purpose: Differentiating between ganglion and synovial cysts by standard histology is difficult, leading to inaccurate statements on frequency for each of these periarticular lesions. The purpose of this study was to use immunohistochemical (IHC) analysis to 1) calculate the accuracy of the histologic diagnoses, 2) determine the frequency of ganglion and synovial cysts of the temporomandibular joint (TMJ), and 3) compare the frequency of these lesions in the TMJ compared with the extracranial skeleton in patients treated at Massachusetts General Hospital (MGH). Materials and Methods: This is a retrospective cohort study of all patients undergoing treatment of TMJ cysts at MGH from 2001 through 2013. IHC analysis of tissue samples for each patient was completed and compared with the original histologic diagnoses. Categorical variables, including age, gender, and sidedness, were recorded. A natural language search of the MGH Department of Pathology database determined the frequency of extracranial periarticular cysts during the same period. Results: Thirteen patients met the inclusion criteria. Eleven cysts were synovial and 2 were ganglion based on histology. IHC analysis identified 2 false-positive synovial cyst diagnoses, resulting in 100% sensitivity and 50% specificity for the original histologic assessment and a percentage error of 22%. Of the periarticular TMJ lesions, 69% were synovial cysts and 31% were ganglion cysts. The frequency of TMJ versus extracranial ganglion cysts was 0.24%, and the frequency of TMJ versus extracranial synovial cysts was 0.60% based on 3,176 extracranial cysts (1,506 synovial; 1,670 ganglion). Conclusion: This study represents the largest single-institution experience with periarticular cysts of the TMJ, and contrary to previous reports, TMJ cysts appear to be more frequently synovial than ganglion. IHC can be used to overcome the relatively poor specificity of histologic diagnosis of synovial cysts. (C) 2016 American Association of Oral and Maxillofacial Surgeons C1 [Partridge, Justin C.; Chuang, Sung K.; Keith, David A.; Lahey, Edward Thomas] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Partridge, Justin C.; Chuang, Sung K.; Keith, David A.; Lahey, Edward Thomas] Harvard Univ, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. [Cipriani, Nicole] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Cipriani, Nicole; Faquin, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Cipriani, Nicole] Univ Chicago Med & Biol Sci, Pathol, Chicago, IL USA. [Faquin, William C.] Massachusetts Gen Hosp, Head & Neck Pathol, Boston, MA 02114 USA. [Faquin, William C.] Massachusetts Gen Hosp, Pathol, Boston, MA 02114 USA. RP Lahey, ET (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Massachusetts Gen Hosp, 188 Longwood Ave, Boston, MA 02115 USA. EM elahey@post.harvard.edu FU Education and Research Fund; Department of Oral and Maxillofacial Surgery; Massachusetts General Hospital; Harvard Medical School Scholars in Medicine Office FX This study was funded by the Education and Research Fund, Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital and the Harvard Medical School Scholars in Medicine Office. NR 18 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 0278-2391 EI 1531-5053 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JUL PY 2016 VL 74 IS 7 BP 1396 EP 1402 DI 10.1016/j.joms.2016.01.036 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DP5ZH UT WOS:000378576200018 PM 26902711 ER PT J AU Glass, HC Shellhaas, RA Wusthoff, CJ Chang, T Abend, NS Chu, CJ Cilio, MR Glidden, DV Bonifacio, SL Massey, S Tsuchida, TN Silverstein, FS Soul, JS AF Glass, Hannah C. Shellhaas, Renee A. Wusthoff, Courtney J. Chang, Taeun Abend, Nicholas S. Chu, Catherine J. Cilio, M. Roberta Glidden, David V. Bonifacio, Sonia L. Massey, Shavonne Tsuchida, Tammy N. Silverstein, Faye S. Soul, Janet S. CA Neonatal Seizure Registry Study TI Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study SO JOURNAL OF PEDIATRICS LA English DT Article ID THERAPEUTIC HYPOTHERMIA; RISK-FACTORS; NEWBORNS AB Objective To determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG). Study design We prospectively collected data from 426 consecutive neonates (56% male, 88% term) <= 44 weeks' postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at 7 US tertiary care pediatric centers following the guidelines of the American Clinical Neurophysiology Society for cEEG for at-risk neonates. Seizure etiology, burden, management, and outcome were determined by chart review by the use of a case report form designed at study onset. Results The most common seizure etiologieswere hypoxic-ischemic encephalopathy (38%), ischemic stroke (18%), and intracranial hemorrhage (11%). Seizure burden was high, with 59% having >= 7 electrographic seizures and 16% having status epilepticus; 52% received >= 2 antiseizure medications. During the neonatal admission, 17% died; 49% of survivors had abnormal neurologic examination at hospital discharge. In an adjusted analysis, high seizure burden was a significant risk factor for mortality, length of hospital stay, and abnormal neurological examination at discharge. Conclusions In this large contemporary profile of consecutively enrolled newborns with seizures treated at centers that use cEEG per the guidelines of the American Clinical Neurophysiology Society, about one-half had high seizure burden, received >= 2 antiseizure medications, and/or died or had abnormal examination at discharge. Greater seizure burden was associated with increased morbidity and mortality. These findings underscore the importance of accurate determination of neonatal seizure frequency and etiology and a potential for improved outcome if seizure burden is reduced. C1 [Glass, Hannah C.; Cilio, M. Roberta] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Neurol, San Francisco, CA 94143 USA. [Glass, Hannah C.; Cilio, M. Roberta] Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA. [Glass, Hannah C.; Glidden, David V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Shellhaas, Renee A.; Silverstein, Faye S.] Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. [Wusthoff, Courtney J.] Stanford Univ, Dept Neurol, Palo Alto, CA 94304 USA. [Wusthoff, Courtney J.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA. [Chang, Taeun; Tsuchida, Tammy N.] George Washington Univ, Sch Med, Dept Neurol, Childrens Natl Hlth Syst, Washington, DC USA. [Abend, Nicholas S.; Massey, Shavonne] Childrens Hosp Philadelphia, Dept Neurol, Philadelphia, PA 19104 USA. [Abend, Nicholas S.; Massey, Shavonne] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. [Abend, Nicholas S.; Massey, Shavonne] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Chu, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Bonifacio, Sonia L.] Stanford Univ, Dept Pediat, Div Neonatal & Dev Med, Palo Alto, CA 94304 USA. [Soul, Janet S.] Boston Childrens Hosp, Dept Neurol, Boston, MA USA. RP Glass, HC (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, Dept Neurol, San Francisco, CA 94143 USA.; Glass, HC (reprint author), Univ Calif San Francisco, Benioff Childrens Hosp, Dept Pediat, San Francisco, CA 94143 USA.; Glass, HC (reprint author), Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. OI Chang, Taeun/0000-0002-1797-8449; Shellhaas, Renee/0000-0002-3175-3908 FU Pediatric Epilepsy Research Foundation (Multi-center Neonatal Seizure Registry) [A120625]; National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke [K23NS066137]; Neonatal Brain Research Institute at University of California, San Francisco; Boston Children's Hospital Intellectual and Developmental Disabilities Research Center [P30 HD18655]; University of California, San Francisco FX Supported by the Pediatric Epilepsy Research Foundation (Multi-center Neonatal Seizure Registry/A120625). H.G. is supported by the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (K23NS066137) and the Neonatal Brain Research Institute at University of California, San Francisco. J.S. is supported by Boston Children's Hospital Intellectual and Developmental Disabilities Research Center (P30 HD18655). REDCap (Research Electronic Data Capture) tools is supported by University of California, San Francisco. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The authors declare no conflicts of interest. NR 20 TC 5 Z9 5 U1 5 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2016 VL 174 BP 98 EP + DI 10.1016/j.jpeds.2016.03.035 PG 7 WC Pediatrics SC Pediatrics GA DP6PX UT WOS:000378620800021 PM 27106855 ER PT J AU Sabino, CP Deana, AM Yoshimura, TM da Silva, DFT Franca, CM Hamblin, MR Ribeiro, MS AF Sabino, Caetano P. Deana, Alessandro M. Yoshimura, Tania M. da Silva, Daniela F. T. Franca, Cristiane M. Hamblin, Michael R. Ribeiro, Martha S. TI The optical properties of mouse skin in the visible and near infrared spectral regions SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE Biophotonics; Tissue spectroscopy; Skin optics; Photodiagnosis; Phototherapy; Radiative transfer ID DIFFUSE-REFLECTANCE SPECTROSCOPY; BIOLOGICAL TISSUES; SCATTERING; MELANIN; RANGE; LIGHT; LASER; NM AB Visible and near-infrared radiation is now widely employed in health science and technology. Pre-clinical trials are still essential to allow appropriate translation of optical methods into clinical practice. Our results stress the importance of considering the mouse strain and gender when planning pre-clinical experiments that depend on light-skin interactions. Here, we evaluated the optical properties of depilated albino and pigmented mouse skin using reproducible methods to determine parameters that have wide applicability in biomedical optics. Light penetration depth (delta), absorption (mu(a)), reduced scattering (mu'(s)) and reduced attenuation (mu'(t)) coefficients were calculated using the Kubellca-Munk model of photon transport and spectrophotometric measurements. Within a broad wavelength coverage (400-1400 nm), the main optical tissue interactions of visible and near infrared radiation could be inferred. Histological analysis was performed to correlate the findings with tissue composition and structure. Disperse melanin granules present in depilated pigmented mouse skin were shown to be irrelevant for light absorption. Gender mostly affected optical properties in the visible range due to variations in blood and abundance of dense connective tissue. On the other hand, mouse strains could produce more variations in the hydration level of skin, leading to changes in absorption in the infrared spectral region. A spectral region of minimal light attenuation, commonly referred as the "optical window", was observed between 600 and 1350 nm. (C) 2016 Elsevier B.V. All rights reserved. C1 [Sabino, Caetano P.; Yoshimura, Tania M.; Ribeiro, Martha S.] IPEN CNEN SP, Nucl & Energy Res Inst, Ctr Lasers & Applicat, Sao Paulo, SP, Brazil. [Sabino, Caetano P.] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo, SP, Brazil. [Sabino, Caetano P.] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, SP, Brazil. [Deana, Alessandro M.; da Silva, Daniela F. T.; Franca, Cristiane M.] Univ Nove de Julho, Biophoton Postgrad Program, Sao Paulo, SP, Brazil. [Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ribeiro, MS (reprint author), IPEN CNEN SP, Nucl & Energy Res Inst, Ctr Lasers & Applicat, Sao Paulo, SP, Brazil. EM marthasr@usp.br RI Ribeiro, Martha/G-3517-2012; Sabino, Caetano/D-4196-2016; Yoshimura, Tania/A-5509-2017 OI Ribeiro, Martha/0000-0002-4203-1134; Sabino, Caetano/0000-0002-2048-2823; Yoshimura, Tania/0000-0003-4099-9739 FU Brazilian funding agency FAPESP [2014/02564-1]; Brazilian funding agency CNPq [307091/2011-2]; US NIH [R01AI050875] FX Authors gratefully recognize the efforts made on histological processing by Cristiano de Loura Santana and Fabiana dos Santos from the Biophotonics Applied to Health Sciences Laboratory at Nove de Julho University (Uninove). The financial support was provided by the Brazilian funding agencies FAPESP (grant 2014/02564-1) and CNPq (307091/2011-2). MR Hamblin was supported by the US NIH grant R01AI050875. NR 32 TC 4 Z9 4 U1 8 U2 14 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD JUL PY 2016 VL 160 BP 72 EP 78 DI 10.1016/j.jphotobiol.2016.03.047 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA DP4GD UT WOS:000378453500009 PM 27101274 ER PT J AU Janssen, SJ Kortlever, JTP Ready, JE Raskin, KA Ferrone, ML Hornicek, FJ Lozano-Calderon, SA Schwab, JH AF Janssen, Stein J. Kortlever, Joost T. P. Ready, John E. Raskin, Kevin A. Ferrone, Marco L. Hornicek, Francis J. Lozano-Calderon, Santiago A. Schwab, Joseph H. TI Complications After Surgical Management of Proximal Femoral Metastasis: A Retrospective Study of 417 Patients SO JOURNAL OF THE AMERICAN ACADEMY OF ORTHOPAEDIC SURGEONS LA English DT Article ID TOTAL HIP-REPLACEMENT; BONE METASTASES; COMORBIDITY INDEX; INTERNAL-FIXATION; FEMUR FRACTURES; NECK FRACTURES; SURVIVAL; DISEASE; PROGNOSTICATION; SURGERY AB Background: Proximal femoral fractures resulting from metastatic disease often require surgical management. Few studies have compared surgical techniques, and physicians' preferred strategies vary. This study compared revision and complication rates among surgical strategies. Methods: The study consisted of a retrospective review of electronic medical records of 417 consecutive patients with proximal femoral metastasis or multiple myeloma who underwent intramedullary nailing (n = 302), endoprosthetic reconstruction (n = 70), and open reduction and internal fixation (n = 45) between 1999 and 2014 at two orthopaedic oncology centers. Primary outcome measures were revisions and 30-day systemic complications. Secondary outcome measures were total estimated blood loss, anesthesia time, duration of hospital admission, and 30-day survival. Results: Revision rates did not differ between strategies (5.3% after intramedullary nailing, 11% after endoprosthetic reconstruction, and 13% after open reduction and internal fixation; P = 0.134). When reasons for revision were assessed separately, fixation failure was most common after open reduction and internal fixation (13% versus 3.0% after intramedullary nailing and none after endoprosthetic reconstruction; P < 0.001), whereas deep infection was most common after endoprosthetic reconstruction (8.6% versus 2.0% after intramedullary nailing and none after open reduction and internal fixation; P = 0.010). Overall systemic complication rates did not differ between strategies (8.3% after intramedullary nailing, 14% after endoprosthetic reconstruction, and 11% after open reduction and internal fixation; P = 0.268). Conclusion: Implant-specific complications and their timing should be considered in the choice of surgical strategy. Analysis of secondary outcomes and risk factors for systemic complications could aid in surgical decision making. C1 [Janssen, Stein J.; Kortlever, Joost T. P.; Ready, John E.; Raskin, Kevin A.; Ferrone, Marco L.; Hornicek, Francis J.; Lozano-Calderon, Santiago A.; Schwab, Joseph H.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Janssen, SJ (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. EM steinjanssen@gmail.com NR 26 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 1067-151X EI 1940-5480 J9 J AM ACAD ORTHOP SUR JI J. Am. Acad. Orthop. Surg. PD JUL PY 2016 VL 24 IS 7 BP 483 EP 494 DI 10.5435/JAAOS-D-16-00043 PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA DP7ET UT WOS:000378662700008 PM 27227983 ER PT J AU McCauley, JL Hyer, JM Ramakrishnan, VR Leite, R Melvin, CL Fillingim, RB Frick, C Brady, KT AF McCauley, Jenna L. Hyer, J. Madison Ramakrishnan, V. Ramesh Leite, Renata Melvin, Cathy L. Fillingim, Roger B. Frick, Christie Brady, Kathleen T. TI Dental opioid prescribing and multiple opioid prescriptions among dental patients Administrative data from the South Carolina prescription drug monitoring program SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE Oxycodone; patient education; prescriptions; drug ID UNITED-STATES; NONMEDICAL USE; OVERDOSE; PAIN; ABUSE; GUIDELINES; THERAPY; RISK; PHARMACOGENETICS; HYDROCODONE AB Background. Despite increased attention to dentists' roles in curbing opioid misuse, abuse, and diversion, information regarding prescribing practices and the frequency of multiple concurrent opioid prescriptions among dental patients is limited. Methods. The authors reviewed South Carolina prescription drug monitoring program data representing dispensed medication for patients prescribed at least 1 opioid by a dentist during the most recently available 2-year time frame (2012-2013). The authors used descriptive analyses to examine the types and frequency of dental opioid prescriptions and the frequency of existing multiple concurrent opioid prescriptions among dental patients. Results. Nearly all dispensed dental opioid prescriptions (99.9%; n = 653,650) were for immediate-release opioids and were initial prescription fills (96.2%). Hydrocodone (76.1%) and oxycodone (12.2%) combination products were the most frequently dispensed opioids prescribed by dentists. People younger than 21 years received 11.2% of dentist-prescribed opioids dispensed. Patients with multiple concurrent opioid prescriptions were identified within 30-day (n = 113,818), 90-day (n = 166,124), and 180-day (n = 205,576) time frames. Conclusions. Dentists prescribed a high volume of the immediate-release opioids dispensed in South Carolina. A notable minority of dental patients had incidents of multiple preexisting opioid prescriptions, a factor implicated in patient misuse, abuse, overdose, and diversion. Practical Implications. Use of a prescription drug monitoring program before prescribing provides a record of controlled substances dispensed to a patient and may inform prescribing, coordination of care, and addiction screening or referral. Patients should receive information regarding misuse behaviors and their risks, as well as the importance of secure storage and disposal of leftover opioid medications. C1 [McCauley, Jenna L.] Med Univ S Carolina, Addict Sci Div, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. [Hyer, J. Madison; Ramakrishnan, V. Ramesh; Melvin, Cathy L.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA. [Leite, Renata] Med Univ S Carolina, Dept Periodont, Charleston, SC 29425 USA. [Fillingim, Roger B.] Univ Florida, Dept Community Dent & Behav Sci, Gainesville, FL USA. [Frick, Christie] S Carolina Dept Hlth & Environm Control, Prescript Drug Monitoring Program, Columbia, SC 29201 USA. [Brady, Kathleen T.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Brady, Kathleen T.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP McCauley, JL (reprint author), Med Univ S Carolina, Addict Sci Div, Dept Psychiat & Behav Sci, 67 President St, Charleston, SC 29425 USA. EM mccaule@musc.edu FU National Institute on Drug Abuse [K12-DA031794, K23-DA036566]; South Carolina Clinical and Translational Research Institute; National Institutes of Health [UL1-TR000062] FX This research was supported by grants K12-DA031794 and K23-DA036566 from the National Institute on Drug Abuse and by the South Carolina Clinical and Translational Research Institute, with an academic home at the Medical University of South Carolina, through grant UL1-TR000062 from the National Institutes of Health. NR 46 TC 1 Z9 1 U1 1 U2 1 PU AMER DENTAL ASSOC PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 EI 1943-4723 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUL PY 2016 VL 147 IS 7 BP 537 EP 544 DI 10.1016/j.adaj.2016.02.017 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DP5ON UT WOS:000378547000007 PM 27055600 ER PT J AU Rodriguez, E Nifong, LW Bonatti, J Casula, R Falk, V Folliguet, TA Kiaii, BB Mack, MJ Mihaljevic, T Smith, JM Suri, RM Bavaria, JE MacGillivray, TE Chitwood, WR AF Rodriguez, Evelio Nifong, L. Wiley Bonatti, Johannes Casula, Roberto Falk, Volkmar Folliguet, Thierry A. Kiaii, Bob B. Mack, Michael J. Mihaljevic, Tomislav Smith, J. Michael Suri, Rakesh M. Bavaria, Joseph E. MacGillivray, Thomas E. Chitwood, W. Randolph, Jr. TI Pathway for surgeons and programs to establish and maintain a successful robot-assisted adult cardiac surgery program SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Editorial Material ID MITRAL-VALVE REPAIRS; MULTICENTER TRIAL; BYPASS SURGERY; ARTERY; EXPERIENCE; SAFETY; GRAFT C1 [Rodriguez, Evelio] St Thomas Heart Hosp, 4230 Harding Rd,Ste 430, Nashville, TN 37205 USA. [Nifong, L. Wiley] East Carolina Heart Inst, Dept Cardiovasc Sci, Greenville, NC USA. [Bonatti, Johannes] Cleveland Clin, Abu Dhabi Heart & Vasc Inst, Cleveland, Qld, Australia. [Casula, Roberto] St Marys Hosp, Imperial Coll Healthcare NHS Trust, London, England. [Casula, Roberto] St Marys Hosp, Dept Cardiothorac Surg, London, England. [Falk, Volkmar] Charite, Deutsch Herzzentrum Berlin, Berlin, Germany. [Folliguet, Thierry A.] Ctr Hosp Univ Brabois ILCV, Vandoeuvre Les Nancy, France. [Kiaii, Bob B.] London Hlth Sci Ctr, Dept Cardiovasc & Thorac Surg, London, ON, Canada. [Mack, Michael J.] Heart Hosp, Baylor Hlth Care Syst, Plano, TX USA. [Mihaljevic, Tomislav] Cleveland Clin Abu Dhabi, Cleveland, OH USA. [Smith, J. Michael] Good Samaritan Hosp, Cincinnati, OH USA. [Suri, Rakesh M.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Bavaria, Joseph E.] Hosp Univ Penn, Div Cardiovasc Surg, 3400 Spruce St, Philadelphia, PA 19104 USA. [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chitwood, W. Randolph, Jr.] Vidant Med Ctr, Greenville, NC USA. [Chitwood, W. Randolph, Jr.] E Carolina Univ, Greenville, NC USA. RP Rodriguez, E (reprint author), St Thomas Heart Hosp, 4230 Harding Rd,Ste 430, Nashville, TN 37205 USA. EM evelio.rodriguez@sth.org NR 14 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5223 EI 1097-685X J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JUL PY 2016 VL 152 IS 1 BP 9 EP 13 DI 10.1016/j.jtcvs.2016.05.018 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA DQ0AG UT WOS:000378858800021 PM 27343904 ER PT J AU Kenagy, RD Civelek, M Kikuchi, S Chen, LH Grieff, A Sobel, M Lusis, AJ Clowes, AW AF Kenagy, Richard D. Civelek, Mete Kikuchi, Shinsuke Chen, Lihua Grieff, Anthony Sobel, Michael Lusis, Aldons J. Clowes, Alexander W. TI Scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN) are hub genes of coexpression network modules associated with peripheral vein graft patency SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SMOOTH-MUSCLE-CELLS; INTERMEDIATE-LAYER PROTEIN; EPIDERMAL-GROWTH-FACTOR; MESENCHYMAL STEM-CELLS; NUCLEOTIDE EXCHANGE FACTOR; EX-VIVO EXPANSION; SAPHENOUS-VEIN; FACTOR-XA; ENDOTHELIAL-CELLS; SELENOPROTEIN P AB Objective: Approximately 30% of autogenous vein grafts develop luminal narrowing and fail because of intimal hyperplasia or negative remodeling. We previously found that vein graft cells from patients who later develop stenosis proliferate more in vitro in response to growth factors than cells from patients who maintain patent grafts. To discover novel determinants of vein graft outcome, we have analyzed gene expression profiles of these cells using a systems biology approach to cluster the genes into modules by their coexpression patterns and to correlate the results with growth data from our prior study and with new studies of migration and matrix remodeling. Methods: RNA from 4-hour serum-or platelet-derived growth factor (PDGF)-BB-stimulated human saphenous vein cells obtained from the outer vein wall (20 cell lines) was used for microarray analysis of gene expression, followed by weighted gene coexpression network analysis. Cell migration in microchemotaxis chambers in response to PDGF-BB and cell-mediated collagen gel contraction in response to serum were also determined. Gene function was determined using short-interfering RNA to inhibit gene expression before subjecting cells to growth or collagen gel contraction assays. These cells were derived from samples of the vein grafts obtained at surgery, and the long-term fate of these bypass grafts was known. Results: Neither migration nor cell-mediated collagen gel contraction showed a correlation with graft outcome. Although 1188 and 1340 genes were differentially expressed in response to treatment with serum and PDGF, respectively, no single gene was differentially expressed in cells isolated from patients whose grafts stenosed compared with those that remained patent. Network analysis revealed four unique groups of genes, which we term modules, associated with PDGF responses, and 20 unique modules associated with serum responses. The "yellow" and "skyblue" modules, from PDGF and serum analyses, respectively, correlated with later graft stenosis (P=.005 and P=.02, respectively). In response to PDGF, yellow was also associated with increased cell growth. For serum, skyblue was also associated with inhibition of collagen gel contraction. The hub genes for yellow and skyblue (ie, the gene most connected to other genes in the module), scavenger receptor class A member 5 (SCARA5) and suprabasin (SBSN), respectively, were tested for effects on proliferation and collagen contraction. Knockdown of SCARA5 increased proliferation by 29.9% +/- 7.8% (P<.01), whereas knockdown of SBSN had no effect. Knockdown of SBSN increased collagen gel contraction by 24.2% +/- 8.6% (P<.05), whereas knockdown of SCARA5 had no effect. Conclusions: Using weighted gene coexpression network analysis of cultured vein graft cell gene expression, we have discovered two small gene modules, which comprise 42 genes, that are associated with vein graft failure. Further experiments are needed to delineate the venous cells that express these genes in vivo and the roles these genes play in vein graft healing, starting with the module hub genes SCARA5 and SBSN, which have been shown to have modest effects on cell proliferation or collagen gel contraction. C1 [Kenagy, Richard D.; Kikuchi, Shinsuke; Chen, Lihua; Grieff, Anthony; Sobel, Michael; Clowes, Alexander W.] Univ Washington, Dept Surg, Seattle, WA 98109 USA. [Civelek, Mete; Lusis, Aldons J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Kikuchi, Shinsuke] Asahikawa Med Univ, Dept Vasc Surg, Asahikawa, Hokkaido, Japan. [Sobel, Michael] VA Puget Sound Hlth Care Syst, Div Vasc Surg, Seattle, WA USA. [Sobel, Michael] Univ Washington, Seattle, WA 98109 USA. [Lusis, Aldons J.] Univ Calif Los Angeles, Dept Microbiol, Los Angeles, CA 90024 USA. [Lusis, Aldons J.] Univ Calif Los Angeles, Dept Immunol & Mol Genet, Los Angeles, CA USA. [Lusis, Aldons J.] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA. RP Kenagy, RD (reprint author), Univ Washington, Ctr Cardiovasc Biol, POB 358050,850 Republican St, Seattle, WA 98109 USA. EM rkenagy@u.washington.edu OI Civelek, Mete/0000-0002-8141-0284 FU CSRD VA [I01 CX000712]; NHLBI NIH HHS [K99 HL121172, P01 HL030568, R01 HL030946, T32 HL069766] NR 111 TC 0 Z9 0 U1 5 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2016 VL 64 IS 1 BP 202 EP + DI 10.1016/j.jvs.2014.12.052 PG 14 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA DP5UI UT WOS:000378562900028 PM 25935274 ER PT J AU Nou, E Lo, J Hadigan, C Grinspoon, SK AF Nou, Eric Lo, Janet Hadigan, Colleen Grinspoon, Steven K. TI Pathophysiology and management of cardiovascular disease in patients with HIV SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; T-CELL-ACTIVATION; INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; EPICARDIAL ADIPOSE-TISSUE; RANDOMIZED CLINICAL-TRIAL; PLACEBO-CONTROLLED TRIAL; MULTICENTER AIDS COHORT AB Results from several studies have suggested that people with HIV have an increased risk of cardiovascular disease, especially coronary heart disease, compared with people not infected with HIV. People living with HIV have an increased prevalence of traditional cardiovascular disease risk factors, and HIV-specific mechanisms such as immune activation. Although older, more metabolically harmful antiretroviral regimens probably contributed to the risk of cardiovascular disease, new data suggest that early and continuous use of modern regimens, which might have fewer metabolic effects, minimises the risk of myocardial infarction by maintaining viral suppression and decreasing immune activation. Even with antiretroviral therapy, however, immune activation persists in people with HIV and could contribute to accelerated atherosclerosis, especially of coronary lesions that are susceptible to rupture. Therefore, treatments that safely reduce inflammation in people with HIV could provide additional cardiovascular protection alongside treatment of both traditional and non-traditional risk factors. C1 [Nou, Eric; Lo, Janet; Grinspoon, Steven K.] Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. [Hadigan, Colleen] NIAID, NIH, Bethesda, MD USA. RP Grinspoon, SK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sgrinspoon@mgh.harvard.edu FU US National Institute of Allergies and Infectious Diseases Intramural Program FX This work was partly supported by the US National Institute of Allergies and Infectious Diseases Intramural Program. NR 137 TC 5 Z9 5 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD JUL PY 2016 VL 4 IS 7 BP 598 EP 610 DI 10.1016/S2213-8587(15)00388-5 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DQ0CD UT WOS:000378864700022 PM 26873066 ER PT J AU Pivonello, R Isidori, AM De Martino, MC Newell-Price, J Biller, BMK Colao, A AF Pivonello, Rosario Isidori, Andrea M. De Martino, Maria Cristina Newell-Price, John Biller, Beverly M. K. Colao, Annamaria TI Complications of Cushing's syndrome: state of the art SO LANCET DIABETES & ENDOCRINOLOGY LA English DT Review ID BONE-MINERAL DENSITY; POLYCYSTIC OVARIAN SYNDROME; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; AUTOIMMUNE THYROID-DYSFUNCTION; CARDIOVASCULAR RISK-FACTORS; CLINICAL-PRACTICE GUIDELINE; ECTOPIC ACTH-SECRETION; LONG-TERM CURE; ENDOGENOUS HYPERCORTISOLISM; DIABETES-MELLITUS AB Cushing's syndrome is a serious endocrine disease caused by chronic, autonomous, and excessive secretion of cortisol. The syndrome is associated with increased mortality and impaired quality of life because of the occurrence of comorbidities. These clinical complications include metabolic syndrome, consisting of systemic arterial hypertension, visceral obesity, impairment of glucose metabolism, and dyslipidaemia; musculoskeletal disorders, such as myopathy, osteoporosis, and skeletal fractures; neuropsychiatric disorders, such as impairment of cognitive function, depression, or mania; impairment of reproductive and sexual function; and dermatological manifestations, mainly represented by acne, hirsutism, and alopecia. Hypertension in patients with Cushing's syndrome has a multifactorial pathogenesis and contributes to the increased risk for myocardial infarction, cardiac failure, or stroke, which are the most common causes of death; risks of these outcomes are exacerbated by a prothrombotic diathesis and hypokalaemia. Neuropsychiatric disorders can be responsible for suicide. Immune disorders are common; immunosuppression during active disease causes susceptibility to infections, possibly complicated by sepsis, an important cause of death, whereas immune rebound after disease remission can exacerbate underlying autoimmune diseases. Prompt treatment of cortisol excess and specific treatments of comorbidities are crucial to prevent serious clinical complications and reduce the mortality associated with Cushing's syndrome. C1 [Pivonello, Rosario; De Martino, Maria Cristina; Colao, Annamaria] Univ Naples Federico II, Sez Endocrinol, Dipartimento Med Clin & Chirurg, I-80131 Naples, Italy. [Isidori, Andrea M.] Univ Roma La Sapienza, Dept Expt Med, Rome, Italy. [Newell-Price, John] Univ Sheffield, Sch Med, Dept Oncol & Metab, Sheffield, S Yorkshire, England. [Newell-Price, John] Sheffield Teaching Hosp NHS Fdn Trust, Royal Hallamshire Hosp, Endocrine Unit, Sheffield, S Yorkshire, England. [Biller, Beverly M. K.] Massachusetts Gen Hosp, Harvard Med Sch, Neuroendocrine Unit, Dept Med, Boston, MA 02114 USA. RP Pivonello, R (reprint author), Univ Naples Federico II, Sez Endocrinol, Dipartimento Med Clin & Chirurg, I-80131 Naples, Italy. EM rosario.pivonello@unina.it RI Isidori, Andrea/F-3062-2010; De Martino, Maria Cristina/K-7090-2016 OI Isidori, Andrea/0000-0002-9037-5417; FU Novartis; Pfizer; HRA Pharma; ViroPharma-Shire; Italfarmaco; Ipsen; Ferring; Menarini; Otsuka; Cortendo; Lilly; Novo Nordisk FX RP reports grants, personal fees, and other from Novartis; grants and personal fees from Pfizer; grants from HRA Pharma; grants and personal fees from ViroPharma-Shire; personal fees from Italfarmaco; personal fees from Ipsen; and personal fees from Ferring, outside the submitted work. AMI reports personal fees from Menarini, personal fees from Otsuka, grants and personal fees from Viropharma-Shire, and personal fees from Novartis, outside the submitted work. JN-P reports grants and personal fees from HRA Pharma, grants and personal fees from Novartis, and grants and personal fees from Ipsen, outside the submitted work. BMKB reports grants and personal fees from Cortendo, grants and personal fees from Novartis, personal fees from HRA Pharma, and personal fees from Ipsen, outside the submitted work. AC reports grants, personal fees, and other from Novartis; grants and personal fees from Pfizer; grants from HRA Pharma; grants and personal fees from Italfarmaco; grants, personal fees, and other from Ipsen; and grants from Ferring, Lilly, and Novo Nordisk, outside the submitted work. MCDM declares no competing interests. NR 155 TC 6 Z9 6 U1 12 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 2213-8587 J9 LANCET DIABETES ENDO JI Lancet Diabetes Endocrinol. PD JUL PY 2016 VL 4 IS 7 BP 611 EP 629 DI 10.1016/S2213-8587(16)00086-3 PG 19 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DQ0CD UT WOS:000378864700023 PM 27177728 ER PT J AU Baldini, EH AF Baldini, Elizabeth H. TI Defining the role of radiotherapy for retroperitoneal sarcoma SO LANCET ONCOLOGY LA English DT Editorial Material ID PREOPERATIVE RADIATION-THERAPY; RECURRENCE; RPS C1 [Baldini, Elizabeth H.] Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. [Baldini, Elizabeth H.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Baldini, EH (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA.; Baldini, EH (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM ebaldini@lroc.harvard.edu NR 9 TC 1 Z9 1 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2016 VL 17 IS 7 BP 857 EP 859 DI 10.1016/S1470-2045(16)30103-6 PG 4 WC Oncology SC Oncology GA DQ1FO UT WOS:000378947100038 PM 27210905 ER PT J AU Antonia, SJ Lopez-Martin, JA Bendell, J Ott, PA Taylor, M Eder, JP Jager, D Pietanza, MC Le, DT de Braud, F Morse, MA Ascierto, PA Horn, L Amin, A Pillai, RN Evans, J Chau, I Bono, P Atmaca, A Sharma, P Harbison, CT Lin, CS Christensen, O Calvo, E AF Antonia, Scott J. Lopez-Martin, Jose A. Bendell, Johanna Ott, Patrick A. Taylor, Matthew Eder, Joseph Paul Jaeger, Dirk Pietanza, M. Catherine Le, Dung T. de Braud, Filippo Morse, Michael A. Ascierto, Paolo A. Horn, Leora Amin, Asim Pillai, Rathi N. Evans, Jeffry Chau, Ian Bono, Petri Atmaca, Akin Sharma, Padmanee Harbison, Christopher T. Lin, Chen-Sheng Christensen, Olaf Calvo, Emiliano TI Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial SO LANCET ONCOLOGY LA English DT Article ID III TRIAL; METASTATIC MELANOMA; UNTREATED MELANOMA; MYASTHENIA-GRAVIS; EXTENSIVE-DISEASE; TREATMENT OPTIONS; COMBINATION; THERAPY; IRINOTECAN; DOCETAXEL AB Background Treatments for small-cell lung cancer (SCLC) after failure of platinum-based chemotherapy are limited. We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens. Methods The SCLC cohort of this phase 1/2 multicentre, multi-arm, open-label trial was conducted at 23 sites (academic centres and hospitals) in six countries. Eligible patients were 18 years of age or older, had limited-stage or extensive-stage SCLC, and had disease progression after at least one previous platinum-containing regimen. Patients received nivolumab (3 mg/kg bodyweight intravenously) every 2 weeks (given until disease progression or unacceptable toxicity), or nivolumab plus ipilimumab (1 mg/kg plus 1 mg/kg, 1 mg/kg plus 3 mg/kg, or 3 mg/kg plus 1 mg/kg, intravenously) every 3 weeks for four cycles, followed by nivolumab 3 mg/kg every 2 weeks. Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg. Depending on tolerability, patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. The primary endpoint was objective response by investigator assessment. All analyses included patients who were enrolled at least 90 days before database lock. This trial is ongoing; here, we report an interim analysis of the SCLC cohort. This study is registered with ClinicalTrials.gov, number NCT01928394. Findings Between Nov 18, 2013, and July 28, 2015, 216 patients were enrolled and treated (98 with nivolumab 3 mg/kg, three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg). At database lock on Nov 6, 2015, median follow-up for patients continuing in the study (including those who had died or discontinued treatment) was 198.5 days (IQR 163.0-464.0) for nivolumab 3 mg/kg, 302 days (IQR not calculable) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 361.0 days (273.0-470.0) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and 260.5 days (248.0-288.0) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. An objective response was achieved in ten (10%) of 98 patients receiving nivolumab 3 mg/kg, one (33%) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg, 14 (23%) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, and ten (19%) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg. Grade 3 or 4 treatment-related adverse events occurred in 13 (13%) patients in the nivolumab 3 mg/kg cohort, 18 (30%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort, and ten (19%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase (none vs 5 [8%] vs none) and diarrhoea (none vs 3 [5%] vs 1 [2%]). No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event. Six (6%) patients in the nivolumab 3 mg/kg group, seven (11%) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group, and four (7%) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events. Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events (myasthenia gravis and worsening of renal failure), and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis. Interpretation Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC. These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 randomised controlled trials in SCLC. C1 [Antonia, Scott J.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Lopez-Martin, Jose A.] Hosp Univ 12 Octubre, Madrid, Spain. [Bendell, Johanna] Tennessee Oncol PLLC, Sarah Cannon Res Inst, Nashville, TN USA. [Ott, Patrick A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Taylor, Matthew] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Eder, Joseph Paul] Yale Comprehens Canc Ctr, New Haven, CT USA. [Jaeger, Dirk] Univ Med Ctr, NCT, Heidelberg, Germany. [Pietanza, M. Catherine] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. [Le, Dung T.] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [de Braud, Filippo] Fdn IRCCS Ist Nazl Tumori Milano, Milan, Italy. [Morse, Michael A.] Duke Univ, Med Ctr, Durham, NC USA. [Ascierto, Paolo A.] Ist Nazl Tumori Fdn Pascale, Naples, Italy. [Horn, Leora] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Amin, Asim] Carolinas Med Ctr, Levine Canc Inst, Charlotte, NC 28203 USA. [Pillai, Rathi N.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Evans, Jeffry] Univ Glasgow, Glasgow, Lanark, Scotland. [Chau, Ian] Royal Marsden Hosp, Sutton, Surrey, England. [Bono, Petri] Helsinki Univ Hosp, Ctr Comprehens Canc, Helsinki, Finland. [Bono, Petri] Univ Helsinki, Helsinki, Finland. [Atmaca, Akin] Krankenhaus Nordwest UCT Univ, Ctr Canc, Frankfurt, Germany. [Sharma, Padmanee] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Harbison, Christopher T.; Lin, Chen-Sheng; Christensen, Olaf] Bristol Myers Squibb Co, Princeton, NJ USA. [Calvo, Emiliano] START Madrid, Ctr Integral Oncol Clara Campal, Calle Ona 10, Madrid 28050, Spain. RP Calvo, E (reprint author), START Madrid, Ctr Integral Oncol Clara Campal, Calle Ona 10, Madrid 28050, Spain. EM emiliano.calvo@start.stoh.com RI de Braud, Filippo/B-9997-2017 OI de Braud, Filippo/0000-0003-0103-730X FU Bristol-Myers Squibb FX Bristol-Myers Squibb. NR 36 TC 38 Z9 39 U1 9 U2 14 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 JUL PY 2016 VL 17 IS 7 BP 883 EP 895 DI 10.1016/S1470-2045(16)30098-5 PG 13 WC Oncology SC Oncology GA DQ1FO UT WOS:000378947100054 PM 27269741 ER PT J AU Choueiri, TK Escudier, B Powles, T Tannir, NM Mainwaring, PN Rini, BI Hammers, HJ Donskov, F Roth, BJ Peltola, K Lee, JL Heng, DYC Schmidinger, M Agarwal, N Sternberg, CN McDermott, DF Aftab, DT Hessel, C Old, CS Schwab, G Hutson, TE Pal, S Motzer, RJ AF Choueiri, Toni K. Escudier, Bernard Powles, Thomas Tannir, Nizar M. Mainwaring, Paul N. Rini, Brian I. Hammers, Hans J. Donskov, Frede Roth, Bruce J. Peltola, Katriina Lee, Jae Lyun Heng, Daniel Y. C. Schmidinger, Manuela Agarwal, Neeraj Sternberg, Cora N. McDermott, David F. Aftab, Dana T. Hessel, Colin Old, Christian Scheff Schwab, Gisela Hutson, Thomas E. Pal, Sumanta Motzer, Robert J. CA METEOR Investigators TI Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomised, open-label, phase 3 trial SO LANCET ONCOLOGY LA English DT Article ID TARGETED THERAPY; PROGNOSTIC-FACTORS; EAU GUIDELINES; III TRIAL; CANCER; COMBINATION; METASTASIS; SORAFENIB; SURVIVAL; EFFICACY AB Background Cabozantinib is an oral inhibitor of tyrosine kinases including MET, VEGFR, and AXL. The randomised phase 3 METEOR trial compared the efficacy and safety of cabozantinib versus the mTOR inhibitor everolimus in patients with advanced renal cell carcinoma who progressed after previous VEGFR tyrosine-kinase inhibitor treatment. Here, we report the final overall survival results from this study based on an unplanned second interim analysis. Methods In this open-label, randomised phase 3 trial, we randomly assigned (1:1) patients aged 18 years and older with advanced or metastatic clear-cell renal cell carcinoma, measurable disease, and previous treatment with one or more VEGFR tyrosine-kinase inhibitors to receive 60 mg cabozantinib once a day or 10 mg everolimus once a day. Randomisation was done with an interactive voice and web response system. Stratification factors were Memorial Sloan Kettering Cancer Center risk group and the number of previous treatments with VEGFR tyrosine-kinase inhibitors. The primary endpoint was progression-free survival as assessed by an independent radiology review committee in the first 375 randomly assigned patients and has been previously reported. Secondary endpoints were overall survival and objective response in all randomly assigned patients assessed by intention-to-treat. Safety was assessed per protocol in all patients who received at least one dose of study drug. The study is closed for enrolment but treatment and follow-up of patients is ongoing for long-term safety evaluation. This trial is registered with ClinicalTrials.gov, number NCT01865747. Findings Between Aug 8, 2013, and Nov 24, 2014, 658 patients were randomly assigned to receive cabozantinib (n=330) or everolimus (n=328). The median duration of follow-up for overall survival and safety was 18.7 months (IQR 16.1-21.1) in the cabozantinib group and 18.8 months (16.0-21.2) in the everolimus group. Median overall survival was 21.4 months (95% CI 18.7-not estimable) with cabozantinib and 16.5 months (14.7-18.8) with everolimus (hazard ratio [HR] 0.66 [95% CI 0.53-0.83]; p=0.00026). Cabozantinib treatment also resulted in improved progression-free survival (HR 0.51 [95% CI 0.41-0.62]; p<0.0001) and objective response (17% [13-22] with cabozantinib vs 3% [2-6] with everolimus; p<0.0001) per independent radiology review among all randomised patients. The most common grade 3 or 4 adverse events were hypertension (49 [15%] in the cabozantinib group vs 12 [4%] in the everolimus group), diarrhoea (43 [13%] vs 7 [2%]), fatigue (36 [11%] vs 24 [7%]), palmar-plantar erythrodysaesthesia syndrome (27 [8%] vs 3 [1%]), anaemia (19 [6%] vs 53 [17%]), hyperglycaemia (3 [1%] vs 16 [5%]), and hypomagnesaemia (16 [5%] vs none). Serious adverse events grade 3 or worse occurred in 130 (39%) patients in the cabozantinib group and in 129 (40%) in the everolimus group. One treatment-related death occurred in the cabozantinib group (death; not otherwise specified) and two occurred in the everolimus group (one aspergillus infection and one pneumonia aspiration). Interpretation Treatment with cabozantinib increased overall survival, delayed disease progression, and improved the objective response compared with everolimus. Based on these results, cabozantinib should be considered as a new standard-of-care treatment option for previously treated patients with advanced renal cell carcinoma. Patients should be monitored for adverse events that might require dose modifications. C1 [Choueiri, Toni K.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Escudier, Bernard] Inst Gustave Roussy, Villejuif, France. [Powles, Thomas] Queen Mary Univ London, Royal Free NHS Trust, Canc Res UK Expt Canc Med Ctr, Barts Canc Inst, London, England. [Tannir, Nizar M.] Univ Texas MD Anderson Canc Ctr Hosp, Houston, TX USA. [Mainwaring, Paul N.] Icon Canc Care, Brisbane, Qld, Australia. [Rini, Brian I.] Cleveland Clin Fdn, 9500 Euclid Ave, Cleveland, OH 44195 USA. [Hammers, Hans J.] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Donskov, Frede] Aarhus Univ Hosp, Aarhus, Denmark. [Roth, Bruce J.] Washington Univ, St Louis, MO USA. [Peltola, Katriina] Univ Helsinki, Cent Hosp, Ctr Canc, Helsinki, Finland. [Lee, Jae Lyun] Univ Ulsan, Coll Med, Asan Med Ctr, Seoul, South Korea. [Heng, Daniel Y. C.] Univ Calgary, Tom Baker Canc Ctr, Calgary, AB, Canada. [Schmidinger, Manuela] Med Univ Vienna, Vienna, Austria. [Agarwal, Neeraj] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Sternberg, Cora N.] San Camillo Hosp, Rome, Italy. [Sternberg, Cora N.] Forlanini Hosp, Rome, Italy. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Aftab, Dana T.; Hessel, Colin; Old, Christian Scheff; Schwab, Gisela] Exelixis, San Francisco, CA USA. [Hutson, Thomas E.] Baylor Sammons Canc Ctr, Texas Oncol, Dallas, TX USA. [Pal, Sumanta] City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. [Motzer, Robert J.] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM toni_choueiri@dfci.harvard.edu FU Exelixis Inc. FX Exelixis Inc. NR 30 TC 48 Z9 48 U1 5 U2 10 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 JUL PY 2016 VL 17 IS 7 BP 917 EP 927 DI 10.1016/S1470-2045(16)30107-3 PG 11 WC Oncology SC Oncology GA DQ1FO UT WOS:000378947100057 PM 27279544 ER PT J AU Weber, JS Gibney, G Sullivan, RJ Sosman, JA Slingluff, CL Lawrence, DP Logan, TF Schuchter, LM Nair, S Fecher, L Buchbinder, EI Berghorn, E Ruisi, M Kong, G Jiang, J Horak, C Hodi, FS AF Weber, Jeffrey S. Gibney, Geoff Sullivan, Ryan J. Sosman, Jeffrey A. Slingluff, Craig L., Jr. Lawrence, Donald P. Logan, Theodore F. Schuchter, Lynn M. Nair, Suresh Fecher, Leslie Buchbinder, Elizabeth I. Berghorn, Elmer Ruisi, Mary Kong, George Jiang, Joel Horak, Christine Hodi, F. Stephen TI Sequential administration of nivolumab and ipilimumab with a planned switch in patients with advanced melanoma (CheckMate 064): an open-label, randomised, phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID UNTREATED MELANOMA; CTLA-4; PD-1 AB Background Concurrent administration of the immune checkpoint inhibitors nivolumab and ipilimumab has shown greater efficacy than either agent alone in patients with advanced melanoma, albeit with more high-grade adverse events. We assessed whether sequential administration of nivolumab followed by ipilimumab, or the reverse sequence, could improve safety without compromising efficacy. Methods We did this randomised, open-label, phase 2 study at nine academic medical centres in the USA. Eligible patients (aged >= 18 years) with unresectable stage III or IV melanoma (treatment-naive or who had progressed after no more than one previous systemic therapy, with an Eastern Cooperative Oncology Group performance status of 0 or 1) were randomly assigned (1: 1) to induction with intravenous nivolumab 3 mg/kg every 2 weeks for six doses followed by a planned switch to intravenous ipilimumab 3 mg/kg every 3 weeks for four doses, or the reverse sequence. Randomisation was done by an independent interactive voice response system with a permuted block schedule (block size four) without stratification factors. After induction, both groups received intravenous nivolumab 3 mg/kg every 2 weeks until progression or unacceptable toxicity. The primary endpoint was treatment-related grade 3-5 adverse events until the end of the induction period (week 25), analysed in the as-treated population. Secondary endpoints were the proportion of patients who achieved a response at week 25 and disease progression at weeks 13 and 25. Overall survival was a prespecified exploratory endpoint. This study is registered with ClinicalTrials.gov, number NCT01783938, and is ongoing but no longer enrolling patients. Findings Between April 30, 2013, and July 21, 2014, 140 patients were enrolled and randomly assigned to nivolumab followed by ipilimumab (n=70) or to the reverse sequence of ipilimumab followed by nivolumab (n=70), of whom 68 and 70 patients, respectively, received at least one dose of study drug and were included in the analyses. The frequencies of treatment-related grade 3-5 adverse events up to week 25 were similar in the nivolumab followed by ipilimumab group (34 [50%; 95% CI 37.6-62.4] of 68 patients) and in the ipilimumab followed by nivolumab group (30 [43%; 31.1-55.3] of 70 patients). The most common treatment-related grade 3-4 adverse events during the whole study period were colitis (ten [15%]) in the nivolumab followed by ipilimumab group vs 14 [20%] in the reverse sequence group), increased lipase (ten [15%] vs 12 [17%]), and diarrhoea (eight [12%] vs five [7%]). No treatment-related deaths occurred. The proportion of patients with a response at week 25 was higher with nivolumab followed by ipilimumab than with the reverse sequence (28 [41%; 95% CI 29.4-53.8] vs 14 [20%; 11.4-31.3]). Progression was reported in 26 (38%; 95% CI 26.7-50.8) patients in the nivolumab followed by ipilimumab group and 43 (61%; 49.0-72.8) patients in the reverse sequence group at week 13 and in 26 (38%; 26.7-50.8) and 42 (60%; 47.6-71.5) patients at week 25, respectively. After a median follow-up of 19.8 months (IQR 12.8-25.7), median overall survival was not reached in the nivolumab followed by ipilimumab group (95% CI 23.7-not reached), whereas over a median follow-up of 14.7 months (IQR 5.6-23.9) in the ipilimumab followed by nivolumab group, median overall survival was 16.9 months (95% CI 9.2-26.5; HR 0.48 [95% CI 0.29-0.80]). A higher proportion of patients in the nivolumab followed by ipilimumab group achieved 12-month overall survival than in the ipilimumab followed by nivolumab group (76%; 95% CI 64-85 vs 54%; 42-65). Interpretation Nivolumab followed by ipilimumab appears to be a more clinically beneficial option compared with the reverse sequence, albeit with a higher frequency of adverse events. C1 [Weber, Jeffrey S.] NYU, Langone Med Ctr, New York, NY USA. [Weber, Jeffrey S.; Gibney, Geoff] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Gibney, Geoff] Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. [Sullivan, Ryan J.; Lawrence, Donald P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sosman, Jeffrey A.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Slingluff, Craig L., Jr.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Logan, Theodore F.; Fecher, Leslie] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Schuchter, Lynn M.] Univ Penn, Philadelphia, PA 19104 USA. [Nair, Suresh] Lehigh Valley Hlth Network, Allentown, PA USA. [Fecher, Leslie] Univ Michigan, Ann Arbor, MI 48109 USA. [Buchbinder, Elizabeth I.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Berghorn, Elmer; Ruisi, Mary; Kong, George; Jiang, Joel; Horak, Christine] Bristol Myers Squibb Co, Princeton, NJ USA. [Hodi, F. Stephen] Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. RP Hodi, FS (reprint author), Dana Farber Canc Inst, 450 Brookline Ave, Boston, MA 02115 USA. EM stephen_hodi@dfci.harvard.edu FU Bristol-Myers Squibb FX Bristol-Myers Squibb. NR 22 TC 13 Z9 13 U1 5 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 EI 1474-5488 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2016 VL 17 IS 7 BP 943 EP 955 DI 10.1016/S1470-2045(16)30126-7 PG 13 WC Oncology SC Oncology GA DQ1FO UT WOS:000378947100059 PM 27269740 ER PT J AU Planchard, D Besse, B Groen, HJM Souquet, PJ Quoix, E Baik, CS Barlesi, F Kim, TM Mazieres, J Novello, S Rigas, JR Upalawanna, A D'Amelio, AM Zhang, PK Mookerjee, B Johnson, BE AF Planchard, David Besse, Benjamin Groen, Harry J. M. Souquet, Pierre-Jean Quoix, Elisabeth Baik, Christina S. Barlesi, Fabrice Kim, Tae Min Mazieres, Julien Novello, Silvia Rigas, James R. Upalawanna, Allison D'Amelio, Anthony M., Jr. Zhang, Pingkuan Mookerjee, Bijoyesh Johnson, Bruce E. TI Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial SO LANCET ONCOLOGY LA English DT Article ID HARBORING BRAF MUTATIONS; 1ST-LINE TREATMENT; V600 MUTATIONS; MELANOMA; CHEMOTHERAPY; CRIZOTINIB; EGFR; ADENOCARCINOMAS; INHIBITION; AMPLIFICATION AB Background BRAF mutations act as an oncogenic driver via the mitogen-activated protein kinase (MAPK) pathway in non-small cell lung cancer (NSCLC). BRAF inhibition has shown antitumour activity in patients with BRAF(V600E)-mutant NSCLC. Dual MAPK pathway inhibition with BRAF and MEK inhibitors in BRAF(V600E)-mutant NSCLC might improve efficacy over BRAF inhibitor monotherapy based on observations in BRAF(V600)-mutant melanoma. We aimed to assess the antitumour activity and safety of dabrafenib plus trametinib in patients with BRAF(V600E)-mutant NSCLC. Methods In this phase 2, multicentre, non-randomised, open-label study, we enrolled adult patients (aged >= 18 years) with pretreated metastatic stage IV BRAF(V600E)-mutant NSCLC who had documented tumour progression after at least one previous platinum-based chemotherapy and had had no more than three previous systemic anticancer therapies. Patients with previous BRAF or MEK inhibitor treatment were ineligible. Patients with brain metastases were allowed to enrol only if the lesions were asymptomatic, untreated (or stable more than 3 weeks after local therapy if treated), and measured less than 1 cm. Enrolled patients received oral dabrafenib (150 mg twice daily) plus oral trametinib (2 mg once daily) in continuous 21-day cycles until disease progression, unacceptable adverse events, withdrawal of consent, or death. The primary endpoint was investigator-assessed overall response, which was assessed by intention to treat in the protocol-defined population (patients who received second-line or later treatment); safety was also assessed in this population and was assessed at least once every 3 weeks, with adverse events, laboratory values, and vital signs graded according to the Common Terminology Criteria for Adverse Events version 4.0. The study is ongoing but no longer recruiting patients. This trial is registered with ClinicalTrials.gov, number NCT01336634. Findings Between Dec 20, 2013, and Jan 14, 2015, 59 patients from 30 centres in nine countries across North America, Europe, and Asia met eligibility criteria. Two patients who had previously been untreated due to protocol deviation were excluded; thus, 57 eligible patients were enrolled. 36 patients (63.2% [95% CI 49.3-75.6]) achieved an investigator-assessed overall response. Serious adverse events were reported in 32 (56%) of 57 patients and included pyrexia in nine (16%), anaemia in three (5%), confusional state in two (4%), decreased appetite in two (4%), haemoptysis in two (4%), hypercalcaemia in two (4%), nausea in two (4%), and cutaneous squamous cell carcinoma in two (4%). The most common grade 3-4 adverse events were neutropenia in five patients (9%), hyponatraemia in four (7%), and anaemia in three (5%). Four patients died during the study from fatal adverse events judged to be unrelated to treatment (one retroperitoneal haemorrhage, one subarachnoid haemorrhage, one respiratory distress, and one from disease progression that was more severe than typical progression, as assessed by the investigator). Interpretation Dabrafenib plus trametinib could represent a new targeted therapy with robust antitumour activity and a manageable safety profile in patients with BRAF(V600E)-mutant NSCLC. C1 [Planchard, David; Besse, Benjamin] Gustave Roussy, Villejuif, France. [Besse, Benjamin] Univ Paris 11, Orsay, France. [Groen, Harry J. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Souquet, Pierre-Jean] Hop Lyon Sud, Pierre Benite, France. [Quoix, Elisabeth] Univ Hosp, Nouvel Hop Civil, Strasbourg, France. [Baik, Christina S.] Univ Washington, Seattle, WA 98195 USA. [Barlesi, Fabrice] Aix Marseille Univ, Hop Nord, Assistance Publ Hop Marseille, Multidisciplinary Oncol & Therapeut Innovat Dept, Marseille, France. [Kim, Tae Min] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Mazieres, Julien] Rangueil Larrey Hosp, Toulouse, France. [Mazieres, Julien] Univ Toulouse 3, F-31062 Toulouse, France. [Novello, Silvia] Univ Turin, Dept Oncol, Orbassano, Italy. [Rigas, James R.] Geisel Sch Med Dartmouth, Hanover, NH USA. [Upalawanna, Allison] Novartis Pharma AG, Basel, Switzerland. [D'Amelio, Anthony M., Jr.; Zhang, Pingkuan; Mookerjee, Bijoyesh] Novartis Pharmaceut, E Hanover, NJ USA. [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Bruce_Johnson@dfci.harvard.edu FU GlaxoSmithKline FX GlaxoSmithKline. NR 37 TC 17 Z9 19 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 JUL PY 2016 VL 17 IS 7 BP 984 EP 993 DI 10.1016/S1470-2045(16)30146-2 PG 10 WC Oncology SC Oncology GA DQ1FO UT WOS:000378947100063 PM 27283860 ER PT J AU Capalonga, L Karsten, M Hentschke, VS Rossato, DD Dornelles, MP Sonza, A Bagnato, VS Ferraresi, C Parizotto, NA Dal Lago, P AF Capalonga, Lucas Karsten, Marlus Hentschke, Vitor Scotta Rossato, Douglas Dalcin Dornelles, Mauricio Pinto Sonza, Anelise Bagnato, Vanderlei Salvador Ferraresi, Cleber Parizotto, Nivaldo Antonio Dal Lago, Pedro TI Light-emitting diode therapy (LEDT) improves functional capacity in rats with heart failure SO LASERS IN MEDICAL SCIENCE LA English DT Article DE Phototherapy; Maximal oxygen uptake; Exercise test; Hemodynamic function ID LEVEL LASER THERAPY; NEUROMUSCULAR ELECTRICAL-STIMULATION; OBSTRUCTIVE PULMONARY-DISEASE; SKELETAL-MUSCLE PERFORMANCE; SUPER-PULSED LASER; EXERCISE; PHOTOTHERAPY; DAMAGE; ENDURANCE; FATIGUE AB The syndrome of heart failure (HF) promotes central and peripheral dysfunctions that result in functional capacity decrease, leading to fatigue, dyspnea, and exercise intolerance. The use of light-emitting diode therapy (LEDT) has shown good results reducing fatigue and exercise intolerance, when applied on skeletal muscles before or after exercises. Thereby, the aim of this study was to compare the effects of LEDT on functional capacity, aerobic power, and hemodynamic function in HF rats. Male Wistar rats (230-260 g) were randomly allocated into three experimental groups: Sham (n = 6), Control-HF (n = 4), and LEDT-HF (n = 6). The animals were subjected to an exercise performance test (ET) with gas analysis coupled in ametabolic chamber for rats performed two times (6 and 14 weeks after myocardial infarction). On the day after the baseline aerobic capacity test, the animals were submitted during 8 weeks to the phototherapy protocol, five times/week, 60 s of irradiation, 6 J delivered per muscle group. Statistical analysis was performed by one-and two-way ANOVAs with repeated measures and Student-Newman-Keuls post hoc tests (p <= 0.05). Comparing the percentage difference (Delta) between baseline and the final ET, there was no significant difference for the VO2max variable considering all groups. However, Sham and LEDT-HF groups showed higher relative values than the Control-HF group, respectively, for distance covered (27.7 and 32.5 %), time of exercise test (17.7 and 20.5 %), and speed (13.6 and 12.2 %). In conclusion, LEDT was able to increase the functional capacity evaluated by distance covered, time, and speed of exercise in rats with HF. C1 [Capalonga, Lucas; Karsten, Marlus; Hentschke, Vitor Scotta; Dornelles, Mauricio Pinto; Sonza, Anelise; Dal Lago, Pedro] UFCSPA, Lab Expt Physiol, Porto Alegre, RS, Brazil. [Capalonga, Lucas; Karsten, Marlus; Sonza, Anelise; Dal Lago, Pedro] UFCSPA, Postgrad Program Rehabil Sci, Porto Alegre, RS, Brazil. [Hentschke, Vitor Scotta; Dal Lago, Pedro] UFCSPA, Postgrad Program Hlth Sci, Porto Alegre, RS, Brazil. [Rossato, Douglas Dalcin] Ctr Univ Franciscano, Santa Maria, RS, Brazil. [Bagnato, Vanderlei Salvador; Ferraresi, Cleber] Univ Sao Paulo, Phys Inst Sao Carlos, BR-09500900 Sao Paulo, Brazil. [Ferraresi, Cleber; Parizotto, Nivaldo Antonio] Univ Fed Sao Carlos UFSCar, Dept Phys Therapy, Lab Electrothermophototherapy, Sao Paulo, Brazil. [Ferraresi, Cleber] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Wellman Ctr Photomed, Boston, MA 02115 USA. [Dal Lago, Pedro] UFCSPA, PPG CR, Rua Sarmento Leite 245, BR-90050170 Porto Alegre, RS, Brazil. RP Dal Lago, P (reprint author), UFCSPA, Lab Expt Physiol, Porto Alegre, RS, Brazil.; Dal Lago, P (reprint author), UFCSPA, Postgrad Program Rehabil Sci, Porto Alegre, RS, Brazil.; Dal Lago, P (reprint author), UFCSPA, Postgrad Program Hlth Sci, Porto Alegre, RS, Brazil.; Dal Lago, P (reprint author), UFCSPA, PPG CR, Rua Sarmento Leite 245, BR-90050170 Porto Alegre, RS, Brazil. EM pdallago@ufcspa.edu.br RI Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016; USP, CePOF/J-3608-2015; Dal Lago, Pedro/K-4414-2013 OI Dal Lago, Pedro/0000-0001-9907-7689 FU Fundacao de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS, PRONEM-Programa de Nucleos Emergentes); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Chamada Universal); Programa Nacional de Pos-doutorado da Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, PNPD Concessao Institucional) FX This research was supported by: Fundacao de Amparo a Pesquisa do Rio Grande do Sul (FAPERGS, PRONEM-Programa de Nucleos Emergentes, 2011), Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Chamada Universal, 2012), and Programa Nacional de Pos-doutorado da Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, PNPD Concessao Institucional, 2011). NR 41 TC 1 Z9 1 U1 2 U2 5 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 JUL PY 2016 VL 31 IS 5 BP 937 EP 944 DI 10.1007/s10103-016-1922-y PG 8 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA DP5NB UT WOS:000378543200016 PM 27059227 ER PT J AU Julius, A Longfellow, K AF Julius, Anthony Longfellow, Katelan TI Movement Disorders A Brief Guide in Medication Management SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Movement disorders; Parkinson's disease; Nonmotor symptoms; Essential tremor; Restless leg syndrome ID RESTLESS LEGS SYNDROME; PLACEBO-CONTROLLED TRIAL; SLEEP BEHAVIOR DISORDER; AGONIST WITHDRAWAL SYNDROME; QUALITY STANDARDS SUBCOMMITTEE; EARLY PARKINSONS-DISEASE; DOUBLE-BLIND TRIAL; TOXIN TYPE-A; ESSENTIAL TREMOR; ORTHOSTATIC HYPOTENSION AB Movement disorders can be challenging to manage and often use a specific set of medications. Because it is a complex and broad field within neurology, many providers are unfamiliar with the classes of medications. This article details medications used for specific conditions, explains why these medications are helpful, and shares pearls and pitfalls related to each agent, focusing on parameters such as dose titration, side effect profiles, and specific drug-drug interactions and challenges. We focus on the most commonly encountered movement disorders, including essential tremor, Parkinson's disease, rapid eye movement sleep behavior disorder, and restless leg syndrome. C1 [Julius, Anthony; Longfellow, Katelan] Univ Washington, Med Ctr, VA Puget Sound, 1660 S Columbian Way, Seattle, WA 98108 USA. RP Longfellow, K (reprint author), Univ Washington, Med Ctr, VA Puget Sound, 1660 S Columbian Way, Seattle, WA 98108 USA. EM katelanlongfellow@catholichealth.net NR 137 TC 0 Z9 0 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 2016 VL 100 IS 4 BP 733 EP + DI 10.1016/j.mcna.2016.03.002 PG 30 WC Medicine, General & Internal SC General & Internal Medicine GA DP6BK UT WOS:000378581700007 PM 27235613 ER PT J AU Allen, C Evans, G Sutton, EL AF Allen, Caitlin Evans, Ginger Sutton, Eliza L. TI Pharmacologic Therapies in Women's Health Contraception and Menopause Treatment SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article DE Long-acting reversible contraception; Combined hormonal contraception; Emergency contraception; Menopause transition; Genitourinary syndrome of menopause; Estrogen therapy ID ACTING REVERSIBLE CONTRACEPTION; RANDOMIZED CONTROLLED-TRIAL; EMERGENCY CONTRACEPTION; INTRAUTERINE-DEVICE; VASOMOTOR SYMPTOMS; ORAL-CONTRACEPTIVES; VENOUS THROMBOEMBOLISM; ULIPRISTAL ACETATE; CLINICAL-TRIAL; HORMONAL CONTRACEPTIVES AB Female hormones play a significant role in the etiology and treatment of many women's health conditions. This article focuses on the common uses of hormonal therapy. When prescribing estrogen-containing regimens throughout the span of a woman's life, the risks are similar (ie, cardiovascular risk and venous thromboembolism), but the degree of risk varies significantly depending on a woman's particular set of risk factors and the details of the hormone regimen. In addition to estrogens and progestogens, this article also touches on the use of selective steroid receptor modulators in emergency contraception and in treatment of menopause symptoms. C1 [Allen, Caitlin] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, MFCB 5120, 1685 Highland Ave, Madison, WI 53705 USA. [Evans, Ginger] Univ Washington, Dept Med, VA Puget Sound Hlth Care Syst, 1660 South Columbian Way,S-123 PCC, Seattle, WA 98108 USA. [Sutton, Eliza L.] Univ Washington, Dept Med, Womens Hlth Care Ctr, 4245 Roosevelt Way Northeast,Box 354765, Seattle, WA 98105 USA. RP Allen, C (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, MFCB 5120, 1685 Highland Ave, Madison, WI 53705 USA. EM callen@uwhealth.org NR 94 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 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 2016 VL 100 IS 4 BP 763 EP + DI 10.1016/j.mcna.2016.03.008 PG 28 WC Medicine, General & Internal SC General & Internal Medicine GA DP6BK UT WOS:000378581700008 PM 27235614 ER PT J AU Joo, MS Kim, WD Lee, KY Kim, JH Koo, JH Kim, SG AF Joo, Min Sung Kim, Won Dong Lee, Ki Young Kim, Ji Hyun Koo, Ja Hyun Kim, Sang Geon TI AMPK Facilitates Nuclear Accumulation of Nrf2 by Phosphorylating at Serine 550 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; GLYCOGEN-SYNTHASE KINASE-3-BETA; TRANSCRIPTION FACTOR NRF2; VEIN ENDOTHELIAL-CELLS; OXIDATIVE STRESS; ANTIOXIDANT RESPONSE; GENE-EXPRESSION; ENERGY SENSOR; INDUCED APOPTOSIS; EXPORT SIGNALS AB Nrf2 (nuclear factor erythroid 2-related factor 2) is an antioxidant transcription factor. AMP-activated protein kinase (AMPK) functions as a central regulator of cell survival in response to stressful stimuli. Nrf2 should be coordinated with the cell survival pathway controlled by AMPK, but so far the mechanistic connections remain undefined. This study investigated the role of AMPK in Nrf2 trafficking and its activity regulation. A subnetwork integrating neighbor molecules suggested direct interaction between AMPK and Nrf2. In cells, AMPK activation caused nuclear accumulation of Nrf2. In the in vitro kinase and peptide competition assays, AMPK phosphorylated Nrf2 at the Ser558 residue (Ser550 in mouse) located in the canonical nuclear export signal. Nrf2 with an S550A mutation failed to be accumulated in the nucleus after AMPK activation. Leptomycin B, a nuclear export inhibitor, did not enhance nuclear accumulation of wild-type Nrf2 (WT-Nrf2) activated by AMPK or a phospho-Ser550-mimetic Nrf2 mutant, corroborating the finding that AMPK facilitated nuclear accumulation of Nrf2, probably by inhibiting nuclear export. Activated glycogen synthase kinase 3 beta (GSK3 beta) diminished the basal nuclear level of Myc-S550A-Nrf2. Taking the data collectively, AMPK phosphorylates Nrf2 at the Ser550 residue, which, in conjunction with AMPK-mediated GSK3 beta inhibition, promotes nuclear accumulation of Nrf2 for antioxidant response element (ARE)-driven gene transactivation. C1 [Joo, Min Sung; Kim, Won Dong; Koo, Ja Hyun; Kim, Sang Geon] Seoul Natl Univ, Coll Pharm, Seoul, South Korea. [Joo, Min Sung; Kim, Won Dong; Koo, Ja Hyun; Kim, Sang Geon] Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. [Lee, Ki Young; Kim, Ji Hyun] Ajou Univ, Sch Med, Dept Biomed Informat, Suwon, South Korea. [Kim, Won Dong] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Kim, Won Dong] Harvard Med Sch, Boston, MA USA. RP Kim, SG (reprint author), Seoul Natl Univ, Coll Pharm, Seoul, South Korea.; Kim, SG (reprint author), Seoul Natl Univ, Pharmaceut Sci Res Inst, Seoul, South Korea. EM sgk@snu.ac.kr OI Koo, Ja Hyun/0000-0001-5738-1105 FU Ministry of Science, ICT and Future Planning (MSIP) [2013R1A2A2A04013317, 2007-0056817, NRF-2014M1A3A3A02034698] FX This work, including the efforts of Min Sung Joo, Won Dong Kim, Ki-Young Lee, Ji Hyun Kim, Ja Hyun Koo, and Sang Geon Kim, was funded by Ministry of Science, ICT and Future Planning (MSIP) (2013R1A2A2A04013317, 2007-0056817, NRF-2014M1A3A3A02034698). NR 52 TC 1 Z9 1 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2016 VL 36 IS 14 BP 1931 EP 1942 DI 10.1128/MCB.00118-16 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DQ0XG UT WOS:000378924500004 PM 27161318 ER PT J AU Wu, C Arora, P Agha, O Hurst, LA Allen, K Nathan, DI Hu, DJ Jiramongkolchai, P Smith, JG Melander, O Trenson, S Janssens, SP Domian, I Wang, TJ Bloch, KD Buys, ES Bloch, DB Newton-Cheh, C AF Wu, Connie Arora, Pankaj Agha, Obiajulu Hurst, Liam A. Allen, Kaitlin Nathan, Daniel I. Hu, Dongjian Jiramongkolchai, Pawina Smith, J. Gustav Melander, Olle Trenson, Sander Janssens, Stefan P. Domian, Ibrahim Wang, Thomas J. Bloch, Kenneth D. Buys, Emmanuel S. Bloch, Donald B. Newton-Cheh, Christopher TI Novel MicroRNA Regulators of Atrial Natriuretic Peptide Production SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-DERIVED CARDIOMYOCYTE; PLURIPOTENT STEM-CELLS; CARDIAC-HYPERTROPHY; MESSENGER-RNA; HEART-TISSUE; EXPRESSION; DIFFERENTIATION; FAILURE; TARGETS AB Atrial natriuretic peptide (ANP) has a central role in regulating blood pressure in humans. Recently, microRNA 425 (miR-425) was found to regulate ANP production by binding to the mRNA of NPPA, the gene encoding ANP. mRNAs typically contain multiple predicted microRNA (miRNA)-binding sites, and binding of different miRNAs may independently or coordinately regulate the expression of any given mRNA. We used a multifaceted screening strategy that integrates bioinformatics, next-generation sequencing data, human genetic association data, and cellular models to identify additional functional NPPA-targeting miRNAs. Two novel miRNAs, miR-155 and miR-105, were found to modulate ANP production in human cardiomyocytes and target genetic variants whose minor alleles are associated with higher human plasma ANP levels. Both miR-155 and miR-105 repressed NPPA mRNA in an allele-specific manner, with the minor allele of each respective variant conferring resistance to the miRNA either by disruption of miRNA base pairing or by creation of wobble base pairing. Moreover, miR-155 enhanced the repressive effects of miR-425 on ANP production in human cardiomyocytes. Our study combines computational, genomic, and cellular tools to identify novel miRNA regulators of ANP production that could be targeted to raise ANP levels, which may have applications for the treatment of hypertension or heart failure. C1 [Wu, Connie; Hu, Dongjian; Smith, J. Gustav; Domian, Ibrahim; Bloch, Kenneth D.; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Wu, Connie; Agha, Obiajulu; Hurst, Liam A.; Allen, Kaitlin; Nathan, Daniel I.; Jiramongkolchai, Pawina; Bloch, Kenneth D.; Buys, Emmanuel S.; Bloch, Donald B.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Wu, Connie; Smith, J. Gustav; Newton-Cheh, Christopher] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA. [Arora, Pankaj] Univ Alabama Birmingham, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. [Hu, Dongjian] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Smith, J. Gustav; Newton-Cheh, Christopher] Massachusetts Gen Hosp, Harvard Med Sch, Ctr Human Genet Res, Boston, MA 02114 USA. [Smith, J. Gustav] Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden. [Smith, J. Gustav] Skane Univ Hosp, Dept Heart Failure & Valvular Dis, Lund, Sweden. [Melander, Olle] Lund Univ, Dept Internal Med, Clin Sci, Malmo, Sweden. [Melander, Olle] Skane Univ Hosp, Malmo, Sweden. [Trenson, Sander; Janssens, Stefan P.] Univ Leuven, Dept Cardiovasc Sci, Leuven, Belgium. [Domian, Ibrahim] Harvard Stem Cell Inst, Cambridge, MA USA. [Wang, Thomas J.] Vanderbilt Univ, Sch Med, Dept Med, Div Cardiovasc Med, Nashville, TN 37212 USA. [Bloch, Donald B.] Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Harvard Med Sch, Boston, MA 02114 USA. RP Buys, ES; Bloch, DB (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.; Bloch, DB (reprint author), Massachusetts Gen Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Harvard Med Sch, Boston, MA 02114 USA. EM EBUYS@mgh.harvard.edu; dbloch@partners.org FU HHS \ National Institutes of Health (NIH) [R01HL098283, R01HL113933, R01HL124262]; Howard Hughes Medical Institute (HHMI); HHS \ NIH \ National Heart, Lung, and Blood Institute (NHLBI) [T32HL007208]; Fondation Leducq FX This work, including the efforts of Thomas J. Wang and Christopher Newton-Cheh, was funded by HHS vertical bar National Institutes of Health (NIH) (R01HL098283). This work, including the efforts of Christopher Newton-Cheh, was funded by HHS vertical bar National Institutes of Health (NIH) (R01HL113933). This work, including the efforts of Christopher Newton-Cheh, was funded by HHS vertical bar National Institutes of Health (NIH) (R01HL124262). This work, including the efforts of Pawina Jiramongkolchai, was funded by Howard Hughes Medical Institute (HHMI). This work, including the efforts of Connie Wu, was funded by HHS vertical bar NIH vertical bar National Heart, Lung, and Blood Institute (NHLBI) (T32HL007208). This work, including the efforts of Connie Wu, Kenneth D Bloch, and Donald B. Bloch, was funded by Fondation Leducq. NR 36 TC 0 Z9 0 U1 4 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2016 VL 36 IS 14 BP 1977 EP 1987 DI 10.1128/MCB.01114-15 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA DQ0XG UT WOS:000378924500007 PM 27185878 ER PT J AU Rich, SS Wang, ZY Sturcke, A Ziyabari, L Feolo, M O'Donnell, CJ Rice, K Bis, JC Psaty, BM AF Rich, Stephen S. Wang, Zeng Y. Sturcke, Anne Ziyabari, Lora Feolo, Mike O'Donnell, Christopher J. Rice, Ken Bis, Joshua C. Psaty, Bruce M. TI Rapid evaluation of phenotypes, SNPs and results through the dbGaP CHARGE Summary Results site SO NATURE GENETICS LA English DT Letter ID GENOME-WIDE ASSOCIATION; DESIGN C1 [Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. [Wang, Zeng Y.; Sturcke, Anne; Ziyabari, Lora; Feolo, Mike] US Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Div Intramural Res, Framingham, MA USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rice, Ken] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Rich, SS (reprint author), Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA. EM ssr4n@virginia.edu NR 8 TC 2 Z9 2 U1 2 U2 4 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 JUL PY 2016 VL 48 IS 7 BP 702 EP 703 DI 10.1038/ng.3582 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA DP9TK UT WOS:000378840100002 PM 27350599 ER PT J AU Li, B Li, TW Pignon, JC Wang, BB Wang, JZ Shukla, SA Dou, RX Chen, QM Hodi, FS Choueiri, TK Wu, C Hacohen, N Signoretti, S Liu, JS Liu, XS AF Li, Bo Li, Taiwen Pignon, Jean-Christophe Wang, Binbin Wang, Jinzeng Shukla, Sachet A. Dou, Ruoxu Chen, Qianming Hodi, F. Stephen Choueiri, Toni K. Wu, Catherine Hacohen, Nir Signoretti, Sabina Liu, Jun S. Liu, X. Shirley TI Landscape of tumor-infiltrating T cell repertoire of human cancers SO NATURE GENETICS LA English DT Article ID RNA-SEQ READS; SEQUENCING DATA; ANTIGEN; IMMUNOTHERAPY; RECOGNITION; RECEPTORS; BLOCKADE; LYMPHOCYTES; RESPONSES; LEUKEMIA AB We developed a computational method to infer the complementarity-determining region 3 (CDR3) sequences of tumor-infiltrating T cells in 9,142 RNA-seq samples across 29 cancer types. We identified over 600,000 CDR3 sequences, including 15% that were full length. CDR3 sequence length distribution and amino acid conservation, as well as variable gene usage, for infiltrating T cells in many tumors, except in brain and kidney cancers, resembled those for peripheral blood cells from healthy donors. We observed a strong association between T cell diversity and tumor mutation load, and we predicted SPAG5 and TSSK6 as putative immunogenic cancer/testis antigens in multiple cancers. Finally, we identified three potential immunogenic somatic mutations on the basis of their co-occurrence with CDR3 sequences. One of them, a PRAMEF4 mutation encoding p. Phe300Val, was predicted to result in peptide binding strongly to both MHC class I and class II molecules, with matched HLA types in its carriers. Our analyses have the potential to simultaneously identify immunogenic neoantigens and tumor-reactive T cell clonotypes. C1 [Li, Bo; Li, Taiwen; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Bo; Liu, Jun S.; Liu, X. Shirley] Harvard Univ, Dept Stat, Boston, MA 02115 USA. [Li, Taiwen; Chen, Qianming] Sichuan Univ, West China Hosp Stomatol, State Key Lab Oral Dis, Chengdu 610064, Peoples R China. [Pignon, Jean-Christophe; Signoretti, Sabina] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. [Wang, Binbin; Wang, Jinzeng] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Shukla, Sachet A.; Wu, Catherine] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Dou, Ruoxu] Sun Yat Sen Univ, Dept Colorectal Surg, Affiliated Hosp 6, Guangzhou 510275, Guangdong, Peoples R China. [Hodi, F. Stephen] Harvard Univ, Sch Med, Ctr ImmunoOncol, Boston, MA USA. [Choueiri, Toni K.] Dana Farber Canc Inst, Kidney Canc Ctr, Boston, MA 02115 USA. [Hacohen, Nir] Massachusetts Gen Hosp, Ctr Canc Immunotherapy, Boston, MA 02114 USA. RP Liu, XS (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.; Liu, JS; Liu, XS (reprint author), Harvard Univ, Dept Stat, Boston, MA 02115 USA. EM jliu@stat.harvard.edu; xsliu@jimmy.harvard.edu FU NCI [1U01 CA180980]; National Natural Science Foundation of China [31329003]; Chinese Scholarship Council; NIH/NCI DF/HCC Kidney Cancer SPORE [P50 CA101942] FX We thank G. Freeman for helpful discussion during manuscript preparation. We also acknowledge the following funding sources for supporting our work: NCI grant 1U01 CA180980, National Natural Science Foundation of China grant 31329003 and a Chinese Scholarship Council Fellowship. This work was supported in part by NIH/NCI DF/HCC Kidney Cancer SPORE P50 CA101942 to S.S. and T.K.C. NR 45 TC 11 Z9 11 U1 6 U2 14 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 JUL PY 2016 VL 48 IS 7 BP 725 EP + DI 10.1038/ng.3581 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA DP9TK UT WOS:000378840100009 PM 27240091 ER PT J AU McPherson, A Roth, A Laks, E Masud, T Bashashati, A Zhang, AW Ha, G Biele, J Yap, D Wan, A Prentice, LM Khattra, J Smith, MA Nielsen, CB Mullaly, SC Kalloger, S Karnezis, A Shumansky, K Siu, C Rosner, J Chan, HL Ho, J Melnyk, N Senz, J Yang, W Moore, R Mungall, AJ Marra, MA Bouchard-Cote, A Gilks, CB Huntsman, DG McAlpine, JN Aparicio, S Shah, SP AF McPherson, Andrew Roth, Andrew Laks, Emma Masud, Tehmina Bashashati, Ali Zhang, Allen W. Ha, Gavin Biele, Justina Yap, Damian Wan, Adrian Prentice, Leah M. Khattra, Jaswinder Smith, Maia A. Nielsen, Cydney B. Mullaly, Sarah C. Kalloger, Steve Karnezis, Anthony Shumansky, Karey Siu, Celia Rosner, Jamie Chan, Hector Li Ho, Julie Melnyk, Nataliya Senz, Janine Yang, Winnie Moore, Richard Mungall, Andrew J. Marra, Marco A. Bouchard-Cote, Alexandre Gilks, C. Blake Huntsman, David G. McAlpine, Jessica N. Aparicio, Samuel Shah, Sohrab P. TI Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer SO NATURE GENETICS LA English DT Article ID BRCA2 MUTATIONS; EVOLUTION; CARCINOMA; INFERENCE; DYNAMICS; DOLLO; TP53 AB We performed phylogenetic analysis of high-grade serous ovarian cancers (68 samples from seven patients), identifying constituent clones and quantifying their relative abundances at multiple intraperitoneal sites. Through whole-genome and single-nucleus sequencing, we identified evolutionary features including mutation loss, convergence of the structural genome and temporal activation of mutational processes that patterned clonal progression. We then determined the precise clonal mixtures comprising each tumor sample. The majority of sites were clonally pure or composed of clones from a single phylogenetic clade. However, each patient contained at least one site composed of polyphyletic clones. Five patients exhibited monoclonal and unidirectional seeding from the ovary to intraperitoneal sites, and two patients demonstrated polyclonal spread and reseeding. Our findings indicate that at least two distinct modes of intraperitoneal spread operate in clonal dissemination and highlight the distribution of migratory potential over clonal populations comprising high-grade serous ovarian cancers. C1 [McPherson, Andrew; Roth, Andrew; Laks, Emma; Masud, Tehmina; Bashashati, Ali; Zhang, Allen W.; Ha, Gavin; Biele, Justina; Yap, Damian; Wan, Adrian; Khattra, Jaswinder; Smith, Maia A.; Mullaly, Sarah C.; Kalloger, Steve; Shumansky, Karey; Siu, Celia; Rosner, Jamie; Huntsman, David G.; Aparicio, Samuel; Shah, Sohrab P.] BC Canc Agcy, Dept Mol Oncol, Vancouver, BC, Canada. [McPherson, Andrew] Simon Fraser Univ, Sch Comp Sci, Burnaby, BC V5A 1S6, Canada. [McPherson, Andrew; Roth, Andrew; Zhang, Allen W.; Ha, Gavin; Smith, Maia A.] Univ British Columbia, Grad Bioinformat Training Program, Vancouver, BC V5Z 1M9, Canada. [McPherson, Andrew; Masud, Tehmina; Nielsen, Cydney B.; Huntsman, David G.; Aparicio, Samuel; Shah, Sohrab P.] Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. [Zhang, Allen W.] Child & Family Res Inst, Ctr Mol Med & Therapeut, Vancouver, BC, Canada. [Ha, Gavin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ha, Gavin] Broad Inst MIT & Harvard, Cambridge, MA USA. [Prentice, Leah M.; Karnezis, Anthony; Chan, Hector Li; Ho, Julie; Melnyk, Nataliya; Senz, Janine; Yang, Winnie; Huntsman, David G.] BC Canc Agcy, Ctr Translat & Appl Gen, Vancouver, BC, Canada. [Moore, Richard; Mungall, Andrew J.; Marra, Marco A.; Shah, Sohrab P.] BC Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. [Bouchard-Cote, Alexandre] Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada. [Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol, 855 W 12Th Ave, Vancouver, BC V5Z 1M9, Canada. [McAlpine, Jessica N.] Univ British Columbia, Dept Gynecol & Obstet, Vancouver, BC V5Z 1M9, Canada. RP Aparicio, S; Shah, SP (reprint author), BC Canc Agcy, Dept Mol Oncol, Vancouver, BC, Canada.; Aparicio, S; Shah, SP (reprint author), Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada.; Shah, SP (reprint author), BC Canc Agcy, Michael Smith Genome Sci Ctr, Vancouver, BC, Canada. EM saparicio@bccrc.ca; sshah@bccrc.ca RI Marra, Marco/B-5987-2008; OI Yap, Damian/0000-0002-5370-4592 FU BC Cancer Foundation; Canadian Breast Cancer Foundation; Canadian Cancer Society Research Institute [701584]; Terry Fox Research Institute; Genome Canada/Genome BC [173-CIC, 177-EVO]; Canadian Institutes for Health Research (CIHR) [MOP-115170, MOP-126119, FDN-143246]; TFRI; Canada Research Chairs; NSERC CGS scholarship; CIHR CGS scholarship; Canadian Breast Cancer Foundation British Columbia/Yukon Postdoctoral Fellowship; [MSH-261515] FX We thank V. Earle for the artwork depicting anatomical sites sampled in the study. We acknowledge generous long-term funding support provided by the BC Cancer Foundation. In addition, the groups of S.P.S. and S.A. receive operating funds from the Canadian Breast Cancer Foundation, the Canadian Cancer Society Research Institute (grant 701584), the Terry Fox Research Institute, Genome Canada/Genome BC (173-CIC and 177-EVO), the Canadian Institutes for Health Research (CIHR) (MOP-115170, MOP-126119, and FDN-143246), a new investigator grant to J.N.M. (MSH-261515), and a TFRI new investigator award to S.P.S. S.P.S. and S.A. are supported by Canada Research Chairs. S.P.S. is a Michael Smith Foundation for Health Research scholar. A.M. is supported by a NSERC CGS scholarship. A.R. is supported by a CIHR CGS scholarship. T.M. is supported by a Canadian Breast Cancer Foundation British Columbia/Yukon Postdoctoral Fellowship. NR 27 TC 10 Z9 10 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 JUL PY 2016 VL 48 IS 7 BP 758 EP + DI 10.1038/ng.3573 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA DP9TK UT WOS:000378840100013 PM 27182968 ER PT J AU Engblom, C Pfirschke, C Pittet, MJ AF Engblom, Camilla Pfirschke, Christina Pittet, Mikael J. TI The role of myeloid cells in cancer therapies SO NATURE REVIEWS CANCER LA English DT Review ID TUMOR-ASSOCIATED MACROPHAGES; COLONY-STIMULATING FACTOR; CD8(+) T-CELLS; INDEPENDENT PROGNOSTIC-FACTOR; DEPENDENT ANTITUMOR IMMUNITY; PLASMACYTOID DENDRITIC CELLS; ANTIGEN-PRESENTING CELLS; BREAST-CANCER; SUPPRESSOR-CELLS; MAST-CELLS AB Recent clinical trials have demonstrated the ability to durably control cancer in some patients by manipulating T lymphocytes. These immunotherapies are revolutionizing cancer treatment but benefit only a minority of patients. It is thus a crucial time for clinicians, cancer scientists and immunologists to determine the next steps in shifting cancer treatment towards better cancer control. This Review describes recent advances in our understanding of tumour-associated myeloid cells. These cells remain less studied than T lymphocytes but have attracted particular attention because their presence in tumours is often linked to altered patient survival. Also, experimental studies indicate that myeloid cells modulate key cancer-associated activities, including immune evasion, and affect virtually all types of cancer therapy. Consequently, targeting myeloid cells could overcome limitations of current treatment options. C1 [Engblom, Camilla; Pfirschke, Christina; Pittet, Mikael J.] Massachusetts Gen Hosp, Res Inst, Ctr Syst Biol, Boston, MA 02114 USA. [Engblom, Camilla; Pfirschke, Christina; Pittet, Mikael J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Engblom, Camilla] Harvard Univ, Sch Med, Grad Program Immunol, Boston, MA 02115 USA. RP Pittet, MJ (reprint author), Massachusetts Gen Hosp, Res Inst, Ctr Syst Biol, Boston, MA 02114 USA.; Pittet, MJ (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM mpittet@mgh.harvard.edu FU Samana Cay MGH Research Scholar Fund; National Institutes of Health (NIH) [P50-CA86355, R21 CA190344, R01-AI084880]; Boehringer Ingelheim Fonds; Deutsche Forschungsgemeinschaft (DFG) [PF809/1-1] FX The authors thank members of the Pittet laboratory and of the Massachusetts General Hospital (MGH) Center for Systems Biology for critical discussions and acknowledge all contributors to the field whose work we could not cite owing to space limitations. This work was supported in part by the Samana Cay MGH Research Scholar Fund, National Institutes of Health (NIH) grants P50-CA86355, R21 CA190344 and R01-AI084880 (to M.J.P.), the Boehringer Ingelheim Fonds (to C.E.) and the Deutsche Forschungsgemeinschaft (DFG) PF809/1-1 (to C.P.). NR 242 TC 9 Z9 9 U1 11 U2 25 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 JUL PY 2016 VL 16 IS 7 BP 447 EP 462 DI 10.1038/nrc.2016.54 PG 16 WC Oncology SC Oncology GA DP9TA UT WOS:000378838900007 PM 27339708 ER PT J AU Malakhov, A Wen, J Zhang, BX Wang, H Geng, H Chen, XD Sun, Y Yeh, CK AF Malakhov, A. Wen, J. Zhang, B-X Wang, H. Geng, H. Chen, X-D Sun, Y. Yeh, C-K TI Rechargeable anticandidal denture material with sustained release in saliva SO ORAL DISEASES LA English DT Article DE Candida-associated denture stomatitis; antifungal treatment; drug delivery; rechargeable biomaterial ID CANDIDA-ALBICANS; BIOFILM FORMATION; IN-VITRO; TISSUE CONDITIONERS; ANTIFUNGAL ACTIVITY; SILVER-ZEOLITE; DRUG-RELEASE; STOMATITIS; MICONAZOLE; RESISTANCE AB ObjectiveCandida-induced denture stomatitis is a common debilitating problem among denture wearers. Previously, we described the fabrication of a new denture material that released antifungal drugs when immersed in phosphate buffered saline. Here, we use more clinically relevant immersion conditions (human saliva; 37 degrees C) and measure miconazole release and bioactivity. Materials and MethodsDisks were prepared by grafting PNVP [poly(N-vinyl-2-pyrrolidinone)] onto PMMA [poly(methylmethacrylate)] using plasma initiation (PMMA-g-PNVP) and then loaded with miconazole. Drug-loaded disks were immersed in 10-100% human saliva (1-30days). Miconazole release was measured and then tested for bioactivity vs miconazole-sensitive and miconazole-resistant Candida isolates. ResultsHPLC was used to quantify miconazole levels in saliva. Miconazole-loaded disks released antifungal drug for up to 30days. Higher drug release was found with higher concentrations of saliva, and, interestingly, miconazole solubility was increased with higher saliva concentrations. The released miconazole retained its anticandidal activity. After immersion, the residual miconazole could be quenched and the disks recharged. Freshly recharged disks displayed the same release kinetics and bioactivity as the original disks. Quenched disks could also be charged with chlorhexidine that displayed anticandidal activity. ConclusionsThese results suggest that PMMA-g-PNVP is a promising new denture material for long-term management of denture stomatitis. C1 [Malakhov, A.; Zhang, B-X; Wang, H.; Chen, X-D; Yeh, C-K] South Texas Vet Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, San Antonio, TX 78229 USA. [Malakhov, A.; Zhang, B-X; Wang, H.; Chen, X-D; Yeh, C-K] South Texas Vet Hlth Care Syst, Res Serv, Audie L Murphy Div, San Antonio, TX 78229 USA. [Malakhov, A.; Zhang, B-X; Wang, H.; Chen, X-D; Yeh, C-K] Univ Texas Hlth Sci Ctr San Antonio, Dept Comprehens Dent, San Antonio, TX 78229 USA. [Wen, J.; Sun, Y.] Univ Massachusetts, Dept Chem, Lowell, MA USA. [Geng, H.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA. RP Yeh, CK (reprint author), South Texas Vet Hlth Care Syst, Educ & Clin Ctr, Geriatr Res, San Antonio, TX 78229 USA.; Yeh, CK (reprint author), South Texas Vet Hlth Care Syst, Res Serv, Audie L Murphy Div, San Antonio, TX 78229 USA. EM yeh@uthscsa.edu FU NIH; NIDCR T-32 [DE021084, DE014318]; COSTAR Program; VA Merit Review [1I01BX001103] FX This study was supported by NIH and NIDCR T-32 grants DE021084, DE014318, the COSTAR Program, and a VA Merit Review (1I01BX001103). We are grateful to Dr. Nathan Wiederhold, Director of the Fungal Testing Laboratory (UTHSCSA), for kindly providing the Candida isolates used in this study and to Dr. David Dean (Professor, Comprehensive Dentistry, UTHSCSA) for his scientific input and careful editing of the manuscript. The authors declared no potential conflict of interests with respect to the authorship and/or publication of this article. NR 33 TC 0 Z9 0 U1 5 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD JUL PY 2016 VL 22 IS 5 BP 391 EP 398 DI 10.1111/odi.12456 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DP6WA UT WOS:000378638800007 PM 26855200 ER PT J AU Poston, CJ Pierce, TC Li, Y Brinson, CW Lu, Z Lauer, AW Leite, RS Huang, Y AF Poston, C. J. Pierce, T. C. Li, Y. Brinson, C. W. Lu, Z. Lauer, A. W. Leite, R. S. Huang, Y. TI Statin intake is associated with MMP-1 level in gingival crevicular fluid of patients with periodontitis SO ORAL DISEASES LA English DT Article DE statin; periodontitis; diabetes mellitus; matrix metalloproteinase-1 ID MATRIX METALLOPROTEINASE-1 EXPRESSION; U937 MONONUCLEAR-CELLS; ALVEOLAR BONE LOSS; HIGH GLUCOSE; CARDIOVASCULAR-DISEASE; INFLAMMATORY RESPONSES; INTERFERON-GAMMA; LIPOPOLYSACCHARIDE; THERAPY; ROSUVASTATIN AB BackgroundThis study was conducted to assess whether statin intake is associated with clinical parameters of periodontitis and matrix metalloproteinase (MMP) levels in gingival crevicular fluid (GCF) of non-diabetic and diabetic patients. MethodsWe first determined the effect of simvastatin on MMP expression in mononuclear cells. We then recruited 117 non-diabetic and diabetic patients, who all had periodontitis and took or did not take statin, and measured periodontal probing depth (PPD) and clinical attachment level (CAL), and collected gingival crevicular fluid (GCF) to quantify MMPs. ResultsThe invitro studies showed that simvastatin potently inhibited the expression of MMP-1, MMP-8, and MMP-9 upregulated by lipopolysaccharide (LPS) and high glucose in mononuclear cells. The patient study showed that, after adjusting for age and smoking status, PPD in diabetic patients on statin was significantly less than that in diabetic patients not on statin. MMP-1 level in GCF of non-diabetic and diabetic patients on statin was lower than that of non-diabetic and diabetic patients not on statin, respectively. No difference was found for MMP-8 and -9 levels in GCF. ConclusionStatin intake is associated with reduced PPD in diabetic patients and MMP-1 level in GCF in either non-diabetic or diabetic patients. C1 [Poston, C. J.; Pierce, T. C.; Leite, R. S.] Med Univ S Carolina, Coll Dent Med, Div Periodont, Dept Stomatol, Charleston, SC 29425 USA. [Li, Y.; Brinson, C. W.; Huang, Y.] Med Univ S Carolina, Coll Med, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. [Lu, Z.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29425 USA. [Lauer, A. W.] Med Univ S Carolina, Coll Med, Dept Publ Hlth Sci, Div Biostat, Charleston, SC 29425 USA. RP Huang, Y (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29425 USA.; Huang, Y (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29425 USA. EM huangyan@musc.edu FU NIH [DE016353]; Merit Review Grant from Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs FX This work was supported by NIH grant DE016353 and Merit Review Grant from the Biomedical Laboratory Research and Development Program of the Department of Veterans Affairs (to Y.H.). NR 45 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1354-523X EI 1601-0825 J9 ORAL DIS JI Oral Dis. PD JUL PY 2016 VL 22 IS 5 BP 438 EP 444 DI 10.1111/odi.12474 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA DP6WA UT WOS:000378638800013 PM 26988924 ER PT J AU Hasegawa, K Linnemann, RW Mansbach, JM Ajami, NJ Espinola, JA Petrosino, JF Piedra, PA Stevenson, MD Sullivan, AF Thompson, AD Camargo, CA AF Hasegawa, Kohei Linnemann, Rachel W. Mansbach, Jonathan M. Ajami, Nadim J. Espinola, Janice A. Petrosino, Joseph F. Piedra, Pedro A. Stevenson, Michelle D. Sullivan, Ashley F. Thompson, Amy D. Camargo, Carlos A., Jr. TI The Fecal Microbiota Profile and Bronchiolitis in Infants SO PEDIATRICS LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; PROBIOTIC SUPPLEMENTATION; IMMUNE-RESPONSES; INFECTION; RHINOVIRUS; CHILDREN; MUCOSAL; DEFENSE; ASTHMA AB BACKGROUND: Little is known about the association of gut microbiota, a potentially modifiable factor, with bronchiolitis in infants. We aimed to determine the association of fecal microbiota with bronchiolitis in infants. METHODS: We conducted a case-control study. As a part of multicenter prospective study, we collected stool samples from 40 infants hospitalized with bronchiolitis. We concurrently enrolled 115 age-matched healthy controls. By applying 16S rRNA gene sequencing and an unbiased clustering approach to these 155 fecal samples, we identified microbiota profiles and determined the association of microbiota profiles with likelihood of bronchiolitis. RESULTS: Overall, the median age was 3 months, 55% were male, and 54% were non-Hispanic white. Unbiased clustering of fecal microbiota identified 4 distinct profiles: Escherichiadominant profile (30%), Bifidobacterium-dominant profile (21%), Enterobacter/Veillonelladominant profile (22%), and Bacteroides-dominant profile (28%). The proportion of bronchiolitis was lowest in infants with the Enterobacter/Veillonella-dominant profile (15%) and highest in the Bacteroides-dominant profile (44%), corresponding to an odds ratio of 4.59 (95% confidence interval, 1.58-15.5; P =.008). In the multivariable model, the significant association between the Bacteroides-dominant profile and a greater likelihood of bronchiolitis persisted (odds ratio for comparison with the Enterobacter/Veillonella-dominant profile, 4.24; 95% confidence interval, 1.56-12.0; P =.005). In contrast, the likelihood of bronchiolitis in infants with the Escherichia-dominant or Bifidobacterium-dominant profile was not significantly different compared with those with the Enterobacter/Veillonella-dominant profile. CONCLUSIONS: In this case-control study, we identified 4 distinct fecal microbiota profiles in infants. The Bacteroides-dominant profile was associated with a higher likelihood of bronchiolitis. C1 [Hasegawa, Kohei; Espinola, Janice A.; Sullivan, Ashley F.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Emergency Med, Boston, MA 02114 USA. [Linnemann, Rachel W.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. [Mansbach, Jonathan M.] Boston Childrens Hosp, Dept Med, Boston, MA USA. [Ajami, Nadim J.; Petrosino, Joseph F.] Baylor Coll Med, Alkek Ctr Metagen & Microbiome Res, Houston, TX 77030 USA. [Piedra, Pedro A.] Baylor Coll Med, Dept Mol Virol & Microbiol & Pediat, Houston, TX 77030 USA. [Stevenson, Michelle D.] Kosair Childrens Hosp, Louisville, KY USA. [Thompson, Amy D.] Alfred I duPont Hosp Children, Delaware, OH USA. RP Hasegawa, K (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 125 Nashua St,Suite 920, Boston, MA 02114 USA. EM khasegawa1@partners.org FU National Institutes of Health (Bethesda, MD) [U01 AI-087881, R01 AI-114552, R01 AI-108588, R21 HL-129909]; National Institutes of Health (NIH) FX Supported by grants U01 AI-087881, R01 AI-114552, R01 AI-108588, and R21 HL-129909 from the National Institutes of Health (Bethesda, MD). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funded by the National Institutes of Health (NIH). NR 40 TC 2 Z9 2 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JUL PY 2016 VL 138 IS 1 AR e20160218 DI 10.1542/peds.2016-0218 PG 9 WC Pediatrics SC Pediatrics GA DP9YD UT WOS:000378853100042 ER PT J AU Lee, J Greenspan, PT Israel, E Katz, A Fasano, A Kaafarani, HMA Linov, PL Raja, AS Rao, SK AF Lee, Jarone Greenspan, Peter T. Israel, Esther Katz, Aubrey Fasano, Alessio Kaafarani, Haytham M. A. Linov, Pamela L. Raja, Ali S. Rao, Sandhya K. TI Emergency Department Utilization Report to Decrease Visits by Pediatric Gastroenterology Patients SO PEDIATRICS LA English DT Article ID CENTERED MEDICAL HOME; ASSOCIATION; CARE; CHILDREN AB BACKGROUND AND OBJECTIVES: Emergency department (ED) utilization is a major driver of health care costs. Specialist physicians have an important role in addressing ED utilization, especially at highly specialized, academic medical centers. We sought to investigate whether reporting of ED utilization to specialist physicians can decrease ED visits. METHODS: This study analyzed an intervention to reduce ED utilization among ED patients who were followed by pediatric gastroenterologists. In May 2013, each pediatric gastroenterologist began receiving reports with rates of ED use by their patients. The reports generated discussion that resulted in a cultural and process change in which patients with urgent gastrointestinal (GI)-related complaints were preferentially seen in the office. Using control charts, we examined GI-related and all-diagnoses ED use over a 2-year period. RESULTS: The rate of GI-related ED visits decreased by 60% after the intervention, from 4.89 to 1.95 per 1000 office visits (P < .001). Similarly, rates of GI-related ED visits during office hours decreased by 59% from 2.19 to 0.89 per 1000 (P < .001). Rates of all-diagnoses ED visits did not change. CONCLUSIONS: Physician-level reporting of ED utilization to pediatric gastroenterologists was associated with physician engagement and a cultural and process change to preferentially treat patients with urgent issues in the office. C1 [Lee, Jarone; Raja, Ali S.] Massachusetts Gen Hosp, Dept Emergency Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. [Lee, Jarone; Kaafarani, Haytham M. A.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Rao, Sandhya K.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Lee, Jarone; Greenspan, Peter T.; Linov, Pamela L.; Rao, Sandhya K.] Massachusetts Gen Phys Org, Boston, MA USA. [Greenspan, Peter T.; Israel, Esther; Katz, Aubrey; Fasano, Alessio] MassGen Hosp Children, Boston, MA USA. RP Lee, J (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM lee.jarone@mgh.harvard.edu NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JUL PY 2016 VL 138 IS 1 AR e20153586 DI 10.1542/peds.2015-3586 PG 7 WC Pediatrics SC Pediatrics GA DP9YD UT WOS:000378853100010 ER PT J AU Perrin, JM Houtrow, A Kelleher, K Hoagwood, K Stein, REK Zima, B AF Perrin, James M. Houtrow, Amy Kelleher, Kelly Hoagwood, Kimberly Stein, Ruth E. K. Zima, Bonnie TI Supplemental Security Income Benefits for Mental Disorders SO PEDIATRICS LA English DT Article ID CHILD HEALTH; DISABILITY AB The Supplemental Security Income Program (SSI) provides financial support to low-income households with children and youth with severe disabilities. The program included children when it began in the early 1970s. The numbers of children receiving SSI benefits increased substantially in the early 1990s, in part through an expansion of the listings of mental health conditions with which children could become eligible. Over the past 20 years, larger numbers of children have received SSI benefits for mental disorders, and these increases have led to questions from the press and Congress regarding these numbers. Do they indicate more of an increase in mental disorders among SSI children than in the general population? The National Academy of Medicine (NAM; formerly the Institute of Medicine) convened a study panel to examine what is known about mental disorders among the child SSI population and how that compares with evidence about mental disorders in children in general. The NAM report provides detailed information about how SSI works, about the changing numbers of children receiving SSI for mental disorders, and some comparisons with other evidence about rising rates of mental disorders in the general population and especially among children living in poverty. The report indicates that increasing numbers of children with mental disorders in SSI mirror similar increases in the population in general. This article summarizes key evidence from the NAM report and suggests the implications for pediatricians. C1 [Perrin, James M.] MassGen Hosp Children, 125 Nashua St,860, Boston, MA 02114 USA. [Perrin, James M.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Houtrow, Amy] Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA USA. [Houtrow, Amy] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA. [Kelleher, Kelly] Nationwide Childrens Hosp, Columbus, OH USA. [Kelleher, Kelly] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Hoagwood, Kimberly] NYU, Sch Med, Dept Child Psychiat, New York, NY USA. [Stein, Ruth E. K.] Childrens Hosp Montefiore, Bronx, NY USA. [Stein, Ruth E. K.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Zima, Bonnie] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Zima, Bonnie] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, 125 Nashua St,860, Boston, MA 02114 USA. EM jperrin@mgh.harvard.edu NR 25 TC 1 Z9 1 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JUL PY 2016 VL 138 IS 1 AR e20160354 DI 10.1542/peds.2016-0354 PG 8 WC Pediatrics SC Pediatrics GA DP9YD UT WOS:000378853100047 ER PT J AU Mazzoni, M Bombardi, C Vallorani, C Sirri, F De Giorgio, R Caio, G Grandis, A Sternini, C Clavenzani, P AF Mazzoni, M. Bombardi, C. Vallorani, C. Sirri, F. De Giorgio, R. Caio, G. Grandis, A. Sternini, C. Clavenzani, P. TI Distribution of alpha-transducin and alpha-gustducin immunoreactive cells in the chicken (Gallus domesticus) gastrointestinal tract SO POULTRY SCIENCE LA English DT Article DE chemosensing; alpha-transducin; alpha-gustducin; gastrointestinal tract; chicken ID BITTER TASTE RECEPTORS; SMALL-INTESTINE; SIGNALING MECHANISMS; CHROMOGRANIN-A; EXPRESSION; GUT; ENDOCRINE; COLOCALIZATION; NUTRIENTS; ONTOGENY AB The expression and distribution patterns of the taste signaling molecules, alpha-gustducin (G(alpha gust)) and alpha-transducin (G(alpha tran)) G-protein subunits, were studied in the gastrointestinal tract of the chicken (Gallus domesticus) using the immunohistochemical method. G(alpha gust) and G(alpha tran) immunoreactive (-IR) cells were observed in the mucosal layer of all examined segments, except the esophagus, crop, and the saccus cranialis of the gizzard. The highest numbers of G(alpha gus)t and G(alpha tran)-IR cells were found in the proventriculus glands and along the villi of the pyloric, duodenum, and rectal mucosa. G(alpha gust) and G(alpha tran)-IR cells located in the villi of the jejunum, ileum, and cloaca were much less numerous, while only a few G(alpha gus)t and G(alpha tran)-IR cells were detected in the mucosa of the proventriculus and cecum. In the crypts, IR cells were observed in the small and large intestine as well as in the cloaca. G(alpha gust) and G(alpha tran)-IR cells displayed elongated ("bottle-" or "pearlike") or rounded shape. The demonstration of G(alpha gust) and G(alpha tran) expression provides evidence for taste receptor mediated mucosal chemosensitivity in the chicken gastrointestinal tract. C1 [Mazzoni, M.; Bombardi, C.; Vallorani, C.; Grandis, A.; Clavenzani, P.] Univ Bologna, Dept Vet Med Sci, Ozzano Dell Emilia, BO, Italy. [Sirri, F.] Univ Bologna, Dept Agr & Food Sci, Ozzano Dell Emilia, BO, Italy. [De Giorgio, R.; Caio, G.] Univ Bologna, Dept Med & Surg Sci, Ozzano Dell Emilia, BO, Italy. [Sternini, C.] Univ Calif Los Angeles, David Geffen Sch Med, CURE DDRC, Div Digest Dis,Dept Med, Los Angeles, CA 90095 USA. [Sternini, C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. [Sternini, C.] Vet Adm Greater Los Angeles Hlth Syst, Los Angeles, CA USA. RP Mazzoni, M (reprint author), Univ Bologna, Dept Vet Med Sci, Ozzano Dell Emilia, BO, Italy. EM m.mazzoni@unibo.it RI Mazzoni, Maurizio/J-1918-2016 OI Mazzoni, Maurizio/0000-0002-7384-5990 FU Department of Veterinary Medical Science, University of Bologna; National Institute of Health [P30DK41301, R01DK98447] FX This study was financed by the Department of Veterinary Medical Science, University of Bologna. CS is supported by the National Institute of Health grants, P30DK41301 and R01DK98447. NR 34 TC 1 Z9 1 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0032-5791 EI 1525-3171 J9 POULTRY SCI JI Poult. Sci. PD JUL PY 2016 VL 95 IS 7 BP 1624 EP 1630 DI 10.3382/ps/pew057 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA DP6PI UT WOS:000378619000018 PM 26957624 ER PT J AU Cabrera, AR Kirkpatrick, JP Fiveash, JB Shih, HA Koay, EJ Lutz, S Petit, J Chao, ST Brown, PD Vogelbaum, M Reardon, DA Chakravarti, A Wen, PY Chang, E AF Cabrera, Alvin R. Kirkpatrick, John P. Fiveash, John B. Shih, Helen A. Koay, Eugene J. Lutz, Stephen Petit, Joshua Chao, Samuel T. Brown, Paul D. Vogelbaum, Michael Reardon, David A. Chakravarti, Arnab Wen, Patrick Y. Chang, Eric TI Radiation therapy for glioblastoma: Executive summary of an American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID NEWLY-DIAGNOSED GLIOBLASTOMA; QUALITY-OF-LIFE; RADIOTHERAPY PLUS CONCOMITANT; RANDOMIZED PHASE-III; ADJUVANT TEMOZOLOMIDE; MALIGNANT GLIOMA; STEREOTACTIC RADIOSURGERY; ELDERLY-PATIENTS; GRADE GLIOMAS; TRIAL AB Purpose: To present evidence-based guidelines for radiation therapy in treating glioblastoma not arising from the brainstem. Methods and materials: The American Society for Radiation Oncology (ASTRO) convened the Glioblastoma Guideline Panel to perform a systematic literature review investigating the following: (1) Is radiation therapy indicated after biopsy/resection of glioblastoma and how does systemic therapy modify its effects? (2) What is the optimal dose-fractionation schedule for external beam radiation therapy after biopsy/resection of glioblastoma and how might treatment vary based on pretreatment characteristics such as age or performance status? (3) What are ideal target volumes for curative-intent external beam radiation therapy of glioblastoma? (4) What is the role of reirradiation among glioblastoma patients whose disease recurs following completion of standard first-line therapy? Guideline recommendations were created using predefined consensus-building methodology supported by ASTRO-approved tools for grading evidence quality and recommendation strength. Results: Following biopsy or resection, glioblastoma patients with reasonable performance status up to 70 years of age should receive conventionally fractionated radiation therapy (eg, 60 Gy in 2-Gy fractions) with concurrent and adjuvant temozolomide. Routine addition of bevacizumab to this regimen is not recommended. Elderly patients (>= 70 years of age) with reasonable performance status should receive hypofractionated radiation therapy (eg, 40 Gy in 2.66-Gy fractions); preliminary evidence may support adding concurrent and adjuvant temozolomide to this regimen. Partial brain irradiation is the standard paradigm for radiation delivery. A variety of acceptable strategies exist for target volume definition, generally involving 2 phases (primary and boost volumes) or 1 phase (single volume). For recurrent glioblastoma, focal reirradiation can be considered in younger patients with good performance status. Conclusions: Radiation therapy occupies an integral role in treating glioblastoma. Whether and how radiation therapy should be applied depends on characteristics specific to tumor and patient, including age and performance status. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Cabrera, Alvin R.] Grp Hlth Phys, Dept Radiat Oncol, Seattle, WA USA. [Kirkpatrick, John P.] Duke Univ, Med Ctr, Dept Radiat Oncol, Durham, NC USA. [Fiveash, John B.] Univ Alabama Birmingham, Dept Radiat Oncol, Birmingham, AL USA. [Shih, Helen A.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Koay, Eugene J.; Brown, Paul D.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Lutz, Stephen] Blanchard Valley Reg Hlth Ctr, Dept Radiat Oncol, Findlay, OH USA. [Petit, Joshua] Univ Colorado Hlth, Dept Radiat Oncol, Ft Collins, CO USA. [Chao, Samuel T.] Cleveland Clin, Dept Radiat Oncol, Cleveland, OH 44106 USA. [Vogelbaum, Michael] Cleveland Clin, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44106 USA. [Reardon, David A.; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. [Chakravarti, Arnab] Ohio State Univ, Dept Radiat Oncol, Columbus, OH 43210 USA. [Chang, Eric] Univ So Calif, Keck Sch Med, Dept Radiat Oncol, Los Angeles, CA 90033 USA. RP Cabrera, AR (reprint author), Grp Hlth Phys, Radiat Oncol CMB A Level,201 16th Ave East, Seattle, WA 98122 USA. EM acabrera@post.harvard.edu OI Kirkpatrick, John/0000-0002-4019-0350 NR 46 TC 1 Z9 1 U1 3 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JUL-AUG PY 2016 VL 6 IS 4 BP 217 EP 225 DI 10.1016/j.prro.2016.03.007 PG 9 WC Oncology SC Oncology GA DP6RQ UT WOS:000378626600011 PM 27211230 ER PT J AU Kishan, AU Wang, PC Upadhyaya, SK Hauswald, H Demanes, DJ Nickols, NG Kamrava, M Sadeghi, A Kupelian, PA Steinberg, ML Prionas, ND Buyyounouski, MK King, CR AF Kishan, Amar U. Wang, Pin-Chieh Upadhyaya, Shrinivasa K. Hauswald, Henrik Demanes, D. Jeffrey Nickols, Nicholas G. Kamrava, Mitchell Sadeghi, Ahmad Kupelian, Patrick A. Steinberg, Michael L. Prionas, Nicolas D. Buyyounouski, Mark K. King, Christopher R. TI SBRT and HDR brachytherapy produce lower PSA nadirs and different PSA decay patterns than conventionally fractionated IMRT in patients with low- or intermediate-risk prostate cancer SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID STEREOTACTIC BODY RADIOTHERAPY; EXTERNAL-BEAM RADIOTHERAPY; DOSE-RATE BRACHYTHERAPY; RADIATION-THERAPY; MULTIINSTITUTIONAL ANALYSIS; ANTIGEN BOUNCE; KINETICS; MONOTHERAPY; FAILURE; LEVEL AB Purpose: To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low-or intermediate-risk prostate cancer (CaP). Methods and materials: Eligible study patients included 439 patients with low-or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables. Results: Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of <0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P < .0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P < .0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P < .001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them. Conclusions: Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Kishan, Amar U.; Wang, Pin-Chieh; Demanes, D. Jeffrey; Nickols, Nicholas G.; Kamrava, Mitchell; Kupelian, Patrick A.; Steinberg, Michael L.; King, Christopher R.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. [Upadhyaya, Shrinivasa K.] Univ Calif Davis, Dept Biol & Agr Engn, Davis, CA 95616 USA. [Hauswald, Henrik] Univ Heidelberg Hosp, Dept Radiat Oncol & Radiat Therapy, Heidelberg, Germany. [Nickols, Nicholas G.; Prionas, Nicolas D.; Buyyounouski, Mark K.] Stanford Univ, Dept Radiat Oncol, Stanford, CA 94305 USA. [Sadeghi, Ahmad] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Radiat Oncol, Los Angeles, CA USA. RP Kishan, AU (reprint author), Dept Radiat Oncol, 200 UCLA Med Plaza,B265, Los Angeles, CA 90095 USA. EM aukishan@gmail.com NR 31 TC 1 Z9 1 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JUL-AUG PY 2016 VL 6 IS 4 BP 268 EP 275 DI 10.1016/j.prro.2015.11.002 PG 8 WC Oncology SC Oncology GA DP6RQ UT WOS:000378626600018 PM 26850649 ER PT J AU Arvold, ND Pinnell, NE Mahadevan, A Connelly, S Silverman, R Weiss, SE Kelly, PJ Alexander, BM AF Arvold, Nils D. Pinnell, Nancy E. Mahadevan, Anand Connelly, Sheila Silverman, Rachel Weiss, Stephanie E. Kelly, Paul J. Alexander, Brian M. TI Steroid and anticonvulsant prophylaxis for stereotactic radiosurgery: Large variation in physician recommendations SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID CLINICAL-PRACTICE GUIDELINE; GAMMA-KNIFE RADIOSURGERY; BRAIN METASTASES; SEIZURE PROPHYLAXIS; CEREBRAL METASTASES; MANAGEMENT; MELANOMA; RADIOTHERAPY; IPILIMUMAB; EFFICACY AB Purpose/Objective(s): The risk of developing symptomatic edema or seizure following stereotactic radiosurgery (SRS) is poorly defined, and many practitioners prescribe prophylactic corticosteroids and/or anticonvulsants. Because there are no clear guidelines regarding appropriate use, we sought to characterize prescribing practices and factors associated with these recommendations. Methods and materials: We conducted a 1-time, internet-based survey among 500 randomly selected radiation oncologists self-described as specializing in central nervous system diseases who were registered in the American Society for Radiation Oncology directory. Physicians were contacted by e-mail and invited to complete the 22-question survey. Results: The response rate was 32% (n = 161). Sixty-six percent of respondents had been in practice for >10 years, and 45% of respondents practiced at an academic medical center. During/after SRS, 53% of respondents "always" or "usually" recommended corticosteroids, whereas 47% "never," " rarely," or "sometimes" recommended them. When prescribing corticosteroids, the recommended duration of use was <1 week, 1-2 weeks, or >2 weeks among 49%, 33%, and 18% of respondents, respectively. Respondents who worked in an academic medical center were less likely to prescribe corticosteroids, although this did not reach significance (P=.09). Seizure prophylaxis was less common overall, as 79% of respondents "rarely" or "never" prescribed anticonvulsants for SRS. Respondentswho prescribed anticonvulsants more frequently had higher estimations of the risk of seizure within 2 weeks of SRS (P<.001), and their recommended duration of anticonvulsant use was <1 week, 1-2 weeks, and >2 weeks among 35%, 25%, and 41% of respondents, respectively. Conclusions: There is extreme variation in physician recommendations regarding prophylactic corticosteroid and anticonvulsant use for patients undergoing SRS. Further investigation of the risks and benefits of these medications for SRS is warranted, which may promote guideline development and more patient-centered, rational prescribing practices. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Arvold, Nils D.; Pinnell, Nancy E.; Connelly, Sheila; Silverman, Rachel; Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA USA. [Arvold, Nils D.; Mahadevan, Anand; Alexander, Brian M.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Mahadevan, Anand] Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. [Weiss, Stephanie E.] Fox Chase Canc Ctr, Dept Radiat Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. [Kelly, Paul J.] Cork Univ Hosp, Dept Radiat Oncol, Cork, Ireland. RP Alexander, BM (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM bmalexander@partners.org NR 30 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JUL-AUG PY 2016 VL 6 IS 4 BP E89 EP E96 DI 10.1016/j.prro.2015.11.004 PG 8 WC Oncology SC Oncology GA DP6RQ UT WOS:000378626600002 PM 26850650 ER PT J AU Li, XA Chen, XJ Zhang, Q Kirsch, DG Petersen, I DeLaney, TF Freeman, CR Trotti, A Hitchcock, Y Bedi, M Haddock, M Salerno, K Dundas, G Wang, DA AF Li, X. Allen Chen, Xiaojian Zhang, Qiang Kirsch, David G. Petersen, Ivy DeLaney, Thomas F. Freeman, Carolyn R. Trotti, Andy Hitchcock, Ying Bedi, Meena Haddock, Michael Salerno, Kilian Dundas, George Wang, Dian TI Margin reduction from image guided radiation therapy for soft tissue sarcoma: Secondary analysis of Radiation Therapy Oncology Group 0630 results SO PRACTICAL RADIATION ONCOLOGY LA English DT Article ID POSTOPERATIVE RADIOTHERAPY AB Purpose: Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume-to-planning target volume (CTV-to-PTV) margin. Methods and materials: Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone a natomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. Results: The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations (P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction (P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. Conclusions: The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations. (C) 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. C1 [Li, X. Allen; Chen, Xiaojian; Bedi, Meena] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Zhang, Qiang] NRG Oncol Stat & Data Management Ctr, Philadelphia, PA USA. [Kirsch, David G.] Duke Univ, Med Ctr, Durham, NC USA. [Petersen, Ivy; Haddock, Michael] Mayo Clin, Rochester, MN USA. [DeLaney, Thomas F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Freeman, Carolyn R.] McGill Univ, Ctr Hlth, Montreal, PQ, Canada. [Trotti, Andy] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Hitchcock, Ying] Univ Utah, Salt Lake City, UT USA. [Salerno, Kilian] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Dundas, George] Univ Alberta, Cross Canc Inst, Edmonton, AB, Canada. [Wang, Dian] Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Li, XA (reprint author), Med Coll Wisconsin, Dept Radiat Oncol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM ali@mcw.edu FU NCI NIH HHS [U10 CA021661, U10 CA037422, U10 CA180818, U10 CA180822, U10 CA180868, U24 CA180803] NR 9 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 1879-8500 J9 PRACT RADIAT ONCOL JI Pract. Radiat. Oncol. PD JUL-AUG PY 2016 VL 6 IS 4 BP E135 EP E140 DI 10.1016/j.prro.2015.11.012 PG 6 WC Oncology SC Oncology GA DP6RQ UT WOS:000378626600007 PM 26852173 ER PT J AU Woolley, JD Arcuni, PA Stauffer, CS Fulford, D Carson, DS Batki, S Vinogradov, S AF Woolley, Josh D. Arcuni, Peter A. Stauffer, Christopher S. Fulford, Daniel Carson, Dean S. Batki, Steve Vinogradov, Sophia TI The effects of intranasal oxytocin in opioid-dependent individuals and healthy control subjects: a pilot study SO PSYCHOPHARMACOLOGY LA English DT Article DE Oxytocin; Heroin; Opioid; Addiction; Tolerability; Craving; Implicit; Social; RMET; Clinical ID SOCIAL COGNITION; NEURAL SYSTEMS; WITHDRAWAL; TOLERANCE; ADDICTION; HUMANS; ALCOHOLICS; METHADONE; IMPLICIT; RELAPSE AB Rationale There has been an explosion of research on the potential benefits of the social neuropeptide oxytocin for a number of mental disorders including substance use disorders. Recent evidence suggests that intranasal oxytocin has both direct anti-addiction effects and pro-social effects that may facilitate engagement in psychosocial treatment for substance use disorders. Objectives We aimed to assess the tolerability of intranasal oxytocin and its effects on heroin craving, implicit association with heroin and social perceptual ability in opioid-dependent patients receiving opioid replacement therapy (ORT) and healthy control participants. Methods We performed a randomized, double-blind, placebo-controlled, within-and between-subjects, crossover, proof-of-concept trial to examine the effects of oxytocin (40 international units) on a cue-induced craving task (ORT patients only), an Implicit Association Task (IAT), and two social perception tasks: the Reading the Mind in the Eyes Task (RMET) and The Awareness of Social Inference Test (TASIT). Results Oxytocin was well tolerated by patients receiving ORT but had no significant effects on craving or IAT scores. There was a significant reduction in RMET performance after oxytocin administration versus placebo in the patient group only, and a significant reduction in TASIT performance after oxytocin in both the patient and healthy control groups. Conclusions A single dose of intranasal oxytocin is well tolerated by patients receiving ORT, paving the way for future investigations. Despite no significant improvement in craving or IAT scores after a single dose of oxytocin and some evidence that social perception was worsened, further investigation is required to determine the role oxytocin may play in the treatment of opioid use disorder. C1 [Woolley, Josh D.; Stauffer, Christopher S.; Batki, Steve; Vinogradov, Sophia] Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA. [Woolley, Josh D.; Arcuni, Peter A.; Stauffer, Christopher S.; Batki, Steve; Vinogradov, Sophia] San Francisco VA Med Ctr, Dept Mental Hlth, 4150 Clement St 116C-1, San Francisco, CA 94121 USA. [Fulford, Daniel] Boston Univ, Sargent Coll Hlth & Rehabil Sci, 635 Commonwealth Ave,SAR 512, Boston, MA 02215 USA. [Carson, Dean S.] Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. RP Woolley, JD (reprint author), Univ Calif San Francisco, Dept Psychiat, 401 Parnassus Ave, San Francisco, CA 94143 USA.; Woolley, JD (reprint author), San Francisco VA Med Ctr, Dept Mental Hlth, 4150 Clement St 116C-1, San Francisco, CA 94121 USA. EM Josh.Woolley@ucsf.edu FU San Francisco Treatment Research Center at the University of California, San Francisco from the National Institute on Drug Abuse [P50 DA009253] FX This project was supported by the San Francisco Treatment Research Center at the University of California, San Francisco, via grant number P50 DA009253 from the National Institute on Drug Abuse. NR 62 TC 1 Z9 1 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2016 VL 233 IS 13 BP 2571 EP 2580 DI 10.1007/s00213-016-4308-8 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA DP5ZE UT WOS:000378575900015 PM 27137199 ER PT J AU Sampath, SC Sampath, SC Bredella, MA Cypess, AM Torriani, M AF Sampath, Srihari C. Sampath, Srinath C. Bredella, Miriam A. Cypess, Aaron M. Torriani, Martin TI Imaging of Brown Adipose Tissue: State of the Art SO RADIOLOGY LA English DT Article ID IN-VIVO; GLUCOSE-UPTAKE; COLD-EXPOSURE; ADULT HUMANS; ENERGY-EXPENDITURE; BLOOD-FLOW; FDG UPTAKE; CONTRAST ULTRASOUND; BEIGE ADIPOCYTES; FAT-CELLS AB The rates of diabetes, obesity, and metabolic disease have reached epidemic proportions worldwide. In recent years there has been renewed interest in combating these diseases not only by modifying energy intake and lifestyle factors, but also by inducing endogenous energy expenditure. This approach has largely been stimulated by the recent recognition that brown adipose tissue (BAT)-long known to promote heat production and energy expenditure in infants and hibernating mammals-also exists in adult humans. This landmark finding relied on the use of clinical fluorine 18 fluorodeoxyglucose positron emission tomography/computed tomography, and imaging techniques continue to play a crucial and increasingly central role in understanding BAT physiology and function. Herein, the authors review the origins of BAT imaging, discuss current preclinical and clinical strategies for imaging BAT, and discuss imaging methods that will provide crucial insight into metabolic disease and how it may be treated by modulating BAT activity. (C) RSNA, 2016 C1 [Sampath, Srihari C.; Sampath, Srinath C.] Novartis Res Fdn, Genom Inst, Dept Pharmacol, Musculoskeletal Biol & Bioimaging, San Diego, CA USA. [Bredella, Miriam A.; Torriani, Martin] Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. [Bredella, Miriam A.; Torriani, Martin] Harvard Univ, Sch Med, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. [Cypess, Aaron M.] NIDDK, Translat Physiol Sect, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Div Musculoskeletal Imaging & Intervent, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA.; Torriani, M (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM mtor-riani@mgh.harvard.edu FU Chugai Pharma; Molecular Metabolism; Pfizer FX Srihari C. Sampath Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is an employee of the Genomics Institute of the Novartis Research Foundation, part of the Novartis Institutes for Biomedical Research. Other relationships: disclosed no relevant relationships. Srinath C. Sampath Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: is an employee of the Genomics Institute of the Novartis Research Foundation, part of the Novartis Institutes for Biomedical Research. Other relationships: disclosed no relevant relationships. M.B. disclosed no relevant relationships. A.M.C. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: received grants from Chugai Pharma and Molecular Metabolism; received personal fees from Pfizer. Other relationships: disclosed no relevant relationships. M.T. disclosed no relevant relationships. NR 100 TC 1 Z9 1 U1 11 U2 11 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2016 VL 280 IS 1 BP 4 EP 19 DI 10.1148/radiol.2016150390 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8BC UT WOS:000378721900002 PM 27322970 ER PT J AU Davarpanah, AH Spektor, M Mathur, M Israel, GM AF Davarpanah, Amir H. Spektor, Michael Mathur, Mahan Israel, Gary M. TI Homogeneous T1 Hyperintense Renal Lesions with Smooth Borders: Is Contrast-enhanced MR Imaging Needed? SO RADIOLOGY LA English DT Article ID CELL CARCINOMA; MASSES; CYSTS; CT; MANAGEMENT AB Purpose: To retrospectively determine if homogeneous high T1 signal intensity (SI) masses with smooth borders on unenhanced magnetic resonance (MR) images can be characterized as benign. Materials and Methods: Institutional review board approval was obtained for this HIPAA-compliant retrospective study, with waiver of informed consent. MR images in 84 patients with hemorrhagic or proteinaceous cysts and 50 patients with renal cell carcinoma (RCC) were evaluated. Sixty-three cysts and 49 RCCs underwent unenhanced computed tomography (CT). SI ratio and CT attenuation were determined. Two radiologists evaluated lesions as follows: score 1, homogeneous with smooth borders; score 2, mildly heterogeneous with mildly lobulated borders; score 3, moderately heterogeneous and irregular borders; and score 4, markedly heterogeneous with markedly irregular borders. Statistical analysis was performed by using multivariable logistic regression, Welch t test, Z test, Fisher-exact test, Shapiro-Wilk test, and receiver operating characteristic curve analysis. A diagnostic criterion was formulated by using classification and regression tree analysis. Results: SI ratio and attenuation of hemorrhagic or proteinaceous cysts were significantly higher than those of RCCs (SI ratio: cyst 2.4 +/- 0.8, RCC 1.5 +/- 0.3; attenuation: cyst 51.9 +/- 21.5, RCC: 34.8 +/- 10.0). Reader 1 scored morphology of 68 (81%) hemorrhagic or proteinaceous cysts as score 1 on MR images and as score 45 (71%) on CT scans. Reader 2 scored morphology of 59 (70%) hemorrhagic or proteinaceous cysts as score 1 on MR images and as score 43 (68%) on CT scans. Two-step classification tree suggested that homogeneous high T1 SI lesions with smooth borders and SI ratio of greater than 1.6 predict the lesion as benign cysts. Similar algorithm for CT suggested threshold of 51 HU. Increasing threshold to 2.5 for SI ratio and 66 for Hounsfield units resulted in 99.9% confidence for characterizing benign cysts. Conclusion: The retrospective assessment shows that morphologic assessment and SI quantification on unenhanced T1weighted MR images can be used to differentiate benign hemorrhagic or proteinaceous cysts from RCC, although prospective assessment will be needed to confirm these results. (C) RSNA,2016 C1 [Davarpanah, Amir H.] Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA USA. [Spektor, Michael; Mathur, Mahan; Israel, Gary M.] Yale New Haven Med Ctr, 20 York St, New Haven, CT 06510 USA. RP Davarpanah, AH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA USA. EM adavarpanah@mgh.harvard.edu NR 16 TC 4 Z9 4 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2016 VL 280 IS 1 BP 128 EP 136 DI 10.1148/radiol.16151240 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8BC UT WOS:000378721900014 PM 26919441 ER PT J AU Hu, RL Besheli, LD Young, J Wu, M Pomerantz, S Lev, MH Gupta, R AF Hu, Ranliang Besheli, Laleh Daftari Young, Joseph Wu, Markus Pomerantz, Stuart Lev, Michael H. Gupta, Rajiv TI Dual-Energy Head CT Enables Accurate Distinction of Intraparenchymal Hemorrhage from Calcification in Emergency Department Patients SO RADIOLOGY LA English DT Article ID IODINATED CONTRAST; INTRACEREBRAL HEMORRHAGE; DIFFERENTIATION AB Purpose: To evaluate the ability of dual-energy (DE) computed tomography (CT) to differentiate calcification from acute hemorrhage in the emergency department setting. Materials and Methods: In this institutional review board-approved study, all unenhanced DE head CT examinations that were performed in the emergency department in November and December 2014 were retrospectively reviewed. Simulated 120kVp single-energy CT images were derived from the DE CT acquisition via postprocessing. Patients with at least one focus of intraparenchymal hyperattenuation on single-energy CT images were included, and DE material decomposition postprocessing was performed. Each focal hyperattenuation was analyzed on the basis of the virtual noncalcium and calcium overlay images and classified as calcification or hemorrhage. Sensitivity, specificity, and accuracy were calculated for single-energy and DE CT by using a common reference standard established by relevant prior and follow-up imaging and clinical information. Results: Sixty-two cases with 68 distinct intraparenchymal hyperattenuating lesions in which the reference standards were available were included in the study, of which 41 (60%) were confirmed as calcification and 27 (40%) were confirmed as hemorrhage. Sensitivity, specificity, and accuracy of DE CT for the detection of hemorrhage were 96% (95% confidence interval [CI]: 81%, 100%), 100% (95% CI: 91%, 100%), and 99% (95% CI: 92%, 100%) and those of single-energy CT were 74% (95% CI: 54%, 89%), 95% (95% CI: 83%, 99%), and 87% (95% CI: 76%, 94%), respectively. Six of 68 (9%) lesions were classified as indeterminate and three (4%) were misinterpreted with single-energy CT alone and were correctly classified with DE CT. Conclusion: DE CT by using material decomposition enables accurate differentiation between calcification and hemorrhage in patients presenting for emergency head imaging and can be especially useful in problem-solving complex cases that are difficult to determine based on conventional CT appearance alone. (C) RSNA, 2016 C1 [Hu, Ranliang; Besheli, Laleh Daftari; Young, Joseph; Wu, Markus; Pomerantz, Stuart; Lev, Michael H.; Gupta, Rajiv] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 273A, Boston, MA 02114 USA. RP Gupta, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,GRB 273A, Boston, MA 02114 USA. EM rgupta1@partners.orgvv OI Wu, Markus/0000-0002-1885-3250 FU GE Healthcare FX R.H. disclosed no relevant relationships. L.D.B. disclosed no relevant relationships. J.Y. disclosed no relevant relationships. M.W. disclosed no relevant relationships. S.P. disclosed no relevant relationships. M.H.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: received a grant for institutional research support and consultancy fees from GE Healthcare. Other relationships: disclosed no relevant relationships. R.G. disclosed no relevant relationships. NR 11 TC 1 Z9 1 U1 1 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2016 VL 280 IS 1 BP 177 EP 183 DI 10.1148/radiol.2015150877 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8BC UT WOS:000378721900019 PM 27322974 ER PT J AU Ware, JB Biester, RC Whipple, E Robinson, KM Ross, RJ Nucifora, PG AF Ware, Jeffrey B. Biester, Rosette C. Whipple, Elizabeth Robinson, Keith M. Ross, Richard J. Nucifora, Paolo G. TI Combat-related Mild Traumatic Brain Injury: Association between Baseline Diffusion-Tensor Imaging Findings and Long-term Outcomes SO RADIOLOGY LA English DT Article ID AXONAL INJURY; SYMPTOMS; VETERANS; RETURN; MODEL; WORK; PTSD; IRAQ AB Purpose: To determine whether functional outcomes of veterans who sustained combat-related mild traumatic brain injury (TBI) are associated with scalar metrics derived from diffusion- tensor (DT) imaging at their initial postdeployment evaluation. Materials and Methods: This HIPAA-compliant retrospective study was approved by the institutional review board, and the requirement to obtain informed consent was waived. From 2010 to 2013, initial postdeployment evaluation, including clinical assessment and brain magnetic resonance (MR) examination with DT imaging, was performed in combat veterans who sustained mild TBI while deployed. Outcomes from chart review encompassed initial postdeployment clinical assessment as well as later functional status, including evaluation of occupational status and health care utilization. Scalar diffusion metrics from the initial postdeployment evaluation were compared with outcomes by using multivariate analysis. Veterans who did and did not return to work were also compared for differences in clinical variables by using t and x(2) tests. Results: Postdeployment evaluation was performed a mean of 3.8 years after injury (range, 0.5-9 years; standard deviation, 2.5 years). After a mean follow-up of 1.4 years (range, 0.5-2.5 years; standard deviation, 0.8 year), 34 of 57 veterans (60%) had returned to work. Return to work was associated with diffusion metrics in multiple regions of white matter, particularly in the left internal capsule and the left frontal lobe (P = .02-.05). Overall, veterans had a mean of 46 health care visits per year during the follow-up period (range, 3-196 visits per year; standard deviation, 41 visits per year). Cumulative health care visits over time were inversely correlated with diffusion anisotropy of the splenium of the corpus callosum and adjacent parietal white matter (P < .05). Clinical measures obtained during initial postdeployment evaluation were not predictive of later functional status (P = .12-.8). Conclusion: Differences in white matter microstructure may partially account for the variance in functional outcomes among veterans who sustained combat-related mild TBI. (C) RSNA, 2016 C1 [Ware, Jeffrey B.; Nucifora, Paolo G.] Philadelphia VA Med Ctr, Dept Radiol, Philadelphia, PA USA. [Biester, Rosette C.; Whipple, Elizabeth; Robinson, Keith M.] Philadelphia VA Med Ctr, Dept Rehabil Med, Philadelphia, PA USA. [Ross, Richard J.] Philadelphia VA Med Ctr, Behav Hlth Serv, Philadelphia, PA USA. [Ware, Jeffrey B.; Nucifora, Paolo G.] Univ Penn, Perelman Sch Med, Dept Radiol, Philadelphia, PA 19104 USA. [Ross, Richard J.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP Nucifora, PG (reprint author), Loyola Univ, Med Ctr, Dept Radiol, Maywood, IL 60153 USA.; Nucifora, PG (reprint author), Loyola Univ, Med Ctr, Dept Neurol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM paolo.nucifora@lumc.edu NR 30 TC 1 Z9 1 U1 5 U2 7 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2016 VL 280 IS 1 BP 212 EP 219 DI 10.1148/radiol.2016151013 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8BC UT WOS:000378721900023 PM 27022770 ER PT J AU Huang, SY Tobyne, SM Nummenmaa, A Witzel, T Wald, LL McNab, JA Klawiter, EC AF Huang, Susie Y. Tobyne, Sean M. Nummenmaa, Aapo Witzel, Thomas Wald, Lawrence L. McNab, Jennifer A. Klawiter, Eric C. TI Characterization of Axonal Disease in Patients with Multiple Sclerosis Using High-GradientDiffusion MR Imaging SO RADIOLOGY LA English DT Article ID HUMAN CONNECTOME PROJECT; VIVO DIFFUSION MRI; DIAMETER DISTRIBUTION; CORPUS-CALLOSUM; SPINAL-CORD; DEMYELINATION; BRAIN AB Purpose: To evaluate the ability of high-gradient-diffusion magnetic resonance (MR) imaging by using gradient strengths of up to 300 mT/m to depict axonal disease in lesions and normal-appearing white matter (NAWM) in patients with multiple sclerosis (MS) and to compare high-gradient-diffusion MR findings in these patients with those in healthy control subjects. Materials and Methods: In this HIPAA-compliant institutional review board-approved prospective study in which all subjects provided written informed consent, six patients with relapsing-remitting MS and six healthy control subjects underwent diffusion- weighted imaging with a range of diffusion weightings performed with a 3-T human MR imager by using gradient strengths of up to 300 mT/m. A model of intraaxonal, extra-axonal, and free water diffusion was fitted to obtain estimates of axon diameter and density. Differences in axon diameter and density between lesions and NAWM in patients with MS were assessed by using the nonparametric Wilcoxon matched-pairs signed rank test, and differences between NAWM in subjects with MS and white matter in healthy control subjects were assessed by using the Mann-Whitney U test. Results: MS lesions showed increased mean axon diameter (10.3 vs 7.9 mu m in the genu, 10.4 vs 9.3 mu m in the body, and 10.6 vs 8.2 mu m in the splenium; P,.05) and decreased axon density ([0.48 vs 1.1] X 10(10)/m(2) in the genu, [0.40 vs 0.70] X 10(10)/m(2) in the body, and [0.35 vs 1.1] X 10(10)/m(2) in the splenium; P < .05) compared with adjacent NAWM. No significant difference in mean axon diameter or axon density was detected between NAWM in subjects with MS and white matter in healthy control subjects. Conclusion: High-gradient-diffusion MR imaging using gradient strengths of up to 300 mT/ m can be used to characterize axonal disease in patients with MS, with results that agree with known trends from neuropathologic data showing increased axon diameter and decreased axon density in MS lesions when compared with NAWM. (C) RSNA, 2016 C1 [Huang, Susie Y.; Nummenmaa, Aapo; Witzel, Thomas; Wald, Lawrence L.] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. [Tobyne, Sean M.; Klawiter, Eric C.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McNab, Jennifer A.] Stanford Univ, Richard M Lucas Ctr Imaging, Dept Radiol, Stanford, CA 94305 USA. RP Huang, SY (reprint author), Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM syhuang@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009; OI Tobyne, Sean/0000-0001-5985-7920 FU NIBIB NIH HHS [R01 EB006847, K99 EB015445, P41 EB015896, R00 EB015445]; NIMH NIH HHS [U01 MH093765]; NINDS NIH HHS [K23 NS078044, K23 NS096056] NR 25 TC 0 Z9 0 U1 2 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2016 VL 280 IS 1 BP 244 EP 251 DI 10.1148/radiol.2016151582 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8BC UT WOS:000378721900027 PM 26859256 ER PT J AU Harvey, HB Brink, JA Frush, DP AF Harvey, H. Benjamin Brink, James A. Frush, Donald P. TI DNA Repair after Exposure to Ionizing Radiation Is Not Error-Free Response SO RADIOLOGY LA English DT Letter C1 [Harvey, H. Benjamin; Brink, James A.] Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA USA. [Harvey, H. Benjamin; Brink, James A.] Harvard Univ, Sch Med, Boston, MA USA. [Frush, Donald P.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. RP Harvey, HB (reprint author), Massachusetts Gen Hosp, Dept Radiol, 175 Cambridge St,Suite 200, Boston, MA USA. EM hbharvey@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2016 VL 280 IS 1 BP 323 EP 323 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP8BC UT WOS:000378721900036 ER PT J AU Villiger, M Lorenser, D McLaughlin, RA Quirk, BC Kirk, RW Bouma, BE Sampson, DD AF Villiger, Martin Lorenser, Dirk McLaughlin, Robert A. Quirk, Bryden C. Kirk, Rodney W. Bouma, Brett E. Sampson, David D. TI Deep tissue volume imaging of birefringence through fibre-optic needle probes for the delineation of breast tumour SO SCIENTIFIC REPORTS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; POLARIZATION MODE DISPERSION; MUELLER-MATRIX; SENSITIVE OCT; CONSERVING SURGERY; ANISOTROPIC MEDIA; CANCER; ORIENTATION; CONTRAST; COLLAGEN AB Identifying tumour margins during breast-conserving surgeries is a persistent challenge. We have previously developed miniature needle probes that could enable intraoperative volume imaging with optical coherence tomography. In many situations, however, scattering contrast alone is insufficient to clearly identify and delineate malignant regions. Additional polarization-sensitive measurements provide the means to assess birefringence, which is elevated in oriented collagen fibres and may offer an intrinsic biomarker to differentiate tumour from benign tissue. Here, we performed polarization-sensitive optical coherence tomography through miniature imaging needles and developed an algorithm to efficiently reconstruct images of the depth-resolved tissue birefringence free of artefacts. First ex vivo imaging of breast tumour samples revealed excellent contrast between lowly birefringent malignant regions, and stromal tissue, which is rich in oriented collagen and exhibits higher birefringence, as confirmed with co-located histology. The ability to clearly differentiate between tumour and uninvolved stroma based on intrinsic contrast could prove decisive for the intraoperative assessment of tumour margins. C1 [Villiger, Martin; Bouma, Brett E.] Harvard Med Sch, Boston, MA USA. [Villiger, Martin; Bouma, Brett E.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Lorenser, Dirk; McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.; Sampson, David D.] Univ Western Australia, Opt Biomed Engn Lab, Perth, WA 6009, Australia. [Bouma, Brett E.] Harvard Massachusetts Inst Technol, Program Hlth Sci & Technol, Cambridge, MA 02142 USA. [Sampson, David D.] Univ Western Australia, Ctr Microscopy Characterisat & Anal, Perth, WA 6009, Australia. [McLaughlin, Robert A.; Quirk, Bryden C.; Kirk, Rodney W.] Univ Adelaide, Fac Hlth Sci, Sch Med, Australian Res Council,Ctr Excellence Nanoscale B, Adelaide, SA 5005, Australia. RP Villiger, M (reprint author), Harvard Med Sch, Boston, MA USA.; Villiger, M (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. EM mvilliger@mgh.harvard.edu RI Sampson, David/B-2931-2011; McLaughlin, Robert/E-1430-2011 OI Sampson, David/0000-0001-6724-3873; McLaughlin, Robert/0000-0001-6947-5061 FU United States National Institutes of Health [P41 EB015903]; National Health and Medical Research Council, Australia; University of Western Australia FX We thank Dr. Greg Sterrett and staff from PathWest Laboratory Medicine WA and The Breast Centre, Sir Charles Gairdner Hospital, Perth, Western Australia, for help with the human breast samples. We acknowledge the facilities, and the scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at the Centre for Microscopy, Characterisation & Analysis, University of Western Australia, a facility funded by the University, State and Commonwealth Governments. Research reported in this publication was supported in part by the United States National Institutes of Health, grants P41 EB015903, and the National Health and Medical Research Council, Australia. M.V. was supported by a Gledden visiting fellowship from The University of Western Australia. NR 58 TC 6 Z9 6 U1 9 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 2045-2322 J9 SCI REP-UK JI Sci Rep PD JUL 1 PY 2016 VL 6 AR 28771 DI 10.1038/srep28771 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA DQ0JA UT WOS:000378884000001 PM 27364229 ER PT J AU Martin, JL AF Martin, Jennifer L. TI What to do about the Growing Number of Veterans with Diagnosed Sleep Disorders SO SLEEP LA English DT Editorial Material ID DISSEMINATION C1 [Martin, Jennifer L.] Univ Calif Los Angeles, Geriat Res Educ & Clin Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Martin, Jennifer L.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Martin, JL (reprint author), VAGLAHS GRECC 11E,16111 Plummer St, North Hills, CA 91343 USA. EM Jennifer.Martin@va.gov NR 11 TC 0 Z9 0 U1 1 U2 1 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 EI 1550-9109 J9 SLEEP JI Sleep PD JUL 1 PY 2016 VL 39 IS 7 BP 1331 EP 1332 DI 10.5665/sleep.5956 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DP9SJ UT WOS:000378837000001 PM 27306268 ER PT J AU Graham, ZA Qin, W Harlow, LC Ross, NH Bauman, WA Gallagher, PM Cardozo, CP AF Graham, Z. A. Qin, W. Harlow, L. C. Ross, N. H. Bauman, W. A. Gallagher, P. M. Cardozo, C. P. TI Focal adhesion kinase signaling is decreased 56 days following spinal cord injury in rat gastrocnemius SO SPINAL CORD LA English DT Article ID INDUCED MUSCLE ATROPHY; SKELETAL-MUSCLE; PROTEIN-SYNTHESIS; GENE-EXPRESSION; FIBER-TYPE; PHOSPHORYLATION; EXERCISE; RESISTANCE; MASS; MEN AB Study design: Descriptive study. Objectives: The goal of this study was to determine the effects of spinal cord injury (SCI) on aspects of the focal adhesion kinase (FAK) signaling pathway 56 days post injury in rat gastrocnemius. Setting: This study was conducted in Bronx, NY, USA. Methods: Three-month-old male Wistar rats were exposed to either a sham surgery (n=10) or complete T4 spinal cord transection (n=10). Rats were killed 56 days following surgery and the muscle was collected. Following homogenization, proteins of the FAK pathway were analyzed by western immunoblotting or reverse transcription-qPCR. In addition, cellular markers for proteins that target the degradation of FAK were investigated. Results: SCI resulted in significantly lower levels of total and phosphorylated FAK, cSrc and p70S6k, and a trend for increased FRNK protein expression. SCI did not change levels of the alpha 7 or beta 1 integrin subunits, total or phosphorylated ERK1/2, phosphorylated Akt and TSC2 or total p70S6k. SCI resulted in a greater expression of total Akt. mRNA expression of FAK and the alpha 7 or beta 1 integrins remained unchanged between sham and SCI groups. Caspase-3/7 activity and Trim72 mRNA and protein expression remained unchanged following SCI. Conclusion: SCI results in diminished FAK signaling and is independent of ERK1/2 and Akt. SCI has no effect on mRNA levels for genes encoding components of the focal adhesion 56 days after injury. C1 [Graham, Z. A.; Qin, W.; Harlow, L. C.; Ross, N. H.; Bauman, W. A.; Cardozo, C. P.] Natl Ctr Excellence Med Consequences Spinal Cord, James J Peters Vet Affairs Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. [Graham, Z. A.; Qin, W.; Bauman, W. A.; Cardozo, C. P.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY USA. [Bauman, W. A.; Cardozo, C. P.] Icahn Sch Med Mt Sinai, Dept Rehabil Med, New York, NY USA. [Gallagher, P. M.] Univ Kansas, Appl Physiol Lab, Lawrence, KS USA. [Cardozo, C. P.] Icahn Sch Med Mt Sinai, Dept Pharmacol & Syst Therapeut, New York, NY USA. RP Cardozo, CP (reprint author), Natl Ctr Excellence Med Consequences Spinal Cord, James J Peters Vet Affairs Med Ctr, 130 West Kingsbridge Rd, Bronx, NY 10468 USA. EM christopher.cardozo@mssm.edu RI Gallagher, Philip/R-9937-2016 OI Gallagher, Philip/0000-0003-4563-4536 FU Department of Veterans Affairs Rehabilitation Research and Development Service [B1313R, B0687R, B9212C]; University of Kansas FX This work was supported by the Department of Veterans Affairs Rehabilitation Research and Development Service (B1313R and B0687R) to WQ, (B9212C) to WAB and CPC, and a University of Kansas General Research Grant to PMG. NR 40 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 1362-4393 EI 1476-5624 J9 SPINAL CORD JI Spinal Cord PD JUL PY 2016 VL 54 IS 7 BP 502 EP 509 DI 10.1038/sc.2015.183 PG 8 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA DQ0FA UT WOS:000378872700003 PM 26481700 ER PT J AU Xu, GF Zhang, WJ Lv, Y Zhang, B Sun, Q Ling, TS Zhang, XQ Zhou, ZH Wang, L Huang, Q Zou, XP AF Xu, Guifang Zhang, Weijie Lv, Ying Zhang, Bin Sun, Qi Ling, Tingsheng Zhang, Xiaoqi Zhou, Zhihua Wang, Lei Huang, Qin Zou, Xiaoping TI Risk factors for under-diagnosis of gastric intraepithelial neoplasia and early gastric carcinoma in endoscopic forceps biopsy in comparison with endoscopic submucosal dissection in Chinese patients SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE Endoscopic forceps biopsies; Endoscopic submucosal dissection; Gastric epithelial neoplasia; Early gastric carcinoma; Chinese ID EPITHELIAL NEOPLASIA; RESECTION SPECIMEN; DISCREPANCY; CANCER; ADENOMA; LESIONS; POLYPS; SYSTEM; KOREA AB Differences in pathologic diagnosis between endoscopic forceps biopsy (EFB) and endoscopic submucosal dissection (ESD) for gastric intraepithelial neoplasia (GIN) and early gastric carcinoma (EGC) in Chinese patients remain unknown. The aim of the study was to investigate risk factors for under-diagnosed pathology in initial EFB, compared to final ESD. We reviewed endoscopic and histopathologic findings for tumor location, size, macroscopic pattern, nodularity, erythema, erosion, GIN (low and high grade), and EGC diagnosed with the WHO criteria. Differences in those features between EFB and ESD were compared and risk factors for under-diagnosis by EFB were analyzed. Although concordant in most (74.9 %) cases between EFBs and ESDs, pathological diagnoses in 57 (25.1 %) cases were upgraded in ESDs. Compared to the concordant group, the lesion size a parts per thousand yen2 cm, and depressed and excavated patterns were significantly more frequent in the upgraded group. Further multivariate regression analysis demonstrated the depressed pattern and lesion size a parts per thousand yen2 cm as independent risk factors for upgraded pathology with the odds ratio of 5.778 (95 % confidence interval 2.893-11.542) and 2.535 (95 % confidence interval 1.257-5.111), respectively. Lesion size a parts per thousand yen2.0 cm and the depressed pattern at initial EFB were independent risk factors for pathologic upgrade to advanced diseases in ESD. Therefore, these endoscopic characteristics should be considered together with the initial EFB diagnosis to guide the optimal clinical management of patients with GIN and EGC. C1 [Xu, Guifang; Lv, Ying; Zhang, Bin; Ling, Tingsheng; Zhang, Xiaoqi; Wang, Lei; Zou, Xiaoping] Nanjing Univ, Sch Med, Dept Gastroenterol, Affiliated Drum Tower Hosp, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. [Zhang, Weijie] Nanjing Univ, Sch Med, Dept Gen Surg, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China. [Sun, Qi; Huang, Qin] Nanjing Univ, Sch Med, Dept Pathol, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China. [Zhou, Zhihua] PLA, Dept Pathol, Hosp 101, Wuxi, Peoples R China. [Huang, Qin] VA Boston Healthcare Syst, Dept Pathol & Lab Med, 1400 VFW Pkwy, West Roxbury, MA USA. [Huang, Qin] Harvard Univ, Sch Med, 1400 VFW Pkwy, West Roxbury, MA USA. RP Xu, GF (reprint author), Nanjing Univ, Sch Med, Dept Gastroenterol, Affiliated Drum Tower Hosp, 321 Zhongshan Rd, Nanjing 210008, Jiangsu, Peoples R China. EM 13852293376@163.com; qinhuang0122@gmail.com; 13770771661@163.com NR 23 TC 0 Z9 1 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 EI 1432-2218 J9 SURG ENDOSC JI Surg. Endosc. PD JUL PY 2016 VL 30 IS 7 BP 2716 EP 2722 DI 10.1007/s00464-015-4534-x PG 7 WC Surgery SC Surgery GA DP9BH UT WOS:000378791200010 PM 26423416 ER PT J AU Zar-Kessler, C Karaa, A Sims, KB Clarke, V Kuo, B AF Zar-Kessler, Claire Karaa, Amel Sims, Katherine Bustin Clarke, Virginia Kuo, Braden TI Understanding the gastrointestinal manifestations of Fabry disease: promoting prompt diagnosis SO THERAPEUTIC ADVANCES IN GASTROENTEROLOGY LA English DT Review DE abdominal pain; diarrhea; lysosomal storage disease; neuropathy ID ENZYME-REPLACEMENT THERAPY; CLINICAL-MANIFESTATIONS; ALPHA-GALACTOSIDASE; PEDIATRIC-PATIENTS; AGALSIDASE-ALPHA; OUTCOME SURVEY; SYMPTOMS; INVOLVEMENT; DYSFUNCTION; FEMALES AB Fabry disease is a rare X-linked lysosomal storage disease characterized by the dysfunction of multiple systems, including significant gastrointestinal involvement such as diarrhea, abdominal pain, early satiety and nausea. The gastrointestinal symptoms of Fabry disease are thought to be due to neuropathic and myopathic changes leading to symptoms of dysmotility that are encountered in many other disorders. The gastrointestinal symptoms can often be one of the presenting signs of the disease in childhood, but can be misdiagnosed by gastroenterologists for many years due to their nonspecific presentation. As the chief treatment for Fabry is enzyme-replacement therapy that has been shown to stabilize and possibly reverse disease course, recognition of these symptoms and early diagnosis in an attempt to prevent progression with treatment, is critical. C1 [Zar-Kessler, Claire] Massachusetts Gen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, MGH Ctr Neurointestinal Hlth, 175 Cambridge St CPZ-575, Boston, MA 02114 USA. [Karaa, Amel] Massachusetts Gen Hosp, Genet Unit, Boston, MA 02114 USA. [Sims, Katherine Bustin; Clarke, Virginia] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Kuo, Braden] Massachusetts Gen Hosp, MGH Ctr Neurointestinal Hlth, GI Unit, Boston, MA 02114 USA. RP Zar-Kessler, C (reprint author), Massachusetts Gen Hosp Children, Div Pediat Gastroenterol Hepatol & Nutr, MGH Ctr Neurointestinal Hlth, 175 Cambridge St CPZ-575, Boston, MA 02114 USA. EM czarkessler@partners.org FU Genzyme FX Claire Zar-Kessler, Katherine Bustin Sims and Braden Kuo participated in a Fabry training fellowship supported by an unrestricted grant from Genzyme. NR 45 TC 0 Z9 0 U1 3 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1756-283X EI 1756-2848 J9 THER ADV GASTROENTER JI Ther. Adv. Gastroenterol. PD JUL PY 2016 VL 9 IS 4 BP 626 EP 634 DI 10.1177/1756283X16642936 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DP9CG UT WOS:000378793700018 PM 27366228 ER PT J AU Fesnak, A Lin, CY Siegel, DL Maus, MV AF Fesnak, Andrew Lin, ChieYu Siegel, Don L. Maus, Marcela V. TI CAR-T Cell Therapies From the Transfusion Medicine Perspective SO TRANSFUSION MEDICINE REVIEWS LA English DT Review DE T cells; Adoptive immunotherapy; Gene transfer; Leukapheresis; Cell processing ID CHIMERIC ANTIGEN RECEPTORS; CYTOKINE RELEASE SYNDROME; 2 APHERESIS SYSTEMS; ADOPTIVE IMMUNOTHERAPY; MONOCYTE ISOLATION; DENDRITIC CELLS; HUMAN CANCER; HUMAN-BLOOD; LEUKEMIA; LEUKAPHERESIS AB The use of chimeric antigen receptor (CAR)-T cell therapy for the treatment of hematologic malignancies has generated significant excitement over the last several years. From a transfusion medicine perspective, the implementation of CAR-T therapy as a potential mainstay treatment for not only hematologic but also solid-organ malignancies represents a significant opportunity for growth and expansion. In this review, we will describe the rationale for the development of genetically redirected T cells as a cancer therapeutic, the different elements that are required to engineer these cells, as well as an overview of the process by which patient cells are harvested and processed to create and subsequently validate CAR-T cells. Finally, we will briefly describe some of the toxicities and clinical efficacy of CAR-T cells in the setting of patients with advanced malignancy. (C) 2016 Elsevier Inc. All rights reserved. C1 [Fesnak, Andrew; Siegel, Don L.] Univ Penn, Dept Pathol & Lab Med, Perelman Sch Med, Div Transfus Med & Therapeut Pathol, Philadelphia, PA USA. [Lin, ChieYu; Maus, Marcela V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. RP Maus, MV (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,Thirteenth St, Charlestown, MA 02129 USA. EM mvmaus@mgh.harvard.edu RI Fesnak, Andrew/M-4753-2016; OI Fesnak, Andrew/0000-0002-2705-803X; Maus, Marcela/0000-0002-7578-0393 FU National Cancer Institute [K08 CA166039]; National Institutes of Health [5T32HL007775] FX MVM was supported by National Cancer Institute K08 CA166039. ADF is supported by National Institutes of Health grant 5T32HL007775. NR 66 TC 2 Z9 2 U1 9 U2 30 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 JUL PY 2016 VL 30 IS 3 BP 139 EP 145 DI 10.1016/j.tmrv.2016.03.001 PG 7 WC Hematology SC Hematology GA DP7GB UT WOS:000378666100005 PM 27067907 ER PT J AU Nguyen, ET Ackman, JB Rajiah, P Little, B Wu, C Bueno, JM Gilman, MD Christensen, JD Madan, R Laroia, AT Lee, C Kanne, JP Collins, J AF Nguyen, Elsie T. Ackman, Jeanne B. Rajiah, Prabhakar Little, Brent Wu, Carol Bueno, Juliana M. Gilman, Mathew D. Christensen, Jared D. Madan, Rachna Laroia, Archana T. Lee, Christopher Kanne, Jeffrey P. Collins, Jannette TI What's New in 10 Years? A Revised Cardiothoracic Curriculum for Diagnostic Radiology Residency with Goals and Objectives Related to General Competencies SO ACADEMIC RADIOLOGY LA English DT Article DE curriculum; cardiothoracic; radiology residency; Accreditation Council for Graduate Medical Education (ACGME); American Board of Radiology (ABR); study guide; examination AB This is a cardiothoracic curriculum document for radiology residents meant to serve not only as a study guide for radiology residents but also as a teaching and curriculum reference for radiology educators and radiology residency program directors. This document represents a revision of a cardiothoracic radiology resident curriculum that was published 10 years ago in Academic Radiology. The sections that have been significantly revised, expanded, or added are (1) lung cancer screening, (2) lung cancer genomic profiling, (3) lung adenocarcinoma revised nomenclature, (4) lung biopsy technique, (5) nonvascular thoracic magnetic resonance, (6) updates to the idiopathic interstitial pneumonias, (7) cardiac computed tomography updates, (8) cardiac magnetic resonance updates, and (9) new and emerging techniques in cardiothoracic imaging. This curriculum was written and endorsed by the Education Committee of the Society of Thoracic Radiology. This curriculum operates in conjunction with the Accreditation Council for Graduate Medical Education (ACGME) milestones project that serves as a framework for semiannual evaluation of resident physicians as they progress through their training in an ACGME-accredited residency or fellowship programs. This cardiothoracic curriculum document is meant to serve not only as a more detailed guide for radiology trainees, educators, and program directors but also complementary to and guided by the ACGME milestones. C1 [Nguyen, Elsie T.] Univ Toronto, Toronto Gen Hosp, Room 1-295,585 Univ Ave, Toronto, ON M5G 2N2, Canada. [Ackman, Jeanne B.; Gilman, Mathew D.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Rajiah, Prabhakar] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Little, Brent] Emory Univ, Emory Univ Hosp, Atlanta, GA 30322 USA. [Wu, Carol] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Bueno, Juliana M.] Univ Virginia, Med Ctr, Charlottesville, VA USA. [Christensen, Jared D.] Duke Univ, Duke Univ Hosp, Durham, NC USA. [Madan, Rachna] Harvard Univ, Brigham & Womens Hosp, Boston, MA 02115 USA. [Laroia, Archana T.] Univ Iowa, Univ Iowa Hosp & Clin, Iowa City, IA USA. [Lee, Christopher] Univ So Calif, Keck Sch Med, Keck Hosp, Los Angeles, CA 90033 USA. [Kanne, Jeffrey P.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Collins, Jannette] Univ Cincinnati, UC Acad Hlth Ctr, Cincinnati, OH USA. RP Nguyen, ET (reprint author), Univ Toronto, Toronto Gen Hosp, Room 1-295,585 Univ Ave, Toronto, ON M5G 2N2, Canada. EM elsie.nguyen@uhn.ca OI Rajiah, Prabhakar/0000-0001-7538-385X NR 6 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 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2016 VL 23 IS 7 BP 911 EP 918 DI 10.1016/j.acra.2016.01.022 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DP4DC UT WOS:000378444600023 PM 27241013 ER PT J AU Lee, SJ Jacobson, MA Johnston, CB AF Lee, Sei J. Jacobson, Margaret A. Johnston, C. Bree TI Improving Diabetes Care for Hospice Patients SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Editorial Material DE diabetes mellitus; hospice; hypoglycemia; glycemic control; glucose lowering medication; hyperglycemia ID PALLIATIVE CARE; BLOOD-GLUCOSE; MANAGEMENT; HYPERGLYCEMIA AB Although type 2 diabetes guidelines recommend less aggressive glycemic control for patients with limited life expectancy, many hospice patients continue their glucose-lowering medications, resulting in an increased risk of hypoglycemia. Three common reasons for overly tight glycemic control in hospice patients include (1) discussions about reducing or stopping chronic medications are uncomfortable; (2) many patients and families believe that mild hyperglycemia can cause symptoms; and (3) until 2014, Healthcare Information and Data Information Set (HEDIS) quality indicators for glycemic control included hospice patients. To address these issues, we recommend (1) providers discuss with patients and families upon hospice enrollment that diabetes medications can be reduced or discontinued as their life-limiting disease progresses; (2) keeping blood glucose levels between 200 and 300 mg/dL; and (3) educate providers that HEDIS measures now exclude hospice patients. Implementing these recommendations should decrease the risk of hypoglycemia in hospice patients and improve their quality of life. C1 [Lee, Sei J.] Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Bldg 1,Rm 220F, San Francisco, CA 94121 USA. [Lee, Sei J.] San Francisco VA Med Ctr, San Francisco, CA USA. [Jacobson, Margaret A.] Whatcom Hosp, Bellingham, WA USA. [Johnston, C. Bree] PeaceHlth Med Syst, Bellingham, WA USA. RP Lee, SJ (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Bldg 1,Rm 220F, San Francisco, CA 94121 USA. EM sei.lee@ucsf.edu NR 9 TC 0 Z9 0 U1 3 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD JUL PY 2016 VL 33 IS 6 BP 517 EP 519 DI 10.1177/1049909115578386 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DP3NJ UT WOS:000378401100001 PM 25852204 ER PT J AU Cruz-Oliver, DM Malmstrom, TK Fernandez, N Parikh, M Garcia, J Sanchez-Reilly, S AF Cruz-Oliver, Dulce M. Malmstrom, Theodore K. Fernandez, Natalia Parikh, Manas Garcia, Jessica Sanchez-Reilly, Sandra TI Education Intervention "Caregivers Like Me" for Latino Family Caregivers Improved Attitudes Toward Professional Assistance at End-of-life Care SO AMERICAN JOURNAL OF HOSPICE & PALLIATIVE MEDICINE LA English DT Article DE family caregivers; Latino; culture; end of life; hospice; palliative; education intervention; pretest-posttest ID UNITED-STATES; CANCER-PATIENTS; ETHNIC-DIFFERENCES; OLDER LATINOS; HOSPICE; HEALTH; DEATH; EXPERIENCE; BURDEN; PLACE AB Objective: This study explores the ability of a culturally sensitive and case-based education intervention, Caregivers Like Me, to improve knowledge and attitudes regarding end-of-life (EOL) resources among Latino caregivers. Methods: A multicentered, cross-sectional study of Latino communities from different geographical regions and cultural backgrounds. An educational intervention was administered to family caregivers of Latino elders using a case-based video telenovela and pretest-posttest questionnaires. Results: Participants (N = 145) were mostly females (79%) with mean age of 56 15 years. They reported active learning from intervention (91%) and high satisfaction (92%) with educational experience. Both caregiver stress self-awareness and willingness to accept professional help improved significantly from pretest to posttest. Conclusion: A culturally sensitive educational intervention increased Latino caregivers' self-awareness about caregiver stress and the need to consider professional assistance for EOL care. C1 [Cruz-Oliver, Dulce M.] St Louis Univ, Div Geriatr Med, South Grand Blvd, St Louis, MO 63104 USA. [Malmstrom, Theodore K.] St Louis Univ, Sch Med, Dept Neurol & Psychiat, 1402 South Grand Blvd M238, St Louis, MO 63104 USA. [Fernandez, Natalia] Univ Puerto Rico, Med Sci Campus, San Juan, PR 00936 USA. [Parikh, Manas] St Louis Univ, Sch Med, Div Geriatr Med, 1402 South Grand Blvd M238, St Louis, MO 63104 USA. [Garcia, Jessica] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr Med, San Antonio, TX 78229 USA. [Garcia, Jessica; Sanchez-Reilly, Sandra] South Texas Vet Hlth Care Syst, GEC, San Antonio, TX USA. [Garcia, Jessica; Sanchez-Reilly, Sandra] South Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. [Sanchez-Reilly, Sandra] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. RP Cruz-Oliver, DM (reprint author), St Louis Univ, Dept Internal Med, Div Geriatr, 1402 South Grand Blvd M238, St Louis, MO 63104 USA. EM dcruzoli@slu.edu FU Health Resources and Services Administration (HRSA) Geriatric Academic Career Award [K01HP20479-03-00] FX The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Health Resources and Services Administration (HRSA) Geriatric Academic Career Award K01HP20479-03-00. NR 44 TC 0 Z9 0 U1 2 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-9091 EI 1938-2715 J9 AM J HOSP PALLIAT ME JI Am. J. Hosp. Palliat. Med. PD JUL PY 2016 VL 33 IS 6 BP 527 EP 536 DI 10.1177/1049909115584315 PG 10 WC Health Care Sciences & Services SC Health Care Sciences & Services GA DP3NJ UT WOS:000378401100003 PM 26019262 ER PT J AU Duncan, MD Vazirani, SS AF Duncan, Mark D. Vazirani, Sondra S. TI An Unusual Rapid Response Call: Malignant Catatonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID ELECTROCONVULSIVE-THERAPY; LORAZEPAM C1 [Duncan, Mark D.; Vazirani, Sondra S.] Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, 757 Westwood Plaza,B7-111, Los Angeles, CA 90095 USA. [Vazirani, Sondra S.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. RP Duncan, MD (reprint author), Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, 757 Westwood Plaza,B7-111, Los Angeles, CA 90095 USA. EM mduncan@mednet.ucla.edu NR 10 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 2016 VL 129 IS 7 BP 678 EP 680 DI 10.1016/j.amjmed.2016.03.005 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA DO8WJ UT WOS:000378065800036 PM 27046246 ER PT J AU Boyce, R Mitton, J Chu, J Finn, K AF Boyce, Ross Mitton, Julian Chu, Jacqueline Finn, Kathleen TI South Sudan to Martha's Vineyard: Malaria Always First! Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Boyce, Ross; Mitton, Julian; Finn, Kathleen] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chu, Jacqueline] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Boyce, R (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. OI Boyce, Ross/0000-0002-9489-6324 NR 4 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 JUL PY 2016 VL 129 IS 7 BP E101 EP E101 DI 10.1016/j.amjmed.2016.01.032 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DO8WJ UT WOS:000378065800024 PM 27320706 ER PT J AU Gaffo, AL Mikuls, TR Stamp, LK Neogi, T AF Gaffo, Angelo L. Mikuls, Ted R. Stamp, Lisa K. Neogi, Tuhina TI Allopurinol Dose Reductions Based on Creatinine Alert Redesign System SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter ID HYPERURICEMIA; CLEARANCE C1 [Gaffo, Angelo L.] Univ Alabama Birmingham, Dept Med, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. [Mikuls, Ted R.] Univ Nebraska Med Ctr, Div Rheumatol, Vet Affairs Nebraska Western Iowa Hlth Care Syst, Omaha, NE USA. [Stamp, Lisa K.] Univ Otago, Dept Med, Christchurch, New Zealand. [Neogi, Tuhina] Boston Univ, Dept Med, Med Sch Med, Boston, MA 02215 USA. RP Gaffo, AL (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35233 USA. NR 5 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 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD JUL PY 2016 VL 129 IS 7 BP E95 EP E95 DI 10.1016/j.amjmed.2015.12.035 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA DO8WJ UT WOS:000378065800021 PM 27320718 ER PT J AU Ramly, EP Bohnen, JD Farhat, MR Razmdjou, S Mavros, MN Yeh, DD Lee, J Butler, K De Moya, M Velmahos, GC Kaafarani, HMA AF Ramly, Elie P. Bohnen, Jordan D. Farhat, Maha R. Razmdjou, Shadi Mavros, Michael N. Yeh, Daniel D. Lee, Jarone Butler, Kathryn De Moya, Marc Velmahos, George C. Kaafarani, Haytham M. A. TI The nature, patterns, clinical outcomes, and financial impact of intraoperative adverse events in emergency surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Intraoperative adverse events; Emergency surgery; Patient safety ID QUALITY-IMPROVEMENT-PROGRAM; GENERAL-SURGERY; PATIENT SAFETY; ABDOMINAL-SURGERY; MULTIVARIABLE PREDICTORS; NONTEACHING HOSPITALS; VASCULAR-SURGERY; HERNIA REPAIR; RISK-FACTORS; MORBIDITY AB BACKGROUND: Little is known about intraoperative adverse events (iAEs) in emergency surgery (ES). We sought to describe iAEs in ES and to investigate their clinical and financial impact. METHODS: The 2007 to 2012 administrative and American College of Surgeons-National Surgical Quality Improvement Program databases at our tertiary academic center were: (1) linked, (2) queried for all ES procedures, and then (3) screened for iAEs using the ICD-9-CM-based Patient Safety Indicator "accidental puncture/laceration". Flagged cases were systematically reviewed to: (1) confirm or exclude the occurrence of iAEs (defined as inadvertent injuries during the operation) and (2) extract additional variables such as procedure type, approach, complexity (measured by relative value units), need for adhesiolysis, and extent of repair. Univariate and multivariate analyses were performed to assess the independent impact of iAEs on 30-day morbidity, mortality, and hospital charges. RESULTS: Of a total of 9,288 patients, 1,284 (13.8%) patients underwent ES, of which 23 had iAEs (1.8%); 18 of 23 (78.3%) of the iAEs involved the small bowel or spleen, 10 of 23 (43.5%) required suture repair, and 8 of 23 (34.8%) required tissue or organ resection. Compared with those without iAEs, patients with iAEs were older (median age 62 vs 50; P = .04); their procedures were more complex (total relative value unit 46.7, interquartile range [27.5 to 52.6] vs 14.5 [.5 to 30.2]; P < .001), longer in duration (>3 hours: 52% vs 8%; P < .001), and more often required adhesiolysis (39.1% vs 13.5% P = .001). Patients with iAEs had increased total charges ($31,080 vs $11,330, P < .001), direct charges ($20,030 vs $7,387, P < .001), and indirect charges ($11,460 vs $4,088, P < .001). On multivariable analyses, iAEs were independently associated with increased 30-day morbidity (odds ratio, 3.56 [CI, 1.10 to 11.54]; P = .03) and prolonged postoperative length of stay (LOS; LOS >7 days; odds ratio, 5.60 [1.54 to 20.35]; P = .01]. A trend toward increased mortality did not reach statistical significance. CONCLUSIONS: In ES, iAEs are independently associated with significantly higher postoperative morbidity and prolonged LOS. (C) 2015 Elsevier Inc. All rights reserved. C1 [Ramly, Elie P.; Bohnen, Jordan D.; Farhat, Maha R.; Razmdjou, Shadi; Mavros, Michael N.; Yeh, Daniel D.; Lee, Jarone; Butler, Kathryn; De Moya, Marc; Velmahos, George C.; Kaafarani, Haytham M. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, 165 Cambridge St Suite 810, Boston, MA 02114 USA. RP Kaafarani, HMA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Surg Crit C, 165 Cambridge St Suite 810, Boston, MA 02114 USA. EM hkaafarani@mgh.harvard.edu NR 39 TC 0 Z9 0 U1 0 U2 0 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 JUL PY 2016 VL 212 IS 1 BP 16 EP 23 DI 10.1016/j.amjsurg.2015.07.023 PG 8 WC Surgery SC Surgery GA DO8VM UT WOS:000378063100003 PM 26601649 ER PT J AU Chen, Q Mull, HJ Rosen, AK Borzecki, AM Pilver, C Itani, KMF AF Chen, Qi Mull, Hillary J. Rosen, Amy K. Borzecki, Ann M. Pilver, Corey Itani, Kamal M. F. TI Measuring readmissions after surgery: do different methods tell the same story? SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Veterans Health Administration; Surgical readmissions; 30-Day all-cause hospital-wide readmissions; Potentially preventable readmissions; Administrative data ID HOSPITAL READMISSION; SURGICAL COMPLICATIONS; QUALITY; PROGRAM; RATES; CARE AB BACKGROUND: Readmission is widely used as a quality metric to assess hospital performance. However, different methods to calculate readmissions may produce various results, leading to differences in classification with respect to hospital performance. This study compared 2 commonly used approaches to measure surgical readmissions: the 30-day all-cause hospital-wide readmissions (HWRs) and the potentially preventable readmissions (PPRs). METHODS: We examined the correlation between hospitals' risk-adjusted HWR and PPR rates and whether there was agreement in categorizing hospital performance between these measures among 111 hospitals with inpatient surgical programs in the Veterans Health Administration. RESULTS: We found that hospitals' HWR and PPR rates were highly correlated (r = .85, P < .0001). The overall agreement between these 2 methods in categorizing hospital performance was 82% for all surgeries, 82% for colectomy, 84% for coronary bypass, and 87% for hip/knee replacement, respectively. CONCLUSIONS: Despite differences in methodologies, the HWR and the PPR measures provided relatively consistent perceptions of hospitals' performance on surgical readmissions. Published by Elsevier Inc. C1 [Chen, Qi; Mull, Hillary J.; Rosen, Amy K.; Pilver, Corey] VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 South Huntington Ave,152M, Boston, MA 02130 USA. [Mull, Hillary J.; Rosen, Amy K.; Itani, Kamal M. F.] Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. [Borzecki, Ann M.] Bedford VAMC, Ctr Healthcare Org & Implementat Res, Bedford, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. [Borzecki, Ann M.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Itani, Kamal M. F.] VA Boston Healthcare Syst, Dept Surg, Boston, MA USA. [Itani, Kamal M. F.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Chen, Q (reprint author), VA Boston Healthcare Syst, Ctr Healthcare Org & Implementat Res, 150 South Huntington Ave,152M, Boston, MA 02130 USA. EM qi.chen2@va.gov FU VA Health Services Research and Development Service [IIR 09-369] FX This study was supported by funding from the VA Health Services Research and Development Service, grant number IIR 09-369 (Rosen, PI). NR 31 TC 1 Z9 1 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 EI 1879-1883 J9 AM J SURG JI Am. J. Surg. PD JUL PY 2016 VL 212 IS 1 BP 24 EP 33 DI 10.1016/j.amjsurg.2015.08.020 PG 10 WC Surgery SC Surgery GA DO8VM UT WOS:000378063100004 PM 26506557 ER PT J AU Naguib, M Brewer, L LaPierre, C Kopman, AF Johnson, KB AF Naguib, Mohamed Brewer, Lara LaPierre, Cristen Kopman, Aaron F. Johnson, Ken B. TI The Myth of Rescue Reversal in "Can't Intubate, Can't Ventilate" Scenarios SO ANESTHESIA AND ANALGESIA LA English DT Article ID FUNCTIONAL RESIDUAL CAPACITY; RAPID-SEQUENCE INDUCTION; MORBIDLY OBESE-PATIENTS; HEMOGLOBIN DESATURATION; NEUROMUSCULAR BLOCKADE; HEALTHY-VOLUNTEERS; INDUCED APNEA; SUCCINYLCHOLINE; SUGAMMADEX; ROCURONIUM AB BACKGROUND: An unanticipated difficult airway during induction of anesthesia can be a vexing problem. In the setting of can't intubate, can't ventilate (CICV), rapid recovery of spontaneous ventilation is a reasonable goal. The urgency of restoring ventilation is a function of how quickly a patient's hemoglobin oxygen saturation decreases versus how much time is required for the effects of induction drugs to dissipate, namely the duration of unresponsiveness, ventilatory depression, and neuromuscular blockade. It has been suggested that prompt reversal of rocuronium-induced neuromuscular blockade with sugammadex will allow respiratory activity to recover before significant arterial desaturation. Using pharmacologic simulation, we compared the duration of unresponsiveness, ventilatory depression, and neuromuscular blockade in normal, obese, and morbidly obese body sizes in this life-threatening CICV scenario. We hypothesized that although neuromuscular function could be rapidly restored with sugammadex, significant arterial desaturation will occur before the recovery from unresponsiveness and/or central ventilatory depression in obese and morbidly obese body sizes. METHODS: We used published models to simulate the duration of unresponsiveness and ventilatory depression using a common induction technique with predicted rates of oxygen desaturation in various size patients and explored to what degree rapid reversal of rocuronium-induced neuromuscular blockade with sugammadex might improve the return of spontaneous ventilation in CICV situations. RESULTS: Our simulations showed that the duration of neuromuscular blockade was longer with 1.0 mg/kg succinylcholine than with 1.2 mg/kg rocuronium followed 3 minutes later by 16 mg/kg sugammadex (10.0 vs 4.5 minutes). Once rocuronium neuromuscular blockade was completely reversed with sugammadex, the duration of hemoglobin oxygen saturation >90%, loss of responsiveness, and intolerable ventilatory depression (a respiratory rate of <= 4 breaths/min) were dependent on the body habitus and duration of oxygen administration. There is a high probability of intolerable ventilatory depression that extends well beyond the time when oxygen saturation decreases <90%, especially in obese and morbidly obese patients. If ventilatory rescue is inadequate, oxygen desaturation will persist in the latter groups, despite full reversal of neuromuscular blockade. Depending on body habitus, the duration of intolerable ventilatory depression after sugammadex reversal may be as long as 15 minutes in 5% of individuals. CONCLUSIONS: The clinical management of CICV should focus primarily on restoration of airway patency, oxygenation, and ventilation consistent with the American Society of Anesthesiologist's practice guidelines for management of the difficult airway. Pharmacologic intervention cannot be relied upon to rescue patients in a CICV crisis. C1 [Naguib, Mohamed; Johnson, Ken B.] Cleveland Clin, Inst Anesthesiol, Dept Gen Anesthesia, 9500 Euclid Ave,NE6-306, Cleveland, OH 44195 USA. [Brewer, Lara] Univ Utah, Dept Anesthesiol, Salt Lake City, UT USA. [LaPierre, Cristen] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Naguib, M (reprint author), Cleveland Clin, Inst Anesthesiol, Dept Gen Anesthesia, 9500 Euclid Ave,NE6-306, Cleveland, OH 44195 USA. EM naguibm@ccf.org NR 41 TC 1 Z9 1 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUL PY 2016 VL 123 IS 1 BP 82 EP 92 DI 10.1213/ANE.0000000000001347 PG 11 WC Anesthesiology SC Anesthesiology GA DO9DA UT WOS:000378083300012 PM 27140684 ER PT J AU Culley, DJ Flaherty, D Reddy, S Fahey, MC Rudolph, J Huang, CC Liu, XX Xie, ZC Bader, AM Hyman, BT Blacker, D Crosby, G AF Culley, Deborah J. Flaherty, Devon Reddy, Srini Fahey, Margaret C. Rudolph, James Huang, Chuan Chin Liu, Xiaoxia Xie, Zhongcong Bader, Angela M. Hyman, Bradley T. Blacker, Deborah Crosby, Gregory TI Preoperative Cognitive Stratification of Older Elective Surgical Patients: A Cross-Sectional Study SO ANESTHESIA AND ANALGESIA LA English DT Article ID NURSING-HOME RESIDENTS; PRIMARY-CARE; POSTOPERATIVE DELIRIUM; CARDIAC-SURGERY; MINI-COG; NONCARDIAC SURGERY; IMPAIRMENT; DEMENTIA; DECLINE; METAANALYSIS AB BACKGROUND: Preexisting cognitive impairment is emerging as a predictor of poor postoperative outcomes in seniors. We hypothesized that preoperative cognitive screening can be performed in a busy preadmission evaluation center and that cognitive impairment is prevalent in elective geriatric surgical patients. METHODS: We approached 311 patients aged 65 years and older presenting for preoperative evaluation before elective surgery in a prospective, observational, single-center study. Forty-eight patients were ineligible, and 63 declined. The remaining 200 were randomly assigned to the Mini-Cog (N = 100) or Clock-in-the-Box [CIB; N = 100)] test. Study staff administered the test in a quiet room, and 2 investigators scored the tests independently. Probable cognitive impairment was defined as a Mini-Cog <= 2 or a CIB <= 5. RESULTS: The age of consenting patients was 73.7 +/- 6.4 (mean +/- SD) years. There were no significant differences between patients randomly assigned to the Mini-Cog and CIB test in age, weight, gender, education, ASA physical status, or Charlston Index. Overall, 23% of patients met criteria for probable cognitive impairment, and prevalence was virtually identical regardless of the test used; 22% screened with the Mini-Cog and 23% screened with the CIB scored as having probable cognitive impairment (P = 1.0 by chi(2) analysis). Both tests had good interrater reliability (Krippendroff alpha = 0.86 [0.72-0.93] for Mini-Cog and 1(1) for CIB). CONCLUSIONS: Preoperative cognitive screening is feasible in most geriatric elective surgical patients and reveals a substantial prevalence of probable cognitive impairment in this population. C1 [Culley, Deborah J.; Flaherty, Devon; Fahey, Margaret C.; Huang, Chuan Chin; Liu, Xiaoxia; Bader, Angela M.; Crosby, Gregory] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Sch Med, Boston, MA 02115 USA. [Reddy, Srini] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Rudolph, James] Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. [Xie, Zhongcong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Boston, MA USA. [Hyman, Bradley T.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. [Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Culley, DJ (reprint author), Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM dculley@partners.org FU Anesthesia Patient Safety Foundation; MSTAR [T 35AG038027-01]; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts FX Supported by Anesthesia Patient Safety Foundation grant (to DJC); an MSTAR grant T 35AG038027-01 (to SR); and the Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts. NR 51 TC 2 Z9 2 U1 6 U2 9 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 JUL PY 2016 VL 123 IS 1 BP 186 EP 192 DI 10.1213/ANE.0000000000001277 PG 7 WC Anesthesiology SC Anesthesiology GA DO9DA UT WOS:000378083300025 PM 27028776 ER PT J AU Singh, JA AF Singh, Jasvinder A. TI Cervical cancer risk with the use of tumour necrosis factor inhibitors in rheumatoid arthritis: to worry or not to worry? SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Editorial Material ID BIOLOGICS REGISTER; FACTOR THERAPY; BRITISH SOCIETY; MALIGNANCY; DIAGNOSIS; LYMPHOMA; TIME C1 [Singh, Jasvinder A.] Birmingham VA Med Ctr, Med Serv, Birmingham, AL USA. [Singh, Jasvinder A.] UAB, Sch Publ Hlth, Sch Med, Dept Med,Div Epidemiol, Birmingham, AL USA. [Singh, Jasvinder A.] Mayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN USA. RP Singh, JA (reprint author), Univ Alabama Birmingham, Fac Off Tower 805B,510 20th St S, Birmingham, AL 35294 USA. EM Jasvinder.md@gmail.com NR 18 TC 0 Z9 0 U1 2 U2 2 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 JUL PY 2016 VL 75 IS 7 BP 1265 EP 1267 DI 10.1136/annrheumdis-2015-208526 PG 3 WC Rheumatology SC Rheumatology GA DO8SZ UT WOS:000378055400013 PM 26951640 ER PT J AU Schoenfeld, SR Lu, L Rai, SK Seeger, JD Zhang, YQ Choi, HK AF Schoenfeld, Sara R. Lu, Leo Rai, Sharan K. Seeger, John D. Zhang, Yuqing Choi, Hyon K. TI Statin use and mortality in rheumatoid arthritis: a general population-based cohort study SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; PROPENSITY SCORE; CARDIOVASCULAR-DISEASE; RISK; CHOLESTEROL; THERAPY; ATORVASTATIN; TRIAL; ROSUVASTATIN AB Background Dual lipid-lowering and anti-inflammatory properties of statins may lead to survival benefits in patients with rheumatoid arthritis (RA). However, data on this topic are limited, and the role of statins in RA remains unclear. Objectives To examine the association of statin use with overall mortality among patients with RA in a general population context. Methods We conducted an incident user cohort study with time-stratified propensity score matching using a UK general population database. The study population included individuals aged >= 20 years who had a diagnosis of RA and had used at least one disease-modifying antirheumatic drug (DMARD) between January 2000 and December 2012. To closely account for potential confounders, we compared propensity score matched cohorts of statin initiators and comparators (non-initiators) within 1-year cohort accrual blocks. Results 432 deaths occurred during follow-up (mean 4.51 years) of the 2943 statin initiators for an incidence rate of 32.6/1000 person-years (PY), while the 513 deaths among 2943 matched comparators resulted in an incidence rate of 40.6/1000 PY. Baseline characteristics were well-balanced across the two groups. Statin initiation was associated with a 21% lower risk of all-cause mortality (HR=0.79, 95% CI 0.68 to 0.91). When we defined RA by its diagnosis code alone (not requiring DMARD use), the corresponding HR was 0.81 (95% CI 0.74 to 0.90). Conclusions Statin initiation is associated with a lower risk of mortality among patients with RA. The magnitude of association is similar to that seen in previous randomised trials among the general population. C1 [Schoenfeld, Sara R.; Lu, Leo; Choi, Hyon K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. [Lu, Leo; Zhang, Yuqing; Choi, Hyon K.] Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02118 USA. [Rai, Sharan K.] Univ British Columbia, Arthrit Res Ctr Canada, Vancouver, BC V5Z 1M9, Canada. [Seeger, John D.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Dept Med,Med Sch, Boston, MA 02115 USA. RP Choi, HK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, 55 Fruit St,Bulfinch 165, Boston, MA 02114 USA. EM choi.hyon@mgh.harvard.edu FU NIH [P60AR047785, T32AR007258-36A1] FX This work was supported in part by grants from the NIH (P60AR047785 and T32AR007258-36A1). NR 39 TC 3 Z9 3 U1 1 U2 3 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 JUL PY 2016 VL 75 IS 7 BP 1315 EP 1320 DI 10.1136/annrheumdis-2015-207714 PG 6 WC Rheumatology SC Rheumatology GA DO8SZ UT WOS:000378055400021 PM 26245753 ER PT J AU Roohipoor, R Karkhaneh, R Farahani, A Ebrahimiadib, N Modjtahedi, B Fotouhi, A Yaseri, M Khodabande, A Zarei, M Fuladi, MI Taheri, A Esfahani, MR Loewenstein, J AF Roohipoor, Ramak Karkhaneh, Reza Farahani, Afsar Ebrahimiadib, Nazanin Modjtahedi, Bobeck Fotouhi, Akbar Yaseri, Mehdi Khodabande, Alireza Zarei, Mohammad Fuladi, Marjan Imani Taheri, Arash Esfahani, Mohammad Riazi Loewenstein, John TI Retinopathy of prematurity screening criteria in Iran: new screening guidelines SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION LA English DT Article ID RISK-FACTORS; COUNTRIES; INFANTS; BABIES AB Objective To test the applicability of existing retinopathy of prematurity (ROP) guidelines on Iranian patients and to develop novel ROP screening criteria in Iran. Methods Both eyes of 1932 infants born <= 37 weeks of gestation and/or weighting <= 3000 g were included in this prospective cohort study that was conducted across nine neonatal intensive care units and a tertiary eye hospital ROP clinic. The patients were examined for ROP and the need for treatment (type 1 ROP or worse). All the patients were screened 4 weeks after birth or at 31 weeks of postmenstrual age, whichever was later. The patients were followed until retinal vascularisation was completed or the patients reached 50 weeks of gestational age (GA) without prethreshold ROP. A receiver operating characteristic curve was used to determine the best screening criteria for ROP. Screening criteria from other countries were applied to our patient data to determine their ability to appropriately detect ROP. Main outcome measure Patients with ROP requiring treatment. Results The mean GA +/- SD and birth weight (BW)+/- SD of the screened patients were 32 +/- 2.7 weeks and 1713 +/- 516 g, respectively. Using criteria of GA <= 32 weeks or BW <= 2000 yielded sensitivity and specificity of 100% and 26.7%, respectively, for treatment requiring ROP regardless of clinical comorbidities. Using screening recommendations of American Academy of Pediatrics would miss 25.4% of ROP and 8.4% ROP requiring treatment in our cohort. Conclusions Other countries screening recommendations would result in a significant amount of missed cases of treatment requiring ROP when applied to Iran. As a result, we have proposed new guidelines for premature babies in Iran. C1 [Roohipoor, Ramak; Karkhaneh, Reza; Farahani, Afsar; Ebrahimiadib, Nazanin; Khodabande, Alireza; Zarei, Mohammad; Fuladi, Marjan Imani; Taheri, Arash; Esfahani, Mohammad Riazi] Univ Tehran Med Sci, Farabi Eye Hosp, Eye Res Ctr, Qazvin Sq,South Kargar St, Tehran 1336616351, Iran. [Modjtahedi, Bobeck; Loewenstein, John] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA USA. [Fotouhi, Akbar; Yaseri, Mehdi] Univ Tehran Med Sci, Sch Publ Hlth, Dept Epidemiol & Biostat, Tehran, Iran. [Esfahani, Mohammad Riazi] Noor Eye Hosp, Retina Serv, Tehran, Iran. RP Esfahani, MR (reprint author), Univ Tehran Med Sci, Farabi Eye Hosp, Eye Res Ctr, Qazvin Sq,South Kargar St, Tehran 1336616351, Iran. EM riazifahimi@yahoo.com RI Fotouhi, Akbar/F-5618-2011; OI Khodabande, Alireza/0000-0002-3957-7515; Yaseri, Mehdi/0000-0002-4066-873X; Taheri, Arash/0000-0003-4068-7575 NR 31 TC 1 Z9 1 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1359-2998 EI 1468-2052 J9 ARCH DIS CHILD-FETAL JI Arch. Dis. Child.-Fetal Neonatal Ed. PD JUL PY 2016 VL 101 IS 4 BP F288 EP F293 DI 10.1136/archdischild-2015-309137 PG 6 WC Pediatrics SC Pediatrics GA DP1MS UT WOS:000378254700005 PM 27073259 ER PT J AU Norrholm, SD Jovanovic, T Gerardi, M Breazeale, KG Price, M Davis, M Duncan, E Ressler, KJ Bradley, B Rizzo, A Tuerk, PW Rothbaum, BO AF Norrholm, Seth Davin Jovanovic, Tanja Gerardi, Maryrose Breazeale, Kathryn G. Price, Matthew Davis, Michael Duncan, Erica Ressler, Kerry J. Bradley, Bekh Rizzo, Albert Tuerk, Peter W. Rothbaum, Barbara O. TI Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE Acoustic startle; Posttraumatic stress disorder; Virtual reality; Psychophysiology; Exposure therapy; Cortisol ID POSTTRAUMATIC-STRESS-DISORDER; CONDITIONED FEAR EXTINCTION; COGNITIVE-BEHAVIORAL TREATMENT; OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CLINICAL-TRIAL; SOCIAL ANXIETY DISORDER; D-CYCLOSERINE; POTENTIATED STARTLE; PROLONGED EXPOSURE; TREATMENT RESPONSE AB Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). Published by Elsevier Ltd. C1 [Norrholm, Seth Davin; Duncan, Erica; Bradley, Bekh] Mental Hlth Serv, Atlanta Vet Affairs Med Ctr, Washington, DC USA. [Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G.; Davis, Michael; Duncan, Erica; Ressler, Kerry J.; Bradley, Bekh; Rothbaum, Barbara O.] Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. [Price, Matthew] Univ Vermont, Dept Psychol, Burlington, VT 05405 USA. [Rizzo, Albert] Univ So Calif, Dept Psychiat, Inst Creat Technol, Los Angeles, CA 90089 USA. [Rizzo, Albert] Univ So Calif, Sch Gerontol, Los Angeles, CA 90089 USA. [Tuerk, Peter W.] Ralph H Johnson VAMC, Charleston, SC USA. [Tuerk, Peter W.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC USA. RP Norrholm, SD (reprint author), Atlanta VAMC, MHSL 116A,1670 Clairmont Rd, Decatur, GA 30033 USA. EM seth.norrholm@va.gov FU Department of Defense Clinical Trial Grant [W81XWH-10-1-1045]; NIMH [U19 MH-069056, R01 MH-70880, R01 MH-094757]; Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant ("Optimal Dose of Early Intervention to Prevent PTSD"); McCormick Foundation ("BraveHeart: MLB's Welcome Back Veterans Southeast Initiative"); Genentech; Posit Science Corporation; National Institute on Drug Abuse FX Dr. Rothbaum is a consultant to and owns equity in Virtually Better, Inc., which creates virtual environments; however, Virtually Better did not create the Virtual Iraq environment tested in this study; the terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies. Dr. Rothbaum also has funding from Department of Defense Clinical Trial Grant W81XWH-10-1-1045 ("Enhancing Exposure Therapy for PTSD: Virtual Reality and Imaginal Exposure With a Cognitive Enhancer"), from NIMH grant U19 MH-069056 ("The Emory-MSSM-GSK-NIMH Collaborative Mood and Anxiety Disorders Initiative"), from NIMH grant R01 MH-70880 ("A Cognitive Enhancer May Facilitate Behavioral Exposure Therapy"), from NIMH grant R01 MH-094757 ("Prospective Determination of Psychobiological Risk Factors for Posttraumatic Stress"), from a Brain and Behavior Research Foundation (NARSAD) Distinguished Investigator Grant ("Optimal Dose of Early Intervention to Prevent PTSD"), and from the McCormick Foundation ("BraveHeart: MLB's Welcome Back Veterans Southeast Initiative"); she has received previous support from Transcept Pharmaceuticals ("A Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Low-Dose Ondansetron for Adjunctive Therapy in Adult Patients With Obsessive Compulsive Disorder Who Have Not Adequately Responded to Treatment With a Serotonin Reuptake Inhibitor"); she receives royalties from Oxford University Press, Guilford, American Psychiatric Publishing, and Emory University; and she received one advisory board payment from Genentech. Drs. Ressler and Davis are founding members of Extinction Pharmaceuticals/Therapade Technologies, which seek to develop D-cycloserine and other compounds for use to augment the effectiveness of psychotherapy; they have received no equity or income from this relationship within the last 3 years; the terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies. Dr. Duncan has received research support from the Posit Science Corporation and grant support from NIMH and the National Institute on Drug Abuse. The remaining authors report no financial relationships with commercial interests. NR 80 TC 1 Z9 1 U1 22 U2 34 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD JUL PY 2016 VL 82 BP 28 EP 37 DI 10.1016/j.brat.2016.05.002 PG 10 WC Psychology, Clinical SC Psychology GA DP0PD UT WOS:000378190800004 PM 27183343 ER PT J AU Wolf, EJ Schnurr, PP AF Wolf, Erika J. Schnurr, Paula P. TI Developing Comprehensive Models of the Effects of Stress and Trauma on Biology, Brain, Behavior, and Body SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID OXIDATIVE STRESS; PTSD; ASSOCIATION; DISORDER C1 [Wolf, Erika J.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. [Schnurr, Paula P.] Natl Ctr PTSD, White River Jct, VT USA. [Schnurr, Paula P.] Geisel Sch Med Dartmouth, Hanover, NH USA. RP Wolf, EJ (reprint author), VA Boston Healthcare Syst 116B 2, Natl Ctr PTSD, 150 South Huntington Ave, Boston, MA 02130 USA. EM erika.wolf@va.gov FU Intramural VA [CDA-2-067-10S] NR 10 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 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2016 VL 80 IS 1 BP 6 EP 8 DI 10.1016/j.biopsych.2016.04.016 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA DO8TB UT WOS:000378055600006 PM 27312232 ER PT J AU Philip, NS Dunner, DL Dowd, SM Aaronson, ST Brock, DG Carpenter, LL Demitrack, MA Hovav, S Janicak, PG George, MS AF Philip, Noah S. Dunner, David L. Dowd, Sheila M. Aaronson, Scott T. Brock, David G. Carpenter, Linda L. Demitrack, Mark A. Hovav, Sarit Janicak, Philip G. George, Mark S. TI Can Medication Free, Treatment-Resistant, Depressed Patients Who Initially Respond to TMS Be Maintained Off Medications? A Prospective, 12-Month Multisite Randomized Pilot Study (vol 9, pg 251, 2016) SO BRAIN STIMULATION LA English DT Correction C1 [Philip, Noah S.] Providence VA Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI USA. [Philip, Noah S.; Carpenter, Linda L.] Butler Hosp, Providence, RI 02906 USA. [Dunner, David L.] Ctr Anxiety & Depress, Mercer Isl, WA USA. [Dowd, Sheila M.; Janicak, Philip G.] Rush Univ, Med Ctr, Chicago, IL 60612 USA. [Aaronson, Scott T.] Sheppard Pratt Hlth Syst, Baltimore, MD USA. [Brock, David G.; Demitrack, Mark A.] Neuronetics Inc, Malvern, PA USA. [Hovav, Sarit] Univ Nebraska Med Ctr, Creighton Univ, Omaha, NE USA. [George, Mark S.] Med Univ S Carolina, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Philip, NS (reprint author), Providence VA Med Ctr, Ctr Neurorestorat & Neurotechnol, Providence, RI USA.; Philip, NS (reprint author), Butler Hosp, Providence, RI 02906 USA. EM Noah_Philip@Brown.edu NR 1 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 JUL-AUG PY 2016 VL 9 IS 4 BP 639 EP 639 DI 10.1016/j.brs.2016.03.015 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA DO8VL UT WOS:000378063000027 ER PT J AU Baltzis, D Bakker, JP Patel, SR Veves, A AF Baltzis, Dimitrios Bakker, Jessie P. Patel, Sanjay R. Veves, Aristidis TI Obstructive Sleep Apnea and Vascular Diseases SO COMPREHENSIVE PHYSIOLOGY LA English DT Article ID POSITIVE AIRWAY PRESSURE; CORONARY-HEART-DISEASE; ENDOTHELIAL PROGENITOR CELLS; PERIPHERAL ARTERIAL-DISEASE; C-REACTIVE PROTEIN; INTERMITTENT HYPOXIA; OXIDATIVE STRESS; BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; SYMPATHETIC ACTIVITY AB Obstructive sleep apnea (OSA) affects a large proportion of adults, and is as an independent risk factor for cerebrovascular and cardiovascular disease. The repetitive airway obstruction that characterizes OSA results in intermittent hypoxia, intrathoracic pressure swings, and sleep fragmentation, which in turn lead to sympathetic activation, oxidative stress, inflammation, and endothelial dysfunction. This review outlines the associations between OSA and vascular diseases and describes basic mechanisms that may be responsible for this association, in both the micro- and macrocirculation. It also reports on interventional studies that aim to ameliorate OSA and thereby reduce vascular disease burden. (C) 2016 American Physiological Society. C1 [Baltzis, Dimitrios; Veves, Aristidis] Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA 02115 USA. [Baltzis, Dimitrios; Veves, Aristidis] Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02115 USA. [Bakker, Jessie P.; Patel, Sanjay R.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep & Circadian Disorders, Boston, MA 02115 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA 02115 USA.; Veves, A (reprint author), Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02115 USA. EM aveves@bidmc.harvard.edu OI Patel, Sanjay/0000-0002-9142-5172 FU National Institutes of Health [R01 NS066205, R01 DK076937, R01 HL110350]; American Heart Association [14SDG20160000]; American Thoracic Society FX This work was partly supported by National Institutes of Health R01 NS066205 (A. Veves), R01 DK076937 (A. Veves), and R01 HL110350 (A. Veves and S. R. Patel), the American Heart Association 14SDG20160000 (J. P. Bakker), and the American Thoracic Society (J. P. Bakker). NR 132 TC 1 Z9 1 U1 4 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2040-4603 J9 COMPR PHYSIOL JI Compr. Physiol. PD JUL PY 2016 VL 6 IS 3 BP 1519 EP 1528 DI 10.1002/cphy.c150029 PG 10 WC Physiology SC Physiology GA DP1EB UT WOS:000378232200013 PM 27347900 ER PT J AU Villar, J Ambros, A Soler, JA Martinez, D Ferrando, C Solano, R Mosteiro, F Blanco, J Martin-Rodriguez, C Fernandez, MD Lopez, J Diaz-Dominguez, FJ Andaluz-Ojeda, D Merayo, E Perez-Mendez, L Fernandez, RL Kacmarek, RM AF Villar, Jesus Ambros, Alfonso Alfonso Soler, Juan Martinez, Domingo Ferrando, Carlos Solano, Rosario Mosteiro, Fernando Blanco, Jesus Martin-Rodriguez, Carmen del Mar Fernandez, Maria Lopez, Julia Diaz-Dominguez, Francisco J. Andaluz-Ojeda, David Merayo, Eleuterio Perez-Mendez, Lina Lidia Fernandez, Rosa Kacmarek, Robert M. CA Stratification Outcome Acute TI Age, Pao(2)/Fio(2), and Plateau Pressure Score: A Proposal for a Simple Outcome Score in Patients With the Acute Respiratory Distress Syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; age; arterial partial pressure of oxygen/fraction of inspired oxygen; plateau pressure; scoring system ID ACUTE LUNG INJURY; BERLIN DEFINITION; MORTALITY; RISK; ARDS; CLASSIFICATION; MULTICENTER; VALIDATION; MEDICINE; SYSTEMS AB Objectives: Although there is general agreement on the characteristic features of the acute respiratory distress syndrome, we lack a scoring system that predicts acute respiratory distress syndrome outcome with high probability. Our objective was to develop an outcome score that clinicians could easily calculate at the bedside to predict the risk of death of acute respiratory distress syndrome patients 24 hours after diagnosis. Design: A prospective, multicenter, observational, descriptive, and validation study. Setting: A network of multidisciplinary ICUs. Patients: Six-hundred patients meeting Berlin criteria for moderate and severe acute respiratory distress syndrome enrolled in two independent cohorts treated with lung-protective ventilation. Interventions: None. Measurements and Main Results: Using individual demographic, pulmonary, and systemic data at 24 hours after acute respiratory distress syndrome diagnosis, we derived our prediction score in 300 acute respiratory distress syndrome patients based on stratification of variable values into tertiles, and validated in an independent cohort of 300 acute respiratory distress syndrome patients. Primary outcome was in-hospital mortality. We found that a 9-point score based on patient's age, Pao(2)/Fio(2) ratio, and plateau pressure at 24 hours after acute respiratory distress syndrome diagnosis was associated with death. Patients with a score greater than 7 had a mortality of 83.3% (relative risk, 5.7; 95% CI, 3.0-11.0), whereas patients with scores less than 5 had a mortality of 14.5% (p < 0.0000001). We confirmed the predictive validity of the score in a validation cohort. Conclusions: A simple 9-point score based on the values of age, Pao(2)/Fio(2) ratio, and plateau pressure calculated at 24 hours on protective ventilation after acute respiratory distress syndrome diagnosis could be used in real time for rating prognosis of acute respiratory distress syndrome patients with high probability. C1 [Villar, Jesus; Blanco, Jesus; Perez-Mendez, Lina; Lidia Fernandez, Rosa] Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain. [Villar, Jesus; Lidia Fernandez, Rosa] Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. [Ambros, Alfonso; Martin-Rodriguez, Carmen] Hosp Gen Ciudad Real, Intens Care Unit, Ciudad Real, Spain. [Alfonso Soler, Juan] Hosp Univ Morales Meseguer, Intens Care Unit, Murcia, Spain. [Martinez, Domingo] Hosp Univ Virgen Arrixaca, Intens Care Unit, Murcia, Spain. [Ferrando, Carlos] Hosp Clin Valencia, Dept Anesthesia, Postsurg Unit, Valencia, Spain. [Solano, Rosario] Hosp Virgen Luz, Intens Care Unit, Cuenca, Spain. [Mosteiro, Fernando] Hosp Univ A Coruna, Intens Care Unit, Coruna, Spain. [Blanco, Jesus] Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. [del Mar Fernandez, Maria] Hosp Univ Mutua Terrassa, Intens Care Unit, Barcelona, Spain. [Lopez, Julia] Hosp Univ La Paz, Intens Care Unit, Madrid, Spain. [Diaz-Dominguez, Francisco J.] Hosp Gen Leon, Intens Care Unit, Leon, Spain. [Andaluz-Ojeda, David] Hosp Clin Valladolid, Intens Care Unit, Valladolid, Spain. [Merayo, Eleuterio] Hosp Bierzo, Intens Care Unit, Leon, Spain. [Perez-Mendez, Lina] Hosp Univ NS Candelaria, Res Unit, Santa Cruz De Tenerife, Spain. [Kacmarek, Robert M.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Dept Anesthesia, Boston, MA 02115 USA. RP Villar, J (reprint author), Inst Salud Carlos III, CIBER Enfermedades Resp, Madrid, Spain.; Villar, J (reprint author), Hosp Univ Dr Negrin, Res Unit, Las Palmas Gran Canaria, Spain. EM jesus.villar54@gmail.com FU Instituto de Salud Carlos III [CB06/06/1088, PI10/0393, PI13/0119]; Fundacion Mutua Madrilena [AP101822012]; Asociacion Cientifica Pulmon y Ventilacion Mecanica; Maquet; Covidien; Venner Medical FX Supported, in part, by Instituto de Salud Carlos III (CB06/06/1088, PI10/0393, and PI13/0119), Fundacion Mutua Madrilena (AP101822012), and Asociacion Cientifica Pulmon y Ventilacion Mecanica. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the article.; Dr. Villar has received a research grant from Maquet. Dr. Kacmarek served as a consultant for Covidien and Orange Med on mechanical ventilators and received research grants from Covidien and Venner Medical for evaluation of mechanical ventilators and airways. The remaining authors have disclosed that they do not have any potential conflicts of interest. NR 31 TC 9 Z9 9 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD JUL PY 2016 VL 44 IS 7 BP 1361 EP 1369 DI 10.1097/CCM.0000000000001653 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA DO9BX UT WOS:000378080400037 PM 27035239 ER PT J AU Davies, E Chodosh, J AF Davies, Emma Chodosh, James TI Infections after keratoprosthesis SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Review DE endophthalmitis; keratoprosthesis; microbial keratitis ID BOSTON TYPE-1 KERATOPROSTHESIS; I KERATOPROSTHESIS; TERM OUTCOMES; RISK-FACTORS; ENDOPHTHALMITIS; IMPLANTATION; PREVENTION; MULTICENTER; RETENTION; KERATITIS AB Purpose of reviewThe purpose is to provide an overview of the recent advancements in the diagnosis and treatment of microbial keratitis and endophthalmitis after keratoprosthesis implantation.Recent findingsThe addition of vancomycin daily to a fluoroquinolone in the postoperative management of keratoprosthesis patients successfully reduced the number of cases of bacterial keratitis and endophthalmitis with an increased number of fungal infections now documented both in the United States and abroad.SummaryCompliance with the regimen of a fluoroquinolone and vancomycin daily for life after keratoprosthesis implantation should be stressed with the patient. Further research is needed to investigate whether intermittent use of 5% povidone-iodine and frequent replacement of the bandage contact lens could reduce fungal infection after keratoprosthesis surgery. Future advancements in the Boston keratoprosthesis design and/or postoperative management are needed to further reduce infection after keratoprosthesis placement. C1 [Davies, Emma; Chodosh, James] Harvard Univ, Cornea & External Dis Serv, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Chodosh, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02115 USA. EM James_Chodosh@meei.harvard.edu FU Research to Prevent Blindness, NY, NY FX This work was supported by an unrestricted grant to the Department of Ophthalmology, Harvard Medical School, from Research to Prevent Blindness, NY, NY. NR 22 TC 0 Z9 0 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8738 EI 1531-7021 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD JUL PY 2016 VL 27 IS 4 BP 373 EP 377 DI 10.1097/ICU.0000000000000270 PG 5 WC Ophthalmology SC Ophthalmology GA DP3TH UT WOS:000378417800017 PM 27138637 ER PT J AU Sarkissian, T Arya, R Gyonjyan, S Taylor, B White, K AF Sarkissian, Tatevik Arya, Richa Gyonjyan, Seda Taylor, Barbara White, Kristin TI Cell death regulates muscle fiber number SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila; Muscle; Apoptosis; FGF ID CENTRAL-NERVOUS-SYSTEM; DROSOPHILA-MELANOGASTER; NEUROBLAST APOPTOSIS; MUSCULAR-DYSGENESIS; ADULT MYOGENESIS; FOUNDER CELLS; EXPRESSION; DIFFERENTIATION; MOTONEURONS; SURVIVAL AB Cell death can have both cell autonomous and non-autonomous roles in normal development. Previous studies have shown that the central cell death regulators grim and reaper are required for the developmentally important elimination of stem cells and neurons in the developing central nervous system (CNS). Here we show that cell death in the nervous system is also required for normal muscle development. In the absence of grim and reaper, there is an increase in the number of fibers in the ventral abdominal muscles in the Drosophila adult. This phenotype can be partially recapitulated by inhibition of cell death specifically in the CNS, indicating a non-autonomous role for neuronal death in limiting muscle fiber number. We also show that FGFs produced in the cell death defective nervous system are required for the increase in muscle fiber number. Cell death in the muscle lineage during pupal stages also plays a role in specifying fiber number. Our work suggests that FGFs from the CNS act as a survival signal for muscle founder cells. Thus, proper muscle fiber specification requires cell death in both the nervous system and in the developing muscle itself. (C) 2016 Elsevier Inc. All rights reserved. C1 [Sarkissian, Tatevik; Arya, Richa; Gyonjyan, Seda; White, Kristin] Harvard Univ, Sch Med, Res Inst, CBRC,Massachusetts Gen Hosp, Boston, MA 02129 USA. [Taylor, Barbara] Oregon State Univ, Dept Integrat Biol, Corvallis, OR 97331 USA. RP White, K (reprint author), Massachusetts Gen Hosp, Res Inst, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. EM kristin.white@mgh.harvard.edu FU N.I.H. grants [GM56920, GM110477, S10RR027673] FX We would like to thank Mary Baylies, the VDRC and the Bloomington Stock Center for important fly stocks, the Developmental Studies Hybridoma Bank, Rachel Wilson and Jim Skeath for antibodies, and the CBRC confocal core. Joyce Fernandes shared important unpublished data and advice. The work was supported by N.I.H. grants GM56920 to BJT and GM110477 and S10RR027673 to KW. NR 47 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 EI 1095-564X J9 DEV BIOL JI Dev. Biol. PD JUL 1 PY 2016 VL 415 IS 1 BP 87 EP 97 DI 10.1016/j.ydbio.2016.04.018 PG 11 WC Developmental Biology SC Developmental Biology GA DP0NY UT WOS:000378187700009 PM 27131625 ER PT J AU Dauriz, M Meigs, JB AF Dauriz, Marco Meigs, James B. TI The power of numbers SO DIABETOLOGIA LA English DT Editorial Material DE Genetic epidemiology; Genome-wide association study; Spectrum bias; Type 2 diabetes; Winner's curse ID ASSOCIATION; SUSCEPTIBILITY C1 [Dauriz, Marco] Univ Verona, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Ple Stefani 1 Pad 22, I-37126 Verona, Italy. [Dauriz, Marco] Osped Civile, Hosp Trust Verona, Ple Stefani 1 Pad 22, I-37126 Verona, Italy. [Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Dauriz, M (reprint author), Univ Verona, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Ple Stefani 1 Pad 22, I-37126 Verona, Italy.; Dauriz, M (reprint author), Osped Civile, Hosp Trust Verona, Ple Stefani 1 Pad 22, I-37126 Verona, Italy. EM marco.dauriz@univr.it RI Dauriz, Marco/S-5843-2016 OI Dauriz, Marco/0000-0002-5542-5941 FU NIDDK NIH HHS [K24 DK080140] NR 12 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0012-186X EI 1432-0428 J9 DIABETOLOGIA JI Diabetologia PD JUL PY 2016 VL 59 IS 7 BP 1400 EP 1402 DI 10.1007/s00125-016-3962-z PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA DO8QH UT WOS:000378047800013 PM 27115413 ER PT J AU Mansouri, M Aran, S Shaqdan, KW Abujudeh, HH AF Mansouri, Mohammad Aran, Shima Shaqdan, Khalid W. Abujudeh, Hani H. TI How often are Patients Harmed When They Visit the Computed Tomography Suite? A Multi-year Experience, in Incident Reporting, in a Large Academic Medical Center SO EUROPEAN RADIOLOGY LA English DT Article DE Safety incident reporting; Safety incident reporting system; CT incident reporting; Incident reporting rate; CT quality and safety ID INTRAVENOUS CONTRAST EXTRAVASATION; ADVERSE EVENTS; HOSPITALIZED-PATIENTS; SAFETY INCIDENTS; INTENSIVE-CARE; ERRORS; RADIOLOGY; SYSTEM; FALLS; CT AB Our goal is to present our multi-year experience in incident reporting in CT in a large medical centre. This is an IRB-approved, HIPAA-compliant study. Informed consent was waived for this study. The electronic safety incident reporting system of our hospital was searched for the variables from April 2006 to September 2012. Incident classifications were diagnostic test orders, ID/documentation, safety/security/conduct, service coordination, surgery/procedure, line/tube, fall, medication/IV safety, employee general incident, environment/equipment, adverse drug reaction, skin/tissue and diagnosis/treatment. A total of 1918 incident reports occurred in the study period and 843,902 CT examinations were performed. The rate of safety incident was 0.22 % (1918/843,902). The highest incident rates were due to adverse drug reactions (652/843,902 = 0.077 %) followed by medication/IV safety (573/843,902 = 0.068 %) and diagnostic test orders (206/843,902 = 0.024 %). Overall 45 % of incidents (869/1918) caused no harm and did not affect the patient, 33 % (637/1918) caused no harm but affected the patient, 22 % (420/1918) caused temporary or minor harm/damage and less than 1 % (10/1918) caused permanent or major harm/damage or death. Our study shows a total safety incident report rate of 0.22 % in CT. The most common incidents are adverse drug reaction, medication/IV safety and diagnostic test orders. aEuro cent Total safety incident report rate in CT is 0.22 %. aEuro cent Adverse drug reaction is the most common safety incident in CT. aEuro cent Medication/IV safety is the second most common safety incident in CT. C1 [Mansouri, Mohammad; Aran, Shima; Shaqdan, Khalid W.; Abujudeh, Hani H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,Founders Bldg,Room 210, Boston, MA 02114 USA. [Abujudeh, Hani H.] Rowan Univ, Cooper Univ Hosp, Dept Radiol, One Cooper Plaza, Camden, NJ 08103 USA. RP Abujudeh, HH (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,Founders Bldg,Room 210, Boston, MA 02114 USA.; Abujudeh, HH (reprint author), Rowan Univ, Cooper Univ Hosp, Dept Radiol, One Cooper Plaza, Camden, NJ 08103 USA. EM mmansouri1@partners.org; aran.shima@mgh.harvard.edu; kshaqdan@partners.org; haniabujudeh@gmail.com RI Mansouri, Mohammad/M-4774-2016 OI Mansouri, Mohammad/0000-0002-7472-1287 NR 68 TC 0 Z9 0 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD JUL PY 2016 VL 26 IS 7 BP 2064 EP 2072 DI 10.1007/s00330-015-4061-0 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA DO7XK UT WOS:000377996200011 PM 26560719 ER PT J AU Attai, DJ Sedrak, MS Katz, MS Thompson, MA Anderson, PF Kesselheim, JC Fisch, MJ Graham, DL Utengen, A Johnston, C Miller, RS Dizon, DS AF Attai, Deanna J. Sedrak, Mina S. Katz, Matthew S. Thompson, Michael A. Anderson, Patricia F. Kesselheim, Jennifer C. Fisch, Michael J. Graham, David L. Utengen, Audun Johnston, Claire Miller, Robert S. Dizon, Don S. CA COSMO TI Social media in cancer care: highlights, challenges & opportunities SO FUTURE ONCOLOGY LA English DT Editorial Material DE cancer; cancer research; clinical trials; communication; crowdsourcing; health information; health promotion; social media; social support; Twitter C1 [Attai, Deanna J.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Sedrak, Mina S.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Katz, Matthew S.] Lowell Gen Hosp, Dept Radiat Med, Lowell, MA USA. [Thompson, Michael A.] Aurora Hlth Care, Aurora Res Inst, Milwaukee, WI USA. [Anderson, Patricia F.] Univ Michigan, Taubman Hlth Sci Lib, Ann Arbor, MI 48109 USA. [Kesselheim, Jennifer C.] Dana Farber Boston Childrens Canc & Blood Disorde, Boston, MA USA. [Fisch, Michael J.] AIM Specialty Hlth, Chicago, IL USA. [Graham, David L.] Levine Canc Inst, Charlotte, NC USA. [Utengen, Audun] Symplur LLC, Los Angeles, CA USA. [Johnston, Claire; Miller, Robert S.] Amer Soc Clin Oncol, Alexandria, VA USA. [Dizon, Don S.] Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol, Boston, MA 02114 USA. RP Attai, DJ (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. EM dattai@mednet.ucla.edu OI Utengen, Audun/0000-0003-4851-269X NR 18 TC 2 Z9 2 U1 4 U2 9 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1479-6694 EI 1744-8301 J9 FUTURE ONCOL JI Future Oncol. PD JUL PY 2016 VL 12 IS 13 BP 1549 EP 1552 DI 10.2217/fon-2016-0065 PG 4 WC Oncology SC Oncology GA DP3RS UT WOS:000378413200003 PM 27025657 ER PT J AU Shelton, E Laharie, D Scott, FI Mamtani, R Lewis, JD Colombel, JF Ananthakrishnan, AN AF Shelton, Edward Laharie, David Scott, Frank I. Mamtani, Ronac Lewis, James D. Colombel, Jean-Frederic Ananthakrishnan, Ashwin N. TI Cancer Recurrence Following Immune-Suppressive Therapies in Patients With Immune-Mediated Diseases: A Systematic Review and Meta-analysis SO GASTROENTEROLOGY LA English DT Review DE Immunosuppression; Melanoma; Lymphoma; IBD ID INFLAMMATORY-BOWEL-DISEASE; MODIFYING ANTIRHEUMATIC DRUGS; NONMELANOMA SKIN-CANCER; NECROSIS FACTOR THERAPY; TNF INHIBITOR THERAPY; RHEUMATOID-ARTHRITIS; ANTI-TNF; IMMUNOSUPPRESSIVE THERAPY; EULAR RECOMMENDATIONS; PSORIATIC-ARTHRITIS AB BACKGROUND & AIMS: Physicians frequently encounter patients with immune-mediated diseases and a history of malignancy. There are limited data on the safety of immunosuppressive therapy for these patients. Published studies have been small with few events, precluding robust estimates of risk. METHODS: We searched Medline, EMBASE, and conference proceedings for terms related to immune-mediated disease, immune-suppressive therapy, and cancer recurrence from inception to April 2015. We included 16 studies (9 of patients with rheumatoid arthritis, 8 of patients with inflammatory bowel disease, and 1 of patients with psoriasis) and stratified studies by type of immune-suppressive therapy (monoclonal antibodies to tumor necrosis factor [anti-TNF], conventional immune-modulatory agents, or no immune suppression). A random-effects meta-analysis was performed to calculate the pooled incidence rates as well as risk differences between the various treatments. RESULTS: Our analysis included 11,702 persons contributing 31,258 person-years (p-y) of follow-up evaluation after a prior diagnosis of cancer. Rates of cancer recurrence were similar among individuals receiving anti-TNF therapy (33.8 per 1000 p-y), immunemodulator therapy (36.2 per 1000 p-y), or no immunosuppression (37.5 per 1000 p-y), but were numerically higher among patients receiving combination immune suppression (54.5 per 1000 p-y) (P > .1 for all). Subgroup analysis of new and recurrent cancers separately, type of immune-modulator therapy, or immune-mediated disease showed similar results, with no increase in risk. We found similar pooled incidence values for new or primary cancers when immunosuppression was initiated within 6 years (33.6 per 1000 p-y for immunemodulatory agents and 43.7 per 1000 p-y for anti-TNF agents) vs more than 6 years after the index cancer (32.9 per 1000 p-y for immune-modulatory agents, P = .86; and 21.0 per 1000 p-y for anti-TNF agents, P = .43). CONCLUSIONS: In a meta-analysis of 16 studies, we observed similar rates of cancer recurrence among individuals with prior cancer who received no immunosuppression, anti-TNF therapy, immune-modulator therapy, or combination treatments. Prospective studies are needed to ascertain optimal intervals for re-initiation of immune-suppressive therapies for individuals with specific cancers. C1 [Shelton, Edward; Ananthakrishnan, Ashwin N.] Massachusetts Gen Hosp, Gastroenterol Unit, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. [Ananthakrishnan, Ashwin N.] Harvard Univ, Sch Med, Boston, MA USA. [Laharie, David] Univ Bordeaux, Lab Bacteriol, Serv Hepatogastroenterol, Bordeaux, France. [Scott, Frank I.; Lewis, James D.] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Mamtani, Ronac] Univ Penn, Div Oncol, Philadelphia, PA 19104 USA. [Colombel, Jean-Frederic] Icahn Sch Med Mt Sinai, Div Gastroenterol, New York, NY 10029 USA. RP Ananthakrishnan, AN (reprint author), Massachusetts Gen Hosp, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM aananthakrishnan@mgh.harvard.edu FU US National Institutes of Health [K23-DK097142, K23-CA187185, K08-DK095951-02, K24-DK078228] FX Supported by funding from the US National Institutes of Health (K23-DK097142 to A.A., K23-CA187185 to R.M., K08-DK095951-02 to F.I.S., and K24-DK078228 to J. D. L.). NR 67 TC 5 Z9 5 U1 2 U2 7 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 JUL PY 2016 VL 151 IS 1 BP 97 EP + DI 10.1053/j.gastro.2016.03.037 PG 17 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DP5QD UT WOS:000378551400026 PM 27039969 ER PT J AU Lynch, PM Morris, JS Wen, SJ Advani, SM Ross, W Chang, GJ Rodriguez-Bigas, M Raju, GS Ricciardiello, L Iwama, T Rossi, BM Pellise, M Stoffel, E Wise, PE Bertario, L Saunders, B Burt, R Belluzzi, A Ahnen, D Matsubara, N Bulow, S Jespersen, N Clark, SK Erdman, SH Markowitz, AJ Bernstein, I De Haas, N Syngal, S Moeslein, G AF Lynch, Patrick M. Morris, Jeffrey S. Wen, Sijin Advani, Shailesh M. Ross, William Chang, George J. Rodriguez-Bigas, Miguel Raju, Gottumukkala S. Ricciardiello, Luigi Iwama, Takeo Rossi, Benedito M. Pellise, Maria Stoffel, Elena Wise, Paul E. Bertario, Lucio Saunders, Brian Burt, Randall Belluzzi, Andrea Ahnen, Dennis Matsubara, Nagahide Bulow, Steffen Jespersen, Niels Clark, Susan K. Erdman, Steven H. Markowitz, Arnold J. Bernstein, Inge De Haas, Niels Syngal, Sapna Moeslein, Gabriela TI A proposed staging system and stage-specific interventions for familial adenomatous polyposis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID CANCER; CELECOXIB AB Background and Aims: It is not possible to accurately count adenomas in many patients with familial adenomatous polyposis (FAP). Nevertheless, polyp counts are critical in evaluating each patient's response to interventions. However, the U.S. Food and Drug Administration no longer recognizes the decrease in polyp burden as a sufficient chemoprevention trial treatment endpoint requiring a measure of "clinical benefit." To develop endpoints for future industry-sponsored chemopreventive trials, the International Society for Gastrointestinal Hereditary Tumors (InSIGHT) developed an FAP staging and intervention classification scheme for lower-GI tract polyposis. Methods: Twenty-four colonoscopy or sigmoidoscopy videos were reviewed by 26 clinicians familiar with diagnosis and treatment of FAP. The reviewers independently assigned a stage to a case by using the proposed system and chose a stage-specific intervention for each case. Our endpoint was the degree of concordance among reviewers staging and intervention assessments. Results: The staging and intervention ratings of the 26 reviewers were highly concordant (rho = 0.710; 95% credible interval, 0.651-0.759). Sixty-two percent of reviewers agreed on the FAP stage, and 90% of scores were within +/- 1 stage of the mode. Sixty percent of reviewers agreed on the intervention, and 86% chose an intervention within +/- 1 level of the mode. Conclusions: The proposed FAP colon polyposis staging system and stage-specific intervention are based on a high degree of agreement on the part of experts in the review of individual cases of polyposis. Therefore, reliable and clinically relevant means for measuring trial outcomes can be developed. Outlier cases showing wide scatter in stage assignment call for individualized attention and may be inappropriate for enrollment in clinical trials for this reason. C1 [Lynch, Patrick M.; Advani, Shailesh M.; Ross, William; Raju, Gottumukkala S.] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, 1515 Holcombe Blvd, Houston, TX 77054 USA. [Morris, Jeffrey S.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Wen, Sijin] W Virginia Univ, Hlth Sci Ctr, Dept Biostat, Morgantown, WV 26506 USA. [Chang, George J.; Rodriguez-Bigas, Miguel] Univ Texas MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. [Ricciardiello, Luigi] Univ Bologna, Dept Med & Surg Sci, Bologna, Italy. [Iwama, Takeo] Saitama Med Univ, Dept Digest Tract & Gen Surg, Saitama, Japan. [Rossi, Benedito M.] Hosp Sirio Libanes, Hereditary Canc Registry, Div Surg Oncol, Sao Paulo, Brazil. [Pellise, Maria] Univ Barcelona, Inst Malalties Digest & Metab, Hosp Clin, Dept Gastroenterol,CIBERehd,IDIBAPS, Barcelona, Spain. [Stoffel, Elena] Univ Michigan Hlth Syst, Div Internal Med, Ann Arbor, MI USA. [Wise, Paul E.] Washington Univ, Sch Med, Sect Colon & Rectal Surg, St Louis, MO USA. [Bertario, Lucio] Fdn IRCCS, Ist Nazl Tumori, Unit Hereditary Digest Tract Tumors, Milan, Italy. [Saunders, Brian] St Marks Hosp, Wolfson Unit Endoscopy, Harrow, Middx, England. [Burt, Randall] Univ Utah, Dept Internal Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. [Belluzzi, Andrea] S Orsola Malpighi Univ Hosp, Dept Med & Surg Sci, Bologna, Italy. [Ahnen, Dennis] Dept Vet Affairs Eastern Colorado Hlth Care Syst, Div Gastroenterol, Denver, CO USA. [Ahnen, Dennis] Univ Colorado, Sch Med, Denver, CO USA. [Matsubara, Nagahide] Hyogo Coll Med, Dept Surg, Nishinomiya, Hyogo 6638501, Japan. [Bulow, Steffen; Jespersen, Niels] Hvidovre Univ Hosp, Gastrointestinal Unit, Danish Polyposis Register, Copenhagen, Denmark. [Clark, Susan K.] St Marks Hosp, Polyposis Registry, Harrow, Middx, England. [Erdman, Steven H.] Ohio State Univ, Nationwide Childrens Hosp, Div Gastroenterol Hepatol & Nutr, Columbus, OH 43210 USA. [Markowitz, Arnold J.] Mem Sloan Kettering Canc Ctr, Serv Gastroenterol & Nutr, 1275 York Ave, New York, NY 10021 USA. [Bernstein, Inge; De Haas, Niels] Aalborg Univ Hosp, Dept Surg Gastroenterol, Aalborg, Denmark. [Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gastroenterol, Div Populat Sci, 75 Francis St, Boston, MA 02115 USA. [Syngal, Sapna] Harvard Univ, Sch Med, Boston, MA USA. [Moeslein, Gabriela] Univ Witten Herdecke, HELIOS Klinikum Wuppertal, Ctr Hereditary Tumors, Wuppertal, Germany. RP Lynch, PM (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, 1515 Holcombe Blvd, Houston, TX 77054 USA. EM plynch@mdanderson.org OI RICCIARDIELLO, LUIGI/0000-0003-2568-6208 FU SLA Pharma (UK) FX The authors thank all of our reviewers for their time and contribution to this study, SLA Pharma (UK) for their funding support, and the entire team who made this study possible. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD JUL PY 2016 VL 84 IS 1 BP 115 EP + DI 10.1016/j.gie.2015.12.029 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DO9HB UT WOS:000378095000018 PM 26769407 ER PT J AU Valentine, SE Gerber, MW Nobles, CJ Shtasel, DL Marques, L AF Valentine, Sarah E. Gerber, Monica W. Nobles, Carrie J. Shtasel, Derri L. Marques, Luana TI Longitudinal Study of Mental Health and Pain-Related Functioning Following a Motor Vehicle Collision SO HEALTH PSYCHOLOGY LA English DT Article DE depression; motor vehicle collisions; pain; physical complaints; posttraumatic stress ID POSTTRAUMATIC-STRESS-DISORDER; MUTUAL MAINTENANCE; WHIPLASH INJURY; GULF-WAR; VETERANS; PTSD; ACCIDENT; SYMPTOMS; DISTRESS; TRAUMA AB Objective: Relations between mental and physical health symptoms are well-established in the literature on recovery following motor vehicle collisions (MVCs). To understand the temporal sequencing and evolution of these relations, we examined the bidirectional association between mental and physical health symptoms at 4 and 16 weeks following a MVC. Methods: The sample consisted of 103 participants recruited through public MVC police reports. The study included self-report assessments for posttraumatic stress symptoms, depressive symptoms, bodily pain, and role limitations attributable to physical health. A series of multivariable linear regression analyses were conducted to estimate the associations between these mental and physical health outcomes. Results: The analysis revealed that mental health symptoms at 4 weeks post-MVC were associated with higher bodily pain at 16 weeks post-MVC (PTSD symptoms: beta = -0.74, 95% CI: -1.06, -0.42; depressive symptoms: beta = -1.34, 95% CI: -1.90, -0.78), but not higher health-related role limitations. Physical health symptoms at 4 weeks post-MVC were not associated with PTSD or depressive symptoms at 16 weeks post-MVC. Conclusions: The results indicate the predictive strength of mental health symptoms at 4 weeks post-MVC in identifying individuals at risk for bodily pain at 16 weeks and shed light on the temporal sequencing of how relations between physical and mental health symptoms emerge over time. This suggests that early assessment of mental health symptoms may have significant implications for the treatment of these patients. C1 [Valentine, Sarah E.; Gerber, Monica W.; Nobles, Carrie J.; Shtasel, Derri L.; Marques, Luana] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Valentine, Sarah E.; Nobles, Carrie J.; Shtasel, Derri L.; Marques, Luana] Harvard Univ, Dept Psychiat, Sch Med, Cambridge, MA 02138 USA. RP Valentine, SE (reprint author), Massachusetts Gen Hosp, Community Psychiat Program Res Implementat & Diss, 70 Everett Ave,Suite 516, Chelsea, MA 02150 USA. EM sevalentine@mgh.harvard.edu OI Nobles, Carrie/0000-0002-2182-8486 FU National Institute of Mental Health (NIMH) [MH075383-02]; Mark Diamond Research Award (State University of New York); K23 Mentored Patient-Oriented Research Career Development Award from the NIMH [K23MH096029] FX This project was supported by grants from the National Institute of Mental Health (NIMH; MH075383-02) and by the Mark Diamond Research Award (State University of New York) awarded to Dr. Marques and mentored by J. Gayle Beck, PhD. Dr. Marques' time is supported by a K23 Mentored Patient-Oriented Research Career Development Award from the NIMH (K23MH096029). NR 47 TC 0 Z9 0 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 EI 1930-7810 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2016 VL 35 IS 7 BP 742 EP 750 DI 10.1037/hea0000329 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA DP1GJ UT WOS:000378238200011 ER PT J AU Januszkiewicz, L Vegh, E Borgquist, R Bose, A Sharma, A Orencole, M Mela, T Singh, JP Parks, KA AF Januszkiewicz, Lukasz Vegh, Eszter Borgquist, Rasmus Bose, Abhishek Sharma, Ajay Orencole, Mary Mela, Theofanie Singh, Jagmeet P. Parks, Kimberly A. TI Reply to the Editor-Prognostic implication of baseline PR interval in patients undergoing cardiac resynchronization therapy SO HEART RHYTHM LA English DT Letter C1 [Januszkiewicz, Lukasz] Med Univ Warsaw, Dept Cardiol 1, Warsaw, Poland. [Vegh, Eszter; Borgquist, Rasmus; Bose, Abhishek; Sharma, Ajay; Orencole, Mary; Mela, Theofanie; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Parks, Kimberly A.] VA Healthcare Syst Boston, West Rozbury, MA 02132 USA. RP Parks, KA (reprint author), VA Healthcare Syst Boston, West Rozbury, MA 02132 USA. EM kimberly1022@gmail.com NR 0 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 1547-5271 EI 1556-3871 J9 HEART RHYTHM JI Heart Rhythm PD JUL PY 2016 VL 13 IS 7 BP 1573 EP 1574 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA DO9FK UT WOS:000378090000032 PM 27018379 ER PT J AU Gokengin, D Madani, N AF Gokengin, Deniz Madani, Navid TI Response to letter to the editor re 'HIV Trends: Defining "The Middle East' SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 [Gokengin, Deniz] Ege Univ, Fac Med, Dept Clin Microbiol & Infect Dis, Izmir, Turkey. [Madani, Navid] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Virol,Dept Global Hlth & Soci, 44 Binney St, Boston, MA 02115 USA. RP Gokengin, D (reprint author), Ege Univ, Fac Med, Dept Clin Microbiol & Infect Dis, Izmir, Turkey. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 EI 1878-3511 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD JUL PY 2016 VL 48 BP 124 EP 124 DI 10.1016/j.ijid.2016.04.015 PG 1 WC Infectious Diseases SC Infectious Diseases GA DO8PW UT WOS:000378046700031 PM 27109106 ER PT J AU Kwon, YM AF Kwon, Young-Min TI Evaluation of the Painful Dual Taper Modular Neck Stem Total Hip Arthroplasty: Do They All Require Revision? SO JOURNAL OF ARTHROPLASTY LA English DT Article DE modular femoral neck stem; taper corrosion; metal ion levels; MARS MRI; adverse local tissue reaction ID METAL-ON-METAL; LOCAL TISSUE REACTION; FEMORAL STEMS; ADVERSE-REACTIONS; CORROSION; RETRIEVAL; REPLACEMENT; JUNCTION; FAILURE; MANAGEMENT AB Although dual taper modular-neck total hip arthroplasty (THA) design with additional neck-stem modularity has the potential to optimize hip biomechanical parameters by facilitating adjustments of leg length, femoral neck version and offset, there is increasing concern regarding this stem design as a result of the growing numbers of adverse local tissue reactions due to fretting and corrosion at the neck-stem taper junction. Implant factors such as taper cone angle, taper surface roughness, taper contact area, modular neck taper metallurgy, and femoral head size play important roles in influencing extent of taper corrosion. There should be a low threshold to conduct a systematic clinical evaluation of patients with dual-taper modular-neck stem THA using systematic risk stratification algorithms as early recognition and diagnosis will ensure prompt and appropriate treatment. Although specialized tests such as metal ion analysis and cross-sectional imaging modalities such as metal artifact reduction sequence magnetic resonance imaging (MARS MRI) are useful in optimizing clinical decision-making, overreliance on any single investigative tool in the clinical decision-making process for revision surgery should be avoided. (C) 2016 Elsevier Inc. All rights reserved. C1 [Kwon, Young-Min] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. NR 52 TC 0 Z9 0 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUL PY 2016 VL 31 IS 7 BP 1385 EP 1389 DI 10.1016/j.arth.2016.01.074 PG 5 WC Orthopedics SC Orthopedics GA DO8WL UT WOS:000378066000003 PM 27118353 ER PT J AU Dimitriou, D Liow, MHL Tsai, TY Leone, WA Li, GA Kwon, YM AF Dimitriou, Dimitris Liow, Ming Han Lincoln Tsai, Tsung-Yuan Leone, William A. Li, Guoan Kwon, Young-Min TI Early Outcomes of Revision Surgery for Taper Corrosion of Dual Taper Total Hip Arthroplasty in 187 Patients SO JOURNAL OF ARTHROPLASTY LA English DT Article DE revision total hip arthroplasty; taper corrosion; clinical outcomes; modular femoral neck stem; dual taper; systematic evaluation ID LOCAL TISSUE REACTION; MODULAR-NECK; FEMORAL IMPLANTS; FOLLOW-UP; METAL; PSEUDOTUMOR; RESURFACINGS; REPLACEMENT; STEMS AB Background: Modular dual taper femoral neck designs have been associated with taper corrosion requiring revision surgery. However, outcomes after revision dual taper total hip arthroplasty in patients with symptomatic adverse local tissue reaction due to taper corrosion remain largely unknown. Methods: A total of 198 revision surgeries in 187 patients with dual taper femoral stem total hip arthroplasty with minimum 12-month follow-up were evaluated. Results: At mean follow-up of 18 months, at least 1 complication had occurred in 39 patients (20%) of 198 revisions. Single episode of dislocation, treated with close reduction, occurred in 16, whereas 2 patients required rerevision due to multiple dislocations. Infection requiring rerevision occurred in 3 patients. Adverse local tissue reaction recurrence requiring reoperation occurred in 6 patients. Implant survivorship for revision for any cause was 86% at 30 months. The reoperation rate of revised dual taper was 8% (16 out of 198 hips). The median serum levels of cobalt, chromium, and cobalt/chromium ratio decreased (P < .01) from 5.3 mu g/L (range: 2.3-48.5 mu g/L), 2.6 mu g/L (range: 0.2-64 mu g/L), and 4.7 (range: 2.1-35) prerevision to 1.4 mu g/L (range: 0.2-8.8 mu g/L), 0.7 mu g/L (range: 0.1-3.9 mu g/L), and 2.2 (range: 0.4-8.8) postrevision, respectively. Conclusion: This pilot study demonstrates that intraoperative tissue necrosis was associated with a high rate of early complications (20%) and revisions (8%), suggesting the importance of a systematic evaluation of these patients including metal ion levels and metal artifact reduction sequence magnetic resonance imaging in optimizing revision outcome, as early diagnosis will facilitate the initiation of appropriate treatment before significant adverse tissue necrosis. (C) 2016 Elsevier Inc. All rights reserved. C1 [Dimitriou, Dimitris; Liow, Ming Han Lincoln; Tsai, Tsung-Yuan; Li, Guoan; Kwon, Young-Min] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. [Leone, William A.] Holy Cross Hosp, Orthoped Ctr, Dept Orthopaed Surg, Ft Lauderdale, FL USA. RP Kwon, YM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. OI Dimitriou, Dimitris/0000-0002-9558-7080; LIOW, MING HAN LINCOLN/0000-0002-4496-8035 NR 25 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 JUL PY 2016 VL 31 IS 7 BP 1549 EP 1554 DI 10.1016/j.arth.2016.01.015 PG 6 WC Orthopedics SC Orthopedics GA DO8WL UT WOS:000378066000032 PM 26895822 ER PT J AU Lozano-Calderon, SA Kaiser, CL Osler, PM Raskin, KA AF Lozano-Calderon, Santiago A. Kaiser, Courtney L. Osler, Polina M. Raskin, Kevin A. TI Cemented Total Hip Arthroplasty With Retrograde Ischioacetabular Steinmann Pin Reconstruction for Periacetabular Metastatic Carcinoma SO JOURNAL OF ARTHROPLASTY LA English DT Article DE acetabulum; periacetabular metastasis; Steinmann pin reconstruction; total hip arthroplasty; modified Harrington technique ID MANAGEMENT; DISEASE; BONE AB Background: Surgical management of advanced periacetabular lesions is challenging because of extensive bone loss, particularly for Modified American Academy of Orthopaedic Surgeons Classification defects type IV (pelvic discontinuity with posterior column involvement). Multiple methods for rebuilding the acetabulum have been described; all involve passing Steinmann pins in a retrograde or an antegrade fashion from the anterior iliac wing or iliac crest around the acetabulum in an attempt to recreate the normal bony anatomy. However, these techniques fail to engage the ischium in its entirety. The ischial contribution to the posterior column is a critical element in a stable acetabular construct. Methods: After curettage of the acetabular lesion, Steinmann pins are passed through the ischial tuberosity and posterior column into the sciatic buttress in a retrograde manner. The number of pins depends on the size of the defect and involvement of the posterior column. Patients and Methods: Medical records of 11 patients with a Modified American Academy of Orthopaedic Surgeons Classification defect type IV treated with retrograde ischioacetabular Steinmann pin reconstruction at our institution between 2007 and 2012 were reviewed. European Quality of Life-5 dimensions and Lower Extremity Functional Scale questionnaires were used to assess patient functional outcomes. Results: The 6 patients (4 females and 2 males; age range, 56-81 years) surviving 12 months post-operatively reported improved mobility and good quality-of-life scores. Conclusion: We described a new method for posterior acetabular column reconstruction that uses the ischial tuberosity and body as additional points of stabilization during the reconstruction of the posterior column. (C) 2016 Elsevier Inc. All rights reserved. C1 [Lozano-Calderon, Santiago A.; Kaiser, Courtney L.; Osler, Polina M.; Raskin, Kevin A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Musculoskeletal Oncol Serv,Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. RP Lozano-Calderon, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Musculoskeletal Oncol Serv,Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. OI Kaiser, Courtney/0000-0002-1405-0442 NR 12 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 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUL PY 2016 VL 31 IS 7 BP 1555 EP 1560 DI 10.1016/j.arth.2016.01.014 PG 6 WC Orthopedics SC Orthopedics GA DO8WL UT WOS:000378066000033 PM 26872586 ER PT J AU Nebergall, AK Freiberg, AA Greene, ME Malchau, H Muratoglu, O Rowell, S Zumbrunn, T Varadarajan, KM AF Nebergall, Audrey K. Freiberg, Andrew A. Greene, Meridith E. Malchau, Henrik Muratoglu, Orhun Rowell, Shannon Zumbrunn, Thomas Varadarajan, Kartik M. TI Analysis of Dual Mobility Liner Rim Damage Using Retrieved Components and Cadaver Models SO JOURNAL OF ARTHROPLASTY LA English DT Article DE total hip arthroplasty; dual mobility; intraprosthetic dislocation; retrievals; cadavers ID TOTAL HIP-ARTHROPLASTY; INTRAPROSTHETIC DISLOCATION; RECURRENT DISLOCATION; PREVENT DISLOCATION; FEMORAL-HEAD; FOLLOW-UP; SOCKET; CUPS; THA; COMPLICATION AB Background: The objective of this study was to assess the retentive rim of retrieved dual mobility liners for visible evidence of deformation from femoral neck contact and to use cadaver models to determine if anterior soft tissue impingement could contribute to such deformation. Methods: Fifteen surgically retrieved polyethylene liners were assessed for evidence of rim deformation. The average time in vivo was 31.4 months, and all patients were revised for reasons other than intraprosthetic dislocation. Liner interaction with the iliopsoas was studied visually and with fluoroscopy in cadaver specimens using a dual mobility system different than the retrieval study. For fluoroscopic visualization, a metal wire was sutured to the iliopsoas and wires were also embedded into grooves on the outer surface of the liner and the inner head. Results: All retrievals showed evidence of femoral neck contact. The cadaver experiments showed that liner motion was impeded by impingement with the iliopsoas tendon in low flexion angles. When observing the hip during maximum hyperextension, 0 degrees, 15 degrees, and 30 degrees of flexion, there was noticeable tenting of the iliopsoas caused by impingement with the liner. Conclusion: Liner rim deformation resulting from contact with the femoral neck likely begins during early in vivo function. The presence of deformation is indicative of a mechanism inhibiting mobility of the liner. The cadaver studies showed that liner motion could be impeded because of its impingement with the iliopsoas. Such soft tissue impingement may be one mechanism by which liner motion is routinely inhibited, which can result in load transfer from the neck to the rim. (C) 2015 Elsevier Inc. All rights reserved. C1 [Nebergall, Audrey K.; Freiberg, Andrew A.; Greene, Meridith E.; Malchau, Henrik; Muratoglu, Orhun; Rowell, Shannon; Zumbrunn, Thomas; Varadarajan, Kartik M.] Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, 55 Fruit St, Boston, MA 02114 USA. RP Varadarajan, KM (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Harris Orthopaed Lab, 55 Fruit St, Boston, MA 02114 USA. NR 26 TC 2 Z9 2 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD JUL PY 2016 VL 31 IS 7 BP 1595 EP 1602 DI 10.1016/j.arth.2015.12.032 PG 8 WC Orthopedics SC Orthopedics GA DO8WL UT WOS:000378066000040 PM 26796773 ER PT J AU Ge, L AF Ge, Liang TI A Characteristic-Based Constitutive Law for Dispersed Fibers SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID HUMAN CORONARY-ARTERIES; MECHANICAL-PROPERTIES; COLLAGENOUS TISSUES; WALL MECHANICS; MODEL; ORIENTATION; KINEMATICS; FRAMEWORK; ANEURYSMS; BEHAVIOR AB Biological tissues are typically constituted of dispersed fibers. Modeling the constitutive laws of such tissues remains a challenge. Direct integration over all fibers is considered to be accurate but requires very expensive numerical integration. A general structure tensor (GST) model was previously developed to bypass this costly numerical integration step, but there are concerns about the model's accuracy. Here we estimate the approximation error of the GST model. We further reveal that the GST model ignores strain energy induced by shearing motions. Subsequently, we propose a new characteristic-based constitutive law to better approximate the direct integration model. The new model is very cost-effective and closely approximates the "true" strain energy as calculated by the direct integration when stress-strain nonlinearity or fiber dispersion angle is small. C1 [Ge, Liang] Univ Calif San Francisco, Dept Surg, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. RP Ge, L (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94121 USA. EM liang.ge@va.gov FU National Institutes of Health [R01 HL119857, HL063348, HL128278, HL118627] FX This work was supported by the National Institutes of Health (Grant Nos. R01 HL119857, HL063348, HL128278, and HL118627). NR 30 TC 0 Z9 0 U1 1 U2 2 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 EI 1528-8951 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD JUL PY 2016 VL 138 IS 7 AR 071006-1 DI 10.1115/1.4033517 PG 8 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA DP1FV UT WOS:000378236800011 ER PT J AU Regan, MM Francis, PA Pagani, O Fleming, GF Walley, BA Viale, G Colleoni, M Lang, I Gomez, HL Tondini, C Pinotti, G Price, KN Coates, AS Goldhirsch, A Gelber, RD AF Regan, Meredith M. Francis, Prudence A. Pagani, Olivia Fleming, Gini F. Walley, Barbara A. Viale, Giuseppe Colleoni, Marco Lang, Istvan Gomez, Henry L. Tondini, Carlo Pinotti, Graziella Price, Karen N. Coates, Alan S. Goldhirsch, Aron Gelber, Richard D. TI Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Early Breast Cancer: TEXT and SOFT Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERNATIONAL EXPERT CONSENSUS; PATIENT-REPORTED OUTCOMES; OVARIAN SUPPRESSION; CLINICAL-TRIALS; TAMOXIFEN; EXEMESTANE; KI-67 AB Purpose Risk of recurrence is the primary consideration in breast cancer adjuvant therapy recommendations. The TEXT (Tamoxifen and Exemestane Trial) and SOFT (Suppression of Ovarian Function Trial) trials investigated adjuvant endocrine therapies for premenopausal women with hormone receptor-positive breast cancer, testing exemestane plus ovarian function suppression (OFS), tamoxifen plus OFS, and tamoxifen alone. We examined absolute treatment effect across a continuum of recurrence risk to individualize endocrine therapy decision making for premenopausal women with human epidermal growth factor receptor 2 (HER2) -negative disease. Patients and Methods The TEXT and SOFT hormone receptor-positive, HER2-negative analysis population included 4,891 women. The end point was breast cancer-free interval (BCFI), defined as time from random assignment to first occurrence of invasive locoregional, distant, or contralateral breast cancer. A continuous, composite measure of recurrence risk for each patient was determined from a Cox model incorporating age, nodal status, tumor size and grade, and estrogen receptor, progesterone receptor, and Ki-67 expression levels. Subpopulation treatment effect pattern plot methodology revealed differential treatment effects on 5-year BCFI according to composite risk. Results SOFT patients who remained premenopausal after chemotherapy experienced absolute improvement of 5% or more in 5-year BCFI with exemestane plus OFS versus tamoxifen plus OFS or tamoxifen alone, reaching 10% to 15% at intermediate to high composite risk; the benefit of tamoxifen plus OFS versus tamoxifen alone was apparent at the highest composite risk. The SOFT no-chemotherapy cohort-for whom composite risk was lowest on average-did well with all endocrine therapies. For TEXT patients, the benefit of exemestane plus OFS versus tamoxifen plus OFS in 5-year BCFI ranged from 5% to 15%; patients not receiving chemotherapy and with lowest composite risk did well with both treatments. Conclusion Premenopausal women with hormone receptor-positive, HER2-negative disease and high recurrence risk, as defined by clinicopathologic characteristics, may experience improvement of 10% to 15% in 5-year BCFI with exemestane plus OFS versus tamoxifen alone. An improvement of at least 5% may be achieved for women at intermediate risk, and improvement is minimal for those at lowest risk. (C) 2016 by American Society of Clinical Oncology C1 [Regan, Meredith M.; Gelber, Richard D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. [Gelber, Richard D.] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA. [Francis, Prudence A.] Univ Melbourne, St Vincents Hosp, MacCallum Canc Ctr, Melbourne, Vic 3010, Australia. [Francis, Prudence A.] Univ Newcastle, Newcastle, NSW 2300, Australia. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Pagani, Olivia] Inst Oncol Southern Switzerland, Lugano Viganello, Switzerland. [Fleming, Gini F.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Walley, Barbara A.] Natl Canc Inst Canada Clin Trials Grp, Calgary, AB, Canada. [Viale, Giuseppe] Univ Milan, I-20122 Milan, Italy. [Viale, Giuseppe; Colleoni, Marco; Goldhirsch, Aron] European Inst Oncol, Milan, Italy. [Tondini, Carlo] Osped Papa Giovanni XXIII, Bergamo, Italy. [Pinotti, Graziella] Osped Circolo & Fdn Macchi, Varese, Italy. [Lang, Istvan] Natl Inst Oncol, Budapest, Hungary. [Gomez, Henry L.] Inst Nacl Enfermedades Neoplast, Lima, Peru. RP Regan, MM (reprint author), Dana Farber Canc Inst, 450 Brookline Ave,Mailstop CLS 11007, Boston, MA 02215 USA. EM mregan@jimmy.harvard.edu FU NCI NIH HHS [U10 CA016116, N01 CA032102, U10 CA012027, U10 CA021115, U10 CA032102, U10 CA037377, U10 CA069651, U10 CA069974, U10 CA077202, U10 CA180821, U24 CA075362] NR 22 TC 9 Z9 10 U1 5 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2016 VL 34 IS 19 BP 2221 EP + DI 10.1200/JCO.2015.64.3171 PG 13 WC Oncology SC Oncology GA DP6YW UT WOS:000378647000005 PM 27044936 ER PT J AU Henry, NL Somerfield, MR Abramson, VG Allison, KH Anders, CK Chingos, DT Hurria, A Openshaw, TH Krop, IE AF Henry, N. Lynn Somerfield, Mark R. Abramson, Vandana G. Allison, Kimberly H. Anders, Carey K. Chingos, Diana T. Hurria, Arti Openshaw, Thomas H. Krop, Ian E. TI Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTERNATIONAL EXPERT CONSENSUS; CHEMOTHERAPY; VALIDATION; EXPRESSION; MANAGEMENT; RECEPTORS; TAMOXIFEN; ESTROGEN; WOMEN AB Purpose An American Society of Clinical Oncology (ASCO) panel considered the Cancer Care Ontario (CCO) recommendations on the role of patient and disease factors in selecting adjuvant therapy for women with early-stage breast cancer for endorsement. Methods ASCO staff reviewed the CCO guideline for methodologic rigor, and an ASCO panel of content experts reviewed the content of the recommendations. CCO Recommendations For making decisions regarding adjuvant therapy, nodal status, tumor size, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, and lymphovascular invasion are relevant; Oncotype DX score and Adjuvant! Online may be used as risk stratification tools; and age, menopausal status, and medical comorbidities should be considered. Chemotherapy should be considered for patients with positive lymph nodes, ER-negative disease, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node-negative tumors (T > 5 mm), triple-negative (ER-negative, PgR-negative, HER2-negative) tumors, lymphovascular invasion positivity, or estimated distant relapse risk of greater than 15% at 10 years based on Oncotype DX recurrence score (RS). Chemotherapy may not be beneficial or required for small node-negative tumors (T < 5 mm) without high-risk features or for patients with HER2-negative, strongly ER-positive, and PgR-positive cancer with micrometastatic nodal disease, T less than 5 mm, or Oncotype DXRS with an estimated distant relapse risk of less than 15% at 10 years. ASCO Panel Conclusion The ASCO panel endorses the recommendations with minor suggested revisions and highlights three areas that warrant further consideration: tumor histology and adjuvant therapy recommendations, risk stratification tools and proposed Oncotype DX RS thresholds to guide decisions about chemotherapy, and patient factors in decision making. (C) 2016 by American Society of Clinical Oncology C1 [Somerfield, Mark R.] Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. [Henry, N. Lynn] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Abramson, Vandana G.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Chingos, Diana T.] Univ So Calif, Young Survival Coalit, Los Angeles, CA USA. [Hurria, Arti] City Hope Natl Med Ctr, Duarte, CA USA. [Anders, Carey K.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Openshaw, Thomas H.] Eastern Maine Med Ctr Canc Care, Brewer, ME USA. [Krop, Ian E.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Henry, NL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. NR 20 TC 6 Z9 6 U1 2 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 1 PY 2016 VL 34 IS 19 BP 2303 EP + DI 10.1200/JCO.2015.65.8609 PG 11 WC Oncology SC Oncology GA DP6YW UT WOS:000378647000015 PM 27001586 ER PT J AU Stockmann, JP Cooley, CZ Guerin, B Rosen, MS Wald, LL AF Stockmann, Jason P. Cooley, Clarissa Z. Guerin, Bastien Rosen, Matthew S. Wald, Lawrence L. TI Transmit Array Spatial Encoding (TRASE) using broadband WURST pulses for RF spatial encoding in inhomogeneous B-0 fields SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Transmit Array Spatial Encoding; Swept RF pulses; Low field imaging; Portable MRI; Quadratic phase modulation ID SINGLE-SCAN; SPIN-ECHO; NUCLEAR-RELAXATION; PHASE GRADIENTS; MAGNETIC-FIELD; IN-VIVO; MRI; NMR; EXCITATION; CPMG AB Transmit Array Spatial Encoding (TRASE) is a promising new MR encoding method that uses transmit RF (B-1(+)) phase gradients over the field-of-view to perform Fourier spatial encoding. Acquisitions use a spin echo train in which the transmit coil phase ramp is modulated to jump from one k-space point to the next. This work extends the capability of TRASE by using swept radiofrequency (RF) pulses and a quadratic phase removal method to enable TRASE where it is arguably most needed: portable imaging systems with inhomogeneous B-0 fields. The approach is particularly well-suited for portable MR scanners where (a) inhomogeneous B-0 fields are a byproduct of lightweight magnet design, (b) heavy, high power consumption gradient coil systems are a limitation to siting the system in non-conventional locations and (c) synergy with the use of spin echo trains is required to overcome intra-voxel dephasing (short T-2*) in the inhomogeneous field. TRASE does not use a modulation of the B-0 field to encode, but it does suffer from secondary effects of the inhomogeneous field. Severe artifacts arise in TRASE images due to off-resonance effects when the RF pulse does not cover the full bandwidth of spin resonances in the imaging FOV. Thus, for highly inhomogeneous B-0 fields, the peak RF power needed for high-bandwidth refocusing hard pulses becomes very expensive, in addition to requiring RF coils that can withstand thousands of volts. In this work, we use swept WURST RF pulse echo trains to achieve TRASE imaging in a highly inhomogeneous magnetic field (Delta B-0/B-0 similar to 0.33% over the sample). By accurately exciting and refocusing the full bandwidth of spins, the WURST pulses eliminate artifacts caused by the limited bandwidth of the hard pulses used in previous realizations of TRASE imaging. We introduce a correction scheme to remove the unwanted quadratic phase modulation caused by the swept pulses. Also, a phase alternation scheme is employed to mitigate artifacts caused by mixture of the even and odd-echo coherence pathways due to defects in the refocusing pulse. In this paper, we describe this needed methodology and demonstrate the ability of TRASE to Fourier encode in an inhomogeneous field (Delta B-0/B-0 similar to 1% over the full FOV). (C) 2016 Elsevier Inc. All rights reserved. C1 [Stockmann, Jason P.; Cooley, Clarissa Z.; Guerin, Bastien; Rosen, Matthew S.; Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. [Rosen, Matthew S.] Harvard Univ, Dept Phys, Cambridge, MA 02141 USA. [Guerin, Bastien; Rosen, Matthew S.; Wald, Lawrence L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Stockmann, JP (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 149 Thirteenth St,Suite 2301, Charlestown, MA 02129 USA. EM jaystock@nmr.mgh.harvard.edu RI Wald, Lawrence/D-4151-2009 FU NIH [R01EB018976, K99 EB019482]; DoD/USAMRRA [W81XWH-11-2-0076 (DM09094)] FX The authors thank Jonathan Sharp, Scott King, Michael Garwood, Robin de Graaf, Soumyajit Mandal, and Mathieu Sarracanie for illuminating discussions, and Lina Colucci for help with relaxation measurements. We also thank the anonymous reviewers of this work for their many helpful insights and suggestions. Support comes from NIH R01EB018976, K99 EB019482 and DoD/USAMRRA W81XWH-11-2-0076 (DM09094). NR 54 TC 1 Z9 1 U1 6 U2 11 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 JUL PY 2016 VL 268 BP 36 EP 48 DI 10.1016/j.jmr.2016.04.005 PG 13 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA DP0NG UT WOS:000378185900005 PM 27155906 ER PT J AU Garrett, GL Lowenstein, SE Singer, JP He, SY Arron, ST AF Garrett, Giorgia L. Lowenstein, Stefan E. Singer, Jonathan P. He, Steven Y. Arron, Sarah T. TI Trends of skin cancer mortality after transplantation in the United States: 1987 to 2013 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE cause of death; cutaneous carcinoma; iatrogenic immunosuppression; mortality outcomes; nonmelanoma skin cancer; organ transplant recipients; rate; solid organ transplantation ID RISK-FACTORS; KIDNEY-TRANSPLANTATION; ORGAN-TRANSPLANTATION; HEART-TRANSPLANT; CELL-CARCINOMA; RECIPIENTS; SURVIVAL; THERAPY; DEATH AB Background: Solid organ transplant recipients are at increased risk of skin cancer, but population-based mortality data are limited. Objective: Mortality and predictors of skin cancer death posttransplantation were investigated. Methods: All US organ transplant recipients between 1987 and 2013, identified through the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, were included. Mortality and hazard ratios (HR) were calculated for the overall population and patient subgroups. Results: The overall mortality was 5308 per 100,000 person-years and the skin cancer-specific mortality was 35.27 per 100,000 person-years. Risk factors associated with skin cancer death included thoracic versus abdominal transplantation (HR 2.90, 95% confidence interval [CI] 2.52-3.34), age over 50 years (HR 2.86, CI 2.43-3.38), white race (HR 6.29, CI 4.63-8.53), and male sex (HR 1.85, CI 1.57-2.19). Mortality was highest for malignant melanoma (mortality of 11.48), followed by squamous cell carcinoma (mortality of 4.94) and Merkel cell carcinoma (mortality of 4.59). Limitations: Limitations of this study included potential underreporting and misclassification of death from skin cancer in the data set. Conclusion: Mortality from posttransplantation skin cancer is reported. Older patients, male patients, white patients, and thoracic transplant recipients had increased mortality from skin cancer. C1 [Garrett, Giorgia L.; Arron, Sarah T.] Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St, San Francisco, CA 94143 USA. [Singer, Jonathan P.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Lowenstein, Stefan E.] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. [He, Steven Y.] Harvard Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. RP Arron, ST (reprint author), Univ Calif San Francisco, Dept Dermatol, 2340 Sutter St, San Francisco, CA 94143 USA. EM Arrons@derm.ucsf.edu RI bebarta, vikhyat/K-3476-2015 FU American Academy of Dermatology Transplant Skin Cancer Network; Galderma FX Drs Arron and Garrett are funded by the American Academy of Dermatology Transplant Skin Cancer Network. Dr Garrett was funded by an unrestricted fellowship award from Galderma. NR 27 TC 1 Z9 1 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD JUL PY 2016 VL 75 IS 1 BP 106 EP 112 DI 10.1016/j.jaad.2016.02.1155 PG 7 WC Dermatology SC Dermatology GA DO9GN UT WOS:000378093300029 PM 27067869 ER PT J AU Aldridge, MD Epstein, AJ Brody, AA Lee, EJ Cherlin, E Bradley, EH AF Aldridge, Melissa D. Epstein, Andrew J. Brody, Abraham A. Lee, Eric J. Cherlin, Emily Bradley, Elizabeth H. TI The Impact of Reported Hospice Preferred Practices on Hospital Utilization at the End of Life SO MEDICAL CARE LA English DT Article DE end of life care; hospice preferred practices; end of life hospitalization; transitions; end of life intensity; hospice ID OF-LIFE; UNITED-STATES; PROFIT STATUS; FOR-PROFIT; CARE; CANCER; MEDICARE; HEALTH; PLACE; INTENSITY AB Background: The Affordable Care Act requires hospices to report quality measures across a range of processes and practices. Yet uncertainties exist regarding the impact of hospice preferred practices on patient outcomes. Objective: Assess the impact of 6 hospice preferred practices and hospice organizational characteristics on hospital utilization and death using the first national data on hospice preferred practices. Design: Longitudinal cohort study (2008-2011) of Medicare beneficiaries (N = 149,814) newly enrolled in a national random sample of hospices (N = 577) from the National Hospice Survey (84% response rate) and followed until death. Outcome Measures: The proportion of patients at each hospice admitted to the hospital, emergency department (ED), and intensive care unit (ICU), and who died in the hospital after hospice enrollment. Results: Hospices that reported assessing patient preferences for site of death at admission had lower odds of being in the highest quartile for hospital death (AOR = 0.36; 95% CI, 0.14-0.93) and ED visits (AOR = 0.27; 95% CI, 0.10-0.76). Hospices that reported more frequently monitoring symptoms had lower odds of being in the highest quartile for ICU stays (AOR = 0.48; 95% CI, 0.24-0.94). In adjusted analyses, a higher proportion of patients at for-profit compared with nonprofit hospices experienced a hospital admission (15.3% vs. 10.9%, P < 0.001), ED visit (21.8% vs. 15.6%, P < 0.001), and ICU stay (5.1% vs. 3.0%, P < 0.001). Conclusions: Hospitalization of patients following hospice enrollment varies substantially across hospices. Two of the 6 preferred practices examined were associated with hospitalization rates and for-profit hospices had persistently high hospitalization rates regardless of preferred practice implementation. C1 [Aldridge, Melissa D.; Lee, Eric J.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. [Aldridge, Melissa D.; Brody, Abraham A.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Epstein, Andrew J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA. [Brody, Abraham A.] NYU, Coll Nursing, New York, NY USA. [Cherlin, Emily; Bradley, Elizabeth H.] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Publ Hlth, New Haven, CT 06520 USA. RP Aldridge, MD (reprint author), Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, One Gustave L Levy Pl,POB 1070, New York, NY 10029 USA. EM melissa.aldridge@mssm.edu OI Brody, Abraham/0000-0002-3405-7043 FU National Institute of Nursing Research [5R01NR013499]; National Cancer Institute [1R01CA116398-01A2]; John D. Thompson Foundation FX Supported by the National Institute of Nursing Research 5R01NR013499 (M.D.A.), the National Cancer Institute 1R01CA116398-01A2 (E.B.), and the John D. Thompson Foundation (E.B.). NR 36 TC 1 Z9 1 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0025-7079 EI 1537-1948 J9 MED CARE JI Med. Care PD JUL PY 2016 VL 54 IS 7 BP 657 EP 663 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DO8UW UT WOS:000378061000004 PM 27299952 ER PT J AU Wang, SY Aldridge, MD Gross, CP Canavan, M Cherlin, E Johnson-Hurzeler, R Bradley, E AF Wang, Shi-Yi Aldridge, Melissa D. Gross, Cary P. Canavan, Maureen Cherlin, Emily Johnson-Hurzeler, Rosemary Bradley, Elizabeth TI End-of-Life Care Intensity and Hospice Use A Regional-level Analysis SO MEDICAL CARE LA English DT Article DE Medicare hospice benefit; health services research; geographic variation; end-of-life care ID MEDICARE BENEFICIARIES; LAST YEAR; HEALTH; DEATH; PATTERNS; FAMILIES; PAYMENTS; QUALITY; CANCER; TRENDS AB Objectives: Despite increased hospice use over the last decade, end-of-life care intensity continues to increase. To understand this puzzle, we sought to examine regional variation in intensive end-of life care and determine its associations with hospice use patterns. Methods: Using Medicare claims for decedents aged 66 years and above in 2011, we assessed end-of-life care intensity in the last 6 months of life across hospital referral regions (HRRs) as measured by proportion of decedents per HRR experiencing hospitalization, emergency department use, intensive care unit (ICU) admission, and number of days spent in hospital (hospital-days) and ICU (ICU days). Using hierarchical generalized linear models and adjusting for patient characteristics, we examined whether these measures were associated with overall hospice use, very short (<7 d), medium (8-179 d), or very long (> 180 d) hospice enrollment, focusing on very short stay. Results: End-of-life care intensity and hospice use patterns varied substantially across HRRs. Regional-level end-of-life care intensity was positively correlated with very short hospice enrollment. Comparing HRRs in the highest versus the lowest quintiles of intensity in end-of-life care, regions with more intensive care had higher rates of very short hospice enrollment, with adjusted odds ratios (AOR) 1.14 [99% confidence interval (CI), 1.04-1.25] for hospitalization; AOR, 1.23 (CI, 1.12-1.36) for emergency department use; AOR, 1.25 (CI, 1.14-1.38) for ICU admission; AOR, 1.10 (CI, 1.00-1.21) for hospital -days; and AOR, 1.20 (CI, 1.08-1.32) for ICU-days. Conclusions: At the regional level, increased end-of-life care intensity was consistently associated with very short hospice use. C1 [Wang, Shi-Yi] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, 60 Coll St, New Haven, CT 06520 USA. [Wang, Shi-Yi; Gross, Cary P.] Yale Canc Ctr, Canc Outcomes Publ Policy & Effectiveness Res COP, New Haven, CT USA. [Wang, Shi-Yi; Gross, Cary P.] Yale Univ, Sch Med, 60 Coll St, New Haven, CT 06520 USA. [Aldridge, Melissa D.] Icahn Sch Med Mt Sinai, Dept Geriatr & Palliat Med, New York, NY 10029 USA. [Aldridge, Melissa D.] James J Peters VA Med Ctr, Bronx, NY USA. [Gross, Cary P.] Yale Univ, Sch Med, Dept Internal Med, Sect Gen Internal Med, 60 Coll St, New Haven, CT 06520 USA. [Canavan, Maureen; Cherlin, Emily; Bradley, Elizabeth] Yale Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 60 Coll St, New Haven, CT 06520 USA. [Johnson-Hurzeler, Rosemary] John D Thompson Hosp Inst Educ Training & Res Inc, Branford, CT USA. RP Wang, SY (reprint author), Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, 60 Coll St, New Haven, CT 06520 USA. EM shiyi.wang@yale.edu FU National Cancer Institute [1R01CA116398-01A2]; John D. Thompson Foundation; National Institute of Nursing Research [1R01NR013499-01A1]; Agency for Healthcare Research and Quality [1K01HS023900-01] FX Supported by grant 1R01CA116398-01A2 from the National Cancer Institute (M.D.A. and E.B.); the John D. Thompson Foundation (E.B.); grant 1R01NR013499-01A1 from the National Institute of Nursing Research (M.D.A.); and grant 1K01HS023900-01 from the Agency for Healthcare Research and Quality (S.-Y.W.). These sources of support were not used for any portion of the current manuscript. NR 20 TC 0 Z9 0 U1 1 U2 4 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 JUL PY 2016 VL 54 IS 7 BP 672 EP 678 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DO8UW UT WOS:000378061000006 PM 27111747 ER PT J AU Lo-Ciganic, WH Gellad, WF Huskamp, HA Choudhry, NK Chang, CCH Zhang, R Jones, BL Guclu, H Richards-Shubik, S Donohue, JM AF Lo-Ciganic, Wei-Hsuan Gellad, Walid F. Huskamp, Haiden A. Choudhry, Niteesh K. Chang, Chung-Chou H. Zhang, Ruoxin Jones, Bobby L. Guclu, Hasan Richards-Shubik, Seth Donohue, Julie M. TI Who Were the Early Adopters of Dabigatran? An Application of Group-based Trajectory Models SO MEDICAL CARE LA English DT Article DE anticoagulants; direct thrombin inhibitor; physician prescribing behavior; dabigatran; group-based trajectory models ID NONVALVULAR ATRIAL-FIBRILLATION; GENERAL-PRACTITIONERS; ORAL ANTICOAGULANTS; UNITED-STATES; RISK-FACTORS; DRUGS; PHYSICIAN; ADOPTION; WARFARIN; PATIENT AB Background: Variation in physician adoption of new medications is poorly understood. Traditional approaches (eg, measuring time to first prescription) may mask substantial heterogeneity in technology adoption. Objective: Apply group-based trajectory models to examine the physician adoption of dabigratran, a novel anticoagulant. Methods: A retrospective cohort study using prescribing data from IMS Xponenem on all Pennsylvania physicians regularly prescribing anticoagulants (n=3911) and data on their characteristics from the American Medical Association Masterfile. We examined time to first dabigatran prescription and group-based trajectory models to identify adoption trajectories in the first 15 months. Factors associated with rapid adoption were examined using multivariate logistic regressions. Outcomes: Trajectories of monthly share of oral anticoagulant prescriptions for dabigatran. Results: We identified 5 distinct adoption trajectories: 3.7% rapidly and extensively adopted dabigatran (adopting in <3 mo with 45% of prescriptions) and 13.4% were rapid and moderate adopters (< 3 mo with 20% share). Two groups accounting for 21.6% and 16.1% of physicians, respectively, were slower to adopt (6-10 mo post-introduction) and dabigatran accounted for <10% share. Nearly half (45.2%) of anticoagulant prescribers did not adopt dabigatran. Cardiologists were much more likely than primary care physicians to rapidly adopt [odds ratio (OR) = 12.2; 95% confidence interval (CI), 9.27-16.1] as were younger prescribers (age 36-45 y: OR= 1.49, 95% CI, 1.13-1.95; age 46-55: OR = 1.34, 95% CI, 1.07-1.69 vs. >55 y). Conclusions: Trajectories of physician adoption of dabigatran were highly variable with significant differences across specialties. Heterogeneity in physician adoption has potential implications for the cost and effectiveness of treatment. C1 [Lo-Ciganic, Wei-Hsuan] Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Drachman Hall Room B307E,1295N Martin Ave, Tucson, AZ 85719 USA. [Lo-Ciganic, Wei-Hsuan; Gellad, Walid F.; Donohue, Julie M.] Univ Pittsburgh, Ctr Pharmaceut Policy & Prescribing, Hlth Policy Inst, Pittsburgh, PA 15260 USA. [Gellad, Walid F.; Chang, Chung-Chou H.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. [Gellad, Walid F.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Huskamp, Haiden A.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Choudhry, Niteesh K.] Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol & Pharmacoecon, 75 Francis St, Boston, MA 02115 USA. [Choudhry, Niteesh K.] Harvard Univ, Sch Med, Boston, MA USA. [Chang, Chung-Chou H.] Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. [Zhang, Ruoxin; Guclu, Hasan] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. [Jones, Bobby L.] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. [Guclu, Hasan] Istanbul Medeniyet Univ, Stat Dept, Istanbul, Turkey. [Richards-Shubik, Seth] Lehigh Univ, Coll Business & Econ, Dept Econ, Bethlehem, PA 18015 USA. RP Lo-Ciganic, WH (reprint author), Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Drachman Hall Room B307E,1295N Martin Ave, Tucson, AZ 85719 USA. EM lociganic@pharmacy.arizona.edu FU National Heart, Lung, and Blood Institute [R01HL119246]; University of Pittsburgh Health Policy Institute, Center for Pharmaceutical Policy and Prescribing FX Supported by National Heart, Lung, and Blood Institute (R01HL119246). W.-H.L.-C. was funded by a post-doctoral fellowship through the University of Pittsburgh Health Policy Institute, Center for Pharmaceutical Policy and Prescribing. NR 49 TC 1 Z9 1 U1 3 U2 4 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 JUL PY 2016 VL 54 IS 7 BP 725 EP 732 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA DO8UW UT WOS:000378061000013 PM 27116109 ER PT J AU Tsai, TY Dimitriou, D Hosseini, A Liow, MHL Torriani, M Li, GA Kwon, YM AF Tsai, Tsung-Yuan Dimitriou, Dimitris Hosseini, Ali Liow, Ming Han Lincoln Torriani, Martin Li, Guoan Kwon, Young-Min TI Assessment of accuracy and precision of 3D reconstruction of unicompartmental knee arthroplasty in upright position using biplanar radiography SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE Unicompartmental knee arthroplasty; Component position; Biplanar radiograph; Lower limb alignment ID COMPUTED-TOMOGRAPHY; POLYETHYLENE WEAR; EARLY FAILURE; IN-VIVO; SYSTEM; ALIGNMENT; REPLACEMENT; KINEMATICS; TORSION AB This study aimed to evaluate the precision and accuracy of 3D reconstruction of UKA component position, contact location and lower limb alignment in standing position using biplanar radiograph. Two human specimens with 4 medial UKAs were implanted with beads for radiostereometric analysis (RSA). The specimens were frozen in standing position and CT-scanned to obtain relative positions between the beads, bones and UKA components. The specimens were then imaged using biplanar radiograph (EOS). The positions of the femur, tibia, UKA components and UKA contact locations were obtained using RSA and EOS-based techniques. Intraclass correlation coefficient (ICC) was calculated for inter-observer reliability of the EOS technique. The average (standard deviation) of the differences between two techniques in translations and rotations were less than 0.18 (0.29) mm and 0.39 degrees (0.66 degrees) for UKA components. The root-mean-square-errors (RMSE) of contact location along the anterior/posterior and medial/lateral directions were 0.84 mm and 0.30 mm. The RMSEs of the knee rotations were less than 1.70 degrees. The ICCs for the EOS-based segmental orientations between two raters were larger than 0.98. The results suggest the EOS-based 3D reconstruction technique can precisely determine component position, contact location and lower limb alignment for UKA patients in weight-bearing standing position. (c) 2016 IPEM. C1 [Tsai, Tsung-Yuan; Dimitriou, Dimitris; Hosseini, Ali; Liow, Ming Han Lincoln; Torriani, Martin; Li, Guoan; Kwon, Young-Min] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Kwon, YM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. EM YMKWON@mgh.harvard.edu OI Dimitriou, Dimitris/0000-0002-9558-7080; LIOW, MING HAN LINCOLN/0000-0002-4496-8035 NR 28 TC 0 Z9 0 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 EI 1873-4030 J9 MED ENG PHYS JI Med. Eng. Phys. PD JUL PY 2016 VL 38 IS 7 BP 633 EP 638 DI 10.1016/j.medengphy.2016.04.002 PG 6 WC Engineering, Biomedical SC Engineering GA DP3AH UT WOS:000378364300005 PM 27117422 ER PT J AU Tan, Y Ren, HX Shi, Z Yao, XL He, CW Kang, JX Wan, JB Li, P Yuan, TF Su, HX AF Tan, Yuan Ren, Huixia Shi, Zhe Yao, Xiaoli He, Chengwei Kang, Jing-X Wan, Jian-Bo Li, Peng Yuan, Ti-Fei Su, Huanxing TI Endogenous Docosahexaenoic Acid (DHA) Prevents A beta 1-42 Oligomer-Induced Neuronal Injury SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Alzheimer's disease; A beta oligomers; DHA; Omega-3; Fat-1 mice ID N-3 FATTY-ACIDS; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; BRAIN; TRIAL; RISK; FISH; SUPPLEMENTATION; OMEGA-3-FATTY-ACIDS; PHOSPHOLIPIDS AB The intake of the polyunsaturated fatty acid docosahexaenoic acid (DHA) or n-3 fatty acid has been associated with reduced risk of Alzheimer's disease (AD) in epidemiological reports. However, the underlying mechanism remains to be elucidated. Here, we report that exogenous DHA administration could protect neurons against A beta oligomer-induced injury both in vitro and in vivo, partly through reducing the endoplasmic reticulum (ER) stress, and preventing cell apoptosis. In transgenic fat-1 mice with enriched omega-3 fatty acids, A beta oligomers induced fewer neuronal losses, when compared to wild-type (WT) mice. We conclude that endogenous DHA are neuroprotective in pathogenesis processes of AD. C1 [Tan, Yuan; Ren, Huixia; Shi, Zhe; He, Chengwei; Wan, Jian-Bo; Li, Peng; Su, Huanxing] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China. [Yao, Xiaoli] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Natl Key Clin Dept & Key Discipline Neurol, Guangzhou 510080, Guangdong, Peoples R China. [Kang, Jing-X] Massachusetts Gen Hosp, Dept Med, Lab Lipid Med & Technol, Boston, MA 02114 USA. [Kang, Jing-X] Harvard Univ, Sch Med, Boston, MA USA. [Yuan, Ti-Fei] Nanjing Normal Univ, Sch Psychol, Nanjing 210097, Jiangsu, Peoples R China. RP Su, HX (reprint author), Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.; Yuan, TF (reprint author), Nanjing Normal Univ, Sch Psychol, Nanjing 210097, Jiangsu, Peoples R China. EM ytf0707@126.com; huanxingsu@umac.mo RI Wan, Jian-Bo/D-8368-2014 OI Wan, Jian-Bo/0000-0002-6750-2617 FU Macao Science and Technology Development Fund [018/2013/A1]; university of Macau [MYRG122 (Y1-L3)-ICMS12-SHX, MYRG110 (Y1-L2)-ICMS13-SHX]; Hundred Talents program; "Qing Lan Project" of Nanjing Normal University; Jiangsu Provincial Natural Science Foundation [BK20140917]; [MRG003/SHX/2014/ICMS] FX This study is supported by the Macao Science and Technology Development Fund (018/2013/A1), matching grant project MRG003/SHX/2014/ICMS, and multi-year research grant, university of Macau, MYRG122 (Y1-L3)-ICMS12-SHX and MYRG110 (Y1-L2)-ICMS13-SHX (H.S.). The study is also supported by "Hundred Talents program," "Qing Lan Project" of Nanjing Normal University, and Jiangsu Provincial Natural Science Foundation (No. BK20140917) (T-F.Y.). NR 29 TC 2 Z9 2 U1 3 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD JUL PY 2016 VL 53 IS 5 BP 3146 EP 3153 DI 10.1007/s12035-015-9224-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA DO7AU UT WOS:000377935400036 PM 26021747 ER PT J AU Yu, ZY Zhang, Y Liu, N Yuan, J Lin, L Zhuge, QC Xiao, J Wang, XY AF Yu, Zhanyang Zhang, Yu Liu, Ning Yuan, Jing Lin, Li Zhuge, Qichuan Xiao, Jian Wang, Xiaoying TI Roles of Neuroglobin Binding to Mitochondrial Complex III Subunit Cytochrome c1 in Oxygen-Glucose Deprivation-Induced Neurotoxicity in Primary Neurons SO MOLECULAR NEUROBIOLOGY LA English DT Article DE Neuroglobin; Complex III; Cytochrome c1; Primary neurons; Oxygen-glucose deprivation; Superoxide anion ID MOUSE CORTICAL-NEURONS; ENDOGENOUS NEUROPROTECTANT; SPECIES GENERATION; CULTURED NEURONS; ROS PRODUCTION; NITRIC-OXIDE; CELL-DEATH; IN-VIVO; MECHANISMS; BRAIN AB Neuroglobin (Ngb) is a tissue globin specifically expressed in brain neurons. Recent studies by our laboratory and others have demonstrated that Ngb is protective against stroke and related neurological disorders, but the mechanisms remain poorly understood. We previously identified cytochrome c1 (Cyc1) as an Ngb-interacting molecule by yeast two-hybrid screening. Cyc1 is a subunit of mitochondria complex III, which is a component of mitochondrial respiratory chain and a major source of reactive oxygen species (ROS) production under both physiological and pathological conditions. In this study, we for the first time defined Ngb-Cyc1 binding, and investigated its roles in oxygen-glucose deprivation (OGD)/reoxygenation-induced neurotoxicity and ROS production in primary neurons. Immunocytochemistry and co-immunoprecipitation validated Ngb-Cyc1 binding, which was significantly increased by OGD and Ngb overexpression. We found 4 h OGD with/without 4 h reoxygenation significantly increased complex III activity, but this activity elevation was significantly attenuated in three groups of neurons: Ngb overexpression, specific complex III inhibitor stigmatellin, or stigmatellin plus Ngb overexpression, whereas there was no significant differences between these three groups, suggesting Ngb-Cyc1 binding may function in suppressing OGD-mediated complex III activity elevation. Importantly, these three groups of neurons also showed significant decreases in OGD-induced superoxide anion generation and neurotoxicity. These results suggest that Ngb can bind to mitochondrial complex III subunit Cyc1, leading to suppression of OGD-mediated complex III activity and subsequent ROS production elevation, and eventually reduction of OGD-induced neurotoxicity. This molecular signaling cascade may be at least part of the mechanisms of Ngb neuroprotection against OGD-induced neurotoxicity. C1 [Yu, Zhanyang; Zhang, Yu; Lin, Li; Zhuge, Qichuan; Xiao, Jian] Wenzhou Med Univ, Dept Neurosurg, Coll Pharm, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China. [Liu, Ning; Yuan, Jing] Hunan Normal Univ, Key Lab Prot Biochem & Dev Biol, State Educ Minist, Coll Life Sci, Changsha 410081, Hunan, Peoples R China. [Yu, Zhanyang; Yuan, Jing; Wang, Xiaoying] Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. [Yu, Zhanyang; Yuan, Jing; Wang, Xiaoying] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. [Yu, Zhanyang; Yuan, Jing; Wang, Xiaoying] Harvard Univ, Sch Med, Program Neurosci, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. RP Yu, ZY (reprint author), Wenzhou Med Univ, Dept Neurosurg, Coll Pharm, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China.; Yu, ZY; Wang, XY (reprint author), Harvard Univ, Sch Med, Neuroprotect Res Lab, Dept Neurol, 149 13th St,Room 2411A, Charlestown, MA 02129 USA.; Yu, ZY; Wang, XY (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 149 13th St,Room 2411A, Charlestown, MA 02129 USA.; Yu, ZY; Wang, XY (reprint author), Harvard Univ, Sch Med, Program Neurosci, 149 13th St,Room 2411A, Charlestown, MA 02129 USA. EM yuzywzmu@126.com; wangxi@helix.mgh.harvard.edu FU National Natural Science Foundation of China [81371351]; NIH [R01-NS049476] FX This work was in part supported by National Natural Science Foundation of China grant 81371351 to Z.Y. and NIH grants R01-NS049476 to X.W. NR 45 TC 2 Z9 2 U1 4 U2 10 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD JUL PY 2016 VL 53 IS 5 BP 3249 EP 3257 DI 10.1007/s12035-015-9273-4 PG 9 WC Neurosciences SC Neurosciences & Neurology GA DO7AU UT WOS:000377935400045 PM 26050086 ER PT J AU Subramaniam, R Mukherjee, S Chen, H Keshava, S Neuenschwander, P Shams, H AF Subramaniam, R. Mukherjee, S. Chen, H. Keshava, S. Neuenschwander, P. Shams, H. TI Restoring cigarette smoke-induced impairment of efferocytosis in alveolar macrophages SO MUCOSAL IMMUNOLOGY LA English DT Article ID INGESTED APOPTOTIC CELLS; GM-CSF; EPIDEMIC INFLUENZA; LUNG INFLAMMATION; PHAGOCYTOSIS; RECEPTOR; RESOLUTION; ENGULFMENT; CLEARANCE; ENDOSOMES AB Cigarette smoke has been associated with susceptibility to different pulmonary and airway diseases. Impaired alveolar macrophages (AMs) that are major phagocytes in the lung have been associated with patients with airway diseases and active smokers. In the current report, we show that exposure to second-hand cigarette smoke (SHS) significantly reduced efferocytosis in vivo. More importantly, delivery of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) to the alveolar space restored and refurbished the efferocytosis capability of AMs. Exposure to SHS significantly reduced expression of CD16/32 on AMs, and treatment with GM-CSF not only restored but also significantly increased the expression of CD16/32 on AMs. GM-CSF treatment increased uptake and digestion/removal of apoptotic cells by AMs. The latter was attributed to increased expression of Rab5 and Rab7. Increased efferocytosis of AMs was also tested in a disease condition. AMs from GM-CSF-treated, influenza-infected, SHS-exposed mice showed significantly better efferocytosis activity, and mice had significantly less morbidity compared with phosphate-buffered saline-treated group. GM-CSF-treated mice had increased amphiregulin levels in the lungs, which in addition to efferocytosis of AMs may have attributed to their protection against influenza. These results will have great implications for developing therapeutic approaches by harnessing mucosal innate immunity to treat lung and airway diseases and protect against pneumonia. C1 [Subramaniam, R.; Mukherjee, S.; Chen, H.; Shams, H.] Univ Texas Hlth Sci Ctr Tyler, CPIDC, Tyler, TX 75708 USA. [Keshava, S.] Univ Texas Hlth Sci Ctr Tyler, Dept Cellular & Mol Biol, Tyler, TX 75708 USA. [Neuenschwander, P.] Univ Texas Hlth Sci Ctr Tyler, Biomed Res, Tyler, TX 75708 USA. [Subramaniam, R.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Subramaniam, R.] Harvard Univ, Sch Med, Boston, MA USA. RP Shams, H (reprint author), Univ Texas Hlth Sci Ctr Tyler, CPIDC, Tyler, TX 75708 USA. EM homayoun.shams@uthct.edu FU Flight Attendant Medical Research Institute [092015, 123020] FX We thank Dr Tvinnereim for her assistance in CT scanning and our vivarium staff for animal studies. This work was, in part, supported by grants to H.S. from the Flight Attendant Medical Research Institute (092015-Clinical Innovator Award and 123020-Clinical Innovator Award). NR 49 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 1933-0219 EI 1935-3456 J9 MUCOSAL IMMUNOL JI Mucosal Immunol. PD JUL PY 2016 VL 9 IS 4 BP 873 EP 883 DI 10.1038/mi.2015.120 PG 11 WC Immunology SC Immunology GA DP2TW UT WOS:000378346800004 PM 26577570 ER PT J AU Renvall, V Witzel, T Wald, LL Polimeni, JR AF Renvall, Ville Witzel, Thomas Wald, Lawrence L. Polimeni, Jonathan R. TI Automatic cortical surface reconstruction of high-resolution T-1 echo planar imaging data SO NEUROIMAGE LA English DT Article DE fMRI registration; Tissue segmentation; Inversion recovery; Functional MRI; FreeSurfer; Surface-based analysis ID MAGNETIZATION-TRANSFER CONTRAST; HUMAN CEREBRAL-CORTEX; IN-VIVO; DISTORTION CORRECTION; GEOMETRIC DISTORTION; BRAIN IMAGES; SENSORY STIMULATION; 7 T; EPI; REGISTRATION AB Echo planar imaging (EPI) is the method of choice for the majority of functional magnetic resonance imaging ( fMRI), yet EPI is prone to geometric distortions and thus misaligns with conventional anatomical reference data. The poor geometric correspondence between functional and anatomical data can lead to severe misplacements and corruption of detected activation patterns. However, recent advances in imaging technology have provided EPI data with increasing quality and resolution. Here we present a framework for deriving cortical surface reconstructions directly from high-resolution EPI-based reference images that provide anatomical models exactly geometric distortion-matched to the functional data. Anatomical EPI data with 1 mm isotropic voxel size were acquired using a fast multiple inversion recovery time EPI sequence (MI-EPI) at 7 T, from which quantitative T-1 maps were calculated. Using these T1 maps, volumetric data mimicking the tissue contrast of standard anatomical data were synthesized using the Bloch equations, and these T-1-weighted data were automatically processed using FreeSurfer. The spatial alignment between T-2(*)-weighted EPI data and the synthetic T-1-weighted anatomical MI-EPI-based images was improved compared to the conventional anatomical reference. In particular, the alignment near the regions vulnerable to distortion due to magnetic susceptibility differences was improved, and sampling of the adjacent tissue classes outside of the cortex was reduced when using cortical surface reconstructions derived directly from the MI-EPI reference. The MI-EPI method therefore produces high-quality anatomical data that can be automatically segmented with standard software, providing cortical surface reconstructions that are geometrically matched to the BOLD fMRI data. (C) 2016 Elsevier Inc. All rights reserved. C1 [Renvall, Ville; Witzel, Thomas; Wald, Lawrence L.; Polimeni, Jonathan R.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Renvall, Ville] Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Espoo, Finland. [Renvall, Ville; Witzel, Thomas; Wald, Lawrence L.; Polimeni, Jonathan R.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Wald, Lawrence L.; Polimeni, Jonathan R.] MIT, Harvard MIT Div Hlth Sci & Technol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Renvall, V (reprint author), Aalto Univ, Sch Sci, Dept Neurosci & Biomed Engn, Espoo, Finland. EM ville.renvall@aalto.fi RI Wald, Lawrence/D-4151-2009; Renvall, Ville/M-4165-2013 OI Renvall, Ville/0000-0002-4070-7030 FU NIH National Institute for Biomedical Imaging and Bioengineering [P41-EB015896, K01-EB011498, R01-EB019437]; Finnish Cultural Foundation Kalle and Dagmar Valimaa Fund; Swedish Cultural Foundation in Finland [11/7793-1166]; Instrumentarium Science Foundation; Academy of Finland [265917]; Athinoula A. Martinos Center for Biomedical Imaging; [S10-RR023401]; [S10-RR023043]; [S10-RR019371]; [S10-RR020948] FX We wish to thank Dr. Himanshu Bhat and Prof. Bruce Fischl for helpful discussions. Support for this research was provided in part by the NIH National Institute for Biomedical Imaging and Bioengineering (P41-EB015896, K01-EB011498, and R01-EB019437), Finnish Cultural Foundation Kalle and Dagmar Valimaa Fund, Swedish Cultural Foundation in Finland (11/7793-1166), Instrumentarium Science Foundation, and the Academy of Finland (grant #265917), and was made possible by the resources provided by Shared Instrumentation Grants S10-RR023401, S10-RR023043, S10-RR019371, and S10-RR020948 as well as the Athinoula A. Martinos Center for Biomedical Imaging. Some of the analysis scripts used in this work were developed by FBIRN (www.nbirn.net). Preliminary accounts of this work have been presented in the annual meetings of the International Society of Magnetic Resonance in Medicine (Renvall et al., 2014c) and the Organization for Human Brain Mapping (Renvall et al., 2014b). NR 74 TC 1 Z9 1 U1 3 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2016 VL 134 BP 338 EP 354 DI 10.1016/j.neuroimage.2016.04.004 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DO8PP UT WOS:000378045900033 PM 27079529 ER PT J AU Konukoglu, E Coutu, JP Salat, DH Fischl, B AF Konukoglu, Ender Coutu, Jean-Philippe Salat, David H. Fischl, Bruce CA ADNI TI Multivariate statistical analysis of diffusion imaging parameters using partial least squares: Application to white matter variations in Alzheimer's disease SO NEUROIMAGE LA English DT Article DE Multivariate analysis; Alzheimer's disease; Partial least squares; Diffusion tensor imaging ID MILD COGNITIVE IMPAIRMENT; INDEPENDENT COMPONENT ANALYSIS; MULTIMODAL FUSION; TRACT INTEGRITY; DISCRIMINATING SCHIZOPHRENIA; FRONTOTEMPORAL DEMENTIA; CONNECTIVITY NETWORKS; SPATIAL STATISTICS; RADIAL DIFFUSIVITY; VOXELWISE ANALYSIS AB Diffusion magnetic resonance imaging (dMRI) is a unique technology that allows the noninvasive quantification of microstructural tissue properties of the human brain in healthy subjects as well as the probing of disease-induced variations. Population studies of dMRI data have been essential in identifying pathological structural changes in various conditions, such as Alzheimer's and Huntington's diseases (Salat et al., 2010; Rosas et al., 2006). The most common form of dMRI involves fitting a tensor to the underlying imaging data (known as diffusion tensor imaging, or DTI), then deriving parametric maps, each quantifying a different aspect of the underlying microstructure, e.g. fractional anisotropy and mean diffusivity. To date, the statistical methods utilized in most DTI population studies either analyzed only one such map or analyzed several of them, each in isolation. However, it is most likely that variations in the microstructure due to pathology or normal variability would affect several parameters simultaneously, with differing variations modulating the various parameters to differing degrees. Therefore, joint analysis of the available diffusion maps can be more powerful in characterizing histopathology and distinguishing between conditions than the widely used univariate analysis. In this article, we propose a multivariate approach for statistical analysis of diffusion parameters that uses partial least squares correlation (PLSC) analysis and permutation testing as building blocks in a voxel-wise fashion. Stemming from the common formulation, we present three different multivariate procedures for group analysis, regressing-out nuisance parameters and comparing effects of different conditions. We used the proposed procedures to study the effects of non-demented aging, Alzheimer's disease and mild cognitive impairment on the white matter. Here, we present results demonstrating that the proposed PLSC-based approach can differentiate between effects of different conditions in the same region as well as uncover spatial variations of effects across the white matter. The proposed procedures were able to answer questions on structural variations such as: "are there regions in the white matter where Alzheimer's disease has a different effect than aging or similar effect as aging?" and "are there regions in the white matter that are affected by both mild cognitive impairment and Alzheimer's disease but with differing multivariate effects?" (C) 2016 Elsevier Inc. All rights reserved. C1 [Konukoglu, Ender; Coutu, Jean-Philippe; Salat, David H.; Fischl, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA USA. [Coutu, Jean-Philippe] MIT, Div Hlth Sci & Technol, Harvard Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Salat, David H.] VA Boston Healthcare Syst, Neuroimaging Res Vet Ctr, Boston, MA USA. [Fischl, Bruce] MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RP Konukoglu, E (reprint author), 149 13th St, Charlestown, MA 02129 USA. EM enderk@nmr.mgh.harvard.edu FU National Institutes of Health grants [R01NR010827, NS042861, NS058793]; Center for Functional Neuroimaging Technologies [P41RR14075]; Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health; NCRR Shared Instrumentation Grant Program; High-End Instrumentation Grant Program; Fonds Quebecois de la Recherche - Sante; National Center for Research Resources [U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [P41EB015896, R01EB006758, R21EB018907, R01EB019956]; National Institute on Aging [AG022381, 5R01AG008122, R01 AG016495]; National Center for Alternativ Medicine [RC1 AT005728-01]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534, 5U01NS086625]; Shared Instrumentation Grants [1S10RR023401, 1S10RR019307, 1S10RR023043]; Autism & Dyslexia Project - the Ellison Medical Foundation; NIH Blueprint for Neuroscience Research [5U01-MH093765]; multi-institutional Human Connectome Project; Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant) [U01 AG024904]; DOD ADNI (Department of Defense) [W81XWH-12-2-0012]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; Canadian Institutes of Health Research; [S10RR021110]; [S10RR023401]; [S10RR019307]; [S10RR019254]; [S10RR023043] FX This study was carried out at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital, using resources provided by the National Institutes of Health grants R01NR010827, NS042861, NS058793 and by the Center for Functional Neuroimaging Technologies, P41RR14075, a P41 Regional Resource supported by the Biomedical Technology Program of the National Center for Research Resources (NCRR), National Institutes of Health. This work also involved the use of instrumentation supported by the NCRR Shared Instrumentation Grant Program and/or High-End Instrumentation Grant Program; specifically, grant numbers S10RR021110, S10RR023401, S10RR019307, S10RR019254 and S10RR023043. Jean-Philippe Coutu was funded by the Fonds Quebecois de la Recherche - Sante.; Support for this research was provided in part by the National Center for Research Resources (U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (P41EB015896, R01EB006758, R21EB018907, R01EB019956), the National Institute on Aging (AG022381, 5R01AG008122, R01 AG016495), the National Center for Alternativ Medicine (RC1 AT005728-01), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01, 1R21NS072652-01, 1R01NS070963, R01NS083534, 5U01NS086625), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation, and by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare;; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern Rev December 5, 2013 California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. NR 64 TC 0 Z9 0 U1 7 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2016 VL 134 BP 573 EP 586 DI 10.1016/j.neuroimage.2016.04.038 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA DO8PP UT WOS:000378045900054 PM 27103138 ER PT J AU Chi, S Jiang, T Tan, L Yu, JT AF Chi, Song Jiang, Teng Tan, Lan Yu, Jin-Tai TI Distinct neurological disorders with C9orf72 mutations: genetics, pathogenesis, and therapy SO NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS LA English DT Review DE C9orf72; Phenotypes; Neuropathology; Genetic; Pathogenesis; Therapy ID AMYOTROPHIC-LATERAL-SCLEROSIS; HEXANUCLEOTIDE REPEAT EXPANSIONS; FRONTOTEMPORAL LOBAR DEGENERATION; G-QUADRUPLEX STRUCTURES; BAC TRANSGENIC MICE; ANTISENSE RNA FOCI; GGGGCC-REPEAT; NUCLEOCYTOPLASMIC TRANSPORT; PATHOLOGICAL FEATURES; CLINICOPATHOLOGICAL CORRELATIONS AB The G(4)C(2) repeat expansion within C9orf72 has been recently identified as the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. This mutation has also been detected in a variety of other neurological diseases with distinct clinical manifestations. The exact mechanisms of how this mutation leads to the wide spectrum of clinical syndromes remain unknown. A series of molecular changes together with some potential modifiers may play a key role. Nucleolar stress, nucleocytoplasmic transport defect, oxidative damage, inhibited stress granules assembly, activated endoplasmic reticulum stress, and inhibited proteasome activity are mechanisms that contribute to the pathogenesis of these diseases. Additional mutations, epigenetic modifiers, and repeat size are potential modifiers that modulate specific phenotypes on the basis of the molecular changes. Here, we summarize distinct C9orf72-related neurological disorders and their corresponding neuropathological changes. Then, we elucidate the existing molecular knowledge and the potential modifiers. Finally, we detail the main target of treatment aiming at controlling expanded RNA transcripts. (C) 2016 Published by Elsevier Ltd. C1 [Chi, Song] Qingdao Univ, Affiliated Hosp, Dept Neurol, Qingdao, Shandong, Peoples R China. [Chi, Song] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Chi, Song; Tan, Lan; Yu, Jin-Tai] Qingdao Univ, Qingdao Municipal Hosp, Sch Med, Dept Neurol, Qingdao 266071, Shandong, Peoples R China. [Jiang, Teng] Nanjing Med Univ, Nanjing Hosp 1, Dept Neurol, Nanjing, Jiangsu, Peoples R China. RP Tan, L; Yu, JT (reprint author), Qingdao Univ, Qingdao Municipal Hosp, Sch Med, Dept Neurol, Qingdao 266071, Shandong, Peoples R China. EM Dr.tanlan@163.com; yu-jintag@163.com FU National Natural Science Foundation of China [81501092, 81471309, 81571245]; Natural Science Foundation of Jiangsu Province [BK20150091]; China Postdoctoral Science Foundation [2015M580448]; Qingdao Key Health Discipline Development Fund; Qingdao Outstanding Health Professional Development Fund; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders FX This work was supported by National Natural Science Foundation of China to T.J. (81501092), J.T.Y. (81471309), and L.T. (81571245); Natural Science Foundation of Jiangsu Province to T.J. (BK20150091); China Postdoctoral Science Foundation to T.J. (2015M580448); Qingdao Key Health Discipline Development Fund; Qingdao Outstanding Health Professional Development Fund; and Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders. NR 142 TC 0 Z9 0 U1 15 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0149-7634 EI 1873-7528 J9 NEUROSCI BIOBEHAV R JI Neurosci. Biobehav. Rev. PD JUL PY 2016 VL 66 BP 127 EP 142 DI 10.1016/j.neubiorev.2016.03.033 PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA DP0KD UT WOS:000378177800010 PM 27139021 ER PT J AU Rosa, KC AF Rosa, Katherine C. TI Integrative Review on the Use of Newman Praxis Relationship in Chronic Illness SO NURSING SCIENCE QUARTERLY LA English DT Review DE chronic disease; healing; Newman's theory of health; nurse-patient relations ID EXPANDING CONSCIOUSNESS; PATTERN-RECOGNITION; AMERICAN WOMEN; LIFE PATTERNS; HEALTH; FAMILIES; CANCER; TRANSFORMATION; CHILDREN; CARE AB Over the past 20 years, many Newman scholars across the globe have investigated health as expanding consciousness with persons living with chronic illness. This integrative review examines the use of the concept, relationship, and its seven dimensionshealth, caring, consciousness, mutual process, patterning, presence, and meaning with persons with chronic illness when engaged in health as expanding consciousness praxis. A regular and sustained pattern of publication of studies that included the seven dimensions was found. Relationships among the dimensions of a Newman praxis relationship, chronic illness, and health as expanding consciousness are discussed. C1 [Rosa, Katherine C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosa, KC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU Connell Nursing Research Scholars Program, Munn Center for Nursing Research, Institute for Patient Care at Massachusetts General Hospital FX Funding for completion of this project/research was supported in part by the Connell Nursing Research Scholars Program, Munn Center for Nursing Research, Institute for Patient Care, at Massachusetts General Hospital. NR 34 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 0894-3184 EI 1552-7409 J9 NURS SCI QUART JI Nurs. Sci. Q. PD JUL PY 2016 VL 29 IS 3 BP 211 EP 218 DI 10.1177/0894318416647776 PG 8 WC Nursing SC Nursing GA DP3TY UT WOS:000378419700009 PM 27271134 ER PT J AU Cavallari, JM Fang, SC Eisen, EA Mittleman, MA Christiani, DC AF Cavallari, Jennifer M. Fang, Shona C. Eisen, Ellen A. Mittleman, Murray A. Christiani, David C. TI Environmental and occupational particulate matter exposures and ectopic heart beats in welders SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATORS; AMBIENT AIR-POLLUTION; CARDIAC-ARRHYTHMIAS; VENTRICULAR-ARRHYTHMIAS; RATE-VARIABILITY; CARDIOVASCULAR-DISEASE; ASSOCIATION; EPIDEMIOLOGY; POPULATION; POLLUTANTS AB Objectives Links between arrhythmias and particulate matter exposures have been found among sensitive populations. We examined the relationship between personal particulate matter <= 2.5 mu m aerodynamic diameter (PM2.5) exposures and ectopy in a panel study of healthy welders. Methods Simultaneous ambulatory ECG and personal PM2.5 exposure monitoring with DustTrak Aerosol Monitor was performed on 72 males during work and non-work periods for 5-90 h (median 40 h). ECGs were summarised hourly for supraventricular ectopy (SVE) and ventricular ectopy (VE). PM2.5 exposures both work and non-work periods were averaged hourly with lags from 0 to 7 h. Generalised linear mixed-effects models with a random participant intercept were used to examine the relationship between PM2.5 exposure and the odds of SVE or VE. Sensitivity analyses were performed to assess whether relationships differed by work period and among current smokers. Results Participants had a mean (SD) age of 38 (11) years and were monitored over 2993 person-hours. The number of hourly ectopic events was highly skewed with mean (SD) of 14 (69) VE and 1 (4) SVE. We found marginally significant increases in VE with PM2.5 exposures in the sixth and seventh hour lags, yet no association with SVE. For every 100 mu g/m(3) increase in sixth hour lagged PM2.5, the adjusted OR (95% CI) for VE was 1.03 (1.00 to 1.05). Results persisted in work or non-work exposure periods and non-smokers had increased odds of VE associated with PM2.5 as compared with smokers. Conclusions A small increase in the odds of VE with short-term PM2.5 exposure was observed among relatively healthy men with environmental and occupational exposures. C1 [Cavallari, Jennifer M.] UConn Hlth Ctr, Div Occupat & Environm Med, Farmington, CT 06032 USA. [Cavallari, Jennifer M.; Fang, Shona C.; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Mittleman, Murray A.] Beth Israel Deaconess Med Ctr, Cardiovasc Epidemiol Res Unit, Boston, MA 02215 USA. [Mittleman, Murray A.] Harvard Univ, Sch Med, Boston, MA USA. [Mittleman, Murray A.; Christiani, David C.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Christiani, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cavallari, JM (reprint author), UConn Hlth Ctr, Div Occupat & Environm Med, Farmington, CT 06032 USA. EM cavallari@uchc.edu FU Flight Attendant Medical Research Institute; National Institute of Environmental Health Sciences; National Institute for Occupational Safety and Health FX Flight Attendant Medical Research Institute; National Institute of Environmental Health Sciences; National Institute for Occupational Safety and Health. NR 34 TC 0 Z9 0 U1 7 U2 7 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 EI 1470-7926 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD JUL PY 2016 VL 73 IS 7 BP 435 EP 441 DI 10.1136/oemed-2015-103256 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA DO9GV UT WOS:000378094300004 PM 27052768 ER PT J AU Underhill, ML Jones, T Habin, K AF Underhill, Meghan L. Jones, Tarsha Habin, Karleen TI Disparities in Cancer Genetic Risk Assessment and Testing SO ONCOLOGY NURSING FORUM LA English DT Editorial Material DE health disparities; genetic testing; risk assessment; breast cancer; ovarian cancer ID BREAST-CANCER; OVARIAN-CANCER; PERSONALIZED MEDICINE; HEREDITARY BREAST; POPULATION; HEALTH; WOMEN; INTERVENTIONS; AWARENESS; GENOMICS C1 [Underhill, Meghan L.; Jones, Tarsha] Dana Farber Canc Inst, Boston, MA 02115 USA. [Habin, Karleen] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Underhill, ML (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM meghanl_underhill@dfci.harvard.edu NR 30 TC 0 Z9 0 U1 2 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2016 VL 43 IS 4 BP 519 EP 523 DI 10.1188/16.ONF.519-523 PG 5 WC Oncology; Nursing SC Oncology; Nursing GA DO9EO UT WOS:000378087400018 PM 27314195 ER PT J AU Flanagan, J Tetler, D Winters, L Post, K Habin, K AF Flanagan, Jane Tetler, Devin Winters, Loren Post, Kathryn Habin, Karleen TI The Experience of Initiating Oral Adjuvant Treatment for Estrogen Receptor-Positive Breast Cancer SO ONCOLOGY NURSING FORUM LA English DT Article DE breast cancer; comorbidities; biologic-based therapies; nursing research; qualitative ID QUALITY-OF-LIFE; ENDOCRINE THERAPY; CLINICAL-PRACTICE; HORMONAL-THERAPY; SURVIVORS; WOMEN; ADHERENCE; SYMPTOMS; INTERVENTIONS; PERSPECTIVES AB Purpose/Objectives: To describe the experience of women with estrogen receptor-positive breast cancer who are initiating oral adjuvant therapy and to determine what they describe as facilitating and/or hindering this experience. Research Approach: Qualitative inquiry. Setting: Massachusetts General Hospital Cancer Center in Boston. Participants: 14 women aged 48-81 years. Methodologic Approach: Qualitative, descriptive study using content analysis. Findings: Five themes were identified: (a) feeling overwhelmed and abandoned despite highly skilled medical care, (b) processing the trauma and putting it in perspective, (c) keeping up the facade while feeling vulnerable, (d) needing to connect cautiously, and (e) moving toward healing and being aware. Conclusions: Each participant who was initiating oral adjuvant treatment described many unmet needs. Women who were caregivers, were older aged, had several chronic illnesses, and were on several medications reported more difficulty transitioning to oral adjuvant therapy. Interpretation: This study suggests that nurses need to collaborate with other members of the healthcare team to assess the needs of and provide comprehensive care to women initiating oral adjuvant therapy. This is particularly true for women who are older aged, selfreported caregivers, and on several medications, and who have chronic comorbid conditions. C1 [Flanagan, Jane] Boston Coll, Adult Gerontol, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. [Tetler, Devin] Portland Community Hlth Ctr, Portland, ME USA. [Winters, Loren; Post, Kathryn; Habin, Karleen] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Flanagan, J (reprint author), Boston Coll, Adult Gerontol, William F Connell Sch Nursing, Chestnut Hill, MA 02167 USA. EM flanagjg@bc.edu NR 31 TC 0 Z9 0 U1 3 U2 3 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X EI 1538-0688 J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2016 VL 43 IS 4 BP E143 EP E152 DI 10.1188/16.ONF.E143-E152 PG 10 WC Oncology; Nursing SC Oncology; Nursing GA DO9EO UT WOS:000378087400001 PM 27314197 ER PT J AU Abud, TB Amparo, F Saboo, US Di Zazzo, A Dohlman, TH Ciolino, JB Hamrah, P Dana, R AF Abud, Tulio B. Amparo, Francisco Saboo, Ujwala S. Di Zazzo, Antonio Dohlman, Thomas H. Ciolino, Joseph B. Hamrah, Pedram Dana, Reza TI A Clinical Trial Comparing the Safety and Efficacy of Topical Tacrolimus versus Methylprednisolone in Ocular Graft-versus-Host Disease SO OPHTHALMOLOGY LA English DT Article ID FLOW-CYTOMETRIC ANALYSIS; SEVERE ALLERGIC CONJUNCTIVITIS; HLA-DR EXPRESSION; CYCLOSPORINE-A; KERATOCONJUNCTIVITIS SICCA; SURFACE DISEASE; CORNEAL TRANSPLANTATION; OPHTHALMIC SUSPENSION; INFLAMMATORY MARKER; IMPRESSION CYTOLOGY AB Purpose: To evaluate the safety and efficacy of topical tacrolimus 0.05% versus topical methylprednisolone 0.5% in patients with ocular graft-versus-host disease (GVHD). Design: Phase 1/2 prospective, randomized, double-masked clinical trial. Participants: Eighty eyes of 40 patients diagnosed with chronic ocular GVHD were enrolled. Methods: Forty patients with ocular GVHD were randomized; 24 patients were treated with topical tacrolimus 0.05% and 16 patients were treated with topical methylprednisolone 0.5% twice daily for 10 weeks, in addition to continuing their baseline treatment regimen. Main Outcome Measures: Safety was evaluated based on occurrence of adverse events. Tolerability was assessed based on subject reports of discomfort after drop instillation. Intraocular pressure (IOP) was monitored. The main efficacy end points were corneal fluorescein staining (CFS), tear film break-up time (TBUT), Schirmer test results, and expression of the ocular surface inflammatory markers human leukocyte antigen-DR (HLA-DR) and intercellular adhesion molecule-1 (ICAM-1). Symptoms were evaluated using the Ocular Surface Disease Index (OSDI). Results: After 10 weeks of treatment, no major adverse events occurred in either treatment group, and there was no significant difference in the composite tolerability scores between the 2 groups (P = 0.06). However, burning sensation was more pronounced with tacrolimus (P = 0.002). Topical tacrolimus was more effective than methylprednisolone in reducing the CFS score at week 10 (55% vs. 23% reduction, respectively; P = 0.01) and achieved significant improvement in TBUT when compared with baseline (P < 0.001). Reduction in OSDI score achieved statistical significance with tacrolimus (27% reduction; P = 0.02), but was marginal with methylprednisolone (32% reduction; P = 0.06). Expression of ICAM-1 by ocular surface epithelium decreased significantly in both groups (tacrolimus, P = 0.003; methylprednisolone, P = 0.008), whereas HLA-DR expression decreased significantly only in the tacrolimus group (P = 0.03). Schirmer test scores did not change significantly in either group during the study; IOP increased significantly with methylprednisolone at week 10 (P = 0.04). Conclusions: Topical tacrolimus 0.05% is safe, generally well tolerated, and effective for the treatment of ocular GVHD without the hypertensive effects of topical corticosteroids. (C) 2016 by the American Academy of Ophthalmology. C1 [Abud, Tulio B.; Amparo, Francisco; Saboo, Ujwala S.; Di Zazzo, Antonio; Ciolino, Joseph B.; Hamrah, Pedram; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA USA. [Abud, Tulio B.] Fed Univ Sao Paulo UNIFESP, Paulista Sch Med, Dept Ophthalmol & Visual Sci, Sao Paulo, Brazil. [Hamrah, Pedram] Tufts Univ, Sch Med, Tufts Med Ctr, Cornea Serv,New England Eye Ctr,Dept Ophthalmol, Boston, MA 02111 USA. [Abud, Tulio B.; Amparo, Francisco; Di Zazzo, Antonio; Dohlman, Thomas H.; Dana, Reza] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Schepens Eye Res Inst,Dept Ophthalmol, Boston, MA USA. RP Dana, R (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM reza_dana@meei.harvard.edu OI Hamrah, Pedram/0000-0002-9313-2939 FU Higher Level Personnel Improvement Commission (CAPES-Ministry of Education, Brazil); Allergan (Irvine, CA); GlaxoSmithKline (Philadelphia, PA); Alcon Laboratories, Inc (Fort Worth, TX); National Eye Institute, National Institutes of Health, Bethesda, Maryland [K24 EY019098]; Research to Prevent Blindness, Inc., New York, New York FX The author(s) have made the following disclosure(s): T.B.A.: Financial support - Higher Level Personnel Improvement Commission (CAPES-Ministry of Education, Brazil); P.H.: Consultant - AllerganInc. (Irvine, CA); Shire (Lexington, MA); Bausch & Lomb (Rochester, NY); Valeant, Laval, (Quebec, Canada); GlaxoSmithKline (Philadelphia, PA); Jade Therapeutics (Waltham, MA); Revision Optics (Lake Forest, CA); Financial support - Allergan (Irvine, CA); GlaxoSmithKline (Philadelphia, PA); Alcon Laboratories, Inc (Fort Worth, TX).; Supported by the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: K24 EY019098); and Research to Prevent Blindness, Inc., New York, New York. The funding organizations had no role in the design or conduct of this research. NR 40 TC 1 Z9 1 U1 1 U2 2 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 JUL PY 2016 VL 123 IS 7 BP 1449 EP 1457 DI 10.1016/j.ophtha.2016.02.044 PG 9 WC Ophthalmology SC Ophthalmology GA DP3KC UT WOS:000378391100016 PM 27086024 ER PT J AU Qazi, Y Hurwitz, S Khan, S Jurkunas, UV Dana, R Hamrah, P AF Qazi, Yureeda Hurwitz, Shelley Khan, Sarosh Jurkunas, Ula V. Dana, Reza Hamrah, Pedram TI Validity and Reliability of a Novel Ocular Pain Assessment Survey (OPAS) in Quantifying and Monitoring Corneal and Ocular Surface Pain SO OPHTHALMOLOGY LA English DT Article ID DN4 DIAGNOSTIC QUESTIONNAIRE; DRY EYE SYMPTOMS; NEUROPATHIC PAIN; PSYCHOMETRIC PROPERTIES; SCREENING QUESTIONNAIRE; CULTURAL-ADAPTATION; LEEDS ASSESSMENT; NERVOUS-SYSTEM; DISEASE-INDEX; ID PAIN AB Purpose: To validate the Ocular Pain Assessment Survey (OPAS), specifically designed to measure ocular pain and quality of life for use by eye care practitioners and researchers. Design: A single-center cohort study was conducted among patients with and without corneal and ocular surface pain at initial and follow-up visits over a 6-month period. The content of the OPAS was guided by literature review, a body of experts, and incorporating conceptual frameworks from existing pain questionnaires. The Wong-Baker FACES Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. Participants: A total of 102 patients aged 18 to 80 years completed the OPAS at the initial visit. A total of 21 patients were followed up after treatment. Methods: Indices of validity and internal consistency (Spearman's rank-order, r(s), or Pearson's correlation coefficients, r(p)), and coefficient of reliability (Cronbach's alpha) were determined in addition to equivalence testing, exploratory factor analysis (EFA), and diagnostic analysis. Main Outcome Measures: Eye pain intensity was the primary outcome measure, and interference with quality of life (QoL), aggravating factors, associated factors, associated non-eye pain intensity, and self-reported symptomatic relief were the secondary outcome measures. Results: The OPAS had criterion validity at both initial (r(s) = 0.71; n = 102; P < 0.01) and follow-up visits (r(s) = 0.97; n = 21; P < 0.01). Equivalence tests yielded OPAS and gold standard equivalence for both the initial and follow-up visits. The EFA supported 6 subscales (eye pain intensity at 24 hours and 2 weeks, non-eye pain intensity, QoL, aggravating factors, and associated factors) confirming multidimensionality. Cronbach's alpha > 0.83 for all subscales established strong internal consistency, which correlated with the gold standard, including 24-hour eye pain intensity and QoL interference scores (r(p) = 0.81, 0.64, respectively P < 0.001). At follow-up, reduction in pain scores was accompanied by improvement in all dimensions of the OPAS. Percentage change in QoL correlated to percentage change in the gold standard (r(p) = 0.53; P < 0.05). The OPAS was sensitive (94%), specific (81%), and accurate (91%), with a diagnostic odds ratio >50. Conclusions: The OPAS is a valid, reliable, and responsive tool with strong psychometric and diagnostic properties in the multidimensional quantification of corneal and ocular surface pain intensity, and QoL. (C) 2016 by the American Academy of Ophthalmology. C1 [Qazi, Yureeda; Khan, Sarosh; Jurkunas, Ula V.; Dana, Reza; Hamrah, Pedram] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv,Dept Ophthalmol, Boston, MA USA. [Hurwitz, Shelley] Harvard Univ, Brigham & Womens Hosp, Sch Med, Biostat Core,Ctr Clin Invest, Boston, MA 02115 USA. [Hamrah, Pedram] Tufts Univ, Sch Med, Dept Ophthalmol, Cornea Serv,New England Eye Ctr,Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. RP Hamrah, P (reprint author), Tufts Univ, Sch Med, Dept Ophthalmol, Cornea Serv,New England Eye Ctr,Tufts Med Ctr, 800 Washington St, Boston, MA 02111 USA. EM phamrah@tuftsmedicalcenter.org FU National Institutes of Health [K08-EY020575]; MEEI Foundation grant; Research to Prevent Blindness Career Development Award; Falk Medical Research Trust FX Funded by the National Institutes of Health K08-EY020575 (P.H.) and an MEEI Foundation grant (P.H.), a Research to Prevent Blindness Career Development Award (P.H.), and the Falk Medical Research Trust (P.H.). The sponsor or funding organization had no role in the design or conduct of this research. NR 72 TC 4 Z9 4 U1 1 U2 2 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 JUL PY 2016 VL 123 IS 7 BP 1458 EP 1468 DI 10.1016/j.ophtha.2016.03.006 PG 11 WC Ophthalmology SC Ophthalmology GA DP3KC UT WOS:000378391100017 PM 27089999 ER PT J AU Balaratnasingam, C Freund, KB Tan, AM Mrejen, S Hunyor, AP Keegan, DJ Dansingani, KK Dayani, PN Barbazetto, IA Sarraf, D Jampol, LM Yannuzzi, LA AF Balaratnasingam, Chandrakumar Freund, K. Bailey Tan, Anna M. Mrejen, Sarah Hunyor, Alex P. Keegan, David J. Dansingani, Kunal K. Dayani, Pouya N. Barbazetto, Irene A. Sarraf, David Jampol, Lee M. Yannuzzi, Lawrence A. TI Bullous Variant of Central Serous Chorioretinopathy Expansion of Phenotypic Features Using Multimethod Imaging SO OPHTHALMOLOGY LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; INDOCYANINE GREEN ANGIOGRAPHY; RETINAL-DETACHMENT; ORGAN-TRANSPLANTATION; NEOVASCULARIZATION; THERAPY AB Purpose: To define the phenotypic characteristics of the bullous variant of central serous chorioretinopathy (CSC) using multimethod imaging. Design: Retrospective, observational case series. Participants: Twenty-one eyes of 14 patients with bullous retinal detachment resulting from CSC (bullous CSC group) and 122 eyes of 84 patients with chronic CSC without bullous retinal detachment (nonbullous CSC group). Methods: We performed a retrospective review of clinical and multimethod imaging data of patients who sought treatment from the authors with bullous retinal detachment resulting from CSC between January 2010 and November 2015. Multimethod imaging comprised color photography, fluorescein angiography, fundus autofluorescence, and high-resolution optical coherence tomography. Consecutive cases of chronic CSC without bullous retinal detachment, seen during the same period, comprised a comparative group. Main Outcome Measures: Qualitative and quantitative characteristics of the choroid, retinal pigment epithelium, and retina were compared between the 2 groups. Results: Mean age of the bullous CSC group was 53.8 years. There was no difference in age, visual acuity, corticosteroid use, or the proportion of white patients and men between the 2 groups (all P > 0.132). Peripheral nonperfusion occurred only in eyes with bullous retinal detachment (38% of cases). Retinal pigment epithelial tears were seen in 95% of eyes in the bullous group and none of the eyes in the nonbullous CSC group. The bullous CSC group demonstrated a greater number of pigment epithelial detachments (PEDs) and more eyes demonstrated PEDs with internal hyperreflectivity (both P < 0.016). Mean subfoveal choroidal thickness in the bullous CSC group (463.1 +/- 83.1 mm) was not different compared with that of the nonbullous CSC group (400.6 +/- 100.6 mm; P = 0.993). More eyes in the bullous CSC group demonstrated hyperreflectivity around large choroidal vessels and at the level of the choriocapillaris on OCT (P < 0.001). Retinal folds and subretinal fibrin were identified in a greater proportion of eyes in the bullous CSC group (both P < 0.001). Conclusions: Bullous retinal detachment is a rare manifestation of chronic CSC and is characterized by a unique constellation of phenotypic and multimethod imaging features. (C) 2016 by the American Academy of Ophthalmology. C1 [Balaratnasingam, Chandrakumar; Freund, K. Bailey; Tan, Anna M.; Mrejen, Sarah; Dansingani, Kunal K.; Barbazetto, Irene A.; Yannuzzi, Lawrence A.] Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10022 USA. [Balaratnasingam, Chandrakumar; Freund, K. Bailey; Tan, Anna M.; Mrejen, Sarah; Dansingani, Kunal K.; Barbazetto, Irene A.; Yannuzzi, Lawrence A.] Vitreous Retina Macula Consultants New York, New York, NY USA. [Balaratnasingam, Chandrakumar; Freund, K. Bailey; Barbazetto, Irene A.] NYU, Dept Ophthalmol, Sch Med, 550 1St Ave, New York, NY 10016 USA. [Balaratnasingam, Chandrakumar] Univ Western Australia, Ctr Ophthalmol & Visual Sci, Lions Eye Inst, Perth, WA 6009, Australia. [Hunyor, Alex P.] Univ Sydney, Sydney Med Sch, Save Sight Inst, Sydney, NSW 2006, Australia. [Hunyor, Alex P.] Retina Associates, Chatswood, NSW, Australia. [Keegan, David J.] Mater Misericordiae Univ Hosp, Dublin, Ireland. [Dayani, Pouya N.] Retina Vitreous Associated Med Grp, Los Angeles, CA USA. [Sarraf, David] Univ Calif Los Angeles, Jules Stein Eye Inst, Retinal Disorders & Ophthalm Genet Div, Los Angeles, CA 90024 USA. [Sarraf, David] Greater Los Angeles VA Healthcare Ctr, Los Angeles, CA USA. [Jampol, Lee M.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Yannuzzi, LA (reprint author), Manhattan Eye Ear & Throat Hosp, LuEsther T Mertz Retinal Res Ctr, New York, NY 10022 USA. EM layannuzzi@gmail.com OI Freund, K. Bailey/0000-0002-7888-9773 FU LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; Macula Foundation, Inc, New York, New York; RANZCO Eye Foundation, NSW, Australia FX Supported by the LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear and Throat Hospital, New York, New York; The Macula Foundation, Inc, New York, New York; and RANZCO Eye Foundation, NSW, Australia. The funding organizations had no role in the design or conduct of this research. NR 36 TC 0 Z9 0 U1 0 U2 4 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 JUL PY 2016 VL 123 IS 7 BP 1541 EP 1552 DI 10.1016/j.ophtha.2016.03.017 PG 12 WC Ophthalmology SC Ophthalmology GA DP3KC UT WOS:000378391100026 PM 27084564 ER PT J AU Seo, A Walsh, T Lee, MK Ho, PA Hsu, EK Sidbury, R King, MC Shimamura, A AF Seo, Aaron Walsh, Tom Lee, Ming K. Ho, Phoenix A. Hsu, Evelyn Kanyu Sidbury, Robert King, Mary-Claire Shimamura, Akiko TI FAM111B Mutation Is Associated With Inherited Exocrine Pancreatic Dysfunction SO PANCREAS LA English DT Article DE exocrine pancreatic dysfunction; inherited bone marrow failure syndromes; Shwachman-Diamond syndrome ID SHWACHMAN-DIAMOND-SYNDROME; CYSTIC-FIBROSIS GENE; IDENTIFICATION; FAILURE; SBDS AB Objectives: Few genetic causes of exocrine pancreatic dysfunction have been described to date. We identified a family with multiple affected members manifesting exocrine pancreatic dysfunction. Additional associated features included facial rash, sparse hair, hypohidrosis, and swelling of the extremities. The transmission pattern of these clinical features was consistent with an autosomal dominant mode of inheritance. The 2 proband siblings also had transient elevated liver transaminases with hepatic steatosis early in life. This study identifies the genetic cause of exocrine pancreatic dysfunction in this family. Methods: Whole exome sequencing was performed to identify the genetic cause of exocrine pancreatic dysfunction. Results: A heterozygous germline in-frame deletion in the gene FAM111B (c. 1261_1263delAAG, p.Lys421del) cosegregated with the phenotype: the variant was present in all affected relatives genotyped and absent in all unaffected relatives genotyped. The variant is also absent from public control sequence databases. Conclusions: Our findings implicate FAM111B in autosomal dominantly inheritable exocrine pancreatic dysfunction. C1 [Seo, Aaron; Walsh, Tom; Lee, Ming K.; King, Mary-Claire] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. [Seo, Aaron] Fred Hutchinson Canc Res Ctr, Div Clin Res, 1124 Columbia St, Seattle, WA 98104 USA. [Walsh, Tom; Lee, Ming K.; King, Mary-Claire] Univ Washington, Div Med Genet, Seattle, WA 98195 USA. [Ho, Phoenix A.] Seattle Childrens Hosp, Pediat Hematol Oncol, Seattle, WA USA. [Hsu, Evelyn Kanyu] Univ Washington, Dept Pediat, Seattle, WA 98195 USA. [Hsu, Evelyn Kanyu] Univ Washington, Pediat Gastroenterol & Hepatol, Seattle, WA 98195 USA. [Sidbury, Robert] Seattle Childrens Hosp, Dept Dermatol, Seattle, WA USA. [Shimamura, Akiko] Boston Childrens Hosp, Dana Farber Canc Inst, Boston, MA USA. [Shimamura, Akiko] Harvard Univ, Sch Med, Boston, MA USA. RP Shimamura, A (reprint author), Dana Farber & Boston Childrens Canc & Blood Disor, 300 Longwood Ave,Karp 08210, Boston, MA 02115 USA. EM Akiko.Shimamura@childrens.harvard.edu FU US National Institutes of Health [R24DK093425, R24DK099808]; Ghiglione Aplastic Anemia Fund; Julian's Dinosaur Guild from Seattle Children's Hospital; Medical Scientist Training Program Training grant [T32GM007266]; Developmental Biology Training Grant [T32HD007183]; ARCS Foundation Fellowship FX This work was supported by US National Institutes of Health grants R24DK093425 and R24DK099808 to A.S. and M.-C.K.; by the Ghiglione Aplastic Anemia Fund and Julian's Dinosaur Guild from Seattle Children's Hospital to A.S.; by Medical Scientist Training Program Training grant T32GM007266 and Developmental Biology Training Grant T32HD007183 to A.S.; by ARCS Foundation Fellowship to A.S. NR 14 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 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD JUL PY 2016 VL 45 IS 6 BP 858 EP 862 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DO9HJ UT WOS:000378095800018 PM 26495788 ER PT J AU Matsuzaka, S Karasaki, H Ono, Y Ogata, M Oikawa, K Tamakawa, S Chiba, S Muraki, M Yokochi, T Funakoshi, H Kono, T Nagashima, K Mizukami, Y AF Matsuzaka, Suguru Karasaki, Hidenori Ono, Yusuke Ogata, Munehiko Oikawa, Kensuke Tamakawa, Susumu Chiba, Shin-ichi Muraki, Miho Yokochi, Tomoki Funakoshi, Hiroshi Kono, Toru Nagashima, Kazuo Mizukami, Yusuke TI Tracking the Clonal Evolution of Adenosquamous Carcinoma, a Rare Variant of Intraductal Papillary Mucinous Neoplasm of the Pancreas SO PANCREAS LA English DT Article DE intraductal papillary mucinous neoplasm; adenosquamous carcinoma; next-generation sequencing ID CONSENSUS AB Adenosquamous carcinoma (ASC) is an uncommon variant of pancreatic neoplasm. We sought to trace the mode of tumor progression using specimens of ASC associated with intraductal papillary mucinous neoplasm (IPMN) of the pancreas. A resected specimen of the primary pancreatic ASC, developed in a 72-year-old man, was subjected to mutation profiling using amplicon-targeted sequencing and digital polymerase chain reaction. DNA was isolated from each histological compartment including noninvasive IPMN, squamous cell carcinoma (SCC), and adenocarcinoma (AC). Histologically, an IPMN with a large mural nodule was identified. The invasive tumor predominantly consisted of SCC, and a smaller AC was found around the lesion. Squamous metaplasias were sporadically distributed within benign IPMNs. Mutation alleles KRAS(G12D) and GNASR(201C) were identified in all specimens of IPMN including the areas of squamous metaplasia. In addition, these mutations were found in SCC and AC. Clear transition from flat/low-papillary IPMN to SCC indicated a potent invasion front, and the SCC compartment was genetically unique, because the area has a higher frequency of mutation KRAS(G12D). The invasive tumors with distinct histological appearances shared the form of noninvasive IPMN as a common precursor, rather than de novo cancer, suggesting the significance of a genetic profiling scheme of tumors associated with IPMN. C1 [Matsuzaka, Suguru] Furano Kyoukai Hosp, Dept Surg, Furano, Hokkaido, Japan. [Karasaki, Hidenori; Ono, Yusuke; Ogata, Munehiko; Kono, Toru; Nagashima, Kazuo; Mizukami, Yusuke] Sapporo Higashi Tokushukai Hosp, Ctr Clin & Biomed Res, Sapporo, Hokkaido, Japan. [Oikawa, Kensuke] Asahikawa Med Univ, Dept Pathol, Asahikawa, Hokkaido, Japan. [Tamakawa, Susumu] Natl Hosp Org Asahikawa Med Ctr, Asahikawa, Hokkaido, Japan. [Chiba, Shin-ichi; Funakoshi, Hiroshi] Asahikawa Med Univ, Ctr Adv Res & Educ, Asahikawa, Hokkaido, Japan. [Muraki, Miho] Life Technol Japan, Tokyo, Japan. [Yokochi, Tomoki] Chiba Tokushukai Hosp, Dept Clin Res, Funabashi, Chiba, Japan. [Mizukami, Yusuke] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. [Mizukami, Yusuke] Harvard Univ, Sch Med, Boston, MA USA. RP Mizukami, Y (reprint author), Sapporo Higashi Tokushukai Hosp, Ctr Clin & Biomed Res, Lab Clin Bioinformat, Higashi Ku, 3-1 North 33,East 14, Sapporo, Hokkaido 0650033, Japan. EM ymizu_ccbr@tohtoku.jp FU Ministry of Education, Culture, Sports, Science and Technology [25461029]; Pancreas Research Foundation in Japan FX This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (25461029 to Y.M.), and Pancreas Research Foundation in Japan (to Y.M.). NR 13 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0885-3177 EI 1536-4828 J9 PANCREAS JI Pancreas PD JUL PY 2016 VL 45 IS 6 BP 915 EP 918 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA DO9HJ UT WOS:000378095800027 PM 27295533 ER PT J AU Patel, SA Wo, JY Hong, TS AF Patel, Sagar A. Wo, Jennifer Y. Hong, Theodore S. TI Advancing Techniques of Radiation Therapy for Rectal dancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID PREOPERATIVE ENDORECTAL BRACHYTHERAPY; PHASE-III TRIAL; POSTOPERATIVE CHEMORADIOTHERAPY; SMALL-BOWEL; ENDOCAVITARY IRRADIATION; PELVIC RECURRENCE; RANDOMIZED-TRIAL; CANCER; RADIOTHERAPY; OXALIPLATIN AB Since the advent of radiation therapy for rectal cancer, there has been continual investigation of advancing technologies and techniques that allow for improved dose conformality to target structures while limiting irradiation of surrounding normal tissue. For locally advanced disease, intensity modulated and proton beam radiation therapy both provide more highly conformal treatment volumes that reduce dose to organs at risk, though the clinical benefit in terms of toxicity reduction is unclear. For early stage disease, endorectal contact therapy and high-dose rate brachytherapy may be a definitive treatment option for patients who are poor operative candidates or those with low-lying tumors that desire sphincter-preservation. Finally, there has been growing evidence that supports stereotactic body radiotherapy as a safe and effective salvage treatment for the minority of patients that locally recur following trimodality therapy for locally advanced disease. This review addresses these topics that remain areas of active clinical investigation. (C) 2016 Elsevier Inc. All rights reserved. C1 [Patel, Sagar A.] Harvard Radiat Oncol Program, Boston, MA USA. [Wo, Jennifer Y.; Hong, Theodore S.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM tshong1@partners.org NR 29 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 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD JUL PY 2016 VL 26 IS 3 BP 220 EP 225 DI 10.1016/j.semradonc.2016.02.005 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA DP0LU UT WOS:000378182100008 PM 27238474 ER PT J AU Jain, R Sharma, N Basu, S Iyer, G Ueta, M Sotozono, C Kannabiran, C Rathi, VM Gupta, N Kinoshita, S Gomes, JAP Chodosh, J Sangwan, VS AF Jain, Rajat Sharma, Namrata Basu, Sayan Iyer, Geetha Ueta, Mayumi Sotozono, Chie Kannabiran, Chitra Rathi, Varsha M. Gupta, Nidhi Kinoshita, Shigeru Gomes, Jose A. P. Chodosh, James Sangwan, Virender S. TI Stevens-Johnson syndrome: The role of an ophthalmologist SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE Stevens-Johnson syndrome; acute; dry eye; keratoprosthesis; stem cell transplantation: PROSE ID TOXIC EPIDERMAL NECROLYSIS; OCULAR SURFACE RECONSTRUCTION; AMNIOTIC MEMBRANE TRANSPLANTATION; STEM-CELL DEFICIENCY; MUCOSAL EPITHELIAL TRANSPLANTATION; OSTEO-ODONTO-KERATOPROSTHESIS; SCLERAL CONTACT-LENSES; NECROSIS-FACTOR-ALPHA; INDUCED HYPERSENSITIVITY REACTIONS; CUTANEOUS ADVERSE-REACTIONS AB Stevens-Johnson syndrome (SJS) is an acute blistering disease of the skin and mucous membranes. Acute SJS leads to the acute inflammation of the ocular surface and chronic conjunctivitis. If not properly treated, it causes chronic cicatricial conjunctivitis and cicatricial lid margin abnormalities. Persistent inflammation and ulceration of the ocular surface with cicatricial complications of the lids leads to chronic ocular sequelae, ocular surface damage, and corneal scarring. The destruction of the glands that secrete the tear film leads to a severe form of dry eye that makes the management of chronic SJS difficult. The option that is routinely used for corneal visual rehabilitation, keratoplasty, is best avoided in such cases. We describe the management strategies that are most effective during the acute and chronic stages of SJS. Although treatments for acute SJS involve immunosuppressive and immunomodulatory therapies, amniotic membrane transplantation is also useful. The options for visual rehabilitation in patients with chronic SJS are undergoing radical change. We describe the existing literature regarding the management of SJS and highlight recent advances in the management of this disorder. (C) 2016 Elsevier Inc. All rights reserved. C1 [Jain, Rajat] DrishtiCONE Eye Care, Dept Ophthalmol, Cornea Segment Serv, New Delhi, India. [Jain, Rajat] DrishtiCONE Eye Care, Dept Ophthalmol, Ocular Surface Segment Serv, New Delhi, India. [Jain, Rajat] DrishtiCONE Eye Care, Dept Ophthalmol, Anterior Segment Serv, New Delhi, India. [Sharma, Namrata] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Cornea Surg Serv, New Delhi 110029, India. [Sharma, Namrata] All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, Refract Surg Serv, New Delhi 110029, India. [Basu, Sayan] LV Prasad Eye Inst, Dept Ophthalmol, Cornea Segment Serv, Hyderabad, Telangana, India. [Basu, Sayan] LV Prasad Eye Inst, Dept Ophthalmol, Anterior Segment Serv, Hyderabad, Telangana, India. [Iyer, Geetha] Sankara Nethralaya, Dr G Sitalakshmi Mem Clin Ocular Surface Disorder, Dept Ophthalmol, CJ Shah Cornea Serv, Chennai, Tamil Nadu, India. [Ueta, Mayumi; Sotozono, Chie; Kinoshita, Shigeru] Kyoto Prefectural Univ Med, Dept Ophthalmol, Kyoto, Japan. [Ueta, Mayumi] Doshisha Univ, Dept Ophthalmol, Kyotanabe, Japan. [Kannabiran, Chitra] LVPEI, Kallam Anji Reddy Mol Genet Lab, Dept Ophthalmol, Hyderabad, Telangana, India. [Rathi, Varsha M.] LV Prasad Eye Inst, Dept Ophthalmol, Cornea Serv, Hyderabad, Telangana, India. [Gupta, Nidhi] Dr Shroff Char Eye Hosp, Dept Ophthalmol, Delhi, India. [Gomes, Jose A. P.] Univ Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Dept Ophthalmol, Cornea & External Dis Serv, Sao Paulo, Brazil. [Gomes, Jose A. P.] Univ Fed Sao Paulo, Escola Paulista Med UNIFESP EPM, Dept Ophthalmol, CASO, Sao Paulo, Brazil. [Chodosh, James] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. [Sangwan, Virender S.] LV Prasad Eye Inst, Srujana Ctr Innovat, Dept Ophthalmol, Hyderabad, Telangana, India. RP Sangwan, VS (reprint author), LV Prasad Eye Inst, Ctr Ocular Regenerat CORE, Dept Ophthalmol, Kallam Anji Reddy Campus,LV Prasad Marg, Hyderabad 500034, Telangana, India. EM vsangwan@lvpei.org NR 238 TC 1 Z9 1 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 EI 1879-3304 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD JUL-AUG PY 2016 VL 61 IS 4 BP 369 EP 399 DI 10.1016/j.survophthal.2016.01.004 PG 31 WC Ophthalmology SC Ophthalmology GA DP4DB UT WOS:000378444500001 PM 26829569 ER PT J AU Taber, DJ Hamedi, M Rodrigue, JR Gebregziabher, MG Srinivas, TR Baliga, PK Egede, LE AF Taber, David J. Hamedi, Mahsa Rodrigue, James R. Gebregziabher, Mulugeta G. Srinivas, Titte R. Baliga, Prabhakar K. Egede, Leonard E. TI Quantifying the Race Stratified Impact of Socioeconomics on Graft Outcomes in Kidney Transplant Recipients SO TRANSPLANTATION LA English DT Article ID SOCIAL ADAPTABILITY INDEX; RENAL-ALLOGRAFT RECIPIENTS; EVENT TIME DATA; RACIAL DISPARITIES; AFRICAN-AMERICANS; RISK-FACTORS; SURVIVAL; DISEASE; MORTALITY; PREDICTS AB Background. Socioeconomic status (SES) is a significant determinant of health outcomes and may be an important component of the causal chain surrounding racial disparities in kidney transplantation. The social adaptability index (SAI) is a validated and quantifiable measure of SES, with a lack of studies analyzing this measure longitudinally or between races. Methods. Longitudinal cohort study in adult kidney transplantation transplanted at a single-center between 2005 and 2012. The SAI score includes 5 domains (employment, education, marital status, substance abuse and income), each with a minimum of 0 and maximum of 3 for an aggregate of 0 to 15 (higher score. better SES). Results. One thousand one hundred seventy-one patients were included; 624 (53%) were African American (AA) and 547 were non-AA. African Americans had significantly lower mean baseline SAI scores (AAs 6.5 vs non-AAs 7.8; P < 0.001). Cox regression analysis demonstrated that there was no association between baseline SAI and acute rejection in non-AAs (hazard ratio [HR], 0.92; 95% confidence interval [95% CI], 0.81-1.05), whereas it was a significant predictor of acute rejection in AAs (HR, 0.89; 95% CI, 0.80-0.99). Similarly, a 2-stage approach to joint modelling of time to graft loss and longitudinal SAI did not predict graft loss in non-AAs (HR, 1.01; 95% CI, 0.28-3.62), whereas it was a significant predictor of graft loss in AAs (HR, 0.23; 95% CI, 0.06-0.93). Conclusions. After controlling for confounders, SAI scores were associated with a lower risk of acute rejection and graft loss in AA kidney transplant recipients, whereas neither baseline nor follow-up SAI predicted outcomes in non-AA kidney transplant recipients. C1 [Taber, David J.; Baliga, Prabhakar K.] Med Univ S Carolina, Coll Med, Div Transplant Surg, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Taber, David J.] Ralph H Johnson VAMC, Dept Pharm, Charleston, SC USA. [Hamedi, Mahsa] Med Univ S Carolina, Coll Med, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Rodrigue, James R.] Harvard Univ, Beth Israel Deaconess Med Ctr, Transplant Inst, Sch Med, Boston, MA 02215 USA. [Gebregziabher, Mulugeta G.] Med Univ S Carolina, Dept Publ Hlth Sci, Coll Med, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Srinivas, Titte R.] Med Univ S Carolina, Div Transplant Nephrol, Coll Med, 96 Jonathan Lucas St,MSC 611, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VAMC, Vet Affairs HSR&D Hlth Equ & Rural Outreach In, Charleston, SC USA. RP Taber, DJ (reprint author), Med Univ S 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 NIDDK NIH HHS [K23 DK099440, T35 DK007431] NR 35 TC 5 Z9 5 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL PY 2016 VL 100 IS 7 BP 1550 EP 1557 DI 10.1097/TP.0000000000000931 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DP0AG UT WOS:000378149300030 PM 26425875 ER PT J AU Rose, C Nickerson, P Delmonico, F Randhawa, G Gill, J Gill, JS AF Rose, Caren Nickerson, Peter Delmonico, Francis Randhawa, Gurch Gill, Jagbir Gill, John S. TI Estimation of Potential Deceased Organ Donors in Canada SO TRANSPLANTATION LA English DT Article ID DONATION; KIDNEY; COHORT; RATES; DEATH AB Background. Development of strategies to increase deceased organ donation is dependent on timely, accurate information regarding the number of potential deceased organ donors. Our objective was to estimate the number of potential deceased organ donors in Canada. Methods. This was a retrospective analysis of information captured from hospital separations in Canadian provinces with the exception of Quebec between 2005 and 2009. We studied individuals 70 years or younger who died in hospital. Our primary outcome measure was potential deceased organ donors (identified by the presence of diagnostic codes compatible with donation, the absence of contraindications to donation defined by Canadian Standards, and the use of mechanical ventilation). Results. Among 335 793 hospital deaths, 8274 potential donors were identified. The study method was 81% sensitive and 93% specific for identification of potential donors, and overestimated potential donors by a factor of 1.6- to 2.1-fold when compared to information from chart audits. After accounting for this overestimation, there are conservatively 400 unrecognized potential deceased donors in Canada annually. Conclusions. These findings suggest there may be significant potential to increase deceased organ donations in Canada. Further studies to fully characterize the number of potential donors identified by the study method are needed. C1 [Rose, Caren; Gill, Jagbir; Gill, John S.] Univ British Columbia, Div Nephrol, Dept Med, Providence Bldg Ward,6a-1080 Burrard St, Vancouver, BC V6Z 1Y6, Canada. [Nickerson, Peter] Univ Manitoba, Renal Transplant Program, Winnipeg, MB, Canada. [Delmonico, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Randhawa, Gurch] Univ Bedfordshire, Inst Hlth Res, Luton, Beds, England. [Gill, Jagbir; Gill, John S.] Ctr Hlth Evaluat & Outcomes Sci, Vancouver, BC, Canada. RP Gill, JS (reprint author), Univ British Columbia, Dept Med, St Pauls Hosp, Providence Bldg Ward,6a-1080 Burrard St, Vancouver, BC V6Z 1Y6, Canada. EM jgill@providencehealth.bc.ca 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 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL PY 2016 VL 100 IS 7 BP 1558 EP 1563 DI 10.1097/TP.0000000000000947 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DP0AG UT WOS:000378149300031 PM 26479283 ER PT J AU Markmann, JF Bartlett, ST Johnson, P Korsgren, O Hering, BJ Scharp, D Kay, TWH Bromberg, J Odorico, JS Weir, GC Bridges, N Kandaswamy, R Stock, P Friend, P Gotoh, M Cooper, DKC Park, CG O'Connell, PJ Stabler, C Matsumoto, S Ludwig, B Choudhary, P Khovatchev, B Rickels, MR Sykes, M Wood, K Kraemer, K Hwa, A Stanley, E Ricordi, C Zimmerman, M Greenstein, J Montanya, E Otonkoski, T AF Markmann, James F. Bartlett, Stephen T. Johnson, Paul Korsgren, Olle Hering, Bernhard J. Scharp, David Kay, Thomas W. H. Bromberg, Jonathan Odorico, Jon S. Weir, Gordon C. Bridges, Nancy Kandaswamy, Raja Stock, Peter Friend, Peter Gotoh, Mitsukazu Cooper, David K. C. Park, Chung-Gyu O'Connell, Philip J. Stabler, Cherie Matsumoto, Shinichi Ludwig, Barbara Choudhary, Pratik Khovatchev, Boris Rickels, Michael R. Sykes, Megan Wood, Kathryn Kraemer, Kristy Hwa, Albert Stanley, Edward Ricordi, Camillo Zimmerman, Mark Greenstein, Julia Montanya, Eduard Otonkoski, Timo TI Executive Summary of IPITA-TTS Opinion Leaders Report on the Future of beta-Cell Replacement SO TRANSPLANTATION LA English DT Review ID PORCINE ISLET XENOTRANSPLANTATION; MEDIATED INFLAMMATORY REACTION; NONHUMAN-PRIMATES; CYNOMOLOGUS MONKEYS; PIG ISLETS; REVERSAL; TRANSPLANTATION; SURVIVAL; IMMUNOSUPPRESSION; AUTOIMMUNITY AB The International Pancreas and Islet Transplant Association (IPITA), in conjunction with the Transplantation Society (TTS), convened a workshop to consider the future of pancreas and islet transplantation in the context of potential competing technologies that are under development, including the artificial pancreas, transplantation tolerance, xenotransplantation, encapsulation, stem cell derived beta cells, beta cell proliferation, and endogenous regeneration. Separate workgroups for each topic and then the collective group reviewed the state of the art, hurdles to application, and proposed research agenda for each therapy that would allow widespread application. Herein we present the executive summary of this workshop that focuses on obstacles to application and the research agenda to overcome them; the full length article with detailed background for each topic is published as an online supplement to Transplantation. C1 [Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. [Bartlett, Stephen T.; Bromberg, Jonathan] Univ Maryland, Sch Med, Dept Surg, Baltimore, MD 21201 USA. [Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. [Johnson, Paul; Friend, Peter; Wood, Kathryn] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [Korsgren, Olle] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden. [Hering, Bernhard J.; Kandaswamy, Raja] Univ Minnesota, Dept Surg, Schulze Diabet Inst, Box 242 UMHC, Minneapolis, MN 55455 USA. [Scharp, David] Prodo Labs LLC, Irvine, CA USA. [Scharp, David] Scharp Lacy Res Inst, Irvine, CA USA. [Kay, Thomas W. H.] St Vincents Inst Med Res, 41 Victoria Parade, Fitzroy, Vic 3065, Australia. [Kay, Thomas W. H.] Univ Melbourne, St Vincents Hosp, Dept Med, Melbourne, Vic 3010, Australia. [Odorico, Jon S.] Univ Wisconsin, Dept Surg, Sch Med & Publ Hlth, Div Transplantat, Madison, WI USA. [Weir, Gordon C.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Weir, Gordon C.] Harvard Univ, Sch Med, Boston, MA USA. [Bridges, Nancy; Kraemer, Kristy] NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. [Stock, Peter] Univ San Francisco, Med Ctr, Div Transplantat, San Francisco, CA 94117 USA. [Gotoh, Mitsukazu] Fukushima Med Univ, Dept Surg, Fukushima, Japan. [Cooper, David K. C.] Univ Pittsburgh, Thomas E Starzl Transplantat Inst, Pittsburgh, PA USA. [Park, Chung-Gyu] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Xenotransplantat Res Ctr,Dept Microbiol & Immunol, Seoul, South Korea. [O'Connell, Philip J.] Univ Sydney, Westmead Hosp, Ctr Transplant & Renal Res, Westmead Millennium Inst, Westmead, NSW 2145, Australia. [Stabler, Cherie] Univ Florida, Dept Biomed Engn, Gainesville, FL USA. [Matsumoto, Shinichi] Otsuka Pharmaceut Factory Inc, Naruto, Japan. [Matsumoto, Shinichi] Natl Ctr Global Hlth & Med, Tokyo, Japan. [Ludwig, Barbara] Tech Univ Dresden, Dept Med 3, D-01062 Dresden, Germany. [Ludwig, Barbara] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Helmholtz Ctr Munich, Paul Langerhans Inst Dresden, Dresden, Germany. [Ludwig, Barbara] DZD German Ctr Diabet Res, Dresden, Germany. [Choudhary, Pratik] Kings Coll London, Weston Educ Ctr, Diabet Res Grp, London WC2R 2LS, England. [Khovatchev, Boris] Univ Virginia, Ctr Diabet Technol, Charlottesville, VA USA. [Rickels, Michael R.] Univ Penn, Dept Med, Perelman Sch Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. [Sykes, Megan] Columbia Univ, Med Ctr, Columbia Ctr Translat Immunol, New York, NY USA. [Hwa, Albert] Juvenile Diabet Res Fdn, New York, NY USA. [Stanley, Edward] Murdoch Childrens Res Inst, Melbourne, Vic, Australia. [Stanley, Edward] Monash Univ, Melbourne, Vic 3004, Australia. [Ricordi, Camillo] Univ Miami, Diabet Res Inst, Coral Gables, FL 33124 USA. [Zimmerman, Mark] BetaLogics, Raritan, NJ USA. [Greenstein, Julia] Juvenile Diabet Res Fdn, Discovery Res, New York, NY USA. [Montanya, Eduard] Univ Barcelona, Hosp Univ Bellvitge, CIBERDEM, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain. [Otonkoski, Timo] Univ Helsinki, Childrens Hosp, Helsinki, Finland. [Otonkoski, Timo] Univ Helsinki, Biomedicum Stem Cell Ctr, Helsinki, Finland. RP Markmann, JF (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT 517, Boston, MA 02114 USA. EM jmarkmann@partners.org RI Stabler, Cherie/E-8227-2011 NR 32 TC 3 Z9 3 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0041-1337 EI 1534-6080 J9 TRANSPLANTATION JI Transplantation PD JUL PY 2016 VL 100 IS 7 BP E25 EP E31 DI 10.1097/TP.0000000000001054 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA DP0AG UT WOS:000378149300001 PM 27082827 ER PT J AU Gleason, CE Dowling, NM Benton, SF Kaseroff, A Gunn, W Edwards, DF AF Gleason, Carey E. Dowling, N. Maritza Benton, Susan Flowers Kaseroff, Ashley Gunn, Wade Edwards, Dorothy Farrar TI Common Sense Model Factors Affecting African Americans' Willingness to Consult a Healthcare Provider Regarding Symptoms of Mild Cognitive Impairment SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE timely diagnosis; mild cognitive impairment; common sense model; health disparities; structural equation modeling ID ALZHEIMERS ASSOCIATION WORKGROUPS; NURSING-HOME PLACEMENT; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE; DEMENTIA DIAGNOSIS; TIMELY DIAGNOSIS; OLDER-ADULTS; DISEASE; SAMPLE; REPRESENTATIONS AB Objective: Although at increased risk for developing dementia compared with white patients, older African Americans are diagnosed later in the course of dementia. Using the common sense model (CSM) of illness perception, we sought to clarify processes promoting timely diagnosis of mild cognitive impairment (MCI) for African American patients. Design, Setting, Participants: In-person, cross-sectional survey data were obtained from 187 African American (mean age: 60.44 years). Data were collected at social and health-focused community events in three southern Wisconsin cities. Measurements: The survey represented a compilation of published surveys querying CSM constructs focused on early detection of memory disorders, and willingness to discuss concerns about memory loss with healthcare providers. Derived CSM variables measuring perceived causes, consequences, and controllability of MCI were included in a structural equation model predicting the primary outcome: Willingness to discuss symptoms of MCI with a provider. Results: Two CSM factors influenced willingness to discuss symptoms of MCI with providers: Anticipation of beneficial consequences and perception of low harm associated with an MCI diagnosis predicted participants' willingness to discuss concerns about cognitive changes. No association was found between perceived controllability and causes of MCI, and willingness to discuss symptoms with providers. Conclusions: These data suggest that allaying concerns about the deleterious effects of a diagnosis, and raising awareness of potential benefits, could influence an African American patient's willingness to discuss symptoms of MCI with a provider. The findings offer guidance to designers of culturally congruent MCI education materials, and healthcare providers caring for older African Americans. C1 [Gleason, Carey E.; Dowling, N. Maritza; Edwards, Dorothy Farrar] Wisconsin Alzheimers Dis Res Ctr, Madison, WI USA. [Gleason, Carey E.; Edwards, Dorothy Farrar] Univ Wisconsin, Dept Med, Div Geriatr, Madison, WI USA. [Dowling, N. Maritza] Univ Wisconsin, Sch Med & Publ Hlth, Dept Biostat & Med Informat, Madison, WI USA. [Gleason, Carey E.] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. [Benton, Susan Flowers; Kaseroff, Ashley] Univ Wisconsin, Sch Educ, Dept Rehabil Psychol & Special Educ, Madison, WI USA. [Gunn, Wade; Edwards, Dorothy Farrar] Univ Wisconsin, Sch Educ, Kinesiol & Occupat Therapy, Madison, WI USA. RP Gleason, CE (reprint author), William S Middleton Mem VA Hosp, 2500 Overlook Terrace,GRECC 11G,D4223, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu RI Edwards, Dorothy/L-6720-2016 FU Wisconsin ADRC Minority Recruitment Satellite Program; Education, Clinical, and Administrative Cores of the Wisconsin ADRC; Community-Academic Aging Research Network (CAARN); Wisconsin Partnership Program of the University of Wisconsin School of Medicine and Public Health; Wisconsin Alzheimer's Disease Research Center (ADRC; NIH-NIA) [P50-AG033514]; Madison VA Geriatric Research, Education, and Clinical Center (GRECC); Community-Academic Aging Research Network; National Institute on Aging [RC4AG038175]; NCATS via the UW Clinical and Translational Science Award (CTSA) [UL1TR000427] FX The authors acknowledge support from the Wisconsin ADRC Minority Recruitment Satellite Program, and the Education, Clinical, and Administrative Cores of the Wisconsin ADRC, and the Community-Academic Aging Research Network (CAARN). Finally, we are grateful for the dedication and support from our Community Partners, Charlestine Daniel, MS, and Paul Rusk from the Alzheimer's and Dementia Alliance; staff Ornella Hills, and Tyrone Dickson from the Wisconsin Alzheimer's Disease Research Center; project assistants Paul Izard and Brianna Harris; and our participants.; This project was funded by the Wisconsin Partnership Program of the University of Wisconsin School of Medicine and Public Health and the Wisconsin Alzheimer's Disease Research Center (ADRC; NIH-NIA grant P50-AG033514), and supported by the Madison VA Geriatric Research, Education, and Clinical Center (GRECC), and the Community-Academic Aging Research Network, award number RC4AG038175 from the National Institute on Aging. Additional support was provided by NCATS grant UL1TR000427 (PI: M. Drezner) via the UW Clinical and Translational Science Award (CTSA) and resources and use of facilities at the UW School of Medicine and Public Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging, the National Institutes of Health, or any other funding agency. This is GRECC manuscript number: 2014-027. NR 34 TC 0 Z9 0 U1 5 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL PY 2016 VL 24 IS 7 BP 537 EP 546 DI 10.1016/j.jagp.2015.08.005 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DO6BH UT WOS:000377866800005 PM 26809602 ER PT J AU Kaufmann, CN Mojtabai, R Hock, RS Thorpe, RJ Canham, SL Chen, LY Wennberg, AMV Chen-Edinboro, LP Spira, AP AF Kaufmann, Christopher N. Mojtabai, Ramin Hock, Rebecca S. Thorpe, Roland J., Jr. Canham, Sarah L. Chen, Lian-Yu Wennberg, Alexandra M. V. Chen-Edinboro, Lenis P. Spira, Adam P. TI Racial/Ethnic Differences in Insomnia Trajectories Among US Older Adults SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Associated-Professional-Sleep-Societies CY JUN 01-05, 2013 CL Baltimore, MD SP Associated Profess Sleep Soc DE Disparities; Aging; Insomnia; Chronic health conditions ID SHORT-SLEEP DURATION; REGRESSION-ANALYSIS; RACIAL-DIFFERENCES; UNITED-STATES; SELF-REPORTS; HEALTH; POPULATION; SYMPTOMS; DISPARITIES; PREVALENCE AB Objectives: Insomnia is reported to be more prevalent in minority racial/ethnic groups. Little is known, however, about racial/ethnic differences in changes in insomnia severity over time, particularly among older adults. We examined racial/ethnic differences in trajectories of insomnia severity among middle-aged and older adults. Design: Data were drawn from five waves of the Health and Retirement Study (2002-2010), a nationally representative longitudinal biennial survey of adults aged > 50 years. Setting: Population-based. Participants: 22,252 participants from non-Hispanic white, non-Hispanic black, Hispanic, and other racial/ethnic groups. Measurements: Participants reported the severity of four insomnia symptoms; summed scores ranged from 4 (no insomnia) to 12 (severe insomnia). We assessed change in insomnia across the five waves as a function of race/ethnicity. Results: Across all participants, insomnia severity scores increased 0.19 points (95% CI: 0.14-0.24; t = 7.52; design df = 56; p < 0.001) over time after adjustment for sex, race/ethnicity, education, and baseline age. After adjusting for the number of accumulated health conditions and body mass index, this trend decreased substantially and even changed direction (B = -0.24; 95% CI: -0.29 to -0.19; t = -9.22; design df = 56; p < 0.001). The increasing trajectory was significantly more pronounced in Hispanics compared with non-Hispanic whites, even after adjustment for number of accumulated health conditions, body mass index, and number of depressive symptoms. Conclusions: Although insomnia severity increases with age-largely due to the accumulation of health conditions-this trend appears more pronounced among Hispanic older adults than in non-Hispanic whites. Further research is needed to determine the reasons for a different insomnia trajectory among Hispanics. C1 [Kaufmann, Christopher N.; Mojtabai, Ramin; Chen, Lian-Yu; Wennberg, Alexandra M. V.; Spira, Adam P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Thorpe, Roland J., Jr.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. [Hock, Rebecca S.] Massachusetts Gen Hosp, Chester M Pierce MD Div Global Psychiat, Boston, MA 02114 USA. [Hock, Rebecca S.] Harvard Univ, Sch Med, Boston, MA USA. [Canham, Sarah L.] Simon Fraser Univ, Gerontol Res Ctr, Vancouver, BC, Canada. [Chen-Edinboro, Lenis P.] Univ N Carolina, Sch Hlth & Appl Human Sci, Wilmington, NC 28401 USA. [Spira, Adam P.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Kaufmann, CN (reprint author), 9500 Gilman Dr 0664, La Jolla, CA 92093 USA. EM cnkaufmann@ucsd.edu RI Wennberg, Alexandra/O-9563-2016 OI Wennberg, Alexandra/0000-0003-4906-1165 FU National Institutes of Health; National Institute on Aging [F31AG044052, K01AG033195]; National Institute of Mental Health [T32MH019934, T32MH093310, T32MH014592]; National Institute on Minority Health and Health Disparities [P60MD000214]; National Institute on Drug Abuse [T32DA007292] FX This work was supported by the National Institutes of Health. Drs. Kaufmann and Spira were supported by the National Institute on Aging (CNK: F31AG044052, APS: K01AG033195). Dr. Kaufmann currently receives funding from the National Institute of Mental Health (T32MH019934). Drs. Hock and Chen-Edinboro were supported by the National Institute of Mental Health (RSH: T32MH093310, LPC-E: T32MH014592). Dr. Thorpe was supported by the National Institute on Minority Health and Health Disparities (P60MD000214). Dr. Canham was supported by the National Institute on Drug Abuse (T32DA007292). All authors report no conflicts of interest. NR 28 TC 0 Z9 0 U1 4 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUL PY 2016 VL 24 IS 7 BP 575 EP 584 DI 10.1016/j.jagp.2016.02.049 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA DO6BH UT WOS:000377866800008 PM 27212222 ER PT J AU Becerra, MB Becerra, BJ Hassija, CM Safdar, N AF Becerra, Monideepa B. Becerra, Benjamin J. Hassija, Christina M. Safdar, Nasia TI Unmet Mental Healthcare Need and Suicidal Ideation Among US Veterans SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MAJOR DEPRESSION; WAR VETERANS; RISK; AFGHANISTAN; SERVICES; DEATH; IRAQ; ASSOCIATION; SYMPTOMS AB Introduction: Suicide prevention remains a national priority, especially among vulnerable populations. With increasing trends in suicide among Veterans, understanding the underlying factors associated with such an outcome is imperative. In this study, the association between unmet mental healthcare need and suicidal ideation among U.S. Veterans was evaluated. Methods: The National Survey on Drug Use and Health, 2008-2013, was used to identify those with mental illness, resulting in a total sample of 2,015 Veterans. Data were analyzed in July 2015. Survey-weighted descriptive and logistic regression analyses were conducted with p<0.05 used to establish significance. Results: Sixteen percent of Veterans reported unmet mental healthcare need and 18% had past-year suicidal ideation. After adjusting for confounders, unmet mental healthcare need was associated with increased likelihood of suicidal ideation (AOR=4.11) in the study population. Other characteristics, such as participating in a governmental assistance program and alcohol dependency in the past year, demonstrated 66% and 103% increased odds of suicidal ideation, respectively. Conclusions: Unmet mental healthcare need is a critical aspect of suicidal ideation among Veterans. Improved access to care for such at-risk populations through means of integrated care is needed to ensure reduced burden of suicide among Veterans. (C) 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved. C1 [Becerra, Monideepa B.] Calif State Univ San Bernardino, Dept Hlth Sci & Human Ecol, San Bernardino, CA 92407 USA. [Becerra, Monideepa B.; Becerra, Benjamin J.; Safdar, Nasia] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Becerra, Benjamin J.] Loma Linda Univ, Sch Allied Hlth Profess, Loma Linda, CA 92350 USA. [Hassija, Christina M.] Calif State Univ San Bernardino, Dept Psychol, San Bernardino, CA 92407 USA. [Safdar, Nasia] Univ Wisconsin, Dept Med, Madison, WI USA. RP Becerra, MB (reprint author), 5500 Univ Pkwy, San Bernardino, CA 92407 USA. EM mbecerra@csusb.edu FU U.S. Department of Veterans Affairs (VA) Merit grant; VA National Center for Patient Safety FX Nasia Safdar is supported by a U.S. Department of Veterans Affairs (VA) Merit grant and by the VA National Center for Patient Safety. NR 33 TC 0 Z9 0 U1 8 U2 11 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 JUL PY 2016 VL 51 IS 1 BP 90 EP 94 DI 10.1016/j.amepre.2016.01.015 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA DO8VR UT WOS:000378063800013 PM 26927480 ER PT J AU Coulon, SM Monroe, CM West, DS AF Coulon, Sandra M. Monroe, Courtney M. West, Delia S. TI A Systematic, Multi-domain Review of Mobile Smartphone Apps for Evidence-Based Stress Management SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID HEALTH-CARE PROVIDERS; GOOD MEDICAL-ETHICS; SOCIOECONOMIC-STATUS; MENTAL-HEALTH; ANXIETY; DEPRESSION; ADHERENCE; QUALITY; TOOLS; PRINCIPLES AB Contex: Chronic stress presents a growing, pervasive burden in healthcare, and mobile smartphone applications (apps) have the potential to deliver evidence-based stress management strategies. This review identified and evaluated stress management apps across domains of (1) evidence-based content; (2) transparency in app development; and (3) functionality of the app interface. Evidence acquisition: The iOS App Store was systematically searched. Apps with descriptions indicating that they targeted the intended audience and included evidence-related terminology, at least one evidence-based stress management strategy, and behavior change components were downloaded and evaluated by two independent raters across the three domains of evidence-based content, transparency, and functionality. Evidence synthesis: A total of 902 apps were identified based on 21 searches. Of these, 60 met study criteria and were downloaded and evaluated between April and June 2015. Twenty (33%) ultimately did not deliver an evidence-based strategy. Of the delivered strategies, the most common were mindfulness and meditation (73%) and diaphragmatic breathing (25%). On average, apps addressed half of the transparency criteria, and nearly all (85%) were acceptable across usability criteria. A total of 32 apps included both evidence-based content and exhibited no problems with usability or functionality; apps affiliated with a non-profit, research-engaged institution comprised 31% of these. Conclusions: This review evaluated 60 iOS apps for stress management across domains of evidence-based content, transparency, and functionality; these apps have the potential to effectively supplement medical care. Findings further indicate that a comprehensive, multi-domain approach can distinguish apps that use evidence-based strategies from those that do not. (C) 2016 Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine C1 [Coulon, Sandra M.; Monroe, Courtney M.; West, Delia S.] Univ S Carolina, Arnold Sch Publ Hlth, Columbia, SC 29208 USA. RP Coulon, SM (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St,Mental Hlth Serv 116, Charleston, SC 29401 USA. EM coulon@mailbox.sc.edu FU Technology Center to Promote Healthy Lifestyles (TecHealth), Arnold School of Public Health, University of South Carolina FX This work was funded in part by the Technology Center to Promote Healthy Lifestyles (TecHealth), Arnold School of Public Health, University of South Carolina. SMC, CMM, and DSW contributed to the manuscript in its conception and writing. SMC and DSW developed the app screening and evaluation methods. SMC and CMM each evaluated the downloaded stress management apps. SMC screened app descriptions and CMM assessed the reliability of the screening. SMC developed data collection tools; extracted, cleaned, and analyzed the data; and wrote the initial drafts of the manuscript. CMM and DSW revised the drafts. The work was performed while SMC was at the University of South Carolina. All authors had full access to all of the data, and read and approved the final manuscript. NR 49 TC 1 Z9 1 U1 10 U2 28 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 JUL PY 2016 VL 51 IS 1 BP 95 EP 105 DI 10.1016/j.amepre.2016.01.026 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupationa